[Evaluation of the training of clinical pharmacy residents in prescription analysis using an ergonomic approach]. / Évaluation de la formation des internes en pharmacie clinique à l'analyse des prescriptions selon une approche ergonomique.

OBJECTIVES: To perform an ergonomic intervention using the methodology of the analysis of the activity of the training process of clinical pharmacy residents in the analysis of prescriptions. METHODS: The evaluation was carried out over two semesters: from May to October 2016 (first study) and from November 2016 to April 2017 (second study). The interviews and observations were conducted by an ergonomist who is an expert in this type of evaluation. The first study was based on observations of the training process and interviews at different time. The second study allowed to support pharmacists and evaluate the changes following the recommendations of the previous study. RESULTS: A total of 6 and 9 residents participated in the first and second study, respectively. During the first study, 6 difficulties were raised which allowed implementation decisions. Feedback from residents on the training process was generally positive for the first part of the training but negative for the last part. The average number of fears expressed by the residents was higher at the beginning (2.9 fears) than at the end (1 fear). CONCLUSIONS: The training process has been adapted to the expectations and feelings of the residents. Follow-up at the beginning and throughout the internship was essential. The next stage of this work will be to evaluate the contribution of the dashboards for monitoring clinical pharmacy skills in the new degree for hospital pharmacy.

Management of hypersensitivity to platinum- and taxane-based chemotherapy: cepo review and clinical recommendations.

BACKGROUND: Although antineoplastic agents are critical in the treatment of cancer, they can potentially cause hypersensitivity reactions that can have serious consequences. When such a reaction occurs, clinicians can either continue the treatment, at the risk of causing a severe or a potentially fatal anaphylactic reaction, or stop the treatment, although it might be the only one available. The objective of the present work was to evaluate the effectiveness of methods used to prevent and treat hypersensitivity reactions to platinum- or taxane-based chemotherapy and to develop evidence-based recommendations. METHODS: The scientific literature published to December 2013, inclusive, was reviewed. RESULTS: Premedication with antihistamines, H2 blockers, and corticosteroids is not effective in preventing hypersensitivity reactions to platinum salts. However, premedication significantly reduces the incidence of hypersensitivity to taxanes. A skin test can generally be performed to screen for patients at risk of developing a severe reaction to platinum salts in the presence of grade 1 or 2 reactions, but skin testing does not appear to be useful for taxanes. A desensitization protocol allows for re-administration of either platinum- or taxane-based chemotherapy to some patients without causing severe hypersensitivity reactions. CONCLUSIONS: Several strategies such as premedication, skin testing, and desensitization protocols are available to potentially allow for administration of platinum- or taxane-based chemotherapy to patients who have had a hypersensitivity reaction and for whom no other treatment options are available. Considering the available evidence, the Comité de l'évolution des pratiques en oncologie made recommendations for clinical practice in Quebec.

Performances of an improved device for skin prick tests.

Every day allergists deal with skin prick testing. Following a recent paper showing that the intravenous needle and the metal lancets are superior to the Stallerpoint® plastic lancet, the manufacturer has improved the device to reach better standards in terms of sensitivity, intra-patient reproducibility and inter-patient reproducibility, as demonstrated on 10 adult patients, comparing the results with skin tests performed with the intravenous needle. We evaluated the sensitivity of the device by calculating the ratio between the number of true-positive tests and the sum of true-positive and false-negative tests. To assess the reproducibility of the test, we calculated the interpatient and the intrapatient coefficient of variation between the mean diameters of the papules induced by the different techniques. The improved device shows performances similar to those obtained with the intravenous needle.

Comparison of five techniques of skin prick tests used routinely in Europe.

BACKGROUND: Skin prick tests represent indispensable tools in allergy, even more than 30 years after their introduction in clinical practice. OBJECTIVES: Few recent European studies have focused on this topic and we thus wanted to compare the instruments most often used today. METHODS: Four instruments were investigated: the 23G intravenous (IV) needle, the ALK Lancet, the Stallergenes (STG) Prick Lancet and the Stallerpoint(®) (using two different methods). Sensitivity, reproducibility, and acceptability were evaluated. In 22 subjects, we calculated the sensitivity and reproducibility (both intra- and interpatient) of these methods by testing the positive control five times. In 50 subjects, we tested the single-blind acceptability of these same five techniques. RESULTS: In terms of sensitivity, the IV needle (100%) and metal lancets (96% for the ALK Lancet and 98% for the STG Prick Lancet) were superior (P < 0.01) to the two Stallerpoint(®) methods (20% and 57%). Intrapatient reproducibility was 16.2%, 14.6%, 15.0%, 97.1% and 18.1%, respectively. The instruments that were best tolerated by the patients were the IV needle and the two metal lancets. CONCLUSION: Metal needles and/or lancets are the tools of choice for skin prick testing.

