Biomedical subjects

Emmanuel Lesaffre

Publications and source records attributed to Emmanuel Lesaffre.

12 recordsLinked to original sources

PubMed2004

Effect of fluvastatin on long-term outcome after coronary revascularization with stent implantation.

We assessed the impact of long-term fluvastatin treatment on adverse atherosclerotic cardiac events (cardiac death, myocardial infarction, and revascularization excluding repeat interventions due to restenosis in the first 6 months) in 847 patients (fluvastatin [n = 417] or placebo [n = 430]) with average cholesterol levels treated with stents in the Lescol Intervention Prevention Study (LIPS). During the 4-year follow-up period, fluvastatin significantly decreased total cholesterol and low-density lipoprotein cholesterol levels and decreased the risk of first adverse atherosclerotic cardiac events by 30% compared with placebo (95% confidence interval -49 to -3.4, p = 0.03).

Adolescent↗

PubMed2003

A note on non-parametric ANCOVA for covariate adjustment in randomized clinical trials.

Koch et al. recently (1998) proposed two covariate-adjusted approaches for the comparison of continuous, ordinal and binary responses in a randomized clinical trial (Statist. Med. 1998; 17: 1863-1892). The first is a randomization approach while the second assumes that the study is a sample of a population. Here, we study the second approach and consider the simplest cases of two treatments with a continuous response and with a binary response. Koch's second approach will be compared with the classical ANCOVA for a continuous response. From this relationship we demonstrate that Koch's method cannot preserve the probability of the type I error. Simulations with continuous responses as well as with binary outcomes confirm the aforementioned theoretical result on the performance of Koch's method under the null hypothesis of no treatment effect. However, this poses only a problem for relatively small to moderate sample sizes. Further, as specified in the original paper of Koch et al., the first approach does preserve the type I error for any sample size, as the P-values can be reported in an exact manner (Statist. Med. 1998; 17: 1863-1892). Finally, we propose a correction factor for Koch's test statistic that better preserves the type I error.

Computer Simulation↗

PubMed2003

A comparison of group sequential methods for binary longitudinal data.

Interim analyses are conducted to allow for early termination of the trial, for ethical as well as economical reasons. Here we consider interim analyses in repeated measurements studies where the measurements are binary. Two methods for analysing this kind of data are compared according to their operating characteristics. A subject-specific approach based on the logistic random-effects model is compared with the population-averaged approach based on the generalized estimating equations. The comparison is illustrated with simulations using a randomized clinical trial for toenail fungal infection.

Antifungal Agents↗

PubMed2003

A retrospective analysis of the effect of noncompliance on time to first major adverse cardiac event in LIPS.

BACKGROUND: In the main publication for LIPS (Lescol Intervention Prevention Study), a 22% relative risk (RR) reduction for major adverse cardiac events (MACE) was found among those who used fluvastatin after a successful first percutaneous coronary intervention (PCI). However, intent-to-treat (ITT) analysis of clinical studies generally provides an observed treatment effect that is likely to underestimate what the treatment effect would be if compliance were perfect, because compliance in a clinical trial is invariably <100% during long-term follow-up. OBJECTIVE: The aim of this study was to analyze the relationship between compliance and treatment effect in LIPS. METHODS: In LIPS, patients who had undergone a successful first PCI were randomized to receive fluvastatin 40 mg BID or placebo BID for 3 to 5 years. The primary end point was survival time free of MACE (ie, cardiac death, nonfatal myocardial infarction, or reintervention procedure), and a Cox proportional hazards regression model with time-dependent covariates was used to predict the effect that fluvastatin would have had if trial medication had been continued. Logistic regression was used to determine factors influencing discontinuation of trial medication. RESULTS: A total of 1677 patients were enrolled in LIPS: 844 in the fluvastatin group and 833 in the placebo group. In the fluvastatin group, 294 patients (34.8%) discontinued taking trial medication and 73 (8.6%) switched to another lipid-lowering medication, compared with 353 (42.4%) and 187 (22.4%) patients in the placebo group, respectively. The risk factor-adjusted RR of MACE with fluvastatin treatment was 0.74 (P = 0.004; 95% CI, 0.61-0.91). When also adjusted for noncompliance, the RR for fluvastatin versus placebo was 0.68 (P = 0.002; 95% CI, 0.53-0.86). Discontinuing fluvastatin without switching to another lipid-lowering medication increased the risk of MACE compared with that of patients who stayed on fluvastatin (RR = 2.27; P < 0.001; 95% CI, 1.60-3.23) and the increase in the risk of MACE was greater than that associated with discontinuing placebo (P = 0.032). CONCLUSIONS: The present study found a 32% RR reduction for experiencing MACE during fluvastatin treatment after a successful PCI in LIPS, when analysis allowed for noncompliance. This suggests that the ITT analysis discussed in the main LIPS publication underestimated the benefit of fluvastatin treatment. Our survival model also provided tentative evidence that discontinuing lipid-lowering medication might lead to a potentially harmful rebound effect in this patient group.

