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Biomedical subjects

R S Roberts

Publications and source records attributed to R S Roberts.

At least 19 recordsLinked to original sources
PubMed1992

Failure of aspirin plus dipyridamole to prevent restenosis after carotid endarterectomy.

OBJECTIVE: To evaluate therapy with aspirin plus dipyridamole in reducing restenosis after carotid endarterectomy. PATIENTS: A total of 163 patients having 175 surgical carotid endarterectomies. INTERVENTION: Eighty-three patients (90 endarterectomies) were randomly assigned to receive oral aspirin, 325 mg, plus dipyridamole, 75 mg, beginning 12 hours preoperatively, followed by a second dose administered within 8 hours after the operation, and given three times daily thereafter for 1 year. Eighty patients (85 endarterectomies) received placebo medication that was identical in appearance to the study drugs. MEASUREMENTS: After the adequacy of the surgical procedure was confirmed by intraoperative angiography, restenosis at the endarterectomy sites was evaluated using serial duplex ultrasound studies before hospital discharge and at 3-month intervals postoperatively for 1 year. RESULTS: Based on the time for developing identifiable restenosis and on efficacy analysis, greater than 50% restenosis developed in 11 operated vessels (16%) in the treated group and in 10 arteries (14%) in the placebo group, yielding an observed risk increase of 14% (95% CI, -52% to 167%; P greater than 0.2). By intention-to-treat analysis, greater than 50% restenosis developed in 16 of 90 operated vessels in treated patients and in 10 of 85 arteries in patients receiving placebo (26% for the treated group and 12% for the placebo group; P = 0.18, Mantel-Haenszel statistic), representing an observed risk increase of 110% (CI, -5% to 365%). Similar differences were observed for greater than 20% restenosis and for the comparison of patients rather than operated vessels by either intention-to-treat or efficacy analyses. CONCLUSIONS: Because therapy not only failed to reduce carotid restenosis but may have actually increased its frequency, treatment with aspirin plus dipyridamole probably has no clinically important benefit on restenosis in patients having carotid endarterectomy.

Aged↗
PubMed1992

Polycyclic aromatic hydrocarbons (PAHs): a possible cause of lung cancer mortality among nickel/copper smelter and refinery workers.

A retrospective industrial hygiene investigation was undertaken to explain the cause of a statistically significant excess lung cancer mortality observed in a subset of a large cohort of nickel workers involved in mining, smelting, and refining of nickel and copper in Ontario. The focus of this paper is to demonstrate how an industrial hygiene follow-up assessment of an epidemiologic finding can help to identify a likely cause. Polycyclic aromatic hydrocarbons (PAHs) alone or in association with particulate and gaseous contaminants (e.g., SO2) were likely the causative agents of the excess lung cancer observed among the lead welders, cranemen, and arc furnace workers of the copper refinery.

Cohort Studies↗
PubMed1992

Design and baseline results of the monosialoganglioside early stroke trial. The EST Study Group.

BACKGROUND AND PURPOSE: The Early Stroke Trial is a randomized, placebo-controlled, double-masked, multicenter study to assess the safety and efficacy of monosialoganglioside in patients who have suffered an ischemic stroke of the cerebral hemispheres. METHODS: Only patients who could be evaluated and treated within 5 hours after the onset of stroke were considered; within each center, subjects were stratified by age, sex, and clinical severity. Patients were randomly allocated to receive a specified sequence of intravenous and intramuscular doses of either monosialoganglioside or identical-appearing placebo for 21 days. Patients were followed up for 4 months after randomization. Neurological status was measured primarily by using the Canadian Neurological Scale. After assessing the effect of treatment on survival, the principal measure of efficacy will be the change in neurological status between baseline and the 4-month follow-up among survivors. RESULTS: Sixteen clinical centers, 15 in Europe and one in North America, entered a total of 792 eligible patients during a 36-month recruitment period (from May 1987 to April 1990). In our series there were more men than women, and the relative frequency of patients increased with advancing age. The most frequently associated cardiovascular conditions were hypertension, atrial fibrillation, and peripheral vascular disease. Approximately 46% of the patients were admitted to a hospital within 1 hour and 81%, within 2 hours after the onset of stroke. About 22% first received the study treatment within 3 hours and 57%, within 4 hours. CONCLUSIONS: This study demonstrates the feasibility of large-scale trials with the onset of treatment within 5 hours after an ischemic stroke.

