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ObjectiveTo determine the optimal combination of imaging and biochemical biomarkers for use in the prediction of knee osteoarthritis (OA) progression.MethodsThe present study was a nested case-control trial from the Foundation of the National Institutes of Health OA Biomarkers Consortium that assessed study participants with a Kellgren/Lawrence grade of 1-3 who had complete biomarker data available (n = 539 to 550). Cases were participants' knees that had radiographic and pain progression between 24 and 48 months compared to baseline. Radiographic progression only was assessed in secondary analyses. Biomarkers (baseline and 24-month changes) that had a P value of

ObjectiveTo evaluate radiographic subchondral trabecular bone texture (TBT) as a predictor of clinically relevant osteoarthritis (OA) progression (combination of symptom and structural worsening).MethodsThe Foundation for the National Institutes of Health (FNIH) OA Biomarkers Consortium undertook a study of progressive knee OA cases (n = 194 knees with both radiographic and pain progression over 24-48 months) and comparators (n = 406 OA knees not meeting the case definition). TBT parameters were extracted from a medial subchondral tibial region of interest by fractal signature analysis of radiographs using validated semiautomated software. Baseline TBT and time-integrated values over 12 and 24 months were evaluated for association with case status and separately with radiographic and pain progression status, adjusted for age, sex, body mass index, race, baseline Kellgren/Lawrence grade, baseline joint space width, Western Ontario and McMaster Universities Osteoarthritis Index pain score, and pain medication use. C statistics were generated from receiver operating characteristic curves.ResultsRelative to comparators, cases were characterized by thinner vertical and thicker horizontal trabeculae. The summed composite of 3 TBT parameters at baseline and over 12 and 24 months best predicted case status (odds ratios 1.24-1.43). The C statistic for predicting case status using the TBT composite score (0.633-0.649) was improved modestly but statistically significantly over the use of covariates alone (0.608). One TBT parameter, reflecting thickened horizontal trabeculae in cases, at baseline and over 12 and 24 months, predicted risk of any progression (radiographic and/or pain progression).ConclusionAlthough associations are modest, TBT could be an attractive means of enriching OA trials for progressors since it can be generated from screening knee radiographs already standard in knee OA clinical trials.

ObjectiveTo investigate a targeted set of biochemical biomarkers as predictors of clinically relevant osteoarthritis (OA) progression.MethodsEighteen biomarkers were measured at baseline, 12 months (M) and 24 M in serum (s) and/or urine (u) of cases (n=194) from the OA initiative cohort with knee OA and radiographic and persistent pain worsening from 24 to 48 M and controls (n=406) not meeting both end point criteria. Primary analyses used multivariable regression models to evaluate the association between biomarkers (baseline and time-integrated concentrations (TICs) over 12 and 24 M, transposed to z values) and case status, adjusted for age, sex, body mass index, race, baseline radiographic joint space width, Kellgren-Lawrence grade, pain and pain medication use. For biomarkers with adjusted p

Background: Candidate selection for upper extremity transplantation remains an inherently subjective process. This work evaluated the effect that psychosocial factors have on outcomes, both to standardize evaluation of potential candidates and in optimizing these factors prior to transplantation. Our goal was to measure and quantify the risk that various psychosocial factors have on transplant outcomes. Methods: Given that we do not have sufficient post-transplant patients to examine specific factors, we chose to have experts in the field evaluate hypothetical patients based on their experience. We used a Generalized Estimating Equation to estimate and compare surgical candidacy scores using patient scenario vignettes based on the presence or absence of permutations of the following: (1) depression; (2) participation in occupational therapy (OT); (3) expectation of post-transplant function; (4) punctuality; and (5) family support were given to experts in the field. Results: This work suggests there is a decrease in predicted success with increasing numbers of negative factors with participation in OT and realistic expectations of outcomes being most important. An increase in the summarizing risk score from 0 to 1.7 was associated with a decrease in the outcome surgical candidacy score from 8.6 to 5.3, meaning candidates with 2 risk factors would often observe a large drop in surgical candidacy score. Conclusions: Focusing on optimizing psychosocial variables in transplant candidates may help improve hand transplant success. [ABSTRACT FROM AUTHOR]

BackgroundTo describe the scoring methodology and MRI assessments used to evaluate the cross-sectional features observed in cases and controls, to define change over time for different MRI features, and to report the extent of changes over a 24-month period in the Foundation for National Institutes of Health Osteoarthritis Biomarkers Consortium study nested within the larger Osteoarthritis Initiative (OAI) Study.MethodsWe conducted a nested case-control study. Cases (n = 406) were knees having both radiographic and pain progression. Controls (n = 194) were knee osteoarthritis subjects who did not meet the case definition. Groups were matched for Kellgren-Lawrence grade and body mass index. MRIs were acquired using 3 T MRI systems and assessed using the semi-quantitative MOAKS system. MRIs were read at baseline and 24 months for cartilage damage, bone marrow lesions (BML), osteophytes, meniscal damage and extrusion, and Hoffa- and effusion-synovitis. We provide the definition and distribution of change in these biomarkers over time.ResultsSeventy-three percent of the cases had subregions with BML worsening (vs. 66 % in controls) (p = 0.102). Little change in osteophytes was seen over 24 months. Twenty-eight percent of cases and 10 % of controls had worsening in meniscal scores in at least one subregion (p

