{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T15:04:42Z","timestamp":1783955082210,"version":"3.55.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2022,7,30]],"date-time":"2022-07-30T00:00:00Z","timestamp":1659139200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,7,30]],"date-time":"2022-07-30T00:00:00Z","timestamp":1659139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100018336","name":"National Institute for Health Research Health Protection Research Unit","doi-asserted-by":"publisher","award":["558969"],"award-info":[{"award-number":["558969"]}],"id":[{"id":"10.13039\/100018336","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019741","name":"Muir Maxwell Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019741","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Hyperammonaemia is a recognised complication of antiseizure treatment but risk factors leading to individual patient susceptibility and outcome remain unclear.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Objective<\/jats:title>\n                <jats:p>To identify risk factors for hyperammonaemia and investigate the impact of its management on clinical outcomes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We carried out a retrospective observational study of adults with epilepsy who had ammonia tested over a 3-year period<jats:bold>.<\/jats:bold> Hyperammonaemia was defined as ammonia level\u2009&gt;\u200935\u00a0\u03bcmol\/L. Patients were classified into two groups: hyperammonaemic and non-hyperammonaemic. Association analyses and linear regression analysis were used to identify risk factors for hyperammonaemia.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We reviewed 1002 ammonia requests in total and identified 76 people with epilepsy who had ammonia concentration measured, including 26 with repeated measurements. 59\/76 (78%) were found to have hyperammonaemia. There was borderline statistical significance of hyperammonaemia being less common in patients with an established monogenic\/metabolic condition than in those with structural or cryptogenic epilepsy (<jats:italic>P<\/jats:italic>\u2009=\u20090.05). Drug resistance, exposure to stiripentol and oxcarbazepine were identified as risk factors for hyperammonaemia. We found a dose-dependent association between valproate and hyperammonaemia (<jats:italic>P<\/jats:italic>\u2009=\u20090.033). Clinical symptoms were reported in 22\/59 (37%) of the hyperammonaemic group. Improved clinical outcomes with concurrent decrease in ammonia concentration were seen in 60% of patients following treatment adjustment.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Drug resistance and exposure to stiripentol, oxcarbazepine or high-dose valproate are associated with an increased risk of hyperammonaemia. Clinicians should consider symptoms related to hyperammonaemia in patients on high-dose valproate or multiple antiseizure treatments. Prompt identification of hyperammonaemia and subsequent treatment adjustments can lead to improved clinical outcomes.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00415-022-11304-7","type":"journal-article","created":{"date-parts":[[2022,7,30]],"date-time":"2022-07-30T06:02:51Z","timestamp":1659160971000},"page":"6395-6405","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Risk factors and outcome of hyperammonaemia in people with epilepsy"],"prefix":"10.1007","volume":"269","author":[{"given":"Angeliki","family":"Vakrinou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay M.","family":"Sisodiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umesh","family":"Vivekananda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5639-1969","authenticated-orcid":false,"given":"Simona","family":"Balestrini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,30]]},"reference":[{"key":"11304_CR1","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1111\/epi.13426","volume":"57","author":"R