In assessing osteoporotic fractures of the proximal femur, the main objective of this in vivo case-control study was to evaluate the performance of quantitative computed tomography (QCT) and a dedicated 3D image analysis tool [Medical Image Analysis Framework-Femur option (MIAF-Femur)] in differentiating hip fracture and non-hip fracture subjects. One-hundred and seven women were recruited in the study, 47 women (mean age 81.6 years) with low-energy hip fractures and 60 female non-hip fracture control subjects (mean age 73.4 years). Bone mineral density (BMD) and geometric variables of cortical and trabecular bone in the femoral head and neck, trochanteric, and intertrochanteric regions and proximal shaft were assessed using QCT and MIAF-Femur. Areal BMD (aBMD) was assessed using dual-energy X-ray absorptiometry (DXA) in 96 (37 hip fracture and 59 non-hip fracture subjects) of the 107 patients. Logistic regressions were computed to extract the best discriminates of hip fracture, and area under the receiver characteristic operating curve (AUC) was calculated. Three logistic models that discriminated the occurrence of hip fracture with QCT variables were obtained (AUC ¼ 0.84). All three models combined one densitometric variable-a trabecular BMD (measured in the femoral head or in the trochanteric region)-and one geometric variable-a cortical thickness value (measured in the femoral neck or proximal shaft). The best discriminant using DXA variables was obtained with total femur aBMD (AUC ¼ 0.80, p ¼ .003). Results highlight a synergistic contribution of trabecular and cortical components in hip fracture risk and the utility of assessing QCT BMD of the femoral head for improved understanding and possible insights into prevention of hip fractures. ß
Background
Autoantibody specificity in autoimmune diseases is variable due to each patient’s individual spectrum of autoantibodies and the inherent differences between detection methods and tests. Since false-positive results have downstream consequences, we conducted a comprehensive assessment of anti-double stranded DNA (anti-dsDNA) specificity from published studies of systemic lupus erythematosus (SLE).
Methods
A systematic review (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Database of Abstracts of Reviews of Effects) identified cross-sectional or case-control studies published January 2004 to August 2019, reporting anti-dsDNA test accuracy data in SLE. Study quality was assessed using Quality Assessment Tool for Diagnostic Accuracy Studies, version 2. A meta-analysis was conducted to estimate specificity by test method or named test where feasible.
Results
Thirty studies were included covering 43 different tests. The Crithidia luciliae indirect immunofluorescence test (CLIFT) and fluorescence enzyme immunoassay methods are likely to be ≥ 90% specific (Euroimmun 97.8% (95% CI 96.2%–98.7%) 4 studies; EliA 94.7% (95% CI 91.7%–96.7%), 6 studies; CLIFT 98.7% (95% CI 96.7%–99.5%), 8 studies/7 tests]. For other test methods, specificity was not fully demonstrated to be ≥ 90% and/or the control group included healthy patients possibly overestimating specificity. More studies are required for NOVA Lite [96.0% (95% CI 87.2%–98.9%), 5 studies], chemiluminescence immunoassays [92.3% (95% CI 83.6%–96.6%), 6 studies/4 tests], multiplex immunoassays [89.3% (95% CI 86.1%–91.8%), 4 studies/2 tests], and Farr fluorescent immunoassays (no estimate, 2 studies). Specificity data reported for Farr radioimmunoassays [93.8% (95% CI 85.4–97.5%), 11 studies, 9 tests] and enzyme-linked immunosorbent assays [93.4% (95% CI 89.9%–95.7%), 15 studies/16 tests] lacked consistency.
Conclusion
Anti-dsDNA testing shows considerable variation in test specificity, with potential impact on the management of SLE patients. This review may help laboratory specialists and clinicians choose and interpret the appropriate anti-dsDNA test for their setting.
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