{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:50:03Z","timestamp":1790884203705,"version":"4.1.0"},"reference-count":85,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T00:00:00Z","timestamp":1663804800000},"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","award":["81960664"],"award-info":[{"award-number":["81960664"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Histamine H2 receptor antagonists (H2RAs) were widely used to inhibit gastric acid secretion, but its association with adverse events remains controversial and unclear. We conducted an umbrella review of meta\u2010analyses to systematically assess the quality and credibility of the correlations between H2RA use with the risk of adverse outcomes through searching 4 major databases from inception to April 30, 2022. Forty\u2010six individual meta\u2010analyses were identified, including 29 meta\u2010analyses of observation studies with 32 unique outcomes and 19 meta\u2010analyses of randomized controlled trials with 3 unique outcomes for comparing the H2RA versus non\u2010H2RA group. A Measurement Tool to Assess Systematic Reviews 2 rating for the included meta\u2010analyses showed that 4 of 46 meta\u2010analyses were assigned as high scores, 3 were assigned as \u201cmoderate,\u201d and 25 were assigned as low scores. Grading of Recommendations Assessment, Development and Evaluation assessment for combined results demonstrated that 6 outcomes were rated as \u201cmoderate,\u201d 9 outcomes were rated as \u201clow,\u201d and 17 outcomes were rated as \u201cvery low.\u201d We confirmed significant associations of H2RA use with pneumonia, peritonitis, necrotizing enterocolitis,\n                    <jats:italic>Clostridium difficile<\/jats:italic>\n                    infection, liver cancer, gastric cancer, and hip fracture diseases. No associations for colorectal cancer, melanoma, kidney cancer, lung cancer, or common reproductive system cancer or renal, neurological, and cardiovascular system diseases were observed. We found a variety of evidence for the associations between H2RAs and adverse outcomes, which would give clinicians more positive guidance on prescription of H2RAs in clinical practice.\n                  <\/jats:p>","DOI":"10.1002\/jcph.2147","type":"journal-article","created":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T01:02:20Z","timestamp":1661821340000},"page":"7-20","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Effectiveness and Safety of Histamine H2 Receptor Antagonists: An Umbrella Review of Meta\u2010Analyses"],"prefix":"10.1002","volume":"63","author":[{"given":"Rui","family":"Meng","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy 920th Hospital of Joint Logistics Support Force of People's Liberation Army  Kunming China"},{"name":"Kunming Medical University  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010Rong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy 920th Hospital of Joint Logistics Support Force of People's Liberation Army  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man\u2010Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy 920th Hospital of Joint Logistics Support Force of People's Liberation Army  Kunming China"},{"name":"Kunming Medical University  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Ke","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Cardio\u2010Thoracic Surgery 920th Hospital of Joint Logistics Support Force of People's Liberation Army  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun\u2010Jun","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy 920th Hospital of Joint Logistics Support Force of People's Liberation Army  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Xin","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy 920th Hospital of Joint Logistics Support Force of People's Liberation Army  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy 920th Hospital of Joint Logistics Support Force of People's Liberation Army  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan\u2010Hua","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy 920th Hospital of Joint Logistics Support Force of People's Liberation Army  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1274-3130","authenticated-orcid":false,"given":"Gong\u2010Hao","family":"He","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy 920th Hospital of Joint Logistics Support Force of People's Liberation Army  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,22]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-200124010-00004"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/236385a0"},{"key":"e_1_2_10_4_1","volume-title":"StatPearls [Internet]","author":"Nugent CC","year":"2022"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.985"},{"issue":"8","key":"e_1_2_10_6_1","first-page":"710","article-title":"Clinical efficacy of proton pump inhibitor combined with ranitidine in the treatment of throat reflux","volume":"34","author":"Liu C","year":"2020","journal-title":"Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.5326\/JAAHA-MS-6634"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2015.156"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.4166\/kjg.2017.70.1.4"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/DER.0000000000000172"},{"issue":"8","key":"e_1_2_10_11_1","first-page":"CD007814","article-title":"Histamine type 2 receptor antagonists as adjuvant treatment for resected colorectal cancer","author":"Deva S","year":"2012","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.5009\/gnl16568"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-020-00688-1"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2020.109989"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0214135"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000018128"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-020-02927-8"},{"issue":"2","key":"e_1_2_10_18_1","first-page":"100","article-title":"Proton pump inhibitors and histamine\u20102 receptor antagonists on the risk of pancreatic cancer: a systematic review and meta\u2010analysis","volume":"113","author":"Laoveeravat P","year":"2020","journal-title":"QJM"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0000000000000448"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.12065"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2011.01.007"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1590\/s0004-2803.201700000-42"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2017-0889"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1000097"},{"issue":"12","key":"e_1_2_10_25_1","first-page":"1408","article-title":"Meta analysis of the risk of hospital\u2010acquired Clostridium difficile infection using different acid suppressants","volume":"30","author":"Luo","year":"2018","journal-title":"Chin J