Methotrexate in rheumatoid arthritis. Feedback on American College of Physicians guidelines.
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Arthritis, Rheumatoid↗
Biomedical subjects
M Gent
Publications and source records attributed to M Gent.
Comparison of high-dose with low-dose subcutaneous heparin to prevent left ventricular mural thrombosis in patients with acute transmural anterior myocardial infarction.
We performed a double-blind randomized trial comparing high doses of subcutaneous heparin (12,500 units every 12 hours) with low doses (5000 units every 12 hours) for 10 days in the prevention of left ventricular mural thrombosis in 221 patients with acute anterior myocardial infarction. Left ventricular mural thrombosis was observed by two-dimensional echocardiography on the 10th day after infarction in 10 of 95 patients (11 percent) in the high-dose group and in 28 of 88 patients (32 percent) in the low-dose group (P = 0.0004). One patient in the high-dose group and four in the low-dose group had nonhemorrhagic strokes (P = 0.17). One patient in the low-dose group had a fatal pulmonary embolism. There was no difference in the frequency of hemorrhagic complications, which occurred in six patients in the high-dose group and four in the low-dose group. The mean (+/- SEM) plasma heparin concentration was 0.18 +/- 0.017 U per milliliter in the high-dose group and 0.01 +/- 0.005 U per milliliter in the low-dose group (P less than 0.0001). In the high-dose group, the mean plasma heparin concentration was 0.10 +/- 0.029 U per milliliter among patients with abnormal two-dimensional echocardiograms, as compared with 0.19 +/- 0.019 U per milliliter among patients with normal echocardiograms (P = 0.01). We conclude that heparin administered subcutaneously in a dosage of 12,500 units every 12 hours to patients with acute anterior transmural myocardial infarction is more effective than a lower dosage (5000 units every 12 hours) in preventing left ventricular mural thrombosis.
Aged↗
Colchicine treatment of cirrhosis: answers.
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Colchicine↗
Tissue plasminogen activator: Toronto (TPAT) placebo-controlled randomized trial in acute myocardial infarction.
The efficacy and safety of recombinant tissue plasminogen activator (rt-PA) administered on a dosing per weight basis was evaluated in a randomized, placebo-controlled, double-blind trial in 115 patients with acute myocardial infarction. The principal outcomes were global and regional left ventricular function in the distribution of the qualifying myocardial infarction, determined 9 days after the onset of symptoms. Global and regional ejection fraction values were significantly better for patients treated with rt-PA than for placebo-treated patients (the differences were 5.8 +/- 2.7% units [p = 0.017] and 7.1 +/- 3.1% units [p = 0.012], respectively). This benefit was also evident from visual assessment of left ventricular segmental wall motion. After adjustment for differences in important prognostic variables at baseline, the estimates of treatment effect were 4.0 +/- 2.4% units (p = 0.048) for global and 4.3 +/- 2.6% units (p = 0.047) for regional ejection fraction. Early patency of the infarct-related vessel was demonstrable in 7 (29%) of 24 placebo-treated patients and 18 (78%) of 23 rt-PA-treated patients, whereas 15 (56%) of 27 patients in the placebo group and 23 (72%) of 32 in the rt-PA group had a patent infarct-related vessel at hospital day 9. There was no significant difference in irreversible or reversible defect size as assessed by thallium scintigraphy on day 7.(ABSTRACT TRUNCATED AT 250 WORDS)
Double-Blind Method↗
Prevention of deep vein thrombosis in potential neurosurgical patients. A randomized trial comparing graduated compression stockings alone or graduated compression stockings plus intermittent pneumatic compression with control.
In a randomized trial of neurosurgical patients, groups wearing graduated compression stockings alone (group 1) or graduated compression stockings plus intermittent pneumatic compression (IPC) (group 2) were compared with an untreated control group in the prevention of deep vein thrombosis (DVT). In both active treatment groups, the graduated compression stockings were continued for 14 days or until hospital discharge, if earlier. In group 2, IPC was continued for seven days. All patients underwent DVT surveillance with iodine 125-labeled fibrinogen leg scanning and impedance plethysmography. Venography was carried out if either test became abnormal. Deep vein thrombosis occurred in seven (8.8%) of 80 patients in group 1, in seven (9.0%) of 78 patients in group 2, and in 16 (19.8%) of 81 patients in the control group. The observed differences among these rates are statistically significant. The results of this study indicate that graduated compression stockings alone or in combination with IPC are effective methods of preventing DVT in neurosurgical patients.
