{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:24:51Z","timestamp":1792686291988,"version":"4.5.0"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T00:00:00Z","timestamp":1717113600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T00:00:00Z","timestamp":1717113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Intern Emerg Med"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Low-dose azithromycin prophylaxis is associated with improved outcomes in people suffering frequent exacerbations of chronic obstructive pulmonary disease (COPD), but the use of macrolides in patients with cardiovascular disease has been debated. To investigate the risk of adverse events after COPD exacerbations in patients with atrial fibrillation (AF) treated with azithromycin prophylaxis. Retrospective cohort study within the TriNetX Platform, including AF patients with COPD exacerbations. Risks of primary and secondary outcomes were recorded up to 30\u00a0days post-COPD exacerbations and compared between <jats:italic>azithromycin users<\/jats:italic> and <jats:italic>azithromycin non-users<\/jats:italic>. The primary outcomes were the risks for a composite of (1) cardiovascular (all-cause death, heart failure, ventricular arrhythmias, ischemic stroke, myocardial infarction, and cardiac arrest), and (2) hemorrhagic events (intracranial hemorrhage (ICH), and gastro-intestinal bleeding). Cox-regression analyses compared outcomes between groups after propensity score matching (PSM). After PSM, <jats:italic>azithromycin users<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009=\u20092434, 71\u2009\u00b1\u200910\u00a0years, 49% females) were associated with a lower 30-day risk of post-exacerbation cardiovascular (HR 0.67, 95% CI 0.61\u20130.73) and hemorrhagic composite outcome (HR 0.45, 95% CI 0.32\u20130.64) compared to <jats:italic>azithromycin non-users<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009=\u20092434, 72\u2009\u00b1\u200911\u00a0years, 51% females)<jats:italic>.<\/jats:italic> The beneficial effect was consistent for each secondary outcomes, except ICH. On sensitivity analyses, the reduced risk of adverse events in <jats:italic>azithromycin users<\/jats:italic> was irrespective of smoking status, exacerbation severity, and type of oral anticoagulation. Azithromycin prophylaxis is associated with a lower risk of all-cause death, thrombotic and hemorrhagic events in AF patients with COPD. The possible role of azithromycin prophylaxis as part of the integrated care management of AF patients with COPD needs further study.<\/jats:p>","DOI":"10.1007\/s11739-024-03653-0","type":"journal-article","created":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T14:03:11Z","timestamp":1717164191000},"page":"1615-1623","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Low-dose azithromycin prophylaxis in patients with atrial fibrillation and chronic obstructive pulmonary disease"],"prefix":"10.1007","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2895-6234","authenticated-orcid":false,"given":"Tommaso","family":"Bucci","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Wat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Sibley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Wootton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Green","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Pignatelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory Y. H.","family":"Lip","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Freddy","family":"Frost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,31]]},"reference":[{"issue":"35","key":"3653_CR1","doi-asserted-by":"publisher","first-page":"3541","DOI":"10.1093\/eurheartj\/ehab453","volume":"42","author":"GF Romiti","year":"2021","unstructured":"Romiti GF, Corica B, Pipitone E, Vitolo M, Raparelli V, Basili S, Boriani G, Harari S, Lip GYH, Proietti M, Group A-CIC (2021) Prevalence, management and impact of chronic obstructive pulmonary disease in atrial fibrillation: a systematic review and meta-analysis of 4,200,000 patients. Eur Heart J 42(35):3541\u20133554","journal-title":"Eur Heart J"},{"issue":"5","key":"3653_CR2","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1007\/s11739-018-1835-9","volume":"13","author":"V Raparelli","year":"2018","unstructured":"Raparelli V, Pastori D, Pignataro SF, Vestri AR, Pignatelli P, Cangemi R, Proietti M, Davi G, Hiatt WR, Lip GYH, Corazza GR, Perticone F, Violi F, Basili S, Collaborators AS (2018) Major adverse cardiovascular events in non-valvular atrial fibrillation with chronic obstructive pulmonary disease: the ARAPACIS study. Intern Emerg Med 13(5):651\u2013660","journal-title":"Intern Emerg Med"},{"key":"3653_CR3","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.ahj.2016.08.011","volume":"181","author":"M