[Prescriptions of statins in the elderly according to the type of healthcare establishment: An example of the usefulness of territorial hospital groups]. / Utilisations des statines chez le sujet âgé selon le type de prise en charge : un exemple de l'intérêt des groupements hospitaliers de territoire.

INTRODUCTION: The challenge of territorial hospital groups is to develop coherent care pathways for optimal patient care. Following the creation of a territorial pharmaceutical team, a common prescription review process was initiated in our health area. The objective of this study is to analyze the uses of statins in the elderly. METHOD: The study included all statin-treated patients older than 75 years at the five participating institutions (including long-term nursing homes). In a prospective multicenter study, the benefit/risk ratio of statin prescription has been assessed up. Depending on the clinical situation, a proposal to stop or adjust the dosage could be made. RESULTS: Nine hundred and forty-seven patients were included. Among them, 184 were treated with a statin. Forty-seven patients (26%) are treated in primary prevention and 137 patients (74%) in secondary prevention. Dosages are lower for long stays. Fifteen treatments interruption were accepted out of 44 proposals, mostly for long stays. The reasons given to continue treatment are the need for a new evaluation by a cardiologist or a high cardiovascular risk. CONCLUSION: The variability of results according to the type healthcare institution makes territorial medical and pharmaceutical collaboration relevant. The challenge is to develop a coherent care pathway for optimal care of elderly patients, with congruent objectives.

[What academic training for pharmacy students for clinical pharmacy? Example of shared medication report]. / Quelle formation académique pour les nouvelles missions de pharmacie clinique à l'officine ? Exemple du bilan partagé de médication du sujet âgé.

OBJECTIVES: In 2018, the implementation of shared medication reports in pharmacy encourages pharmacists to cooperate with other healthcare professionals. This job allows a decrease of medication errors in elderly. This requires a reorganization of the training offered by universities (initial and continuing training). The aim is to present the results of this pedagogical experimentation. METHODS: The experimentation (years 2017-2018 and 2018-2019) required the creation of a course to allow students to carry out a pharmaceutical analysis suitable to elderly people, to set up and carry out a shared medication report in pharmacy. Then, during their 6th year internship, students had to carry out at least one shared medication report per month. A monthly follow-up was organized with a database online. RESULTS: Sixty-four students and 35 internship supervisors participated in the experimentation. All the students improved their ease in using clinical pharmacy tools (pharmaceutical analysis, pharmaceutical interventions, assessment of adherence, etc.). They carried out 345 shared medication reports. In 24.3% of cases, an improvement in the prescription was proposed to the doctor (general practitioner or specialist). For 80% of the internship supervisors, the initial training of the students helped to set up this new pharmacy activity. CONCLUSIONS: This teaching is appreciated by students and internship supervisors. It enabled the adoption of the various tools essential for carrying out shared medication reports in pharmacy. Shared medication reports reinforce the multidisciplinary work of pharmacists, especially with general practitioners.

[Retrocession, a risk area in care pathway]. / Les rétrocessions, une zone à risque dans le parcours des patients.

OBJECTIVES: Medication errors are common at transitions points in care pathway. The pharmacist can secure patient care in "retrocession" (dispensing specific drugs by hospital pharmacy to outpatient) due to his prescription analysis (both regulatory and pharmacotherapeutic). The "retrocession" is a risk area in care pathway. The objective of this study is to evaluate iatrogenic and economic risks in "retrocession" dispense by identifying pharmaceutical interventions. MATERIAL AND METHODS: This is a prospective monocentric study performed during 8months in university hospital. All the prescriptions have been analyzed and divided into 3 categories: "first prescription" (a new prescription for a new treatment or a new patient), continued therapy with new prescription and prescription renewal. Therapeutic optimizations and regulatory pharmaceutical interventions performed have been systematically recorded. RESULTS: Among 7166 prescriptions analyzed, 161 pharmaceutical interventions (2.2%) are done. The highest rate of therapeutic optimizations and regulatory pharmaceutical interventions concern the "first prescription" category (9.3%). The most involved drugs in medication errors on a "first prescription" are cancer drugs (36%) and anti-infectives (24%). CONCLUSION: The first dispensation in "retrocession" is the riskiest step, especially with pharmacotherapeutic intervention. Thanks to pharmacist counseling sessions, especially in oncology, this risk is better controlled. This study demonstrates the interest of developing pharmacist counseling sessions for the treatment's introduction regardless of therapeutic class.

