Identifizierung von Prädiktionsfaktoren für die Verbesserung der Lebensqualität nach Tiefer Hirnstimulation beim Idiopathischen Parkinsonsyndrom

Das idiopathische Parkinsonsyndrom ist eine chronische, neurodegenerative Erkrankung aufgrund einer Störung der Dopaminproduktion. Es kommt dadurch zu diversen motorischen und nicht-motorischen Symptomen. Das IPS kann medikamentös, aber auch operativ durch die Tiefe Hirnstimulation behandelt werden. Bei der THS werden Elektroden in bestimmte Hirnregionen eingesetzt, um mithilfe von Stromimpulsen die durch die Krankheit hervorgerufenen Symptome zu lindern. Bisher zeigte sich, dass diese Behandlung zwar einige Krankheitssymptome verbessern kann, sich die krankheitsbezogene Lebensqualität der Betroffenen aber nicht immer im gleichen Maße verbessert. In dem in dieser Arbeit vorgestellten Paper wurde ermittelt, ob und wie man die Verbesserung der Lebensqualität von IPS-PatientInnen nach einer THS vorhersagen kann. Hierbei wurde insbesondere das prädiktive Potenzial von nicht-motorischen Symptomen untersucht. In der besprochenen Studie wurden mit THS-behandelte IPS-PatientInnen prä- und postoperativ untersucht und die Ergebnisse mithilfe verschiedener statistischer Methoden ausgewertet. Es zeigte sich auch hier eine Verbesserung der Lebensqualität bei nur knapp der Hälfte der Teilnehmenden. Als Prädiktoren für diese konnten mehrere Faktoren bestimmt werden: - Nicht-motorische Symptome (neuropsychiatrische Störungen, Miktionsstörungen, sowie Schmerzen und Gewichtsveränderungen) - Die präoperativ bestehende Lebensqualität - Demographische Faktoren (Alter und Geschlecht) Insbesondere um eine effiziente und personalisierte Behandlung eines IPS zu planen, sind die vorliegenden Ergebnisse wertvoll. Sie können dazu beitragen, die relativ aufwändige und kostenintensive THS weiter zu optimieren, indem geeignete PatientInnen, die voraussichtlich von der Behandlung profitieren, gezielter identifiziert werden. Für die Beratung eben dieser Menschen ist genaueres Wissen über mögliche Behandlungsergebnisse ebenfalls relevant

Web 2.0-Anwendungen in den Kommunen des Landes Sachsen-Anhalt

Der vorliegende Bericht ist das Ergebnis eines einjährigen Studienprojekts am Fachbereich Verwaltungswissenschaften der Hochschule Harz, in dem der derzeitige Einsatz und die potenziellen Einsatzmöglichkeiten von Web 2.0-Anwendungen in den Kommunen des Landes Sachsen-Anhalts untersucht wurden. Im Rahmen des Projekts wurden alle 134 Kommunen des Landes in einem Online-Survey befragt, darüber hinaus wurden in drei Kommunen vertie-fende Interviews durchgeführt und einzelne Aspekte der Web 2.0-Nutzung in einem Online-Forum mit Verwaltungsbeschäftigten und weiteren Expertinnen und Experten diskutiert. Insgesamt ist festzustellen, dass bislang nur ein Bruchteil der Kommunen in Sachsen-Anhalt - wir gehen von maximal 25% aus - Web 2.0-Anwendungen nutzt. Am Stärksten werden bis-lang offene, privatwirtschaftlich betriebene soziale Netzwerke, wie zum Beispiel Facebook, eingesetzt. Auf Basis der vorliegenden Ergebnisse muss bezweifelt werden, dass Kommunen von der Nutzung konventioneller sozialer Netzwerke grundsätzlich in einem Maß profitieren können, das den notwendigen Aufwand rechtfertigen würde. Kommunen, die entsprechende Anwen-dungen nutzen, sehen zwar zumindest teilweise einen Mehrwert. Die Argumente sind aber überwiegend sehr subjektiv. Die Nutzung konventioneller sozialer Netzwerke, wie zum Beispiel Facebook, kann daher nicht pauschal empfohlen werden. Dagegen liegt mit sogenannten Anliegenmanagementsystemen ein Beispiel für eine spezifisch von Kommunen nutzbare Web 2.0-Anwendung vor, aus dem auch Konsequenzen für weiter-führende Nutzungsformen und Neuentwicklungen gezogen werden können. Spezifisch für kommunale Verwaltungen entwickelte, kooperativ implementiert und genutzte Anwendungen, die eine elektronische Kollaboration zwischen Verwaltungen und Stakeholdern in Kernprozes-sen der Kommunalverwaltung ermöglichen, scheinen eine durchaus erfolgsversprechende Option. Neben einer thematischen Erweiterung auf allgemeine und alltägliche Themen der Interaktion von Bürgerinnen und Bürgern mit der kommunalen Verwaltung müssen auch die kooperativen Strukturen zur Entwicklung und zum Betrieb entsprechender Lösungen noch weiter entwickelt werden