Adult↗
PubMed1992

Hypertrophic sternal scars: silicone gel sheet versus Kenalog injection treatment.

A prospective, randomized trial was designed to compare the standard Kenalog injection of established hypertrophic sternal scars with topical silicone gel sheets (Spenco). Fourteen poststernotomy cardiac patients with symptomatic scars were randomized to treatment in one-half of the scar with Kenalog injection. Simultaneously, the other half of the scar received the silicone gel sheet. The standard Kenalog injection used was 40 mg/ml x 1 cc, mixed with 1 cc of 1% Xylocaine with epinephrine. The gel sheets were worn continuously for 12 hours for 12 weeks. Pretreatment and posttreatment photographs were compared for color and appearance by blindfolded observers. Scar measurements (length, width, and height) were taken weekly in each area, and the patients were asked to rank their symptoms within each half as worse, the same, or better. The primary outcome of patient preference was analyzed sequentially, and the recruitment was terminated after 11 patients had completed the study, 10 of whom favored the silicone gel treatment (p < 0.05). Three patients remained in the treatment phase at the time of termination and completed the study subsequently. For the total sample of 14 subjects, 11 preferred the silicone gel, 1 expressed no preference, and 2 preferred the injection. The average time to improvement was 3.9 +/- 0.62 days (gel) versus 6.8 +/- 1.86 days (Kenalog). This study demonstrates that silicone gel sheets provide earlier symptomatic relief and a more aesthetic scar and are the preferred treatment of patients with symptomatic hypertrophic sternal scars.

Administration, Topical↗
PubMed1991

How should results from completed studies influence ongoing clinical trials? The CAFA Study experience.

Seven randomized studies during the past 5 years have evaluated or are evaluating the efficacy of warfarin or aspirin or both in decreasing the risk of embolic events in patients with nonrheumatic atrial fibrillation. By March 1990, two of the studies had been published, both of which showed a statistically significant decrease in embolic events in patients treated with warfarin and a low rate of major bleeding events. The investigators associated with the other ongoing studies were forced to consider how these results should affect the decision to recruit and continue follow-up of patients in their own studies. The Steering Committee of the Canadian Atrial Fibrillation Anticoagulation (CAFA) study thought the newly published results from other studies were valid, clinically important, and generalizable. The committee considered the following options for the CAFA study: continue patient recruitment as planned, provide the data available in CAFA to its External Safety and Efficacy Monitoring Committee for analysis to determine whether the CAFA data already showed a benefit of warfarin, stop patient recruitment but continue to follow patients in the group to which they were assigned, stop the trial immediately and perform a final analysis, and attempt to perform a meta-analysis of all data available from all trials. The Steering Committee of CAFA decided that the evidence of benefit with warfarin, from the two published studies, was sufficiently compelling as to stop recruitment into CAFA without any preliminary examination of the CAFA data.

Aspirin↗
PubMed1991

Canadian Atrial Fibrillation Anticoagulation (CAFA) Study.

The Canadian Atrial Fibrillation Anticoagulation Study was a randomized double-blind placebo-controlled trial to assess the potential of warfarin to reduce systemic thromboembolism and its inherent risk of hemorrhage. As a result of the publication of two other "positive" studies of similar design and objective, this study was stopped early before completion of its planned recruitment of 630 patients. There were 187 patients randomized to warfarin and 191 to placebo. Permanent discontinuation of study medication occurred in 26% of warfarin-treated and 23% of placebo-treated patients. The target range of the international normalized ratio was 2 to 3. For the warfarin-treated patients, the international normalized ratio was in the target range 43.7% of the study days, above it 16.6% of the study days and below it 39.6% of the study days. Fatal or major bleeding occurred at annual rates of 2.5% in warfarin-treated and 0.5% in placebo-treated patients. Minor bleeding occurred in 16% of patients receiving warfarin and 9% receiving placebo. The primary outcome event cluster was nonlacunar stroke, noncentral nervous systemic embolism and fatal or intracranial hemorrhage. Events were included in the primary analysis of efficacy if they occurred within 28 days of permanent discontinuation of the study medication. The annual rates of the primary outcome event cluster were 3.5% in warfarin-treated and 5.2% in placebo-treated patients, with a relative risk reduction of 37% (95% confidence limits, -63.5%, 75.5%, p = 0.17).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Coronary patency, infarct size and left ventricular function after thrombolytic therapy for acute myocardial infarction: results from the tissue plasminogen activator: Toronto (TPAT) placebo-controlled trial. TPAT Study Group.

