{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T03:38:51Z","timestamp":1768966731525,"version":"3.49.0"},"reference-count":106,"publisher":"National Institute for Health and Care Research","issue":"15","license":[{"start":{"date-parts":[[2020,3,1]],"date-time":"2020-03-01T00:00:00Z","timestamp":1583020800000},"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":["12\/33\/12"],"award-info":[{"award-number":["12\/33\/12"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"<jats:sec id=\"abs1-1\"><jats:title>Background<\/jats:title><jats:p>Most patients presenting with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in primary care are prescribed antibiotics, but these may not be beneficial, and they can cause side effects and increase the risk of subsequent resistant infections. Point-of-care tests (POCTs) could safely reduce inappropriate antibiotic prescribing and antimicrobial resistance.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-2\"><jats:title>Objective<\/jats:title><jats:p>To determine whether or not the use of a C-reactive protein (CRP) POCT to guide prescribing decisions for AECOPD reduces antibiotic consumption without having a negative impact on chronic obstructive pulmonary disease (COPD) health status and is cost-effective.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-3\"><jats:title>Design<\/jats:title><jats:p>A multicentre, parallel-arm, randomised controlled open trial with an embedded process, and a health economic evaluation.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-4\"><jats:title>Setting<\/jats:title><jats:p>General practices in Wales and England. A UK NHS perspective was used for the economic analysis.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-5\"><jats:title>Participants<\/jats:title><jats:p>Adults (aged \u2265\u200940 years) with a primary care diagnosis of COPD, presenting with an AECOPD (with at least one of increased dyspnoea, increased sputum volume and increased sputum purulence) of between 24 hours\u2019 and 21 days\u2019 duration.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-6\"><jats:title>Intervention<\/jats:title><jats:p>CRP POCTs to guide antibiotic prescribing decisions for AECOPD, compared with usual care (no CRP POCT), using remote online randomisation.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-7\"><jats:title>Main outcome measures<\/jats:title><jats:p>Patient-reported antibiotic consumption for AECOPD within 4 weeks post randomisation and COPD health status as measured with the Clinical COPD Questionnaire (CCQ) at 2 weeks. For the economic evaluation, patient-reported resource use and the EuroQol-5 Dimensions were included.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-8\"><jats:title>Results<\/jats:title><jats:p>In total, 653 participants were randomised from 86 general practices. Three withdrew consent and one was randomised in error, leaving 324 participants in the usual-care arm and 325 participants in the CRP POCT arm. Antibiotics were consumed for AECOPD by 212 out of 274 participants (77.4%) and 150 out of 263 participants (57.0%) in the usual-care and CRP POCT arm, respectively [adjusted odds ratio 0.31, 95% confidence interval (CI) 0.20 to 0.47]. The CCQ analysis comprised 282 and 281 participants in the usual-care and CRP POCT arms, respectively, and the adjusted mean CCQ score difference at 2 weeks was 0.19 points (two-sided 90% CI \u20130.33 to \u20130.05 points). The upper limit of the CI did not contain the prespecified non-inferiority margin of 0.3. The total cost from a NHS perspective at 4 weeks was \u00a317.59 per patient higher in the CRP POCT arm (95% CI \u2013\u00a334.80 to \u00a369.98;<jats:italic>p<\/jats:italic>\u2009=\u20090.408). The mean incremental cost-effectiveness ratios were \u00a3222 per 1% reduction in antibiotic consumption compared with usual care at 4 weeks and \u00a315,251 per quality-adjusted life-year gained at 6 months with no significant changes in sensitivity analyses. Patients and clinicians were generally supportive of including CRP POCT in the assessment of AECOPD.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-9\"><jats:title>Conclusions<\/jats:title><jats:p>A CRP POCT diagnostic strategy achieved meaningful reductions in patient-reported antibiotic consumption without impairing COPD health status or increasing costs. There were no associated harms and both patients and clinicians valued the diagnostic strategy.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-10\"><jats:title>Future work<\/jats:title><jats:p>Implementation studies that also build on our qualitative findings could help determine the effect of this intervention over the longer term.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-11\"><jats:title>Trial registration<\/jats:title><jats:p>Current Controlled Trials ISRCTN24346473.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-12\"><jats:title>Funding<\/jats:title><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. 24, No. 15. See the NIHR Journals Library website for further project information.