[First French-speaking days of users of decision support system in clinical pharmacy: Feedback and perspectives]. / Premières journées francophones des utilisateurs de système d'aide à la décision en pharmacie clinique : retour d'expériences et perspectives.

Clinical decision support systems (CDSS) are tools that have been used for several years by clinical pharmacy teams to support pharmaceutical analysis, with a perspective of contributing to the quality of care in collaboration with the other health care team members. These tools require both technical, logistical and human resources. The growing use of these systems in different establishments in France and in Europe gave birth to the idea of meeting to share our experiences. The days organized in Lille in September 2021 aimed at proposing a time of exchange and reflection on the use of these CDSS in clinical pharmacy. A first session was devoted to feedback from each establishment. These tools are essentially used to optimize pharmaceutical analysis and to secure patient medication management. This session outlined the clear advantages and common limitations of these CDSS. Two research projects were also presented to put the use of these tools into perspective. The second session of these days, in the form of workshops, addressed 4 themes that surround the implementation of CDSS: their usability, the legal aspect, the creation of rules and their possible valorization. Common problems were raised, the resolution of which requires close collaboration. This is a first step proposing a beginning of harmonization and sharing that should be deepened in order not to lose the dynamics created between the different centers. This event ended with the proposal to set up two working groups around these systems: the creation and structuring of rules for the detection of risk situations and the common valorization of the work.

[Evaluation of simulation-based training program intended to improve interprofessional communication skills of community pharmacy and general medicine students]. / Formation des étudiants en pharmacie d'officine et en médecine générale à la communication interprofessionnelle : évaluation d'un programme de simulation.

OBJECTIVES: The objective of this work is to assess the impact of a simulation session on the ability of pharmacy and medicine students in general practice to communicate in the resolution of patient-facing situations. METHODS: The evaluation of the impact of the session on the representation of the professions used a questionnaire to be completed before and after the session by the students. The evaluation of the impact of the session on the perception of communication and associated skills was based on an audio recording of the debriefings, which, after transcription and thematic analysis, was used as a preliminary analysis for the drafting of a questionnaire proposed the following year. This questionnaire focused on the issues of interprofessional communication and on the seminar process. RESULTS: During the 2018 and 2019 seminars, 518 students attended, 39% were pharmacy students (n=201) and 61% were medical students (n=317). The majority of medical students initially responded that physician-pharmacist communication was confraternal and rare. More pharmacy students felt that the quality of the physician-pharmacist relationship was poor. However, there was a marked improvement for all students on this aspect of communication after the seminar. Both groups also generally agreed that this relationship could be improved. CONCLUSIONS: The evaluation shows that an interprofessional simulation program improves the ability of pharmacy and general practice students to communicate in patient-facing situations.

[Development of a methodological guide on the implementation of a pharmaceutical decision support system: Feedback from a French university hospital]. / Élaboration d'un guide méthodologique sur l'implantation d'un système d'aide à la décision pharmaceutique : retour d'expérience d'un centre hospitalier universitaire français.

OBJECTIVE: Develop a methodological guide on the implementation of a PDSS (pharmaceutical decision support system). METHOD: Observational study, retrospective conducted at Lille University Hospital from May 2017 to December 2020, corresponding to the period of implementation and then use of the software. The different phases of the project are described as well as the methodology at each stage. RESULTS: Four stages seem necessary for the establishment of the PDSS: reflection and preparation of the project, contracting, implementation, use and evaluation. Based on these results and our experience, in particular the difficulties encountered, a methodological diagram of the various steps necessary for the implementation of a PDSS is proposed. CONCLUSION: The establishment of a PDSS, especially in the field of clinical pharmacy, is a long multidisciplinary process. Several steps, from project preparation to production start-up are necessary. Planning the different stages is essential for the proper implementation of the SADP so that the installation is as efficient as possible.

