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Objectives: The use of extended intermittent infusion (EII) or continuous infusion (CI) of meropenem is recommended in intensive care unit (ICU) patients, but few data comparing these two options are available. This retrospective cohort study was conducted between 1 January 2019 and 31 March 2020 in a teaching hospital ICU. It aimed to determine the meropenem plasma concentrations achieved with CI and EII., Methods: The study included septic patients treated with meropenem who had one or more meropenem plasma trough (Cmin) or steady-state concentration (Css) measurement(s), as appropriate. It then assessed the factors independently associated with attainment of the target concentration (Cmin or Css ≥ 10 mg/L) and the toxicity threshold (Cmin or Css ≥ 50 mg/L) using logistic regression models., Results: Among the 70 patients analysed, the characteristics of those treated with EII (n = 33) and CI (n = 37) were balanced with the exception of estimates glomerular filtration rate (eGFR): median 30 mL/min/m 2 (IQR 30, 84) vs. 79 mL/min/m 2 (IQR 30, 124). Of the patients treated with EII, 21 (64%) achieved the target concentration, whereas 31 (97%) of those treated with CI achieved it (P < 0.001). Factors associated with target attainment were: CI (OR 16.28, 95% CI 2.05-407.5), daily dose ≥ 40 mg/kg (OR 12.23, 95% CI 1.76-197.0; P = 0.03) and eGFR (OR 0.98, 95% CI 0.97-0.99; P = 0.02). Attainment of toxicity threshold was associated with daily dose > 70 mg/kg (OR 35.5, 95% CI 5.61-410.3; P < 0.001)., Conclusion: The results suggest the use of meropenem CI at 40-70 mg/kg/day, particularly in septic ICU patients with normal or augmented renal clearance., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

(1) Incomplete or wrong medication histories can lead to missed diagnoses of Adverse Drug Effects (ADEs). We aimed to evaluate pharmacist-identified ED errors in the medication histories obtained by physicians, and their consequences for ADE detection. (2) This prospective monocentric study was carried out in an ED of a university hospital. We included adult patients presenting with an ADE detected in the ED. The best possible medication histories collected by pharmacists were used to identify errors in the medication histories obtained by physicians. We described these errors, and identified those related to medications involved in ADEs. We also identified the ADEs that could not have been detected without the pharmacists' interventions. (3) Of 735 patients presenting with an ADE, 93.1% had at least one error on the medication list obtained by physicians. Of the 1047 medications involved in ADEs, 51.3% were associated with an error in the medication history. In total, 23.1% of the medications involved in ADEs were missing in the physicians' medication histories and were corrected by the pharmacists. (4) Medication histories obtained by ED physicians were often incomplete, and half the medications involved in ADEs were not identified, or were incorrectly characterized in the physicians' medication histories.

Objectives: Severe trauma patients are at higher risk of infection and often exposed to antibiotics, which could favor acquisition of antimicrobial resistance. In this study, we aimed to assess prevalence, acquisition, and factors associated with acquisition of extended-spectrum cephalosporin-resistant Gram-negative bacteria (ESCR-GNB) in severe trauma patients., Methods: We conducted a retrospective monocentric cohort study in a French level one Regional Trauma Centre between 01 January 2010and 31 December 2015. Patients admitted for ≥ 7 days, with an Injury Severity Score ≥ 15, and ≥ 1 microbiological sample were included in the analysis. Prevalence and acquisition rate of ESCR-GNB were determined then, factors associated with ESCR-GNB acquisition were assessed using a Cox model., Results: Of 1873 patients admitted during the study period, 507 were included (median Injury Severity Score = 29 [22-34] and median intensive care unit length of stay = 16 days [10-28]). Most of them (450; 89%) had an antimicrobial therapy. Prevalence of ESCR-GNB increased from 13% to 33% during intensive care unit stay, bringing the ESCR-GNB acquisition rate to 29%. Acquisition of ESCR-GNB was mainly related to AmpC beta-lactamase Enterobacterales and was independently associated with mechanical ventilation needs (hazard ratio [HR] = 6.39; 95% confidence interval [CI] [1.51-27.17]; P = 0.01), renal replacement therapy needs (HR = 2.44; 95% CI [1.24-4.79]; P = 0.01), exposure to cephalosporins (HR = 1.06; 95% CI [1.01-1.12]; P = 0.02), and/or combination therapy with non-beta-lactam antibiotics such as vancomycin, linezolid, clindamycin, or metronidazole (HR = 1.03; 95% CI [1.01-1.06]; P = 0.02)., Conclusions: Acquisition of ESCR-GNB was prevalent in severe trauma patients. Our results suggest selecting antibiotics with caution, particularly in the most severely ill., Competing Interests: Competing interests The authors report there are no competing interests to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Given the rapidly evolving pandemic of COVID-19 in 2020, authorities focused on the repurposing of available drugs to develop timely and cost-effective therapeutic strategies. Evidence suggested the potential utility of remdesivir in the framework of an early access program. REMDECO-19 is a multicenter national cohort study assessing the ability of remdesivir to improve the outcome of patients hospitalized with COVID-19., Methods: We conducted a retrospective real-life study that included all patients from the early access program of remdesivir in France. The primary endpoint was the clinical course evolution of critically ill and hospitalized COVID-19 patients treated with remdesivir. Secondary endpoints were the SOFA score evolution within 29 days following the admission and mortality at 29 and 90 days., Results: Eighty-five patients were enrolled in 22 sites from January to April 2020. The median WHO and SOFA scores were respectively reduced by two and six points between days 1 and 29. Improvement in the WHO-CPS and the SOFA score were observed in 83.5% and 79.3% of patients, respectively, from day 10. However, there was no effect of remdesivir on the 90-day survival based on the control cohort for hospitalized COVID-19 patients with invasive ventilation., Conclusions: SOFA score appeared to be an attractive approach to assess remdesivir efficacy and stratify its utilization or not in critically ill patients with COVID-19. This study brings a new clinical benchmark for therapeutic decision making and supports the use of remdesivir for some hospitalized COVID-19 patients.

