Effectiveness of triple antibiotic paste as an intra-canal medication for the root canal treatment of non-vital teeth with apical periodontitis: A systematic review

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This review will assess post-operative pain, flare-up incidence, and clinical and radiographic healing. Methods: Nine electronic databases (Pubmed, CENTRAL, VHL, Scopus, EBSCOhost, Web of Science, Trip, OpenGrey, Proquest) were searched along with two major clinical trial registries. Conference proceedings, reference lists and citations of the included studies were also searched. A total of 537 records were identified and 392 were obtained after duplicate removal. Six records were identified after screening and three studies were included after full text eligibility assessment. Results: Three comparators were reported in the included studies: calcium hydroxide paste, 2% chlorhexidine gel and ledermix paste. There was no statistically significant difference between triple antibiotic paste and calcium hydroxide regarding postoperative pain, and clinical and radiographic healing of periapical lesions. There was no difference between triple antibiotic paste and chlorhexidine regarding flare-up incidence. However, triple antibiotic paste reduced the level of post-operative pain more than ledermix, which was statistically significant. Conclusions: The evidence is still insufficient surrounding the use of triple antibiotic paste; therefore more clinical investigations with high levels of evidence and rigorous methodologies are needed." } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/7-1627", "name": "Effectiveness of triple antibiotic paste as an intra-canal medication..." } } ] } Home Browse Effectiveness of triple antibiotic paste as an intra-canal medication... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Abdel Hamid E, Abdel Aziz S, Sadek HS and Ibrahim AM. Effectiveness of triple antibiotic paste as an intra-canal medication for the root canal treatment of non-vital teeth with apical periodontitis: A systematic review [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2018, 7 :1627 ( https://doi.org/10.12688/f1000research.16423.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Systematic Review Effectiveness of triple antibiotic paste as an intra-canal medication for the root canal treatment of non-vital teeth with apical periodontitis: A systematic review [version 1; peer review: 1 approved, 1 approved with reservations] Ehab Abdel Hamid https://orcid.org/0000-0002-8876-6582 1 , Saied Abdel Aziz https://orcid.org/0000-0002-1035-0093 1 , Hany Samy Sadek 1 , Ahmed Mohamed Ibrahim https://orcid.org/0000-0001-9855-9600 1 Ehab Abdel Hamid https://orcid.org/0000-0002-8876-6582 1 , Saied Abdel Aziz https://orcid.org/0000-0002-1035-0093 1 , Hany Samy Sadek 1 , Ahmed Mohamed Ibrahim https://orcid.org/0000-0001-9855-9600 1 PUBLISHED 11 Oct 2018 Author details Author details 1 Department of Endodontics, Faculty of Oral and Dental Medicine, Cairo University, Cairo, 11553, Egypt Ehab Abdel Hamid Roles: Writing – Review & Editing Saied Abdel Aziz Roles: Supervision Hany Samy Sadek Roles: Supervision Ahmed Mohamed Ibrahim Roles: Writing – Original Draft Preparation OPEN PEER REVIEW DETAILS REVIEWER STATUS Abstract Background: This is a systematic review to assess and provide a pooled effect estimate, if possible, for the effects of triple antibiotic paste as an intra-canal medication for root canal treatment of mature permanent non-vital teeth with apical periodontitis. This review will assess post-operative pain, flare-up incidence, and clinical and radiographic healing. Methods: Nine electronic databases (Pubmed, CENTRAL, VHL, Scopus, EBSCOhost, Web of Science, Trip, OpenGrey, Proquest) were searched along with two major clinical trial registries. Conference proceedings, reference lists and citations of the included studies were also searched. A total of 537 records were identified and 392 were obtained after duplicate removal. Six records were identified after screening and three studies were included after full text eligibility assessment. Results: Three comparators were reported in the included studies: calcium hydroxide paste, 2% chlorhexidine gel and ledermix paste. There was no statistically significant difference between triple antibiotic paste and calcium hydroxide regarding postoperative pain, and clinical and radiographic healing of periapical lesions. There was no difference between triple antibiotic paste and chlorhexidine regarding flare-up incidence. However, triple antibiotic paste reduced the level of post-operative pain more than ledermix, which was statistically significant. Conclusions: The evidence is still insufficient surrounding the use of triple antibiotic paste; therefore more clinical investigations with high levels of evidence and rigorous methodologies are needed. READ ALL READ LESS Keywords Root canal therapy, postoperative pain, nonvital tooth Corresponding Author(s) Ehab Abdel Hamid ( [email protected] ) Close Corresponding author: Ehab Abdel Hamid Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2018 Abdel Hamid E et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Abdel Hamid E, Abdel Aziz S, Sadek HS and Ibrahim AM. Effectiveness of triple antibiotic paste as an intra-canal medication for the root canal treatment of non-vital teeth with apical periodontitis: A systematic review [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2018, 7 :1627 ( https://doi.org/10.12688/f1000research.16423.1 ) First published: 11 Oct 2018, 7 :1627 ( https://doi.org/10.12688/f1000research.16423.1 ) Latest published: 11 Oct 2018, 7 :1627 ( https://doi.org/10.12688/f1000research.16423.1 ) Introduction Pulpal tissue infection initiates inflammation of periapical tissues and results in apical periodontitis 1 . Root canal treatment aims to prevent or manage apical periodontitis by decreasing the intra-canal microbial load 2 . The