Appropriateness of small molecule agents for patients with IBD of childbearing age - a RAND/UCLA appropriateness panel.

Background: Many women of childbearing age with inflammatory bowel disease (IBD) require advanced therapies. While biologics are largely low risk during pregnancy, the novel small molecules tofacitinib, filgotinib, upadacitinib and ozanimod (TFUO) have shown concerning teratogenic effects, and decreased fertility in animal studies. Therefore, their use in women of childbearing age needs careful consideration.

Transitioning from emicizumab prophylaxis to valoctocogene roxaparvovec gene therapy: A simulation study for individuals with severe haemophilia A.

Introduction: Valoctocogene roxaparvovec, a gene therapy evaluated in the phase 3 GENEr8-1 trial, supports endogenous factor VIII (FVIII) production to prevent bleeding in people with severe haemophilia A. Individuals receiving emicizumab, an antibody mimicking the function of activated FVIII, were excluded from GENEr8-1 enrolment since emicizumab was an investigational therapy at the time of trial initiation.

Aim: Utilize pharmacokinetic simulations to provide guidance on best practices for maintaining haemostatic control while transitioning from emicizumab prophylaxis to valoctocogene roxaparvovec.

Comparative Effectiveness of Valoctocogene Roxaparvovec and Prophylactic Factor VIII Replacement in Severe Hemophilia A.

Introduction: A prospective, non-interventional study (270-902) followed 294 adults with severe hemophilia A (SHA) receiving prophylactic factor VIII (FVIII). From these participants, 112 rolled over into a single-arm, multicenter, phase 3 trial (GENEr8-1; NCT03370913) that evaluated efficacy and safety of valoctocogene roxaparvovec, a gene therapy that provides endogenous FVIII in individuals with SHA. Participants from 270-902 who did not roll over provide an opportunity for a contemporaneous external control.

Out of fright, out of mind: impaired memory for information negated during looming threat.

People often need to update representations of information upon discovering them to be incorrect, a process that can be interrupted by competing cognitive demands. Because anxiety and stress can impair cognitive performance, we tested whether looming threat can similarly interfere with the process of updating representations of a statement's truthfulness. On each trial, participants saw a face paired with a personality descriptor.

Failures of executive function when at a height: Negative height-related appraisals are associated with poor executive function during a virtual height stressor.

It is difficult to maintain cognitive functioning in threatening contexts, even when it is imperative to do so. Research indicates that precarious situations can impair subsequent executive functioning, depending on whether they are appraised as threatening. Here, we used virtual reality to place participants at ground level or at a virtual height in order to examine the impact of a threat-related context on concurrent executive function and whether this relationship was modulated by negative appraisals of heights.