Microecol"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2007.01275.x"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2012.108"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1017\/ice.2014.39"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056498"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0033-1333671"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpt.12769"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-017-1937-1"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc9312"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e3181d69ccf"},{"issue":"5","key":"e_1_2_10_35_1","first-page":"632","article-title":"Proton pump inhibitors for the prevention of stress\u2010related mucosal disease in critically\u2010ill patients: a meta\u2010analysis","volume":"92","author":"Pongprasobchai S","year":"2009","journal-title":"J Med Assoc Thai"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e3182758734"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2011.474"},{"issue":"4","key":"e_1_2_10_38_1","first-page":"221","article-title":"Meta\u2010analysis of H2 receptor antagonists and proton pump inhibitors for the prevention of stress ulcer bleeding and pneumonia in intensive care unit patients","volume":"22","author":"Zhou JF","year":"2010","journal-title":"Zhongguo Wei Zhong Bing Ji Jiu Yi Xue"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.321.7269.1103"},{"issue":"2","key":"e_1_2_10_40_1","first-page":"S44","article-title":"Prophylaxis of stress ulcer bleeding. A meta\u2010analysis","volume":"13","author":"Tryba M","year":"1991","journal-title":"J Clin Gastroenterol"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-015-1107-2"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-016-1305-6"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcrc.2017.03.005"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.2172"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2019.02.041"},{"issue":"9","key":"e_1_2_10_46_1","first-page":"1032","article-title":"Systematic evaluation and re\u2010evaluation of proton pump inhibitors and H2 receptor blockers to prevent stress ulcers","volume":"20","author":"Xing","year":"2017","journal-title":"Pract Pharm Clin Remedies"},{"issue":"5","key":"e_1_2_10_47_1","first-page":"536","article-title":"H2 receptor antagonists are applied in meta\u2010analysis of the dangers associated with the development of pneumonia","volume":"17","author":"Hu","year":"2012","journal-title":"Chin J Clin Pharm Ther"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.092129"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v19.i16.2560"},{"issue":"05","key":"e_1_2_10_50_1","first-page":"462","article-title":"Meta\u2010analysis of proton pump inhibitors and H2 receptor antagonists on the risk of pancreatic cancer","volume":"24","author":"Zhuang","year":"2019","journal-title":"Lingnan J Emerg Med"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-017-4725-5"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.14157"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11255-018-1908-8"},{"issue":"6","key":"e_1_2_10_54_1","first-page":"8893","article-title":"Acid\u2010suppressive medications and risk of fracture: an updated meta\u2010analysis","volume":"8","author":"Cai D","year":"2015","journal-title":"Int J Clin Exp Med"},{"issue":"02","key":"e_1_2_10_55_1","first-page":"1401","article-title":"Meta analysis of the effect of H2 receptor antagonists on hip fracture risk","volume":"16","author":"Fan","year":"2016","journal-title":"Chin J Evid\u2010Based Med"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.712939"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-021-03245-3"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2010.12.015"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-021-03248-0"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1159\/000489165"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1012592"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003731"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12942-021-00260-6"},{"issue":"1","key":"e_1_2_10_64_1","first-page":"103","article-title":"Beta\u2010blocker efficacy across different cardiovascular indications: an umbrella review and meta\u2010analytic assessment","volume":"18","author":"Ziff OJ","year":"2020","journal-title":"BMC"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1093\/advances\/nmaa077"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.j4008"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.39489.470347.AD"},{"issue":"8","key":"e_1_2_10_68_1","first-page":"972","article-title":"The clinical diagnosis and therapy of Clostridium infection: progress review","volume":"25","author":"Tan B","year":"2013","journal-title":"Chin J Microecol"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2011-0796"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.01.013"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2010.02511.x"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-7223com"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2007.32"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2006.04541.x"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.06.004"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-020-02897-x"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-019-05382-x"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-308810"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-5378.2000.00032.x"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.46.5.615"},{"issue":"3","key":"e_1_2_10_81_1","first-page":"215","article-title":"Histamine and histamine receptor regulation of gastrointestinal cancers","volume":"1","author":"Kennedy L","year":"2012","journal-title":"Transl Gastrointest Cancer"},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph16091571"},{"key":"e_1_2_10_83_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu7042176"},{"key":"e_1_2_10_84_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurjpc\/zwac122"},{"key":"e_1_2_10_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2021.08.008"},{"key":"e_1_2_10_86_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10157-021-02066-z"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.2147","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.2147","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.2147","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T18:54:49Z","timestamp":1692557689000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.2147"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,22]]},"references-count":85,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,1]]}},"alternative-id":["10.1002\/jcph.2147"],"URL":"https:\/\/doi.org\/10.1002\/jcph.2147","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.22541\/au.165470056.65364202\/v1","asserted-by":"object"}]},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,22]]},"assertion":[{"value":"2022-06-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}