anatomy of the root canal system makes it almost impossible to completely eliminate the bacteria using conventional mechanical and chemical techniques, even with the highest technical standards 3 . Therefore, an effective intra-canal medication in the root canal is required to kill any remaining bacteria 4 , thereby reducing postoperative pain and inducing periapical healing 5 . Calcium hydroxide has been considered the gold standard for optimally disinfecting root canals; however, it had been reported that Enterococcus faecalis the dominant bacteria in resistant endodontic infections, is resistant to calcium hydroxide 6 . Recently, triple antibiotic paste (a mixture of ciprofloxacin, metronidazole and minocycline) has been used as an intra-canal medication for root canal disinfection 7 . It had been shown that triple antibiotic paste could kill any remaining bacteria in the root canal system 8 . To the best of our knowledge, the effectiveness of triple antibiotic paste as an intra-canal medication in the treatment of non-vital permanent teeth with apical periodontitis hasn’t yet been subjected to systematic review. Thus, the purpose of this study is to systematically review and provide a pooled effect estimate, if possible, for the effects of triple antibiotic paste as an intra-canal medication for root canal treatment of mature permanent non-vital teeth with apical periodontitis. This review will assess post-operative pain, flare-up incidence, and clinical and radiographic healing. Methods This systematic review was reported according to PRISMA Statement 9 . Supplementary File 1 contains the completed PRISMA checklist. The protocol was registered in PROSPERO database, registration number: CRD42018106518 . Eligibility criteria Population: adult patients who had non-vital permanent mature teeth with apical periodontitis or previously root canal-treated teeth with apical periodontitis, undergoing root canal treatment in multiple visits. Primary teeth, immature, vital teeth and single visit root canal treatment were excluded. Intervention: triple antibiotic paste, which is a mixture of ciprofloxacin, metronidazole and minocycline. Comparators: placebo, no intra-canal medication or any other intra-canal medication other than the intervention. Outcome measures: primary outcomes were post-operative pain and flare-up incidence after the first visit as defined by the trial authors. Secondary outcome was clinical and radiographic healing as defined by the trial authors with at least one year follow-up. Study designs: randomized and quasi randomized controlled clinical trials were included. Non-randomized clinical trials, observational, i n vitro or animal studies were excluded. Other: there were no restrictions on language, timing or settings. Information sources The following electronic databases were searched: CENTRAL , Medline via Pubmed , Virtual Health Library , Trip , Scopus , Web of Science , EBSCOhost , OpenGrey , ProQuest thesis and dissertation. Ongoing clinical trial registries were searched: ICTRP and ClinicalTrials.gov. The search was conducted until 5/7/2018. Other sources included searching reference lists of included studies and relevant systematic reviews 10 , 11 , citation searching of included studies done in Google Scholar and searching conference proceedings of International Association of Dental Research (IADR), European Society of Endodontology (ESE) and American Association of Endodontists (AAE). Search strategy was conducted using free text terms and controlled terms (MeSH) regarding the population and intervention. A sensitivity and precision filter maximizing randomized clinical trials was used in PubMed to help identify randomized clinical trials as recommended by Cochrane handbook 12 . The full search strategy for CENTRAL database is shown in Table 1 . Table 1. Full search strategy used for CENTRAL database. ID Search Number of hits #1 triple antibiotic paste 57 #2 tri antibiotic paste 12 #3 tri-antibiotic paste 1 #4 triantibiotic paste 1 #5 TAP 1786 #6 antibiotic paste 153 #7 antibiotic mix 124 #8 {or #1-#7} 2042 #9 MeSH descriptor: [Root Canal Therapy] explode all trees 1051 #10 endodontic 1178 #11 endodontic therapy 569 #12 endodontic treatment 701 #13 endodontic filling 311 #14 endodontically treated teeth 228 #15 root canal therapy 926 #16 root canal treatment 909 #17 root canal filling 671 #18 {or #9-#17} 2225 #19 intracanal medication 60 #20 intra-canal medication 7 #21 root canal medication 138 #22 intra-canal medicament 1 #23 intracanal medicament 43 #24 root canal medicament 61 #25 intra-canal dressing 4 #26 intracanal dressing 42 #27 root canal dressing 75 #28 intracanal disinfectant 4 #29 intra-canal disinfectant 0 #30 root canal disinfictant 0 #31 {or #19-#30} 242 #32 #8 and #31 and #18 19 Study selection After searching the electronic sources 534 records were identified, and an additional three records were identified through searching other sources. After duplicate removal by Endnote X7 reference manager software, 392 records were identified. Two independent reviewers (EAH, AMI) screened the search results by title and abstract then by full text assessment to determine included studies. Data collection process A data extraction sheet was written according to the main data extraction items recommended by the Cochrane handbook 12 . Data items The following items were extracted from each included study: methods - study design, setting and country; participants - selection criteria, tooth type, tooth condition, diagnostic criteria, gender/age, number randomized/analyzed and unit of randomization/analysis; interventions - groups, cleaning and shaping technique, irrigation method, intra-canal medication placement technique and period; outcomes - outcome domain, outcome measurement, time points and the outcome assessor. Risk of bias To assess the risk of bias in the included randomized clinical trials, the revised RoB 2.0 domain-based tool was