Prise en charge des patients douloureux chroniques (analyse de besoins des patients vis-à-vis de leurs médicaments antalgiques)

La douleur chronique et ses conséquences plurielles sur la vie quotidienne des personnes qui en souffrent, nécessitent une prise en charge complexe, personnalisée et adaptée à chaque patient. Une analyse de besoins des patients douloureux chroniques centrée sur leurs médicaments antalgiques a été envisagée à l aide d auto-questionnaires distribués auprès de patients douloureux chroniques (hors douleur cancéreuse) fréquentant différents types d établissements (centres hospitaliers, officines, cabinets médicaux). Le profil des 86 patients ayant répondus à cette enquête est représentatif de la population douloureuse chronique. Les patients expriment un besoin d informations important quant à leurs effets indésirables et à la gestion de leur traitement au quotidien. Ils aimeraient également que les soignants soient plus à l écoute . De plus, ils seraient intéressés par des rencontres entre patients afin d échanger sur les stratégies possibles pour la prise en charge de leur douleur chronique. Plusieurs pistes d actions peuvent être proposées : formations des soignants développant des connaissances professionnelles et des compétences en communication / création d offres éducatives ciblant la problématique des effets indésirables, imaginant des outils d aide à la gestion du traitement au quotidien, associant des séances de groupe et des entretiens individuels, par exemple à l officine / renforcer les offres de soutien et d évaluation des besoins au cours du temps Ces différentes propositions pourraient compléter les offres éducatives existantes. De plus, il semble nécessaire de continuer à renforcer les liens entre les soignants afin d optimiser leur prise en charge.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

Early Ultrafast Ultrasound Imaging of Cerebral Perfusion correlates with Ischemic Stroke outcomes and responses to treatment in Mice

International audienceIn the field of ischemic cerebral injury, precise characterization of neurovascular hemodynamic is required to select candidates for reperfusion treatments. It is thus admitted that advanced imaging-based approaches would be able to better diagnose and prognose those patients and would contribute to better clinical care. Current imaging modalities like MRI allow a precise diagnostic of cerebral injury but suffer from limited availability and transportability. The recently developed ultrafast ultrasound could be a powerful tool to perform emergency imaging and long term follow-up of cerebral perfusion, which could, in combination with MRI, improve imaging solutions for neuroradiologists. Methods: In this study, in a model of in situ thromboembolic stroke in mice, we compared a control group of non-treated mice (N=10) with a group receiving the gold standard pharmacological stroke therapy (N=9). We combined the established tool of magnetic resonance imaging (7T MRI) with two innovative ultrafast ultrasound methods, ultrafast Doppler and Ultrasound Localization Microscopy, to image the cerebral blood volumes at early and late times after stroke onset and compare with the formation of ischemic lesions. Results: Our study shows that ultrafast ultrasound can be used through the mouse skull to monitor cerebral perfusion during ischemic stroke. In our data, the monitoring of the reperfusion following thrombolytic within the first 2 h post stroke onset matches ischemic lesions measured 24 h. Moreover, similar results can be made with Ultrasound Localization Microscopy which could make it applicable to human patients in the future. Conclusion: We thus provide the proof of concept that in a mouse model of thromboembolic stroke with an intact skull, early ultrafast ultrasound can be indicative of responses to treatment and cerebral tissue fates following stroke. It brings new tools to study ischemic stroke in preclinical models and is the first step prior translation to the clinical settings

Molecular magnetic resonance imaging discloses endothelial activation after transient ischaemic attack

