Predictive Capability of an iPad-Based Medical Device (medx) for the Diagnosis of Vertigo and Dizziness

Background:Making the correct diagnosis of patients presenting with vertigo and dizziness in clinical practice is often challenging. Objective:In this study we analyzed the usage of the iPad based program medx in the prediction of different clinical vertigo and dizziness diagnoses . We examined the power of medx to distinguish between different vertigo diagnoses. Patients and methods:The data collection was done in the outpatient clinic of the German Center of Vertigo and Balance Disorders. The “gold standard diagnosis” was defined as the clinical diagnosis of the specialist during the visit of the patient standardized history and clinical examination. Another independent and blinded physician finalized each patient’s case in constellatory diagnostic of medx by entering all available clinical information in the system. The accuracy, sensitivity, specificity as well as positive and negative predictive values for the most common diagnoses were determined. Sixteen possible different vertigo and dizziness diagnoses could be provided by medx constellatory diagnostic system. These diagnoses were compared to the “gold standard” by retrospective review of the charts of the patients over the study period. Results:610 patients (mean age58.1±16.3 years, 51.2 female) were included. The accuracy for the most common diagnoses was between 82.1- 96.6 with a sensitivity from 40- 80.5 and a specificity of more than 80. When analyzing the quality of medx in a multiclass-problem for the six most common clinical diagnoses the sensitivity, specificity, positive and negative predictive value were as follows: Bilateral vestibulopathy (81.6, 97.1, 71.1, 97.5), Menière's disease (77.8, 97.6, 87., 95.3), benign paroxysmal positional vertigo (61.7, 98.3, 86.6, 93.4), downbeat nystagmus syndrome (69.6, 97.7, 71.1, 97.5), vestibular migraine (34.7, 97.8, 76.1, 88.3) and phobic postural vertigo (80.5, 82,5, 52.5, 94.6), Conclusions:This study demonstrates that medx is a new and easy approach to screen for different diagnoses. With the high specificity and high negative predictive value the system helps to rule out differential diagnoses and can therefore also lead to a cost reduction in health care system. However, the sensitivity was unexpectedly low, especially for vestibular migraine. All in all, this device can only be a complementary tool, in particular for non-experts in the field

A Randomized, Placebo-Controlled Trial

Objective: To examine whether treatment with epigallocatechin gallate (EGCG) influences progression of brain atrophy, reduces clinical and further radiologic disease activity markers, and is safe in patients with progressive multiple sclerosis (PMS). Methods: We enrolled 61 patients with primary or secondary PMS in a randomized double-blind, parallel-group, phase II trial on oral EGCG (up to 1,200 mg daily) or placebo for 36 months with an optional open-label EGCG treatment extension (OE) of 12-month duration. The primary end point was the rate of brain atrophy, quantified as brain parenchymal fraction (BPF). The secondary end points were radiologic and clinical disease parameters and safety assessments. Results: In our cohort, 30 patients were randomized to EGCG treatment and 31 to placebo. Thirty-eight patients (19 from each group) completed the study. The primary endpoint was not met, as in 36 months the rate of decrease in BPF was 0.0092 +/- 0.0152 in the treatment group and -0.0078 +/- 0.0159 in placebo-treated patients. None of the secondary MRI and clinical end points revealed group differences. Adverse events of EGCG were mostly mild and occurred with a similar incidence in the placebo group. One patient in the EGCG group had to stop treatment due to elevated aminotransferases (>3.5 times above normal limit). Conclusions: In a phase II trial including patients with multiple sclerosis (MS) with progressive disease course, we were unable to demonstrate a treatment effect of EGCG on the primary and secondary radiologic and clinical disease parameters while confirming on overall beneficial safety profile. Clinicaltrial.gov Identifier NCT00799890. Classification of Evidence This phase II trial provides Class II evidence that for patients with PMS, EGCG was safe, well tolerated, and did not significantly reduce the rate of brain atrophy

Altered Coupling of Psychological Relaxation and Regional Volume of Brain Reward Areas in Multiple Sclerosis

