Introduction Patients discharged from intensive care units (ICUs) are at high risk of adverse long-term outcomes including cardiovascular and/or renal events and a 1-year mortality of approximately 22%. Plasma biomarkers measured at ICU discharge have demonstrated strong prognostic value, with elevated cardiac or renal biomarkers identifying patients at particularly high risk of poor outcomes. Sodium-glucose cotransporter 2 inhibitors are now widely recognised for their cardioprotective and nephroprotective effects in chronic conditions such as type 2 diabetes, heart failure or chronic kidney disease. These agents improve both morbidity and mortality across a range of high-risk populations. We hypothesise that a therapeutic strategy aimed at preventing the progression of cardiovascular and/or renal injury following ICU discharge may improve long-term outcomes in ICU survivors.Method and analysis This is a multicentre, double-blind, randomised, placebo-controlled clinical trial conducted across 16 teaching and non-teaching ICUs in France. We will enrol 600 adult patients (18 years of age or older) who have received mechanical ventilation and/or vasopressors for at least 24 hours during their ICU stay, and who meet at least one of the following criteria at ICU discharge: N-terminal pro-B-type natriuretic peptide (NT-proBNP) >800 pg/mL or BNP >90 ng/L, an estimated glomerular filtration rate between 25 and 90 mL/min/m². Eligible patients will be randomised in a 1:1 ratio to receive either dapagliflozin (10 mg once daily) or a matching placebo for a duration of 1 year. The primary outcome is a composite endpoint assessed at 1 year after randomisation, comprising: all-cause mortality, unscheduled hospitalisation for acute heart failure and decrease in renal function. Feasibility will be assessed based on patient and clinical acceptability and recruitment performance, including enrolment rates across participating centres.Ethics and dissemination This study has been approved by the Institutional Review Board (CPP Ile-de-France 5). Written informed consent will be obtained from all participants prior to enrolment and the initiation of any study-related procedures. Dapagliflozin is a widely available medication with an established safety profile. If proven effective, it would represent a readily deployable strategy to improve long-term outcomes in ICU survivors. The study is described in accordance with the Standard Protocol Items: Recommendations for Interventional Trials framework, and key design features and methodological decisions are outlined accordingly. DAPA-ICU aims to evaluate the efficacy of dapagliflozin in cardiorenal protection among critically ill patients following ICU discharge. The main trial results will be submitted for publication in a peer-reviewed journal as soon as they become available after final analysis.Trial registration number NCT07025629.
BACKGROUND:Sleep disturbances are frequent in the intensive care unit (ICU) and are associated with delirium or delayed mechanical ventilation weaning. Although international guidelines recommend structured screening and non-pharmacological management, their implementation in daily practice is poorly reported. This study aimed to evaluate the prevalence, screening practices, and management strategies for sleep disturbances in French ICUs. METHODS:This was a secondary analysis of the ESPRIT study, a national, multicenter, cross-sectional study conducted in 128 ICUs. All adult patients admitted on the study day were eligible. Data on unit-level practices and patient-level disturbances were collected. Sleep disturbances were identified by bedside physician. A multivariable multilevel logistic regression identified factors independently associated with sleep disturbances. RESULTS:Among 1,361 patients, 445 (33%) were reported to have sleep disturbances. Only 18% of ICUs conducted routine screening, and no center had implemented a multicomponent protocol. Environmental measures such as light and noise reduction were common, whereas earplugs 51/128 (40%) and eye masks 18/128 (14%) were rarely used. Pharmacological treatments were given to 219 patients (16%), mainly Z-drugs and hydroxyzine. In multivariable analysis, overnight family presence (OR 2.06 [1.12-3.81], p = 0.021) and physical restraints (OR 2.26 [1.39-3.70], p = 0.001) were independently associated with increased risk of sleep disturbances. Optimization of nursing tasks was the only intervention that tended to reduce sleep disturbances (OR 0.57 [0.31-1.04], p = 0.069). CONCLUSION:Sleep disturbances are common in ICUs, yet routine screening and structured management remain rare. Standardized, nurse-led screening and broader adoption of non-pharmacological protocols are needed to improve sleep quality and patient outcomes.
