Continuous infusion of beta-lactam antibiotics in pediatric intensive care unit: A monocenter before/after implementation study.

CONTEXT: Beta-lactam continuous infusion (CI) is currently recommended in adult intensive care units to achieve target concentrations. In pediatric intensive care (PICU), few studies suggest the value of Beta-lactam CI to achieve target concentration. Our objective was to analyze the impact of Beta-lactam CI protocolization on the achievement of target concentration in PICU patients. MATERIAL AND METHODS: We conducted a single-center retrospective study in patients with beta-lactam treatment for more than 2 days and at least one sample for therapeutic drug monitoring (TDM). From January 2018 to February 2022 (period 1, P1), BL were administered as an intermittent infusion with TDM upon request. From February to September 2022 (period 2, P2), Beta-lactam CI with TDM at day one was protocolized. The primary endpoint concerned achieving fT>4× Minimum Inhibitory Concentration = 100%. RESULTS: In P1, 214 assays involved 103 patients; in P2, 199 assays involved 72 patients. Target concentration achievement was more frequent in P2 (P2 = 73.7% vs. P1 = 29.1%; p < 0.001). At day 5/6 after Beta-lactam initiation, c-reactive protein concentrations were P1 = 84.9 ± 79.2 mg/L; P2 = 53.7±49.8 mg/L (p < 0.05). In the multivariable logistic regression model: P2, BSA, and albumin were positively associated with target achievement; urea, and male sex were negatively associated with target achievement. The daily average cost of beta-lactam vial consumption per child was: P1 = 5.04 ± 2.6 € vs. P2 = 3.21 ± 2.7 € (p-value < 0.001). The daily average reconstitution time of Beta-lactam syringes per child was: P1 = 23.5 ± 8.7 min, P2 = 13.9 ± 9.2 min (p-value < 0.001). CONCLUSION: Protocolization of Beta-lactam continuous infusion was associated with more frequent target concentration achievements in PICU. This implementation could be cost-effective and nurse time-saving.

Elderly patients whose hospitalization was medication-related were more likely to receive medication recommendations by clinical pharmacist than patients whose hospitalization was unlikely medication-related in non-geriatric units.

BACKGROUND: Elderly patients are often polymedicated, and drug-related hospitalizations are common in this population. In our hospital, pharmacists from the mobile geriatric team (MGT) coordinate medication reviews (MR) for elderly patients hospitalized in non-geriatric wards, to prevent iatrogenic. OBJECTIVE: The aim of this work is to determine whether the drug-related origin of hospitalizations can be considered as a targeting criterion for performing MRs. MATERIAL AND METHOD: We conducted a retrospective study of data from patients who received a MGT's MR between March 2021 and December 2022, from a single center of more than 1000 beds. The drug-related origin of the hospitalization was estimated as probable or unlikely by the AT-HARM10 tool. Between the two groups, we compared the number of potentially inappropriate prescriptions detected by the PIM-check and START/STOPP tools, drug-drug interactions (DI), unintended discrepancies (UDI) at entry reconciliation, the drug burden index (DBI), and the number of drug-related problems (DRP) i.e., START/STOPP score + DI + UDI. Linear regression of the number of DRP by AT-HARM10 score was computed. RESULTS: 110 patients were included. 56 hospitalizations were estimated MRH and 54 non-MRH. Mean age (85.1 ± 7.0), ADL (3.8 ± 1.9), IADL (2.0 ± 1.6), and number of medications at entry (8.9 ± 3.8) were comparable in the 2 groups. Compared with non-MRH group, MRH group had a higher number of START/STOPP criteria (5.7 ± 3.5 vs 3.0 ± 2.6; p < 0.05), PIM-check overuses (2.1 ± 1.7 vs 1.4 ± 1.4; p < 0.05), DI (8.4 ± 9.0 vs 4.7 ± 4.7; p < 0.05), UDI at entry (4.0 ± 3.34 vs 2.2 ± 2.1; p < 0.05), and higher DBI score (0.9 ± 0.7 vs 0.3 ± 0.4; p < 0.05). The number of DRP was higher in group P (17.6 ± 10.8 vs 9.8 ± 6.3; p < 0.00.5). Linear regression showed a positive correlation between AT-HARM10 score and the number of DRP (r = 0.5, p < 0.05) with a coefficient of 7.7 (CI95% = [4.3; 11.1]) and an intercept of 9.8. DISCUSSION: These results allow us to consider AT-HARM10 score as a targeting criterion for performing MR for elderly patients, as part of a curative approach to drug iatrogenic for these patients.

