14 research outputs found
Impact of Vutrisiran on Quality of Life and Physical Function in Patients with Hereditary Transthyretin-Mediated Amyloidosis with Polyneuropathy
INTRODUCTION: Hereditary transthyretin (ATTRv; v for variant) amyloidosis, also known as hATTR amyloidosis, is a progressive and fatal disease associated with rapid deterioration of physical function and patients' quality of life (QOL). Vutrisiran, a subcutaneously administered RNA interference (RNAi) therapeutic that reduces hepatic production of transthyretin, was assessed in patients with ATTRv amyloidosis with polyneuropathy in the pivotal HELIOS-A study. METHODS: The phase 3 open-label HELIOS-A study investigated the efficacy and safety of vutrisiran in patients with ATTRv amyloidosis with polyneuropathy, compared with an external placebo group from the APOLLO study of the RNAi therapeutic patisiran. Measures of QOL and physical function were assessed. RESULTS: At month 18, vutrisiran improved Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) total score (least squares mean difference [LSMD] in change from baseline [CFB]: –21.0; p = 1.84 × 10–10) and Norfolk QOL-DN domain scores, compared with external placebo. This benefit relative to external placebo was evident across all baseline polyneuropathy disability (PND) scores and most pronounced in patients with baseline PND scores I–II. Compared with external placebo, vutrisiran also demonstrated benefit in EuroQoL-Visual Analog Scale (EQ-VAS) score (LSMD in CFB: 13.7; nominal p = 2.21 × 10–7), 10-m walk test (LSMD in CFB: 0.239 m/s; p = 1.21 × 10–7), Rasch-built Overall Disability Score (LSMD in CFB: 8.4; p = 3.54 × 10–15), and modified body mass index (mBMI) (LSMD in CFB: 140.7; p = 4.16 × 10–15) at month 18. Overall, Norfolk QOL-DN, EQ-VAS, and mBMI improved from pretreatment baseline with vutrisiran, whereas all measures worsened from baseline in the external placebo group. At month 18, Karnofsky Performance Status was stable/improved from baseline in 58.2/13.1% with vutrisiran versus 34.7/8.1% with external placebo. CONCLUSION: Vutrisiran treatment provided significant clinical benefits in multiple measures of QOL and physical function in patients with ATTRv amyloidosis with polyneuropathy. Benefits were most pronounced in patients with earlier-stage disease, highlighting the importance of early diagnosis and treatment
Hijacking Europe: Counter‐European Strategies and Radical Right Mainstreaming during the Humanitarian Crisis Debate 2015–16*
Radical right European contestation is analyzed mainly as claims denouncing European integration. Less focus is put on narratives suggesting how a supposed 'truly European' political process should be and work. This paper explores how radical right actors use such counter-European claims within their competition strategies. Computer-assisted qualitative analysis of communication by Front National, Alternative for Germany and Fidesz during the humanitarian crisis debate 2015-16 demonstrates that radical right counter-Europeanism constitutes a nuanced tactical resource deployed to normalize nativist supply in the name of Europe. Unlike Eurorejectionist FN, Fidesz and AfD redefined Europe in nativist terms, attempting to draw legitimacy from association with European identity and cooperation. Concurrently, both actors justified Euronativism not only as antithetical to current EU values and political principles, but mainly as their more fundamental practice juxtaposed against 'not (truly) European elites', effectively 'hijacking' Europe from within. The findings deepen our understanding of radical right Europe-contesting competition strategies
Red Europe versus no Europe? The impact of attitudes towards the EU and the economic crisis on radical-left voting
Protecting Us, Protecting Europe? Public Concern about Immigration and Declining Support for European Integration in Italy
This article investigates the effect of immigration on attitudes towards Europe in Italy. This question resonates throughout the European Union (EU), but does so particularly in Italy – one of EU's most exposed external borders, especially under recent global challenges such as the economic crisis and the Arab Spring. Over the last two decades, Italy received more than four million migrants and refugees, which has put immigration on top of the political agenda ever since. Using data from the European Values Study (EVS), we find that concerns about immigration, especially in the context of the economic crisis of 2007, is a factor of declining support for European integration and that these effects vary across regions. In particular, we demonstrate the mediating effect of context by showing that the effect of being concerned about immigration is more corrosive for support in regions with higher immigration rates than in regions with lower rates
Motor unit number index as an individual biomarker: Reference limits of intra-individual variability over time in healthy subjects.
Motor unit number index (MUNIX) is proposed to monitor neuromuscular disorders. Our objective is to determine the intra-individual variability over time of the MUNIX.
In 11 different hospital centres, MUNIX was assessed twice, at least 3 months apart (range 90-360 days), in tibialis anterior (TA), abductor pollicis brevis (APB), abductor digiti minimi (ADM) and deltoid muscles in 118 healthy subjects. MUNIX sum score 2, 3 and 4 were respectively the sum of the MUNIX of the TA and ADM, of the TA, APB and ADM and of the TA, APB, ADM and deltoid muscles.
The repeatability of the MUNIX was better for sum scores than for single muscle recordings. The variability of the MUNIX was independent of sex, age, interval between measurements and was lower for experienced than non-experienced operators. The 95th percentile of the coefficient of variability of the MUNIX sum score 2, 3 and 4 were respectively 22%, 18% and 15% for experienced operators.
The MUNIX technique must be performed by experienced operators on several muscles to reduce its variability and improve its reliability.
A variation of the MUNIX sum score ≥20% can be interpreted as a significant change of muscle innervation
A red letter day: Investigating the renaissance of the French far left in the 2012 presidential election
Measuring Attitudes Towards Social Europe: A Multidimensional Approach
Although the notion of ‘Social Europe’ can refer to different principles and policy options, most research narrows down attitudes towards Social Europe to a unidimensional construct. In this study, we instead propose a multi-dimensional approach, and contribute to the literature in three ways. First, we elaborate the notion of ‘Social Europe’ conceptually, and distinguish between the decision-making level for social policy, European social citizenship, harmonization, member-state solidarity and interpersonal solidarity. Second, analysing the 2014 Belgian National Election Study by means of confirmatory factor analysis we evidence that citizens indeed have distinct attitudes towards the policy principles and instruments of Social Europe. Although these attitudinal dimensions are interrelated, they cannot be reduced to a single Social Europe factor, meaning that citizens differentiate in their attitudes between various aspects of Social Europe. In addition, our research indicates that member-state solidarity is the primary aspect of Social Europe in public opinion, whereas the feature that has received most scholarly attention in empirical research to date—the preferred decision-making level for social policy—cannot be considered as a key component of attitudes towards Social Europe. Third, we investigate whether citizens with different educational levels conceptualize Social Europe similarly using multigroup confirmatory factor analysis. Results indicate that the attitudinal factor structure of Social Europe is largely equivalent among lower and higher-educated citizens