A safety evaluation of intermittent high-dose inhaled nitric oxide in viral pneumonia due to COVID-19: a randomised clinical study

{ 'indexed': {'date-parts': [[2024, 7, 28]], 'date-time': '2024-07-28T00:19:25Z', 'timestamp': 1722125965374}, 'reference-count': 55, 'publisher': 'Springer Science and Business Media LLC', 'issue': '1', 'license': [ { 'start': { 'date-parts': [[2024, 7, 26]], 'date-time': '2024-07-26T00:00:00Z', 'timestamp': 1721952000000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by-nc-nd/4.0'}, { 'start': { 'date-parts': [[2024, 7, 26]], 'date-time': '2024-07-26T00:00:00Z', 'timestamp': 1721952000000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by-nc-nd/4.0'}], 'funder': [{'name': 'Beyond Air Inc.'}], 'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False}, 'DOI': '10.1038/s41598-024-68055-w', 'type': 'journal-article', 'created': {'date-parts': [[2024, 7, 27]], 'date-time': '2024-07-27T00:03:07Z', 'timestamp': 1722038587000}, 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'A safety evaluation of intermittent high-dose inhaled nitric oxide in viral pneumonia due to ' 'COVID-19: a randomised clinical study', 'prefix': '10.1038', 'volume': '14', 'author': [ {'given': 'Talya', 'family': 'Wolak', 'sequence': 'first', 'affiliation': []}, {'given': 'D.', 'family': 'Dicker', 'sequence': 'additional', 'affiliation': []}, {'given': 'Y.', 'family': 'Shifer', 'sequence': 'additional', 'affiliation': []}, {'given': 'A.', 'family': 'Grossman', 'sequence': 'additional', 'affiliation': []}, {'given': 'A.', 'family': 'Rokach', 'sequence': 'additional', 'affiliation': []}, {'given': 'M.', 'family': 'Shitrit', 'sequence': 'additional', 'affiliation': []}, {'given': 'A.', 'family': 'Tal', 'sequence': 'additional', 'affiliation': []}], 'member': '297', 'published-online': {'date-parts': [[2024, 7, 26]]}, 'reference': [ { 'key': '68055_CR1', 'doi-asserted-by': 'publisher', 'unstructured': 'Ichinose, F., Roberts, J. D. Jr. & Zapol, W. M. Inhaled nitric oxide: A ' 'selective pulmonary vasodilator: Current uses and therapeutic potential. ' 'Circulation. 109, 3106–3111. ' 'https://doi.org/10.1161/01.CIR.0000134595.80170.62 (2004).', 'DOI': '10.1161/01.CIR.0000134595.80170.62'}, { 'key': '68055_CR2', 'doi-asserted-by': 'publisher', 'unstructured': 'Rossaint, R., Lewandowski, K. & Zapol, W. M. Our paper 20 years later: ' 'Inhaled nitric oxide for the acute respiratory distress ' 'syndrome—discovery, current understanding, and focused targets of future ' 'applications. Intensive Care Med. 40, 1649–1658. ' 'https://doi.org/10.1007/s00134-014-3458-6 (2014).', 'DOI': '10.1007/s00134-014-3458-6'}, { 'key': '68055_CR3', 'doi-asserted-by': 'publisher', 'unstructured': 'Adusumilli, N. C., Zhang, D., Friedman, J. M. & Friedman, A. J. ' 'Harnessing nitric oxide for preventing, limiting and treating the severe ' 'pulmonary consequences of COVID-19. Nitric Oxide. 103, 4–8. ' 'https://doi.org/10.1016/j.niox.2020.07.003 (2020).', 'DOI': '10.1016/j.niox.2020.07.003'}, { 'key': '68055_CR4', 'doi-asserted-by': 'publisher', 'unstructured': 'Bogdan, C. Nitric oxide and the immune response. Nat. Immunol. 