used 13 to assess the risk of bias in the included randomized clinical trials. Studies were judged to be of “low risk”, “some concerns of risk” or “high risk” based on these domains: bias arising from the randomization process, bias due to deviation from intended interventions, bias due to missing outcome data, bias in measurement of the outcome and bias in selection of the reported results. The individually randomized, parallel group trials template of the RoB 2.0 tool was used on the outcome level for each study. Summary measures and data synthesis Single tooth or a patient with a single tooth was chosen as a unit of analysis. For dichotomous outcome, risk ratio and its 95% CI was used as a measure for the effect size. For the continuous outcome, mean difference and its 95% CI was used as a measure for the effect size. Meta-analysis was not possible due to studies assessing different outcomes and could not be combined. A qualitative synthesis was done instead. Results Study selection After screening 392 records by title and abstract; 386 records were irrelevant, Six records were identified for full text eligibility assessment: one study 14 was excluded due to using another combination of antibiotics (metronidazole, ciprofloxacin and clindamycin); two studies were awaiting assessment due to unavailable full text 15 and no separate results for non-vital teeth 16 (the authors of these previous two studies were contacted to obtain the missing data with no response). Therefore, three studies 17 – 19 were included in this systematic review ( Figure 1 ). Figure 1. PRISMA flow chart showing identification and selection process of articles included. Study characteristics Characteristics of the included studies are presented in Table 2 . All the included studies were randomized parallel multi-arm clinical trials conducted in a single center. The settings of the included studies were done in university or dental college hospitals. There were two studies 17 , 18 in India and one study in Turkey 19 . A total of 171 patients with 174 teeth were enrolled in the three included studies and 167 teeth were analyzed. All types of teeth were included, either single or multiple rooted teeth. Table 2. Characteristics of the included studies. Study ID Study design Participants Age (years) Number of patients Groups Cleaning/ shaping Period of ICM placement Outcome domain Tool of measurement Time points J ohns et al . 2014 12 RCT Patients who had periapical lesions in the maxillary anterior region 15–30 60 Ca(OH) 2 TAP PAD Step back with K files and 1% NaOCL solution Not mentioned Treatment success and failure Clinical and radiographic assessment 3,6,12,18 months S inhal et al . 2017 15 RCT Diabetic patients with primary endodontic lesion ≥ 20 36 Ca(OH) 2 TAP CHX Crown down technique and 2.5% NaOCL solution 2 weeks Incidence of inter- appointment flare-up VRS 1,2,3,7,14 days U yan et al . 2018 16 RCT Failed asymptomatic root-canal- treated permanent maxillary and mandibular multi-rooted teeth with a periapical lesion 2–5 mm 18–45 75 patients (78 teeth), single visit Ledermix TAP Ca(OH) 2 Protaper retreatment kit with no solvents, 2.5% NaOCL solution 1 week Post- operative pain intensity Heft parker VAS 0–170 mm 6,12,24,48 hours RCT, randomized clinical trial; Ca (OH) 2 , calcium hydroxide paste; TAP, triple antibiotic paste; PAD, Photo activated disinfection; CHX, chlorhexidine; ICM, intra-canal medication; VRS, verbal rating scale; VAS, visual analogue scale. The intervention of interest was a combination of three antibiotics (metronidazole, ciprofloxacin and minocycline) mixed with inert vehicles to form a paste. In the included studies, three comparators were reported - either calcium hydroxide paste, 2% chlorhexidine gel or ledermix paste. J ohns et al . 2014 17 evaluated clinical and radiographic healing of periapical lesions in which treatment success was based on either strict criteria (absence of clinical signs and symptoms with complete radiographic healing) or loose criteria (absence of clinical signs and symptoms with complete healing or reduction of lesion size). U yan et al . 2018 19 evaluated postoperative pain after root canal retreatment. S inhal et al . 2017 18 evaluated incidence of interappointment flare up in diabetic patients in which flare-up incidence was defined as score 4 and 5 of the verbal rating scale. Risk of bias assessment Risk of bias summary is presented in Table 3 . Two studies 17 , 18 had overall high risk of bias due to high risk of bias in domains regarding bias in selection of the reported results and bias in the measurement of the outcome. One study 18 reported the results of flare-up incidence with no time points, while the other study 17 reported only the results of clinical and radiographic healing for one time point and did not mention any data about the blinding of the outcome assessors. Table 3. Risk of bias summary. Study ID Bias arising from randomization Bias due to deviation from intended interventions Bias due to missing data Bias in measurement of the outcome Bias in the selection of reported results Overall bias Post-operative pain U yan et al . 2018 16 Low risk Low risk Low risk Low risk Low risk Low risk Flare up incidence U yan et al . 2018 16 Low risk Low risk Low risk Low risk Low risk Low risk S inhal et al . 2017 15 Some concerns Low risk Some concerns Low risk High risk High risk Radiographic healing J ohns et al . 2014 12 Low risk Low risk Low risk High risk High risk High risk Results of individual studies It was not possible to combine the results of the studies in a meta-analysis, due to different outcomes being assessed with different time points and one study was reported in each outcome. A narrative synthesis was done for each study separately. Triple antibiotic paste VS calcium hydroxide . Regarding post-operative pain, U yan et al . 