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Biomedical subjects

M Cucherat

Publications and source records attributed to M Cucherat.

At least 37 records · Page 2Linked to original sources
PubMed2000

Comparison of long versus short duration of anticoagulant therapy after a first episode of venous thromboembolism: a meta-analysis of randomized, controlled trials.

OBJECTIVE: To assess the length of oral anticoagulant therapy (short versus long duration) after a first episode of venous thromboembolism (VTE). DESIGN: Meta-analysis of randomized controlled trials, comparing two durations of anticoagulation, identified in 1999 by a computerized search of the Cochrane Controlled Trial Register, Medline and Embase, completed by an extensive review of the references of pertinent articles. SETTING AND SUBJECTS: The meta-analysis was performed on literature data. Seven published controlled trials were included. Relative risks with 95% confidence intervals were computed using the relative risk logarithm method. Statistical significance was set up at 0.01 for the test of association. MAIN OUTCOME MEASURES: Outcomes are major haemorrhage and recurrence after a 12-month follow-up. RESULTS: For the recurrence end-point (sample size of 2304 patients), a duration treatment of 12-24 weeks seems preferable to a 3-6 week regimen, with a relative risk (RR) of 0.60 (95% CI: 0.45-0.79, P < 0.001). For the major haemorrhage end-point (1823 patients), the RR is not significantly different from 1 (RR = 1.43, 95% CI: 0.51-4.01, P = 0. 5). The results were similar for the subgroup 'permanent risk factors' or 'idiopathic VTE' (RR for recurrence = 0.48, 95% CI: 0. 34-0.68, P < 0.001). The tendency was similar, although not reaching statistical significance, for the 'temporary risk factors' subgroup (RR for recurrence = 0.34, 95% CI: 0.13-0.93, P = 0.035). CONCLUSIONS: After a first episode of VTE, a long-term treatment regimen allows a significant reduction in the incidence of recurrences without increasing the incidence of bleeding events.

Acute Disease↗
PubMed2000

Optimal duration of anticoagulant therapy after an episode of venous thromboembolism.

The optimal duration of oral anticoagulant therapy after a first episode of venous thromboembolism (VTE) is still a matter of debate. It is essential to balance the desired effect of the anticoagulants in reducing recurrences against the risk of major bleeding. The aims of this paper are to describe the current concepts in this field. Recent data, based on randomized controlled trials, suggest that it is necessary to tailor the duration of anticoagulation individually according to the topography of VTE and the presence of risk factors. A 6-week treatment for patients with isolated calf vein thrombosis is sufficient. For proximal thrombosis and/or pulmonary embolism, a short anticoagulant course is sufficient in patients with temporary risk factors (3 months), and a longer anticoagulant course (6 months at least) is recommended for cases with permanent risk factors or idiopathic VTE. For these high-risk of recurrence patients, an assessment of low- or fixed-dose oral anticoagulation is necessary in order to reduce the bleeding risk. It is not possible to precisely determine the optimal duration with the available data. We have already performed a meta-analysis on summary data that suggests a long course of oral anticoagulant therapy is superior to a short course. An individual meta-analytic approach is needed to draw more precise conclusions on an interesting and important clinical topic.

Anticoagulants↗
PubMed2000

Prevention of venous thromboembolism in internal medicine with unfractionated or low-molecular-weight heparins: a meta-analysis of randomised clinical trials.