Implementation of a patient-teaching workshop to improve pharmacy students' competencies in patient-centered communication: a case report.

BACKGROUND: The pharmacist-patient relationship has evolved over recent decades and the development of clinical pharmacy requires pharmacists to take patient-centered responsibilities. This requires a specific set of skills, such as patient-centered communication. Evaluation of students' competencies in patient-centered communication is challenging in academic settings and complementary assessment methods may be designed in order to overcome the limits of traditional preceptors' ratings or objective structured clinical examination (OSCE). There is increasing interest in a more active patient role in healthcare professional education and there are very few reports about patient-led education in pharmacies. Thus, the objective of this work was to implement a patient-teaching workshop and to assess its impact on pharmacy students' competencies in patient-centered communication. METHODS: The workshop was developed in collaboration between four patients, a senior clinical pharmacist and a lecturer in education sciences and implemented in the hospital pharmacy residency program. The main course objective was acquiring the three competencies of the Calgary-Cambridge guide to the medical interview: (i) building a relationship, (ii) conducting structured interview and (iii) gathering information. The learning process integrated: working on participants' perception of pharmacists-patient communication, a first simulated interview, didactic learning and a second simulated interview. After simulated interviews, patients and peer residents assessed learner's performance with a competency chart and provided individual feedback. Assessment methods included comparisons between the first and second interview scores and an anonymous post-course survey. RESULTS: Forty-seven residents and 19 patient teachers attended the session. Competency scores were higher after the second interview in all three competencies as rated by both patients (+ 25%) and peer residents (+ 29%). Residents expressed a high satisfaction and reported learning about conducting interviews and soft skills contributing to the development of a relationship with patients. "The involvement of patients" was expressed as most appreciated in the majority of the evaluation charts (87%) and the residents valued the importance of collaborative and interprofessional learning during the workshop. Three themes emerged: (1) patients' expertise, (2) reliability and (3) relationship, which underlined that the students estimated the patients were credible sources of information in this pedagogical context. CONCLUSION: This patient-teaching approach improved patient-centered competencies of pharmacy residents and promoted partnership between patients and pharmacy students.

Monitoring Breast Cancer Care Quality at National and Local Level Using the French National Cancer Cohort.

PURPOSE: The French National Cancer Institute has developed, in partnership with the French National Authority for Health, breast cancer-specific Care Quality, and Safety Indicators (BC QIs). With regard to the most common form of cancer, our aim is to support local and national quality initiatives, to improve BC pathways and outcomes, reduce heterogeneity of practice and regional inequities. In this study, we measure the BC QIs available in the French National medico-administrative cancer database, the French Cancer Cohort, for 2018. MATERIALS AND METHODS: BC QIs are developed according to the RAND method. QIs are based on good clinical practice and care pathway recommendations. QI computation should be automatable without any additional workload for data collection. They will be published annually for all stakeholders, and especially hospitals. RESULTS: Finally, ten feasible and pertinent QIs were selected. In France, BC care was found to be close to compliance with most QIs: proportion of patients undergoing biopsy prior to first treatment (94.5%), proportion of patients undergoing adjuvant radiotherapy after breast-conserving surgery for BC (94.5%), proportion of women undergoing radiotherapy within 12 weeks after surgery and without chemotherapy (86.2%), proportion of DCIS patients undergoing immediate breast reconstruction (54.3%) and proportion of women with NMIBC undergoing breast reintervention (14.4%). However, some are still far from their recommended rate. In particular, some QIs vary considerably from one region, or one patient, to another. CONCLUSION: Each result needs to be analyzed locally to find care quality leverage. This will strengthen transparency actions aimed at the public.

