Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A 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. Results In 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 < 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. Conclusions Tocilizumab 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).

The present investigation was aimed at determining the prevalence and the blood pressure (BP) profile of isolated ambulatory hypertension, defined as an elevated ambulatory BP with normal office blood pressure, in a series of 1488 consecutive outpatients referred for routine clinical evaluation of suspected or established arterial hypertension. All patients underwent both office BP (OBP) measurement by a physician and 24-h ambulatory blood pressure monitoring (ABPM). Using OBP values (cutoff for diagnosis of hypertension X140/ 90 mmHg) and daytime ABPM (cutoff for diagnosis of hypertension X135/85 mmHg), patients were classified into eight subgroups. In the whole series we found that, independent of treatment status, the prevalence of isolated ambulatory hypertension exceeded 10%. More importantly, 45.3% of individuals who presented with normal OBP values, showed elevated BP at ABPM. Night-time BP, 24-h pulse pressure, and BP variability were significantly higher in isolated ambulatory hypertensives than in normotensive or in white-coat hypertensive individuals. Therefore, isolated ambulatory hypertension is characterized by a blood pressure profile that is similar to that observed in sustained hypertension. These findings suggest that isolated ambulatory hypertension is very common and probably the indications for ABPM should be more extensive in outpatients referred to hypertensive centre.

The positive inotropic effect of dopamine has been studied in isolated ventricular strips of guinea-pig heart. The concentration-inotropic response curve for dopamine was significantly shifted to the right by pretreatment with reserpine. In preparations obtained from animals pretreated with reserpine (2.5 mg/kg, 24 h prior to the experiment) the dose-response curve was not significantly affected by haloperidol, a dopamine vascular receptor antagonist (10(-6)-3X10(-6) M). The inotropic effect of dopamine was antagonized by practolol (3X10(-7)-10(-6) M), but not by phentolamine (3X10(-6)-10(-5) M); moreover the alpha-adrenoceptor blocking drug (10(-5) M) did not affect the curve for dopamine in the presence of practolol (3X10(-7) M). In preparations in which fast sodium channels were blocked by K+ -rich medium, slow electrical responses (calcium-mediated action potentials) as well as contractions were induced by high concentrations of dopamine (10(-4)-3X10(-4) M); again these responses were unaffected by phentolamine or haloperidol, but were blocked by practolol. It was concluded that in the guinea-pig ventricular muscle dopamine induced a positive inotropic effect through both indirect and direct action, and that the latter is due to the activation of beta-adrenoceptors.

The delirium feature that nurses were best able to recognize was cognitive fluctuations. The nonmotor subtype was associated with a lower recognition rate. Routine observation and registration of delirium features by nurses in clinical practice might be helpful to increase formal diagnosis of delirium.

Objective: Sensory deficits are important risk factors for delirium but have been investigated in single-center studies and single clinical settings. This multicenter study aims to evaluate the association between hearing and visual impairment or bi-sensory impairment (visual and hearing impairment) and delirium. Design: Cross-sectional study nested in the 2017 "Delirium Day" project. Setting and Participants: Patients 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes, and hospices in Italy. Methods: Delirium was assessed with the 4AT (a short tool for delirium assessment) and sensory deficits with a clinical evaluation. We assessed the association between delirium, hearing and visual impairment in multivariable logistic regression models, adjusting for: Model 1, we included predisposing factors for delirium (ie, dementia, weight loss and autonomy in the activities of daily living); Model 2, we added to Model 1 variables, which could be considered precipitating factors for delirium (ie, psychoactive drugs and urinary catheters). Results: A total of 3038 patients were included; delirium prevalence was 25%. Patients with delirium had a higher prevalence of hearing impairment (30.5% vs 18%; P < .001), visual impairment (24.2% vs 15.7%; P < .01) and bi-sensory impairment (16.2% vs 7.5%) compared with those without delirium. In the multivariable logistic regression analysis, the presence of bi-sensory impairment was associated with delirium in Model 1 [odds ratio (OR) 1.5, confidence interval (CI) 1.2e2.1; P ¼ .00] and in Model 2 (OR 1.4; CI 1.1e1.9; P ¼ .02), whereas the presence of visual and hearing impairment alone was not associated with delirium either in Model 1 (OR 0.8; CI 0.6e1.2, P ¼ .36; OR 1.1; CI 0.8e1.4; P ¼ .42) or in Model 2 (OR 0.8, CI 0.6e1.2, P ¼ .27; OR 1.1, CI 0.8e1.4, P ¼ .63).

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Late-onset dyspnea rate is notably lower than early-onset one; nevertheless prescribing clinicians should be aware that about one in 20 outpatients with a stabilized ticagrelor treatment might develop a dyspnea leading to an emergency department visit, and they should consider ticagrelor replacement only in patients who cannot tolerate dyspnea.

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