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Biomedical subjects

J E Buring

Publications and source records attributed to J E Buring.

At least 145 records · Page 8Linked to original sources

Circadian variation of acute myocardial infarction and the effect of low-dose aspirin in a randomized trial of physicians.

Increased platelet aggregation in the morning and upon assuming an upright posture may account at least in part for the observed circadian variation in onset of acute myocardial infarction. The Physicians' Health Study, a randomized, double-blind, placebo-controlled trial of alternate-day aspirin intake (325 mg) among 22,071 US male physicians, afforded the opportunity to assess this circadian pattern and examine whether it is altered by aspirin therapy. During a 5-year period of follow-up, 342 cases of nonfatal myocardial infarction were confirmed, of which the time of onset was available in 211 (62%). The placebo group showed a bimodal circadian variation in onset of myocardial infarction with a primary peak between 4:00 AM and 10:00 AM (p less than 0.001). In the aspirin group, however, this circadian variation was minimal (p = 0.16), due primarily to a marked reduction in the morning peak of infarction. Specifically, aspirin was associated with a 59.3% reduction in the incidence of infarction during the morning waking hours, compared with a 34.1% reduction for the remaining hours of the day. The greater reduction was observed during the 3-hour interval immediately after awakening, a period with a risk of infarction twice that of any other comparable time interval (p less than 0.001). Aspirin intake was associated with a mean reduction in the incidence of infarction of 44.8% over the entire 24-hour cycle. These data support the hypothesis that increased platelet aggregability in the morning and upon arising contributes to the occurrence of myocardial infarction and that aspirin reduces the risk of infarction by inhibiting platelet aggregation during these critical periods.

Adult↗

Methodologic considerations in the design and conduct of randomized trials: the U.S. Physicians' Health Study.

For treatments whose hypothesized risk reductions are small to moderate in size, on the order of 10%-30%, observational epidemiologic studies may not be reliable, since the amount of uncontrolled confounding could easily be as great as the likely reduction in risk. In such cases, randomized trials may be the only epidemiologic design strategy able to provide clear answers to research questions. However, the choice of design features and proper conduct of a randomized trial are crucial to the ability of the study to provide reliable results. In planning a study, five principal issues should be considered: design efficiency, completeness of follow-up, level of compliance, size of the probable risk reduction, and accumulation of sufficient numbers of outcome measures. Careful attention to these design considerations will enhance a trial's ability to provide definitive research results. The importance of these issues can be illustrated by examining the design and conduct of the ongoing Physicians' Health Study, a randomized, double-blind, placebo-controlled trial of aspirin in the reduction of cardiovascular disease and beta-carotene in the prevention of cancer.

Adult↗

An overview of randomized trials of rehabilitation with exercise after myocardial infarction.

Of 22 randomized trials of rehabilitation with exercise after myocardial infarction (MI), one trial had results that achieved conventional statistical significance. To determine whether or not these studies, in the aggregate, show a significant benefit of rehabilitation after myocardial infarction, we performed an overview of all randomized trials, involving 4,554 patients; we evaluated total and cardiovascular mortality, sudden death, and fatal and nonfatal reinfarction. For each endpoint, we calculated an odds ratio (OR) and 95% confidence interval (95% CI) for the trials combined. After an average of 3 years of follow-up, the ORs were significantly lower in the rehabilitation than in the comparison group: specifically, total mortality (OR = 0.80 [0.66, 0.96]), cardiovascular mortality (OR = 0.78 [0.63, 0.96]), and fatal reinfarction (OR = 0.75 [0.59, 0.95]). The OR for sudden death was significantly lower in the rehabilitation than in the comparison group at 1 year (OR = 0.63 [0.41, 0.97]). The data were compatible with a benefit at 2 (OR = 0.76 [0.54, 1.06]) and 3 years (OR = 0.92 [0.69, 1.23]), but these findings were not statistically significant. For nonfatal reinfarction, there were no significant differences between the two groups after 1 (OR = 1.09 [0.76, 1.57]), 2 (OR = 1.10 [0.82, 1.47]), or 3 years (OR = 1.09 [0.88, 1.34]) of follow-up. The observed 20% reduction in overall mortality reflects a decreased risk of cardiovascular mortality and fatal reinfarction throughout at least 3 years and a reduction in sudden death during the 1st year after infarction and possibly for 2-3 years. With respect to the independent effects of the physical exercise component of cardiac rehabilitation, the relatively small number of "exercise only" trials, combined with the possibility that they may have had a formal or informal nonexercise component precludes the possibility of reaching any definitive conclusion. To do so would require a randomized trial of sufficient size to distinguish between no effect and the most plausible effect based on the results of this overview.

Clinical Trials as Topic↗

Low-density lipoprotein subclass patterns and risk of myocardial infarction.