2, ' '907–916. https://doi.org/10.1038/ni1001-907 (2001).', 'DOI': '10.1038/ni1001-907'}, { 'issue': '10', 'key': '68055_CR5', 'doi-asserted-by': 'publisher', 'first-page': '820', 'DOI': '10.1038/nrmicro1004', 'volume': '2', 'author': 'FC Fang', 'year': '2004', 'unstructured': 'Fang, F. C. Antimicrobial reactive oxygen and nitrogen species: Concepts ' 'and controversies. Nat. Rev. Microbiol. 2(10), 820–832. ' 'https://doi.org/10.1038/nrmicro1004 (2004).', 'journal-title': 'Nat. Rev. Microbiol.'}, { 'key': '68055_CR6', 'doi-asserted-by': 'publisher', 'unstructured': 'Hajian, B. et al. Pulmonary vascular effects of pulsed inhaled nitric ' 'oxide in COPD patients with pulmonary hypertension. Int. J. Chron. ' 'Obstruct. Pulmon Dis. 11, 1533–1541. ' 'https://doi.org/10.2147/COPD.S106480 (2016).', 'DOI': '10.2147/COPD.S106480'}, { 'key': '68055_CR7', 'doi-asserted-by': 'publisher', 'unstructured': 'Ricciardolo, F. L. Multiple roles of nitric oxide in the airways. ' 'Thorax. 58, 175–182. https://doi.org/10.1136/thorax.58.2.175 (2003).', 'DOI': '10.1136/thorax.58.2.175'}, { 'key': '68055_CR8', 'doi-asserted-by': 'publisher', 'unstructured': 'Sorbo, L. D. et al. High doses of inhaled nitric oxide as an innovative ' 'antimicrobial strategy for lung infections. Biomedicines. 10, 1525. ' 'https://doi.org/10.3390/biomedicines10071525 (2022).', 'DOI': '10.3390/biomedicines10071525'}, { 'key': '68055_CR9', 'doi-asserted-by': 'publisher', 'unstructured': 'Di Fenza, R. et al. High-dose inhaled nitric oxide in acute hypoxemic ' 'respiratory failure due to COVID-19: A multicenter phase 2 trial. Am. J. ' 'Respir. Crit. Care Med. 208, 1293–1304. ' 'https://doi.org/10.1164/rccm.202304-0637OC (2023).', 'DOI': '10.1164/rccm.202304-0637OC'}, { 'key': '68055_CR10', 'doi-asserted-by': 'publisher', 'unstructured': 'Flume, P. A. et al. Inhaled nitric oxide for adults with pulmonary ' 'non-tuberculous mycobacterial infection. Respir. Med. 206, 107069. ' 'https://doi.org/10.1016/j.rmed.2022.107069 (2023).', 'DOI': '10.1016/j.rmed.2022.107069'}, { 'key': '68055_CR11', 'doi-asserted-by': 'publisher', 'unstructured': 'Bentur, L. et al. Pilot study to test inhaled nitric oxide in cystic ' 'fibrosis patients with refractory Mycobacterium abscessus lung ' 'infection. J. Cyst. Fibros. 19, 225–231. ' 'https://doi.org/10.1016/j.jcf.2019.05.002 (2020).', 'DOI': '10.1016/j.jcf.2019.05.002'}, { 'key': '68055_CR12', 'doi-asserted-by': 'publisher', 'unstructured': 'Akerström, S. et al. Nitric oxide inhibits the replication cycle of ' 'severe acute respiratory syndrome coronavirus. J. Virol. 79, 1966–1969. ' 'https://doi.org/10.1128/JVI.79.3.1966-1969.2005 (2005).', 'DOI': '10.1128/JVI.79.3.1966-1969.2005'}, { 'key': '68055_CR13', 'doi-asserted-by': 'publisher', 'first-page': '1', 'DOI': '10.1016/j.virol.2009.09.007', 'volume': '395', 'author': 'S Åkerström', 'year': '2009', 'unstructured': 'Åkerström, S. et al. Dual effect of nitric oxide on SARS-CoV ' 'replication: Viral RNA production and palmitoylation of the S protein ' 'are affected. Virology. 395, 1–9 (2009).', 'journal-title': 'Virology.'