{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T09:51:58Z","timestamp":1777542718678,"version":"3.51.4"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,6,9]],"date-time":"2017-06-09T00:00:00Z","timestamp":1496966400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,6,9]],"date-time":"2017-06-09T00:00:00Z","timestamp":1496966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This systematic review and cumulative analysis aimed to explore the efficacy and safety of the combination of intravesical mitomycin C (MMC) plus bacillus Calmette-Guerin (BCG) for non-muscle-invasive bladder cancer (NMIBC) patients. A comprehensive literature search using Pubmed, Embase, Medline, Cochrane Library, CBM, CNKI and VIP databases was performed to identify studies applying intravesical MMC plus BCG therapy on NMIBC patients up to June 2016. Summarized unadjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the efficacy and safety of the combination therapy. A total of 25 studies containing 2749 NMIBC patients were included in this systematic review. Compared with BCG monotherapy, the combination therapy could significantly reduce the tumor recurrence rate (OR\u2009=\u20090.64, 95% CI: 0.44\u20130.94, <jats:italic>P<\/jats:italic>\u2009=\u20090.02) and cancer-specific mortality (OR\u2009=\u20090.54, 95% CI: 0.34\u20130.87, <jats:italic>P<\/jats:italic>\u2009=\u20090.01), without more toxicities (OR\u2009=\u20090.58, 95% CI: 0.17\u20131.94, <jats:italic>P<\/jats:italic>\u2009=\u20090.37). The combination therapy could also lead to significant lower tumor recurrence rate than MMC monotherapy (OR\u2009=\u20090.41, 95% CI: 0.24\u20130.69, <jats:italic>P<\/jats:italic>\u2009=\u20090.0009). Our study indicates that the combination of MMC plus BCG instillation is an effective and safe adjuvant treatment for NMIBC patients.<\/jats:p>","DOI":"10.1038\/s41598-017-03421-5","type":"journal-article","created":{"date-parts":[[2017,6,5]],"date-time":"2017-06-05T10:38:32Z","timestamp":1496659112000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Systematic Review and Cumulative Analysis of the Combination of Mitomycin C plus Bacillus Calmette-Gu\u00e9rin (BCG) for Non\u2013Muscle-Invasive Bladder Cancer"],"prefix":"10.1038","volume":"7","author":[{"given":"Tuo","family":"Deng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaolu","family":"Duan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Cai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guohua","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,6,9]]},"reference":[{"key":"3421_CR1","doi-asserted-by":"publisher","first-page":"225","DOI":"10.3322\/caac.20006","volume":"59","author":"A Jemal","year":"2009","unstructured":"Jemal, A. et al. Cancer statistics. CA Cancer J Clin \n                           59, 225\u2013249 (2009).","journal-title":"CA Cancer J Clin"},{"key":"3421_CR2","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1093\/jnci\/83.10.682","volume":"83","author":"BL Lum","year":"1991","unstructured":"Lum, B. L. & Torti, F. M. Adjuvant intravesicular pharmacotherapy for superficial bladder cancer. J Natl Cancer Inst \n                           83, 682\u2013694 (1991).","journal-title":"J Natl Cancer Inst"},{"key":"3421_CR3","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1097\/01.ju.0000162039.38023.5f","volume":"174","author":"JE Rosenberg","year":"2005","unstructured":"Rosenberg, J. E., Carroll, P. R. & Small, E. J. Update on chemotherapy for advanced bladder cancer. J Urol. \n                           174, 14\u201320 (2005).","journal-title":"J Urol."