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D L DeMets

Publications and source records attributed to D L DeMets.

At least 19 recordsLinked to original sources
PubMed1992

Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer.

BACKGROUND AND METHODS: Tamoxifen, a synthetic antiestrogen, increases disease-free and overall survival when used as adjuvant therapy for primary breast cancer. Because it is given for long periods, it is important to know whether tamoxifen affects the skeleton, particularly since it is used extensively in postmenopausal women who are at risk for osteoporosis. Using photon absorptiometry, we studied the effects of tamoxifen on the bone mineral density of the lumbar spine and radius and on biochemical measures of bone metabolism in 140 postmenopausal women with axillary-node-negative breast cancer, in a two-year randomized, double-blind, placebo-controlled trial. RESULTS: In the women given tamoxifen, the mean bone mineral density of the lumbar spine increased by 0.61 percent per year, whereas in those given placebo it decreased by 1.00 percent per year (P less than 0.001). Radial bone mineral density decreased to the same extent in both groups. In a subgroup randomly selected from each group, serum osteocalcin and alkaline phosphatase concentrations decreased significantly in women given tamoxifen (P less than 0.001 for each variable), whereas serum parathyroid hormone and 1,25-dihydroxyvitamin D concentrations did not change significantly in either group. CONCLUSIONS: In postmenopausal women, treatment with tamoxifen is associated with preservation of the bone mineral density of the lumbar spine. Whether this favorable effect on bone mineral density is accompanied by a decrease in the risk of fractures remains to be determined.

Alkaline Phosphatase↗
PubMed1991

Effects of tamoxifen on cardiovascular risk factors in postmenopausal women.

OBJECTIVE: To determine the effects of tamoxifen on risk factors for cardiovascular disease in disease-free postmenopausal women. DESIGN: Double-blind, placebo-controlled, randomized 2-year clinical trial. SETTING: University health sciences center. PATIENTS: Clinically postmenopausal women (140) with a diagnosis of axillary node-negative breast cancer, who were disease-free by laboratory and clinical evaluations. MEASUREMENTS: Levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, apolipoprotein A-I, apolipoprotein B, glucose, weight, blood pressure, and reported exercise and work activity were measured. MAIN RESULTS: Postmenopausal women receiving tamoxifen were evaluated at 3- or 6-month intervals during a 2-year assessment period and showed a mean decrease of 12% in total cholesterol levels (at 24 months -0.672 mmol/L; 95% CI, -0.839 to -0.505 mmol/L) and a mean decrease of 20% in calculated low-density lipoprotein (LDL) cholesterol levels (at 24 months, -0.725 mmol/L; 95% CI, -0.868 to -0.583 mmol/L) (P less than 0.001). Women with greater baseline cholesterol levels had greater decreases with tamoxifen treatment. Levels of HDL cholesterol decreased in patients treated with tamoxifen, but this decrease was only statistically significant at one of five measurement times. Apolipoprotein A-I levels increased significantly at the two time points at which it was measured (P = 0.02), and apolipoprotein B levels decreased significantly at these times (P less than 0.01) in patients treated with tamoxifen. Plasma glucose levels, reported exercise and work activity, reported smoking, weight, and systolic and diastolic blood pressures did not change with treatment. CONCLUSION: During 2 years of treatment, tamoxifen showed generally favorable effects on the lipid and lipoprotein profile of treated postmenopausal women. These effects may partially explain the decrease in adverse events and in mortality related to coronary heart disease seen in patients receiving adjuvant tamoxifen treatment.

Apolipoprotein A-I↗
PubMed1991

Design issues for a breast cancer chemoprevention trial.

A design to evaluate the efficacy of tamoxifen as a chemopreventive agent for breast cancer in healthy, high-risk women is proposed. Factors to be considered include basic incidence rates in the general population, definition of high risk, screening efforts, sample size, and compliance to protocol. Assuming a breast cancer incidence of 3/1,000/year in women 50-59 years old with a first degree relative with breast cancer, we estimate that approximately 16,000 subjects would need to be randomized into a tamoxifen-placebo controlled trial to detect a 50% reduction in incidence. This assumes a 5% (two-sided) significance level and 90% power. Such a trial would need to be multicentered and might cost $64 million over a 5-year period.

