Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The community-acquired pneumonia symptom questionnaire: a new, patient-based outcome measure to evaluate symptoms in patients with community-acquired pneumonia.

STUDY OBJECTIVE: s: To develop and validate a patient-based outcome measure to evaluate symptoms in patients with community-acquired pneumonia (CAP). DESIGN: A psychometric study within an international, prospective, randomized, double-blind study. The CAP-symptom questionnaire (CAP-Sym) is a new, 18-item, patient-reported outcome measure that evaluates the bothersomeness of CAP-related symptoms during the past 24 h using a 6-point Likert scale. We used "gold standard" psychometric methods to comprehensively evaluate the acceptability, reliability, validity, and responsiveness of the CAP-Sym. SETTING: Sixty-four centers in 13 countries (France, Germany, Hungary, Israel, Italy, Norway, Poland, Portugal, South Africa, Spain, Sweden, Switzerland, United Kingdom). PATIENTS: Five hundred fifty-six patients with CAP, recruited from outpatient clinics, general practice, and hospital centers. INTERVENTIONS: Randomization 1:1 to moxifloxacin (400 mg once daily), oral or standard oral treatment (amoxicillin, 1 g tid, or clarithromycin, 500 mg bid), alone or in combination, for up to 14 days. RESULTS: Standard psychometric tests confirmed the acceptability (item nonresponse, item-endorsement frequencies, item/scale floor and ceiling effects), reliability (internal consistency, item-total and inter-item correlations, test-retest reliability), validity (content, construct, convergent, discriminant, known groups), and responsiveness of the CAP-Sym. CONCLUSIONS: The CAP-Sym is a practical and scientifically sound patient-based outcome measure of CAP-related symptoms that has been developed using "gold standard" methods. As the only fully validated measure of symptoms in patients with CAP, which is quick and easy to administer and is more responsive than the generic Medical Outcomes Study 36-Item Short-Form Health Survey, the CAP-Sym provides a practical and rigorous method for improving the evaluation of outcomes in clinical trials and audit

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BnF-Partenariats, Collection sonore - BelieveContient une table des matière

Safety and Outcome of Carotid Dissection Stenting During the Treatment of Tandem Occlusions: A Pooled Analysis of TITAN and ETIS

International audienceBackground and Purpose: The efficacy of endovascular therapy in patients with acute ischemic stroke due to tandem occlusion is comparable to that for isolated intracranial occlusion in the anterior circulation. However, the optimal management of acute cervical internal carotid artery lesions is unknown, especially in the setting of carotid dissection, but emergency carotid artery stenting (CAS) is frequently considered. We investigated the safety and efficacy of emergency CAS for carotid dissection in patients with acute stroke with tandem occlusion in current clinical practice. Methods: We retrospectively analyzed a prospectively maintained database composed of 2 merged multicenter international observational real-world registries (Endovascular Treatment in Ischemic Stroke and Thrombectomy in Tandem Lesion). Data from endovascular therapy performed in the treatment of tandem occlusions related to acute cervical carotid dissection between January 2012 and January 2019 at 24 comprehensive stroke centers were analyzed. Results: The study assessed 136 patients with tandem occlusion due to dissection, including 65 (47.8%) treated with emergency CAS and 71 (52.2%) without. The overall rates of favorable outcome (90-day modified Rankin Scale score, 0–2) and successful reperfusion (modified Thrombolysis in Cerebral Infarction, 2b–3) were 58.0% (n=76 [95% CI, 49.6%–66.5%]) and 77.9% (n=106 [95% CI, 71.0%–85.0%]), respectively. In subgroup analyses, the rate of successful reperfusion (89.2% versus 67.6%; adjusted odds ratio, 2.24 [95% CI, 1.33–3.77]) was higher after CAS, whereas the 90-day favorable outcome (54.3% versus 61.4%; adjusted odds ratio, 0.84 [95% CI, 0.58–1.22]), symptomatic intracerebral hemorrhage (sICH; 10.8% versus 5.6%; adjusted odds ratio, 1.59 [95% CI, 0.79–3.17]), and 90-day mortality (8.0% versus 5.8%; adjusted odds ratio, 1.00 [95% CI, 0.48–2.09]) did not differ. In sensitivity analyses of patients with successful intracranial reperfusion, CAS was not associated with an improved clinical outcome. Conclusions: Emergency stenting of the dissected cervical carotid artery during endovascular therapy for tandem occlusions seems safe, whatever the quality of the intracranial reperfusion

