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Biomedical subjects

B I Graubard

Publications and source records attributed to B I Graubard.

At least 19 recordsLinked to original sources

Does beta-carotene explain why reduced cancer risk is associated with vegetable and fruit intake?

Increased intake of vegetables, fruits, and carotenoids and elevated blood levels of beta-carotene are consistently associated with reduced risk of lung cancer in epidemiologic studies. Epidemiologic research also suggests that carotenoids may reduce the risk of other cancers, although the evidence is less extensive and consistent. The simplest explanation is that beta-carotene is protective. However, the possible roles of other carotenoids, other constituents of vegetables and fruits, and associated dietary patterns have not been adequately explored. To evaluate these alternative hypotheses, we are undertaking three lines of research. (a) With dietary data from the 1987 National Health Interview Survey and the 1982-1984 Epidemiologic Follow-up of the first National Health and Nutrition Examination Study, we have determined which food groups and nutrients are highly correlated with vegetable and fruit intake. (b) We have developed and characterized a liquid chromatography method for optimal recovery and resolution of the common carotenoids in blood, specifically lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, and beta-carotene. (c) In a population-based case-control study of lung cancer in white men in New Jersey, we are assessing whether estimates of the intake of the individual carotenoids might produce stronger inverse associations than estimates of provitamin A carotenoids based on current food composition tables.

Carotenoids

Statistical validation of intermediate endpoints for chronic diseases.

We discuss the implementation of a criterion due to Prentice for the statistical validation of intermediate endpoints for chronic disease. The criterion involves examining in a cohort or intervention study whether an exposure or intervention effect, adjusted for the intermediate endpoint, is reduced to zero. For example, to examine whether serum cholesterol level is an intermediate endpoint for coronary heart disease (CHD), we may investigate the effect of the cholesterol lowering drug cholestyramine on CHD incidence adjusted for serum cholesterol levels. We show that use of this criterion will usually demand some form of model selection. When the unadjusted exposure or treatment effect is less than four times its standard error, the analysis can usually lead only to a weak form of validation, a conclusion that the data are not inconsistent with the validation criterion. More significant unadjusted exposure effects offer the potential for stronger types of validation statement such as 'the intermediate endpoint explains at least 50 per cent (or 75 per cent) of the exposure effect'.

Biomarkers

Factors influencing milk insufficiency and its long-term health effects: the Bedouin Infant Feeding Study.

Women who breastfeed have frequently reported milk insufficiency as the reason for introducing the bottle, but no one has addressed its potential long-term health effects. This paper described the factors associated with milk insufficiency versus another reason for introducing the bottle and its potential health effects based on an analysis of a prospective cohort study of 1005 Bedouin Arab women who delivered healthy newborns in 1981 and 1982. By two months postpartum, 72% introduced the infant to the bottle with 72% reporting milk insufficiency as the reason for introducing the bottle. The percentage of milk insufficiency declined with increasing age of the infant. Based on multiple logistic regression analyses, birth season was statistically significantly associated with the odds ratio (OR) of milk insufficiency versus another reason for introducing the bottle during the first two months. Women who delivered in the spring-summer had an increased OR = 1.65 of reported milk insufficiency compared with those who delivered during the rest of the year. Parity was directly related to the OR = 1.04 of milk insufficiency (but just missed significance) during one to two months and was statistically significantly associated with the OR = 1.12 of reported milk insufficiency during 3-18 months. The rates of stunting after the infant was introduced to the bottle and the duration of breastfeeding did not differ by reason for introducing the bottle. Thus the high frequency of reported milk insufficiency was not associated with adverse health effects.

Adolescent

The effect of dietary intake of fruits and vegetables on the odds ratio of lung cancer among Yunnan tin miners.

