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Biomedical subjects

J E Buring

Publications and source records attributed to J E Buring.

161 records · Page 9Linked to original sources
PubMed1984

Pooled analyses of randomized trials of streptokinase and heparin in phlebographically documented acute deep venous thrombosis.

Although thrombolysis with streptokinase has been compared with heparin anticoagulation for treating acute proximal deep venous thrombosis in several randomized trials, no individual study has had a sample of sufficient size to determine with adequate power both efficacy and safety. Therefore, results were pooled from six randomized studies in which phlebography was used to confirm the diagnosis and to assess therapy. Thrombolysis was achieved 3.7 times more often among patients treated with streptokinase than among patients treated with heparin (95 percent confidence limits 2.5, 5.7; p less than 0.0001). Only three studies allowed comparison of these drugs for major bleeding complications, which were 2.9 times greater with streptokinase than with heparin (95 percent confidence limits 1.1, 8.1; p = 0.04). Thus, in aggregate, streptokinase-treated patients achieved thrombolysis but also seemed to experience major bleeding complications more frequently than those assigned at random to receive heparin. Future trials of sufficient sample size should be undertaken to evaluate efficacy and safety. Such trials, which should include newer fibrinolytic agents, are necessary to determine optimal therapy for acute proximal deep venous thrombosis.

Clinical Trials as Topic↗
PubMed1984

Interruption of the inferior vena cava by clip or filter.

Interruption of the inferior vena cava is usually performed with either external clipping or transvenous filter placement. For patients unable to tolerate general anesthesia and laparotomy, the advantages of transvenous filters rather than clips are obvious. However, for some patients, the use of either clips or filters is possible. In general, retrospective observational studies of inferior vena caval interruption have not adequately accounted for baseline patient characteristics such as age, presence of cancer, and history of prior venous thromboembolism. These confounding factors can independently affect subsequent rates of both recurrent embolism and overall mortality. A comparative, controlled, prospective evaluation of inferior vena caval clipping versus transvenous filter placement among patients who are appropriate candidates for either procedure has not been undertaken. It is suggested that, among patients with good long-term prognoses, a randomized controlled trial would be necessary to help determine whether clipping or transvenous filter placement is more efficacious.

Clinical Trials as Topic↗
PubMed1984

An international study of smoking and bladder cancer.

The effects of smoking cigarettes and other forms of tobacco on the development of cancer of the lower urinary tract (bladder cancer) were evaluated in Boston, Massachusetts, Manchester, United Kingdom and Nagoya, Japan. Population-based series of incident cases and controls were identified and interviewed in each area. The present analyses were based on 592 cases and 533 controls in Boston, 553 cases and 731 controls in Manchester, and 290 cases and 588 controls in Nagoya. Smokers of cigarettes had about twice the incidence of bladder cancer as nonsmokers. In men the strength of the association between cigarette smoking and bladder cancer was similar in the 3 study areas. The strength of the association varied somewhat from area to area among women. Bladder cancer risk increased with frequency of cigarette smoking and with deep inhaling. In Boston men who smoked 2 or more packs of cigarettes per day and inhaled deeply had nearly 7 times the risk of nonsmokers. Ex-smokers had a level of risk between that of current smokers and nonsmokers. However, there was no clear relationship between risk and age at which cigarette smoking began, time since discontinuation among ex-smokers and use of filters. Over-all, there was little difference in bladder cancer risk between men who had and who had not smoked pipes but pipe smoking did appear to be associated with risk among men who had never smoked cigarettes. Cigar smoking was unrelated to bladder cancer.

Adolescent↗
PubMed1982

Coffee drinking and cancer of the lower urinary tract.

The relation of coffee drinking to the incidence rate of cancer of the lower urinary tract ("bladder cancer") was evaluated. Broadly based series of cases and series of controls drawn from the general population of each area were assembled and interviewed in Boston, Massachusetts (587 cases, 528 controls), Manchester, England (541 cases, 725 controls), and Nagoya, Japan (289 cases, 586 controls). Compared to drinkers of an average of less than 1 cup of coffee per day, those who drank more had a relative risk of bladder cancer estimated as 1.0 (0.8-1.2, 95% confidence interval). With adjustment for cigarette smoking habits, only small and irregular changes in risk were seen with increasing frequency of coffee consumption. Duration of coffee drinking showed little relation to risk of bladder cancer may be due to incomplete control of the effect of cigarette smoking. If there is a true association of coffee drinking and bladder cancer it is likely to be weak.

