{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:49:58Z","timestamp":1791589798396,"version":"4.3.4"},"reference-count":87,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e0 degli Studi di Bari Aldo Moro"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Intern Emerg Med"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Opioid-induced constipation (OIC) remains one of the most frequent and distressing gastrointestinal side effects encountered by patients on chronic opioid therapy. Despite the high prevalence, OIC is frequently underdiagnosed and inadequately managed, with critical effects on the quality of life of patients. Aim of this review is to promote the awareness about OIC in the context of internal medicine. We examined the statement EnhanCing Healthcare Outcomes in Opioid-Induced Constipation (ECHO OIC) by European experts to streamline the diagnosis and management of OIC in clinical practice. Such guidelines have been further discussed by an Italian expert consensus to provide national customization and a multidisciplinary approach. The key finding is the implementation of a multi-step clinical pathway for prevention, diagnosis, treatment, and long-term management of OIC, taking into account the improvement of quality of life of patients. In conclusion, we urge to expand awareness about OIC. The seven-step diagnostic\u2013therapeutic pathway approach formulated by ECHO OIC is a pragmatic and scalable model to improve OIC management with emphasis on education, early intervention, monitoring, tailored pharmacologic strategies, and coordinated referral when necessary.<\/jats:p>","DOI":"10.1007\/s11739-025-04091-2","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T15:57:00Z","timestamp":1756396620000},"page":"1695-1704","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Opioid-induced constipation in internal medicine: recognition and management pathways"],"prefix":"10.1007","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5359-1471","authenticated-orcid":false,"given":"Piero","family":"Portincasa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara Valentina","family":"Luglio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Sozzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Conforti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Bitonto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Papavero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyorgy","family":"Baffy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agostino","family":"Di Ciaula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"issue":"2","key":"4091_CR1","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1016\/j.pain.2008.04.027","volume":"138","author":"MD Sullivan","year":"2008","unstructured":"Sullivan MD, Edlund MJ, Fan MY, DeVries A, Braden JB, Martin BC (2008) Trends in use of opioids for non-cancer pain conditions 2000\u20132005 in commercial and Medicaid insurance plans: the TROUP study. Pain 138(2):440\u2013449. https:\/\/doi.org\/10.1016\/j.pain.2008.04.027","journal-title":"Pain"},{"issue":"4","key":"4091_CR2","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1097\/01.j.pain.0000460357.01998.f1","volume":"156","author":"KE Vowles","year":"2015","unstructured":"Vowles KE, McEntee ML, Julnes PS, Frohe T, Ney JP, van der Goes DN (2015) Rates of opioid misuse, abuse, and addiction in chronic pain: a systematic review and data synthesis. Pain 156(4):569\u2013576. https:\/\/doi.org\/10.1097\/01.j.pain.0000460357.01998.f1","journal-title":"Pain"},{"issue":"4","key":"4091_CR3","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1002\/ejp.1337","volume":"23","author":"C Bosetti","year":"2019","unstructured":"Bosetti C, Santucci C, Radrezza S, Erthal J, Berterame S, Corli O (2019) Trends in the consumption of opioids for the treatment of severe pain in Europe, 1990\u20132016. Eur J Pain 23(4):697\u2013707. https:\/\/doi.org\/10.1002\/ejp.1337","journal-title":"Eur J Pain"},{"issue":"3","key":"4091_CR4","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1038\/nrgastro.2017.141","volume":"15","author":"E Szigethy","year":"2018","unstructured":"Szigethy E, Knisely M, Drossman D (2018) Opioid misuse in gastroenterology and non-opioid management of abdominal pain. Nat Rev Gastroenterol Hepatol 15(3):168\u2013180. https:\/\/doi.org\/10.1038\/nrgastro.2017.141","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"1","key":"4091_CR5","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1177\/2050640618818305","volume":"7","author":"AD Farmer","year":"2019","unstructured":"Farmer AD, Drewes AM, Chiarioni G, De Giorgio R, O\u2019Brien T, Morlion B, Tack J (2019) Pathophysiology and management of opioid-induced constipation: European expert consensus statement. United Eur Gastroenterol J 7(1):7\u201320","journal-title":"United Eur Gastroenterol J"},{"issue":"5","key":"4091_CR6","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1177\/02692163251325711","volume":"39","author":"A Davies","year":"2025","unstructured":"Davies A, Fagan N, Power J, Taylor A (2025) \u201cConstipation\u201d: one word, many meanings amongst persons with cancer: an observational