Biomedical subjects

Dominique Deplanque

Publications and source records attributed to Dominique Deplanque.

At least 19 recordsLinked to original sources

PubMed2006

Antithrombotic agents' use in patients with atrial fibrillation and acute cerebral ischemia.

BACKGROUND: although trials suggest a benefit of aspirin, and not of anticoagulation (AC), in the acute stage of cerebral ischemia associated with atrial fibrillation (AF), many neurologists still use heparin. OBJECTIVE: to evaluate how antithrombotic agents were used at the acute stage of cerebral ischemia in AF patients after the publication of trials and guidelines. METHODS: we reviewed the charts of all patients with AF who were admitted between 1996 and 2002 as primary care patients, within 48 hours after onset of an ischemic stroke (IS) or transient ischemic attacks (TIAs). We recorded the first antithrombotic treatment prescribed at admission. RESULTS: in 763 consecutive patients (42% men; median age 79 years), the use of AC on admission decreased over time from 70% to 22% (p<0.001), while antiplatelet agents increased from 27% to 78% (p<0.001). Patients who received AC were more likely to be younger, to have a Barthel index >60, no hemorrhagic changes, and to have been admitted in 1996 or 1997. Results were similar between patients with IS and TIAs and in patients who were not under AC before. In patients who were under oral AC before, AC use at admission did not decline over time (p=0.366). CONCLUSION: there was a clear decrease in AC use during the study period, except in patients who were already under AC before, and in TIA patients.

Acute Disease↗

PubMed2006

Insular infarcts and electrocardiographic changes at admission: results of the PRognostic of Insular CErebral infarctS Study (PRINCESS).

BACKGROUND AND PURPOSE: Previous studies showed that insular strokes are associated with electrocardiographic (ECG) changes. However, they did not take into account the 1(st) ECG recorded at admission, but continuous ECG recorded up to 72 hours after onset. Whether these changes are the consequence of the infarct, or are associated with a cardiac source of cerebral ischemia, remains unsettled. If ECG changes are the consequence of insular infarcts, they should not have developed by the time of admission. The aim of this study was to test the hypothesis that ECG changes in patients with insular infarcts are not present at admission. METHODS: We recruited consecutive patients admitted within 48 hours (median 3 hours) after the onset of symptoms of acute hemispheric cerebral ischemia. We compared ECG variables between patients with and without insular infarcts, and with left and right insular infarcts. RESULTS: The study population consisted of 208 patients (94 men; median age: 69 years). Seventy patients had a recent insular infarct (right in 33). ECG variables did not significantly differ between patients with and without insular infarcts, and with left and right insular infarcts. These results were not explained by a lack of statistical power (1-beta >/= 0.90). CONCLUSION: The lack of statistical link between insular infarcts and ECG changes at admission, suggests that ECG changes are not associated with the cause of insular infarcts, but are their consequence.

Adolescent↗

PubMed2006

Influence of dementia on antithrombotic therapy prescribed before stroke in patients with atrial fibrillation.

BACKGROUND AND PURPOSE: Oral anticoagulation (OAC) decreases the risk of stroke in patients with nonvalvular atrial fibrillation (NVAF), but remains underused in practice. The aim of this study was to test the hypothesis that prestroke dementia influenced the nonprescription of OAC before stroke. METHODS: This is an ancillary study of Stroke in Atrial Fibrillation Ensemble II, an observational study conducted in patients with a previously known NVAF, consecutively admitted for an acute stroke to French and Italian centers. Prestroke dementia was evaluated by the clinical physician and validated by an Informant Questionnaire for Cognitive Decline in the Elderly score of >or=104 in patients with a reliable informant. RESULTS: Of 204 patients, 24 patients met criteria for prestroke dementia according to GP's opinion. The only variables independently associated with OAC before stroke were follow-up by a cardiologist (adjusted OR: 3.33; 95% CI: 1.47-7.53) and a younger age of patients (adjusted OR: 0.94; 95% CI: 0.89-0.99). Variables independently associated with any antithrombotic drug therapy before stroke were follow-up by a general practitioner (adjusted OR: 2.78; 95% CI: 1.09-7.11), and by a cardiologist (adjusted OR: 3.15; 95% CI: 1.48-6.69). CONCLUSION: In daily practice, the under-prescription of OAC in patients with NVAF mainly depends on co-morbidity and on characteristics of the physician, not on prestroke dementia.

