[Prospective risk analysis in a retrocession unit: Focus on drug dispensation process]. / Analyse des risques a priori en unité de rétrocession hospitalière : focus sur le processus de dispensation.

OBJECTIVES: Failure mode effect analysis (FMEA) improves safety in the drug life cycle. As the drug dispensation by hospital's pharmacy can be at risk, the FMEA tool has been used to evaluate and enhance the process. METHODS: After detailing the process, a first FMEA has been run in 2015. Corrective actions were implemented every time criticality indexes (CI) were above 15. One year later, we have evaluated potential impacts of these actions by running a new FMEA. RESULTS: In 2015, 11 failure modes were prioritized (CI>15) and the total CI for the overall process was 397. Corrective actions were implemented and one year later this amount has decreased by 14% (340) with 6 failure modes still prioritized. Thus, thanks to the FMEA, risks could be identified in year "y", they were taken into account and corrected and then effectively reassessed in year "y+1". CONCLUSION: This study showed us the interest of performing FMEA analysis in the drug dispensation process by hospital. The renewal of this risk analysis after a year helped us to monitor corrective actions, to evaluate their effectiveness and to improve safety. Finally, FMEA seems to be an effective way to steer the drug dispensation process.

[Pharmaceutical interviews for rheumatoid arthritis patients: Perceptions and expectations of community pharmacists]. / Entretiens pharmaceutiques destinés aux patients atteints de polyarthrite rhumatoïde : perceptions et attentes des pharmaciens d'officine.

INTRODUCTION: Rheumatoid arthritis has a low level of medication adherence. Abroad, the community pharmacist has a positive impact on the patients' adherence in several chronic diseases. In France, community pharmacists' missions are developing with the implementation of pharmaceutical interviews. OBJECTIVE: To evaluate community pharmacists' perceptions on the interest and feasibility of pharmaceutical interviews targeting patients with rheumatoid arthritis. METHOD: Semi-structured interviews were conducted between August and October 2017, with pharmacists in the Auvergne-Rhône-Alpes region. The inductive analysis of the interview verbatim was realized by two independent persons. RESULTS: Fifteen community pharmacists highlighted barriers in recruiting patients for the interviews currently possible at the pharmacy, the complexity of the organization and the financing, a weakness of the hospital-to-community liaison. Nevertheless pharmacists were motivated to expand the service to other pathologies. Regarding rheumatoid arthritis, pharmacists would see them in the form of structured interviews preferentially at the pharmacy, in connection or even "prescribed" by physicians for optimal and multi-professional information sharing. Prior training and funding for these interviews should be considered to motivate pharmacists to this activity. CONCLUSION: This study allowed to discuss with community pharmacists their expectations and needs to widen the service of pharmaceutical interviews in the rheumatoid arthritis. These results will have to be taken into account to build a support interviews model for rheumatoid arthritis patients who can be integrated in their daily pharmaceutical activity.

[Management of outpatient medications in care units: An audit of clinical practices]. / Traitement personnel du patient hospitalisé : audit de pratiques.

OBJECTIVES: To assess the outpatient medication management in care units two years after the release of an institutional procedure. To assess the patients' satisfaction with their treatment and with the information transmitted by healthcare professionals. METHODS: An audit of clinical practices was conducted in 23 units of our universitary hospital - general, surgery, emergency departments. Questionnaires were developed and validated by an institutional working group and were composed of three themes: management of the outpatient medication at the admission, awareness of tools and information transmission. Two physicians (a senior and a resident), a registered nurse, a head nurse and a patient were interviewed. RESULTS: Eighty-one medical and paramedical team members and 21 patients were interviewed for the study. According to statements collected, the procedure was unknown by 100% of the interviewed surgeons and 69% of the interviewed physicians. The practices being used by the medical units were more in line with recommendations than the surgery units. Among the patients interviewed, 19 (86%) were satisfied with the information they received during their hospitalization and 4 (19%) managed their own medication treatment with the help of a nurse in only 36% of the cases according to their statements. CONCLUSIONS: The management of outpatient medications during hospitalization is representative of the difficulties to master the continuity of pharmaceutical care at the various transition points. Coordination and cooperation between the different healthcare professionals and patients are the major key success to ensure an optimized healthcare procedure.