study. Palliat Med 39(5):553\u2013562. https:\/\/doi.org\/10.1177\/02692163251325711","journal-title":"Palliat Med"},{"issue":"1","key":"4091_CR7","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.jpainsymman.2012.01.009","volume":"45","author":"W Rhondali","year":"2013","unstructured":"Rhondali W, Nguyen L, Palmer L, Kang DH, Hui D, Bruera E (2013) Self-reported constipation in patients with advanced cancer: a preliminary report. J Pain Symptom Manage 45(1):23\u201332. https:\/\/doi.org\/10.1016\/j.jpainsymman.2012.01.009","journal-title":"J Pain Symptom Manage"},{"issue":"3","key":"4091_CR8","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.hoc.2018.01.003","volume":"32","author":"J Arthur","year":"2018","unstructured":"Arthur J, Hui D (2018) Safe opioid use: management of opioid-related adverse effects and aberrant behaviors. Hematol Oncol Clin North Am 32(3):387\u2013403. https:\/\/doi.org\/10.1016\/j.hoc.2018.01.003","journal-title":"Hematol Oncol Clin North Am"},{"issue":"1","key":"4091_CR9","doi-asserted-by":"publisher","first-page":"31ARTN31","DOI":"10.1186\/s12904-019-0416-7","volume":"18","author":"ECW Neefjes","year":"2019","unstructured":"Neefjes ECW, van der Wijngaart H, van der Vorst MJDL et al (2019) Optimal treatment of opioid induced constipation in daily clinical practice\u2014an observational study. BMC Palliat Care 18(1):31ARTN31. https:\/\/doi.org\/10.1186\/s12904-019-0416-7","journal-title":"BMC Palliat Care"},{"issue":"9","key":"4091_CR10","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1097\/AJP.0000000000000852","volume":"36","author":"CE Argoff","year":"2020","unstructured":"Argoff CE (2020) Opioid-induced constipation: a review of health-related quality of life, patient burden, practical clinical considerations, and the impact of peripherally acting mu-opioid receptor antagonists. Clin J Pain 36(9):716\u2013722. https:\/\/doi.org\/10.1097\/AJP.0000000000000852","journal-title":"Clin J Pain"},{"issue":"4","key":"4091_CR11","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1097\/ACO.0b013e32834873e5","volume":"24","author":"B Rachinger-Adam","year":"2011","unstructured":"Rachinger-Adam B, Conzen P, Azad SC (2011) Pharmacology of peripheral opioid receptors. Curr Opin Anaesthesiol 24(4):408\u2013413. https:\/\/doi.org\/10.1097\/ACO.0b013e32834873e5","journal-title":"Curr Opin Anaesthesiol"},{"issue":"10","key":"4091_CR12","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1111\/nmo.12417","volume":"26","author":"M Camilleri","year":"2014","unstructured":"Camilleri M, Drossman DA, Becker G, Webster LR, Davies AN, Mawe GM (2014) Emerging treatments in neurogastroenterology: a multidisciplinary working group consensus statement on opioid-induced constipation. Neurogastroenterol Motil 26(10):1386\u20131395. https:\/\/doi.org\/10.1111\/nmo.12417","journal-title":"Neurogastroenterol Motil"},{"issue":"2","key":"4091_CR13","doi-asserted-by":"publisher","first-page":"125","DOI":"10.5114\/wo.2012.28792","volume":"16","author":"W Leppert","year":"2012","unstructured":"Leppert W (2012) The impact of opioid analgesics on the gastrointestinal tract function and the current management possibilities. Contemp Oncol (Pozn) 16(2):125\u2013131. https:\/\/doi.org\/10.5114\/wo.2012.28792","journal-title":"Contemp Oncol (Pozn)"},{"issue":"2 Suppl","key":"4091_CR14","doi-asserted-by":"publisher","first-page":"S105","DOI":"10.36076\/ppj.2008\/11\/S105","volume":"11","author":"R Benyamin","year":"2008","unstructured":"Benyamin R, Trescot AM, Datta S, Buenaventura R, Adlaka R, Sehgal N, Glaser SE, Vallejo R (2008) Opioid complications and side effects. Pain Phys 11(2 Suppl):S105-120","journal-title":"Pain Phys"},{"issue":"2","key":"4091_CR15","doi-asserted-by":"publisher","first-page":"163","DOI":"10.5055\/jom.0918","volume":"21","author":"T Hammack","year":"2025","unstructured":"Hammack T, Hamilton CJ, Martinson A (2025) Examining the effect of a whole health primary care pain education and opioid monitoring program (PC-POP) at preventing opioid-induced constipation. J Opioid Manag 21(2):163\u2013169. https:\/\/doi.org\/10.5055\/jom.0918","journal-title":"J Opioid Manag"},{"issue":"1","key":"4091_CR16","doi-asserted-by":"publisher","first-page":"17397","DOI":"10.1038\/s41598-025-01770-0","volume":"15","author":"A Hashimoto","year":"2025","unstructured":"Hashimoto A, Morioka Y, Wada S, Koretaka Y, Sonohata M (2025) Incidence of opioid-induced constipation in non-cancer patients using weak opioids for chronic pain in Japan: a cohort study. Sci Rep 15(1):17397. https:\/\/doi.org\/10.1038\/s41598-025-01770-0","journal-title":"Sci Rep"},{"issue":"6","key":"4091_CR17","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1097\/MCG.0000000000002185","volume":"59","author":"N Mehta","year":"2025","unstructured":"Mehta N, Laitman AP, Brookfield RB, Harris LA (2025) Treatment of opioid-induced constipation: inducing laxation and understanding the risk of gastrointestinal perforation. J Clin Gastroenterol 59(6):491\u2013496. https:\/\/doi.org\/10.1097\/MCG.0000000000002185","journal-title":"J Clin Gastroenterol"},{"issue":"3","key":"4091_CR18","doi-asserted-by":"publisher","first-page":"236","DOI":"10.18553\/jmcp.2016.22.3.236","volume":"22","author":"RJ LoCasale","year":"2016","unstructured":"LoCasale RJ, Datto C, Wilson H, Yeomans K, Coyne KS (2016) The burden of opioid-induced constipation: discordance between patient and health care provider reports. J Manag Care Spec Pharm 22(3):236\u2013245. https:\/\/doi.org\/10.18553\/jmcp.2016.22.3.236","journal-title":"J Manag Care Spec Pharm"},{"issue":"8","key":"4091_CR19","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.1177\/2050640618786145","volume":"6","author":"V Andresen","year":"2018","unstructured":"Andresen V, Banerji V, Hall G, Lass A, Emmanuel AV (2018) The patient burden of opioid-induced constipation: new insights from a large, multinational survey in five European countries. United Eur Gastroenterol J 6(8):1254\u20131266. https:\/\/doi.org\/10.1177\/2050640618786145","journal-title":"United Eur Gastroenterol J"},{"key":"4091_CR20","doi-asserted-by":"publisher","first-page":"2255","DOI":"10.2147\/JPR.S318564","volume":"14","author":"F Coluzzi","year":"2021","unstructured":"Coluzzi F, Alvaro D, Caraceni AT, Gianni W, Marinangeli F, Massazza G, Pinto C, Varrassi G, Lugoboni F (2021) Common clinical practice for opioid-induced constipation: a physician survey. J Pain Res 14:2255\u20132264. https:\/\/doi.org\/10.2147\/JPR.S318564","journal-title":"J Pain Res"},{"issue":"2","key":"4091_CR21","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1007\/s40122-022-00354-4","volume":"11","author":"D Alvaro","year":"2022","unstructured":"Alvaro D, Coluzzi F, Gianni W, Lugoboni F, Marinangeli F, Massazza G, Pinto C, Varrassi G (2022) Opioid-induced constipation in real-world practice: a physician survey, 1 year later. Pain Ther 11(2):477\u2013491. https:\/\/doi.org\/10.1007\/s40122-022-00354-4","journal-title":"Pain Ther"},{"issue":"1","key":"4091_CR22","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1053\/j.gastro.2018.07.016","volume":"156","author":"SD Crockett","year":"2019","unstructured":"Crockett SD, Greer KB, Heidelbaugh JJ, Falck-Ytter Y, Hanson BJ, Sultan S, American Gastroenterological Association Institute Clinical Guidelines C (2019) American gastroenterological association institute guideline on the medical management of opioid-induced constipation. Gastroenterology 156(1):218\u2013226. https:\/\/doi.org\/10.1053\/j.gastro.2018.07.016","journal-title":"Gastroenterology"},{"key":"4091_CR23","doi-asserted-by":"publisher","first-page":"iv111","DOI":"10.1093\/annonc\/mdy148","volume":"29","author":"PJ Larkin","year":"2018","unstructured":"Larkin PJ, Cherny NI, La Carpia D, Guglielmo M, Ostgathe C (2018) Diagnosis, assessment and management of constipation in advanced cancer: ESMO Clinical Practice Guidelines. Ann Oncol 29:iv111\u2013iv125. https:\/\/doi.org\/10.1093\/annonc\/mdy148","journal-title":"Ann Oncol"},{"issue":"2","key":"4091_CR24","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13762","volume":"32","author":"J Serra","year":"2020","unstructured":"Serra J, Pohl D, Azpiroz F et al (2020) European society of neurogastroenterology and motility guidelines on functional constipation in adults. Neurogastroenterol Motil 32(2):e13762. https:\/\/doi.org\/10.1111\/nmo.13762","journal-title":"Neurogastroenterol Motil"},{"issue":"5","key":"4091_CR25","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1002\/ejp.1744","volume":"25","author":"N Krcevski Skvarc","year":"2021","unstructured":"Krcevski Skvarc N, Morlion B, Vowles KE et al (2021) European clinical practice recommendations on opioids for chronic noncancer pain - Part 2: Special situations. Eur J Pain 25(5):969\u2013985. https:\/\/doi.org\/10.1002\/ejp.1744","journal-title":"Eur J Pain"},{"key":"4091_CR26","unstructured":"Enhancing healthcare outcomes in opioid-induced constipation (ECHO OIC): developing a simplified pathway for primary care [https:\/\/efic-congress.org\/wp-content\/uploads\/2022\/04\/ABSTRACT-BOOK-2022.pdf]"},{"issue":"7","key":"4091_CR27","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1007\/s11864-022-00976-y","volume":"23","author":"T Dzierzanowski","year":"2022","unstructured":"Dzierzanowski T, Mercadante S (2022) Constipation in cancer patients - an update of clinical evidence. Curr Treat Options Oncol 23(7):936\u2013950. https:\/\/doi.org\/10.1007\/s11864-022-00976-y","journal-title":"Curr Treat Options Oncol"},{"key":"4091_CR28","doi-asserted-by":"publisher","DOI":"10.14309\/ctg.0000000000000876","author":"K Liu","year":"2025","unstructured":"Liu K, Chen A, Rajaram P, Buning G, Lee AA, Singh P (2025) PAMORAs in opioid-induced constipation: Are we following the guidelines? Clin Transl Gastroenterol. https:\/\/doi.org\/10.14309\/ctg.0000000000000876","journal-title":"Clin Transl Gastroenterol"},{"key":"4091_CR29","unstructured":"Enhancing healthcare outcomes in opioid-induced constipation (ECHO OIC) - an expert consensus group\u2019s recommendation on improving opioid patients\u2019 outcomes [https:\/\/efic-congress.org\/wp-content\/uploads\/2022\/04\/ABSTRACT-BOOK-2022.pdf]"},{"key":"4091_CR30","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13226689","author":"G Varrassi","year":"2024","unstructured":"Varrassi