Compliance with antibiotic prophylaxis guidelines in surgery: Results of a targeted audit in a large-scale region-based French hospital network.

INTRODUCTION: While regional monitoring of antibiotic use has decreased since 2011 by 3.2%, in some healthcare facilities a significant increase (+43%) has occurred. The purpose of this study was to assess regional antibiotic prophylaxis (ABP) compliance with national guidelines. MATERIAL AND METHODS: In 2015, 26 healthcare facilities, both public and private, were requested to audit five items: utilization of antibiotic prophylaxis, the antimicrobial agent (the molecule) administered, time between injection and incision, initial dose, number of intraoperative and postoperative additional doses. Seven surgical procedures were selected for assessment: appendicectomy (APP), cataract (CAT), cesarean section (CES), colorectal cancer surgery (CCR), hysterectomy (HYS), total hip arthroplasty (THA) and transurethral resection of the prostate (TURP). A statistical analysis of the 2303 records included was carried out. RESULTS: The general rate of antibiotic prophylaxis compliance was 64%. The antimicrobial agent used and initial dose were in compliance with the guidelines for 93% and 97.4% of cases respectively, and administration of antibiotic prophylaxis was achieved 60minutes before incision in 77.6% of the records included. Regarding gastrointestinal surgery, amoxicillin/clavulanic acid was used in 32% of patients. In 26% of appendectomy files, administration occurred after incision, and one out of two files showed non-complaint perioperative and postoperative consumption. CONCLUSION: Compliance with nationwide ABP guidelines is in need of pronounced improvement, especially with regard to time interval between injection and incision and the molecule prescribed. An action plan based on specific recommendations addressed to each establishment and an updated regionwide ABP protocol are aimed at achieving better and reduced consumption of antimicrobial agents.

[How to write, how to implement and how to evaluate a practice guideline in order to improve quality of care?]. / La qualité pour les nuls: de la rédaction d'un mode opératoire à son évaluation, en passant par sa mise en œuvre.

Initiatives of clinical practices improvement have been gradually developing in France for 20 years. Nevertheless, effective implementation of change is still difficult for numerous reasons. The use of clinical practices guidelines is one of the different ways of improvement. It is however necessary to adapt these national guidelines to the specificities of the hospital and the team, to ensure implementation and appropriation by the professionals. These recommendations are thus translated into applicable and concrete standard operating procedures. These documents have to be built by and for the concerned professionals. They are also communication and training tools, precise, directive, uniform in terms of presentation and attractive visually. Once drafted, they have to be distributed widely to the professionals to facilitate implementation. The simple distribution of the recommendations is insufficient to modify the clinical practices and require association of several methods of promotion for an optimal appropriation. How then to make sure of their effective use? Practices evaluation is one of the steps of continuous professional development, including continuous training and analysis of clinical practices by using methods promoted by the "Haute Autorité de santé". One of them is the clinical audit; use of method assessing non-pertinent treatment is interesting too. Analysis of the non-conformities and gaps between theory and practice allows identifying various possible causes (professional, institutional, organizational or personal) in order to implement corrective action plans, in a logic of continuous improvement.

Numerical predictions and experiments for optimizing hidden corrosion detection in aircraft structures using Lamb modes.

To increase the sensitivity of Lamb waves to hidden corrosion in aircraft structures, a preliminary step is to understand the phenomena governing this interaction. A hybrid model combining a finite element approach and a modal decomposition method is used to investigate the interaction of Lamb modes with corrosion pits. The finite element mesh is used to describe the region surrounding the corrosion pits while the modal decomposition method permits to determine the waves reflected and transmitted by the damaged area. Simulations make easier the interpretation of some parts of the measured waveform corresponding to superposition of waves diffracted by the corroded area. Numerical results permit to extract significant information from the transmitted waveform and thus to optimize the signal processing for the detection of corrosion at an early stage. Now, we are able to detect corrosion pits down to 80-mum depth distributed randomly on a square centimeter of an aluminum plate. Moreover, thickness variations present on aircraft structures can be discriminated from a slightly corroded area. Finally, using this experimental setup, aircraft structures have been tested.

A combined finite element and modal decomposition method to study the interaction of Lamb modes with micro-defects.

This paper presents a combined finite element and modal decomposition method to study the interaction of Lamb waves with damaged area. The finite element mesh is used to describe the region around the defects. On the contrary to other hybrid models already developed, the interaction between Lamb waves and defects is computed in the temporal domain. Then, the modal decomposition method permits to determine the wave reflected and transmitted by the damaged area. Modal analysis allows also identifying the mode conversions induced by the defects. These numerical results agree with previous finite element results concerning the interaction of Lamb modes with a notch. Experiments, carried out with gauged defects on an aluminum plate, are also compared to numerical predictions to validate the simulation. Compared to classical techniques of simulation, this new method allows us to investigate the interaction of Lamb modes generated at high frequency-thickness product with micro-defects as corrosion pitting.

Reversal of advanced colchicine toxicity in mice with goat colchicine-specific antibodies.

