En France, les prescriptions hospitalières de médicaments exécutées en ville (PHMEV) représentent près de 30 % du montant total (18 milliards d’euros) de médicaments remboursés sur l’enveloppe de soins de ville. L’objectif de ce travail était d’étudier les trois classes thérapeutiques ayant le plus d’impact sur les dépenses liées aux PHMEV de notre établissement et de proposer une stratégie d’optimisation. A partir de la base Open-PHMEV (Assurance maladie), les données concernant notre établissement pour 2017 ont été analysées. Les dépenses liées aux PHMEV de notre établissement représentent 12,5 millions d’euros, dont principalement les antirétroviraux (ARV), les médicaments de la procréation médicalement assistée (PMA) et les antidiabétiques. Quatre axes d’amélioration sont proposés : promotion de la prescription d’ARV inscrits au répertoire des génériques via un logiciel d’aide à la prescription, tout en maintenant le nombre de prises afin de préserver l’observance, diffusion de fiches sur les coût des stratégies thérapeutiques (VIH, diabète), mise en place d’ordonnances types incluant les génériques et biosimilaires (PMA), et bilans annuels par service prescripteur. La maîtrise de l’évolution des dépenses engendrées par les PHMEV est un enjeu majeur qui s’inscrit dans une démarche d’amélioration de la pertinence des soins.

Background The World Health Organisation calls for the eradication of the hepatitis C virus (HCV) by 2030. Direct-acting antivirals (DAAs) drugs promise shorter treatment times, much higher cure rates and fewer side effects. However, some patients failed to achieve sustained virological response (SVR) after DAAs regimens. Experts recommend retreatment based on an individual decision of the multidisciplinary team (MDT). Purpose The aim of this study was to describe the cases of our hospital's patients who failed to achieve SVR after DAAs regimens. Material and methods The study of the MDT reports between February 2014 and July 2018 allowed us to identify retreated patients who failed to achieve SVR after DAAs regimens. Patient information was collected based on the analysis of consultations' reports of the hepatology department: age, sex, viral genotype, co-infection with hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV), cirrhosis, presumed cause of failure of the first treatment with DAA. Results Of the 385 cases evaluated by the MDT, 12 patients were identified. Patients mean age was 57±12 years, sex ratio M/F was 1:4, four patients were cirrhotic, one was co-infected with HBV and two were co-infected with HIV. The genotypes found were: 1 (n=4), 2 (n=2), 3 (n=2) and 4 (n=4). First DAA treatment was either combinations of NS5B+NS5A inhibitors (such as sofosbuvir with daclatasvir/ledispavir/velpatasvir, n=8), or NS5A+NS3 inhibitors (grazoprevir/elbasvir or paritaprevir/ombitasvir, n=3) or NS5B+NS5A+NS3 inhibitors (dasbuvir/ombitasvir/paritaprevir, n=1). Four treatments were associated with ribavirine. The presumed cause of failures was HCV resistance to NS5A inhibitors, since the other causes (non-compliance, drug interactions, re-infection, premature discontinuation) had been discarded. During retreatment, the duration of treatment was lengthened and/or ribavirin was added. The molecules used for retreatment were NS5B and NS3 inhibitors in 2016 and 2017 (simeprevir/sofosbuvir, n=2). In 2018, NS5B+NS5A inhibitors associated with ribavirine (sofosbuvir/velpatasvir, n=1), NS5B+NS5A+NS3 inhibitors (glecaprevir/pibrentasvir/sofosbuvir with ribavirine n=4, sofosbuvir/voxilaprevir/velpatasvir n=4) and NS5A+NS3 (glecaprevir/pibrentasvir, n=1) were used. Conclusion Failed SVR were mainly caused by NS5A mutations. Second-generation DAAs marketing approval has allowed the retreatment of several patients. Therapeutic strategies for retreatment comply with European Association of the Study of the Liver guidelines. However, these patients should be monitored closely to evaluate SVR. References and/or acknowledgements http://www.easl.eu/medias/cpg/2018/EASL%20Recommendations%20on%20Treatment%20of%20Hepatitis%20C%202018/English-report.pdf No conflict of interest.

