Real-life experience with switching TNF-α inhibitors in ankylosing spondylitis

Objective: The aim of this study was to evaluate the efficacy, reasons for switching and drug survival of TNF-α inhibitors (TNFis) used as first- and second-line drugs in ankylosing spondylitis (AS). Methods: Data on patients suffering from AS and treated with at least one TNFi between November 2005 and 2013 were extracted retrospectively from the database of a single clinical centre. Beside demographic data, the disease activity measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the response rates (BASDAI50), reasons for switching and survival curves of TNFis were analysed in general and in subgroups of patients treated with each of the available TNFis. The reasons for switching were defined as inefficacy, side effects of the given drug, patient's request and occurrence of extra-articular manifestations. Results: Altogether, 175 patients were on TNFis and 77 of them received at least two TNFis. The patients' age at the initiation of the first TNFi was higher among switchers compared to non-switchers (42.5 ± 12.6 vs. 38.8 ± 11.2 years, p = 0.049); otherwise, gender, disease duration and initial disease activity had no influence on the risk of switching. The decrease of the BASDAI was similar among non-switchers and switchers using either the first or second TNFi, but the response rates to the first and second TNFi were worse in switchers than in non-switchers. Following the failure of the first TNFi, the retention on therapy was unfavourable, especially in patients on infliximab after 1 year of treatment. The main reason for switching from the first drug was inefficacy. The frequency of side effects that led to switching was higher in the infliximab group than in patients treated with other agents. Conclusion: Although the retention rate to a second-line TNFi was somewhat worse than that to the first-line TNFi, the switching of TNFis is a good therapeutic option in AS patients who failed to respond to the first TNFi. © Springer-Verlag 2014

The media’s portrayal of hacking, hackers, and hacktivism before and after September 11

This paper provides a thorough analysis of the mainstream media representation of hackers, hacking, hacktivism, and cyberterrorism. The intensified U.S. debate on the security of cyberspace after September 11, 2001, has negatively influenced the movement of online political activism, which is now forced to defend itself against being labeled by the authorities as a form of cyberterrorism. However, these socially or politically progressive activities often remain unknown to the public, or if reported, they are presented in a negative light in the mass media. In support of that claim, I analyze five major U.S. newspapers in a one–year period with 9–11 in the middle. I argue that certain online activities are appropriated for the goals of the political and corporate elite with the help of the mass media under their control to serve as pretext for interventions to preserve the status quo. Thus, the media portrayal of hacking becomes part of the elite’s hegemony to form a popular consensus in a way that supports the elite’s crusade under different pretexts to eradicate hacking, an activity that may potentially threaten the dominant order

Hacktivists or Cyberterrorists? The Changing Media Discourse on Hacking

This paper scrutinizes the language of government reports and news media sources to shed light on their role in forming a negative image of politically motivated hacking in general, and online political activism, in particular. It is argued that the mass media's portrayal of hacking conveniently fits the elite's strategy to form a popular consensus in a way that supports the elite's crusade under different pretexts to eradicate hacking, an activity that may potentially threaten the dominant order

Cuarteto Vegh de Budapest, Sandor Vegh (primer violín), Georges Janzer (viola), Sandor Zoldy (segundo violín), Paul Szabo (violoncello) : concierto VIII (166 [i.e. 196] de la Sociedad), Martes, 11 de Mayo de 1954 : [programa].

Precede al tít.: Sociedad Filarmónica de Pontevedra, año XXXIV, 1953-1954Precede ó tít.: Sociedad Filarmónica de Pontevedra, año XXXIV, 1953-195

Cuarteto Vegh de Budapest, Sandor Vegh (primer violín), Georges Janzer (viola), Sandor Zoldy (segundo violín), Paul Szabo (violoncello), con la colaboración de Eva Czako : concierto VIII (221 de la Sociedad), Lunes 6 de Mayo de 1957 : [programa].