Prognosis and risk factors associated with asymptomatic intracranial hemorrhage after endovascular treatment of large vessel occlusion stroke: a prospective multicenter cohort study

International audienceBackground and purpose: Asymptomatic intracranial hemorrhage (aICH) is a common occurrence after endovascular treatment (EVT) for acute ischemic stroke (AIS). The aims of this study were to address its impact on 3-month functional outcome and to identify risk factors for aICH after EVT. Methods: Patients with AIS attributable to anterior circulation large vessel occlusion who underwent EVT were enrolled in a multicenter prospective registry. Based on imaging performed 22–36 h post-EVT, we included patients with no intracranial hemorrhage (ICH) or aICH. Poor outcome defined as a 3-month modified Rankin Scale (mRS) score 4–6 and overall 3-month mRS score distribution were compared according to presence/absence of aICH, and aICH subtype using logistic regression. We assessed the risk factors of aICH using a multivariate logistic regression model. Results: Of the 1526 patients included in the study, 653 (42.7%) had aICH. Patients with aICH had a higher rate of poor outcome: odds ratio (OR) 1.88 (95% confidence interval [CI] 1.44–2.44). Shift analysis of mRS score found a fully adjusted OR of 1.79 (95% CI 1.47–2.18). Hemorrhagic infarction (OR 1.63 [95% CI 1.22–2.18]) and parenchymal hematoma (OR 2.99 [95% CI 1.77–5.02]) were associated with higher risk of poor outcome. Male sex, diabetes, coronary artery disease, baseline National Institutes of Health Stroke Scale score and Alberta Stroke Program Early Computed Tomography Score, number of passes and onset to groin puncture time were independently associated with aICH. Conclusions: Patients with aICH, irrespective of the radiological pattern, have a worse functional outcome at 3 months compared with those without ICH after EVT for AIS. The number of EVT passes and the time from onset to groin puncture are factors that could be modified to reduce deleterious ICH

Endovascular therapy with or without intravenous thrombolysis in acute stroke with tandem occlusion

International audienceBackground Endovascular therapy (EVT) is effective and safe in patients with tandem occlusion. The benefit of intravenous thrombolysis (IVT) prior to EVT in acute tandem occlusion is debatable. Objective To compare EVT alone with EVT plus IVT in patients with acute ischemic stroke due to anterior circulation tandem occlusions. Methods This is an individual patient pooled analysis of the Thrombectomy In TANdem lesions (TITAN) and Endovascular Treatment in Ischemic Stroke (ETIS) Registries. Patients were divided into two groups based on prior IVT treatment: (1) IVT+ group, which included patients who received IVT prior to EVT, (2) IVT− group, which included patients who did not receive IVT prior to EVT. Propensity score (inverse probability of treatment weighting (IPTW)) was used to reduce baseline between-group differences. The primary outcome was favorable outcome—that is, modified Rankin Scale (mRS) score 0 to 2 at 90 days. Results Overall, 602 consecutive patients with an acute stroke with tandem occlusion were included (380 and 222 in the bridging therapy and EVT alone groups, respectively). Onset to imaging time was shorter in the IVT+ group (median 103 vs 140 min). In contrast, imaging to puncture time was longer in the IVT+ group (median 107 vs 91 min). In IPTW analysis, the IVT+ group had higher odds of favorable outcome, excellent outcome (90-day mRS score 0–1), and successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2b/3 at the end of EVT). There was no difference in the risk of significant hemorrhagic complications between groups. In secondary analysis of patients treated with acute cervical internal carotid artery stenting, bridging therapy was associated with higher odds of favorable outcome and lower odds of mortality at 90 days. Conclusions Our results suggest that bridging therapy in patients with acute ischemic stroke due to anterior tandem occlusion is safe and may improve functional outcome, even in the setting of acute cervical internal carotid artery stenting during EVT

Thrombectomy complications in large vessel occlusions: Incidence, predictors, and clinical impact in the ETIS registry

