Effect of single-unit transfusion in patients treated for haematological disease including acute leukemia: A multicenter randomized controlled clinical trial.

BACKGROUND: Retrospective studies in hematological unit have suggested that single red blood cell (1-RBC) unit transfusion policy may reduce the number of RBC used without negative clinical impact. METHOD: Acute leukemia patients requiring intensive chemotherapy or patients receiving autologous or allogeneic transplantation were randomly assigned to receive either single RBC (1-RBC arm) or double RBC (2-RBC arm) per transfusion with a hemoglobin trigger of 8 g/dL. The primary composite endpoint was the percentage of patients experiencing serious complications, such as a non-hematological adverse event grade ≥ 3 or intensive care admission or death. FINDINGS: A total of 981 and 592 RBC transfusions were required in the 1-RBC arm (n = 125) and the 2-RBC arm (n = 120), respectively. The mean pre-transfusion hemoglobin levels were 7.49 ± 0.83 g/dL in the 1-RBC arm and 7.46 ± 0.67 g/dL in the 2-RBC arm (p = 0.275). The predefined non-inferiority criteria was achieved with 28/125 patients reaching the primary endpoint in the 1-RBC arm (22.4 %) and 28/120 patients in the 2-RBC arm (23.3 %) (Risk difference 0.009; 95 %, Confidence interval [-0.0791 to 0.0978], p = 0.021). The median (IQR) of RBC units transfused per patient was 7 (4-12) in the 1-RBC arm and 8 (4-12) in 2-RBC arm. Hemoglobin levels at discharge were also comparable in both arms. INTERPRETATION: The results of this trial indicate that a single RBC transfusion policy is not inferior to a double RBC transfusion policy for patients receiving a bone marrow transplant or intensive chemotherapy in a hematological intensive care unit. However, the single RBC transfusion policy did not reduce the number of RBC units transfused per stay. FUNDING: This trial was funded by a grant from the French Ministry of Health.

Mitochondrial DNA as a tool for reconstructing past life-history traits in mammals.

Reconstructing the ancestral characteristics of species is a major goal in evolutionary and comparative biology. Unfortunately, fossils are not always available and sufficiently informative, and phylogenetic methods based on models of character evolution can be unsatisfactory. Genomic data offer a new opportunity to estimate ancestral character states, through (i) the correlation between DNA evolutionary processes and species life-history traits and (ii) available reliable methods for ancestral sequence inference. Here, we assess the relevance of mitochondrial DNA--the most popular molecular marker in animals--as a predictor of ancestral life-history traits in mammals, using the order of Cetartiodactyla as a benchmark. Using the complete set of 13 mitochondrial protein-coding genes, we show that the lineage-specific nonsynonymous over synonymous substitution rate ratio (dN/dS) is closely correlated with the species body mass, longevity and age of sexual maturity in Cetartiodactyla and can be used as a marker of ancestral traits provided that the noise introduced by short branches is appropriately dealt with. Based on ancestral dN/dS estimates, we predict that the first cetartiodactyls were relatively small animals (around 20 kg). This finding is in accordance with Cope's rule and the fossil record but could not be recovered via continuous character evolution methods.

Oral thromboprophylaxis following total hip replacement: the issue of compliance.

INTRODUCTION: Thirty-five to 40 days' thromboprophylaxis is recommended following total hip replacement (THR). Low molecular weight heparin (LMWH) injected by a health professional ensures good compliance. Compliance with recent oral anticoagulants has not been precisely assessed. Oral self-administration, without coagulation monitoring tests, may be a worrying issue in the management of what is a potentially catastrophic adverse event, without prodromal symptoms alerting the patient to the need for regular intake throughout the prescription period. HYPOTHESIS: It was hypothesized that compliance with these new oral anticoagulants is good over the entire treatment period. PATIENTS AND METHOD: The present cohort study prospectively assessed compliance with oral medication (two capsules of dabigatran etexilate [Pradaxa(®)] per day in a single dose at a set time) following THR. An electronic device continuously monitored the day and time of extraction of capsules from the package. All included patients underwent clinical and echo-Doppler examination at day 30±5 after the start of the study. RESULTS: Fifty-six patients were included at their discharge home. Overall compliance was 98.1% (3,188/3246 capsules correctly taken), falling off slightly over time but never below 97.1%. One patient was diagnosed with symptomatic thrombophlebitis 34 days postoperatively, associated with non-compliance at day 11. End of follow-up echo-Doppler found four cases of asymptomatic distal venous thrombosis. There were no hemorrhagic complications. DISCUSSION: The risk of thromboembolic complications diminishes over time, while oral anticoagulants have a wide therapeutic window and relatively long half-life (15-17 hrs). Efficacy was demonstrated, with improved patient comfort and cost-saving. Compliance in the present series was satisfactory. This, however, should not mean that patients not be appropriately informed, as in the present study, so as to improve compliance. LEVEL OF EVIDENCE: Level III, prospective diagnostic.

