Examining patient preferences in the treatment of rheumatoid arthritis using a discrete-choice approach.

BACKGROUND: Biological disease-modifying antirheumatic drugs (bDMARDs) used in second-line treatment of rheumatoid arthritis (RA) are administered parenterally. However, so-called targeted synthetic DMARDs (tsDMARDs) - developed more recently - offer alternative (ie, oral) administration forms in second-line treatment. Since bDMARDs and tsDMARDs can be regarded as equal in terms of efficacy, the present study examines whether such characteristics as route of administration drive RA patients' treatment choice. This may ultimately suggest superiority of some second-line DMARDs over equally effective options, at least according to RA-patient preferences. OBJECTIVE: The current study assessed the importance of oral administration among other treatment characteristics differing between available second-line DMARDs for RA patients' preferences using a discrete-choice experiment (DCE). MATERIALS AND METHODS: The DCE involved scenarios of three hypothetical treatment options in a d-efficient design with varying levels of key attributes (route and frequency of administration, time till onset of drug effect, combination therapy, possible side effects), as defined by focus groups. Further patient characteristics were recorded by an accompanying questionnaire. In the DCE, patients were asked to choose best and worst options (best-worst scaling). Results were analyzed by count analysis and adjusted regression analysis. RESULTS: A total of 1,588 subjects completed the DCE and were eligible for final analyses. Across all characteristics included in the DCE, "oral administration" was most desired and "intravenous infusion" was most strongly rejected. This was followed by "no combination with methotrexate" being strongly preferred and "intake every 1-2 weeks" being strongly rejected. On average, levels of route of administration showed strongest influences on patients' decisions in post hoc bootstrapping analysis. CONCLUSION: According to the results, an oral DMARD that does not have to be combined with methotrexate and is not administered (only) every 1-2 weeks appears a highly favorable treatment option for patients with RA. DMARDs meeting these preferences may increase compliance and adherence in RA treatment.

Autistic adolescents show atypical activation of the brain's mentalizing system even without a prior history of mentalizing problems.

Some autistic children pass classic Theory of Mind (ToM) tasks that others fail, but the significance of this finding is at present unclear. We identified two such groups of primary school age (labelled ToM+ and ToM-) and a matched comparison group of typically developing children (TD). Five years later we tested these participants again on a ToM test battery appropriate for adolescents and conducted an fMRI study with a story based ToM task. We also assessed autistic core symptoms at these two time points. At both times the ToM- group showed more severe social communication impairments than the ToM+ group, and while showing an improvement in mentalizing performance, they continued to show a significant impairment compared to the NT group. Two independent ROI analyses of the BOLD signal showed activation of the mentalizing network including medial prefrontal cortex, posterior cingulate and lateral temporal cortices. Strikingly, both ToM+ and ToM- groups showed very similar patterns of heightened activation in comparison with the NT group. No differences in other brain regions were apparent. Thus, autistic adolescents who do not have a history of mentalizing problems according to our ToM battery showed the same atypical neurophysiological response during mentalizing as children who did have such a history. This finding indicates that heterogeneity at the behavioural level may nevertheless map onto a similar phenotype at the neuro-cognitive level.

Emotion effects on the n170: a question of reference?

We investigated whether face-specific processes as indicated by the N170 in event-related brain potentials (ERPs) are modulated by emotional significance in facial expressions. Results yielded that emotional modulations over temporo-occipital electrodes typically used to measure the N170 were less pronounced when ERPs were referred to mastoids than when average reference was applied. This offers a potential explanation as to why the literature has so far yielded conflicting evidence regarding effects of emotional facial expressions on the N170. However, spatial distributions of the N170 and emotion effects across the scalp were distinguishable for the same time point, suggesting different neural sources for the N170 and emotion processing. We conclude that the N170 component itself is unaffected by emotional facial expressions, with overlapping activity from the emotion-sensitive early posterior negativity accounting for amplitude modulations over typical N170 electrodes. Our findings are consistent with traditional models of face processing assuming face and emotion encoding to be parallel and independent processes.

Does processing of emotional facial expressions depend on intention? Time-resolved evidence from event-related brain potentials.

We assessed the automaticity of emotional face processing with respect to the intentionality criterion, holding that automatic processes are triggered independently of intention. For this purpose, we observed emotion processing in event-related brain potential (ERP) components under five different task conditions. ERP components included the P1, N170, the early posterior negativity (EPN), and the late positive complex (LPC). Enhanced processing at perceptual stages as indicated by P1, N170, and EPN effects occurred independently of intention in angry expressions. In contrast, the emotion-related LPC, a putative manifestation of higher-level, more elaborative processing stages, depended on the intentional state of the participants. This suggests an automatic threat-related processing bias at perceptual stages, while higher cognitive emotion encoding is subject to voluntary control. Moreover, an independent component analyses (ICA) showed that EPN and LPC activity occurred simultaneously, indicating perceptual and higher cognitive emotion encoding to occur in parallel.

Automaticity in attractive face processing: brain potentials from a dual task.

Attractive faces have a special status, possibly because of evolutionary reasons. We assessed the automaticity of facial attractiveness processing in a dual-task paradigm manipulating the availability of cognitive resources to face processing by a primary tone task presented at varying stimulus onset asynchrony (SOA). In event-related brain potentials, attractive relative to neutral faces induced an increased posterior negativity from 260 ms onwards indicating enhanced stimulus encoding at the cortical level. Interestingly, effects of attractive faces on event-related brain potentials were most pronounced at high temporal overlap with the primary task (short stimulus onset asynchrony). This indicates that a shortage of cognitive resources may enhance the processing of attractive faces, revealing hard-wired processing biases of the human information processing system for evolutionarily prepared stimuli.

On the automaticity of emotion processing in words and faces: event-related brain potentials evidence from a superficial task.

The degree to which emotional aspects of stimuli are processed automatically is controversial. Here, we assessed the automatic elicitation of emotion-related brain potentials (ERPs) to positive, negative, and neutral words and facial expressions in an easy and superficial face-word discrimination task, for which the emotional valence was irrelevant. Both emotional words and facial expressions impacted ERPs already between 50 and 100 ms after stimulus onset, possibly reflecting rapid relevance detection. Following this initial processing stage only emotionality in faces but not in words was associated with an early posterior negativity (EPN). Therefore, when emotion is irrelevant in a task which requires superficial stimulus analysis, automatically enhanced sensory encoding of emotional content appears to occur only for evolutionary prepared emotional stimuli, as reflected in larger EPN amplitudes to faces, but not to symbolic word stimuli.