{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T02:27:36Z","timestamp":1785896856636,"version":"3.56.0"},"reference-count":93,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T00:00:00Z","timestamp":1699315200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Nocebo effects are unavoidable in randomized clinical trials. We aimed to assess the magnitude of nocebo effects and explore the influencing factors in chronic constipation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We searched the PubMed, Embase, and Cochrane Library databases up to July 2022.<\/jats:p><jats:p>Randomized, placebo\u2010controlled trials investigating interventions in chronic constipation were included. We conducted a random effects meta\u2010analysis of the proportion of adverse events (AEs) in placebo\u2010treated participants and evaluated the effect of trial characteristics on nocebo effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>We identified 20,204 studies from the databases, of which 61 were included in the final analysis. The pooled placebo AE rate was 30.41%, and AE\u2010related withdrawal rate was 1.53%. The most commonly reported AEs were headache (5.67%), diarrhea (4.45%), abdominal pain (3.98%), nasopharyngitis (3.39%), nausea (3.36%), and flatulence (2.95%). The placebo AE rate was lower in trials conducted in Asia compared to those in Europe, North America, and international trials. It was also lower in trials diagnosed by Rome III compared to clinician's opinion and Rome II. Additionally, the placebo AE rate was lower in single\u2010center trials compared to multicenter trials, lower in 5\u20138\u2009weeks therapy compared to 9\u201312\u2009weeks therapy, lower in participants with FC compared to those with IBS\u2010C and CC, lower in trials with 2 arms compared to 3 arms, and higher in trials with prokinetic drugs compared to secretagogues and laxatives.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>The placebo AE rate was 30.41% in patients with chronic constipation. Based on our findings, we recommend that researchers take the nocebo effects into consideration when designing and conducting clinical trials and adopt specific measures to mitigate the negative influence of nocebo effects.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.14708","type":"journal-article","created":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T06:28:36Z","timestamp":1699424916000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Nocebo effects and influencing factors in the randomized clinical trials of chronic constipation: A systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"36","author":[{"given":"Jingze","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Union Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlu","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Union Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Union Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4018-2502","authenticated-orcid":false,"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology Union Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9697-8510","authenticated-orcid":false,"given":"Tao","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Union Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Union Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,7]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2011.164"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2016.53"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.2165\/00019053-200523050-00006"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-011-1639-5"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2007.03376.x"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(19)30246-8"},{"issue":"4","key":"e_1_2_13_8_1","first-page":"S63","article-title":"Managing costs and care for chronic idiopathic constipation","volume":"25","author":"McCormick D","year":"2019","journal-title":"Am J Manag Care"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2006.03238.x"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.14309\/ctg.0000000000000255"},{"key":"e_1_2_13_11_1","first-page":"203","article-title":"The nocebo reaction","volume":"95","author":"Kennedy WP","year":"1961","journal-title":"Med World"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2019.04.015"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euf.2020.10.010"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.115"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/15265161.2011.652798"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1000097"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjz087"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d5928"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.1018713"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1907805"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.14279"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.2072"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8820443"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-019-02104-x"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004004"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2020.11.004"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2017.03.024"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfma.2019.02.017"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/ner.12946"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM196809262791304"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-4356(96)00177-1"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2019.00242"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/PSY.0b013e3182294a50"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.3920\/BM2018.0163"},{"issue":"9","key":"e_1_2_13_35_1","first-page":"44","article-title":"Chinese herbal medicine for functional constipation: a randomized controlled trial","volume":"19","author":"Bian ZX","year":"2013","journal-title":"Hong Kong Med J"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41395-018-0026-7"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0800670"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2006.03230.x"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000001334"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2013.197"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2010.305"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu11051130"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2011.162"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2012.254"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2017.41"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000000516"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000001056"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1159\/000070202"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1097\/DCR.0000000000000098"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2010.10.011"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.15073"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2013.12.005"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2019.02.018"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.14086"},{"key":"e_1_2_13_55_1","article-title":"Synbiotic preparation in men suffering from functional constipation: a randomized controlled trial","volume":"141","author":"Fateh R","year":"2011","journal-title":"Swiss Med Wkly"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2011.01668.x"},{"key":"e_1_2_13_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2014.08.026"},{"key":"e_1_2_13_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13275"},{"key":"e_1_2_13_59_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13444"},{"key":"e_1_2_13_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13442"},{"key":"e_1_2_13_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13487"},{"key":"e_1_2_13_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2020.03.019"},{"key":"e_1_2_13_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2010.04456.x"},{"key":"e_1_2_13_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.15907"},{"key":"e_1_2_13_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2013.03.004"},{"key":"e_1_2_13_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1542-3565(04)00356-8"},{"key":"e_1_2_13_67_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2007.01524.x"},{"key":"e_1_2_13_68_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2008.03629.x"},{"key":"e_1_2_13_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2005.40749.x"},{"key":"e_1_2_13_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2011.03.026"},{"key":"e_1_2_13_71_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-018-01545-7"},{"key":"e_1_2_13_72_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2012.01983.x"},{"key":"e_1_2_13_73_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0134349"},{"key":"e_1_2_13_74_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.12.050"},{"key":"e_1_2_13_75_1","first-page":"761","article-title":"Acupuncture for chronic severe functional constipation: a randomized trial","volume":"165","author":"Liu Z","year":"2016","journal-title":"Ann Intern Med"},{"key":"e_1_2_13_76_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756283X17734697"},{"key":"e_1_2_13_77_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2016.611"},{"issue":"991","key":"e_1_2_13_78_1","article-title":"A double\u2010blind, placebo\u2010controlled study of prucalopride in elderly patients with chronic constipation","volume":"22","author":"M\u00fcller\u2010Lissner S","year":"2010","journal-title":"Neurogastroenterol"},{"key":"e_1_2_13_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(18)30123-7"},{"key":"e_1_2_13_80_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-019-01581-x"},{"key":"e_1_2_13_81_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.2002.01372.x"},{"key":"e_1_2_13_82_1","doi-asserted-by":"publisher","DOI":"10.1080\/00365520310006748"},{"key":"e_1_2_13_83_1","doi-asserted-by":"publisher","DOI":"10.5009\/gnl210478"},{"key":"e_1_2_13_84_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11655-020-3267-4"},{"key":"e_1_2_13_85_1","doi-asserted-by":"publisher","DOI":"10.1111\/1751-2980.13081"},{"key":"e_1_2_13_86_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2008.03884.x"},{"key":"e_1_2_13_87_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2012.255"},{"key":"e_1_2_13_88_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2017.230"},{"key":"e_1_2_13_89_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2008.162404"},{"key":"e_1_2_13_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2014.04.005"},{"key":"e_1_2_13_91_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12602-021-09855-8"},{"key":"e_1_2_13_92_1","doi-asserted-by":"publisher","DOI":"10.1111\/1751-2980.13058"},{"key":"e_1_2_13_93_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2015.115"},{"key":"e_1_2_13_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2022.101407"}],"container-title":["Neurogastroenterology &amp; Motility"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nmo.14708","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T18:15:45Z","timestamp":1716833745000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nmo.14708"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,7]]},"references-count":93,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1111\/nmo.14708"],"URL":"https:\/\/doi.org\/10.1111\/nmo.14708","archive":["Portico"],"relation":{},"ISSN":["1350-1925","1365-2982"],"issn-type":[{"value":"1350-1925","type":"print"},{"value":"1365-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,7]]},"assertion":[{"value":"2022-10-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14708"}}