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C Chastang

Publications and source records attributed to C Chastang.

At least 145 records · Page 8Linked to original sources
PubMed1991

Analysis of phase II clinical trials in haematology and oncology: comparison of the triangular test to the usual methods.

Phase II cancer clinical trials are non-comparative trials which are designed to determine whether the response rate p to the treatment under study is greater than a certain value p0, that is, to test H0, given by p less than or equal to p0 against H1 given by p greater than po. By choosing type I error alpha and the power 1-beta and by specifying H1, that is, by choosing a clinically relevant improvement p1), one can compute the number of patients N to be included for a fixed-sample approach. Various other approaches have been proposed such as multistage methods and Wald's continuous sequential probability ratio test (SPRT). As an alternative approach, we extended the triangular test (TT), proposed by Whitehead for comparative trials, to the situation of non-comparative trials with a binary outcome. We expressed H0 and H1 in terms of the log odds-ratio statistics, namely log [p(1-p0)/p0-(1-p)]. With this choice, the two statistics of interest, Z and V, have simple expressions: Z is the difference between the observed number of positive outcomes and the expected number under H0 and V is the variance of Z under H0. After every group of n patients, Z is plotted against V, and the trial proceeds until a boundary is crossed. In our simulations, type I error alpha and the power 1-beta were close to nominal values with the TT and the average sample size was close to Wald's continuous SPRT and compared favourably with the multistage methods proposed by Herson and Fleming. Given its statistical properties and its easy use, the TT should be considered for planning and analysing cancer phase II trials.

Clinical Trials as Topic↗
PubMed1991

Continuous infusion of high-dose metoclopramide: comparison of pharmacokinetically adjusted and standard doses for the control of cisplatin-induced acute emesis.

Metoclopramide was administered by continuous infusion to two groups each of 14 patients on chemotherapy, randomized to receive either doses adjusted to individual pharmacokinetic parameters or doses adjusted as usual to body weight. The mean plasma concentration at the end of the infusion in the adjusted group was 1.01 mg.l-1, close to that aimed for (1.20 mg.l-1). It was significantly different from that in the other group. v 0.54 mg.l-1. Antiemetic efficacy, defined as less than or equal to 2 emetic events in the 24 h following cisplatin, was similar in both groups (being found in 12/14 (86%) and 10/14 patients (71%), respectively). Analysis of the cumulative percentage of responders according to plasma concentration showed a clear plasma concentration-effect relationship. Routine MCP pharmacokinetic dosage adjustment is not indicated, but this therapeutic approach can be used to optimize antiemetic therapy in poor responder patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Acute carbon monoxide intoxication and hyperbaric oxygen in pregnancy.

Modalities of oxygen therapy for pregnant women intoxicated with carbon monoxide (CO) are ill defined. Hyperbaric oxygen (HBO) is presumed to be hazardous to the pregnancy. On the other hand CO entails anoxic injuries in the mother and fetus. We have entered 44 pregnant women who sustained an acute carbon monoxide poisoning at home, into a prospective study in order to assess HBO tolerance. They were treated within 5.3 +/- 3.7 h (range: 1-12) of the intoxication with a combination of 2 h of HBO at a pressure of 2 atmospheres absolute (ATA) and 4 h of normobaric oxygen, irrespective of the clinical severity of the intoxication and of the age of pregnancy. Six patients were lost to obstetric follow-up. Only 2 patients sustained a spontaneous abortion: 1 within 12 h and 1 within 15 days of the intoxication. Thirty-four women gave birth to normal newborns. Finally 1 elected to undergo abortion for reasons unrelated to the intoxication and 1 gave birth to a baby with Down's syndrome. There is no evidence that HBO was involved with either abortion of our study. We conclude that HBO may be carried out in pregnant women acutely intoxicated with carbon monoxide.

Acute Disease↗
PubMed1991

Anti-Toxoplasma effects of dapsone alone and combined with pyrimethamine.