Albadareen","year":"2016","unstructured":"Albadareen R, Gronseth G, Landazuri P et al (2016) Postictal ammonia as a biomarker for electrographic convulsive seizures: a prospective study. Epilepsia 57:1221\u20131227. https:\/\/doi.org\/10.1111\/epi.13426","journal-title":"Epilepsia"},{"key":"11304_CR2","doi-asserted-by":"publisher","first-page":"S9","DOI":"10.1016\/j.ccc.2005.05.007","volume":"21","author":"W Smith","year":"2005","unstructured":"Smith W, Kishnani PS, Lee B et al (2005) Urea cycle disorders: clinical presentation outside the newborn period. Crit Care Clin 21:S9-17. https:\/\/doi.org\/10.1016\/j.ccc.2005.05.007","journal-title":"Crit Care Clin"},{"key":"11304_CR3","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1001\/archneur.1982.00510210061016","volume":"39","author":"JV Murphy","year":"1982","unstructured":"Murphy JV (1982) Asymptomatic hyperammonemia in patients receiving valproic acid. Arch Neurol 39:591\u2013592. https:\/\/doi.org\/10.1001\/archneur.1982.00510210061016","journal-title":"Arch Neurol"},{"key":"11304_CR4","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1097\/00007691-198507030-00009","volume":"7","author":"D Haidukewych","year":"1985","unstructured":"Haidukewych D, John G, Zielinski JJ et al (1985) Chronic valproic acid therapy and incidence of increases in venous plasma ammonia. Ther Drug Monit 7:290\u2013294. https:\/\/doi.org\/10.1097\/00007691-198507030-00009","journal-title":"Ther Drug Monit"},{"key":"11304_CR5","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1111\/j.1440-1819.1986.tb03182.x","volume":"40","author":"T Kugoh","year":"1986","unstructured":"Kugoh T, Yamamoto M, Hosokawa K (1986) Blood ammonia level during valproic acid therapy. Jpn J Psychiatry Neurol 40:663\u2013668. https:\/\/doi.org\/10.1111\/j.1440-1819.1986.tb03182.x","journal-title":"Jpn J Psychiatry Neurol"},{"key":"11304_CR6","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.eplepsyres.2012.04.001","volume":"101","author":"Y Yamamoto","year":"2012","unstructured":"Yamamoto Y, Takahashi Y, Suzuki E et al (2012) Risk factors for hyperammonemia associated with valproic acid therapy in adult epilepsy patients. Epilepsy Res 101:202\u2013209. https:\/\/doi.org\/10.1016\/j.eplepsyres.2012.04.001","journal-title":"Epilepsy Res"},{"key":"11304_CR7","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1177\/0883073810377235","volume":"26","author":"S Sharma","year":"2011","unstructured":"Sharma S, Gulati S, Kabra M et al (2011) Blood ammonia levels in epileptic children on 2 dose ranges of valproic acid monotherapy: a cross-sectional study. J Child Neurol 26:109\u2013112. https:\/\/doi.org\/10.1177\/0883073810377235","journal-title":"J Child Neurol"},{"key":"11304_CR8","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1177\/088307389701200709","volume":"12","author":"S Altunbsak","year":"1997","unstructured":"Altunbsak S, Baytok V, Tasouji M et al (1997) Asymptomatic hyperammonemia in children treated with valproic acid. J Child Neurol 12:461\u2013463. https:\/\/doi.org\/10.1177\/088307389701200709","journal-title":"J Child Neurol"},{"key":"11304_CR9","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000000066","volume":"93","author":"Y-L Tseng","year":"2014","unstructured":"Tseng Y-L, Huang C-R, Lin C-H et al (2014) Risk factors of hyperammonemia in patients with epilepsy under valproic acid therapy. Medicine (Baltimore) 93:e66. https:\/\/doi.org\/10.1097\/MD.0000000000000066","journal-title":"Medicine (Baltimore)"},{"key":"11304_CR10","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/s0022-3476(81)80489-1","volume":"99","author":"DL Coulter","year":"1981","unstructured":"Coulter DL, Allen RJ (1981) Hyperammonemia with valproic acid therapy. J Pediatr 99:317\u2013319. https:\/\/doi.org\/10.1016\/s0022-3476(81)80489-1","journal-title":"J Pediatr"},{"key":"11304_CR11","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1016\/j.jhep.2010.11.031","volume":"55","author":"CCP