All newly diagnosed cases of lung cancer (N = 183) among male tin miners of Yunnan Province, China and age-sex matched occupational controls (N = 183 aged 45-79 years) were interviewed within 3 months following cancer diagnosis. The questionnaire included information about usual adult diet as well as employment and smoking histories. Over 95% of cases and controls were current smokers. The 27-item food frequency questionnaire included 11 fruits and vegetables rich in vitamin A and/or carotenoids. The effect of dietary intake of fruits and vegetables on risk of lung cancer was examined with adjustment for exposures to radon, arsenic, and smoking as previously documented risk factors for lung cancer. Tin miners with reduced intake of yellow and light green vegetables had statistically significant increased odds ratios (OR) of lung cancer (OR = 2.26 and OR = 2.39 for the lowest two quartiles of intake; P value for trend = 0.02) among cases compared with controls after multiple logistic regression adjustment for covariates; and this relationship was monotonic. Tin miners with reduced intake of tomatoes had statistically significant increased adjusted OR of lung cancer (OR = 2.64, OR = 3.09, OR = 2.36 for the three lowest quartiles of intake; P value for trend = 0.04). This is the first study to demonstrate a protective effect of vegetable intake versus the strong effects of smoking and occupational exposures on lung cancer risk.

Aged

Barrier contraceptive methods and preeclampsia.

Recent investigations have suggested that women who use barrier methods of contraception may be at increased risk for preeclampsia. We used data from two prospective pregnancy studies to examine the relationship between contraceptive use before conception and preeclampsia. The preeclampsia rates among women using barrier contraceptives were not significantly higher than the rates in women using nonbarrier contraceptives or the rates in women using no contraceptives in either study. The odds ratios for preeclampsia in barrier contraceptive users in the two studies were 0.89 (95% confidence interval [Cl], 0.71 to 1.12) and 0.85 (95% Cl, 0.49 to 1.45) compared with nonbarrier contraceptive users and 0.91 (95% Cl, 0.71 to 1.16) and 0.81 (95% Cl, 0.48 to 1.35) compared with women using no contraceptives. After adjusting for other risk factors, we found no association between preeclampsia and barrier contraceptive use. Additional studies are needed to resolve this issue; however, we would recommend that women not be advised to avoid barrier contraceptives unless more data linking their use to preeclampsia appear.

Adolescent

Anemia and spontaneous preterm birth.

The association between anemia during pregnancy and spontaneous preterm birth was studied with a two-stage case-control design in a large, multiethnic cohort. Results of all hematologic measurements were abstracted from the prenatal and delivery records of 1706 of the 26,901 women in the cohort. Among women delivered of infants at term, mean hematocrit value was low during the early phase of the second trimester, stable until near term, then reached a maximum at 40 weeks' gestation. The mean hematocrit value of black women was consistently lower than that of Asian, Mexican, and white women. Anemia (hematocrit value less than the tenth percentile for ethnic group and duration of pregnancy) at any time during the second trimester was positively associated with subsequent spontaneous preterm birth (odds ratio, 1.9; 95% confidence interval, 1.3 to 2.8). Compared with white women, the odds ratios for preterm birth were 2.0 (95% confidence interval, 1.6 to 2.4) for black, 1.2 (95% confidence interval, 0.9 to 1.6) for Asian, and 1.2 (95% confidence interval, 1.0 to 1.5) for Mexican women. Adjustment for second-trimester anemia had minimal influence on the odds ratios. We conclude that anemia during the second trimester was associated with preterm birth. However, it does not account for the large ethnic differences in preterm birth.

Anemia

Epidemiologic studies utilizing surveys: accounting for the sampling design.

BACKGROUND: Since large-scale health surveys usually have complicated sampling schemes, there is often a question as to whether the sampling design must be considered in the analysis of the data. A recent disagreement concerning the analysis of a body iron stores-cancer association found in the first National Health and Nutrition Examination Survey and its follow-up is used to highlight the issues. METHODS: We explain and illustrate the importance of two aspects of the sampling design: clustering and weighting of observations. The body iron stores-cancer data are reanalyzed by utilizing or ignoring various aspects of the sampling design. Simple formulas are given to describe how using the sampling design of a survey in the analysis will affect the conclusions of that analysis. RESULTS: The different analyses of the body iron stores-cancer data lead to very different conclusions. Application of the simple formulas suggests that utilization of the sample clustering in the analysis is appropriate, but that a standard utilization of the sample weights leads to an uninformative analysis. The recommended analysis incorporates the sampling weights in a nonstandard way and the sample clustering in the standard way. CONCLUSIONS: Which particular aspects of the sampling design to use in the analysis of complex survey data and how to use them depend on certain features of the design. We give some guidelines for when to use the sample clustering and sample weights in the analysis.