2018 19 found that at six hours, the mean and standard deviation values for pain intensity were 24.44 ± 3.13 in the triple antibiotic paste group and were 19.77 ± 3.18 for calcium hydroxide (mean difference = 4.67, 95% CI 2.72-6.63). At 12 hours, the mean and standard deviation values for pain intensity were 40.15 ± 3.54 in the triple antibiotic paste group and were 28.38 ± 3.59 for calcium hydroxide (mean difference = 11.77, 95% CI 9.56-13.98). At 24 hours, the mean and standard deviation values for pain intensity were 44.95 ± 3.51 in the triple antibiotic paste group and were 36.92 ± 3.56 for calcium hydroxide (mean difference = 8.04, 95% CI 5.85-10.23). At 48 hours, the mean and standard deviation values for pain intensity were 36.82 ± 3.14 in the triple antibiotic paste group and were 38.75 ± 3.19 for calcium hydroxide (mean difference = -1.93, 95% CI -3.89-0.03) after first visit of treatment. Calcium hydroxide decreased the level of post-operative pain more than triple antibiotic paste in a statistically significant way at 6, 12 and 24 hours. There was no statistically significant difference at 48 hours. Regarding flare-up incidence, S inhal et al . 2017 18 reported that 40% of patients in calcium hydroxide group experienced interappointment flare-up, with no flare-up seen in triple antibiotic paste group. However, the presented data in this study was insufficient to calculate the effect size and its 95% confidence intervals. U yan et al . 2018 19 reported no flare-up incidence with either calcium hydroxide or triple antibiotic paste groups. Regarding clinical and radiographic healing, J ohns et al . 2014 17 presented data only at 18 months follow-up. Based on the strict criteria of success, 13 out of 20 participants were healed in the triple antibiotic paste group and 7 out of 20 participants were healed in calcium hydroxide group (RR 1.86, 95% CI 0.94-3.66). Based on the loose criteria of success, 19 out of 20 participants were healed in triple antibiotic paste group and 17 out of 20 participants were healed in calcium hydroxide group (RR 1.12, 95% CI 0.91-1.38). There was no statistically significant difference between the two groups at 18 months follow-up based on either of the criteria of success. Triple antibiotic paste VS 2% chlorhexidine gel . Only flare-up incidence was evaluated by S inhal et al . 2017 18 , who reported no flare-up incidence in either chlorhexidine or triple antibiotic paste groups. However, the presented data in this study was insufficient to calculate the effect size and its 95% confidence intervals. Triple antibiotic paste VS ledermix paste . Regarding post-operative pain, U yan et al . 2018 19 found that at six hours, the mean and standard deviation values for pain intensity were 24.44 ± 3.13 for triple antibiotic paste and were 54.89 ± 3.31 for ledermix (mean difference = -30.45, 95% CI -32.47 to -28.43). At 12 hours, the mean and standard deviation values for pain intensity were 40.15 ± 3.54 in the triple antibiotic paste group and were 64.27 ± 3.74 for ledermix (mean difference = -24.12, 95% CI -26.41 to -21.83). At 24 hours, the mean and standard deviation values for pain intensity were 44.95 ± 3.51 in the triple antibiotic paste group and were 61.77 ± 3.71 for ledermix (MD -16.82, 95% CI -19.09 to -14.55). At 48 hours, the mean and standard deviation values for pain intensity were 36.82 ± 3.14 in the triple antibiotic paste group and were 44.32 ± 3.32 for ledermix (mean difference = -7.50, 95% CI -9.53 to -5.47) after first visit of treatment. Triple antibiotic paste reduced the level of post-operative pain more than ledermix in a statistically significant way at all time points. Regarding flare-up incidence, U yan et al . 2018 19 reported no flare-up incidence with either triple antibiotic paste or ledermix groups. Discussion Use of antibiotics agents had been suggested by various authors for the eradication of bacteria associated with persistent endodontic infections 20 . Due to side effects of systemic application, and ineffectiveness in necrotic teeth, local application of antibiotics would be more effective in endodontics 21 . Research showed that a combination of metronidazole, ciprofloxacin and minocycline could destroy any bacteria in the infected root canal dentin and periapical lesions 8 . The purpose of this systematic review was to assess the effectiveness of triple antibiotic paste as an intra-canal medication for endodontic treatment of non-vital teeth with apical periodontitis in terms of post-operative pain, flare-up incidence, clinical and radiographic healing. The search strategy in this systematic review was comprehensive to identify all published and unpublished articles. Seven electronic databases were searched along with two clinical trial registries. Also, grey literature, conference proceedings, backward and forward searches were included in the search strategy to identify all relevant articles. Risk of bias was assessed using the revised RoB 2.0 tool 13 , which had some advantages over the originally developed tool in the Cochrane handbook 12 . The RoB 2.0 tool assessed risk of bias on outcome level for each study and provided templates for different study designs at which the overall risk of bias assessment was easier to reach. Regarding post-operative pain, the evidence could be regarded as insufficient since only one study 19 provided data for this outcome. Also, this study suffered from some limitations such as: adding new patients to replace the ones that were lost to follow-up, excluding patients from the analysis after treatment and unclear unit of randomization and analysis, since the number of teeth exceeded the number of patients with no mention if they were randomized an equal number of times. Therefore, this study had a unit of analysis issue 22 . Regarding flare-up incidence, the evidence could be regarded as insufficient since only one study 18 that had high risk of bias reported data for this outcome, which was insufficient to calculate the effect size and its 95% confidence