BACKGROUND: The prevention of venous thromboembolic disease is less studied in medical patients than in surgery. METHODS: We performed a meta-analysis of randomised trials studying prophylactic unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) in internal medicine, excluding acute myocardial infarction or ischaemic stroke. Deep-vein thrombosis (DVT) systematically detected at the end of the treatment period, clinical pulmonary embolism (PE), death and major bleeding were recorded. RESULTS: Seven trials comparing a prophylactic heparin treatment to a control (15,095 patients) were selected. A significant decrease in DVT and in clinical PE were observed with heparins as compared to control (risk reductions = 56% and 58% respectively, p <0.001 in both cases), without significant difference in the incidence of major bleedings or deaths. Nine trials comparing LMWH to UFH (4,669 patients) were also included. No significant effect was observed on either DVT, clinical PE or mortality. However LMWH reduced by 52% the risk of major haemorrhage (p = 0.049). CONCLUSIONS: This meta-analysis, based on the pooling of data available for several heparins, shows that heparins are beneficial in the prevention of venous thromboembolism in internal medicine.

Anticoagulants↗
PubMed1999

Identification of responders to a therapy: an example of validation of a predictive model.

The general objective of randomized clinical trials is to assess if the treatment effect on a given population is clinically meaningful. In this way, one obtains an average estimate of the treatment effect over the trial population. However, a growing need for medical practitioners is to be able to predict with sufficient precision the efficiency of a given treatment for a given patient. There is little information in the literature about this issue. We have previously proposed a treatment-startified Cox model including interaction between treatment and patient's covariates, to identify and predict the responders to a therapy. In this paper, we focus on the assessment of the predictive power of the model. The performance of the predictive model for a population and for an individual was statistically validated internally and externally from several aspects. The prediction correlates well with the observation. Thus, we suggest that this approach would be useful in identifying and predicting the responders to a therapy, subject to an appropriate and more extensive validation process in real setting.

Female↗
PubMed1999

Implication of evidence-based medicine in prescription guidelines taught to French medical students: current status in the cardiovascular field.

OBJECTIVES: To study how satisfactory the contents of introductory courses in cardiovascular therapeutics, given to medical students in France, are with respect to the concepts of evidence-based medicine. METHODS: Medical school lecturers were asked to provide written course material used as part of medical school courses. Best-available evidence was classified as existent (including two therapeutic subclasses: indicated and contraindicated), and nonexistent. Four scores (from 0 to 10) were given, according to conformity with best-available evidence, and citation of randomized clinical trials (RCT), meta-analyses and therapeutic objectives. RESULTS: Thirty-four written documents were obtained from 43 faculties. Although the score (mean +/- SEM) of conformity with best-available evidence was 5.43 +/- 0.28 for the existent best-available evidence class, the corresponding scores for the citation of RCT, meta-analyses, and therapeutic objectives were, respectively, 1 +/- 0.2, 0.16 +/- 0.07, and 2.7 +/- 0.3. The four scores were highest when the best-available evidence belonged to the indicated class, intermediate when best-available evidence was nonexistent, and lowest for the contraindicated class (P < .05). These scores were significantly higher when the printed material was intended for specialists. CONCLUSION: Despite some limitations, the extent of agreement with the best-available evidence is only moderate. Pathophysiologic reasoning is largely preferred to justify the choice of therapeutics recommended to medical students.

Analysis of Variance↗
PubMed1999

Severe morbidity after coronary artery surgery: development and validation of a simple predictive clinical score.

AIMS: To develop a predictive clinical risk score of post-operative morbidity after coronary artery bypass grafting. METHODS AND RESULTS: Data were collected retrospectively from 679 patients undergoing emergency or planned bypass surgery between 1 January and 31 December 1996. The incidence of morbidity was 23%. Multivariate stepwise logistic regression analysis on two-thirds of the patients identified eight independent risk factors for severe morbidity. Six of these were pre-operative: symptomatic right heart failure, previous ventricular arrhythmias, previous coronary bypass surgery, chronic pulmonary disease, ST changes on pre-operative electrocardiogram, body mass index <24 kg. m-2, and two were intra-operative factors: the surgeon who operated, and the cardiopulmonary bypass time. A predictive clinical risk score was developed with the six pre-operative risk factors. The negative predictive value of the model is 87% and the area under the receiver operating characteristic curve is 0.77. When tested on the remaining patients not used for developing the model, the area under the curve is 0.65. CONCLUSION: This pre-operative risk score provides a simple method of risk stratification for patients undergoing coronary artery surgery. However, as for all predictive models, the performance of the score decreases when applied to a population other than that used to develop it.

