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Biomedical subjects

J Benichou

Publications and source records attributed to J Benichou.

At least 55 records · Page 3Linked to original sources

Alcohol and pancreatic cancer in blacks and whites in the United States.

A population-based, case-control study of pancreatic cancer based on direct interviews with 307 white and 179 black incident cases and 1164 white and 945 black population controls was conducted in three areas of the United States to determine the role alcohol drinking plays as a risk factor for pancreatic cancer and to estimate the extent to which it may explain the higher incidence of pancreatic cancer in blacks compared to whites. Our findings indicate that alcohol drinking at the levels typically consumed by the general population of the United States is probably not a risk factor for pancreatic cancer. Our data suggest, however, that heavy alcohol drinking may be related to pancreatic cancer risk. Among men, blacks and white who drank at least 57 drinks/week had odds ratios (ORs) of 2.2 [95% confidence interval (CI) = 0.9-5.6] and 1.4 (95% CI = 0.6-3.2), respectively. Among women, blacks who drank 8 to < 21 drinks/week had an OR of 1.8 (95% CI = 0.8-4.0), and those who drank at least 21 drinks/week had an OR of 2.5 (95% CI = 1.02-5.9), but whites with the same levels of alcohol intake experienced no increased risk. Compared to whites, blacks had significantly higher ORs associated with heavy alcohol drinking (> or = 57 drinks/week) in men (P = 0.04) and with moderate-to-heavy drinking (> or = 8 drinks/week) in women (P = 0.03). Additional research is needed to determine whether heavy alcohol drinking is causally related to pancreatic cancer and whether the risk of alcohol-related pancreatic cancer is greater in blacks than in whites.

Adult↗

Genetic and clinical features of 42 kindreds with resistance to thyroid hormone. The National Institutes of Health Prospective Study.

OBJECTIVE: To determine the genetic and clinical features of resistance to thyroid hormone in a study from a single institution. DESIGN: Prospective, controlled study. SETTING: National Institutes of Health. PATIENTS: 104 patients with resistance to thyroid hormone from 42 kindreds and 114 unaffected relatives sharing the patients' environmental and genetic backgrounds. MEASUREMENTS: Thyroid, cardiovascular, psychometric, hearing, speech, and growth testing; thyroid tests done at baseline and after TSH-releasing hormone stimulation; and DNA analysis for detection of mutations in the thyroid hormone receptor beta (TR beta) gene (exons 9 and 10). Assessment of tissue-specific compensation for resistance. RESULTS: Inheritance was autosomal dominant in 22 families, sporadic in 14 families, and unknown in 6 families. We found mutations in 25 kindreds (64 patients); 16 mutations were in exon 9 and 9 were in exon 10 of the TR beta gene. In persons with resistance to thyroid hormone, we measured the increased incidence of goiter (65%), attention-deficit hyperactivity disorder (60%), IQ less than 85 (38%), speech impediment (35%), and short stature (18%). We also described new clinical features, such as frequent ear, nose, and throat infections (56%); low weight-for-height in children (32%); hearing loss (21%); and cardiac abnormalities (18%). Genotype, age, whether the mother had resistance to thyroid hormone, and sex influenced the phenotype. Tissue resistance varied from kindred to kindred and involved, in decreasing order, the pituitary gland, the brain, the bone, the liver, and the heart. CONCLUSIONS: This study underscores the incidence of classic features of resistance to thyroid hormone, describes new clinical characteristics of this condition for the first time, and stresses the heterogeneity of the phenotype.

Adolescent↗

Attributable risks for stomach cancer in northern Italy.

The proportions of gastric cancer cases attributable (or attributable risks, AR) to consumption of traditional foods (i.e., pasta, rice and maize), low intake of beta-carotene and vitamin C, short duration of use of an electric refrigerator, low educational level, and family history of gastric cancer were computed using data from a case-control study conducted in Northern Italy. Between 1985 and June 1993 a total of 746 incident, histologically confirmed gastric cancer cases and 2,053 controls admitted to the same network of hospitals for acute, nonneoplastic, non-digestive-tract diseases, unrelated to long-term modifications of diet, were interviewed. The ARs were 48% for low intake of beta-carotene, 40% for high consumption of traditional foods, and 16% for low intake of vitamin C. Overall, these 3 dietary factors explained 73% of the gastric cancer cases in the population. Five percent of all cases were attributable to less than 30 years' use of an electric refrigerator, 15% to low educational level, and 5% to family history of gastric cancer. In individuals over age 60, a greater proportion of cases was attributable to traditional foods, low education and late adoption of electric refrigeration (58% vs. 32% aged under 60), suggesting that correlates of lower social class, influenced lifestyle, and dietary habits more markedly in earlier than in more recent generations. According to our estimates, over 3 quarters of the gastric cancer cases in this area are explainable in terms of the risk factors considered. Increased consumption of vitamin C and beta-carotene, and reduced consumption of traditional foods, would help to avoid over 10,000 out of 14,000 stomach-cancer deaths in Italy every year. Consequently, stomach cancer, which is still the third leading cause of cancer death in Italy, would represent only about 2% of all cancer deaths.