[Clinical pharmacy in four French-speaking university hospitals, integration and supervision of clinical pharmacists: An exploratory study]. / Pharmacie clinique au sein de quatre CHU de la francophonie, intégration et encadrement des pharmaciens cliniciens : une étude exploratoire.

BACKGROUND: Pharmacy practice continues to evolve worldwide. The clinical role of the pharmacists is increasingly recognized and their integration into the health care team is irreversible. Despite this progress, there are still a wide disparity in the scope of practice provided by hospital pharmacists around the world. This disparity can be attributed to a variety of factors. OBJECTIVES: The primary objective is to describe the organization of clinical pharmacy in four university hospitals in four French-speaking countries. The secondary objective is to identify similarities and differences and to identify perspectives for the future. METHODS: This is an exploratory cross-sectional descriptive study. The study targeted a university hospital (CHU) in France, Belgium, Switzerland and Canada (Quebec). A volunteer expert pharmacist involved in the management of clinical pharmacy at each hospital was approached at the initiative of a team member. A working group of five pharmacists was set up. RESULTS: During the year 2021, the group met virtually on ten occasions. Although all institutions have an academic mission, they have very different numbers of beds and volumes of activity. The number of pharmacists is also very different (0.83 FTE pharmacist/1000 admissions in Belgium, 0.22 in France, 0.59 in Switzerland and 2.39 in Quebec). In all countries, pharmacists provide clinical pharmacy services to patients in a centralised or decentralised manner, including, to various extent, prescription analysis, medication reconciliation, pharmaceutical interviews and discharge plans. CONCLUSIONS: Clinical pharmacy practice is very heterogeneous in a selection of four French-speaking teaching hospitals. Identification of similarities and differences may inspire improvements in the organization of clinical pharmacy activity. This work has contributed to the establishment of a community of practice on clinical pharmacy in the French-speaking world.

[Standardized computer recording of clinical pharmacy procedures in health care institution: Feedback and evaluation of potential economic value]. / Enregistrement informatique normalisé des actes de pharmacie clinique en établissement de santé : retour d'expérience et évaluation de la valorisation économique potentielle.

Clinical pharmacy procedures are clearly defined by the French society of clinical pharmacy. However, clinical pharmacists do not have efficient tools for their traceability. This need has increased following the publication of the instruction on the day hospital management of patients. Indeed, the action of the clinical pharmacist is included in it. In order to improve our traceability of clinical pharmacy acts and to take advantage of the implementation of the instruction, we worked with the medical information department to integrate our activity into their business software and to model the pathways valued by the intervention of the clinical pharmacist in outpatient care and in day hospital.

[Treatment options for drug-induced sialorrhea: Prescribing guidelines]. / Prise en charge de l'hypersialorrhée iatrogène : revue de la littérature et recommandations pratiques.