}, { 'key': '68055_CR14', 'doi-asserted-by': 'publisher', 'unstructured': 'Garren, M. R. et al. Nitric oxide and viral infection: Recent ' 'developments in antiviral therapies and platforms. Appl. Mater Today. ' '22, 100887. https://doi.org/10.1016/j.apmt.2020.100887 (2021).', 'DOI': '10.1016/j.apmt.2020.100887'}, { 'key': '68055_CR15', 'doi-asserted-by': 'publisher', 'unstructured': 'Hu, Z. et al. Overview of viral pneumonia associated with influenza ' 'virus, respiratory syncytial virus, and coronavirus, and therapeutics ' 'based on natural products of medicinal plants. Front. Pharmacol. 12: ' '630834. https://doi.org/10.3389/fphar.2021.630834 (2021).', 'DOI': '10.3389/fphar.2021.630834'}, { 'key': '68055_CR16', 'doi-asserted-by': 'publisher', 'unstructured': 'Wu, Z. & McGoogan, J. M. Characteristics of and important lessons from ' 'the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a ' 'report of 72,314 cases from the Chinese Center for disease control and ' 'prevention. JAMA. 323,1239–1242. https://doi.org/10.1001/jama.2020.2648 ' '(2020).', 'DOI': '10.1001/jama.2020.2648'}, { 'key': '68055_CR17', 'doi-asserted-by': 'publisher', 'unstructured': 'Tin Tin Htar, M., Yerramalla, M. S., Moïsi, J. C. & Swerdlow, D. L. The ' 'burden of respiratory syncytial virus in adults: A systematic review and ' 'meta-analysis. Epidemiol. Infect. 148: e48. ' 'https://doi.org/10.1017/S0950268820000400 (2020).', 'DOI': '10.1017/S0950268820000400'}, { 'key': '68055_CR18', 'unstructured': 'Centers for Disease Control and Prevention, National Center for ' 'Immunization and Respiratory Diseases (NCIRD). Preliminary Estimated ' 'Influenza Illnesses, Medical visits, Hospitalizations, and Deaths in the ' 'United States – 2021–2022 influenza ' 'seasonhttps://www.cdc.gov/flu/about/burden/2021-2022.htm#:~:text=The%20overall%20burden%20of%20influenza,flu%20deaths%20 ' '(2022).'}, { 'key': '68055_CR19', 'unstructured': 'U.S. Food and Drug Administration, The Center for Devices and ' 'Radiological Health (CDRH). LungFit® PH - P200044 ' 'https://www.fda.gov/medical-devices/recently-approved-devices/lungfit-ph-p200044 ' '(2022).'}, { 'key': '68055_CR20', 'unstructured': 'European Medicines Agency. INOmax nitric ' 'chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.ema.europa.eu/en/documents/overview/inomax-epar-summary-public_en.pdf ' '(2011).'}, { 'key': '68055_CR21', 'doi-asserted-by': 'publisher', 'unstructured': 'Valsecchi, C. et al. High-dose inhaled nitric oxide for the treatment of ' 'spontaneously breathing pregnant patients with severe coronavirus ' 'disease 2019 (COVID-19) Pneumonia. Obstet. Gynecol. 140, 195–203. ' 'https://doi.org/10.1097/AOG.0000000000004847 (2022).', 'DOI': '10.1097/AOG.0000000000004847'}, { 'key': '68055_CR22', 'doi-asserted-by': 'publisher', 'unstructured': 'Safaee, F. B. et al. Inhaled high dose nitric oxide is a safe and ' 'effective respiratory treatment in spontaneous breathing hospitalized ' 'patients with COVID-19 pneumonia. Nitric Oxide. 