[Aseptic process validation and stability study of an injectable preparation of fructose (5%)-glycerol (10%) as part of a hospital clinical research program on endoscopic curative treatment for early epithelial neoplastic lesions of the gastrointestinal tract]. / Validation du procédé aseptique et étude de stabilité d'une préparation injectable de fructose (5 %)-glycérol (10 %) dans le cadre d'un programme hospitalier de recherche clinique portant sur le traitement curatif endoscopique des lésions néoplasiques épithéliales précoces du tube digestif.

INTRODUCTION: As part of a hospital clinical research program on endoscopic curative treatment for early epithelial neoplastic lesions of the gastrointestinal tract, a new hospital sterile and non-pyrogenic preparation of fructose (5%)-glycerol (10%) was realized. Under pharmaceutical legislation, the provision of this hospital preparation involves of aseptic process validation and achieve a stability study. MATERIALS AND METHODS: After the aseptic process validation with Mediafill Test, the preparation was made under aseptic conditions associated with a sterilizing filtration according to the good practices preparation. Prepared flexible bags (100mL of solution) were stored for one year in a climatic chamber (25±2°C). To assess stability, the physicochemical controls (fructose concentration, glycerol concentration, hydroxy-methyl-5 furfural [5-HMF] concentration, sodium concentration, pH measure, osmolality and sub-visible particles count) and microbiological (bioburden, bacterial endotoxin and sterility) were performed at regular intervals for one year. RESULTS: Neither significant decrease of fructose concentration, glycerol concentration and sodium concentration nor pH, 5-HMF, osmolality variations out of specifications were observed for one year. The sub-visible particles count, the bacterial endotoxin and sterility were in accordance with the European pharmacopoeia attesting limpidity, apyrogenicity and sterility of this injectable preparation. DISCUSSION AND CONCLUSION: The hospital preparation was stable over one year at 25±2°C, ensuring safe administration in humans within the framework of this clinical research.

[Advantages and special features of hospital preparations of parenteral nutrition in neonatalogy]. / Avantages et spécificités des préparations hospitalières de nutrition parentérale en néonatalogie.

INTRODUCTION: The care of premature infants requires specific, suitable parenteral nutrition, in which the dosage must be frequently adjusted. METHOD: A comparative analysis of four industrial standard parenteral nutrition formulations NP 100®, Pediaven AP-HP Nouveau-né 1®, Pediaven AP-HP Nouveau-né 2® and Numetah G13% E® and of two hospital preparations made specifically in hospital pharmacies produced by two separate university hospitals (Nutrine® HCL and Formule standardisée début de nutrition) was conducted. The comparison between the formulations focused on electrolytic compositions and protein/energy ratio. RESULTS: Formule standardisée début de nutrition and Pediaven AP-HP Nouveau-né 1® are free from (i) sodium and potassium, (ii) potassium respectively. Almost equivalent sodium concentration (19-27 mM) and more variable potassium concentration (∼9-26 mM) characterize the other formulations. Protein/energy ratio of Numetah G13% E®, Nutrine® HCL and Formule standardisée début de nutrition is 58% higher than that of NP 100®, Pediaven AP-HP Nouveau-né 1® and Pediaven AP-HP Nouveau-né 2®. DISCUSSION: Formule standardisée début de nutrition and Pediaven AP-HP Nouveau-né 1® are in accordance with the recommendations about hydro-electrolytic supplies during transition phase. Nutrine® HCL complies best to the recommendations about hydro-electrolytic account during stabilization phase. CONCLUSION: Hydro-electrolytic composition and protein/energy ratio of standard hospital parenteral nutrition formulations comply best to nutritional needs of premature infants.

[Injectable hospital preparation of valine labeled with the carbon 13 and nitrogen 15 (5 mg/mL) for a clinical trial on the brain tumor metabolism: Pharmaceutical control of active pharmaceutical ingredient and stability study of the finished product]. / Préparation hospitalière injectable de valine marquée au carbone 13 et à l'azote 15 (5mg/mL) pour un essai clinique sur le métabolisme tumoral cérébral : contrôle pharmaceutique de la substance active et étude de stabilité du produit fini.