Proietti","year":"2016","unstructured":"Proietti M, Laroche C, Drozd M, Vijgen J, Cozma DC, Drozdz J, Maggioni AP, Boriani G, Lip GY, Investigators E-A (2016) Impact of chronic obstructive pulmonary disease on prognosis in atrial fibrillation: a report from the EURObservational research programme pilot survey on atrial fibrillation (EORP-AF) general registry. Am Heart J 181:83\u201391","journal-title":"Am Heart J"},{"issue":"7","key":"3653_CR4","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.123.032785","volume":"13","author":"T Bucci","year":"2024","unstructured":"Bucci T, Romiti GF, Shantsila A, Teo WS, Park HW, Shimizu W, Corica B, Proietti M, Tse HF, Chao TF, Frost F, Lip GYH (2024) Asia-Pacific heart rhythm society atrial fibrillation registry I. Risk of death and cardiovascular events in Asian patients with atrial fibrillation and chronic obstructive pulmonary disease: a report from the prospective APHRS registry. J Am Heart Assoc 13(7):e032785","journal-title":"J Am Heart Assoc"},{"issue":"18","key":"3653_CR5","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.121.024350","volume":"11","author":"MT Dransfield","year":"2022","unstructured":"Dransfield MT, Criner GJ, Halpin DMG, Han MK, Hartley B, Kalhan R, Lange P, Lipson DA, Martinez FJ, Midwinter D, Singh D, Wise R, Kunisaki KM (2022) Time-dependent risk of cardiovascular events following an exacerbation in patients with chronic obstructive pulmonary disease: post hoc analysis from the IMPACT trial. J Am Heart Assoc 11(18):e024350","journal-title":"J Am Heart Assoc"},{"issue":"8","key":"3653_CR6","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1513\/AnnalsATS.201710-815OC","volume":"15","author":"KJ Rothnie","year":"2018","unstructured":"Rothnie KJ, Connell O, Mullerova H, Smeeth L, Pearce N, Douglas I, Quint JK (2018) Myocardial infarction and ischemic stroke after exacerbations of chronic obstructive pulmonary disease. Ann Am Thorac Soc 15(8):935\u2013946","journal-title":"Ann Am Thorac Soc"},{"issue":"4","key":"3653_CR7","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1111\/resp.14486","volume":"28","author":"A Agusti","year":"2023","unstructured":"Agusti A, Celli BR, Criner GJ, Halpin D, Anzueto A, Barnes P, Bourbeau J, Han MK, Martinez FJ, de Oca MM, Mortimer K, Papi A, Pavord I, Roche N, Salvi S, Sin DD, Singh D, Stockley R, Varela MVL, Wedzicha JA, Vogelmeier CF (2023) Global initiative for chronic obstructive lung disease 2023 report: GOLD executive summary. Respirology 28(4):316\u2013338","journal-title":"Respirology"},{"key":"3653_CR8","unstructured":"(NICE) NIfHaCE (2019) Chronic obstructive pulmonary disease in over 16s: diagnosis and management. Chronic obstructive pulmonary disease in over 16s: diagnosis and management, London, 2019."},{"issue":"20","key":"3653_CR9","doi-asserted-by":"publisher","first-page":"1881","DOI":"10.1056\/NEJMoa1003833","volume":"366","author":"WA Ray","year":"2012","unstructured":"Ray WA, Murray KT, Hall K, Arbogast PG, Stein CM (2012) Azithromycin and the risk of cardiovascular death. N Engl J Med 366(20):1881\u20131890","journal-title":"N Engl J Med"},{"issue":"12","key":"3653_CR10","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1056\/NEJMoa1707914","volume":"377","author":"PM Ridker","year":"2017","unstructured":"Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ, Group CT (2017) Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 377(12):1119\u20131131","journal-title":"N Engl J Med"},{"key":"3653_CR11","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202309-1699LE","author":"T Bucci","year":"2024","unstructured":"Bucci T, Wat D, Nazareth D, Sibley S, Wootton D, Lip GY, Frost F (2024) Risk of cardiovascular events after acute exacerbations of chronic obstructive pulmonary disease in patients receiving long-term low-dose azithromycin. Am J Respir Crit Care Med. https:\/\/doi.org\/10.1164\/rccm.202309-1699LE","journal-title":"Am J Respir Crit Care Med"},{"issue":"9","key":"3653_CR12","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1164\/rccm.201306-1170OC","volume":"188","author":"AR Patel","year":"2013","unstructured":"Patel AR, Kowlessar BS, Donaldson GC, Mackay AJ, Singh R, George SN, Garcha DS, Wedzicha JA, Hurst JR (2013) Cardiovascular risk, myocardial injury, and exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 188(9):1091\u20131099","journal-title":"Am J Respir Crit Care Med"},{"issue":"12","key":"3653_CR13","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1164\/rccm.201402-0207OC","volume":"189","author":"MK Han","year":"2014","unstructured":"Han MK, Tayob N, Murray S, Dransfield MT, Washko G, Scanlon PD, Criner GJ, Casaburi R, Connett J, Lazarus SC, Albert R, Woodruff P, Martinez FJ (2014) Predictors of chronic obstructive