11, 7–13. ' 'https://doi.org/10.1016/j.niox.2021.08.003 (2021).', 'DOI': '10.1016/j.niox.2021.08.003'}, { 'key': '68055_CR23', 'doi-asserted-by': 'publisher', 'unstructured': 'Safaee, F. B. et al. High concentrations of nitric oxide inhalation ' 'therapy in pregnant patients with severe coronavirus disease 2019 ' '(COVID-19). Obstet. Gynecol. 136, 1109–1113; ' 'https://doi.org/10.1097/AOG.0000000000004128 (2020).', 'DOI': '10.1097/AOG.0000000000004128'}, { 'key': '68055_CR24', 'doi-asserted-by': 'publisher', 'unstructured': 'Wiegand, S. B. et al. Rescue treatment with high-dose gaseous nitric ' 'oxide in spontaneously breathing patients with severe coronavirus ' 'disease 2019. Crit. Care Explor. 2, e0277. ' 'https://doi.org/10.1097/CCE.0000000000000277 (2020).', 'DOI': '10.1097/CCE.0000000000000277'}, { 'key': '68055_CR25', 'doi-asserted-by': 'publisher', 'unstructured': 'Kamenshchikov, N. O., Berra, L. & Carroll, R. W. therapeutic effects of ' 'inhaled nitric oxide therapy in COVID-19 patients. Biomedicines. 10, ' '369. https://doi.org/10.3390/biomedicines10020369 (2022).', 'DOI': '10.3390/biomedicines10020369'}, { 'key': '68055_CR26', 'doi-asserted-by': 'publisher', 'unstructured': 'Tal, A. et al. Nitric oxide inhalations in bronchiolitis: A pilot, ' 'randomized, double-blinded, controlled trial. Pediatr Pulmonol. 53, ' '95–102.https://doi.org/10.1002/ppul.23905 (2018).', 'DOI': '10.1002/ppul.23905'}, { 'key': '68055_CR27', 'doi-asserted-by': 'publisher', 'unstructured': 'Goldbart, A. et al. Inhaled nitric oxide therapy in acute bronchiolitis: ' 'A multicenter randomized clinical trial [published correction appears in ' 'Sci Rep. 2020 Oct 14;10(1):17640]. Sci. Rep. 10, 9605. ' 'https://doi.org/10.1038/s41598-020-66433-8 (2020).', 'DOI': '10.1038/s41598-020-66433-8'}, { 'key': '68055_CR28', 'doi-asserted-by': 'publisher', 'unstructured': 'Goldbart, A. et al. Inhaled nitric oxide for the treatment of acute ' 'bronchiolitis: A multicenter randomized controlled clinical trial to ' 'evaluate dose response. Ann. Am. Thorac. Soc. 20, 236–244. ' 'https://doi.org/10.1513/AnnalsATS.202103-348OC (2023).', 'DOI': '10.1513/AnnalsATS.202103-348OC'}, { 'key': '68055_CR29', 'doi-asserted-by': 'publisher', 'first-page': '48', 'DOI': '10.1016/j.niox.2013.03.007', 'volume': '31', 'author': 'G Regev-Shoshani', 'year': '2013', 'unstructured': 'Regev-Shoshani, G. et al. Gaseous nitric oxide reduces influenza ' 'infectivity in vitro. Nitric Oxide. 31, 48–53. ' 'https://doi.org/10.1016/j.niox.2013.03.007 (2013).', 'journal-title': 'Nitric Oxide.'}, { 'key': '68055_CR30', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.redox.2020.101734', 'volume': '37', 'author': 'D Akaberi', 'year': '2020', 'unstructured': 'Akaberi, D. et al. Mitigation of the replication of SARS-CoV-2 by nitric ' 'oxide in vitro. Redox Biol. 37, 101734 (2020).', 'journal-title': 'Redox Biol.'}, { 'key': '68055_CR31', 'doi-asserted-by': 'publisher', 'first-page': '1147', 'DOI': '10.1016/j.bbrc.2005.02.085', 'volume': '329', 'author': 'E Keyaerts', 'year': '2005', 'unstructured': 'Keyaerts, E. et al. Growth kinetics of SARS-coronavirus in vero E6 ' 'cells. Biochem. Biophys. Res. Commun. 329, 1147–2115 (2005).', 'journal-title': 'Biochem. Biophys. Res. Commun.'