Adult↗

PubMed2003

Mammography screening attendance: meta-analysis of the effect of direct-contact invitation.

BACKGROUND: Personal or telephone contact methods are often used to increase attendance for mammography screening. A meta-analysis of the literature was performed to assess the overall effect of direct-contact recruitment on mammography participation. METHODS: Two independent reviewers conducted two different search strategies. Each reviewer screened the search results for (quasi-)randomized-controlled trials that tested single women-targeted interventions. Twenty-one of 22 candidate studies that met the inclusion criteria could be included. These studies described 25 eligible interventions. Guided by a standardized protocol, a reviewer assessed the methodologic quality of each intervention and extracted the following data: (1) the number of women (from experimental and control groups) before and after the intervention, (2) details of the study population, (3) the type of intervention, and (4) the control condition. On the basis of a quality ranking, a cumulative random-effects meta-analysis was performed using relative risk as an indicator of intervention effect. RESULTS: Depending on the cumulative step, the analysis revealed that direct-contact strategies improved attendance from 21% (95% confidence interval [CI]; 10%-34%) to 46% (95% CI; 32%-61%). CONCLUSIONS: Evidence from experimental studies supports the effect of direct-contact strategies in which women are invited to participate in mammography screening. Future research will have to define the specific modalities in which these interventions can be adopted in a cost-effective manner.

Adult↗

PubMed2003

The emergence of permanent teeth in Flemish children.

The aim of the present study was to investigate the timing of emergence of permanent teeth in Flanders (Belgium). Data were obtained in the Signal-Tandmobiel projecta, a longitudinal study in a sample of 4468 Flemish children. Survival analysis with a log-logistic distribution was performed to calculate median (and mean) values and 95% CI's for all permanent teeth. The analysis indicated significantly earlier emergence ages in girls than in boys. The emergence pattern turned out to be symmetric in both sexes. Most mandibular teeth emerged significantly before their antagonists, in boys as well as in girls. These findings are in agreement with other studies on the emergence of permanent teeth.

Belgium↗

PubMed2003

Impact of caries experience in the deciduous molars on the emergence of the successors.

The purpose of this study was to evaluate the effect of caries experience in a primary molar (decayed and/or restored vs. extracted) on the timing of emergence of its successor. Data were obtained from a longitudinal epidemiological study in a sample of 4468 Flemish children. Survival analyses with log-logistic distribution were performed to calculate median emergence ages and 95% confidence intervals (CI); caries experience was added as a covariate. The results indicate that the emergence of the maxillary and mandibular premolars was accelerated by 2-8 months when its predecessor had been decayed and or restored but had not been extracted. Premature loss of maxillary primary molars resulted in a significant acceleration of the emergence of the premolars; this was not observed in the mandible. In conclusion, when considering permanent tooth emergence ages, caries experience in the primary dentition should be taken into account.

Child↗

PubMed2003

Continuous retrograde blood cardioplegia is associated with lower hospital mortality after heart valve surgery.

OBJECTIVE: Myocardial preservation studies comparing blood and crystalloid cardioplegia techniques were almost exclusively performed on patients undergoing coronary bypass, and they were unable to show a difference in hospital mortality. We investigated possible factors, including cardioplegia techniques, influencing hospital mortality in patients undergoing cardiac valve surgery. METHODS: We evaluated hospital mortality in 1098 consecutive patients undergoing cardiac valve surgery by using a multivariate logistic regression with propensity score balancing of the groups. In 25% of the patients, multiple valve or Bentall procedures were performed, and in 46% of all patients, coronary bypass grafting was associated with valve surgery. A first cohort of 504 consecutive patients were operated on by using single-shot antegrade cold crystalloid cardioplegia, and a second cohort of 594 patients were operated on by using continuous retrograde cold blood cardioplegia. RESULTS: After correction for patient-related and operative risk factors, lower hospital mortality was found in patients who received retrograde blood cardioplegia (P =.020). The odds ratio of in-hospital death when using blood cardioplegia was 0.44 (95% confidence interval, 0.22-0.88). Further predictors of hospital mortality were age, advanced New York Heart Association functional class, cardiopulmonary bypass time, reoperation, active endocarditis, and renal failure. CONCLUSIONS: This study shows that continuous retrograde blood cardioplegia is associated with lower hospital mortality in heart valve operations.

