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Biomedical subjects

G A Colditz

Publications and source records attributed to G A Colditz.

At least 451 records · Page 25Linked to original sources

Weight, diet, and the risk of symptomatic gallstones in middle-aged women.

To assess the risk factors for symptomatic gallstones, 88,837 women in the Nurses' Health Study cohort (age range, 34 to 59 years) were followed for four years after completing a detailed questionnaire about food and alcohol intake in 1980. A total of 433 cholecystectomies and 179 cases of newly symptomatic, unremoved gallstones, diagnosed by ultrasonographic examination or x-ray films, were reported during the four-year follow-up. The age-adjusted relative risk for very obese women, who had a Quetelet index of relative weight (weight in kilograms divided by the square of the height in meters) of more than 32 kg per square meter, was 6.0 (95 percent confidence interval, 4.0 to 9.0), as compared with women whose relative weight was less than 20 kg per square meter. For slightly overweight women (relative weight, 24 to 24.9 kg per square meter), the relative risk was 1.7 (95 percent confidence interval, 1.1 to 2.7). Overall, we observed a roughly linear relation between relative weight and the risk of gallstones. Among the 59,306 women whose relative weight was less than 25 kg per square meter, a high energy intake (greater than 8200 J per day), as compared with a low energy intake (less than 4730 J per day), was associated with an increased incidence of symptomatic gallstones (relative risk, 2.1; 95 percent confidence interval, 1.4 to 3.3), and an alcohol intake of at least 5 g per day was associated with a decreased incidence as compared with abstention (relative risk, 0.6; 95 percent confidence interval, 0.4 to 0.8). Parity did not appear to be an important risk factor after an adjustment was made for relative weight. These data support a strong association between obesity and symptomatic gallstones and suggest that even moderate overweight may increase the risk.

Adult↗

Moles and site-specific risk of nonfamilial cutaneous malignant melanoma in women.

We examined the relationship between self-reported mole counts and cutaneous melanoma with respect to anatomic site in 110 case and 231 control female nurses. Counts of moles on the lower leg were better predictors of melanoma risk than were counts of moles on the arm. The relative risk for the highest quintile of lower leg mole counts versus no lower leg moles was 4.2. Mole counts at each site (arm, thigh, and lower leg) were associated with risk of melanoma of the trunk and lower leg, but none were associated with the risk of melanoma of the upper extremity. The absence of direct site-specificity suggests that mole counts primarily indicate systemic melanoma risk, rather than direct risk from the moles themselves.

Adult↗

How study design affects outcomes in comparisons of therapy. I: Medical.

We analysed 113 reports published in 1980 in a sample of medical journals to relate features of study design to the magnitude of gains attributed to new therapies over old. Overall we rated 87 per cent of new therapies as improvements over standard therapies. The mean gain (measured by the Mann-Whitney statistic) was relatively constant across study designs, except for non-randomized controlled trials with sequential assignment to therapy, which showed a significantly higher likelihood that a patient would do better on the innovation than on standard therapy (p = 0.004). Randomized controlled trials that did not use a double-blind design had a higher likelihood of showing a gain for the innovation than did double-blind trials (p = 0.02). Any evaluation of an innovation may include both bias and the true efficacy of the new therapy, therefore we may consider making adjustments for the average bias associated with a study design. When interpreting an evaluation of a new therapy, readers should consider the impact of the following average adjustments to the Mann-Whitney statistic: for trials with non-random sequential assignment a decrease of 0.15, for non-double-blind randomized controlled trials a decrease of 0.11.

Clinical Trials as Topic↗

How study design affects outcomes in comparisons of therapy. II: Surgical.