Expanding the genotypic and phenotypic spectrum of severe serine biosynthesis disorders.

Serine biosynthesis disorders comprise a spectrum of very rare autosomal recessive inborn errors of metabolism with wide phenotypic variability. Neu-Laxova syndrome represents the most severe expression and is characterized by multiple congenital anomalies and pre- or perinatal lethality. Here, we present the mutation spectrum and a detailed phenotypic analysis in 15 unrelated families with severe types of serine biosynthesis disorders. We identified likely disease-causing variants in the PHGDH and PSAT1 genes, several of which have not been reported previously. Phenotype analysis and a comprehensive review of the literature corroborates the evidence that serine biosynthesis disorders represent a continuum with varying degrees of phenotypic expression and suggest that even gradual differences at the severe end of the spectrum may be correlated with particular genotypes. We postulate that the individual residual enzyme activity of mutant proteins is the major determinant of the phenotypic variability, but further functional studies are needed to explore effects at the enzyme protein level.We are indebted to all families for participating in this study. We would like to acknowledge Dr. Natasha Laidlew, who initially suggested the diagnosis in one of the cases and provided important phenotypic information, and Dr. María-Luisa Martínez-Fernández for the critical management of biosamples in ECEMC Program of Spain. Financial assistance was received in support of the study by grants from the German Federal Ministry of Education and Research (BMBF) (GeNeRARe, FKZ: 01GM1519D) to M. Z. and from the Institute of Health Carlos III: Convenio ISCIII-ASEREMAC, and Fundación 1000 sobre Defectos Congénitos, of Spain to E. B.-S. and I. R. G.S

Improved upper limb function in non-ambulant children with SMA type 2 and 3 during nusinersen treatment: a prospective 3-years SMArtCARE registry study

Background The development and approval of disease modifying treatments have dramatically changed disease progression in patients with spinal muscular atrophy (SMA). Nusinersen was approved in Europe in 2017 for the treatment of SMA patients irrespective of age and disease severity. Most data on therapeutic efficacy are available for the infantile-onset SMA. For patients with SMA type 2 and type 3, there is still a lack of sufficient evidence and long-term experience for nusinersen treatment. Here, we report data from the SMArtCARE registry of non-ambulant children with SMA type 2 and typen 3 under nusinersen treatment with a follow-up period of up to 38 months. Methods SMArtCARE is a disease-specific registry with data on patients with SMA irrespective of age, treatment regime or disease severity. Data are collected during routine patient visits as real-world outcome data. This analysis included all non-ambulant patients with SMA type 2 or 3 below 18 years of age before initiation of treatment. Primary outcomes were changes in motor function evaluated with the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM). Results Data from 256 non-ambulant, pediatric patients with SMA were included in the data analysis. Improvements in motor function were more prominent in upper limb: 32.4% of patients experienced clinically meaningful improvements in RULM and 24.6% in HFMSE. 8.6% of patients gained a new motor milestone, whereas no motor milestones were lost. Only 4.3% of patients showed a clinically meaningful worsening in HFMSE and 1.2% in RULM score. Conclusion Our results demonstrate clinically meaningful improvements or stabilization of disease progression in non-ambulant, pediatric patients with SMA under nusinersen treatment. Changes were most evident in upper limb function and were observed continuously over the follow-up period. Our data confirm clinical trial data, while providing longer follow-up, an increased number of treated patients, and a wider range of age and disease severity

Coefficient of Friction and Height Loss: Two Criteria Used to Determine the Mechanical Property and Stability of Regenerated Versus Natural Articular Cartilage