Administration, Oral↗

PubMed2006

Secondary prevention of stroke in patients with atrial fibrillation: factors influencing the prescription of oral anticoagulation at discharge.

BACKGROUND: Oral anticoagulation (OAC) is the only treatment that has shown a significant benefit to reduce the risk of recurrence in patients with ischemic stroke and nonvalvular atrial fibrillation (NVAF). However, OAC is still underused, even at discharge from neurological centers. The objective of this study was to identify the reasons underlying the prescription of OAC at discharge after an ischemic stroke in patients with NVAF. METHODS: We investigated the reasons why ischemic stroke patients with NVAF were not treated with OAC at discharge from 40 centers located in 5 European countries (Austria, Belgium, France, Italy, and Portugal). RESULTS: Of 320 ischemic stroke survivors at discharge, 186 (58.1%) received OAC, while 260 (81.3%) patients were theoretically eligible according to guidelines and the absence of contraindications. There were significant differences between countries and the logistic regression analysis found being already under OAC before stroke, having no leukoaraiosis, having no potential contraindication, being younger than 75 years, being married and suffering from angina pectoris as independent predictors of being discharged under OAC. CONCLUSION: This study suggests that besides patient-related factors, the prescription of OAC is also significantly influenced by the social environment and national practices.

Administration, Oral↗

PubMed2005

Secondary prevention after ischemic stroke. Evolution over time in practice.

BACKGROUND AND OBJECTIVE: An optimal management of vascular risk factors, associated with antithrombotic drugs and carotid surgery when appropriate, reduces the risk of a new vascular event after stroke. Although secondary prevention is not optimal in many patients in practice, the question of whether there is an improvement over time remains unanswered. The aim of our study was to test the hypothesis that secondary prevention measures after cerebral ischemia improve over time. METHOD: We included 123 consecutive patients in 1994, and 125 consecutive patients in 2002, who were admitted to a neurological department for any reason and had had an episode of cerebral ischemia less than 6 years earlier. We compared the groups for the management of arterial hypertension, hypercholesterolemia, diabetes mellitus and smoking. We recorded the values of blood pressure, biological parameters, and presence of antithrombotic therapy, lipid-lowering and anti-hypertensive drugs. Whether patients were properly treated or not, was determined by a comparison between their current treatment and guidelines available when recruited. RESULTS: Prevention was not optimal in 96 of 123 (78%) patients in 1994, and in 77 of 125 (62 %) in 2002. Vascular risk factors were better identified and managed in 2002 than in 1994, especially for hypercholesterolemia. Antithrombotic therapies, statins and antihypertensive drugs, except calcium channel blockers, were more often used in 2002. The proportion of patients in whom arterial hypertension and hypercholesterolemia were identified was higher in 2002, but the proportion of patients identified as diabetics remained stable. However, the proportion of patients with blood pressure >140/90 mmHg, glycemia >or = 126 mg/dl, total cholesterol level > or = 240 mg/dl, or being current smokers, were significantly lower in 2002 than in 1994. CONCLUSION: Although most of patients with previous cerebral ischemia did not receive an optimal management of their risk factors in 2002, there was an improvement over an 8-year period.

Aged↗

PubMed2004

Brain ischemic preconditioning is abolished by antioxidant drugs but does not up-regulate superoxide dismutase and glutathion peroxidase.