Clinical Trials as Topic↗
A randomized trial of less intense postoperative warfarin or aspirin therapy in the prevention of venous thromboembolism after surgery for fractured hip.
A randomized trial was carried out with 194 patients to compare the effectiveness of sodium warfarin or aspirin with that of placebo in the prevention of venous thromboembolism after surgery for fractured hip. Prophylaxis was commenced postoperatively and continued for 21 days or until patient discharge, whichever was earlier. All patients underwent surveillance with iodine 125-fibrinogen leg scanning and impedance plethysmography, with subsequent venography. Venous thromboembolism occurred in 13 patients (20.0%) in the warfarin group, 27 patients (40.9%) in the aspirin group, and 29 patients (46.0%) in the placebo group. Proximal vein thrombosis or pulmonary embolism occurred in 6 patients (9.2%) in the warfarin group, 7 patients (10.6%) in the aspirin group, and 19 patients (30.2%) in the placebo group. The results of this study show that sodium warfarin therapy is safe and effective in preventing thromboembolic complications in patients undergoing surgery for fractured hip, and that aspirin therapy is an equally safe and effective method for preventing proximal vein thrombosis or pulmonary embolism.
Adult↗
Colchicine in the treatment of cirrhosis of the liver.
There is preliminary evidence that colchicine, an inhibitor of collagen synthesis, may be beneficial in the treatment of cirrhosis of the liver. To evaluate the use of colchicine (1 mg per day, five days per week) in the treatment of hepatic cirrhosis, we performed a randomized, double-blind, placebo-controlled trial in which 100 patients were followed for up to 14 years. Forty-five patients had alcoholic cirrhosis, 41 had posthepatitic cirrhosis, and the remaining 14 had cirrhosis with various other causes. Histologic studies were available for 92 percent of patients. Seventy-three patients were in Child-Turcotte class A, 26 were in class B, and one was in class C. Fifty-four patients received colchicine, and 46 received placebo. The overall survival in the colchicine group was markedly better than in the placebo group (median survival, 11 and 3.5 years, respectively; P less than 0.001). The cumulative 5-year survival rates were 75 percent in the colchicine group and 34 percent in the placebo group; the corresponding 10-year survival rates were 56 percent and 20 percent. Among the 30 patients treated with colchicine who underwent repeated liver biopsies, histologic improvement was seen in 9; the liver appeared normal in 2, and 7 had minimal portal fibrosis. No histologic improvement was observed in the 14 members of the placebo group who had two or more biopsies. Few side effects were observed in either group.
Clinical Trials as Topic↗
Randomised comparison of two intensities of oral anticoagulant therapy after tissue heart valve replacement.
After tissue heart valve replacement 108 patients were randomised to standard anticoagulant control with rabbit brain thromboplastin (Dade C reagent, therapeutic range 18-24 s; international normalised ratio 2.5-40) and 102 to a less intensive regimen controlled with human brain thromboplastin (Manchester Comparative Reagent, therapeutic range 26-30 s; INR 2.0-2.25). Treatment was continued for three months, outcome measures being major or minor embolism or haemorrhage. 2 patients in each group had major embolic events and 11 in each group had minor embolic events. The 95% confidence intervals on the differences are -3.4% to 3.2% for major embolism and -9.3% to 8.2% for minor embolism. Haemorrhagic complications were significantly more frequent with standard treatment (15 patients) than with the less intensive regimen (6 patients); and of the 5 patients with major haemorrhagic complications, all were in the standard treatment group, again a significant difference. The less intensive regimen is thus no less effective and safer than standard anticoagulant therapy in patients with tissue heart valve replacement.
Administration, Oral↗
The thrombogenic effect of anticancer drug therapy in women with stage II breast cancer.
Thromboembolic disease has long been recognized as a complication of cancer. Recent reports have suggested that drugs used in the treatment of cancer, including chemotherapeutic agents and hormones, may contribute to this risk, but it has not been possible to separate the effect of these drugs from that of the cancer. We performed a randomized trial comparing 12 weeks of chemohormonal therapy (using cyclophosphamide, methotrexate, fluorouracil, vincristine, prednisone, doxorubicin, and tamoxifen) with 36 weeks of chemotherapy (using cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone) in patients with Stage II breast cancer. Among 205 patients randomly assigned to treatment, there were 14 episodes of thrombosis (6.8 percent). These 14 episodes occurred during 979 patient-months of chemotherapy; by comparison, there were no events during 2413 patient-months without therapy. During the first 12 weeks of the study, five patients in the 12-week group and four patients in the 36-week group had thrombosis. During the subsequent 24 weeks, when only patients in the 36-week group were still receiving chemotherapy, there was no thrombosis in the 12-week group, but there were five additional events in the 36-week group (P = 0.03). These findings suggest that chemotherapy contributes to thrombosis in patients with breast cancer.