intervals. Regarding clinical and radiographic healing, the evidence could be regarded as insufficient since it was provided by one study 17 that had high risk of bias. One of the limitations of this review is the low numbers of studies that were identified despite the comprehensive search strategy conducted. Also, there were two studies awaiting assessment 15 , 16 , which, if they were available, might have changed the results of this review. Most of the studies suffered from high risk of bias so that the results of the included studies should be interpreted with caution. It could be concluded that, the evidence of effectiveness of triple antibiotic paste is insufficient regarding post-operative pain, flare-up incidence, and clinical and radiographic healing. The number of randomized clinical studies assessing triple antibiotic paste effectiveness as an intra-canal medication is few. Consequently, we recommend conducting clearly reported, well designed, high quality, large randomized clinical trials to assess the effectiveness of triple antibiotic paste as an intra-canal medication in endodontic treatment of non-vital teeth with apical periodontitis or failed cases concerning relevant patient outcomes. Data availability All data underlying the results are available as part of the article and no additional source data are required. Grant information The author(s) declared that no grants were involved in supporting this work. Supplementary material Supplementary File 1: PRISMA checklist. Click here to access the data Faculty Opinions recommended References 1. Sundqvist G: Bacteriologic studies of necrotic dental pulps [PhD thesis]. Umeå, Sweden: University of Umeå ; 1976. Reference Source 2. Möller AJ, Fabricius L, Dahlén G, et al. : Influence on periapical tissues of indigenous oral bacteria and necrotic pulp tissue in monkeys. Scand J Dent Res. 1981; 89 (6): 475–84. PubMed Abstract | Publisher Full Text 3. Gursoy H, Ozcakir-Tomruk C, Tanalp J, et al. : Photodynamic therapy in dentistry: a literature review. Clin Oral Investig. 2013; 17 (4): 1113–25. PubMed Abstract | Publisher Full Text 4. Spångberg LSW, Haapasalo M: Rationale and efficacy of root canal medicaments and root filling materials with emphasis on treatment outcome. Endod Topics. 2002; 2 (1): 35–58. Publisher Full Text 5. Calişkan MK: Prognosis of large cyst-like periapical lesions following nonsurgical root canal treatment: a clinical review. Int Endod J. 2004; 37 (6): 408–16. 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PubMed Abstract | Publisher Full Text | Free Full Text 10. Anjaneyulu K, Nivedhitha MS: Influence of calcium hydroxide on the post-treatment pain in Endodontics: A systematic review. J Conserv Dent. 2014; 17 (3): 200–7. PubMed Abstract | Publisher Full Text | Free Full Text 11. Sanu N, Sindhu R: Comparative evaluation of postoperative pain with different intracanal medicaments? A Systematic Review. AJPTR. 2016; 6 (5): 34–61. Reference Source 12. Higgins JPT, Green S: Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Reference Source 13. Higgins JPT, Sterne JAC, Savović J, et al. : A revised tool for assessing risk of bias in randomized trials. In: CHANDLER J, MCKENZIE J, BOUTRON I, WELCH V (editors). Cochrane Methods. Cochrane Database of Systematic Reviews , 2016. 14. Prasad LK, Tanwar BS, Kumar KN: Comparison of calcium hydroxide and triple antibiotic paste as intracanal medicament in emergency pain reduction: in vivo study. Int J Oral Care Res. 2016; 4 (4): 244–6. Publisher Full Text 15. Sanu N, Sindhu R: Comparative evaluation of inter appointment pain with calcium hydroxide and triple antibiotic paste as intracanal medicaments in patients with apical periodontitis: A randomized controlled clinical trial. J Dent Res. 2016; 95 : 0272. Reference Source 16. Pai S, Vivekananda Pai AR, Thomas MS, et al. : Effect of calcium hydroxide and triple antibiotic paste as intracanal medicaments on the incidence of inter-appointment flare-up in diabetic patients: An in vivo study. J Conserv Dent. 2014; 17 (3): 208–11. PubMed Abstract | Publisher Full Text | Free Full Text 17. Johns DA, Varughese JM, Thomas K, et al. : Clinical and radiographical evaluation of the healing of large periapical lesions using triple antibiotic paste, photo activated disinfection and calcium hydroxide when used as root canal disinfectant. J Clin Exp Dent. 2014; 6 (3): e230–6. PubMed Abstract | Publisher Full Text | Free Full Text 18. Sinhal TM, Shah RRP, Shah N, et al. : Comparative evaluation of 2% chlorhexidine gel and triple antibiotic paste with calcium hydroxide paste on incidence of interappointment flare-up in diabetic patients: A randomized double-blinded clinical study. Endodontology. 2017; 29 (2): 136–41. Publisher Full Text 19. Uyan HM, Olcay K, Özcan M: Comparative evaluation of postoperative pain intensity after single-visit and multiple-visit retreatment cases: a prospective randomized clinical trial. Brazilian Dent Sci. 2018; 21 (1): 26–36. Publisher Full Text 20. Abbott PV: Medicaments: aids to success in endodontics. Part 2. Clinical recommendations. Aust Dent J. 1990; 35 (6): 491–496. PubMed Abstract | Publisher Full Text 21. Mohammadi Z, Abbott PV: On the local applications of antibiotics and antibiotic-based agents in endodontics and dental traumatology. Int Endod J. 2009; 42 (7): 555–67. PubMed Abstract | Publisher Full Text 22. Fergusson D, Aron SD, Guyatt G, et al. : Post-randomisation exclusions: the intention to treat principle and excluding patients from analysis. BMJ. 2002; 325 (7365): 652–4. PubMed Abstract | Publisher Full Text | Free Full Text Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 11 Oct 2018 ADD YOUR COMMENT Comment Author details Author details 1 Department of Endodontics, Faculty of Oral and Dental Medicine, Cairo University, Cairo, 11553, Egypt Ehab Abdel Hamid Roles: Writing – Review & Editing Saied Abdel Aziz Roles: Supervision Hany Samy Sadek Roles: Supervision Ahmed Mohamed Ibrahim Roles: Writing – Original Draft Preparation Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (1) version 1 Published: 11 Oct 2018, 7:1627 https://doi.org/10.12688/f1000research.16423.1 Copyright © 2018 Abdel Hamid E et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Abdel Hamid E, Abdel Aziz S, Sadek HS and Ibrahim AM. Effectiveness of triple antibiotic paste as an intra-canal medication for the root canal treatment of non-vital teeth with apical periodontitis: A systematic review [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2018, 7 :1627 ( https://doi.org/10.12688/f1000research.16423.