The efficacy of dapsone alone or combined with pyrimethamine against Toxoplasma gondii was investigated experimentally. For in vitro studies, a sensitive immunoassay was used for assessment of Toxoplasma growth in tissue cultures; dapsone was found to have a significant inhibitory effect at a concentration of 0.5 micrograms/ml in the cultures, and the 50% inhibitory concentration was estimated to be 0.55 micrograms/ml. When pyrimethamine and dapsone were combined, an important synergistic effect which was associated with morphological alterations of the parasites was observed. In vivo studies were performed in a murine model of acute toxoplasmosis in which a tissue culture method was used to estimate the parasite burden in the blood, lungs, and brains of infected mice. Dapsone alone, which was administered at 100 mg/kg/day for 10 days from day 1 after infection, was unable to prevent parasite dissemination and only delayed the time to death of treated mice compared with the time of death of untreated controls. When dapsone and pyrimethamine (18.5 mg/kg/day) were administered in combination from day 4 after infection, parasites were cleared from blood and organs within 6 days, but relapses were observed 15 days after the cessation of therapy. When treatment was started at day 1 after infection, 100% of mice survived and relapses were not observed, suggesting a good efficacy of this combination for preventive therapy.

Animals↗
PubMed1991

Chronic diffuse interstitial lung disease: diagnostic value of chest radiography and high-resolution CT.

The diagnostic value of chest radiography and high-resolution computed tomography (CT) in chronic diffuse interstitial lung disease (CDILD) was assessed in 140 consecutive patients with diffuse infiltration of the lung visible at radiography. Radiographs and CT scans were separately read by three independent observers without knowledge of clinical and pathologic data. The observers listed the three most likely diagnoses and recorded the degree of confidence they had in their choice on a 0%-100% probability scale. Findings at radiography and high-resolution CT were recorded by each observer and were used for a stepwise discriminant analysis between diagnoses. First-choice diagnoses of all three observers that were made with a high level of confidence (probability, greater than or equal to 75%) were more accurate with CT than with radiography (P less than .001). The superiority of high-resolution CT over radiography was most obvious for histiocytosis X and sarcoidosis; in cases of pulmonary fibrosis, CT was not significantly different from radiography. The interobserver agreement for the proposed diagnosis was significantly better with high-resolution CT (P less than .001). Twenty-one of 26 radiographic findings and 21 of 25 CT findings were discriminant. Stepwise discriminant analysis revealed the superiority of CT over radiography, since the ranking of all findings showed that the four most discriminant findings, and eight of the first 12 findings, were revealed with CT.

Adolescent↗
PubMed1991

[Cardiovascular risks induced by estrogens prescribed at low doses. 208 years of observation--137 patients].

The cardiovascular risk induced by oestrogen treatment appears to be minimal when oestrogens are prescribed at low doses (daily dose less than 3 mg/day) and when this drug is not prescribed in patients with a history of cardiovascular disease. The Prostatic Cancer Cooperative Study Group compared the course of 137 patients treated by oestrogens with a French male population matched for age: ten accidents were observed versus nine expected and one death was observed versus 3 expected. By selecting patients, oestrogens can therefore still be part of the range of treatments available for advanced prostatic cancer.

Aged↗
PubMed1991

Selective contraindications based on multivariate analysis for operative cholangiography in biliary lithiasis.

This study was done to select patients with a low risk of common bile duct (CBD) stones in whom operative cholangiography could be avoided. Operative cholangiography was performed upon 511 patients. Two different groups of patients were identified--patients with CBD stones visualized by CBD exploration (n = 90) and patients with no CBD stones at the time of operative cholangiography (n = 421). Multivariate analysis (stepwise logistic regression) showed that five variables were correlated with the presence of CBD stones--size of CBD equal to or greater than 12 millimeters, gallstones equal to or less than 10 millimeters, advanced age, chronic or acute cholecystitis and past history of biliary colic. Using a scoring system, a group of patients with a low risk (less than 2 percent) of CBD stones could be easily determined. In this group of patients, operative cholangiography may be avoided.

Adult↗
PubMed1990

Failure of the perioperative PCV neoadjuvant polychemotherapy in resectable bronchogenic non-small cell carcinoma. Results from a randomized phase II trial.