We analysed the results of 221 comparisons of an innovation with a standard treatment in surgery published in six leading surgery journals in 1983 to relate features of study design to the magnitude of gain. For each comparison we measured the gain attributed to the innovation over the standard therapy by the Mann-Whitney statistic and the difference in proportion of treatment successes. For primary treatments (aimed at curing or ameliorating a patient's principal disease), an average gain of 0.56 was produced by 20 randomized controlled trials. This was less than the 0.62 average for four non-randomized controlled trials, 0.63 for 19 externally controlled trials, and 0.57 for 73 record reviews (0.50 represents a toss-up between innovation and standard). For secondary therapies (used to prevent or treat complications of therapy), the average gain was 0.53 for 61 randomized controlled trials, 0.58 for eleven non-randomized controlled trials, 0.54 for eight externally controlled trials, and 0.55 for 18 record reviews. Readers of studies evaluating new treatments, particularly for primary treatments, may consider adjustment of the gain according to the study type.

Clinical Trials as Topic↗

Angiodysplasia. Natural history and efficacy of therapeutic interventions.

Angiodysplasia, a disease for which the optimal treatment is uncertain, is a frequent cause of lower intestinal bleeding among older patients. To study the natural history of angiodysplasia and compare the efficacy of medical therapy, endoscopic electrocoagulation, and surgery, the course of 101 patients evaluated from 1974 through 1983 at the Massachusetts General Hospital was reviewed. Angiodysplasia caused bleeding that ranged from occult blood in stools to massive hemorrhage and was also observed incidentally in nonbleeding patients. Patients were followed for up to 10 years (mean of 22 months). Rebleeding was defined as evidence of hemorrhage requiring hospital admission, transfusion, or surgery. Thirty-one patients were treated surgically, 19 patients were treated endoscopically, and 36 patients were treated medically. Using life table analysis we observed similar rebleeding rates among medically and endoscopically treated groups. The surgically treated group had a frequency of rebleeding less than half that of the other groups (P = 0.15). A multivariate regression analysis failed to identify any factors other than coagulopathy to explain the different incidence of rebleeding in the patients treated by endoscopic electrocoagulation and surgery.

Diverticulum↗

Cimetidine and adverse reactions: a meta-analysis of randomized clinical trials of short-term therapy.

PURPOSE: We pooled data from randomized, double-blind, placebo-controlled trials to determine the frequency of adverse reactions among patients treated with cimetidine for acute acid-peptic disorders. METHODS: Meta-analysis was used to analyze data obtained from a search of English language reports of trials of cimetidine in the ambulatory treatment of acute acid-peptic disorders that were published between January 1982 and April 1987. RESULTS: Of 161 trials of cimetidine that we identified, 84 provided complete reporting of data on adverse reactions and, of these, 24 employed a randomized, double-blind, placebo-controlled design. Across these 24 trials, the overall rate of reported adverse reactions among 622 patients randomly assigned to receive cimetidine was 10.9%; the corresponding rate among 516 patients randomly assigned to receive placebo was 10.1%. This difference was not statistically significant (p greater than 0.10), nor were any significant differences noted in the frequencies of reported central nervous system or gastrointestinal adverse reactions (p greater than 0.10). Rates of adverse reactions also did not differ by dosage or trial duration. The overall rate of adverse reactions reported in the 60 trials that did not utilize a randomized, double-blind, placebo-controlled design was similar to the rate reported in those that did. CONCLUSIONS: Our findings suggest that the frequency of adverse reactions among patients receiving cimetidine for acute acid-peptic disorders is not significantly different from that of patients receiving placebo.

Acute Disease↗

Food-based validation of a dietary questionnaire: the effects of week-to-week variation in food consumption.

