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Figure 6.
Reasons for exclusion of studies included by previous SRs_
| Authors | Title | Reason | Exclusion stage |
|---|---|---|---|
| Adiaens et al. (1990) | The use of ‘Fluor Protector®’, a fluoride varnish, as a caries prevention method under orthodontic molar bands. | In vitro | Title/abstract screen |
| Twetman et al. (1995) | Effect of an antibacterial varnish on mutans streptococci in plaque from enamel adjacent to orthodontic appliances | Surrogate outcome | Title/abstract screen |
| Madléna et al. (2000) | Effect of chlorhexidine varnish on bacterial levels in plaque and saliva during orthodontic treatment | Surrogate outcome | Title/abstract screen |
| Demito et al (2004) | The efficacy of a fluoride varnish in reducing enamel demineralization adjacent to orthodontic brackets: an in vitro study. | In vivo | Title/abstract screen |
| Skold-Larsson, K. et al. (2004) | Effect of topical applications of a chlorhexidine/thymol-containing varnish on fissure caries assessed by laser fluorescence | Non RCT | Title/abstract screen |
| Luther et al. (2005) | Fluoride releasing glass beads in orthodontic treatment to reduce decay: a randomized, controlled clinical trial. | Outcome not reported | Title/abstract screen |
| Vivaldi-Rodrigues et al. (2006) | The effectiveness of a fluoride varnish in preventing the development of white spot lesions | Split mouth + <6 months | Title/abstract screen |
| Farhadian N, et al (2008) | Effect of fluoride varnish on enamel demineralization around brackets: an in-vivo study | In vivo | Title/abstract screen |
| Bailey et al. (2009) | Regression of post-orthodontic lesions by a remineralizing cream | Post-orthodontic | Title/abstract screen |
| Beerens et al. (2010) | Effects of casein phosphopeptide amorphous calcium fluoride phosphate paste on white spot lesions and dental plaque after orthodontic treatment: a 3-month follow-up | < 6 months | Title/abstract screen |
| Baeshen et al. (2011) | Effect of fluoridated chewing sticks (Miswaks) on white spot lesions in postorthodontic patients | Post-orthodontic | Title/abstract screen |
| Brochner et al. (2011) | Treatment of post-orthodontic white spot lesions with casein phosphopeptide-stabilised amorphous calcium phosphate | Post-orthodontic | Title/abstract screen |
| Enaia et al. (2011) | White-spot lesions during multibracket appliance treatment: A challenge for clinical excellence. | Non RCT | Title/abstract screen |
| Richter et al. (2011) | Incidence of caries lesions among patients treated with comprehensive orthodontics | Retrospective | Title/abstract screen |
| Robertson et al. (2011) | MI Paste Plus to prevent demineralization in orthodontic patients: a prospective randomized controlled trial | < 6 months | Title/abstract screen |
| Shinaishin et al. (2011) | Efficacy of light-activated sealant on enamel demineralization in orthodontic patients: an atomic force microscope evaluation | Ex vivo | Title/abstract screen |
| Akin et al. (2012) | Can white spot lesions be treated effectively? | Post-orthodontic | Title/abstract screen |
| Du et al. (2012) | Randomized controlled trial on fluoride varnish application for treatment of white spot lesion after fixed orthodontic treatment | Post-orthodontic | Title/abstract screen |
| Jumanca et al. (2012) | Infiltration Therapy-an Alternative to Fluoride Varnish Application for Treatment of White Spot Lesion After Fixed Orthodontic Treatment. | Post-orthodontic | Title/abstract screen |
