Introduction. R. G. de Amorim 1 & J. E. Frencken 2 & D. P. Raggio 3 & X. Chen 4 & X. Hu 4 & S. C. Leal 5

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1 Clinical Oral Investigations (2018) 22: REVIEW Survival percentages of atraumatic restorative treatment (ART) restorations and sealants in posterior teeth: an updated systematic review and meta-analysis R. G. de Amorim 1 & J. E. Frencken 2 & D. P. Raggio 3 & X. Chen 4 & X. Hu 4 & S. C. Leal 5 Received: 5 September 2018 /Accepted: 6 September 2018 /Published online: 19 September 2018 # Springer-Verlag GmbH Germany, part of Springer Nature 2018 Abstract Objective The aim of the present study is to update the results of two previous meta-analyses, published in 2006 and 2012, on the survival percentages of atraumatic restorative treatment (ART) restorations and ART sealants. The current meta-analysis includes Chinese publications not investigated before. Materials and methods Until February 2017, six databases were interrogated (two English, one Portuguese, one Spanish and two Chinese). Using six exclusion criteria, a group of six independent reviewers selected 43 publications from a total of 1958 potentially relevant studies retrieved. Confidence intervals and/or standard errors were calculated and the heterogeneity variance of the survival rates was estimated. Results The survival percentages and standard errors of single-surface and multiple-surface ART restorations in primary posterior teeth over the first 2 years were 94.3% (± 1.5) and 65.4% (± 3.9), respectively; for single-surface ART restorations in permanent posterior teeth over the first 3 years, they were 87.1% (± 3.2); and for multiple-surface ART restorations in permanent posterior teeth over the first 5 years, they were 77% (± 9.0). The mean annual dentine-carious-lesion-failure percentages in previously sealed pits and fissures using ART sealants in permanent posterior teeth over the first 3 and 5 years were 0.9 and 1.9%, respectively. Conclusions ART single-surface restorations presented high survival percentages in both primary and permanent posterior teeth, whilst ART multiple-surface restorations presented lower survival percentages. ART sealants presented a high-caries-preventive effect. Clinical relevance ART is an effective evidence-based option for treating and preventing carious lesions in primary and permanent posterior teeth. Keywords Sealant. Restoration. Atraumatic restorative treatment. Survival. Meta-analysis. Systematic review Electronic supplementary material The online version of this article ( contains supplementary material, which is available to authorized users. * R. G. de Amorim Present address: Brasília, Brazil Department of Oral Function and Prosthetic Dentistry, Radboud University Medical Centre, Nijmegen, The Netherlands Orthodontics and Pediatric Dentistry Department, School of Dentistry, University of São Paulo, São Paulo, Brazil State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China Department of Dentistry, Faculty of Health Sciences, University of Brasília, Brasília, Brazil Introduction It has been more than 30 years since the atraumatic restorative treatment (ART) was introduced at the 1986 scientific meeting of the Tanzanian Dental Association [1]. Twenty years later, the results of the first meta-analysis on the survival percentages of ART sealants and ART restorations in primary and permanent teeth were published [2]. One of the conclusions was that the survival percentage of ART restorations performed with high-viscosity glass-ionomer cements (HVGIC) was significantly higher than for those performed with lowand medium-viscosity glass-ionomers. Another conclusion was that the retention percentage of ART/HVGIC sealants was significantly higher than that of low- and mediumviscosity glass-ionomer.

