{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T12:15:12Z","timestamp":1785500112626,"version":"3.56.0"},"reference-count":40,"publisher":"National Institute for Health and Care Research","issue":"36","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.nationalarchives.gov.uk\/doc\/non-commercial-government-licence\/non-commercial-government-licence.htm"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment programme","doi-asserted-by":"publisher","award":["16\/79\/03"],"award-info":[{"award-number":["16\/79\/03"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journalslibrary.nihr.ac.uk"],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"<jats:sec id=\"abs1-1\">\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Therapeutic hypothermia is standard of care for babies with moderate to severe hypoxic\u2013ischaemic encephalopathy. There is limited evidence to inform provision of nutrition during hypothermia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-2\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To assess the association during therapeutic hypothermia between (1) enteral feeding and outcomes, such as necrotising enterocolitis and (2) parenteral nutrition and outcomes, such as late-onset bloodstream infection.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-3\">\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>A retrospective cohort study using data held in the National Neonatal Research Database and applying propensity score methodology to form matched groups for analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-4\">\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>NHS neonatal units in England, Wales and Scotland.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-5\">\n                  <jats:title>Participants<\/jats:title>\n                  <jats:p>Babies born at \u2265\u200936 gestational weeks between 1 January 2010 and 31 December 2017 who received therapeutic hypothermia for 72 hours or who died during treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-6\">\n                  <jats:title>Interventions<\/jats:title>\n                  <jats:p>Enteral feeding analysis \u2013 babies who were enterally fed during therapeutic hypothermia (intervention) compared with babies who received no enteral feeds during therapeutic hypothermia (control). Parenteral nutrition analysis \u2013 babies who received parenteral nutrition during therapeutic hypothermia (intervention) compared with babies who received no parenteral nutrition during therapeutic hypothermia (control).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-7\">\n                  <jats:title>Outcome measures<\/jats:title>\n                  <jats:p>Primary outcomes were severe and pragmatically defined necrotising enterocolitis (enteral feeding analysis) and late-onset bloodstream infection (parenteral nutrition analysis). Secondary outcomes were survival at neonatal discharge, length of neonatal stay, breastfeeding at discharge, onset of breastfeeding, time to first maternal breast milk, hypoglycaemia, number of days with a central line in situ, duration of parenteral nutrition, time to full enteral feeds and growth.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-8\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A total of 6030 babies received therapeutic hypothermia. Thirty-one per cent of babies received enteral feeds and 25% received parenteral nutrition. Seven babies (0.1%) were diagnosed with severe necrotising enterocolitis, and further comparative analyses were not conducted on this outcome. A total of 3236 babies were included in the matched enteral feeding analysis. Pragmatically defined necrotising enterocolitis was rare in both groups (0.5% vs. 1.1%) and was lower in babies who were fed during hypothermia (rate difference \u20130.5%, 95% confidence interval \u20131.0% to \u20130.1%; <jats:italic>p<\/jats:italic>\u2009=\u20090.03). Higher survival to discharge (96.0% vs. 90.8%, rate difference 5.2%, 95% confidence interval 3.9% to 6.6%; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and higher breastfeeding at discharge (54.6% vs. 46.7%, rate difference 8.0%, 95% confidence interval 5.1% to 10.8%; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) rates were observed in enterally fed babies who also had a shorter neonatal stay (mean difference \u20132.2 days, 95% confidence interval \u20133.0 to \u20131.2 days). A total of 2480 babies were included in the matched parenteral nutrition analysis. Higher levels of late-onset bloodstream infection were seen in babies who received parenteral nutrition (0.3% vs. 0.9%, rate difference 0.6%, 95% confidence interval 0.1% to 1.2%; <jats:italic>p<\/jats:italic>\u2009=\u20090.03). Survival was lower in babies who did not receive parenteral nutrition (90.0% vs. 93.1%, rate difference 3.1%, 95% confidence interval 1.5% to 4.7%; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-9\">\n                  <jats:title>Limitations<\/jats:title>\n                  <jats:p>Propensity score methodology can address imbalances in observed confounders only. Residual confounding by unmeasured or poorly recorded variables cannot be ruled out. We did not analyse by type or volume of enteral or parenteral nutrition.