}, { 'key': '68055_CR32', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.redox.2020.101826', 'volume': '39', 'author': 'SB Wiegand', 'year': '2021', 'unstructured': 'Wiegand, S. B. et al. Antimicrobial effects of nitric oxide in murine ' 'models of Klebsiella pneumonia. Redox. Biol. 39, 101826 (2021).', 'journal-title': 'Redox. Biol.'}, { 'key': '68055_CR33', 'doi-asserted-by': 'publisher', 'unstructured': 'Gottlieb, R. L. et al. Early remdesivir to prevent progression to severe ' 'Covid-19 in outpatients. N. Engl. J. Med. 386, 305–315. ' 'https://doi.org/10.1056/NEJMoa2116846 (2022).', 'DOI': '10.1056/NEJMoa2116846'}, { 'key': '68055_CR34', 'doi-asserted-by': 'publisher', 'unstructured': 'Buchanan, J., Li, M., Hendrickson, B., Bhargava, P., & Roychoudhury S. ' 'Assessing adverse events in clinical trials during the era of the ' 'COVID-19 pandemic. J. Biopharmaceut. Stat. 33, 466–475. ' 'https://doi.org/10.1080/10543406.2023.2170398 (2023).', 'DOI': '10.1080/10543406.2023.2170398'}, { 'key': '68055_CR35', 'unstructured': 'Centers for Disease Control and Prevention. Nitrogen Dioxide ' 'https://www.cdc.gov/niosh/idlh/10102440.html (2018).'}, { 'key': '68055_CR36', 'doi-asserted-by': 'publisher', 'unstructured': 'Mayorga, M.\xa0Overview of nitrogen dioxide effects on lung with ' 'emphasis on military. relevance, Toxicology. 89, 175–192. ' 'https://doi.org/10.1016/0300-483x(94)90097-3 (1994).', 'DOI': '10.1016/0300-483x(94)90097-3'}, { 'key': '68055_CR37', 'doi-asserted-by': 'publisher', 'unstructured': 'Lolascon, A. et al. Recommendations for diagnosis and treatment of ' 'methemoglobinemia. Am. J. Hematol. 96, 1666–1678. ' 'https://doi.org/10.1002/ajh.26340 (2021).', 'DOI': '10.1002/ajh.26340'}, { 'key': '68055_CR38', 'doi-asserted-by': 'publisher', 'unstructured': 'Pagliano, P. et al. Characteristics of viral pneumonia in the COVID-19 ' 'era: An update.\xa0Infection. 49, 607–616. ' 'https://doi.org/10.1007/s15010-021-01603-y (2021).', 'DOI': '10.1007/s15010-021-01603-y'}, { 'key': '68055_CR39', 'unstructured': 'Freeman, A. M. & Leigh, Jr T. R. Viral Pneumonia. (StatPearls, 2022). ' 'https://www.ncbi.nlm.nih.gov/books/NBK513286/.'}, { 'key': '68055_CR40', 'doi-asserted-by': 'publisher', 'unstructured': 'Wang, M. et al. Remdesivir and chloroquine effectively inhibit the ' 'recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 30, ' '269–271. https://doi.org/10.1038/s41422-020-0282-0 (2020).', 'DOI': '10.1038/s41422-020-0282-0'}, { 'key': '68055_CR41', 'doi-asserted-by': 'publisher', 'unstructured': 'Ader, F. et al. Remdesivir plus standard of care versus standard of care ' 'alone for the treatment of patients admitted to hospital with COVID-19 ' '(DisCoVeRy): A phase 3, randomised, controlled, open-label trial. Lancet ' 'Infect Dis. 22, 209–221. https://doi.org/10.1016/S1473-3099(21)00485-0 ' '(2022).', 'DOI': '10.1016/S1473-3099(21)00485-0'}, { 'key': '68055_CR42', 'doi-asserted-by': 'publisher', 'unstructured': 'Srivastava, S., et al. Assessment of nitric oxide (NO) potential to ' 'mitigate COVID-19 severity. Virusdisease. 