Assessment of the role of randomized clinical trials in establishing treatment policies.
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Biomedical subjects
Publications and source records attributed to R Flamant.
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The effect of five days of antibiotic prophylaxis with cefazolin injections (beginning just before surgery) on postoperative infections (beginning just before surgery) on postoperative infectious complications was evaluated in a double-blind, randomised, placebo-controlled trial in nine centres on 2137 patients undergoing hip replacement. Antibiotic prophylaxis reduced the number of hip infections significantly from 3.3% (placebo) to 0.9% (cefazolin). Positive peroperative blood samples and positive bacteriological examination of the drain were risk factors for hip infection but the prognostic value of obesity, diabetes, or previous hip surgery was not confirmed. Development of a urinary infection was not related to hip infection. Hip infections were less common in the four centres with hypersterile operating theatres, and the benefits of prophylactic antibiotics were restricted to patients having hip replacement operations in conventional theatres.
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Systematic investigations testing for the presence of polyps and cancers of the large bowel were conducted in a population of 1,369 inpatients and outpatients, aged 45-70 years, in eight university departments of gastroenterology or abdominal surgery (Toulouse, Dijon, Paris, Marseille, and Strasbourg). Double-contrast barium enema and proctosigmoidoscopy examinations were carried out in all cases, whereas total coloscopy was performed only in the case of detected tumors. A questionnaire including 233 parameters (age, sex, family, and personal history and symptoms) was completed for each patient. A total of 414 lesions were detected in 252 patients, including 245 adenomatous or villous polyps, 8 transformed polyps, and 30 carcinomas; 3 of 4 lesions were located in the rectum or sigmoid. Cancer or adenomatous or villous polyps were found in 13% of the patients. The prevalence of these lesions in the population studied was increased in patients with rectorrhagia (19%) or with a personal history of surgery for colorectal cancer or polyp (23%). In the patients without rectorrhagia or a history of intestinal tumor, the incidence was 9.7%. It was significantly increased in males and patients more than 50 year old. The efficacy of proctosigmoidoscopy and double-contrast barium enema was compared in 909 patients. Sensitivity and specificity were, respectively, 35% and 99% for endoscopy, 96% and 94% for radiology.
Five hundred and twelve children with Wilms' tumor Stages I, II, and III registered to the International Society of Pediatric Oncology (SIOP) nephroblastoma trial were analyzed as to the prognostic value of metastatic lymph node involvement. The lymph nodes of 300 patients were submitted for microscopic examination; malignant invasion was reported in 15%. The disease-free and the actuarial survival rates for patients with metastatic lymph node invasion were significantly worse than for those without metastatic lymph node involvement. Radical lymph node dissection neither improved the cure rate nor decreased the rate of abdominal recurrence in patients with lymph node metastases.
Appreciating the impact, on the progress of our knowledge, of randomized therapeutic trials performed over a period of thirty years leads to a two-fold approach: a) Drawing up the list of randomized trials and assessing the impact of their conclusions on the progress of our knowledge and on the improvement of standard therapy; b) from recognised progress in oncology, appraising the part played by randomized trials in the acquisition of that knowledge.
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The direct method and life-table methods (actuarial and Kaplan-Meier) for estimating survival rates are described here. The difference between direct method and lifetable method is the use of information about the patients who are still alive. Practical examples of calculation are given with recommandations for graphical displays.
The analgesic effect of acupuncture was evaluated by a double-blind controlled trial in 90 patients undergoing gastroscopy. The endoscopy was much easier and better tolerated after real acupuncture had been performed.
Several studies of descriptive and analytic epidemiology have permitted the investigation of cancers linked to the use of tobacco and alcohol. The tobacco and alcohol cancer group consists of the upper respiratory and alimentary tract, lung and bladder, which accounts for 50% of the cancer in men. When both factors are implicated, the proper role of each could be established. These data should be considered in decision-making for cancer prevention.
The existence of dietary risk factors in breast cancer of post-menopausal women is a recent, and yet unproven hypothesis. A French survey made possible by the cooperation of general surgeons and radiotherapists practising in private clinics is currently in progress in a number of metropolitan departments. A preliminary evaluation of the first 654 questionnaires has proved entirely negative. There was no difference between women with breast cancer and a population of age-matched controls with regard to weight, height or the various traditionnal indices of obesity. However, the number of patients studied is too small to allow this hypothesis to be still rejected.
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A statistical analysis of 248 histologically proven cases of Wilms' tumor treated at the Institut Gustave-Roussy, Villejuif, France, from 1952 to 1967, is presented. Two years recurrence-free survival and five years survival have been selected as prognostic criteria. Patients under two years of age have significantly fewer metastases and a better five-year survival rate than those over two. Stage is stronly correlated with recurrences and survival. Influence of tumor size, number of tumor nodules, tumor rupture, adhesions, regional lymph node involvement, and renal vein infiltration is shown. Detailed analysis of histopathologic features indicates that a favorable clinical course is significantly related to the number of different varieties of epithelial differentiation (tubular, glomerular, microcystic) found in any tumor, whatever the abundance of each of them. Presence of striated muscular cells, however abundant, does not influence survival or metastatic rates. Cases where irradiation given prior to surgery resulted in complete destruction of tumor cells, form a distinctive group of very unfavorable prognosis. Relapse of tumor occurs in 54% of cases, 10% presenting with metastases. Involved sites are listed. No correlation is found between date of metastases and other parameters. The three major prognostic factors of age, stage, histologic pattern, bear prognostic value separately. Stage and age are linked, as well as histology and age. Stage and histology are not linked. Age in itself therefore seems less important. It is concluded that these well-defining treatment for each individual case.
The preliminary results of a controlled clinical trial organized by the S.I.O.P. of radiotherapy and chemotherapy in patients with nephroblastoma are presented. Forty-two centers have participated. Between September 1971 and October 1974, 398 patients were registered; 195 were eligible for the trial and were randomized. The remaining 203 patients were excluded from the trial, but were followed in the same way as the patients in the trial. The results were evaluated in terms of recurrence-free survival rate and survival rate. Results in patients who received preoperative and postoperative radiotherapy (group A, 73 patients) were compared with the results in patients who recieved only postoperative radiotherapy (group B, 64 patients). The tumor ruptured at surgery in three patients of group A, and in 20 patients of group B, a difference that is statistically significant. No significant difference in survival and recurrence-free survival between groups A and B is observed at present. Results in patients treated with a single course of actinomycin D (group I, 80 patients) were compared with the results in patients treated with multiple courses (group II, 80 patients). At present, no significant difference is found between the two groups.
Descriptive epidemiology in which population groups are studied can be of considerable value in drawing attention to a potential carcinogen. This must be followed by analytical studies which might either lead with a fair degree of certainty to the identification of the responsible factor or at least help to identify the high-risk group who could then be screened for the suspected cancer. Such epidemiological research must always take into account the results of experimental studies.
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