Biomedical subjects
Publications and source records attributed to Michel Bertrand.
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BACKGROUND: The EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease (EUROPA) trial has recently reported. OBJECTIVE: To assess the cost effectiveness of perindopril in stable coronary heart disease in the UK. METHODS: Clinical and resource use data were taken from the EUROPA trial. Costs included drugs and hospitalisations. Health-related quality of life values were taken from published sources. A cost-effectiveness analysis is presented as a function of the risk of a primary event (non-fatal myocardial infarction, cardiac arrest or cardiovascular death) in order to identify people for whom treatment offers greatest value for money. RESULTS: The median incremental cost of perindopril for each quality-adjusted life year (QALY) gained across the heterogeneous population of EUROPA was estimated as 9700 pounds(interquartile range 6400-14,200 pounds). Overall, 88% of the EUROPA population had an estimated cost per QALY below 20,000 pounds and 97% below 30,000 pounds. For a threshold value of cost effectiveness of 30,000 pounds per QALY gained, treatment of people representing the 25th, 50th (median) and 75th centiles of the cost effectiveness distribution for perindopril has a probability of 0.999, 0.99 and 0.93 of being cost effective, respectively. Cost effectiveness was strongly related to higher risk of a primary event under standard care. CONCLUSIONS: Whether the use of perindopril can be considered cost effective depends on the threshold value of cost effectiveness of healthcare systems. For the large majority of patients included in EUROPA, the incremental cost per QALY gained was lower than the apparent threshold used by the National Institute for Health and Clinical Excellence in the UK.
The chemical composition of propolis from two regions in Canada was studied: Boreal forest and Pacific coastal forest that lay outside the area of distribution of Aigeiros poplars, the usual propolis source plants. In the sample from Victoria, p-hydroxyacetophenone, benzyl hydroxybenzoate and cinnamic acid were the major components, accompanied by significant amounts of dihydrochalcones, which allowed the identification of its plant source: Populus trichocarpa of Section Tacamahaca. Three dihydrochalcones were new for propolis. The sample from Richmond was characterized by large amounts of p-coumaric and cinnamic acid, typical for poplars of Section Leuce, subsection Trepidae, its plant source was identified as P. tremuloides. Both samples showed good radical scavenging activity against DPPH. Obviously, Northern type propolis is a promising potential source of biologically active substances and deserves further investigation.
AIMS: Patients with stable coronary artery disease (CAD) are at increased risk. Estimation of individual risk is difficult. We developed a cardiovascular risk model based on the EUROPA study population and investigated whether benefit of long-term administration of the angiotensin-converting enzyme (ACE)-inhibitor perindopril was modified by risk level. METHODS AND RESULTS: A total of 12 218 patients with stable CAD were treated with 8 mg perindopril or placebo. Baseline patient characteristics were assessed for association with 1091 cardiovascular deaths or non-fatal myocardial infarction (MI). Risk factors were age over 65 years, male gender [hazard ratio (HR) 1.2], previous MI (HR 1.5), previous stroke and/or peripheral vascular disease (HR 1.7), diabetes, smoking, angina (all HR 1.5), and high serum cholesterol and systolic blood pressure. Treatment benefit by perindopril was consistent among high, intermediate, and low risk patients (HRs 0.88, 0.68, and 0.83, respectively). Risk reduction was thus not modified by absolute risk level. CONCLUSION: Risk factors such as age, male gender, smoking, total cholesterol, and blood pressure continue to play an important role once clinical sequellae of coronary heart disease have developed. Patients at moderate-to-high risk because of uncontrolled risk factors and those with other indications for ACE-inhibitors have the most to gain from ACE-inhibition.
We investigated the feasibility of using echo-strain images to visualize the extent of high-intensity ultrasound (US)-induced thermal lesions during their formation. Echo-strain, defined as the relative deformation of the backscattered ultrasonic signal, is due to tissue expansion and to changes in the speed of sound during heating. First, a theoretical framework was developed to predict the influence of these effects on the echo signal. Then, a simulation tool was developed to create simulated echo-strain images in thermal lesions. Finally, experimental echo-strain images were acquired in 10 porcine liver samples in vitro for various exposure durations and ultrasonic intensities (resulting in lesions that extended 3 to 8 mm deep from the surface). For this purpose, radiofrequency (RF) frames were acquired at 8 frames per s while heating. For each consecutive pair of RF frames, an echo-strain image was calculated using standard elastographic processing. The echo-strain images were cumulated and displayed. The experimental echo-strain images were compared with gross pathology. The (isoechoic) lesions were visible both in simulated and in experimental cumulated echo-strain images as apparent expansion areas (tensile echo-strain), whereas surrounding tissues exhibited apparent compression. The tensile echo-strain area underestimated the lesion in simulations, but was representative of the lesion in experiments. High correspondence was found between the lesion depth measured from experimental cumulative echo-strain images (y) and from gross pathology (x) (Pearson's correlation = 0.90, linear regression y = x-0.1 mm, residual error = 0 +/- 0.9 mm). We hypothesized that significant tissue expansion made the thermal lesions highly visible in the experimental echo-strain images. In two cases, the ultrasonic intensity was too low to induce a lesion, and the corresponding experimental echo-strain images showed no visible lesion. We conclude that cumulative echo-strain images have the potential to monitor the formation of high-intensity US-induced thermal lesions.