INTRODUCTION: The L-Valine labeled (L-[U-(13)C,(15)N] Val) is a stable isotopic tracer administered by parenteral route within the framework of a new clinical research program concerning the brain tumor metabolism. To meet regulatory requirements and have ready to use solution with an expiration date, a pharmaceutical control of active pharmaceutical ingredient followed by stability study of hospital preparation were realised. MATERIALS AND METHODS: After the pharmaceutical control of the L-[U-(13)C,(15)N] Val, the hospital preparation was prepared according to the good manufacturing preparation. Prepared bottles were stored at 5°C±3°C and 25°C±2°C for six months. The stability of the preparation was determined by physico-chemical controls (pH, osmolality, sub-visible particles, L-[U-(13)C,(15)N] Val concentration, sodium concentration, isotopic enrichment) and microbiological (bacterial endotoxin and sterility). RESULTS: Concentrations of L-[U-(13)C, (15)N] Val and sodium does not significantly decrease during the stability study. In parallel, no change in pH and osmolality were highlighted. Isotopic enrichment higher than 99.9% reflected the stability of labeling of L-valine molecule. The sub-visible particles, the bacterial endotoxin and sterility were in accordance with the European Pharmacopoeia attesting limpidity, apyrogenicity and sterility of this injectable preparation. DISCUSSION AND CONCLUSION: The stability of this hospital preparation of L-[U-(13)C, (15)N] Val has been demonstrated for six months at 5°C±3°C and 25°C±2°C, ensuring a parenteral administration as part of the clinical trial.

[Pharmacist's interventions on outpatient prescriptions in a university hospital drugs sales service]. / Interventions des pharmaciens sur les prescriptions ambulatoires dans le cadre de l'activité de rétrocession d'un centre hospitalier universitaire.

UNLABELLED: For public health reasons, some drugs are only available in hospital drugs sales service. This activity takes place in a specific risk context of organization, patients and/or drugs. A systematic prescription analysis by pharmacist contributes to securise treatment dispensed. The aim of this paper is to present the main drugs problems in the analysis of outpatient prescriptions and pharmaceutical interventions in three units of hospital drugs sales service belong to university hospital. METHODS: Throughout the year 2013, drug problems detected were recorded prospectively and systematically. RESULTS: Of the 22,279 prescriptions analyzed, 247 pharmaceutical interventions (1.1%) were detected including 27.6% of problems concerning the dosages, 15.4% the unconformity, 6.9% contraindications. Regarding ATC drugs classes, we found 43.7% for anti-infectives and 17.4% for antineoplatics. The overall acceptance rate is 81.8%. CONCLUSION: These results show the importance of the analysis of outpatient prescriptions before dispensing and the need to have all prescriptions, clinical and biological elements and to develop interprofessionality. The implementation of a platform for dematerialized data exchanges between professionals, including data from the pharmaceutical patient record should contribute to improving drug management of the patient.

[Pharmaceutical involvement in academic clinical trials: Quality assessment of pharmaceutical manufacturing operations]. / Implication pharmaceutique dans le cadre d'essais cliniques institutionnels : évaluation de la qualité des opérations de mise sous forme pharmaceutique.

INTRODUCTION: For academic clinical trials, the hospital pharmacy may be required to perform the specific activity of preparing investigational drugs. MATERIAL AND METHODS: With regards to such activity, and in light of the recent changes in the regulatory environment, the main objective of this study was to evaluate whether quality levels and traceability were in compliance with the applicable regulatory standards. In order to do so, two internal audits have been conducted, the first on the compliance of operations with existing regulatory standards and the second on the quality of traceability of the operations. RESULTS: The proportion of academic clinical trials is constantly growing and currently represents 41% of the total clinical trials in the establishment. An average of 29,000 therapeutic units of investigational drugs are prepared each year (84% under the form of capsules). An overall conformity level of 75% and 88% has been identified in the aforementioned audits, respectively. Such audits have also allowed for the identification of weaknesses in current practices as well as potential improvement areas to achieve better compliance. DISCUSSION: The hospital pharmacy can provide expertise for the preparation of specific dosage or drugs that are not available on the market. It also can be involved for the conception of appropriated packaging function of the study design. CONCLUSION: Results of audits encourage us to continue this activity with a satisfactory level of quality in accordance with the necessary requirements to ensure the safety of patients and the quality of clinical trials conducted.