<\/jats:p><\/jats:sec>","DOI":"10.3310\/hta24150","type":"journal-article","created":{"date-parts":[[2020,3,23]],"date-time":"2020-03-23T13:12:21Z","timestamp":1584969141000},"page":"1-108","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":29,"title":["C-reactive protein point-of-care testing for safely reducing antibiotics for acute exacerbations of chronic obstructive pulmonary disease: the PACE RCT"],"prefix":"10.3310","volume":"24","clinical-trial-number":[{"clinical-trial-number":"isrctn24346473","registry":"10.18810\/isrctn","type":"results"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8939-7312","authenticated-orcid":true,"given":"Nick A","family":"Francis","sequence":"first","affiliation":[{"name":"Division of Population Medicine, School of Medicine, Cardiff University, Cardiff, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6934-2928","authenticated-orcid":true,"given":"David","family":"Gillespie","sequence":"additional","affiliation":[{"name":"South East Wales Trials Unit, Centre for Trials Research, Cardiff University, Cardiff, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2047-8787","authenticated-orcid":true,"given":"Patrick","family":"White","sequence":"additional","affiliation":[{"name":"Department of Primary Care & Public Health Sciences, King\u2019s College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3610-2415","authenticated-orcid":true,"given":"Janine","family":"Bates","sequence":"additional","affiliation":[{"name":"South East Wales Trials Unit, Centre for Trials Research, Cardiff University, Cardiff, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7306-0085","authenticated-orcid":true,"given":"Rachel","family":"Lowe","sequence":"additional","affiliation":[{"name":"South East Wales Trials Unit, Centre for Trials Research, Cardiff University, Cardiff, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5471-922X","authenticated-orcid":true,"given":"Bernadette","family":"Sewell","sequence":"additional","affiliation":[{"name":"Swansea Centre for Health Economics, College of Human and Health Sciences, Swansea University, Swansea, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4256-4598","authenticated-orcid":true,"given":"Rhiannon","family":"Phillips","sequence":"additional","affiliation":[{"name":"Division of Population Medicine, School of Medicine, Cardiff University, Cardiff, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0197-3667","authenticated-orcid":true,"given":"Helen","family":"Stanton","sequence":"additional","affiliation":[{"name":"South East Wales Trials Unit, Centre for Trials Research, Cardiff University, Cardiff, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0863-3673","authenticated-orcid":true,"given":"Nigel","family":"Kirby","sequence":"additional","affiliation":[{"name":"South East Wales Trials Unit, Centre for Trials Research, Cardiff University, Cardiff, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2227-3355","authenticated-orcid":true,"given":"Mandy","family":"Wootton","sequence":"additional","affiliation":[{"name":"Specialist Antimicrobial Chemotherapy Unit, University Hospital of Wales, Cardiff, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7716-2786","authenticated-orcid":true,"given":"Emma","family":"Thomas-Jones","sequence":"additional","affiliation":[{"name":"South East Wales Trials Unit, Centre for Trials Research, Cardiff University, Cardiff, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5268-8631","authenticated-orcid":true,"given":"Kerenza","family":"Hood","sequence":"additional","affiliation":[{"name":"South East Wales Trials Unit, Centre for Trials Research, Cardiff University, Cardiff, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6644-717X","authenticated-orcid":true,"given":"Carl","family":"Llor","sequence":"additional","affiliation":[{"name":"University Institute in Primary Care Research Jordi Gol, Via Roma Health Centre, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9550-5674","authenticated-orcid":true,"given":"Jochen","family":"Cals","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, CAPHRI Care and Public Health Research Institute, Maastricht University, Maastricht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9773-3141","authenticated-orcid":true,"given":"Hasse","family":"Melbye","sequence":"additional","affiliation":[{"name":"General Practice Research Unit, Department of Community Medicine, Faculty of Health Sciences, University of Troms\u00f8 \u2013 The Arctic University of Norway, Troms\u00f8, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7946-2042","authenticated-orcid":true,"given":"Gurudutt","family":"Naik","sequence":"additional","affiliation":[{"name":"Department of Wound Healing, University Hospital Wales, Cardiff, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1326-190X","authenticated-orcid":true,"given":"Micaela","family":"Gal","sequence":"additional","affiliation":[{"name":"Wales Primary and Emergency Care Research Centre, Division of Population Medicine, School of Medicine, Cardiff University, Cardiff, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7286-8410","authenticated-orcid":true,"given":"Deborah","family":"Fitzsimmons","sequence":"additional","affiliation":[{"name":"Swansea Centre for Health Economics, College of Human and Health Sciences, Swansea University, Swansea, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2590-851X","authenticated-orcid":true,"given":"Mohammed Fasihul","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Public Health, College of Health Sciences, Qatar University, Doha, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6772-7771","authenticated-orcid":true,"given":"Evgenia","family":"Riga","sequence":"additional","affiliation":[{"name":"Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1502-6719","authenticated-orcid":true,"given":"Ann","family":"Cochrane","sequence":"additional","affiliation":[{"name":"Department