Connaître les attentes des pharmaciens hospitaliers sur le livret thérapeutique dématérialisé. Enquête nationale par un questionnaire de 26 items. Il a été obtenu 248 réponses. Le livret thérapeutique dématérialisé « idéal » pour les pharmaciens devrait contenir : le nom commercial, la dénomination commune internationale (DCI), la classe ATC, le statut, le prix et les modalités de conservation. Les fonctionnalités suivantes devraient être présentes : un lien vers une base de données sur le médicament, un moteur de recherche des équivalences thérapeutiques, des liens vers les recommandations de bon usage, la possibilité de télécharger des formulaires et un module de génération de messages d’alerte. Notre travail est la première étude sur ce sujet. To evaluate the expectations of pharmacists on the online drug formulary. A national study by a 26-item questionnaire. Two hundred forty-eight responses were obtained. The online drug formulary must contains, for each medicinal product, the trade name, the international non-proprietary name (INN), the ATC class, the status, the price and the conditions of conservation. The following features should be present: a link to a drug database, a therapeutic equivalency search engine, links to recommendations for proper use, possibility of downloading forms and an alert message generation module. Our work is the first study on this subject.

OBJECTIVES:The efficacy and safety of an oral pentobarbital suspension for sedation during pediatric MR imaging were assessed.METHODS:Data were recorded from October 2016 to January 2017. The exact dose of oral pentobarbital suspension was given for each child with an oral syringe. Parameters recorded included the patient's age and weight, the time required to sedate, the duration of sedation, the time required to discharge, and quality of MR imaging. The adverse effects were recorded.RESULTS:Oral pentobarbital suspension was administered to 81 children aged from 8 months to 8 years at a dose of 5mg/kg of body weight. The mean time required to sedate was 30±21min, a mean time of sedation of 47±23min, and a mean time to discharge of 77±32min. Sedation occurred a satisfied quality of MR imaging in 67% of patients. The failure of examination was essentially due to bad taste of the drug suspension. The overall success rate of sedation in patients less than 12 months was 100%. For ages 1 to 3 years, the success rate decreased to 76% and for ages 4 to 8 years, it decreased to 42%.CONCLUSIONS:Oral pentobarbital suspension used in MR imaging demonstrated its high rate of successful sedation in infants less than 12 months with no adverse effects during the study period.

Comme dans la vie quotidienne, les smartphones et les Apps ont investi le monde médical. Cette pénétration du monde médical a commencé dès l’apparition des premiers PDAs (Personal Digital Assistants), ancêtre des smartphones, à la fin des années 1980 et s’est accrue à partir de 2007 et l’apparition de l’iPhone. Suite à cette émergence de la m-health, le pharmacien se trouve en face de 3 questions que nous avons étudié dans cette revue : (1) Quelles sont les Apps disponibles pour la pratique et comment les trouver ? (2) Qu’est-ce qui est utile pour la pratique ? (3) Quelles sont les précautions à prendre ?

Since the advent of PDAs (Personal Digital Assistants), smartphones and Apps have been widely adopted by medical professionals. This craze has increased since 2007 and the first generation iPhone. In this context, 3 questions emerged for the pharmacist that we studied in this review: (1) What Apps are available for practice and how to find them? (2) What is useful for practice? (3) What precautions should be taken?

Background Belimumab is a monoclonal antibody indicated as add-on treatment in adult patients with active systemic lupus erythematosus (SLE) despite standard treatment. Given its modest efficacy and the lack of data for severe forms, the improvement in actual benefit (IAB) of belimumab was assessed to be minor. Thus, Health Authorities approved the hospital use of belimumab but its administration in hospital settings is not supported by health insurance. Purpose To assess the cost impact of belimumab treatment in adult patients with SLE in our hospital. Material and methods Data available from the SLE population in the Internal Medicine Department was used as input in the model. An Excel model was adopted for the analysis, which was performed from our hospital perspective. The recommended dose regimen was 10 mg/kg on days 0, 14 and 28 and at 4-week intervals thereafter. Patients received their treatment as part of a day hospital admission. Total charges and costs details were obtained from the National Tariffs Databases. Results A retrospective analysis was conducted on a dataset of 12 female patients followed over a period of 15 months (from January 2013 to May 2014). Based on a cost of €162.65 for a 120 mg vial and €542.15 for a 400 mg vial, the cost of belimumab per course and per patient was estimated at €972.5 whereas only €30 (drug-related reimbursement in the total hospital daily costs) were refunded to the hospital. 113 courses of treatment were recorded during this period. Therefore, a total of €106,504 remained chargeable to the hospital. Conclusion Despite some evidence of its clinical effectiveness, the health benefits could be outweighed by the significant costs associated with belimumab. It is important to target patients most likely to benefit from belimumab, to establish well-defined optimal treatment duration, or even to consider other therapeutic alternatives. References and/or Acknowledgements Thanks to N. MEBARKI JVR Bondy. No conflict of interest.

