Biomedical subjects

N R Cook

Publications and source records attributed to N R Cook.

At least 37 records · Page 2Linked to original sources

PubMed2001

Low-dose aspirin for migraine prophylaxis in women.

Although migraine is more common among women than men, the only two large, randomized trials of low-dose aspirin for migraine prophylaxis have been conducted in men. As part of the Women's Health Study, an ongoing randomized trial of low-dose aspirin and vitamin E among 39 876 female health professionals aged 45 and older, 1001 women with frequent migraine attacks were assigned to 100 mg of aspirin every other day (n = 525) or aspirin placebo (n = 476). Migraine frequency, as well as severity, duration, and degree of incapacitation, were assessed by self-report on questionnaires 12 months and 36 months after randomization, and also by monthly diaries kept before and after randomization. Women assigned to aspirin reported small and consistent decreases in migraine frequency (59.6% vs. 56.4% assigned to placebo reporting improvement at 36 months; odds ratio 1.13, 95% confidence interval, 0.86--1.48), as well as decreases in severity, duration, and migraine-related incapacitation. These reductions were not, however, statistically significant. These data are compatible with a small treatment effect of low-dose aspirin in the prophylaxis of migraine among middle-aged women.

Adult↗

PubMed2001

Serologic evaluations of women exposed to breast implants.

OBJECTIVE: There continues to be uncertainty whether women with silicone breast implants experience activation of their immune system and show increased prevalence of serologic markers of connective tissue diseases. We conducted laboratory tests in a large number of women with and without breast implants, and in diabetic patients with presumed silicone exposure via insulin syringes. METHODS: Subjects were chosen from women enrolled in the run-in phase of the Women's Health Study (WHS, a randomized trial testing aspirin and vitamin E in preventing cardiovascular disease and cancer), and included 298 women without breast implants, 298 women with breast implants, and 52 diabetic patients diagnosed before age 30. Comparison groups were matched on age, race, date of blood provided to the WHS, and randomization status. We compared the proportion with abnormal results in 16 serologic tests among the 3 groups of women, stratifying by the matching factors. We also tested for monoclonal immunoglobulins by electrophoresis. RESULTS: For 14 of the 16 serologic tests, the proportions with abnormal results among the 3 groups of women were not significantly different. Of the remaining tests, C3 levels were decreased in 8 (2.7%) women without breast implants and 22 (7.4%) women with breast implants (p = 0.003). C4 levels were decreased in 31 (10.4%) women without breast implants and 48 (16.1%) women with breast implants (p = 0.03). Women without breast implants and diabetic patients did not differ significantly in the proportions having decreased C3 and C4 levels. Women with breast implants did not have higher frequency of monoclonal immunoglobulins detected by electrophoresis. CONCLUSION: We found little evidence for activation of the immune system in women with breast implants. The clinical significance of isolated reductions in C3 and C4 levels, in the absence of other abnormalities such as elevated levels of antinuclear antibody, is unknown.

Antibodies, Antinuclear↗

PubMed2000

Combining annual blood pressure measurements in childhood to improve prediction of young adult blood pressure.

Tracking correlations of blood pressure (BP) have been reported between levels measured in a single year during both childhood and adulthood. Because of the variability of BP, these correlations increase with the number of visits and measurements per visit in each year. It remains unclear, however, whether such correlations would improve further by combining BP data collected over several years. From 1978-1981, BP was measured annually in a cohort of 339 children in East Boston, MA, at four visits one week apart with three measurements per visit. Of this cohort, then aged 18-26 years, 316 were re-examined in 1989-1990 at three visits one week apart with three measures per visit. Tracking correlations were estimated from levels measured in a single year as well as means averaged over several years in childhood, adjusting for age, year of measurement, as well as smoking, alcohol and oral contraceptive use. Multivariate models were fit to estimate tracking correlations from childhood to young adulthood adjusting for within-person variability. Using a single year in childhood, these were 0.49 in boys and 0.59 in girls for systolic BP and 0.39 and 0.48 for diastolic BP (all p<0.001). Using the long-term average in childhood and adjusting for variability across years, these values were 0.55 in boys and 0.66 in girls for systolic BP and 0.47 and 0.57 for diastolic BP (all p<0.001). We observed concomitant increases in the predictive value of childhood BP for young adult BP. These results suggest that averaging BP over at least two years during childhood increases tracking correlations and improves the prediction of adult values from childhood levels.