Antineoplastic Combined Chemotherapy Protocols↗
The Canadian American Ticlopidine Study (CATS) in thromboembolic stroke. Design, organization, and baseline results.
The Canadian American Ticlopidine Study is a randomized, placebo-controlled, double-blind, multicenter study to assess the efficacy and safety of ticlopidine hydrochloride in patients who have suffered a thromboembolic stroke no less than 1 week and no more than 4 months before entry into the study. The primary assessment of efficacy will be based on the cluster of outcome events recurrent stroke, myocardial infarction, or vascular death. Twenty-five clinical centers, 12 in Canada and 13 in the United States, entered a total of 1,072 patients during a 3-year recruitment period; these patients were randomly allocated to receive either 250 mg ticlopidine or identical-appearing placebo tablets twice daily for up to 3 years. Patient recruitment was completed in December 1986. Patients were followed for a maximum of 3 years or until the close of the study in December 1987; at that time an average follow-up of 25 months had been achieved. We summarize the protocol and organization of the study and document the methods of execution and analysis, with corresponding criteria, before disclosure of the treatment code to any of the study investigators. We also provide a clinical description of the patients at entry into the study.
Aged↗
Quality of life in stage II breast cancer: an instrument for clinical trials.
A questionnaire has been developed for use as an outcome measure in clinical trials of adjuvant chemotherapy in women with stage II breast cancer. The selection of items for this Breast Cancer Chemotherapy Questionnaire (BCQ) was based on the problems and experiences felt to be most important by women undergoing adjuvant chemotherapy. The BCQ consists of 30 questions that focus on loss of attractiveness, fatigue, physical symptoms, inconvenience, emotional distress, and feelings of hope and support from others. The BCQ, other instruments that evaluate quality-of-life (Spitzer, Karnofsky, and Rand), and patient and physician global assessments were administered serially to 418 patients taking part in a randomized trial comparing a 12-week regimen and a 36-week regimen of adjuvant chemotherapy. The validity of the BCQ is supported by its correlation with the Rand Emotional (r = .58), Rand Physical (r = .60), and Spitzer (r = .62) questionnaires. The BCQ correlated more strongly with global ratings of both physical and emotional function by the patients and their physicians than the other instruments. A comparison of the quality-of-life outcomes of patients in the two treatment groups in the period beyond 3 months after initiation of treatment, when one group had completed the treatment course and the other was still on treatment, revealed that the BCQ and Karnofsky were the only instruments able to demonstrate differences between the groups (P less than .0001). Hence, the BCQ is a valid and responsive method of assessing treatment-related morbidity in patients receiving adjuvant chemotherapy for stage II breast cancer.
Antineoplastic Agents↗
Effects of immunosuppression with cyclosporine in insulin-dependent diabetes mellitus of recent onset: the Canadian open study at 44 months.
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Adolescent↗
Immunosuppression and type I diabetes.
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Cyclosporins↗
Double-blind randomised trial of Org 10172 low-molecular-weight heparinoid in prevention of deep-vein thrombosis in thrombotic stroke.
In a double-blind, randomised trial Org 10172 low-molecular-weight (LMW) heparinoid was compared with placebo in the prevention of deep-vein thrombosis in patients with acute thrombotic stroke. Prophylaxis was started within 7 days of the onset of stroke with a loading dose of 1000 anti-factor-Xa units intravenously followed by a fixed dose of 750 anti-factor-Xa units twice a day subcutaneously; it was continued for 14 days or until hospital discharge, if earlier. 50 patients were randomised to receive Org 10172 and 25 to receive placebo. All patients underwent surveillance with I125-fibrinogen leg scanning and impedance plethysmography. Venography was carried out if either test became positive. Venous thrombosis occurred in 2 of 50 patients (4.0%) given Org 10172 and 7 of 25 patients (28.0%) given placebo (p = 0.005); the corresponding rates of proximal-vein thrombosis were 0% and 16%, respectively (p = 0.01). There was one major haemorrhage in the Org 10172 group and one minor bleed in the placebo group.
Acute Disease↗
Effects of cyclosporine in recent-onset juvenile type 1 diabetes: impact of age and duration of disease.