PURPOSE:The objective of this study was to reduce the risk of errors when administering oral medications to infants aged 28 days to 2 years.MATERIAL AND METHODS:The method of the preliminary risk analysis (PRA) was implemented by a multidisciplinary group in a hospital service of pediatrics. The study focused on the phase of preparation of drugs by nurses before administration.RESULTS:This analysis revealed 41 scenari, 16 were criticality unacceptable. In particular, their analysis highlighted the impact of the drug dosage form, the lack of scientific information and the human factor on this preparation. Eleven action sheets have been written.DISCUSSION:The risk management requires significant human investment, material resources and organizational solutions: formations, information, i.e. computerized prescribing, dispensing and administering system, centralized drug preparations, automated drugs cabinets or unit drug daily dispensing system.CONCLUSION:Control these risks means to get specific actions at pediatric wards, enhance dispensing system by the hospital pharmacist and the support of the pharmaceutical industry to get commercially available pediatric drugs.

Two investigations, one carried out throughout France (PediA D) and the other exclusively in Robert Debre pediatric hospital (PediEM), focus on the difficulties encountered by v nursing staff when achministering drugs to children, and the risk of medication errors. Medication errors can arise from dysfunctions at all stages of the drugs circuit, and may involve doctors, pharmacists or nursing staff In pediatric hospitals they are mainly related to the lack of commercial products specifically designed for children. In Robert Debre Hospital, only one-third of commercial products in stock are authorized for pediatric use with no age limit. Thus, even in a hospital where drug distribution is entirely computerised (PCS (R) Patient Care System software), where dispensing is based on the DIP system (daily, individual, and personal) but is not controlled, and where almost all requirements for sterile and non sterile preparations arc met but where validation is only 1, partial, the system is far-from being error-free. Two major improvements are planned First, dispensing will be automated in 2006. With the current shortage of pharmacy technicians, this will securitize drug dispensing and provide for therapeutic and economic traceability. Second, integration of a pharmacist within each medical team is being compared with validation of prescriptions by a pharmacist in the hospital pharmacy.

BACKGROUND: The proteasome inhibitor bortezomib (BTZ), used in antineoplastic chemotherapy, must be diluted in NaCl 0.9% for injection and stored for no more than 3 hours in a syringe or 8 hours in a vial. Better information on its stability could improve storage. OBJECTIVE: To assess the stability of BTZ solution (1 mg/mL) in syringes and vials. METHODS: BTZ 1-mg/mL solutions were prepared by adding sterile NaCl 0.9% to Velcade vials containing 3.5 mg of lyophilized BTZ. Syringes were filled with 1 mL of solution and stored in the dark at 5 °C or 60 °C; others were not protected from light and stored at 22 °C. Velcade vials containing 1 mL of solution were stored at 5 °C in the dark. Samples were taken at various times over 23 days and assayed in duplicate. An HPLC method for assaying the stability of BTZ was validated. Appearance and pH were recorded. RESULTS: There was no color change or precipitation in the samples, and the pH was stable. Oxidation, light, and storage temperature all affected the chemical stability of BTZ. The mean concentrations of BTZ in syringes stored for 2, 3, and 5 days at 60, 22, and 5 °C were >95% of the initial concentration. The mean concentration of BTZ in vials stored for 5 days at 5 °C was >95% of the initial concentration. CONCLUSIONS: BTZ stored refrigerated in vials or syringes and protected from light is chemically stable for 5 days after reconstitution.