Adolescent↗

PubMed2000

Self-selected posttrial aspirin use and subsequent cardiovascular disease and mortality in the physicians' health study.

BACKGROUND: The randomized aspirin component of the Physicians' Health Study (PHS) was terminated early, after 5 years, primarily because of the emergence of a statistically extreme (P<.00001) 44% reduction of first myocardial infarction (MI) among those assigned to aspirin. As a result, there were insufficient numbers of strokes or cardiovascular disease (CVD)-related deaths to evaluate these end points definitively. METHODS: Data on self-selected aspirin use were collected until the beta carotene component ended as scheduled after 12 years. Posttrial use of aspirin was assessed at the 7-year follow-up among 18 496 participants with no previous reported CVD. Randomized and posttrial observational results in the PHS were compared, and differences between those self-selecting aspirin and those not were examined. RESULTS: At 7 years, 59.5% of participants without CVD reported self-selected aspirin use for at least 180 d/y, and 20.8% for 0 to 13 d/y. Use was significantly associated with family history of MI, hypertension, elevated cholesterol levels, body mass index, alcohol consumption, exercise, and use of vitamin E supplements. In multivariate analyses, self-selected aspirin use for at least 180 vs 0 to 13 d/y was associated with lower risk for subsequent MI (relative risk [RR], 0.72; 95% confidence interval [CI], 0.55-0.95), no relation with stroke (RR, 1.02; 95% CI, 0.74-1.39), and significant reductions in CVD-related (RR, 0.65; CI, 0.47-0.89) and total mortality (RR, 0.64; CI, 0.54-0.77). CONCLUSION: These associations between self-selected aspirin use and CVD risk factors increase the likelihood of residual confounding and emphasize the need for large-scale randomized trials, such as the ongoing Women's Health Study, to detect reliably the most plausible small to moderate effects of aspirin in the primary prevention of stroke and CVD-related death.

Adult↗

PubMed2000

Effects of beta-carotene supplementation on cancer incidence by baseline characteristics in the Physicians' Health Study (United States).

OBJECTIVES: The Physicians' Health Study (PHS) was a randomized trial of beta-carotene (50 mg, alternate days) and aspirin in primary prevention of cancer and cardiovascular disease among 22,071 US male physicians. This report updates results for beta-carotene and examines effect modification by baseline characteristics. METHODS: Beta-carotene's effect on cancer over nearly 13 years was examined overall and within subgroups defined by baseline characteristics using proportional-hazards models. RESULTS: 2667 incident cancers were confirmed, with 1117 prostate, 267 colon, and 178 lung cancers. There were no significant differences with supplementation in total (relative risk (RR) = 1.0, 95% confidence interval (CI) = 0.9-1.0); prostate (RR = 1.0, 95% CI = 0.9-1.1); colon (RR = 0.9, 95% CI = 0.7-1.2); or lung (RR = 0.9, 95% CI = 0.7-1.2) cancer, and no differences over time. In subgroup analyses, total cancer was modestly reduced with supplementation among those aged 70+ years (RR = 0.8, 95% CI = 0.7-1.0), daily drinkers of alcohol (RR = 0.9, 95% CI = 0.8-1.0), and those in the highest BMI quartile (RR = 0.9, 95% CI = 0.7-1.0). Prostate cancer was reduced with supplementation among those in the highest BMI quartile (RR = 0.8, 95% CI = 0.6-1.0), and colon cancer was reduced among daily drinkers of alcohol (RR = 0.5, 95% CI = 0.3-0.8). CONCLUSIONS: The PHS found no overall effect of beta-carotene on total cancer, or the three most common site-specific cancers. The possibility of risk reduction within specific subgroups remains.