of Primary Care & Public Health Sciences, King\u2019s College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0102-3453","authenticated-orcid":true,"given":"Christopher C","family":"Butler","sequence":"additional","affiliation":[{"name":"Primary Care and Vaccines Collaborative Clinical Trials Unit, University of Oxford, John Radcliffe Hospital, Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"6221","published-online":{"date-parts":[[2020,3]]},"reference":[{"key":"key20200317105932192_ref1-bib1","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.cca.2013.09.018","article-title":"From biomarkers to medical tests: the changing landscape of test evaluation","volume":"427","author":"Horvath","year":"2014","journal-title":"Clin Chim Acta"},{"key":"key20200317105932192_ref1-bib2","unstructured":"US Food and Drug Administration. Medical Devices: Overview of IVD Regulation. Silver Spring, MO: US Food and Drug Administration. URL: www.fda.gov\/medicaldevices\/deviceregulationandguidance\/ivdregulatoryassistance\/ucm123682.htm (accessed 29 June 2018)."},{"key":"key20200317105932192_ref1-bib3","doi-asserted-by":"publisher","first-page":"e686","DOI":"10.1136\/bmj.e686","article-title":"Assessing the value of diagnostic tests: a framework for designing and evaluating trials","volume":"344","author":"Ferrante di Ruffano","year":"2012","journal-title":"BMJ"},{"key":"key20200317105932192_ref1-bib4","volume-title":"Rapid Diagnostics: Stopping Unnecessary Use of Antibiotics","author":"O\u2019Neill","year":"2015"},{"key":"key20200317105932192_ref1-bib5","doi-asserted-by":"publisher","first-page":"c2096","DOI":"10.1136\/bmj.c2096","article-title":"Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis","volume":"340","author":"Costelloe","year":"2010","journal-title":"BMJ"},{"key":"key20200317105932192_ref1-bib6","unstructured":"Prescribing and Primary Care Team Health and Social Care Information Centre. Quality and Outcomes Framework, Achievements, Prevalence and Exception Data: 2011\u201312. Leeds: NHS Digital; 2012."},{"key":"key20200317105932192_ref1-bib7","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1093\/fampra\/cmt055","article-title":"Predictors of exacerbations of asthma and COPD during one year in primary care","volume":"30","author":"Al-ani","year":"2013","journal-title":"Fam Pract"},{"key":"key20200317105932192_ref1-bib8","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.1056\/NEJMoa0909883","article-title":"Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators","volume":"363","author":"Hurst","year":"2010","journal-title":"N Engl J Med"},{"key":"key20200317105932192_ref1-bib9","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1177\/1753465812472387","article-title":"Predictors for antibiotic prescribing in patients with exacerbations of COPD in general practice","volume":"7","author":"Llor","year":"2013","journal-title":"Ther Adv Respir Dis"},{"key":"key20200317105932192_ref1-bib10","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/S0954-6111(99)90004-5","article-title":"Treatment of chronic obstructive pulmonary disease and its exacerbations in general practice","volume":"93","author":"Miravitlles","year":"1999","journal-title":"Resp Med"},{"key":"key20200317105932192_ref1-bib11","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1183\/09031936.00109906","article-title":"Exacerbations of chronic obstructive pulmonary disease","volume":"29","author":"Celli","year":"2007","journal-title":"Eur Respir J"},{"key":"key20200317105932192_ref1-bib12","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1136\/thorax.58.1.37","article-title":"Respiratory viruses in exacerbations of chronic obstructive pulmonary disease requiring hospitalisation: a case-control study","volume":"58","author":"Rohde","year":"2003","journal-title":"Thorax"},{"key":"key20200317105932192_ref1-bib13","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1164\/rccm.200906-0837OC","article-title":"Antibiotics in addition to systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease","volume":"181","author":"Daniels","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"key20200317105932192_ref1-bib14","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1164\/rccm.200506-859OC","article-title":"Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations","volume":"173","author":"Papi","year":"2006","journal-title":"Am J Respir Crit Care Med"},{"key":"key20200317105932192_ref1-bib15","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1016\/S0140-6736(05)70799-6","article-title":"Outpatient antibiotic use in Europe and association with resistance: a cross-national database study","volume":"365","author":"Goossens","year":"2005","journal-title":"Lancet"},{"key":"key20200317105932192_ref1-bib16","doi-asserted-by":"publisher","first-page":"9s","DOI":"10.1183\/09031936.02.00400302","article-title":"Exacerbations of chronic obstructive pulmonary disease: when are bacteria important?","volume":"36","author":"Miravitlles","year":"2002","journal-title":"Eur Respir J Suppl"},{"key":"key20200317105932192_ref1-bib17","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1086\/432062","article-title":"In vivo development of high-level fluoroquinolone resistance in Streptococcus pneumoniae in chronic obstructive pulmonary disease","volume":"41","author":"P\u00e9rez-Trallero","year":"2005","journal-title":"Clin Infect