International audienceAbout 20% of patients with ischaemic stroke have a preceding transient ischaemic attack, which is clinically defined as focal neurological symptoms of ischaemic origin resolving spontaneously. Failure to diagnose transient ischaemic attack is a wasted opportunity to prevent recurrent disabling stroke. Unfortunately, diagnosis can be difficult, due to numerous mimics, and to the absence of a specific test. New diagnostic tools are thus needed, in particular for radiologically silent cases, which correspond to the recommended tissue-based definition of transient ischaemic attack. As endothelial activation is a hallmark of cerebrovascular events, we postulated that this may also be true for transient ischaemic attack, and that it would be clinically relevant to develop non-invasive in vivo imaging to detect this endothelial activation. Using transcriptional and immunohistological analyses for adhesion molecules in a mouse model, we identified brain endothelial P-selectin as a potential biomarker for transient ischaemic attack. We thus developed ultra-sensitive molecular magnetic resonance imaging using antibody-based microparticles of iron oxide targeting P-selectin. This highly sensitive imaging strategy unmasked activated endothelial cells after experimental transient ischae-mic attack and allowed discriminating transient ischaemic attack from epilepsy and migraine, two important transient ischaemic attack mimics. We provide preclinical evidence that combining conventional magnetic resonance imaging with molecular magnetic resonance imaging targeting P-selectin might aid in the diagnosis of transient ischaemic attack

Antibodies Preventing the Interaction of Tissue-Type Plasminogen Activator With N-Methyl- d -Aspartate Receptors Reduce Stroke Damages and Extend the Therapeutic Window of Thrombolysis

International audienceBackground and Purpose— Tissue-type plasminogen activator (tPA) is the only drug approved for the acute treatment of ischemic stroke but with two faces in the disease: beneficial fibrinolysis in the vasculature and damaging effects on the neurovascular unit and brain parenchyma. To improve this profile, we developed a novel strategy, relying on antibodies targeting the proneurotoxic effects of tPA. Methods— After production and characterization of antibodies (αATD-NR1) that specifically prevent the interaction of tPA with the ATD-NR1 of N-methyl- d -aspartate receptors, we have evaluated their efficacy in a model of murine thromboembolic stroke with or without recombinant tPA-induced reperfusion, coupled to MRI, near-infrared fluorescence imaging, and behavior assessments. Results— In vitro, αATD-NR1 prevented the proexcitotoxic effect of tPA without altering N-methyl- d -aspartate-induced neurotransmission. In vivo, after a single administration alone or with late recombinant tPA-induced thrombolysis, antibodies dramatically reduced brain injuries and blood–brain barrier leakage, thus improving long-term neurological outcome. Conclusions— Our strategy limits ischemic damages and extends the therapeutic window of tPA-driven thrombolysis. Thus, the prospect of this immunotherapy is an extension of the range of treatable patients

Efficacy of Alteplase in a Mouse Model of Acute Ischemic Stroke

BACKGROUND AND PURPOSE: The debate over the fact that experimental drugs proposed for the treatment of stroke fail in the translation to the clinical situation, has attracted considerable attention in the literature. In this context, we present a retrospective pooled analysis of a large dataset from pre-clinical studies, in order to examine the effects of early versus late administration of intravenous recombinant tissue type plasminogen activator (rt-PA). METHODS: We collected data from 26 individual studies from 9 international centers (13 researchers, 716 animals) that compared rt-PA to controls, in a unique mouse model of thromboembolic stroke induced by an in situ injection of thrombin into the middle cerebral artery. Studies were classified into early (<3h) versus late (≥3h) drug administration. Final infarct volumes, assessed by histology or MRI, were compared in each study and the absolute differences were pooled in a random-effect meta-analysis. The influence of time of administration was tested. RESULTS: When compared to saline controls, early rt-PA administration was associated with a significant benefit (absolute difference = −6.63 mm(3); 95%CI, −9.08 to −4.17; I(2)=76%) whereas late rt-PA treatment showed a deleterious effect (+5.06 mm(3); 95%CI, +2.78 to +7.34; I(2)=42%, P(int)<0.00001). Results remained unchanged following subgroup analyses. CONCLUSION: Our results provide the basis needed for the design of future pre-clinical studies on recanalization therapies using this model of thromboembolic stroke in mice. The power analysis reveals that a multi-center trial would require 123 animals per group instead of 40 for a single center trial