{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T15:16:31Z","timestamp":1779203791962,"version":"3.51.4"},"reference-count":44,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:00:00Z","timestamp":1501545600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:00:00Z","timestamp":1501545600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Auris Nasus Larynx"],"published-print":{"date-parts":[[2017,8]]},"DOI":"10.1016\/j.anl.2016.10.002","type":"journal-article","created":{"date-parts":[[2016,11,1]],"date-time":"2016-11-01T03:46:04Z","timestamp":1477971964000},"page":"390-397","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":13,"title":["Randomized controlled trial of juzen-taiho-to in children with recurrent acute otitis media"],"prefix":"10.1016","volume":"44","author":[{"given":"Makoto","family":"Ito","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumiko","family":"Maruyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Kitamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshimitsu","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruo","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noboru","family":"Yamanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuaki","family":"Harabuchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideki","family":"Origasa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomokazu","family":"Yoshizaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.anl.2016.10.002_bib0225","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1542\/peds.99.3.318","article-title":"Otitis media in 2253 Pittsburgh-area infants: prevalence and risk factors during the first two years of life","volume":"99","author":"Paradise","year":"1997","journal-title":"Pediatrics"},{"key":"10.1016\/j.anl.2016.10.002_bib0230","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1097\/00006454-199812000-00002","article-title":"Otitis media: back to basics","volume":"17","author":"Faden","year":"1998","journal-title":"Pediatr Infect Dis J"},{"key":"10.1016\/j.anl.2016.10.002_bib0235","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1056\/NEJMcp010944","article-title":"Clinical practice. Otitis media","volume":"347","author":"Hendley","year":"2002","journal-title":"N Engl J Med"},{"key":"10.1016\/j.anl.2016.10.002_bib0240","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1093\/infdis\/160.1.83","article-title":"Epidemiology of otitis media during the first seven years of life in children in greater Boston: a prospective, cohort study","volume":"160","author":"Teele","year":"1989","journal-title":"J Infect Dis"},{"key":"10.1016\/j.anl.2016.10.002_bib0245","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s004310100754","article-title":"The microbiologic and immunologic basis for recurrent otitis media in children","volume":"160","author":"Faden","year":"2001","journal-title":"Eur J Pediatr"},{"key":"10.1016\/j.anl.2016.10.002_bib0250","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1097\/01.inf.0000151024.11703.4a","article-title":"A randomized, multicenter, double blind, double dummy trial of single dose azithromycin versus high dose amoxicillin for treatment of uncomplicated acute otitis media","volume":"24","author":"Arguedas","year":"2005","journal-title":"Pediatr Infect Dis J"},{"key":"10.1016\/j.anl.2016.10.002_bib0255","first-page":"186","article-title":"High-dose azithromycin or amoxicillin-clavulanate for recurrent otitis media?","volume":"53","author":"Ables","year":"2004","journal-title":"J Fam Pract"},{"issue":"Suppl.","key":"10.1016\/j.anl.2016.10.002_bib0260","doi-asserted-by":"crossref","first-page":"S115","DOI":"10.1097\/01.inf.0000112525.88779.8b","article-title":"Management of recurrent and persistent acute otitis media: new options with familiar antibiotics","volume":"23","author":"Arrieta","year":"2004","journal-title":"Pediatr Infect Dis J"},{"key":"10.1016\/j.anl.2016.10.002_bib0265","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1097\/00129492-200205000-00021","article-title":"Nasopharyngeal penicillin-resistant Streptococcus pneumoniae strains among young children in Japan","volume":"23","author":"Ito","year":"2002","journal-title":"Otol Neurotol"},{"key":"10.1016\/j.anl.2016.10.002_bib0270","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.ijporl.2010.05.008","article-title":"Clonal