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-10\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Necrotising enterocolitis is rare in babies receiving therapeutic hypothermia, and the introduction of enteral feeding is associated with a lower risk of pragmatically defined necrotising enterocolitis and other beneficial outcomes, including rates of higher survival and breastfeeding at discharge. Receipt of parenteral nutrition during therapeutic hypothermia is associated with a higher rate of late-onset infection but lower mortality. These results support introduction of enteral feeding during therapeutic hypothermia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-11\">\n                  <jats:title>Future work<\/jats:title>\n                  <jats:p>Randomised trials to assess parenteral nutrition during therapeutic hypothermia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-12\">\n                  <jats:title>Trial registration<\/jats:title>\n                  <jats:p>Current Controlled Trials ISRCTN474042962.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-13\">\n                  <jats:title>Funding<\/jats:title>\n                  <jats:p>This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in <jats:italic>Health Technology Assessment<\/jats:italic>; Vol. 25, No. 36. See the NIHR Journals Library website for further project information.<\/jats:p>\n               <\/jats:sec>","DOI":"10.3310\/hta25360","type":"journal-article","created":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T08:53:55Z","timestamp":1623056035000},"page":"1-106","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":15,"title":["Nutritional management in newborn babies receiving therapeutic hypothermia: two retrospective observational studies using propensity score matching"],"prefix":"10.3310","volume":"25","clinical-trial-number":[{"clinical-trial-number":"isrctn474042962","registry":"10.18810\/isrctn","type":"results"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0707-876X","authenticated-orcid":true,"given":"Chris","family":"Gale","sequence":"first","affiliation":[{"name":"Neonatal Medicine, School of Public Health, Faculty of Medicine, Imperial College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8209-9694","authenticated-orcid":true,"given":"Dusha","family":"Jeyakumaran","sequence":"additional","affiliation":[{"name":"Neonatal Medicine, School of Public Health, Faculty of Medicine, Imperial College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2898-553X","authenticated-orcid":true,"given":"Cheryl","family":"Battersby","sequence":"additional","affiliation":[{"name":"Neonatal Medicine, School of Public Health, Faculty of Medicine, Imperial College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6724-1867","authenticated-orcid":true,"given":"Kayleigh","family":"Ougham","sequence":"additional","affiliation":[{"name":"Neonatal Medicine, School of Public Health, Faculty of Medicine, Imperial College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5668-4227","authenticated-orcid":true,"given":"Shalini","family":"Ojha","sequence":"additional","affiliation":[{"name":"Division of Graduate Entry Medicine, School of Medicine, University of Nottingham, Nottingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4542-2659","authenticated-orcid":true,"given":"Lucy","family":"Culshaw","sequence":"additional","affiliation":[{"name":"Bliss, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1125-7712","authenticated-orcid":true,"given":"Ella","family":"Selby","sequence":"additional","affiliation":[{"name":"Bliss, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1691-3221","authenticated-orcid":true,"given":"Jon","family":"Dorling","sequence":"additional","affiliation":[{"name":"Dalhousie University, Halifax, NS, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4129-9726","authenticated-orcid":true,"given":"Nicholas","family":"Longford","sequence":"additional","affiliation":[{"name":"Neonatal Medicine, School of Public Health, Faculty of Medicine, Imperial College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"6221","published-online":{"date-parts":[[2021,6]]},"reference":[{"key":"key20210604131254782_ref1-bib1","unstructured":"National Institute for Health and Care Excellence (NICE). Therapeutic Hypothermia with Intracorporeal Temperature Monitoring for Hypoxic Perinatal Brain Injury \u2013 Interventional Procedures Guidance. London: NICE; 2010."