Background:Psychological stress can influence the severity of multiple sclerosis (MS), but little is known about neurobiological factors potentially counteracting these effects. Objective:To identify gray matter (GM) brain regions related to relaxation after stress exposure in persons with MS (PwMS). Methods:36 PwMS and 21 healthy controls (HCs) reported their feeling of relaxation during a mild stress task. These markers were related to regional GM volumes, heart rate, and depressive symptoms. Results:Relaxation was differentially linked to heart rate in both groups (t= 2.20,p= 0.017), i.e., both markers were only related in HCs. Relaxation was positively linked to depressive symptoms across all participants (t= 1.99,p= 0.045) although this link differed weakly between groups (t= 1.62,p= 0.108). Primarily, the volume in medial temporal gyrus was negatively linked to relaxation in PwMS (t= -5.55, p(family-wise-error(FWE)corrected)= 0.018). A group-specific coupling of relaxation and GM volume was found in ventromedial prefrontal cortex (VMPFC) (t= -4.89, p(FWE)= 0.039). Conclusion:PwMS appear unable to integrate peripheral stress signals into their perception of relaxation. Together with the group-specific coupling of relaxation and VMPFC volume, a key area of the brain reward system for valuation of affectively relevant stimuli, this finding suggests a clinically relevant misinterpretation of stress-related affective stimuli in MS

Lack of association of MRI determined subclinical cardiovascular disease with dizziness and vertigo in a cross-sectional population-based study

OBJECTIVE We investigated the association between subclinical cardiovascular diseases assessed by MRI examination and symptoms of dizziness and vertigo in participants of a population-based sample. METHODS Data from 400 participants (169 women) aged from 39 to 73 of a cross-sectional MRI sub-study of the \dqKooperative Gesundheitsforschung in der Region Augsburg\dq (KORA) FF4 study from the south of Germany was used. MRI determined subclinical cardiovascular diseases include left and right ventricular structure and function as well as the presence of carotid plaque and carotid wall thickness. Cerebrum diseases include white matter lesions (WML) and cerebral microbleeds (CMB). The main outcomes of dizziness and vertigo were assessed by standardized interview. Logistic regression models were applied and adjusted odds ratios (OR) with 95% confidence intervals (CI) were provided. RESULTS Lifetime and 12-month prevalence of dizziness and vertigo were 30% (95%CI 26% to 35%) and 21% (95%CI 17% to 26%) respectively in this sample. On multivariable analysis, cardiac and carotid measurements were not associated with dizziness and vertigo excluding orthostatic vertigo (20%, 95CI 16% to 24%). Only in male participants, there was a significant association between WML and the presence of dizziness and vertigo (OR = 2.95, 95%CI 1.08 to 8.07). There was no significant association of CMB with dizziness and vertigo. However, CMB and WML were tending to associate with a higher risk of dizziness and vertigo in the whole sample (CMB: OR = 1.48, 95%CI 0.70; 3.15; WML: OR = 1.71, 95%CI 0.80 to 3.67;), in persons with prediabetes and diabetes (WML: OR = 2.71, 95%CI 0.89 to 8.23) and in men with normal glucose metabolism (CMB: OR = 2.60, 95%CI 0.56 to 12.0; WML: OR = 3.08, 95%CI 0.58 to 16.5). CONCLUSIONS In this sample of participants without manifest cardiovascular diseases, subclinical left and right ventricular function and carotid structure were consistently not associated with dizziness and vertigo. Subclinical cerebrum measurements, however, tend to increase the risk for dizziness and vertigo, especially in men and in persons with prediabetes or diabetes

Analysis of Lymphocytic DNA Damage in Early Multiple Sclerosis by Automated Gamma-H2AX and 53BP1 Foci Detection: A Case Control Study