OBJECTIVES: Drug-induced hypersalivation is a frequent drug adverse event of psychotropic drugs. This excess salivary pooling in the mouth can cause an impairment of a patient's quality of life leading to low rates of medication adherence. The optimal management of hypersalivation is thus crucial to improve patient care. To date, no recommendations for limiting drug-induced hypersalivation have been published. In this study, we conducted a systematic review to investigate the effectiveness of interventions aimed at reducing drug-induced hypersalivation. METHODS: Treatment of drug-induced sialorrhea based on case reports and clinical studies were sought in May 2021 from PubMed, Google Scholar and Science Direct (keywords : « treatment ¼, « hypersalivation ¼, « induced ¼, « drug ¼, « clozapine ¼). Articles published between 1966 to May 2021 on the treatment of drug-induced hypersalivation were included in this study. RESULTS: Sixty-seven articles were selected in this narrative review. First, patient education associated with non-drug related management are essential to improve the compliance to drugs inducing hypersalivation. The non-drug related management should be initiated with an increase in the frequency of swallowing with chewing gum. In the case of ineffectiveness, the dosage of drug responsive of sialorrhea can be adjusted according to the patient's response and his/her medical history (i.e. reducing the dose or splitting the daily dose). Finally, if the problem persists, a symptomatic treatment can be added according to the type of sialorrhea (diurnal or nocturnal), preferred galenic by patient, tolerance and availability of drugs. Several drugs have been tested to reduce hypersalivation induced by clozapine (61/67), risperidone (3/67), quetiapine (2/67) and aripiprazole (2/67). Among the 63 articles targeting a specific corrective treatment, anticholinergic agents were most described in the literature (41 cases out of 63) with atropine, glycopyrrolate and scopolamine (6/41 each). Other agents were described as clinically effective on hypersalivation: dopamine antagonists (9/63) with amisulpride (5/9), alpha-2-adrenergic agonists (5/63) with clonidine (3/5), botulinic toxin (4/63), and terazosine, moclobemide, bupropion and N-acetylcysteine (for each 1/63). CONCLUSIONS: In the case of drug-induced hypersalivation, after failure of non-drug therapies and dosage optimization of the causative treatment, an anticholinergic drug can be initiated. In case of insufficient response, the different treatments presented can be used depending on the galenic form, tolerance and access to those medications. The assessment of the risk-benefit balance should be systematic. The heterogeneity of the studies, the little knowledge about the pharmacological mechanism of saliva flow modulation and the unavailability of corrective drugs are different factors contributing to the complexity of therapeutic optimization.

[Implementation of a multi-interventional approach to improve medication safety in older hospitalized patients: Feasibility and impact on 30-day rehospitalization rate]. / Mise en place d'une procédure multi-interventionnelle de prise en charge médicamenteuse chez la personne âgée hospitalisée : faisabilité et efficacité sur la réhospitalisation à 30jours.

BACKGROUND: The impact of a multi-interventional approach for medication safety (MIMS) on rehospitalization rate have been inconstant in the literature. This would be due to difficulty in implementing the interventions and insufficient information transmission at discharge. The purpose of this study was to determine the effect of a MIMS on the 30-day rehospitalization rate after discharge from an acute geriatric unit (AGU). METHOD: This was a single-center interventional randomized controlled trial that included patients hospitalized in an AGU and were at least 75 years old. The intervention group benefited from a MIMS including medication reconciliation at admission and at discharge, medication review, and standardized transmission of hospital's medication changes sent to community practitioners (general practitioners and pharmacists) at discharge. The control group benefited from the usual approach applied in the AGU. RESULTS: One hundred nine patients (mean age 87,5±6,1 years) were included. At intention-totreat analysis, the rehospitalization rate was 30% in the intervention group and 15,2% in the control group. The difference was non-significant before and after adjustments (P=0,27 and 0,28 respectively). However, the intervention protocol was not effectively completed in 40% of patients in the intervention group and no intervention was performed in 10%. CONCLUSION: The implementation of a MIMS in an AGU showed a non-significant decrease in the number of rehospitalizations. Other indicators should be analysed, such as the reason for rehospitalisation or the maintenance of treatment at 30 days.

[Evaluation of the training of clinical pharmacy residents in prescription analysis using an ergonomic approach]. / Évaluation de la formation des internes en pharmacie clinique à l'analyse des prescriptions selon une approche ergonomique.

OBJECTIVES: To perform an ergonomic intervention using the methodology of the analysis of the activity of the training process of clinical pharmacy residents in the analysis of prescriptions. METHODS: The evaluation was carried out over two semesters: from May to October 2016 (first study) and from November 2016 to April 2017 (second study). The interviews and observations were conducted by an ergonomist who is an expert in this type of evaluation. The first study was based on observations of the training process and interviews at different time. The second study allowed to support pharmacists and evaluate the changes following the recommendations of the previous study. RESULTS: A total of 6 and 9 residents participated in the first and second study, respectively. During the first study, 6 difficulties were raised which allowed implementation decisions. Feedback from residents on the training process was generally positive for the first part of the training but negative for the last part. The average number of fears expressed by the residents was higher at the beginning (2.9 fears) than at the end (1 fear). CONCLUSIONS: The training process has been adapted to the expectations and feelings of the residents. Follow-up at the beginning and throughout the internship was essential. The next stage of this work will be to evaluate the contribution of the dashboards for monitoring clinical pharmacy skills in the new degree for hospital pharmacy.