The present work examined the hypothesis that brain ischemic tolerance induced by ischemic preconditioning (IPC) is triggered by an initial oxidative stress and is associated with an increase in antioxidant enzyme activities as one end-effector of the neuroprotection. Wistar rats were preconditioned by a single 3-min occlusion of the middle cerebral artery. After a various duration of reperfusion (30 min, 24, 72 or 168 h), rats were subjected to a 60-min focal ischemia and sacrificed 24 h later. Cerebral infarcts were significantly reduced when performed during the 24- to 72-h time window after IPC. The pretreatment with the protein synthesis inhibitor, cycloheximide (1 mg/kg, i.p., 30 min prior to IPC), completely suppressed the neuroprotection. The free radical scavenger, dimethylthiourea (DMTU; 300 mg/kg, i.p., 30 min prior to IPC) and the antioxidant ebselen (10 mg/kg, oral cramming, 2 h before and 12 h after IPC) also abolished the IPC-induced protection of the brain. Nevertheless, IPC did not induce any delayed changes in antioxidant enzyme (superoxide dismutase, glutathion peroxidase) activities nor in the neuronal expression of Mn and Cu/Zn superoxide dismutase. These results indicate that an initial oxidative stress could be involved as a trigger of IPC, while antioxidant enzymes do not play a key role as end-effectors in such a neuroprotection.

Analysis of Variance↗

PubMed2004

Comparison of secondary vascular prevention in practice after cerebral ischemia and coronary heart disease.

BACKGROUND: Secondary prevention measures in patients with cerebral ischemia or coronary heart disease (CHD) consist of vascular risk factors management and antithrombotic therapy. The aim of this study was to compare how secondary prevention measures are applied in practice between patients with a history of CHD or cerebral ischemia. METHOD: We compared vascular risk factors management and antithrombotic therapy between patients with a history of CHD and patients with a history of cerebral ischemia that occurred 2 months to 6 years earlier. Whether patients were properly treated or not was determined by a comparison between their current treatments and European guidelines for stroke and CHD management. RESULTS: We included 107 consecutive patients with a history of cerebral ischemia and 85 consecutive patients with a history of CHD. We found that: (i). most patients did not receive an appropriate secondary prevention in both groups: 76 of 107 patients with previous cerebral ischemia (71 %) and 73 of 85 patients with CHD (85.9 %); (ii). identification of risk factors, such as hypercholesterolemia, diabetes mellitus and smoking, did not differ between both groups, but arterial hypertension was more frequent in CHD patients; (iii). an inappropriate management of risk factors was more frequent in patients with TIA vs. ischemic stroke, and angina pectoris vs. myocardial infarction; (iv). arterial hypertension and hypercholesterolemia were the 2 more frequent risk factors that were not properly treated; (v). more than half diabetic patients had hyperglycemia > or= 126 mg/dl in both groups; (vi). patients with previous CHD had twice more frequently stopped smoking than those with cerebral ischemia. CONCLUSION: Many patients were not properly treated in both groups, and differences between practice and guidelines were more frequent in the CHD group, where guidelines are more strict.

Aged↗

PubMed2004

Mean Deviation of Inter-rater Scoring (MDIS): a simple tool for introducing conformity into groups of clinical investigators.

In spite of considerable progress over the past decade, training investigators for inter-rater reliability for clinical trials remains a major problem. The aim of the present study was to promote a new tool to increase data homogeneity by introducing conformity into groups of clinical investigators. The investigators scoring grid we are proposing-the Mean Deviation of Inter-rater Scoring (MDIS)-involves the calculation of the score deviation for each investigator relative to the median score of an expert group who had evaluated the same videotape-recorded clinical case. Whatever the scale, the score deviation is calculated as the absolute deviation value from the median score obtained by the experts for each item. The MDIS value is then evaluated from all the scores given by an investigator by dividing the total sum of the previously defined values by the number of items of the scale. Some examples from practice are given using several rating scales: (i) Hamilton Anxiety Rating Scale; (ii) Hamilton Depression Rating Scale; (iii) Montgomery Asberg Depression Rating Scale; and (iv) Positive And Negative Symptoms Scale. Finally, such a method could also be employed by experts to evaluate the quality of videotape-recorded clinical cases used in clinical trials, as well as by teachers to evaluate initial or continuous medical training.

Anxiety Disorders↗

PubMed2004

Stroke prevention and atrial fibrillation: reasons leading to an inappropriate management. Main results of the SAFE II study.