Adult↗
PubMed1998

Clinical effects of beta-adrenergic blockade in chronic heart failure: a meta-analysis of double-blind, placebo-controlled, randomized trials.

BACKGROUND: beta-Blockers have improved symptoms and reduced the risk of cardiovascular events in studies of patients with heart failure, but it is unclear which end points are most sensitive to the therapeutic effects of these drugs. METHODS AND RESULTS: We combined the results of all 18 published double-blind, placebo-controlled, parallel-group trials of beta-blockers in heart failure. From this combined database of 3023 patients, we evaluated the strength of evidence supporting an effect of treatment on left ventricular ejection fraction, NYHA functional class, hospitalizations for heart failure, and death. beta-Blockers exerted their most persuasive effects on ejection fraction and on the combined risk of death and hospitalization for heart failure. beta-Blockade increased the ejection fraction by 29% (P<10(-9)) and reduced the combined risk of death or hospitalization for heart failure by 37% (P<0.001). Both effects remained significant even if >90% of the trials were eliminated from the analysis or if a large number of trials with a neutral result were added to the analysis. In contrast, the effect of beta-blockade on NYHA functional class was of borderline significance (P=0.04) and disappeared with the addition or removal of only 1 moderate-size study. Although beta -blockade reduced all-cause mortality by 32% (P=0.003), this effect was only moderately robust and varied according to the type of ss-blocker tested, ie, the reduction of mortality risk was greater for nonselective beta-blockers than for beta1-selective agents (49% versus 18%, P=0.049). However, selective and nonselective beta-blockers did not differ in their effects on other measures of clinical efficacy. CONCLUSIONS: These analyses indicate that there is persuasive evidence supporting a favorable effect of beta-blockade on ejection fraction and the combined risk of death and hospitalization for heart failure. In contrast, the effect of these drugs on other end points requires additional study.

Adrenergic beta-Antagonists↗
PubMed1998

Antibiotic prophylaxis for permanent pacemaker implantation: a meta-analysis.

BACKGROUND: Infection remains a serious complication after permanent pacemaker implantation. Antibiotic prophylaxis is frequently prescribed at the time of insertion to reduce its incidence, although results of well-designed, controlled studies are lacking. METHODS AND RESULTS: We performed a meta-analysis of all available randomized trials to evaluate the effectiveness of antibiotic prophylaxis to reduce infection rates after permanent pacemaker implantation. Reports of trials were identified through a Medline, Embase, Current Contents, and an extensive bibliography search. Trials that met the following criteria were included: (1) prospective, randomized, controlled, open or blind trials; (2) patients assigned to a systemic antibiotic group or a control group; (3) end point events related to any infection after pacemaker implantation: wound infection, septicemia, pocket abscess, purulent secretion, right infective endocarditis, inflammatory signs, a positive culture, septic pulmonary embolism, or repeat operation for an infective complication. Seven trials met the inclusion criteria. They included 2023 patients with established permanent pacemaker implantation (new implants or replacements). The incidence of end point events in control groups ranged from 0% to 12%. The meta-analysis suggested a consistent protective effect of antibiotic pretreatment (P=.0046; common odds ratio: 0.256, 95% confidence interval: 0.10 to 0.656). CONCLUSIONS: Results of the present meta-analysis suggest that systemic antibiotic prophylaxis significantly reduces the incidence of potentially serious infective complications after permanent pacemaker implantation. They support the use of prophylactic antibiotics at the time of pacemaker insertion to prevent short-term pocket infection, skin erosion or septicemia.

Adult↗
PubMed1998

Cytomegalovirus prophylaxis with antiviral agents in solid organ transplantation: a meta-analysis.

