Objective:The effect of adalimumab on hand osteoporosis was examined and related to radiographic joint damage in the three treatment arms of the PREMIER study: adalimumab plus methotrexate, adalimumab and methotrexate monotherapy. Predictors of hand bone loss were also searched for.Methods:768 patients (537 fulfilled 2 years) with rheumatoid arthritis (RA) for less than 3 years, never treated with methotrexate, were included. Hand bone loss was assessed by digital x ray radiogrammetry (DXR) on the same hand radiographs scored with modified Sharp score at baseline, 26, 52 and 104 weeks. For DXR, metacarpal cortical index (MCI) was the primary bone measure.Results:At all time points the rate of percentage DXR–MCI loss was lowest in the combination group (−1.15; −2.16; −3.03) and greatest in the methotrexate monotherapy group (−1.42; −2.87; −4.62), with figures in between for the adalimumab monotherapy group (−1.33; −2.45; −4.03). Significant differences between the combination group and the methotrexate group were seen at 52 (p = 0.009) and 104 weeks (p<0.001). The order of hand bone loss across the three treatment arms was similar to the order of radiographic progression. Older age, elevated C-reactive protein and non-use of adalimumab were predictors of hand bone loss.Conclusion:This study supports a similar pathogenic mechanism for hand bone loss and erosions in RA. The combination of adalimumab and methotrexate seems to arrest hand bone loss less effectively than radiographic joint damage. Quantitative measures of osteoporosis may thus be a more sensitive tool for assessment of inflammatory bone involvement in RA.
Several methods of quantifying prepulse inhibition (PPI) of eyeblink responding were compared in adult volunteers. Blink-eliciting stimuli were noise bursts at 85 or 100 dB, and prepulses were also noise bursts, at 55 or 70 dB and lead intervals of 60 or 120 ms. PPI was evaluated by comparing reactivity on prepulse and control trials within participants using the following methods: (1) difference between reactivity on prepulse and control trials; (2) reactivity on prepulse trials divided by that on control trials (proportion of control); (3) difference between reactivity on prepulse and control trials, divided by that on control trials (proportion of the difference from control); (4) range correction (maximum minus minimum reactivity, divided by the range of reactivity), across all control and prepulse trials; (5) z scores across all prepulse and control trials. Prepulses inhibited eyeblink response magnitude in all cases. Proportion of difference was the method least affected by differences in control reactivity, and is the preferred method to use when quantifying PPI, both from a practical and a neurophysiological perspective.
BackgroundAnti-TNF therapy has been shown to reduce radiographic joint damage in rheumatoid arthritis (RA) independent of clinical response. This has previously not been examined for periarticular bone loss, the other characteristic feature of bone involvement in RA.The objective of this study was to examine if treatment with the TNF-α inhibitor adalimumab also could reduce periarticular bone loss in RA patients independent of disease activity.MethodsRA patients were recruited from the PREMIER study and included 214 patients treated with methotrexate (MTX) plus adalimumab and 188 patients treated with MTX monotherapy. Periarticular bone loss was assessed by digital X-ray radiogrammetry metacarpal cortical index (DXR-MCI). Change in DXR-MCI was evaluated in patients with different levels of clinical response, as assessed by changes in DAS28 score at 52 weeks and in mean C-reactive protein (CRP) levels during follow-up.ResultsIn the MTX group, there was a greater median DXR-MCI loss among patients with moderate and high disease activity compared to those in remission or with low disease activity (-3.3% vs. -2.2%, p = 0.01). In contrast, periarticular bone loss was independent of disease activity (-1.9% vs. -2.4%, p = 0.99) in the combination group. In the MTX group patients with a mean CRP of ≥ 10 mg/l lost significantly more DXR-MCI than patients with low CRP (-3.1% vs. -1.9%, p <0.01) whereas in the combination group no significant differences between the two CRP groups was seen (-2.4% vs. -2.0%, p = 0.48).ConclusionAdalimumab in combination with MTX reduces periarticular bone loss independently of clinical response. These results support the hypothesis that TNF-α stimulates the osteoclast not only by the inflammatory pathway but do also have a direct effect on the osteoclast.Trial RegistrationClinicalTrials (NCT): NCT001195663
Nowadays, erotic behaviour in cyberspace is customary. Online dating is a million dollar industry. Within the everyday politics of erotic-romantic relationships, however, males and females still blush in each other's presence, caress tenderly and trade hickeys. Mainstream social science researches cyber-behaviour voluminously, but totally ignores commonplace fleshy phenomena. Our study probes this discrepancy. What does it mean that virtual sex is winning the current war between desire and technology? Why is the 'flesh' becoming increasingly marginalized? To accomplish our aim, we use a phenomenological-hermeneutic method. Our basic results are two narratives: (1) interpretations about Internet flirting; and (2) descriptive finding about the hickey. Then, in order to reach general conclusions, we interpret the two studies in light of each other. It is a double hermeneutic. The two target phenomena share the similarity of manifesting the same "lovemap," "solicitation and allure." But they also differ sharply. Internet flirting exemplifies "mirror enchantment"; whereas the hickey showcases a phenomenology of the eyes, touch, dialogue and physical presence. We explain Western culture's preference for technology to the neglect of 'live' embodiment as manifesting a repetition of Platonic-Christendom's contempt for the flesh and horror of passionate tenderness. Our culture, on the cusp between modernity and post-modernity, displays dread concerning the flesh by obsessive concerns with safety-security and with modulating excesses. Are not absolute control and perfect security, however, merely illusions? We showcase the positive aspects of seemingly unsafe values: psychological vulnerability, daring, and risk.
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