Colchicine-specific antibody (IgG(C] was tested in mice for reversal of colchicine toxicity. The mouse model was chosen because it reflects human pathophysiology in colchicine poisoning. IgG(C) was administered when at least 85% of colchicine was distributed in tissues. It resulted in a dramatic decrease in lethality from 85% (control group) to 10% (treated group). The decrease in toxic effects was confirmed by evaluating physiological parameters. The recovery of thermoregulation was very rapid in mice treated with IgG(C), while recovery in body weight was less marked. IgG(C) administration, therefore, decreases the intensity but may extend the duration of colchicine toxicity (reversible binding). The total neutralizing binding capacity of IgG(C) used was such that administered IgG(C) neutralizing binding sites were either 7 or 15% of the injected colchicine dose. In spite of this low neutralizing capacity the treatment was successful because of the ability of IgG(C) to buffer the amount of colchicine molecules on the critical slope of the dose-lethality curve.

Influence of goat colchicine specific antibodies on murine colchicine disposition.

The potential use of colchicine-specific antibodies (IgG(C)) to overcome colchicine intoxication in mice is of interest in human poisoning. Pharmacokinetics in mice are similar to those in humans. A short distribution half-life (t 1/2 a = 34 min) is associated with a long elimination half-life (t1/2 beta = 48 h) together with a large volume of distribution at steady-state (Vss = 2.5 l/kg) and a low total body clearance (ClT = 1 ml/min/kg). This extensive and rapid distribution to tissues impairs the success of conventional therapies. Despite the administration of a relatively low amount of IgG (C) (15% binding sites vs, colchicine molecules), the beneficial effect of IgG(C) is demonstrated by the alteration in colchicine pharmacokinetics which occurs rapidly following IgG(C) administration as demonstrated by rise in blood toxin concentrations (4-fold relative to IgG(N)-treated controls). This sequestration in the blood is associated with a colchicine redistribution from peripheral to the blood compartment. This extraction effect is revealed by lower colchicine tissue levels in IgG(C)-treated mice than in controls. As a consequence, Vss decreased in the IgG(C) group. Moreover, ClT is diminished in the IgG(C)-treated group because the relatively large immunoglobulin can not be excreted renally. In addition to this toxin displacement, study of free and bound colchicine plasma levels shows a lower percentage of free toxin in the IgG(C)-treated group (33 to 0%) compared to 70% in the control group. This pharmacokinetic study provides evidence that the administration of IgG(C) alters the colchicine disposition by sequestrating and extracting colchicine in blood compartment.

The effect of colchicine-specific active immunization on colchicine toxicity and disposition in the rabbit.

Anti-colchicine antibodies raised in rabbits are effective at protecting rabbits from acute colchicine intoxication. The positive effect depends on the ratio between the binding site capacity of the specific antibodies and the colchicine dose. Immunized rabbits receiving 6 mg/kg colchicine intravenously (LD100) died within 8 h as rapidly as those of the non-immunized control group. In contrast, if the colchicine dose was reduced to 3 mg/kg (LD83), rabbits were protected and mortality decreased to 17%. Study of plasma colchicine pharmacokinetics indicated that colchicine was totally sequestrated by antibodies in the 3 mg/kg group and only 55-80% sequestrated in 6 mg/kg group. This sequestration contributed to reducing colchicine diffusion into tissues (the volume of distribution decreased 7-fold) and to increasing the terminal half-life and the total body clearance of the drug. Moreover, as the slope of the dose-lethality curve was steep, a small binding capacity was sufficient to neutralize colchicine toxicity at 3 mg/kg. Results clearly indicate that anti-colchicine antibodies are able to effectively sequestrate colchicine. Moreover, the amount of circulating antibodies is a crucial limiting factor for the effectiveness of immunotoxicotherapy.

Immunotoxicotherapy: present status and future trends.

Immunotoxicotherapy (ITT) is currently used in humans for the treatment of snake venom and cardiac glycoside poisoning. Other toxins have been studied in animals or in vitro to assess their suitability as candidates for detoxification by specific antibodies. Testing conditions are often empirical suggesting that numerous improvements need to be introduced in ITT. Basic mechanisms in ITT include three phases: sequestration, extraction and elimination. The pharmacokinetics of these three phases depend on the type of antidotal binding site (ABS). IgG or its Fab2, Fab or Fv fragment are the possible choices. The Fab fragment is the most frequently used ABS because of its diffusion properties in the peripheral compartments and its renal excretion by glomerular filtration. Toxicokinetic and pharmacokinetic considerations indicate that the dosage cannot be satisfactorily calculated from stoichiometric principles. Study of the toxin dose-lethality curves shows that ABS dosage can be lowered. Moreover, clinical data reveal that some FAb fragments are directly eliminated without acting on toxin molecules. In order to counteract these drawbacks, a compromise between dosage and duration of infusion is suggested. Other improvements will stem from advances in immunologic methodology. Monoclonal and chimeric antibodies are new tools that will help resolve the clinical problems of immunogenicity and adverse reactions associated with polyclonal ABS.

[Immunotoxicotherapy: protective effect of anti-colchicine antibodies in acute colchicine poisoning in rabbits and mice]. / Immunotoxicothérapie: effet protecteur d'anticorps anticolchicine lors de l'intoxication aiguë à la colchicine chez le lapin et la souris.

Anti-colchicine antibodies are able to neutralize toxic effects of colchicine after acute intoxication in rabbits and mice. The protecting effect is demonstrated by active immunization (rabbits) or passive immunization (mice). These data suggest that the immunotoxicotherapy may be useful for compounds (colchicine) with intracellular action.