The transdermal formulation of rivastigmine improves caregiver burden and treatment adherence of patients with Alzheimer's disease under daily practice conditions.

BACKGROUND: Rivastigmine is the only cholinesterase inhibitor (ChEI) available as transdermal patch. The patch was developed to improve gastrointestinal tolerability and treatment adherence to higher dosages as compared with oral medication. Preferences of patients and caregivers for the patch were reported; however, neither patient compliance nor caregiver burden has yet been measured under routine practice conditions. METHODS: This was a prospective, multi-centre, observational study in patients with Alzheimer's disease treated with rivastigmine patch in Germany. To compare the transdermal with oral dosage forms, physicians were asked to enrol patients who recently switched from oral to transdermal medication. Beyond effectiveness and tolerability, outcome measures were drug adherence evaluated by the Morisky questionnaire, and caregiver burden, measured as the daily time expenditure for dressing the patient, controlling appearance and administration of medication. RESULTS: In total, 1104 outpatients (57.5% female gender; mean age 77 ± 7 years) were enrolled in 220 sites. After 6 months of treatment, 67.5% of patients had an improved Clinical Global Impression and the Mini-Mental State Examination score increased from 19.0 ± 5.1 to 20.0 ± 5.2 (p < 0.001); 84.1% of patients were still on treatment, 64.6% on the target dose of 9.5 mg/day. Compliance and patient satisfaction with therapy continuously increased over the study period and average time savings of caregivers added up to 20 min/day. In general, tolerability was deemed good and there were no unexpected adverse events. CONCLUSIONS: Transdermal rivastigmine is an effective treatment alternative, which may improve adherence and treatment satisfaction of the patient and relieve the caregiver. Controlled parallel-group trials are warranted. CLINICAL TRIALS REGISTRATION: none (observational study).

Rapid Onset and Sustained Efficacy (ROSE) study: results of a randomised, multicentre trial comparing the effect of zoledronic acid or alendronate on bone metabolism in postmenopausal women with low bone mass.

SUMMARY: The ROSE study compared a once-yearly intravenous dose of zoledronic acid with a once-weekly oral dose of alendronate in postmenopausal women. Once-yearly zoledronic acid showed a greater and faster reduction in the levels of two markers of bone turnover and may be an effective option for the treatment of osteoporosis. INTRODUCTION: The open-label Rapid Onset and Sustained Efficacy (ROSE) study was designed to compare a once-yearly intravenous (iv) dose of zoledronic acid with a once-weekly oral dose of alendronate with respect to markers of bone turnover in approximately 600 postmenopausal women in Germany. METHODS: Levels of N-telopeptide of collagen type I (NTx) and procollagen 1 C terminal extension peptide (P1NP) were assessed during the study. The primary objective was to assess if zoledronic acid was superior to alendronate in reducing serum NTx levels after 12 months' treatment. RESULTS: A significantly greater reduction in NTx levels from baseline to month 12 (as determined by the area under the curve) was observed in patients treated with zoledronic acid (n = 408) versus those receiving alendronate (n = 196; 0.282 ng/mL vs. 0.270 ng/mL; P = 0.012). The reduction in levels of P1NP after 1 year was also significantly greater in patients treated with zoledronic acid compared with those receiving alendronate (28.21 vs. 25.53 ng/mL; P = 0.0024). The overall incidence of adverse events was similar between groups; both treatments were generally well tolerated. Although post-dose symptoms, including the incidence of influenza-like symptoms, were higher with zoledronic acid than alendronate initially, the incidence was similar between groups from days 4-360. Gastrointestinal symptoms were more frequent with alendronate than zoledronic acid throughout the study. CONCLUSION: In this study, once-yearly iv zoledronic acid provided a greater and faster reduction in the levels of NTx and P1NP versus once-weekly oral alendronate.

Quality of life and health status with zoledronic acid and generic alendronate--a secondary analysis of the Rapid Onset and Sustained Efficacy (ROSE) study in postmenopausal women with low bone mass.

SUMMARY: The ROSE study compared annual infusion with zoledronic acid and weekly generic alendronate. No significant differences in quality of life or health status between treatment groups were observed. Adherence to alendronate during the study was high, with 80.9% of patients achieving adequate adherence. INTRODUCTION: A secondary analysis to evaluate quality of life, health status, adherence to alendronate and therapy preference in postmenopausal women with low bone mass who received treatment with zoledronic acid or alendronate was conducted. METHODS: Postmenopausal women with low bone mass were randomised 2:1 to receive an annual infusion of zoledronic acid or weekly oral generic alendronate in this open-label, multicentre study. Changes in quality of life and health status were assessed using questionnaires at baseline and month 12. Adherence to alendronate was assessed by the investigator and/or study personnel, and subjective therapy preference was assessed using a questionnaire at month 12. RESULTS: Patients were randomised to zoledronic acid (n = 408) and alendronate (n = 191). Overall, there were no significant differences in quality of life between zoledronic acid and alendronate. However, improvements in quality of life with zoledronic acid versus alendronate could be detected by posthoc analysis in patients with previous fractures. There were no significant differences in health status between patients receiving zoledronic acid or alendronate. Adherence to alendronate during the study was high, with 80.9% of patients achieving adequate adherence. A total of 81% of patients who had received zoledronic acid indicated that they would prefer to continue with that treatment, and 43% of the patients who received oral alendronate would like to switch to zoledronic acid. CONCLUSIONS: There were no significant differences in quality of life between patients receiving zoledronic acid or alendronate.

