Colon cancer in Argentina. II: Risk from fibre, fat and nutrients.

A case-control study has been conducted to investigate the relationship between total energy intake, fibre and nutrients and colon cancer in Argentina. Cases are 110 newly diagnosed patients from 10 hospitals between 1985 and 1986. Two neighbourhood controls per case were matched on age, sex and place of residence. The intake of calories, fibre and nutrients was estimated from the information collected on food consumption during the 5-year period up to 6 months prior to interview of subjects, based on a pilot study and standard portion sizes in Argentina. In conditional regression models, dietary fibre is highly protective (odds ratio (OR) = 0.07 per 19.02 g/day; 95% confidence interval (CI): 0.02 to 0.25) and total energy intake increases risk (RR = 1.82 per 1000 kcal/day; 95% CI: 1.20 to 2.77), each with adjustment for the other. Analysis of caloric components (fat, protein and carbohydrates) reveals that carbohydrates are the most important factor driving the total energy effect. Other nutrients make little apparent contribution to risk.

Colon cancer in Argentina. I: Risk from intake of dietary items.

A case-control study has been conducted to investigate the relationship between dietary components and risk of colon cancer in the La Plata area of Argentina. Cases are 110 patients newly diagnosed with colon cancer in 10 major hospitals between 1985 and 1986. Two neighbourhood controls per case were individually matched by age, sex and place of residence. Personal interviews elicited information on frequency of consumption of 140 food items during the 5-year period up to 6 months prior to interview. Risk is analyzed by quartiles of individual food items and groups of items. Multivariate conditional logistic regression modelling indicates that consumption of eggs is associated with increased risk for colon cancer (odds ratios by quartile: 1.0, 1.58, 2.02, 4.66), as are some dairy products (ORs of 1.93 for the highest quartile of consumption of cheese). Intake of vegetables, fish and poultry is associated with statistically significant decreasing risk (ORs of 0.075, 0.39 and 0.39, for the highest categories of consumption of vegetables, fish and poultry, respectively). The risk for red meat does not consistently increase as consumption increases. Risks are not altered by the inclusion of potential confounders such as education or body mass index. These findings confirm those of several previous studies and are of particular interest, since the Argentinean diet typically includes a high intake of red meat.

Oral contraceptives and risk of benign proliferative epithelial disorders of the breast.

In a case-control study conducted in Adelaide, South Australia, we investigated the hypothesis that use of oral contraceptives is associated with increased risk of benign proliferative epithelial disorders (BPED) of the breast, conditions strongly associated with increased risk of breast cancer and thought to have pre-malignant potential. The study was restricted to women with no prior history of breast biopsy, and involved 383 cases of biopsy-confirmed BPED, 192 controls whose biopsy did not show epithelial proliferation, and 383 unbiopsied community controls individually matched to cases by age and socio-economic grading of area of residence. When cases were compared with community controls, the adjusted odds ratio (OR) for the association between ever-use of oral contraceptives and risk of BPED was 1.1 (95% CI 0.7 to 1.7), while when cases were compared with biopsy controls, the adjusted OR was 0.9 (95% CI 0.5 to 1.5). There was little variation in risk of BPED with total duration of use of oral contraceptives, and with duration of use before first pregnancy, while current users had a statistically significant 60% reduction in risk, irrespective of the control group used for comparative purposes. Also, there was little variation in risk with years since first and last use of oral contraceptives, and there was no trend in the association between ever-use of oral contraceptives and risk of BPED by degree of cytological atypia.

Incorporating variations in the quality of individual randomized trials into meta-analysis.

Meta-analysis is a method of synthesizing evidence from multiple sources. It has been increasingly applied to combine results from randomized trials of therapeutic strategies. Unfortunately there is often variation in the quality of the trials that are included in meta-analyses, limiting the value of combining the results in an overview. This variation in quality can lead to both bias and reduction in precision of the estimate of the therapy's effectiveness. There are a number of methods for quantifying the quality of trials including the detailed Chalmers system and simple scales. The nature of the relationship between these quality scores and the true estimate of effectiveness is unknown at this time. We discuss four methods of incorporating quality into meta-analysis: threshold score as inclusion/exclusion criterion, use of quality score as a weight in statistical pooling, visual plot of effect size against quality score and sequential combination of trial results based on quality score. The last method permits an examination of the relation between quality and both bias and precision on the pooled estimates. We conclude that while it is possible to incorporate the effect of variation of quality of individual trials into overviews, this issue requires more study.

Cancer mortality in workers exposed to chlorophenoxy herbicides and chlorophenols.