In 1985, the authors began a phase II study to assess the PCV perioperative polychemotherapy (cisplatin 100 mg/m2, cyclophosphamide 600 mg/m2, vindesine 3 mg/m2) in patients with resectable bronchogenic non-small cell carcinoma. Patients were randomized to receive either two preoperative courses of PCV chemotherapy, surgery, and two postoperative courses of PCV chemotherapy (PCV group) or immediate surgery (surgery group). A staging procedure using the CT scan was performed before randomization and, additionally, before surgery in the PCV group. There were 26 randomized patients, 13 in each group. In the PCV group, 11 patients agreed to receive the two preoperative courses of chemotherapy. A response was observed in five patients (45%), and a progression was observed in four patients (36%) leading to a cancellation of surgery in two of them. Postoperative care was the same for each group. Although no death could be related to chemotherapy, it was decided to stop entering new patients into this trial because of the rate of preoperative progression in the PCV group.

Adult↗
PubMed1990

Application of the triangular test to phase II cancer clinical trials.

Phase II cancer clinical trials are primarily designed to determine whether the response rate p to the treatment under study is greater than a specified value p0, that is to test the null hypothesis H0: p less than or equal to p0 against an alternative hypothesis H1 : p greater than p0 specified by p = p1. As an alternative to the single and multistage procedures and to Wald's continuous sequential probability ratio test (SPRT), we applied the group sequential methods proposed by Jones and Whitehead, namely the triangular test (TT) and the discrete SPRT, to the comparison of p with p0, and we expressed H0 and H1 in terms of the log odds-ratio statistic log [p(1 - p0)/p0(1 - p)]. A stimulation study showed that both the TT and the discrete SPRT had type I error and power close to the nominal values, and they compared favourably with multistage methods in terms of the average sample size.

Clinical Trials as Topic↗
PubMed1990

Effect of the microbial lactase (EC 3.2.1.23) activity in yoghurt on the intestinal absorption of lactose: an in vivo study in lactase-deficient humans.

Breath hydrogen excretion was measured in eight lactase (EC 3.2.1.108)-deficient volunteers ingesting 18 g lactose in the form of milk, yoghurt and heated yoghurt. Total excess hydrogen excretion (area under curve) was significantly lower after yoghurt and heated yoghurt, than after milk: 103 (SE 29), 191 (SE 32), and 439 (SE 69) respectively (P less than 0.001). The oro-caecal transit time of fermentable components from yoghurt and heated yoghurt (mainly lactose) was longer than that from milk: 165 (SE 17), 206 (SE 19), v. 103 (SE 19) min (P less than 0.01). An intestinal perfusion technique was used in the same subjects after ingestion on two consecutive days of 18 g lactose in yoghurt and heated yoghurt. Significantly less lactose was recovered from the terminal ileum after yoghurt than after heated yoghurt meals: 1740 (SE 260) v. 2825 (SE 461) mg (P less than 0.05), and approximately one-fifth of the lactase activity contained in yoghurt reached the terminal ileum. These findings indicate that more than 90% of the lactose in yoghurt is digested in the small intestine of lactase-deficient subjects and suggest that both the lactase activity contained in the viable starter culture and a slow oro-caecal transit time are responsible for this excellent absorption.

Adult↗
PubMed1990

Methodological aspects of a clinical trial in chronic lymphocytic leukemia: necessity to develop new biostatistical methods.

The CLL protocol allowed a better understanding of the natural history of Chronic Lymphocytic Leukemia and an assessment of several treatment strategies. From the point of view of biostatistical research, it raised several important problems. In this paper, we show the interest of applying sequential methods, particularly the triangular test. Other biostatistical problems raised by the CLL 80 protocol are still not, or only partially, resolved. They include taking into account prior belief about treatment benefit in sample size calculations, using surrogate endpoints, developing methods to take into account the causes of death, to analyse repeated measurements, and to assess and compare staging systems.

Biometry↗
PubMed1990

[Microbiological study of male genital ulcers. Apropos of 75 cases].

Between November 1986 and June 1987, the microbial aetiology of genital ulcers was assessed in 75 male patients attending the Sexually Transmitted Disease (STD) clinic in Hôpital Saint-Louis, Paris. Evidence of Haemophilus ducreyi was found in 18 patients (24%), Herpes simplex virus in 19 (25.3%). Syphilis was diagnosed on the basis of dark field microscopy and/or positive serology test in 19 patients (25.3%). Lymphogranuloma venereum was not diagnosed in any patient. Primary pathogens were not identified from the remaining 19 (25.3%) men. Neisseria gonorrhoea was isolated in five patients, from the ulcer in three cases, from the urethra in two. Asymptomatic urethral carriage of Chlamydia trachomatis was culture proven in seven cases. The presence of IgM antibodies to C. trachomatis at a titre greater than 40 found in 17 patients was a indication of a current chlamydial infection. Three patients (4%) were discovered to be HIV-1 positive.