Total knee arthroplasty three-dimensional kinematic estimation prevision. From a two-dimensional fluoroscopy acquired dynamic model.

INTRODUCTION: To determine six-degree of freedom of total knee arthroplasty kinematics (TKA), optimized matching algorithms for single fluoroscopic image system may be used. Theoretical accuracy of these systems was reported. Nevertheless, all reports were done under idealized laboratory experimental conditions. The aim of this study was to evaluate the "true" accuracy of a flat panel single plane video-fluoroscopy system based on computed-assisted design (CAD) model matching and compare it to TKA kinematics obtained from optoelectronic measurements as gold standard. HYPOTHESIS: The estimation of the error produced by 2D/3D fluoroscopic registration in daily practice is misjudged in most available laboratory reports. MATERIAL AND METHODS: The experimental set-up used a TKA implanted into femoral and tibial cadaver bones. Thirty flexions were simultaneously registered using single plane fluoroscopy and an active optical tracking system. Kinematics registered were compared using the root mean square error (RMS), the concordance correlation coefficient and Bland & Altman plot analysis. RESULTS: The mean range of motion of flexion during the experiment was 106°. The respective RMS for flexion, varus-valgus and internal-external rotation were 0.68, 0.67 and 1.02°. The respective RMS for antero-posterior, medio-lateral and proximo-distal displacement were 1.3, 2.4 and 1.06 mm. Extreme values of the measured error concerning medio-lateral displacement were -5.4 and 22,1mm. DISCUSSIONS: Analysis found some outliners in all degree of freedom with a systematic error and larger standard deviation than already published data. One should make sure that during the experiment the motion of interest is in the in-plane direction. Moreover, this study brings out the true threshold detection of this type of analysis.

Dual mobility hip arthroplasty wear measurement: Experimental accuracy assessment using radiostereometric analysis (RSA).

INTRODUCTION: The use of dual mobility cups is an effective method to prevent dislocations. However, the specific design of these implants can raise the suspicion of increased wear and subsequent periprosthetic osteolysis. HYPOTHESIS: Using radiostereometric analysis (RSA), migration of the femoral head inside the cup of a dual mobility implant can be defined to apprehend polyethylene wear rate. STUDY OBJECTIVES: The study aimed to establish the precision of RSA measurement of femoral head migration in the cup of a dual mobility implant, and its intra- and interobserver variability. MATERIAL AND METHODS: A total hip prosthesis phantom was implanted and placed under weight loading conditions in a simulator. Model-based RSA measurement of implant penetration involved specially machined polyethylene liners with increasing concentric wear (no wear, then 0.25, 0.5 and 0.75mm). Three examiners, blinded to the level of wear, analyzed (10 times) the radiostereometric films of the four liners. There was one experienced, one trained, and one inexperienced examiner. Statistical analysis measured the accuracy, precision, and intra- and interobserver variability by calculating Root Mean Square Error (RMSE), Concordance Correlation Coefficient (CCC), Intra Class correlation Coefficient (ICC), and Bland-Altman plots. RESULTS: Our protocol, that used a simple geometric model rather than the manufacturer's CAD files, showed precision of 0.072mm and accuracy of 0.034mm, comparable with machining tolerances with low variability. Correlation between wear measurement and true value was excellent with a CCC of 0.9772. Intraobserver reproducibility was very good with an ICC of 0.9856, 0.9883 and 0.9842, respectively for examiners 1, 2 and 3. Interobserver reproducibility was excellent with a CCC of 0.9818 between examiners 2 and 1, and 0.9713 between examiners 3 and 1. DISCUSSION: Quantification of wear is indispensable for the surveillance of dual mobility implants. This in vitro study validates our measurement method. Our results, and comparison with other studies using different measurement technologies (RSA, standard radiographs, Martell method) make model-based RSA the reference method for measuring the wear of total hip prostheses in vivo. LEVEL OF EVIDENCE: Level 3. Prospective diagnostic study.

Coevolution within and between genes.

Interacting biological systems do not evolve independently, as exemplified many times at the cellular, organismal and ecosystem levels. Biological molecules interact tightly, and should therefore coevolve as well. Here we review the literature about molecular coevolution, between residues within RNAs or proteins, and between proteins. A panel of methodological and bioinformatic approaches have been developed to address this issue, yielding contrasting results: a strong coevolutionary signal is detected in RNA stems, whereas proteins show only moderate, uneasy to interpret departure from the independence hypothesis. The reasons for this discrepancy are discussed.

BAOBAB: a Java editor for large phylogenetic trees.

SUMMARY: BAOBAB is a Java user interface dedicated to viewing and editing large phylogenetic trees. Original features include: (i) a colour-mediated overview of magnified subtrees; (ii) copy/cut/paste of (sub)trees within or between windows; (iii) compressing/ uncompressing subtrees; and (iv) managing sequence files together with tree files. AVAILABILITY: http://www.univ-montp2.fr/~genetix/.