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Background: Stroke is the leading cause of long-term disability in North America and best practice care requires effective interprofessional collaboration (IPC). Situational awareness, communication, and coordination of services are critical elements of IPC and patient safety, but assessment of IPC is challenging and often relies solely on communication analysis. Little research has focused on how differences in attention allocation amongst team members might relate to effective IPC in the stroke care context. Methods: In this pilot study we explored whether eye movements may provide additional insight into effective IPC in simulation. Sixteen participants (students enrolled in Medicine, Pharmacy, Occupational Therapy, Physiotherapy, Speech/Language Pathology, and Nursing) participated in an interprofessional module and were randomly assigned to four interprofessional teams. Participants wore SMI mobile eye-trackers during a simulation consisting of a 25-minute team meeting followed by a 25-minute simulated patient assessment. SMI BeGazeTM software was used for eye movement analysis (saccades, fixations, and area-of-interest analyses). Team performance was ranked separately for IPC and stroke competency by a panel of trained experts. Findings: Preliminary results suggest the teams ranked higher on IPC had shorter fixation durations, higher frequency of fixations/sec, less variability in saccade velocity, and higher areas of interest (AOI) frequencies on the patient's chart. Next steps include event-based analyses of "critical incidents" identified by experts to determine if looking patterns at pivotal moments distinguish high from low ranked teams. Results will be compared to audio recording qualitative analysis and self-ranked IPC scores. Further results to be shared at the conference. [ABSTRACT FROM AUTHOR]

Interprofessional collaboration (IPC) in stroke care is accepted as best practice and necessary given the multi-system challenges and array of professionals involved. Our two-part stroke team simulations offer an intentional interprofessional educational experience (IPE) embedded in pre-licensure occupational therapy, physical therapy, pharmacy, medicine, nursing and speech-language pathology curricula. This six-year mixed method program evaluation aimed to determine if simulation delivery differences necessitated by COVID-19 impacted students' IPC perception, ratings, and reported learning. Following both simulations, the Interprofessional Collaborative Competency Assessment Scale (ICCAS) and free-text self-reported learning was voluntarily and anonymously collected. A factorial ANOVA using the ICCAS interprofessional competency factors compared scores across delivery methods. Content and category analysis was done for free-text responses. Overall, delivery formats did not affect positive changes in pre-post ICCAS scores. However, pre and post ICCAS scores were significantly different for interprofessional competencies of roles/responsibilities and collaborative patient/family centered approach. Analysis of over 10,000 written response to four open-ended questions revealed the simulation designs evoked better understanding of others' and own scope of practice, how roles and shared leadership change based on context and client need, and the value of each team member's expertise. Virtual-experience-only students noted preference for an in-person stroke clinic simulation opportunity.

Interprofessional practice (IPP) is the accepted standard of care for clients following a stroke. A brief, embedded and evidence-based IPP team simulation was designed to address stroke care knowledge and IPP competencies for students within limited curriculum space. Each team was required to construct a collaborative care plan for their patient during the simulation and submit the care plan for evaluation of best practice stroke care knowledge and implementation with evidence of interprofessional collaboration (IPC). A total of 302 students (274 on-site, 28 by distance technology) representing four professions comprised of 55 teams took part in this experience. Post-simulation, voluntary and anonymous programme evaluations were completed using the standardised interprofessional collaborative competency assessment scale (ICCAS) and open-ended free-text responses to five questions. There was a significant improvement for all pre-post ratings on the ICCAS regardless of profession or previous interprofessional experience. Additionally, the open-ended responses indicated perceived changes to role clarification, communication, and teamwork. The combined interpretation of the programme evaluation results supports interprofessional team simulation as an effective and efficient learning experience for students regardless of previous interprofessional experience, and demonstrated positive changes in stroke best-practice knowledge and IPC competencies.

Inflammatory signals such as pathogen- and danger-associated molecular patterns have been hypothesized as risk factors for the initiation of the anti-factor VIII (FVIII) immune response seen in 25% to 30% of patients with severe hemophilia A (HA). In these young patients, vaccines may be coincidentally administered in close proximity with initial exposure to FVIII, thereby providing a source of such stimuli. Here, we investigated the effects of 3 vaccines commonly used in pediatric patients on FVIII immunogenicity in a humanized HA murine model with variable tolerance to recombinant human FVIII (rhFVIII). Mice vaccinated intramuscularly against the influenza vaccine prior to multiple infusions of rhFVIII exhibited a decreased incidence of rhFVIII-specific neutralizing and nonneutralizing antibodies. Similar findings were observed with the addition of an adjuvant. Upon exposure to media from influenza- or FVIII-stimulated lymph node or splenic lymphocytes, naïve CD4(+) lymphocytes preferentially migrated toward media from influenza-stimulated cells, indicating that antigen competition, by means of lymphocyte recruitment to the immunization site, is a potential mechanism for the observed decrease in FVIII immunogenicity. We also observed no differences in incidence or titer of rhFVIII-specific antibodies and inhibitors in mice exposed to the live-attenuated measles-mumps-rubella vaccine regardless of route of administration. Together, our results suggest that concomitant FVIII exposure and vaccination against influenza does not increase the risk of inhibitor formation and may in fact decrease anti-FVIII immune responses., (© 2016 by The American Society of Hematology.)