The chemical composition of propolis from two regions in Canada was studied: Boreal forest and the Pacific coastal forest that lie outside the area of distribution of Aigeiros poplars, the usual propolis source plants. In the sample from Victoria, p-hydroxyacetophenone, benzyl hydroxybenzoate and cinnamic acid were the major components, accompanied by significant amounts of dihydrochalcones, which allowed the identification of its plant source: Populus trichocarpa of section Tacamahaca. Three dihydrochalcones were new for propolis. The sample from Richmond was characterized by large amounts of p-coumaric and cinnamic acid, typical for poplars of section Leuce, subsection Trepidae, its plant source was identified as P. tremuloides. Both samples showed a good radical scavenging activity against DPPH. Obviously, the Northern type propolis is a promising potential source of biologically active substances and deserves further investigation.
BACKGROUND: Patients with acute coronary syndromes (ACS; unstable angina and non-ST-segment elevation myocardial infarction) are at significant risk for death and myocardial infarction. Early angiography followed by revascularization is considered the treatment of choice for moderate- to high-risk patients with ACS. However, despite the integration of newer therapies including stents, glycoprotein IIb/IIIa inhibitors, and thienopyridines, the rate of adverse ischemic events still remains unacceptably high, and the intensive pharmacologic regimens used to stabilize the disrupted atherosclerotic plaque and support angioplasty and surgical revascularization procedures elicit a high rate of bleeding complications. Pilot trials suggest that the thrombin-specific anticoagulant bivalirudin may improve clinical outcomes in ACS. STUDY DESIGN: In the Acute Catheterization and Urgent Intervention Triage strategY (ACUITY) trial, 13,800 patients with moderate- to high-risk ACS are being prospectively randomly assigned at up to 600 centers to unfractionated heparin or enoxaparin + IIb/IIIa inhibition, versus bivalirudin + IIb/IIIa inhibition, versus bivalirudin + provisional IIb/IIIa inhibition. All patients undergo cardiac catheterization within 72 hours, followed by percutaneous or surgical revascularization when appropriate. In a second random assignment, patients assigned to receive IIb/IIIa inhibitors are subrandomized to upstream drug initiation, versus IIb/IIIa inhibitor administration during angioplasty only. The primary study end point is the composite of death, myocardial infarction, unplanned revascularization for ischemia, and major bleeding at 30 days. Clinical follow-up will continue for 1 year. CONCLUSIONS: The ACUITY trial is the largest study yet performed in patients with ACS undergoing an invasive strategy. In addition to evaluating the utility of bivalirudin in ACS, this study will also provide important guidance regarding the necessity for and timing of IIb/IIIa inhibitor administration.
Changes in vessel wall elasticity may be indicative of vessel pathologies. It is known, for example, that the presence of plaque stiffens the vascular wall, and that the heterogeneity of its composition may lead to plaque rupture and thrombosis. Another domain of application where ultrasound elastography may be of interest is the study of vascular wall elasticity to predict the risk of aneurysmal tissue rupture. In this paper, this technology is introduced as an approach to noninvasively characterize superficial arteries. In such a case, a linear array ultrasound transducer is applied on the skin over the region of interest, and the arterial tissue is dilated by the normal cardiac pulsation. The elastograms, the equivalent elasticity images, are computed from the assessment of the vascular tissue motion. Investigating the forward problem, it is shown that motion parameters might be difficult to interpret; that is because tissue motion occurs radially within the vessel wall while the ultrasound beam propagates axially. As a consequence of that, the elastograms are subjected to hardening and softening artefacts, which are to be counteracted. In this paper, the Von Mises (VM) coefficient is proposed as a new parameter to circumvent such mechanical artefacts and to appropriately characterize the vessel wall. Regarding the motion assessment, the Lagrangian estimator was used; that is because it provides the full two-dimensional strain tensor necessary to compute the VM coefficient. The theoretical model was validated with biomechanical simulations of the vascular wall properties. The results allow believing in the potential of the method to differentiate hard plaques and lipid pools from normal vascular tissue. Potential in vivo implementation of noninvasive vascular elastography to characterize abdominal aneurysms and superficial arteries such as the femoral and the carotid is discussed.
