Assessment of continuous low-dose and high-dose burst of inhaled nitric oxide in spontaneously breathing COVID-19 patients: A randomized controlled trial.

BACKGROUND: Inhaled nitric oxide (iNO) showed to improve oxygenation at low doses by reducing intrapulmonary shunt and to display antiviral properties at high doses. To assess the safety and potential benefits, we designed an exploratory clinical trial comparing low-dose with intermittent high-dose iNO to only intermittent high-dose iNO in hypoxemic COVID-19 patients. METHODS: In this single-center interventional non-inferiority randomized trial (ClinicalTrials.gov, NCT04476992), twenty oxygen-dependent COVID-19 patients were randomly assigned to the high-dose (200 ppm for 30 min) + continuous low-dose (20 ppm) iNO group (iNO200/20) or the high-dose iNO group (iNO200). Methemoglobinemia (MetHb) assessed 48 h after iNO initiation was the primary endpoint. Reverse-transcription polymerase chain reaction for SARS-CoV-2, inflammatory markers during hospitalization, and heart ultrasounds during the iNO200 treatments were evaluated. RESULTS: MetHb difference between iNO groups remained within the non-inferiority limit of 3 %, indicating comparable treatments despite being statistically different (p-value<0.01). Both groups presented similar SpO2/FiO2 ratio at 48 h (iNO200 vs. iNO200/20 341[334-356] vs. 359 [331-380], respectively, p-value = 0.436). Both groups showed the same time to SARS-CoV-2 negativization, hospital length of stay, and recovery time. iNO-treated patients showed quicker SARS-CoV-2 negativization compared to a similar group of non-iNO patients (HR 2.57, 95%CI 1.04-6.33). During the 228 treatments, iNO200 and iNO200/20 groups were comparable for safety, hemodynamic stability, and respiratory function improvement. CONCLUSIONS: iNO200/20 and iNO200 are equally safe in non-intubated patients with COVID-19-induced respiratory failure with regards to MetHb and NO2. Larger studies should investigate whether iNO200/20 leads to better outcomes compared to non-iNO treated patients.

Thyrotropin levels and severity of symptoms in migraine patients of tertiary headache center.

BACKGROUND: The role of thyroid regulation in migraine is poorly understood, and data is contradictory. OBJECTIVE: To study the possible association of clinical features of migraine with patients' thyroid function. PATIENTS AND METHODS: One hundred and thirty migraine patients of a tertiary headache center took part in an open-label, cross-sectional comparative study. The Migraine Disability Assessment questionnaire, Spielberger State-Trait Anxiety Inventory, Beck Depression Inventory, Vanderbilt's Questionnaire of Pain Management, Gothenburg Quality of Life Questionnaire and Migraine-Specific Quality of Life questionnaire were used. The effectiveness of the attacks' therapy was assessed according to the Migraine Assessment of Current Therapy questionnaire. Levels of thyrotropine (thyroid stimulating hormone), thyroxine, and triiodothyronine were studied by standard immune chemiluminescent method using the Immulite-2000 set. RESULTS: An inverse correlation between levels of thyroid stimulating hormone in serum and duration of headache attacks was revealed. The effectiveness of abortive therapy for attacks showed a statistically significant positive correlation with thyroid stimulating hormone level. Quality of life measured by a general quality of life questionnaire, as well as the functional and social indices of a migraine-specific questionnaire, showed direct correlation with serum thyroid stimulating hormone. CONCLUSION: These results show an association of a more severe clinical course of migraine with lower thyroid stimulating hormone levels.