Investigation of a cluster of anencephaly and spina bifida.

Environmental factors remain undefined as possible causes of spina bifida and anencephaly. The authors noted a fivefold increased incidence for 1979-1980 in the Antioch-Pittsburg , California area, prompting a case-control study. They studied nine case and 27 control mothers as well as eight case and 17 control fathers to evaluate factors including residence, occupation, drug use, illnesses, and pesticide or chemical exposure. Except for fathers' smoking (p less than 0.05), no exposure was associated with neural tube defects.

Screening for possible drug carcinogenicity: second report of findings.

Cancer development was followed up through 1978 in 143,574 outpatients who were identified on the basis of computer-stored drug-dispensing data as users of various medicinal drugs during the 4-year period starting in July 1969. Screening analyses were repeated for the 95 most commonly used drugs and drug groups, which were reported previously after a shorter follow-up, and it was found that several drug-cancer associations had either gained or lost statistical significance since the report. Screening of 120 additional less commonly used drugs revealed one negative and 43 positive drug-cancer associations. A few of these associations suggested interesting new hypotheses about possible drug effects, but further study is required before conclusions on causality can be drawn. The absence of association with cancer for many drugs provides some provisional assurance for the absence of carcinogenicity, but further follow-up is needed to rule out later effects.

Psychological questionnaire score, cigarette smoking, and myocardial infarction: a continuing enigma.

The ability of a group of 94 psychological questions to discriminate between men in whom cigarette smoking was associated with increased risk of myocardial infarction and men in whom smoking was not so associated remains puzzling. Further analyses, controlling for reported alcohol consumption and for a questionnaire item that might reflect physical activity, failed to alter this finding. This interaction of the questionnaire responses with smoking was not found with two other major coronary risk factors, serum cholesterol and systolic blood pressure. Believing that these observations may provide (a) a clue to how cigarette smoking affects risk of myocardial infarction, or (b) some means of identifying greater or lesser susceptibility to the effects of smoking, we invite other investigators to join in the pursuit of this matter. A list of ten selected yes-or-no questions with strong interaction with smoking is provided to assist others in studying this phenomenon; these are similar to ten items on the Minnesota Multiphasic Personality Inventory.

Breast cancer and serum cholesterol.

Recent studies have suggested a role for dietary fat in the etiology of breast cancer. The relation of serum cholesterol and other serum lipid measures to breast cancer incidence was investigated in a cohort of 95, 179 women who had multiphasic health checkups from 1964 through 1972. Through 1977, 1,035 new breast cancer cases occurred in over 752,000 person-years of follow-up. Age-adjusted incidence rates were 1.45, 1.37, 1.31, and 1.40/1,000 person-years from the lowest to the highest quartile of serum cholesterol level, respectively. Similarly, no statistically significant relation was detected between beta-lipoprotein or total lipids and breast cancer. The sample size was sufficiently large to have detected a relative risk of 1.4 or larger with a probability of 99.9% at the 0.05 level of significance. The expected relation od breast cancer to established risk factors was confirmed by univariate analysis, and serum cholesterol and breast cancer were not associated after simultaneous consideration of nine other risk factors by multivariate analysis. These data suggest that the postulated causal relation between dietary fat and breast cancer does not act via an effect on circulating lipid levels.

Initial screening for carcinogenicity of commonly used drugs.

Computer-stored drug-dispensing data for 143,574 outpatients were used to identify users of various medicinal drugs during the 4-year period beginning in July 1969. These patients were followed through 1976 for the development of cancer. This report presents the results of screening analyses for 95 commonly used drugs and drug groups in relation to 56 primary cancer sites and combinations of sites. Statistically significant positive or negative associations with at least one site were found for 53 drugs. Some of these associations were undoubtedly due to chance sampling variation; some confirmed previous reports; some suggested interesting new hypotheses concerning possible drug effects or other etiologic or preventive factors. Further study is required before conclusions as to causality can be reached. Although the duration of follow-up in this study is relatively short so far, the absence of associations for many of the drugs studied provides some provisional assurance of their lack of carcinogenic effects.

Lack of association between cancer incidence and residence near petrochemical industry in the San Francisco Bay area.

Estimated age-adjusted incidence rates for cancer during 1971--77 among Kaiser Foundation Health Plan (KFHP) members living in a portion of the San Francisco Bay area (SFBA) characterized by a heavy concentration of petroleum and chemical industries were compared to estimated rates among KFHP members in the remainder of the SFBA. One hundred fifty-four comparisons were done for 41 selected cancer sites. The number of significant differences did not appear inconsistent with what might be expected by chance alone; furthermore, in most of these instances the so-called exposed area showed the lower rate. These findings provided some assurance that place of residence near petrochemical industries is not associated with increased cancer risk.

On approximate sample sizes for comparing two independent proportions with the use of Yates' correction.

An investigator wishes to compare two independent proportions, based on perhaps unequal sample sizes, by means of the chi squared test with the Yates' correction. A simple approximation is given to the sample size(s) required for the Yates-corrected chi squared test to have specified power; it is then compared with other approximations and with the exact sample size for the equal sample case. In that case the proposed approximation is quite similar to the approximate formula recently put forward by Casagrande, Pike and Smith (1978, Biometrics 34, 483-486).

A simple approximation for calculating sample sizes for comparing independent proportions.