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 11 Oct 2018 Views 0 Cite How to cite this report: Aggarwal V. Reviewer Report For: Effectiveness of triple antibiotic paste as an intra-canal medication for the root canal treatment of non-vital teeth with apical periodontitis: A systematic review [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2018, 7 :1627 ( https://doi.org/10.5256/f1000research.17944.r90674 ) The direct URL for this report is: https://f1000research.com/articles/7-1627/v1#referee-response-90674 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 29 Jul 2021 Vivek Aggarwal , Department of Conservative Dentistry and Endodontics, Faculty of Dentistry, Jamia Millia Islamia, New Delhi, Delhi, India Approved VIEWS 0 https://doi.org/10.5256/f1000research.17944.r90674 The authors have presented a systematic review evaluating the efficacy of triple antibiotic paste (vs other medications) in patients with apical periodontitis. The study has been initially published on 11-Oct-2018. This is an invited review (invitation by the Editorial Team, ... Continue reading READ ALL The authors have presented a systematic review evaluating the efficacy of triple antibiotic paste (vs other medications) in patients with apical periodontitis. The study has been initially published on 11-Oct-2018. This is an invited review (invitation by the Editorial Team, F1000Research, and dated 28-Jul 2021) of this paper. Triple antibiotic pastes are commonly used in regenerative endodontics. However, potential discoloration has led to the use of double antibiotic paste. Since the review is performed 3 years after the publication of the study, I shall limit my comments to the methodology and the reliability of the data. The systematic review (SR) and meta-analysis are considered the highest evidence for treatment planning. The SRs require a ‘priori’ design/protocol to be prospectively registered at databases such as PROSPERO. This manuscript has been registered at PROSPERO on 28-Aug-2018 and subsequently revised on 31-Oct-2018. The protocol matches with the reported data and there has been no selective reporting. Introduction: A rationale for the study is required. The introduction should be expanded to include a suitable background for this study. For an accurate SR analysis, a good PICO question should be developed. The current review states ‘primary outcomes were post-operative pain and flare-up incidence after the first visit as defined by the trial authors. The secondary outcome was clinical and radiographic healing as defined by the trial authors with at least one-year follow-up’. Out of three included studies, Johns et al . did not evaluate the post-operative pain (i.e. the primary outcome), and rest other two studies did not evaluate the secondary outcome. Considering the limitations of the data, the authors have accurately decided to perform a narrative review. It would be better to report the 95% confidence intervals for all the data. Raw data, if required, can be requested from the individual authors. Are the rationale for, and objectives of, the Systematic Review clearly stated? Partly Are sufficient details of the methods and analysis provided to allow replication by others? Yes Is the statistical analysis and its interpretation appropriate? Not applicable Are the conclusions drawn adequately supported by the results presented in the review? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: There are limited studies on this topic. The authors have included all the studies and presented a narrative review. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Aggarwal V. Reviewer Report For: Effectiveness of triple antibiotic paste as an intra-canal medication for the root canal treatment of non-vital teeth with apical periodontitis: A systematic review [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2018, 7 :1627 ( https://doi.org/10.5256/f1000research.17944.r90674 ) The direct URL for this report is: https://f1000research.com/articles/7-1627/v1#referee-response-90674 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Pai ARV and Kumbargere Nagraj S. Reviewer Report For: Effectiveness of triple antibiotic paste as an intra-canal medication for the root canal treatment of non-vital teeth with apical periodontitis: A systematic review [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2018, 7 :1627 ( https://doi.org/10.5256/f1000research.17944.r45204 ) The direct URL for this report is: https://f1000research.com/articles/7-1627/v1#referee-response-45204 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 23 May 2019 A. R. Vivekananda Pai , Department of Conservative Dentistry and Endodontics, Faculty of Dentistry, Melaka-Manipal Medical College (Manipal Academy of Higher Education [MAHE]), Malacca City, Malaysia Sumanth Kumbargere Nagraj , Department of Oral Medicine and Oral Radiology, Faculty of Dentistry, Melaka-Manipal Medical College (Manipal Academy of Higher Education [MAHE]), Malacca City, Malaysia Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.17944.r45204 Introduction: No comments. Methods: The authors have to mention if the data was extracted in duplicate or not. If so, who were those authors? ... Continue reading READ ALL Introduction: No comments. Methods: The authors have to mention if the data was extracted in duplicate