Biomedical subjects
Publications and source records attributed to H Brenner.
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Although many authors have argued against inferring individual-level exposure-disease relations from ecologic data because of the potential "ecological fallacy." the availability of data from diverse populations promotes the continued use of this rapid and inexpensive study design. In ecologic studies, the exposure status of groups is often defined by the proportion of individuals exposed. In these studies, nondifferential exposure misclassification of individuals is shown to produce overestimation of exposure-disease associations that may be extreme when the ecologically derived rate ratios are applied to individuals. This overestimation contrasts with the bias toward the null resulting from nondifferential misclassification of a binary exposure in epidemiologic studies conducted at the individual level. Given the magnitude of the potential bias from nondifferential exposure misclassification and other sources, quantitative estimates of individual-level rate ratios from ecologic data should be interpreted with extreme caution.
Based on a critical review of the literature, we assess the consequences of restrictive smoking policies at the worksite on smoking habits of active smokers. The majority of the fourteen studies reported to date (eleven studies from the United States, one study from Canada, one from Australia and one from the FRG) suggest that restrictive smoking policies might have a major impact on reduction of cigarette smoking and eventual smoking cessation of active smokers. However, most of the studies suffer from serious methodologic limitations, and more stringent scientific investigations should be carried out. Nevertheless, implementation of restrictive smoking policies at the worksite appears to be a reasonable measure of nonsmoker protection, even before definitive evaluation of the impact on smoking behavior of active smokers. Such implementation should take place without discrimination of smokers in the context of comprehensive worksite prevention programs and should be accompanied by thorough scientific evaluation.
Between January 1982 and January 1990, 120 newly diagnosed pediatric patients were treated at The Chaim Sheba Medical Center. Sixty three (52.5%) tumors arose in the posterior fossa and 57 (47.5%) appeared supratentorially. A wide variety of histologic subtypes was seen, each requiring tumor-specific treatment. The modern imaging techniques-CT and MRI-offered better planning of operation, treatment and follow up. All children with highly malignant tumors were treated with combination chemotherapy besides the 'conventional radiotherapy'. Since 1987 the "eight in one day" protocol has been used extensively pre- and post-irradiation. Five-year survival, varied significantly according to tumor type, location and stage. The average delay from presentation of symptoms to diagnosis was 6 months. A multidisciplinary approach has been used in the treatment, rehabilitation and follow-up of these children. In this study, the results of treatment are presented and the role of chemotherapy is discussed.
Three courses of intraperitoneal cisplatin chemotherapy with systemic thiosulfate protection were administered to 31 stage II-IV ovarian carcinoma patients who were clinically in complete remission after completion of postoperative cisplatin-based combination chemotherapy. The 5-year survival rate was 60.4% and the median progression-free interval 35 months. Among 25 patients who underwent second-look laparotomy, the survival and the duration of the progression-free interval were significantly better in those with a pathologically confirmed complete response. Short-term intraperitoneal cisplatin chemotherapy should be considered for consolidation of treatment in ovarian carcinoma patients who are clinically in complete remission.
BACKGROUND: The relationship between prohibition of smoking at the workplace and smoking cessation was assessed in a national sample survey conducted in the Federal Republic of Germany in 1987. METHODS: Four hundred thirty-nine men and women ages 21 to 65, who were actively engaged in the workforce for at least 20 hr per week and were either current or former smokers, were included in the study. RESULTS: Quit ratios were substantially higher among women who worked at worksites designated as smokefree compared with women who were allowed to smoke at their workplace. Among men, there were only minor differences between both types of worksites. After simultaneously controlling for age, marital status, and level of education by multiple logistic regression, the odds ratio of being a current smoker (vs former smoker) was 0.80 (95% confidence interval, 0.44-1.45) for men and 0.22 (95% confidence interval, 0.09-0.50) for women working at places where smoking was prohibited (compared with men and women who were allowed to smoke at the workplace). CONCLUSION: These results suggest that prohibition of smoking at the workplace may help a substantial proportion of smokers, particularly female smokers, to quit. Prohibition of smoking at the workplace might therefore be a particularly cost-effective public health measure.