Adult↗

PubMed1999

Beta-carotene supplementation and incidence of cancer and cardiovascular disease: the Women's Health Study.

BACKGROUND: In observational studies, individuals with high intakes of fruits and vegetables containing beta-carotene experience lower risks of developing cancer. However, the few randomized trials of beta-carotene supplementation show no overall benefits; some even suggest harm. This trial was designed to test the effects of beta-carotene supplementation in women. METHODS: The Women's Health Study is a randomized, double-blind, placebo-controlled trial originally testing aspirin, vitamin E, and beta-carotene in the prevention of cancer and cardiovascular disease among 39 876 women aged 45 years or older. The beta-carotene component was terminated early after a median treatment duration of 2.1 years (range = 0.00-2. 72 years). Statistical tests were two-sided. RESULTS: Among women randomly assigned to receive beta-carotene (50 mg on alternate days; n = 19 939) or placebo (n =19 937), there were no statistically significant differences in incidence of cancer, cardiovascular disease, or total mortality after a median of 4.1 years (2.1 years' treatment plus another 2.0 years' follow-up). There were 378 cancers in the beta-carotene group and 369 cancers in the placebo group (relative risk [RR] = 1.03; 95% confidence interval [CI] = 0.89-1. 18). There were no statistically significant differences for any site-specific cancer or during years 1 and 2 combined and years 3 and up combined. For cardiovascular disease, there were no statistically significant differences for myocardial infarction (42 in the beta-carotene group versus 50 in the placebo group), stroke (61 versus 43), deaths from cardiovascular causes (14 versus 12), or the combined end point of these three events (116 versus 102; among women with more than one event, only the first was counted). Deaths from any cause were similar in the two groups (59 versus 55). Among smokers at baseline (13% of all women), there were no statistically significant differences in overall incidence of cancer (RR = 1.11; 95% CI = 0.78-1.58) or cardiovascular disease (RR = 1.01; 95% CI = 0. 62-1.63). CONCLUSION: Among apparently healthy women, there was no benefit or harm from beta-carotene supplementation for a limited period on the incidence of cancer and of cardiovascular disease.

Aged↗

PubMed1999

Beta-carotene supplementation for patients with low baseline levels and decreased risks of total and prostate carcinoma.

BACKGROUND: The Physicians' Health Study was a randomized, double-blind, placebo-controlled trial using a 2x2 factorial design including supplementation with beta-carotene (50 mg every other day) in the primary prevention of cancer among 22,071 U.S. male physicians ages 40-84 years at randomization. Before randomization, the authors collected baseline blood specimens to determine whether any benefit was greater among or confined to those with low baseline levels of beta-carotene. METHODS: Baseline blood samples were collected from 14,916 participants. These samples were assayed, according to a nested case-control design, from 1439 men subsequently diagnosed with cancer over 12 years of follow-up (631 with prostate carcinoma) and 2204 controls matched by age and smoking habits. RESULTS: Men in the lowest quartile for plasma beta-carotene at baseline had a marginally significant (P = 0.07) increased risk of cancer compared with those in the highest quartile (relative risk [RR] = 1.30, 95% confidence interval [CI], 0.98-1.74). Men in the lowest quartile assigned at random to beta-carotene supplementation had a possible but nonsignificant decrease in overall cancer risk (RR = 0.83, 95% CI, 0.63-1.09) compared with those assigned to placebo. This was primarily due to a significant reduction in the risk of prostate carcinoma (RR = 0.68, 95% CI, 0. 46-0.99) in this group. After the first 2 years of follow-up were excluded, the results were virtually unchanged. CONCLUSIONS: These prespecified subgroup analyses appeared to support the idea that beta-carotene supplementation may reduce risk of prostate carcinoma among those with low baseline levels. Further follow-up of this population will help determine whether these findings are valid.

Adult↗

PubMed1999

Comparison of self-reported diagnosis of connective tissue disease with medical records in female health professionals: the Women's Health Cohort Study.