[Mucositis after allogeneic stem cell transplantation: Risk factors, clinical consequences and prophylaxis]. / La mucite post-allogreffe de cellules souches hématopoïétiques: facteurs de risque, conséquences cliniques et prévention.

AIM: Oral mucositis is a very common complication of allograft. However, preventive treatments are still limited. The objective of this study is to identify risk factors for onset of oral mucositis in patients undergoing allogeneic hematopoietic stem cells transplantation (HSCT), to measure clinical consequences and to study their evolution according to type of prevention. PATIENTS AND METHODS: All patients undergoing HSCT in hematology unit of CHU Besançon between January 2009 and August 2010 were included, and received according to their choice, either the standard protocol: solution of sodium bicarbonate 1.4% associated with chlorhexidine-chlorobutanol (Eludril(®)) (n=49), or the experimental treatment by the ionic solution, Caphosol(®) (n=42). RESULTS: The overall incidence of severe mucositis and mucositis is respectively 69% and 36%. In multivariate analysis, a myeloablative conditioning (OR=11.1) and prevention of GVHD (graft-versus-host disease) including methotrexate (OR=7.5) appear such as the two significant mucositis risk factors. The presence of mucositis resulting in a significant increase in the incidence of febrile aplasia (P=0.008) and the use of opioid analgesics and parenteral nutrition (P<10(-3)). The risk of acute gastrointestinal GVHD is also increased in severe mucositis (P=0.01). The duration of post-transplant hospitalization is not changed. The type of prevention does not influence the incidence of mucositis (P=0.11). CONCLUSION: The consequences of mucositis are significant and the risk factors identified. The interest of the ionic solution Caphosol(®) seems limited, the incidence of mucositis is not decreased by this prevention.

Incidence and risk-factors of CHOP/R-CHOP-related cardiotoxicity in patients with aggressive non-Hodgkin's lymphoma.

WHAT IS KNOWN AND OBJECTIVE: The CHOP regimen with rituximab (R-CHOP) remains the standard for chemotherapy in patients with aggressive non-Hodgkin's lymphoma (NHL). The cardiotoxicity of doxorubicin appears to be a key problem in clinical practice. We studied the cardiotoxicity of CHOP/R-CHOP regimen in a retrospective series. The prognostic factors of congestive heart failure (CHF) were investigated, including the impact of empirical cardioprotection by dexrazoxane. METHODS: Patients with an aggressive NHL between 1994 and 2005 were included. Cardiac events were defined as either a decline in resting left ventricular ejection fraction (LVEF) <50%, a decline in LVEF of ≥20% from baseline or as clinical evidence of CHF. The risk of cardiotoxicity was explored by the Kaplan-Meier method. RESULTS: The study included 180 consecutive patients. During the second period of the survey, cardioprotective therapy by dexrazoxane was administered to 45% of patients. The 5-year cumulative risks of cardiac events (29% vs. 8%) and clinical CHF (17% vs. 1·5%) varied significantly between the two periods of study (1994-2000 vs. 2001-2005). In multivariate analysis, use of dexrazoxane (HR = 0·1 [0·01-0·75], P = 0·02) and age  < 60 years (HR = 0·4 [0·17-0·9], P = 0·03) appeared as protective factors of cardiac events. WHAT IS NEW AND CONCLUSION: Our study confirmed the weight of cardiac toxic effect of CHOP ± R regimen. Even if the use of dexrazoxane is highly debatable in curative situations, it may be an effective prevention of cardiotoxicity in aggressive NHL patients.

Economic impact of prescribing error prevention with computerized physician order entry of injectable antineoplastic drugs.