Progressive symmetrical erythrokeratoderma: report of a Turkish family and evaluation for loricrin and connexin gene mutations.

We report here the first Turkish patient with progressive symmetric erythrokeratoderma. The patient's skin lesions appeared in the axillae at 3 months of age, and gradually spread to other flexural areas and to the trunk. Dermatological examination of the boy at 3.5 years of age revealed symmetric, hyperkeratotic plaques with erythematous outlines on the neck, wrists, armpits, trunk and posterior knees. The histopathological changes were nonspecific, including marked hyperkeratosis, irregular acanthosis, focal papillomatosis and perivascular lymphocytic infiltrates. Molecular studies of the loricrin (LOR), connexin 31 (GJB3) and connexin 30.3 (GJB4) genes did not identify a disease-causing mutation. These results further underline the genetic heterogeneity of the erythrokeratodermas.

National French observatory of the quality of blood components for transfusion.

PURPOSE: Since 1998, prestorage leucoreduction of cellular blood components (BC) is mandatory in France. The French Blood Service needs to follow the data on the quality of the BC prepared by blood centers. This article gives an overview of the quality control (QC) data from 2001 to 2006. MATERIAL AND METHODS: QC data are submitted to a central data bank by each centre. The data are stratified according to preparation process for analysis of key performance criteria - residual leukocytes and haemoglobin or platelet content. BC preparation processes, methods for measuring haemoglobin and platelet content, and for counting residual leukocytes are those routinely employed by centers. RESULTS: The preparation process of red cell concentrates (RCC) influences the haemoglobin content: 57.6+/-6.8 g per unit versus 50.9+/-5.4 g per unit for whole blood or RCC filtration, respectively. Apheresis RCC exhibits a reduced variability (51.2+/-3.4 g per unit). For apheresis platelet concentrates, the median residual leukocyte count remains low for all separators (0.019-0.044 x 10(6)leukocytes per unit, in 2006). However, the percentage of units exceeding 1 x 10(6)leukocytes per unit is significantly higher with one separator (1.8% versus 0.8%, in 2006). For pooled buffy-coat derived platelets, we observed a significant increase in platelet recovery throughout the years (0.66-0.77 x 10(11)platelets per buffy-coat in 2001 and 2006, respectively). CONCLUSION: Our QC data show an overall compliance with the requirements for cellular BC. Our data bank is useful to inform on the performance of leucoreduced BC preparation processes carried out with market available devices.

Distribution, location, and transcriptional profile of Peyer's patch conventional DC subsets at steady state and under TLR7 ligand stimulation.

The initiation of the mucosal immune response in Peyer's patch (PP) relies on the sampling, processing, and efficient presentation of foreign antigens by dendritic cells (DCs). Among PP DCs, CD11b+ conventional DCs (cDCs) and lysozyme-expressing DCs (LysoDCs) have distinct progenitors and functions but share many cell surface markers. This has previously led to confusion between these two subsets. In addition, another PP DC subset, termed double-negative (DN), remains poorly characterized. Here we show that both DN and CD11b+ cDCs belong to a unique SIRPα+ cDC subset. At steady state, cDCs and TIM-4+ macrophages are mainly located in T-cell zones, i.e., interfollicular regions, whereas a majority of subepithelial phagocytes are monocyte-derived cells, namely, LysoDCs and TIM-4- macrophages. Finally, oral administration of a Toll-like receptor 7 ligand induces at least three TNF-dependent events: (i) migration of dome-associated villus cDCs in interfollicular regions, (ii) increase of CD8α+ interfollicular cDC number, and (iii) activation of both CD11b+ and CD8α+ interfollicular cDCs. The latter is marked by a genetic reprograming leading to the upregulation of type I interferon-stimulated and of both immuno-stimulatory and -inhibitory gene expression.

Analysis of plasticizers in PVC medical devices: Performance comparison of eight analytical methods.