The clinical pharmacist's role in enhancing the relevance of a clinical decision support system.

BACKGROUND: Clinical decision support systems (CDSSs) can improve the quality of patient care by helping physicians to review their prescriptions and thus to optimize drug treatments. Nevertheless, the "alert fatigue" brought on by a large number of irrelevant alerts can decrease a CDSS's effectiveness and thus clinical value. Involving a clinical pharmacist in the development and management of a CDSS can reduce the number of irrelevant alerts presented to physicians. Clinical pharmacists screen alerts and suggest PIs for physicians, corresponding to any proposed therapeutic change about health products, only for relevant alerts could improve the relevance and the acceptance of the information given to physicians about the risks faced by their patients. OBJECTIVE: To assess the value of involving clinical pharmacists in the development and maintenance of decision support rules for generating alerts and pharmaceutical interventions (PIs) and to describe the level of acceptance of these PIs by the physicians. METHOD: In a retrospective, single-centre study, we evaluated the number of PIs accepted from alerts generated by the CDSS when a clinical pharmacist had developed and managed this tool. During the first 7 months of development of the CDSS, a clinical pharmacist analyzed alerts triggered by the CDSS according to its technical validity and pharmaceutical relevance. Lastly, for alerts that led to a PI, the level of acceptance by physicians was documented. RESULTS: During the study, 1430 alerts were analysed: 186 (13%) were considered to be technically invalid - mainly due to the characteristics of the interface. Of the 1244 (87.0%) technically valid alerts, 353 (24.6%) were pharmaceutically relevant and led to a PI. The three main causes of pharmaceutical irrelevance were a lack of specificity in the CDSS (70.8%), lack of relevance with regard to the ward's habits (15.6%), and the pharmacist's decision to recommend monitoring for the patient rather than sending a PI immediately (10.8%). 64.6% of the submitted PIs were accepted by the physicians. CONCLUSION: The standardized analysis of alerts by a clinical pharmacist appears to be a good way of improving the development of CDSS by limiting the generation of irrelevant alerts and the latter's transmission to physicians. The involvement of a clinical pharmacist in the development and implementation of a CDSS appears to be novel and may help to optimize drug treatment.

A new pharmacokinetic model for 90Y-ibritumomab tiuxetan based on 3-dimensional dosimetry.

Monoclonal antibodies (mAbs) are key components in several therapies for cancer and inflammatory diseases but current knowledge of their clinical pharmacokinetics and distribution in human tissues remains incomplete. Consequently, optimal dosing and scheduling in clinics are affected. With sequential radiolabeled mAb-based imaging, radiation dosing in tissues/organs can be calculated to provide a better assessment of mAb concentrations in tissues. This is the first pharmacokinetic model of 90Y-Ibritumomab tiuxetan (90Y-IT) in humans to be described, based on three-dimensional (3D) dosimetry using single-photon emission computed-tomography coupled with computed-tomography. 19 patients with follicular lymphoma were treated initially with 90Y-IT in the FIZZ trial. Based on a compartmental approach individualising the vascular compartment within studied organs, this study proposes a reliable pharmacokinetic (PK) five-compartment model replacing the currently used two-compartment model and constitutes a new direction for further research. This model provides exchange constants between the different tissues, Area Under the Curve of 111In-IT in blood (AUC) and Mean Residence Time (MRT) that have not been reported so far for IT. Finally, the elimination process appears to occur in a compartment other than the liver or the spleen and suggests the metabolism of mAbs may take place mainly on the vascular compartment level.

Prospective assessment of patients' knowledge and informational needs and of surgeon-to-patient information transfer before and after knee or hip arthroplasty.

