Validation de la mesure de l'oedème postopératoire par bioimpédance chez les patients opérés d'une prothèse totale du genou : une expérience de collaboration entre physiothérapeutes et ingénieurs

Fondements : La recherche sur l'oedème postopératoire consécutif à la chirurgie prothétique du genou est peu développée, notamment en raison de l'absence d'une méthode de mesure adaptée. Une collaboration entre physiothérapeutes et ingénieurs a permis de développer et valider une méthode de mesure innovante et facilement applicable. Les physiothérapeutes ont identifié un besoin clinique, les ingénieurs ont apporté leur savoir technologique, et l'équipe a conjointement élaboré le protocole de mesure et effectué l'étude de validation. Introduction : La bioimpédance est fréquemment utilisée pour évaluer l'oedème par l'analyse d'un signal électrique passant au travers du corps, en extrapolant la résistance théorique à une fréquence égale à zéro (R0). La mesure s'avère fiable et rapide, mais n'a jamais été appliquée et validée pour l'évaluation de l'oedème en chirurgie orthopédique. Objectif : L'objectif de l'étude est de valider la mesure de l'oedème du membre inférieur par bioimpédance, chez des patients ayant bénéficié d'une prothèse totale de genou (PTG). Questionnement : Après nous être assurés de l'absence d'influence de l'implant métallique de la PTG sur la mesure, nous nous questionnions sur la validité et la fiabilité des mesures de bioimpédance dans ce contexte. Méthodes : Deux évaluateurs ont mesuré à tour de rôle et à deux reprises successives l'oedème chez 24 patients opérés d'une PTG, à trois temps différents (préopératoire, J+2, J+8). L'oedème a été évalué par bioimpédance (R0) et par conversion en volume de mesures centimétriques du membre inférieur (MI). Nous avons calculé le ratio moyen des MI pour chaque méthode. Nous avons évalué la reproductibilité intra- et inter-observateurs de la bioimpédance (coefficient de corrélation intraclasse, CCI) et la corrélation entre méthodes (Spearman). Résultats : Le ratio moyen opéré/sain du volume des MI est de 1.04 (SD ± 0.06) en préopératoire, 1.18 (SD ± 0.09) à J+2 et 1.17 (SD ± 0.10) à J+8. Le ratio sain/opéré des MI de R0 est de 1.04 (SD ± 0.07) en préopératoire, 1.51 (SD ± 0.22) à J+2 et 1.65 (SD ± 0.21) à J+8. En préopératoire, à J+2 et J+8, les CCI tous supérieurs à 0.95 pour la reproductibilité intra- et inter-observateurs de la bioimpédance. La corrélation entre méthodes est de 0.71 en préopératoire, 0.61 à J2 et 0.33 à J8. Analyse et conclusion : La variation du ratio des MI entre les temps préopératoire, J+2 et J+8 est plus marquée pour R0. La mesure de bioimpédance bénéficie d'une excellente reproductibilité intra- et inter-observateurs. L'évolution dans le temps de la corrélation entre méthodes peut être expliquée par l'influence potentielle de facteurs confondants sur R0 (modification de la composition liquidienne) et par l'influence de l'atrophie musculaire postopératoire sur la mesure de volume. La collaboration physiothérapeutes-ingénieurs a permis le développement et l'évaluation d'une nouvelle méthode de mesure.

A Monte Carlo-based procedure for independent monitor unit calculation in IMRT treatment plans.

Intensity-modulated radiotherapy (IMRT) treatment plan verification by comparison with measured data requires having access to the linear accelerator and is time consuming. In this paper, we propose a method for monitor unit (MU) calculation and plan comparison for step and shoot IMRT based on the Monte Carlo code EGSnrc/BEAMnrc. The beamlets of an IMRT treatment plan are individually simulated using Monte Carlo and converted into absorbed dose to water per MU. The dose of the whole treatment can be expressed through a linear matrix equation of the MU and dose per MU of every beamlet. Due to the positivity of the absorbed dose and MU values, this equation is solved for the MU values using a non-negative least-squares fit optimization algorithm (NNLS). The Monte Carlo plan is formed by multiplying the Monte Carlo absorbed dose to water per MU with the Monte Carlo/NNLS MU. Several treatment plan localizations calculated with a commercial treatment planning system (TPS) are compared with the proposed method for validation. The Monte Carlo/NNLS MUs are close to the ones calculated by the TPS and lead to a treatment dose distribution which is clinically equivalent to the one calculated by the TPS. This procedure can be used as an IMRT QA and further development could allow this technique to be used for other radiotherapy techniques like tomotherapy or volumetric modulated arc therapy.