To compare self-report of connective tissue disease (CTD) with medical records, subjects were selected from 395,543 female health professionals with and without breast implants who reported CTD on mailed questionnaires from 1992 to 1995. The authors identified 220 women with breast implants (exposed) who self-reported CTD and a random sample of 879 women without breast implants (unexposed) who also self-reported CTD, matched by age and date of diagnosis. Medical records were reviewed using classification criteria from the American College of Rheumatology or other published criteria. After up to three requests and a telephone call, 27.7% of the women provided consent for medical record review. Exposed women appeared somewhat more likely (33.2% vs. 26.3%, p = 0.04) to provide consent. Using medical record reviews for 90% of the women who provided consent, confirmation rates of definite CTD were similar among the exposed and unexposed (22.7% vs. 24.0%, p = 0.83). This study demonstrates the difficulty of obtaining consent for medical record review of CTD reported to have occurred years ago in women with and without breast implants. Confirmation rates were low but were similar in exposed and unexposed. Despite the fact that the study had low participation rates, the data suggest that relative risk estimates for any definite CTD among women with breast implants compared with women without breast implants would be similar in analyses of self-reported or medical record-confirmed cases.

Adult↗

PubMed1999

Moderate alcohol consumption and the risk of sudden cardiac death among US male physicians.

BACKGROUND: Individuals who consume high amounts of alcohol (>5 drinks/d) have increased risks of ventricular arrhythmia and sudden cardiac death (SCD). However, the relationship is less clear for drinkers of light-to-moderate amounts. METHODS AND RESULTS: We prospectively assessed whether light-to-moderate alcohol drinkers have a decreased risk of SCD among 21 537 male participants in the Physicians Health Study who were free of self-reported cardiovascular disease and provided complete information on alcohol intake at study entry. Over 12 years of follow-up, 141 SCDs were confirmed. After control for multiple confounders, men who consumed 2 to 4 drinks/wk (RR=0.40; 95% CI, 0.22 to 0.75; P=0.004) or 5 to 6 drinks/wk (RR=0.21; 95% CI, 0.08 to 0.56; P=0.002) at baseline had significantly reduced risks of SCD compared with those who rarely or never consumed alcohol. The relationship for SCD was U-shaped (P=0. 002), with the risk approaching unity at >/=2 drinks/d. In contrast, the relationship of alcohol intake and nonsudden CHD death was L-shaped or linear (P for trend=0.02). CONCLUSIONS: In these prospective data, men who consumed light-to-moderate amounts of alcohol (2 to 6 drinks/wk) had a significantly reduced risk of SCD compared with those who rarely or never consumed alcohol.

Alcohol Drinking↗

PubMed1999

A retrospective cohort study of cigarette smoking and risk of rheumatoid arthritis in female health professionals.

OBJECTIVE: To study the association of cigarette smoking with risk of rheumatoid arthritis (RA), among 377,481 female health professionals in the Women's Health Cohort Study. METHODS: Subjects completed mailed questionnaires regarding demographics, health habits, including cigarette smoking history, and medical history, including RA diagnosis made by a physician and date of diagnosis. Of 7,697 women who self-reported RA, 3,416 reported seropositive RA. Cox proportional hazards regression models were used to retrospectively assess the associations of smoking intensity and duration with the risk of developing RA or seropositive RA. Cigarette smoking status was treated as a time-varying exposure in these regression models. RESULTS: In multivariate analyses controlling for age, race, education, age at menarche, pregnancy history, menopausal status, and postmenopausal hormone use, duration of smoking was associated with a significantly increased risk of both RA and seropositive RA (both P < 0.01 for trend), after adjusting for smoking intensity. Women who smoked > or =25 cigarettes/day for more than 20 years experienced a 39% increased risk of RA and 49% increased risk of seropositive RA. However, smoking intensity (number of cigarettes/day) was unrelated to risk of RA or seropositive RA (both P = 0.3 for trend), after adjusting for duration of smoking. CONCLUSION: Duration, but not intensity, of cigarette smoking is associated with a modest increased risk of RA in women.

Arthritis, Rheumatoid↗

PubMed1998

Effect of change in sodium excretion on change in blood pressure corrected for measurement error. The Trials of Hypertension Prevention, Phase I.