spread of beta-lactamase-producing amoxicillin-clavulanate-resistant (BLPACR) strains of non-typeable Haemophilus influenzae among young children attending a day care in Japan","volume":"74","author":"Ito","year":"2010","journal-title":"Int J Pediatr Otorhinolaryngol"},{"key":"10.1016\/j.anl.2016.10.002_bib0275","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1128\/AAC.48.5.1509-1514.2004","article-title":"Rapidly increasing prevalence of beta-lactamase-nonproducing, ampicillin-resistant Haemophilus influenzae type b in patients with meningitis","volume":"48","author":"Hasegawa","year":"2004","journal-title":"Antimicrob Agents Chemother"},{"issue":"Pt 1","key":"10.1016\/j.anl.2016.10.002_bib0280","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1099\/jmm.0.45819-0","article-title":"Antimicrobial resistance in the nasopharyngeal flora of children with acute otitis media and otitis media recurring after amoxicillin therapy","volume":"54","author":"Brook","year":"2005","journal-title":"J Med Microbiol"},{"key":"10.1016\/j.anl.2016.10.002_bib0285","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1126\/science.257.5073.1064","article-title":"The crisis in antibiotic resistance","volume":"257","author":"Neu","year":"1992","journal-title":"Science"},{"key":"10.1016\/j.anl.2016.10.002_bib0290","doi-asserted-by":"crossref","first-page":"3375","DOI":"10.1128\/AAC.00373-06","article-title":"Effect of tigecycline on normal oropharyngeal and intestinal microflora","volume":"50","author":"Nord","year":"2006","journal-title":"Antimicrob Agents Chemother"},{"key":"10.1016\/j.anl.2016.10.002_bib0295","first-page":"CD004741","article-title":"Grommets (ventilation tubes) for recurrent acute otitis media in children","author":"McDonald","year":"2008","journal-title":"Cochrane Database Syst Rev"},{"issue":"Suppl.","key":"10.1016\/j.anl.2016.10.002_bib0300","doi-asserted-by":"crossref","first-page":"S134","DOI":"10.1016\/S0264-410X(00)00292-9","article-title":"Surgical prevention of otitis media","volume":"19","author":"Rosenfeld","year":"2000","journal-title":"Vaccine"},{"key":"10.1016\/j.anl.2016.10.002_bib0305","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1016\/j.ijporl.2011.05.009","article-title":"A systematic review of the effect of tympanostomy tubes in children with recurrent acute otitis media","volume":"75","author":"Lous","year":"2011","journal-title":"Int J Pediatr Otorhinolaryngol"},{"key":"10.1016\/j.anl.2016.10.002_bib0310","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1136\/bmj.322.7298.1327","article-title":"Effect of long term consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial","volume":"322","author":"Hatakka","year":"2001","journal-title":"BMJ"},{"key":"10.1016\/j.anl.2016.10.002_bib0315","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1017\/S0007114508116282","article-title":"Specific probiotics in reducing the risk of acute infections in infancy \u2013 a randomised, double-blind, placebo-controlled study","volume":"101","author":"Rautava","year":"2009","journal-title":"Br J Nutr"},{"key":"10.1016\/j.anl.2016.10.002_bib0320","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1159\/000235581","article-title":"Effect of long-term consumption of milk supplemented with probiotic lactobacilli and fluoride on dental caries and general health in preschool children: a cluster-randomized study","volume":"43","author":"Stecksen-Blicks","year":"2009","journal-title":"Caries Res"},{"key":"10.1016\/j.anl.2016.10.002_bib0325","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1016\/j.ijporl.2007.07.009","article-title":"Use of complementary and alternative medicine in pediatric otolaryngology patients attending a tertiary hospital in the UK","volume":"71","author":"Shakeel","year":"2007","journal-title":"Int J Pediatr Otorhinolaryngol"},{"key":"10.1016\/j.anl.2016.10.002_bib0330","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1177\/0009922806289307","article-title":"The use of complementary\/alternative therapies among children attending an urban pediatric emergency department","volume":"46","author":"Sawni","year":"2007","journal-title":"Clin