},{"key":"3421_CR4","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/S0094-0143(05)70238-X","volume":"27","author":"JT Hsieh","year":"2000","unstructured":"Hsieh, J. T., Dinney, C. P. & Chung, L. W. The potential role of gene therapy in the treatment of bladder cancer. Urol Clin North Am \n                           27, 103\u2013113 (2000).","journal-title":"Urol Clin North Am"},{"key":"3421_CR5","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.eururo.2009.04.038","volume":"56","author":"PU Malmstrom","year":"2009","unstructured":"Malmstrom, P. U. et al. An individual patient data meta-analysis of the long-term outcome of randomised studies comparing intravesical mitomycin C versus bacillus Calmette-Guerin for non-muscle-invasive bladder cancer. Eur Urol. \n                           56, 247\u2013256 (2009).","journal-title":"Eur Urol."},{"key":"3421_CR6","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1016\/j.eururo.2013.06.003","volume":"64","author":"M Babjuk","year":"2013","unstructured":"Babjuk, M. et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2013. Eur Urol \n                           64, 639\u201353 (2013).","journal-title":"Eur Urol"},{"key":"3421_CR7","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1016\/S0022-5347(17)35678-1","volume":"150","author":"TL Ratliff","year":"1993","unstructured":"Ratliff, T. L., Ritchey, J. K., Yuan, J. J., Andriole, G. L. & Catalona, W. J. T-cell subsets required for intravesical BCG immunotherapy for bladder cancer. J Urol. \n                           150, 1018\u20131023 (1993).","journal-title":"J Urol."},{"key":"3421_CR8","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1159\/000111737","volume":"80","author":"P Oliveira","year":"2008","unstructured":"Oliveira, P., Palmeira, C., Cola\u00e7o, A., De la Cruz P., L. F. & Lopes, C. Cell Proliferation and DNA Content in Rat Urothelial Lesions after Repeat Intravesical Instillations of Mitomycin C and Bacillus Calmette-Guerin. Urol Int. \n                           80, 90\u201397 (2008).","journal-title":"Urol Int."},{"key":"3421_CR9","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3892\/ol.2010.217","volume":"2","author":"M Matsushima","year":"2011","unstructured":"Matsushima, M. et al. Enhanced antitumor effect of combination intravesical mitomycin C and bacillus Calmette-Guerin therapy in an orthotopic bladder cancer model. Oncology letter \n                           2, 13\u201319 (2011).","journal-title":"Oncology letter"},{"key":"3421_CR10","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1590\/S1677-55382012000400006","volume":"38","author":"\u00d6 G\u00fclpinar","year":"2012","unstructured":"G\u00fclpinar, \u00d6., Halilioglu, A. H., G\u00f6k\u00e7e, M. I., G\u00f6\u011f\u00fc\u015f, \u00c7. & Baltaci, S. The value of perioperative mitomycin C instillation in improving subsequent bacillus calmette-guerin instillation efficacy in intermediate and high-risk patients with non-muscle invasive bladder cancer: a prospective randomized study. Int Braz J Urol \n                           38, 474\u2013479 (2012).","journal-title":"Int Braz J Urol"},{"key":"3421_CR11","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/S1470-2045(05)70472-1","volume":"7","author":"SM Di Stasi","year":"2006","unstructured":"Di Stasi, S. M. et al. Sequential BCG and electromotive mitomycin versus BCG alone for high-risk superficial bladder cancer: a randomised controlled trial. Lancet Oncol. \n                           7, 43\u201351 (2006).","journal-title":"Lancet Oncol."},{"key":"3421_CR12","doi-asserted-by":"publisher","first-page":"411","DOI":"10.3109\/00365599.2012.694906","volume":"46","author":"R J\u00e4rvinen","year":"2012","unstructured":"J\u00e4rvinen, R., Kaasinen, E., Rintala, E. & Group, T. F. Long-term results of maintenance treatment of mitomycin C or alternating mitomycin C and bacillus Calmette-Guerin instillation therapy of patients with carcinoma in situ of the bladder: a subgroup analysis of the prospective FinnBladder 2 study with a 17-year follow-up. Scand J Urol Nephrol \n                           46, 411\u2013417 (2012).","journal-title":"Scand J Urol Nephrol"},{"key":"3421_CR13","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1016\/j.eururo.2014.09.026","volume":"67","author":"E Solsona","year":"2015","unstructured":"Solsona, E. et al. Sequential Combination of Mitomycin C Plus Bacillus Calmette-Guerin (BCG) Is More Effective but More Toxic Than BCG Alone in Patients with Non-Muscle-invasive Bladder Cancer in Intermediate- and High-risk Patients: Final Outcome of CUETO 93009, a Randomized Prospective Trial. Eur Urol. \n                           67, 508\u2013516 (2015).","journal-title":"Eur Urol."