Age Factors↗
PubMed1980

Artificial sweeteners and cancer of the lower urinary tract.

We evaluated the relation between cancer of the lower urinary tract and the use of artificial sweeteners in a case-control study of 592 patients with lower-urinary-tract cancer (94 per cent of whom had a bladder tumor) and 536 controls chosen from the general population of the study area. A history of use or artificial sweeteners and exposure to other known or suspected risk factors was determined by interview. In those who had used dietetic beverages and in those who had used sugar substitutes, the relative risk of lower-urinary-tract cancer was estimated as 0.9 (0.7 to 1.2, 95 per cent confidence interval), as compared with 1 in nonusers of artificial sweeteners. Among men, the relative risk was 0.8 (0.6 to 1.1) in those who had used dietetic beverages and 0.8 (0.5 to 1.1) in those who had used sugar substitutes. Among women, the corresponding relative risks were 1.6 (0.9 to 2.7) and 1.5 (0.9 to 2.6). Increasing frequency of duration of use of artificial sweeteners was not consistently associated with increasing relative risk. This study suggests that, as a group, users of artificial sweeteners have little or no excess risks of cancer of the lower urinary tract.

Adult↗
PubMedDate not supplied

Adherence to aspirin in the prevention of myocardial infarction. The Physicians' Health Study.

BACKGROUND: The primary aim of this article was to explore, in subgroup analyses, whether participants with differing frequencies of aspirin consumption in a randomized, double-blind, placebo-controlled, primary prevention trial had different magnitudes of benefit in the prevention of myocardial infarction. Secondary aims were to identify factors associated with adherence and to examine the relationship of adherence with cardiovascular outcomes in the placebo group. METHODS: The Physicians' Health Study randomized 22071 US male physicians who were free of myocardial infarction and cerebrovascular disease at baseline. The average follow-up during the aspirin component of the trial was 60.2 months. Baseline cardiovascular risk factors and adherence to therapy during the trial were assessed by questionnaire; cardiovascular outcomes were reported by questionnaire and confirmed by record review by an Endpoints Committee. RESULTS: Several cardiovascular disease risk factors assessed at baseline were related to poor adherence (taking < 50% of study tablets): cigarette smoking, obesity, lack of exercise, and history of angina. After adjusting for baseline differences in risk factors, participants in the aspirin group with excellent adherence (taking at least 95% of study tablets) had a statistically significant 51% reduction in myocardial infarction compared with those with excellent adherence in the placebo group. Those in the aspirin group with poor adherence had a smaller, non-significant reduction in risk of myocardial infarction (a 17% reduction associated with taking < 50% of study tablets). In the placebo group better adherence was not associated with decreased risk of myocardial infarction, but was strongly associated with decreased risk of death. CONCLUSIONS: These subgroup data raise the possibility that a less than alternate day aspirin regimen may yield lower benefits in the prevention of myocardial infarction. Alternate explanations are that these analyses reflect either the play of chance or effects of uncontrolled confounding since comparisons were no longer randomized. Randomized trials are necessary to address the question of frequency of administration of aspirin to achieve optimal benefits in primary prevention of myocardial infarction.

Adult↗
PubMedDate not supplied

The 2 x 2 factorial design: its application to a randomized trial of aspirin and carotene in U.S. physicians.

The 2 x 2 factorial design calls for randomizing each participant to treatment A or B to address one question and further assignment at random within each group to treatment C or D to examine a second issue, permitting the simultaneous test of two different hypotheses. This design can increase the efficiency of large-scale clinical trials. The Physicians' Health Study, a randomized trial of aspirin and beta-carotene among U.S. physicians, illustrates some features and potential problems in the design and analysis of a factorial trial. The most common concern, interaction between treatments, is generally an advantage rather than a limitation of this design. Although such interactions are relatively uncommon, this design provides a means to measure an effect which otherwise might not be apparent. If the interaction is sufficiently severe, however, then loss of power is possible.

Aspirin↗
PubMedDate not supplied

Implications of overviews of randomized trials.

Many randomized trials are of insufficient sample size to detect with adequate power the small to moderate effects that are most likely to occur. As a result, a single such trial can produce a null finding that is, in fact, uninformative, but none the less is misinterpreted as demonstrating no effect. An overview considers all available trials and can increase the statistical power to detect an effect if present. Thus overviews can provide perhaps the most precise estimate of the magnitude of a treatment effect based on existing data. This may have implications for the formulation of public policy but certainly should influence the conduct and planning of randomized trials. Public policy may be influenced in circumstances where further trials are unlikely to be conducted. Overviews can also provide guidance as to whether changes in protocols of ongoing studies are recommended as a result of new evidence. Perhaps most importantly, overviews can provide information about whether additional trials are warranted, and, if so, the sample size that would be required to answer the research question definitively.