Background In response to DNA double-strand breaks, the histone protein H2AX becomes phosphorylated at its C-terminal serine 139 residue, referred to as γ-H2AX. Formation of γ-H2AX foci is associated with recruitment of p53-binding protein 1 (53BP1), a regulator of the cellular response to DNA double-strand breaks. γ-H2AX expression in peripheral blood mononuclear cells (PBMCs) was recently proposed as a diagnostic and disease activity marker for multiple sclerosis (MS). Objective To evaluate the significance of γ-H2AX and 53BP1 foci in PBMCs as diagnostic and disease activity markers in patients with clinically isolated syndrome (CIS) and early relapsing-remitting MS (RRMS) using automated γ-H2AX and 53BP1 foci detection. Methods Immunocytochemistry was performed on freshly isolated PBMCs of patients with CIS/early RRMS (n = 25) and healthy controls (n = 27) with γ-H2AX and 53BP1 specific antibodies. Nuclear γ-H2AX and 53BP1 foci were determined using a fully automated reading system, assessing the numbers of γ-H2AX and 53BP1 foci per total number of cells and the percentage of cells with foci. Patients underwent contrast enhanced 3 Tesla magnetic resonance imaging (MRI) and clinical examination including expanded disability status scale (EDSS) score. γ-H2AX and 53BP1 were also compared in previously frozen PBMCs of each 10 CIS/early RRMS patients with and without contrast enhancing lesions (CEL) and 10 healthy controls. Results The median (range) number of γ-H2AX (0.04 [0–0.5]) and 53BP1 (0.005 [0–0.2]) foci per cell in freshly isolated PBMCs across all study participants was low and similar to previously reported values of healthy individuals. For both, γ-H2AX and 53BP1, the cellular focus number as well as the percentage of positive cells did not differ between patients with CIS/RRMS and healthy controls. γ-H2AX and 53BP1 levels neither correlated with number nor volume of T2-weighted lesions on MRI, nor with the EDSS. Although γ-H2AX, but not 53BP1, levels were higher in previously frozen PBMCs of patients with than without CEL, γ-H2AX values of both groups overlapped and γ-H2AX did not correlate with the number or volume of CEL. Conclusion γ-H2AX and 53BP1 foci do not seem to be promising diagnostic or disease activity biomarkers in patients with early MS. Lymphocytic DNA double-strand breaks are unlikely to play a major role in the pathophysiology of MS

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Die digitale Revolution im Klassenzimmer : der Einsatz von Tablets zur Steigerung der Lernfreude und Motivation

Strobl KatharinaAlpen-Adria-Universität Klagenfurt, Diplomarbeit, 2015(VLID)241176

Ökologische Bewertung unterschiedlicher Uferstrukturierungsmaßnahmen zur Renaturierung der Ufervegetation eines anthropogen geprägten Flusses