UNLABELLED: A cost-benefit analysis was carried out to determine the potential economic costs and benefits of pharmaceutical analysis in preventing prescribing errors for full standardized injectable antineoplastic drugs computerized physician order entry, in a pharmaceutical unit (University teaching hospital), compared with theoretical setting with no pharmaceutical analysis. The viewpoint is that of the payer or the French national Public Health Insurance system, and is limited to hospital cost (only direct medical costs related to net cost and net benefit. A decision analysis model was performed to compare two strategies: with pharmaceutical analysis (± pharmacy intervention) and without pharmaceutical analysis. RESULTS: are expressed in terms of benefit-to-cost ratio and total benefit. The robustness of the results was assessed through a series of one-way sensitivity analyses. Over 1 year, prescribing error incidence was estimated at 1.5% [1.3-1.7], i.e. 218 avoided prescribing errors. Potential avoidance of hospital stay was estimated at 419 days or 1.9 ± 0.3 days per prescribing error. Cost-benefit analysis could estimate a net benefit-to-cost ratio of 33.3 (€17.34/€0.52) and a total benefit at €16.82 per pharmaceutical analysis or €249,844 per year. The sensitivity analysis showed robustness of results. Our study shows a substantial economic benefit of pharmaceutical analysis and intervention in the prevention of prescribing errors. The clinical pharmacist adds both value and economic benefit, making it possible to avoid additional use of expensive antineoplastic drugs and hospitalization. Computerized physician order entry of antineoplastic drugs improves the relevance of clinical pharmacist interventions, expanding pharmaceutical analysis and also the role of the pharmacist.

Physicochemical and microbiological stability of insulin eye drops in an artificial tear vehicle used in the treatment of refractory neurotrophic keratopathy.

Neurotrophic keratopathy (NK) is a degenerative corneal disease with a loss of corneal sensitivity and impairment of corneal healing. Low dose insulin eyedrops have been shown to be a simple and effective treatment for refractory NK when the response to the usual treatment is incomplete. At present, there are no commercially available forms, and there is no data regarding the stability of these products as prepared by compounding pharmacies. In this work, we studied the physicochemical and microbiological stability of an insulin ophthalmic formulation obtained by mixing insulin lispro in artificial tears with a polyethylene and propylene glycol base. The stability of this 1IU/mL insulin ophthalmic formulation was analysed for 12 months in low-density polyethylene (LDPE) multidose eye droppers at 4°C. The studied parameters of physicochemical stability were: visual inspection, turbidity, UV spectral absorption, osmolality and pH. In addition, insulin and m-cresol concentrations and quantification of impurities (insulin covalent aggregates and insulin fragments) were studied thanks to the development of a new Size Exclusion Chromatographic method. For unopened eye droppers, all tested physicochemical parameters remained stable for 12 months at 4°C, and excellent microbiological stability was obtained. In conditions of simulated use, these parameters also remained stable for one month at 4°C, and no impact of potential temperature rises on the insulin and m-cresol concentrations in the insulin eyedropper was observed.

Influenza vaccination coverage at community pharmacies: Positioning, needs, expectations and involvement of community pharmacists in the Franche-Comté region.

INTRODUCTION: Influenza vaccination coverage currently remains below the 75% recommended threshold by the World Health Organization. To correct this situation, experiments have been successively carried out in France to enable community pharmacists to vaccinate at-risk populations. In this context, a study was conducted with pharmacists from the French Franche-Comté region to evaluate their positioning, needs and expectations regarding influenza vaccination at community pharmacies. MATERIALS AND METHODS: A survey was created and sent to licensed pharmacists in March of 2018. This consisted of 4 parts: characteristics of the community pharmacy; positioning of the pharmacist regarding vaccinations carried out at the pharmacy; training needs and expectations; and willingness to implement vaccinations. RESULTS: The participation rate in this survey was 32% (137/427). More than 90% of the pharmacists agreed that community pharmacies' assets were adequate for the implementation of these vaccinations (accessibility and availability), although 52% considered this complicated. Their main fears were reluctance from patients and conflicts of interest with other health professionals authorized to vaccinate (58%). The needs and expectations regarding pharmacy student training were essential for 94% of them as well as continuous training of practicing pharmacists (96%). The willingness of pharmacists to vaccinate stemmed from the fact that influenza vaccination coverage would increase for at-risk subjects (36%). CONCLUSION: This survey allowed us to assess the favorable positioning and the real interest of pharmacists from Franche-Comté regarding the influenza vaccination done at community pharmacies, given the proviso that they were given relevant training and allocated adequate resources.