G, Casale G, De Marinis MG et al (2024) Improving diagnosis and management of opioid-induced constipation (OIC) in clinical practice: an Italian expert opinion. J Clin Med. https:\/\/doi.org\/10.3390\/jcm13226689","journal-title":"J Clin Med"},{"key":"4091_CR31","doi-asserted-by":"publisher","first-page":"269","DOI":"10.2147\/CEOR.S61602","volume":"6","author":"KS Coyne","year":"2014","unstructured":"Coyne KS, LoCasale RJ, Datto CJ, Sexton CC, Yeomans K, Tack J (2014) Opioid-induced constipation in patients with chronic noncancer pain in the USA, Canada, Germany, and the UK: descriptive analysis of baseline patient-reported outcomes and retrospective chart review. Clinicoecon Outcomes Res 6:269\u2013281. https:\/\/doi.org\/10.2147\/CEOR.S61602","journal-title":"Clinicoecon Outcomes Res"},{"issue":"7","key":"4091_CR32","doi-asserted-by":"publisher","first-page":"3589","DOI":"10.1007\/s12325-021-01766-y","volume":"38","author":"R De Giorgio","year":"2021","unstructured":"De Giorgio R, Zucco FM, Chiarioni G et al (2021) Management of opioid-induced constipation and bowel dysfunction: expert opinion of an Italian multidisciplinary panel. Adv Ther 38(7):3589\u20133621. https:\/\/doi.org\/10.1007\/s12325-021-01766-y","journal-title":"Adv Ther"},{"issue":"8","key":"4091_CR33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072608","volume":"8","author":"P Iovino","year":"2013","unstructured":"Iovino P, Chiarioni G, Bilancio G, Cirillo M, Mekjavic IB, Pisot R, Ciacci C (2013) New onset of constipation during long-term physical inactivity: a proof-of-concept study on the immobility-induced bowel changes. PLoS ONE 8(8):e72608. https:\/\/doi.org\/10.1371\/journal.pone.0072608","journal-title":"PLoS ONE"},{"issue":"1","key":"4091_CR34","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1111\/j.1526-4637.2008.00495.x","volume":"10","author":"TJ Bell","year":"2009","unstructured":"Bell TJ, Panchal SJ, Miaskowski C, Bolge SC, Milanova T, Williamson R (2009) The prevalence, severity, and impact of opioid-induced bowel dysfunction: results of a US and European patient survey (PROBE 1). Pain Med 10(1):35\u201342. https:\/\/doi.org\/10.1111\/j.1526-4637.2008.00495.x","journal-title":"Pain Med"},{"key":"4091_CR35","doi-asserted-by":"publisher","first-page":"CD006605","DOI":"10.1002\/14651858.CD006605.pub2","volume":"1","author":"M Noble","year":"2010","unstructured":"Noble M, Treadwell JR, Tregear SJ, Coates VH, Wiffen PJ, Akafomo C (2010) Schoelles KM (2010) Long-term opioid management for chronic noncancer pain. Cochrane Database Syst Rev 1:CD006605. https:\/\/doi.org\/10.1002\/14651858.CD006605.pub2","journal-title":"Cochrane Database Syst Rev"},{"key":"4091_CR36","unstructured":"Bristol Stool Chart. [https:\/\/www.continence.org.au\/bristol-stool-chart]"},{"issue":"8","key":"4091_CR37","first-page":"960","volume":"15","author":"R De Giorgio","year":"2011","unstructured":"De Giorgio R, Cestari R, Corinaldesi R, Stanghellini V, Barbara G, Felicani C, Di Nardo G, Cucchiara S (2011) Use of macrogol 4000 in chronic constipation. Eur Rev Med Pharmacol Sci 15(8):960\u2013966","journal-title":"Eur Rev Med Pharmacol Sci"},{"issue":"10","key":"4091_CR38","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1002\/j.1552-4604.1997.tb04264.x","volume":"37","author":"MD Freedman","year":"1997","unstructured":"Freedman MD, Schwartz HJ, Roby R, Fleisher S (1997) Tolerance and efficacy of polyethylene glycol 3350\/electrolyte solution versus lactulose in relieving opiate induced constipation: a double-blinded placebo-controlled trial. J Clin Pharmacol 37(10):904\u2013907. https:\/\/doi.org\/10.1002\/j.1552-4604.1997.tb04264.x","journal-title":"J Clin Pharmacol"},{"key":"4091_CR39","unstructured":"Gazzetta Ufficiale Italiana [https:\/\/www.aifa.gov.it\/documents\/20142\/1171956\/Nota-90_GU-111-del-30.04.2020).pdf]"},{"issue":"10","key":"4091_CR40","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1007\/s00520-024-08898-1","volume":"32","author":"A Davies","year":"2024","unstructured":"Davies A, Fagan N, Gonzalez-Barboteo J et al (2024) Inadequate management of opioid-induced constipation in European cancer pain patients: results of a real-world, multicentre, observational study (\u201cE-StOIC\u201d). Support Care Cancer 32(10):701. https:\/\/doi.org\/10.1007\/s00520-024-08898-1","journal-title":"Support Care Cancer"},{"issue":"10","key":"4091_CR41","doi-asserted-by":"publisher","first-page":"1932","DOI":"10.1093\/pm\/pnw240","volume":"18","author":"A Emmanuel","year":"2017","unstructured":"Emmanuel A, Johnson M, McSkimming P, Dickerson S (2017) Laxatives do not improve symptoms of opioid-induced constipation: results of a patient survey. Pain Med 18(10):1932\u20131940. https:\/\/doi.org\/10.1093\/pm\/pnw240","journal-title":"Pain Med"},{"key":"4091_CR42","unstructured":"Gupta OSRGM (2023) Opioid-induced constipation. StatPearls [Internet] Treasure Island (FL): StatPearls Publishing; 2024 Jan"},{"issue":"6","key":"4091_CR43","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1053\/j.gastro.2016.02.031","volume":"150","author":"F Mearin","year":"2016","unstructured":"Mearin F, Lacy BE, Chang L, Chey WD, Lembo