pulmonary disease exacerbation reduction in response to daily azithromycin therapy. Am J Respir Crit Care Med 189(12):1503\u20131508","journal-title":"Am J Respir Crit Care Med"},{"key":"3653_CR14","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.rmed.2018.03.035","volume":"138","author":"N Naderi","year":"2018","unstructured":"Naderi N, Assayag D, Mostafavi-Pour-Manshadi SM, Kaddaha Z, Joubert A, Ouellet I, Drouin I, Li PZ, Bourbeau J (2018) Long-term azithromycin therapy to reduce acute exacerbations in patients with severe chronic obstructive pulmonary disease. Respir Med 138:129\u2013136","journal-title":"Respir Med"},{"issue":"8","key":"3653_CR15","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1056\/NEJMoa1104623","volume":"365","author":"RK Albert","year":"2011","unstructured":"Albert RK, Connett J, Bailey WC, Casaburi R, Cooper JA Jr, Criner GJ, Curtis JL, Dransfield MT, Han MK, Lazarus SC, Make B, Marchetti N, Martinez FJ, Madinger NE, McEvoy C, Niewoehner DE, Porsasz J, Price CS, Reilly J, Scanlon PD, Sciurba FC, Scharf SM, Washko GR, Woodruff PG, Anthonisen NR, Network CCR (2011) Azithromycin for prevention of exacerbations of COPD. N Engl J Med 365(8):689\u2013698","journal-title":"N Engl J Med"},{"issue":"10","key":"3653_CR16","first-page":"CD009764","volume":"10","author":"SC Herath","year":"2018","unstructured":"Herath SC, Normansell R, Maisey S, Poole P (2018) Prophylactic antibiotic therapy for chronic obstructivea pulmonary disease (COPD). Cochrane Database Syst Rev 10(10):CD009764","journal-title":"Cochrane Database Syst Rev"},{"issue":"10","key":"3653_CR17","doi-asserted-by":"publisher","first-page":"5784","DOI":"10.21037\/jtd.2018.09.145","volume":"10","author":"J Kang","year":"2018","unstructured":"Kang J, Kim YJ, Shim TS, Jo KW (2018) Risk for cardiovascular disease in patients with nontuberculous mycobacteria treated with macrolide. J Thorac Dis 10(10):5784\u20135795","journal-title":"J Thorac Dis"},{"issue":"18","key":"3653_CR18","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1056\/NEJMoa1300799","volume":"368","author":"H Svanstrom","year":"2013","unstructured":"Svanstrom H, Pasternak B, Hviid A (2013) Use of azithromycin and death from cardiovascular causes. N Engl J Med 368(18):1704\u20131712","journal-title":"N Engl J Med"},{"issue":"12","key":"3653_CR19","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1001\/jama.2013.2290","volume":"309","author":"DJ Serisier","year":"2013","unstructured":"Serisier DJ, Martin ML, McGuckin MA, Lourie R, Chen AC, Brain B, Biga S, Schlebusch S, Dash P, Bowler SD (2013) Effect of long-term, low-dose erythromycin on pulmonary exacerbations among patients with non-cystic fibrosis bronchiectasis: the BLESS randomized controlled trial. JAMA 309(12):1260\u20131267","journal-title":"JAMA"},{"key":"3653_CR20","doi-asserted-by":"publisher","first-page":"2105","DOI":"10.2147\/COPD.S166534","volume":"13","author":"CY Chen","year":"2018","unstructured":"Chen CY, Liao KM (2018) The impact of atrial fibrillation in patients with COPD during hospitalization. Int J Chron Obstruct Pulmon Dis 13:2105\u20132112","journal-title":"Int J Chron Obstruct Pulmon Dis"},{"issue":"3","key":"3653_CR21","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1016\/j.chest.2020.02.046","volume":"158","author":"M Wang","year":"2020","unstructured":"Wang M, Lin EP, Huang LC, Li CY, Shyr Y, Lai CH (2020) Mortality of cardiovascular events in patients with COPD and preceding hospitalization for acute exacerbation. Chest 158(3):973\u2013985","journal-title":"Chest"},{"issue":"5","key":"3653_CR22","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1093\/eurheartj\/ehaa822","volume":"42","author":"SO Simons","year":"2021","unstructured":"Simons SO, Elliott A, Sastry M, Hendriks JM, Arzt M, Rienstra M, Kalman JM, Heidbuchel H, Nattel S, Wesseling G, Schotten U, van Gelder IC, Franssen FME, Sanders P, Crijns H, Linz D (2021) Chronic obstructive pulmonary disease and atrial fibrillation: an interdisciplinary perspective. Eur Heart J 42(5):532\u2013540","journal-title":"Eur Heart J"},{"issue":"2","key":"3653_CR23","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1111\/bcp.15531","volume":"89","author":"T Yagi","year":"2023","unstructured":"Yagi T, Mannheimer B, Reutfors J, Ursing J, Giunta DH, Kieler H, Linder M (2023) Bleeding events among patients concomitantly treated with direct oral anticoagulants and macrolide or fluoroquinolone antibiotics. Br J Clin Pharmacol 89(2):887\u2013897","journal-title":"Br J Clin Pharmacol"},{"issue":"1","key":"3653_CR24","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1055\/s-0041-1739411","volume":"122","author":"TF Chao","year":"2022","unstructured":"Chao TF, Joung B, Takahashi Y, Lim TW, Choi EK, Chan YH, Guo Y, Sriratanasathavorn