{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T12:40:14Z","timestamp":1756471214021,"version":"3.44.0"},"reference-count":46,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mycoses"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>\n<jats:bold>\n<jats:styled-content style=\"fixed-case\">Introduction<\/jats:styled-content>\n<\/jats:bold>\n<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">Onychomycosis<\/jats:styled-content> remains a challenging condition due to varying cure rates and the risk of recurrence. Topical 40% urea has been proposed as an adjuvant to antifungals to enhance efficacy. Many trials have been done, presenting mixed results.<\/jats:p><\/jats:sec><jats:sec><jats:title>\n<jats:bold>\n<jats:styled-content style=\"fixed-case\">Methods<\/jats:styled-content>\n<\/jats:bold>\n<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">Four<\/jats:styled-content> databases (<jats:styled-content style=\"fixed-case\">PubMed<\/jats:styled-content>, Web of Science, Scopus, and <jats:styled-content style=\"fixed-case\">EBSCO<\/jats:styled-content>), two registers (Cochrane), and grey literature sources were used to identify randomised controlled trials (<jats:styled-content style=\"fixed-case\">RCTs<\/jats:styled-content>) and non\u2010randomised studies (<jats:styled-content style=\"fixed-case\">NRSs<\/jats:styled-content>) published until February 2025. Cure rates (clinical, mycological, and total) were analysed in the meta\u2010analysis, analysing cure rates and comparing urea as an adjuvant to antifungal therapy with antifungals alone. We independently selected eligible articles and extracted relevant data before assessing the quality of the studies. A summary of the findings table was made with <jats:styled-content style=\"fixed-case\">GRADEpro GDT<\/jats:styled-content> using the results of the meta\u2010analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>\n<jats:bold>\n<jats:styled-content style=\"fixed-case\">Results<\/jats:styled-content>\n<\/jats:bold>\n<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">Based<\/jats:styled-content> on six <jats:styled-content style=\"fixed-case\">RCTs<\/jats:styled-content> and six <jats:styled-content style=\"fixed-case\">NRSs<\/jats:styled-content> involving 424 participants treated with antifungals plus topical 40% urea\u2014130 of which were compared to 129 participants who received antifungals without urea\u2014 we found that adding topical 40% urea as an adjuvant significantly improved the clinical cure rate compared to therapy using antifungals alone (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>: 2.05, 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: 1.03\u20134.11, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). However, there were no significant differences in mycological and total cure rates (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>: 1.71; 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: 0.63\u20134.61; <jats:italic>p<\/jats:italic>\u2009&gt;\u20090.25 and <jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content> 1.23; 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: 0.47\u20133.23; <jats:italic>p<\/jats:italic>\u2009&gt;\u20090.5). The reported adverse effects were localised.<\/jats:p><\/jats:sec><jats:sec><jats:title>\n<jats:bold>\n<jats:styled-content style=\"fixed-case\">Conclusions<\/jats:styled-content>\n<\/jats:bold>\n<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">Topical<\/jats:styled-content> 40% urea can be used to improve the clinical efficacy of antifungals for onychomycosis. However, evidence for mycological and total efficacy is lacking. Thus, more rigorous trials are needed to confirm its efficacy and safety.<\/jats:p><\/jats:sec><jats:sec><jats:title>\n<jats:bold>Protocol <jats:styled-content style=\"fixed-case\">Registration<\/jats:styled-content><\/jats:bold>\n<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">PROSPERO<\/jats:styled-content>\u2014<jats:styled-content style=\"fixed-case\">CRD42025638277<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/myc.70097","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T10:29:10Z","timestamp":1755599350000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and Safety of 40% Urea as an Adjuvant to Antifungals for Onychomycosis: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1111","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4674-6033","authenticated-orcid":false,"given":"Fitra Tri","family":"Kurniasari","sequence":"first","affiliation":[{"name":"Department of Dermatology, Venereology, and Aesthetics Universitas Airlangga Faculty of Medicine\u2013Dr. Soetomo Regional General Hospital  Surabaya East Java Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2443-014X","authenticated-orcid":false,"given":"Evy","family":"Ervianti","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology, and Aesthetics Universitas Airlangga Faculty of Medicine\u2013Dr. Soetomo Regional General Hospital  Surabaya East Java Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2388-6740","authenticated-orcid":false,"family":"Damayanti","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology, and Aesthetics Universitas Airlangga Faculty of Medicine\u2013Dr. Soetomo Regional General Hospital  Surabaya East Java Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5180-957X","authenticated-orcid":false,"given":"Citrawati Dyah Kencono","family":"Wungu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Medical Biochemistry Universitas Airlangga Faculty of Medicine  Surabaya East Java Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5486-5291","authenticated-orcid":false,"given":"Dwi","family":"Murtiastutik","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology, and Aesthetics Universitas Airlangga Faculty of