Acceptance of inflammatory bowel disease treatment recommendations based on appropriateness ratings: do practicing gastroenterologists agree with experts?

BACKGROUND: Appropriateness criteria for the treatment of Crohn's disease (CD) and ulcerative colitis (UC) have been developed by expert panels. Little is known about the acceptance of such recommendations by care providers. The aim was to explore how treatment decisions of practicing gastroenterologists differ from those of experts, using a vignette case study and a focus group. METHODS: Seventeen clinical vignettes were drawn from clinical indications evaluated by the expert panel. A vignette case questionnaire asking for treatment options in 9 or 10 clinical situations was submitted to 26 practicing gastroenterologists. For each vignette case, practitioners' answers on treatments deemed appropriate were compared with panel decisions. Qualitative analysis was performed on focus group discussion to explore acceptance and divergence reasons. RESULTS: Two hundred thirty-nine clinical vignettes were completed, 98 for CD and 141 for UC.Divergence between proposed treatments and panel recommendations was more frequent for CD (34%) than for UC (27%). Among UC clinical vignettes, the main divergences with the panel were linked to 5-aminosalicylate (5-ASA) failure assessment and to situations in which stopping treatment was the main decision. For CD, the propositions of care providers diverged from the panel in mild to moderate active disease, for which practitioners were more prone to an accelerated step-up than the panel's recommendations. CONCLUSIONS: In about one-third of vignette cases, inflammatory bowel disease treatment propositions made by practicing gastroenterologists diverged from expert recommendations. Practicing gastroenterologists may experience difficulty in applying recommendations in daily practice.

Evidence for a role of oxytocin receptors in the long-term establishment of dominance hierarchies.

Exposure to stress can affect the establishment of dominance hierarchies. In our model, a social hierarchy established by two male rats during a first encounter is not maintained 1 week later. If one of the two rats is stressed, the stressed rat becomes subordinate and the hierarchy that is formed is maintained. In this study, we investigated the changes in the expression of oxytocin (Otr) and vasopressin (V1aR) receptor genes in the medial amygdala (MeA) and the lateral septum (LS) in the hours following hierarchy establishment under both stressed and basal conditions. We found that the potentiation of a social hierarchy induced by stress is accompanied by social status- and region-specific changes in the expression of Otr mRNA in the MeA 3 h after the social encounter. At this time point, no evidence was found for the regulation of V1aR mRNA in any of the brain regions examined. Results from pharmacological experiments involving the microinfusion of a specific OTR antagonist immediately after the acquisition of a subordinate status under basal, non-stress conditions suggested a role for this receptor in the MeA on the long-term establishment of the subordinate status. Altogether, these findings highlight a role for the oxytocinergic system in the mechanisms through which stress facilitates the long-term establishment of a social hierarchy.

A role for glucocorticoids in the long-term establishment of a social hierarchy.

Stress can affect the establishment and maintenance of social hierarchies. In the present study, we investigated the role of increasing corticosterone levels before or just after a first social encounter between two rats of a dyad in the establishment and the long-term maintenance of a social hierarchy. We show that pre-social encounter corticosterone treatment does not affect the outcome of the hierarchy during a first encounter, but induces a long-term memory for the hierarchy when the corticosterone-injected rat becomes dominant during the encounter, but not when it becomes subordinate. Post-social encounter corticosterone leads to a long-term maintenance of the hierarchy only when the subordinate rat of the dyad is injected with corticosterone. This corticosterone effect mimics previously reported actions of stress on the same model and, hence, implicates glucocorticoids in the consolidation of the memory for a recently established hierarchy.

Regional differences in hippocampal PKA immunoreactivity after training and reversal training in a spatial Y-maze task.

It is suggested that the hippocampus functions as a comparator by making a comparison between the internal representation and actual sensory information from the environment (for instance, comparing a previously learned location of a food reward with an actual novel location of a food reward in a Y-maze). However, it remains unclear to what extent the various hippocampal regions contribute to this comparator function. One of the proteins known to be crucially involved in the formation of hippocampus-dependent long-term memory is the adenosine 3',5' cyclic monophosphate dependent protein kinase (PKA). Here, we examined region-specific changes in immunoreactivity (ir) of the regulatory IIalpha,beta subunits of PKA (PKA RIIalpha,beta-ir) in the hippocampus during various stages of spatial learning in a Y-maze reference task. Thereafter, we compared changes in hippocampal PKA RIIalpha,beta-ir induced by training and reversal training in which the food reward was relocated to the previously unrewarded arm. We show that: (1) There was a clear correlation between behavioral performance and elevated PKA RIIalpha,beta-ir during the acquisition phase of both training and reversal training in area CA3 and dentate gyrus (DG), (2) PKA RIIalpha,beta-ir was similarly enhanced in area CA1 during the acquisition phase of reversal training, but did not correlate with behavioral performance, (3) PKA RIIalpha,beta-ir did not change during training or reversal training in the subiculum (SUB), (4) No changes in PKA RIIalpha,beta protein levels were found using Western blotting, and (5) AMPA receptor phosphorylation at serine 845 (S845p; the PKA site on the glutamate receptor 1 subunit (GluR1)), was enhanced selectively during the acquisition phase of reversal training. These findings reveal that training and reversal training induce region-specific changes in hippocampal PKA RIIalpha,beta-ir and suggest a differential involvement of hippocampal subregions in match-mismatch detection in case of Y-maze reference learning. Alterations in AMPA receptor regulation at the S845 site seems specifically related to the novelty detector function of the hippocampus important for match-mismatch detection.