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Recently, several authors have encouraged the use of dual measurement strategies to correct for bias due to nondifferential misclassification in epidemiologic research. Among these, latent class techniques, which give unbiased results if both measurements are independent conditional on the true value, have become most popular. In practice, however, measurement errors are usually more likely to be positively correlated, and hence reliability studies cannot replace studies of validity. I offer here a quantitative illustration and a comparison of the performance of latent class approaches and other dual response strategies in situations of positive error covariance. I conclude that, except under very special circumstances, dual measurement strategies are likely to remove only part, if any, of the effect attenuation due to nondifferential exposure misclassification. Under certain conditions, it may make sense, however, to estimate a "minimum" effect of the exposure on the basis of the strongest association found in various dual and single measurement strategies.
Estimation of overall linear trend and statistical tests for trend are commonly applied in epidemiologic studies to evaluate the association between ordinal exposure variables and dichotomous health outcomes. In the discussion of these studies, the assertion is commonly made that the observed trends can only be conservative and reported P-values can only be too high owing to the occurrence of exposure misclassification that is supposed to be nondifferential, that is, unrelated to the health outcome of interest. This paper illustrates that this assertion is not generally justified without additional sensitivity analyses. Overestimation of trends and an erroneous reduction of P-values due to nondifferential exposure misclassification are unlikely, but not impossible, for monotonic exposure-disease associations. These may be common occurrences, however, if the observed exposure-disease association is nonmonotonic.
In ecologic studies, covariate levels of groups are often quantified as the prevalence of a dichotomous covariate. We show that, under certain conditions, nondifferential misclassification of such a binary covariate does not reduce the ability to control confounding by the covariate in ecologic studies. Thus, any remaining exposure-disease association in an adjusted ecologic analysis cannot be ascribed to incomplete control for confounding due to nondifferential misclassification of the dichotomy under those conditions, although residual confounding by the underlying covariate may still be present. This point is illustrated by ecologic analyses of the association between population density and mortality from lung cancer in women in 30 administrative districts of the Federal Republic of Germany, in which control for cigarette smoking is required.
STUDY OBJECTIVE: The aims were (1) to monitor and compare incidence rates of cancer from successive birth cohorts in Saarland over the period from 1968 to 1987; (2) to project cancer incidence in Saarland in 1988-2002 in order to provide guidelines for health policy planning. DESIGN: This was an ecological study of overlapping birth cohorts of women and men. SETTING: The study was population based involving the whole state of Saarland. PATIENTS: 80,028 cases of malignant neoplasms (other than non-melanoma skin cancer) diagnosed from 1968 to 1987 and reported to the cancer registry of Saarland were included. MEASUREMENTS AND MAIN RESULTS: Age specific, sex specific, and period specific cancer incidence rates were analysed and extrapolated by multiplicative age-cohort models. Due to a steady rise in birth cohort specific cancer incidence rates in males, a substantial rise in incidence of total cancer is projected, while a moderate decline is expected for females. Analogous analyses are presented for the most common single forms of cancer in women and men. Alternative strategies of analysis, such as age-period-cohort modelling, are discussed. CONCLUSIONS: The age-cohort model is well suited for monitoring incidence of most forms of cancer. The projections provide quantitative guidelines for planning of health care resources and underline and quantify the challenge for primary and secondary cancer prevention in Saarland.
Effective second line chemotherapy schedules for recurrent ovarian carcinoma are not available. The combination of cisplatin and VP-16 given as a single dose in such patients gave inconsistent results. Since VP-16 is a dose-schedule dependent drug it was given in this pilot study as a continuous 72 hour infusion at a dose of 100 mg/m2/day. No objective response was observed among 7 patients with refractory or recurrent ovarian carcinoma who received a median of 3 treatment courses.
This study was carried out by the Regional Office for Europe of the World Health Organization. It contains information obtained by 31 December 1990 from 31 countries under the headings: illegal use of drugs; AIDS among intravenous drug users; HIV seropositivity among drug users; measures to prevent HIV infection among drug users; training programmes for drug workers.
