Biomedical subjects

Marc Hommel

Publications and source records attributed to Marc Hommel.

11 recordsLinked to original sources

PubMed2006

[Stroke centers and stroke networks].

Admission to a stroke unit represents an established and efficient treatment for acute stroke. However, stroke care is yet not enough developed in many countries. In France, the organisational model is based on stroke unit admission for acute stroke patients associated with a network of stroke units covering the majority of the territory. That model fulfils the commitment of equity of access to medical care for the whole population, and optimises use of resources. The task of the five-year organisational plan Schéma régional d'organisation sanitaire is aimed achieve that goal.

Acute Disease↗

PubMed2006

French adaptation and preliminary validation of a questionnaire to evaluate understanding of informed consent documents in phase I biomedical research.

The content of informed consent documents (ICD) is a crucial element in the process of providing information to participants in biomedical research. Clear comprehension of the information, i.e. the ability to understand its meaning and its consequences, is of utmost importance. The objective of this study was to describe the different steps in the French adaptation and preliminary validation of the Qualité de Compréhension des Formulaires d'information et de consentement (QCFic) questionnaire (http://www.lyon.inserm.fr/cic-grenoble) based on the American Quality of Informed Consent (QuIC) questionnaire. Adaptation and preliminary validation of the QuIC for use in France was composed of five principal steps: translation, scientific validation, lexical validation, edition of gold-standard answers and a pilot study. Each stage was conducted by independent groups of experts, under the coordination of the study board. Thirteen questions were added and one was suppressed. Two steps were required for the scientific validation and for lexical validation, 21 modifications were proposed. Relative to gold-standard answers, the three experts gave the same answer for 24 questions and for nine other questions, two of the three gave identical answers, which were validated by the study board. Results of a pilot study showed a global QCFic score of 88.99 (84.13-90.92) and no specific commentary was made about the content of the questions, so no more modification needed to be made. A preliminary validated French questionnaire, the QCFic, is now available to evaluate the quality of an informed consent document in phase I clinical trials. It is quick and easy to use.

Adult↗

PubMed2005

Vicarious function within the human primary motor cortex? A longitudinal fMRI stroke study.

While experimental studies in the monkey have shown that motor recovery after partial destruction of the hand motor cortex was based on adjacent motor reorganization, functional MRI (fMRI) studies with isolated primary motor cortical stroke have not yet been reported in humans. Based on experimental data, we designed a study to test if recovery after stroke within primary motor cortex (M1) was associated with reorganization within the surrounding motor cortex, i.e. the motor cortex was able to vicariate. Since motor recovery is time-dependent and might be inflected according to the tested task, the delay after stroke and two motor tasks were included in our design. We examined four patients with one ischaemic stroke limited to M1, and four sex- and age-matched healthy controls in a temporally balanced prospective longitudinal fMRI study over three sessions: <20 days, 4 months and 2 years after stroke. The paradigm included two motor tasks, finger tapping (FT) and finger extension (FE). Distinct patterns of motor activation were observed with time for FT and FE. At the first session, FT-related activation was lateralized in the ipsilateral hemisphere while FE-related activation was contralateral, involving bilateral cerebellar regions for both tasks. From 4 months, skilled motor recovery was associated with contralateral dorsal premotor and sensorimotor cortex and ipsilateral cerebellum motor-related activations, leading to lateralized motor patterns for both tasks. For the left recovered hand, FT and FE-related activations within M1 were more dorsal in patients than in controls. This dorsal shift progressively increased over 2 years, reflecting functional reorganization in the motor cortex adjacent to the lesion. In addition, patients showed a reverse representation of FT and FE within M1, corresponding to a greater dorsal shift for FT than for FE. This functional dissociation might reflect the structural subdivision of M1 with two distinct finger motor representations within M1. Recovery of FT, located within the lesioned depth of the rolandic sulcus in controls, might be related to the re-emergence of a new representation in the intact dorsal M1, while FE, located more dorsally, underwent minor reorganization. This is the first fMRI study of humans presenting with isolated M1 stroke comparable with experimental lesions in animals. Despite the small number of patients, our findings showing the re-emergence of a fingers motor task in the intact dorsal M1 instead of in ventral M1 are consistent with 'vicariation' models of stroke recovery.

Aged↗

PubMed2005

Impact of French 'Comités de Protection des Personnes' on the readability of informed consent documents (ICD) in biomedical research: more information, but not better information.

Information is the keystone to the participation of subjects in biomedical research. Clear comprehension of the informed consent documents (ICDs) is primordial and a necessary requirement is that they are readable. While submission of a protocol to a French 'Comités de Protection des Personnes' (CPP) is a mandatory step with regard to the French legislation on biomedical research, no published data are available concerning its influence on ICDs readability. The aim of our study was to determine the impact of French CPP on the readability of ICDs, using lexico-syntactic readability indexes and ICDs from four clinical research centres and one clinical research unit. Twenty-five ICDs were analysed. The Flesch score was not modified after CPP review, while the Cordial score was significantly lower [from 4 (1-14) to 1 (1-13), P = 0.014]. The information was longer and more complex following CPP review. No protocol characteristics had any impact on the variation before and after review for either the Flesch or the Cordial indexes, nor on the number of syllables per word. Changes in the total number of words before and after review varied considerably between study centre, supporting heterogeneity of CPP review. Since August 2004, French CPP have to study the intelligibility of ICDs in addition to the scientific and ethic aspects of a research. We show that their current reviews do not increase the readability, while increasing the length of ICDs.