Redistribution of critical drugs in shortage during the first wave of COVID-19 in France: from operating theaters to intensive care units.

BACKGROUND: Tension in the supply of highly consumed drugs for patients with COVID-19 (propofol, midazolam, curares) led the French government to set up a centralized supply of hospitals with distribution based on the number of resuscitation beds in March 2020. The French Societies of Clinical Pharmacy and of Anesthesia and Critical Care aimed to evaluate the changes in total needs and the distribution between anesthesia and critical care activities (CCU), to prepare resumed surgical activity. METHODS: National declarative survey among pharmacists, via an online form (SurveyMonkey®), was conducted in April and May 2020. The analysis focused on quantities dispensed during the whole year 2019, and March and April of year 2019 and 2020 for the drugs subject to quota, and on their distribution in CCU and operating theaters. RESULTS: For the 358 establishments (47% public, 53% private), dispensations in CCU in March 2020 compared to March 2019 increased, respectively: propofol (+81%), midazolam (+125%), cisatracurium (+311%), atracurium (+138%), rocuronium (+119%); and decreased for anaesthesia: propofol (-27%), midazolam (-10%), cisatracurium (-19%), atracurium (-27%), rocuronium (+16%). CONCLUSIONS: Variation of dispensations between CCU and others was directly related to the increase of COVID patients in CCU and the decrease in surgical activity. Each establishment could receive up to five or six different presentations and concentrations, leading to a major risk of medication error. This collaborative national survey provided accurate data on the drugs' usual consumption. This work emphasized the need for a strong collaboration between pharmacists and anesthesiologists and intensive care physicians. It was further used by the Health Ministry to adjust the drug distribution.

Telemedication Reviews to Optimize Medication Prescription for Older People in Nursing Homes.

Introduction: Older people living in nursing homes (NH) are at a higher risk of preventable drug-related adverse events because of age-related physiological changes, polypathology, and polypharmacy. NH residents are particularly exposed to potentially inappropriate medications (PIMs). Many strategies have been developed to improve the quality and the safety of drug prescription in NH, including medication reviews (MRs). Methods: In the context of the application of telemedicine, we developed and are currently implementing a novel hospital expert-based MRs through tele-expertise (or "telemedication review," telemedication reviews hereafter [TMR]) in French NH residents. The impact of these TMR on unplanned hospitalizations 3 months after implementation is assessed. TMR consider all available sociodemographic, clinical, biological, and pharmaceutical data pertaining to the patient and are performed in accordance with their health care objectives. Results: The preliminary results for the 39 TMRs performed to date (September 2021) showed that a total of 402 PIMs were detected, and all residents had at least one PIM. We also present the feasibility and the usefulness of this novel TMR for NH, illustrating these preliminary results with two concrete TMR experiences. Among the 39 TMR performed, the average acceptance rate of expert recommendations made to general practitioners (GP) working in NH was ∼33%. Discussion and Conclusions: The success of this novel TMR depends on how the proposed prescription adjustments made by the hospital expert team are subsequently integrated into health care practices. The low acceptance rate by GP highlights the need to actively involve these professionals in the process of developing TMR, with a view to encouraging them to act on proposed adjustments.

Drug repurposing against SARS-CoV-1, SARS-CoV-2 and MERS-CoV.

Since the beginning of the COVID-19 pandemic, large in silico screening studies and numerous in vitro studies have assessed the antiviral activity of various drugs on SARS-CoV-2. In the context of health emergency, drug repurposing represents the most relevant strategy because of the reduced time for approval by international medicines agencies, the low cost of development and the well-known toxicity profile of such drugs. Herein, we aim to review drugs with in vitro antiviral activity against SARS-CoV-2, combined with molecular docking data and results from preliminary clinical studies. Finally, when considering all these previous findings, as well as the possibility of oral administration, 11 molecules consisting of nelfinavir, favipiravir, azithromycin, clofoctol, clofazimine, ivermectin, nitazoxanide, amodiaquine, heparin, chloroquine and hydroxychloroquine, show an interesting antiviral activity that could be exploited as possible drug candidates for COVID-19 treatment.