Precede al tít.: Sociedad Filarmónica de Pontevedra, año XXXVII, 1956-1957Precede ó tít.: Sociedad Filarmónica de Pontevedra, año XXXVII, 1956-195

Effects of 1-year anti-TNF-α therapies on bone mineral density and bone biomarkers in rheumatoid arthritis and ankylosing spondylitis

Objectives Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have been associated with generalized and localized bone loss. We conducted a comprehensive study using imaging (dual-energy X-ray absorptiometry, DXA) and laboratory biomarkers in order to determine bone health and to study the effects of anti-tumor necrosis factor (TNF) biologics in RA and AS. Patients and methods Thirty-six RA and 17 AS patients undergoing 1-year etanercept (ETN) or certolizumab-pegol (CZP) therapy were studied. Bone density was assessed by DXA at baseline and after 12 months. Serum C-reactive protein (CRP), calcium, phosphate, parathyroid hormone (PTH), vitamin D3, osteocalcin, procollagen type I N-propeptide (P1NP), C-terminal telopeptide (βCTX), osteoprotegerin, sclerostin (SOST), Dickkopf-1 (DKK-1), soluble receptor activator nuclear kappa B ligand (sRANKL), and cathepsin K (cathK) levels were determined at baseline and after 6 and 12 months. Results TNF-α inhibition was clinically effective. Anti-TNF-α halted further bone loss over 1 year. In general, anti-TNF therapy significantly increased P1NP, SOST levels, and the P1NP/βCTX ratios, while decreased DKK-1 and CathK production at different time points in most patient subsets. In the full cohort and in RA, baseline and/or 12-month bone mineral density (BMD) at multiple sites exerted inverse relationships with CRP and βCTX, and positive correlation with SOST. In AS, L2-4 BMD after 1-year biologic therapy inversely correlated with baseline βCTX, while femoral neck BMD rather showed inverse correlations with CRP. Conclusions Anti-TNF therapy slowed down generalized bone loss, in association with clinical improvements, in both diseases. TNF blockade may enhance bone formation and suppress joint destruction. Anti-TNF therapy may act inversely on DKK-1 and SOST. Independent predictors of BMD were SOST and βCTX in RA, whilst CRP in AS

Peripheral quantitative computed tomography in the assessment of bone mineral density in anti-TNF-treated rheumatoid arthritis and ankylosing spondylitis patients

Introduction Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are associated with osteoporosis. There have not been many peripheral quantitative computed tomography (QCT) studies in patients receiving biologics. We assessed volumetric and areal bone mineral density (BMD) by forearm QCT and dual-energy X-ray absorptiometry (DXA), respectively in addition to laboratory biomarkers in these arthritides. Methods Forty RA and AS patients treated with either etanercept (ETN) or certolizumab pegol (CZP) were undergoing follow-ups for one year. Volumetric and areal BMD, as well as parathyroid hormone (PTH), osteocalcin, RANKL, 25-hydroxyvitamin D (VITD), P1NP, CTX, sclerostin (SOST), Dickkopf 1 (DKK-1) and cathepsin K (CATHK) were determined. Results We did not observe any further bone loss during the 12-month treatment period. Volumetric and areal BMD showed significant correlations with each other (p<0.017 after Bonferroni's correction). Trabecular QCT BMD at baseline (p=0.015) and cortical QCT BMD after 12 months (p=0.005) were inversely determined by disease activity at baseline in the full cohort. Trabecular QCT BMD at baseline also correlated with CTX (p=0.011). In RA, CRP negatively (p=0.014), while SOST positively (p=0.013) correlated with different QCT parameters. In AS, RANKL at baseline (p=0.014) and after 12 months (p=0.007) correlated with cortical QCT BMD. In the full cohort, 12-month change in QTRABBMD was related to TNF inhibition together with elevated VITD-0 levels (p=0.031). Treatment and lower CATHK correlated with QCORTBMD changes (p=0.006). In RA, TNF inhibition together with VITD-0 (p<0.01) or CATHK-0 (p=0.002), while in AS, treatment and RANKL-0 (p<0.05) determined one-year changes in QCT BMD. Conclusions BMD as determined by QCT did not change over one year of anti-TNF treatment. Disease activity, CATHK, RANKL and VITD may be associated with the effects of anti-TNF treatment on QCT BMD changes. RA and AS may differ in this respect