Background: The coefficient of friction (CoF) serves as an indicator for the mechanical properties of natural and regenerated articular cartilage (AC). After tribological exposure, a height loss (HL) of the cartilage pair specimens can be measured. Our aim was to determine the CoF and HL of regenerated AC tissue and compare them with those of natural AC from non-operated joints and AC from joints where the regenerated tissues had been created after different treatments. Methods: In partial-thickness defects of the trochleae of the stifle joints of 60 Göttingen Minipigs, regenerated AC was created. In total, 40 animals received a Col I matrix, 20 laden with autologous chondrocytes, and 20 without. The defects of 20 animals were left empty. The healing periods were 24 and 48 weeks. A total of 10 not-operated animals, delivered the “external” control specimens. Osteochondral pins were harvested from defect and non-defect areas, the latter serving as “internal” controls. Using a pin-on-plate tribometer, we measured the CoF and the HL. Results: The CoF of the regenerated AC ranged from 0.039 to 0.069, and the HL, from 0.22 mm to 0.33 mm. The differences between the regenerated AC of the six groups and the “external” controls were significant. The comparison with the “internal” controls revealed four significant differences for the CoF and one for the HL in the operated groups. No differences were seen within the operated groups. Conclusions: The mechanical quality of the regenerated AC tissue showed inferior behavior with regard to the CoF and HL in comparison with natural AC. The comparison of regenerated AC tissue with AC from untreated joints was more promising than with AC from the treated joints

Short-term quality of life after subthalamic stimulation depends on non-motor symptoms in Parkinson's disease

Background: Subthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL), motor, and non-motor symptoms (NMS) in advanced Parkinson's disease (PD). However, considerable inter-individual variability has been observed for QoL outcome. Hypothesis: We hypothesized that demographic and preoperative NMS characteristics can predict postoperative QoL outcome. Methods: In this ongoing, prospective, multicenter study (Cologne, Manchester, London) including 88 patients, we collected the following scales preoperatively and on follow-up 6 months postoperatively: PDQuestionnaire-8 (PDQ-8), NMSScale (NMSS), NMSQuestionnaire (NMSQ), Scales for Outcomes in PD (SCOPA)-motor examination, -complications, and -activities of daily living, levodopa equivalent daily dose. We dichotomized patients into QoL responders/non-responders and screened for factors associated with QoL improvement with (1) Spearman-correlations between baseline test scores and QoL improvement, (2) step-wise linear regressions with baseline test scores as independent and QoL improvement as dependent variables, (3) logistic regressions using aforementioned responders/nonresponders as dependent variable. Results: All outcomes improved significantly on follow-up. However, approximately 44% of patients were categorized as QoL non-responders. Spearman-correlations, linear and logistic regression analyses were significant for NMSS and NMSQ but not for SCOPA-motor examination. Post-hoc, we identified specific NMS (flat moods, difficulties experiencing pleasure, pain, bladder voiding) as significant contributors to QoL outcome. Conclusions: Our results provide evidence that QoL improvement after STN-DBS depends on preoperative NMS characteristics. These findings are important in the advising and selection of individuals for DBS therapy. Future studies investigating motor and non-motor PD clusters may enable stratifying QoL outcomes and help predict patients' individual prospects of benefiting from DBS. (C) 2018 Published by Elsevier Inc

Das Lagemanagement des Robert Koch-Instituts während der COVID-19-Pandemie und der Austausch zwischen Bund und Ländern

The Robert Koch Institute (RKI) plays a central role in Germany in the management of health hazards of biological origin. The RKI's crisis management aims to contribute to protecting the health of the population in Germany in significant epidemic situations and to maintain the RKI's working ability over a long period of time even under high load. This article illustrates the crisis management of the RKI in general as well as during the COVID-19 pandemic. The generic RKI crisis management structures and the setup of the RKI emergency operations centre (EOC), their operationalisation in the context of the COVID-19 pandemic and the resulting challenges as of 31 October 2020 are described in this paper. The exchange between the federal and state governments during the pandemic is also described.The COVID-19 pandemic has led to extraordinary circumstances. During the epidemic situation, good communication and coordination has been essential, both within the RKI and with other federal or state authorities and expert groups. Under great pressure, the RKI produces and regularly updates recommendations, statements and assessments on various topics. To provide operational support for all COVID-19 related activities, an EOC was activated at the RKI. During the COVID-19 pandemic, there are various challenges regarding personnel and structures. It became apparent that good preparation (e.g. existing task descriptions and premises) has an important positive impact on crisis management