France↗

PubMed2004

Mathematical modelling of an ischemic stroke: an integrative approach.

Understanding the mechanisms and the time and spatial evolution of penumbra following an ischemic stroke is crucially important for developing therapeutics aimed at preventing this area from evolving towards infarction. To help in integrating the available data, we decided to build a formal model. We first collected and categorised the major available evidence from animal models and human observations and summarized this knowledge in a flow-chart with the potential key components of an evolving stroke. Components were grouped in ten sub-models that could be modelled and tested independently: the sub-models of tissue reactions, ionic movements, oedema development, glutamate excitotoxicity, spreading depression, NO synthesis, inflammation, necrosis, apoptosis, and reperfusion. Then, we figured out markers, identified mediators and chose the level of complexity to model these sub-models. We first applied this integrative approach to build a model based on cytotoxic oedema development following a stroke. Although this model includes only three sub-models and would need to integrate more mechanisms in each of these sub-models, the characteristics and the time and spatial evolution of penumbra obtained by simulation are qualitatively and, to some extent, quantitatively consistent with those observed using medical imaging after a permanent occlusion or after an occlusion followed by a reperfusion.

Animals↗

PubMed2003

The French stroke program.

The French healthcare system is organised according to a political, geographical and demographic framework. In France today, less than 20 hospitals have dedicated intensive care units for acute stroke patients. In the 1999 national survey, 94% of stroke patients were admitted to public hospitals, 35% were treated in neurological wards and 4% had access to an intensive care stroke unit. To improve the quality of care and resource utilisation, a national plan for stroke will be implemented at regional level during the next five-year plan. After a long period of status quo, many positive actions for stroke care have been initiated within a couple of years, based on the evidence of more effective stroke treatments, such as thrombolysis and the specialist care provided by stroke units.

France↗

PubMed2002

Physiologically based model of acute ischemic stroke.

In the treatment of acute ischemic stroke most of the clinical trials have failed, contrasting with promising results in the preclinical stages. This continuing discrepancy suggests some misconceptions in the understanding of acute ischemic stroke. One possible method for identifying the shortcomings of present-day approaches is to integrate all the available knowledge into a single mathematical model and to subject that model to challenges via simulations with available experimental data. As a first stage, then, the authors developed a simplified model, defining the structure and the different parameters that represent the phenomena that occur during the hyperacute phase of ischemic stroke. First, the different critical points of the evolution of ischemic stroke, based on the available evidence on the pathophysiology of stroke, were identified. Those key steps were then related to the quantitative data obtained by magnetic resonance imaging and positron emission tomography scan. These two techniques allow the measurement of diverse key markers of cerebral metabolism: cerebral blood flow (CBF), oxygen extraction factor, cerebral metabolism rate of oxygen, and the apparent diffusion coefficient of water, among others. Those markers were organized together through mathematical equations, and changed over time in order to describe the evolution of an acute ischemic stroke. At each time during the evolution of stroke those parameters are summarized in a parameter called survival delay. This parameter made possible the definition of three different states for tissues-functional, infarcted, salvageable-as end point. Once the model was designed, simulations were performed to explore its internal validity. Simulation results were consistent with the reality of acute ischemic stroke and did not reveal any major drawbacks in the use of the model. The more rapid the decrease in CBF, the larger is the final infarcted area. The model also allowed for the characterization of two types of tissue in the penumbra: tissues with an initial metabolic impairment and tissues altered owing to the closeness of the ischemic area. The results of this experiment were consistent with what is known of acute ischemic stroke. The model integrated different markers of acute ischemic stroke into a single entity in order to mimic acute ischemic stroke, and has been shown to have a reasonable degree of internal validity.

Animals↗

PubMed2002

Significance of early CT signs in acute stroke. A CT scan-diffusion MRI study.

OBJECTIVE: To study the pathophysiology of early CT signs. BACKGROUND: Early CT signs, due to an increase in tissue water content, are commonly attributed to cytotoxic edema and development of irreversible injury. This may have important implications for thrombolysis. METHODS: In patients with acute ischemic stroke in the middle cerebral artery territory, the areas of early CT signs and diffusion weighted imaging (DWI) hypersignal were independently assessed and drawn on a standardized atlas. Then, patients were classified into three groups (early CT signs larger than, similar to or smaller than DWI hypersignal) and compared with perfusion weighted imaging (PWI). RESULTS: Of 16 patients, CT scanning was performed with a median time of 3 h after onset and early CT scan signs were recorded in 10/16 patients (62.5%). DWI signal hyperintensity was present in 15/16 (94%) patients. In 7/16 (43%) patients, the area with early CT scan signs was larger than the DWI lesion ('CT-larger group'). Only in 2/16 (12%) patients were the areas matching ('matching group'). In 7/16 (43%) the DWI lesion was larger than the early CT scan signs area ('DWI-larger group'). When compared with PWI, the areas of early CT signs were larger than DWI hypersignal and were matching with PWI abnormalities (rMTT) in 2 cases, suggesting that they may represent a reversible process. CONCLUSIONS: Early CT signs might have a potential dual fate: infarction or reversibility. Other techniques of recognizing reversible ischemic damage, such as DWI-PWI, are needed to improve acute stroke diagnosis and management.

