Suchergebnisse

In the assessment of developmental and reproductive effects, the timing and duration of exposures to chemical compounds or other environmental contaminants are of particular interest, as the gestational cycle is known to have periods of increased sensitivity. The goal of this research is to identify optimal experimental designs for conducting developmental toxicity studies when the effects of both exposure level and duration of exposure are of interest. The elements of the study design considered in this evaluation are the allocation of animals to dose‐duration exposure groups and the determination of the most efficient intermediate exposure levels. The optimality of various designs is assessed via the accuracy of the estimated excess risk as well as testing criteria. Simulation studies are conducted to compare these criteria and determine optimal design strategies under various underlying dose‐response patterns. Asymptotic results are also derived to lend support to the simulation studies.

OBJECTIVES: To evaluate inter-rater reliability of the modified Radiographic Union Score for Tibial (mRUST) fractures among patients with open, diaphyseal tibia fractures with a bone defect treated with intramedullary nails (IMNs), plates, or definitive external fixation (ex-fix). DESIGN: Retrospective cohort study. SETTING: 15 level one civilian trauma centers; 2 military treatment facilities. PATIENTS/PARTICIPANTS: Patients ≥18-years-old with open, diaphyseal tibia fractures with a bone defect ≥1 centimeter surgically treated between 2007 and 2012. INTERVENTION: Three of six orthopaedic traumatologists reviewed and applied mRUST scoring criteria to radiographs from the last clinical visit within 13 months of injury. MAIN OUTCOME MEASUREMENTS: Inter-rater reliability was assessed using Krippendorff's Alpha (KA) statistic; Intraclass correlation coefficient (ICC) is presented for comparison to previous publications. RESULTS: 213 patients met inclusion criteria including 115 IMNs, 24 plates, 29 ex-fixes, and 45 cases that no longer had instrumentation at evaluation. All reviewers agreed on the pattern of scoreable cortices for 90.4% of IMNs, 88.9% of those without instrumentation, 44.8% of rings, and 20.8% of plates. Thirty-one (15%) cases, primarily plates and ex-fixes, did not contribute to KA and ICC estimates because <2 raters scored all cortices. The overall KA for the 85% that could be analyzed was 0.64 (ICC 0.71). For IMNs, plates, ex-fixes, and no instrumentation, KA (ICC) was 0.65 (0.75), 0.88 (0.90), 0.47 (0.62), and 0.48 (0.57), respectively. CONCLUSIONS: In tibia fractures with bone defects, the mRUST appears similarly reliable to prior work in patients treated with IMN but is less reliable in those with plates or ex-fixes, or after removal of instrumentation. LEVEL OF EVIDENCE: Diagnostic, Level I