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Biomedical subjects

J M Orgogozo

Publications and source records attributed to J M Orgogozo.

At least 37 records · Page 2Linked to original sources
PubMed2000

Glycine antagonist (gavestinel) in neuroprotection (GAIN International) in patients with acute stroke: a randomised controlled trial. GAIN International Investigators.

BACKGROUND: Early treatment may improve acute ischaemic stroke outcome. Gavestinel is a selective antagonist at the glycine site of the N-methyl-D-aspartate (NMDA) receptor, and is neuroprotective in animal models of ischaemic stroke. METHODS: We did a randomised, double-blind, placebo-controlled trial to test whether gavestinel could improve functional outcome after acute stroke in human beings. Conscious patients with stroke involving limb weakness received either gavestinel at an intravenous loading dose of 800 mg followed by 200 mg every 12 h for five doses, or matching placebo, within 6 h of stroke onset. Stratification variables were age and stroke severity. A computed tomography brain scan within 18 h of stroke onset identified the primary efficacy population with ischaemic stroke. Outcome was assessed by an independent observer with the Barthel index at 3 months. Three outcome categories were applied: good (Barthel index 95-100), moderate (60-90), and poor (0-55 or dead). Analysis was by intention to treat. FINDINGS: Of 1804 patients randomised, 16 received no treatment, and 333 had primary intracranial haemorrhage. 891 patients received gavestinel and 897 received placebo. Outcome in 721 patients who received gavestinel and were analysed for the primary endpoint at 3 months was good in 246 (34.1%), moderate in 136 (18.8%), and poor in 339 (47.0%), compared with 256 (34.9%), 133 (18.1%), and 345 (47.0%), respectively, of 734 patients who received placebo (p=0.8). Mortality at 3 months was 147 (20.4%) in the gavestinel group and 138 (18.8%) in the placebo group. Outcomes within preplanned subgroup and secondary analyses were also neutral. There were no significant differences in serious side-effects between the groups. INTERPRETATION: Treatment with gavestinel within 6 h of acute ischaemic stroke did not improve outcome.

Acute Disease↗
PubMed2000

European Stroke Initiative (EUSI) recommendations for stroke management. The European Stroke Initiative Writing Committee.

The European Stroke Initiative (EUSI) is the common body of stroke-related activities within the European Federation of Neurological Societies (EFNS), the European Neurological Society (ENS) and the European Stroke Council (ESC). The Executive committee of the EUSI has authorized the writing committee of the EUSI to create recommendations for stroke management covering all areas of stroke treatment. The recommendations are listed according to levels of evidence pre-specified and modified according to several proposals in the literature. The recommendations have been approved by the executive committees of the EUSI, the ESC, the EFNS and the ENS. They are called recommendations rather than guidelines in order to underline the large amount of individual decision making due to the fact that for many important questions, no data of high evidence level is available. The EUSI plans to review and update the recommendations on a regular basis.

Anticoagulants↗
PubMed1999

Marital status and risk of Alzheimer's disease: a French population-based cohort study.

OBJECTIVE: To analyze the relationship between marital status and risk of AD or dementia. METHODS: This study was carried out from the Personnes Agées QUID (PAQUID) cohort, an epidemiologic study on normal and pathologic aging after age 65 years. The PAQUID cohort began in 1988. Individuals were followed up at 1, 3, and 5 years, with an active detection of dementia. Marital status was divided into four categories: widowed, never married, divorced or separated, and the reference category, married or cohabitant. The longitudinal relationship between marital status and risk of incident AD or dementia was analyzed by a Cox model with delayed entry. RESULTS: Among the 3,675 individuals initially not demented, 2,106 were married or cohabitants, 1,287 were widowers, 179 were never married, and 103 were divorced or separated. Among the 2,881 individuals reevaluated at least once for the risk of dementia during the 5-year follow-up, 190 incident cases of dementia were identified, including 140 with AD. The relative risks (RRs) of dementia (RR = 1.91, p = 0.018) and of AD (RR = 2.68, p<0.001) were increased for the never-married individuals compared with those who were married or cohabitants. This excess of risk was specifically associated with AD. Adjustment for other risk factors of dementia (education, wine consumption), or for factors reflecting social environment, leisure activities, and depression, did not modify the risk of AD for never-married individuals (RR = 2.31, p = 0.02). CONCLUSIONS: We confirmed an association between marital status and AD, with an excess risk observed among never-married individuals. This association may provide clues about the pathogenesis of AD.