The reproducibility and validity of responses for 55 specific foods and beverages on a self-administered food frequency questionnaire were evaluated. One hundred and seventy three women from the Nurses' Health Study completed the questionnaire twice approximately 12 months apart and also recorded their food consumption for seven consecutive days, four times during the one-year interval. For the 55 foods, the mean of correlation coefficients between frequencies of intake for first versus second questionnaire was 0.57 (range = 0.24 for fruit punch to 0.93 for beer). The mean of correlation coefficients between the dietary records and first questionnaire was 0.44 (range = 0.09 for yellow squash to 0.83 for beer and tea) and between the dietary records and the second questionnaire was 0.52 (range = 0.08 for spinach to 0.90 for tea). Ratios of within- to between-person variance for the 55 foods were computed using the mean four one-week dietary records for each person as replicate measurements. For most foods this ratio was greater than 1.0 (geometric mean of ratios = 1.88), ranging from 0.25 (skimmed milk) to 14.76 (spinach). Correlation coefficients comparing questionnaire and dietary record for the 55 foods were corrected for the within-person variation (mean corrected value = 0.55 for dietary record versus first questionnaire and 0.66 versus the second). Mean daily amounts of each food calculated by the questionnaire and by the dietary record were also compared; the observed differences suggested that responses to the questionnaire tended to over-represent socially desirable foods. This analysis documents the validity and reproducibility of the questionnaire for measuring specific foods and beverages, as well as the large within-person variation for food intake measured by dietary records. Differences in the degree of validity for specific foods revealed in this type of analysis can be useful in improving questionnaire design and in interpreting findings from epidemiological studies that use the instrument.

Adult↗

A prospective study of high blood pressure and cardiovascular disease in women.

The relation of self-reported high blood pressure to the subsequent development of coronary heart disease and stroke was examined in a cohort of 119,963 women, aged 30-55 years, who were initially free from cardiovascular disease. Participants in the Nurses' Health Study reported high blood pressure and other cardiovascular risk factors on baseline questionnaires mailed in 1976. During six years of follow-up, there were 308 incident cases of coronary heart disease (66 fatal and 242 nonfatal myocardial infarctions) and 175 strokes (50 fatal and 125 nonfatal). Fatal as well as nonfatal coronary heart disease and stroke were all significantly more frequent among the women who had reported high blood pressure. After adjusting simultaneously for age and other risk factors, the relative risks were 3.5 (95% confidence interval (Cl) 2.8-4.5) for total coronary heart disease and 2.6 (95% Cl 1.8-3.5) for total stroke. This association was evident at all levels of relative weight. The results emphasize the importance of high blood pressure as an independent predictor of coronary heart disease and stroke in middle-aged women and suggest that the increased risk occurs in both lean and obese women.

Adult↗

An assessment of the role of 123I-N-isopropyl-p-iodoamphetamine with single-photon emission computed tomography in the diagnosis of stroke and Alzheimer's disease.

The role of 123I-N-isopropyl-p-iodoamphetamine (123I-IMP), a new agent used in brain imaging with single-photon emission computed tomography (SPECT), has been assessed in the early diagnosis of acute infarctive stroke and Alzheimer's disease (AD). The diagnosis of these conditions in their early stages has remained problematic, principally due to limitations of existing technologies. To more formally assess this new technology, we estimated the sensitivity and specificity of 123I-IMP SPECT scanning in the diagnosis of stroke and AD. We based our assessment on a review of all published studies that reported on 123I-IMP SPECT scans and which included three or more patients. The results from three major studies indicate that 123I-IMP SPECT scanning has a higher sensitivity (92% to 100%) than computerized tomography (55% to 86%) in the early diagnosis of acute cerebral infarction. Preliminary findings from studies using 123I-IMP SPECT in the diagnosis of early AD are promising and show a sensitivity of at least 69%. Furthermore, 123I-IMP SPECT scanning clearly discriminates patients with advanced AD from normals: sensitivity has ranged from 50% to 100%, while specificity has ranged from 97% to 100%. Studies also suggest that it can discriminate AD patients from those with multi-infarct dementia. Our review indicates that 123I-IMP SPECT may have an important future role in the early diagnosis and management of patients with acute infarctive stroke and AD.

Alzheimer Disease↗

A prospective study of nutritional factors and hypertension among US women.

