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M Cucherat

Publications and source records attributed to M Cucherat.

At least 19 recordsLinked to original sources

Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature.

We performed a meta-analysis of all published studies relating intratumoural microvessel density (MVD) (45 studies) or vascular endothelial growth factor (VEGF) expression (27 studies), both reflecting angiogenesis, to relapse free (RFS) and overall survival (OS) in colorectal cancer (CRC). For each study, MVD impact was measured by risk ratio between the two survival distributions with median MVD as cutoff. Eleven studies did not mention survival data or fit inclusion criteria, six were multiple publications of same series, leaving 32 independent studies for MVD (3496 patients) and 18 for VEGF (2050 patients). Microvessel density was assessed by immunohistochemistry, using antibodies against factor VIII (16 studies), CD31 (10 studies) or CD34 (seven studies). Vascular endothelial growth factor expression was mostly assessed by immunohistochemistry. Statistics were performed for MVD in 22 studies (the others lacking survival statistics) including nine studies (n = 957) for RFS and 18 for OS (n = 2383) and for VEGF in 17 studies, including nine studies for RFS (n = 1064) and 10 for OS (n = 1301). High MVD significantly predicted poor RFS (RR = 2.32 95% CI: 1.39-3.90; P < 0.001) and OS (RR = 1.44; 95% CI: 1.08-1.92; P = 0.01). Using CD31 or CD34, MVD was inversely related to survival, whereas it was not using factor VIII. Vascular endothelial growth factor expression significantly predicted poor RFS (RR = 2.84; 95% CI: 1.95-4.16) and OS (RR=1.65; 95% CI: 1.27-2.14). To strengthen our findings, future prospective studies should explore the relation between MVD or VEGF expression and survival or response to therapy (e.g. antiangiogenic therapy). Assessment of these angiogenic markers should be better standardised in future studies.

Adenocarcinoma↗

Relationship between lower urinary tract symptoms frequency assessed by the IPSS and bothersomeness (SPI) among men older than 50 years old.

OBJECTIVE: The International Prostatic Symptom Score (IPSS) evaluates urinary disorder symptoms frequently associated with benign prostatic obstruction, but does not take into account the bothersomeness they induce. The Symptom Problem Index (SPI) evaluates the degree of discomfort associated with each question on the IPSS. Our objective was to explore the relationships between these two rating scales. METHODS: The IPSS and SPI self-administered scores were administrated to a cohort of 907 patients presenting with LUTS suggestive of BPO (Benign Prostatic Obstruction), for which 722 patients were evaluable. This diagnosis was made by GP (General Practitioner) in the 3-month period before their inclusion in the study. The correlation between SPI and IPSS was investigated and each symptom was classified according to its frequency and according to the bothersomeness it induced. The degree of bothersomeness associated with each IPSS symptom was evaluated and quantified based on quadratic function estimates. RESULTS: The mean IPSS score was 12.6+/-6.4, the mean SPI score was 12.2+/-6.5. The correlation coefficient between the IPSS and SPI scores was 0.70; the scores from the 2 rating scales showed a very high variability. On a 0-100% scale, where 100% represents a maximum bothersomeness, the induced bothersomeness ranged from 0 to 22.6% depending on the 7 symptoms. CONCLUSIONS: The two questionnaires do not collect the same information. The extent of variability between the two scales confirms that one scale cannot be replaced by the other. Considering the importance of bothersomeness associated with lower urinary tract symptoms for the therapy decision, the joint use of the IPSS and SPI seems appropriate.

Aged↗

[Correlation between cranial vault size and brain size over time: preliminary MRI evaluation].

OBJECTIVES: To correlate changes of cranial vault measurements of an adult population during the aging process with brain size using the maximum width of the third ventricle in the axial AC-PC plane. MATERIALS AND METHODS: Prospective study of 126 adult subjects (range: 20 to 80 years) with normal brain MRI and without history of neuropsychiatric disorder. MEASUREMENTS INCLUDED: Cranial vault (Maximum length: Glabella-Opisthocranion, Maximum width: euryon-euryon, and maximum height: Basion-Vertex) measurements and maximum width of the third ventricle in the A C-PC plane. RESULTS: Vault measurements (length, width, high) were similar for every age group, irrespective of gender. The variability of cranial vault measurements between individuals was low (<1 cm). Cranial vault measurements were larger for men, but this was not significant when adjusted for body height Comparatively, a gradual widening of the third ventricle, with an exponential behavior, was observed with advancing age. CONCLUSION: Our results indicate that cranial vault measurements are stable over time (between 20-80 years) comparatively to brain atrophy with advancing age. The low variability of cranial vault measurements and their stability over time should be taken into account during segmentation and normalization of brain parenchymal structures.