Aged↗
PubMed1999

A 24-month, double-blind, placebo-controlled multicentre pilot study of the efficacy and safety of nicergoline 60 mg per day in elderly hypertensive patients with leukoaraiosis.

In this pilot study, 72 non-demented and non-depressive elderly hypertensive patients with evidence of leukoaraiosis on cerebral computed tomography scan (Rezek score: > 16) were randomly assigned to receive either nicergoline 30 mg b.i.d. (n = 36) or a placebo (n = 36) for 24 months. All patients received antihypertensives and their hypertension was controlled under treatment. They were evaluated by nine neuropsychological tests exploring memory, concentration, verbal and motor performances, administered at baseline and at every six-month interval during the study period. At baseline, the two groups were comparable for all demographic and clinical characteristics, including cognitive functions, except for the delayed recall of the Auditory Verbal Learning Test (AVLT), which was better in the placebo group (P = 0.04). Changes in scores over time were compared between the two groups. At the last visit, patients on nicergoline (n = 31) were found to have deteriorated less or to have improved more on test scores than the patients on placebo (n = 30). Significant differences were observed for memory function (AVLT short term recall, P = 0.026; AVLT delayed recall, P = 0.013; and, Benton Visual Retention Test, P = 0.002) and attention and concentration (Letter Cancellation Test, P = 0.043; and, WAIS-R Digit Symbol subtest, P = 0.006). The Rezek score remained unchanged in the two groups. Tolerance of nicergoline was similar to that of placebo. In conclusion, this study shows that nicergoline 30 mg b.i. d. administered over a 24-month period attenuates the deterioration in cognitive functions in elderly hypertensive patients with leukoaraiosis. Whether these effects were specific for this type of white matter changes could not be determined in the context of this pilot study.

Aged↗
PubMed1999

Piracetam in the treatment of acute stroke.

The neuroprotective properties of the nootropic agent piracetam together with reported hemorrheologic and antithrombotic effects provided the rationale for the evaluation of piracetam in acute stroke. Pilot studies showed an increase in compromised regional cerebral blood flow and improvement in motor function, aphasia and level of consciousness. Subsequently the Piracetam in Acute Stroke Study (PASS) was performed and the chief results have recently been reported (Stroke 28 (1997) 2347-2352). This was a multicenter double-blind trial in 927 patients to determine whether, compared with placebo, piracetam improved outcome when given within 12 hours of the onset of acute ischemic stroke, confirmed by computed tomography within 24 hours of admission (but not necessarily prior to treatment). Patients received an initial iv bolus of placebo or 12g piracetam, 12g piracetam daily for 4 weeks and maintenance treatment for a further 8 weeks. Neurologic status at 4 weeks was the primary end point; secondary outcome measures were functional outcome and aphasia at 12 weeks. Results in aphasic patients have not previously been reported. Analysis was planned both in all patients (n = 927) and an early treatment subgroup (n = 460) treated within 6 hours of stroke onset. This period was subsequently redefined as 7 hours. Intention-to-treat analyses in the total population showed a significant (P = 0.04) increase compared with placebo in the number of patients recovered from aphasia but no significant neurologic or functional improvement. Post hoc analysis in the early treatment subgroup showed improved neurologic outcome (P = 0.07), better function (P = 0.02) and a greater recovery rate from aphasia (P = 0.02). Additional analysis in this early treatment subgroup confined to 360 patients with moderate and severe stroke showed significant improvement in all 3 outcomes. There was no significant difference in mortality between treatment groups after 12 weeks. There were fewer deaths in piracetam-treated patients in those patients in the intention-to-treat population admitted with primary hemorrhagic stroke.

Acute Disease↗
PubMed1999

Are sex and educational level independent predictors of dementia and Alzheimer's disease? Incidence data from the PAQUID project.