},{"key":"key20210604131254782_ref1-bib2","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD003311.pub3","article-title":"Cooling for newborns with hypoxic\u2013ischaemic encephalopathy","volume":"1","author":"Jacobs","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"key":"key20210604131254782_ref1-bib3","doi-asserted-by":"publisher","first-page":"e000022","DOI":"10.1136\/bmjpo-2017-000022","article-title":"Survey of nutritional practices during therapeutic hypothermia for hypoxic\u2013ischaemic encephalopathy","volume":"1","author":"Hazeldine","year":"2017","journal-title":"BMJ Paediatr Open"},{"key":"key20210604131254782_ref1-bib4","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1159\/000487848","article-title":"Enteral feeding as an adjunct to hypothermia in neonates with hypoxic\u2013ischemic encephalopathy","volume":"113","author":"Chang","year":"2018","journal-title":"Neonatology"},{"key":"key20210604131254782_ref1-bib5","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1111\/apa.12838","article-title":"Minimal enteral nutrition during neonatal hypothermia treatment for perinatal hypoxic\u2013ischaemic encephalopathy is safe and feasible","volume":"104","author":"Thyagarajan","year":"2015","journal-title":"Acta Paediatr"},{"key":"key20210604131254782_ref1-bib6","doi-asserted-by":"publisher","first-page":"A441","DOI":"10.1136\/archdischild-2014-307384.1223","article-title":"PO-0581 Nutrition during therapeutic hypothermia in neonates","volume":"99","author":"Allen","year":"2014","journal-title":"Arch Dis Child"},{"key":"key20210604131254782_ref1-bib7","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.pediatrneurol.2004.06.015","article-title":"Moderate hypothermia in neonatal encephalopathy: safety outcomes","volume":"32","author":"Eicher","year":"2005","journal-title":"Pediatr Neurol"},{"key":"key20210604131254782_ref1-bib8","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1056\/NEJMoa0900854","article-title":"Moderate hypothermia to treat perinatal asphyxial encephalopathy","volume":"361","author":"Azzopardi","year":"2009","journal-title":"N Engl J Med"},{"key":"key20210604131254782_ref1-bib9","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1001\/archpediatrics.2011.43","article-title":"Whole-body hypothermia for term and near-term newborns with hypoxic-ischemic encephalopathy: a randomized controlled trial","volume":"165","author":"Jacobs","year":"2011","journal-title":"Arch Pediatr Adolesc Med"},{"key":"key20210604131254782_ref1-bib10","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD001970.pub5","article-title":"Delayed introduction of progressive enteral feeds to prevent necrotising enterocolitis in very low birth weight infants","volume":"12","author":"Morgan","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"key20210604131254782_ref1-bib11","doi-asserted-by":"publisher","first-page":"e1260","DOI":"10.1542\/peds.2011-2379","article-title":"Early or delayed enteral feeding for preterm growth-restricted infants: a randomized trial","volume":"129","author":"Leaf","year":"2012","journal-title":"Pediatrics"},{"key":"key20210604131254782_ref1-bib12","first-page":"1","article-title":"Breastfeeding and maternal and infant health outcomes in developed countries","volume":"153","author":"Ip","year":"2007","journal-title":"Evid Rep Technol Assess"},{"key":"key20210604131254782_ref1-bib13","doi-asserted-by":"publisher","first-page":"F541","DOI":"10.1136\/archdischild-2014-306284","article-title":"New horizons for newborn brain protection: enhancing endogenous neuroprotection","volume":"100","author":"Hassell","year":"2015","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"key":"key20210604131254782_ref1-bib14","doi-asserted-by":"publisher","first-page":"A47","DOI":"10.1136\/archdischild-2014-306576.135","article-title":"PC.34 Current practice regarding feeding\/nutrition in babies being cooled for HIE in the UK","volume":"99","author":"Kimkool","year":"2014","journal-title":"Arch Dis Child"},{"key":"key20210604131254782_ref1-bib15","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1056\/NEJMoa1514762","article-title":"Early