The role of 3-D treatment planning for carcinoma of the nasopharynx was assessed in a four institution study. Two patients were worked up and had an extensive number of CT scans on which target volumes and normal tissues were defined. Treatment planning was then performed using state of the art dose planning systems for these patients to assess the value of the new technology. In general, it was demonstrated that multi-field conformal plans could achieve good tumor dose coverage, while at the same time reducing normal tissue doses, compared to standard treatment planning techniques. The role of inhomogeneity corrections, beam energy, and the use of CT vs. simulation films for defining target volumes were also discussed. In addition, techniques to evaluate 3-D plans for the nasopharynx were considered, and some analysis of this problem is presented in this paper.
The role of three-dimensional (3-D) treatment planning in the definitive treatment of carcinoma of the larynx with radiation was evaluated at four institutions as part of an NCI contract. A total of 30 different treatment approaches were devised for two patients with larynx cancer. CT scans were obtained for both patients and various treatment planning tools were employed to optimize beam arrangements and to evaluate the resulting dose distribution. The effect on dose distribution of a number of factors was also examined: 1) the use of dose calculation algorithms which correct for tissue inhomogeneities, 2) the variation of the CT numbers used for inhomogeneity corrections to simulate inaccuracies in the knowledge of the CT numbers, and 3) the modification of beam energy. A multitude of data was used in plan evaluation and a numerical score was given to each plan to estimate the tumor control probability and the normal tissue complication probability. We found 3-D treatment planning to be of potential value in optimizing treatment plans in larynx cancer. Improved target coverage was achieved when complete information describing 3-D geometry of the anatomy was utilized. In some cases, the treatment planning tools employed, such as the beam's eye view, helped devise novel beam arrangements which were useful alternatives to standard techniques. We found little effect of change in CT number on dose distributions. A comparison between dose distributions calculated with tissue inhomogeneity corrections to those calculated without this correction showed little difference. We did find some improvement in the dose to the primary tumor volume at lower beam energies, but with an increased larynx volume potentially receiving doses above tolerance.
In the human immune system, very late antigen 1 (VLA-1), a putative collagen receptor, is expressed on the surface of T lymphocytes that have undergone mitogenic or antigenic stimulation. A new VLA-1-specific monoclonal antibody, 1B3.1, was used to probe the expression and function of VLA-1 on T lymphocytes in patients with arthritis. Synovial mononuclear cells from the joints of patients with rheumatoid arthritis or other joint diseases contained 32.9 +/- 13.8% 1B3.1-positive cells (42.8 +/- 10.4% in patients with rheumatoid arthritis and 28 +/- 12.6% in non rheumatoid patients). In the peripheral blood, patients with active rheumatoid arthritis expressed VLA-1 on 11.7 +/- 6.0% of their mononuclear cells, compared to 1.9 +/- 1.5% in controls (P less than 0.001). Using dual fluorescence analysis, virtually all the 1B3.1-positive synovial cells were CD3+ T lymphocytes and included both CD4+ and CD8+ T cells. When 1B3.1-expressing synovial mononuclear cells or in vitro activated T lymphocytes were triggered with anti-CD3 antibodies, marked augmentation of their proliferation occurred if they were simultaneously cross-linked with mab 1B3.1. Collagen type IV, a putative ligand of VLA-1, also augmented T-cell proliferation to anti-CD3. The data suggest that the VLA-1 molecule could play an important role in the pathophysiology of arthritis by modulating T-cell activation in these diseases.
In Germany only a few persons take part in cancer screening programs. In order to raise participation rates one needs to ask which subgroups of the population these efforts should focus on. Studies from other countries unanimously show that participation rates decrease with decreasing education and income. Based on this results it was hypothesized that in Germany participation rates also decrease with decreasing education. In a secondary analysis of data from a population survey conducted in Germany in 1987, the hypothesis could be supported only for employed women, whereas for men a non-significant and for not employed women a significant, association was found in the opposite direction.