BACKGROUND: Patients are playing an increasingly large role in their own management and must therefore receive clear, complete, and comprehensible information. In the field of hip and knee arthroplasty, little is known about the level of patient knowledge and effectiveness of surgeon-to-patient information transfer. We therefore designed a prospective observational study with the objective of assessing four factors: patient knowledge during management, quality of information transfer, informational needs, and factors associated with the level of knowledge. HYPOTHESIS: The level of patient knowledge changes during the management process. PATIENTS AND METHODS: A prospective single-centre study was conducted between January 2014 and March 2015 during the outpatient visits and inpatient stays of 63 patients who underwent arthroplasty of the hip (n=36) or knee (n=27). A single observer attended all patient visits and recorded the information provided by the surgeon. Each patient completed a self-questionnaire after the outpatient visit (T1), at admission (T2), and at discharge after surgery (T3). Semi-quantitative scores were used to assess knowledge and informational needs. The effectiveness of information transfer was evaluated by comparing the information provided by the surgeon to the replies made by the patients. RESULTS: The mean overall knowledge score (on a 0-42 scale) increased from 17.22±6.33 at T1 to 19.44±6.89 at T3 (P=0.0028). In contrast, knowledge about complications was better at T1 than at T3 (2.67±1.98 vs. 2.19±1.91; P<0.05). Agreement between information given by the surgeon and replies made by patients varied across items from 23% to 100%. The mean informational needs score (on a scale from 0 to 21) ranged from 3.67 to 4.83 and was higher at T3 than at T2 (4.83±3.77 vs. 3.67±4.86; P=0.03). The proportion of patients who wanted written information was higher at T3. Most patients sought information before the outpatient visit. At each step of the management process, the main areas about which the patients wanted information were the surgical procedure, the rehabilitation programme, and the prosthesis. Several socio-demographic or management-related factors influenced the level of knowledge. Thus, older age and lower educational attainment were associated with lower knowledge scores, whereas previous lower-limb orthopaedic surgery and amount of information provided by the surgeon were associated with higher knowledge scores. Knowledge scores were not associated with being employed vs. retired, gender, replacement of a hip vs. a knee, the surgeon, or being accompanied by another person. DISCUSSION: Our study is original in that we assessed changes in patient knowledge during the management process for hip or knee arthroplasty. The level of patient knowledge was fairly low and varied considerably across individuals and time points in the management process. These data highlight the importance of providing patients with information throughout their management and particularly at discharge, when the desire for information seems greatest. LEVEL OF EVIDENCE: IV, prospective observational study with no control group.

Factors Generating Glucose Degradation Products In Sterile Glucose Solutions For Infusion: Statistical Relevance Determination Of Their Impacts.

Sterilising glucose solutions by heat promotes the generation of a large number of glucose degradation products (GDPs). It has been shown that high levels of GDPs may result in Advanced Glycation End products that have an impact on cellular homeostasis and health in general. If data is available for peritoneal dialysis solutions, little has been published for glucose infusion fluids. It is essential to identify the parameters causing the formation of GDPs and so limit the risk of exposing patients to them. After quantifying both 5-hydroxymethyl-2-furfural, considered as an important indicator of degradation, and 2-furaldehyde, an ultimate GDP of one degradation pathway, in marketed solutions, the aim of this work is to build a model integrating all the parameters involved in the formation rates of these two GDPs: supplier, glucose amount, container material, oxygen permeability coefficient and time-lapse since manufacture. Our results show a good logarithmic relationship between GDP formation rates and time-lapse since manufacture for both GDPs. The amount of GDPs in the glucose solutions for infusion depends on the initial glucose amount, the polymer of the container, the time elapsed since manufacturing and the supplier.

[The roles and the impacts of pharmacists in the management of medical devices at the hospital: A literature review]. / Rôles et retombées des pharmaciens dans la gestion des dispositifs médicaux en établissement de santé : une revue de littérature.

