Hemophilic bleeding into joints causes synovial and microvascular proliferation and inflammation (hemophilic synovitis) that contribute to end-stage joint degeneration (hemophilic arthropathy), the major morbidity of hemophilia. New therapies are needed for joint deterioration that progresses despite standard intravenous (IV) clotting factor replacement. To test whether factor IX within the joint space can protect joints from hemophilic synovitis, we established a hemophilia B mouse model of synovitis. Factor IX knockout (FIX ؊/؊ ) mice received a puncture of the knee joint capsule with a needle to induce hemarthrosis; human factor IX (hFIX) was either injected through the needle into the joint space (intraarticu- larly IntroductionThe most significant morbidity resulting from congenitally deficient factor VIII or IX activity (hemophilia A or hemophilia B) is the progressive destruction of joints resulting from recurrent intraarticular (IA) hemorrhage. Although bleeding at other sites does occur in persons with hemophilia, the musculoskeletal system is by far the most common site; 85% of all bleeding events occur in joints, and 80% of these affect 6 problem joints: the elbows, knees, and ankles. 1 Joint hemorrhage is treated by intravenous (IV) infusion of clotting factor to raise the circulating plasma activity. There is a need for adjunctive therapies directed specifically to the pathology within the hemophilic joint.An understanding of the pathophysiology of hemophilic joint disease is only now emerging. [2][3][4] Joint bleeding results in a chronic inflammatory disorder known as hemophilic synovitis, which in time evolves into a complex arthritis termed hemophilic arthropathy, in which the synovial disease is accompanied by degenerative changes in cartilage and underlying bone. 3,4 As the inflammatory environment that develops in response to blood in a joint stimulates neoangiogenesis of fragile blood vessels, one or more "target" joints for recurrent bleeding develop. Joint-surface erosions secondary to chronic synovitis often occur in early childhood. 5 If aggressive early prophylactic factor replacement is not instituted, 90% of persons with severe hemophilia (Ͻ 1% factor VIII or factor IX activity) will have chronic degenerative changes in 1 to 6 joints by 25 years of age.A limited number of treatment options exist for recurrent joint bleeding and hemophilic synovitis. 6 The mainstay of therapy is replacement clotting factor dosed to achieve a circulating plasma activity level adequate to provide hemostasis throughout the body. Factor replacement in response to ongoing bleeding does not halt the progression of existing arthropathy. 5 Instead, institution of uninterrupted preventive (prophylactic) factor infusions at an early age, before the onset of recurrent joint bleeding, should be the standard of care. 7 The major costs of hemophilia to the healthcare system in dollars, to society in lost productivity and to the person with hemophilia in terms of quality of life, result from bleeding into joints. 8 F...
Introduction We developed a first-person serious game, PediatricSim, to teach and assess performances on seven critical pediatric scenarios (anaphylaxis, bronchiolitis, diabetic ketoacidosis, respiratory failure, seizure, septic shock, and supraventricular tachycardia). In the game, players are placed in the role of a code leader and direct patient management by selecting from various assessment and treatment options. The objective of this study was to obtain supportive validity evidence for the PediatricSim game scores. Methods Game content was developed by 11 subject matter experts and followed the American Heart Association's 2011 Pediatric Advanced Life Support Provider Manual and other authoritative references. Sixty subjects with three different levels of experience were enrolled to play the game. Before game play, subjects completed a 40-item written pretest of knowledge. Game scores were compared between subject groups using scoring rubrics developed for the scenarios. Validity evidence was established and interpreted according to Messick's framework. Results Content validity was supported by a game development process that involved expert experience, focused literature review, and pilot testing. Subjects rated the game favorably for engagement, realism, and educational value. Interrater agreement on game scoring was excellent (intraclass correlation coefficient = 0.91, 95% confidence interval = 0.89–0.9). Game scores were higher for attendings followed by residents then medical students (P c < 0.01) with large effect sizes (1.6–4.4) for each comparison. There was a very strong, positive correlation between game and written test scores (r = 0.84, P < 0.01). Conclusions These findings contribute validity evidence for PediatricSim game scores to assess knowledge of pediatric emergency medicine resuscitation.
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