Background: High flow nasal cannula oxygen therapy (HFT) is increasingly used in intensive and emergency care departments. Patients suffering from respiratory failure, who are likely to benefit from HFT, may require aerosolized bronchodilators; therefore, combining nebulization with HFT may be relevant. This study aimed to identify the optimal settings for the implementation of nebulization within an adult HFT circuit. Methods: We assessed the mass and the particle size distribution of the aerosol emitted from the nasal cannula (inhalable mass) using mesh- and jet-nebulizers placed at various positions in the HFT circuit. Thereafter, the most relevant combination was used to evaluate the mass of salbutamol delivered downstream of an anatomical model reproducing aerosol deposition and leakage at the nasal and pharyngeal levels (respirable mass). The influence of HFT flow rate (30, 45, and 60 L/min), of breathing pattern ( quiet and respiratory distress pattern) as well as of opened and closed mouth breathing was assessed. Results: The most efficient position was that of a nebulizer placed upstream from the humidification chamber (inhalable mass ranging from 26% to 32% of the nebulizer charge). Using a mesh nebulizer, we observed a respirable mass ranging from 2% to 10% of the nebulizer charge. Higher HFT flow rates and open mouth breathing were associated with a lower efficiency. Simulating respiratory distress (i.e., increasing the simulated patient inspiratory flow) did not hamper drug delivery as compared to a quiet breathing pattern. Conclusions: Placing nebulizers within a HFT circuit upstream from the humidification chamber may enable to deliver clinically relevant masses of aerosol at the cannula outlet, but more importantly downstream of the nose and pharynx, even in case of high patients' inspiratory flow. This method of aerosol therapy is expected to produce a bronchodilatatory effect to be evaluated in the clinical settings.

Background Tacrolimus (TAC) is the cornerstone of immunosuppressive regimen in liver transplantation (LT). Its pharmacokinetics is characterized by a high interpatient and intrapatient variability (IPV) leading to an unpredictable dose-response relationship. The aim of our study was to evaluate the impact of TAC IPV (IPV) on graft and patient outcomes after LT. Methods We retrospectively analyzed 812 LT recipients treated with TAC. The IPV of TAC concentrations was estimated by calculating the coefficient of variation (CV) of whole blood trough concentrations. Patients were categorized in 2 groups: low IPV (CV < 40%) and high IPV (CV ≥ 40%). Results There were significantly more neurologic complications (31.2% vs 16.6%, P < 0.001), cardiovascular complications (19.7% vs 9.7%, P < 0.001), and acute renal failure requiring dialysis (8.5% vs 2.2%, P < 0.001) in the high CV group than in the low CV group. Moreover, graft survival was significantly poorer in the high CV group (hazard ratio, 1.42; 95% confidence interval, 1.04-1.95; P = 0.03). A pretransplantation elevated Model for End-Stage Liver Disease score (P < 0.001) and Child-Pugh grade (P < 0.001) were identified as risk factors for presenting a high CV. Conclusions A high CV of TAC concentrations was found to be predictive of TAC-related toxicity and poorer survival.

Summary: Background: There are limited data concerning infliximab drug monitoring during de‐escalation of the treatment of inflammatory bowel disease (IBD).Aim: To define the rate and the predictors of relapse following infliximab de‐escalation in IBD patients in remission.Methods: All IBD patients at a single referral centre in clinical and biological remission and in whom the dose of infliximab had been de‐escalated were included. Patients in remission with a high trough level of infliximab (>7 mg/L) were considered to be trough level‐based de‐escalation patients. The data were retrieved from a prospective IBD database. Actuarial analysis was performed for statistical purposes.Results: A total of 146 de‐escalations were performed in 96 patients (Crohn's disease/ulcerative colitis: 68%/32%); 54 (37%) were based on clinical remission only, and 92 (63%) were based on clinical remission associated with a trough level above 7 mg/L. The cumulative probabilities of relapse following infliximab de‐escalation were 16% and 47% at 1 and 2 years, respectively. Ulcerative colitis was associated with an increased risk of relapse (HR = 3.2, P = 0.005). Conversely, combination therapy at infliximab initiation (HR = 0.39, P = 0.0110) and trough level‐based de‐escalation were associated with decreased risk of relapse (HR = 0.45, P = 0.024). Trough levels before and after de‐escalation were well correlated; a decrease by half was observed following a 2‐week interval increase or a half‐dose decrease.Conclusion: The use of trough levels to assess the feasibility of dose de‐escalation seems to be a prerequisite for decreasing the risk of relapse.