Adult↗

Prevention of venous thromboembolism in orthopedic surgery with vitamin K antagonists: a meta-analysis.

BACKGROUND: The benefit-to-risk ratio of vitamin K antagonists (VKA), relative to active comparators, especially low-molecular-weight heparins (LMWH), for preventing venous thromboembolism in patients undergoing major orthopedic surgery is debated. OBJECTIVES: We performed a meta-analysis of all randomized trials in orthopedic surgery comparing adjusted doses of VKA to control treatments. PATIENTS AND METHODS: An exhaustive literature search, both manual and computer-assisted, was performed. Studies were selected on the basis of randomization procedure (VKA vs. a control group). At least one of the following outcome measures was to be evaluated: deep vein thrombosis (DVT), pulmonary embolism (PE), death, major hemorrhage or wound hematoma. Four reviewers assessed each article to determine eligibility for inclusion and outcome measures. RESULTS: VKAs were more effective than placebo or no treatment in reducing DVT [567 patients, relative risk (RR) = 0.56, 95% confidence interval (CI) 0.37, 0.84, P < 0.01] and clinical PE (651 patients, RR = 0.23, 95% CI 0.09, 0.59, P < 0.01). These results were obtained at the cost of a higher rate of wound hematoma (162 patients, RR = 2.91, 95% CI 1.09, 7.75, P = 0.03). VKAs were also more effective than intermittent pneumatic compression (534 patients, RR = 0.46, 95% CI 0.25, 0.82, P = 0.009) in preventing proximal DVT. In contrast, VKAs were less effective than LMWH in preventing total DVT and proximal DVT (9822 patients, RR = 1.51, 95% CI 1.27, 1.79, P < 0.001; and 6131 patients, RR = 1.51, 95% CI 1.04, 2.17, P = 0.028, respectively). The differences between VKA and LMWH in major hemorrhage and wound hematoma were not significant. CONCLUSIONS: In patients undergoing major orthopedic surgery, VKAs are less effective than LMWH, without any significant difference in the bleeding risk.

Fibrinolytic Agents↗

[Meta-analysis of surgery trials in refractory epilepsy].

OBJECTIVE: To examine the evidence for efficacy of surgery in the treatment of intractable epilepsy. METHOD: Meta-analysis of randomized clinical trials. RESULTS: One randomized clinical trial (n=80) and 3 observational studies are available. INTERPRETATION: Compared to medical treatment, the surgery increases the proportion of patients who were free of seizure impairing awareness at 1 year (relative risk: 7.67, IC 95% 2.5 à 23.51) CONCLUSION: The available evidence about the clinical efficacy of surgery for patient with intractable epilepsies is limited to an unique open randomized clinical trial, that enrolled patient in a single centre, without concealment of the randomization and with a partially subjective primary endpoint. However, this trial shows a substantial effect corresponding to a 8 fold increase in the number of patient without seizure at 1 year. The informational situation will be better when the results of a currently ongoing trial will be available.

Adult↗

Efficacy of pneumococcal polysaccharide vaccine in immunocompetent adults: a meta-analysis of randomized trials.

The use of pneumococcal polysaccharide vaccine (PPV) is low in some countries, maybe because of doubts regarding its efficacy. This meta-analysis aims at combining evidence from randomized trials of PPV assessing its efficacy in preventing Streptococcus pneumoniae related diseases in immunocompetent adults. In the fourteen trials totalling 48,837 patients retrieved, PPV prevents definite pneumococcal pneumonia by 71%, presumptive pneumococcal pneumonia by 40%, and mortality due to pneumonia by 32%, but not all-cause pneumonia or death. No preventive effect was seen in the subgroup of patients aged 55 years or more, possibly due to a lack of statistical power.