Intraperson variability in both blood pressure (BP) and sodium excretion dilutes associations and leads to underestimates of the dose-response relation. The authors applied statistical correction techniques to data from the Trials of Hypertension Prevention (TOHP), Phase I, carried out 1987-1990. Men and women with high normal diastolic BP (80-89 mmHg) were randomized to sodium reduction (n = 327) or a usual care comparison group (n = 417). Regression estimates of the effects of change in sodium and sodium/potassium ratio (Na/K ratio) on blood pressure change in the pooled sample were corrected for both the within-person variance of the excretion measures and the within-person covariance with blood pressure using a multivariate error correction. The estimated cross-sectional reliability was 0.36 for square root(Na) and 0.42 for square root(Na/K ratio) and that for change was 0.31 and 0.28, respectively. Corrected coefficients suggested a decrease of 4.4 mmHg in systolic BP (95% confidence interval (CI) 0.1-8.8) and 2.8 mmHg in diastolic BP (95% CI -0.2 to 5.8) per 100 mmol/24 hour reduction in sodium, and of 3.4 mmHg in systolic BP (95% CI 0.8-6.1) and 1.7 mmHg in diastolic BP (95% CI 0.0-3.5) per unit decrease in Na/K. These results are comparable with those from the Intersalt Study, and suggest that the true effect of sodium change on blood pressure change in normotensives over 18 months is underestimated by more than half in uncorrected data.

Adult↗

PubMed1998

Angiotensinogen genotype, sodium reduction, weight loss, and prevention of hypertension: trials of hypertension prevention, phase II.

The angiotensinogen gene has been linked to essential hypertension and increased blood pressure. A functional variant believed to be responsible for hypertension susceptibility occurs at position -6 in the promoter region of the gene in which an A for G base pair substitution is associated with higher angiotensinogen levels. To test whether an allele within the angiotensinogen gene is related to subsequent incidence of hypertension and blood pressure response to sustained sodium reduction, 1509 white male and female subjects participating in phase II of the Trials of Hypertension Prevention were genotyped at the angiotensinogen locus. Participants had diastolic blood pressures between 83 and 89 mm Hg and were randomized in a 2x2 factorial design to sodium reduction, weight loss, combined intervention, or usual care groups. Persons in the usual care group with the AA genotype at nucleotide position -6 had a higher 3-year incidence rate of hypertension (44.6%) compared with those with the GG genotype (31.5%), with a relative risk of 1.4 (95% confidence interval [0.87, 2.34], test for trend across all 3 genotypes, P=0.10). In contrast, the incidence of hypertension was significantly lower after sodium reduction for persons with the AA genotype (relative risk=0.57 [0.34, 0.98] versus usual care) but not for persons with the GG genotype (relative risk=1.2 [0.79, 1.81], test for trend P=0.02). Decreases of diastolic blood pressure at 36 months in the sodium reduction group versus usual care showed a significant trend across all 3 genotypes (P=0.01), with greater net blood pressure reduction in those with the AA genotype (-2.2 mm Hg) than those with the GG genotype (+1.1 mm Hg). A similar trend across the 3 genotypes for net systolic blood pressure reduction (-2.7 for AA versus -0.2 mm Hg for GG) was not significant (P=0.17). Trends across genotypes for the effects of weight loss on hypertension incidence and decreases in blood pressure were similar to those for sodium reduction. We conclude that the angiotensinogen genotype may affect blood pressure response to sodium or weight reduction and the development of hypertension.

Adult↗

PubMed1997

An imputation method for non-ignorable missing data in studies of blood pressure.

In studies with repeated measures of blood pressure (BP), particularly in trials of hypertension prevention, BP measurements often become censored once a participant commences antihypertensive medication. When prescribed by non-study physicians under uncontrolled conditions, the missing data mechanism is non-ignorable and may bias the BP effects of interest. I propose a method that models the distribution of BPs measured by non-study physicians and their relation to study BPs using random effects models. If treated for hypertension, I assume that BP measured outside the study is greater than a clinical cutpoint, such as diastolic BP > or = 90 mmHg. I then compute estimates for the missing study BPs conditional on previously observed study BPs and treatment for hypertension. Multiple imputation is used to model the variability of the BP values and adjust the standard error estimates of the parameters. Examples are given using simulated data and data from the weight loss intervention of phase I of the Trials of Hypertension Prevention.