Aged↗

Cigarette smoking and alcohol consumption and the risk of pancreatic cancer: a case-control study in Shanghai, China.

Cancer of the pancreas has been rising in incidence in Shanghai, China since the early 1970s. In 1987-89, this malignancy ranked eighth in cancer incidence among men and ninth among women in Shanghai. To examine risk factors for this tumor in urban Shanghai, a population-based case-control study was conducted. Cases (n = 451) were permanent residents of Shanghai, 30 to 74 years of age, newly diagnosed with pancreatic cancer between 1 October 1990 and 30 June 1993. Deceased cases (19 percent) were excluded from the study. Controls (n = 1,552) were selected among Shanghai residents, frequency-matched to cases by gender and age. Cases and controls were interviewed about their demographic background and potential risk factors, including tobacco, alcohol and beverage consumption, diet, and medical history. Adjusted odds ratios (OR) and 95 percent confidence intervals (CI) were estimated using logistic regression models. Current cigarette smoking was associated with excess risk of pancreatic cancer in both men (OR = 1.6, CI = 1.1-2.2) and women (OR = 1.4, CI = 0.9-2.4). ORs increased significantly with number of cigarettes smoked per day, and with duration and pack-years of smoking. Risk increased three- to sixfold among those in the highest categories of cigarette consumption, while risk decreased with increasing years since smoking cessation. Former smokers who stopped smoking for 10 or more years had risks comparable to nonsmokers.

Adult↗

Attributable risk of lung cancer in lifetime nonsmokers and long-term ex-smokers (Missouri, United States).

A population-based, case-control study of incident lung cancer among women in Missouri (United States) who were lifetime nonsmokers and long-term ex-smokers was conducted between 1986 and 1992. The study included 618 lung cancer cases and 1,402 population-based, age matched controls. Information on lung-cancer risk factors was obtained by interviewing cases, next-of-kin of cases (36 percent and 64 percent of the cases, respectively) and controls. Year-long radon measurements also were sought in every dwelling occupied for the previous five to 30 years. Population attributable risks (PAR) for specific risk factors were computed for all subjects, for lifetime nonsmokers, for long-term ex-smokers, by histologic cell type (i.e., adenocarcinoma cf nonadenocarcinoma) and for direct interviews with case (for living cases) and for next-of-kin interviews (for dead cases or cases too ill to complete an interview). The mean age at lung cancer diagnosis was 71 years, and nearly 50 percent of the lung cancers were histologically confirmed adenocarcinomas. Almost 40 percent of all lung cancers among lifetime nonsmokers and almost 50 percent of lung cancers among all subjects could be explained by the risk factors under study. Dietary intake of saturated fat and nonmalignant lung disease were the two leading identified risk factors for lung cancer among the lifetime nonsmokers, followed by environmental tobacco smoke, and occupational exposures to known carcinogens. A small nonsignificant risk was found for study subjects exposed to median domestic radon concentration of 4 pCi/l (25-year time-weight average).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Attributable risks for bladder cancer in northern Italy.

Attributable risks (ARs) for bladder cancer were computed in relationship to cigarette smoking, coffee consumption, low intake of vegetables, history of cystitis, and occupation using data from a case-control study conducted in northern Italy between 1985 and 1993. Cases were 431 patients with histologically confirmed bladder cancer, and controls were 491 patients admitted to the same network of hospitals for acute, nonneoplastic, and non-urinary-tract diseases. Overall, the AR estimates were 49% for cigarette smoking, 23% for coffee consumption, 16% for low intake of vegetables, 12% for history of cystitis, and 4% for occupation. These five factors together explained more than 70% of bladder cancer cases in this population. The AR for cigarette smoking was significantly higher among men (56%) than women (17%), whereas coffee consumption, low vegetable intake, and cystitis were more important (but not significantly so) among women. These results suggest that more than 2500 of the 5400 deaths due to bladder cancer in Italy in 1990 could have been prevented by the elimination of cigarette smoking. With some appropriate dietary modification and intervention to prevent urinary tract infections and occupational exposures, this figure could approach 4000 avoidable deaths. Thus, bladder cancer could become a rare cause of death in this population.