},{"key":"3421_CR14","first-page":"5890","volume":"18","author":"GM Badalato","year":"2011","unstructured":"Badalato, G. M., Hruby, G., Razmjoo, M. & McKiernan, J. M. Maximizing intravesical therapy options: is there an advantage to the administration of perioperative mitomycin C prior to an induction course of BCG? Can J Urol \n                           18, 5890\u20135895 (2011).","journal-title":"Can J Urol"},{"key":"3421_CR15","first-page":"730","volume":"9","author":"LH Ye","year":"2003","unstructured":"Ye, L. H., Chen, Y. L., Tao, S. X. & Qian, S. X. Effect of mitomycin C instilled immediately after TUR added with low dose BCG maintenance therapy to prevent recurrence of superficial bladder cancer. Chin J Rehabil Theory Practice \n                           9, 730\u2013731 (2003).","journal-title":"Chin J Rehabil Theory Practice"},{"key":"3421_CR16","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1016\/j.eururo.2010.11.038","volume":"59","author":"W Oosterlinck","year":"2011","unstructured":"Oosterlinck, W. et al. Sequential intravesical chemoimmunotherapy with mitomycin C and bacillus Calmette-Guerin and with bacillus Calmette-Guerin alone in patients with carcinoma in situ of the urinary bladder: results of an EORTC genito-urinary group randomized phase 2 trial (30993). Eur Urol. \n                           59, 438\u2013446 (2011).","journal-title":"Eur Urol."},{"key":"3421_CR17","first-page":"948","volume":"12","author":"AR He","year":"2013","unstructured":"He, A. R., Song, H. F., Wan, Q. F. & Du, J. B. Clinical observation on Bacillus Calmette-Guerin combined with mitomycin C in prevention of post-operative recurrence of superficial transitional cell carcinoma in bladder. Journal of Clinical and Experimental Medicine \n                           12, 948\u2013949 (2013).","journal-title":"Journal of Clinical and Experimental Medicine"},{"key":"3421_CR18","first-page":"205","volume":"20","author":"SM Liu","year":"2007","unstructured":"Liu, S. M. & Liu, Y. L. Intravesical instillation of mitomycin C and bacillus Calmette-Guerin for the prevention of post-operative recurrence of superficial transitional cell carcinoma of the bladder. Chinese Medicine of Factory and Mine \n                           20, 205\u2013206 (2007).","journal-title":"Chinese Medicine of Factory and Mine"},{"key":"3421_CR19","first-page":"60","volume":"1","author":"SL Ma","year":"2001","unstructured":"Ma, S. L., Li, S. X. & Zhong, Q. G. Sequential intravesical mitomycin plus bacillus Calmette-Guerin for preventing recurrence of superficial bladder cancer. Chinese Journal of Misdiagnostics \n                           1, 60 (2001).","journal-title":"Chinese Journal of Misdiagnostics"},{"key":"3421_CR20","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/S0022-5347(05)67446-0","volume":"164","author":"E Kaasinen","year":"2000","unstructured":"Kaasinen, E. et al. Weekly mitomycin C followed by monthly bacillus Calmette-Guerin or alternating monthly interferon-alpha2B and bacillus Calmette-Guerin for prophylaxis of recurrent papillary superficial bladder carcinoma. J Urol. \n                           164, 47\u201352 (2000).","journal-title":"J Urol."