AIMS: The aim of the Stroke and Atrial Fibrillation Ensemble (SAFE) II study was to identify the reasons underlying the under-utilization of oral anticoagulation (OAC) in patients with nonvalvular atrial fibrillation (NVAF). METHODS: We investigated from all available sources the reasons why patients hospitalized for a stroke, who had a previously known NVAF, were not receiving OAC beforehand. We interviewed general practitioners (GPs) and cardiologists with a structured questionnaire, to identify the reasons for their therapeutic choice. RESULTS: Of 370 patients, 257 were theoretically eligible for OAC according to guidelines and the presence of contra-indications, but only 82 (22.2%) of them had actually received OAC before. We found that factors independently associated with the prescription of OAC were being followed-up by a cardiologist and having a younger GP. The leading reason evoked by GPs or cardiologists to explain why patients were not treated with OAC was the presence of a 'potential contra-indication', which was often inappropriate, followed by 'there was no indication', 'low compliance' and 'fear of bleeding'. CONCLUSIONS: An important reason for not prescribing OAC was the lack of knowledge about trials and guidelines. Medical education about OAC in NVAF should therefore be improved.

Aged↗

PubMed2003

Involvement of thrombolysis in recombinant tissue plasminogen activator-induced cerebral hemorrhages and effect on infarct volume and postischemic endothelial function.

BACKGROUND AND PURPOSE: In a model of mechanical focal ischemia, we investigated the involvement of thrombolysis products (TLP) in recombinant tissue plasminogen activator (rtPA)-induced intracerebral complications and the effects on infarct volume and postischemic endothelial function. METHODS: Hemorrhage incidence and severity were evaluated by histomorphometric analysis in male spontaneously hypertensive rats (SHR) subjected to 60-minute intraluminal middle cerebral artery (MCA) occlusion and receiving intravenously 5 hours later either saline, rtPA (3, 10, or 30 mg/kg), or rtPA (10 mg/kg) associated with TLP (rtPA+TLP). In addition, MCA reactivity was assessed in rtPA- or rtPA+TLP-treated SHR versus control Wistar-Kyoto rats or SHR. RESULTS: No hemorrhage was observed visually in SHR receiving saline. In contrast, rtPA administration induced hemorrhagic complications in infarcted areas in a dose-independent manner. Administration of rtPA+TLP solution, containing a high concentration of plasmin, did not affect hemorrhage incidence but significantly increased hemorrhage severity (8.8+/-2.3 petechiae versus 3.0+/-1.0 petechiae in rtPA group; P<0.001). This increased severity was associated with a significant increase of both infarct volume (182+/-10 versus 144+/-15 mm3 in rtPA group; P<0.01) and postischemic impairment of MCA endothelium-dependent relaxation (9+/-0.5% versus 13+/-1% in rtPA group; P<0.05). CONCLUSIONS: Treatment with rtPA led to intracerebral hemorrhages, in contrast to saline-treated animals, and the presence of TLP increased the severity of these hemorrhages, in parallel with increased infarct volume and worsened endothelial function.

Animals↗

PubMed2003

Peroxisome proliferator-activated receptor-alpha activation as a mechanism of preventive neuroprotection induced by chronic fenofibrate treatment.

The treatment of ischemic strokes is limited to the prevention of cerebrovascular risk factors and to the modulation of the coagulation cascade during the acute phase. A new therapeutic strategy could be to preventively protect the brain against noxious biological reactions induced by cerebral ischemia such as oxidative stress and inflammation to minimize their neurological consequences. Here, we show that a peroxisome proliferator-activated receptor (PPAR-alpha) activator, fenofibrate, protects against cerebral injury by anti-oxidant and anti-inflammatory mechanisms. A 14 d preventive treatment with fenofibrate reduces susceptibility to stroke in apolipoprotein E-deficient mice as well as decreases cerebral infarct volume in C57BL/6 wild-type mice. The neuroprotective effect of fenofibrate is completely absent in PPAR-alpha-deficient mice, suggesting that PPAR-alpha activation is involved as a mechanism of the protection against cerebral injury. Furthermore, this neuroprotective effect appears independently of any improvement in plasma lipids or glycemia and is associated with (1) an improvement in middle cerebral artery sensitivity to endothelium-dependent relaxation unrelated to an increase in nitric oxide synthase (NOS) type III expression, (2) a decrease in cerebral oxidative stress depending on the increase in numerous antioxidant enzyme activities, and (3) the prevention of ischemia-induced expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in cerebral vessels without any change in NOS II expression. These data demonstrate that PPAR-alpha could be a new pharmacological target to preventively reduce the deleterious neurological consequences of stroke in mice and suggest that PPAR-alpha activators could preventively decrease the severity of stroke in humans.

