Multiple chemical sensitivity: discriminant validity of case definitions.

In this study, the authors used the University of Toronto's Health Survey self-administered questionnaire to determine discriminant validity of multiple chemical sensitivity definitions. The authors distributed a total of 4,126 questionnaires to adults who attended general, allergy, occupational, and environmental health practices. The authors then matched responses to features selected from existing case definitions posited by Thomson et al.; the National Research Council; Cullen; Ashford and Miller; Randolph; Nethercott et al.; and the 1999 Consensus (references 4-7, 2, 9, and 10, respectively, herein). The overall response rate was 61.7%. The prevalence of reported symptoms was lowest in general practices, was intermediate in occupational health and allergy practices, and was highest in environmental health practices. Features from the definitions presented by Nethercott et al. and the 1999 Consensus (references 9 and 10, respectively, herein) correctly identified more than 80% of environmental health practice patients and more than 70% of general practice patients. Combinations of 4 symptoms (i.e., having a stronger sense of smell than others, feeling dull/groggy, feeling "spacey," and having difficulty concentrating) also discriminated successfully. In summary, features from 2 of 7 case definitions assessed by the University of Toronto Health Survey achieved good discrimination and identified patients with an increased likelihood of multiple chemical sensitivity.

Reproducibility of the University of Toronto self-administered questionnaire used to assess environmental sensitivity.

Environmental sensitivity patients report symptoms provoked by low-level exposure to a wide range of substances. Features of published case definitions include nature of onset, chronicity, symptom provocation by multiple substances, symptom provocation by an escalating number of exposures, involvement of multiple body systems including the nervous system, provocation by unrelated substances, and addictive behaviors. This study assessed the reproducibility of a Canadian self-administered questionnaire, the University of Toronto Health Survey, designed to determine the prevalence of the features described in these case definitions. A total of 191 eligible respondents aged 16-70 years who attended several types of medical practices in 1994 were invited to complete a second questionnaire 5-7 months after the first; 134 (70.2%) complied. Total agreement on whether patients satisfied each of seven case definitions ranged from 80% to 90%. After adjustment for chance, major agreement was observed for three of the seven case definitions (kappa = 0.69, 0.68, and 0.78). The survey achieved good reproducibility regarding self-report of symptoms described in published case definitions of environmental sensitivity.

A randomized trial of a low fat high fibre diet in the recurrence of colorectal polyps. Toronto Polyp Prevention Group.

After polypectomy for adenomatous colorectal polyps, 201 persons were randomized to receive counselling on a diet low in fat (the lesser of 50 g/day or 20% of energy) and high in fibre (50 g/day) (LFHF), or to follow a normal western diet (ND), high in fat and low in fibre. After 12 months of counselling, fat consumption was about 25% of energy in the LFHF group and 33% in the ND group; fibre consumption was 35 g and 16 g respectively. After an average of two years of follow-up, an intention to treat analysis led to a ratio of cumulative incidence rates of 1.2 (95% CL 0.6-2.2) for recurrence of neoplastic polyps, a finding which suggests no significant difference between dietary groups over the period of observation. An exploratory analysis conducted among 142 persons with substantial diet counselling indicated a reduced risk of neoplastic polyp recurrence in women (RR = 0.5), associated with reduced concentrations of faecal bile acids while on the LFHF diet, but indicated an increased risk of recurrence in men (RR = 2.1), associated with increased faecal bile acids. Although a larger study would be needed to rule out the role of chance, these findings of gender-specific associations between diet counselling and both faecal bile acid concentrations and recurrence of colorectal neoplasia are consistent with recently published evidence of differences between genders.

Implications of measurement error in exposure for the sample sizes of case-control studies.

In this paper, recent results describing the effects of measurement error on estimation of the association between an exposure and a disease are applied to sample size calculation in case-control studies. Models of the relation between true exposure and a surrogate exposure measure assessed with error are used to derive equations for sample size determination. The results show that the sample size of a study based on an exposure variable which is measured with error must be larger by a factor of 1/rho 2 than if exposure were measured without error, where rho is the correlation between the true exposure and the surrogate exposure measure. Review of the magnitude of measurement error in dietary assessments suggests that failure to account for measurement error in sample size determination for case-control studies of diet and disease could lead to marked underestimation of the required sample size.