A 24-week, multicentre, open evaluation of the clinical effectiveness of the rivastigmine patch in patients with probable Alzheimer's disease.

BACKGROUND: Cholinesterase inhibitors form the mainstay of treatment for persons with mild-to-moderate Alzheimer's disease (AD). The rivastigmine patch may increase compliance and the proportion of patients maintaining an efficacious dose compared with oral cholinesterase inhibitors. OBJECTIVE: To investigate the proportion of patients who reached and maintained the target rivastigmine patch dose compared with the target rivastigmine capsule dose reported in clinical trials. METHODS: This was a multicentre, 24-week, open-label study in persons with probable AD and a Mini-Mental State Examination (MMSE) score of ≥ 10 and ≤ 26. The primary outcome was the proportion of patients (ITT population) treated with 9.5 mg/24 h rivastigmine patch for at least 8 weeks at week 24. Secondary outcomes included week 24 MMSE, Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC), Trail Making Test Part A (TMT-A) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scores. RESULTS: Overall, 208 participants received treatment and 155 (74.5%) completed the study. Within the ITT population, 147/182 patients (80.8%; 95% CI 75.0-86.5%) were treated for at least 8 weeks with the 9.5 mg/24 h rivastigmine patch; 135/182 patients (74.2%; 95% CI 67.8-80.5%) were treated for at least 8 weeks and completed the study. The most common adverse events were nausea (10.1% of patients), erythema (8.7%), pruritus (8.2%) and vomiting (7.2%). At week 24, patients treated with the rivastigmine patch showed improvements on MMSE, ADCS-ADL, ADCS-CGIC and TMT-A scores. Caregivers reported acceptance, preference and satisfaction with the patch. CONCLUSION: Transdermal delivery may allow more patients to reach and maintain therapeutic doses of rivastigmine compared with oral rivastigmine.

Development and validation of a semiautomatic image analysis system for measuring skin desquamation with D-Squames.

BACKGROUND: D-Squames, have gained wide acceptance for assessing skin desquamation. The amount of corneocytes adhering to D-Squames can be assessed visually by trained observers or by computerized image analysis. Different image analysis algorythms for the evaluation of D-Squames have been published but have not been compared with each other. It was our aim to develop an image analysis system that does not require an expensive image analysis programming tool but should be optimized for routine tasks of analysing large numbers of samples. A second objective of this study was to compare two published image analysis algorythms and visual grading. MATERIAL AND METHODS: The hardware components of the system are a CCD camera connected to a frame grabber card and a light box equipped with fluorescent tubes on two sides that provide a relatively cool, diffuse and even illumination of the sample. The following features were included into the software: generation and identification of bar codes for sample identification; semiautomatic recognition of ROI (region of interest), integration of study design into the analysing process, rapid calculation of desquamation index (DI: integration of the per cent area covered by scales and their thickness distribution) and/or scaling index (SI: distribution of grey values), data storage and export for further analysis. In a first step the system was validated by examining D-Squames covering a wide range of desquamation, by examining different ROI shapes (circle and square), by performing repeat measurements with different positions of the samples and by repeat measurements after re-callibrating the system. In a second step the effect of treatment with different moisturizers was evaluated by the two image analysis parameters DI and SI and compared with hydration measurements (Corneometer). RESULTS: The shape of the ROI showed no influence on the results (variability < 5%). Reproducibility of measurements was satisfactory (COV CDI): 1.7%, COV (SI): 2.6%). There was a good correlation between image analysis results and visual evaluation (means of 3 technicians) (r = 0.986) as well as between the two different image analysis parameters DI and SI (r = 0.971). In the clinical study moisturizer treatment resulted in variable reduction of desquamation that was closely correlated with increase in stratum corneum hydration (r = 0.97). CONCLUSION: Analysing D-Squames with the image analysis system proved to be reproducible, independent of the shape of ROI, cost effective and fast and easy to operate. It has shown to be a suitable and reliable method for the objective determination of desquamation levels.

Scale-sensitive fractal analysis using the patchwork method for the assessment of skin roughness.

BACKGROUND/AIMS: As skin roughness and wrinkles are easily perceived by the consumer, quantifying skin surface structures is a vital parameter for cosmetic product development. As more tools are available for measuring three-dimensional (3-D) surface data, instead of two-dimensional (2-D) profile lines, new algorithms are desirable, to take advantage of the information gathered. METHODS: The patchwork method tiles topographic data sets virtually and analyzes the change in apparent area as a function of tile scale. The patchwork method and conventional 2-D profilometric analysis were applied to 24 topographic skin data sets. The data sets were derived before and after application of 15% glycerol solution on the skin of eight volunteers. RESULTS: One hour after application, skin roughness decreased by 20.8%, as measured by conventional analysis, and by 23.3%, as measured by the patchwork method. For both methods, the differences were not significant. CONCLUSIONS: The patchwork method can be applied to skin data and renders results similar in intensity and direction to conventional 2-D analysis. It is advantageous over conventional 2-D analysis in three ways: it makes use of the full topologic information, it requires no high-pass or low-pass filtering, and it is independent of the anisotropy of the skin.