OBJECTIVES: To examine the age specific risk of Alzheimer's disease according to sex, and to explore the role of education in a cohort of elderly community residents aged 65 years and older. METHODS: A community based cohort of elderly people was studied longitudinally for 5 years for the development of dementia. Dementia diagnoses were made according to the DSM III R criteria and Alzheimer's disease was assessed using the NINCDS-ADRDA criteria. Among the 3675 non-demented subjects initially included in the cohort, 2881 participated in the follow up. Hazard ratios of dementia were estimated using a Cox model with delayed entry in which the time scale is the age of the subjects. RESULTS: During the 5 year follow up, 190 incident cases of dementia, including 140 cases of Alzheimer's disease were identified. The incidence rates of Alzheimer's disease were 0.8/100 person-years in men and 1.4/100 person-years in women. However, the incidence was higher in men than in women before the age of 80 and higher in women than in men after this age. A significant interaction between sex and age was found. The hazard ratio of Alzheimer's disease in women compared with men was estimated to be 0.8 at 75 years and 1.7 at 85 years. The risks of dementia and Alzheimer's disease were associated with a lower educational attainment (hazard ratio=1.8, p<0.001). The increased risk of Alzheimer's disease in women was not changed after adjustment for education. CONCLUSION: Women have a higher risk of developing dementia after the age of 80 than men. Low educational attainment is associated with a higher risk of Alzheimer's disease. However, the increased risk in women is not explained by a lower educational level.

Aged↗
PubMed1999

A multicentre, randomized, double-blind, placebo-controlled study to evaluate the efficacy, tolerability and safety of two doses of metrifonate in patients with mild-to-moderate Alzheimer's disease: the MALT study.

BACKGROUND: Metrifonate is a long-lasting acetylcholinesterase inhibitor being developed for the symptomatic treatment of Alzheimer's disease (AD). OBJECTIVES: This study compared the efficacy, tolerability and safety of two doses of metrifonate in patients with mild-to-moderate AD, over a 26-week treatment period. METHODS: Six hundred and five patients were randomized to placebo (n=208), a 40/50 mg dose (40 or 50 mg by weight; n=200) or a 60/80 mg dose (60 or 80 mg by weight; n=197) metrifonate. Patients randomized to receive metrifonate were administered a once-daily loading dose of 80 or 120 mg based on weight for 2 weeks, followed by the relevant maintenance dose for 24 weeks. Four main clinical domains of AD were assessed: cognition (ADAS-cog and MMSE), psychiatric and behavioural symptoms (ADAS-noncog and NPI), instrumental and basic activities of daily living (DAD) and global functioning (CIBIC-plus, CIBIS-plus and GDS). RESULTS: ADAS-cog performance was significantly improved in the 60/80 mg and 40/50 mg dose groups, compared with placebo, in the intention-to-treat (ITT) population. In addition, statistically significant treatment differences were demonstrated between the 60/80 mg dose group and placebo on MMSE, ADAS-noncog, the NPI subitems of hallucinations and apathy, DAD, CIBIC-plus, CIBIS-plus and the GDS. The performance of the 40/50 mg dose group was also significantly superior to placebo on the CIBIS-plus and the NPI subitem aberrant motor behaviour. CONCLUSIONS: Metrifonate significantly improved a wide range of symptoms across all four clinical domains of AD in a dose-dependent manner, and was safe and well tolerated at both doses studied.

Activities of Daily Living↗
PubMed1998

The application of the International Statistical Classification of Diseases to neurology: ICD-10 NA.

Rapid advances in the clinical neurosciences in the last decade have led to considerable amplification of our ability to classify neurological diseases. For these classifications to be widely used, they must be compatible with the 'International Statistical Classification of Diseases and related health problems' (ICD) of the World Health Organization (WHO), which system is used throughout the world for classification of diseases and reasons of death. The 'Ninth' revision of the ICD (ICD-9), published in 1976, is currently in use in a number of Member States of the World Health Organization, including the United States. However, it is expected that by the end of this decade virtually all Member States will have introduced the 10th Revision of the ICD (ICD-10), published in 1992. An 'Application of ICD-10 to neurology' (ICD-10 NA) has been developed, with a specific coding system for virtually every neurological disease currently recognized. This article describes the structure and background of this work, that is offered as a definitive international classification of neurological disease to be used by clinical and research organizations, governmental and nongovernmental bodies, and for epidemiological and research purposes. It is concordant with the new and proposed classifications of subspecialty neurological organizations.