Administration of cyclosporine resulted in reduced insulin requirements and improved glycemic control in patients with insulin-dependent diabetes mellitus of recent onset, but the drug was less effective in young children. Renal toxic effects and other problems related to therapy resolved after discontinuation of the drug. Sustained remission seemed dependent on continued administration of cyclosporine. Although short-term control of diabetes may be achieved in some patients, more studies are needed to determine whether cyclosporine can be given safely as maintenance therapy to maintain glycemic control and prevent the long-term consequences of the disease.
Adolescent↗
Methotrexate in rheumatoid arthritis. Indications, contraindications, efficacy, and safety.
Evidence on the safety and efficacy of methotrexate as a second- or third-line agent for treating patients with rheumatoid arthritis is reviewed. Four placebo-controlled clinical trials have documented short-term benefit from methotrexate; although true remission is rare, patients receiving methotrexate showed a 26% (95% confidence interval [CI], 17% to 35%) greater improvement in their inflamed joint count and a 39% (95% CI, 26% to 51.5%) greater improvement in pain than did controls receiving nonsteroidal anti-inflammatory agents with or without prednisone. With respect to long-term benefit, improvement usually occurs within 1 month, reaching a maximum at 6 and then leveling off for the duration of treatment; in some patients, the benefit may wane after an initial satisfactory response in the first 4 to 6 months. In one third of those given methotrexate, treatment had to be discontinued because of adverse effects, less than 1% of which were life threatening. Careful baseline and follow-up monitoring is recommended until more data on the safety of methotrexate are available.
Administration, Oral↗
Adjusted subcutaneous heparin or continuous intravenous heparin in patients with acute deep vein thrombosis. A randomized trial.
STUDY OBJECTIVE: To determine the efficacy and safety of adjusted subcutaneous calcium heparin compared with continuous intravenous calcium heparin as the initial treatment for acute deep vein thrombosis. DESIGN: Randomized control trial. SETTING: University-affiliated general hospital. PATIENTS: Of 111 consecutive patients considered, 103 had acute proximal or calf vein thrombosis confirmed by ascending venography and met all other eligibility criteria. INTERVENTIONS: PATIENTS were randomly assigned to receive subcutaneous or intravenous heparin. The subcutaneous regimen consisted of an initial dose of 15,000 U, adjusted thereafter to prolong the activated partial thromboplastin time to 50 to 70 seconds. The continuous intravenous regimen was begun as a bolus injection of 5000 U, followed by an infusion of 1250 U/h, adjusted to maintain the activated partial thromboplastin time at 50 to 70 seconds. MEASUREMENTS AND MAIN RESULTS: There was no significant difference in the rate of new pulmonary embolism between the two groups, as defined by new high-probability defect on repeat ventilation-perfusion scintigrams of the lung in 96 (93%) of the patients after 7 to 10 days of treatment. Five of forty-seven patients in the subcutaneous group and 5 of 49 in the intravenous group developed pulmonary embolism (95% confidence interval [CI] for the difference, -13.1% to 12.2%). Similarly, there was no significant difference in the frequency of hemorrhagic complications. Five of fifty-one patients in the subcutaneous group and 5 of 52 in the intravenous group had hemorrhagic complications (95% CI for the difference, -11.2% to 11.6%). CONCLUSION: Adjusted subcutaneous calcium heparin may be an effective and safe alternative to continuous intravenous calcium heparin in the initial treatment of acute proximal deep vein thrombosis.
Acute Disease↗
Low dose cyclosporine in rheumatoid arthritis: a pilot study.
A 6 month open trial of cyclosporine (CyA) was conducted in 20 patients with active rheumatoid arthritis unresponsive to second line therapy. The dosage was monitored to achieve a serum blood level of 75-150 ng/ml. A 25% reduction in ARA joint count (baseline mean 38.2; 6 month or time of CyA withdrawal mean 28.7; p less than 0.001) was observed for all patients. Fifteen completed the 6 month CyA regimen and 5 developed toxicity requiring CyA to be permanently withdrawn. For the 15 patients completing 6 months of CyA, improvement was 36% (baseline 34.7; 6 month mean 22.2; p less than 0.001). Corresponding improvements were also observed on the other main study outcomes of pain and functional ability. Improvement occurred between 12-20 weeks, somewhat later than in other studies. Toxicity included mild hypertension (4 patients) and gastrointestinal intolerance (2). Three patients were withdrawn from CyA due to nephrotoxicity. There was a clinically significant reduction in calculated creatinine clearance but this returned to baseline within 6 months after CyA was withdrawn for all except 2 patients who took 12 months to return to baseline.
Adult↗