Rare missense mutations in the von Willebrand factor (VWF) A3 domain that disrupt collagen binding have been found in patients with a mild bleeding phenotype. However, the analysis of these aberrant VWF-collagen interactions has been limited. Here, we have developed mouse models of collagen-binding mutants and analyzed the function of the A3 domain using comprehensive in vitro and in vivo approaches. Five loss-of-function (p.S1731T, p.W1745C, p.S1783A, p.H1786D, A3 deletion) and 1 gain-of-function (p.L1757A) variants were generated in the mouse VWF complementary DNA. The results of these various assays were consistent, although the magnitude of the effects were different: the gain-of-function (p.L1757A) variant showed consistent enhanced collagen binding whereas the loss-of-function mutants showed variable degrees of functional deficit. We further analyzed the impact of direct platelet-collagen binding by blocking glycoprotein VI (GPVI) and integrin α2β1 in our ferric chloride murine thrombosis model. The inhibition of GPVI demonstrated a comparable functional defect in thrombosis formation to the VWF(-/-) mice whereas α2β1 inhibition demonstrated a milder bleeding phenotype. Furthermore, a delayed and markedly reduced thrombogenic response was still evident in VWF(-/-), GPVI, and α2β1 blocked animals, suggesting that alternative primary hemostatic mechanisms can partially rescue the bleeding phenotype associated with these defects., (© 2014 by The American Society of Hematology.)

Genetic variation in or near the C-type lectin domain family 4 member M (CLEC4M) has been associated with plasma levels of von Willebrand factor (VWF) in healthy individuals. CLEC4M is a lectin receptor with a polymorphic extracellular neck region possessing a variable number of tandem repeats (VNTR). A total of 491 participants (318 patients with type 1 von Willebrand disease [VWD] and 173 unaffected family members) were genotyped for the CLEC4M VNTR polymorphism. Family-based association analysis on kindreds with type 1 VWD demonstrated an excess transmission of VNTR 6 to unaffected individuals (P = .0096) and an association of this allele with increased VWF:RCo (P = .029). CLEC4M-Fc bound to VWF. Immunofluorescence and enzyme-linked immunosorbent assay demonstrated that HEK 293 cells transfected with CLEC4M bound and internalized VWF. Cells expressing 4 or 9 copies of the CLEC4M neck region VNTR showed reduced interaction with VWF relative to CLEC4M with 7 VNTR (CLEC4M 4%-60% reduction, P < .001; CLEC4M 9%-45% reduction, P = .006). Mice expressing CLEC4M after hydrodynamic liver transfer have a 46% decrease in plasma levels of VWF (P = .0094). CLEC4M binds to and internalizes VWF, and polymorphisms in the CLEC4M gene contribute to variable plasma levels of VWF.

Type 1 VWD is the mild to moderate reduction of VWF levels. This study examined the mechanisms underlying 2 common type 1 VWD mutations, the severe R1205H and more moderate Y1584C. In vitro biosynthesis was reduced for both mutations in human and mouse VWF, with the effect being more severe in R1205H. VWF knockout mice received hydrodynamic injections of mouse Vwf cDNA. Lower VWF antigen levels were demonstrated in both homozygous and heterozygous forms for both type 1 mutations from days 14-42. Recombinant protein infusions and hydrodynamic-expressed VWF propeptide to antigen ratios demonstrate that R1205H mouse VWF has an increased clearance rate, while Y1584C is normal. Recombinant ADAMTS13 digestions of Y1584C demonstrated enhanced cleavage of both human and mouse VWF115 substrates. Hydrodynamic-expressed VWF shows a loss of high molecular weight multimers for Y1584C compared with wild-type and R1205H. At normal physiologic levels of VWF, Y1584C showed reduced thrombus formation in a ferric chloride injury model while R1205H demonstrated similar thrombogenic activity to wild-type VWF. This study has elucidated several novel mechanisms for these mutations and highlights that the type 1 VWD phenotype can be recapitulated in the VWF knockout hydrodynamic injection model.

Type 2B von Willebrand disease (2B VWD) results from von Willebrand factor (VWF) A1 mutations that enhance VWF-GPIbalpha binding. These "gain of function" mutations lead to an increased affinity of the mutant VWF for platelets and the binding of mutant high-molecular-weight VWF multimers to platelets in vivo, resulting in an increase in clearance of both platelets and VWF. Three common 2B VWD mutations (R1306W, V1316M, and R1341Q) were independently introduced into the mouse Vwf cDNA sequence and the expression vectors delivered to 8- to 10-week-old C57Bl6 VWF(-/-) mice, using hydrodynamic injection. The resultant phenotype was examined, and a ferric chloride-induced injury model was used to examine the thrombogenic effect of the 2B VWD variants in mice. Reconstitution of only the plasma component of VWF resulted in the generation of the 2B VWD phenotype in mice. Variable thrombocytopenia was observed in mice expressing 2B VWF, mimicking the severity seen in 2B VWD patients: mice expressing the V1316M mutation showed the most severe thrombocytopenia. Ferric chloride-induced injury to cremaster arterioles showed a marked reduction in thrombus development and platelet adhesion in the presence of circulating 2B VWF. These defects were only partially rescued by normal platelet transfusions, thus emphasizing the key role of the abnormal plasma VWF environment in 2B VWD.