Biomechanical Behavior of a Variable Angle Locked Tibiotalocalcaneal Construct.

This paper examines the mechanics of the tibiotalocalcaneal construct made with a PHILOS plating system. A failed device consisting of the LCP plate and cortical, locking, and cannulated screws was used to perform the analysis. Visual, microstructure, and fractographic examinations were carried out to characterize the fracture surface topology. These examinations revealed the presence of surface scratching, inclusions, discoloration, corrosion pits, beach marks, and cleavage and striations on the fracture surface. Further examination of the material crystallography and texture revealed an interaction of S, Ni, and Mo-based inclusions that may have raised pitting susceptibility of the device made with Stainless Steel 316L. These features suggest that the device underwent damage by pitting the corrosion-fatigue mechanism and overloading towards the end to fail the plate and screws in two or more components. The screws failed via conjoint bending and torsion fatigue mechanisms. Computer simulations of variable angle locking screws were performed in this paper. The material of construction of the device was governed by ASTM F138-8 or its ISO equivalent 5832 and exhibited inconsistencies in chemistry and hardness requirements. The failure conditions were matched in finite element modeling and those boundary conditions discussed in this paper.

How to translate therapeutic recommendations in clinical practice guidelines into rules for critiquing physician prescriptions? Methods and application to five guidelines.

BACKGROUND: Clinical practice guidelines give recommendations about what to do in various medical situations, including therapeutical recommendations for drug prescription. An effective way to computerize these recommendations is to design critiquing decision support systems, i.e. systems that criticize the physician's prescription when it does not conform to the guidelines. These systems are commonly based on a list of "if conditions then criticism" rules. However, writing these rules from the guidelines is not a trivial task. The objective of this article is to propose methods that (1) simplify the implementation of guidelines' therapeutical recommendations in critiquing systems by automatically translating structured therapeutical recommendations into a list of "if conditions then criticize" rules, and (2) can generate an appropriate textual label to explain to the physician why his/her prescription is not recommended. METHODS: We worked on the therapeutic recommendations in five clinical practice guidelines concerning chronic diseases related to the management of cardiovascular risk. We evaluated the system using a test base of more than 2000 cases. RESULTS: Algorithms for automatically translating therapeutical recommendations into "if conditions then criticize" rules are presented. Eight generic recommendations are also proposed; they are guideline-independent, and can be used as default behaviour for handling various situations that are usually implicit in the guidelines, such as decreasing the dose of a poorly tolerated drug. Finally, we provide models and methods for generating a human-readable textual critique. The system was successfully evaluated on the test base. CONCLUSION: We show that it is possible to criticize physicians' prescriptions starting from a structured clinical guideline, and to provide clear explanations. We are now planning a randomized clinical trial to evaluate the impact of the system on practices.

Is flow cytometry accurate enough to screen platelet autoantibodies?

BACKGROUND: The diagnosis of immune thrombocytopenic purpura (ITP) is a diagnosis of exclusion, as stated by international guidelines. Nevertheless, the assessment of platelet (PLT) antibodies has been reported as helpful for the diagnosis and the follow-up of ITP patients. PLT antibodies are detected by highly specialized assays, such as monoclonal antibody-specific immobilization of PLT antigen (MAIPA) test. Flow cytometry for PLT-associated immunoglobulin G (PAIgG) detection has been described more recently. This study was meant to evaluate the utility of flow cytometry to screen accurately patients needing further MAIPA testing. STUDY DESIGN AND METHODS: PAIgG, PAIgM, and PAIgA were determined in 107 consecutive patients and in 147 healthy controls in parallel. MAIPA testing was performed in all patients. The accuracy of flow cytometry was assessed with a receiver operating characteristics (ROC) curve analysis versus MAIPA. RESULTS: MAIPA assay found PLT-specific IgG in 27 patients (25%). The ROC curve analysis showed that no false-negative result in flow cytometry was obtained for a mean fluorescence intensity (MFI) cutoff of 0.2. With this cutoff, PAIgG were positive in 61 patients (57%). In this series, MAIPA was unnecessary in 42 percent of patients (corresponding to true-negative results). When MAIPA was positive, PAIgM values ranged from 0.1 to 1.0, and PAIgA from 0.1 to 2. CONCLUSION: Flow cytometry for PAIgG assessment may be used to accurately decide whether or not MAIPA must be subsequently performed. In this series, MAIPA was unnecessary in 42 percent of patients. Moreover, PAIgM results suggested that its determination combined with PAIgG may be of interest in ITP investigation.

Platelet VASP phosphorylation assessment in clopidogrel-treated patients: lack of agreement between Western blot and flow cytometry.

Vasodilator-stimulated phosphoprotein (VASP) 239 phosphorylation flow cytometric assessment has been reported as a tool to evaluate the responsiveness to clopidogrel in coronary heart disease (CHD) patients. We report for the first time the comparison between flow cytometry and two challenger assays, aggregometry and Western blot. We studied 21clopidogrel-treated CHD patients, and 28 healthy volunteers. Aggregometry showed platelet function inhibition inpatients. VASP 239 phosphorylation was assessed using flow cytometry and Western blot. ADP receptor response index (RI) were calculated using the formula (PGE1) - (PGE1 + ADP)/(PGE1) x 100. Flow cytometry was not able to detect clopidogrel intake, as RI were 99 +/- 10% [68-130] in healthy volunteers, and 91 +/- 17% [66-127] in treated patients (ns). On the contrary, RI mean in Western blot was 91 + 8% [76-127] in healthy volunteers, and 37 i 25% [4-80] in patients (p<0.05). The extreme values in Western blot revealed inter-individual variability in response to treatment. The comparison between both tests showed a total lack of agreement. Flow cytometric VASP 239 phosphorylation assay lacks sensitivity to detect clopidogrel intake, contrary to Western blot and aggregometry. Caution is required before classifying patients as 'low-responders' to thienopyridines using such method.