Epidemiologic Methods

Intelligence at six years in relation to neonatal bilirubin levels: follow-up of the National Institute of Child Health and Human Development Clinical Trial of Phototherapy.

Results of the National Institute of Child Health and Human Development Randomized Controlled Trial of Phototherapy were examined for the relationship of neonatal bilirubin level to neurological and developmental outcome at 6-year follow-up. This analysis focused on 224 control children with birth weight of less than 2000 g. Bilirubin levels were maintained below previously specified levels by the use of exchange transfusion only (24%). Rates of cerebral palsy were not significantly higher for children with elevated maximum bilirubin level than for those whose level remained low. No association was evident between maximum bilirubin level and IQ (Full Scale, Verbal, or Performance) by simple correlation analysis (r = -.087, P = .2 for Full Scale) or by multiple linear regression adjusting for factors that covary with IQ (beta = -.15, P = .58). IQ was not associated with mean bilirubin level, time and duration of exposure to bilirubin, or measures of bilirubin-albumin binding. Thus, over the range of bilirubin levels permitted in this clinical trial, there was no evidence of bilirubin toxicity to the central nervous system. Measures used to control the level of bilirubin in low birth weight neonates appear to prevent effectively the risk of bilirubin-induced neurotoxicity.

Bilirubin

Risk of neural tube defects in relation to maternal fertility and fertility drug use.

In a case-control study to investigate whether women who use drugs to induce ovulation are at increased risk of conception of a child with a neural tube defect, 571 women who had a fetus or child with a neural tube defect, 546 women who had a fetus or child with other abnormalities, and 573 women who had an apparently normal fetus or child were questioned about infertility, fertility drug use, and related obstetric problems. The rate of maternal fertility drug use around the time of conception was not significantly higher for neural tube defects than for other abnormalities (odds ratio 1.28; 95% confidence interval 0.39, 4.51) or no abnormalities (odds ratio 0.80; 95% Cl 0.27, 2.27). Fertility drug use at any time was not significantly more frequent for neural tube defects than for other abnormalities (odds ratio 1.37; 95% Cl 0.70, 2.74) or no abnormalities (odds ratio 1.05; 95% Cl 0.56, 1.98).

Abnormalities, Drug-Induced

Population-based study of the developmental outcome of children exposed to chloride-deficient infant formula.

In 1978 and 1979 a large number of US children were fed chloride-deficient soy-based infant formula. A representative sample of such children was identified in a southern county through a mailing to the homes of 3639 first- and second-grade children in the public schools. Of the 2329 (64%) who responded, 56 reported use of deficient formula and were invited to have developmental testing by one of four study psychologists at their school. Of the 310 users of other soy formulas, 112 were selected for testing as matched controls on the basis of their sex, feeding history, age, birth weight, and socioeconomic status (as indicated by school attended). After exclusions and refusals, 42 children who used deficient formula and 66 control children were tested using the McCarthy Scales of Children's Abilities. Examiners were unaware of the child's history of formula use. The mean General Cognitive Index was 102.8 in those using deficient formula and 105.4 in controls. After adjustment for demographic differences the children who used chloride-deficient formula were found to average 4.9 points less than the controls (P = .04, 1-tailed). The largest difference was in the Quantitative subscale (P = .005). These data show a statistically significant although small effect of chloride-deficient formula on the long-term developmental outcome of exposed children; however, further study of these results is needed for full confirmation.

Child

Effects of cluster sampling on epidemiologic analysis in population-based case-control studies.

We consider population-based case-control designs in which controls are selected by one of three cluster sampling plans from the entire population at risk. The effects of cluster sampling on classical epidemiologic procedures are investigated, and appropriately modified procedures are developed. In particular, modified procedures for testing the homogeneity of odds ratios across strata, and for estimating and testing a common odds ratio are presented. Simulations that use the data from the 1970 Health Interview Survey as a population suggest that classical procedures may be fairly robust in the presence of cluster sampling. A more extreme example based on a mixed multinomial model clearly demonstrates that the classical Mantel-Haenszel (1959, Journal of the National Cancer Institute 22, 719-748) and Woolf-Haldane tests of no exposure effect may have sizes exceeding nominal levels and confidence intervals with less than nominal coverage under an alternative hypothesis. Classical estimates of odds ratios may also be biased with non-self-weighting cluster samples. The modified procedures we propose remedy these defects.