Breast Neoplasms↗
PubMed1991

Data integrity.

Explore the source record for details and available documents.

Clinical Trials as Topic↗
PubMed1991

Issues in the early termination of the aspirin component of the Physicians' Health Study. Data Monitoring Board of the Physicians' Health Study.

The Physicians' Health Study is a randomized, double-blind, placebo-controlled prevention trial of 22,071 US physicians, using a factorial design to evaluate the role of aspirin in the prevention of cardiovascular mortality and beta carotene in the reduction of cancer incidence. After approximately 5 years of follow-up, the aspirin component was terminated, 3 years ahead of schedule. Several factors were considered in the decision to terminate, including a cardiovascular mortality rate markedly lower than expected in both aspirin and placebo subjects, precluding the evaluation of the primary aspirin hypothesis, and a highly significant (P < .00001) and impressive (44%) reduction in the risk of first myocardial infarction in the aspirin group. Issues in the decision to terminate are described in this report.

Adult↗
PubMed1991

Exact statistical inference for group sequential trials.

This paper considers clinical trials comparing two treatments with dichotomous responses where the data are examined periodically for early evidence of treatment difference. The existing group sequential methods for such trials are based on the large-sample normal approximation to the joint distribution of the estimators of treatment difference over interim analyses. We demonstrate through extensive numerical studies that, for small and even moderate-sized trials, these approximate procedures may lead to tests with supranominal size (mainly when unpooled estimators of variance are used) and confidence intervals with under-nominal coverage probability. We then study exact methods for group sequential testing, repeated interval estimation, and interval estimation following sequential testing. The new procedures can accommodate any treatment allocation rules. An example using real data is provided.

Biometry↗
PubMed1990

Effects of tamoxifen therapy on lipid and lipoprotein levels in postmenopausal patients with node-negative breast cancer.

We conducted a 2-year, randomized, double-blind, placebo-controlled toxicity trial of therapy with tamoxifen (10 mg twice a day) in 140 postmenopausal women with a history of breast cancer and histologically negative axillary lymph nodes. These women had been treated with surgery with or without radiotherapy. At a 3-month evaluation, tamoxifen-treated women showed a significant decrease in fasting plasma levels of total cholesterol and low-density lipoprotein (LDL) cholesterol, which persisted at 6- and 12-month evaluations. During the first 12 months, plasma triglyceride levels increased; small but significant decreases in high-density lipoprotein cholesterol (HDL) were observed in tamoxifen-treated women, but ratios of total cholesterol to HDL cholesterol and of LDL to HDL cholesterol changed favorably. While data relating lipid/lipoprotein profiles and cardiovascular disease are limited in women, current evidence suggests that total cholesterol and possibly low-density lipoprotein cholesterol are risk factors. We conclude that during the first 12 months of treatment, tamoxifen exerts a favorable effect on the lipid profile in postmenopausal women with early stage breast cancer.

Breast Neoplasms↗
PubMed1990

Early methodological developments for clinical trials at the National Heart, Lung and Blood Institute.

The National Heart Institute, now known as the National Heart, Lung and Blood Institute (NHLBI), initiated its first multicentre randomized clinical trials of rheumatic fever and rheumatic heart disease in 1951. The modern era of multicentre trials began, however, when the Coronary Drug Project was initiated in the 1960s. This trial and subsequent NHLBI trials stimulated a wide variety of research on clinical trial methodology. This paper reviews early methodologic developments in four areas. First, an organizational structure for multicentre clinical trials was developed and codified in the 'Greenberg Report' in 1967. Second, design considerations related to patient risk, non-compliance, a lag in treatment effect, and changing risk were explored. The 'intention-to-treat' principle was implicit in these investigations. Thirdly, the concept of periodic review of accumulating data, recommended in the Greenberg report, stimulated research on methods for sequential analysis. Three statistical approaches were developed and investigation of their statistical properties continues today. These approaches are usually described as group sequential, stochastic curtailment, and Bayesian methods. Finally, comparison of treatments in longitudinal studies has been an increasing part of NHLBI research and methods have been developed for design and analysis of longitudinal studies.

Blood↗
PubMed1990

Wisconsin Epidemiologic Study of Diabetic Retinopathy. XII. Relationship of C-peptide and diabetic retinopathy.