Comparisons of diet and biochemical characteristics of stool and urine between Chinese populations with low and high colorectal cancer rates.

In an investigation of the roles of diet and stool biochemistry in human colorectal carcinogenesis, 24-hour food, urine, and stool samples were collected from randomly selected participants from two populations with a fourfold difference in colorectal cancer risk: Chinese in Sha Giao, People's Republic of China (low risk), and Chinese-Americans of similar ages in San Francisco County, Calif, in the United States (high risk). The findings supported the hypotheses that colorectal cancer risk is increased by the consumption of high-fat, high-protein, and low-carbohydrate diets and is associated with high levels of cholesterol in stool as well as increased daily outputs of 3-methyl-histidine and malonaldehyde in urine. However, risk does not increase with low stool bulk and low total stool fibers.

Validity and reproducibility of a screening examination for neurological abnormality in persons exposed to methylmercury.

The validity and reliability of methods of screening for neurologic abnormality were assessed as part of an investigation of an outbreak of methylmercury exposure in two northern Canadian communities. Four hundred and forty-five Cree Indians were examined by one of five neurologists in a complete neurologic examination and by a trained paramedical observer in a short screening examination which included a selection of tests from the complete examination. The screening examinations were recorded on videotape and those for 176 men were reviewed by the five neurologists and the paramedical observer 1 year after the field studies. The prevalence of abnormality assessed in the field screening examination was greater than that assessed during the complete neurologic examination, for neurologic features included in both examinations. However, agreement between examinations in identifying individuals with abnormality was poor with the sensitivity of the screening examination falling under 50% for half of the neurologic features examined. In contrast, specificity was over 80% for 14 of 18 features. Review of the videotapes revealed marked interobserver variation in the assessment of the prevalence of neurologic abnormality and poor agreement with the neurologic examinations in the identification of abnormality in individuals, with kappa less than 0.2 for most neurologic features. The levels of agreement between the neurologic examinations and the screening examinations conducted in the field and by videotape review suggest that neither screening examination provides equivalent information in the identification of the presence of abnormality to that obtained in the neurologic examination.

Fiber intake in different populations and colon cancer risk.

It has been suggested that consumption of fiber may reduce the risk for colon cancer. A negative association has been reported between national rates of mortality from colon cancer and estimates of dietary fiber from cereals, based on the fiber content of foods available in the national diets. Total dietary fiber consumption estimated from dietary surveys also was negatively associated with bowel cancer rates in a comparison of four regions of Denmark and Finland, and nonstarch polysaccharides were negatively associated with regional cancer rates in Britain. However, no association with estimates of fiber consumption has been observed in three case-control studies, and one case-control study reported a positive association between fiber intake and colorectal cancer among women. Other epidemiological investigations have examined the relationship between bowel cancer and use of cereals, fruit, and vegetables, foods that contain fiber as well as other nutrients but have failed to produce consistent results among investigations employing different study designs. The National Academy of Sciences found in 1982 that there was "no conclusive evidence to indicate that dietary fiber exerts a protective effect against colorectal cancer in humans," and the present data still do not satisfy the epidemiological criteria required to establish beyond doubt a protective effect of fiber. Nevertheless, dietary guidelines, such as those from the National Academy of Sciences, which recommend reduced fat consumption and increased consumption of cereals, fruit, and vegetables represent the current state of knowledge and form the basis of a diet that is unlikely to do harm and may have the potential for reducing cancer rates in North America.

Assessment of past diet in epidemiologic studies.

The reproducibility of recall of diet was examined for 44 men in Toronto, Ontario, Canada, by comparing estimates of consumption obtained from a dietary questionnaire in 1982 with estimates of consumption made by recalling the original diet at an interview conducted one year later in 1983. Estimates of average consumption obtained by recall were significantly lower than those originally reported for most foods and nutrients, but the magnitude of the differences was never greater than 20% of the original estimate. Correlations between individuals' levels of consumption were greater than 0.7 for nine of the 13 foods and nutrients studied. Current diet, assessed from two-day food records, was also associated with consumption originally reported for some nutrients. Fecal levels of hemicellulose were associated with fiber consumption originally reported and with current fiber consumption, and urine levels of 3-methylhistidine were associated with past meat consumption. The best prediction of past consumption of fiber and fat, however, was obtained from the recalled diet. No significant additional contribution to the prediction was made from estimates of current consumption or from biochemical measures.