Infarct size, left ventricular function and infarct-related coronary artery patency were examined in 108 patients who took part in a previously reported placebo-controlled trial of recombinant tissue-type plasminogen activator (rt-PA) in acute myocardial infarction. Coronary angiography was performed 17 +/- 0.8 h after initiation of treatment in 47 patients (group A) or at 10 days in 61 patients (group B). Both groups underwent radionuclide ventriculography 3.8 +/- 0.8 h and again on day 9 after treatment and quantitative thallium scintigraphy on day 8. In group A, the infarct-related artery was patent in 53%; these patients had a smaller global (15.1 +/- 2.5% vs. 25.7 +/- 4.7%, p = 0.029) and regional (14.7 +/- 2.5% vs. 24.1 +/- 4.7%, p = 0.044) fixed thallium defect than did those with an occluded artery. Infarct regional ejection fraction improved by 10.1 +/- 2.1% between early and late studies when the infarct-related artery was patent and by 4.8 +/- 1.4% if it was occluded (p = 0.048); changes in global and noninfarct regional ejection fraction were similar irrespective of perfusion status. Infarct regional ejection fraction and fixed thallium defect were inversely related only when the infarct-related artery was occluded (r = -0.83, p less than 0.0001). In group B, 10 day patency of the infarct-related artery was 67%; there was no difference in patency by treatment assignment or in left ventricular function or infarct size between patients with and without infarct-related artery patency. There was no evidence of an effect of rt-PA therapy beyond that expressed through coronary patency alone in either group A or group B.

Coronary Vessels↗
PubMed1991

Prolonged hemorrhagic shock does not impair regeneration of plasma coagulant masses in the rabbit.

BACKGROUND AND METHODS: Twelve adult male albino rabbits were assigned alternately to normotensive and hypotensive groups to assess the effect of hypovolemic shock on spontaneous correction of dilutional coagulopathy. All animals underwent dilutional exchange transfusion with 200 mL of rabbit RBCs and 5% human albumin. Half the animals were then acutely hemorrhaged and subsequent aliquots of blood removed as needed to maintain the mean arterial pressure at 40 mm Hg. RESULTS: By 6 hr after production of dilutional coagulopathy, masses and plasma concentrations of fibrinogen and Factor II had increased modestly but significantly, and Factor VII mass and concentration and in vitro coagulation had returned almost to normal; plasma volume was unchanged in the normotensive animals. In the hypovolemic shock animals, where coagulant mass regeneration was as rapid as in the normotensive animals, a doubling of total plasma volume (p less than .01) prevented the concentrations of fibrinogen and Factor II, and hence the coagulation times, from improving. CONCLUSIONS: Dilutional coagulopathy corrects spontaneously within hours. Normovolemic shock prolongs dilutional coagulopathy not by impairment of factor regeneration but because of further (internal) dilution due to plasma expansion. Rapid correction of dilutional coagulopathy is likely to necessitate cryoprecipitate administration.

Animals↗
PubMed1990

Therapeutic priorities of Canadian internists.

We surveyed 175 members of the Canadian Society of Internal Medicine to determine how they would rank seven commonly used treatments as to their clinical usefulness. A total of 70% of the respondents judged that the treatment of severe hypertension was the most beneficial. Coronary artery bypass surgery and treatment with acetylsalicylic acid for transient ischemic attacks were ranked next most useful. Cholestyramine therapy for hypercholesterolemia, the treatment of mild hypertension, isoniazid therapy for inactive tuberculosis and carotid endarterectomy in patients with mild stroke formed the final cluster. Except for treatment of severe hypertension there was a wide variation in the physicians' enthusiasm for the various treatments. Possible explanations for this variation include physicians' lack of awareness of the results of clinical trials, the wide range of risk reductions found in various trials of the same therapy, an unwillingness by physicians to generalize from clinical trials to individual patients, individual physicians' placement of different values on the morbidity associated with various diseases, and the fact that physicians may rarely explicitly compare the usefulness of therapies. In general, the number of patients needed to be treated to save one life better reflected the physicians' judgements than did the relative risk reduction.