Pediatr"},{"key":"10.1016\/j.anl.2016.10.002_bib0335","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1007\/s11418-009-0375-z","article-title":"Comparison of the contents of Kampo decoctions containing ephedra herb when prepared simply or by re-boiling according to the traditional theory","volume":"64","author":"Hayashi","year":"2010","journal-title":"J Nat Med"},{"key":"10.1016\/j.anl.2016.10.002_bib0340","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.ijporl.2012.01.011","article-title":"Probiotics and otitis media in children","volume":"76","author":"Niittynen","year":"2012","journal-title":"Int J Pediatr Otorhinolaryngol"},{"key":"10.1016\/j.anl.2016.10.002_bib0345","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/1472-6882-8-56","article-title":"Echinacea purpurea and osteopathic manipulative treatment in children with recurrent otitis media: a randomized controlled trial","volume":"8","author":"Wahl","year":"2008","journal-title":"BMC Complement Altern Med"},{"key":"10.1016\/j.anl.2016.10.002_bib0350","doi-asserted-by":"crossref","first-page":"716","DOI":"10.5414\/CPP47716","article-title":"Juzentaihoto (TJ-48), a traditional Japanese herbal medicine, influences hemoglobin recovery during preoperative autologous blood donation and after hip surgery","volume":"47","author":"Kishida","year":"2009","journal-title":"Int J Clin Pharmacol Ther"},{"issue":"Suppl. 2","key":"10.1016\/j.anl.2016.10.002_bib0355","first-page":"S9","article-title":"Orally administrated Juzen-taiho-to\/TJ-48 ameliorates erythropoietin (rHuEPO)-resistant anemia in patients on hemodialysis","volume":"12","author":"Nakamoto","year":"2008","journal-title":"Hemodial Int"},{"key":"10.1016\/j.anl.2016.10.002_bib0360","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0162-3109(99)00166-6","article-title":"Orally administered decoction of Kampo (Japanese herbal) medicine, Juzen-Taiho-To modulates cytokine secretion and induces NKT cells in mouse liver","volume":"46","author":"Matsumoto","year":"2000","journal-title":"Immunopharmacology"},{"key":"10.1016\/j.anl.2016.10.002_bib0365","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.intimp.2005.01.004","article-title":"Juzentaihoto, a Kampo medicine, enhances IL-12 production by modulating Toll-like receptor 4 signaling pathways in murine peritoneal exudate macrophages","volume":"5","author":"Chino","year":"2005","journal-title":"Int Immunopharmacol"},{"key":"10.1016\/j.anl.2016.10.002_bib0370","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.3390\/ijms9071142","article-title":"IL-12 and IL-18 induction and subsequent NKT activation effects of the Japanese botanical medicine Juzentaihoto","volume":"9","author":"Fujiki","year":"2008","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.anl.2016.10.002_bib0375","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/j.1442-200X.2004..x","article-title":"Management for fistula-in-ano with Ginseng and Tang-kuei Ten combination","volume":"46","author":"Ohya","year":"2004","journal-title":"Pediatr Int"},{"key":"10.1016\/j.anl.2016.10.002_bib0380","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1080\/00016480801998838","article-title":"Effects of Japanese herbal medicine, Juzen-taiho-to, in otitis-prone children \u2013 a preliminary study","volume":"129","author":"Maruyama","year":"2009","journal-title":"Acta Otolaryngol"},{"key":"10.1016\/j.anl.2016.10.002_bib0385","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.anl.2014.09.006","article-title":"Clinical practice guidelines for the diagnosis and management of acute otitis media (AOM) in children in Japan \u2013 2013 update","volume":"42","author":"Kitamura","year":"2015","journal-title":"Auris Nasus Larynx"},{"key":"10.1016\/j.anl.2016.10.002_bib0390","doi-asserted-by":"crossref","first-page":"427","DOI":"10.3233\/JAD-2010-1381","article-title":"The therapeutic effects of the herbal medicine, Juzen-taiho-to, on amyloid-beta burden in a mouse model of Alzheimer's disease","volume":"20","author":"Hara","year":"2010","journal-title":"J Alzheimers Dis"},{"key":"10.1016\/j.anl.2016.10.002_bib0395","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1620\/tjem.233.113","article-title":"Juzen-Taiho-to an herbal medicine, promotes the differentiation of transplanted bone marrow cells into microglia in the mouse brain injected with fibrillar