AJ, Simren M, Spiller R (2016) Bowel disorders. Gastroenterology 150(6):1393-1407.e1395. https:\/\/doi.org\/10.1053\/j.gastro.2016.02.031","journal-title":"Gastroenterology"},{"issue":"1","key":"4091_CR44","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1080\/17474124.2020.1708718","volume":"14","author":"I Aziz","year":"2020","unstructured":"Aziz I, Whitehead WE, Palsson OS, Tornblom H, Simren M (2020) An approach to the diagnosis and management of Rome IV functional disorders of chronic constipation. Expert Rev Gastroenterol Hepatol 14(1):39\u201346. https:\/\/doi.org\/10.1080\/17474124.2020.1708718","journal-title":"Expert Rev Gastroenterol Hepatol"},{"key":"4091_CR45","unstructured":"Foundation TR Rome IV criteria: C6 \u2013 Opioid-induced constipation, diagnostic criteria"},{"issue":"4","key":"4091_CR46","doi-asserted-by":"publisher","first-page":"371","DOI":"10.3111\/13696990903430481","volume":"12","author":"AM Rentz","year":"2009","unstructured":"Rentz AM, Yu R, Muller-Lissner S, Leyendecker P (2009) Validation of the bowel function index to detect clinically meaningful changes in opioid-induced constipation. J Med Econ 12(4):371\u2013383. https:\/\/doi.org\/10.3111\/13696990903430481","journal-title":"J Med Econ"},{"issue":"e2","key":"4091_CR47","doi-asserted-by":"publisher","first-page":"e446","DOI":"10.1136\/bmjspcare-2020-002754","volume":"13","author":"AN Davies","year":"2023","unstructured":"Davies AN, Leach C, Butler C, Patel SD, Shorthose K, Batsari K (2023) Opioid-induced constipation: a stepwise treatment algorithm feasibility study. BMJ Support Palliat Care 13(e2):e446\u2013e453. https:\/\/doi.org\/10.1136\/bmjspcare-2020-002754","journal-title":"BMJ Support Palliat Care"},{"issue":"1","key":"4091_CR48","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1177\/147323001103900106","volume":"39","author":"MA Ueberall","year":"2011","unstructured":"Ueberall MA, Muller-Lissner S, Buschmann-Kramm C, Bosse B (2011) The bowel function index for evaluating constipation in pain patients: definition of a reference range for a non-constipated population of pain patients. J Int Med Res 39(1):41\u201350. https:\/\/doi.org\/10.1177\/147323001103900106","journal-title":"J Int Med Res"},{"key":"4091_CR49","doi-asserted-by":"publisher","first-page":"447","DOI":"10.2147\/JPR.S220859","volume":"13","author":"J Gudin","year":"2020","unstructured":"Gudin J, Fudin J (2020) Peripheral opioid receptor antagonists for opioid-induced constipation: a primer on pharmacokinetic variabilities with a focus on drug interactions. J Pain Res 13:447\u2013456. https:\/\/doi.org\/10.2147\/JPR.S220859","journal-title":"J Pain Res"},{"key":"4091_CR50","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.2147\/DDDT.S221278","volume":"14","author":"JV Pergolizzi Jr","year":"2020","unstructured":"Pergolizzi JV Jr, Christo PJ, LeQuang JA, Magnusson P (2020) The use of peripheral mu-opioid receptor antagonists (PAMORA) in the management of opioid-induced constipation: an update on their efficacy and safety. Drug Des Devel Ther 14:1009\u20131025. https:\/\/doi.org\/10.2147\/DDDT.S221278","journal-title":"Drug Des Devel Ther"},{"issue":"7","key":"4091_CR51","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.16201","volume":"13","author":"M Rekatsina","year":"2021","unstructured":"Rekatsina M, Paladini A, Drewes AM, Ayob F, Viswanath O, Urits I, Corli O, Pergolizzi J Jr, Varrassi G (2021) Efficacy and safety of peripherally acting mu-opioid receptor antagonist (PAMORAs) for the management of patients with opioid-induced constipation: a systematic review. Cureus 13(7):e16201. https:\/\/doi.org\/10.7759\/cureus.16201","journal-title":"Cureus"},{"issue":"3","key":"4091_CR52","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1124\/jpet.119.264515","volume":"373","author":"T Kanemasa","year":"2020","unstructured":"Kanemasa T, Koike K, Takase K, Arai T, Nakamura A, Morioka Y, Hasegawa M (2020) Pharmacological profile of naldemedine, a peripherally acting mu-opioid receptor antagonist: comparison with naloxone and naloxegol. J Pharmacol Exp Ther 373(3):438\u2013444. https:\/\/doi.org\/10.1124\/jpet.119.264515","journal-title":"J Pharmacol Exp Ther"},{"issue":"8","key":"4091_CR53","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1016\/S2468-1253(17)30105-X","volume":"2","author":"M Hale","year":"2017","unstructured":"Hale M, Wild J, Reddy J, Yamada T, Arjona Ferreira JC (2017) Naldemedine versus placebo for opioid-induced constipation (COMPOSE-1 and COMPOSE-2): two multicentre, phase 3, double-blind, randomised, parallel-group trials. Lancet Gastroenterol Hepatol 2(8):555\u2013564. https:\/\/doi.org\/10.1016\/S2468-1253(17)30105-X","journal-title":"Lancet Gastroenterol Hepatol"},{"issue":"5","key":"4091_CR54","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1097\/j.pain.0000000000001174","volume":"159","author":"LR Webster","year":"2018","unstructured":"Webster LR, Nalamachu S, Morlion B, Reddy J, Baba Y, Yamada T, Arjona Ferreira JC (2018) Long-term use of naldemedine in the treatment of opioid-induced constipation in patients with chronic noncancer pain: a randomized, double-blind, placebo-controlled