Adverse drug events (ADEs) are a major public health concern, given their consequences in terms of morbi-mortality and associated healthcare costs. Many studies have focused on the elderly, who are considered particularly vulnerable in this respect. We aimed to determine and compare the frequency, characteristics, and predictive factors of ADEs according to age in an adult population. A prospective seven-year cross-sectional study was conducted in a university hospital emergency department. Structured medication reviews and ADE detection were performed. Patient data and ADE characteristics were collected. Descriptive statistics and logistic regression were performed in two age groups: Group 1 (age < 65 years) and 2 (age ≥ 65 years). Among the 13,653 patients included, 18.4% in Group 1 and 22.6% in Group 2 experienced an ADE. Differences were identified in terms of the ADE type (more ADEs due to noncompliance in Group 1) and ADE symptoms (greater bleeding in Group 2). In the multivariable analysis, several specific predictive factors were identified, including kidney failure and antidiabetic drug use in Group 1 and inappropriate prescription and antithrombotic treatment in Group 2. Analysis by age provided a more refined vision of ADEs as we identified distinct profiles of iatrogenesis. These results will lead to a better detection of ADEs., Competing Interests: The authors declare no conflicts of interest.

Background and Objectives : Vaccination coverage is suboptimal in people living with diabetes. The objectives of this study were to determine the impact of hospitalization on vaccination coverage and the variables associated with vaccination during hospital stay. Materials and Methods : This observational study was conducted from May 2019 to December 2019 in the Endocrinology-Nutrition-Diabetes Department of the University Hospital of Montpellier, France. This department encompasses three medical units, two of which have a full-time clinical pharmacist involved in the multidisciplinary management of patients. All adult diabetic patients who completed a questionnaire about vaccines were prospectively included by a clinical pharmacist and followed until department discharge. Coverage at the time of admission for the tetanus, diphtheria, pertussis (Tdap), pneumococcal, influenza, and herpes zoster vaccines was assessed from patient interviews and/or contact with the general practitioner and/or with the community pharmacist. Multivariable logistic regression analysis was performed to identify the factors associated with a vaccination update during the hospital stay. Results : A total of 222 patients were included (mean age: 59.4 years, 68.5% type 2 diabetes). Vaccination coverage increased by 26.7% (47.3% to 59.9%), 188.0% (10.8% to 31.1%) and 8.9% (45.9% to 50.0%), respectively, for the Tdap, pneumococcal and influenza vaccines during hospital stay. Female sex, admission to a diabetes care unit with a full-time pharmacist, favorable feelings about vaccination, unknown immunization coverage for pneumococcal vaccines, and evaluation and recording of vaccine coverage at admission in the patient medical records were associated with at least one vaccination during hospital stay. Conclusions : Our real-life study highlights that hospitalization and multidisciplinary management (i.e., physician-pharmacist) may be key points in the diabetes care pathway to improve vaccination coverage, especially for patients with advanced diabetes and comorbidities.