Adult↗

Gastrointestinal tract involvement in polyarteritis nodosa and Churg-Strauss syndrome.

OBJECTIVE: To study the nature and incidence of gastrointestinal (GI) manifestations in polyarteritis nodosa (PAN) and Churg-Strauss syndrome (CSS) and define their therapeutic and prognostic implications. METHODS: Fifty-three patients (29 males, 24 females) affected with PAN or CSS and followed in our institution were included in a retrospective study. Patients were divided into 2 groups: patients without GI manifestations (group A) and patients with GI manifestations (group B). Among patients with GI manifestations we have studied a subgroup with a possibly poorer prognosis in whom the following symptoms were present: GI tract hemorrhage, intestinal perforation, digestive tract surgery due to PAN manifestations, intractable abdominal pain and weight loss greater than 20% of normal weight due to GI tract ischemia. RESULTS: The clinical manifestations were those that are classically encountered in PAN and CSS. Every patient fulfilled the American College of Rheumatology (ACR) criteria for PAN and CSS. Thirty-five patients without GI manifestations were included in group A and 18 patients (34%) with GI manifestations in group B. The mean age of the group at the time of diagnosis was 56.9 +/- 19.1 years (range: 21-71 years) in group A and 47.5 +/- 16.8 years (range: 12-82) in group B. GI manifestations were considered as one of the symptoms revealing PAN in 7 (13.2%) cases. Six of the 18 patients with GI manifestations had definite organ involvement related to vasculitis. Abdominal pain without characteristic organ involvement or surgical emergency was present in 12/18 patients. HBV infection was more frequently observed in group B than in group A. Survival curves showed that at 10 years, 80% of the patients in group A were alive versus 67% in group B (P not significant). For the 9 patients with severe GI manifestations, the survival curves showed that, at 10 years, 44% of them were alive versus 80% in the other group A (p < 0.001). CONCLUSIONS: GI manifestations are frequent in PAN and CSS and were present in 34% of our patients. Prognosis of PAN with GI manifestations is not statistically different than in PAN without GI involvement, except for patients with severe digestive complications.

Adolescent↗

Methods of inference for estimates of absolute risk derived from population-based case-control studies.

The absolute risk is the probability of developing a given disease over a specified time interval given age and risk factors. Gail, et al. (1989, Journal of the National Cancer Institute 81, 1879-1888) obtained point estimates from population-based case control data by combining relative risk estimates from the case control data and composite incidence estimates from the cohort data. They also obtained variance estimates, but they only took into account the variability in estimating relative risks. In this paper, we present variance estimates that take into account all components of variability, namely the variance of relative risk estimates and of baseline incidence estimates, as well as the covariance between the two, the latter term being obtained by using implicit delta method arguments (Benichou and Gail, 1989, The American Statistician 43, 41-44). Simulations demonstrate the validity of such variance estimates as well as of corresponding confidence intervals. These methods are applied to a population-based case control study of breast cancer.

Age Factors↗

Attributable risk: advantages of a broad definition of exposure.

Classification of exposure into two levels--one consisting exclusively of unexposed individuals and the other consisting of exposed and perhaps unexposed ones--yields an unbiased estimate of attributable risk when misclassification is nondifferential. The authors advocate, therefore, the use of a broad definition of exposure when estimating attributable risk. Based on this idea, they justify a simple and robust method for estimating the overall attributable risk from several exposures that is based on a division of subjects into two groups, a baseline consisting of those unexposed to all exposures and everyone else.

Asbestos↗

Risk factors for esophageal cancer in Shanghai, China. I. Role of cigarette smoking and alcohol drinking.

A population-based case-control study of esophageal cancer was conducted in urban Shanghai involving interviews with 902 cases and 1,552 controls. Risk of esophageal cancer was increased among tobacco smokers and alcohol drinkers. Odds ratios (OR) for smoking were 2.1 and 1.6 for men and women, respectively, and increased with number of cigarettes smoked per day, duration of smoking, number of pack-years and decreasing age at start of smoking. For men who were current alcohol drinkers OR was 1.4, with the excess risk primarily among heavy drinkers. Few women drank alcoholic beverages. The combined effect of heavy smoking and drinking among men was pronounced: OR was 12.0 for those who smoked more than 1 pack per day and drank more than 750 g of ethanol per week. The relation with smoking appeared stronger for cancers of the middle and lower thirds of the esophagus than for the upper third, while patterns of risk for squamous cell carcinoma and adenocarcinoma were similar. Heavy drinking affected all 3 subsites, with increased risks mainly limited to squamous cell carcinoma. Cigarette smoking and alcohol drinking combined accounted for almost 50% of all esophageal cancers among men in Shanghai; among women, 14% of cases were attributed to smoking. Our study confirms that smoking and drinking are important risk factors for esophageal cancer in China, thereby paralleling findings from developed countries.