Dis"},{"key":"key20200317105932192_ref1-bib18","doi-asserted-by":"publisher","first-page":"337","DOI":"10.3109\/15412555.2010.510162","article-title":"Antibiotic resistance in sputum isolates of Streptococcus pneumoniae in chronic obstructive pulmonary disease is related to antibiotic exposure","volume":"7","author":"Desai","year":"2010","journal-title":"COPD"},{"key":"key20200317105932192_ref1-bib19","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1183\/09031936.99.14510159","article-title":"Airway inflammation and bronchial microbial patterns in patients with stable chronic obstructive pulmonary disease","volume":"14","author":"Soler","year":"1999","journal-title":"Eur Respir J"},{"key":"key20200317105932192_ref1-bib20","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1016\/S1473-3099(07)70263-3","article-title":"The role of evidence in the decline of antibiotic use for common respiratory infections in primary care","volume":"7","author":"Cosby","year":"2007","journal-title":"Lancet Infect Dis"},{"key":"key20200317105932192_ref1-bib21","unstructured":"Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Fontana, WI: Global Initiative for Chronic Obstructive Lung Disease; 2016."},{"key":"key20200317105932192_ref1-bib22","doi-asserted-by":"publisher","first-page":"196","DOI":"10.7326\/0003-4819-106-2-196","article-title":"Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease","volume":"106","author":"Anthonisen","year":"1987","journal-title":"Ann Intern Med"},{"key":"key20200317105932192_ref1-bib23","doi-asserted-by":"publisher","first-page":"CD010257","DOI":"10.1002\/14651858.CD010257","article-title":"Antibiotics for exacerbations of chronic obstructive pulmonary disease","volume":"12","author":"Vollenweider","year":"2012","journal-title":"Cochrane Database Syst Rev"},{"key":"key20200317105932192_ref1-bib24","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1164\/rccm.201206-0996OC","article-title":"Efficacy of antibiotic therapy for acute exacerbations of mild to moderate chronic obstructive pulmonary disease","volume":"186","author":"Llor","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"key20200317105932192_ref1-bib25","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1164\/rccm.200604-506OC","article-title":"Use of plasma biomarkers at exacerbation of chronic obstructive pulmonary disease","volume":"174","author":"Hurst","year":"2006","journal-title":"Am J Respir Crit Care Med"},{"key":"key20200317105932192_ref1-bib26","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1136\/thoraxjnl-2012-201924","article-title":"Changes in prevalence and load of airway bacteria using quantitative PCR in stable and exacerbated COPD","volume":"67","author":"Garcha","year":"2012","journal-title":"Thorax"},{"key":"key20200317105932192_ref1-bib27","first-page":"660","article-title":"Value of C-reactive protein measurement in hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease","volume":"27","author":"Ding","year":"2006","journal-title":"Med J Wuhan University"},{"key":"key20200317105932192_ref1-bib28","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.ejim.2005.09.020","article-title":"C-reactive protein \u2013 can it be used as a marker of infection in patients with exacerbation of chronic obstructive pulmonary disease?","volume":"17","author":"Weis","year":"2006","journal-title":"Eur J Internal Med"},{"key":"key20200317105932192_ref1-bib29","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1378\/chest.09-2927","article-title":"Procalcitonin vs. C-reactive protein as predictive markers of response to antibiotic therapy in acute exacerbations of COPD","volume":"138","author":"Daniels","year":"2010","journal-title":"Chest"},{"key":"key20200317105932192_ref1-bib30","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s12875-015-0256-3","article-title":"Predictors of treatment with antibiotics and systemic corticosteroids for acute exacerbations of asthma and chronic obstructive pulmonary disease in primary care","volume":"16","author":"Salwan","year":"2015","journal-title":"BMC Fam Pract"},{"key":"key20200317105932192_ref1-bib31","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1378\/chest.13-0518","article-title":"Is it possible to identify exacerbations of mild to moderate COPD that do not require antibiotic treatment?","volume":"144","author":"Miravitlles","year":"2013","journal-title":"Chest"},{"key":"key20200317105932192_ref1-bib32","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1007\/s10198-010-0239-1","article-title":"Resource use and costs of treating acute cough\/lower respiratory tract infections in 13 European countries: results and challenges","volume":"12","author":"Oppong","year":"2011","journal-title":"Eur J Health Econ"},{"key":"key20200317105932192_ref1-bib33","doi-asserted-by":"publisher","first-page":"b1374","DOI":"10.1136\/bmj.b1374","article-title":"Effect of point of care testing for C-reactive protein and training in communication skills on antibiotic use in lower respiratory tract infections: cluster randomised trial","volume":"338","author":"Cals","year":"2009","journal-title":"BMJ"},{"key":"key20200317105932192_ref1-bib34","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1016\/S0140-6736(13)60994-0","article-title":"Effects of internet-based training on antibiotic prescribing rates for acute respiratory-tract infections: a multinational, cluster, randomised, factorial, controlled trial","volume":"382","author":"Little","year":"2013","journal-title":"Lancet"},{"key":"key20200317105932192_ref1-bib35","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1111\/j.1365-2753.2010.01472.x","article-title":"C-reactive