[Injectable preparation of labeled leucine with the carbon 13 for a clinical research program on the Alzheimer disease: pharmaceutical control of raw materials and the finished product and stability study]. / Préparation injectable de leucine marquée au carbone 13 pour un programme de recherche clinique sur la maladie d'Alzheimer : contrôle pharmaceutique des matières premières et du produit fini et étude de stabilité

INTRODUCTION: The L-leucine labeled (L-[U-(13)C] Leu) is a stable isotopic tracer administered by parenteral route within the framework of a new clinical research program concerning the diagnosis of the Alzheimer's disease. To meet regulatory requirements and have ready to use solution with an expiration date, a pharmaceutical control of raw materials and the finished product followed by a stability study were realised. MATERIALS AND METHOD: After the pharmaceutical control of raw materials, the solution of L-[U-(13)C] Leu was prepared according to the good practices preparation. Prepared bottles were stored for 1 year of a share in a climatic chamber (25 °C±2 °C) and the other in a refrigerator (5 °C±3 °C). To assess stability, the physicochemical controls (pH, osmolality, sub-visible particles, L-[U-(13)C] Leu concentration, sodium concentration, isotopic enrichment) and microbiological (bacterial endotoxin and sterility) were performed at regular intervals for 1 year. RESULTS: Neither significant decrease of L-[U-(13)C] Leu concentration and sodium concentration nor pH and osmolality variation were observed for 1 year. Isotopic enrichment higher than 99.9% reflected the stability of labelling of L-leucine molecule. The sub-visible particles, the bacterial endotoxin and sterility were in accordance with the European pharmacopoeia attesting limpidity, apyrogenicity and sterility of this injectable preparation. DISCUSSION AND CONCLUSION: The injectable preparation of L-[U-(13)C] Leu was stable after 1 year for two preservation conditions, ensuring to safety for administration for human within the framework of this clinical research.

[Integration of a hospital pharmacist in the ICU]. / Intégration d'un pharmacien hospitalier en service de réanimation.

The French regulatory system strongly encourages strict regulation of health products' production and distribution, especially concerning risk management and economic aspects. An ICU is an unusual environment for a local pharmacy practice (a nurse for every 2.5 patients, continuous adaptation of therapeutics…). However, a literature review reports interesting data concerning risk management and economics. This article aims to relate the experience of a pharmacist integration in a French teaching hospital ICU (half-time position).

Ex vivo absorption of promestriene from oil-in-water emulsion into infant foreskin.

Hypospadias is a birth defect in which the urinary tract opening is not at the tip of the penis. Hypospadias surgery is frequently complicated by healing deficiencies. Topical treatments with oestrogens were reported to improve healing. In the present study, ex vivo percutaneous absorption of promestriene, a synthetic oestrogen resulting of the double esterification of estradiol was conducted as a pre-requisite for further clinical trial in infants. Penetration of promestriene into infant foreskin treated with commercial oil in water emulsion (10 µg mg(-1)) for 24 h was characterized showing controlled release properties enabling epidermal concentration more than six times higher than dermal concentration (4.13±2.46 mg g(-1) versus 0.62±0.84 mg g(-1), respectively). Furthermore, apparent promestriene fluxes into and through the skin (i.e., 1.5 µg cm(-2) h(-1) and<0.89 µg cm(-2) h(-1), respectively) were calculated from (i) drug amount retained into epidermis and dermis, or (ii) the limit of detection into the receptor fluid. In conclusion, less than 2% of initial dose were absorbed within 24h which compared well with others steroids applied topically in colloidal systems.

[Innovative therapeutic strategies for intravesical drug administration]. / Stratégies thérapeutiques innovantes pour l'administration médicamenteuse intravésicale.

INTRODUCTION: Perspectives for innovative pharmaceutical molecules and intravesical administration of pharmacological agents are presented in the present review carried out from a recent literature. MATERIALS AND METHODS: This review of the literature was built by using the PubMed and ScienceDirect databases running 20keywords revealing 34publications between 1983 and 2012. The number of referenced articles on ScienceDirect has increased in recent years, highlighting the interest of scientists for intravesical drug administration and the relevance of innovating drug delivery systems. RESULTS: Different modalities of intravesical administration using physical (e.g., iontophoresis, electroporation) or chemical techniques (e.g., enzyme, solvent, nanoparticles, liposomes, hydrogels) based on novel formulation methods are reported. Finally, the development of biopharmaceuticals (e.g., bacillus Calmette-Guérin, interferon α) and gene therapies is also presented and analyzed in this review. CONCLUSION: The present review exhibits new development in the pipeline for emerging intravesical drug administration strategies. Knowledge of all these therapies allows practitioners to propose a specific and tailored treatment to each patient with limiting systemic side effects.