Attitude of Health Personnel↗
PubMed1990

N of 1 randomized trials for investigating new drugs.

Presently, in the process of new drug development, large sample parallel group randomized trials are often begun without the detailed knowledge of optimal dose, most responsive patient group, and optimal outcomes which would be desirable. We propose that randomized trials in individual subjects (N of 1 RCTs) could be used to elucidate these issues at an early stage of drug development. In appropriate conditions N of 1 RCTs can be used to define the rapidity with which a drug begins and ceases its clinical action, the likely range of the optimal drug dose, and the optimal outcomes on which subsequent trials should focus. N of 1 RCTs can also generate initial estimates of the proportion of patients who respond to a new agent and for determining sample size, inclusion criteria, and dosage regimen(s) for subsequent parallel group trials. We provide an example of 14 N of 1 RCTs of amitriptyline in fibrositis that illustrate the ways in which N of 1 RCTs can elucidate these issues. The multiple uses of N of 1 RCTs suggest that the method has immense potential for use in the early phases of drug development programs.

Amitriptyline↗
PubMed1990

Assessment of observer variation in measuring the Radiographic Vertebral Index in patients with multiple myeloma.

The Radiographic Vertebral Index (RVI) was assessed as a possible outcome measure for bone disease in myeloma by evaluating within and between reader reproducibility. Four readers (2 radiologists and 2 clinical hematologists) independently scored, on two separate occasions, the RVI on 40 radiographs from patients with myeloma. Each vertebra from third thoracic (T3) to fifth lumbar (L5) received a score of "1" if normal, "2" if biconcave and "4" if crushed or fractured. RVI global scores, therefore, could vary from a minimum of 15, for no damage, to a potential maximum of 60 in which all vertebrae are collapsed. Agreement was determined for each vertebra using crude percentage agreement and the kappa statistic (which corrects for chance-expected agreement) for categorical data, and for global score using analysis of variance and calculating intra-class correlation. With increasing mean abnormality score on individual vertebrae there was a corresponding increase in kappa and reduction in crude percentage agreement. Within readers, the mean percentage agreement across all vertebrae varied from 85.6 to 90.3% and the observed differences just reach statistical significance (p = 0.048). Mean kappa values ranged from 0.48 to 0.63 and were similar across readers. Differences in intra-reader agreement were not related to subspecialty. When between reader percentage agreement and kappa scores were assessed for radiologists and non-radiologist clinicians, no difference could be detected. Agreement with respect to intra-reader mean global RVI scores was excellent as illustrated by the intra-class correlation coefficient which varied from 0.89 to 0.94. The mean intra-class correlation for radiologists was 0.92, compared with 0.91 for non-radiologists.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1990

Problem resolution and repetition of parasuicide. A prospective study.

Resolution of presenting problems at three-month follow-up was studied in 228 parasuicides. 'Non-resolvers' presented with less severe problems, but prodromes were longer, prior episodes more frequent, and they experienced more powerlessness and internally directed hostility than the resolvers. At follow-up resolvers had improved more on measures of depression, externally and internally directed hostility, locus of control, powerlessness, self-esteem, sensitivity to criticism, and social adjustment. Baseline problem severity, powerlessness (negatively), and 'normlessness' 'predicted' degree of problem resolution, while baseline problem severity, the number of previous parasuicide episodes, and baseline internal hostility (the latter two variables negatively) were associated with problem resolution as a dichotomous variable. Resolvers improved more in social functioning during the follow-up than non-resolvers, but a similar proportion (16%) in each group reported repeat episodes of parasuicide at follow-up.

Adolescent↗
PubMed1990

Why parasuicides repeat despite problem resolution.

To discover why parasuicides who resolved their difficulties repeated self-harm within three-month follow-up at the same rate as those who had not resolved problems, a group of 30 repeaters was compared with 156 non-repeaters. The repeaters had a history of more frequent episodes, beginning younger. Their problems were more severe, the acts of self-harm potentially less lethal. They experienced greater feelings of externally directed hostility, powerlessness, and 'normlessness'. A constellation of nine variables correctly predicted 81.5% of the repeaters and 77.5% of the non-repeaters. At follow-up the non-repeaters had improved on several parameters but the repeaters were essentially unchanged. The resolvers among the subgroup of repeaters were more like repeaters in the overall sample than the resolvers, which may explain why some parasuicides repeat in spite of resolving their problems.