protein point of care testing and physician communication skills training for lower respiratory tract infections in general practice: economic evaluation of a cluster randomized trial","volume":"17","author":"Cals","year":"2011","journal-title":"J Eval Clin Pract"},{"key":"key20200317105932192_ref1-bib36","doi-asserted-by":"publisher","first-page":"e465","DOI":"10.3399\/bjgp13X669185","article-title":"Cost-effectiveness of point-of-care C-reactive protein testing to inform antibiotic prescribing decisions","volume":"63","author":"Oppong","year":"2013","journal-title":"Br J Gen Pract"},{"key":"key20200317105932192_ref1-bib37","unstructured":"Geary M, Pl\u00fcddemann A, Thompson M, Wolstenholme J, Heneghan C, Price CP. Diagnostic Technology: Point-of-care test (POCT) for C-reactive Protein (CRP). Horizon Scan Report 0017. Department of Primary Health Diagnostic Horizon Scanning Centre; 2011. URL: www.community.healthcare.mic.nihr.ac.uk\/reports-and-resources\/horizon-scanning-reports\/horizon-scan-reports-non-dec-funded (accessed 8 March 2019)."},{"key":"key20200317105932192_ref1-bib38","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1186\/s13063-017-2144-8","article-title":"General practitioner use of a C-reactive protein point-of-care test to help target antibiotic prescribing in patients with acute exacerbations of chronic obstructive pulmonary disease (the PACE study): study protocol for a randomised controlled trial","volume":"18","author":"Bates","year":"2017","journal-title":"Trials"},{"key":"key20200317105932192_ref1-bib39","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.1378\/chest.10-1747","article-title":"Procalcitonin and C-reactive protein in hospitalized adult patients with community-acquired pneumonia or exacerbation of asthma or COPD","volume":"139","author":"Bafadhel","year":"2011","journal-title":"Chest"},{"key":"key20200317105932192_ref1-bib40","unstructured":"Great Britain. Data Protection Act 1998. London: The Stationery Office; 1998."},{"key":"key20200317105932192_ref1-bib41","unstructured":"European Parliament, Council of the European Union. Regulation (EU) 2016\/679 of the European Parliament and of the Council of 27 April 2016 on the Protection of Natural Persons with Regard to the Processing of Personal Data and on the Free Movement of Such Data, and Repealing Directive 95\/46\/EC (General Data Protection Regulation). Brussels: European Parliament; 1996."},{"key":"key20200317105932192_ref1-bib42","author":"BronkoTest"},{"key":"key20200317105932192_ref1-bib43","doi-asserted-by":"publisher","first-page":"1638","DOI":"10.1378\/chest.117.6.1638","article-title":"Relationship of sputum color to nature and outpatient management of acute exacerbations of COPD","volume":"117","author":"Stockley","year":"2000","journal-title":"Chest"},{"key":"key20200317105932192_ref1-bib44","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1477-7525-1-13","article-title":"Development, validity and responsiveness of the Clinical COPD Questionnaire","volume":"1","author":"van der Molen","year":"2003","journal-title":"Health Qual Life Outcomes"},{"key":"key20200317105932192_ref1-bib45","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/0168-8510(90)90421-9","article-title":"EuroQol \u2013 a new facility for the measurement of health-related quality of life","volume":"16","author":"EuroQol Group","year":"1990","journal-title":"Health Policy"},{"key":"key20200317105932192_ref1-bib46","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/0168-8510(96)00822-6","article-title":"EuroQol: the current state of play","volume":"37","author":"Brooks","year":"1996","journal-title":"Health Policy"},{"key":"key20200317105932192_ref1-bib47","doi-asserted-by":"publisher","first-page":"1727","DOI":"10.1007\/s11136-011-9903-x","article-title":"Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L)","volume":"20","author":"Herdman","year":"2011","journal-title":"Qual Life Res"},{"key":"key20200317105932192_ref1-bib48","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.1007\/s11136-012-0322-4","article-title":"Measurement properties of the EQ-5D-5L compared to the EQ-5D-3L across eight patient groups: a multi-country study","volume":"22","author":"Janssen","year":"2013","journal-title":"Qual Life Res"},{"key":"key20200317105932192_ref1-bib49","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1378\/chest.124.4.1421","article-title":"A comparison of the original chronic respiratory questionnaire with a standardized version","volume":"124","author":"Sch\u00fcnemann","year":"2003","journal-title":"Chest"},{"key":"key20200317105932192_ref1-bib50","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1186\/1465-9921-7-62","article-title":"Health status measurement in COPD: the minimal clinically important difference of the clinical COPD questionnaire","volume":"7","author":"Kocks","year":"2006","journal-title":"Respir Res"},{"key":"key20200317105932192_ref1-bib51","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1370\/afm.1090","article-title":"Point-of-care C-reactive protein testing and antibiotic prescribing for respiratory tract infections: a randomized controlled trial","volume":"8","author":"Cals","year":"2010","journal-title":"Ann Fam Med"},{"key":"key20200317105932192_ref1-bib52","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1177\/009286150704100105","article-title":"Multiple co-primary endpoints: medical and statistical solutions \u2013 a report from the Multiple Endpoints Expert Team of the Pharmaceutical Research and Manufacturers of America","volume":"41","author":"Offen","year":"2007","journal-title":"Drug Inf J"},{"key":"key20200317105932192_ref1-bib53","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/j.pain.2008.06.025","article-title":"Analyzing multiple endpoints in clinical trials of pain treatments: IMMPACT recommendations. Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials","volume":"139","author":"Turk","year":"2008","journal-title":"Pain"},{"key":"key20200317105932192_ref1-bib54","doi-asserted-by":"publisher","first-page":"2557","DOI":"10.1001\/jama.2009.1866","article-title":"Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: a randomized controlled trial","volume":"302","author":"Green","year":"2009","journal-title":"JAMA"},{"key":"key20200317105932192_ref1-bib55","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1080\/01621459.1996.10476902","article-title":"Identification of causal effects using instrumental variables","volume":"91","author":"Angrist","year":"1996","journal-title":"J Am Stat Assoc"},{"key":"key20200317105932192_ref1-bib56","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1056\/NEJMoa1803185","article-title":"C-reactive protein testing to guide antibiotic prescribing for COPD exacerbations","volume":"381","author":"Butler","year":"2019","journal-title":"N Engl J Med"},{"key":"key20200317105932192_ref1-bib57","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1136\/bmj.332.7538.413","article-title":"Health services research: process evaluation in randomised controlled trials of complex interventions","volume":"332","author":"Oakley","year":"2006","journal-title":"BMJ"},{"key":"key20200317105932192_ref1-bib58","doi-asserted-by":"publisher","first-page":"h1258","DOI":"10.1136\/bmj.h1258","article-title":"Process evaluation of complex interventions: Medical Research Council guidance","volume":"350","author":"Moore","year":"2015","journal-title":"BMJ"},{"key":"key20200317105932192_ref1-bib59","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1177\/1525822X05279903","article-title":"How many interviews are enough? An experiment with data saturation and variability","volume":"18","author":"Guest","year":"2006","journal-title":"Field Methods"},{"key":"key20200317105932192_ref1-bib60","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/1471-2288-13-117","article-title":"Using the framework method for the analysis of qualitative data in multi-disciplinary health research","volume":"13","author":"Gale","year":"2013","journal-title":"BMC Med Res Methodol"},{"key":"key20200317105932192_ref1-bib61","first-page":"72","article-title":"Framework analysis: a qualitative methodology for applied policy research","volume":"4","author":"Srivastava","year":"2009","journal-title":"J Admin Governance"},{"key":"key20200317105932192_ref1-bib62","volume-title":"Analyzing Qualitative Data","author":"Ritchie","year":"1994"},{"key":"key20200317105932192_ref1-bib63","volume-title":"Qualitative Research and Practice","author":"Ritchie","year":"2003"},{"key":"key20200317105932192_ref1-bib64","first-page":"1408","article-title":"Are we there yet? Data saturation in qualitative research","volume":"20","author":"Fusch","year":"2015","journal-title":"The Qualitative Report"},{"key":"key20200317105932192_ref1-bib65","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1007\/s11606-014-3076-6","article-title":"Clinicians\u2019 views and experiences of interventions to enhance the quality of antibiotic prescribing for acute respiratory tract infections","volume":"30","author":"Anthierens","year":"2015","journal-title":"J Gen Intern Med"},{"key":"key20200317105932192_ref1-bib66","doi-asserted-by":"publisher","first-page":"14026","DOI":"10.1038\/npjpcrm.2014.26","article-title":"Exploring patients\u2019 views of primary care consultations with contrasting interventions for acute cough: a six-country European qualitative study","volume":"24","author":"Tonkin-Crine","year":"2014","journal-title":"NPJ Prim Care Respir Med"},{"key":"key20200317105932192_ref1-bib67","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1093\/fampra\/cmr031","article-title":"A multi-country qualitative study of clinicians\u2019 and patients\u2019 views on point of care tests for lower respiratory tract infection","volume":"28","author":"Wood","year":"2011","journal-title":"Fam Pract"},{"key":"key20200317105932192_ref1-bib68","doi-asserted-by":"publisher","first-page":"e009959","DOI":"10.1136\/bmjopen-2015-009959","article-title":"Point-of-care C-reactive protein for the diagnosis of lower respiratory tract infection in NHS primary care: a qualitative study of barriers and facilitators to adoption","volume":"6","author":"Huddy","year":"2016","journal-title":"BMJ Open"},{"key":"key20200317105932192_ref1-bib69","doi-asserted-by":"publisher","first-page":"31","DOI":"10.2147\/COPD.S1089","article-title":"Optimizing antibiotic selection in treating COPD exacerbations","volume":"3","author":"Siddiqi","year":"2008","journal-title":"Int J Chron Obstruct Pulmon Dis"},{"key":"key20200317105932192_ref1-bib70","doi-asserted-by":"publisher","first-page":"CD003539","DOI":"10.1002\/14651858.CD003539.pub2","article-title":"Interventions to improve antibiotic prescribing practices in ambulatory care","volume":"4","author":"Arnold","year":"2005","journal-title":"Cochrane Database Syst