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BackgroundIn Alzheimer's disease, there is a marked decline in the function of cholinergic neurons in the brain. However, studies of treatment with cholinesterase inhibitors have produced conflicting results. We conducted a multicenter trial to evaluate whether the cholinesterase inhibitor tacrine (1,2,3,4-tetrahydro-9-acridinamine monohydrochloride monohydrate) could improve cognition in patients with Alzheimer's disease.MethodsOf 632 eligible patients with probable Alzheimer's disease, 215 improved while receiving tacrine during a preliminary crossover phase to determine responsiveness and the best dose. The 215 patients were randomly assigned to receive either placebo or their best dose of tacrine (10 or 20 mg four times a day) in a six-week, double-blind trial. The primary measures of efficacy were the cognitive subscale of the Alzheimer's Disease Assessment Scale and the Clinical Global Impression of Change scale; the secondary measures included the Mini-Mental State Examination and the assessment of the activities of daily living.ResultsAt the end of the six-week trial, the patients receiving tacrine had a mean adjusted cognitive-subscale score of 30.3 (Alzheimer's Disease Assessment Scale) as compared with 32.7 in patients receiving placebo. This represents a smaller decline (by 2.4 points) in cognitive performance in the tacrine group (P < 0.001). There were no differences between the groups in their global-rating scores. The tacrine group had a significantly smaller decline in the activities of daily living. The results of the Mini-Mental State Examination favored tacrine, but the differences were small and not statistically significant (a score of 16.0 with tacrine vs. 15.3 with placebo; P = 0.08). Gastrointestinal symptoms, elevation of aminotransferase levels, and headache were the most frequent side effects; all could be reversed by reducing the dose or discontinuing treatment.ConclusionsIn this short-term study in patients with Alzheimer's disease who were selected for apparent responsiveness to tacrine, treatment with tacrine resulted in a statistically significant reduction in the decline of cognitive function, although this reduction was not large enough to be detected by the study physicians' global assessments of the patients.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jsat.2008.09.011 Byline: Sarra L. Hedden (a)(b)(c), Robert F. Woolson (a), Rickey E. Carter (a), Yuko Palesch (a), Himanshu P. Upadhyaya (b), Robert J. Malcolm (b) Keywords: Substance abuse clinical trial; Loss to follow-up; Treatment effect; Hypothesis tests; Longitudinal data Abstract: 'Loss to follow-up' can be substantial in substance abuse clinical trials. When extensive losses to follow-up occur, one must cautiously analyze and interpret the findings of a research study. Aims of this project were to introduce the types of missing data mechanisms and describe several methods for analyzing data with loss to follow-up. Furthermore, a simulation study compared Type I error and power of several methods when missing data amount and mechanism varies. Methods compared were the following: Last observation carried forward (LOCF), multiple imputation (MI), modified stratified summary statistics (SSS), and mixed effects models. Results demonstrated nominal Type I error for all methods; power was high for all methods except LOCF. Mixed effect model, modified SSS, and MI are generally recommended for use; however, many methods require that the data are missing at random or missing completely at random (i.e., 'ignorable'). If the missing data are presumed to be nonignorable, a sensitivity analysis is recommended. Author Affiliation: (a) Department of Biostatistics, Bioinformatics and Epidemiology, Medical University of South Carolina, Charleston, SC 29425, USA (b) Department of Psychiatry and Behavioral Research, Medical University of South Carolina, Charleston, SC 29425, USA (c) Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA Article History: Received 20 March 2008; Revised 23 September 2008; Accepted 24 September 2008

We analyzed cardiovascular disease mortality risks associated with obesity using participant-level meta-analysis of data from the Black Pooling Project for Black and White individuals. The adjusted relative risks (ARRs) were stronger among White participants than among Black participants for coronary heart disease AAR = 1.21 (95% confidence interval [CI]=1.07, 1.36) versus 0.87 (95% CI=0.69, 1.09), respectively, and cardiovascular disease ARR=1.18 (95% CI=1.07, 1.29) versus 0.91 (95% CI=0.77, 1.05), repectively. The results suggest that obesity is an independent risk factor in White people, and additional study of body size and disease progression is necessary in the assessment of racial disparities. (Am J Public Health. 2008;98:63-66. doi:10. 2105/AJPH.2006.093781)

We sought to analyze the self-reported hospitalization, emergency department visits, and outpatient visits of Persian Gulf War (deployed; n = 1896) and Persian Gulf War--era (nondeployed; n = 1799) military personnel 5 years postconflict to determine whether these groups had different rates of health care use. Compared with personnel who had not been deployed, personnel who had been deployed were more likely to have visited an emergency department (25% vs 21%; odds ratio [OR] = 1.24; 95% confidence interval [CI]=1.06, 1.51]). Among these groups, the National Guard and Reserve personnel were more likely to have been hospitalized than were the regular military personnel (OR = 1.65; 95% CI = 1.21, 2.26).