Advances in orthopaedic outcomes research.

As the field of orthopaedic surgery continues to expand in terms of indications and technologies, there has been increasing emphasis placed on validated patient-derived outcome measures in clinical orthopaedic research. As concerns mount regarding rising health care costs, declining quality, and variability in clinical practice patterns, outcome measures become important tools in assessing quality. Furthermore, outcome measures can be utilized to justify the clinical benefits of existing and new diagnostic modalities and surgical interventions. This review provides a brief overview of traditional outcomes approaches in orthopaedics followed by a discussion of the current trend toward patient-centered outcomes research and its role in the emerging field of cost-effectiveness analysis in orthopaedics.

Symptomatic coalition between the first and second metatarsals in a child.

Coalitions of the foot are relatively uncommon abnormalities, occurring in approximately 1% of the population. Talocalcaneal and calcaneonavicular are the most common types of coalitions. Coalitions in the forefoot, however, are rare, with only a small number of case reports in the literature. We report on a unilateral, symptomatic coalition between the first and second metatarsals in a 12-year-old girl who presented with a several-month history of intermittent medial-sided, dorsal forefoot pain and difficulty with shoe wear. Her preoperative examination was notable for a firm, nontender dorsal medial forefoot mass centered between the first and second metatarsals. While the first metatarsal head was level with the second metatarsal head in the sagittal plane, the metatarsals were rigidly fixed to one another. First metatarsal-medial cuneiform motion was reduced compared to the unaffected foot. Preoperative magnetic resonance imaging demonstrated a bony and cartilaginous coalition between the first and second metatarsals. Following resection, an immediate improvement was noted in motion between the first and second metatarsals, as well as the first metatarsal and medial cuneiform. In our patient, rigidity between the first and second metatarsals contributed to a stiff first ray with higher plantar pressures beneath the first metatarsal head with walking. The abnormal kinematics likely contributed to her medial forefoot pain with prolonged ambulation and sports activities. Prompt identification and resection of these less common coalitions affecting the forefoot allows symptomatic relief and restoration of normal kinematics.

The cost-effectiveness of computer-assisted navigation in total knee arthroplasty.

BACKGROUND: Total knee arthroplasty is one of the most clinically successful and cost-effective interventions in medicine. However, implant malalignment, especially in the coronal plane, is a common cause of early failure following total knee arthroplasty. Computer-assisted surgery has been employed during total knee arthroplasty to improve the precision of component alignment. The purpose of the present study was to evaluate the cost-effectiveness of computer-assisted surgery to determine whether the improved alignment achieved with computer navigation provides a sufficient decrease in failure rates and revisions to justify the added cost. METHODS: A decision-analysis model was used to estimate the cost-effectiveness of computer-assisted surgery in total knee arthroplasty. Model inputs, including costs, effectiveness, and clinical outcome probabilities, were obtained from a review of the literature. Sensitivity analyses were performed to evaluate the impact of component-alignment precision with use of computer-assisted and mechanical alignment guides, total knee arthroplasty failure rates secondary to malalignment, and costs of computer-assisted surgery systems on the cost-effectiveness of computer navigation in total knee arthroplasty. RESULTS: Computer-assisted surgery is both more effective and more expensive than mechanical alignment systems. Given an additional cost of $1500 per operation, a 14% improvement in coronal alignment precision (within 3 degrees of neutral mechanical axis), and an elevenfold increase in revision rates at fifteen years with coronal malalignment (54% compared with 4.7%), the incremental cost of using computer-assisted surgery is $45,554 per quality-adjusted life-year gained. Cost-savings is achieved if the added cost of computer-assisted surgery is $629 or less per operation. Variability in published clinical outcomes, however, introduces uncertainty in determining the cost-effectiveness. CONCLUSIONS: Computer-assisted surgery is potentially a cost-effective or cost-saving addition to total knee arthroplasty. However, the cost-effectiveness is sensitive to variability in the costs of computer navigation systems, the accuracy of alignment achieved with computer navigation, and the probability of revision total knee arthroplasty with malalignment.

Defining antigen-specific responses with human MHC class II tetramers.

Antigen-specific CD4(+) T lymphocytes play key roles in the orchestration of immune responses, including the initiation and amplification of allergic and immune-mediated disorders. Direct detection and quantitation of these cells is made possible by the use of HLA class II tetramers, soluble recombinant forms of a complex of HLA molecule and antigenic peptide that bind the antigen-specific T-cell receptor used for T-cell recognition. By using flow cytometry with fluorescent tetramers, specific T cells can be identified, recovered, and analyzed for functional markers and transcripts, helping to characterize the lineage and commitment program for individual lymphocytes. Several newly emerging uses for tetramers in clinical immunology are under development for patient management or prognosis when the number or nature of antigen-specific T cells can be clinically important. Tetramers might be useful as patient-monitoring tools for evaluating response to immunotherapy, providing a surrogate marker for the immunologic response foreshadowing a clinical response to either immune stimulation, suppression, or deviation therapeutic modalities.

Detection of GAD65-specific T-cells by major histocompatibility complex class II tetramers in type 1 diabetic patients and at-risk subjects.

Soluble HLA-DR401 or -DR404 tetramers containing a peptide corresponding to an immunodominant epitope from human GAD65 were used to analyze peripheral blood T-cells of newly diagnosed type 1 diabetic patients and at-risk subjects. Peripheral blood mononuclear cells were expanded on antigen-presenting cells presenting GAD65 peptide and subsequently activated with specific plate-bound class II-peptide monomers. T-cell activation defined in flow cytometry by CD4(high) and/or CD25 markers were observed in all type 1 diabetic patients and some at-risk subjects, but not in normal control subjects. The activated T-cells stained positive with tetramers containing the GAD65 epitope 555-567. Tetramer-positive cells were CD4(high) T-cells with high avidity for an immunodominant GAD65 T-cell epitope. Phenotyping of T-cells utilizing HLA class II tetramers provides a new tool to characterize the autoimmune response in type 1 diabetes.

HLA class II tetramers: tools for direct analysis of antigen-specific CD4+ T cells.

Immunotherapies for human autoimmune and immune-mediated diseases are proliferating rapidly, and with these changes comes the opportunity to monitor patients for immune responses to therapy based on early surrogate markers for clinical responses. Class II tetramers have the potential to serve as these sorts of markers for immune monitoring, and thereby assist with patient management, therapy selection, and improved outcomes. However, important issues of TCR avidity require resolution, because much is still unknown regarding location, quantitation, and characterization of the human T cell response. Opportunities for application of tetramer technologies in the near future will enable both clinical progress and the development of new insights into human CD4+ T cell biology in vivo.