Fokus auf der Untersuchung des Einflusses biometrischer Faktoren auf das Ergebnis der nTMS Messung sprachrelevanter Areale neurochirurgischer Patienten

Objective: Navigated transcranial magnetic stimulation (nTMS) is a non-invasive mapping tool to locate functional areas of the brain, gaining importance as a preoperative diagnostic device. This is a summary of three studies, Schwarzer et al., Rosenstock et al. and Zdunczyk et al., whose aim it is to increase the accuracy and usability of nTMS in different neurosurgical patient groups. They intend to describe neurophysiological data gained through nTMS as a supportive measure for surgical planning to increase patient safety and improve outcome. Methods: All patients and healthy subjects were examined via bihemispheric nTMS. Schwarzer et al. ascertained a baseline picture naming performance and used repetitive nTMS (rnTMS) to induce speech disruptions to identify individual language areas in patients with language eloquent lesions. Nine biometric factors were analyzed for correlation with elevated error occurrence. Rosenstock et al. concentrated on the primary motor cortex of patients with motor-eloquent glioma and performed correlation analyses to test the association of nTMS-related variables and postoperative motor outcome. Zdunczyk et al. examined patients with degenerative cervical myelopathy (DCM) and healthy volunteers to see differences in neurophysiological nTMS data due to disease severity. Results: Schwarzer et al. showed a significant increase in error occurrence with increased severity of cognitive impairment (p8mm (p=0.014). New postoperative deficits could be seen in patients with pathological excitability of the motor cortex (resting motor threshold ratio 110%, p=0.031). Patients with DCM had a reduced corticospinal excitability estimated by the recruitment curve (p=0.022), and patients with mild symptoms showed an increased activation on non- primary motor areas (p<0.005). Patients with severe symptoms showed a higher cortical inhibition (p<0.05) and a reduced motor area (p<0.05). Conclusion: Most patients are eligible for rnTMS language mapping. A new protocol for language mapping is proposed for secure identification of patients eligible for reliable rnTMS in Schwarzer et al. Rosenstock et al. introduce a new risk stratification model, based on objective functional-anatomical and neurophysiological measures, which enables physicians to counsel patients about the risk of functional deterioration or the potential for recovery and supports surgical planning. Zdunczyk et al. propose a new concept for functional compensation for DCM on the cortical and spinal level: the corticospinal reserve capacity. nTMS is a viable diagnostic tool to characterize this and its parameters serve as valuable prognostic factors.Fragestellung: Navigierte transkranielle Magnetstimulation (nTMS) ist eine nicht-invasive Untersuchungsmethode, um kortikale Funktionsareale zu identifizieren, welche zunehmend an Bedeutung als präoperatives diagnostisches Mittel gewinnt. Dies ist eine Zusammenfassung dreier Studien, Schwarzer et al., Rosenstock et al. und Zdunczyk et al. Die Studien haben als Ziel, die Benutzerfreundlichkeit und Genauigkeit von nTMS für unterschiedliche neurochirurgische Patientengruppen zu verbessern. Neurophysiologische Parameter wurden mittels nTMS erhoben, um die operative Planung zu unterstützen und das individuelle Patientenrisiko korrekt einzuschätzen und zu verbessern. Methodik: Alle Patienten und Probanden wurden bihemisphärisch mittels nTMS untersucht. Schwarzer et al. erhoben vorher die individuelle Fähigkeit zur Objektbenennung (baseline) und nutzten repetitive nTMS (rnTMS), um Sprachunterbrechungen hervorzurufen und somit Kortexareale bei Patienten mit sprachrelevanten Hirnläsionen zu identifizieren. Neun biometrische Patienteneigenschaften wurden in ein Verhältnis mit der Fehleranfälligkeit gesetzt. Rosenstock et al. untersuchten den primär motorischen Kortex bei Gliompatienten und analysierten den Zusammenhang von nTMS-ermittelten Parametern mit dem postoperativen Patientenzustand. Zdunczyk et al. betrachteten Patienten mit degenerativer zervikaler Myelopathie (DCM), sowie gesunde Probanden und ermittelten die unterschiedlichen nTMS-Parameter in Abhängigkeit von der Symptomschwere. Ergebnisse: Die meisten biometrischen Faktoren zeigten keinen statistischen Zusammenhang mit dem Stimulationsergebnis bei Schwarzer et al. Je schwerer der Aphasiegrad und die kognitiven Einschränkungen waren, desto mehr Sprachfehler wurden in der rnTMS Untersuchung gemacht (je p8mm zwischen Tumor und kortikospinalem Trakt keine neuen permanenten postoperativen Defizite auftraten (p=0.014). Neue postoperative Defizite traten bei Patienten mit präoperativ pathologischer Kortexerregbarkeit (Ruhemotorschwellenverhältnis RMT 110%, p=0.031) auf. DCM Patienten wiesen eine reduzierte kortikospinale Erregbarkeit, gekennzeichnet durch ein Abflachen der recruitment curve, auf (p=0.022). Ein vergrößertes motorisch relevantes Kortexareal mit Aktivierung sekundärer Motorareale zeigte sich bei Patienten mit milder Symptomatik (p<0.005), während bei schwer betroffenen Patienten eine erhöhte kortikale Hemmung (CSP, p<0.05) und reduzierte motorische Kortexfläche auffiel (p<0.05). Schlussfolgerung: Schwarzer et al. stellen ein neues Prüfungsprotokoll für die Eignung von Patienten für ein reliables rnTMS Ergebnis vor, wobei die statistische Analyse ergab, dass die meisten Patienten für eine reliable rnTMS Sprachuntersuchung geeignet sind. Rosenstock et al. präsentieren ein neues Risikostratifikationsmodell für Patienten mit motorisch relevanten Gliomen, wodurch der Operateur anhand von funktionell-anatomischen und neurophysiologischen Parametern das individuelle Patientenrisiko für den postoperativen Verlauf einschätzen kann. Zdunczyk et al. beschreiben einen möglichen funktionellen Kompensationsmechanismus bei DCM Patienten auf kortikaler und spinaler Ebene: die kortikospinale Reservekapazität. Die durch nTMS ermittelten Parameter lassen damit objektivierbare prognostische Aussagen zu