},{"key":"3421_CR21","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1016\/j.eururo.2015.02.022","volume":"68","author":"R J\u00e4rvinen","year":"2015","unstructured":"J\u00e4rvinen, R. et al. Long-term Outcome of Patients with Frequently Recurrent Non-muscle-invasive Bladder Carcinoma Treated with One Perioperative Plus Four Weekly Instillations of Mitomycin C Followed by Monthly Bacillus Calmette-Guerin (BCG) or Alternating BCG and Interferon-alpha2b Instillations: Prospective Randomised FinnBladder-4 Study. Eur Urol. \n                           68, 611\u2013617 (2015).","journal-title":"Eur Urol."},{"key":"3421_CR22","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1158\/1078-0432.CCR-14-1781","volume":"21","author":"RS Svatek","year":"2015","unstructured":"Svatek, R. S. et al. Sequential intravesical mitomycin plus Bacillus Calmette-Guerin for non-muscle-invasive urothelial bladder carcinoma: translational and phase I clinical trial. Clin Cancer Res \n                           21, 303\u2013311 (2015).","journal-title":"Clin Cancer Res"},{"key":"3421_CR23","first-page":"92","volume":"27","author":"GX Cai","year":"2012","unstructured":"Cai, G. X. Clinical observation on intravesical mitomycin C plus bacillus Calmette-Guerin instillation for superficial bladder cancer. China Health Industry \n                           27, 92 (2012).","journal-title":"China Health Industry"},{"key":"3421_CR24","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/S0302-2838(03)00140-4","volume":"43","author":"E Kaasinen","year":"2003","unstructured":"Kaasinen, E. et al. Alternating mitomycin C and BCG instillations versus BCG alone in treatment of carcinoma in situ of the urinary bladder: a nordic study. Eur Urol. \n                           43, 637\u2013645 (2003).","journal-title":"Eur Urol."},{"key":"3421_CR25","first-page":"281","volume":"14","author":"YH Zhang","year":"2009","unstructured":"Zhang, Y. H., Ma, L. W., Wu, Y., Chen, J. G. & Luo, D. Q. Bacillus Calmette-Guerin vaccine and mitomycin C alternation for irrigation of bladder to prevent the recurrence of superficial bladder carcinoma. Journal Of Modern Urology \n                           14, 281\u2013282 (2009).","journal-title":"Journal Of Modern Urology"},{"key":"3421_CR26","first-page":"65","volume":"12","author":"MZ Sun","year":"2010","unstructured":"Sun, M. Z. & Zhang, Y. H. Alternating intravesical instillation of mitomycin C plus bacillus Calmette-Guerin for preventing recurrence of superficial bladder cancer. Chinese Community Doctors \n                           12, 65\u201366 (2010).","journal-title":"Chinese Community Doctors"},{"key":"3421_CR27","first-page":"650","volume":"24","author":"GJ Bao","year":"2007","unstructured":"Bao, G. J. Effect of Mitomycin C Instilled after Operation Added with Bacillus Calmette-Guerir Maintenance Therapy to Prevent Recurrence of Bladder Cancer. The Chinese Journal Of Modern Applied Pharmacy \n                           24, 650\u2013652 (2007).","journal-title":"The Chinese Journal Of Modern Applied Pharmacy"},{"key":"3421_CR28","first-page":"328","volume":"24","author":"WJ Fang","year":"2002","unstructured":"Fang, W. J., Zhang, B. B. & Cai, S. L. Prevention of recurrence of bladder cancer by intravesical instillation with combination of Mitomycin C and Bacillus Calmette-Guerir after TURBT. Zhejiang Medical Journal \n                           24, 328\u2013329 (2002).","journal-title":"Zhejiang Medical Journal"},{"key":"3421_CR29","first-page":"7876","volume":"22","author":"BE Weiss","year":"2015","unstructured":"Weiss, B. E., Pietzak, E. J., Wein, A. J., Malkowicz, S. B. & Guzzo, T. J. Single instillation of mitomycin C plus bacillus Calmette-Gu\u00e9rin (BCG) versus BCG alone in high grade non-muscle invasive bladder cancer. Can J Urol \n                           22, 7876\u20137881 (2015).","journal-title":"Can J Urol"},{"key":"3421_CR30","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.1016\/j.juro.2016.01.103","volume":"195","author":"C Gan","year":"2016","unstructured":"Gan, C. et al. Sequential bacillus Calmette-Gu\u00e9rin\/Electromotive Drug Administration of Mitomycin C as the Standard Intravesical Regimen in High Risk Nonmuscle Invasive Bladder Cancer: 2-Year Outcomes. J Urol. \n                           195, 1697\u2013703 (2016).","journal-title":"J Urol."