Impact of intravenous lipid emulsion infusion on the stratum corneum barrier function in patients receiving parenteral nutrition.

The importance of the lipid matrix of stratum corneum (SC) in epidermal barrier function is well documented. Intravenous lipid emulsions (ILE) provide essential fatty acids (EFAs), main components of the SC lipid matrix. The objective of this study was to investigate the influence of ILE upon SC barrier function. The skin barrier was assessed by measuring transepidermal water loss (TEWL). Patients receiving lipid-containing parenteral nutrition (LCPN) were compared to patients receiving lipid-free PN (LFPN). In addition, a before/after LCPN introduction study was set up to limit the influence of inter-individual variability. Twenty-six patients receiving LCPN and seven patients receiving LFPN were included. Median age was not significantly different between the two groups. The TEWL of the LCPN group (9.05 g/m2/h) was significantly lower than the TEWL of the LFPN group (12.1 g/m2/h; Wilcoxon test: p = 0.016). The relative variation of TEWL before and after ILE treatment of 5 studied patients was 21.29 ± 10.28 %. ILE improve epidermal barrier function when compared to lipid-free parenteral treatments. Results of the before/after study confirm this conclusion and the usefulness of ILE intake for preventing excessive TEWL. SC barrier function improvement could be a choice criterion between the different ILE generations, in particular in burn patients and premature neonates.

[Depyrogenation test regarding inox and glass containers in the preparation of parenteral nutrition mixtures]. / Test de dépyrogénation des conteneurs en inox et en verre pour la préparation des mélanges pour nutrition parentérale.

INTRODUCTION: The preparation of parenteral nutrition mixture (PNM) in an open chamber requires the use of intermediate containers sterile and non-pyrogenic. A sterilization of containers by moist heat in large autoclaves is the suitable method. However, sterilization by moist heat is not a depyrogenation method. In our study, we report the validation of a sterilization and depyrogenation method for containers by dry heat using a convection oven. MATERIALS AND METHODS: Sterilization and depyrogenation of material by dry heat have been audited by the reduction of at least three logarithms of original endotoxin rate. The containers were initially artificially contaminated with a suspension of endotoxin for 16 hours. Contaminated containers were placed in an oven with revolving heat at 250 °C for 1 hour. After treatment with dry heat, the residual endotoxin levels in the containers were determined by a kinetic chromogenic method. RESULTS: After treatment with dry heat, the average log reductions of endotoxin levels were respectively, for glass and steel containers, 4.78 ± 0.07 and 4.87 ± 0.03. DISCUSSION AND CONCLUSION: The present validation study confirms the effectiveness of treatment with dry heat for sterilization and depyrogenation of glass and steel containers. This method of sterilization and depyrogenation meets the microbiological quality requirements for the preparation of MNP.

[Hospital pharmacist has a rule for best practice use and French hospital activity tariffs. Example of a pharmaceutical quality control for drugs reimbursed in addition of DRGs]. / Le pharmacien hospitalier au cœur des enjeux du bon usage des médicaments et de la tarification à l'activité. Exemple d'une organisation de contrôle qualité pharmaceutique pour le remboursement des médicaments en sus des GHS.

The best practice contract has given a new objective to the hospital pharmacists for the reimbursement in addition to Diagnosis Related Groups' (DRGs) tariffs. We built our pharmaceutical quality control for the administration traceability follow-up regarding the DRGs and the cost of care, for two reasons: the nominal drugs dispensation in link with the prescription made by pharmacist and the important expenditure of these drugs. Our organization depends on the development level of the informatized drugs circuit and minimizes the risk of financial shortfalls or wrong benefits, possible causes of economic penalties for our hospital. On the basis of this follow-up, we highlighted our activity and identified problems of management and drugs circuit organization. The quality of the administration traceability impacts directly on the quality of the medical records and the reimbursements of the expensive drugs. A better knowledge of prescription software is also required for a better quality and security of the medical data used in the medical informatic systems. The drugs management and the personal treatment in and between the care units need to be improved too. We have to continue and improve our organization with the future financial model for ATU drugs and the FIDES project. The health personnel awareness and the development of best informatic tools are also required.