ObjectiveTo highlight the opportunities and challenges of developing and implementing performance outcome measures in rheumatology for accountability purposes.MethodsWe constructed a hypothetical performance outcome measure to demonstrate the benefits and challenges of designing quality measures that assess patient outcomes. We defined the data source, measure cohort, reporting period, period at risk, measure outcome, outcome attribution, risk adjustment, reliability and validity, and reporting approach. We discussed outcome measure challenges specific to rheumatology and to fields where patients have predominantly chronic, complex, ambulatory care-sensitive conditions.ResultsOur hypothetical outcome measure was a measure of rheumatoid arthritis disease activity intended for evaluating Accountable Care Organization performance. We summarized the components, benefits, challenges, and tradeoffs between feasibility and usability. We highlighted how different measure applications, such as for rapid cycle quality improvement efforts versus pay for performance programs, require different approaches to measure development and testing. We provided a summary table of key take-home points for clinicians and policymakers.ConclusionPerformance outcome measures are coming to rheumatology, and the most effective and meaningful measures can only be created through the close collaboration of patients, providers, measure developers, and policymakers. This study provides an overview of key issues and is intended to stimulate a productive dialogue between patients, practitioners, insurers, and government agencies regarding optimal performance outcome measure development.

ObjectiveTo determine the association between changes in semiquantitative magnetic resonance imaging (MRI) biomarkers over 24 months and radiographic and pain progression over 48 months in knees with mild-to-moderate osteoarthritis (OA).MethodsWe undertook a nested case-control study as part of the Foundation for the National Institutes of Health Biomarkers Consortium Project. We used multivariable logistic regression models to examine the association between change over 24 months in semiquantitative MRI markers and radiographic and pain progression in knee OA. MRIs were read according to the MRI OA Knee Score system. We focused on changes in cartilage, osteophytes, meniscus, bone marrow lesions, Hoffa-synovitis, and effusion-synovitis.ResultsThe most parsimonious model included changes in cartilage thickness and surface area, effusion-synovitis, Hoffa-synovitis, and meniscal morphology (C statistic 0.740). Compared with no worsening, worsening in cartilage thickness in ≥3 subregions was associated with 2.8-fold (95% confidence interval [95% CI] 1.3-5.9) greater odds of being a case, and worsening in cartilage surface area in ≥3 subregions was associated with 2.4-fold (95% CI 1.3-4.4) greater odds of being a case. Worsening of meniscal morphology in any region was associated with 2.2-fold (95% CI 1.3-3.8) greater odds of being a case. Worsening effusion-synovitis and Hoffa-synovitis were also associated with a greater odds of being a case (odds ratios 2.7 and 2.0, respectively).ConclusionTwenty-four-month changes in cartilage thickness, cartilage surface area, effusion-synovitis, Hoffa-synovitis, and meniscal morphology were independently associated with OA progression, suggesting that these factors may serve as efficacy biomarkers in clinical trials of disease-modifying interventions for knee OA.

ObjectiveThe impact of increasing utilization of total knee arthroplasty (TKA) on lifetime costs in persons with knee osteoarthritis (OA) is understudied.MethodsWe used the Osteoarthritis Policy Model to estimate total lifetime costs and TKA utilization under a range of TKA eligibility criteria among US persons with symptomatic knee OA. Current TKA utilization was estimated from the Multicenter Osteoarthritis Study and calibrated to Health Care Cost and Utilization Project data. OA treatment efficacy and toxicity were drawn from published literature. Costs in 2013 dollars were derived from Medicare reimbursement schedules and Red Book Online. Time costs were derived from published literature and the US Bureau of Labor Statistics.ResultsEstimated average discounted (3% per year) lifetime costs for persons diagnosed with knee OA were $140,300. Direct medical costs were $129,600, with $12,400 (10%) attributable to knee OA over 28 years. OA patients spent a mean ± SD of 13 ± 10 years waiting for TKA after failing nonsurgical regimens. Under current TKA eligibility criteria, 54% of knee OA patients underwent TKA over their lifetimes. Estimated OA-related discounted lifetime direct medical costs ranged from $12,400 (54% TKA uptake) when TKA eligibility was limited to Kellgren/Lawrence grades 3 or 4 to $16,000 (70% TKA uptake) when eligibility was expanded to include symptomatic OA with a lesser degree of structural damage.ConclusionBecause of low efficacy of nonsurgical regimens, knee OA treatment-attributable costs are low, representing a small portion of all costs for OA patients. Expanding TKA eligibility increases OA-related costs substantially for the population, underscoring the need for more effective nonoperative therapies.

Historically disease knowledge development and treatment innovation in osteoarthritis (OA) has been considered to be slow. One of the many reasons purported as responsible for this slow pace has been the alleged lack of valid and responsive biomarkers to ascertain efficacy, which itself has been dependent upon the slow evolution of the understanding of the complex nature of joint tissue biology. This narrative review outlines the rationale for why we need OA biomarkers with regard to biomarker validation and qualification. The main biomarkers in current development for OA are biochemical and imaging markers. We describe an approach to biomarker validation and qualification for OA clinical trials that has recently commenced with the Foundation of NIH OA Biomarkers Consortium study cosponsored by the Osteoarthritis Research Society International (OARSI). With this approach we endeavor to identify, develop, and qualify biological markers (biomarkers) to support new drug development, preventive medicine, and medical diagnostics for osteoarthritis.