Adolescent↗
PubMed1989

The Canadian American Ticlopidine Study (CATS) in thromboembolic stroke.

The Canadian American Ticlopidine Study (CATS) is a randomised, double-blind, placebo-controlled trial to assess the effect of ticlopidine (250 mg twice daily) in reducing the rate of subsequent occurrence of stroke, myocardial infarction, or vascular death in patients who have had a recent thromboembolic stroke. Twenty-five centres entered 1072 patients into the study between 1 week and 4 months after their qualifying stroke. The patients were treated and followed for up to 3 years (mean 24 months). In the efficacy analysis, the event rate per year for stroke, myocardial infarction or vascular death, considered together, was 15.3% in the placebo group and 10.8% in the ticlopidine group, representing a relative risk reduction with ticlopidine of 30.2% (95% confidence interval 7.5-48.3%; p = 0.006). Ticlopidine was beneficial for both men and women (relative risk reductions 28.1%, p = 0.037, and 34.2%, p = 0.045, respectively). Analysis by intention-to-treat gave a smaller estimate of risk reduction (23.3%, p = 0.020) for stroke, myocardial infarction, or vascular death. Adverse experiences associated with ticlopidine included neutropenia (severe in about 1% of cases) and skin rash and diarrhoea (severe in 2% of cases each); all were reversible. This study provides evidence of a beneficial effect of ticlopidine in both men and women with a recent thromboembolic stroke.

Aged↗
PubMed1989

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↗
PubMed1989

Improvement in airway responsiveness and asthma severity during pregnancy. A prospective study.

In the myometrium and gut, smooth muscle becomes less contractile during pregnancy, probably because of the effect of progesterone and estrogen. It is not known whether these hormones cause similar changes in airway smooth muscle, and therefore, this study examined airway responsiveness during the large hormonal changes of pregnancy and evaluated whether changes in responsiveness are associated with changes in (1) progesterone and estrogen and (2) the clinical severity of asthma. Twenty nonpregnant asthmatic women were assessed every 3 months until conception. In the 16 who conceived, assessments were repeated once during the second and third trimesters and 1 month after delivery. Data collected preconception and from those who did not conceive within 1 yr were used for control subjects. There was a 2-fold improvement in airway responsiveness during pregnancy from a preconception mean PC20 0.35 to 0.72 mg/ml during the second trimester and 0.58 mg/ml during the third (p = 0.03). Post-delivery responsiveness (0.48 mg/ml) was not significantly different from preconception. The improvements during pregnancy were greater than the 3 monthly fluctuations when not pregnant (p = 0.04) and were greatest in those who were most hyperresponsive initially (p = 0.01). There was an associated improvement in clinical asthma severity as indicated by a reduction in minimum medication requirements (p = 0.03) and this was not at the expense of good symptoms control; both symptoms and spirometry remained unchanged during pregnancy. Changes in responsiveness were not closely related to progesterone or estriol, suggesting that other nonhormonal factors may also contribute to the improvement during pregnancy and that the control of asthmatic airway smooth muscle may not be exactly the same as that of the myometrium and gut.

Adult↗
PubMed1989

A study of mortality in workers engaged in the mining, smelting, and refining of nickel. I: Methodology and mortality by major cause groups.

Following the publication of the NIOSH nickel criteria document in 1977, the Joint Occupational Health Committee of the International Nickel Company (INCO) commissioned a mortality study of the company's Ontario workforce. This paper describes the detailed methodology and primary mortality results of the ensuing study; subsequent papers will describe more detailed findings of cause-specific mortality. An historical prospective mortality study of approximately 54,000 INCO workers has been conducted. Men with six months or more of service were followed for mortality during a 35-year period by computerized record linkage to the Canadian National Mortality Data Base. From a company-provided list of men known to have died and through independent follow-up of a random sample of 1,000 subjects of unknown status, we estimate a mortality ascertainment rate of 95%. Cause-specific standardized mortality ratios calculated with respect to Ontario provincial mortality rates indicate an excess of accidental deaths in men working in the Sudbury area and an excess of cancer deaths at the company's Port Colborne nickel refinery. A strong healthy worker effect was found for both all-disease mortality ad cancer mortality. The lower than expected mortality persisted for about 15 years beyond initial hiring.

Adolescent↗