Medicine\u2013Dr. Soetomo Regional General Hospital  Surabaya East Java Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9996-1199","authenticated-orcid":false,"given":"Diah Mira","family":"Indramaya","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology, and Aesthetics Universitas Airlangga Faculty of Medicine\u2013Dr. Soetomo Regional General Hospital  Surabaya East Java Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5259-714X","authenticated-orcid":false,"given":"Sylvia","family":"Anggraeni","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology, and Aesthetics Universitas Airlangga Faculty of Medicine\u2013Dr. Soetomo Regional General Hospital  Surabaya East Java Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5192-4631","authenticated-orcid":false,"given":"Fajar","family":"Avicenna","sequence":"additional","affiliation":[{"name":"Medical Doctor Program Universitas Airlangga Faculty of Medicine  Surabaya East Java Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"volume-title":"A Text Atlas of Nail Disorders","year":"2003","author":"Tosti A.","key":"e_1_2_11_2_1"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinmicnews.2023.01.002"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/1872213X13666191026090713"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijd.13392"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3314\/jjmm.46.171"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof8010060"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof8050464"},{"issue":"1","key":"e_1_2_11_9_1","first-page":"E20","article-title":"Incidence and Epidemiology of Onychomycosis in Patients Visiting a Tertiary Care Hospital in India","volume":"95","author":"Adekhandi S.","year":"2015","journal-title":"Cutis"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.18311\/jnr\/2023\/33695"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.14273"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00105\u2010015\u20103755\u20101"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof9070712"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.36106\/IJAR"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/myc.13652"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13047\u2010019\u20100332\u20103"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.2174\/1573399819666230403132241"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3109\/09546634.2015.1109029"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cl2.1230"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l4898"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102288\u201014\u201025"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.CEGH.2023.101484"},{"key":"e_1_2_11_23_1","unstructured":"McMaster University and Evidence Prime Inc. \u201cGRADEpro GDT: GRADEpro Guideline Development Tool. Handbook \u201d(2024)."},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2010.07.015"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3109\/09546634.2011.588191"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0011\u2010393X(97)80040\u20109"},{"issue":"2","key":"e_1_2_11_27_1","first-page":"67","article-title":"Onychomycosis With Dermatophytoma. A Comparison Among the Results of Treatments With Oral Terbinafine, Topical 40% Urea in Monotherapy and Combination Therapy","volume":"15","author":"Escalante K.","year":"2013","journal-title":"Dermatologia Kliniczna"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20104362.1991.tb02648.x"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365\u20104362.1997.00024.x"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1159\/000345105"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749\u20106632.1988.tb40457.x"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20104362.1995.tb00625.x"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439\u20100507.1991.tb00867.x"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/myc.1990.33.4.167"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102230.1988.tb01961.x"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.3109\/09546639009086714"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/1745\u20106215\u201015\u2010456"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0269009"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/1471\u20100528.15199"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13063\u2010023\u201007215\u20101"},{"issue":"11","key":"e_1_2_11_41_1","first-page":"38","article-title":"Risk Factors and Comorbidities for Onychomycosis: Implications for Treatment With Topical Therapy","volume":"8","author":"Elewski B. E.","year":"2015","journal-title":"Journal of Clinical and Aesthetic Dermatology"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0190\u20109622(98)70481\u20105"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.2147\/CCID.S362635"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.5826\/dpc.1402a74"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajd.13686"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2023.102325"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.MR000039.pub2"}],"container-title":["Mycoses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/myc.70097","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T12:02:36Z","timestamp":1756468956000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/myc.70097"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":46,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1111\/myc.70097"],"URL":"https:\/\/doi.org\/10.1111\/myc.70097","archive":["Portico"],"relation":{},"ISSN":["0933-7407","1439-0507"],"issn-type":[{"type":"print","value":"0933-7407"},{"type":"electronic","value":"1439-0507"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"2025-06-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70097"}}