Impact of lack of knowledge on risk perception and protective practices of home nurses handling antineoplastic drugs.

Introduction: Health care workers handling antineoplastic drugs (ADs) are at risk of carcinogenic, mutagenic and reproductive toxic risks (CMR). The aim of this study was to assess the impact of the lack of knowledge (K) on risk perception (P) and on protective practices (PP) related to the handling of home-based chemotherapy (HC) by home nurses. Methods: This study was conducted in Normandy among home nurses. A questionnaire was developed to explore the K, P and PP related to handling ADs by home nurses working with four different providers from two hospitals. Results: Among the 28 home nurses included, 25.93% had received initial training on the specific treatment of ADs, 48.15% scored below average on risk management K, 52.00% scored below average on personal PP. Conclusion: This study reveals the importance of adapted and regular training on the handling of ADs. It will help develop a climate of safety and reinforce adherence to wearing personal protective equipment to protect health care workers from contamination.

Impact of low- and high-risk operators handling irinotecan on the blood contamination of health care workers in oncology day care units.

INTRODUCTION: Health care workers handling antineoplastic drugs (ADs) are at risk of mutagenicity and adverse reproductive effects. Despite protective equipment and AD handling guidelines, AD levels are still detected in caregivers in oncology units. This study attempted to assess blood contamination by irinotecan and its metabolites in all health care workers in oncology day hospital units according to activities specific to each employment category. METHODS: The study was performed at two different hospitals: a university hospital and a comprehensive cancer centre. Forty-four participants were categorized according to their daily activity as a high-risk operator (29 nurses/ward aides and 5 cleaning staff) and a low-risk operator (7 doctors and 3 secretaries). The collected blood samples were subjected to UHPLC-MS/MS. The plasma and red blood cell (RBC) levels of irinotecan and its metabolites (SN-38; APC) were determined using a validated analytical method detection test. RESULTS: Two hundred sixty-four assay results were collected (132 plasma results and 132 RBC results). The comparison between low- and high-risk operator-contaminated workers was not significant (18.33% positive results in low-risk operators vs. 25.98% positive results in high-risk operators; P = 0.22). This homogeneity showed overall contamination within the unit. Positive results were obtained in 21.43% of physicians, 11.11% of secretaries, 25.86% of nurses/ward aides and 26.67% of cleaning staff. These results could be explained by the lack or failure of personal and collective protective equipment. A lack of protection and inadequate decontamination procedures can result in surface contamination. CONCLUSIONS: This study evaluated blood contamination with irinotecan and its metabolites in health care workers from day hospital care units. Among the 24.24% of contaminations observed in care units, the difference between low- and high-risk operator contamination was not significant (P = 0.22). The impact on blood contamination found is the same between low- and high-risk caregivers. This implies that the protective precautions associated with the handling of anticancer drugs must therefore be followed by all staff, including those believed to be at low risk of exposure.

[Quality management of the experimental health products circuit in hospital pharmacies: National inventory and proposed standardised tools]. / Management de la qualité du circuit des produits de santé expérimentaux dans les pharmacies hospitalières : enquête nationale et développement d'outils standardisés.

OBJECTIVES: Carry out a national inventory of the current situation regarding the quality management of the investigational health products circuit, to develop adapted standardised tools. METHODS: A survey of 76 questions, developed by a regional working group, was conducted among clinical research pharmacists in French facilities. Tools were developed to meet the identified needs and validated by participating pharmacists, using the Delphi method. The consensus was defined by achieving a score above 80% on relevance, clarity and evaluability. RESULTS: Among 94 pharmacists participating in the survey, 88 were interested in standardised tools. The score for the implementation of a quality approach depended on the type of health facility (P<0.0005) and increased with the number of active trials (P<0.0005). All nine proposed tools were useful for over two thirds of pharmacists, but the self-assessment and audit grids have been prioritised. Indeed, only 26% of pharmacies carried out a prior risk assessment and 14% carried out internal audits. The review of both grids led to a consensus on 89% and 97% of the criteria respectively. The validated grids include 62 and 72 criteria respectively. DISCUSSION: The quality approach of the investigational health products circuit is heterogeneous in the participating centres, with a strong need for standardised tools. The two grids are relevant tools developed by and for professionals. CONCLUSION: The tools developed will enable to optimise the quality approach by identifying the non-conformities of the investigational health products circuit.

