[Implementation of a new gene therapy in ophthalmology: Regulatory and organizational issues]. / Mise en place d'une nouvelle thérapie génique en ophtalmologie : aspects réglementaires et organisationnels.

Voretigene neparvovec (VN) is the first gene therapy in ophthalmology for patients with RPE65-mediated hereditary retinal dystrophy. It has recently obtained European market approval, which is subject to strict regulatory and organizational conditions for its use. Here, we analyze the main studies supporting the authorization of this new therapy and describe the necessary steps to take at a hospital level for optimal administration to patients following current regulations.

[Retrospective cohort study of rituximab biosimilar (Rixathon®) adverse events in adult hematology and pediatric nephrology]. / Etude de cohorte rétrospective sur les effets indésirables du biosimilaire du rituximab (Rixathon®) en hématologie adulte et néphrologie pédiatrique.

The purpose of this study was to describe rituximab biosimilar safety in adult hematology and pediatric nephrology units. Adverse events were classified using the Common Terminology Criteria for Adverse Events (CTCAE) classification. Fifty adult patients were enrolled for a total of 126 cures and 11 pediatric patients for a total of 24 biosimilar cures. Among adults, three infusion-related reactions of biosimilar occurred : a bronchospasm, a reaction at the injection site and emesis. Among children, infusion-related reactions were: a bronchospasm, an injection site reaction, an emesis, and diarrhea. For adults, the most common adverse events included neutropenia (13.5 %) with 9 severe grade 3/4 cases, anemia (8.7 %), grade 1 thrombocytopenia (6.3 %), asthenia (2.4 %), infection (2.4 %), and chills (1.6 %). For children, a case of severe grade 4 neutropenia, a fever and conjunctivitis were observed. Results of this study show a confident safety profile of rituximab biosimilar in adults and children in «real life¼.

L'objectif de ce travail est de décrire les effets indésirables du biosimilaire du rituximab en «vie réelle¼ dans les services d'Hématologie adulte et de Néphrologie pédiatrique. Les effets indésirables ont été codés selon la classification des «Common Terminology Criteria for Adverse Events¼ (CTCAE). Cinquante patients adultes ont été inclus pour un total de 126 cures et 11 enfants pour un total de 24 cures de biosimilaire. Chez l'adulte, des réactions liées à la perfusion du biosimilaire ont été caractérisées par un bronchospasme avec frissons, une réaction au point d'injection et un cas de vomissements. Chez les enfants, les réactions liées à la perfusion étaient similaires avec un bronchospasme, une réaction au point d'injection, un cas de vomissements, et un cas de selles liquides. Chez les adultes, les effets indésirables les plus fréquents étaient la neutropénie (13,5 %), une anémie (8,7 %), une thrombopénie de grade 1 (6,3 %), une asthénie (2,4 %), une infection (2,4 %). Chez les enfants, un cas de neutropénie de grade 4, une fièvre et une conjonctivite ont été enregistrés. Le profil d'effets indésirables du biosimilaire du rituximab chez les adultes et les enfants est rassurant.

[Antibiotic consumption and bacterial sensitivity in a teaching hospital: A 5-year study]. / Profil de consommation et de sensibilité aux antibiotiques utilisés dans un centre hospitalier universitaire : étude rétrospective sur cinq ans.

INTRODUCTION: To reduce risks of antibiotic resistance, governmental and learned societies decreed the optimal use of antibiotics. The relation between antibiotic consumption and bacterial resistance increase has been clearly demonstrated over the last several years. Antibiotic consumption data and bacterial sensitivity data are regularly published, but very few publications have searched for a correlation between these two variables. This study focused on antibiotic use and consumption as well as bacterial sensitivity to these antibiotics. OBJECTIVES: The main objective was to describe the changes in antibiotic consumption and bacterial sensitivity in a mother-child teaching hospital. The secondary objectives were to explore whether antibiotic use and bacterial sensitivity were correlated and to comment on the usefulness of these data for clinicians. METHODS: This was a 5-year retrospective, descriptive, cross-sectional study. All samples from usually sterile biologic liquids of hospitalized pediatric patients were included in the study. The samples from outpatient clinics were excluded. All types of bacteria identified in more than 30 isolates were included in the study. The antibiotics usually used to treat these bacteria were included. To assess antibiotic consumption, we calculated the number of days of therapy per 1000 patient-days for hospitalized pediatric patients and we calculated the Pearson correlation coefficient between antibiotic consumption and sensitivity rates to these antibiotics. Two scenarios were explored: one with correlation by year and one with the next year for bacterial sensitivity. RESULTS: During the study period (2010-2011 to 2014-2015), overall antibiotics consumption remained relatively stable. Concerning bacterial sensitivity, we noted important changes (sensitivity rates increased for 12 antibiotic-bacteria pairs, remained stable for five, and decreased for 15). We found three significant correlations for the first scenario: Pseudomonas aeruginos-ceftazidime (P=0.01), P. aeruginosa-ciprofloxacin and fluoroquinolone consumption (P=0.02), Enterococcus sp-ampicillin and penicillin consumption (P=0.04). For the second scenario, we found only two significant correlations: coagulase-negative Staphylococcus-oxacilline and penicillin consumption (P=0.02), P. aeruginosa/piperacillin (P=0.04). CONCLUSION: This exploratory study allowed us to describe antibiotic consumption and bacterial sensitivity progression. To our knowledge, this is the first study exploring the correlation between antibiotic consumption and the bacterial sensitivity rate in pediatrics in Canada. It remains very difficult to show this correlation between these two variables because of the multiple sources of bacterial resistance. These data are particularly useful for the antimicrobial stewardship programs and for clinicians.