Clinical Trials as Topic↗
PubMedDate not supplied

Cost and efficiency in clinical trials: the U.S. Physicians' Health Study.

The U.S. Physicians' Health Study, a primary prevention trial of low-dose aspirin in the reduction of cardiovascular disease and of beta-carotene in lowering cancer risk, implemented a number of design strategies to decrease costs and increase efficiency. These included the choice of physicians as the study population, use of a factorial design, implementation of a pre-randomization run-in phase, and the collection of pre-randomization blood specimens. The use of these strategies enabled us to enroll 22,071 subjects and maintain high compliance and long-term follow-up at a fraction of the usual cost of large-scale trials of primary prevention.

Aspirin↗
PubMedDate not supplied

Prevention of cardiovascular disease: risks and benefits of aspirin.

Aspirin has been tested for its benefit in preventing cardiovascular disease in randomized trials in three categories of patients. In secondary prevention among those with a history of myocardial infarction (MI), stroke or transient cerebral ischemia, or unstable angina pectoris, 25 randomized trials demonstrated significant reductions from aspirin of 25% for the occurrence of an "important vascular event" (nonfatal MI, nonfatal stroke, or vascular death), 32% for nonfatal MI, 27% for nonfatal stroke, and 15% for vascular mortality. Among those evolving an MI, the Second International Study of Infarct Survival (ISIS-2) showed a significant reduction of 23% in five-week vascular mortality among those started on a one-month regimen of daily aspirin within 24 hours of the onset of symptoms of suspected MI. Aspirin also significantly reduced reinfarction, nonfatal stroke, and important vascular events. Finally, in primary prevention, the US Physicians' Health Study (PHS) showed a significant 44% reduction in the occurrence of a first MI among apparently healthy male physicians; numbers of strokes and vascular deaths were insufficient to permit conclusions for these endpoints. Thus, aspirin is of clear benefit in reducing MI, stroke, and vascular death in secondary prevention and among those evolving an MI. It is also beneficial in the primary prevention of MI among men over 40, but data concerning its effects on stroke and vascular death remain inconclusive.

Aspirin↗
PubMedDate not supplied

Baseline characteristics of participants in the Women's Health Study.

The Women's Health Study (WHS) is a randomized, double-blind, placebo-controlled trial designed to evaluate the balance of benefits and risks of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer in women. A total of 39,876 female health professionals, age 45 years or older and without a history of cardiovascular disease or cancer (other than nonmelanoma skin cancer), were randomized in a 2x2 factorial design to one of four treatment groups: active aspirin and vitamin E placebo, aspirin placebo and active vitamin E, both active agents, or both placebos. The process of randomization was successful, as evidenced by the equal distribution of a large number of baseline demographic, lifestyle, and health history characteristics among the four treatment groups. Similar distribution of known potential confounders, as well as the large sample size, provides reassuring evidence that unmeasured or unknown potential confounders are also equally distributed. As expected in a clinical trial, the women in the study are healthier in some respects than the general population, but they have very comparable rates of obesity, hypertension, and elevated cholesterol. With adequate duration of treatment and follow-up, this trial will provide important and relevant information on the balance of benefits and risks of aspirin and vitamin E supplementation in the primary prevention of cardiovascular disease and cancer in women.

Aged↗
PubMedDate not supplied

Randomized trials of aminoglycoside antibiotics: quantitative overview.

Individual randomized trials comparing aminoglycosides have usually involved a sample size inadequate for reliable detection of small to moderate differences. In a search for overall effects that might not be apparent from any single trial, a quantitative overview of all randomized studies comparing amikacin, gentamicin, netilmicin, sisomicin, and tobramycin was performed. These aminoglycosides appeared equally efficacious, except that tobramycin seemed less effective than sisomicin. Patients given gentamicin or sisomicin seemed to run a higher risk of nephrotoxicity than those given amikacin; the risk for patients receiving tobramycin was lower than that for patients given gentamicin but higher than that for those given netilmicin. The only statistically significant difference with regard to auditory toxicity was a lower risk among patients receiving netilmicin than among those given amikacin or tobramycin. Meaningful differences in toxicity may exist for individual aminoglycosides given in efficacious doses. Future trials must include sample sizes sufficient to detect differences of the magnitudes observed in this overview. In the absence of such data, the overview may guide clinicians in determining the risk-to-benefit ratio for a particular aminoglycoside, especially for patients at high risk of toxicity.