Atherothrombotic disease is a growing health problem, and is increasingly more costly to manage. Clopidogrel is an advanced, specific adenosine diphosphate receptor antagonist, which has been shown to be a highly potent antiplatelet agent. Data from the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) study have demonstrated the significantly superior clinical benefit of clopidogrel over aspirin for secondary prevention of atherothrombotic disease, with a relative risk reduction in myocardial infarction, stroke or vascular death of 8.7% (95% confidence interval 0.3, 16.5; P = 0.043). Moreover, clopidogrel demonstrated an amplified clinical benefit versus aspirin in patients at high risk of atherothrombotic events, such as those with a previous history of symptomatic atherothrombotic disease or with major risk factors such as diabetes mellitus or hypercholesterolaemia. On the basis of commonly accepted threshold criteria (Euros 20000 per life-year gained; LYG), clopidogrel in comparison with aspirin is cost-effective for the secondary prevention of atherothrombotic disease (cost per LYG ranging from Euros 19462 to Euros 3256). Economic analyses have demonstrated consistent cost-effectiveness results with clopidogrel in different countries. Moreover, in high-risk patient subgroups the cost-effectiveness of clopidogrel in comparison with aspirin was evenbetter (cost per LYG ranging from Euros 5900 to Euros 6310). Compared with other treatment strategies used for the prevention of ischaemic or atherothrombotic events, the cost-effectiveness of clopidogrel in comparison with aspirin based on CAPRIE is favourable, with most analyses in the intermediate range of cost-effectiveness. The available data thus support the use of clopidogrel as a clinically efficient and cost-effective option for secondary prevention of atherothrombotic disease, particularly in high-risk patients.
The recent multinational, randomised, prospective studies Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE), Percutaneous Coronary Intervention substudy of CURE (PCI-CURE) and Clopidogrel for the Reduction of Events During Observation (CREDO) have demonstrated the clinical efficacy and safety of clopidogrel for the treatment of patients with non-ST-segment elevation acute coronary syndromes (ACS), including those undergoing percutaneous coronary intervention. In these settings, clopidogrel significantly reduces the risk of atherothrombotic events, with relative risk reductions of 20-30% (absolute risk reduction 1.9-3.0%). Health economic evaluations based on data from these studies conducted in Europe and the United States have clearly demonstrated the cost-effectiveness of clopidogrel in combination with aspirin compared with aspirin alone for the management of ACS. Within-trial evaluations based on CURE and PCI-CURE data showed that treatment with clopidogrel on top of standard therapy reduced the cost of initial hospitalisation as well as the total cost associated with hospitalisations. Long-term economic analyses based on the CURE study demonstrate that clopidogrel is cost saving in the Netherlands and that the cost per life-year gained (LYG) in other European countries is between Euros 549 and Euros 5048. In the United States, the cost per LYG for clopidogrel has been assessed at US dollars 6173 on the basis of CURE, US dollars 5910 for PCI-CURE and US dollars 3685 for CREDO, all of which are considerably lower than that associated with common cardiovascular benchmarks. The results are robust and consistent across different countries using varying costing strategies and estimates of survival. In conclusion, these data demonstrate that clopidogrel in combination with aspirin for the management of ACS is both clinically effective and cost-effective in this setting.
Pterygosoma livingstonei sp. n. collected from the Kenyan lizard Agama caudospinosa Meek shows morphological affinities with other South African congener species parasitizing lizards of the genus Agama, especially with P. triangulare Lawrence, 1936, but it differs in having glabrous genua II and III. P. livingstonei shows affinities with the Lawrence's hispida species group in the characters of genital and peripheral setae. This new species was found concentrated in a nuchal "mite pocket-like structure", a behaviour previously unreported among species belonging to the genus Pterygosoma. Mite pockets (or acarodomatia, acarinaria) of lizards typically house damaging chigger mites, and are usually interpreted as the evolutionary host's response to limit damage caused by parasites. Because scale mites are permanent ectoparasites and less damaging than seasonally occurring larval trombiculids, the heavy infestation by P. livingstonei in the nuchal skin folds of its host is interpreted as a consequence of the best utilisation of an available protected site by these mites that spend their entire life cycle on their host and whose primitive body shape prevents them from seeking shelter beneath the scales of their lizard host.