| Huang et al. (2013) | Effectiveness of MI Paste Plus and PreviDent fluoride varnish for treatment of white spot lesions: a randomized controlled trial | Post-orthodontic | Title/abstract screen |
| Baroni et al. (2014) | A SEM and non-contact surface white light profilometry in vivo study of the effect of a creme containing CPP-ACP and fluoride on young etched enamel | In vivo | Title/abstract screen |
| Restrepo et al. (2015) | Control of white spot lesion adjacent to orthodontic bracket with use of fluoride varnish or chlorhexidine gel | In vivo | Title/abstract screen |
| He et al. (2016) | Comparative assessment of fluoride varnish and fluoride film for remineralization of postorthodontic white spot lesions in adolescents and adults over a 6-month period: a single-center, randomized controlled clinical trial, | Post-orthodontic | Title/abstract screen |
| Restrepo et al. (2016) | Control of White Spot Lesions with Use of Fluoride Varnish or Chlorhexidine Gel During Orthodontic Treatment A Randomized Clinical Trial. | < 6 months | Title/abstract screen |
| Kirschneck et al. (2016) | Efficacy of fluoride varnish for preventing white spot lesions and gingivitis during orthodontic treatment with fixed appliances-a prospective randomized controlled trial | < 6 months | Title/abstract screen |
| Singh et al. (2016) | Effects of various remineralizing agents on the outcome of post-orthodontic white spot lesions (WSLs): a clinical trial | Post-orthodontic | Title/abstract screen |
| Turska-Szybka et al. (2016) | Randomised Clinical Trial on Resin Infiltration and Fluoride Varnish vs Fluoride Varnish Treatment Only of Smooth-surface Early Caries Lesions in Deciduous Teeth. | Non-orthodontic | Title/abstract screen |
| Bock et al. (2017) | Changes in white spot lesions following post-orthodontic weekly application of 1.25 per cent fluoride gel over 6 months-a randomized placebo-controlled clinical trial. Part I: photographic data evaluation | Post-orthodontic | Title/abstract screen |
| Bock et al. (2017) | Changes in white spot lesions following post-orthodontic weekly application of 1.25 per cent fluoride gel over 6 months-a randomized placebo-controlled clinical trial. Part II: clinical data evaluation | Post-orthodontic | Title/abstract screen |
| Ebrahimi et al. (2017) | The effects of three remineralizing agents on regression of white spot lesions in children: a two week, single-blind, randomized clinical trial | < 6 months | Title/abstract screen |
| Karabekiroglu et al. (2017) | Treatment of post-orthodontic white spot lesions with CPP-ACP paste: A three year follow up study | Post-orthodontic | Title/abstract screen |
| Beerens et al. (2018) | Long-term remineralizing effect of MI Paste Plus on regression of early caries after orthodontic fixed appliance treatment: a 12-month follow-up randomized controlled trial | Post-orthodontic | Title/abstract screen |
| Heravi et al. (2018) | Effectiveness of MI Paste Plus and Remin Pro on remineralization and color improvement of postorthodontic white spot lesions | Post-orthodontic | Title/abstract screen |
Previous systematic reviews and meta-analyses_
| Systematic reviews | |||||||
|---|---|---|---|---|---|---|---|
| Author | Pre-registered? | Intervention | Studies used | Risk of bias done? | GRADE? | Guideline? | Comments |
