[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.

[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.

Impact of Real-Time Therapeutic Drug Monitoring on the Prescription of Antibiotics in Burn Patients Requiring Admission to the Intensive Care Unit.

As pharmacokinetics after burn trauma are difficult to predict, we conducted a 3-year prospective, monocentric, randomized, controlled trial to determine the extent of under- and overdosing of antibiotics and further evaluate the impact of systematic therapeutic drug monitoring (TDM) with same-day real-time dose adaptation to reach and maintain antibiotic concentrations within the therapeutic range. Forty-five consecutive burn patients treated with antibiotics were prospectively screened. Forty fulfilled the inclusion criteria; after one patient refused to participate and one withdrew consent, 19 were randomly assigned to an intervention group (patients with real-time antibiotic concentration determination and subsequent adaptations) and 19 were randomly assigned to a standard-of-care group (patients with antibiotic administration at the physician's discretion without real-time TDM). Seventy-three infection episodes were analyzed. Before the intervention, only 46/82 (56%) initial trough concentrations fell within the range. There was no difference between groups in the initial trough concentrations (adjusted hazard ratio = 1.39 [95% confidence interval {CI}, 0.81 to 2.39], P = 0.227) or the time to reach the target. However, thanks to real-time dose adjustments, the trough concentrations of the intervention group remained more within the predefined range (57/77 [74.0%] versus 48/85 [56.5%]; adjusted odd ratio [OR] = 2.34 [95% CI, 1.17 to 4.81], P = 0.018), more days were spent within the target range (193 days/297 days on antibiotics [65.0%] versus 171 days/311 days in antibiotics [55.0%]; adjusted OR = 1.64 [95% CI, 1.16 to 2.32], P = 0.005), and fewer results were below the target trough concentrations (25/118 [21.2%] versus 44/126 [34.9%]; adjusted OR = 0.47 [95% CI, 0.26 to 0.87], P = 0.015). No difference in infection outcomes was observed between the study groups. Systematic TDM with same-day real-time dose adaptation was effective in reaching and maintaining therapeutic antibiotic concentrations in infected burn patients, which prevented both over- and underdosing. A larger multicentric study is needed to further evaluate the impact of this strategy on infection outcomes and the emergence of antibiotic resistance during long-term burn treatment. (This study was registered with the ClinicalTrials.gov platform under registration no. NCT01965340 on 27 September 2013.).

Does the type of parenteral lipids matter? A clinical hint in critical illness.

BACKGROUND & AIMS: An altered lipid profile is common among intensive care unit (ICU) patients, but evidence regarding the impact of different fatty acid (FA) emulsions administered to patients requiring parenteral nutrition (PN) is scarce. This study aimed to compare the plasma triglycerides (TG) response to two types of commercial lipid emulsions: a structured mixture of long- and medium-chain triglycerides (LCT/MCT) or LCTs with n-9 FA (LCT+) in ICU patients. METHODS: In this retrospective observational study conducted in a multidisciplinary ICU: two groups were defined by the type of emulsion used. Inclusion criteria were: consecutive patients on PN staying ≥4 days with one TG determination before commencing PN and at least one during PN. Recorded variables included energy intake, amount and type of nutritional lipids, propofol dose, glucose and protein intake, laboratory parameters, and all drugs received. Hypertriglyceridemia (hyperTG) was defined as TG >2 mmol/L. RESULTS: The dynamic impact of the emulsion was analyzed in 187/757 patients completing the inclusion criteria (112 LCT/MCT and 75 LCT+). The demographic variables, severity indices, diagnostic categories, and outcomes did not differ between the two groups. Seventy-seven patients (41%) presented hyperTG. Both groups received similar daily energy (1604 versus 1511 kcal/day), lipids (60 versus 61 g/day), and glucose intake (233 versus 197 g/day). There was no increase of TG concentration in those receiving the LCT/MCT emulsion compared to those receiving the LCT+ emulsion (0 and 0.2 mmol/L, respectively, p < 0.05). CONCLUSION: LCT/MCT emulsions are associated with a less pronounced increase of plasma TG levels than LCT+ emulsions.

Staphylococcus aureus carriage at admission predicts early-onset pneumonia after burn trauma.

