Quality of life and life circumstances in German myasthenia gravis patients

<p>Abstract</p> <p>Background</p> <p>Myasthenia gravis (MG) is a chronic neuromuscular disease. Advances in medical therapy have continuously increased the life expectancy of MG patients, without definitively curing the disease. To analyze life circumstances and quality of life (QoL), a large German MG cohort was investigated.</p> <p>Methods and Sample</p> <p>In cooperation with the German Myasthenia Association, 2,150 patients with confirmed MG were asked to respond to a mailed questionnaire. The standardized questions related to demographic data, impairments, therapeutic course, use of complementary therapies, illness-related costs, and quality of life (SF-36). In total, 1,518 patients participated, yielding a response rate of 70.6%. The average age was 56.7 years, and the proportion of females 58.6%.</p> <p>Results</p> <p>Despite receiving recommended therapy, many patients still suffered from MG-related impairments. In particular, mobility and mental well-being were reduced; moreover, quality of life was markedly reduced. Stepwise linear regression analysis revealed illness stability, impairments, mental conditions, comorbid diseases, and employment to be determinants of QoL.</p> <p>Conclusion</p> <p>Results indicate that despite prolonged life expectancy among MG patients, health-related quality of life is low. This outcome resulted mainly from impaired mobility and depression. Physical and mental well-being might be improved by additional therapy options. Additionally, health care resources could be used more efficiently in these patients.</p

Frequency and predictors of relapses following SARS-CoV-2 vaccination in patients with multiple sclerosis: interim results from a longitudinal observational study

Despite protection from severe COVID-19 courses through vaccinations, some people with multiple sclerosis (PwMS) are vaccination-hesitant due to fear of post-vaccination side effects/increased disease activity. The aim was to reveal the frequency and predictors of post-SARS-CoV-2-vaccination relapses in PwMS. This prospective, observational study was conducted as a longitudinal Germany-wide online survey (baseline survey and two follow-ups). Inclusion criteria were age ≥18 years, MS diagnosis, and ≥1 SARS-CoV-2 vaccination. Patient-reported data included socio-demographics, MS-related data, and post-vaccination phenomena. Annualized relapse rates (ARRs) of the study cohort and reference cohorts from the German MS Registry were compared pre- and post-vaccination. Post-vaccination relapses were reported by 9.3% PwMS (247/2661). The study cohort’s post-vaccination ARR was 0.189 (95% CI: 0.167–0.213). The ARR of a matched unvaccinated reference group from 2020 was 0.147 (0.129–0.167). Another reference cohort of vaccinated PwMS showed no indication of increased post-vaccination relapse activity (0.116; 0.088–0.151) compared to pre-vaccination (0.109; 0.084–0.138). Predictors of post-vaccination relapses (study cohort) were missing immunotherapy (OR = 2.09; 1.55–2.79; p < 0.001) and shorter time from the last pre-vaccination relapse to the first vaccination (OR = 0.87; 0.83–0.91; p < 0.001). Data on disease activity of the study cohort in the temporal context are expected for the third follow-up

Entscheidungsgrundlagen zur Einführung räumlicher spritzgegossener Schaltungsträger (3-D MID)