Adult↗

Beta-blocker treatment in heart failure.

Heart failure treatment has markedly changed during the last few decades, with demonstration of benefit of afterload reduction by vasodilator therapy and introduction of the concept of the deleterious consequences of the neuro-hormonal compensatory stimulation. Blockade of beta-adrenergic receptors, initially contra-indicated in heart failure, provide a marked reduction of mortality and morbidity in combination with diuretics and angiotensin-converting enzyme inhibitors, as demonstrated in many clinical trials. We performed a review of all clinical trials that compare beta-blockers vs. placebo in chronic heart failure. Beta-blockers with different pharmacological profiles have been tested, mainly metoprolol, bisoprolol, bucindolol and carvedilol. With progressive dose increment, tolerance of such treatment was generally good, left ventricular function improved, hospitalisations for heart failure were less frequent and mortality was reduced. The meta-analysis of the 16 randomised trials, with at least one death in each treatment group, provides a 24% relative risk reduction for such hospitalisations (95% CI=19%-29%) and 22% reduction for mortality (95% CI=16%-28%). Heterogeneity of beta-blocker effect for mortality was found and related to the non-significant benefit obtained in the BEST trial with bucindolol. When such a trial is excluded, the effect model analysis shows that relative risk reduction (beta-blocker induced benefit) is constant whatever the severity of the disease. The mechanism of beta-blocker induced benefit remains unclear, but is at least partly related to left ventricular function improvement and prevention of severe ventricular arrhythmias. In conclusion, beta-blocker treatment has become an established therapy for heart failure, in combination with diuretics and ACE inhibitors. Complementary informations will be needed to clarify the mechanism of benefit and to define the best therapeutic strategy according to the individual characteristics of patients with heart failure.

Adrenergic beta-Antagonists↗

[Antihypertensive therapy and improved life expectancy without cerebrovascular accident or coronary artery disease].

The absolute benefit from antihypertensive therapy increases with the baseline risk. However, age is a major determinant of cardiovascular risk, so it is important to express therapeutic efficacy with indices for which age is not a confounder. With this aim we explored the expected gain in life expectancy without cardiovascular events according to age at the initiation of the treatment. The treatment effect estimated from the INDANA meta-analysis, was applied to the cardiovascular risk of a French hypertensive population, simulated from national vital statistics. The gain in life expectancy was estimated from the area between survival curves without events. The treatment effect varied according three different hypotheses: increasing, decreasing or constant effect. When assuming a constant treatment effect, our results show a 29 month gain without stroke for a man who began his treatment at 40 years, and 15 months if hypertension is screened and treatment initiated at 75 years. The gains without coronary heart disease are respectively of 11 and 6 months. The variation of treatment effect over time could have a major impact on the treatment benefit. The gain in life expectancy without events is a relevant decision tool, completing usefully the absolute benefit, since it takes into account the influence of age.

Adult↗

[Local control in the management of cancer: a few thoughts].

Cancer is still considered from a physiopathological point of view as a disease of the cell. This concept is underlying the idea of cure. Treatment with curative intent should aim at eradicating all the tumoral cells. Local control is mandatory and essential in cancers localized in organ with vital function. In breast cancer a complex and controversial relationship exists between local relapse and increased risk of fatal distant metastasis. In case of organ preserving treatment, a complete local control is necessary from the start. If a too high risk of local relapse is foreseable, conservative treatment should not be recommended.

Breast Neoplasms↗

[Clinical benefits of cholesterol lowering treatments. Meta-analysis of randomized therapeutic trials].