Adenocarcinoma↗

A microcomputer program for the design and analysis of phase II cancer clinical trials with two group sequential methods, the sequential probability ratio test, and the triangular test.

We developed an interactive and menu-driven computer program to help investigators design and analyze phase II cancer clinical trials with a group sequential method, namely the sequential probability ratio test or the triangular test. Based on the values selected for the parameters of the trial, the "Design" option allows one to obtain, using simulations, the statistical properties (type I and II error rates and the probability that the test accepts the hypothesis of inefficacy under 21 different assumptions) and the average sample size (under the same assumptions) of the selected test. The "Analysis" option (i) computes, at each analysis, the two statistics V and Z on which the sequential method is based and plots the sample path from the number of successes observed, and (ii), using asymptotic properties, gives the significance level of the test and a point estimate (with its 95% confidence interval) of the parameter of interest at the last analysis.

Algorithms↗

A comparison of methods for phase II cancer clinical trials: advantages of the triangular test, a group sequential method.

In cancer, the purpose of Phase II studies is to determine whether the response rate p to a new treatment is greater than a prespecified value p0, defined as the largest response rate for which Phase III studies are not worthwhile. It concerns, for example, determining whether the response rate to a new drug is greater than 20%. The main problem is of a decision making nature, and amounts to the comparison of an observed percentage with a theoretical percentage. One way of resolving it is to perform a single statistical analysis after the inclusion of a predetermined number of patients N, but it is not always possible because of high values of N. Furthermore, this approach presents ethical problems when elements in favor of inefficacy or efficacy are available early in the trial. For these reasons, several authors have developed methods which allow to perform repeated analyses and possibly to reach an early conclusion of the study: two-stage, multistage, sequential and group sequential methods. This article considers the main decision making methods proposed in the literature for Phase II studies in oncology. The bibliographic study, which highlights the interest of using group sequential methods, and especially the Triangular Test, is confirmed by a comparative study of the statistical properties of the different methods.

Clinical Trials, Phase II as Topic↗

Malignant mesothelioma: attributable risk of asbestos exposure.

OBJECTIVES: To evaluate a case-control study of malignant mesothelioma through patterns of exposure to asbestos based upon information from telephone interviews with next of kin. METHODS: Potential cases, identified from medical files and death certificates, included all people diagnosed with malignant mesothelioma and registered during 1975-1980 by the Los Angeles County Cancer Surveillance Program, the New York State Cancer Registry (excluding New York City), and 39 large Veterans Administration hospitals. Cases whose diagnosis was confirmed in a special pathology review as definite or probable mesothelioma (n = 208) were included in the analysis. Controls (n = 533) had died of other causes, excluding cancer, respiratory disease, suicide, or violence. Direct exposure to asbestos was determined from responses to three types of questions: specific queries as to any exposure to asbestos; occupational or non-vocational participation in any of nine specific activities thought to entail exposure to asbestos; and analysis of life-time work histories. Indirect exposures were assessed through residential histories and reported contact with family members exposed to asbestos. RESULTS: Among men with pleural mesothelioma the attributable risk (AR) for exposure to asbestos was 88% (95% confidence interval (95% CI) 76-95%). For men, the AR of peritoneal cancer was 58% (95% CI 20-89%). For women (both sites combined), the AR was 23% (95% CI 3-72%). The large differences in AR by sex are compatible with the explanations: a lower background incidence rate in women, lower exposure to asbestos, and greater misclassification among women. CONCLUSIONS: Most of the pleural and peritoneal mesotheliomas in the men studied were attributable to exposure to asbestos. The situation in women was less definitive.

Adult↗

[Estimation by the Hui and Walter method of the sensitivity and specificity of a diagnostic test in the absence of a reference test: results of a simulation study].

Hui and Walter proposed an approach to directly estimate the parameters of diagnostic tests (sensitivity and specificity for dichotomous tests) and the prevalence of the disease in the absence of a reference error-free test, and without imposing any constraint. We performed a simulation study to investigate the finite-sample properties of the proposed estimators for the situation of three tests. We obtained the following results: i) in screening situations (prevalence < or = 0.10), severe bias and poor precision in the parameter estimates occur and this approach should not be used except for studies with a very large sample size (n > or = 2500); ii) in diagnostic situations (prevalence > or = 0.30), the approach is much more reliable and very little or no bias occurs even for small sample sizes (n = 50, 100), except when both the prevalence is very high (p > or = 0.90) and the performances of the tests mediocre (sensitivity and specificity lower than 0.80).

Algorithms↗