Ziel dieser Arbeit war es, die zur Einführung der MID-Technologie relevanten Entscheidungskriterien durch systematische Analyse möglichst umfassend zu erarbeiten und transparent zu machen. Hierzu wurden verschiedene Konzepte entwickelt und Maßnahmen umgesetzt, die potentielle Anwender bei der Entscheidungsfindung unterstützen. Ein Schwerpunkt der Arbeit lag auf der Entwicklung und Anpassung organisatorischer Konzepte hinsichtlich des Unternehmensaufbaus. Aufgrund der stark vernetzten Produktstruktur bietet sich für MID-Entwicklungen die enge Kooperation von kompetenten Partnern aus verschiedenen Disziplinen geradezu an. Das „Simultaneous Engineering”, das Entwicklungsabläufe parallelisiert, muß zum „Holonic Engineering” mit integrativen Entwicklungskonzepten weitergeführt werden. Ist dies in einem Unternehmen nicht möglich, so bietet sich besonders die Zusammenarbeit in virtuellen Unternehmen an. Im Rahmen von verschiedenen Projekten wurden Aspekte der praktischen Umsetzung eines solchen Netzwerkes erforscht, wobei meist ein Mischtyp Verwendung fand. Ein weiterer Schwerpunkt der Arbeit war die Adaption von systematischen Strukturen der Ablauforganisation an die Spezifika der MID-Technologie. Besonders bei komplexen Baugruppen mit starken Interdependenzen von Funktion und Herstellprozeß und zahlreichen Variationsmöglichkeiten ist die Anwendung der technisch-wirtschaftlichen Produktkonstruktion mit entsprechenden Bewertungsmechanismen eine wichtige Voraussetzung für eine zielführende Entwicklung der Baugruppe. Die entwickelten Methoden und Modelle wurden am Beispiel der Einführung einer Datenträgerkarte verifiziert. Bei der Entwicklung eines Produktes und der Entscheidung für eine bestimmte Technologie müssen natürlich immer die Anforderungen der Märkte - wie auch der Produktionsverfahren - im Auge behalten werden. Hier konnten Ansätze zur kundenneutralen Formulierung von Spezifikationen ausgearbeitet werden, die in einem Handbuch für Entwickler und Hersteller von MIDs Einfluß fanden. Gleichzeitig wurden bestehende Normen für Testverfahren und die Akzeptanz von Leiterplatten auf die bei räumlichen, thermoplastischen Schaltungsträgern anzutreffenden Randbedingungen angepaßt. Häufig ist Unsicherheit über die Leistungsfähigkeit und Belastbarkeit spritzgegossener Substrate ein Grund für zögernde Akzeptanz der MID-Technologie. In umfangreichen Untersuchungen zur Strombelastbarkeit konnte nachgewiesen werden, daß thermoplastische Kunststoff-Basismaterialien mindestens so leistungsfähig sind wie die konventionellen, duroplastischen. Dabei wurde der Aussagebereich der DIN IEC 326 [152] wesentlich erweitert. Zur Beurteilung der Eignung eines bestimmten Herstellverfahrens für die in Betracht gezogene Anwendung wurden Eignungsprofile entwickelt, die mit den aus den Anforderungen abzuleitenden Anforderungsprofilen korreliert werden können und so entsprechende Aussagen zulassen. Einige Beispiele zeigen, daß die Anwendung der Profile ein einfach handhabbares Mittel zur Verfahrensauswahl ist. Ein weiterer zentraler Punkt der Arbeit ist die Aufstellung eines Kostenmodells über die gesamte MID-Herstellkette und die Darstellung der Kostenfaktoren. Hierzu wurde zuerst die Prozeßkostenrechnung als geeignetes Rechenmodell ausgewählt. Anschließend wurden die relevanten Einflußfaktoren für alle Schritte der Prozeßkette erarbeitet und verknüpft. Gleichzeitig wurden anhand eines Beispiels die Grenzkosten für den Übergang von chemischer auf chemisch-galvanische Beschichtung berechnet. Die Ausarbeitung von Gestaltungsrichtlinien für die fertigungsgerechte MID-Konstruktion unter Berücksichtigung der besonderen, durch die Technologie gegebenen Randbedingungen und verschiedener Wege zur Vermittlung der bereitzustellenden Information runden die Unterstützung der Entscheidungsfindung hinsichtlich der Einführung der MID-Technologie ab. Eine wichtige Rolle spielt dabei auch eine durchgeführte Patentrecherche, die Aufschluß über die rechtliche Situation bei der Wahl bestimmter Fertigungsverfahren bietet. Während der Analyse der industriellen Strukturen und der derzeitigen Grenzen zeigten sich auch einige Punkte, die Gegenstand weiterführender Arbeiten sein könnten: Eine durch Datenverarbeitungssysteme gestützte Vorkalkulation von MID Bauteilen, die nach Eingabe einiger weniger Grundparameter eine möglichst genaue Abschätzung der zu erwartenden Teilekosten ergibt und eine automatisierte Auswahl des für eine Applikation am besten geeigneten Fertigungsverfahrens ermöglicht, wäre wünschenswert, erfordert aber den Aufbau eines Wissenspools aus Fertigungsdaten und eine genauere Untersuchung der Kostenstrukturen. Die für statistisch gesicherte Aussagen und die anbieterneutrale Abstraktion erforderliche breite Datenbasis steht jedoch aufgrund der noch geringen Verbreitung der Technologie nicht zur Verfügung. Simulationsbasierte Methoden des Virtual Product Development können z.B. durch Bestimmung der Oberflächenausbildung und der daraus resultierenden Metallisierbarkeit einen Beitrag zur wichtigen Verkürzung der Entwicklungszeiten leisten. Dies kann zukünftig weiter gestützt werden durch Verfahren des Rapid Prototyping und Rapid Tooling, wobei die Herausforderung vor allem in der selektiven Metallisierbarkeit der entstehenden Körper liegt. Hinsichtlich der Informationsvermittlung wäre eine gute Möglichkeit, interessierten Firmen und ihren Mitarbeitern den entwickelten ’’Technologie-Lehrpfad” vor Ort vorzustellen. Dies könnte z.B. durch ein auch für Veranstaltungen geeignetes mobiles Informationszentrum geschehen, was jedoch nicht zuletzt eine Frage der Finanzierung ist. Die erarbeiteten Erweiterungen der bestehenden Testnormen sollten nicht nur, wie geschehen, durch Fachpublikationen bekanntgemacht, sondern über die entsprechenden Gremien zum festen Bestandteil internationaler Normen ausgebaut werden. Hierbei muß langfristig auch der Zusammenhang mit anderen für dreidimensionale Schaltungen geeigneten Technologien in Betracht gezogen und Synergien genutzt werden. Die Anwendung der im Rahmen dieser Arbeit vorgestellten Konzepte und Methoden wird es zusammen mit möglichen zukünftigen