Early-onset pneumonia (EOP) is frequent after burn trauma, increasing morbidity in the critical resuscitation phase, which may preclude early aggressive management of burn wounds. Currently, however, preemptive treatment is not recommended. The aim of this study was to identify predictive factors for EOP that may justify early empirical antibiotic treatment. Data for all burn patients requiring ≥4 h mechanical ventilation (MV) who were admitted between January 2001 and October 2012 were extracted from the hospital's computerized information system. We reviewed EOP episodes (≤7 days) among patients who underwent endotracheal aspiration (ETA) within 5 days after admission. Univariate and multivariate analyses were performed to identify independent factors associated with EOP. Logistic regression was used to identify factors predicting EOP development. During the study period, 396 burn patients were admitted. ETA was performed within 5 days in 204/290 patients receiving ≥4 h MV. One hundred and eight patients developed EOP; 47 cases were caused by Staphylococcus aureus, 37 by Haemophilus influenzae, and 23 by Streptococcus pneumoniae. Among the 33 patients showing S. aureus positivity on ETA samples, 16 (48.5 %) developed S. aureus EOP. Among the 156 S. aureus non-carriers, 16 (10.2 %) developed EOP. Staphylococcus aureus carriage independently predicted EOP (p < 0.0001). We identified S. aureus carriage as an independent and strong predictor of EOP. As rapid point-of-care testing for S. aureus is readily available, we recommend testing of all patients at admission for burn trauma and the consideration of early preemptive treatment in all positive patients. Further studies are needed to evaluate this new strategy.

Hypertriglyceridemia: a potential side effect of propofol sedation in critical illness.

PURPOSE: Hypertriglyceridemia (hyperTG) is common among intensive care unit (ICU) patients, but knowledge about hyperTG risk factors is scarce. The present study aims to identify risk factors favoring its development in patients requiring prolonged ICU treatment. METHODS: Prospective observational study in the medicosurgical ICU of a university teaching hospital. All consecutive patients staying ≥4 days were enrolled. Potential risk factors were recorded: pathology, energy intake, amount and type of nutritional lipids, intake of propofol, glucose intake, laboratory parameters, and drugs. Triglyceride (TG) levels were assessed three times weekly. Statistics was based on two-way analysis of variance (ANOVA) and linear regression with potential risk factors. RESULTS: Out of 1,301 consecutive admissions, 220 patients were eligible, of whom 99 (45 %) presented hyperTG (triglycerides >2 mmol/L). HyperTG patients were younger, heavier, with more brain injury and multiple trauma. Intake of propofol (mg/kg/h) and lipids' propofol had the highest correlation with plasma TG (r (2) = 0.28 and 0.26, respectively, both p < 0.001). Infection and inflammation were associated with development of hyperTG [C-reactive protein (CRP), r (2) = 0.19, p = 0.004]. No strong association could be found with nutritional lipids or other risk factors. Outcome was similar in normo- and hyperTG patients. CONCLUSIONS: HyperTG is frequent in the ICU but is not associated with adverse outcome. Propofol and accompanying lipid emulsion are the strongest risk factors. Our results suggest that plasma TG should be monitored at least twice weekly in patients on propofol. The clinical consequences of propofol-related hyperTG should be investigated in further studies.

In vitro biotransformation of the selective serotonin reuptake inhibitor citalopram, its enantiomers and demethylated metabolites by monoamine oxidase in rat and human brain preparations.

This study was conducted to identify enzyme systems eventually catalysing a local cerebral metabolism of citalopram, a widely used antidepressant of the selective serotonin reuptake inhibitor type. The metabolism of citalopram, of its enantiomers and demethylated metabolites was investigated in rat brain microsomes and in rat and human brain mitochondria. No cytochrome P-450 mediated transformation was observed in rat brain. By analysing H2O2 formation, monoamine oxidase A activity in rat brain mitochondria could be measured. In rat whole brain and in human frontal cortex, putamen, cerebellum and white matter of five brains monoamine oxidase activity was determined by the stereoselective measurement of the production of citalopram propionate. All substrates were metabolised by both forms of MAO, except in rat brain, where monoamine oxidase B activity could not be detected. Apparent Km and Vmax of S-citalopram biotransformation in human frontal cortex by monoamine oxidase B were found to be 266 microM and 6.0 pmol min(-1) mg(-1) protein and by monoamine oxidase A 856 microM and 6.4 pmol min(-1) mg(-1) protein, respectively. These Km values are in the same range as those for serotonin and dopamine metabolism by monoamine oxidases. Thus, the biotransformation of citalopram in the rat and human brain occurs mainly through monoamine oxidases and not, as in the liver, through cytochrome P-450.

Cytochrome P-450 activities in human and rat brain microsomes.