OBJECTIVE:To assess the nature and the number of potential adverse drug interactions by analysis of outpatient prescriptions for elderly patients, of medications taken during the week before hospitalization in a general surgery department.METHOD:The study of 56 patients older than 65 years was conducted from November 2002 through February 2003. The outpatient prescriptions corresponding to medications taken during the 7 days before admission were analyzed by a pharmacy resident, who used data-processing tools and databases.RESULTS:Most patients (83%) knew the reason for their prescription. Thirteen (28%) reported using over-the-counter medication. Only 89% of the patients reported complete compliance with the prescription. The average age of the patients was 72.1 +/- 6.3 years and the median was 71 years [65-91]; 43% were women and 57% men. The 257 lines of prescriptions analyzed averaged 5.7 +/- 2.6 drugs (range: 2-10) per prescription. The average number of possible interactions was 3.1 +/- 2.8 per prescription for a total of 89 listed potential interactions. The levels observed were 3 warnings (3%), 37 precautions (42%) and 49 possible adverse interactions (55%). No contraindication was noted. The drugs mentioned most often were benzodiazepines, diuretics, conversion enzyme inhibitors, angiotensin II inhibitors, and beta-blockers. The potential risks most often found were hypotension, depression of the central nervous system, hypoglycemia and acute renal failure. The drug interactions were mainly due to the accumulation of the effects of separate drug classes. Deterioration in renal function was often noted as plasma concentration of the second drug increased.DISCUSSION:This exploratory study shows the reality of the iatrogenic risk for elderly patients. This analysis of outpatient prescriptions is consistent with findings in the literature. Analysis of interactions is conducted on a pairwise basis. It is thus difficult to envisage the consequences of the association of 5 or more drugs in patients with complex illnesses and diminished physiological and metabolic capacity. Patient files kept by the pharmacist could provide information about individual combinations ofthe prescription and over-the-counter drugs.

PURPOSE:To study the stability of levamisole oral solutions (25 mg/mL) prepared from powder and tablets stored at 4 +/- 3 degrees C and 23 +/- 2 degrees C in amber glass prescription bottles.METHODS:Levamisole 25 mg/mL solutions were prepared from commercially available 50-mg tablets or from pure powder in sterile water. Levamisole concentrations were determined in duplicate by a stability-indicating HPLC method at 0, 1, 2, 3, 4, 7, 14, 30, 60 and 90 days. The initial and final pHs of solutions were measured.RESULTS:The recovery of levamisole from tablets was 100 +/- 2.1%. No color or odour changes were observed during the study period. The oral solutions prepared from powder were stable at least 90 days stored at 4 and 23 degrees C. The oral solutions prepared from tablets were stable at least 90 days at 4 degrees C and 15 days when stored at 23 degrees C. The initial pH of solutions prepared from powder and tablets were 5.30 and 4.55, respectively. Initial and final pH values were significantly different (p<0.001) for the two solutions.CONCLUSIONS:Levamisole 25 mg/mL oral solutions can be prepared from tablets or powder with sterile water for irrigation and stored for 90 days under refrigeration, taking account of the lack of microbiological contamination.

OBJECTIVE:. To quantify the type and frequency of drug administration errors to pediatric in-patients and to identify associated factors.DESIGN:Prospective direct-observation study of drug administration errors from April 2002 to March 2003.SETTING:Four clinical units in a pediatric teaching hospital.STUDY PARTICIPANTS:Twelve observers accompanied nurses giving medications and witnessed the preparation and administration of all drugs to all patients on all weekday mornings.INTERVENTION:None.MAIN OUTCOME MEASURE:Discrepancies between physicians' orders and actual drug administration.RESULTS:During the 1719 observed administrations to 336 patients by 485 nurses, 538 administration errors were detected, involving timing (36%), route (19%), dosage (15%), unordered drug (10%), or form (8% form). These errors occurred for 467 (27%) of the 1719 administrations. Intravenous drugs (OR = 0.28; CI = 0.16-0.49; versus miscellaneous) were associated with fewer errors. Error rates were higher for cardiovascular (OR = 3.38; CI = 1.24-9.27; versus miscellaneous) and central nervous system drugs (OR = 2.65; CI = 1.06-6.59; versus miscellaneous); unspecified dispensing system (OR = 2.06; CI = 1.29-3.29; versus store in the unit); non-intravenous non-oral administration (OR = 4.44; CI = 1.81-10.88; versus oral administration); preparation by the pharmacy (OR = 1.66; CI = 1.10-2.51); and administration by a hospital pool nurse, temporary staffing agency nurse, or nurse intern (OR = 1.67; CI = 1.04-2.68; versus registered full-time nurse). Each additional management procedure in the patient increased the risk of error (OR = 1.22; CI = 1.01-1.48).CONCLUSIONS:The risk factors identified in our study should prove useful for designing preventive strategies, thereby improving the quality of care.