Rev"},{"key":"key20200317105932192_ref1-bib71","doi-asserted-by":"publisher","first-page":"e76691","DOI":"10.1371\/journal.pone.0076691","article-title":"Are patient views about antibiotics related to clinician perceptions, management and outcome? A multi-country study in outpatients with acute cough","volume":"8","author":"Coenen","year":"2013","journal-title":"PLOS ONE"},{"key":"key20200317105932192_ref1-bib72","doi-asserted-by":"publisher","first-page":"2831","DOI":"10.2147\/COPD.S104136","article-title":"COPD care delivery pathways in five European Union countries: mapping and health care professionals\u2019 perceptions","volume":"11","author":"Kayyali","year":"2016","journal-title":"Int J Chron Obstruct Pulmon Dis"},{"key":"key20200317105932192_ref1-bib73","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/j.pec.2014.05.011","article-title":"Primary and secondary care clinicians\u2019 views on self-treatment of COPD exacerbations: a multinational qualitative study","volume":"96","author":"Davies","year":"2014","journal-title":"Patient Educ Couns"},{"key":"key20200317105932192_ref1-bib74","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1016\/S0140-6736(07)61380-4","article-title":"Global burden of COPD: risk factors, prevalence, and future trends","volume":"370","author":"Mannino","year":"2007","journal-title":"Lancet"},{"key":"key20200317105932192_ref1-bib75","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1093\/her\/cys067","article-title":"Health literacy programs for older adults: a systematic literature review","volume":"27","author":"Manafo","year":"2012","journal-title":"Health Educ Res"},{"key":"key20200317105932192_ref1-bib76","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1007\/s11606-009-1105-7","article-title":"Developing predictive models of health literacy","volume":"24","author":"Martin","year":"2009","journal-title":"J Gen Intern Med"},{"key":"key20200317105932192_ref1-bib77","volume-title":"CCEMG-EPPI-Centre Cost Converter","year":"2016"},{"key":"key20200317105932192_ref1-bib78","volume-title":"Unit Costs of Health and Social Care 2016","author":"Curtis","year":"2016"},{"key":"key20200317105932192_ref1-bib79","volume-title":"Monthly Index of Medical Specialities","author":"Monthly Index of Medical Specialities","year":"2017"},{"key":"key20200317105932192_ref1-bib80","volume-title":"British National Formulary","author":"Joint Formulary Committee","year":"2017"},{"key":"key20200317105932192_ref1-bib81","unstructured":"Department of Health and Social Care. NHS Reference Costs 2015 to 2016. London: Department of Health and Social Care; URL: www.gov.uk\/government\/publications\/nhs-reference-costs-2015-to-2016 (accessed 29 June 2018)."},{"key":"key20200317105932192_ref1-bib82","doi-asserted-by":"crossref","DOI":"10.1093\/oso\/9780198529446.001.0001","volume-title":"Methods for Economic Evaluation of Health Care Programmes","author":"Drummond","year":"2005","edition":"3rd edn"},{"key":"key20200317105932192_ref1-bib83","unstructured":"Office for National Statistics. EARN01: Average Weekly Earnings Dataset. Newport: Office for National Statistics; 2017. URL: www.ons.gov.uk\/employmentandlabourmarket\/peopleinwork\/earningsandworkinghours\/datasets\/averageweeklyearningsearn01 (accessed 29 June 2018)."},{"key":"key20200317105932192_ref1-bib84","unstructured":"NICE. Position Statement on Use of the EQ-5D-5L Valuation Set. London: NICE; 2017. URL: www.nice.org.uk\/Media\/Default\/About\/what-we-do\/NICE-guidance\/NICE-technology-appraisal-guidance\/eq5d5l_nice_position_statement.pdf (accessed 3 July 2018)."},{"key":"key20200317105932192_ref1-bib85","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1007\/s40273-014-0193-3","article-title":"A guide to handling missing data in cost-effectiveness analysis conducted within randomised controlled trials","volume":"32","author":"Faria","year":"2014","journal-title":"PharmacoEconomics"},{"key":"key20200317105932192_ref1-bib86","unstructured":"NICE. Pneumonia in Adults: Diagnosis and Management. Clinical guideline [CG191]. London: NICE; 2014. URL: www.nice.org.uk\/guidance\/CG191 (accessed 29 June 2018)."},{"key":"key20200317105932192_ref1-bib87","doi-asserted-by":"crossref","DOI":"10.1002\/9780470316696","volume-title":"Multiple Imputation for Nonresponse in Surveys","author":"Rubin","year":"1987"},{"key":"key20200317105932192_ref1-bib88","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.jval.2013.08.2291","article-title":"Budget impact analysis-principles of good practice: report of the ISPOR 2012 Budget Impact Analysis Good Practice II Task Force","volume":"17","author":"Sullivan","year":"2014","journal-title":"Value Health"},{"key":"key20200317105932192_ref1-bib89","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1136\/thoraxjnl-2016-209023","article-title":"A prospective, observational cohort study of the seasonal dynamics of airway pathogens in the aetiology of exacerbations in COPD","volume":"72","author":"Wilkinson","year":"2017","journal-title":"Thorax"},{"key":"key20200317105932192_ref1-bib90","unstructured":"Office for National Statistics. Deaths Registered in England and Wales: 2016. Newport: Office for National Statistics; 2017. URL: www.ons.gov.uk\/peoplepopulationandcommunity\/birthsdeathsandmarriages\/deaths\/bulletins\/deathsregistrationsummarytables\/2016 (accessed 29 June 2018)."