Author's response to reviews Title:Is there a place for Tooth Mousse(R) in the prevention and treatment of early dental caries? A systematic review. Authors: Sarah L Raphael (sarah.raphael@sydney.edu.au) Anthony S Blinkhorn (anthony.blinkhorn@sydney.edu.au) Version:4Date:30 July 2015 Author's response to reviews: see over
Dr Sarah Raphael 30 July, 2015 The Editors BMC Oral Health Journal RE: Article entitled Is there a place for Tooth Mousse in the prevention and treatment of dental early caries? A systematic review. Authors: Sarah Raphael and Anthony Blinkhorn. MS: 1816462470164267 Please find the revised article uploaded on the biomed central website. Outlined on the following page is a point-by-point response addressing the points in the reviewer s report and how they are reflected in the revised article. With regard to the editorial requests please also find attached a completed PRISMA checklist and the PRISMA flowchart included as the new Figure 1 for the manuscript. There have been no amendments with regard to Acknowledgements as there are no additional people who have made a contribution to this paper. All of the stages of the review and writing of the paper have been performed by the two authors. The format of the figures and references have been amended to conform with the journal style. With kind regards Sarah Raphael Dr Sarah Raphael BDS, MDSC, GRAD CERT (HIGHER ED), FRACDS, ICD, PFA Faculty of Dentistry The University of Sydney 1 Mons Road WESTMEAD NSW 2145 T +61 4 12918848 T +61 2 92295748 E sarah.raphael@sydney.edu.au
Response to Reviewer s Report: Title 1. We dispute the assertion that TM and TM Plus have only been used to reduce demineralisation and promote remineralistion, not to treat caries lesions made by the reviewer. Please see below the titles of 3 articles included in this systematic review Sitthisettapong T, Phantumvanit P, Huebner C, Derouen T. Effect of CPP-ACP paste on dental caries in primary teeth: a randomized trial. J Dent Res 2012;91(9):847-52. Plonka KA, Pukallus ML, Holcombe TF, et al. Randomized controlled trial: a randomized controlled clinical trial comparing a remineralizing paste with an antibacterial gel to prevent early childhood caries. Pediatr Dent 2013;35(1):8-12. Altenburger MJ, Gmeiner B, Hellwig E, Wrbas KT, Schirrmeister JF. The evaluation of fluorescence changes after application of casein phosphopeptides (CPP) and amorphous calcium phosphate (ACP) on early carious lesions. Am J Dent 2010;23(4):188-92. We have therefore modified the title to Is there a place for Tooth Mousse in the prevention and treatment of early dental caries? A systematic review. Lines 4-5 Abstract 2. Method. Addition of statement regarding inclusion criteria: Inclusion criteria were clinical trials of participants of any age, comparing the use of Tooth Mousse (MI Paste ) or Tooth Mousse Plus (MI Paste Plus ) to a routine oral care regimen and reporting recognised clinical outcome measures or early caries lesions. Lines 34-37 3. Inclusion criteria have been documented in Table 1 and added to the Methods section 4. The results section of the abstract has been amended: The overall findings of this review did not show any significant benefits of using Tooth Mousse (MI Paste ) products over brushing with a fluoride toothpaste for the prevention of early dental caries. With regard to the regression of white spot lesions in orthodontic patients there is a tendency towards a benefit for the use of Tooth Mousse (MI Paste ) but the quality of evidence is limited. There is a lack of evidence to support the use of Tooth Mousse Plus (MI Paste Plus ) over Tooth Mousse (MI Paste ) at this time. Lines 43-48
5. The Conclusion of the abstract has been reworded: This review suggests that further well-designed randomized controlledtrials are required prior to the widespread recommendation of Tooth Mousse products for the prevention and treatment of early dental caries in the general population. Lines 50-52 Introduction 6. The introduction sets the scene for the systematic review and includes a discussion of the two main materials being reviewed and the role of fluoride products in the prevention of caries. 7. Line 111: Amended to: Placement of pit and fissure sealants, to address the increase in occlusal caries 13. Line 94 8. Line 134: References added: Reynolds EC ADJ 2008; 53: 268-73. Cross KJ et al. Biomaterials 2004; 25: 5061-69. Line 115 9. Line 147: Amended to The aim of the systematic review is to answer the question. Is there sufficient clinical evidence available to support the use of Tooth Mousse and Tooth Mousse Plus over a routine fluoride oral care regimen for the prevention and treatment of dental caries? Lines 128-130 Methods 10. The one reference that contained both an in vitro and in vivo study Uysal et al. 2010 is able to be included in the review as the in vivo study and results are reported separately to the in vitro study. The in vivo study was a single-blinded controlled trial and therefore meets the inclusion criteria. 11. The inclusion and exclusion criteria can be found in the newly created Table 1. The suggestions of the reviewer have also been addressed in the revised methods and results sections of the paper. 12. The limited years of searching have been addressed in the methods and results section of the paper. It is not possible to extend the literature search to 2015. However, now that the literature search date is identified readers are informed of the time limits of the systematic review. A broad search of the literature was carried out in December 2013 Line 147 giving 20 studies dating from 2007 to 2013 for final review (Figure 1). Line 159