| Derks (2004) | N | F, CHX, GIC | RCTs and split mouth studies | N | N | N | Split mouth studies-clustering effect not considered (11/16 = 69% of included studies). Overall risk of bias not calculated. |
| Benson et al (2013) | Y | F | RCTs | Y | Y | N | Cochrane review |
| Lapenaite et al (2016) | N | F and CPP-ACP | RCTs and quasi-RCTs | N | N | N | No risk of bias assessment |
| Rahimi et al (2017) | N | F varnish | RCTs, in vitro and in vivo | N | N | N | in vitro, in vivo studies used |
| Imani et al (2019) | N | CPP-ACP | RCTs | Y | N | N | Post orthodontic WSL reduction. |
| Pithon et al (2019) | Y | CPP-ACP | RCTS and non-RCTs | Y | N | N | Non-RCTs used |
| Sardana et al (2019) | Y | Self applied F | RCTs and quasi-RCTs | Y | Y | N | During and post-orthodontic studies included without sub group analyses. Both control and intervention are F. |
Data from studies included in the qualitative synthesis_
| Study (year, country) | Sample size | Age of participants | Intervention | Control/Comparison |
|---|---|---|---|---|
| Ogaard et al. (1997, Sweden) | 198 (101 experimental; 97 controls) | 12-15 | Fluoride varnish (Fluor Protector); Antimicrobial varnish (Cervitec) | Placebo and F varnish |
| Alexander et al. (2000, US) | 72 (22:25:25 – controls, 2*experimental groups) | Mean 13.93 | Group 1: Tooth brush instruction, high potency and frequency F gel; Group 2: Tooth brush instruction, high potency and frequency dentrifice | Tooth brush instruction, low potency, high frequency F rinse |
| Weiss et al. (2005, Germany) | 68 (34 per group) | Mean 14.1 | Chlorhexidine gel in chair and 2.26% NaF varnish | 40% chlorhexidine varnish and 2.26% NaF varnish |
| Al Mulla et al. (2010, Saudi Arabia) | 100 (51 experimentals; 49 controls) | Mean 16.9 | Modified F toothpaste technique: minimal rinsing of paste after brushing (1450 ppm F) | Regular brushing (1450 ppm F) |
| Hoffman et al. (2015, USA) | 48 (24 per group) | Mean 15.6 in experimental group 15.3 in control | 5000ppm NaF with 5% NovaMin paste | 1500ppm F toothpaste |
| Suetenkov et al. (2015, Russia) | 60 (30 per group) | 12-13. | Laser therapy (OPTODAN and FotoSan) with control goup regime | Twice daily brushing with 1400ppm F paste, 0.05% CHX mouthrinse for 10 days, F gel |
| Esenlik et al. (2016, Turkey) | 40 (20 per group) | Mean 17 | CPP-ACP paste | No treatment |
| Alavi et al. (2018, Iran) | 40 (10 in each group) | Mean 23 | Group 1: 0.2% CHX varnish; Group 2: 5% NaF varnish | Group 3: placebo varnish; Group 4: control |
| Gomeza et al. (2018, Spain) | 20 (10 per group) | Mean 15.0 in experimental group 14.2 in control | Photodynamic therapy – Methylene blue activated by laser at 670nm | Ultrasonic scaler clean |
| Janatschke et al. (2001, Germany) | 33 (18 experimentals; 15 controls) | Median 15 | 40% chlorhexidine varnish | Placebo |
| Ogaard et al. (2006, Sweden) | 97 (50 experimentals; 47 controls) | Mean 14.4 | AmF/SnF2 (1400ppm F) toothpaste and 250ppm F rinse | NaF (1400ppm F) toothpaste and 250ppm F rinse |
| Steckson-Blicks et al. (2007, Sweden) | 257 (132 experimentals; 125 controls) | 12-15. | F varnish (0.1% F) | Placebo varnish |
| Jiang et al. (2013, China) | 95 (48 experimentals; 47 controls) | 10-20. | 1.23% APF foam | Placebo foam |
| Fretty (2014, USA) | 55 | 13 | 1.23% APF foam | Placebo foam |
| Sonesson et al. (2014, Sweden) | 391 (188 experimentals; 192 controls) | 11-16. | 5000ppm NaF paste | 1450ppm NaF paste |
| van der Kaaij et al. (2015, Netherlands) | 81 (36 experimentals; 45 controls) | Mean 13.3 | 250ppm F rinse (100ppm AmF, 150ppm NaF) | Placebo rinse |