OBJECTIVES: Identify the training profile and the published evidences about the roles and the impacts of hospital pharmacists in medical devices. METHODS: A literature review was conducted using Google, Google Scholar and Pubmed for 1990-2016 associated with a manual search conducted in three non-indexed pharmaceutical journals for 2000-2016. RESULTS: The analysis of training programs available did not allow us to identify a specific training profile. A total of 72 articles related to the roles and the impacts of the pharmacist were identified, 52 of which came from non-indexed journals. Those articles did not deal specifically about the roles and the impacts of pharmacist; however, articles were analyses for three spheres including the referencing of medical devices (n=36), the evaluation (n=19) and the distribution system (n=13). CONCLUSIONS: French pharmacists have many theoretical and practical training opportunities. There are a few articles describing precisely the roles and the impacts of hospital pharmacists in medical device. It appears urgent to better document this activity in professional and indexed literature.

Analysis of plasticizers in PVC medical devices: Performance comparison of eight analytical methods.

A wide variety of medical devices (MDs) used in hospitals are made of flexible plasticized polyvinylchloride (PVC). Different plasticizers are present in variable amounts in the PVC matrix of the devices and can leach out into the infused solutions and may enter into contact with the patients. The ARMED1 project aims to assess the migration of these plasticizers from medical devices and therefore the level of exposure in patients. For the first task of the project, eight methods were developed to directly detect and quantify the plasticizers in the PVC matrix of the MDs. We compared the overall performances of the analytical methods using standardized and validated criteria in order to provide the scientific community with the guidance and the technical specifications of each method for the intended application. We have shown that routine rapid screening could be performed directly on the MDs using the FTIR technique, with cost-effective analyses. LC techniques may also be used, but with limits and only with individual quantification of the main plasticizers expected in the PVC matrix. GC techniques, especially GC-MS, are both more specific and more sensitive than other techniques. NMR is a robust and specific technique to precisely discriminate all plasticizers in a MD but is limited by its cost and its low ability to detect and quantify plasticizer contamination, e.g. by DEHP. All these results have been confirmed by a real test, called the " blind test " carried out on 10 MD samples.

Migration of plasticizers from PVC medical devices: Development of an infusion model.

Alternatives to DEHP plasticizers are used in various PVC medical devices (MD) for infusion. As they are able to migrate from these MDs into infused solutions, they may come into contact with patient. Different and specific clinical parameters influence their migration in at-risk situations such as infusion. In contrast to the regulations for Food Contact Materials (MCDA), there is currently no acceptable migration limits for the use of these plasticizers in clinical situations. In order to assess their migration, and thus control the risks linked to these MDs, we developed a migration model for the plasticizers in MDs. To this end, we applied a cross-disciplinary methodological process similar to that used in the food-processing industry, taking into account the MDs' conditions of use in clinical practice. The simulation model is simple and includes the following conditions: MD should be tested with a dynamic method that respects our established clinical assumption (2 L of infused solutions via 13 dm(2) of plasticized PVC), at a temperature of 25 °C and during 24 h of contact, using a 50/50 (v/v) ethanol/water simulant. This model could be proposed as a tool for the safety evaluation of the patients' exposure risk to plasticizers from PVC medical devices for infusions.

Assessment of anti-factor Xa activity of heparin in binary parenteral nutrition admixtures for premature neonates.

An in vitro study was carried out to determine the anti-Xa activity of heparin in binary parenteral nutrition (BPN) admixtures for premature neonates in our neonatal intensive care unit (NICU) after a 24-hour infusion, as well as to assess drug interaction with a 50% glucose solution. Two types of bags were prepared: (1) BPN admixtures (composition defined in the NICU) including sodium heparin at 77 UI/mL and (2) bags containing only G50% with sodium heparin at 193 UI/mL. The anti-Xa activity of heparin was measured in bags at T0, after the 24-hour infusion and in eluates at the outlet of the infusion line after 24hours, using a validated chromogenic anti-Xa method. Comparisons of the mean concentration observed with the theoretical value for anti-Xa activity were performed with the Student t-test. Mean values of anti-Xa activity do not differ significantly from the values expected for all conditions. We found a slight variation in anti-Xa activity when infused over 24hours for both types of bags, with and without in-line filtration, showing that heparin remains stable during this infusion period in both BPN admixtures and G50%.