Erweiterungen der MID-Technologie ermöglichen, einen festen Platz im Reigen der für die Elektronikproduktion verfügbaren Technologien einzunehmen und die Entscheidung der Entwickler durch das Bereitstellen fundierter Informationen zu erleichtern.The aim of this work was to systematically analyze the decision criteria relevant to the introduction of MID technology as comprehensively as possible and to make them transparent. Various concepts were developed and measures implemented to support potential users in their decision-making. One focus of the work was on the development and adaptation of organizational concepts with regard to the company structure. Due to the strongly networked product structure, the close cooperation of competent partners from various disciplines is ideal for MID developments. "Simultaneous engineering", which parallelizes development processes, must be continued to "holonic engineering" with integrative development concepts. If this is not possible in a company, cooperation in virtual companies is particularly suitable. Aspects of the researched the practical implementation of such a network, mostly using a mixed type. Another focus of the work was the adaptation of systematic structures of the process organization to the specifics of the MID technology. Particularly in the case of complex assemblies with strong interdependencies between function and manufacturing process and numerous possible variations, the application of the technical and economic product design with appropriate evaluation mechanisms is an important prerequisite for the targeted development of the assembly. The developed methods and models were verified using the example of the introduction of a data carrier card. When developing a product and deciding on a certain technology, the requirements of the markets - as well as the production processes - must always be kept in mind. Here approaches to customer-neutral formulation of specifications could be worked out, which were influenced in a manual for developers and manufacturers of MIDs. At the same time, existing standards for test procedures and the acceptance of printed circuit boards were adapted to the boundary conditions encountered with spatial, thermoplastic circuit carriers. Uncertainty about the performance and resilience of injection molded substrates is often a reason for hesitant acceptance of MID technology. Extensive investigations of the current carrying capacity have shown that thermoplastic base materials are at least as efficient as conventional, thermosetting ones. The information range of DIN IEC 326 [152] has been significantly expanded. To assess the suitability of a particular manufacturing process for the application under consideration, suitability profiles have been developed that can be correlated with the requirement profiles to be derived from the requirements and thus allow appropriate statements to be made. Some examples show that the use of the profiles is an easy-to-use means of selecting a process. Another central point of the work is the establishment of a cost model across the entire MID manufacturing chain and the presentation of the cost factors. For this purpose, process cost accounting was first selected as a suitable calculation model. The relevant influencing factors for all steps in the process chain were then developed and linked. At the same time, an example was used to calculate the marginal costs for the transition from chemical to chemical-galvanic coating. The elaboration of design guidelines for the MID design suitable for production, taking into account the special boundary conditions given by the technology and various ways of conveying the information to be provided, round off the support for decision-making regarding the introduction of MID technology. An important role is also played by a patent search that provides information about the legal situation when choosing certain manufacturing processes. During the analysis of the industrial structures and the current limits, there were also some points that could be the subject of further work: A precalculation of MID components supported by data processing systems, which, after entering a few basic parameters, gives the most accurate possible estimate of the expected part costs and an automated one Selection of the most suitable manufacturing process for an application would be desirable, but requires the creation of a knowledge pool from manufacturing data and a more detailed analysis of the cost structures. However, the broad data base required for statistically reliable statements and the provider-neutral abstraction is not available due to the fact that the technology is not yet widely used. Simulation-based methods of virtual product development can e.g. make a contribution to the important reduction in development times by determining the surface formation and the resulting metallizability. This can be further supported in the future by methods of rapid prototyping and rapid tooling, whereby the challenge lies above all in the selective metallizability of the resulting bodies. With regard to the transfer of information, a good opportunity would be to present the developed ’’ Technology Education Path ”to interested companies and their employees on site. This could e.g. through a mobile information center that is also suitable for events, but this is not least a question of financing. The developed extensions of the existing test standards should not only be published through specialist publications, as was done, but should also be expanded to become an integral part of international standards via the relevant bodies. In the long term, the connection with other technologies suitable for three-dimensional circuits must also be considered and synergies must be used. The application of the concepts and methods presented in this work, together with possible future extensions of the MID technology, will enable it to take a firm place in the ranks of the technologies available for electronic production and to facilitate the decision of the developers by providing well-founded information