PRIMARY PREVENTION: A meta-analysis of the 7 available randomized cholesterol lowering trials (2 on statins, 2 on fibrates, 2 on resins and 1 on diet) demonstrates a significant 24% relative reduction in the frequency of fatal and non-fatal coronary events, leading to a significant 14% relative reduction in coronary disease related mortality. For total mortality, the statin trials were not comparable with other treatments where there was a trend to overmortality. With the 2 statin trials, there was a nonsignificant 13% reduction in total mortality. SECONDARY PREVENTION: A meta-analysis of the 13 available randomized trials (3 with clofribrate, 1 with gemfibrozil, 2 with nicotinic acid, and 4 with diet) showed a significant 21% reduction in the frequency of fatal and non-fatal coronary events, coronary mortality and total mortality. For total mortality, only the result of the 2 statin trials was significant (-20%). BENEFICIAL EFFECT OF STATINS, ABSOLUTE VALUES: Measured as the number of patients to treat for 5 years in order to avoid 1 event (NNT), there is a clinically pertinent benefit of secondary prevention (NNT = 15 for events, NNT = 30 for coronary mortality). The absolute value is weaker when patients with minimally elevated cholesterol levels are included. For primary prevention, the absolute value is low with NNT = 44 for events and NNT = 300 for coronary mortality. In addition, as these results were obtained in trials including populations with a much higher risk than the general French population, the absolute beneficial effect may not be pertinent in France except in high-risk patients who present, in addition to a high cholesterol level, other cardiovascular risk factors.

Anticholesteremic Agents↗

[The results of a single clinical trial-is it sufficient information?].

Meta-analysis is a systematic and quantified synthesis of all clinical trials studying the same question. It is systematic because it implies an exhaustive search for all trials of the studied treatment, favourable or not, published and unpublished. It is quantified because it is based on statistical calculations leading to an estimation of the degree of the effect of the treatment. The use of statistical techniques allows to take into account the fact that different results can be obtained in different studies only by chance. Meta-analysis can be used to assess the efficacy of a treatment or to study the factors that modify this efficacy.

Clinical Trials as Topic↗

Primary angioplasty versus intravenous thrombolysis for acute myocardial infarction.

BACKGROUND: Intravenous thrombolytic therapy is the standard care for patients with acute myocardial infarction, based upon its widespread availability and ability to reduce patient mortality well demonstrated in randomised trials. Despite its proven efficacy, thrombolytic therapy has limitations. Many patients are ineligible for treatment with thrombolytics. Of those given thrombolytic therapy, 10 to 15 percent have persistent occlusion or reocclusion of the infarct-related artery. Consequently, primary angioplasty (primary PTCA) has been advocated as a better treatment of myocardial infarction. OBJECTIVES: To determine whether primary coronary angioplasty is superior to thrombolytic therapy for the treatment of patients with acute myocardial infarction. SEARCH STRATEGY: Electronic search of The Cochrane Library (1998; Issue 2). MEDLINE (to January 1998); references from reviews, trials and previously published meta-analyses; and experts. Date of most recent searches January 1998. SELECTION CRITERIA: All unconfounded, randomised controlled trials comparing primary angioplasty against intravenous thrombolysis in patients with acute myocardial infarction DATA COLLECTION AND ANALYSIS: At least two independent reviewers abstracted data on morbidity and mortality and trial characteristics. The following outcomes were assessed: total mortality at the end of the study, reinfarction, stroke of any type, composite endpoint of death and reinfarction, recurrent ischemia, severe bleeding and coronary artery bypass grafting. MAIN RESULTS: Ten trials including 2573 subjects were identified. Compared to thrombolytic therapy, primary angioplasty was associated with a significant reduction in short-term mortality at the end of the studies (relative reduction in risk RRR = 32% 95%CI = 5%;50%). Similar reductions were observed for the rate of reinfarction (RRR = 52%, 95%CI = 30%;67%), recurrent ischemia (RRR = 54%; 95%CI = 39%, 66%) and for the combined criteria death or reinfarction (RRR = 46%; 95%CI=30%;58%). The frequency of strokes of any cause was significantly decreased by 66% (95%CI=28%;84%). No significant difference was observed for the incidence of major bleeding (relative risk RR =1.18, 95%CI = 0.73;1.90) but the confidence interval was large. The superiority of the primary angioplasty over thrombolysis in terms of the composite endpoint (mortality and reinfarction) was less with accelerated t-PA (RR=0.70, 95%CI=0.51;0. 97) than with streptokinase (RR=0.30, 95%CI=0.17;0.53). The biggest and most recent trial, Gusto 2B ( approximately approximately GUSTO-2B 97 approximately approximately ), which involved general as well as higly specialised centres, obtained less favorable results. REVIEWER'S CONCLUSIONS: This meta-analysis suggests that angioplasty provides a short-term clinical advantage over thrombolysis which may not be sustained. Primary angioplasty when available promptly at experienced centres, may be considered the preferred strategy for myocardial reperfusion. In most situations, however, optimal thrombolytic therapy should still be regarded as an excellent reperfusion strategy.