A simple, robust and rapid approach to detect carbapenemases in Gram-negative isolates by MALDI-TOF mass spectrometry: validation with triple quadripole tandem mass spectrometry, microarray and PCR.

Carbapenemases should be accurately and rapidly detected, given their possible epidemiological spread and their impact on treatment options. Here, we developed a simple, easy and rapid matrix-assisted laser desorption ionization-time of flight (MALDI-TOF)-based assay to detect carbapenemases and compared this innovative test with four other diagnostic approaches on 47 clinical isolates. Tandem mass spectrometry (MS-MS) was also used to determine accurately the amount of antibiotic present in the supernatant after 1 h of incubation and both MALDI-TOF and MS-MS approaches exhibited a 100% sensitivity and a 100% specificity. By comparison, molecular genetic techniques (Check-MDR Carba PCR and Check-MDR CT103 microarray) showed a 90.5% sensitivity and a 100% specificity, as two strains of Aeromonas were not detected because their chromosomal carbapenemase is not targeted by probes used in both kits. Altogether, this innovative MALDI-TOF-based approach that uses a stable 10-μg disk of ertapenem was highly efficient in detecting carbapenemase, with a sensitivity higher than that of PCR and microarray.

Ruling out coronary heart disease in primary care: external validation of a clinical prediction rule.

BACKGROUND: The Marburg Heart Score (MHS) aims to assist GPs in safely ruling out coronary heart disease (CHD) in patients presenting with chest pain, and to guide management decisions. AIM: To investigate the diagnostic accuracy of the MHS in an independent sample and to evaluate the generalisability to new patients. DESIGN AND SETTING: Cross-sectional diagnostic study with delayed-type reference standard in general practice in Hesse, Germany. METHOD: Fifty-six German GPs recruited 844 males and females aged ≥ 35 years, presenting between July 2009 and February 2010 with chest pain. Baseline data included the items of the MHS. Data on the subsequent course of chest pain, investigations, hospitalisations, and medication were collected over 6 months and were reviewed by an independent expert panel. CHD was the reference condition. Measures of diagnostic accuracy included the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, likelihood ratios, and predictive values. RESULTS: The AUC was 0.84 (95% confidence interval [CI] = 0.80 to 0.88). For a cut-off value of 3, the MHS showed a sensitivity of 89.1% (95% CI = 81.1% to 94.0%), a specificity of 63.5% (95% CI = 60.0% to 66.9%), a positive predictive value of 23.3% (95% CI = 19.2% to 28.0%), and a negative predictive value of 97.9% (95% CI = 96.2% to 98.9%). CONCLUSION: Considering the diagnostic accuracy of the MHS, its generalisability, and ease of application, its use in clinical practice is recommended.

La validation des techniques en chirurgie laparoscopique [Validation of laparoscopic surgical techniques].

The use of laparoscopic surgery has increased rapidly. However, a technically feasible procedure is not automatically recommendable. Thus, if cholecystectomy and fundoplication are currently fully validated techniques, this does not hold true for gastroplasty and kidney harvesting for transplantation: these operations are feasible indeed but their efficacy remains to be proved. Laparoscopic oncology has been shown to be feasible too, but its efficacy has not been documented yet.

Validation of two echocardiographic indexes to improve the diagnosis of complex coarctations.