REBISTART: Adherence of Patients with Multiple Sclerosis to Treatment with Subcutaneous Interferon Beta in the Context of a Patient Support Program.

INTRODUCTION Treatment adherence is a critical success factor in the disease-modifying therapy (DMT) of multiple sclerosis (MS). The REBISTART study prospectively evaluated adherence in patients using components of a patient support program (PSP). METHODS The 12-month non-interventional multicenter study examined the real-world adherence to subcutaneously (sc) injected interferon beta-1a (Rebif®). Patient-assessed adherence was measured by a visual analog scale (VAS) and the Morisky Medication Adherence Scale (MMAS). Objective adherence data were obtained by readouts from the RebiSmart® injection device. RESULTS Of 333 patients, 70.9% used the nursing service as the core component of the PSP. Self-assessed VAS-based adherence was stable over time at 94.0-96.3%. Similarly, MMAS score (maximum 4) was 3.8-3.9 at all visits, also reflecting high self-assessed adherence. In 269 patients using the RebiSmart® injection device, mean readout-based objective adherence was similarly high (93.0-98.4% throughout visits). At last available visit, VAS-based adherence was independent of participation in the PSP nursing service (93.1% with participation versus 91.7% without it). Adherence was also independent of injection method or disease-related measures, including fatigue, depression, cognition, and quality of life. The most frequent reason for the premature discontinuations (38.7% of patients) was "change of treatment" (10.0%). DISCUSSION We suggest that subgroups that may specifically benefit from PSP include patients who live alone, use multiple comedications, and are affected by cognitive impairment, depression, and/or fatigue. Further studies should investigate the potential usefulness of PSPs in these populations. CONCLUSIONS Very high adherence rates independent of the PSP nursing service over 1 year of treatment indicate that IFN beta-1a sc is an easy-to-use and well-tolerated disease-modifying drug. TRIAL REGISTRATION NUMBER Vfa.de: No. 892. https://www.vfa.de/de/arzneimittel-forschung/datenbanken-zu-arzneimitteln/nisdb/nis-details/_892

Successful treatment of methicillin-resistant Staphylococcus aureus meningitis using linezolid without removal of intrathecal infusion pump

Infection of an intrathecal pump system is a rare but serious complication and usually leads to the removal of the pump. The authors report the first case of methicillin-resistant Staphylococcus aureus (MRSA) meningitis in a patient with such a pump successfully treated with linezolid without the need for removal of the intrathecal pump. A 77-year-old woman with cervical myelopathy underwent implantation of an intrathecal pump system for baclofen administration. Two weeks after the procedure she developed meningitis caused by MRSA as isolated in cerebrospinal fluid (CSF) cultures, blood samples, and serum obtained from the pump pouch. Clinically she presented with meningism, somnolence, and signs of sepsis. When a combined intravenous antibiotic treatment regimen of vancomycin and rifampicin resulted in no clinical improvement, that regimen was discontinued and linezolid was administered intravenously as monotherapy. Within 3 days clinical and laboratory findings showed significant improvement. After 1 week of linezolid treatment, blood and CSF cultures were sterile. Intravenous treatment was administered for a total of 3 weeks, after which the patient was treated with oral linezolid for 3 months. During 18 months of follow-up, no new clinical or laboratory signs of infection were observed. These results confirm previous reports of the efficacy of linezolid for the treatment of severe infections of the central nervous system caused by multidrug-resistant Gram-positive bacteria, especially postneurosurgical infections