Early combination therapy with hydroxychloroquine and azithromycin reduces mortality in 10,429 COVID-19 outpatients.

We evaluated the age-specific mortality of unselected adult outpatients infected with SARS-CoV-2 treated early in a dedicated COVID-19 day hospital and we assessed whether the use of hydroxychloroquine (HCQ) + azithromycin (AZ) was associated with improved survival in this cohort. A retrospective monocentric cohort study was conducted in the day hospital of our center from March to December 2020 in adults with PCR-proven infection who were treated as outpatients with a standardized protocol. The primary endpoint was 6-week mortality, and secondary endpoints were transfer to the intensive care unit and hospitalization rate. Among 10,429 patients (median age, 45 [IQR 32-57] years; 5597 [53.7%] women), 16 died (0.15%). The infection fatality rate was 0.06% among the 8315 patients treated with HCQ+AZ. No deaths occurred among the 8414 patients younger than 60 years. Older age and male sex were associated with a higher risk of death, ICU transfer, and hospitalization. Treatment with HCQ+AZ (0.17 [0.06-0.48]) was associated with a lower risk of death, independently of age, sex and epidemic period. Meta-analysis evidenced consistency with 4 previous outpatient studies (32,124 patients-Odds ratio 0.31 [0.20-0.47], I2 = 0%). Early ambulatory treatment of COVID-19 with HCQ+AZ as a standard of care is associated with very low mortality, and HCQ+AZ improve COVID-19 survival compared to other regimens.

Low concentrations of vorinostat decrease EB1 expression in GBM cells and affect microtubule dynamics, cell survival and migration.

Glioblastoma multiform (GBM) is the most frequent primitive brain tumor with a high recurrence and mortality. Histone deacetylase inhibitors (HDACi) have evoked great interest because they are able to change transcriptomic profiles to promote tumor cell death but also induce side effects due to the lack of selectivity. We show in this paper new anticancer properties and mechanisms of action of low concentrations of vorinostat on various GBM cells which acts by affecting microtubule cytoskeleton in a non-histone 3 (H3) manner. Indeed, vorinostat induces tubulin acetylation and detyrosination, affects EB stabilizing cap on microtubule plus ends and suppresses microtubule dynamic instability. We previously identified EB1 overexpression as a marker of bad prognostic in GBM. Interestingly, we show for the first time to our knowledge, a strong decrease of EB1 expression in GBM cells by a drug. Altogether, our results suggest that low dose vorinostat, which is more selective for HDAC6 inhibition, could therefore represent an interesting therapeutic option for GBM especially in patients with EB1 overexpressing tumor with lower expected side effects. A validation of our hypothesis is needed during future clinical trials with this drug in GBM.

Combination of Hydroxychloroquine Plus Azithromycin As Potential Treatment for COVID-19 Patients: Safety Profile, Drug Interactions, and Management of Toxicity.

The coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2, has recently emerged worldwide. In this context, there is an urgent need to identify safe and effective therapeutic strategies for treatment of such highly contagious disease. We recently reported promising results of combining hydroxychloroquine and azithromycin as an early treatment option. Although ongoing clinical trials are challenging the efficacy of this combination, many clinicians claim the authorization to or have already begun to use it to treat COVID-19 patients worldwide. The aim of this article is to share pharmacology considerations contributing to the rationale of this combination, and to provide safety information to prevent toxicity and drug-drug interactions, based on available evidence.

Medication reconciliation in the geriatric unit: impact on the maintenance of post-hospitalization prescriptions.

