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PURPOSE: Eslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED) indicated for partial-onset seizures (POS). Clinical studies of gradual conversion to ESL 1,200 and 1,600 mg QD monotherapies were previously conducted in patients with POS who were not well-controlled by 1 or 2 AEDs. This report describes modeling and simulation of plasma eslicarbazepine (primary active metabolite of ESL) concentrations and time to monotherapy study exit to predict efficacy for conversion to ESL monotherapy at a lower dose of 800 mg, as an option for patients requiring or not tolerating higher doses since this regimen is effective in adjunctive therapy for POS. PATIENTS AND METHODS: A previously developed population pharmacokinetic model for ESL monotherapy was used to predict minimum plasma eslicarbazepine concentration (Cmin) in 1,500 virtual patients taking 1 (n=1,000) or 2 (n=500) AEDs at baseline, treated with ESL 400 mg QD for 1 week, followed by 800 mg QD for 17 weeks (similar to ESL monotherapy trials where the other AEDs were withdrawn during the first 6 weeks following titration to the randomized ESL dose). Model-predicted Cmin as a time-varying covariate and number of baseline AEDs were used to determine the weekly probability of each patient meeting exit criteria (65.3% threshold) indicative of worsening seizure control in 500 simulated ESL monotherapy trials. A previously developed extended Cox proportional hazards exposure-response model was used to relate time-varying eslicarbazepine exposure to the time to study exit. RESULTS: For virtual patients receiving ESL monotherapy (800 mg QD), the 95% upper prediction limit for exit rate at 112 days of 34.9% in patients taking 1 AED at baseline was well below the 65.3% threshold from historical control trials, while the estimate for patients taking 2 AEDs (70.6%) was slightly above the historical control threshold. CONCLUSION: This model-based assessment supports conversion to ESL 800 mg QD monotherapy for POS in adults taking 1 AED. For patients taking 2 concomitant AEDs, however, prescribers should consider maintenance doses of 1,200 or 1,600 mg ESL QD to reduce the likelihood of seizure worsening if conversion to ESL monotherapy is contemplated.
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OBJECTIVE: Clinical review of the epidemiology, morbidity, mortality, medical and economic costs of being overweight or obese; recommendations on obesity from the National Institutes of Health; and how these factors relate to the elderly. DATA SOURCES: Medline search was used to identify relevant articles. Additional references were found in review articles and consensus guidelines. STUDY SELECTION: Fifty-nine articles were identified and 40 were selected based on findings related to geriatric patients or obesity overall. Studies done in the United States as well as in European populations were included. DATA EXTRACTION: Data were abstracted per findings for: epidemiology of being overweight and obese for adults and elderly, mortality and morbidity of being overweight or obese, issues with weight loss in the elderly, changes in physiology with aging that may impact on weight, whether increased body mass index (BMI) is directly associated with mortality in the elderly, whether the National Institutes of Health guidelines for BMI in obesity should be applied to elderly persons, mortality associated with weight, and costs of obesity. DATA SYNTHESIS: The main findings suggest that being underweight results in a higher mortality for elderly persons as compared with being overweight. CONCLUSION: The primary conclusion is that it is still not yet defined if the elderly should be held to the NIH standards for "overweight" and "obesity." More research is needed to determine if overweight and obese elderly benefit from weight loss measures or if they should be kept at their current weight.
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OBJECTIVE: The objective of this paper is to review the current practice guidelines as developed by the American Academy of Neurology (AAN) for the diagnosis of dementia. DATA SOURCES: The data sources were the Report of the Quality Standards Subcommittee of the American Academy of Neurology paper, which was published in the May 2001 issue of the journal Neurology. STUDY SELECTION: The studies used in this paper are those reviewed by the AAN Practice Parameter Committee, which reviewed the literature for evidence-based human studies pertaining to the diagnosis of dementia. Studies on Alzheimer's disease (AD) included had to have more than 25 subjects. Each article was classified based on the quality of evidence. After review of the evidence, the committee drafted recommendations and placed the evidence into Practice Standards, Guidelines, or Options. DATA SYNTHESIS: The main results of this review were the guidelines for diagnosing dementia of various forms. To diagnose dementia, the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-IIIR) should be used. For AD, the NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer s Disease and Related Disorders Association) criteria should be used. The Modified Hachinski Ischemic Score criteria can be used in the diagnosis of vascular dementia. The Consortium for DLB (Dementia with Lewy Bodies) criteria may be of use in clinical practice. Neuroimaging with a noncontrast CT or MRI scan in the routine initial evaluation of persons with dementia is appropriate; other methods of neuroimaging are not recommended at this time. Genetic testing and use of apolipoprotein E (ApoE) genotyping is not recommended at this time. Depression, B12 deficiency, and hypothyroidism should be screened for and treated in patients with dementia. Unless the patient lives in an area in the United States with a high rate of syphilis, screening for tertiary syphilis is not warranted. CONCLUSION: The guidelines and their clinical applications are pertinent and important knowledge for consultant pharmacists. This practice parameter will need to be updated every few years to include new studies and information that becomes available.