Angioplasty, Balloon, Coronary↗

Evidence of clinical efficacy of homeopathy. A meta-analysis of clinical trials. HMRAG. Homeopathic Medicines Research Advisory Group.

OBJECTIVE: To establish, using a systematic review and meta-analysis, whether there is any evidence from randomised controlled clinical trials of the efficacy of homeopathic treatment in patients with any disease. DATA SOURCES: Published and unpublished reports of controlled clinical trials available up to June 1998, identified by searching bibliographic databases (Medline, Embase, Biosis, PsychInfo, Cinahl, British Library Stock Alert Service, SIGLE, Amed), references lists of selected papers, hand searching homeopathic journals and conference abstracts, and contacting pharmaceutical companies. TRIALS SELECTION: Trials were selected using an unblinded process by two reviewers. The selection criteria were randomised, controlled trials in which the efficacy of homeopathic treatment was assessed relative to placebo in patients using clinical or surrogate endpoints. Prevention trials or those evaluating only biological effects were excluded. One hundred and eighteen randomised trials were identified and evaluated for inclusion. Sixteen trials, representing 17 comparisons and including a total of 2,617 evaluated patients, fulfilled the inclusion criteria. DATA EXTRACTION: Data were extracted by two reviewers independently, using a summary form. Disagreements were resolved by a third person. DATA SYNTHESIS: The evidence was synthesised by combining the significance levels (P values) for the primary outcomes from the individual trials. The combined P value for the 17 comparisons was highly significant P = 0.000036. However, sensitivity analysis showed that the P value tended towards a non-significant value (P = 0.08) as trials were excluded in a stepwise manner based on their level of quality. CONCLUSIONS: There is some evidence that homeopathic treatments are more effective than placebo; however, the strength of this evidence is low because of the low methodological quality of the trials. Studies of high methodological quality were more likely to be negative than the lower quality studies. Further high quality studies are needed to confirm these results.

Homeopathy↗

Trial summary software.

Medical practice is most strongly founded when based on the results of well conducted clinical trials. Clinical trial results normally enter the domain of medical knowledge and practice through their publication in scientific journals. This in itself poses problems of accessibility and selection. The results of this is a slow and selective diffusion of new medical facts which has a consequent cost in human lives and human suffering. In an attempt to shorten this information path initiatives such as the Cochrane collaboration produce and maintain systematic reviews by speciality of the current state of knowledge. The ability to store a representation of a clinical trial in a standard form seems to us to be a necessary condition for the efficient and reproducible preparation of systematic reviews. Furthermore the consequent increased accessibility of research results due to the existence of the summaries would itself be of great use. In this aim a relational database client server system was developed and we publish here the results of our preliminary findings, including the data model, which we feel is an important contribution to the future discussion and development of computer based representations of clinical trial protocols and results and their use in clinical decision making.

Clinical Trials as Topic↗

Comparison of bioprosthesis and mechanical valves, a meta-analysis of randomised clinical trials.

The main purpose of this meta-analysis was to compare the outcomes of patients who randomly received mechanical valves or bioprosthesis, over a long-term clinical follow-up. We found only three trials meeting our selection criteria with a total of 1229 patients (8069. 5 patient-yr). Bleeding was more frequent in patients with mechanical prostheses both after 5 yr (RR=2.6; IC=[1.9;3.5]; P<0.0001) and 11 yr (RR=1.6; IC=[1.2;2.2]; P<0.001) of follow-up. However, the increased risk of bleeding at 11 yr was only statistically significant with mechanical prostheses in the aortic position (RR=1.93; IC=[1.36;2. 74]; P=0.0002). Reoperation was significantly more frequent in patients with bioprosthesis after 11 yr follow-up (RR=0.4; IC=[0.3;0. 6]; P<0.001). Endocarditis was more frequent after 11 yr (RR=0.6; IC=[0.3;0.95]; P<0.05) in patients with mechanical prostheses but these results were heterogeneous between mitral and aortic valves. The choice of valve type does not significantly influence survival.

Bioprosthesis↗