Aminoglycosides↗
PubMedDate not supplied

Baseline characteristics of participants in the Physicians' Health Study: a randomized trial of aspirin and beta-carotene in U.S. physicians.

The Physicians' Health Study is a randomized, double-blind, placebo-controlled trial of primary prevention designed to assess the effects of low-dose aspirin on cardiovascular disease and of beta-carotene on risks of cancer. A total of 22,071 U.S. male physicians 40 to 84 years of age were randomized to one of four treatment groups: active aspirin and active beta-carotene, active aspirin and beta-carotene placebo, aspirin placebo and active beta-carotene, or both placebos. Whereas the beta-carotene component of the trial is ongoing, the blinded aspirin component was terminated early primarily because of a statistically extreme benefit of aspirin on first myocardial infarction. We obtained data relating to a large number of variables, including demographics, personal medical history, family history, health habits, and diet before randomization and compared them among the four treatment groups. As expected in a randomized trial of this sample size, the distribution of baseline characteristics was virtually identical among the treatment groups. This comparison indicates certainly no confounding by the baseline variables that were collected and suggests that other unmeasured or unknown potential confounders are also likely to be distributed evenly between the treatment groups. Thus, any observed differences in outcome between these groups likely result from the effects of the treatments themselves.

Adult↗
PubMedDate not supplied

Alternative data sources in a case-control study of conjugated estrogens and cancer.

In a case-control study of the relationship of conjugated estrogen use to endometrial and breast cancer, we compared the availability and quality of information on risk factors from hospital charts and gynecologists' records. Of the women for whom an indication of Premarin use was recorded in either source, 19 percent would have been classified as nonusers by the hospital chart alone, a proportion that was similar for the breast (18 percent) and uterine (14 percent) cancer cases and controls (23 percent). However, for current use of Premarin, a higher proportion (28 percent) of users were identified solely through the gynecologists' records, and this proportion was even higher among controls (42 percent) than among either breast (18 percent) or uterine (15 percent) cancer cases. As a result, relative risk estimates varied according to the source of exposure date. Physicians' records also provided substantially more detail than hospital records on duration of Premarin use, especially for controls. Most demographic, medical, and reproductive variables were adequately available from the hospital charts alone. However, certain reproductive variables, such as age at first birth, presence or absence of ovaries, and age at menarche, were not adequately recorded in either source. These results suggest that gynecologists' records provide more accurate exposure data than hospital charts to determine current use of conjugated estrogens. Moreover, in the assessment of certain reproductive variables, the use of both these record-based sources may not be sufficient.

Adenocarcinoma↗
PubMedDate not supplied

Ethnic distribution of factor V Leiden in 4047 men and women. Implications for venous thromboembolism screening.

OBJECTIVE: To estimate ethnic-specific prevalence rates of factor V Leiden, an inherited defect of hemostasis associated with risk of venous thrombosis. DESIGN: Survey of 4047 American men and women participating in the Physicians' Health Study (PHS) or in the Women's Health Study (WHS). All study participants were free of myocardial infarction, stroke, or venous thrombosis. MAIN OUTCOME MEASURE: Prevalence of G1691A Leiden mutation in the gene coding for coagulation factor V was determined in the PHS group using polymerase chain reaction techniques and, in the WHS group, a second-generation activated protein C (APC)-resistance screening test with genetic confirmation of all borderline and low-value results. RESULTS: In 2468 Caucasian Americans, carrier frequency of factor V Leiden was 5.27% (95% confidence interval [CI], 4.42%-6.22%). Carrier frequency was 2.21% in 407 Hispanic Americans, 1.23% in 650 African Americans, 0.45% in 442 Asian Americans, and 1.25% in 80 Native Americans. Thus, prevalence of factor V Leiden was less among minority subjects (P=.001). Carrier frequencies were similar in Caucasian men and women (5.53% vs 4.85% respectively, P=.5). CONCLUSION: These data indicate that prevalence of factor V Leiden is greater among Caucasians than minority Americans. These data have implications for clinicians considering whether to screen for factor V Leiden in high-risk groups such as those with prior venous thromboses or coexistent defects of anticoagulation and women at risk for postpartum thrombosis or seeking oral contraceptives.

Black People↗