| Zotti et al. (2016, Italy) | 80 (40 per group) | Mean 14.1 in study group 13.6 in control | Whatsapp based reminder re OH | No app based reminders |
| Rechmann et al. (2018, USA) | 37 (19 experimentals, 18 controls) | Mean 15.9 | 1100ppm F paste with MI Varnish (10% w/v CPP-ACP, 5% NaF) and MI Paste Plus (10% w/v CPP-ACP, 0.2% 900ppm NaF) | 1100ppm F paste with 0.05% NaF rinse |
Reasons for exclusion following full-text assessment_
| Study | Reason for exclusion |
|---|---|
| Dimitriadis AG, Sassouni V, and Draus FJ (1974). | Non randomised |
| Boyd RL (1992). | Non randomised |
| Boyd RL (1993). | Non randomised |
| Turner PJ (1993). | Non randomised |
| Banks PA and Richmond S (1994). | Split mouth |
| Boyd RL and Rose CM (1994). | Non randomised |
| Silverman E, Cohen M, Demke RS, and Silverman M (1995). | Non randomised |
| Trimpeneers LM and Dermaut LR (1996). | Non randomised |
| Marini I, Pellicioni GA, Vecchiet F, Bonetti GA, Checchi L. (1999). | Baseline data not available |
| Wenderoth CJ, Weinstein M, and Borislow AJ (1999). | Split mouth |
| Banks PA, Chadwick SM, Asher-McDade C, Wright JL (2000). | Baseline data not available |
| Hsu CYS, Jordan TH, Dederich DN, and Wefel JS (2000). | Non randomised |
| Harazaki M, Hayakawa K, Fukui T, Isshiki Y, and Powell LG (2001). | Non randomised |
| Ogaard B, Larsson E, Henriksson T, Birkhed D, and Bishara SE (2001). | Baseline data not available |
| Donly KJ (2003). | Ex-vivo |
| Zimmer BW and Rottwinkel Y (2004). | Non randomised |
| Abdullah AZ, Stafford SM, Brookes SJ, and Duggal MS (2006). | In-vitro |
| Miura KK, Ito IY, Enoki C, Elias AM, and Matsumoto MAN (2007). | < 6 months |
| Shafi I (2008). | Non-randomised |
| Dong YN, Chen M, and Ren XM (2009). | Split mouth |
| Tenuta LMA, Zamataro CB, Del Bel Cury AA, Tabchoury CPM, and Cury JA (2009). | Split mouth |
| Akkurt MD, Amasyali M, Ozcan S, Yagci A, Basak F, and Sagdic D (2011). | < 6 months |
| Buck T, Pellegrini P, Sauerwein R, Leo MC, Covell Jr DA, Maier T, and Machida CA (2011). | Split mouth |
| Demito CF, Rodrigues GV, Ramos AL, and Bowman SJ (2011). | Split mouth |
| Najibfard K, Chedjieu I, Ramalingam K, and Amaechi BT (2011). | < 6 months |
| Stafford GL (2011). | Non-randomised |
| Sollenius O, Karlsson L, Petersson LG, and Twetman S (2013). | < 6 months |
| Atwa ALDA,. AbuShahba RY, Mostafa M, and Hashem MI (2014). | < 6 months |
| Melo MA, Morais WA, Passos VF, Lima JP, and Rodrigues LK (2014). | In-vitro |
| Ghajari MF, Eslamian L, Rad AN, and Morovati SP (2015). | Baseline data not available |
| Masoud MI, Allarakia R, Alamoudi NM, Nalliah R, and Allareddy V (2015). | Outcome data not available |
| Paschoal MA, Moura CMZ, Jeremias F, Souza JF, Bagnato VS, Giusti JSM, and Santos-Pinto L (2015). | < 6 months |
| Restrepo M, Bussaneli DG, Jeremias F, Cordeiro RCL, Magalhaes AC, Palomari Spolidorio DM, and Santos-Pinto L (2015). | Ex-vivo |
| Zhang N, Chen C, Weir MD, Bai Y, and Xu HH (2015). | Ex-vivo |
| Bussaneli DG, Jeremias F, Cordeiro RC, Raveli DB, Magalhaes AC, Candolo C, and Santos-Pinto L (2016). | < 6 months |
| Gizani S, Petsi G, Twetman S, Caroni C, Makou M, Papagianoulis L (2016). | Baseline data not available |
| Hammad S and Abdellatif A (2016). | Baseline data not available |
| Miller CC, Burnside G, Higham SM, Flannigan NL (2016). | Baseline data not available |
| Oosterkamp BCM, Wafae A, Schols JGJH, van der Sanden WJM, and Wensing M (2016). | Different topic |