Aires","year":"2011","unstructured":"Aires CCP, van Cruchten A, Ijlst L et al (2011) New insights on the mechanisms of valproate-induced hyperammonemia: inhibition of hepatic N-acetylglutamate synthase activity by valproyl-CoA. J Hepatol 55:426\u2013434. https:\/\/doi.org\/10.1016\/j.jhep.2010.11.031","journal-title":"J Hepatol"},{"key":"11304_CR12","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1016\/j.yebeh.2007.11.004","volume":"12","author":"J Nicolai","year":"2008","unstructured":"Nicolai J, Carr RB (2008) The measurement of ammonia blood levels in patients taking valproic acid: Looking for problems where they do not exist? Epilepsy Behav 12:494\u2013496. https:\/\/doi.org\/10.1016\/j.yebeh.2007.11.004","journal-title":"Epilepsy Behav"},{"key":"11304_CR13","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1007\/s005990050060","volume":"29","author":"A Verrotti","year":"1999","unstructured":"Verrotti A, Greco R, Morgese G et al (1999) Carnitine deficiency and hyperammonemia in children receiving valproic acid with and without other anticonvulsant drugs. Int J Clin Lab Res 29:36\u201340. https:\/\/doi.org\/10.1007\/s005990050060","journal-title":"Int J Clin Lab Res"},{"key":"11304_CR14","first-page":"100","volume":"22","author":"RN Ratnaike","year":"1986","unstructured":"Ratnaike RN, Schapel GJ, Purdie G et al (1986) Hyperammonaemia and hepatotoxicity during chronic valproate therapy: enhancement by combination with other antiepileptic drugs. Br J Clin Pharmacol 22:100\u2013103","journal-title":"Br J Clin Pharmacol"},{"key":"11304_CR15","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1212\/wnl.54.1.230","volume":"54","author":"HM Hamer","year":"2000","unstructured":"Hamer HM, Knake S, Schomburg U et al (2000) Valproate-induced hyperammonemic encephalopathy in the presence of topiramate. Neurology 54:230\u2013232. https:\/\/doi.org\/10.1212\/wnl.54.1.230","journal-title":"Neurology"},{"key":"11304_CR16","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1046\/j.1528-1157.2002.42401.x","volume":"43","author":"E Longin","year":"2002","unstructured":"Longin E, Teich M, Koelfen W et al (2002) Topiramate enhances the risk of valproate-associated side effects in three children. Epilepsia 43:451\u2013454. https:\/\/doi.org\/10.1046\/j.1528-1157.2002.42401.x","journal-title":"Epilepsia"},{"key":"11304_CR17","first-page":"25","volume":"18","author":"C Bles","year":"2014","unstructured":"Bles C, Hoeven J, Hoedemaekers C (2014) Acetozolamide induced hyperammonaemia: a case report and review of the literature. Neth J Crit Care 18:25\u201327","journal-title":"Neth J Crit Care"},{"key":"11304_CR18","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1111\/epi.12125","volume":"54","author":"Y Yamamoto","year":"2013","unstructured":"Yamamoto Y, Takahashi Y, Imai K et al (2013) Risk factors for hyperammonemia in pediatric patients with epilepsy. Epilepsia 54:983\u2013989. https:\/\/doi.org\/10.1111\/epi.12125","journal-title":"Epilepsia"},{"key":"11304_CR19","volume-title":"StatPearls","author":"R Ali","year":"2021","unstructured":"Ali R, Nagalli S (2021) Hyperammonemia. StatPearls. StatPearls Publishing, Treasure Island"},{"key":"11304_CR20","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/s00467-011-1838-5","volume":"27","author":"A Auron","year":"2012","unstructured":"Auron A, Brophy PD (2012) Hyperammonemia in review: pathophysiology, diagnosis, and treatment. Pediatr Nephrol 27:207\u2013222. https:\/\/doi.org\/10.1007\/s00467-011-1838-5","journal-title":"Pediatr Nephrol"},{"issue":"6859","key":"11304_CR21","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1136\/bmj.305.6859.905","volume":"305","author":"R Smith","year":"1992","unstructured":"Smith R (1992) Audit and research. BMJ 305(6859):905\u2013906. https:\/\/doi.org\/10.1136\/bmj.305.6859.905","journal-title":"BMJ"},{"key":"11304_CR22","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1111\/epi.13709","volume":"58","author":"IE