[Clinical audit on the use of expensive systemic antifungals in the Besançon University Hospital]. / Audit clinique des prescriptions d'antifongiques systémiques couteux au centre hospitalier universitaire de Besançon.

UNLABELLED: The continuous improvement policy for healthcare quality requires practice evaluation. The principle of a clinical audit is to compare practice to guidelines. Prescription guidelines on antifungal agent use has been available in our hospital since 2003. It was updated in 2005 and 2006. OBJECTIVE: The aim of this study was to assess compliance to guidelines, with an audit of prescriptions: amphotericin B lipid formulation, voriconazole and caspofungin, expensive antifungals concerned by the budget allowance correlated to activity, subject to supplementary reimbursement to the coded Homogeneous Group of Diseases. METHOD: The assessment criteria were: relevance of the indication, absence of a better alternative, complying to recommended dosage, loading dose and timing. This retrospective study dealt with all prescriptions of all departments, from January to May 2007. RESULTS: Hundred and eighteen prescriptions were retrospectively analyzed for 81 patients. The rate of overall conformity was 54%. Antifungal therapy was justified for 113 prescriptions (96%). In 30% of the cases, a more efficient alternative was advised, cheaper or less toxic. The dosage and the charge dosing were right in 92% and 80% of the cases respectively. CONCLUSION: This audit allowed assessing good-use of antifungals. We showed an over-prescription of caspofungin and sometimes insufficient regimen of voriconazole dosages for children. Reporting these audit results and development of new international guidelines stress the need to update local recommendations regularly.

PRODIG (Prevention of new onset diabetes after transplantation by a short term treatment of Vildagliptin in the early renal post-transplant period) study: study protocol for a randomized controlled study.

BACKGROUND: Post-transplant diabetes is a frequent and serious complication of kidney transplantation. There is currently no treatment to prevent or delay the disease. Nevertheless, identification of risk factors make it possible to target a population at risk of developing de novo diabetes. We hypothesized that a short-term treatment with vildagliptin may prevent new onset diabetes after transplantation (NODAT) in high-risk patients. METHODS/DESIGN: This is a multicenter, double-blind, placebo-controlled randomized clinical trial. Patients undergoing first kidney transplantation will be included from ten French transplant centers. Included patients will be randomized (1:1) to receive either vildagliptin 100 or 50 mg/day (depending on glomerular filtration rate) during 2 months (the first dose being administered before entering the operating theatres) or placebo. Additional antidiabetic therapy could be administered according to glycemic control. The primary outcome is the proportion of diabetic patients 1 year after transplantation, defined as patients receiving a diabetic treatment, or having a fasting glucose above 7 mmol/l, and/or with an abnormal oral glucose tolerance test. Secondary outcomes include glycated hemoglobin, the occurrence of acute rejection, infection, graft loss and patient death at 3 months, 6 months, and 12 months after transplantation. Outcomes will be correlated to clinical and general characteristics of the patient, cardiovascular history, nephropathy, dialysis history, transplantation data, biological data, health-related quality of life, and the cost-effectiveness of prevention of diabetes with vildagliptin. DISCUSSION: We have scarce data on the pharmacological prevention of post-transplant diabetes. If our hypothesis is verified, our results will have a direct application in clinical practice and could limit diabetes-associated morbidity, reduce cardiovascular complications, increase quality of life of renal transplant patients, and consequently promote graft and patient survival. Our results may possibly serve for non-transplant patients carrying a high-risk of diabetes associated with other co-morbidities. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02849899 . Registered on 8 February 2016.

Hospital costs of renal transplant management.

