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More recently, probiotics have also been suggested as a promising adjunctive treatment for periodontal diseases due to their antimicrobial and anti-inflammatory properties. Therefore, the aim of this randomized clinical trial (RCT) is to evaluate the clinical, microbiological, and immunological effects of probiotics as adjuncts to SRP alone or with MTZ+AMX in the treatment of periodontitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Subjects with periodontitis are being randomly assigned to receive (i) SRP alone, or with (ii) two probiotic lozenges\/day for 90\u2009days (Prob), (iii) MTZ (400\u2009mg) and AMX (500\u2009mg) thrice a day (TID) for 14\u2009days (MTZ+AMX), or (iv) Prob and MTZ+AMX. Subjects are being monitored for up to 12\u2009months post-treatment. Nine subgingival plaque samples per patient are being collected at baseline and at 3, 6, and 12\u2009months post-therapy and analyzed by checkerboard DNA\u2013DNA hybridization for 40 bacterial species. Peripheral blood and gingival crevicular fluid (GCF) of four randomly selected periodontal sites will be analyzed by means of a multiplex fluorescent bead-based immunoassay for 17 cyto\/chemokines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Statistical analyses<\/jats:title>\n                    <jats:p>The significance of differences in each group (over the course of the study) will be sought using repeated measures ANOVA or Friedman tests and among groups (at each time point) using either ANOVA\/ANCOVA or Kruskal-Wallis tests, depending on normality of the data. The chi-square test will be used to compare differences in the frequency of subjects achieving the clinical endpoint for treatment (\u2264\u20094 sites with PD\u2009\u2265\u20095\u2009mm) at 1\u2009year and of self-perceived adverse effects. A stepwise forward logistic regression analysis will be performed in order to investigate the impact of different predictor variables on the percentage of patients achieving the clinical endpoint for treatment. The Number Needed to Treat (NNT) with different treatment protocols will be also calculated. Statistical significance will be set at 5%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/clinicaltrials.gov\/NCT03733379\/November\">ClinicalTrials.gov NCT03733379. Registered on November<\/jats:ext-link>\n                      7, 2018.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13063-021-05246-0","type":"journal-article","created":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T06:18:21Z","timestamp":1618467501000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Clinical, microbiological, and immunological effects of systemic probiotics in periodontal treatment: study protocol for a randomized controlled trial"],"prefix":"10.1186","volume":"22","author":[{"given":"Belen","family":"Retamal-Valdes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim","family":"Teughels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laryssa Macedo","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebeca Nascimento","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aretuza","family":"Fritoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Gomes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geisla Mary Silva","family":"Soares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Tempor\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila Pinheiro","family":"Furquim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poliana Mendes","family":"Duarte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helio","family":"Doyle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"Faveri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2766-526X","authenticated-orcid":false,"given":"Luciene Cristina","family":"Figueiredo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magda","family":"Feres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,15]]},"reference":[{"issue":"5","key":"5246_CR1","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1111\/j.1600-051X.1997.tb00765.x","volume":"24","author":"AD Haffajee","year":"1997","unstructured":"Haffajee AD, Cugini MA, Dibart S, Smith C, Kent RL Jr, Socransky SS. 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