Estrogen receptor status of breast cancer in Ontario.

Data from a number of studies of breast cancer have suggested that after the ages associated with the menopause the rates of estrogen-receptor-positive tumours increase with age, whereas the rates of estrogen-receptor-negative tumours do not. Previous investigators studied cases in specific treatment centres, so there was a possibility that the findings were influenced by differences in patterns of case referral by age. A review of all the cases of breast cancer diagnosed in Ontario women in 1981 and assayed for estrogen receptors, however, confirmed the earlier findings. The results showed that the incidence of estrogen-receptor-positive and estrogen-receptor-negative tumours increased at about the same rate before age 45, but thereafter an increase in incidence was seen only for estrogen-receptor-positive tumours. These differences in patterns of incidence suggest the possibility that the two types of tumour may have different etiologic factors.

Cervical dysplasia: association with sexual behavior, smoking, and oral contraceptive use?

Information on possible risk factors of cervical dysplasia, including indices of sexual behavior, smoking habits, and the use of oral contraceptives was obtained from a case-control study in Ontario in which 250 cases of histologically proved cervical dysplasia and 500 age-matched neighborhood controls were interviewed. Initial analysis showed an increased risk associated with more than one sexual partner, an early age at first intercourse, current smoking, the use and duration of use of oral contraceptives, and education. However, the increased risk of use and duration of use of oral contraceptives and education was reduced after adjustment for indices of sexual behavior and smoking. This finding does not confirm previously reported large adverse effects of pill use. The relationship between smoking and cervical dysplasia might be explained by some agent in cigarette smoke which depresses the immune mechanism, thus permitting a sexually transmitted agent to result in abnormal cellular development that leads to the onset of cervical dysplasia.

PIP: Information on possible risk factors of cervical dysplasia, including indices of sexual behavior, smoking habits, and use of oral contraceptives (OCs) was obtained from a case-control study in Ontario in which 250 cases of histologically proven cervical dysplasia and 500 age-matched neighborhood controls were interviewed. Initial analysis showed an increased risk associated with more than 1 sexual partner, an early age at 1st intercourse, current smoking, use and duration of use of OCs, and education. However, the increased risk of use and duration of use of OCs and education ws reduced after adjustment for indices of sexual behavior and smoking. This finding does not confirm previously reported large adverse effects of pill use. The relationship between smoking and cervical dysplasia might be explained by some agent in cigarette smoke which depresses the immune mechanism, thus permitting a sexually transmitted agent to result in abnormal cellular development that leads to the onset of cervical dysplasia.

Sample size determination in case-control studies: the influence of the distribution of exposure.

In the design of case-control studies, the determination of the required number of cases and controls is based on consideration of the strength of the relationship between the disease and exposure to the putative cause, the variability in exposure within the population under study, and the desired size and power of the statistical test. This paper derives sample size equations for studies with a continuous exposure which allow the investigator to specify the strength of the relationship between disease and exposure in terms of relative risk, etiologic fraction or the slope of an exposure response relationship. With these formulations it becomes apparent that the size of the sample increases with decreasing variability in exposure in the population under study, a finding not apparent in the use of conventional methods of sample size determination for continuous data. The ability of a case-control study to detect a significant association between disease and exposure therefore depends critically on the distribution of exposure which exists in the community to be studied. Implications of these findings for studies of diet and cancer are discussed.

Approaches to understanding the relationship between diet and colon cancer.

Epidemiological research into the etiology of colon cancer has failed to provide consistent evidence on the role of diet. This may have arisen, in part, from two methodological limitations of the studies: the difficulty of obtaining accurate measurements of diet and the lack of variability in diet among the subjects studied. In case-control studies, diet measurement might be improved if current rather than past diet could be studied and this might be appropriate if studies were based on patients with precursor lesions rather than cancer. Precursor lesions might also serve as endpoints for randomized trials of dietary interventions. In both types of studies, laboratory measurements of specific dietary variables should be used to supplement diet questionnaires. Further, controls should not be selected from patients with diet-related diseases and studies should be conducted in communities with sufficient dietary variability to ensure the presence of an appropriate gradient in risk.