Renal transplantation is considered to be a cost-effective therapy, but hospital medical costs are not accurately known. The aim of this work was to evaluate the costs of hospital stay for renal transplantation. This retrospective study included all patients who underwent renal transplantation between January 1, 2004, and December 31, 2005, in our University hospital. The incurred costs were determined using our center's analytical accounting (AA). The mean local cost was then compared with the median national cost of hospitalization for renal transplantation, based on a sample of participating centers contributing to the National Cost Scale (NCS) per homogenous diagnosis-related group (DRG). These mean costs were weighed against the financing obtained by national rates of the case-mix based payment system (termed T2A). Data were collected from 77 patients. Their mean length of stay was 19.4 days. AA determined the cost of management to be euro14,100 per patient. National economic approaches were significantly higher: euro16,389 for NCS and euro17,369 for national rates. Thus, the specific DRG rate (case mix index) of renal transplantation covers the expenses incurred by our center. These results are rather interesting; however, it is unlike those obtained for the management of other diseases such as acute myeloid leukemia, where T2A underestimates the actual cost by 2-4 times. Last, the hospital budget and T2A must be considered as a whole. The fact that DRGs with favorable and unfavorable pricing balance out should be taken into account.

[Prescribed and dispensed in the third trimester of pregnancy drugs: What practices and risks?]. / Médicaments prescrits et dispensés au cours du troisième trimestre de grossesse : quelles pratiques et quels risques ?

OBJECTIVE: The aim of the study was to describe the prescribing of drugs to pregnant women during the third trimester of pregnancy. PATIENTS AND METHODS: The retrospective analysis is interested by pregnant women from August 2009 to April 2011, living in Franche-Comté. The used data are recorded in the database of the French Health Insurance Service. Drugs prescribing were analyzed and classified according to three categories: drugs that are contraindicated, not recommended drugs and drugs that are used. This classification is based on two databases: the Summaries of Product Characteristics of Vidal 2010 and data from the National Security Agency of Medicines. The potential exposure of patients was pointed out. RESULTS: On 15,027 patients, 80% had a prescription. Six percent of prescriptions containing drugs not recommended and 1% drugs that contraindicated. Therapeutic classes identified are analgesics, anti-infective drugs and medicines supplementing with vitamins and minerals. Contraindicated drugs (10%) are NSAIDs, rubella vaccine, cyclins and ACE inhibitors and ARBs. Approximately 2.7% of women were potentially exposed to these drugs. DISCUSSION AND CONCLUSION: Despite the recommendations of the ANSM, some drugs that are contraindicated are prescribed for pregnant women in their third trimester of pregnancy. In the absence of studies, the decision must be made on a case by case basis by assessing the risk-benefit ratio. Particular care is to bring about the drugs taken in self-medication. Information and advice are key steps to avoid incidents.

[New immunotherapeutic approaches in oncology and hematology]. / Nouvelles approches d'immunothérapie en onco-hématologie.

Scientific advances in the last decade have demonstrated the critical role of host immune system in the elimination and suppression of cancer cells. Better knowledge of signaling pathways has enabled the development of new cancer immunotherapy. The discovery of negative feedback mechanisms following the lymphocyte activation has promoted the development of new antibodies targeting molecule inhibitors such as PD1, PDL1 or CTLA-4. Dramatic results were obtained with melanoma. Checkpoint inhibitors (pembrolizumab and ipilimumab) have many advantages in terms of rate of objective response and overall survival. Recent studies in translational research aimed to understand and analyze mechanisms of action of anti-PD1/anti-PDL1. Expression of PDL1 in the tumor is associated with a significantly greater objective response rate (immunohistochemistry). Nevertheless, limits with tumor immunohistochemical analysis encourage new biomarkers research. Other immunotherapy approaches, such as cell and gene therapies using engineered T cells call for further advancements to broaden their applicability. However, these therapies are very expensive and their manufacturing process very restrictive, which could lately limit their use in case of inefficiency of checkpoint inhibitors or when lymphocytic infiltration in tumor is absent. In this case, the objective would be to engineer ex vivo the patient's immune system by restoring the ability of T cells to identify and suppress tumor cells. Currently, two gene-reprogramming tools are under development: chimeric antigen receptor and TCR modified T cells.