A simple approximation is provided to the formula for the sample sizes needed to detect a difference between two binomial probabilities with specified significance level and power. The formula for equal sample sizes was derived by Casagrande, Pike and Smith (1978, Biometrics 34 , 483-486) and can be easily generalized to the case of unequal sample sizes. It is shown that over fairly wide ranges of parameter values and ratios of sample sizes, the percentage error which results from using the approximation is no greater than 1%. The approximation is especially useful for the inverse problem of estimating power when the sample sizes are given.

A case-control study of relationships of diet and other traits to colorectal cancer in American blacks.

Ninety-nine black colorectal cancer patients and 280 matched controls from hospitals and multiphasic health checkup clinics were interviewed about past dietary habits and other traits. The colon cancer cases tended to report less frequent use of foods with at least 0.5% fiber content than did their controls. This relationship, though small, showed a consistent dose-response gradient, appeared in both case-hospital control and case-multiphasic health checkup control comparisons, and could not be accounted for by the effects of other variables. Colon and rectosigmoid junction cancer patients tended to have eaten foods with at least 5% saturated fat somewhat more often than controls. When consumption of these two groups of foods was considered in combination, significantly more colon cancer patients than controls reported a high saturated fat foods-low fibrous foods eating pattern, as opposed to a low saturated fat foods-high fibrous foods diet. Statistically significant excesses of the following traits were also reported by the colorectal cancer patients: prolonged cigar smoking in men, nulliparity in women, and history of colorectal polyps.

Mortality in middle-aged smokers and nonsmokers.

We assessed the relation of cigarette smoking to mortality in an 11-year follow-up study of 4004 men and women, 35 to 54 years of age, who responded to urging to have multiphasic health checkups. Accounting for 48 other characteristics, both individually and in combination, failed to eliminate the association of smoking with mortality from all causes or with mortality from coronary heart disease. The smoker-to-nonsmoker mortality ratios, crude and adjusted respectively, were 2.6 and 2.1 for all causes and 4.7 and 3.6 for coronary heart disease. This analysis did not support the counterhypothesis that the association of cigarette smoking with mortality is secondary to some underlying characteristic.

An improper use of statistical significance testing in studying covariables.

How badly a covariable confounds the association between a disease and a primary trait depends on the strength of two other associations: between covariable and disease, and between covariable and primary trait. To assess the confounding potential by testing one of these associations for statistical significance, using a 'traditional' critical level, is inadequate. Such a preliminary test places the burden of proof in the wrong direction, ignores a major aspect of confounding potential, and may be inappropriately influenced by other factors. If it must be used at all, the significance level should be 0.25 or 0.50, possibly even higher.

Cigarette smoking habits and urine characteristics: urinalysis abnormalities are more common is smokers, but the reasons are unclear.

Voided urines of 53,000 white and 9,3000 black cigarette smokers and nonsmokers were studied. Proteinuria was found to be commoner in smokers of both races and sexes. Heavy smokers showed proteinuria more frequently than light smokers. Of eight possible explanatory variables, one, alcohol consumption history, showed some interrelationship in that the smoking status-proteinuria association disappeared among heavy drinkers. Stopping smoking was not associated with a relative decline in proteinuria prevalence. Proteinuria associated with smoking did not appear to be indicative of more serious renal disease. There was a smoker-nonsmoker difference in urine glucose response to oral glucose challenge, apparently explained by higher average 1-hour serum glucose values for smokers, of unknown mechanism but partially explained by differences in alcohol usage. Hematuria, bacteriuria, and high urine acidity tended to be more prevalent in smokers, though these relationships were not consistently significant.

Clindamycin and diarrhea.

Of 298 outpatients receiving clindamycin for a variety of indications, diarrhea developed in ten (3.4%); none were diagnosed as having pseudo-membranous colitis. This is well within the range of relative frequencies of diarrhea development (0% to 22.2%) reported in 45 previous studies. Reliance solely on computer-recorded instances of diarrhea yielded a substantial underestimate of diarrhea occurence, but the rate was still significantly higher (P less than .05) in clindamycin users than in nonusers.

Efficiency of case-control studies with multiple controls per case: continuous or dichotomous data.

The statistical efficiency of a study design which matches each case with k controls is compared with that of the standard matched-pairs setup. For the situation in which the distribution of measurements on the factor under investigation is continuous, the comparison criterion used is the reciprocal of the variance ratio of the corresponding case-control difference estimators; for dichotomous observations, the Pitman efficiency of Miettinen's test [1969] or of Pike and Morrow's test [1970] relative to McNemar's test is used. When the variances for continuously distributed case and control measurements are equal to the same result, 2k/(k + 1), is obtained for both situations and, more generally, the efficiency of k1 controls relative to k2 controls is given by k1(k2 + 1)/k2(k1 + 1). The Pitman efficiency is compared with the "practical efficiency" for large-sample dichotomous situations.

Characteristics of heavy users of outpatient prescription drugs.

One hundred fifty-eight users of eight or more different prescription drugs in a three-month period were identified, using computerstored pharmacy data. Compared with 99 "light" users of only one or two different drugs, these heavy users were more likely to be older, female, and white and to have blue collar occupations, if male, or to be housewives, if female. Heavy drug use was associated with greater use of other medical care and was usually a persistent characteristic. Prepayment for drug prescriptions was not associated with heavy use. Among heavy users were found some severely ill individuals, and some with emotional problems that appear to contribute to symptoms and requests for drugs. In a 21-month period, adverse drug reactions were experienced by 28% of heavy users as compared with 8% of light users.