amyloid \u03b2","volume":"233","author":"Liu","year":"2014","journal-title":"Tohoku J Exp Med"},{"key":"10.1016\/j.anl.2016.10.002_bib0400","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2172-8-1","article-title":"Transcriptional profiling of the LPS induced NF-kappaB response in macrophages","volume":"12","author":"Sharif","year":"2007","journal-title":"BMC Immunol"},{"key":"10.1016\/j.anl.2016.10.002_bib0405","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1055\/s-0033-1360391","article-title":"Biomarker-guided screening of Juzen-taiho-to, an oriental herbal formulation for immunostimulation","volume":"80","author":"Takaoka","year":"2014","journal-title":"Planta Med"},{"key":"10.1016\/j.anl.2016.10.002_bib0410","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.bmcl.2014.12.036","article-title":"Uncovering potential \u2018herbal probiotics\u2019 in Juzen-taiho-to through the study of associated bacterial populations","volume":"25","author":"Montenegro","year":"2015","journal-title":"Bioorg Med Chem Lett"},{"key":"10.1016\/j.anl.2016.10.002_bib0415","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S1473-3099(10)70012-8","article-title":"Otitis media and its consequences: beyond the earache","volume":"10","author":"Vergison","year":"2010","journal-title":"Lancet Infect Dis"},{"key":"10.1016\/j.anl.2016.10.002_bib0420","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1080\/00016489950180667","article-title":"Antibody responses to the outer membrane protein P6 of non-typeable Haemophilus influenzae and pneumococcal capsular polysaccharides in otitis-prone children","volume":"119","author":"Hotomi","year":"1999","journal-title":"Acta Otolaryngol"},{"key":"10.1016\/j.anl.2016.10.002_bib0425","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/S0022-3476(06)80115-0","article-title":"Antibody response to outer membrane protein of nontypeable Haemophilus influenzae in otitis-prone children","volume":"122","author":"Yamanaka","year":"1993","journal-title":"J Pediatr"},{"key":"10.1016\/j.anl.2016.10.002_bib0430","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/S0944-7113(00)80070-7","article-title":"Orally administered Kampo (Japanese herbal) medicine, Juzen-Taiho-To modulates cytokine secretion in gut associated lymphoreticular tissues in mice","volume":"6","author":"Matsumoto","year":"2000","journal-title":"Phytomedicine"},{"key":"10.1016\/j.anl.2016.10.002_bib0435","first-page":"118","article-title":"Protective effect of the Japanese traditional medicine juzentaihoto on myelosuppression induced by the anticancer drug TS-1 and identification of a potential biomarker of this effect","volume":"2","author":"Ogawa","year":"2011","journal-title":"BMC Complement Altern Med"},{"key":"10.1016\/j.anl.2016.10.002_bib0440","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1471-2164-13-30","article-title":"Microarray analysis on germfree mice elucidates the primary target of a traditional Japanese medicine juzentaihoto: acceleration of IFN-alpha response via affecting the ISGF3-IRF7 signaling cascade","volume":"13","author":"Munakata","year":"2012","journal-title":"BMC Genomics"}],"container-title":["Auris Nasus Larynx"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0385814616304503?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0385814616304503?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T19:33:13Z","timestamp":1759951993000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0385814616304503"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8]]},"references-count":44,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2017,8]]}},"alternative-id":["S0385814616304503"],"URL":"https:\/\/doi.org\/10.1016\/j.anl.2016.10.002","relation":{},"ISSN":["0385-8146"],"issn-type":[{"value":"0385-8146","type":"print"}],"subject":[],"published":{"date-parts":[[2017,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Randomized controlled trial of juzen-taiho-to in children with recurrent acute otitis media","name":"articletitle","label":"Article Title"},{"value":"Auris Nasus Larynx","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.anl.2016.10.002","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2016 Published by Elsevier Ireland Ltd.","name":"copyright","label":"Copyright"}]}}