Background and objectives: Renal failure is a contraindication for some glucose-lowering drugs and requires dosage adjustment for others, particularly biguanides, sulfonylureas, and inhibitors of dipeptidyl peptidase 4. In this study, we assessed adherence to prescription recommendations for glucose-lowering drugs according to renal function in hospitalized diabetic subjects. Materials and Methods : This prospective cohort study was carried out over a 2-year period in a university hospital. Glomerular filtration rate (GFR) was determined by averaging all measurements performed during hospitalization. Glucose-lowering drug dosages were analyzed according to the recommendations of the relevant medical societies. Results : In total, 2071 diabetic patients (53% hospitalized in cardiology units) were examined. GFR was <30 mL/min/1.73 m 2 in 13.4% of these patients, 30-44 in 15.1%, 45-60 in 18.3%, and >60 in 53.3%. Inappropriate oral glucose-lowering treatments were administered to 273 (13.2%) patients, including 53 (2.6%) with a contraindication. In cardiology units, 53.1% and 14.3% of patients had GFRs of <60 and <30 mL/min/1.73 m 2 , respectively, and 179 (15.4%) patients had a contraindication or were prescribed an excessive dose of glucose-lowering drugs. Conclusions : We showed that the burden of inappropriate prescriptions is high in diabetic patients. Given the high number of patients receiving these medications, particularly in cardiology units, a search for potential adverse effects related to these drugs should be performed.

Objectives: Adverse drug events (ADEs) are a major public health issue in hospitals. They are difficult to detect because of incomplete or unavailable medication history. In this study, we aimed to assess the rate and characteristics of ADEs identified by pharmacists in an emergency department (ED) to identify factors associated with ADEs., Methods: In this prospective observational study, we included consecutive adult patients presenting to the ED of a French 2600-bed tertiary care university hospital from November 2011 to April 2015. Clinical pharmacists conducted structured interviews and collected the medication history to detect ADEs (i.e., injuries resulting directly or indirectly from adverse drug reactions and noncompliance to medication prescriptions). Unsure ADE cases were reviewed by an expert committee. Relations between patient characteristics, type of ED visit, and ADE risk were analyzed using logistic regression., Results: Among the 8275 included patients, 1299 (15.7%) presented to the ED with an ADE. The major ADE symptoms were bleeding, endocrine problems, and neurologic disorders. Moreover, ADEs led to the ED visit, hospitalization, and death in 87%, 49.3%, and 2.2% of cases, respectively. Adverse drug event risk was independently associated with male sex, ED visit for neurological symptoms, visit to the ED critical care unit, or ED short stay hospitalization unit, use of blood, anti-infective, antineoplastic, and immunomodulating drugs., Conclusions: This study improves the knowledge about ADE characteristics and on the patients at risk of ADE. This could help ED teams to better identify and manage ADEs and to improve treatment quality and safety., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: The aim of this study was to evaluate the clinical, economic, and organizational impact of clinical pharmacist services added to an adult orthopedic and trauma surgery unit in a university hospital., Methods: This was a prospective, observational study performed from January to February 2017. All pharmacists' interventions were documented, and their clinical, economic, and organizational impact and the probability of adverse drug events (ADEs) were assessed using the clinical, economic and organizational scale three-dimensional scale. An expert panel composed of three clinical pharmacists, one surgeon and one anesthetist classified the pharmacist intervention. The potential clinical impact was determined through a consensus by the expert panel. Cost avoidance was calculated for serious ADEs with a major impact by avoiding an additional cost of €4912 per event and taking into account the probability of ADE occurrence., Results: The pharmacists performed 1014 interventions for 28 days with a 95.3% acceptance rate by prescribers. Thirty-nine interventions were rated to have a major clinical impact (3.8%). The organizational impact was estimated favorable for 856 (84.4%) pharmacist interventions. Cost avoidance was estimated at €24,364, and the indirect costs benefit was estimated at €11,864 during the study. The cost-benefit ratio of the clinical pharmacist intervention was €1.94 in savings for every €1 invested., Conclusions: Clinical pharmacist services in an orthopedic and trauma surgery department have the potential to improve patient outcomes and avoid healthcare costs. Furthermore, the presence of a pharmacist in surgical units allows for communication between the unit and the pharmacy, which produces better fluidity and improves the quality of care., (Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.)