Antihypertensive Agents↗

PubMed1997

Prediction of young adult blood pressure from childhood blood pressure, height, and weight.

To assess the ability of childhood blood pressure, height, and weight to predict young adult blood pressure, the authors examined data obtained over multiple visits for four years on 339 children aged 8-18 years in East Boston, Massachusetts. These subjects were again seen 8-12 years later when they were aged 20-26 years. Multivariate regression models were used to predict true blood pressure in young adulthood from observed childhood measurements closest to age 10 (n = 219), adjusting for within-person variability. Without adjusting for childhood blood pressure, childhood height, weight and body mass index were at least marginally associated with young adult systolic blood pressure in boys and girls, with similar coefficients for each gender. The strongest predictor was weight (beta = 0.6 mmHg/10 lbs for girls, and beta = 0.7 mmHg/10 lbs for boys), and height was no longer predictive with weight in the model. With childhood blood pressure included, neither childhood height nor weight were predictors of future systolic blood pressure. However, change in height and weight were predictors of future systolic blood pressure. Weight change was a stronger predictor in girls than boys with beta = 0.9 mmHg/10 lbs. For diastolic blood pressure, height and weight had limited predictive ability in these data. These models, which allow for both between- and within-person variability in young adulthood, may be used to estimate the predictive value for future high blood pressure of a child's current blood pressure, height and weight, as well as future change in height and weight. These data suggest that the effects of childhood height and weight on future blood pressure may be negligible given childhood blood pressure, but that later height and weight remain predictive.

Adolescent↗

PubMed1997

Adult height and incidence of cancer in male physicians (United States).

Adult height has been found in some but not all studies to be associated positively with overall cancer incidence as well as several site-specific cancers. The Physicians' Health Study (PHS), a randomized trial of beta-carotene and aspirin in the primary prevention of cancer and cardiovascular disease in men, provided an opportunity to examine the association between height and total malignant neoplasms (excluding non-melanoma skin cancer), as well as site-specific cancers including prostate, colorectal, and lung cancer. The PHS is comprised of 22,071 US male physicians in the United States, a population homogeneous for adult socioeconomic status, aged 40 to 84 years in 1982. Participants were classified into five height categories at study entry. After an average follow-up of over 12 years, there were 2,566 cases of incident total malignant neoplasms, including 1,047 prostate, 341 colorectal, and 170 lung cancer cases. Height was associated positively with both total malignant neoplasms and prostate cancer. Compared with men in the shortest category (<67 inches), relative risks and 95 percent confidence intervals (CI) for total malignant neoplasms for men whose height (in inches) was 68-69, 70-71, 72, and 73+ were, respectively: 1.13 (CI = 0.99-1.28), 1.15 (CI = 1.02-1.30), 1.29 (CI = 1.12-1.49), and 1.21 (CI = 1.05-1.39), P trend 0.001, adjusted for age, randomized treatment assignments, body mass index (wt/ht2), cigarette smoking, alcohol use, and exercise frequency. For prostate cancer, the corresponding RR values were 1.23 (CI = 1.00-1.51), 1.26 (CI = 1.04-1.54), 1.59 (CI = 1.27-1.98), and 1.26 (CI = 1.00-1.59), P trend 0.005. For colorectal cancer, in some but not all height categories compared with the shortest, there were elevated RRs without a significant linear trend: RR = 1.51 (CI = 1.06-2.14), 1.14 (CI = 0.80-1.62), 1.19 (CI = 0.79-1.80), and 1.53 (CI = 1.04-2.25), P trend 0.23. In contrast, there was no evidence of an association of height with lung cancer. These data indicate a positive association between height and risk of total malignant neoplasms, as well as of prostate cancer and, possibly, colorectal cancer.