The association of low-density lipoprotein (LDL) subclass patterns with coronary heart disease was investigated in a case-control study of nonfatal myocardial infarction. Subclasses of LDL were analyzed by gradient gel electrophoresis of plasma samples from 109 cases and 121 controls. The LDL subclass pattern characterized by a preponderance of small, dense LDL particles was significantly associated with a threefold increased risk of myocardial infarction, independent of age, sex, and relative weight. Plasma levels of high-density lipoprotein cholesterol were decreased, and levels of triglyceride, very low-density lipoproteins, and intermediate-density lipoproteins were increased in subjects with this LDL subclass pattern. Multivariate logistic regression analyses showed that both high-density lipoprotein cholesterol and triglyceride levels contributed to the risk associated with the small, dense LDL subclass pattern. Thus, the metabolic trait responsible for this LDL subclass pattern results in a set of interrelated lipoprotein changes that lead to increased risk of coronary heart disease.

Aged↗

Occupation and risk of death from coronary heart disease.

Conflicting data have been reported regarding the association between occupation and coronary heart disease. We evaluated data on a series of 568 married men who died of coronary heart disease and an equal number of controls matched for age, sex, and neighborhood of residence. Information was collected from the wives of both cases and controls on a larger number of variables, including usual occupation, job-related and leisure-time physical activity, medical history, and life-style. Usual occupation was dichotomized into blue-collar and white-collar work according to the Edwards' classification. White-collar workers had a statistically significant 30% decreased risk of fatal coronary heart disease compared with blue-collar workers once the effects of reported coronary risk factors were considered (relative risk, 0.70; 95% confidence limits, 0.5 to 0.96). These data suggest that occupation is significantly associated with fatal coronary heart disease, and that this increased risk is not explained by a large number of known coronary risk factors. It still remains unclear, however, whether other uncontrolled variables explain the observed association.

Adult↗

Clinical suspicion of autopsy-proven thrombotic and tumor pulmonary embolism in cancer patients.

Cancer patients are prone to both thrombotic and tumor pulmonary embolism (PE). To identify similarities and differences in their clinical features, we reviewed all autopsies from 1978 to 1982 at Brigham and Women's Hospital and the Dana Farber Cancer Institute. Of 73 patients with solid malignant tumors and PE, 56 had major thrombotic PE and 17 had major tumor embolism to the lungs. Of the 56 with cancer and thrombotic PE, 25 (45%) had the correct diagnosis suspected antemortem. By contrast, only 1 of 17 (6%) patients with tumor embolism was diagnosed correctly antemortem (p = 0.005). Most presenting symptoms, signs, laboratory values, and associated conditions were not markedly different in patients with thrombotic PE and tumor embolism. These findings indicate that tumor PE is more difficult to diagnose clinically and may be misdiagnosed as thrombotic PE. Finally, these data suggest that in all cancer patients, the presence of both thrombotic and tumor PE should be considered because of similarities in their clinical features.

Autopsy↗

A prospective cohort study of postmenopausal hormone use and risk of breast cancer in US women.

The association between history of postmenopausal hormone use as of 1976 and breast cancer incidence during 1976-1980 was examined prospectively among 33,335 married, postmenopausal registered nurses aged 30-55 years at entry. Half the women reported postmenopausal hormone use, and one fourth had taken these drugs for over five years. During 1976-1980, 221 new cases of breast cancer were identified. The relative risk (RR) for those who had used postmenopausal hormones when compared with women who had never used them was 1.1 (95% confidence limits (CL) 0.8, 1.4); for current and past users, the relative risks were 1.0 (95% CL 0.7, 1.4) and 1.3 (95% CL 0.9, 1.8), respectively. These ratios were not substantially modified by whether or not a woman's ovaries had been removed or by other known breast cancer risk factors. No increase in breast cancer risk was apparent among women who had used postmenopausal hormones for less than five years (RR = 1.0, 95% CL 0.5, 1.6). An apparent effect among the subgroup of women who had used them for five to nine years (RR = 1.5, 95% CL 1.0, 2.2) was not present among the few women with longer-term use (RR = 0.9, 95% CL 0.4, 1.6). These findings are moderately reassuring, but since there are as yet few women in this cohort with long-term durations of use and, particularly, with long intervals since first use, continued follow-up of this and other cohorts will be required before firm conclusions can be drawn, especially among specific subgroups.

Adult↗

Apolipoprotein B-gene DNA polymorphisms associated with myocardial infarction.