A wide variety of medical devices (MDs) used in hospitals are made of flexible plasticized polyvinylchloride (PVC). Different plasticizers are present in variable amounts in the PVC matrix of the devices and can leach out into the infused solutions and may enter into contact with the patients. The ARMED1 project aims to assess the migration of these plasticizers from medical devices and therefore the level of exposure in patients. For the first task of the project, eight methods were developed to directly detect and quantify the plasticizers in the PVC matrix of the MDs. We compared the overall performances of the analytical methods using standardized and validated criteria in order to provide the scientific community with the guidance and the technical specifications of each method for the intended application. We have shown that routine rapid screening could be performed directly on the MDs using the FTIR technique, with cost-effective analyses. LC techniques may also be used, but with limits and only with individual quantification of the main plasticizers expected in the PVC matrix. GC techniques, especially GC-MS, are both more specific and more sensitive than other techniques. NMR is a robust and specific technique to precisely discriminate all plasticizers in a MD but is limited by its cost and its low ability to detect and quantify plasticizer contamination, e.g. by DEHP. All these results have been confirmed by a real test, called the " blind test " carried out on 10 MD samples.

The BamHI fragment 9 of pseudorabies virus contains genes homologous to the UL24, UL25, UL26, and UL 26.5 genes of herpes simplex virus type 1.

The genomes of pseudorabies virus (PrV) and of herpes simplex virus type 1 (HSV1) are colinear, excepting an inversion in the unique long region, of which one extremity resides within the BamHI fragment 9. This fragment (4088 bp) encodes the counterparts of HSV1 UL24, UL25, UL26 and UL26.5 that are transcribed into four 3'-coterminal mRNAs. Multiple alignments of UL24, UL25 and UL26 protein homologs from alpha-, beta- and gamma-herpesviruses were performed. The PrV UL24 protein is shorter than its counterparts, missing the non-conserved COOH-terminal region. The region which is common to all viruses contains a basic NH2-terminus and a hydrophobic COOH-end, suggesting that UL24 may function as a matrix protein. The UL25 proteins are well conserved, particularly among the alpha-herpesviruses. All the domains involved in the proteolytic activity of theUL26 protein are highly conserved, as well as the two cleavage sites. Thus, its function and processing may be similar in PrV as in other herpesviruses. Due to the fact that in PrV the UL26 and UL44 genes are adjacent and their ends are conserved, the right border of the inversion must lie within their intergenic region.

The left border of the genomic inversion of pseudorabies virus contains genes homologous to the UL46 and UL47 genes of herpes simplex virus type 1, but no UL45 gene.

The genome of pseudorabies virus (PrV) is collinear with the herpes simplex virus type 1 (HSV1) genome, except for an inversion in the unique long region, the right extremity of which resides within the BamHI fragment 9 and the left within the BamHI fragment 1. We previously sequenced the right border of the inversion which is situated next to the UL44-gC gene and found that it encodes the UL24, UL25, UL26 and UL26.5 gene counterparts of HSV1. We have now sequenced 5317 base pairs of the BamHI fragment 1, upstream of the UL27-gB gene. We found two open reading frames homologous to UL46 and UL47 of HSV1 yet UL45 was absent and replaced by a set of strictly repeated sequences. PrV UL46 and UL47 are transcribed into two 3' co-terminal messenger RNAs with early and late kinetics, respectively. Comparison of the PrV UL46 and UL47 protein sequences with their counterparts from alphaherpesviruses indicated a strong similarity. The genome is rearranged in this region with respect to HSV1 and the inversion must have taken place, on the left side, within the UL46-UL27 intergenic region. Thus, the inversion should include genes UL27 to UL44.

Soluble Fas is a marker of coronary artery disease in patients with end-stage renal disease.

Coronary artery disease (CAD) is the leading cause of death in patients with end-stage renal disease (ESRD). Recent evidence suggests that the expression of Fas, a molecule implicated in the initiation of apoptosis in various cell types, is increased at sites of atherosclerotic plaques. However, the significance of plasma levels of the soluble form of Fas (sFas) and its ligand (sFas-L) as markers of atherosclerosis has yet to be defined. The present report is a cross-sectional analysis of baseline data from an ongoing prospective study designed to evaluate the role of sFas and sFas-L as markers of CAD in ESRD. We evaluated the association between plasma levels of sFas and sFas-L and evidence of CAD in a cohort of 107 chronic hemodialysis patients. Plasma levels of sFas were significantly greater (P = 0.04) among subjects with (n = 64) than without evidence of CAD (n = 43). Plasma levels of sFas-L were similar in both groups. Using multivariate analysis, sFas level was found to be independently associated with CAD (P = 0.01) after adjustment for classic risk factors for CAD (hyperlipidemia, diabetes, hypertension, and smoking), markers of inflammation (C-reactive protein [CRP], intercellular adhesion molecule 1), and other confounders. An increase of one quintile in plasma concentration of sFas was associated with an odds ratio for CAD of 1.64 (95% confidence interval, 1.11 to 2.41). Models that incorporated sFas were significantly better at identifying patients with CAD than models limited to classic risk factors for atherosclerosis, alone (P = 0.008) or in combination with CRP levels (P = 0.006). In summary, increased plasma levels of sFas are associated with CAD in stable patients with ESRD. These results suggest that sFas may represent a novel and independent marker of CAD.

