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rev port estomatol med dent cir maxilofac . 2020;61(2):57-63             59



           Material and methods                                Results
           This review was registered with the identification number   The study selection process is summarized in Figure 1. The
           CRD42019131541 in the PROSPERO International Prospective   search strategy resulted in seven papers. All data were ex-
           Register of Systematic Reviews hosted by the National Insti-  tracted by two reviewers (VR and PO), independently and in
           tute for Health Research, University of York, Centre for Re-  duplicate, using data extraction forms.
           views and Dissemination.                              All data collected were loaded to the Review Manager soft-
              An electronic search without time or language restrictions   ware and checked. The following information was recorded:
           was undertaken between January and May 9, 2018, in the fol-
           lowing databases: PubMed, Lilacs, and Cochrane, using the   a.  Publication status and year of publication.
           following keywords and Mesh terms: “hyaluronic acid”; “peri-  b.  Study design and duration of the follow-up.
           odontitis; “treatment of periodontitis”; “scaling.”   c.  Participants’ features: sample size, with at least 20
              In this systematic review, only randomized controlled clin-  teeth, with ≥ five sites of PPD ≥ 5 mm.
           ical trials (RCTs) on the treatment of CP with SRP + HA were   d.  Methodology of the trials: inclusion and exclusion cri-
           included. Either the test or control treatment group of each   teria, randomization, conclusions, and clinical variables.
           selected RCT was included in the article if the following in-  e.  Characteristics of the interventions and control.
           clusion criteria were met: healthy participants; moderate to   f.  Source of funding and conflicts of interest.
           severe CP with ≥ five sites of probing pocket depth (PPD) ≥ 5
           mm; patients with at least 20 teeth; follow-up ≥ 12 weeks;   After reading the title or abstract, 137 articles were exclud-
           human-based studies; HA applied during the non-surgical   ed (inter-reader agreement k = 0.944±0.056; the following web-
           treatment of CP. Individuals were excluded if they had re-  site was used for kappa calculation: https://www.graphpad.
           ceived periodontal treatment in the previous year and/or an-  com/quickcalcs/kappa1.cfm). When the authors (VR and PO)
           tibiotics 6 months before the study, were smokers, had chron-  disagreed in selecting an article for exclusion, judgment by a
           ic diseases (diabetes mellitus or rheumatoid arthritis), or were   third author (PM) was solicited.
           pregnant.                                             All authors of the included studies were contacted and
              This systematic review applied the Preferred Reporting   asked if they had more information or unpublished material.
           Items Systematic review and Meta-Analyses (PRISMA) state-  Just one of the authors replied. 10
           ment and checklist, as well as the population, intervention,   The full-text reports of the remaining ten articles led to the
                                                                                                             14
           comparison, outcomes (PICO) method, as follows:     exclusion of three due to not meeting the inclusion criteria,
                                                                                               15
                                                               as they included patients with PPD <4 mm,  smokers, and also
              •  P: Patients with CP                           administered chlorohexidine in the test group. 16
              •  I: SRP + HA                                     The initial screening of titles and abstracts, in the Lilac
              •  C: Treatment of CP with either SRP + HA or SRP alone  database, resulted in two papers for full-text analysis. The two
              •  O: Clinical attachment level (CAL) gain, PPD, bleeding on   full-text reports were excluded due to not fitting the scope of
                                                                                     8
               probing (BOP), plaque index (PI), gingival index (GI), and   this work. One of the articles  was obtained by manual search.
               relative attachment level (RAL)                   All of the selected studies were randomized clinical trials
                                                               with a 12-month follow-up. Four studies 8-12  evaluated the ap-
              The risk of bias analysis was performed with the Cochrane   plication of 0.8% HA combined with SRP and three articles 2,11,13
           Collaboration Tool, by two authors (VR and PO). The risk of bias   evaluated the application of 0.2% HA combined with SRP. Most
           was classified as low when studies provided detailed informa-  studies suggested that a combined treatment composed of
           tion on all parameters analyzed. Studies that did not provide   full-mouth SRP and topical administration of HA promoted
           information on two or more parameters were considered as   periodontal healing in CP. 8-11,13
           high-risk. Studies that provided information on only one of the   Shah et al.  detected a significant reduction in PI and GI in
                                                                         9
           parameters were classified as having a moderate risk of bias.   both a HA group and a control group at 12 weeks (p<0.05). It
           All the included trials were described as randomized con-  also observed a significant reduction in PPD and an increase
           trolled trials, and all of the studies showed an unclear risk of   in RAL in both groups compared to baseline (p<0.05). Com-
           the randomization method. Allocation in three of the included   pared to the control, the HA group demonstrated a statistical-
           trials was classified as unclear since the method of allocation   ly significant reduction in PPD and an increase in RAL (p<0.05)
           was not described. 2,8,9  In two of the studies included allocation   at 12 weeks (Table 1). PI, GI, PPD, and CAL had also improved
           was classified as high-risk 10,11  and in other two as low-risk. 12,13    at 12 weeks (p<0.05) in both groups. Clinically, all indices ex-
           Blinding for participants was well conducted in three tri-  cept CAL had a more statistically significant reduction in tests
           als; 8,12,13  the other trials did not have all the information re-  than controls at 12 weeks. There were statistically significant
           quired for this analysis, so they are classified as unclear 2,9-11   differences between tests and controls at 12 weeks for GI. For
           and considered as having an unclear risk for blinding bias at   PI, no significant differences were found between tests and
           outcome measuring. All of the included studies reported fol-  controls at 12 weeks, with p-values >0.05 (Table 1). PPD at 12
           low-up and whether the proposed outcomes were assessed,   weeks had lower significant levels in tests than controls, at
           as described in the protocol. Subsequently, most studies, after   p=0.4475 with 95% CI (0.0715, 0.8234). Regarding CAL, no sig-
           the risk of bias assessment, were classified as having a high   nificant differences were found between control and test sites
           risk of bias.                                       for all time points. 11
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