BACKGROUND: The aim of this meta-analysis was to assess the efficacy of antiviral agents to prevent, in solid organ transplant recipients, cytomegalovirus infection and symptomatic disease and to decrease the incidence of acute rejection, graft loss, and death. METHODS: Of the studies identified, 13 met the following inclusion criteria: prospective randomized study, in adults or pediatric recipients of a solid organ transplant, where one group in the study received a prophylactic treatment with acyclovir and/or ganciclovir begun before the cytomegalovirus infection and a control group was not treated or receive placebo. RESULTS: Prophylactic treatment was found to be associated with a significant decrease of cytomegalovirus disease compared with placebo or no treatment, using the logarithm of relative risk method (relative risk=0.50; 95% confidence interval, 0.40-0.62; P-value for chi-square association <0.001). Prophylactic treatment decreased also the rate of cytomegalovirus infection (relative risk=0.74; 95% confidence interval, 0.62-0.88; P<0.001). Our analysis failed to show a significant decrease of graft loss, acute rejection, and death in the prophylactic treatment group. Subgroup analysis based on the type of antiviral agent (acyclovir or ganciclovir) and on the type of organ (kidney or liver) gave comparable results. CONCLUSION: The use of antiviral agents for the prevention of cytomegalovirus disease and cytomegalovirus infection in solid organ transplantation is supported by this meta-analysis.

Acyclovir↗
PubMed1998

A meta-analysis of the effects of cognitive therapy in depressed patients.

BACKGROUND: Cognitive therapy (CT) has been studied in 78 controlled clinical trials from 1977 to 1996. METHOD: The meta-analysis used Hedges and Olkin d+ and included 48 high-quality controlled trials. The 2765 patients presented non-psychotic and non-bipolar major depression, or dysthymia of mild to moderate severity. RESULTS: At post-test CT appeared significantly better than waiting-list, antidepressants (P < 0.0001) and a group of miscellaneous therapies (P < 0.01). But, CT was equal to behaviour therapy. As between-trial homogeneity was not met, the comparisons of CT with waiting-list or placebo, and other therapies should be taken cautiously. In contrast, between-trial homogeneity was high for the comparisons of CT with behaviour therapy and antidepressants. A review of eight follow-up studies comparing CT with antidepressants suggested that CT may prevent relapses in the long-term, while relapse rate is high with antidepressants in naturalistic studies. CONCLUSION: CT is effective in patients with mild or moderate depression.

Adult↗
PubMed1998

Revisiting the effect compartment through timing errors in drug administration.

The variations in the pharmacological effects induced by timing errors in drug intake are compared for two drugs, one acting by way of an effect compartment and the other directly from the central compartment. A simulation was performed for two drugs having the same concentration-effect relationship at the receptor site, the same mean effect at equilibrium and identical concentrations in the central compartment. In this article. Patrice Nony, Michel Cucherat and Jean-Pierre Boissel discuss how, for the same variability of concentrations in the central compartment, the variations in mean effects are different. When there is a large variability in the interval separating two consecutive doses, the model that includes an effect compartment dampens the pharmacokinetic variability present in the central compartment. Such an approach may be useful for the prescription recommendations of drugs, especially those with narrow therapeutic indices.

Dose-Response Relationship, Drug↗
PubMed1998

[Local control of the primary tumor. Necessary step in control of cancer].

There is clear evidence for a cancer cure. The hypothesis behind a treatment with curative intent is the ability to eradicate all the cancer cells of a tumour. Out of three cancer deaths, one is related to local failure. In some cancers like breast carcinoma, death is mainly in relation with the development of distant metastases. Even in such a tumour, an improvement in local control can translate as better survival. Radiation therapy, often in association with surgery, is playing a major role in tumour local control. Such a local control is mandatory if cure is at aim. One of the main goals of clinical research is to find a good compromise between local control of the disease and a non mutilating surgical approach.