phase 3 study. Pain 159(5):987\u2013994. https:\/\/doi.org\/10.1097\/j.pain.0000000000001174","journal-title":"Pain"},{"issue":"5","key":"4091_CR55","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1097\/MEG.0000000000002746","volume":"36","author":"H Imai","year":"2024","unstructured":"Imai H, Fujita Y, Hiruta E et al (2024) Efficacy and safety of naldemedine for opioid-induced constipation in older patients with cancer: a retrospective study. Eur J Gastroenterol Hepatol 36(5):571\u2013577. https:\/\/doi.org\/10.1097\/MEG.0000000000002746","journal-title":"Eur J Gastroenterol Hepatol"},{"issue":"10","key":"4091_CR56","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1089\/jpm.2024.0018","volume":"27","author":"R Miura","year":"2024","unstructured":"Miura R, Utano T, Miura Y et al (2024) Efficacy and safety of naldemedine for opioid-induced constipation in children. J Palliat Med 27(10):1354\u20131358. https:\/\/doi.org\/10.1089\/jpm.2024.0018","journal-title":"J Palliat Med"},{"issue":"7","key":"4091_CR57","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1089\/jpm.2014.0362","volume":"18","author":"J Bull","year":"2015","unstructured":"Bull J, Wellman CV, Israel RJ, Barrett AC, Paterson C, Forbes WP (2015) Fixed-dose subcutaneous methylnaltrexone in patients with advanced illness and opioid-induced constipation: results of a randomized, placebo-controlled study and open-label extension. J Palliat Med 18(7):593\u2013600. https:\/\/doi.org\/10.1089\/jpm.2014.0362","journal-title":"J Palliat Med"},{"issue":"2","key":"4091_CR58","doi-asserted-by":"publisher","first-page":"73","DOI":"10.2217\/pmt-2019-0045","volume":"10","author":"BH Chamberlain","year":"2020","unstructured":"Chamberlain BH, Rhiner M, Slatkin NE, Stambler N, Israel RJ (2020) Subcutaneous methylnaltrexone for opioid-induced constipation in advanced-illness patients with or without active cancer. Pain Manag 10(2):73\u201384. https:\/\/doi.org\/10.2217\/pmt-2019-0045","journal-title":"Pain Manag"},{"issue":"1","key":"4091_CR59","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.jval.2010.11.003","volume":"14","author":"SS Iyer","year":"2011","unstructured":"Iyer SS, Randazzo BP, Tzanis EL, Schulman SL, Zhang H, Wang W, Manley AL (2011) Effect of subcutaneous methylnaltrexone on patient-reported constipation symptoms. Value Health 14(1):177\u2013183. https:\/\/doi.org\/10.1016\/j.jval.2010.11.003","journal-title":"Value Health"},{"issue":"7","key":"4091_CR60","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1016\/j.jcyt.2016.04.010","volume":"18","author":"D You","year":"2016","unstructured":"You D, Jang MJ, Kim BH et al (2016) Bone marrow-derived mesenchymal stromal cell therapy in a rat model of cavernous nerve injury: preclinical study for approval. Cytotherapy 18(7):870\u2013880. https:\/\/doi.org\/10.1016\/j.jcyt.2016.04.010","journal-title":"Cytotherapy"},{"issue":"5","key":"4091_CR61","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1016\/j.jpain.2010.11.008","volume":"12","author":"E Michna","year":"2011","unstructured":"Michna E, Blonsky ER, Schulman S, Tzanis E, Manley A, Zhang H, Iyer S, Randazzo B (2011) Subcutaneous methylnaltrexone for treatment of opioid-induced constipation in patients with chronic, nonmalignant pain: a randomized controlled study. J Pain 12(5):554\u2013562. https:\/\/doi.org\/10.1016\/j.jpain.2010.11.008","journal-title":"J Pain"},{"issue":"9","key":"4091_CR62","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1016\/j.pain.2013.04.024","volume":"154","author":"L Webster","year":"2013","unstructured":"Webster L, Dhar S, Eldon M, Masuoka L, Lappalainen J, Sostek M (2013) A phase 2, double-blind, randomized, placebo-controlled, dose-escalation study to evaluate the efficacy, safety, and tolerability of naloxegol in patients with opioid-induced constipation. Pain 154(9):1542\u20131550. https:\/\/doi.org\/10.1016\/j.pain.2013.04.024","journal-title":"Pain"},{"issue":"5","key":"4091_CR63","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1177\/2050640615604543","volume":"3","author":"J Tack","year":"2015","unstructured":"Tack J, Lappalainen J, Diva U, Tummala R, Sostek M (2015) Efficacy and safety of naloxegol in patients with opioid-induced constipation and laxative-inadequate response. United Eur Gastroenterol J 3(5):471\u2013480. https:\/\/doi.org\/10.1177\/2050640615604543","journal-title":"United Eur Gastroenterol J"},{"issue":"7","key":"4091_CR64","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1111\/apt.12899","volume":"40","author":"L Webster","year":"2014","unstructured":"Webster L, Chey WD, Tack J, Lappalainen J, Diva U, Sostek M (2014) Randomised clinical trial: the long-term safety and tolerability of naloxegol in patients with pain and opioid-induced constipation. Aliment Pharmacol Ther 40(7):771\u2013779. https:\/\/doi.org\/10.1111\/apt.12899","journal-title":"Aliment Pharmacol Ther"},{"issue":"1","key":"4091_CR65","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.clinthera.2016.11.012","volume":"39","author":"KS Coyne","year":"2017","unstructured":"Coyne KS, Poon JL, Thompson C, Hu Y, Datto CJ, Sostek M (2017) Translating clinical findings into