The EU’s incremental adjustments to the eurocrisis may not be enough to meet the coming challenges to its governance and democratic legitimacy.

Since the beginning of the eurozone debt crisis three years ago, the member states have been forced to change the governance of the eurozone in a long period of crisis management. Daniela Schwarzer looks over the major changes to the EU’s governance structure, arguing that the European Council, Germany, and the European Central Bank have moved to the centre stage, often leading to the marginalization of other supranational actors and smaller member states in decision making. She argues that while the eurozone has shown a remarkable capacity to adjust thus far, it may need far more fundamental reform to its institutional set-up if it is to cope with looming problems of governance and legitimacy

Wochenbericht LI17-14 [Littorina, L17-14]

24.08. – 01.09.201

1. Wochenbericht AL511

25.06. – 01.07.201

1. Wochenbericht AL480

27.06. – 03.07.201

Market uptake of pegylated interferons for the treatment of hepatitis C in Europe : meeting abstract

Introduction and Objectives Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease with life threatening sequelae such as end-stage liver cirrhosis and liver cancer. It is estimated that the infection annually causes about 86,000 deaths, 1.2 million disability adjusted life years (DALYs), and ¼ of the liver transplants in the WHO European region. Presently, only antiviral drugs can prevent the progression to severe liver disease. Pegylated interferons combined with ribavirin are considered as current state-of-the-art treatment. Objective of this investigation was to assess the market uptake of these drugs across Europe in order to find out whether there is unequal access to optimised therapy. Material and Methods We used IMS launch and sales data (April 2000 to December 2005) for peginterferons and ribavirin for 21 countries of the WHO European region. Market uptake was investigated by comparing the development of country-specific sales rates. For market access analysis, we converted sales figures into numbers of treated patients and related those to country-specific hepatitis C prevalence. To convert sales figures into patient figures, the amount of active pharmaceutical ingredients (API) sold was divided by average total patient doses (ATPD), derived by a probability tree-based calculation algorithm accounting for genotype distribution, early stopping rules, body weight, unscheduled treatment stops and dose reductions Ntotal=APIPegIFNalpha-2a/ATPDPegIFNalpha-2a+APIPegIFN&alpha-2b/ATPDPegIFNalpha-2b For more concise result presentation the 21 included countries were aggregated into four categories: 1. EU founding members (1957): Belgium, France, Germany, Italy and Netherlands; 2. Countries joining EU before 2000: Austria (1995), Denmark (1973), Finland (1995), Greece (1981), Republic of Ireland (1973), Spain (1986), Sweden and UK (1973) 3. Countries joining EU after 2000: Czech Republic (2004), Hungary (2004), Poland (2004) and Romania (2007); 4. EU non-member states: Norway, Russia, Switzerland and Turkey. Results Market launch and market uptake of the investigated drugs differed considerably across countries. The earliest, most rapid and highest increases in sales rates were observed in the EU founding member states, followed by countries that joined the EU before 2000, countries that joined the EU after 2000, and EU non-member states. Most new EU member states showed a noticeable increase in sales after joining the EU. Market access analysis yielded that until end of 2005, about 308 000 patients were treated with peginterferon in the 21 countries. Treatment rates differed across Europe. The number of patients ever treated with peginterferon per 100 prevalent cases ranged from 16 in France to less than one in Romania, Poland, Greece and Russia. Discussion Peginterferon market uptake and prevalence adjusted treatment rates were found to vary considerably across 21 countries in the WHO European region suggesting unequal access to optimised therapy. Poor market access was especially common in low-resource countries. Besides budget restrictions, national surveillance and prevention policy should be considered as explanations for market access variation. Although our results allowed for the ranking of countries in order of market access, no final conclusions on over- or undertreatment can be drawn, because the number of patients who really require antiviral treatment is unknown. Further research based on pan-European decision models is recommended to determine the fraction of not yet successfully treated but treatable patients among those ever diagnosed with HCV. ..

Evidence that process simulations reduce anxiety in patients receiving dental treatment: randomized exploratory trial

Process simulations – mental simulations that ask people to imagine the process of completing a task – have been shown to decrease anxiety in students facing hypothetical or psychological threats in the short term. The aim of the present study was to see whether process simulations could reduce anxiety in a sample of the general population attending a dental practice, and whether these effects could be sustained throughout treatment. Participants (N = 75) were randomized to an experimental condition where they were asked to simulate mentally the process of seeing the dentist, or to a control condition where they were asked to simulate mentally the outcome of seeing the dentist. Findings showed that participants in the experimental condition were significantly less anxious both before and after their consultations. Self-efficacy and self-esteem remained unchanged. This study suggests that process simulation is one active ingredient in anxiety treatment programs and further research is required to enhance its effects