A Literature Review of Methodologies Used in Randomized Clinical Trials of Agitation in Alzheimer's Disease.

Agitation is a common and burdensome symptom associated with Alzheimer's disease (AD). This is a narrative literature review of the designs and methods used in randomized clinical trials of agitation in patients with AD; sources range from published, to completed but not published, to ongoing studies in the past 10 years. Selection for review included blinded, randomized trials conducted to assess the effect of a pharmacological intervention for which agitation in patients with AD was among the prespecified end points. Key criteria for exclusion included open-label studies, trials of dementia not specific to AD, or mixed populations of AD and unspecified dementia. A search of PubMed and clinicaltrials.gov databases identified 36 trials for which agitation was among the prespecified end points: 18 were published trials and 18 were completed but not published or ongoing. There was significant heterogeneity among AD studies in terms of diagnostic criteria, assessment of severity of disease and agitation, sample size and powering assumptions, treatment duration, patient age and cognitive status, and outcomes measurements. Few studies used a mitigation strategy for placebo response. Accumulating evidence suggests that it is important to consider the following in trial design: thresholds for baseline severity of agitation and AD; use of prespecified accepted criteria to define agitation; and use of standardized, validated tools to measure treatment effects during a trial. Adoption of these design strategies might help improve signal detection and bring us closer to identifying the most appropriate, effective, and safe treatments for agitation in patients with AD.

Peroneal F-wave characteristics under submaximal stimulation.

PURPOSE: F-wave studies are valuable tools in clinical neurophysiology. F-wave parameter estimation must be based on multiple F-wave traces due to their inherent variability. Repetitive supramaximal stimulation is uncomfortable for many patients. This study tested the hypothesis that submaximally stimulated nerves yield F-wave parameters equivalent to those obtained with supramaximal stimulation. METHODS: Thirty-five peroneal nerves from 27 subjects were stimulated both supramaximally and submaximally. CMAP and F-wave responses from the extensor digitorum brevis muscle were recorded and analyzed offline. Automated algorithms were used to determine F-wave parameters. RESULTS: Mean, minimum, maximum F-wave latencies, F-wave duration, and chronodispersion showed no statistically significant difference under the two stimulation conditions. F-wave persistence, amplitude, and subject's discomfort level, were lower with statistical significance. The correlation coefficient of submaximal and supramaximal mean F-wave latencies was 0.977 and their intraclass correlation coefficient was 0.976. The bias of the mean latencies was 0.21 ms and the 95% limits of agreement were less than 5% of the mean F-wave latency. CONCLUSIONS: F-waves acquired with submaximal stimulation possess characteristics statistically equivalent to those obtained under supramaximal stimulation, as measured by the latency and duration parameters. Persistence and amplitude were lower. Reduction in discomfort level was also achieved.

Enteral nutrition and corticosteroids in the treatment of acute Crohn's disease in children.

BACKGROUND: The optimal treatment of acute Crohn's disease in children remains controversial. In adults, steroid therapy has been shown to be superior to exclusive enteral nutrition. However, enteral nutrition is effective at inducing a remission in many children with acute Crohn's disease. Steroid usage in children has been associated with adverse side effects, particularly with delayed growth and pubertal development. METHODS: Randomized clinical trials comparing exclusive enteral nutrition with corticosteroids were identified. Two independent reviewers extracted data from selected studies. Studies were assessed for heterogeneity and relative risks for remission induction with enteral nutrition were obtained. Sensitivity analyses were performed in partially randomized studies. Estimates were made of the number of studies needed to overturn the current result. Other outcome measures were qualitatively assessed. RESULTS: In five randomized clinical trials comprising 147 patients, enteral nutrition was as effective as corticosteroids at inducing a remission (RR = 0.95 [95% confidence interval 0.67, 1.34]). Addition of two further nonrandomized trials did not significantly alter the result. A minimum of 10 further studies, equal in size and outcome to the largest reported pediatric trial to date (n = 68, RR = 0.84), would be required to demonstrate a significant benefit of steroid therapy over enteral nutrition. CONCLUSIONS: There is no difference in efficacy between enteral nutrition and corticosteroid therapy in the treatment of acute Crohn's disease in children. Improved growth and development, without the side effects of steroid therapy, make enteral nutrition a better choice for first-line therapy in children with active Crohn's disease.