| Korkmaz YN and Yagci A (2018). | < 6 months |
| Liptak L, Szabo K, Nagy G, Marton S, and Madlena M (2018). | Split mouth |
| Benson PE, Alexander-Abt J, Cotter S, Dyer F, Fenesha F, Patel A, Campbell C, Crowley N & Millett D (2019). | Baseline data not available |
| Enerback H, Moller M, Nylen C, Odman Bresin C, Ostman Ros I, and Westerlund A (2019). | Different topic |
| Sonesson M, Brechter A, Abdulraheem S, Lindman R, Twetman S (2019). | Baseline data not available |
Risk of bias assessment of RCTs included in the qualitative analysis_
| Trial | Bias from randomisation process | Bias from deviations from intended interventions | Bias from missing outcome data | Bias from measurement of the outcome | Bias from selection of the reported result | Overall bias |
|---|---|---|---|---|---|---|
| Ogaard et al. (1997) | High | Low | Low | Some concerns | Low | High |
| Alexander et al. (2000) | High | Some concerns | Low | Some concerns | Low | High |
| Jenatschke et al. (2001) | Some concerns | Low | Low | Some concerns | Some concerns | Some concerns |
| Weiss et al. (2005) | Some concerns | Some concerns | Low | High | Some concerns | High |
| Ogaard et al. (2006) | Some concerns | Low | Low | Low | Low | Some concerns |
| Steckson-Blicks et al. (2007) | Some concerns | Low | Low | Low | Some concerns | Some concerns |
| Al Mulla et al. (2010) | Some concerns | Low | Low | High | Some concerns | High |
| Jiang et al. (2013) | Low | Low | Low | Low | Some concerns | Some concerns |
| Fretty (2014) | Low | Low | Low | High | Some concerns | High |
| Sonesson et al. (2014) | Low | Some concerns | Low | Low | Some concerns | Some concerns |
| Hoffman et al. (2015) | Some concerns | Low | High | High | Some concerns | High |
| Suetenkov et al. (2015) | Some concerns | Some concerns | Low | High | Some concerns | High |
| van der Kaaij et al. (2015) | Low | Low | Low | Low | Some concerns | Some concerns |
| Esenlik et al. (2016) | High | Some concerns | High | High | Some concerns | High |
| Zotti et al. (2016) | Low | Low | Low | Low | Some concerns | Some concerns |
| Alavi et al. (2018) | Some concerns | Some concerns | High | High | Some concerns | High |
| Gómez et al. (2018) | High | Low | Some concerns | Low | Some concerns | High |
| Rechmann et al. (2018) | Low | Some concerns | Low | Low | Low | Some concerns |
MEDLINE OVID search strategy_
| Search key words | |
|---|---|
| 1 | Prevent* |
| 2 | Fluoride* or toothpaste* or tooth paste or mouthrinse* or mouth rinse* or mouth wash* or gel or varnish or NaF or SMFP |
| or SnF or APF or amine F or f releas* or dentrific* | |
| 3 | tooth brushing or dental devices, home care/ |
| 4 | Exp cariostatic agents/or cariostatic |
| 5 | Chlorhexidine or chlor hexidine |
| 6 | CPP ACP or casein phosphopeptide amorphous calcium phosphate |
| 7 | RMGI or resin modified glass ionomer* |
| 8 | SAP or self assembling peptide* |
| 9 | Oral hygiene or OHI |
| 10 | Or/1-9 |
| 11 | caries or incipient lesion* or WSL or cavity or cavities or white spot |
| 12 | demineralization or demineralisation |
| 13 | or/11-12 |
| 14 | fixed or orthodont* or brace* or edgewise or begg |
| 15 | removable or removed or appliance* |
| 16 | exp orthodontics/ |
| 17 | or/14 -16 |
| 18 | 10 AND 13 AND 17 |
| 19 | randomized controlled trial.pt |
| 20 | controlled clinical trial.pt |
| 21 | random* or blind* |
| 22 | trial or trials |
| 23 | or/19 – 22 |
| 24 | 18 AND 23 |
| 25 | limit 24 to English language |