International audienceBACKGROUND AND PURPOSE: Procedural complications in thrombectomy for large vessel occlusions of the anterior circulation are not well described. We investigated the incidence, risk factors, and clinical implications of thrombectomy complications in daily clinical practice. METHODS: We used data from the ongoing prospective multicenter observational Endovascular Treatment in Ischemic Stroke Registry in France. The present study is a retrospective analysis of 4029 stroke patients with anterior large vessel occlusions treated with thrombectomy between January 2015 and May 2020 in 18 centers. We systematically collected procedural data, incidence of embolic complications, perforations and dissections, clinical outcome at 90 days, and hemorrhagic complications. RESULTS: Procedural complications occurred in 7.99% (95% CI, 7.17%–8.87%), and embolus to a new territory (ENT) was the most frequent (5.2%). Predictors of ENTs were terminal carotid/tandem occlusion (odds ratio [OR], 5 [95% CI, 2.03–12.31]; P<0.001) and an increased total number of passes (OR, 1.22 [95% CI, 1.05–1.41]; P=0.006). ENTs were associated to worse clinical outcomes (90-day modified Rankin Scale score, 0–2; adjusted OR, 0.4 [95% CI, 0.25–0.63]; P<0.001), increased mortality (adjusted OR, 1.74 [95% CI, 1.2–2.53]; P<0.001), and symptomatic intracerebral hemorrhage (adjusted OR, 1.87 [95% CI, 1.15–3.03]; P=0.011). Perforations occurred in 1.69% (95% CI, 1.31%–2.13%). Predictors of perforations were terminal carotid/tandem occlusions (39.7% versus 27.6%; P=0.028). 40.7% of patients died at 90 days, and the overall rate of poor outcome was 74.6% in case of perforation. Dissections occurred in 1.46% (95% CI, 1.11%–1.88%) and were more common in younger patients (median age, 64.2 versus 70.2 years; P=0.002). Dissections did not affect the clinical outcome at 90 days. Besides dissection, complications were independent of the thrombectomy technique. CONCLUSIONS: Thrombectomy complication rate is not negligible, and ENTs were the most frequent. ENTs and perforations were associated with disability and mortality, and terminal carotid/tandem occlusions were a risk factor

Successful Thrombectomy Improves Functional Outcome in Tandem Occlusions with a Large Ischemic Core

International audienceBackground: Emergent stenting in tandem occlusions and mechanical thrombectomy (MT) of acute ischemic stroke related to large vessel occlusion (LVO-AIS) with a large core are tested independently. We aim to assess the impact of reperfusion with MT in patients with LVO-AIS with a large core and a tandem occlusion and to compare the safety of reperfusion between large core with tandem and nontandem occlusions in current practice. Methods: We analyzed data of all consecutive patients included in the prospective Endovascular Treatment in Ischemic Stroke Registry in France between January 2015 and March 2023 who presented with a pretreatment ASPECTS (Alberta Stroke Program Early CT Score) of 0–5 and angiographically proven tandem occlusion. The primary end point was a favorable outcome defined by a modified Rankin Scale (mRS) score of 0–3 at 90 days. Results: Among 262 included patients with a tandem occlusion and ASPECTS 0–5, 203 patients (77.5%) had a successful reperfusion (modified Thrombolysis in Cerebral Infarction grade 2b-3). Reperfused patients had a favorable shift in the overall mRS score distribution (adjusted odds ratio [aOR], 1.57 [1.22–2.03]; P < 0.001), higher rates of mRS score 0–3 (aOR, 7.03 [2.60–19.01]; P < 0.001) and mRS score 0–2 at 90 days (aOR, 3.85 [1.39–10.68]; P = 0.009) compared with nonreperfused. There was a trend between the occurrence of successful reperfusion and a decreased rate of symptomatic intracranial hemorrhage (aOR, 0.5 [0.22–1.13]; P = 0.096). Similar safety outcomes were observed after large core reperfusion in tandem and nontandem occlusions. Conclusions: Successful reperfusion was associated with a higher rate of favorable outcome in large core LVO-AIS with a tandem occlusion, with a safety profile similar to nontandem occlusion