Levels of apolipoprotein B, the protein component of low-density lipoproteins, correlate with the risk of coronary heart disease. We examined whether genetic variation in apolipoprotein B is associated with myocardial infarction by studying apolipoprotein B-gene restriction-fragment-length polymorphisms in 84 patients with myocardial infarction and an equal number of matched controls. Southern blot analysis with apolipoprotein B-gene probes, performed after DNA was digested with the endonucleases XbaI and EcoRI, revealed alleles that we designated as X1, X2, and X3 and as R1 and R2, respectively. Similar studies with the endonuclease MspI revealed alleles of many different sizes (the difference was due to an insertion-deletion polymorphism), which we grouped as larger and smaller alleles and designated as ID1 and ID2, respectively. The frequencies of the X1, R1, and ID1 alleles were all significantly higher (P less than 0.01) in the cases than in the controls. None of the alleles, however, was significantly associated with variation in levels of low-density lipoprotein cholesterol or apolipoprotein B, and the functional importance of these alleles is therefore uncertain. Nonetheless, in addition to quantitative variation in apolipoprotein B levels in plasma, genetic variation at the apolipoprotein B locus may be a new and independent risk factor for myocardial infarction.

Alleles↗

Oral contraceptives and breast cancer. A prospective cohort study.

In 1976, information on oral contraceptive (OC) use as well as numerous risk factors for breast cancer was provided by 121,964 married female registered nurses aged 30 to 55 years. Ninety-two percent of women in the cohort completed follow-up questionnaires, and vital records were systematically searched to ascertain deaths among nonrespondents. After four years of follow-up, 592 incident cases of breast cancer were identified. Compared with never users, the age-adjusted relative risk (RR) of breast cancer, regardless of menopausal status, among all women who had ever used OCs was 1.0. Among premenopausal women compared with those who had never used OCs, the RR of breast cancer was 1.5 for current use of OCs in 1976 and 1.0 for past use. Among postmenopausal women, the RR for past use of OCs was 1.0. These estimates were essentially unaltered after controlling for other known risk factors for breast cancer in multiple logistic regression analysis. Furthermore, there was no modification of these effects by family history of breast cancer, age at first use, timing of the first birth, or other breast cancer risk factors. Data on past use of OCs provide substantial reassuring evidence that there is no large excess risk of breast cancer within a few years of cessation of pill use. The observed moderate elevation of breast cancer risk with current use was of borderline statistical significance. However, the observation was based on 29 cases and may reflect the effect of sampling variability, as most other studies have not observed a relationship between current use of OCs and breast cancer in women of this age.

Adult↗

Conjugated estrogen use and risk of endometrial cancer.

The relation between use of conjugated estrogens and the risk of uterine cancer was examined among 188 white women with newly diagnosed endometrial cancer and 428 controls hospitalized for nonmalignant conditions requiring surgery at the Boston Hospital for Women-Parkway Division, Boston, Massachusetts, in January 1970-June 1975. As in prior studies, the greatest increases in risk were associated with dosages of 0.625 mg or greater (relative risk (RR) = 3.8, 95% confidence interval (CI) = 2.2-6.6) and duration of use of 10 or more years (RR = 7.6). Risk was elevated whether or not use was cyclic. Cyclic use was associated with a higher risk (RR = 3.6, 95% CI = 2.2-6.6) than continuous use (RR = 2.4, 95% CI = 1.3-4.1), but the difference between these risk estimates was not statistically significant. Risk remained increased even among women who had discontinued use of conjugated estrogens five or more years previously (RR = 4.5). Cases who were previous users had less advanced lesions at diagnosis than had never users. The highest risk associated with use of conjugated estrogens was that for stage I, grade 1 disease with no myometrial invasion. However, increases in risk of more advanced disease were seen among long-term users.

Adult↗

Health experiences of operating room personnel.

In an attempt to evaluate health experiences of operating room personnel using previously published reports, the authors calculated summary relative risks (RRs) for each outcome under investigation by combining data from six studies. For each summary RR, they also calculated 95% confidence limits; when the range of the confidence interval excludes 1.0, the increased risk is statistically significant at the 0.05 level. The most consistent evidence was for spontaneous abortion among pregnant physicians and nurses who work in operating rooms, where the RR was 1.3 (95% confidence limits from 1.2 to 1.4). For liver disease there were statistically significant increased RRs among both men (1.6, 1.3-1.9) and women (1.5, 1.2-1.9), but these were based on smaller numbers of studies. Although the results of pooled analyses are suggestive, most studies of this issue have relied on voluntary responses and self-reported outcomes, so that response and/or recall bias could explain these findings. In addition, these investigations generally have examined working in operating rooms rather than actual exposure to anesthetic gases. Finally, there have been considerable improvements in operating room scavenging systems during the last decade. Thus, prospective cohort studies are needed to determine whether there is a relationship between current levels of occupational exposure to anesthetic gases and adverse outcomes, particularly spontaneous abortion and liver disease.

Abortion, Spontaneous↗