The relation of various nutritional factors with hypertension was examined prospectively among 58,218 predominantly white US female registered nurses, aged 34-59 years. In 1980, all women completed an independently validated dietary questionnaire. During 4 years of follow-up, 3,275 women reported a diagnosis of hypertension; the validity of the self-report was shown in a subsample. Age, relative weight, and alcohol consumption were the strongest predictors for the development of hypertension. Dietary calcium and magnesium had independent and significant inverse associations with hypertension. For women with a calcium intake of at least 800 mg/day, the relative risk of hypertension was 0.78 (95% confidence interval, 0.69-0.88) when compared with an intake of less than 400 mg/day. The relative risk for magnesium intake of 300 mg/day or more compared with an intake of less than 200 mg/day was 0.77 (95% confidence interval, 0.67-0.88). For women with high intakes of both calcium and magnesium compared with those having low intakes of both, the relative risk of hypertension was 0.65 (95% confidence interval, 0.53-0.80). No independent associations with hypertension were observed for intakes of potassium, fiber, and saturated and polyunsaturated fatty acids. These prospective findings add to the growing evidence to support the need for randomized trials to determine whether there is a protective role of dietary calcium and magnesium in the regulation of blood pressure.

Adult↗

Nonfamilial cutaneous melanoma incidence in women associated with sun exposure before 20 years of age.

Despite strong evidence that sun exposure causes malignant melanoma, the details of this relation remain unclear. A nested case-control analysis was conducted within the Nurses' Health Study cohort to examine the relation between timing of severe sun exposure and incidence of melanoma. The subjects were 130 white women aged 38 to 65 years with confirmed cutaneous melanoma (other than acral lentigenous) who reported no history of melanoma in first-degree relatives. The control subjects were 300 women matched by race, date of birth, and cycle of questionnaire who also reported no history of melanoma in first-degree relatives. We used conditional logistic regression to evaluate the relation of sun damage after 30 years of age and sun damage from 15 to 20 years of age to the incidence of melanoma. Blistering sunburns between 15 to 20 years of age were associated with risk of melanoma (relative risk = 2.2 for five or more burns vs none, 95% confidence interval 1.2 to 3.8). This association persisted when a history of burns after 30 years of age was controlled in the analysis. No material association was found between blistering sunburns after 30 years of age and melanoma. Similarly, a more equatorial latitude of residence between 15 and 20 years of age was positively associated with melanoma; latitude after 30 years of age was less strongly and not significantly related to melanoma risk. Sun exposure prior to 20 years of age is more closely associated with melanoma risk than sun exposure after 30 years of age.

Adolescent↗

A prospective study of past use of oral contraceptive agents and risk of cardiovascular diseases.

We evaluated the effects of past use of oral contraceptive agents on the risk of various cardiovascular diseases among women in the Nurses' Health Study cohort. We studied 119,061 women who were 30 to 55 years of age in 1976, who provided information on their use of oral contraceptives, and who at entry had had no previous coronary disease or stroke. End points were documented by medical records. During eight years of follow-up (484,096 person-years among those who had never used oral contraceptives, 415,488 among past users, and 22,376 among current users), there were 485 new cases of major coronary disease (380 nonfatal myocardial infarctions and 105 deaths from coronary disease), 282 strokes (205 nonfatal and 77 fatal), and 48 other deaths from cardiovascular causes. We found no evidence to suggest an increase in the risk of cardiovascular diseases among past users of oral contraceptives, even with prolonged previous use. After adjustment for a variety of risk factors, the relative risk of major coronary disease for women who had used oral contraceptives in the past, as compared with those who had never used such agents, was 0.8 (95 percent confidence interval, 0.6 to 1.0); of stroke, 1.0 (95 percent confidence interval, 0.7 to 1.3); and of death from all cardiovascular causes, 0.9 (95 percent confidence interval, 0.7 to 1.2). We found neither evidence of increased risk with longer use nor any trend with the amount of time since the last use. According to these prospective data, the use of oral contraceptive agents in the past does not materially raise a woman's risk of subsequent cardiovascular disease.

Adult↗

A prospective study of moderate alcohol consumption and the risk of coronary disease and stroke in women.

