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Biomedical subjects

J Benichou

Publications and source records attributed to J Benichou.

103 records · Page 6Linked to original sources

An approach to estimating exposure-specific rates of breast cancer from a two-stage case-control study within a cohort.

The Breast Cancer Detection and Demonstration Project (BCDDP) included a large cohort of women followed for incidence of breast cancer and from whom an initial case-control sample was drawn and standard risk factors obtained. In order to study the effect of mammographic features on breast cancer risk, a nested subsample of cases and controls was drawn. Therefore, these data can be viewed as two-stage case-control data within a cohort, or as cohort data with two nested levels of missingness, since basic characteristics like age were measured on all members of the cohort, standard risk factors were elicited only in the initial case-control sample, and mammographic features were assessed only in the nested subsample of cases and controls. We present a Poisson pseudo-likelihood approach to estimating age- and exposure-specific breast cancer incidence rates based on the three types of variables. This approach takes into account the nested missingness as well as two other type of missingness namely, that for basic variables and standard risk factors, some levels (i) were omitted by design in the nested subsample of case and controls or (ii) were empty because of the sparsity of the data in that subsample. Estimates of standard errors are obtained from a parametric bootstrap. The approach seems to be efficient when applied to the BCDDP data and is flexible for modelling breast cancer rates and taking the special missingness features of these data into account.

Adult↗

A simulation study of three sequential methods for the comparison of two treatment groups when the response criterion is censored.

Three recent sequential methods, group sequential analysis (GSA), the sequential probability ratio test (SPRT) and the triangular test (TT) are well suited to randomized clinical trials with a censored response criterion, as they do not require matched pairs of patients. We undertook a simulation study to investigate their statistical properties and to compare these three methods with the fixed-sample design. Our results suggest that the three methods have the expected statistical properties for size and power; they allow an important reduction of the average number of events before stopping, except with GSA when there is no treatment difference; the triangular test (closed design) appears the optimal design, as the variance of the number of events is smaller than with the sequential probability ratio test (open design) and analysis after every twenty new events does not alter the statistical properties of these sequential methods and enhances their usefulness.

Biometry↗

Patient accrual and interim statistical analysis in long-term randomized clinical trials: the French chronic lymphocytic leukemia CLL 80 protocol as a case study.

The CLL 80 clinical trial of treatment for chronic lymphocytic leukemia was designed using a three-stage prognostic classification. Within each stage patients received one of two treatments allocated by randomization, two adjacent stages having a common treatment. The fixed-sample design required 850 patients entered over a period of 8.5 years. Active patient recruitment led to 741 patients being randomized in four years. The first interim analysis, carried out at this point, showed a treatment difference in one stage which was statistically significant (p = 0.001) and justified an early termination of the protocol. This paper discusses practical aspects of patient accrual and interim analysis in this study.

Antineoplastic Combined Chemotherapy Protocols↗

A comparison of three approaches to estimate exposure-specific incidence rates from population-based case-control data.

In population-based case-control studies, an attempt is made to identify all incident cases diagnosed in a specified population during a fixed time interval. Assuming that this goal is met allows one to obtain measures of risk other than relative risks. In this paper, we describe three approaches to estimate exposure-specific incidence rates. Approach 1 relies on estimating crude incidence rates of the disease in strata defined, for instance, by age and geographic area, and combining them with relative risk estimates from the case-control data. In approaches 2 and 3, baseline incidence rates and relative risks are estimated jointly. Approach 2 is based on a pseudo-likelihood, while, in approach 3, the problem is regarded as a missing data problem and a full likelihood is maximized. We applied these three approaches to a study of bladder cancer. Our three sets of estimates of exposure-specific incidence rates were in close agreement, while there appeared to be greater precision with approaches 2 and 3.

Adult↗

Mortality from cancer of the male reproductive tract and environmental exposure to the anti-androgen p,p'-dichlorodiphenyldichloroethylene in the United States.

The association of prostate cancer mortality and testicular cancer mortality with environmental exposure to the anti-androgen dichlorodiphenyltrichloroethane (DDT) derivative p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) in the USA was explored in the period 1971-1994 using multiple linear regression analysis. Environmental p,p'-DDE contamination by state was estimated by p,p'-DDE concentrations in the subcutaneous fat of population samples and by measurements of p,p'-DDE in tree bark. On average, African Americans had adipose p,p'-DDE levels 74% higher than Whites (8.49 vs. 4.88 microg/g; p < 0.001). Neither prostate cancer mortality nor testicular cancer mortality showed a positive association with either indicator of p,p'-DDE environmental contamination. On the contrary, the regression coefficient for prostate cancer was constantly inverse for adipose p,p'-DDE along the period of study, although it approached statistical significance only for African Americans in 1981-1985 (P=-0.755; 0.10 > p > 0.05). This ecologic study does not provide support to the hypothesis of a link between environmental exposure to DDT derivatives and cancer of the male reproductive tract.

Adipose Tissue↗

[Evaluation of the diagnosis of pigmented tumors of the skin and factors leading to a decision to excise. Dermatologists of the Postgraduate Association of Haute-Normandie].