Effect of a prospective audit with intervention and feedback on Clostridioides difficile infection management.

Background Clostridioides difficile infections are associated with morbidity and mortality in several countries. Their increasing incidence and frequent recurrence make them an urgent public health threat. The lack of adherence to international treatment guidelines for Clostridioides difficile infections is a proven mortality risk factor. Objective To evaluate long-term prescribers' adherence to recommendations on the management of Clostridioides difficile infections and its impact on clinical outcomes after an educational and Clostridioides difficile-prospective audit with intervention and feedback period. Setting All patients admitted to a 1500-bed university hospital with positive Clostridioides difficile tests identified were included. Methods Data were collected retrospectively over a baseline period (May-November 2014) and prospectively over a Clostridioides difficile-prospective audit with intervention and feedback period (November 2015-May 2016) and an observation period (November 2017-September 2018). All Clostridioides difficile cases were reviewed by a Clostridioides difficile-prospective audit with intervention and feedback team composed of pharmacists, an infectious diseases specialist and a microbiologist to obtain a complete overview of patient records in each area of expertise. Main outcome measures Percentage of conformity to the protocol, percentage of recovery at 10 days and percentage of relapse, as well as Clostridioides difficile incidence and percentage of Fidaxomicin use. Results A total of 183 patients were included over the three periods. A significant improvement in conformity to the local protocol was observed between the intervention period (23.9%) and the observation period (67.3%) (P < 10-3). Fidaxomicin prescriptions increased significantly (P = 0.006). Clinical outcomes improved significantly with an increase in the percentage of recovery at 10 days (P = 0.001) and a decrease in the percentage of relapse (P = 0.016). The Clostridioides difficile incidence rate improved significantly to 1.3 per 10,000 patient-days during the observation period. Conclusion This study shows the lasting effect of an educational and Clostridioides difficile-prospective audit with intervention and feedback period on prescribers' adherence to recommendations and a significant impact on clinical outcomes.

Does equipment change impact blood contamination with irinotecan and its two major metabolites in a centralized cytotoxic pharmacy unit?

BACKGROUND: Antineoplastic drugs exposure is a major problem for caregivers' health. The aim of this study is to assess blood contamination with irinotecan and its two metabolites in a centralized pharmacy unit for cytotoxic drug preparations workers before and after protective equipment changes. METHODS: The study took place in a university hospital centralized pharmacy unit for cytotoxic drug and was performed in two parts, before (Round 1: R1) and after equipment changes (Round 2: R2). Collection of pharmacy staff blood samples was performed in UHPLC-MS/MS. Plasma and red blood cell irinotecan and its metabolites (SN38; APC) were determined with a validated analytical method detection test. RESULTS: A total of 15/36 (41.6%) assays were positive in R1 and 16/72 (22.2%) in R2 with a significant decrease between periods (P = 0.035). For plasma dosages, no difference between the two periods was found (P = 0.71); respectively 4/18 (22.2%) assays were positive in R1 and 6/36 (16.6%) in R2. For red blood cells dosages, a significant decrease between periods was found (P = 0.01); respectively 11/18 (61%) were positive in R1 and 10/36 (27.8%) in R2. CONCLUSIONS: These dosages make it possible to have the very first evaluation for plasma and red blood cell contamination with irinotecan and its metabolites in the context of equipment changes, both at individual and collective levels. This work would help to protect health workers from the potential risks represented by these molecules, especially by revealing a contamination of workers in order to objectify the results of exposure.

Subcutaneously administered antibiotics.

The subcutaneous route is a widely used route of administration in routine clinical practice, particularly in elderly patients, when the intravenous route cannot be used. This review of the literature highlights the lack of randomized studies and the lack of pharmacokinetic data on the use of this route of administration. Three antibiotics administered subcutaneously can be used for severe infections, with acceptable pharmacokinetic and pharmacodynamic data, when the intravenous administration is not possible: ceftriaxone, ertapenem, and teicoplanin.