Adult↗

PubMed2002

On the variability of covariate adjustment. experience with Koch's method for evaluating the absolute difference in proportions in randomized clinical trials.

Recently Koch et al. suggested an interesting approach for covariate adjustment in randomized clinical trials. Here we report our experience with the approach in Assent II, a large randomized trial comparing 30-day mortality rates of two thrombolytic treatments. Data from the Gusto-I study and a recent successor to the Assent II study will also be used. Further, we balance the advantage of covariate adjustment (with Koch's method) to the extra efforts and resources necessary. In this context we highlight the fact that there is a potential risk of using a covariate-adjusted analysis as primary analysis and show that covariate adjustment has the least effect when it is needed most. Analytic results will be given to quantify this risk and a simulation study illustrates our findings.

Data Interpretation, Statistical↗

PubMed2002

Valved jugular vein segments for right ventricular outflow tract reconstruction in young sheep.

OBJECTIVE: This study was undertaken to investigate the degeneration and calcification of valved bovine jugular vein segments for right ventricular outflow tract reconstruction in juvenile sheep. METHODS: Seven valved bovine jugular vein conduits (Contegra model 220; VenPro Corporation, Irvine, Calif) and 3 control conduits (MH100; Medtronic, Inc, Minneapolis, Minn) were implanted in the pulmonary artery in young sheep. After 20 weeks the conduits were explanted and qualitatively analyzed by epicardial echocardiography, gross examination, x-ray analysis, light microscopy, and transmission electron microscopy. Calcification was determined quantitatively by flame atomic absorption spectrometry. RESULTS: Two Contegra conduits could not be analyzed because of endocarditis. All other Contegra conduits functioned well, with preserved structure and minimal calcification. The control MH100 conduits exhibited extensive fibrous sheathing, with calcification of the aortic wall portion and the commissural part of the Hancock valve. CONCLUSIONS: The Contegra conduit's performance was clearly superior to that of the control MH100 conduit when implanted in the pulmonary artery position in juvenile sheep for 5 months.

Animals↗

PubMed2002

Group sequential methods for an ordinal logistic random-effects model under misspecification.

Interim analyses in clinical trials are planned for ethical as well as economic reasons. General results have been published in the literature that allow the use of standard group sequential methodology if one uses an efficient test statistic, e.g., when Wald-type statistics are used in random-effects models for ordinal longitudinal data. These models often assume that the random effects are normally distributed. However, this is not always the case. We will show that, when the random-effects distribution is misspecified in ordinal regression models, the joint distribution of the test statistics over the different interim analyses is still a multivariate normal distribution, but a sandwich-type correction to the covariance matrix is needed in order to obtain the correct covariance matrix. The independent increment structure is also investigated. A bias in estimation will occur due to the misspecification. However, we will also show that the treatment effect estimate will be unbiased under the null hypothesis, thus maintaining the type I error. Extensive simulations based on a toenail dermatophyte onychomycosis trial are used to illustrate our results.

Biometry↗

PubMed2001

The Lescol(R) Intervention Prevention Study (LIPS): a double-blind, placebo-controlled, randomized trial of the long-term effects of fluvastatin after successful transcatheter therapy in patients with coronary heart disease.

BACKGROUND: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) inhibit atherosclerosis and reduce both morbidity and mortality in patients with coronary heart disease. No randomised prospective study, however, has investigated the long-term effect of statins on clinical outcomes in patients who have undergone first successful transcatheter therapy. METHODS: The Lescol((R)) Intervention Prevention Study (LIPS) is a double-blind randomized trial designed to compare the effect of fluvastatin (Lescol) with that of placebo on the time which patients with serum cholesterol >/= 3.5 mmol/l and < 7.0 mmol/l (135-270 mg/dl) remain free of major adverse cardiac events (MACE) after successful first transcatheter therapy (TCT). Patients, aged 18-80 years inclusive, will be randomized in a 1 : 1 ratio to receive fluvastatin, 40 mg, or placebo, twice daily for three to five years. The primary endpoint is the survival time during which patients remain MACE free after first TCT. Secondary endpoints are the incidence of MACE, noncardiac death, hospitalization for other atherosclerotic diseases, changes in serum lipid concentrations and anginal status. SUMMARY: LIPS is unique because it is the first study that will investigate whether MACE can be prevented or reduced by fluvastatin in patients who have undergone successful first transcatheter therapy for coronary heart disease.

Journal Article↗