13. The independent evaluation of the articles by two researchers has been identified including resolution of discrepancy between authors. Both authors reviewed the final 20 studies independently and reached consensus on which papers were included in the final review. Lines 167-168 14. The results of the included studies were unable to be analysed as there was insufficient concordance between the studies. Differences in the studies including prevention versus regression studies, use of control versus placebo pastes or other preventive regimens, choice of outcome measures, general population versus orthodontic patients, all made pooling of data impossible in the final group of studies. Results 15. The sentence has been modified as requested The remaining six [24-29] studies were found on closer examination to have used outcome measures not recognised as clinical care measures or employed artificially demineralised tooth substance in an in situ model which were exclusion criteria (See Table 1). Lines 164-167 16. The Table and text of Line 199 have been amended to reflect corrections. However, one study [39] did not specify whether fluoride toothpaste was used, a second study did not fully specify the use of fluoride toothpaste in all groups [38] and in another [37] a non-fluoride toothpaste was used in the test group but fluoride toothpaste was used in the control group. Lines 184-187 17. The conclusion has been amended with regard to the advantage of Tooth Mousse in regression of white spot lesions: With regard to the use of Tooth Mousse (MI Paste ) and Tooth Mousse Plus (MI Paste Plus ) for the regression of white spot lesions associated with orthodontic treatment there is a tendency towards the balance of evidence in support of their use but the quality of evidence is limited. Lines 274-276 18. The reporting of side effects of using Tooth Mousse has been added. With regard to safety, no serious side effects or adverse events were found in any of the studies included in the final review. However, five studies [35,37,39-41] did not report side effects or adverse events in their papers. One study [33] recorded one participant with non-serious gastrointestinal symptoms that were possibly related to the use of Tooth Mousse and another [38] made the statement although CPP-ACP had side effects but did not make any reference to what the side effects were. Lines 213-217
19. All studies except one by Plonka et al. used only Tooth Mousse vs a placebo, control or fluoride product. This has been noted in the results: Of the twelve studies included in this systematic review, three studies were direct comparisons of Tooth Mousse versus a control group [34,36,40] and two studies versus a placebo crème [31,33]. The remaining six studies compared the efficacy of Tooth Mousse (MI Paste ) and/or Tooth Mousse Plus (MI Paste Plus ) to other products and techniques with or without a control group - including fluoride toothpaste [37], fluoride mouthrinse [38,39], fluoride gel [30], fluoride varnish [41], chlorhexidine gel [32] and microabrasion [38]. The studies by Beerens et al. [35], Krithidkadatta et al.[39] and Huang et al. [41] involved comparisons with Tooth Mousse Plus (MI Paste Plus ) - containing 900ppm Fluoride, all other studies utilised only the non-fluoride containing Tooth Mousse (MI Paste ). Lines 205-212 Discussion 20. References added: If one considers the orthodontic publications there is a some degree of evidence for the benefits of regression of white spot lesions, with four studies[33, 37, 38, 40] showing positive results and three[35, 36, 41] showing no significant difference to the control groups. Lines 244-247 21. An additional explanation about the factors compromising the results from included studies has been added: The strength of evidence of the group of studies included in this systematic review are further weakened by short observation periods (five studies with duration shorter than 3 months[30, 34, 36, 38, 41]), varying outcome measures (clinical indices[31-34, 39, 40], enamel microhardness[30], laser and light-induced fluorescence[34-36, 39, 40] and visual scoring of photographs[36-38, 41]) and small number of total participants (939 participants for the three prevention studies[30-32] and 542 participants for the nine regression studies[33-41]). Lines 223-228 22. A discussion on very young children has been added: Whilst Tooth Mousse (MI Paste ) has the advantage of being fluoride-free, making it suitable for use in very young children, the risk of development of fluorosis of the permanent teeth from the excessive ingestion of fluoride toothpaste is not a concern for children 6 years of age and older. The two papers [31,32] in this review that studied the efficacy of Tooth Mousse (MI Paste ) in children under 6 years of age do not support its use over the twice-daily use of either 1000ppm [31] or 400ppm [32] fluoride toothpaste. As it is also much more expensive than fluoride toothpaste the recommendation of this product in very young children cannot be supported. Lines 257-264
23. There was no advantage to the use of Tooth Mousse Plus over Tooth Mousse. This was added to the discussion: When three studies [35,39,41] utilising Tooth Mouth Plus are considered Krithikadatta et al. [39] was the only one with a direct comparison between Tooth Mousse and Tooth Mousse Plus. The results of this study did not show a significant difference between the non-fluoride and fluoride-containing forms of the CPP-ACP crème and the authors suggested that further studies would be required to confirm these results. Lines 247-251 The recommended age for using Tooth Mousse Plus has been added: The manufacturer instructions recommend Tooth Mousse (MI Paste ) for patients of any age except those with milk protein allergies but limits the indication of Tooth Mousse Plus (MI Paste Plus ) to patients over six years of age because of the fluoride content. Lines 121-124 25. Table 1: has been removed and is included as an additional file. The new Table 1 is the Inclusion and Exclusion criteria. 26. Table 2: The years of publication have been added to the tables and the tables have been re-ordered according to reference number. 27. Table 3: reference numbers have been corrected 28. Table 3: Sitthisettapong this is not the only study where Tooth Mousse was used after brushing with fluoride toothpaste. In the prevention studies - Plonka et al. also applied Tooth Mousse after brushing with fluoride toothpaste. The use of fluoride toothpaste is clearly noted in Table 3. 29. Tables 3 and 4: Tooth Mousse method has been added and randomisation of studies. References 30. References have been revised according to journal author guidelines