Assessing the relevance of carbapenem prescriptions by an antibiotic stewardship team.

OBJECTIVES: To assess the level and factors of compliance of carbapenem prescriptions with guidelines and to determine the impact of an antibiotic stewardship team in a university hospital. PATIENTS AND METHODS: Five-month prospective study in the intensive care, surgery, and medicine units to measure the compliance of carbapenem prescriptions with guidelines from French scientific societies; compliance was assessed by an infectious disease specialist warned by the pharmacy, and the prescribers' compliance with the infectious disease specialist's advice was then assessed. RESULTS: One hundred and four treatment initiations for 94 patients were included. Prescriptions were mostly empirical (64%), for pulmonary (35%), urinary tract (23%), and intra-abdominal (17%) infections. Prescriptions were mostly made in an intensive care unit (50%), by a junior physician (66%), with the use of imipenem (74%), and were followed by an objective reassessment (80%). Compliance with guidelines (82%) was significantly higher for empirical than documented prescriptions (91% vs 65%, P<0.001). Compliance was higher in intensive care units than medicine units (87% vs 61%, P=0.037). No change in the compliance rate was observed during the study. Compliance with the infectious disease specialist's advice (68%) improved, although not significantly (P=0.066). CONCLUSIONS: Because of a higher than expected compliance of carbapenem prescriptions with guidelines and a lower than expected inclusions in the study, we did not show any impact. The diffusion of guidelines and long-term control of carbapenem prescriptions seem to be possible and necessary in hospitals to limit their ecological impact.

[Pharmaceutical system of fecal microbiota transplantation: Heterogeneous practices]. / Circuit pharmaceutique, transplantation de microbiote fécal : Des pratiques hétérogènes.

OBJECTIVE: To describe current pharmaceutical practice in French hospitals regarding fecal microbiota transplantation in terms of prescription, preparation and compounding, as well as local legislation. MATERIAL AND METHODS: A national survey was conducted at 28 French university hospital centers followed by the sending of a GoogleForm® questionnaire from June to August 2018 in the 16 respondent centers either performing or subcontracting fecal microbiota transplant. RESULTS: All hospitals performing or subcontracting fecal transplant (n=16,%57) report prescription indication of recurrent Clostridium difficile infection treatment, and 6 of them also as part of a clinical trial protocol. In hospitals performing fecal transplant themselves (n=11), the number of pre-donation consultations with donors varies from one (n=6) to two (n=5). Fecal sample is collected at the donor's home in 45% of cases. Route of administration for transplant is either naso-gastric administration (n=4), rectal (n=4) or both (n=5). Fecal samples for transplant are compounded either in the hospital pharmacy (n=73%) or in the laboratory (27%). Thawing methods include refrigeration between 2-8°C (50%), room temperature (25%) and water bath (25%). Billing system and reporting to health authorities are highly heterogeneous from one hospital to another. CONCLUSION: This survey shows significant pharmaceutical practice heterogeneity within French hospitals regarding fecal microbiota transplantation despite the existence of national and European recommendations.

[Professional practice evaluation of injectable drug preparation and administration in neonatology]. / Évaluation des pratiques de préparation et d'administration des médicaments injectables en néonatalogie.

AIM: Adverse drug events are a daily concern in neonatology departments. The aim of this study was to assess the professional practices of preparation and administration of injectable forms of medications in neonatology. MATERIALS AND METHODS: A professional practice evaluation with regard to the preparation and administration of various injectable forms of medications in different neonatology units within a given department was conducted by a pharmacy intern based on an assessment grid comprising ten criteria. Following an initial assessment, the results were presented to the care team, which validated the corrective measures put forward by a multiprofessional work group. A second assessment was conducted following the same methodology. RESULTS: Fifty of the department's 76 pediatric nurses were assessed during the first round of the audit and 21 during the second round. Two improvement priorities were identified: taking account of the dead volume of medication in needles and syringe hubs, together with complete identification of syringes used to administer medication. During the second round, these two aspects were improved, progressing from 38% to 100% and from 59% to 89%, respectively. CONCLUSION: To improve drug administration in neonatology and consequently, to improve patient safety, professional practice evaluation is an essential tool that requires close collaboration between the paramedical team, physicians and pharmacists. Its main value lies in the mobilization of the entire team around the subject in question, hence generating improved understanding and application of corrective measures.