32, 589–594. ' 'https://doi.org/10.1007/s13337-021-00702-6 (2021).', 'DOI': '10.1007/s13337-021-00702-6'}, { 'key': '68055_CR43', 'doi-asserted-by': 'publisher', 'unstructured': 'Alqahtani, J. S. et al. Inhaled nitric oxide for clinical management of ' 'COVID-19: A systematic review and meta-analysis. Int. J. Environ. Res. ' 'Public Health. 19, 12803. https://doi.org/10.3390/ijerph191912803 ' '(2022).', 'DOI': '10.3390/ijerph191912803'}, { 'key': '68055_CR44', 'doi-asserted-by': 'crossref', 'unstructured': 'Nathan, C. Reactive oxygen and nitrogen intermediates in the ' 'relationship between mammalian hosts and microbial pathogens. Proc. ' 'Natl. Acad. Sci. USA. 97, 8841–8848.', 'DOI': '10.1073/pnas.97.16.8841'}, { 'key': '68055_CR45', 'doi-asserted-by': 'publisher', 'first-page': '2003895', 'DOI': '10.1002/advs.202003895', 'volume': '8', 'author': 'F Lisi', 'year': '2021', 'unstructured': 'Lisi, F., Zelikin, A. N. & Chandrawati, R. Nitric oxide to fight viral ' 'infections. Adv. Sci. 8, 2003895 (2021).', 'journal-title': 'Adv. Sci.'}, { 'key': '68055_CR46', 'doi-asserted-by': 'publisher', 'unstructured': 'Zhao, Y. et al. Inhaled nitric oxide: can it serve as a savior for ' 'COVID-19 and related respiratory and cardiovascular diseases? Front. ' 'Microbiol. 14, 1277552. https://doi.org/10.3389/fmicb.2023.1277552 ' '(2023).', 'DOI': '10.3389/fmicb.2023.1277552'}, { 'key': '68055_CR47', 'doi-asserted-by': 'publisher', 'first-page': '157', 'DOI': '10.7150/ijms.3880', 'volume': '9', 'author': 'I Darwish', 'year': '2012', 'unstructured': 'Darwish, I., Miller, C., Kain, K. C. & Liles, W. C. Inhaled nitric oxide ' 'therapy fails to improve outcome in experimental severe influenza. Int. ' 'J. Med. Sci. 9, 157–162. https://doi.org/10.7150/ijms.3880 (2012).', 'journal-title': 'Int. J. Med. Sci.'}, { 'key': '68055_CR48', 'doi-asserted-by': 'publisher', 'unstructured': 'Feng, L. et al. Impact of COVID-19 outbreaks and interventions on ' 'influenza in China and the United States. Nat. Commun. 12, 3249. ' 'https://doi.org/10.1038/s41467-021-23440-1 (2021).', 'DOI': '10.1038/s41467-021-23440-1'}, { 'key': '68055_CR49', 'doi-asserted-by': 'publisher', 'unstructured': 'Kanda, N. et al. Indirect impact of the COVID-19 pandemic on the ' 'incidence of non-COVID-19 infectious diseases: A region-wide, ' 'patient-based database study in Japan. Public Health. 214, 20–24. ' 'https://doi.org/10.1016/j.puhe.2022.10.018 (2023).', 'DOI': '10.1016/j.puhe.2022.10.018'}, { 'key': '68055_CR50', 'doi-asserted-by': 'publisher', 'unstructured': 'Liu, Q., Zhou, Y. H. & Yang, Z. Q. The cytokine storm of severe ' 'influenza and development of immunomodulatory therapy. Cell Mol. ' 'Immunol. 13, 3–10. https://doi.org/10.1038/cmi.2015.74 (2016).', 'DOI': '10.1038/cmi.2015.74'}, { 'key': '68055_CR51', 'doi-asserted-by': 'publisher', 'unstructured': 'Ragab, D. et al. The COVID-19 cytokine storm; What we know so far. ' 'Front. Immunol. 11, 1446. https://doi.org/10.3389/fimmu.2020.01446 ' '(2020).', 'DOI': '10.3389/fimmu.2020.01446'}, { 'key': '68055_CR52', 'doi-asserted-by': 'publisher', 'first-page': '1071', 'DOI': '10.3390/v14051071', 'volume': '14', 'author': 'C Achangwa', 'year': '2022', 'unstructured': 'Achangwa, C. et al. Collateral impact of public health and social ' 'measures on respiratory virus activity during the COVID-19 pandemic ' '2020–2021. Viruses. 