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Introduction: The multicenter PHRC REAL-FR cohort study was designed to follow community-dwelling patients with a diagnosis of Alzheimer's Disease. The present study describes the evolution of neuropsychiatric symptoms (NPS) over 4 years. Method: 686 patients were recruited at baseline from 16 French clinical centers. 151 patients were followed over the 4-year interval with 5 Neuropsychiatric evaluations. Neuropsychiatric symptoms were assessed using the Neuropsychiatric inventory (NPI). NPS symptoms were divided into 4 subgroups according to the European Alzheimer Disease Consortium NPI analysis; psychotic subgroup (hallucinations, delusions), hyperactivity subgroup (agitation, aggression, euphoria, disinhibition, irritability, aberrant motor behavior), apathy subgroup (apathy, eating) and affective subgroup (depression, anxiety). Secondly we studied the evolution of the population divided in 4 groups: Apathy only, Hyperactivity only, both Apathy and Hyperactivity, no Apathy no Hyperactivity. Results: At baseline, 100 patients (66%) presented with one or more clinically significant NPI symptoms. This figure increased to 88% at the end of 4-year follow-up (Linear by linear chi square, p<0, 0012). Five NPI symptoms showed significant increases in prevalence: agitation (17,9 to 29,1%), apathy (43,0 to 62,9%), disinhibition (2,6 to 14,6%), hallucination (2 to 4,6%) and aberrant motor behavior (13,9 to 29,1%). Prevalence of hyperactivity and apathy subgroups increased significantly during the follow-up while the prevalence of affective and psychotic subgroups did not. The number of patients with both apathy and hyperactivity increased (27% to 44%) during the follow-up period whereas the number of patients without these symptoms decreased (p =.009). Conclusion: The present study shows that 2 types of symptoms increased primarily over time: Apathy and Hyperactivity. The coexistence of such opposite symptoms over time according to our result should be taken into consideration by clinicians treating those patients. [ABSTRACT FROM AUTHOR]

Unlabelled: The end-points of this study upon 134 cases reports by the french Poison Centers from 1979 to 1988 (10 years) were to specify the acute toxicity of diltiazem (DTZ). There were 83 self-poisonings in adults, with diltiazem alone (36 cases) or associated with other non cardiotoxic drugs (47), the doses of DTZ ranging from 300 to 5400 mg, and 51 acute accidental overdose in children, the doses of DTZ ranging from 60 to 420 mg. One case of hypotension was observed in a child, without rhythmic disorder, occurring twelve hours post-ingestion of 180 mg of DTZ. In adults, the clinical effects were observed following 360 mg of dose DTZ, occurring 1 1/2 hour post-ingestion. There were discomfort, brady-cardia in 16% of the cases, hypotension in 23% of the cases, cardiogenic shock in 4% of the cases and cardiac arrest in 2.4% of the cases. The rhythmic disorders occurred 2 to 15 hours post-ingestion. There were conduction defects like atrio-ventricular heart bloc I degree in 9% of the cases, II degree in 2.4% of the cases and III degree in 9% of the cases. Less frequently, sinusal bradycardia in 11% of the cases or sino-auricular heart block in 4% of the cases with sometimes auriculo ventricular heart block. These cardiac disorders occurred with 600 mg of DTZ. A cardiac arrest happened in a young healthy man who had absorbed 5400 mg of DTZ. The cardiogenic shocks occurred in patients with an history of coronary on heart disease. The poison removal is likely to prevent the occurrence of clinical or EKG effects when performed within 2 hours post-ingestion, whatever toxic the dose is. The inotropic drugs have been used in 18% of the cases; a percutaneous ventricular pacing was always effective in patients with II or III degree atrio-ventricular block or/and cardiogenir shock. These data confirm the data in thirteen patients of the literature., In Conclusion: The acute diltiazem poisoning can occur after 600 mg of DTZ and can induce severe cardiac disorders which can be prevented with poison removal or treated with supportive care.