the patient\u2019s perspective: post-hoc pooled analysis of bowel movement changes as a predictor of improvement in patients\u2019 opioid-induced constipation symptoms and outcomes. Clin Ther 39(1):75\u201388. https:\/\/doi.org\/10.1016\/j.clinthera.2016.11.012","journal-title":"Clin Ther"},{"key":"4091_CR66","unstructured":"Moventig (naloxegol oxalate) summary of product characteristics [https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/moventig-epar-product-information_en.pdf]"},{"key":"4091_CR67","unstructured":"Rizmoic (naldemedine) summary of product characteristics"},{"key":"4091_CR68","unstructured":"Relistor (methylnaltrexone bromide) summary of product characteristics [https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/relistor-epar-product-information_en.pdf]"},{"issue":"5","key":"4091_CR69","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.3390\/cancers14051128","volume":"14","author":"A Davies","year":"2022","unstructured":"Davies A, Cinieri S, Dupoiron D et al (2022) A prospective, real-world, multinational study of Naloxegol for patients with cancer pain diagnosed with opioid-induced constipation\u2014The NACASY study. Cancers 14(5):1128. https:\/\/doi.org\/10.3390\/cancers14051128","journal-title":"Cancers"},{"issue":"4","key":"4091_CR70","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1177\/104990910502200411","volume":"22","author":"S Mercadante","year":"2005","unstructured":"Mercadante S, Arcuri E (2005) Hyperalgesia and opioid switching. Am J Hosp Palliat Care 22(4):291\u2013294. https:\/\/doi.org\/10.1177\/104990910502200411","journal-title":"Am J Hosp Palliat Care"},{"issue":"Suppl 10","key":"4091_CR71","doi-asserted-by":"publisher","first-page":"x294","DOI":"10.1093\/annonc\/mds360","volume":"23","author":"CI Ripamonti","year":"2012","unstructured":"Ripamonti CI (2012) Pain management. Ann Oncol Off J Eur Soc Med Oncol 23(Suppl 10):x294-301. https:\/\/doi.org\/10.1093\/annonc\/mds360","journal-title":"Ann Oncol Off J Eur Soc Med Oncol"},{"issue":"6","key":"4091_CR72","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1017\/S1092852924002189","volume":"29","author":"RS McIntyre","year":"2024","unstructured":"McIntyre RS, Harris ME, Todtenkopf MS, Akerman S, Burgett J (2024) Opioid antagonists: clinical utility, pharmacology, safety, and tolerability. CNS Spectr 29(6):542\u2013548. https:\/\/doi.org\/10.1017\/S1092852924002189","journal-title":"CNS Spectr"},{"issue":"1","key":"4091_CR73","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1080\/15360288.2024.2427324","volume":"39","author":"B Wobbe","year":"2025","unstructured":"Wobbe B, Gerner M, Kohne CH (2025) Safety of naldemedine for opioid-induced constipation - a systematic review and meta-analysis. J Pain Palliat Care Pharmacother 39(1):96\u2013113. https:\/\/doi.org\/10.1080\/15360288.2024.2427324","journal-title":"J Pain Palliat Care Pharmacother"},{"issue":"12","key":"4091_CR74","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2024-086001","volume":"14","author":"Y Long","year":"2024","unstructured":"Long Y, Li L, Chen X, Tian L, He H, Li YL (2024) Traditional laxatives in preventing opioid-induced constipation in adult patients with cancer: a systematic review and meta-analysis protocol. BMJ Open 14(12):e086001. https:\/\/doi.org\/10.1136\/bmjopen-2024-086001","journal-title":"BMJ Open"},{"key":"4091_CR75","doi-asserted-by":"publisher","DOI":"10.6004\/jadpro.2024.15.8.18","author":"S Pandey","year":"2024","unstructured":"Pandey S, Goldberg JI, Haviland K (2024) Effects of a revision to the standard admission order set on laxative prescribing for opioid-induced constipation. J Adv Pract Oncol. https:\/\/doi.org\/10.6004\/jadpro.2024.15.8.18","journal-title":"J Adv Pract Oncol"},{"issue":"1","key":"4091_CR76","doi-asserted-by":"publisher","DOI":"10.1002\/jgh3.70070","volume":"9","author":"U Akram","year":"2025","unstructured":"Akram U, Rehman OU, Fatima E, Nadeem ZA, Usman O, Rasheed W, Ali R, Rehman KA, Nashwan AJ (2025) The efficacy of lubiprostone in patients of constipation: an updated systematic review and meta-analysis. JGH Open 9(1):e70070. https:\/\/doi.org\/10.1002\/jgh3.70070","journal-title":"JGH Open"},{"issue":"2","key":"4091_CR77","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/s00520-025-09154-w","volume":"33","author":"Y Okuda","year":"2025","unstructured":"Okuda Y, Kuriyama T, Tsukiyama Y, Shimokawa T, Wan K, Kawamata T (2025) Efficacy of prophylactic laxatives against opioid-induced constipation: retrospective propensity score matching analysis. Support Care Cancer 33(2):115. https:\/\/doi.org\/10.1007\/s00520-025-09154-w","journal-title":"Support Care Cancer"},{"issue":"2","key":"4091_CR78","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1021\/acsmedchemlett.4c00529","volume":"16","author":"Z Wang","year":"2025","unstructured":"Wang Z, Li ZZ, Han XM, Dong J, Yin MY, Song J, Zhuang T, Wang Y (2025) Discovery of novel pH-sensitive mu-opioid receptor agonists as potent analgesics with reduced side effects. ACS Med Chem Lett 16(2):285\u2013293. https:\/\/doi.org\/10.1021\/acsmedchemlett.4c00529","journal-title":"ACS Med Chem