Objective To assess the nature and the number of potential adverse drug interactions by analysis of outpatient prescriptions for elderly patients, of medications taken during the week before hospitalization in a general surgery department.Method The study of 56 patients older than 65 years was conducted from November 2002 through February 2003. The outpatient prescriptions corresponding to medications taken during the 7 days before admission were analyzed by a pharmacy resident, who used data-processing tools and databases.Results Most patients (83%) knew the reason for their prescription. Thirteen (28%) reported using over-the-counter medication. Only 89% of the patients reported complete compliance with the prescription. The average age of the patients was 72.1 +/- 6.3 years and the median was 71 years [65-91]; 43% were women and 57% men. The 257 lines of prescriptions analyzed averaged 5.7 +/- 2.6 drugs (range: 2-10) per prescription. The average number of possible interactions was 3.1 +/- 2.8 per prescription for a total of 89 listed potential interactions. The levels observed were 3 warnings (3%), 37 precautions (42%) and 49 possible adverse interactions (55%). No contraindication was noted. The drugs mentioned most often were benzodiazepines, diuretics, conversion enzyme inhibitors, angiotensin II inhibitors, and beta-blockers. The potential risks most often found were hypotension, depression of the central nervous system, hypoglycemia and acute renal failure. The drug interactions were mainly due to the accumulation of the effects of separate drug classes. Deterioration in renal function was often noted as plasma concentration of the second drug increased.Discussion This exploratory study shows the reality of the iatrogenic risk for elderly patients. This analysis of outpatient prescriptions is consistent with findings in the literature. Analysis of interactions is conducted on a pairwise basis. It is thus difficult to envisage the consequences of the association of 5 or more drugs in patients with complex illnesses and diminished physiological and metabolic capacity. Patient files kept by the pharmacist could provide information about individual combinations of the prescription and over-the-counter drugs.

To assess the nature and the number of potential adverse drug interactions by analysis of outpatient prescriptions for elderly patients, of medications taken during the week before hospitalization in a general surgery department.The study of 56 patients older than 65 years was conducted from November 2002 through February 2003. The outpatient prescriptions corresponding to medications taken during the 7 days before admission were analyzed by a pharmacy resident, who used data-processing tools and databases.Most patients (83%) knew the reason for their prescription. Thirteen (28%) reported using over-the-counter medication. Only 89% of the patients reported complete compliance with the prescription. The average age of the patients was 72.1 +/- 6.3 years and the median was 71 years [65-91]; 43% were women and 57% men. The 257 lines of prescriptions analyzed averaged 5.7 +/- 2.6 drugs (range: 2-10) per prescription. The average number of possible interactions was 3.1 +/- 2.8 per prescription for a total of 89 listed potential interactions. The levels observed were 3 warnings (3%), 37 precautions (42%) and 49 possible adverse interactions (55%). No contraindication was noted. The drugs mentioned most often were benzodiazepines, diuretics, conversion enzyme inhibitors, angiotensin II inhibitors, and beta-blockers. The potential risks most often found were hypotension, depression of the central nervous system, hypoglycemia and acute renal failure. The drug interactions were mainly due to the accumulation of the effects of separate drug classes. Deterioration in renal function was often noted as plasma concentration of the second drug increased.This exploratory study shows the reality of the iatrogenic risk for elderly patients. This analysis of outpatient prescriptions is consistent with findings in the literature. Analysis of interactions is conducted on a pairwise basis. It is thus difficult to envisage the consequences of the association of 5 or more drugs in patients with complex illnesses and diminished physiological and metabolic capacity. Patient files kept by the pharmacist could provide information about individual combinations ofthe prescription and over-the-counter drugs.

Objective: To assess the stability of doxorubicin combined with Radioselectan((R)).Methods: Solutions of doxorubicin 5 mg/mL were prepared from commercially available 50 mg powder with 10 mL of Radioselectan((R)). They were stored in glass syringes at 4, 25 and 45 degrees C. The concentrations of doxorubicin were determined using a stability-indicating high-performance liquid chromatography method. The initial and final pHs of solutions were compared. The times (t(90)) needed for doxorubicin to fall to 90% of its initial concentration were calculated by a linear regression analysis.Results: The t(90) [95% confidence limits] were 79 [75-83], 56 [53-59] and 22 [21-23] hours for the solutions stored at 4, 25 and 40 degrees C respectively. The initial pH of the solutions stored at 4, 25 and 40 degrees C were 6.52, 6.50 and 6.51 respectively. The final pH of solutions stored at 25 and 40 degrees C decreased significantly by 0.3 and 0.9 respectively. No change of pH solution stored at 4 degrees C was observed.Conclusion: Doxorubicin combined with Radioselectan((R)) stored at room temperature is stable for 48 h.