Adolescent↗
PubMed1990

[Lymph node involvement: the only prognostic factor after curative resection of cancer of the stomach. Results of a multivariate analysis].

The aim of this study was to evaluate the independent influence of clinical and pathological variables on survival of patients with gastric carcinoma using the Cox regression proportional hazard model. Of 156 patients operated on for gastric adenocarcinoma, 46 (29.5%) underwent palliative operation, 24 (15.5%) had a palliative resection, and 86 (55%) had a curative resection. The overall 5-year survival rate was 25 +/- 4%. After curative resection, the 5-year survival rate was 44 +/- 6%. Univariate analysis applied to these patients showed that poor survival was related (p less than 0.01) to: age (over 80 years), absence of epigastric pain, vomiting and dysphagia, total gastrectomy, tumor size (more than 4 cm), lymph node involvement (LNI), invasion through the muscularis propria, absence of intestinal metaplasia near the tumor, and linitis plastica. In multivariate analysis, lymph node involvement was found to be the only independent prognostic factor. The 5-year survival rate was 75.5 +/- 8% without LNI, 28 +/- 10% with proximal LNI and 7 +/- 6% with distal LNI. Our results suggest that classification into 3 LNI groups is the best staging system for curative resection in gastric carcinoma.

Adenocarcinoma↗
PubMed1989

Trial of normobaric and hyperbaric oxygen for acute carbon monoxide intoxication.

The value of hyperbaric oxygen in the treatment of acute carbon monoxide intoxication was assessed in 629 adults who had been poisoned at home in the 12 h before admission to hospital. In patients without initial impairment of consciousness (group A) the effect of 6 h of normobaric oxygen (NBO) (group A0, n = 170) was compared with that of 2 h of hyperbaric oxygen (HBO) at 2 atmospheres absolute (ATA) plus 4 h NBO (group A1, n = 173). At the 1 month follow-up 66% of A0 and 68% of A1 patients had recovered. In patients with initial impairment of consciousness the effect of one session of HBO (group B1, n = 145) was compared with that of two sessions (group B2, n = 141); all group B patients also received 4 h of NBO. At 1 month of follow-up 54% group B1 and 52% group B2 patients had recovered. The 7 patients left with neuropsychiatric sequelae (3 B1, 4 B2) and the 4 who died (2 B1, 2 B2) had all presented with coma. HBO was not useful in patients who did not lose consciousness during carbon monoxide intoxication, irrespective of their carboxyhaemoglobin level, nor were two sessions of HBO in patients who sustained only a brief loss of consciousness. The prognosis is poorest for those presenting with coma; the trial needs to be pursued in this group of patients until the power of the study is sufficient to demonstrate the value or otherwise of HBO.

Accidents, Home↗
PubMed1989

Diagnostic and prognostic significance of myelomonocytic cell surface antigens in acute myeloid leukaemia.

Thirty-six cases of acute myeloid leukaemia (AML) were tested with a large battery of monoclonal antibodies (moAbs) detecting surface markers normally expressed by myelomonocytic, T and B lymphoid, megakaryocytic and erythroid lineages. Differences in antigenic expression were observed among the various FAB subgroups: HLA-class II molecules were found in almost all AML cases but not in the promyelocytic subgroup (M3); CD14 and CD36 antigens were detected in monocytic leukaemias (M4 and M5); the CD34 moAb (MY10) recognizing an epitope described on myeloid stem cells was positive in 88% of the M1 and 80% of the M3 cases. By a multivariate analysis, only the CD14b (MY4) discriminated significantly between M1-M2 and M4-M5 subgroups. Using Cox's model to assess the prognostic importance of variables including immunophenotyping on survival, we undertook a one by one analysis and found that the presence of CD17 antigen predicted for a shorter survival (P = 0.03). In addition this marker appeared more significant than other clinical and biological parameters.

Adolescent↗