14, 1071. https://doi.org/10.3390/v14051071 (2022).', 'journal-title': 'Viruses.'}, { 'key': '68055_CR53', 'doi-asserted-by': 'publisher', 'unstructured': 'Schulz, K. F., Altman, D. G., Moher, D. & CONSORT Group. CONSORT 2010 ' 'Statement: Updated guidelines for reporting parallel group randomised ' 'trials. BMJ. 340, c332. https://doi.org/10.1136/bmj.c332 (2010).', 'DOI': '10.1136/bmj.c332'}, { 'key': '68055_CR54', 'unstructured': 'COVID-19 Treatment Guidelines. National Institutes of Health ' 'https://www.covid19treatmentguidelines.nih.gov/ (2023).'}, { 'issue': '3', 'key': '68055_CR55', 'doi-asserted-by': 'publisher', 'first-page': '325', 'DOI': '10.1093/cid/ciq076', 'volume': '52', 'author': 'SR Majumdar', 'year': '2011', 'unstructured': 'Majumdar, S. R., Eurich, D. T., Gamble, J. M., Senthilselvan, A. & ' 'Marrie, T. J. Oxygen saturations less than 92% are associated with major ' 'adverse events in outpatients with pneumonia: A population-based cohort ' 'study. Clin. Infect. Dis. 52(3), 325–331. ' 'https://doi.org/10.1093/cid/ciq076 (2011).', 'journal-title': 'Clin. Infect. Dis.'}], 'container-title': 'Scientific Reports', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://www.nature.com/articles/s41598-024-68055-w.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41598-024-68055-w', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41598-024-68055-w.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2024, 7, 27]], 'date-time': '2024-07-27T00:15:10Z', 'timestamp': 1722039310000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.nature.com/articles/s41598-024-68055-w'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2024, 7, 26]]}, 'references-count': 55, 'journal-issue': {'issue': '1', 'published-online': {'date-parts': [[2024, 12]]}}, 'alternative-id': ['68055'], 'URL': 'http://dx.doi.org/10.1038/s41598-024-68055-w', 'relation': {}, 'ISSN': ['2045-2322'], 'subject': [], 'container-title-short': 'Sci Rep', 'published': {'date-parts': [[2024, 7, 26]]}, 'assertion': [ { 'value': '7 March 2024', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '19 July 2024', 'order': 2, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '26 July 2024', 'order': 3, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': 'Because of the perception of a conflict of interest and in the interest of full ' 'transparency, we are disclosing the relationships between Profs. Talya Wolak, ' 'Asher Tal, Alon Grossman and Dr. Dror Dicker and Beyond Air Inc. All four ' 'authors have signed contracts with the company. Prof Wolak received payment ' 'including traveling fees for attending a conference and all payments were made ' 'through her affiliated institution. Prof. Tal bought stocks, received a stock ' 'option grant, and consulting fees. Drs. Dicker and Grossman received payment ' 'through their affiliated institutions.', 'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}], 'article-number': '17201'}