The relationship between plasma C-peptide and the frequency and severity of diabetic retinopathy was examined in a population-based study in Wisconsin in 1984-1986. Individuals with younger- (n = 835) and older- (n = 940) onset diabetes were included. C-peptide was measured by radioimmunoassay with Heding's M1230 antiserum. Retinopathy was determined from stereoscopic fundus photographs. The highest frequencies and most severe retinopathy were found in insulin-using individuals with undetectable or low plasma C-peptide (less than 0.3 nM), whereas the lowest frequencies of retinopathy were found in older-onset overweight individuals not using insulin. In older-onset individuals using insulin, having no detectable C-peptide was significantly associated with the presence of proliferative retinopathy. Otherwise, within each group (younger onset using insulin, older onset using insulin, and older onset not using insulin), after controlling for other characteristics associated with retinopathy, there was no relationship between higher levels of C-peptide and lower frequency of or less severe retinopathy.

C-Peptide↗
PubMed1989

The Wisconsin Epidemiologic Study of Diabetic Retinopathy. IX. Four-year incidence and progression of diabetic retinopathy when age at diagnosis is less than 30 years.

Population-based epidemiologic data on the incidence and progression of diabetic retinopathy are important in medical counseling and rehabilitative services and for developing approaches to preventing diabetic retinopathy. We performed a population-based study in southern Wisconsin of insulin-taking diabetic persons diagnosed before 30 years of age. Of the 271 who had no retinopathy at the first visit, 160 (59%) developed it by the time they were reexamined four years later, and 75 (11%) of the 713 free of proliferative diabetic retinopathy developed it. Overall, worsening of retinopathy occurred in 41% of the population, whereas improvement occurred in only 7%. The incidence of proliferative retinopathy rose with increasing duration until 13 to 14 years of diabetes, thereafter remaining between 14% and 17%. These incidence data underscore the need for careful ophthalmologic follow-up of these people.

Adolescent↗
PubMed1989

The Wisconsin Epidemiologic Study of Diabetic Retinopathy. X. Four-year incidence and progression of diabetic retinopathy when age at diagnosis is 30 years or more.

The four-year incidence and progression of retinopathy were investigated in a population-based sample of people with diabetes diagnosed at 30 years of age or older. For insulin users, 73 (47%) of the 154 who did not have any retinopathy at the first visit developed it in the four-year interval, and 31 (7%) of the 418 free of proliferative retinopathy developed it. Worsening of retinopathy occurred in a total of 34% (142/418). For nonusers of insulin, corresponding rates were 34% (110/320) for incidence of any retinopathy, 2% (11/486) for developing proliferative retinopathy, and 25% (121/486) for worsening. These population-based data clearly indicate the risk of retinopathy worsening in a short interval (four years) in a large proportion of people with older-onset diabetes, a group previously thought to be relatively protected from retinopathy. Such patients who make up the largest proportion of diabetic patients in the United States need examination when diabetes is first diagnosed and regular follow-up.

Adult↗
PubMed1989

The Wisconsin epidemiologic study of diabetic retinopathy. XI. The incidence of macular edema.

As part of a population-based study of diabetes mellitus, the 4-year incidence of macular edema and its relationship to various risk factors was examined in a group of younger onset insulin-taking persons (n = 610) and older onset persons (n = 652). The presence of macular edema at the baseline and follow-up examinations was determined from gradings of stereoscopic fundus photographs. The overall incidence of macular edema in the younger onset group was 8.2% (50/610); in the group of older onset persons using insulin, 8.4% (23/273) and in the group of those not using insulin, 2.9% (11/379). The incidence of macular edema was associated with higher level of glycosylated hemoglobin, longer duration of diabetes, and more severe retinopathy at the baseline examination in both younger and older onset groups. These data provide accurate population-based estimates of incidence of macular edema, and suggest that the level of glycemia is a significant risk factor for the development of macular edema.

Adolescent↗
PubMed1989

Is blood pressure a predictor of the incidence or progression of diabetic retinopathy?