Biometry

Infant feeding and childhood cancer.

A case-control study was used to assess whether inadequate exposure to the immunological benefits of human milk may affect infants' response to infection and make them more susceptible to childhood malignancies. 201 Denver children with cancer diagnosed at 1.5-15 years of age were compared with 181 controls, who were selected to be similar to cases for age, sex, and area of residence. Infant feeding categories were: breast feeding (BF) greater than 6 months; BF less than or equal to 6 months; and artificial feeding (AF, or exclusive non-human milk feeding). Compared with BF greater than 6 months, a raised risk for total cancers was found in both BF less than or equal to 6 month and AF groups. This increased risk was largely due to an increased incidence of lymphoma (n = 26).

Adolescent

Examining neighbourhood confounding in a survey: an example using the National Health and Nutrition Examination Survey II.

This paper demonstrates a methodology for examining whether neighbourhood stratification lessens the confounding bias of some specific risk-factor/disease associations in analysis of the National Health and Nutrition Examination Survey II (NHANES II). The fortuitous clustering of the sample design of NHANES allows us to estimate risk-factor/disease associations with and without controlling for neighbourhood effects on the same population. We briefly discuss the implications of this methodology for neighbourhood matching in case-control studies.

Adolescent

Neuropsychological performance and treatment outcome in male alcoholics.

Commonly used neuropsychological tests were administered to 91 detoxified alcoholics at the beginning of treatment. Statistically significant relationships were observed between test scores and post-treatment consumption determined 8 months after completing treatment for 72 patients. The results varied depending upon the particular measure of posttreatment consumption evaluated and the type of statistical analysis used. The most consistent relationships were often counter to the notion that increased neuropsychological performance is correlated with a more favorable treatment outcome. Neuropsychological evaluation is of limited clinical utility in predicting posttreatment alcohol consumption.

Adult

Developmental outcome in children exposed to chloride-deficient formula.

The developmental outcome of 2- and 4-year-old children who had been exposed as infants to chloride-deficient formula was studied. A negative dose-response relationship was demonstrated between use of the formula without additional nutritional supplementation and cognitive outcome as measured by the Bayley Scales of Infant Development (Pearson r = -.55, P = .01) at 2 years of age. A similar negative relationship was demonstrated between this exclusive use of the defective formula and perceptual (Pearson r = -.51, P less than .05), motor (Pearson r = -.52, P less than .05), and fine motor (Pearson r = -.75, P less than .002) ability as measured by the McCarthy Scales of Children's Abilities at 4 years of age. When other know predictors of developmental outcome were taken into account by means of multiple linear regression analyses, exclusive formula use emerged as an important predictor of the children's cognitive functioning at 2 years (model R2 = .59, P less than .005) and of quantitative (model R2 = .58, P less than .006), perceptual (model R2 = .63, P less than .009), and fine motor ability (model R2 = .74, P less than .003) at 4 years of age. These data raise concern about the developmental outcome of the children exposed to chloride-deficient formula.

Child, Preschool

Choice of column scores for testing independence in ordered 2 X K contingency tables.

The numerous statistical methods for testing no association between a binary response (rows) and K ordered categories (columns) group naturally into two classes: those that require preassigned numerical column scores and those that do not. An example of the former would be a logistic regression analysis, and of the latter would be a Wilcoxon rank-sum test. In this paper we demonstrate that the perceived advantage of not preassigning scores is illusory. We do this by presenting an example from our consulting experience in which the midrank scores used by the rank tests that do not require preassigned scores are clearly inappropriate. Our recommendations are to assign reasonable column scores whenever possible, and to consider equally spaced scores when the choice is not apparent. Midranks as scores should always be examined for their appropriateness before a rank test is applied.

Abnormalities, Drug-Induced