Adult↗

PubMed1997

Efficacy of nonpharmacologic interventions in adults with high-normal blood pressure: results from phase 1 of the Trials of Hypertension Prevention. Trials of Hypertension Prevention Collaborative Research Group.

Phase 1 of the Trials of Hypertension Prevention was conducted in 2182 adults, aged 35-54 y, with diastolic blood pressure of 80-89 mm Hg to test the feasibility and blood pressure-lowering effects of seven nonpharmacologic interventions (weight loss, sodium reduction, stress management, and supplementation with calcium, magnesium, potassium, and fish oil). At 6 and 18 mo, weight loss and sodium reduction were well-tolerated and produced significant declines in systolic and diastolic blood pressures (-2.9/-2.4 and -2.1/-1.2 mm Hg for weight loss and sodium reduction, respectively, at 18 mo). None of the other interventions lowered blood pressure significantly at either the 6- or 18-mo follow-up visits. These results suggest that both weight loss and sodium reduction provide an effective means to prevent hypertension. The long-term effects of both of these interventions are being tested in phase 2 of the trial.

Adult↗

PubMed1996

Estimating predictive values for blood pressure measurements from multivariate regression models with covariates.

Predictive values are useful in estimating the probability distribution of a 'true' or underlying measurement, that is, without measurement error or within-person variability. They have been applied to blood pressure data to estimate the true probability that a person is hypertensive currently, or that he/she will become hypertensive based on previous data from childhood. The current work extends these results to situations where covariates are of interest. One can use multivariate regression models to model predictive values for future levels as functions of covariates as well as current measured levels. I compare predictive value estimates obtained from these models to those obtained from ordinary linear regression and from logistic regression with use of data on childhood blood pressure from East Boston, MA. Estimates obtained using the multivariate model are preferable either in terms of bias in the estimates themselves or in terms of their variability. This is particularly true with covariates included in the model. The difference between the multivariate and ordinary regression estimates depends on the conditional reliability of future levels given current blood pressure levels and covariates. I also discuss predictive value estimates for true current level given observed level as well as covariates. These also depend on the reliability of the current measure given values of covariates.

Adult↗

PubMed1996

Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease.

BACKGROUND: Observational studies suggest that people who consume more fruits and vegetables containing beta carotene have somewhat lower risks of cancer and cardiovascular disease, and earlier basic research suggested plausible mechanisms. Because large randomized trials of long duration were necessary to test this hypothesis directly, we conducted a trial of beta carotene supplementation. METHODS: In a randomized, double-blind, placebo-controlled trial of beta carotene (50 mg on alternate days), we enrolled 22,071 male physicians, 40 to 84 years of age, in the United States; 11 percent were current smokers and 39 percent were former smokers at the beginning of the study in 1982. By December 31, 1995, the scheduled end of the study, fewer than 1 percent had been lost to follow-up, and compliance was 78 percent in the group that received beta carotene. RESULTS: Among 11,036 physicians randomly assigned to receive beta carotene and 11,035 assigned to receive placebo, there were virtually no early or late differences in the overall incidence of malignant neoplasms or cardiovascular disease, or in overall mortality. In the beta carotene group, 1273 men had any malignant neoplasm (except nonmelanoma skin cancer), as compared with 1293 in the placebo group (relative risk, 0.98; 95 percent confidence interval, 0.91 to 1.06). There were also no significant differences in the number of cases of lung cancer (82 in the beta carotene group vs. 88 in the placebo group); the number of deaths from cancer (386 vs. 380), deaths from any cause (979 vs. 968), or deaths from cardiovascular disease (338 vs. 313); the number of men with myocardial infarction (468 vs. 489); the number with stroke (367 vs. 382); or the number with any one of the previous three end points (967 vs. 972). Among current and former smokers, there were also no significant early or late differences in any of these end points. CONCLUSIONS: In this trial among healthy men, 12 years of supplementation with beta carotene produced neither benefit nor harm in terms of the incidence of malignant neoplasms, cardiovascular disease, or death from all causes.

Adult↗