{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T23:51:32Z","timestamp":1786751492031,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Recreational nitrous oxide (N\n                      <jats:sub>2<\/jats:sub>\n                      O) misuse is an increasing public health problem associated with functional cobalamin (B\n                      <jats:sub>12<\/jats:sub>\n                      ) deficiency and severe neurological complications. Despite growing recognition of its harms, the dose\u2013response relationship and clinical value of biomarkers remain unclear. This study aimed to characterize the demographics, patterns of use, outcomes, and biomarker utility in patients hospitalized with N\n                      <jats:sub>2<\/jats:sub>\n                      O toxicity, as well as to examine the relationship between exposure and toxicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This retrospective cohort study included hospitalized individuals with N\n                      <jats:sub>2<\/jats:sub>\n                      O toxicity (2020\u20132025) across six Sydney hospitals. Weekly and cumulative N\n                      <jats:sub>2<\/jats:sub>\n                      O exposure volumes were estimated. Exposure volumes were compared with clinical outcomes and biomarker results to assess correlations and biomarker utility.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eighty\u2010one individuals across 100 presentations were included. Higher cumulative N\n                      <jats:sub>2<\/jats:sub>\n                      O exposure was associated with worse neurological impairment, including subacute combined degeneration of the spinal cord (SCD,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.006) and peripheral neuropathy (PN,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.036), and correlated with greater neuropathy severity (Spearman's\n                      <jats:italic>\u2374<\/jats:italic>\n                      \u2009=\u20090.43,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.001). Median\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.guidetopharmacology.org\/GRAC\/LigandDisplayForward?ligandId=5198\">homocysteine<\/jats:ext-link>\n                      was 50\u2009\u03bcmol\/L (IQR:32\u2013114;normal 5\u201315) with a median half\u2010life of 14.59\u2009h. Median\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.guidetopharmacology.org\/GRAC\/LigandDisplayForward?ligandId=9633\">methylmalonic acid<\/jats:ext-link>\n                      (MMA) was 0.68\u2009\u03bcmol\/L (IQR:0.18\u20133.16;normal&lt;0.27). B\n                      <jats:sub>12<\/jats:sub>\n                      and holotranscobalamin showed high specificity (87% and 98%) but low sensitivity (22% and 5%) for detecting cases associated with SCD, while homocysteine and MMA showed high sensitivity (95% and 93%) but lower specificity (13% and 45%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Cumulative N\n                      <jats:sub>2<\/jats:sub>\n                      O exposure is the strongest predictor of severe neurological outcomes, demonstrating a dose\u2010dependent relationship with neurotoxicity. Homocysteine and MMA were sensitive markers associated with neurological toxicity, making them useful screening biomarkers; however, their limited specificity reduces their utility as confirmatory tests. These findings reinforce the importance of clinical assessment and exposure history in diagnosing toxicity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70699","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:33:59Z","timestamp":1784594039000},"source":"Crossref","is-referenced-by-count":1,"title":["Relationships among nitrous oxide exposure, neurological injury and biomarkers"],"prefix":"10.1002","author":[{"given":"Laxna","family":"Bhujel","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Health, School of Clinical Medicine University of New South Wales  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0079-5056","authenticated-orcid":false,"given":"Angela L.","family":"Chiew","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health, School of Clinical Medicine University of New South 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