Plateletpheresis concentrates produced with the COMTEC cell separator: the French experience.

The latest generation of cell separators such as Trima (Gambro), Amicus (Baxter) and AS-TEC 204 (Fresenius), allow the collection of leucocyte-reduced platelet concentrates without secondary filtration. Fresenius has recently developed the COMTEC cell separator whose performance has been evaluated by several teams in France. This new cell separator is an improved version of the Fresenius AS-TEC 204 cell separator, designed to allow more efficient platelet collections. This study reports on the experience of six French teams (from Bordeaux, Clermont-Ferrand, Creteil, Dijon, Lille and Nancy) who obtained 696 leucocyte-reduced plateletpheresis concentrates in the course of collection using the new Fresenius COMTEC cell separator. All healthy volunteer donors fulfilled French selection criteria for platelet apheresis. Donors were eligible if they had suitable venous accesses, if their bodyweight was *50 kg and if their pre-apheresis platelet count was >150 x 10(9) l(-1). Between 4606 and 5229 ml of blood were processed. The mean volume of the platelet concentrates was between 439 and 493 ml (mean 460 +/- 63 ml). The platelet yield was of the order of 5.18 +/- 1.02 x 10(11) with only one platelet concentrate below the norm of 2 x 10(11) platelets (0.91 x 10(11)). No plausible explanation for this was found. The residual leucocyte levels conform to current norms. The platelet concentrates contained less than 1 x 10(6) leucocytes per concentrate (mean 0.233 +/- 0.150 x 10(6) leucocytes) in more than 97% of the components produced with >95% statistical confidence. The efficacy of the cell separator (52.44 +/- 7.35%) is comparable to that of other separators. The Fresenius COMTEC cell separator makes it possible to obtain leucocyte-reduced platelet concentrates which comply with current standards both in terms of platelet content and residual leucocyte level.

Modulation of HLA-DR and CD1a expression on human cornea with low-dose UVB irradiation.

PURPOSE: To evaluate the effects of low-dose UVB irradiation of HLA and CD1a expression and the toxic effects of UVB on human corneas. METHODS: 24 pairs of human corneas from 24 donors were studied. One cornea from each pair was randomly irradiated with UVB (100 mJ/cm2) after enucleation. All corneas were then organ-cultured for 2, 7, 14 or 21 days. Endothelium was studied after enucleation and organ culture. Following preservation, corneas were evaluated by means of light microscopy, morphometry and TEM. HLA and CD1a staining was performed using an immuno-alkaline-phosphatase technique. RESULTS: Endothelial cell loss during organ culture averaged 9.1% in the UVB group and 9.2% in the control group (NS). The number of rosette and reformation figures (p = 0.004) and the coefficient of variation (p = 0.014) were higher in the control group. Epithelial sloughing was more accentuated in the UVB group. We observed the same moderate ultrastructural injuries in both groups. In the epithelium, the average number of HLA-DR+ cells per field was 0.12 in the UVB group and 0.42 in the control group (p = 0.035). In the stroma, these figures were respectively 1.04 and 1.34 (p = 0.026). In the epithelium, the average number of CD1a + cells was respectively 0. 025 and 0.078 (p = 0.019). In the preservation mediums, the average percentage of CD1a + cells was 0.07% in the UVB group and 0.27% in the control group (p = 0.014). CONCLUSIONS: Low-dose UVB (100 mJ/cm2) decreases HLA-DR and CD1a expression of organ-cultured human corneas and induces moderate corneal injuries. Low-dose UVB might be useful for preventing allograft rejection.

[Quality of platelet products: current methods of in vitro assessment]. / Qualité des produits plaquettaires: méthodes actuelles d'exploration in vitro.

Efficiency of platelet transfusion is closely related to the quality of the preparation and also to the optimization of storage conditions at 20 degrees C. During this last years, processes for obtaining platelet suspensions became different (platelet rich plasma platelet, pooled or single buffy coat platelet, apheresis platelet), process for purification were developed (filtration, gamma or UV-irradiation, synthetic media for storage, virus inactivation), duration of storage was extended to 5 or 7 days and clinical applications were intensified. According to this advance, noted in some European countries, multicenter consensus on methods of quality control must be defined by different study groups. In the recent past, many publications have described a lot of in vitro tests for estimating functions, morphology, metabolic activity, lysis and activation of platelets. Current available methods for routine quality control or for development of new procedures, such as pH measurement inspection of swirling, percent of discoid shape, mean platelet volume, hypotonic shock response or total ATP level should be considered, in accordance with the in vivo viability.