Identification and prioritization of bioaccumulable pharmaceutical substances discharged in hospital effluents.

The consumption of pharmaceuticals and their excretion in wastewater is a continuous source of pollution for aquatic ecosystems. In certain cases these compounds are found in the environment at concentrations high enough to cause disturbance in aquatic organisms. Aware of this problem hospitals are giving increasing attention to the nature of their effluents and their impact on the environment, by implementing more efficient effluent management policies. This concern is justified in view of the large volumes of toxic products consumed (detergents, disinfectants, pharmaceuticals, chemical reagents, radioactive elements, etc.). Moreover, these effluents usually do not undergo any specific treatment before being discharged into urban sewage networks. In this article, we present a method for selecting the pharmaceuticals discharged in hospital effluents that have the worst impact on the aquatic ecosystem, primarily based on their bioaccumulation potential. This study focused on the pharmaceuticals consumed at the Hospices Civils de Lyon (HCL), the second largest hospital structure in France (5200 hospital beds). Of the 960 substances consumed in HCL hospitals, a shortlist of 70 substances considered as being potentially bioaccumulable was established. The use of aggravating factors of risk has then led to the final selection of 14 priority compounds. They include 4 compounds consumed in large quantities in HCL hospitals, 6 endocrine disruptors and 4 potentially ecotoxic compounds. For all these compounds, it is now advisable to verify their bioaccumulation potential experimentally and confirm their presence in the environment. In addition, in order to monitor the risk relating to possible contamination of the food chain, it will be necessary to measure accumulated dose levels in species of different trophic levels. Lastly, chronic ecotoxicity tests will permit evaluating the danger and risk that some of these substances may represent for aquatic ecosystems.

[Validation of pharmaceutical quality of a [6,6-(2)H(2)]-glucose parenteral solution used for insulin-resistance measurement during human clinical trials]. / Validation de la qualité pharmaceutique de préparations de [6,6-(2)H(2)]-glucose en solution aqueuse administrées par voie parentérale pour la mesure de l'insulino-résistance dans le cadre d'essais cliniques.

INTRODUCTION: Deuterated glucose ([6,6-(2)H(2)]-glucose) is a stable isotopic tracer administered parenterally in healthy volunteers, obese or diabetic patients in clinical trial to study glucose metabolism during euglycemic hyperinsulinemic clamps. In accordance with the Health Authorities on drug safety, we evaluated the pharmaceutical quality of this preparation for biomedical research with a stability study. METHODS: After pharmaceutical qualification of the raw material, the [6,6-(2)H(2)]-glucose was dissolved in water for injection, then sterile, filtered under positive pressure of nitrogen and then autoclaved. Two batch products (500mg/10mL and 2g/15mL) were sampled to evaluate glucose alteration, isotope shift, limpidity, apyrogenicity and sterility at regular intervals for 2 years. Deuterated glucose solutions were stored in the dark, at +2°C+8°C, in type II glass bottles. RESULTS: Neither significant decrease of glucose concentration nor pH variation were observed for 2 years. The 5-hydroxymethylfurfural concentration was below the human harmful levels, attesting a non-generation of metabolites during autoclaving. Isotopic enrichment higher than 99% reflected the stability of deuterated label on the 6-carbon of glucose molecules. The non-visible particle concentration below the minimal permissible concentration tolerated by the European Pharmacopoeia and the absence of bacterial endotoxin and bacterial growth attested limpidity, apyrogenicity and sterility of the [6,6-(2)H(2)]-glucose solutions. CONCLUSION: After the 2-year study, 500mg/10mL and 2g/15mL deuterated glucose solutions stored in the dark at +2°C+8°C were stable in aqueous solution, allowing to ensure safety administration for human clinical trials using euglycemic hyperinsulinemic clamps.

Assessment of sodium hyaluronate gel as vehicle for intracameral delivery of cefuroxime in endophthalmitis prophylaxis.