},{"key":"3421_CR31","doi-asserted-by":"publisher","first-page":"1668","DOI":"10.1016\/S0022-5347(01)62377-2","volume":"160","author":"JA Witjes","year":"1998","unstructured":"Witjes, J. A., Caris, C. T., Mungan, N. A., Debruyne, F. M. & Witjes, W. P. Results of a randomized phase III trial of sequential intravesical therapy with mitomycin C and bacillus Calmette-Guerin versus mitomycin C alone in patients with superficial bladder cancer. J Urol. \n                           160, 1668\u201371 (1998).","journal-title":"J Urol."},{"key":"3421_CR32","first-page":"199","volume":"29","author":"AP Van der Meijden","year":"1996","unstructured":"Van der Meijden, A. P. et al. Marker tumour responses to the sequential combination of intravesical therapy with mitomycin-C and BCG-RIVM in multiple superficial bladder tumours. Report from the European Organisation for Research and Treatment on Cancer-Genitourinary Group (EORTC 30897). Eur Urol. \n                           29, 199\u2013203 (1996).","journal-title":"Eur Urol."},{"key":"3421_CR33","doi-asserted-by":"publisher","first-page":"2050","DOI":"10.1016\/S0022-5347(01)66691-6","volume":"154","author":"E Rintala","year":"1995","unstructured":"Rintala, E. et al. Alternating mitomycin C and bacillus Calmette-Guerin instillation therapy for carcinoma in situ of the bladder. The Finnbladder Group. J Urol. \n                           154, 2050\u20133 (1995).","journal-title":"J Urol."},{"key":"3421_CR34","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/S0022-5347(01)65936-6","volume":"156","author":"E Rintala","year":"1996","unstructured":"Rintala, E., Jauhiainen, K., Kaasinen, E., Nurmi, M. & Alfthan, O. Alternating mitomycin C and bacillus Calmette-Guerin instillation prophylaxis for recurrent papillary (stages Ta to T1) superficial bladder cancer. Finnbladder Group. J Urol. \n                           156, 56\u20139 (1996).","journal-title":"J Urol."},{"key":"3421_CR35","first-page":"1762","volume":"47","author":"TL Ratliff","year":"1987","unstructured":"Ratliff, T. L., Palmer, J. O., McGarr, J. A. & Brown, E. J. Intravesical Bacillus Calmette-Guerin therapy for murine bladder tumors: initiation of the response by fibronectin-mediated attachment of Bacillus Calmette-Guerin. Cancer Res. \n                           47, 1762\u20131766 (1987).","journal-title":"Cancer Res."},{"key":"3421_CR36","first-page":"3843","volume":"50","author":"MA Hudson","year":"1990","unstructured":"Hudson, M. A., Ritchey, J. K., Catalona, W. J., Brown, E. J. & Ratliff, T. L. Comparison of the fibronectin-binding ability and antitumor efficacy of various mycobacteria. Cancer Res. \n                           50, 3843\u20133847 (1990).","journal-title":"Cancer Res."},{"key":"3421_CR37","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1172\/JCI114434","volume":"85","author":"LR Kavoussi","year":"1990","unstructured":"Kavoussi, L. R., Brown, E. J., Ritchey, J. K. & Ratliff, T. L. Fibronectin-mediated Calmette-Guerin bacillus attachment to murine bladder mucosa. Requirement for the expression of an antitumor response. J Clin Invest \n                           85, 62\u201367 (1990).","journal-title":"J Clin Invest"},{"key":"3421_CR38","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1111\/j.1365-3083.1986.tb01994.x","volume":"23","author":"BT Tan","year":"1986","unstructured":"Tan, B. T., Limpens, J., Koken, M., Valster, H. & Scheper, R. J. Local administration of various cytostatic drugs after subcutaneous immunization enhances delayed-type hypersensitivity reaction to sheep red blood cells in mice. Scand J Immunol. \n                           23, 605\u2013609 (1986).","journal-title":"Scand J Immunol."