Animals↗

PubMed2003

Delayed cerebrovascular protective effect of lipopolysaccharide in parallel to brain ischemic tolerance.

Cerebrovascular abnormalities, in endothelium and smooth muscle compartments, occur in the course of cerebral ischemia-reperfusion as evidenced by the impairment of endothelium-dependent relaxation and decrease in potassium inward rectifier density in occluded middle cerebral arteries (MCAs). The authors investigated whether a delayed vascular protection occurred in a model of brain ischemic tolerance. A low dose of lipopolysaccharide (0.3 mg/kg) administered 72 h before MCA occlusion induced a significant decrease in infarct volume. In parallel to this delayed neuroprotective effect, lipopolysaccharide prevented the ischemia-reperfusion-induced impairment of endothelium relaxation. In addition, lipopolysaccharide prevented the postischemic alteration of potassium inward rectifier-dependent smooth muscle relaxation as well as the decrease in potassium inward rectifier density measured by patch-clamp in dissociated vascular smooth muscle cells originated from the occluded MCA. These results suggest that during brain ischemic tolerance, lipopolysaccharide is able to induce both a delayed neuroprotective and vasculoprotective effect.

Animals↗

PubMed2002

Stroke prevention: management of modifiable vascular risk factors.

Stroke prevention is a crucial issue because (i) stroke is a frequent and severe disorder, and (ii) acute stroke therapies that are effective at the individual level have only a little impact in term of public health. Stroke prevention consists of the combination of 3 strategies: an optimal management of vascular risk factors, associated when appropriate with antithrombotic therapies, carotid surgery, or both. Primary prevention trials have shown that reducing blood pressure in hypertensive subjects reduces their vascular risk, including stroke. The association of perindopril plus indapamide reduces the vascular risk in patients who have had a stroke or TIA during the last 5 years, irrespective of their baseline blood pressure. Lowering serum cholesterol with statins or gemfibrozil in patients with hypercholesterolemia or coronary heart disease (CHD), reduces the risk of stroke. However, no trial of cholesterol-lowering therapy has been completed in stroke patients. A strict control of high cholesterol levels should be encouraged, because of benefits in terms of CHD. Statins should be prescribed for stroke patients with CHD, or increased cholesterol levels. Cigarette smoking is associated with an increased risk of stroke and should be avoided. Careful control of all risk factors, especially arterial hypertension in type 1 and type 2 diabetics is recommended, together with a strict glycemic control to reduce systemic microvascular complications. Estrogens prescribed in hormone replacement or oral contraceptive therapies are not recommended after an ischemic stroke. It is also recommended to reduce alcohol consumption and obesity, and to increase physical activity in patients at risk for first-ever or recurrent stroke. An optimal management of risk factors for stroke is crucial to reduce the risks of first-ever stroke, recurrent stroke, any vascular event after stroke and vascular death. One of the major public health issues for the coming years will be to focus more on risk factor recognition and management.

Alcoholism↗

PubMedDate not supplied

Atrial fibrillation and stroke: from scientific evidence to practice.

Nonvalvular atrial fibrillation (NVAF) is the most frequent cause of cardioembolic stroke. Due to the aging of the population, NVAF is becoming an important public health issue. Despite the impressive results of trials with oral anticoagulation (OAC) in primary and secondary prevention of stroke in NVAF patients, OAC remains underused or misused in practice. Beyond the risk of bleeding, there also are several arguments for a lack of knowledge about trials and guidelines. Medical education could then be one of the most effective way to improve stroke prevention in NVAF patients in practice.