Antineoplastic Agents↗
PubMed1998

A mathematical model for the determination of the optimum value of the treatment threshold for a continuous risk factor.

Hypercholesterolemia or hypertension are continuous risk factors for coronary heart disease. When a preventive action is carried out against such a risk factor, it is necessary to specify a risk factor level value, named the treatment threshold, above which a subject should be treated. But a non-arbitrary determination of this threshold value is impossible from the epidemiological data. A method for the non-arbitrary determination of the treatment threshold value is presented, based upon mathematical modelling of the clinical and economics consequences of the prevention policy in the whole population. In a cost-effectiveness approach, the model was used to estimate the cost per coronary event prevented according to the threshold value for blood cholesterol. It was found that a minimum in this outcome proposed as the optimum treatment threshold. It is possible, from a public health point of view, to determine an optimum, non-arbitrary treatment threshold value in the prevention of coronary heart disease with cholesterol-lowering interventions. The model proposed here could be useful in decision making processes.

Anticholesteremic Agents↗
PubMed1998

[Identification and prediction of responders to a therapy. A model and its preliminary application to hypertension].

The effect of a given treatment for a given disease may be estimated from randomized controlled clinical trials, expressed as a single treatment effect averaged over the trial population. However, in recent years there has been an increasing willingness to individualize therapeutic decisions. The method we report here identifies responders by assessing the individual probability of an event, according to the treatment group. We used a treatment-stratified Cox regression model including interaction between treatment and patient's covariates, with common regression coefficients for treated and untreated, except for the special case of a prognostic variable which has an interaction with treatment. Further, we used a discriminate function based on the final model, representing the absolute individual therapeutic effect, to identify the patients to be treated according to a given threshold of clinical efficacy. The model was explored on the INDANA database (which pools individual patient data from clinical trials of anti-hypertensive drug intervention). Data on 36,444 patients, from five randomized controlled trials were included. The results show the relationship between the proportion of avoided events among the avoidable ones, and the proportion of patients treated who were responders, as a function of the threshold of absolute benefit defining responders. The confidence intervals of the absolute therapeutic benefit for each individual were calculated, by using the Monte Carlo simulation method. A comparison of the survival of treated and controlled individuals, in both subgroups of responders and non responders, illustrated the relevance of the model. We conclude that the tools for predicting individual therapeutic benefit do exist. It will be important to assess the reproducibility of these results in other models or in other populations before widespread application. It will be necessary to have a properly computerized environment and to train doctors to use these tools.

Decision Support Techniques↗
PubMed1997

Persistent reduction of mortality for five years after one year of acebutolol treatment initiated during acute myocardial infarction. The APSI Investigators. Acebutolol et Prévention Secondaire de l'Infarctus.

The APSI trial was a randomized placebo-controlled trial designed to assess the efficacy of 1 year of treatment by acebutolol in high-risk patients who had survived an acute myocardial infarction. At 1 year there was a statistically significant 48% relative reduction in total mortality (p = 0.019) in favor of acebutolol. In 1995 a long-term mortality survey was undertaken through an administrative inquiry and contacts with investigators. The vital status of 586 of the 607 (96.5%) patients enrolled was known at the cutoff date and all these patients were followed up for at least 5 years. During follow-up (in-trial and post-trial period), 74 deaths (24.8%) occurred in the acebutolol group and 96 (31.1%) in the placebo group (p = 0.10). No difference between the 2 groups was observed for the number of deaths that occurred after the end of the trial: 55 deaths (19.6%) among the 281 survivors in the acebutolol group and 59 deaths (21.7%) (p = 0.70) among the 272 survivors in the placebo group. The annual hazard rate (annual death rate), calculated year by year using the actuarial method, was significantly different (p < 0.01) only for the first year and was not significantly different thereafter. Thus, the initial benefit obtained in 1 year of treatment by acebutolol lasts for 5 years.

Acebutolol↗