In 1980, 87,526 female nurses 34 to 59 years of age completed a dietary questionnaire that assessed their consumption of beer, wine, and liquor. By 1984, during 334,382 person-years of follow-up, we had documented 200 incident cases of severe coronary heart disease (164 nonfatal myocardial infarctions and 36 deaths due to coronary disease), 66 ischemic strokes, and 28 subarachnoid hemorrhages. Follow-up was 98 percent complete. As compared with nondrinkers, women who consumed 5 to 14 g of alcohol per day (three to nine drinks per week) had a relative risk of coronary disease of 0.6 (95 percent confidence interval, 0.4 to 0.9); for 15 to 24 g per day the relative risk was 0.6 (0.3 to 1.1), and for 25 g or more per day it was 0.4 (0.2 to 0.8), after adjustment for risk factors for coronary disease. Alcohol intake was also associated with a decreased risk of ischemic stroke. For 5 to 14 g of alcohol per day the relative risk was 0.3 (0.1 to 0.7), and for 15 g per day or more it was 0.5 (0.2 to 1.1). In contrast, although the number of cases of subarachnoid hemorrhage was small, alcohol intake tended to be associated with an increased risk of this disorder; for 5 to 14 g per day the relative risk was 3.7 (1.0 to 13.8). These prospective data suggest that among middle-aged women, moderate alcohol consumption decreases the risks of coronary heart disease and ischemic stroke but may increase the risk of subarachnoid hemorrhage.

Adult↗

Cigarette smoking and risk of stroke in middle-aged women.

It is known that cigarette smoking is associated with increased risk of both thrombotic and hemorrhagic stroke among men. To test for such an association among women, we examined the incidence of stroke in relation to cigarette smoking in a prospective cohort study of 118,539 women 30 to 55 years of age and free from coronary heart disease, stroke, and cancer in 1976. During eight years of follow-up (908,447 person-years), we identified 274 strokes, comprising 71 subarachnoid hemorrhages, 26 intracerebral hemorrhages, 122 thromboembolic strokes, and 55 strokes about which information was insufficient to permit classification. The number of cigarettes smoked per day was associated positively with the risk of stroke. Compared with the women who had never smoked, those who smoked 1 to 14 cigarettes per day had an age-adjusted relative risk of 2.2 (95 percent confidence interval, 1.5 to 3.3), whereas those who smoked 25 or more cigarettes per day had a relative risk of 3.7 (95 percent confidence interval, 2.7 to 5.1). For women in this latter group, the relative risk of subarachnoid hemorrhage was 9.8 (95 percent confidence interval, 5.3 to 17.9), as compared with those who had never smoked. Adjustment for the effects of relative weight, hypertension, diabetes, history of high cholesterol, previous use of oral contraceptives, postmenopausal estrogen therapy, and alcohol intake did not appreciably alter the association between cigarette use and incidence of stroke. These prospective data support a strong causal relation between cigarette smoking and stroke among young and middle-aged women.

Adult↗

Randomized clinical trials of transdermal nitroglycerin systems for the treatment of angina: a meta-analysis.

The efficacy of transdermal nitrate patches at 24 hours after application remains controversial. Definitive evaluation has been limited because most randomized trials have had relatively small sample sizes. Therefore, we performed a meta-analysis and combined the results of 17 trials. We assessed exercise test duration as the primary end point. At 3 to 4 hours after patch application, there was a 77-second increase in exercise duration (p = 0.02) for a 5 mg/24 hour dose and a 114-second increase in exercise duration (p = 0.001) for a 10 mg/24 hour dose. At 24 hours, however, the 29-second increase in exercise duration for a 10 mg/24 hour dose was not significant (p greater than 0.1), despite persistent decreases in systolic blood pressure, an increase in heart rate, and a "therapeutic" plasma nitroglycerin concentration. The findings indicate that the 10 mg/24 hour dose is not efficacious at 24 hours after application and support the hypothesis that nitroglycerin's effect on exercise performance is attenuated by nitrate tolerance even though hemodynamic effects and adequate blood levels persist.

Administration, Cutaneous↗