Background Medication reconciliation prevents medication errors at care transition points. This process improves communication with general practitioners regarding the reasons for therapeutic changes, allowing those changes to be maintained after hospital discharge. Objective To investigate the impact of medication reconciliation in geriatrics on the sustainability of therapeutic optimization after hospital discharge. Setting This study was conducted in a geriatric unit in a University Hospital Centre in France. Method This was a retrospective study. For 6 months, all patients over 65 years who underwent the process of medication reconciliation performed by a clinical hospital pharmacist and a physician at admission and discharge, were included. A comparison between drug prescriptions at hospital discharge and the first prescription made outside the hospital was made to identify any differences. Main outcome measure The main outcome measures were the provision of the results of the medication reconciliation performed in the hospital to the relevant general practitioner, the subsequent acceptance of that information, the type of medication discrepancies one month after discharge and the therapeutic classes affected by the modifications. Results Among the 112 patients, medication reconciliation allowed us to identify and correct 87 unintentional discrepancies at admission (88% corrected) and 54 at discharge (92% corrected). Patients were discharged to homes or nursing homes (61%), geriatric rehabilitation units (38%) or psychiatric clinics (1%). A general practitioner wrote the first prescription renewal a mean of 36 ± 23 days after discharge, having been made aware of the medication reconciliation in only 24% of the cases (received and taken into account). The impact was a decrease in the number of patients with at least one discrepancy. Twenty-five percent of general practitioners who were aware about the medication reconciliation process accepted all therapeutic changes, while only 7% of those who were not informed did so (p = 0.02). The number of medication discrepancies observed was correlated with the number of medications for which prescriptions were renewed (p < 0.01). Conclusion Medication reconciliation involving therapeutic optimization and the justification of changes is essential to ensure the safety of the prescriptions written for patients. However, its impact after discharge is hampered by the fact that the results are often not received or taken into account by general practitioners. Taking medication reconciliation into account was associated with a significant increase in prescriptions that maintained therapeutic changes made in the hospital, confirming the positive impact of communication between care providers on therapeutic optimization.

Acceptability of a Novel Telemedication Review for Older Adults in Nursing Homes in France: A Qualitative Study.

PURPOSE: In France, polypharmacy among older people living in nursing homes (NH) is a major public health concern. In this context, the randomized controlled trial TEM-EHPAD was recently launched in various NH in southern France to evaluate the impact of implementing a novel telemedication review (TMR) on hospital admission rates of NH residents at high risk of iatrogenic disease. A qualitative study was integrated into the main trial study to assess general practitioners' (GP) and other NH healthcare professionals' (HP) acceptability of the proposed TMR before its implementation. MATERIAL AND METHODS: A qualitative study using face-to-face semi-structured interviews was conducted with 16 HP before the beginning of the intervention. A manual thematic analysis was performed on the transcribed interviews. RESULTS: Four main themes emerged from the thematic analysis: HP perceptions of the TMR, difficulties related to medication management for NH residents, HP perceptions of the roles of different professionals, and facilitators of good practices. Most participants were favorable to the TMR, but some GP expressed fears about loss of control over their prescription writing. CONCLUSION: This study fulfilled its objective to assess pre-intervention acceptability by GP and other HP. Results provided important information about how to adapt the TMR intervention to make it more acceptable to HP who will be involved in TEM-EHPAD. One of the main recommendations is the importance of providing participating GP with the opportunity to take part in the process of reviewing prescriptions.

Acute kidney injury in patients treated with anti-programmed death receptor-1 for advanced melanoma: a real-life study in a single-centre cohort.