C, Oh S, Okumura K, Lip GYH (2022) 2021 focused update consensus guidelines of the Asia pacific heart rhythm society on stroke prevention in atrial fibrillation: executive summary. Thromb Haemost 122(1):20\u201347","journal-title":"Thromb Haemost"},{"issue":"5","key":"3653_CR25","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1093\/eurheartj\/ehaa612","volume":"42","author":"G Hindricks","year":"2021","unstructured":"Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomstrom-Lundqvist C, Boriani G, Castella M, Dan GA, Dilaveris PE, Fauchier L, Filippatos G, Kalman JM, La Meir M, Lane DA, Lebeau JP, Lettino M, Lip GYH, Pinto FJ, Thomas GN, Valgimigli M, Van Gelder IC, Van Putte BP, Watkins CL, Group ESCSD (2021) 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European association for cardio-thoracic surgery (EACTS): the task force for the diagnosis and management of atrial fibrillation of the European society of cardiology (ESC) developed with the special contribution of the European heart rhythm association (EHRA) of the ESC. Eur Heart J 42(5):373\u2013498","journal-title":"Eur Heart J"},{"issue":"11","key":"3653_CR26","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1038\/nrcardio.2017.153","volume":"14","author":"GYH Lip","year":"2017","unstructured":"Lip GYH (2017) The ABC pathway: an integrated approach to improve AF management. Nat Rev Cardiol 14(11):627\u2013628","journal-title":"Nat Rev Cardiol"},{"issue":"3","key":"3653_CR27","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1055\/a-1515-9630","volume":"122","author":"GF Romiti","year":"2022","unstructured":"Romiti GF, Pastori D, Rivera-Caravaca JM, Ding WY, Gue YX, Menichelli D, Gumprecht J, Koziel M, Yang PS, Guo Y, Lip GYH, Proietti M (2022) Adherence to the \u201catrial fibrillation better care\u201d pathway in patients with atrial fibrillation: impact on clinical outcomes-a systematic review and meta-analysis of 285,000 patients. Thromb Haemost 122(3):406\u2013414","journal-title":"Thromb Haemost"},{"issue":"4","key":"3653_CR28","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1016\/j.jacasi.2023.04.008","volume":"3","author":"T Bucci","year":"2023","unstructured":"Bucci T, Proietti M, Shantsila A, Romiti GF, Teo WS, Park HW, Shimizu W, Tse HF, Lip GYH, Chao TF, Investigators A-AR (2023) Integrated care for atrial fibrillation using the ABC pathway in the prospective APHRS-AF registry. JACC Asia 3(4):580\u2013591","journal-title":"JACC Asia"},{"key":"3653_CR29","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/hcad219","author":"R Krittayaphong","year":"2023","unstructured":"Krittayaphong R, Treewaree S, Wongtheptien W, Kaewkumdee P, Lip GYH (2023) Clinical phenotype classification to predict risk and optimize the management of patients with atrial fibrillation using the atrial fibrillation better care (ABC) pathway: a report from the COOL-AF registry. QJM. https:\/\/doi.org\/10.1093\/qjmed\/hcad219","journal-title":"QJM"}],"container-title":["Internal and Emergency Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11739-024-03653-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11739-024-03653-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11739-024-03653-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T12:17:42Z","timestamp":1726489062000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11739-024-03653-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,31]]},"references-count":29,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["3653"],"URL":"https:\/\/doi.org\/10.1007\/s11739-024-03653-0","relation":{},"ISSN":["1828-0447","1970-9366"],"issn-type":[{"value":"1828-0447","type":"print"},{"value":"1970-9366","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,31]]},"assertion":[{"value":"11 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 May 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 May 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"GYHL is a consultant and speaker for BMS\/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos. No fees are received personally. GYHL is a National Institute for Health and Care Research (NIHR) Senior Investigator and co-principal investigator of the AFFIRMO project on multimorbidity in AF, which has received funding from the European Union\u2019s Horizon 2020 research and innovation program under grant agreement No 899871. All other authors report no disclosures.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"As a federated research network, studies using the TriNetX health research network do not need ethical approval as no patient identifiable identification is received.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"For this type of study formal consent is not required.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}