Cause of Death↗
PubMed1998

Illustration of analysis taking into account complex survey considerations: the association between wine consumption and dementia in the PAQUID study. Personnes Ages Quid.

Epidemiologists are increasingly looking to large-scale sample surveys to provide data for studies of the associations between known or suspected risk factors and disease. More often than not, widely available statistical software packages have been used to analyze such data, particularly when multivariable modeling is involved. Such packages assume that the data have resulted from simple random samples. However, when the survey design incorporates such features as clustering and stratification, the results of statistical analyses based on this assumption can be incorrect. The authors utilized data from the PAQUID (Personnes Agees Quid) study, collected periodically from 1988 to 1996, to illustrate the ease of performing a "design-based" (vs. a "model-based") analysis of complex survey data, and they compared the results obtained using both approaches. The PAQUID study is a stratified cluster sample of elderly community residents in the southwestern departments of Gironde and Dordogne, France. In the illustration presented-in which 3,777 community residents aged 65 years or older were selected to permit identification of baseline and lifetime factors that might be related to cognitive loss, dementia, and Alzheimer's disease--measures of association (such as odds ratios and their associated standard errors) were comparable for both analytical strategies. However, this may not be the case for other examples. Descriptive measures (such as estimates of means and proportions) may be more seriously compromised by the decision to ignore the sampling design. The availability of modern statistical packages with survey analysis capabilities should encourage data analysts to perform design-based analyses whenever possible.

Aged↗
PubMed1998

Analysis of error types in the trial making test evidences an inhibitory deficit in dementia of the Alzheimer type.

Several studies have reported low performances of patients with dementia of the Alzheimer Type (DAT) on the Trial Making Test (TMT), however, these studies were not designed to identify specific operations underlying this impairment. To better understand the attentional disorder in DAT, we analyzed the performances of patients with DAT and matched elderly adults on the TMT, with a detailed analysis of error types. The analysis showed that 67% of patients' errors were related to an inhibitory deficit versus only 24% in normal elderly adults. Therefore, it was suggested that inefficient inhibitory mechanisms are responsible, to a large extent, for the poor TMT performance of patients with DAT, supporting the hypothesis of an inhibitory dysfunction in DAT.

Adult↗
PubMed1998

Cognitive process in preclinical phase of dementia.

Several recent prospective studies have demonstrated the existence of a preclinical stage of dementia, identifiable by neuropsychological assessment showing impairments with a great variety of cognitive tests. However, test scores are often colinear, largely because common cognitive components are involved in different tests; in spite of an apparent heterogeneity, it is still possible that a common cognitive component may be responsible for the deterioration shown in different tests in the preclinical phase. We studied the cognitive performances of 1159 elderly residents in the PAQUID (Personnes Agées quid) cohort, at a fixed lag time of 2 years before the clinical diagnosis of dementia. Seven neuropsychological tests were administered (Mini-Mental Status Examination, Benton Visual Retention Test, Wechsler Paired-Associates Test, Isaacs Set Test, Zazzo's Cancellation Task, Digit Symbol Substitution Test and Wechsler Similarities Test). Among the initially non-demented 1159 subjects, 25 developed a dementia 2 years later, of whom 16 were classified as cases of Alzheimer's disease. In order to dissect the multicolinearity of the tests we used a multivariate approach with principal component analysis (PCA). The patients' loading on each of the first four PCA factors were subsequently correlated with the risk of dementia and Alzheimer's disease 2 years later. The logistic regression with backward stepwise selected only the first factor as an independent predictor of dementia or Alzheimer's disease. Analysis shows that there are good reasons to suspect that the first PCA factor represents a general factor corresponding to aspects of control in the tasks used. Our results therefore seem to show that preclinical deficits in dementia and Alzheimer's disease reflect the deterioration of a general cognitive factor, which may be interpreted as the disturbance of central, control processes.

Aged↗