versus late parenteral nutrition in critically ill children","volume":"374","author":"Fivez","year":"2016","journal-title":"N Engl J Med"},{"key":"key20210604131254782_ref1-bib16","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1056\/NEJMoa1102662","article-title":"Early versus late parenteral nutrition in critically ill adults","volume":"365","author":"Casaer","year":"2011","journal-title":"N Engl J Med"},{"key":"key20210604131254782_ref1-bib17","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1038\/ejcn.2011.225","article-title":"Cost analysis of neonatal and pediatric parenteral nutrition in Europe: a multi-country study","volume":"66","author":"Walter","year":"2012","journal-title":"Eur J Clin Nutr"},{"key":"key20210604131254782_ref1-bib18","unstructured":"Department of Health and Social Care (DHSC). Toolkit for High Quality Neonatal Services. London: DHSC; 2009."},{"key":"key20210604131254782_ref1-bib19","volume-title":"Supporting Information: National Neonatal Data Set Overview","author":"NHS Digital"},{"key":"key20210604131254782_ref1-bib20","doi-asserted-by":"publisher","first-page":"e0201815","DOI":"10.1371\/journal.pone.0201815","article-title":"The United Kingdom National Neonatal Research Database: a validation study","volume":"13","author":"Battersby","year":"2018","journal-title":"PLOS ONE"},{"key":"key20210604131254782_ref1-bib21","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/S2468-1253(16)30117-0","article-title":"Incidence and enteral feed antecedents of severe neonatal necrotising enterocolitis across neonatal networks in England, 2012\u201313: a whole-population surveillance study","volume":"2","author":"Battersby","year":"2017","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"key20210604131254782_ref1-bib22","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1001\/jamapediatrics.2016.3633","article-title":"Development of a gestational age-specific case definition for neonatal necrotizing enterocolitis","volume":"171","author":"Battersby","year":"2017","journal-title":"JAMA Pediatr"},{"key":"key20210604131254782_ref1-bib23","unstructured":"Royal College of Paediatrics and Child Health (RCPCH). National Neonatal Audit Programme (NNAP) 2018 Annual Report on 2017 Data. London: RCPCH; 2018."},{"key":"key20210604131254782_ref1-bib24","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1080\/00273171.2011.568786","article-title":"An introduction to propensity score methods for reducing the effects of confounding in observational studies","volume":"46","author":"Austin","year":"2011","journal-title":"Multivariate Behav Res"},{"key":"key20210604131254782_ref1-bib25","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1080\/01621459.1984.10477060","article-title":"From association to causation in observational studies: the role of tests of strongly ignorable treatment assignment","volume":"79","author":"Rosenbaum","year":"1984","journal-title":"J Am Stat Assoc"},{"key":"key20210604131254782_ref1-bib26","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1017\/CBO9781139025751","volume-title":"Causal Inference for Statistics, Social, and Biomedical Sciences","author":"Imbens","year":"2015"},{"key":"key20210604131254782_ref1-bib27","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1017\/CBO9781139025751.017","volume-title":"Causal Inference for Statistics, Social, and Biomedical Sciences","author":"Imbens","year":"2015"},{"key":"key20210604131254782_ref1-bib28","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1017\/CBO9781139025751.018","volume-title":"Causal Inference for Statistics, Social, and Biomedical Sciences","author":"Imbens","year":"2015"},{"key":"key20210604131254782_ref1-bib29","volume-title":"What is Public Involvement in Research?","author":"NIHR INVOLVE"},{"key":"key20210604131254782_ref1-bib30","doi-asserted-by":"publisher","first-page":"k4738","DOI":"10.1136\/bmj.k4738","article-title":"Impact of patient and public involvement on enrolment and retention in clinical trials: systematic review and meta-analysis","volume":"363","author":"Crocker","year":"2018","journal-title":"BMJ"},{"key":"key20210604131254782_ref1-bib31","doi-asserted-by":"publisher","first-page":"2041","DOI":"10.1016\/S0140-6736(14)60989-2","article-title":"Top 15 UK research priorities for preterm birth","volume":"383","author":"Duley","year":"2014","journal-title":"Lancet"},{"key":"key20210604131254782_ref1-bib32","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1186\/s12884-019-2654-3","article-title":"Top research priorities for preterm birth: