Prevalence, Duration and Severity of Parkinson’s Disease in Germany: A Combined Meta-Analysis from Literature Data and Outpatient Samples

Background: Epidemiological data on the prevalence of Parkinson’s disease (PD) in Germany are limited. The aims of this study were to estimate the age- and gender-specific prevalence of PD in Germany as well as the severity and illness duration. Summary: A systematic literature search was performed in 5 different databases. European studies were included if they reported age- and gender-specific numbers of prevalence rates of PD. Meta-analytic approaches were applied to derive age- and gender-specific pooled prevalence estimates. Data of 4 German outpatient samples were incorporated to calculate the proportion of patients with PD in Germany grouped by Hoehn and Yahr (HY) stages and disease duration. In the German population, 178,169 cases of PD were estimated (prevalence: 217.22/100,000). The estimated relative illness duration was 40% with less than 5 years, 31% with 5–9 years, and 29% with more than 9 years. The proportions for different HY stages were estimated at 13% (I), 30% (II), 35% (III), 17% (IV), and 4% (V), respectively. Key Message: We provide an up-to-date estimation of age and gender-specific as well as severity-based prevalence figures for PD in Germany. Further community studies are needed to estimate population-based severity distributions and distributions of non-motor symptoms in PD

Semi-Analytic Correlation for Predicting Permeability of Micro-Square-Pillar Array

In this study, we consider the permeability of hexagonal arrays of micro-square pillars. A semi-analytic model for predicting the permeability of micro-square pillar arrays is developed. In addition, a numerical analysis is performed with taking into account the effect of meniscus curvature. The analytic and numerical results are in good agreement, within an error of 3%. Based on our analytic and numerical results, the effects of the contact angle (0 < theta < 90 degrees), nondimensional pillar diagonal length (0.1 < d* < 0.5), and nondimensional pillar height (0.5 < H* < 2.5) are investigated The meniscus curvature is shown to reduce the permeability significantly, particularly when the contact angle is small or the pillar height is low The permeability of the square pillar array is shown to be larger than that of a circular pillar arra.ope

Down-regulation of S1P1 Receptor Surface Expression by Protein Kinase C Inhibition*

The sphingosine 1-phosphate receptor type 1 (S1P1) is important for the maintenance of lymphocyte circulation. S1P1 receptor surface expression on lymphocytes is critical for their egress from thymus and lymph nodes. Premature activation-induced internalization of the S1P1 receptor in lymphoid organs, mediated either by pharmacological agonists or by inhibition of the S1P degrading enzyme S1P-lyase, blocks lymphocyte egress and induces lymphopenia in blood and lymph. Regulation of S1P1 receptor surface expression is therefore a promising way to control adaptive immunity. Hence, we analyzed potential cellular targets for their ability to alter S1P1 receptor surface expression without stimulation. The initial observation that preincubation of mouse splenocytes with its natural analog sphingosine was sufficient to block TranswellTM chemotaxis to S1P directed subsequent investigations to the underlying mechanism. Sphingosine is known to inhibit protein kinase C (PKC), and PKC inhibition with nanomolar concentrations of staurosporine, calphostin C, and GF109203X down-regulated surface expression of S1P1 but not S1P4 in transfected rat hepatoma HTC4 cells. The PKC activator phorbol 12-myristate 13-acetate partially rescued FTY720-induced down-regulation of the S1P1 receptor, linking PKC activation with S1P1 receptor surface expression. FTY720, but not FTY720 phosphate, efficiently inhibited PKC. Cell-based efficacy was obvious with 10 nm FTY720, and in vivo treatment of mice with 0.3–3 mg/kg/day FTY720 showed increasing concentration-dependent effectiveness. PKC inhibition therefore may contribute to lymphopenia by down-regulating S1P1 receptor cell surface expression independently from its activation

An Observational Study of the Effect of Levodopa-Carbidopa Intestinal Gel on Activities of Daily Living and Quality of Life in Advanced Parkinson's Disease Patients

Continuous delivery of levodopa-carbidopa intestinal gel (LCIG) by percutaneous endoscopic gastrojejunostomy (PEG-J) in advanced Parkinson's disease (PD) patients reduces variability in plasma levels, providing better control of motor fluctuations ("on" and "off" states). The MONOTREAT study assessed the effect of LCIG on activities of daily living, motor and non-motor symptoms, and quality of life in advanced PD patients. This prospective, observational study included patients with advanced, levodopa-responsive PD with either 2-4 h of "off" time or 2 h of dyskinesia daily. Patients received LCIG via PEG-J for 16 h continuously. Effectiveness was assessed using Unified PD Rating Scale parts II and III, the Non-Motor Symptom Scale, and the PD Questionnaire-8. The mean (SD) treatment duration was 275 (157) days. Patients experienced significant improvement from baseline in activities of daily living at final visit (p < 0.05) as well as at months 3 and 6 (p < 0.0001). Patients also experienced significant improvements from baseline in quality of life and non-motor symptoms at all time points (p < 0.001 for all). Specifically, patients manifested significant improvements in mean change from baseline at every study visit in five of nine non-motor symptom score domains: sleep/fatigue, mood/cognition, gastrointestinal tract, urinary, and miscellaneous. One-third of patients (32.8%) experienced an adverse event; 21.9% experienced a serious adverse event; 11.1% discontinued because of an adverse event. This study demonstrated significant and clinically relevant improvements in measures of activities of daily living, quality of life, and a specific subset of non-motor symptoms after treatment with LCIG. AbbVie Inc. The online version of this article (doi:10.1007/s12325-017-0571-2) contains supplementary material, which is available to authorized users