Effect of cell determinant (CD)34+ cell dose on the cost and consequences of peripheral blood stem cell transplantation for non-Hodgkin's lymphoma patients in front-line therapy.

The aim of this study was to assess the effect of cell determinant (CD)34+ cell dose on the cost and consequences of peripheral blood stem cell transplantation for non-Hodgkin's lymphoma (NHL) patients in front-line therapy. Resource utilisation, length of aplasia, overall (OS) and event-free survival (EFS) were assessed for 63 patients. Economic data were calculated taking into account harvest, hospitalisation, blood product requirements and drugs required until discharge. The point of view of the Hospital Institution was chosen. A significantly earlier haematopoietic engraftment was achieved in patients with a count of more than 5 x 10(6) CD34+/kg. There were no differences for OS and EFS. A high CD34+ cell content resulted in a total cost saving of $4210. This was principally related to a significant reduction in the length of hospitalisation (-$3010) and platelet and red blood cell transfusions (-$815), although the latter was not significant. Several sensitivity analyses showed the robustness of our results. A CD34+ cell dose higher than 5 x 10(6)/kg appeared to be optimal for clinical and economic considerations in NHL patients undergoing transplantation in front-line therapy.

Cost comparative study of autologous peripheral blood progenitor cells (PBPC) and bone marrow (ABM) transplantations for non-Hodgkin's lymphoma patients.

Intensive high-dose chemotherapy with autologous stem-cell support has become a common treatment strategy for non-Hodgkin's lymphomas. A cost-identification analysis was conducted comparing 10 patients autografted with PBSC to 10 others autografted with BM. The analysis included harvest and graft until graft day +100 and was carried out from the point of view of the hospital setting. Resources used, logistic and direct medical costs per patient were identified, and sensitivity analyses performed. The cost distribution was different. Stem cell harvest was more expensive for PBPC ($9030) and BM ($4745); on the other hand, hospitalization from graft to discharge from hospital cost savings with PBSC were about $10666. After discharge from hospital, costs were similar and cheaper in both groups. For the overall study the PBPC procedure was less expensive than ABMT, $35381 and $41759 respectively, with cost savings of $6378. The number of days spent in hospital and blood bank costs were the major cost factors. This study was based on a single pathology, non-Hodgkin's lymphoma, and the actual hospital records for each patient situation as opposed to a clinical trial, and our results were consistent with different previous studies carried out in different health care systems.

Cost-effectiveness of CD34+ dose in peripheral blood progenitor cell transplantation for non-Hodgkin's lymphoma patients: a single centre study.

Intensive high-dose chemotherapy with peripheral blood progenitor cell (PBPC) transplantation is a common strategy for aggressive non-Hodgkin's lymphomas (NHL). A retrospective cost-effectiveness analysis of CD34+ cell dose was carried out. Between 1994 and 1998, 28 patients were included. Efficacy was measured by the length of aplasia. Data collection concerned the period from graft day until discharge from hospital, and the post-graft period until graft day +100. Patients transplanted using a cell dose greater than 5 x 106/kg were found to have a faster hematological recovery. Average length of post-graft hospitalization was shorter and fewer blood products were required for patients with more than 5 x 106/kg CD34+ cells transplanted. Hospitalization was the major cost driver. A large reduction in procedure cost was obtained with a CD34+ cell count higher than 5 x 106/kg (-US$2740, -11%). This difference was directly related to hospitalization (-US$860) and platelet units transfused (-US$1,340). A sensitivity analysis showed the robustness of results. Our findings indicated that a CD34+ cell dose higher than 5 x 106/kg was more cost-effective than a lower dose in NHL patients. The collection of 5 x 106/kg CD34+ cells appeared necessary to optimize the PBPC procedure.

[Antibiotic therapy of febrile neutropenic patients: prospective study at a hematologic department]. / Antibiothérapie du patient neutropénique fébrile: enquête de pratiques d'un service d'hématologie.