results of a prioritisation partnership between people affected by preterm birth and healthcare professionals","volume":"19","author":"Oliver","year":"2019","journal-title":"BMC Pregnancy and Childbirth"},{"issue":"6","key":"key20210604131254782_ref1-bib33","doi-asserted-by":"publisher","DOI":"10.3310\/pgfar07060","article-title":"Developing routinely recorded clinical data from electronic patient records as a national resource to improve neonatal health care: the Medicines for Neonates Research Programme","volume":"7","author":"Modi","year":"2019","journal-title":"Programme Grants Appl Res"},{"key":"key20210604131254782_ref1-bib34","doi-asserted-by":"publisher","first-page":"e026739","DOI":"10.1136\/bmjopen-2018-026739","article-title":"Study protocol: optimising newborn nutrition during and after neonatal therapeutic hypothermia in the United Kingdom: observational study of routinely collected data using propensity matching","volume":"8","author":"Battersby","year":"2018","journal-title":"BMJ Open"},{"key":"key20210604131254782_ref1-bib35","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/S2352-4642(18)30131-7","article-title":"Early versus late parenteral nutrition in critically ill, term neonates: a preplanned secondary subgroup analysis of the PEPaNIC multicentre, randomised controlled trial","volume":"2","author":"van Puffelen","year":"2018","journal-title":"Lancet Child Adolesc Health"},{"key":"key20210604131254782_ref1-bib36","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1111\/dmcn.13586","article-title":"Nutritional intervention and neurodevelopmental outcome in infants with suspected cerebral palsy: the Dolphin infant double-blind randomized controlled trial","volume":"60","author":"Andrew","year":"2018","journal-title":"Dev Med Child Neurol"},{"key":"key20210604131254782_ref1-bib37","doi-asserted-by":"publisher","first-page":"125","DOI":"10.3109\/14767058.2012.663172","article-title":"Therapeutic hypothermia in a late preterm infant","volume":"25","author":"Laura","year":"2012","journal-title":"J Matern Fetal Neonatal Med"},{"key":"key20210604131254782_ref1-bib38","doi-asserted-by":"publisher","first-page":"125","DOI":"10.3233\/NPM-1365912","article-title":"Risk factors, characteristics and outcomes of necrotizing enterocolitis in late preterm and term infants","volume":"6","author":"Al Tawil","year":"2013","journal-title":"J Neonatal Perinatal Med"},{"key":"key20210604131254782_ref1-bib39","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/S0140-6736(15)01027-2","article-title":"Bifidobacterium breve BBG-001 in very preterm infants: a randomised controlled phase 3 trial","volume":"387","author":"Costeloe","year":"2016","journal-title":"Lancet"},{"key":"key20210604131254782_ref1-bib40","doi-asserted-by":"publisher","first-page":"F388","DOI":"10.1136\/archdischild-2017-313320","article-title":"Therapeutic hypothermia in mild neonatal encephalopathy: a national survey of practice in the UK","volume":"103","author":"Oliveira","year":"2018","journal-title":"Arch Dis Child Fetal Neonatal Ed"}],"container-title":["Health Technology Assessment"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/njl-admin.nihr.ac.uk\/document\/download\/2036796","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.journalslibrary.nihr.ac.uk\/publications\/hta25360\/hta25360.xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/njl-admin.nihr.ac.uk\/document\/download\/2036796","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,15]],"date-time":"2023-08-15T15:57:58Z","timestamp":1692115078000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.journalslibrary.nihr.ac.uk\/hta\/hta25360"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6]]},"references-count":40,"journal-issue":{"issue":"36","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["10.3310\/hta25360"],"URL":"https:\/\/doi.org\/10.3310\/hta25360","relation":{},"ISSN":["1366-5278","2046-4924"],"issn-type":[{"value":"1366-5278","type":"print"},{"value":"2046-4924","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6]]},"assertion":[{"value":"This content has been made freely available to all.","name":"free","label":"Free to read"},{"value":"9-2017","name":"contractual_start_date","label":"Contractual start date","group":{"name":"article_history","label":"Article History"}},{"value":"12-2019","name":"editorial_review_begun","label":"Editorial review begun","group":{"name":"article_history","label":"Article History"}},{"value":"6-2020","name":"accepted_for_publication","label":"Accepted for publication","group":{"name":"article_history","label":"Article History"}}]}}