Acute Disease↗

PubMed2002

AMPA antagonist ZK200775 in patients with acute ischemic stroke: possible glial cell toxicity detected by monitoring of S-100B serum levels.

BACKGROUND AND PURPOSE: S-100B and neuron-specific enolase (NSE) serum concentrations can be used as peripheral markers of glial cell and neuronal damage, respectively. We investigated these markers in a clinical trial with the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) antagonist ZK200775 in acute ischemic stroke patients. METHODS: In a multicenter, double-blind, randomized, placebo-controlled phase 2 trial, 61 ischemic stroke patients were treated with either placebo or active drug in a dose-finding design. Twenty-five patients received placebo, 12 patients received a total dose of 262.5 mg in 48 hours (dose group 1), and 13 patients received a total dose of 525 mg in 48 hours (dose group 2). Eleven patients received a total dose of 105 mg over a period of 6 hours (dose group 3; reduction of total dose and infusion time because of adverse events in group 2). Serum concentrations of S-100B and NSE were analyzed with the use of a monoclonal sandwich immunoluminometric assay. Neurological outcome was assessed with the National Institutes of Health Stroke Scale (NIHSS). RESULTS: In group 2 there was a significant transient worsening in the mean NIHSS score 48 hours after the start of treatment. The mean increase was 11 points. This was due to reduction of consciousness (stupor and coma) in 8 of 13 patients. Neurological deterioration in group 2 was associated with a higher increase of S-100B concentrations, but not of NSE concentrations, than in the placebo group. The trial was stopped prematurely for safety reasons. CONCLUSIONS: The AMPA antagonist ZK200775 transiently worsened the neurological condition in patients with acute ischemic stroke. Our results suggest that in addition to neuronal dysfunction, glial cell toxicity may have occurred. It may be useful to introduce monitoring of serum markers of brain damage in phase 2 trials with glutamate receptor antagonists.

Acute Disease↗

PubMed1996

Thrombolytic therapy with streptokinase in acute ischemic stroke.

BACKGROUND: In patients with acute ischemic stroke, early treatment with thrombolytic agents is thought to permit reperfusion of ischemic neurons and to promote recovery of function. The Multicenter Acute Stroke Trial-Europe (MAST-E) was designed to assess the efficacy and safety of streptokinase in patients with acute ischemic stroke. METHODS: Patients with moderate-to-severe ischemia in the territory of the middle cerebral artery were randomly assigned to receive streptokinase (1.5 million units over a period of one hour) or placebo within six hours after the onset of stroke. The primary efficacy outcome was a binary criterion combining mortality and severe disability at six months, with severe disability defined as a score of 3 or higher on the Rankin scale. The primary safety outcomes were mortality at 10 days and cerebral hemorrhage. RESULTS: All randomized patients (156 in the streptokinase group and 154 in the placebo group) were evaluated at six months. The incidence of the primary efficacy outcome was similar in the two groups (124 patients in the streptokinase group and 126 in the placebo group died or had a Rankin score > or = 3). However, the mortality rate at 10 days was significantly higher in the streptokinase group than in the placebo group (34.0 percent vs. 18.2 percent, P = 0.002). The higher rate in the streptokinase group was mainly due to the hemorrhagic transformation of ischemic cerebral infarcts. At six months, more deaths had occurred in the streptokinase group than in the placebo group (73 vs. 59, P = 0.06). CONCLUSIONS: In patients with acute ischemic stroke, treatment with streptokinase resulted in an increase in mortality. The routine use of streptokinase cannot be recommended in acute ischemic stroke.

Acute Disease↗

PubMedDate not supplied

[Satisfaction of subjects enrolled in clinical studies].

OBJECTIVE: The Grenoble clinical research centre carried out a prospective satisfaction survey of subjects taking part in clinical studies undertaken in its buildings. MATERIALS AND METHODS: A questionnaire adapted from Grenoble teaching hospital's inpatient satisfaction survey was sent to 198 subjects. It comprised 24 items pooled in categories on which were calculated average scores. The participation rate of the survey was 82.6%. On the whole, 94.4% of the questioned subjects would accept to take part in a new study if we requested them, and 72.2% were satisfied or very satisfied with their stay; 24% had no opinion. The mean overall satisfaction score was 8.6 (95% confidence interval: 7.6-9.6) out of 10. CONCLUSION: This investigation shows that the assumption of responsibility of the subjects by specific personnel and in an adapted place, within the framework of clinical protocol of research, is associated with a high satisfaction of the subjects. However, we still have to improve the transmission of the clinical study results to the patients.

Clinical Trials as Topic↗