OBJECTIVES: Many antibiotics have been studied in clinical trials in neutropenic patients with fever. Few have been evaluated in the everyday clinical setting. The aim of our study was to analyze the antibiotic strategy used in an adult hematology unit after guidelines had been set up. METHODS: A prospective study was conducted by a pharmacy team not directly working with the prescribing unit. Parameters recorded were drug use, treatment duration and reasons for changing successive drugs. Bacterial ecology data were analyzed. RESULTS: Seventy-four patients were included in the study. Mean treatment duration was 14.8 days and was related to degree of neutropenia: 10 days in case of short neutropenia and 16.2 days for prolonged neutropenia. The most frequent first intention prescription was for non-anti-pseudomonas fl-lactams plus tobramycin, modifications made were: substitution with an anti-pseudomonas fl-lactam and introduction of a glycopeptide as second or third intention drugs. Imipenem and fluoroquinolones were used little. Mean duration of each regimen was 4 days. Initial treatment was generally empirical (7% of the prescriptions were based on documented susceptibility data). The highest rate of bacteriological data (20%) was obtained during the first intention regiment (42% coagulase-negative staphylococci, 14% Pseudomonas aeruginosa). The main reason for changing antibiotics was persistent or renewed fever. No bacterial caused deaths were recorded. No multiresistant Gram negative bacilli were selected. DISCUSSION: Reasonable use of antibiotics is possible in neutropenic patients with fever. First intention anti-pseudomonas fl-lactams and glycopeptides are not indispensable in most of these patients. An analysis of practice in the everyday clinical setting is required for optimal use of antibiotics.

[Galenic and analytic development of tacrolimus 0.06% eye drops]. / Développement galénique et analytique d'un collyre à base de tacrolimus 0,06 %

PURPOSE: The administration of topical tacrolimus (FK506) eye drops or ointment is effective in treating certain immunologic corneal diseases and in the prevention of rejection of high-risk corneal grafts. The purpose of this study is to determine the optimal formulation of tacrolimus 0.06% eye drops. A procedure for preparation is presented and discussed. METHODS: Tacrolimus monohydrate powder and virgin castor oil are used in this new formulation. The manufacturing process guarantees consistency of product sterility. Measurement by high-performance liquid chromatography allows precise control of the concentration of tacrolimus. RESULTS: The manufacture and packaging of tacrolimus 0.06% eye drops involve numerous controls allowing for guaranteed sterility and stability. The drops remained sterile and stabile for 28 days after opening regardless of storage conditions and can be stored for 3 months after manufacture. Tolerability studies are currently being performed.

Incidence and risk factors of anemia in patients with early breast cancer treated by adjuvant chemotherapy.

BACKGROUND: The study's objective was to assess the predictive factors of anemia induced by chemotherapy in early breast cancer patients. PATIENTS AND METHODS: Patients treated by adjuvant or neo-adjuvant anthracyclin-based regimens with or without taxanes between 1998 and 2006 in a French university hospital were studied. Chemotherapy included. Anemia was defined as a hemoglobin (Hb) concentration lower than 12 g/dL. Multivariate analysis by logistic regression was used to search for baseline risk factors linked to the occurrence of anemia. RESULTS: Among 378 patients, anemia was observed in 64% of cases. The occurrence of anemia was significantly related to 6 risk factors: exposure to taxanes (HR 11.5, 95% CI, 2.5-52.6), high dose of anthracyclin (epirubicin 100 mg/m²)(HR 4.3; 95% CI, 2.8-8), Hb at baseline < 13.5 g/d (HR 4.3; 95% CI, 2.6-7.1), mastectomy (HR 2.5; 95% CI, 1.4-3.3), age >60 (HR 2.5; 95% CI, 1.4-5) years old (HR 2.5; 95% CI, 1.4-5) and Body Mass Index (BMI) ≤ 25 kg/m² (HR 1.7; 95% CI, 1.0-2.8). CONCLUSION: Taking into account the following factors: type of chemotherapy, BMI, age, Hb at baseline should allow a better identification of patients at risk of anemia.