References of "Comté, Laetitia"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailEstimation of HIV treatment-efficacy by combining structural nested mean models with pharmacokinetic models of antiretroviral drug exposure
Comté, Laetitia ULg; Vansteelandt, Stijn; Rode, Richard et al

in Statistics and its interface (2011), 4(4), 511-520

The aim of treating HIV-1-infected patients is to achieve and maintain suppression of viral load (VL). Achievement of this aim is thwarted by variable adherence to prescribed anti-retroviral drugs ... [more ▼]

The aim of treating HIV-1-infected patients is to achieve and maintain suppression of viral load (VL). Achievement of this aim is thwarted by variable adherence to prescribed anti-retroviral drugs. Variable adherence to an antiretroviral regimen creates variability in the patient’s internal exposure to the drugs. Structural nested mean models (SNMMs) enabled us to estimate, during the initial phase of treatment, the relationship between variable internal exposure and VL, accounting for measured time-varying confounders and feedback relations using an antiretroviral regimen containing lopinavir/ritonavir (LPV/RTV, LPV/r). Our final SNMM predicts that the short term effect of treatment is modified by the most recent past VL, with higher initial VL’s being associated with larger treatment-induced reductions in VL for a given internal exposure to the drugs. Variation in internal exposure to LPV/r in the interquartile interval (P25%–P75%) only slightly affects the overall reduction in VL, supporting the conclusion that the relatively long duration of action of LPV/r lessens the impact on VL of the most frequently recurring intermittent lapses in dosing. [less ▲]

Detailed reference viewed: 19 (4 ULg)
Full Text
Peer Reviewed
See detailLinear and loglinear structural mean models to evaluate the benefits of an on-demand dosing regimens
Comté, Laetitia ULg; Vansteelandt, Stijn; Tousset, Eric et al

in Clinical Trials : Journal of the Society for Clinical Trials (2009), 6(5), 403-415

Background Structural mean models (SMM) can be used to estimate treatment efficacy when drug exposure varies. We applied SMM to evaluate the clinical benefits of a proton pump inhibitor prescribed to be ... [more ▼]

Background Structural mean models (SMM) can be used to estimate treatment efficacy when drug exposure varies. We applied SMM to evaluate the clinical benefits of a proton pump inhibitor prescribed to be taken as needed to alleviate epigastric pain. We also investigated a new diagnostic approach to evaluate model assumptions. Methods All patients were suffering from non-erosive reflux disease or functional ulcer-like dyspepsia and were prescribed a proton pump inhibitor to be taken as needed for relief of epigastric pain. The primary endpoint was a score variable that expresses the magnitude of gastro-intestinal symptoms at 8 weeks after randomization. We developed linear and loglinear versions of the SMM to derive an unbiased estimator of the reduction in symptom score as a function of exposure to the test drug. Semi-parametric models based on splines and corresponding simultaneous confidence bands identified the presence of potential interactions between drug exposure and baseline covariates. Results The on-demand dosing regimen generated a wide range of drug exposure. Application of SMM showed that the potential treatment induced reduction in symptom score was much greater than the average treatment reduction observed in this population of patients. Our diagnostic tool was useful for detecting the interaction between drug exposure and baseline covariates. Limitations Analysis could only be performed over the two first months after randomization because, afterwards, many patients dropped out from the placebo group. Conclusions The structural mean model approach allows one to estimate treatment efficacy in the presence of variable drug exposure. Similar results were obtained using linear and loglinear SMM. [less ▲]

Detailed reference viewed: 42 (9 ULg)
Full Text
Peer Reviewed
See detailEstimation of the comparative therapeutic superiority of QD and BID dosing regimens, based on integrated analysis of dosing history data and pharmacokinetics
Comté, Laetitia ULg; Vrijens, Bernard ULg; Tousset, Eric et al

in Journal of Pharmacokinetics and Pharmacodynamics (2007), 34(4), 549-558

Once-daily dosing almost invariably shows a slightly higher percentage of prescribed doses taken than does twice-daily dosing. Many pharmaceutical scientists, regulators, and prescribers have considered ... [more ▼]

Once-daily dosing almost invariably shows a slightly higher percentage of prescribed doses taken than does twice-daily dosing. Many pharmaceutical scientists, regulators, and prescribers have considered this finding to signify the therapeutic superiority of once-daily dosing. The therapeutically more relevant question, however, is not the percentage of prescribed doses taken but the comparative impact of missed doses on the pharmacologic effects of a drug under the two dosing regimens. A key point in this regard is that the pharmacokinetic equivalent of a single missed once-daily dose is 2-3 sequentially omitted twice-daily doses. Thus, an important parameter in comparing the two regimens is the probability of two or three twice-daily doses being sequentially omitted, versus the probability of missing a single once-daily dose. Our data indicate that the probability of sequential omission of 2-3 twice daily doses is half the probability of omission of a single once-daily dose. For that reason, a twice-daily regimen could prove to be superior to a once-daily regimen in maintaining drug concentrations within a therapeutically desirable range. A more important consideration, however, is to maintain not just the concentration of drug in plasma, but the drug's therapeutic action. The duration of therapeutic drug action following a last-taken dose is not only drug-specific, but also, for some drug, dependent on the pharmacodynamic properties. Judging the comparative superiority of one dosing regimen over another requires knowledge of the drug's duration action after a last-taken dose, plus knowledge of the comparative probabilities of the various patterns of dose omission. When applied to HIV protease inhibitors, a twice-daily regimen appears to be better than an once-daily regimen in maintaining therapeutically effective drug actions. [less ▲]