The role of cytochrome P450 in the metabolism of dextromethorphan, amitriptyline, midazolam, S-mephenytoin, citalopram, fluoxetine and sertraline was investigated in rat and human brain microsomes. Depending on the parameters, the limit of quantification using gas chromatography-mass spectrometry methods was between 1.6 and 20 pmol per incubation, which generally contained 1500 microg protein. Amitriptyline was shown to be demethylated to nortriptyline by both rat and human microsomes. Inhibition studies using ketoconazole, furafylline, sulfaphenazole, omeprazole and quinidine suggested that CYP3A4 is the isoform responsible for this reaction whereas CYP1A2, CYP2C9, CYP2C19 and CYP2D6 do not seem to be involved. This result was confirmed by using a monoclonal antibody against CYP3A4. Dextromethorphan was metabolized to dextrorphan in rat brain microsomes and was inhibited by quinidine and by a polyclonal antibody against CYP2D6. Only the addition of exogenous reductase allowed the measurement of this activity in human brain microsomes. Metabolites of the other substrates could not be detected, possibly due to an insufficiently sensitive method. It is concluded that cytochrome P450 activity in the brain is very low, but that psychotropic drugs could undergo a local cerebral metabolism which could have pharmacological and/or toxicological consequences.

Pharmacokinetic consequences of a citalopram treatment discontinuation.

In this pilot study, the pharmacokinetics of citalopram (CIT) were examined in five hospitalized depressed patients after an abrupt discontinuation of a treatment with 40 mg/d of this selective serotonin reuptake inhibitor (SSRI). During the 8-day study period, clinical ratings were regularly carried out. Between days 5 and 8, the patients were treated with clomipramine (75 mg/d). The enantiomers of CIT and its metabolites, demethyl-CIT (DCIT) and CIT-propionic acid derivative (CIT-PROP), were measured repeatedly from day 0 to day 8 by a stereoselective high-performance liquid chromatography (HPLC) procedure. The following drug plasma half-lives were measured (means +/- SD): R-CIT: 66+/-11 h; S-CIT: 42+/-13 h; R-DCIT: 228+/-148 h; S-DCIT: 93+/-35 h; R-CIT-PROP: 82+/-31 h; S-CIT-PROP: 186+/-93 h.

Psychotropic drug prescription in a psychiatric university hospital.

A retrospective survey on drug prescription over a one-year period (1989) in 1083 patients (48.3% of whom were male) hospitalized in a psychiatric university hospital in Switzerland and a 35-day prospective study (1992) on the prescription of "as needed" (prn) medication in a closed and an open ward were carried out. Their aim was to establish a basis for a monitoring of prescription habits and for pharmacoeconomic considerations. In the retrospective study, 48.3% of the patients were male. The mean duration of hospitalization of the patients was 47.0 +/- 68.1 days (mean +/- s.d.). Only 11 out of the 1083 patients (1%) were without psychotropic medication. The mean (+/- SD) number of drugs/day the patients were prescribed was 4.6 +/- 2.8, including 3.2 +/- 1.7 psychotropic drugs. Patients suffering from schizophrenia (67 d) or from unipolar depression (67.4 d) were hospitalized for the longest periods. Antipsychotics (67.5% of the patients) were the most frequently prescribed psychotropic drugs, followed by anxiolytics (42.2%), antidepressants (28.3%), hypnotics (31.4%) and mood stabilizers (7.1%). Antiparkinsonian agents accounted for 4.6% of all prescriptions. Levomepromazine, haloperidol (30.9% of all patients) and clotiapine were the most often prescribed neuroleptics, and clozapine was administered to only 6.4% of all patients. Among the antidepressants, maprotiline (11.9% of all patients) was more frequently prescribed than the classical tricyclic antidepressant amitriptyline, while the only available SSRI fluvoxamine and MAO inhibitors were rarely used. The most frequently prescribed anxiolytics were clorazepate (28.2% of all patients), lorazepam, bromazepam, and prazepam. Among the hypnotic drugs, chloral hydrate (11.5%) was more frequently administered than the first-ranking benzodiazepine flunitrazepam (7.8%). In the prospective study, 97% and 77% of the patients (n = 55) of the closed (n = 29) and of the open ward, respectively, were prescribed "as needed" (prn) drugs. However, only 71 and 80%, respectively, of these patients finally received the drug. The frequency of prescription was 34.9% for neuroleptics, 15.1% for anxiolytic drugs, 8.2% for non-benzodiazepine hypnotics and only 2.1% for benzodiazepine hypnotics. The most frequently prescribed neuroleptic drug was clotiapine (18% of all patients), but finally, only 29% of the prescribed doses were administered. Studies of this type are biased by the fact that local habits of prescription do not allow generalisation of the findings. Such surveys should be carried out more frequently and simultaneously in different centers. Critical comparisons could help to optimize treatment.