Early use of tocilizumab in patients with severe pneumonia secondary to severe acute respiratory syndrome coronavirus 2 infection and poor prognostic criteria: Impact on mortality rate and intensive care unit admission.

ABSTRACT: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, keeps spreading globally. Evidence suggests that a subgroup of patients with severe symptomatology might have cytokine storms, which increases mortality. The use of interleukin-6 (IL-6) inhibitors may help in controlling the pathological immune response to the virus. Tocilizumab, a monoclonal antibody against IL-6, stands as an optional treatment for COVID-19 patients presenting this inflammatory hyper-response.We conducted a retrospective, observational, cohort study including 50 patients affected by COVID-19 with severe pneumonia and poor prognosis criteria, who have also undergone standard treatment; 36 of these patients additionally received tocilizumab in an early stage. The need for intensive care unit (ICU) admission, mortality, recovery of respiratory function, and improvement of biochemical and hematological parameters were compared between cohorts.Most patients were men, non-smokers and the most frequently reported comorbidities were hypertension and diabetes. Recurrent symptoms were fever, cough, and dyspnoea. 54.8% of patients from the tocilizumab group needed intubation, while in the control group 85.7% needed it. Treatment with tocilizumab significatively increased IL-6 levels, (554.45; CI 95% 186.69, 1032.93; P < .05) while C-reactive protein mean levels were reduced (-108.19; CI 95% -140.15, -75.33; P < .05), but no significant difference was found between cohorts. In comparison with the controls, tocilizumab reduced mortality (25.0% vs 42.9%, P = .021) and the number of ICU admissions (63.9% vs 100.0%, P = .021). 44.1% of patients treated with tocilizumab showed favorable radiological evolution, when compared with 15.4% of patients from the control group.Tocilizumab may improve clinical symptoms and mitigate deterioration observed in severe COVID-19 patients, and could be considered as an effective therapeutic option in subjects experiencing a significant inflammatory response to the disease.

Monophonic and Polyphonic Wheezing Classification Based on Constrained Low-Rank Non-Negative Matrix Factorization.

The appearance of wheezing sounds is widely considered by physicians as a key indicator to detect early pulmonary disorders or even the severity associated with respiratory diseases, as occurs in the case of asthma and chronic obstructive pulmonary disease. From a physician's point of view, monophonic and polyphonic wheezing classification is still a challenging topic in biomedical signal processing since both types of wheezes are sinusoidal in nature. Unlike most of the classification algorithms in which interference caused by normal respiratory sounds is not addressed in depth, our first contribution proposes a novel Constrained Low-Rank Non-negative Matrix Factorization (CL-RNMF) approach, never applied to classification of wheezing as far as the authors' knowledge, which incorporates several constraints (sparseness and smoothness) and a low-rank configuration to extract the wheezing spectral content, minimizing the acoustic interference from normal respiratory sounds. The second contribution automatically analyzes the harmonic structure of the energy distribution associated with the estimated wheezing spectrogram to classify the type of wheezing. Experimental results report that: (i) the proposed method outperforms the most recent and relevant state-of-the-art wheezing classification method by approximately 8% in accuracy; (ii) unlike state-of-the-art methods based on classifiers, the proposed method uses an unsupervised approach that does not require any training.

Economic Impact and Clinical Outcomes of Omalizumab Add-On Therapy for Patients with Severe Persistent Asthma: A Real-World Study.

BACKGROUND: Omalizumab is a fully humanized monoclonal antibody indicated as add-on therapy to improve asthma control in patients with severe persistent allergic asthma. AIMS: The aim of this study was to evaluate social, healthcare expenditure and clinical outcomes changes after incorporating omalizumab into standard treatment in the control of severe asthma. METHODS: In this multicentre retrospective study, a total of 220 patients were included from 15 respiratory medicine departments in the regions of Andalusia and Extremadura (Spain). Effectiveness was calculated as a 3-point increase in the Asthma Control Test (ACT) and a reduction in the annual number of exacerbations. The economic evaluation included both direct and indirect costs. Incremental cost-effectiveness ratio (ICER) was calculated. Results from the year before and the year after incorporation of omalizumab were compared. RESULTS: After adding omalizumab, improvement of lung function, asthma and rhinitis according to patient perception, as well as the number of exacerbations and asthma control measured by the ACT score were observed. Globally, both healthcare resources and pharmacological costs decreased after omalizumab treatment, excluding omalizumab cost. When only direct costs were considered, the ICER was €1712 (95% CI 1487-1995) per avoided exacerbation and €3859 (95% CI 3327-4418) for every 3-point increase in the ACT score. When both direct and indirect costs were considered, the ICER was €1607 (95% CI 1385-1885) for every avoided exacerbation and €3555 (95% CI 3012-4125) for every 3-point increase. CONCLUSIONS: Omalizumab was shown to be an effective add-on therapy for patients with persistent severe asthma and allowed reducing key drivers of asthma-related costs.