The relationship between blood pressure and the 4-year incidence and progression of diabetic retinopathy was examined in a population-based study in Wisconsin. Younger- (n = 891) and older-onset (n = 987) persons participating in baseline and follow-up examinations were included. Blood pressure was measured using the Hypertension Detection and Follow-up Program protocol. Retinopathy was determined from stereoscopic fundus photographs. In the younger-onset group, comparing the highest with the lowest quartile of systolic blood pressure, the relative risk for developing any diabetic retinopathy was 1.8 and for diastolic blood pressure it was 1.2; for progression of diabetic retinopathy, it was 1.1 and 1.3 for systolic and diastolic blood pressure, respectively. After controlling for other risk variables, systolic blood pressure remained a significant predictor of the incidence of diabetic retinopathy; diastolic blood pressure was of borderline significance in predicting progression in the younger-onset group. Blood pressure was not related to incidence or progression of retinopathy either in the older-onset group using insulin or the older-onset group not using insulin.

Age Factors↗
PubMed1989

Changing frequency of interim analysis in sequential monitoring.

In clinical trial data monitoring, one can either introduce a discrete sequential boundary for a set of specified decision times or adopt a use function and then derive the boundary when data are monitored. If the use function approach is employed, one can adjust the frequency of data monitoring as long as the decision is not data-dependent. However, if the frequency of future data monitoring is affected by the observed data, then the probability of Type I error will no longer be preserved exactly. But the effect on the significance level and power is very small, perhaps negligible, as indicated by simulation results.

Biometry↗
PubMed1989

Factors associated with visual outcome after photocoagulation for diabetic retinopathy. Diabetic Retinopathy Study Report #13.

Six risk factors for severe visual loss despite panretinal (scatter) photocoagulation were identified by analyzing data collected during the first 5 years after randomization in the Diabetic Retinopathy Study. Proportional hazards regression revealed NVD (neovascularization on/around the optic disc) to be the most important risk factor. The risk of severe visual loss rose with increasing NVD, hemorrhages/microaneurysms, retinal elevation, proteinuria, and hyperglycemia and fell with increasing "treatment density." These results are similar to previous DRS findings on untreated eyes. The importance of "treatment density" as an independent predictor of visual outcome is a new finding and lends support to the common clinical practice of repeating photocoagulation if initial treatment does not reduce or stabilize retinal neovascularization.

Aged↗
PubMed1989

Relation of ocular and systemic factors to survival in diabetes.

The relationship of survival to systemic and ocular factors in diabetic persons was studied using data collected as part of the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Six years after the baseline examination, 9.5% of 996 insulin-taking people who were younger than age 30 years when their diabetes was diagnosed (younger onset) had died. Of 1370 people whose diabetes was diagnosed after age 30 years (older onset), 35.3% had died. After adjusting for age and sex, longer duration of diabetes, presence of proteinuria, a history of cardiovascular disease, higher blood pressure, diuretic use, a history of smoking, poorer visual acuity, and more severe retinopathy were significantly associated with decreased survival in both groups. Glaucoma was associated with decreased survival in the younger onset group and cataract in the older onset group. These findings suggest that some ocular complications are important risk indicators for death. Their presence in diabetic patients suggests the need for frequent examinations to detect systemic complications and to intervene to minimize their effect.

Adult↗
PubMed1988

Glycosylated hemoglobin predicts the incidence and progression of diabetic retinopathy.

The relationship between hyperglycemia, measured by glycosylated hemoglobin at the initial examination, and the four-year incidence and progression of diabetic retinopathy was examined in a population-based study in Wisconsin. Younger- (n = 891) and older-onset (n = 987) persons participating in baseline and follow-up examinations were included. Glycosylated hemoglobin was measured by microcolumn. Retinopathy was determined from stereoscopic fundus photographs. In the younger-onset group, comparing the highest with the lowest quartile of glycosylated hemoglobin, the relative risk for developing any diabetic retinopathy was 1.9; for proliferative retinopathy, 21.8; and for progression, 4.0. Among older-onset persons taking insulin, the corresponding relative risks were 1.9, 4.0, and 2.1. Among older-onset persons not taking insulin, relative risks were 4.0 for any retinopathy and 6.2 for progression. A positive relationship between incidence and progression of retinopathy and glycosylated hemoglobin remained after controlling for duration of diabetes, age, sex, and baseline retinopathy. These data suggest a strong and consistent relationship between hyperglycemia and incidence and progression of retinopathy.

Adult↗