Objective. To develop longitudinal 3-dimensional (3-D) measures of outcomes of inflammation and bone erosion in murine arthritis using contrast-enhanced magnetic resonance imaging (CE-MRI) and in vivo microfocal computed tomography (micro-CT) and, in a pilot study, to determine the value of entry criteria based on age versus synovial volume in therapeutic intervention studies.Methods. CE-MRI and in vivo micro-CT were performed on tumor necrosis factor-transgenic (TNFTg) mice and their wild-type littermates to quantify the synovial and popliteal lymph node volumes and the patella and talus bone volumes, respectively, which were validated histologically. These longitudinal outcome measures were used to assess the natural history of erosive inflammatory arthritis. We also performed anti-TNF versus placebo efficacy studies in TNF-Tg mice in which treatment was initiated according to either age (4-5 months) or synovial volume (3 mm 3 as detected by CE-MRI). Linear regression was performed to analyze the correlation between synovitis and focal erosion.Results. CE-MRI demonstrated the highly variable nature of TNF-induced joint inflammation. Initiation of treatment by synovial volume produced significantly larger treatment effects on the synovial volume (P ؍ 0.04) and the lymph node volume (P < 0.01) than did initiation by age. By correlating the MRI and micro-CT data, we were able to demonstrate a significant relationship between changes in synovial and patellar volumes (R 2 ؍ 0.75, P < 0.01).Conclusion. In vivo CE-MRI and micro-CT 3-D outcome measures are powerful tools that accurately demonstrate the progression of erosive inflammatory arthritis in mice. These methods can be used to identify mice with arthritis of similar severity before intervention studies are initiated, thus minimizing heterogeneity in outcome studies of chronic arthritis seen between genetically identical littermates.Although murine models of inflammatory arthritis have significantly advanced our understanding of erosive inflammatory arthritis (1,2), they are limited by a lack of longitudinal translational outcome measures of disease progression or interventional therapy. This issue presents 3 problems for prototypical preclinical investigations of drug effects on inflammation, erosion, and healing (3,4). First, most cross-sectional studies in mice with "established arthritis" do not include an objective
The objective of this research was to assess the implementation of collecting patient-reported outcomes data in the outpatient clinics of a large academic hospital and identify potential barriers and solutions to such an implementation. Three PROMIS computer adaptive test instruments, (1) physical function, (2) pain interference, and (3) depression, were administered at 23,813 patient encounters using a novel software platform on tablet computers. The average time to complete was 3.50 ± 3.12 min, with a median time of 2.60 min. Registration times for new patients did not change significantly, 6.87 ± 3.34 to 7.19 ± 2.69 min. Registration times increased for follow-up (p = .007) from 2.94 ± 1.57 (p < .01) min to 3.32 ± 1.78 min. This is an effective implementation strategy to collect patient-reported outcomes and directly import the results into the electronic medical record in real time for use during the clinical visit.
New healthcare demands for quality measures of elective procedures, such as anterior cruciate ligament (ACL) reconstructive surgery, warrant the establishment of high through-put outcomes for high volume clinics. To this end we evaluated the PROMIS and GAITRite as physical function outcome measures to quantify early healing and post-operative complications in 106 patients at pre-op and 3, 10, 20 and 52 weeks post-ACL reconstruction with bone-tendon-bone autograft, and compared the results to the current IKDC validated outcome measure. The results showed that both PROMIS and GAITRite were significantly quicker to administer versus IKDC (p < 0.0001). Additional advantages were that PROMIS and GAITRite detected a significant decrease in physical function at 3 weeks post-op, and a significant improvement at 10 weeks post-op, versus pre-op (p<0.001), which were not detected with IKDC. GAITRite was limited by a low ceiling that could not detect improvement of physical function beyond 20 weeks, while both PROMIS and IKDC detected significant improvement out to 52 weeks postop (p<0.001). Linear regressions demonstrated a significant relationship between IKDC and PROMIS, with a combined correlation value of 0.8954 (p<.001) for all time points. Finally, ROC curve analysis demonstrated that PROMIS is a diagnostic test for poor outcomes.
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