Effectiveness and tolerability of transdermal rivastigmine in the treatment of Alzheimer’s disease in daily practice

Johannes Seibert1, Ferenc Tracik2,3, Konstantin Articus2, Stefan Spittler41Outpatient Clinic, Heidelberg, Germany; 2Novartis Pharma, Nürnberg, Germany; 3Department of Neurology, Heinrich-Heine University, Düsseldorf, Germany; 4Alexianer Krefeld, Maria Hilf Clinic, Krefeld, GermanyBackground: Oral cholinesterase inhibitors at doses efficacious for the treatment of Alzheimer’s disease (AD) are often prematurely discontinued due to gastrointestinal side effects. In controlled clinical trials, transdermal rivastigmine demonstrated less such effects at similar efficacy. The current study aimed to verify the validity of this data in daily practice.Methods: This was a prospective, multicenter, observational study on transdermal rivastigmine in Germany. Eligible patients were those with AD who had not yet been treated with rivastigmine. Outcome measures were changes in clock-drawing test, Mini-Mental State Examination (MMSE), Caregiver Burden Scale, Clinical Global Impression (CGI), physicians’ assessments of tolerability, and the incidence of adverse events (AEs) over 4 months of treatment.Results: In 257 centers 1113 patients were enrolled; 614 women and 499 men, mean age 76.5 years. In 58% of patients AD was treated for the first time and in 42% therapy was switched to transdermal rivastigmine, mostly due to lack of tolerability (13.6%) or effectiveness (26.9%). After 4 months, 67.4% of patients were on the target dose of 9.5 mg/day and 21.8% were still on 4.6 mg/day. MMSE significantly improved in patients with and without pretreatment (ΔMMSE, 0.9 ± 3.4 and 0.8 ± 3.4, respectively, both P < 0.001); the CGI score improved in 60.9% and 61.3% of patients, respectively. Overall 11.7% of patients had AEs, mainly affecting the skin or the gastrointestinal tract; in 1.1% of cases AEs were serious; 14.7% of patients discontinued therapy, 6.0% due to AEs. With rivastigmine treatment the percentage of patients taking psychotropic comedication decreased, particularly in first-time treated rivastigmine patients (from 27.1% to 22.6%; P < 0.001).Conclusion: Results were in line with data from controlled clinical trials. Switching from any other oral acetylcholinesterase inhibitor to transdermal rivastigmine may improve cognition.Keywords: rivastigmine patch, Alzheimer’s disease, treatment practic

Fractal Analysis of Surface Topography by the Directional Blanket Covering Method

A new method, called directional blanket covering (DBC) method, was developed in this study to quantify the roughness of surfaces in a multi-scale manner. Unlike the ASME and ISO standards on surface texture that provide a single fractal dimension (FD, roughness measure) for the entire surface, the new method calculates FDs at individual scales and directions. Also, it is invariant to affine transformations of grey-scale levels of surface image. The method calculates FDs using slopes of lines fitted to data point subsets of log-log plots of relative surface areas (differences between surface volumes) against scales of calculation. The scales are ranking from an instrument spatial resolution to 1/10 of the image shortest size. Each FD calculated has its individual scale corresponding to the centre of the subset. A flat surface criterion based on the relative areas was proposed. Using the criterion, a flat surface was identified in computer images of circle, sine wave and fractal surface. The DBC method was applied to computer-generated fractal surfaces with increasing roughness and microscope images of isotropic (sandblasted) and anisotropic (ground) surfaces of steel plates. Results showed that the method is accurate in the measurement of surface roughness and the detection of minute changes in roughness of the steel surfaces over a wide range of scales