Since anthropogenic activities have become concentrated along rivers, river regulations have strongly reduced the lateral connectivity by separating rivers from their floodplains. Consequently riparian habitat heterogeneity and the related species diversity are degrading, especially in highly modified prealpine rivers. Riverbank revitalisation measures aim at mitigating this degradation and river restoration projects have become widespread. Nonetheless, little knowledge exists about their specific outcome, as standardised monitoring programs are missing. The aim of this study is to systematically compare vegetation change in response to three contrasting measures of bank diversification, i.e. embankment removal, sand input or gravel addition. Moreover, the influence of these measures on adjacent vegetation is studied. Conclusions were drawn on the basis of three common goals of restoration projects: (i) improvement of vegetation structure, (ii) increase of species diversity, and (iii) characteristic species composition. The field work was done along River Inn northeast of Munich. Vegetation structure, species identity and cover as well as selected habitat variables were recorded in a stratified randomised sampling design; variation between measures was analysed using uni- and multivariate statistics. We detected great differences in the effect of the three measures two years after implementation. Embankment removal initiated highly dynamic habitats where plant establishment was difficult. The input of sand led to a rather homogenous species composition, at least partly because the habitats were productive and therefore most likely will develop to tall reed stands or riparian forests. After gravel addition the restored sites remained relatively open, while riparian pioneer species could colonise. Vegetation structure and composition of adjacent reed stands were positively affected. The results indicate how restoration outcomes can vary depending on the specific measures chosen. This confirms the need for careful consideration of the pursued goals and site-specific conditions prior to implementation as well as long-term monitoring after implementation.Einleitung: Fließgewässer und ihre Auen gehören zu den artenreichsten Ökosystemen der Welt (WARD et al. 1999). Mit der Intensivierung der anthropogenen Nutzung in Flussauen wurden Flüsse zunehmend verbaut und ihre Gewässerstruktur sowie die natürliche Fließgewässerdynamik beeinträchtigt (HABERSACK & PIÉGAY 2008). Dabei sind das Auftreten regelmäßiger Störungen und eine intakte laterale Konnektivität notwendig für den Artenreichtum der Aue (WARD et al. 1999). Besonders in den stark verbauten Voralpenflüssen wird die Revitalisierung im Sinne einer Strukturverbesserung zur Dynamisierung der Auen zu einer dringenden Notwendigkeit. Eine Studie von BERNHARDT et al. (2005) belegt eine starke Zunahme von Renaturierungsprojekten an Flüssen. Standardisierte, langjährige Monitoringprogramme sind dabei bisher selten (CHAPMAN & UNDERWOOD 2000), aber unbedingt nötig, um den Erfolg der Maßnahmen bewerten und zukünftige Projekte zielgerichteter durchführen zu können. Ziel dieser Arbeit ist ein systematischer Vergleich unterschiedlicher Uferstrukturierungsmaßnahmen und die Untersuchung des Einflusses dieser Maßnahmen auf die Vegetation. Die abschließende Bewertung erfolgte anhand von drei in Renaturierungsprojekten häufig verfolgten Zielen: (1) Verbesserung der Vegetationsstruktur, (2) Erhöhung der Artenvielfalt und (3) charakteristische Artenzusammensetzung. Material und Methoden: Das Untersuchungsgebiet liegt an einem stark anthropogen überprägten Fluss des bayerischen Voralpenlandes, dem Inn südlich und nördlich von Wasserburg. Dort wurden mit dem Ziel der Dynamisierung des Flusses die Ufer umstrukturiert. Die durchgeführten Maßnahmen lassen sich in drei Gruppen einteilen: Uferanbruch (Entsteinung, Aufbrechen), Kies- und Sandzugabe. In einem stratifiziert-randomisierten Aufnahmedesign wurden gezielt die Vegetationsstruktur, die Deckung der Arten und ausgewählte abiotische Größen (pH-Wert, Uferentfernung, Uferneigung) erhoben. Als Straten dienten die vorgefundenen Strukturtypen "Röhricht" und "Pionierfluren". Die Datenauswertung erfolgte anhand uni- und multivariater Analysen. Ergebnisse: Alle drei Maßnahmentypen unterschieden sich bezüglich der Vegetationsstruktur. Die Rohbodendeckung war maximal nach Revitalisierung durch Uferanbruch. Die Vegetationshöhe und -deckung am Flussufer waren am höchsten nach Zugabe von Sand. Die Probeflächen mit Uferanbruch wiesen eine starke Streuung der Artenzahl auf, und auch die Diversität der angrenzenden Röhrichte war erhöht. Alle drei Maßnahmen unterscheiden sich deutlich in ihrer Artenzusammensetzung, wobei erneut die Maßnahme des Uferanbruchs eine sehr heterogene Entwicklung bewirkte. An Renaturierungsflächen angrenzende Röhrichte zeigten eine veränderte Artenzusammensetzung im Vergleich mit Kontrollflächen. Diskussion: Zwei Jahre nach der Durchführung führten die drei untersuchten Maßnahmen zu großen Unterschieden in der Vegetationsentwicklung. Durch die Entfernung der Uferbefestigung entstehen dynamische Habitate, auf denen sich nur wenige Pflanzen etablieren. Wie auch in der Studie von JÄHNIG et al. (2009) führt die Kieszugabe zu einer vergleichsweise offenen Vegetationsstruktur, in der sich auentypische Pionierarten ansiedeln. Auf Sandflächen stellt sich eine homogene Artenzusammensetzung ein; diese lässt sich zumindest teilweise durch die hohe Produktivität der Standorte erklären, die sich vermutlich entweder in Richtung Röhricht (FRIESE et al. 2000) oder Auwald (KARRENBERG et al. 2002) entwickeln werden, jedenfalls wenn Störungsereignisse ausbleiben. Die beobachteten Entwicklungen zeigen die kurzfristige Reaktion der Auepflanzen auf die Uferstrukturierungsmaßnahmen. Für eine abschließende Beurteilung der Wirksamkeit der Maßnahmen ist jedoch ein längerfristiges Monitoring nötig (JANUSCHKE 2014). Wenn die natürliche Dynamik des Flusses nicht ausreicht, müsste über geeignete Managementstrategien zur Offenhaltung von Pionierstandorten nachgedacht werden. Perspektiven für die Renaturierung: Die Ergebnisse zeigen, wie unterschiedlich die Wirkungen einzelner Renaturierungsmaßnahmen sein können. Dies unterstreicht, wie wichtig es ist, vor den Maßnahmen abzuwägen, welche Renaturierungsziele unter den gegebenen lokalen Bedingungen verfolgt werden sollen. Nach Maßnahmendurchführung ist ein Langzeitmonitoring wünschenswert