Migrability of PVC plasticizers from medical devices into a simulant of infused solutions.

Medical devices (MD) for infusion and artificial nutrition are essentially made of plasticized PVC. The plasticizers in the PVC matrix can leach out into the infused solutions and may enter into contact with the patients. In order to assess the risk of patient exposure to these plasticizers we evaluated the migration performance of DEHP, DEHT, DINCH, and TOTM using a model adapted to the clinical use of the MDs. Each PVC tubing sample was immersed in a simulant consisting of a mixture of ethanol/water (50/50v/v) at 40°C and migration tests were carried out after 24h, 72h, and 10 days.DEHP had the highest migration ability, which increased over time. The amount of TOTM released was more than 20 times less than that of DEHP, which makes it an interesting alternative. DEHT is also promising, with a migration level three times smaller than DEHP. However, the migration ability of DINCH was similar to DEHP, with the released amounts equaling 1/8th of the initial amount in the tubing after 24h of contact. Taking into account the available toxicological data, TOTM and DEHT appear to be of particular interest. However, these data should be supplemented and correlated with clinical and toxicological studies on plasticizers and their metabolites.

An in vitro evaluation of infusion methods using a syringe pump to improve noradrenaline administration.

BACKGROUND: International guidelines recommend noradrenaline (NA) as the vasopressor of choice to treat septic shock. The aim of this study was to determine the best way to infuse patients with NA. METHODS: The in vitro study was designed to measure NA concentration at the end of each studied assembly line. Three infusion systems used the double pump method and three single pumps, which differed as regards NA concentrations (0,2 - 0,5 - 1 mg/h), dead space volume of the devices and the use of saline. Infusion systems were compared according to the time necessary to reach an NA mass flow rate steady-state plateau after the onset of infusion or after a flow change. RESULTS: Times were significantly different between the six methods for infusing NA. The system using the double syringe method with a standard extension set was the longest to reach the steady state after the onset of infusion [40.00 min (19.57 - 49.22)]. The steady-state plateau was obtained most rapidly with the double-syringe pump systems using very low dead-space volume extension sets and single-syringe pump systems containing diluted noradrenaline at the beginning of NA infusion. CONCLUSION: A combination of a low dead-space volume extension set and a double pump method with a constant saline flow rate at 5 ml/h might be the solution to provide the most reliable NA infusion delivery.

Analytical methods for the determination of DEHP plasticizer alternatives present in medical devices: a review.

Until 2010, diethylhexylphthalate (DEHP) was the plasticizer most commonly used to soften PVC medical devices (MDs), because of a good efficiency/cost ratio. In flexible plasticized PVC, phthalates are not chemically bound to PVC and they are released into the environment and thus may come into contact with patients. The European Directive 2007/47/CE, classified DEHP as a product with a toxicity risk and restricted its use in MDs. MD manufacturers were therefore forced to quickly find alternatives to DEHP to maintain the elasticity of PVC nutrition tubings, infusion sets and hemodialysis lines. Several replacement plasticizers, so-called "alternative to DEHP plasticizers" were incorporated into the MDs. Nowadays, the risk of exposure to these compounds for hospitalized patients, particularly in situations classified "at risk", has not yet been evaluated, because migrations studies, providing sufficient exposure and human toxicity data have not been performed. To assess the risk to patients of DEHP plasticizer alternatives, reliable analytical methods must be first developed in order to generate data that supports clinical studies being conducted in this area. After a brief introduction of the characteristics and toxicity of the selected plasticizers used currently in MDs, this review outlines recently analytical methods available to determine and quantify these plasticizers in several matrices, allowing the evaluation of potential risk and so risk management.