Estimation of per capita crude and dietary fiber supply in 38 countries.

Per capita availability of crude and dietary fiber was estimated from 1972-74 FAO Food Disappearance Tables and factors derived from data on the fiber composition of foods. Total dietary and crude fiber, as well as dietary fiber from total cereals, wheat, rice, maize, other cereals, roots and tubers, pulses, vegetables, and fruits, was calculated for 38 countries. Total dietary fiber correlated highly with total crude fiber (r = 0.92). Cereals were the major source of fiber for most countries. With a few exceptions the estimated total dietary fiber and dietary fiber from cereals appear to be in reasonable agreement with other values obtained by a variety of methods for a number of developed countries. The reasons for some of the discrepancies found and the need for additional, more precise information on dietary fiber intake are discussed.

Dietary factors in colon cancer: international relationships.

The relationship between dietary factors and mortality from colon cancer was explored by an analysis of the correlation between age-adjusted colon cancer death rates for men in 38 countries and estimates of the availability of a number of dietary components. Cereals were the only source of fiber found to be negatively associated with colon cancer mortality after adjustment for the availability of total or animal fats, or total or red meats, foods that were themselves positively associated with mortality. The estimate of dietary fiber from cereals was more closely associated with mortality than that of crude fiber. The previously postulated protective effects of vitamins C and A and of cruciferous vegetables were not supported by the international data; we found no evidence of a negative association between colon cancer mortality and availability of these dietary factors. The positive association previously reported between colon cancer and beer consumption disappeared following adjustment for animal fat.

Factors associated with outcome of renal transplantation.

To explore the associations between a number of preoperative risk factors and the failure of renal grafts 99 consecutive patients were followed for up to 7 years after transplantation. The patients had all received their grafts from nonliving donors; the operations were performed at one hospital. Statistical analysis in relation to several outcomes showed that rapidly progressive glomerulonephritis, pre-existing cardiovascular disease, the degree of presensitization to histocompatibility antigens and the donor's being of blood group B were associated with an increased risk of graft rejection or death after transplantation. The risks of acute and accelerated rejection were associated with different factors, which suggests that distinct pathogenetic processes may be involved. The risk of technical failure was associated with immunologic factors, which suggests the possibility that this outcome was not caused by surgical difficulties alone.

Methyl mercury exposure in northern Quebec. I. Neurologic findings in adults.

Cree Indians of northern Quebec were exposed to methyl mercury through contamination of local fish. The relationship between measures of exposure and neurologic abnormalities was studied in two communities in 1978 by comparing the exposure of 41 "cases" with selected neurologic abnormalities with that of 179 normal "controls." In the community of Mistassini, a significant positive association was found between neurologic abnormalities and methyl mercury exposure; in Great Whale, the association, although also positive, was not statistically significant. However, although allowance was made for confounding variables, it remains possible that the effects are not entirely attributable to methyl mercury. Further, the data do not permit estimation of a threshold level of exposure above which excess neurologic abnormalities might occur, because recent levels of exposure do not reflect those of the past. Whether the abnormalities observed in this study will remain stable, regress, or progress can only be determined by continued surveillance.

Methyl mercury exposure in northern Quebec. II. Neurologic findings in children.

The relationship between prenatal exposure to methyl mercury and neurologic and developmental abnormalities was ascertained among 234 Cree Indian children aged 12 to 30 months from four northern Quebec communities. A pediatric neurologist, "blinded" to the children's level of exposure, assessed neurologic, physical, mental, and psychosocial development. Methyl mercury exposure was estimated from maternal hair segments representing the period of pregnancy. Abnormality of the tendon reflexes, observed in 13 boys (11 per cent) and in 14 girls (12 per cent), was positively associated with methyl mercury exposure only in boys and there was no consistent dose-response relationship. Other neurologic disorders were less prevalent and none was positively associated with exposure; indeed, incoordination was negatively associated with exposure in girls. The mild, isolated neurologic abnormalities found after prenatal exposure to methyl mercury in northern Quebec were different from the effects of prenatal exposure described in other areas, and their clinical importance can be determined only by continued medical surveillance.