OBJECTIVES: Coarctation of the aorta is one of the most common congenital heart defects. Its diagnosis may be difficult in the presence of a patent ductus arteriosus, of other complex defects or of a poor echocardiographic window. We sought to demonstrate that the carotid-subclavian artery index (CSA index) and the isthmus-descending aorta ratio (I/D ratio), two recently described echocardiographic indexes, are effective in detection of isolated and complex aortic coarctations in children younger and older than 3 months of age. The CSA index is the ratio of the distal aortic arch diameter to the distance between the left carotid artery and the left subclavian artery. It is highly suggestive of a coarctation when it is <1.5. The I/D ratio defined as the diameter of the isthmus to the diameter of the descending aorta, suggests an aortic coarctation when it is less than 0.64. METHODS: This is a retrospective cohort study in a tertiary care children's hospital. Review of all echocardiograms in children aged 0-18 years with a diagnosis of coarctation seen at the author's institution between 1996 and 2006. An age- and sex-matched control group without coarctation was constituted. Offline echocardiographic measurements of the aortic arch were performed in order to calculate the CSA index and I/D ratio. RESULTS: Sixty-eight patients were included in the coarctation group, 24 in the control group. Patients with coarctation had a significantly lower CSA index (0.84+/-0.39 vs 2.65+/-0.82, p<0.0001) and I/D ratio (0.58+/-0.18 vs 0.98+/-0.19, p<0.0001) than patients in the control group. Associated cardiac defects and age of the child did not significantly alter the CSA index or the I/D ratio. CONCLUSIONS: A CSA index less than 1.5 is highly suggestive of coarctation independent of age and of the presence of other cardiac defects. I/D ratio alone is less specific than CSA alone at any age and for any associated cardiac lesion. The association of both indexes improves sensitivity and permits diagnosis of coarctation in all patients based solely on a bedside echocardiographic measurement.

Mico-cocktail validation for CYP3A and CYP2D6 assessment using a low dose of midazolam (0.075 mg) and dextromethorphan (2.5 mg)

Background/Aim: Cocktail approach is generally preferred to individual administration of probes in order to characterize the activity of multiple enzymes. However, cocktail strategy has several drawbacks such as drug-drug interactions, tolerability and toxicity. Hence, there is a need to develop cocktails using low doses of probes. Our aim was to investigate whether the simultaneous oral administration of microdoses of midazolam (MDZ) and dextromethorphan (DEM) can be used to assess the simultaneous activities of CYP3A and CYP2D6. Methods: As part of a 5 arm randomized cross-over control trial on the analgesic efficacy of oxycodone, ten healthy young non-smoking males received the following combinations of drugs: Quinidine (Q)+ ketoconazole (K) or Q+placebo (P) or K+P or P+P. In all cases MDZ (0.075 mg) and DEM (2.5 mg) were administrated 1 hour after Q, K or P. CYP2D6 and CYP3A activities were determined after urine collection during 8 hours (ratio DEM/DOR), and a blood sample (EDTA) after 30 min (ratio 1-OH-MDZ/MDZ). DEM and DOR analysis was performed using LC-fluorescence. MDZ and 1-OH-MDZ determination was performed using GC-MS. Allele's variants of CYP2D6 were detected using the AmpliChipTMCYP450 (Roche). Results: CYP2D6 genotype predicted 1 poor (PM), 1 intermediate (IM), 7 extensive (EM) and 2 ultra rapid (UM) metabolizers. A good correlation was obtained between the predicted and the measured phenotypes except for 1 EM phenotyped as UM. Two duplications for alleles *41/*41xN and *1/*2xN were detected and the two volunteers were phenotyped as UM. A potent inhibition of CYP2D6 or CYP3A4 was obtained when Q or K were used. Mean metabolic ratio DEM/DOR in P and K groups were 0.015 (±0.028) and 0.015 (±0.019). It significantly increased in Q and QK groups (0.668 (±0.676) and 0.743 (±1.038)). Mean 1-OH-MDZ/MDZ in P, Q were 2.73 (±1.05) and 2.55 (±1.40) while it significantly decreased in K and QK groups (0.11 (±0.05), 0.10 (±0.05)). Moreover, there were no statistically significant differences between QK and K sessions for CYP3A and between QK and Q for CYP2D6 which indicate that there is no interaction between the two metabolic pathways. Conclusion: Simultaneous assessment of CYP3A and CYP2D6 activities can be obtained by low oral doses (micro-cocktail) of MDZ and DEM. Specific inhibitors such as Q or K modulates selectively CYP2D6 or CYP3A activities.