[Pilot study evaluating the ratio of medication errors related to antimicrobials compared to their consumption]. / Étude pilote des erreurs médicamenteuses liées aux anti-infectieux par rapport à leur consommation.

INTRODUCTION: As part of our antimicrobial stewardship program, we were interested in the use of anti-infectious drugs and the prevalence of medication errors associated with the use of these drugs. METHODS: The retrospective and descriptive study was conducted over a 1-year-period between 1 April 2012 and 31 March 2013 in a teaching mother-child hospital. The aim of the study was to determine the number and the type of medication errors related to anti-infectious drugs. We evaluated the importance, the significance, and the severity of medication errors and at the same time we evaluated antimicrobial consumption. Therefore, we determined the ratio of medication errors per 10,000 defined daily doses (DDD) or 10,000 days of therapy (DOT). The secondary objective of the study was to compare the medication errors related to anti-infectious drugs with the data published in the Quebec Registry of Incidents and Accidents. RESULTS: We found a total of 2164 medication errors including 301 (14%) medication errors related to anti-infectious drugs during the 2012-2013 fiscal year. The majority (95%) of the medication errors related to anti-infectious drugs was not harmful, with no consequences for the patient. Seventy-four percent of medication errors related to anti-infectious drugs were part of the C class on the severity scale. Omission (26%) and wrong dose administration were the two most frequently reported events. Eighty percent (n=242/301) of medication errors occurred during the administration step while only 8% (n=24/301) occurred during the prescribing step. Three anti-infectious drugs had the highest ratio of medication errors per 10,000 DDD or DOT: linezolid (376 medication errors per 10,000 DDD), doxycycline (357 medication errors per 10,000 DDD), and acyclovir (202 medication errors per 10,000 DDD). The nonparametric tests showed no significant differences between frequently used and infrequently used anti-infectious drugs for the ratio of medication errors per 10,000 DOT. This pilot study showed a ratio of 65.4 medication errors/10,000 DDD of anti-infectious drugs and a ratio of 41.9 medication errors/10,000 DOT of anti-infectious drugs. CONCLUSION: The use of these ratios could contribute to focusing on monitoring anti-infectious drugs and improving the risk management system associated with this class of drugs. It also shows that less frequently used anti-infectious drugs should be managed with greater caution. Anti-infectious stewardship programs should also consider ratios of medication errors for anti-infectious drugs used in order to improve patient safety and optimize use of drugs.

[Pilot study evaluating the ratio of adverse drug reactions related to antimicrobials over their consumption in 2012-2013]. / Étude pilote permettant de calculer le ratio d'effets indésirables médicamenteux par 10 000 doses définies journalières et 10 000jours de traitement d'anti-infectieux en 2012-2013.

OBJECTIVES: As part of our antimicrobials stewardship program, we were interested in the use of antimicrobials and prevalence of adverse drug reactions associated with the use of these drugs. METHODS: The retrospective and descriptive study was conducted over a one year-period between April 1st 2012 and March 31st 2013 in a mother-child Hospital. We determined the ratio: number of adverse drug reactions over 10,000 defined daily dose or 10,000days of therapy. We identified the ratios higher than average for which the confidence interval did not cross the calculated average. The severity of the adverse drug reactions was codified using the Common Terminology Criteria for Adverse Events. RESULTS: We found 570 adverse drug reactions including 100 (17.5%) adverse drug reactions related to antimicrobials during the financial year 2012-2013. It represented 96 patients. Thus, five antimicrobials, for which the confidence interval does not cross the calculated average value, may be targeted in risk management because they have a higher ratio than average: piperacillin (290 [113-722]), valganciclovir (244 [43-1260]), ceftriaxone (114 [56-234]), acyclovir (76 [26-220]) and liposomal amphotericin B (72 [20-258]). CONCLUSION: In a mother-child university hospital, we calculated a ratios of 19 [15-23] and 13 [10-15], it allows us targeting some antimicrobials in our approach to prevention and management of adverse drug reactions.