Scheffer","year":"2017","unstructured":"Scheffer IE, Berkovic S, Capovilla G et al (2017) ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia 58:512\u2013521. https:\/\/doi.org\/10.1111\/epi.13709","journal-title":"Epilepsia"},{"key":"11304_CR23","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1111\/j.1528-1167.2009.02397.x","volume":"51","author":"P Kwan","year":"2010","unstructured":"Kwan P, Arzimanoglou A, Berg AT et al (2010) Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 51:1069\u20131077. https:\/\/doi.org\/10.1111\/j.1528-1167.2009.02397.x","journal-title":"Epilepsia"},{"issue":"1","key":"11304_CR24","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/ajg.2016.517","volume":"112","author":"PY Kwo","year":"2017","unstructured":"Kwo PY, Cohen SM, Lim JK (2017) ACG clinical guideline: evaluation of abnormal liver chemistries. Am J Gastroenterol 112(1):18\u201335. https:\/\/doi.org\/10.1038\/ajg.2016.517","journal-title":"Am J Gastroenterol"},{"issue":"11","key":"11304_CR25","doi-asserted-by":"publisher","first-page":"825","DOI":"10.7326\/0003-4819-158-11-201306040-00007","volume":"158","author":"PE Stevens","year":"2013","unstructured":"Stevens PE, Levin A (2013) Kidney disease: improving global outcomes chronic kidney disease guideline development work group members. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med 158(11):825\u2013830. https:\/\/doi.org\/10.7326\/0003-4819-158-11-201306040-00007","journal-title":"Ann Intern Med"},{"issue":"2","key":"11304_CR26","first-page":"65","volume":"6","author":"S Holm","year":"1979","unstructured":"Holm S (1979) A simple sequentially rejective multiple test procedure. Scand J Stat 6(2):65\u201370","journal-title":"Scand J Stat"},{"key":"11304_CR27","doi-asserted-by":"publisher","DOI":"10.13140\/RG.2.1.4466.9927","author":"J Gaetano","year":"2013","unstructured":"Gaetano J (2013) Holm-Bonferroni sequential correction: an EXCEL calculator. OSF Home. https:\/\/doi.org\/10.13140\/RG.2.1.4466.9927","journal-title":"OSF Home"},{"key":"11304_CR28","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1124\/pr.120.019539","volume":"72","author":"W L\u00f6scher","year":"2020","unstructured":"L\u00f6scher W, Potschka H, Sisodiya SM et al (2020) Drug resistance in epilepsy: clinical impact, potential mechanisms, and new innovative treatment options. Pharmacol Rev 72:606. https:\/\/doi.org\/10.1124\/pr.120.019539","journal-title":"Pharmacol Rev"},{"key":"11304_CR29","doi-asserted-by":"publisher","first-page":"712","DOI":"10.3389\/fneur.2017.00712","volume":"8","author":"A Strzelczyk","year":"2017","unstructured":"Strzelczyk A, Griebel C, Lux W et al (2017) The burden of severely drug-refractory epilepsy: a comparative longitudinal evaluation of mortality, morbidity, resource use, and cost using german health insurance data. Front Neurol 8:712. https:\/\/doi.org\/10.3389\/fneur.2017.00712","journal-title":"Front Neurol"},{"key":"11304_CR30","volume-title":"GeneReviews\u00ae","author":"N Ah Mew","year":"1993","unstructured":"Ah Mew N, Simpson KL, Gropman AL et al (1993) Urea cycle disorders overview. In: Adam MP, Ardinger HH, Pagon RA (eds) GeneReviews\u00ae. University of Washington, Seattle"},{"key":"11304_CR31","doi-asserted-by":"publisher","DOI":"10.1136\/practneurol-2020-002654","author":"R Meijer","year":"2020","unstructured":"Meijer R, Vivekananda U, Balestrini S et al (2020) Ammonia: what adult neurologists need to know. Pract Neurol. https:\/\/doi.org\/10.1136\/practneurol-2020-002654","journal-title":"Pract Neurol"},{"key":"11304_CR32","doi-asserted-by":"publisher","first-page":"2435","DOI":"10.1111\/epi.16684","volume":"61","author":"Q Zulfiqar Ali","year":"2020","unstructured":"Zulfiqar Ali Q, Marques P, Selvarajah A et al (2020) Starting stiripentol in adults with Dravet syndrome? Watch for ammonia and