Detailed reference viewed: 65 (2 ULg)
Full Text
Peer Reviewed
See detailAortic valve surgery in octogenarians: predictive factors for operative and long-term results
Kolh, Philippe ULg; Kerzmann, Arnaud ULg; Honoré, Charles ULg et al

in European Journal of Cardio - Thoracic Surgery (2007), 31(4), 600-605

Objective: To assess factors influencing operative and tong-term outcome in octogenarians undergoing aortic valve surgery (AVR). Methods: Records of 220 consecutive octogenarians having AVR between 1992 ... [more ▼]

Objective: To assess factors influencing operative and tong-term outcome in octogenarians undergoing aortic valve surgery (AVR). Methods: Records of 220 consecutive octogenarians having AVR between 1992 and 2004 were reviewed, and follow-up obtained (99% complete). Of the group (mean age: 82.8 years; 174 females), 142 patients (65%) were in New York Heart Association (NYHA) class III-IV, 22 (10%) had previous myocardial infarction, 11 (5%) had previous coronary artery bypass grafting (CABG), and 8 (4%) had percutaneous aortic valvuloplasty. There were 44 urgent procedures (20%), and additional CABG was performed in 58 patients (26%). Results: Operative mortality was 13% (9% for AVR, 24% for AVR + CABG). Among the 29 patients who died, 14 (48%) were operated on urgently (32% mortality for urgent procedures). Causes of hospital death were respiratory insufficiency or infection in 16 patients (16/29 = 55%), myocardial, infarction in 8 (28%), stroke in 2 (7%), sepsis in 2 (7%), and renal failure in 1 (3%). Significant postoperative complications were atrial fibrillation in 48 patients (22%), respiratory insufficiency in 46 (21%), permanent atrio-ventricular bloc in 12 (5%), myocardial infarction in 10 (5%), hemodialysis in 4 (2%), and stroke in 4 (2%). Mean hospital and intensive care unit (ICU) stays were 17.6 +/- 5.2 and 6.9 +/- 3.4 days, respectively. Multivariate predictors (p < 0.05) of hospital death were urgent procedure, associated CABG, NYHA class IV, and percutaneous aortic valvuloplasty. Age, associated CABG, and urgent procedure were predictors of prolonged ICU stay. Mean follow-up was 58.2 months and actuarial 5-year survival was 73.2 +/- 6.9%. Age, preoperative myocardial infarction, urgent procedure, and duration of ICU stay were independent predictors of late death. Among 130 patients alive at follow-up, 91% were angina free and 81% in class I-II. Conclusions: AVR in octogenarians can be performed with acceptable mortality, although significant morbidity. These results stress the importance of early operation on elderly patients with aortic valve disease, avoiding urgent procedures. Associated coronary artery disease is a harbinger of poor operative outcome. Long-term survival and functional recovery are excellent. (c) 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved. [less ▲]

Detailed reference viewed: 41 (8 ULg)
Full Text
Peer Reviewed
See detailConcurrent coronary and carotid artery surgery: factors influencing perioperative outcome and long-term results
Kolh, Philippe ULg; Comté, Laetitia ULg; Tchana-Sato, Vincent ULg et al

in European Heart Journal (2006), 27(1), 49-56

Aims To assess risk factors for early and late outcome after concurrent carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG). Methods and results Records of all 311 consecutive patients ... [more ▼]

Aims To assess risk factors for early and late outcome after concurrent carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG). Methods and results Records of all 311 consecutive patients having concurrent CEA and CABG from 1989 to 2002 were reviewed, and follow-up obtained (100% complete). In the group (mean age 67 years; 74% males), 62% had triple-vessel disease, 57% unstable angina, 31% left main coronary stenosis, 19% congestive heart failure, and 35% either a history of vascular procedures or existing vasculopathies. Preoperative assessment revealed transient ischaemic attack in 16%, stroke in 7%, and bilateral carotid disease in 20%. There were 7% emergent and 19% urgent operations, and ascending aorta was described as atheromatous or calcified in 21%. Hospital death occurred in 19 patients, myocardial infarction in seven, and permanent stroke in 12. Significant multivariable predictors of hospital death were aortic calcifications, coexisting vasculopathy, and emergent procedure. Significant predictors of postoperative stroke were calcified or dilated aorta, and of prolonged hospital stay were advanced age, unstable angina, and coexisting vascular disease. For hospital survivors, 10-year actuarial late event-free rates were: death, 50%; myocardial infarction, 84%; stroke, 93%; percutaneous angioplasty, 95%; redo CABG, 98%; and all morbidity and mortality, 48%. Significant multivariable predictors of late deaths were coexisting vasculopathy, age, renal insufficiency, previous cardiac surgery, tobacco abuse, calcified or atheromatous aorta, and duration of intensive care unit stay. Conclusion Concurrent CEA and CABG can be performed with acceptable operative mortality and morbidity, and good long-term freedom from coronary and neurologic events. Atheromatous aortic disease is a harbinger of poor operative and long-term outcome. [less ▲]

Detailed reference viewed: 18 (1 ULg)
Full Text
Peer Reviewed
See detailConcomitant coronary and carotid artery surgery: operative outcome and long-term results
Kolh, Philippe ULg; Tchana-Sato, Vincent ULg; Honoré, Charles ULg et al

in European Heart Journal (2004), 25(Suppl. S), 360-361

Detailed reference viewed: 13 (2 ULg)