Epidemiological studies have revealed an increased risk of cancer, notably soft-tissue sarcomas and non-Hodgkin's lymphomas, in people occupationally exposed to chlorophenoxy herbicides, including those contaminated by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD). We report here a historical cohort study of mortality in an international register of 18,910 production workers or sprayers from ten countries. Exposure was reconstructed through questionnaires, factory or spraying records, and job histories. Cause-specific national death rates were used as reference. No excess was observed in all-cause mortality, for all neoplasms, for the most common epithelial cancers, or for lymphomas. A statistically non-significant two-fold excess risk, based on 4 observed deaths, was noted for soft-tissue sarcoma with a standardised mortality ratio (SMR) of 196 and 95% confidence interval (Cl) 53-502; this was concentrated as a six-fold statistically significant excess, occurring 10-19 years from first exposure in the cohort as a whole (SMR = 606 [165-1552]) and, for the same time period, as a nine-fold excess among sprayers (SMR = 882 [182-2579]). Risks appeared to be increased for cancers of the testicle, thyroid, other endocrine glands, and nose and nasal cavity, based on small numbers of deaths. The excess of soft-tissue sarcomas among sprayers is compatible with a causal role of chlorophenoxy herbicides but the excess does not seem to be specifically associated with those herbicides probably contaminated by TCDD.

A collaborative study of cancer incidence and mortality among vinyl chloride workers.

A large European multicentric cohort study has been coordinated by the International Agency for Research on Cancer with the objectives of investigating the dose-response relationship between liver cancer and exposure to vinyl chloride and assessing cancer risk for sites other than the liver. A nearly threefold increase in liver cancer was detected on the basis of 24 observed deaths and 8.4 expected (standardized mortality ratio 286, 95% confidence interval 186-425). The excess from liver cancer was clearly related to time since first exposure, duration of employment, and estimated ranked and quantitative exposures. Other cancer sites investigated on the basis of a priori hypotheses were either not in excess (lung) or apparently unrelated to the exposure variables (brain and lymphoma).

Liver cancer in Thailand. I. A case-control study of cholangiocarcinoma.

Potential risk factors for cholangiocarcinoma were investigated in a case-control study among inhabitants of north-east Thailand, which included 103 cases from 3 hospitals, with age- and sex-matched controls. A clear association with past or present infection with Opisthorchis viverrini, as indicated by raised serum antibodies, was found (o.r. 5.0), and at least two-thirds of cases can be attributed to this cause. The results suggest that males may be at higher risk than females. There was no association with hepatitis B infection, with aflatoxin intake as estimated from albumin adducts in serum or with any particular dietary patterns. Alcohol consumption was very low in the population, and the risk associated with regular drinking was non-significant. Regular users of betel nut-predominantly female-had a high risk (o.r. 6.4), a possible mechanism being through their increased exposure to nitrosamines.

Liver cancer in Thailand. II. A case-control study of hepatocellular carcinoma.

Potential risk factors for hepatocellular carcinoma were investigated in a case-control study among inhabitants of north east Thailand. Sixty-five cases from 3 hospitals, with matched controls, were included. Infection with hepatitis-B virus was the major risk factor-chronic carriers of HB surface antigen had an estimated relative risk of 15.2. Infection with hepatitis-C virus appeared to be rare. No increase in risk was found with recent aflatoxin intake, as estimated by consumption of possibly contaminated foods, or by measuring aflatoxin-albumin adducts in serum. Regular use of alcohol (2 or more glasses of spirits per week) was associated with a non-significant elevation in risk (o.r. = 3.4, 95% c.i. 0.8-14.6), but the number of regular drinkers in the population was small. The meaning of an apparent protection conferred by certain food items is uncertain, but a possible role of betel nut in the aetiology deserves further investigation.

Radon exposure, cigarette smoking, and other mining experience in the beaverlodge uranium miners cohort.

A nested case-control study within the Beaverlodge Uranium Miners Cohort was undertaken to assess any possible contribution of confounding by smoking and other mining experience to the risk estimate derived from the original cohort study. Next of kin have been interviewed for 46 lung cancer cases and 95 controls enrolled in the Beaverlodge Uranium Miners Cohort Study who died between 1950 and 1980. Confounding by cigarette smoking and other mining experience appears unlikely to have contributed to the relative risk coefficient for exposure to Rn decay products derived in the parent study. Data for smoking and exposure to Rn decay products are consistent with a multiplicative model, although considerable caution must be applied to this interpretation.

Interaction between human carcinogens.