},{"key":"key20200317105932192_ref1-bib91","volume-title":"Cutisoft Wipes","author":"Medisupplies"},{"key":"key20200317105932192_ref1-bib92","volume-title":"One Touch Ultra Soft Lancets","author":"Amazon"},{"key":"key20200317105932192_ref1-bib93","volume-title":"Multisorb Gauze Swabs","author":"Medisupplies"},{"key":"key20200317105932192_ref1-bib94","volume-title":"GlovePlus Vinyl Gloves","author":"Scientific Laboratory Supplies"},{"key":"key20200317105932192_ref1-bib95","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1016\/j.jclinepi.2008.12.011","article-title":"A pragmatic-explanatory continuum indicator summary (PRECIS): a tool to help trial designers","volume":"62","author":"Thorpe","year":"2009","journal-title":"J Clin Epidemiol"},{"key":"key20200317105932192_ref1-bib96","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1038\/s41533-017-0046-6","article-title":"Self-management behaviour and support among primary care COPD patients: cross-sectional analysis of data from the Birmingham Chronic Obstructive Pulmonary Disease Cohort","volume":"27","author":"Khan","year":"2017","journal-title":"NPJ Prim Care Respir Med"},{"key":"key20200317105932192_ref1-bib97","doi-asserted-by":"publisher","first-page":"e75221","DOI":"10.1371\/journal.pone.0075221","article-title":"Overtreatment of COPD with inhaled corticosteroids \u2013 implications for safety and costs: cross-sectional observational study","volume":"8","author":"White","year":"2013","journal-title":"PLOS ONE"},{"key":"key20200317105932192_ref1-bib98","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/1471-2296-15-80","article-title":"Usefulness of C-reactive protein testing in acute cough\/respiratory tract infection: an open cluster-randomized clinical trial with C-reactive protein testing in the intervention group","volume":"15","author":"Andreeva","year":"2014","journal-title":"BMC Fam Pract"},{"key":"key20200317105932192_ref1-bib99","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1093\/fampra\/cmv020","article-title":"An intervention with access to C-reactive protein rapid test reduces antibiotic overprescribing in acute exacerbations of chronic bronchitis and COPD","volume":"32","author":"Strykowski","year":"2015","journal-title":"Fam Pract"},{"key":"key20200317105932192_ref1-bib100","doi-asserted-by":"publisher","first-page":"160073","DOI":"10.1183\/16000617.0073-2016","article-title":"Procalcitonin to guide antibiotic administration in COPD exacerbations: a meta-analysis","volume":"26","author":"Mathioudakis","year":"2017","journal-title":"Eur Respir Rev"},{"key":"key20200317105932192_ref1-bib101","doi-asserted-by":"publisher","first-page":"CD010130","DOI":"10.1002\/14651858.CD010130.pub2","article-title":"Biomarkers as point-of-care tests to guide prescription of antibiotics in patients with acute respiratory infections in primary care","volume":"11","author":"Aabenhus","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"key20200317105932192_ref1-bib102","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1093\/fampra\/cmp088","article-title":"C-reactive protein point-of-care testing for lower respiratory tract infections: a qualitative evaluation of experiences by GPs","volume":"27","author":"Cals","year":"2010","journal-title":"Fam Pract"},{"key":"key20200317105932192_ref1-bib103","doi-asserted-by":"publisher","first-page":"e012503","DOI":"10.1136\/bmjopen-2016-012503","article-title":"Qualitative study of primary care clinicians\u2019 views on point-of-care testing for C-reactive protein for acute respiratory tract infections in family medicine","volume":"7","author":"Hardy","year":"2017","journal-title":"BMJ Open"},{"key":"key20200317105932192_ref1-bib104","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/s12325-015-0180-x","article-title":"Cost-effectiveness of point-of-care C-reactive protein tests for respiratory tract infection in primary care in England","volume":"32","author":"Hunter","year":"2015","journal-title":"Adv Ther"},{"key":"key20200317105932192_ref1-bib105","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1136\/thoraxjnl-2015-207782","article-title":"The EQ-5D-5L health status questionnaire in COPD: validity, responsiveness and minimum important difference","volume":"71","author":"Nolan","year":"2016","journal-title":"Thorax"},{"key":"key20200317105932192_ref1-bib106","volume-title":"Unit Costs of Health and Social Care 2015","author":"Curtis","year":"2015"}],"container-title":["Health Technology Assessment"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.journalslibrary.nihr.ac.uk\/publications\/hta24150\/hta24150.xml","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/njl-admin.nihr.ac.uk\/document\/download\/2010940","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.journalslibrary.nihr.ac.uk\/publications\/hta24150\/hta24150.xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/njl-admin.nihr.ac.uk\/document\/download\/2032172","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T19:16:27Z","timestamp":1722626187000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.journalslibrary.nihr.ac.uk\/hta\/hta24150"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3]]},"references-count":106,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["10.3310\/hta24150"],"URL":"https:\/\/doi.org\/10.3310\/hta24150","relation":{},"ISSN":["1366-5278","2046-4924"],"issn-type":[{"value":"1366-5278","type":"print"},{"value":"2046-4924","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3]]},"assertion":[{"value":"This content has been made freely available to all.","name":"free","label":"Free to read"}]}}