BACKGROUND: Immune checkpoints inhibitors have transformed the prognosis of advanced melanoma but are associated with immune-related adverse events (irAEs). We evaluated the incidence, risk factors and causes of acute kidney injury (AKI) in a monocentric real-life cohort of patients treated with anti-programmed death receptor-1 (anti-PD1) antibodies for advanced melanoma. METHODS: Retrospective collection of medical charts and comprehensive analysis of lab results from patients treated with nivolumab or pembrolizumab for advanced melanoma between 2014 and 2018 was carried out. AKI was defined by Kidney Disease Improving Global Outcomes criteria, and causes were determined by chart review. Overall survival, survival without AKI and impact of AKI on survival were analysed. Risk factors for death and for AKI were identified. RESULTS: Two hundred and thirty-nine patients were included. Forty-one (17%) had at least one episode of AKI. Independent risk factors for AKI were treatment with renin-angiotensin-aldosterone system inhibitors (RAASi), pre-existing chronic kidney disease (CKD) and cumulated doses of anti-PD1. The main cause of AKI was prerenal, and only eight patients (3.3%) developed acute interstitial nephritis; 8% of patients developed CKD. The median overall survival was 13.4 months and was not affected by AKI. In multivariate analysis, the overall mortality was lower in overweight and obese patients and higher in patients treated with proton-pump inhibitors (PPI) or corticosteroids. CONCLUSIONS: AKI is common in patients treated with anti-PD1 for advanced melanoma but is mostly prerenal and favoured by the use of RAASi; renal irAE is rare. PPI and corticosteroids were associated with poor survival in this population, while overweight/obesity was protective.

Comparison of rituximab originator (MabThera®) to biosimilar (Truxima®) in patients with multiple sclerosis.

BACKGROUND: Rituximab's originator MabThera® or Rituxan® has demonstrated high efficacy in multiple sclerosis (MS). Because of the patent expiration, rituximab biosimilars have been developed. However, because a biosimilar is not the exact copy of the originator, the efficacy and safety of a biosimilar may significantly differ. OBJECTIVES: To compare the efficacy and safety of the biosimilar Truxima® and the originator MabThera® in MS. METHODS: Consecutive MS patients receiving MabThera® or Truxima® were prospectively followed during 1 year after treatment introduction. Allocation to each treatment depended on the period of introduction and not the physician's choice. Lymphocyte count, clinical and magnetic resonance imaging (MRI) activity, Expanded Disability Status Scale (EDSS), and adverse events were compared. RESULTS: In total, 105 and 40 patients received MabThera® and Truxima®, respectively. The two groups did not differ in baseline characteristics. Effect on CD19+ lymphocytes and disease activity were similar during follow-up. EDSS remained stable, with no difference between groups. Adverse events were similar between groups. CONCLUSION: The efficacy and safety of the rituximab biosimilar Truxima® seem equivalent to the originator MabThera® in MS patients. Truxima® could represent a relatively cheap and safe therapeutic alternative to MabThera® and could improve access to highly efficient therapy for MS in low- or middle-income countries.

Medication Reconciliation Associated with Comprehensive Geriatric Assessment in Older Patients with Cancer: ChimioAge Study.

BACKGROUND: Polymorbidity induces polypharmacy in older patients may lead to potential drug-drug interactions (DDI) which can modify the tolerance and safety of oncological treatments and alter the intended therapeutic effect. The objective of our study was to describe the decision-making process for oncological treatment and related outcomes, in a population of older adults undergoing a comprehensive geriatric assessment (CGA) associated to a comprehensive medication reconciliation (CMR) prior to initiating oncological treatment. METHODS: ChimioAge is a prospective observational study conducted between 01/2017 and 07/2018 at Marseille University Hospital and approved by the French National Ethics Committee. It comprised all consecutive patients aged 70 years and over who were referred for a CGA as part of CMR, before initiating systemic treatment. RESULTS: One hundred and seventy-one cancer patients were included. Mean age was 79.2 years, over half had metastatic cancers, 75% had an ECOG performance status zero or one, and two-thirds were independent in daily activities. Two-thirds of the patients had polypharmacy and the CMR identified potential DDI with systemic treatment in 43.3% of patients. Following the CGA, the CMR and the hospital oncologists decision, 30% of the patients received adapted systemic treatment with reduced doses at initiation. They presented fewer toxicities - irrespective of grade and type - than patients who received standard treatment (p<0.001) and had comparable overall survival (Log rank p=0.21). CONCLUSION: This is one of the first studies to highlight the value in conducting CMR and a CGA simultaneously before initiating systemic treatment in older patients with cancer. These two evaluations could give oncologists decisive information to personalize cancer treatment of older patients and optimize treatment dose to offer the best efficacy and minimize toxicity.