[Current data on the counting of weak leukocyte concentrations in labile blood products]. / Données actuelles sur le comptage de faibles concentrations leucocytaires des produits sanguins labiles.

The precise measurement of low numbers of leukocyte below 0.1 WBC/microliter in filtered red cell or platelet suspensions meet both aims: to check the compliance with previously determined requirements and to evaluate the performances of novel filtering material (5 log depletion or more), justified by more and more important clinical use. The reliability of results, obtained with the chosen method, is ensured by applying of validation protocol, including training of technologist, assessment of the analytical range and the detection limit, assessment of precision and accuracy. The flow cytometry (FC) and Nageotte Chamber (NC) method are the both techniques which are currently used in routine Quality Control (QC) and validated by multicenter studies. Recent developments are made for increasing the sensibility of these counting methods, thanks to higher concentration or volume of the sample to be analysed. Among the experimental techniques, requiring more advances before implementing in QC program, quantitative PCR must become essential as reference method for evaluating the efficiency of filtration, in the future.

Universal leukoreduction of cellular and plasma components: process control and performance of the leukoreduction process.

Many countries in Europe and over the world are currently or will be concerned in the near future, by the implementation of universal leukoreduction (ULR) for red blood cells (RBC), platelets (PT) and now also for plasma. Recommended by several advisory committees, this decision to implement ULR must be considered as a recognition of the benefit of early leukocyte removal, and also as a precautionary measure to increase blood safety. The leukodepletion technology for RBC, PT and plasma has become increasingly more elaborated and integrated in the collection or in the component preparation process. To reach this aim and to assure that the end-products meet local specifications (1 or 5 x 10(6) residual leukocytes), a process control and validation program for leukoreduction has been described in the specific guidelines. Tested on a wide scale by a group of centers, flow cytometry is emerging as reference method for residual leukocyte enumeration. Validation protocols (linearity, precision, accuracy) have been defined in numerous national or international studies (PSL and BEST Working Party). The sensitivity of the method is greatly improved by concentration of the sample, with a detection limit equivalent to 10 cells/mL for RBC or PT, and 0.5 cells/mL for plasma. Furthermore, monitoring of the performance of the leukoreduction process includes a quality control program based on a general statistical model with a parametric or non parametric approach, sampling plan, ongoing control, process capability assessment, confidence limit, detection of failure, and estimation of the non conforming units rate.

[Surveillance of biocontamination of the environment of labile blood products: its role in a quality assurance program]. / Suivi de la biocontamination de l'environnement des produits sanguins labiles: place dans une démarche d'action qualité.

As part of a quality assurance approach aiming at reducing the risk of bacterial contamination of labile blood components (BC), their environment was submitted to a twofold quality control. A yearly control was carried out by the University Hospital Laboratory of Hygiene (UH-LH). Another control was regularly implemented by our Quality Control Laboratory. In accordance with this quality system, we focused our attention on decontamination procedures, control targets and the definition of an acceptable threshold. The analysis of results over 1 year showed that they can be considered as satisfactory when less than 40 CFU/100 cm2 are found. Quality sheets were developed, aimed at motivating our staff, adapting the decontamination procedures and initiating corrective measures. This quality programme allowed us to develop close collaboration links with the UH-LH and to play a role in the prevention of hospital-acquired infections.

[Quality control of labile blood products. Why and howto properly take a specimen? Labile Blood Products Group of the French Blood Transfusion Society]. / Le contrôle de qualité des produits sanguins labiles. Pourquoi et comment bien prélever un échantillon? Groupe de produits sanguins labiles de la Société française de transfusion sanguine.

This article reviews the various techniques of sampling used for the quality control of blood cell products. The importance of this stage for the validity of quality control results is emphasized. Three sampling methods, i.e., stripping, the sterile connection of sampling bag and the destructive method, are described in the form of operating modes and analyzed according to their advantages and drawbacks. The results of a comparative study carried out by the working group 'Blood Cell Products' of the French Society of Blood Transfusion are presented, showing that each method is valid and permits one to obtain a representative sample of the product to be controlled. Thus the diversity of the sampling methods allows us to select the one most adapted to the product to be controlled and to the analyses to be carried out afterward.