Non-carbapenem therapy of urinary tract infections caused by extended-spectrum ß-lactamase-producing Enterobacteriaceae.

PURPOSE: We determined the prevalence of ESBL Enterobacteriaceae in urinary tract infections among inpatients, identified risk factors of acquisition, and evaluated the effectiveness of alternatives to carbapenems. METHODS: The clinical, microbiological, and therapeutic data as well as the outcomes were recorded for all ESBL-E positive urine samples for three months. RESULTS: Thirty-one (4%) of the 762 Enterobacteriaceae positive cultures were ESBL producers. The predisposing conditions for being infected with those strains were: immunodepression (61%), recent hospitalization (52%), recent antibiotic therapy (52%), and urinary catheterization (61%). 19% of infections were community acquired. The seven cases of acute pyelonephritis and five of prostatitis were treated with piperacillin-tazobactam (5), fluoroquinolones (4), ceftazidime (2), or carbapenems (only 1) after specialized advice. Four (33%) patients relapsed at week 10: three were immunodepressed and three presented with bacteremia. CONCLUSIONS: Alternatives to carbapenems (especially piperacillin-tazobactam) seem to be a good option for non-bacteremic UTI in immunocompetent patients.

Influence of the introduction of a solubility enhancer on the formulation of lipidic nanoparticles with improved drug loading rates.

The objective of the present paper is to develop lipidic nanoparticles (NP) able to encapsulate drugs presenting limited solubility in both water and lipids, with high loading rates, and without using organic solvents. In this goal, a solubility enhancer, a macrogolglyceride (Labrasol), was incorporated in a formulation process based on a low-energy phase inversion temperature method. From electrical conductivity through the temperature scans, it appears that presence of Labrasol does not prevent the phase inversion, and it takes part in the microemulsion structuring, probably of bicontinuous type. After screening pseudo-ternary diagrams, the feasibility of NP was established. From results of a partial least square analysis, it appears that these NP present a core-shell structure where Labrasol is well encapsulated and contributes to the formation of the oily liquid core of the NP. The diameter of the NP, assessed by dynamic light scattering, remains kinetically stable. These NP, smaller than 200 nm, spherical in shape as attested by cryo-transmission electron micrographs, are able to encapsulate a tripentone, a new anticancer agent, with drug loading rates up to 6.5% (w/w). So highly drug-loaded lipidic nanocarriers were developed without using the slightest organic solvent trace, and making it easily possible dose adjustment.

Influence of carrier on the performance of dry powder inhalers.

The aim of this work is to study carriers which can become alternatives to monohydrate lactose in dry powder inhalers and to consider particle parameters that influence adhesion between drug and carrier in dry powder inhalers. Different forms of mannitol, lactose and maltitol were mixed with either terbutaline sulphate or formoterol fumarate. The blends were submitted to different adhesion tests where drug detachment from the carrier was obtained either through mechanical vibration or by aspiration. Parameters like particle shape, roughness, amorphous content and cristalline form may affect interactions between drug and carrier. In our case, crystallized forms of the carrier offered lower adhesion but better release of the active ingredient than spray-dried forms. The crystallized mannitol produced maximal fine particle dose. The blends of the mannitols and the two active ingredients gave different results. The two techniques used to assess the adhesion of drugs to carrier particles provide complementary information about drug/carrier interactions and detachment. The mechanical sieving allows to assess blend stability and the air-jet sieving makes it possible to determine how easily the drug separates from carrier. For the drugs tested, the results of fine particle doses are in agreement with the Alpine air-jet sieve results. The tests used are helpful for the choice of a new carrier in the field of the development of new carriers for dry powder inhalers.