Sodium cefuroxime is a second-generation cephalosporin widely used at 10mg/mL for endophthalmitis prophylaxis after cataract surgery. Sodium cefuroxime solution is usually conditioned in pre-filled syringes then frozen for storage. In the present study, 0.2% sodium hyaluronate gel, natural extracellular polymer used in wound healing, was compared to conventional saline solution (0.9% sodium chloride) as drug delivery systems for cefuroxime loading in pre-filled syringes. Therefore, the temperature (4 and 25 degrees C) and time of storage (up to 21 days) varied in order to appreciate both cefuroxime and vehicle stability. Furthermore, the kinetics of drug release from both hyaluronate gel and saline solution were compared since in vitro sets of dialysis experiments. Results indicated that cefuroxime loaded in either saline solution or hyaluronate hydrogel was found stable in pre-filled syringes stored at 4 degrees C for 21 days, whereas cefuroxime degradations products appeared from the 2nd day of storage at 25 degrees C. Both drug delivery systems were found bioequivalent, although statistically slower cefuroxime dialysis was evidenced by using sodium hyaluronate vehicle. Noteworthy, cefuroxime concentration in drug delivery systems during dialysis experiment remained greater than the minimum inhibitory concentrations reported for resistant strains. In conclusion, the present stability and release study confirmed that sodium hyaluronate hydrogel is a promising vehicle for cefuroxime intracameral delivery in endophthalmitis prophylaxis.

[Best practice agreement: implementation of best practice guidelines in HCL hospitals in Lyon, France]. / Contrat de bon usage : mise en oeuvre opérationnelle des référentiels de bon usage aux hospices civils de Lyon.

Since 2004, the Hospices Civils de Lyon (HCL) hospitals are committed to comply with best practice guidelines for healthcare products that are reimbursed in addition to diagnosis related groups' (DRGs) tariffs in France, and that, even before the publication of the law concerning best practice agreement. It has been necessary to adapt national drugs best practice guidelines to every-day practice. A working group, COPIL RBU, has been created in HCL hospitals to manage the best practice guidelines locally. This group has two main activities: it conducts a scientific and regulatory information watch and follows up emerging indications at HCL. The group's best practice guidelines contain a classification of indications into three categories: approved indications (market authorization and temporary protocol of treatment), currently-assessed indications and contra-indications. Our best practice guidelines are more than a rewriting of national guidelines since they include emerging indications validated by prescribing physicians at HCL hospitals. A scientific argumentation is made for each emerging indication that is classified in our guidelines, based on the level of scientific evidence available. The practical use of our best practice guidelines is made through a best practice prescription that enables the traceability of drugs from the prescription to the administration to the patient. These prescriptions are accompanied with best practice guidelines made by medical and pharmaceutical professional groups. Audits will then be conducted to assess the indications' conformity to our guidelines and to have a better knowledge of current medical practice.

[Effectiveness of combined vancomycin and pefloxacine in gastrointestinal decontamination for preventing infections after chemotherapy-induced bone marrow aplasia. A randomized double-blind study]. / Intérêt d'associer la vancomycine à la péfloxacine en décontamination digestive pour la prévention des infections après chimiothérapie aplasiante. Etude randomisée en double insu.

OBJECTIVE: To test the value of the combination of pefloxacin and vancomycin as gastro-intestinal tract decontamination for the prevention of infections in patients with chemotherapy-induced neutropenia. PATIENTS AND METHODS: Oral pefloxacin plus vancomycin (48 patients), pefloxacin alone (51 patients), or placebo (52 patients) were administered in a randomized double-blind study. Evaluation was done by determining site and documentation of infections, organisms responsible for bacteriologically documented infections, organisms acquired in surveillance cultures and number of days with fever during aplasia. RESULTS: Patients receiving pefloxacin had significantly fewer episodes of bacteremia with enterobacteriacae. No differences were noted between patients treated by pefloxacin and those who received a combination of pefloxacin with vancomycin regarding gram-positive (Gram+) infections and infections with gram-negative (Gram-) organisms usually resistant to pefloxacin. However, placebo gave similar results. There was no induction of resistance to pefloxacin during the study. Tolerance of treatment was excellent. Only a prolonged aplasia has been observed in patients receiving pefloxacin. CONCLUSION: Thus, the combination of vancomycin with pefloxacin was not more efficacious than pefloxacin only for the prevention of Gram+ infections in the neutropenic patient. The systematic use of antibiotics as gastrointestinal tract decontamination for the prevention of infections in patients with aplasia may be questionable.