Time to hospital admission and start of treatment in patients with ischemic stroke in northern Italy and predictors of delay

Background and Purpose: Early treatment (i.e. thrombolysis) is crucial for a successful care of ischemic stroke. In the management of stroke, two phases are crucial: the pre-hospital and the in-hospital interval. This work investigated factors influencing pre- and in-hospital delay in a large geographic area of Northern Italy. Methods: Enrolled were patients presenting with ischemic stroke in four administrative districts of Northern Italy (Como, Lecco, Sondrio and Varese) over a 4-month period. Pre-hospital time and in-hospital time with single management steps were recorded prospectively. Age, gender, recruiting hospital, EMS transport and triage codes, clinical severity and thrombolytic treatment were also recorded. Univariate and multivariate analysis of factors predicting pre- and in-hospital delay were performed. Results: Median pre-hospital time and in-hospital time were, respectively, 120 min (interquartile range, IQR 62-271) and 150 min (IQR 80-214). Pre-hospital time was halved in patients hospitalized via EMS (p < 0.001) and clinically more severe (p < 0.001). At multivariate analysis, transport code was associated with delay at any time (p < 0.05). Conclusions: EMS use and transport code predicted treatment delay in patients with ischemic stroke. A more intensive use of EMS and high urgency codes could help increase the number of stroke patients treated appropriately

Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial

BackgroundTocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.MethodsA multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival.ResultsIn the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P=0.52) and 22.4% (97.5% CI: 17.2-28.3, P&lt;0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline.ConclusionsTocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline.Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092)