Population Pharmacokinetics of Cabotegravir Following Oral Administration and Long-Acting Intramuscular Injection in Real-World People with HIV.

Long-acting cabotegravir has been studied mainly in the stringent framework of clinical trials, which does not necessarily reflect the situation of people with HIV (PWH) in routine clinical settings. The present population pharmacokinetic analysis aims to build real-world reference percentile curves of cabotegravir concentrations, accounting for patient-related factors that may affect cabotegravir exposure. The second objective is to simulate whether dosing interval adjustments of cabotegravir could be considered in specific subpopulations. Overall, 238 PWH contributed to 1,038 cabotegravir levels (186 during the initial oral administration phase and 852 after intramuscular injection). Cabotegravir pharmacokinetics was best described using a one-compartment model with distinct first order-absorption for oral and intramuscular administrations, and identical volume and clearance. Our model showed almost 40% faster absorption and 30% higher clearance than previously reported, resulting in a time to steady-state of 8 months and an elimination half-life of 4.6 weeks for long-acting cabotegravir. Sex and body mass index significantly influenced absorption, and bodyweight affected clearance. Model-based simulations showed that cabotegravir trough concentrations in females were 25% lower 4 weeks after the intramuscular loading dose, but 42% higher during the late maintenance phase. Finally, simulations indicated that in females, despite significantly higher cabotegravir concentrations, longer intervals between injections may not consistently ensure levels above the 4-fold protein-adjusted 90% inhibitory target concentration.

[Cockpit: a tool to support interprofessional communication and collaboration]. / Cockpit : un outil d'aide à la communication et à la collaboration interprofessionnelle.

In hospitals, many different professions work together with the same goal: optimal patient care. This challenge requires effective coordination and communication as well as good knowledge of each other's work. Due to an ever-increasing administrative workload and a large patient flow, time dedicated to this interprofessional collaboration is dwindling. Some hospitals, particularly in North America, have been using lean management concepts for some years, as an organizational aid and aiming at continuous improvement. A cockpit is a tool that aims at dedicating a space and a period of time to interprofessional communication and collaboration.

Au sein d'un hôpital, de nombreux corps de métiers travaillent ensemble dans un même but : la prise en charge optimale des patients. Ce défi nécessite une coordination et une communi­cation performantes ainsi qu'une bonne connaissance du travail de chacun. En raison d'un travail administratif en constante augmentation et d'un flux de patients important, le temps dédié à cette collaboration interprofessionnelle s'amenuise. Certains hôpitaux, notamment en Amérique du Nord, utilisent depuis quelques années des concepts issus du « lean management ¼, comme aide organisationnelle et dans une perspective d'amélioration continue. Un « cockpit ¼ ou « salle de pilotage ¼ est un outil qui a pour but de consacrer un espace et une période de temps à la communication et à la collaboration interprofessionnelle.

Therapeutic drug monitoring of cefepime in a non-critically ill population: retrospective assessment and potential role for model-based dosing.

Objectives: To describe the therapeutic drug monitoring (TDM) of cefepime in non-critically ill adults and compare four different ways of dosing: conventional table-based; empirically adjusted following TDM; individualized based on a population pharmacokinetic (PopPK) model without TDM; and TDM-adjusted with a Bayesian approach integrating TDM and PopPK. Methods: We conducted a retrospective study in a tertiary centre to examine the current practice of TDM and to evaluate the potential for improvement by PopPK-based software individualization. The prediction of trough concentrations and the total daily doses (TDD) prescribed according to each approach were compared by calculating the mean logarithmic bias and the root mean squared error, complemented by linear regression and variance analysis. Results: Among 168 trough concentrations in 119 patients (median: 12 mg/L), 38.6% of measurements exceeded 15 mg/L, the reported threshold for neurotoxicity. Nine patients developed neurotoxicity. The prediction performance of PopPK alone for trough concentrations was moderate, but clearly improved after integration of TDM. Accordingly, TDD were significantly lower for a priori PopPK-based dosage (mean: 2907 mg/24 h) compared with actual table-based dosage (4625 mg/24 h, P < 0.001). They were also lower for a posteriori dosage based on PopPK and TDM (3377 mg/24 h) compared with actual dosage after empirical TDM (4233 mg/24 h, P < 0.001), as model-based adjustment privileged more frequent administrations. Conclusions: Our observations support routine TDM of cefepime to prevent overdosing and subsequent toxicity in the non-critically ill. Software-based individualization seems promising to optimize the benefits of TDM, but has little potential to replace it.