INTRODUCTION: The necessity of excising melanomas characterized by a slight thickness at an early stage, leads dermatologists to remove pigmented lesions which do not correspond to melanomas. The aims of this study were: a) to prospectively assess the accuracy of melanoma diagnosis, b) to quantify the number of excisions performed according to the degree of melanoma suspicion, c) to determine the specific clinical sign or signs of relevant diagnostic value. PATIENTS AND METHODS: This study was conducted prospectively from January 1996 to August 1997 by dermatologists in private practice and dermatologists from a University Hospital staff. When it was decided to excise a pigmented lesion, a form was filled out choosing the most appropriate clinical diagnosis, the degree of melanoma suspicion, and clinical signs which lead to surgery. Based on histological findings as the reference, the sensitivity, specificity, accuracy of melanoma diagnosis and the kappa test that evaluates the concordance between clinical and histological diagnosis, were performed. The diagnostic value of clinical signs was assessed by variance analysis. RESULTS: Of the 353 excised lesions, 38 (10.7 p. 100) were identified as melanoma on histologic examination. The sensitivity, the specificity and diagnostic accuracy were: 79 p. 100, 94 p. 100 and 53 p. 100 respectively. The kappa test concordance between clinical and histological diagnosis was 0.66. Two hundred and two lesions (57 p. 100) were excised even though the clinical suspicion of melanoma was poorly considered. Only one of these 202 lesions was identified histologically as a true melanoma. Thirty seven (24.5 p. 100) of the 151 remaining excised lesions with an "average" or "strong" suspicion were true melanomas. The clinical signs considered, alone or associated, had a poor predictive positive value (< 38 p. 100). An analytical approach performed with a logistic model permitted the identification of two associated signs suggesting a best diagnostic value. DISCUSSION: This is the only study, to our knowledge, reported in the literature which prospectively assesses the sensitivity, specificity and concordance between clinical and histological diagnosis of melanoma. Results were considered from average to good. The originality of this study was to assess the number of pigmented lesions excised according to the degree of melanoma suspicion, suggesting the possibility of reducing the number of nevi removed when the melanoma risk was considered clinically poor. Finally, this study emphasizes the limits of clinical semiology and the need for future diagnostic methods in the assessment of melanoma.

Adult↗

The value of clinical characteristics from a standard questionnaire to discriminate cardiac from neurological syncope in the elderly.

OBJECTIVES: To identify signs and symptoms to differentiate cardiac from neurological syncope in patients over 70 using a standardized questionnaire. DESIGN: Prospective cohort study. SETTING: Five short-stay units in a French university hospital. PARTICIPANTS: One hundred thirty-one in-patients with syncope aged 70 and older. MEASUREMENTS: Patients were interviewed about the signs and symptoms that had been present before, during or after syncope. When possible, a witness who had been present during syncope was also interviewed to compare theirs and the patients' answers. The sensitivity and specificity of 35 questions were calculated among 3 groups defined according to the cause of syncope: cardiac (n = 58), neurological (n = 31) and syncope of unknown origin (n = 42). Statistical analyses were performed to determine discriminating signs and symptoms among the causes and crude agreement was calculated for answers from patients and witnesses. RESULTS: Only 8 and 3 of 35 questions had a sensitivity of at least 0.5 for cardiac and neurological causes respectively. A feeling of impending syncope, thoracic oppression, recall of events preceding syncope and a history of arrhythmia were independently and significantly discriminant among groups. Recall of events preceding syncope (Odds Ratio (OR) = 7.5; 95% confidence interval (CI) = 2.2-25.3) and a personal history of arrhythmia (OR = 4.8; 95% CI = 1.6-14.2) were discriminant between cardiac and neurological causes suggesting mostly a cardiac cause. Agreement between patients and witnesses was only found for questions on the patient's medical history or the circumstances surrounding the onset of syncope. CONCLUSIONS: Recall of events preceding syncope and a history of arrhythmia are strongly suggestive of a cardiac rather than a neurological cause of syncope. Interviews of witnesses are not helpful in suggesting a cause for syncope.

Aged↗

[Use of an isolator (so-called "bubble") in orthopaedic surgery (author's transl)].

The results of 2 series of casualties presenting with femoral neck fractures and operated with Moore prostheses are compared. The first was operated between September 18, 1972 and July 17, 1975 in a conventional way; the other between July 18, 1975 and January 10, 1977 under an Isolator. The rate of infection was much reduced in the latter. It seems to indicate the important function of this apparatus in the prevention of postoperative infection.

Aged↗

An alternative test for trend in exposure-response analysis.

The Mantel-extension chi-square test for overall trend is commonly used in evaluating dose-response relationships in epidemiologic studies. As illustrated by others, it is not an optimal test for a monotonic dose-response. In addition, the result of this test depends heavily upon the scores assigned to the exposure categories. The selection of the score may have a substantial impact on the test statistic and consequently, on the interpretation of the study results. A monotonic dose-response relationship exists when risk increases (or decreases) with increasing exposure. Although the Mantel-extension test is one of the most cited test for trend, it is not a sensitive test to reflect the incremental risk change of a dose-response relationship which may potentially generate misleading results. We propose an alternative test for the evaluation of monotonic dose-response, which reconfigurates the Mantel-Haenszel chi square test for dichotomous exposure series into a polychotomous exposure series. The proposed test generates chi values that are sensitive to incremental increase (or decrease) in risk at each exposure category and does not require exposure scores. The test is a simple summation of Mantel-Haenszel chi statistics obtained in for 2 x 2 tables over adjacent exposure categories (i.e., the sum of Mantel-Haenszel chi values between categories 1 and 2, 2 and 3, 3 and 4 and 1-1 and 1). Several examples are presented to illustrate that the proposed test generates more realistic chi values than those obtained by the Mantel-extension test for trend.

Chi-Square Distribution↗