AIMS:Subcutaneous implantable cardioverter defibrillator (S-ICD) therapy is a well-established therapy for the prevention of sudden cardiac death. Although general anaesthesia (GA) was initially advocated for implantation, non-GA has emerged as a feasible alternative in clinical practice. This study evaluated the early and long-term outcomes associated with anaesthetic modality during S-ICD implantation procedures. METHODS AND RESULTS:The nationwide, single-arm, observational HONEST cohort study included all patients implanted with an S-ICD (EMBLEM™, Boston Scientific) in France between 2012 and 2019. GA was characterised by controlled unconsciousness with airway management, while non-GA included all alternative techniques. Among 4924 patients, 1041 (21.1%) underwent non-GA. The proportion of non-GA use increased from 2.5% to 26.9% between 2012 and 2019 (P < 0.001). Patients undergoing implantation under non-GA tended to be older (51 ± 14 vs. 50 ± 15 years), had lower left ventricular ejection fraction (41 ± 16 vs. 43 ± 17%), and fewer secondary prevention indications (33 vs. 38%) (all P < 0.01). The 30-day complication rate was 3.4% in the non-GA group (vs. 3.7% in the GA group; P = 0.85). At follow-up, the incidence of overall complications (4.29 events per 100 person-years for non-GA vs. 4.73 for GA; P = 0.937), reintervention (1.21 vs. 1.62; P = 0.963), inappropriate shocks (2.88 vs. 2.78; P = 0.782), and all-cause mortality (2.93 vs. 2.56; P = 0.938) were similar between groups. Multivariable analysis confirmed that there were no differences across outcomes (all P values >0.1). CONCLUSION:The anaesthesia strategy used for S-ICD implantation was not associated with poorer short- or long-term clinical outcomes, supporting non-general anaesthesia as a feasible alternative in appropriately selected patients. CLINICALTRIALS.GOV ID:NCT05302115.
9576 Background: Anti-PD-1 immunotherapies and BRAF+MEK inhibitors (BRAFi/MEKi) (specifically for BRAF V600E/K-mutant melanoma) have been shown to improve recurrence-free survival (RFS) in patients (pts) with resected stage III metastatic melanoma in phase III trials. However, none of these studies has demonstrated a significant improvement in overall survival (OS). Notably, adjuvant BRAFi/MEKi therapy has shown better OS only in the BRAF V600E subgroup of patients. In this context, we evaluated the real-world impact of adjuvant therapies on OS. Methods: TAMARIS is a national multicenter retrospective study designed to evaluate the efficacy of adjuvant treatment (anti-PD-1 or BRAFi/MEKi) in pts with resected AJCC 8 th edition stage III melanoma using data from the French RIC-Mel prospective database. The primary endpoint was OS analyzed using the Kaplan-Meier method, comparing pts who received adjuvant treatment (adjuvant group) within 3 months of surgery to those who did not (control group). Demographic and clinical characteristics were compared using chi-square analyses. Secondary endpoints included OS in specific subgroups and RFS. Results: A total of 1,172 pts (median age: 65 years [IQR: 53–74]) with resected stage III melanoma were included between 2018 and 2023. Among them, 796 pts (68%) received adjuvant treatment with anti-PD-1 (n=676) or BRAFi/MEKi (n=120). The median treatment duration was 10.8 months (IQR: 5.6–11.9). Most pts had a history of SSM (54%) with a median Breslow thickness of 2.8 mm [range, 0-47] and stage IIIB (31%) or IIIC disease (49%). Surgical interventions for metastases prior to adjuvant treatment included lymph node dissection in 53% of cases, sentinel lymph node biopsy in 38%, and cutaneous metastasis resection in 8%. Pts in the control group were older (median age: 69.7 vs. 63.0 years, p < 0.0001). The median follow-up was 30.4 months (IQR: 16.7-43.3). OS was significantly longer in the adjuvant group compared to the control group (HR: 0.617; 95% CI: 0.474-0.802; p = 0.0003), with a 2-year OS of 90% (95% CI: 88-92) in the adjuvant group versus 79% (95% CI: 74-83) in the control group. There was a trend toward better OS with BRAFi/MEKi compared to anti-PD-1 (HR: 0.569; 95% CI: 0.312-1.037; p = 0.065). Subgroup analyses demonstrated a significant positive impact of adjuvant treatment on OS across most subgroups, except for pts aged ≤75 years, those with stage IIIA disease, primary melanomas with a Breslow thickness <2.8 mm, or without ulceration. RFS also favored the adjuvant group (HR: 0.545; 95% CI: 0.458-0.649; p < 0.0001), with a 2-year RFS of 67% (95% CI: 63-70) and 45% (95% CI: 40-50) in the control group. Conclusions: Adjuvant treatment appears to provide an OS benefit in patients with resected stage III melanoma in real-world settings. Further research is required as age-related differences may influence prognosis.
