Safety of low- to medium-dose glucocorticoid treatment in rheumatoid arthritis: myths and reality over the years

Low- to medium-dose glucocorticoids have been shown to have not only anti-inflammatory but also disease-modifying properties in rheumatoid arthritis. The evidence for the benefit of its early use in combination with disease-modifying antirheumatic drugs underlines the need for a close evaluation of their risk-benefit ratio. Over time, numerous myths and fears about glucocorticoid toxicity in rheumatoid arthritis have arisen from observational studies, and many concerns have been unduly extrapolated from observations with higher-dose treatment. Furthermore, we cannot exclude the possibility of a powerful effect of bias by indication in these studies. Low- to medium-dose glucocorticoid regimens continued to be evaluated in randomized clinical trials, particularly in early disease, but these studies also have relevant methodological limitations in assessing safety, particularly due to small size and/or short duration. At present, the evidence on which to support clear recommendations about glucocorticoid toxicity remains remarkably weak. A large prospective pragmatic trial dedicated to the toxicity of low-dose glucocorticoids is dearly needed. Meanwhile, adherence to recommendations on standardized methodologies for registration and report of glucocorticoid adverse events is essential for improving our knowledge and competence in the best management of these important medications

Surveys as cultural artefacts : applying the international self-report delinquency study to Latin American adolescents

Survey instruments are often watermarked with the language, thought patterns, experience and expectations of their designers’ cultural world. This creates some evident challenges when using surveys in international research projects (for example, in finding equivalent terms in translation), but also some less evident ones deriving from potentially hidden local variations in social experience, values and cognition. Using examples from the International Self-Report Delinquency Study, this article identifies several potential challenges to measurement that arise when an instrument designed with the youth of industrialized democracies in mind is presented to adolescents in a Latin American country (Venezuela). Some strategies for addressing these challenges are outlined

A case of infliximab-induced lupus in a patient with ankylosing spondylitis: is it safe switch to another anti-TNF-α agent?

Anti-TNF-α therapies are the latest class of medications found to be associated with drug-induced lupus, a distinctive entity known as anti-TNF-α-induced lupus (ATIL) (Williams et al., Rheumatology (Oxford) 48:716-20, 2009; De Rycke et al., Lupus 14:931-7, 2005; De Bandt et al., Clin Rheumatol 22:56-61, 2003). With the widespread use of these agents, it is likely that the incidence of ATIL will increase. The onset of ATIL in patients with rheumatoid arthritis and Crohn's disease has been described, but the literature regarding the occurrence of this entity in patients with ankylosing spondylitis (AS) is scarce (De Bandt et al., Clin Rheumatol 22:56-61, 2003; Ramos-Casals et al., Autoimmun Rev 9:188-93, 2010; Perez-Garcia et al., Rheumatology 45:114-116, 2006). To our knowledge, few reports of switching anti-TNF-α therapy after ATIL in AS have been reported (Akgül et al., Rheumatol Int, 2012). Therefore, it is not clear whether the development of ATIL should prohibit switch to another therapy, since patients may respond to another anti-TNF-α agent (Akgül et al., Rheumatol Int, 2012; Bodur et al., Rheumatol Int 29:451-454, 2009; Mounach et al., Clin Exp Rheumatol 26:1116-8, 2008; Williams and Cohen, Int J Dermatol 50:619-625, 2011; Ye et al., J Rheumatol 38:1216, 2011; Wetter and Davis, Mayo Clin Proc 84:979-984, 2009; Cush, Clin Exp Rheumatol 22:S141-147, 2004; Kocharla and Mongey, Lupus 18:169-7, 2009). A lack of published experience of successful anti-TNF-α switching is a cause of concern for rheumatologists faced with this challenging clinical scenario. We report the case of a 69-year-old woman with AS who developed infliximab-induced lupus, which did not recur despite the subsequent institution of etanercept. The authors review and discuss ATIL and the possible implications for subsequent treatment with alternative anti-TNF-α agents

Coexisting primary Sjögren’s syndrome and sarcoidosis: coincidence, mutually exclusive conditions or syndrome?

Herein, we describe a 44-year-old female diagnosed with histologically proven coexistence of primary Sjögren's syndrome and sarcoidosis with pulmonary and muscular involvement. The differential diagnosis may be difficult, but this is not an exceptional case, which highlights the need to critically revise the consideration of sarcoidosis as an exclusion for primary Sjögren's syndrome, as established in current classification criteria

Psychological factors associated with response to treatment in rheumatoid arthritis

This paper presents a comprehensive review of research relating psychological domains with response to therapy in patients with rheumatoid arthritis. A holistic approach to the disease was adopted by incorporating not only disease activity but also dimensions of the impact of disease on patients' lives. Psychological distress, including depression and anxiety, is common among patients with rheumatoid arthritis and has a significant negative impact on response to therapy and on patients' abilities to cope with chronic illness. Evidence regarding the influence of positive psychological dimensions such as acceptance, optimism, and adaptive coping strategies is scarce. The mechanisms involved in these interactions are incompletely understood, although changes in neuro-endocrine-immune pathways, which are common to depression and rheumatoid arthritis, seem to play a central role. Indirect psychological influences on therapeutic efficacy and long-term effectiveness include a myriad of factors such as adherence, placebo effects, cognition, coping strategies, and family and social support. Data suggest that recognition and appropriate management of psychological distress may improve response to treatment and significantly reduce disease burden

Flavor Phenomenology in General 5D Warped Spaces

We have considered a general 5D warped model with SM fields propagating in the bulk and computed explicit expressions for oblique and non-oblique electroweak observables as well as for flavor and CP violating effective four-fermion operators. We have compared the resulting lower bounds on the Kaluza-Klein (KK) scale in the RS model and a recently proposed model with a metric modified towards the IR brane, which is consistent with oblique parameters without the need for a custodial symmetry. We have randomly generated 40,000 sets of O(1) 5D Yukawa couplings and made a fit of the quark masses and CKM matrix elements in both models. This method allows to identify the percentage of points consistent with a given KK mass, which in turn provides us with a measure for the required fine-tuning. Comparison with current experimental data on Rb, FCNC and CP violating operators exhibits an improved behavior of our model with respect to the RS model. In particular, allowing 10% fine-tuning the combined results point towards upper bounds on the KK gauge boson masses around 3.3 TeV in our model as compared with 13 TeV in the RS model. One reason for this improvement is that fermions in our model are shifted, with respect to fermions in the RS model, towards the UV brane thus decreasing the strength of the modifications of electroweak observables.Comment: 28 pages, 7 figures, 4 table