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BACKGROUND: The platelet glycoprotein IIb/IIIa receptor inhibitor abciximab, a monoclonal antibody, has been shown to improve early and late outcomes among diabetic patients undergoing percutaneous coronary intervention (PCI). It is unknown whether small-molecule agents confer similar benefits. METHODS AND RESULTS: In 18 countries, 4809 patients undergoing PCI with stent implantation were randomized to tirofiban or abciximab. At the time of enrollment, patients were stratified according to diabetes status. As compared with non-diabetic patients, patients with diabetes (n=1117) showed similar 30-day ischemic outcomes, an increased incidence of any target vessel revascularization (TVR) at 6 months (10.3% versus 7.8%; P= 0.008), and a trend toward higher 1-year mortality (2.5% versus 1.6%; P=0.056). Among diabetic patients randomized to tirofiban (n=560), the incidence of death, myocardial infarction (MI), or urgent TVR at 30 days was 6.2%, and among those randomized to abciximab (n=557) it was 5.4% (hazard ratio [HR] 1.16; P=0.540). At 6 months, the composite of death, MI, or any TVR occurred in 15.7% and in 16.9% of tirofiban and abciximab patients, respectively (HR 0.93; P=0.610). Any TVR occurred in 9.5% and 11.1%, respectively (HR 0.84; P= 0.366). The 1-year mortality was 2.1% in the tirofiban group and 2.9% in the abciximab group (HR 0.74; P= 0.436). CONCLUSIONS: Among diabetic patients undergoing PCI, tirofiban and abciximab were associated with comparable event rates, including similar rates of 6-month TVR and 1-year mortality. These findings suggest that the non-glycoprotein IIb/IIIa properties of abciximab do not translate into a discernible long-term clinical benefit among diabetic patients.
BACKGROUND: Although glycoprotein IIb/IIIa inhibitors have been shown to reduce periprocedural and late ischemic events in patients undergoing stent implantation, the relative safety and efficacy of different agents in this class is less established. Also unknown is whether the acuity of the presenting clinical syndrome, which may affect the degree of platelet inhibition required or achieved, influences the response to different antiplatelet agents. METHODS AND RESULTS: A prospective, multicenter, double-blind, randomized trial was performed in which 4809 patients undergoing planned stenting were randomized to receive abciximab or tirofiban. In patients with acute coronary syndromes (ACS; n=3025), abciximab resulted in lower rates of myocardial infarction at 30 days (5.8% versus 8.5%; P=0.004) and 6 months (7.2% versus 9.8%; P=0.013), although 6-month mortality rates were identical (1.39% in both groups; P=0.99). Conversely, in patients without ACS (n=1784), myocardial infarction rates were not significantly lower with tirofiban, survival was similar, and target vessel revascularization was reduced, which translated into a trend toward enhanced 6-month event-free survival with tirofiban (89.7% versus 86.6%; P=0.056). CONCLUSIONS: In patients with ACS undergoing stent implantation, abciximab use compared with tirofiban results in greater suppression of periprocedural myonecrosis, although a survival benefit has not been demonstrated. Patients with stable coronary syndromes may have equivalent or better outcomes with tirofiban relative to abciximab, with fewer adverse hematologic and hemorrhagic events. These data raise important issues regarding the relative pharmacodynamic inhibition of platelet function required in varying clinical scenarios and have important implications for the cost-effective utilization of glycoprotein IIb/IIIa inhibitors.
Elastography is an imaging technique based on strain estimation in soft tissues under quasi-static compression. The stress is usually created by a compression plate, and the target is imaged by an ultrasonic linear array. This configuration is used for breast elastography, and has been investigated both theoretically and experimentally. Phenomena such as strain decay with tissue depth and strain concentrations have been reported. However in some in vivo situations, like prostate or blood vessels imaging, this set-up cannot be used. We propose a device to acquire in vivo elastograms of the prostate. The compression is applied by inflating a balloon that covers a transrectal sector probe. The 1D algorithm used to calculate the radial strain fails if the center of the imaging probe does not correspond to the center of the compressor. Therefore, experimental elastograms are calculated with a 2D algorithm that accounts for tangential displacements of the tissue. In this article, in order to gain a better understanding of the image formation process, the use of ultrasonic sector scans to image the radial compression of a target is investigated. Elastograms of homogeneous phantoms are presented, and compared with simulated images. Both show a strain decay with tissue depth. Then experimental and simulated elastograms of a phantom that contains a hard inclusion are presented, showing that strain concentrations occur as well. A method to compensate for strain decay and therefore to increase the contrast of the strain elastograms is proposed. It is expected that such information will help to interpret and possibly improve the elastograms obtained via radial compression.