Anticoagulants↗

PubMedDate not supplied

Thrombolysis beyond the three-hour time window.

Intravenous (i.v.) thrombolysis with tissue plasminogen activator (rt-PA, i.v. 0.9 mg/kg body weight) has been approved by European health authorities in 2002, with a 3-hr time window. The meta-analysis of i.v. rt-PA trials suggests efficacy of rt-PA up to 4.5 to 6 hr. However, treatment efficacy declines rapidly over time: the numbers of patients needed to treat to prevent 1 death or dependency are respectively 7, 12, and > 30 in the 0-3 hr, 0-6 hr, and 3-6 hr time windows. Magnetic resonance imaging may be the best way to select candidates for thrombolysis beyond 3 hr, on the basis of the presence of arterial occlusion and mismatch between diffusion and perfusion images. New trials are testing the possibility of extending the time window. Trials with new thrombolytic agents, ultrasound thrombolysis, and mechanical thrombolysis also are running or planned in the 3- to 6-hr time window. The 3-hr limit is just a matter of safety. Patients should be treated as soon as possible, and the earliest is the best.

Drug Administration Schedule↗

PubMedDate not supplied

Hypolipemic agents for stroke prevention.

An important issue for stroke prevention is identification and treatment of risk factors such as hypercholesterolemia. The four reasons to test hypolipidemic agents in stroke prevention are: (i) a statistical link between elevated low-density lipoprotein cholesterol (LDL-c) or decreased high-density lipoprotein cholesterol (HDL-c) and ischemic stroke; (ii) a reduction in vascular risk in randomized trials in patients with coronary heart disease; (iii) evidence of a decreased plaque progression under statins, (iv) pooled analyses of primary and secondary prevention trials showing that reduction of total serum cholesterol reduces the incidence of stroke, especially with the highest rate of cholesterol reduction, and in patients with the highest risk of stroke (i.e., with statins in secondary prevention trials), and (v) prophylactic neuroprotection induced by hypolipidemic agents in animal models of cerebral ischemia. Data provided by trials conducted in subjects with coronary heart disease and in asymptomatic individuals should now be confirmed in stroke patient.

Animals↗

PubMedDate not supplied

Statins and stroke.

An important issue for stroke prevention is the identification and treatment of risk factors such as hypercholesterolaemia. The 4 reasons to test if the statins have a role in stroke prevention are: (i) a statistical link between elevated low density lipoprotein-cholesterol or decreased high density lipoprotein-cholesterol and ischaemic stroke; (ii) a reduction in vascular risk with statins in randomised trials in patients with coronary heart disease; (iii) evidence of a decreased plaque progression under statins; and (iv) pooled analyses of primary and secondary prevention trials showing that reduction of total serum cholesterol reduces the incidence of stroke, especially with the highest rate of cholesterol reduction, and in patients with the highest risk of stroke (i.e. with statins in secondary prevention trials). The question of whether statins also have a neuroprotective effect in humans and reduce the risk of post-stroke dementia remains unsettled.

Animals↗

PubMedDate not supplied

[Antilipemics: from prevention to protection].

Statins and fibrates have been demonstrated to prevent both cardiovascular events and stroke. While this preventive effect was initially thought to be related to their lipid-lowering effects, in particular hypocholesterolaemic effect, analysis of primary and secondary prevention trials suggest that these preventive effects could be partly independent of their effects on lipid disorders. The pleiotropic effects, such as vascular, anti-inflammatory or anti-oxidants effects, were described for both the statins and fibrates. In addition to the preventive effects, these pleiotropic effects could partially explain the decrease in myocardial or cerebral ischemia consequences in experimental models. These cellular protective effects may have a therapeutic interest to decrease severity of stroke or coronary acute syndrome. They could also explain the drugs' lipid-lowering preventive effects independent of the treatment of lipid disorders. Beyond vascular pathologies, the pleiotropic effects of lipid-lowering drugs could explain their potentially beneficial effect in different diseases, such as dementia or cancer.

Anticholesteremic Agents↗