Lett"},{"issue":"1","key":"4091_CR79","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.78212","volume":"17","author":"M Sonohata","year":"2025","unstructured":"Sonohata M, Kitamura M, Hashimoto A, Morioka Y (2025) Prescription pattern of laxatives for opioid-induced constipation in Japanese patients with chronic non-cancer pain: a retrospective cohort study of a health insurance claims database. Cureus 17(1):e78212. https:\/\/doi.org\/10.7759\/cureus.78212","journal-title":"Cureus"},{"issue":"3","key":"4091_CR80","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1007\/s40122-025-00720-y","volume":"14","author":"A De Vincentis","year":"2025","unstructured":"De Vincentis A, Cai B, Moscarda M, Barnes PMF, Antonelli Incalzi R (2025) Naldemedine use and healthcare resource utilization in patients treated with opioid analgesics for chronic non-cancer pain: results of a real-world study in the USA. Pain Ther 14(3):957\u2013969. https:\/\/doi.org\/10.1007\/s40122-025-00720-y","journal-title":"Pain Ther"},{"key":"4091_CR81","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17050865","author":"JM Sabate","year":"2025","unstructured":"Sabate JM, Beato-Zambrano C, Cobo M, Lemaire A, Montesarchio V, Serna-Montros J, Namane R, Martin Baccarelli S, Rico-Villademoros F (2025) Naloxegol for the treatment of opioid-induced constipation in patients with cancer pain: a pooled analysis of real-world data. Cancers (Basel). https:\/\/doi.org\/10.3390\/cancers17050865","journal-title":"Cancers (Basel)"},{"key":"4091_CR82","doi-asserted-by":"publisher","first-page":"1550296","DOI":"10.3389\/fphar.2025.1550296","volume":"16","author":"C Li","year":"2025","unstructured":"Li C, Chu J, Jia X, Su H (2025) Transdermal fentanyl induced paralytic intestinal obstruction in advanced liver cancer: a case report. Front Pharmacol 16:1550296. https:\/\/doi.org\/10.3389\/fphar.2025.1550296","journal-title":"Front Pharmacol"},{"key":"4091_CR83","doi-asserted-by":"publisher","DOI":"10.3390\/pharmacy13020047","author":"T Matsumoto","year":"2025","unstructured":"Matsumoto T, Mura T, Wada T, Tsugo Y, Mukai N, Hamaoka T, Horita S, Semba Y, Watanabe S (2025) Timing of naldemedine initiation and occurrence of diarrhea in patients receiving strong opioid analgesics: a retrospective study. Pharmacy. https:\/\/doi.org\/10.3390\/pharmacy13020047","journal-title":"Pharmacy"},{"issue":"8","key":"4091_CR84","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.70553","volume":"29","author":"M Liu","year":"2025","unstructured":"Liu M, Sheng Y, He Y, Wu S, Jin C, Shen L (2025) Progresses in questing for the truth of opioid-related constipation in cancer patients. J Cell Mol Med 29(8):e70553. https:\/\/doi.org\/10.1111\/jcmm.70553","journal-title":"J Cell Mol Med"},{"key":"4091_CR85","doi-asserted-by":"publisher","DOI":"10.1097\/FBP.0000000000000831","author":"NM Beltran","year":"2025","unstructured":"Beltran NM, Garcia TI, Naime GM, Minervini V, Serafine KM (2025) The effects of high fat diet consumption on morphine-induced constipation. Behav Pharmacol. https:\/\/doi.org\/10.1097\/FBP.0000000000000831","journal-title":"Behav Pharmacol"},{"issue":"3","key":"4091_CR86","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.21873\/invivo.13965","volume":"39","author":"T Kanie","year":"2025","unstructured":"Kanie T, Mizuno T, Koseki T et al (2025) Factors for discontinuation of naldemedine therapy in a palliative ward. In Vivo 39(3):1647\u20131653. https:\/\/doi.org\/10.21873\/invivo.13965","journal-title":"In Vivo"},{"issue":"1","key":"4091_CR87","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1186\/s12916-025-04118-7","volume":"23","author":"BB Yimer","year":"2025","unstructured":"Yimer BB, Soomro M, McBeth J, Medina CRR, Lunt M, Dixon WG, Jani M (2025) Comparative risk of severe constipation in patients treated with opioids for non-cancer pain: a retrospective cohort study in Northwest England. BMC Med 23(1):288. https:\/\/doi.org\/10.1186\/s12916-025-04118-7","journal-title":"BMC Med"}],"container-title":["Internal and Emergency Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11739-025-04091-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11739-025-04091-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11739-025-04091-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T15:20:27Z","timestamp":1758986427000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11739-025-04091-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,28]]},"references-count":87,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["4091"],"URL":"https:\/\/doi.org\/10.1007\/s11739-025-04091-2","relation":{},"ISSN":["1828-0447","1970-9366"],"issn-type":[{"value":"1828-0447","type":"print"},{"value":"1970-9366","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,28]]},"assertion":[{"value":"1 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 August 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All the authors report having no relevant conflicts of interest for this article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Not applicable","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Human and animal rights statement and Informed consent"}}]}}