In the absence of direct information on the carcinogenicity of a complex mixture, assessment of its risk requires not only knowledge of the risks due to the separate components, but also assumptions about the interaction between the components. A formal definition of interaction is given, followed by a discussion of the theoretical basis for different kinds of interactions. Epidemiological studies which have considered the simultaneous effect of two chemical carcinogens are reviewed, and shown to provide examples of additivity, multiplicativity and interaction both intermediate between the two and greater than multiplicative. Finally, implications for the risk assessment of mixtures are discussed.

Visits to physicians before and after exposure to urea formaldehyde foam insulation.

The average number of visits to a physician made by a sample of 351 residents of homes insulated with urea formaldehyde foam insulation in Montreal in the one year period before exposure was 5.25, and in the year following 5.62, an increase of 7 per cent (odds ratio 1.07, 95% CI = 1.00, 1.15). The increase in visits in the post insulation year was limited to subjects who had the product installed in the winter (OR = 1.48, 95% CI = 1.18,1.85), and was not seen for study subjects who insulated their homes during other seasons of the year.

Meta-analysis in clinical research.

Meta-analysis is the process of combining study results that can be used to draw conclusions about therapeutic effectiveness or to plan new studies. We review important design and statistical issues of this process. The design issues include protocol development, objectives, literature search, publication bias, measures of study outcomes, and quality of the data. The statistical issues include consistency (homogeneity) of study outcomes, and techniques for pooling results from several studies. Guidelines are provided to assess the quality of meta-analyses based on our discussion of the design and statistical issues. Limitations and areas for further development of this approach are discussed; researchers should come to a general agreement on how to conduct meta-analysis. As an explicit strategy for summarizing results, meta-analysis may help clinicians and researchers better understand the findings of clinical studies.

Do interns and residents order more tests than attending staff? Results of a house staff strike.

Between October 30 and November 5, 1980, the Professional Association of Interns and Residents of Ontario called a strike of house staff in Ontario's teaching hospitals. The authors obtained data concerning utilization of laboratory tests and radiology procedures during that period and for the same days 2 weeks before and after the strike. During the strike period, the number of tests performed per patient day decreased by only 8.3%. After accounting for proportional changes in emergency and nonemergency admissions, there was no significant change in the number of tests or relative value units performed per patient day as a result of the strike. These results suggest that the volume of tests performed in teaching hospitals is more likely related to the case mix and severity of illness of patients admitted to these institutions than to a pure "teaching effect."

Quality of life of patients on long-term total parenteral nutrition at home.

Quality of life and quality-adjusted survival were measured for a cohort of 73 patients maintained on long-term parenteral nutrition at home (HPN) for periods ranging from six months to 12 years. Quality-adjusted survival was also modeled (although not directly observed) for this cohort under alternative therapeutic strategies (e.g., parenteral nutrition in hospital as needed). Using three utility assessment techniques (category scaling, time-tradeoff, direct questioning of objectives), quality of life was measured through interviews with 37 patients. The quality of life of the patients interviewed was good (mean value 0.73 where 0 represents death and 1.0 represents perfect health); for those who had experienced a period of chronic malnutrition before HPN, quality of life had improved. For the entire cohort, the estimate of quality-adjusted survival was four times greater with HPN than with the alternative therapeutic strategies (p less than 0.001). In comparison with alternative strategies, HPN significantly improves the quality of life of patients unable to sustain themselves with oral alimentation. Quality of life (utility) techniques can be used to evaluate the effectiveness of interventions for patients with chronic diseases.

A cost-utility analysis of the home parenteral nutrition program at Toronto General Hospital: 1970-1982.

We performed an economic evaluation of a home parenteral nutrition (HPN) program by measuring the incremental costs and health outcomes for a cohort of 73 patients treated at our institution from November 1970 to July 1982. Over a 12-year time frame, we estimate that HPN resulted in a net savings in health care cost of $19,232 per patient and an increase in survival, adjusted for quality of life, of 3.3 years, compared with the alternative of treating these patients in hospital with intermittent nutritional support when needed. This result was sensitive to assumptions made about the cost of the alternative treatment strategy. When these assumptions were most unfavorable to the HPN program, we estimated that HPN resulted in incremental costs of $48,180 over 12 years, $14,600 per quality-adjusted life-year gained. We conclude that the cost-utility of HPN compares favorably with other health care programs, when HPN is used to treat patients with gut failure secondary to conditions such as Crohn's disease or acute volvulus. Since only one patient with active malignancy was enrolled in our HPN program, these results should not be extrapolated to patients with active malignancy.