},{"key":"3421_CR39","first-page":"2353","volume":"62","author":"AK Nowak","year":"2002","unstructured":"Nowak, A. K., Robinson, B. W. & Lake, R. A. Gemcitabine exerts a selective effect on the humoral immune response: implications for combination chemoimmunotherapy. Cancer Res. \n                           62, 2353\u20132358 (2002).","journal-title":"Cancer Res."},{"key":"3421_CR40","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/nri2216","volume":"8","author":"L Zitvogel","year":"2008","unstructured":"Zitvogel, L., Apetoh, L., Ghiringhelli, F. & Kroemer, G. Immunological aspects of cancer chemotherapy. Nat Rev Immunol \n                           8, 59\u201373 (2008).","journal-title":"Nat Rev Immunol"},{"key":"3421_CR41","doi-asserted-by":"publisher","first-page":"967","DOI":"10.4149\/neo_2016_616","volume":"63","author":"Y Lan","year":"2016","unstructured":"Lan, Y., Liu, D. & Lin, M. Comparison of the combination therapy of bacillus Calmette-Gu\u00e9rin and mitomycin C with the monotherapy for non-muscle-invasive bladder cancer: a meta-analysis. Neoplasma. \n                           63, 967\u2013976 (2016).","journal-title":"Neoplasma."},{"key":"3421_CR42","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3892\/ol.2010.217","volume":"2","author":"M Matsushima","year":"2011","unstructured":"Matsushima, M. et al. Enhanced antitumor effect of combination intravesical mitomycin C and bacillus Calmette-Guerin therapy in an orthotopic bladder cancer model. Oncol Lett \n                           2, 13\u201319 (2011).","journal-title":"Oncol Lett"},{"key":"3421_CR43","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1136\/bmj.39489.470347.AD","volume":"336","author":"GH Guyatt","year":"2008","unstructured":"Guyatt, G. H. et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. \n                           336, 924\u2013926 (2008).","journal-title":"BMJ."},{"key":"3421_CR44","doi-asserted-by":"publisher","first-page":"d5928","DOI":"10.1136\/bmj.d5928","volume":"343","author":"JP Higgins","year":"2011","unstructured":"Higgins, J. P. et al. The Cochrane Collaboration\u2019s tool for assessing risk of bias in randomised trials. BMJ. \n                           343, d5928 (2011).","journal-title":"BMJ."},{"key":"3421_CR45","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1136\/bmj.327.7414.557","volume":"327","author":"JP Higgins","year":"2003","unstructured":"Higgins, J. P., Thompson, S. G., Deeks, J. J. & Altman, D. G. Measuring inconsistency in meta-analyses. BMJ. \n                           327, 557\u2013560 (2003).","journal-title":"BMJ."},{"key":"3421_CR46","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1136\/bmj.315.7109.629","volume":"315","author":"M Egger","year":"1997","unstructured":"Egger, M., Davey Smith, G. & Schneider, M. & Minder, C. Bias in meta-analysis detected by a simple, graphical test. BMJ. \n                           315, 629\u2013634 (1997).","journal-title":"BMJ."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-03421-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-03421-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-03421-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T05:15:11Z","timestamp":1671772511000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-03421-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,9]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["3421"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-03421-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,9]]},"assertion":[{"value":"23 August 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 May 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 June 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"3172"}}