or not. If so, who were those authors? If not, why was it not considered? Same applies to risk of bias assessment. "Risk of bias" could be abbreviated as "RoB" when it is used as a term for the first time in the text as the expanded word for the abbreviation RoB, which is mostly stated in the text as a tool, is not found. Risk of bias table should have quotes or relevant statements from the article to justify the risk judgement. It is not clear what measures were adopted to address any disagreement among the authors while following methodology such as data extraction and risk of bias assessment. It is not clear why the randomized clinical trial (RCT) filter was not used in the search strategy. As there were no restrictions in the language, the authors could have searched in Asian and Latin American databases. The search dates for each database are not clear. It is good practice to grade the quality of evidence. Discussion: Suggested grammatical corrections: Page no. 7, Paragraph no. 1, Sentence line no. 12: - Stated as: post-operative pain, flare-up incidence, clinical and radiographic healing. - Suggested correction: post-operative pain, flare-up incidence, and clinical and radiographic healing. Page no. 7, Paragraph no. 6, Sentence line no. 4: - Stated as: assessment 15,16 , which, if they were available, might have… - Suggested correction: assessment 15,16 , which if were available, might have… Page no. 7, Paragraph no. 7, Sentence line no. 4-6: - Stated as: The number of randomized clinical studies assessing triple antibiotic paste effectiveness as an intra-canal medication is few. - Suggested correction: The number of randomized clinical studies assessing triple antibiotic paste effectiveness as an intra-canal medication is less. Note: Since the answer is "Partly" to the 2nd evaluation criteria in the peer review form i.e. “Are sufficient details of the methods and analysis provided to allow replication by others?”, the following suggestions are recommended to the authors: Need for data extraction and risk of bias assessment in duplicate. Provide quotes or relevant statements from the article to justify the risk judgement in the risk of bias table. State clearly measures adopted to address any disagreement among the authors during data extraction and risk of bias assessment. Use randomized clinical trial (RCT) filter in the search strategy. Further search for articles in Asian and Latin American databases. State the search dates for each database. Specify the grade of the quality of evidence. Are the rationale for, and objectives of, the Systematic Review clearly stated? Yes Are sufficient details of the methods and analysis provided to allow replication by others? Partly Is the statistical analysis and its interpretation appropriate? Yes Are the conclusions drawn adequately supported by the results presented in the review? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Dr A. R. Vivekananda Pai: Restorative dental materials, Restorative & Esthetic dentistry, and Endodontics. Dr Sumanth Kumbargere Nagraj: Evidence Based Health Care. We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however we have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Pai ARV and Kumbargere Nagraj S. Reviewer Report For: Effectiveness of triple antibiotic paste as an intra-canal medication for the root canal treatment of non-vital teeth with apical periodontitis: A systematic review [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2018, 7 :1627 ( https://doi.org/10.5256/f1000research.17944.r45204 ) The direct URL for this report is: https://f1000research.com/articles/7-1627/v1#referee-response-45204 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 11 Oct 2018 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 1 11 Oct 18 read read A. R. Vivekananda Pai , Melaka-Manipal Medical College (Manipal Academy of Higher Education [MAHE]), Malacca City, Malaysia Sumanth Kumbargere Nagraj , Melaka-Manipal Medical College (Manipal Academy of Higher Education [MAHE]), Malacca City, Malaysia Vivek Aggarwal , Jamia Millia Islamia, New Delhi, India Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2021 Aggarwal V. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 29 Jul 2021 | for Version 1 Vivek Aggarwal , Department of Conservative Dentistry and Endodontics, Faculty of Dentistry, Jamia Millia Islamia, New Delhi, Delhi, India 0 Views copyright © 2021 Aggarwal V. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The authors have presented a systematic review evaluating the efficacy of triple antibiotic paste (vs other medications) in patients with apical periodontitis. The study has been initially published on 11-Oct-2018. This is an invited review (invitation by the Editorial Team, F1000Research, and dated 28-Jul 2021) of this paper. Triple antibiotic pastes are commonly used in regenerative endodontics. However, potential discoloration has led to the use of double antibiotic paste. Since the review is performed 3 years after the publication of the study, I shall limit my comments to the methodology and the reliability of the data. The systematic review (SR) and meta-analysis are considered the highest evidence for treatment planning. The SRs require a ‘priori’ design/protocol to be prospectively registered at databases such as PROSPERO. This manuscript has been registered at PROSPERO on 28-Aug-2018 and subsequently revised on 31-Oct-2018. The protocol matches with the reported data and there has been no selective reporting. Introduction: A rationale for the study is required. The introduction should be expanded to include a suitable background for this study. For an accurate SR analysis, a good PICO question should be developed. The current review states ‘primary outcomes were post-operative pain and flare-up incidence after the first visit as defined by the trial authors. The secondary outcome was clinical and radiographic healing as defined by the trial authors with at least one-year follow-up’. Out of three included studies, Johns et al . did not evaluate the post-operative pain (i.e. the primary outcome), and rest other two studies did not evaluate the secondary outcome. Considering the limitations of the data, the authors have accurately decided to perform a narrative review. It would be better to report the 95% confidence intervals for all the data. Raw data, if required, can be requested from the individual authors. Are the rationale for, and objectives of, the Systematic Review clearly stated? Partly Are sufficient details of the methods and analysis provided to allow replication by others? Yes Is the statistical analysis and its interpretation appropriate? Not applicable Are the conclusions drawn adequately supported by the results presented in the review? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise There are limited studies on this topic. The authors have included all the studies and presented a narrative review. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Aggarwal V. Peer Review Report For: Effectiveness of triple antibiotic paste as an intra-canal medication for the root canal treatment of non-vital teeth with apical periodontitis: A systematic review [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2018, 7 :1627 ( https://doi.org/10.5256/f1000research.17944.r90674) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/7-1627/v1#referee-response-90674 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2019 Pai A et al. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 23 May 2019 | for Version 1 A. R. Vivekananda Pai , Department of Conservative Dentistry and Endodontics, Faculty of Dentistry, Melaka-Manipal Medical College (Manipal Academy of Higher Education [MAHE]), Malacca City, Malaysia Sumanth Kumbargere Nagraj , Department of Oral Medicine and Oral Radiology, Faculty of Dentistry, Melaka-Manipal Medical College (Manipal Academy of Higher Education [MAHE]), Malacca City, Malaysia 0 Views copyright © 2019 Pai A et al. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Introduction: No comments. Methods: The authors have to mention if the data was extracted in duplicate or not. If so, who were those authors? If not, why was it not considered? Same applies to risk of bias assessment. "Risk of bias" could be abbreviated as "RoB" when it is used as a term for the first time in the text as the expanded word for the abbreviation RoB, which is mostly stated in the text as a tool, is not found. Risk of bias table should have quotes or relevant statements from the article to justify the risk judgement. It is not clear what measures were adopted to address any disagreement among the authors while following methodology such as data extraction and risk of bias assessment. It is not clear why the randomized clinical trial (RCT) filter was not used in the search strategy. As there were no restrictions in the language, the authors could have searched in Asian and Latin American databases. The search dates for each database are not clear. It is good practice to grade the quality of evidence. Discussion: Suggested grammatical corrections: Page no. 7, Paragraph no. 1, Sentence line no. 12: - Stated as: post-operative pain, flare-up incidence, clinical and radiographic healing. - Suggested correction: post-operative pain, flare-up incidence, and clinical and radiographic healing. Page no. 7, Paragraph no. 6, Sentence line no. 4: - Stated as: assessment 15,16 , which, if they were available, might have… - Suggested correction: assessment 15,16 , which if were available, might have… Page no. 7, Paragraph no. 7, Sentence line no. 4-6: - Stated as: The number of randomized clinical studies assessing triple antibiotic paste effectiveness as an intra-canal medication is few. - Suggested correction: The number of randomized clinical studies assessing triple antibiotic paste effectiveness as an intra-canal medication is less. Note: Since the answer is "Partly" to the 2nd evaluation criteria in the peer review form i.e. “Are sufficient details of the methods and analysis provided to allow replication by others?”, the following suggestions are recommended to the authors: Need for data extraction and risk of bias assessment in duplicate. Provide quotes or relevant statements from the article to justify the risk judgement in the risk of bias table. State clearly measures adopted to address any disagreement among the authors during data extraction and risk of bias assessment. Use randomized clinical trial (RCT) filter in the search strategy. Further search for articles in Asian and Latin American databases. State the search dates for each database. Specify the grade of the quality of evidence. Are the rationale for, and objectives of, the Systematic Review clearly stated? Yes Are sufficient details of the methods and analysis provided to allow replication by others? Partly Is the statistical analysis and its interpretation appropriate? Yes Are the conclusions drawn adequately supported by the results presented in the review? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Dr A. R. Vivekananda Pai: Restorative dental materials, Restorative & Esthetic dentistry, and Endodontics. Dr Sumanth Kumbargere Nagraj: Evidence Based Health Care. We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however we have significant reservations, as outlined above. reply Respond to this report Responses (0) Pai ARV and Kumbargere Nagraj S. Peer Review Report For: Effectiveness of triple antibiotic paste as an intra-canal medication for the root canal treatment of non-vital teeth with apical periodontitis: A systematic review [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2018, 7 :1627 ( https://doi.org/10.5256/f1000research.17944.r45204) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/7-1627/v1#referee-response-45204 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. 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