carnitine. Epilepsia 61:2435\u20132441. https:\/\/doi.org\/10.1111\/epi.16684","journal-title":"Epilepsia"},{"key":"11304_CR33","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1007\/s13760-015-0487-z","volume":"115","author":"P Hantson","year":"2015","unstructured":"Hantson P, Frederick A, van Rijckevorsel K (2015) Hyperammonemic encephalopathy after adjunction of phenobarbital to chronic topiramate and oxcarbazepine therapy. Acta Neurol Belg 115:777\u2013778. https:\/\/doi.org\/10.1007\/s13760-015-0487-z","journal-title":"Acta Neurol Belg"},{"key":"11304_CR34","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1111\/j.1600-0404.2006.00793.x","volume":"116","author":"SK Velio\u011flu","year":"2007","unstructured":"Velio\u011flu SK, Gazio\u011flu S (2007) Non-convulsive status epilepticus secondary to valproic acid-induced hyperammonemic encephalopathy. Acta Neurol Scand 116:128\u2013132. https:\/\/doi.org\/10.1111\/j.1600-0404.2006.00793.x","journal-title":"Acta Neurol Scand"},{"key":"11304_CR35","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1111\/j.1528-1157.2000.tb00263.x","volume":"41","author":"A Kifune","year":"2000","unstructured":"Kifune A, Kubota F, Shibata N et al (2000) Valproic acid-induced hyperammonemic encephalopathy with triphasic waves. Epilepsia 41:909\u2013912. https:\/\/doi.org\/10.1111\/j.1528-1157.2000.tb00263.x","journal-title":"Epilepsia"},{"key":"11304_CR36","doi-asserted-by":"publisher","first-page":"695","DOI":"10.2165\/00023210-200216100-00004","volume":"16","author":"E Perucca","year":"2002","unstructured":"Perucca E (2002) Pharmacological and therapeutic properties of valproate: a summary after 35 years of clinical experience. CNS Drugs 16:695\u2013714. https:\/\/doi.org\/10.2165\/00023210-200216100-00004","journal-title":"CNS Drugs"},{"key":"11304_CR37","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/B978-0-443-06803-4.00005-8","volume-title":"Laboratory tests in liver disease. Practical hepatic pathology: a diagnostic approach","author":"R Vuppalanchi","year":"2011","unstructured":"Vuppalanchi R, Chalasani N (2011) Laboratory tests in liver disease. Practical hepatic pathology: a diagnostic approach. Elsevier, Amsterdam, pp 55\u201362. https:\/\/doi.org\/10.1016\/B978-0-443-06803-4.00005-8"},{"issue":"1","key":"11304_CR38","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1159\/000315034","volume":"64","author":"K-T Liu","year":"2010","unstructured":"Liu K-T et al (2010) Postictal transient hyperammonemia as an indicator of seizure disorder. Eur Neurol 64(1):46\u201350. https:\/\/doi.org\/10.1159\/000315034","journal-title":"Eur Neurol"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-022-11304-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00415-022-11304-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-022-11304-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,30]],"date-time":"2022-10-30T12:05:05Z","timestamp":1667131505000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00415-022-11304-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,30]]},"references-count":38,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["11304"],"URL":"https:\/\/doi.org\/10.1007\/s00415-022-11304-7","relation":{},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,30]]},"assertion":[{"value":"11 April 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 July 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 July 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 July 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no relevant financial or non-financial interests to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"For the present service evaluation, ethics committee approval or individual participant consent was not required, as service evaluation and clinical audit by definition do not involve intervention beyond usual clinical management.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}