2 2704 Clin Oral Invest (2018) 22: The second meta-analysis on ART sealants and restorations covered the literature up to February 2010 and was published in 2012 [3]. The review concluded that ART is a good option for treating single-surface cavities in primary and permanent teeth and for sealing caries-prone pits and fissures of permanent molars. More recently, during the International Caries Consensus Collaboration (ICCC) meeting held in Leuven in 2015, ART was recognised by experts in cariology and paediatric dentistry as a treatment for managing carious lesions. Its restorative component is based on the selective removal of carious tissues down to the soft dentine in deep/very deep lesions and to firm dentine in non-deep lesions [4, 5]. The consensus meeting recommended that clinicians use ART as an option for treating primary and permanent teeth that presented non-cleansable cavitated dentine-carious lesions. Originally developed for use in underserved communities, ART exceeded expectations. Its use has now been extended to private practice in wealthy developed countries [6]. The rationale for its widespread use lies in the fact that the principles of ART are in accordance with the contemporary philosophy of dental caries management, which is minimal intervention dentistry (MID) [7]. In addition, ART may increase access to oral health care [1] and turn cavity treatment into a non- or less-traumatic experience at any age in comparison to the traditional rotary treatment [8 10]. It is also worth noting that ART is being considered as a suitable option for treating root carious lesions in the elderly [11] and in patients with special needs [12]. Because of the continuously extending applications of the use of ART in oral health care, an update of the meta-analyses on the survival percentages of ART sealants and ART restorations is required. The aim of the present article is to report the findings of a systematic review with meta-analyses on the survival of ART restorations in primary and permanent posterior teeth and on the retention and dentine-carious-lesionpreventive effect of ART sealants in permanent posterior teeth. Materials and methods This systematic review and meta-analysis was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Details of the protocol for this systematic review with meta-analysis were registered on PROSPERO and can be accessed at: record.asp?id=crd Data collection The literature search comprised publications indexed in English language databases (PubMed and Embase), which included publications written in Dutch, German and French; Portuguese and Spanish language databases (LILACS and BBO); and Chinese language databases (CNKI and VIP). All publications listed until 1 February 2017 were analysed. For the English language databases, the search strategy in PubMed was (Dental Atraumatic Restorative Treatment [MeSH Terms]) OR (Atraumatic Restorative Treatment) OR (ART AND Dental Restoration, Permanent [MeSH Terms]) OR (ART AND Pit and Fissure Sealants [MeSH Terms]) OR (dental AND survival AND ART AND approach) OR (dental AND survival AND ART AND technique) OR (Glass Ionomer Cements [MeSH Terms] AND Pit and Fissure Sealants [MeSH Terms]). In the Embase database, the search strategy was to use the following categories: (Dental Atraumatic Restorative Treatment) OR (Atraumatic Restorative Treatment) OR (ART AND Dental Restoration, Permanent) OR (ART AND Pit and Fissure Sealants) OR (dental AND survival AND ART AND approach) OR (dental AND survival AND ART AND technique) OR (Glass Ionomer Cements AND Pit and Fissure Sealants). For the Portuguese and Spanish language databases, the search strategies were, respectively: (Tratamento Dentário Restaurador sem Trauma) OR (Cimentos de Ionômeros de Vidro AND Restauração Dentária Permanente) OR (Cimentos de Ionômeros de Vidro AND Selantes de Fossas e Fissuras); (Tratamiento Restaurativo Atraumático Dental) OR (Cementos de Ionómero Vitreo AND Restauración Dental Permanente) OR (Cementos de Ionómero Vitreo AND Selladores de Fosas y Fisuras). The search strategy in the Chinese databases was ( 非创伤性充填治疗 )OR( 非创伤性修复 ) OR (ART AND 非创性修复 ) OR (ART AND 无创伤性 ) OR (ART AND 微创 ) OR (ART AND 龋 )OR(ARTAND 充填 )OR(ARTAND 牙 ). From the search results, all publications whose titles or abstracts reported on the survival of ART restorations or ART sealants were selected. Those that did not meet this inclusion criterion were immediately excluded. The lists of references of selected publications were cross-checked for additional studies suitable for inclusion. The exclusion criteria for the purpose of this meta-analysis were (1) survival results < 1 year, (2) incorrect (or missing) statistical survival analysis, (3) ART performed by non-graduated dentist/non-graduated dental therapist, (4) low- or medium-viscosity glass-ionomer or other material used with ART restoration or ART sealant, (5) evaluations performed by non-graduated dentists/non-graduated dental therapists and (6) use of rotary instruments in restorations termed ART. If the content of a publication was unclear, the authors were contacted by and requested to replywithinamonthinordertoallowthepublicationto be included. Table 1 shows the reason(s) for excluding 103 publications. The sequence followed from retrieving a publication in any of the six mentioned databases to its inclusion in the

3 Clin Oral Invest (2018) 22: Table 1 Listing of and reasons for exclusion of publications that reported survival of ART restorations and ART sealants Publication Language Survival <1 year Non-graduated dentist/nongraduated dental therapist Incorrect statistical survival analysis Non- HVGIC ART with rotary instruments Followed up by a publication of longer duration de Souza et al., 2003 [13] English x Mallow et al., 1998 [14] English x x Wang et al., 2004 [15] English x Van den Dungen et al., 2004 [16] Dutch x Motsei et al., 2001 [17] English x Abid et al., 2002 [18] English x Holmgren et al., 2000 [19] English x Frencken et al., 1994 [20] English x Smith et al., 1990 [21] English x Kalf-Scholte et al., 2003 [22] English x Phantumvanit et al., 1996 [23] English x Mandari et al., 2001 [24] English x Mandari et al., 2003 [25] English x Frencken et al., 1998 [26] English x Ho et al., 1999 [27] English x Oba et al., 2009 [28] English x Faccin et al., 2009 [29] English x x Roeleveld et al., 2006 [30] English x Kemoli et al., 2009 [31] English x x Barata et al., 2008 [32] English x Dülgergil et al., 2005 [33] English x Lopez et al., 2005 [34] English x Cefaly et al., 2005 [35] English x Bresciani et al., 2005 [36] English x Lo & Holmgren, 2001 [37] English x Yee, 2001 [38] English x Zanata et al., 2003 [39] English x de Amorim et al., 2014 [40] English x Chen et al., 2012 [41] English x Chen et al., 2012 [42] English x Taifour et al., 2003 [43] English x Frencken et al., 1996 [44] English x Hesse et al., 2015 [45] English x da Mata et al., 2014 [46] English x Ferreira et al., 2013 [47] English x Bonifácio et al., 2013 [48] English x Monse et al., 2012 [49] English x Bonifácio et al., 2013 [50] English x Phonghanyudh et al., 2012 [51] English x Roshan et al., 2011 [52] English x Kemoli et al., 2011 [53] English x da Franca et al., 2011 [54] English x Kemoli et al., 2010 [55] English x Carvalho et al., 2010 [56] English x Kemoli et al., 2010 [57] English x da Mata et al., 2015 [11] English x

4 2706 Clin Oral Invest (2018) 22: Table 1 (continued) Publication Language Survival <1 year Non-graduated dentist/nongraduated dental therapist Incorrect statistical survival analysis Non- HVGIC ART with rotary instruments Followed up by a publication of longer duration Kemoli & Amerongen, 2011 English x [58] Hesse et al., 2016 [59] English x Gonçalves et al., 2015 [60] English x Hesse et al., 2016 [61] English x Bonifácio et al., 2013 [62] English x Arrow, 2015 [63] English x Hilgert et al., 2016 [64] English x Dulgergil et al., 2016 [65] English x Kemoli, 2014 [66] English x Jordan et al., 2011 [67] English x Jordan et al., 2010 [68] English x Unal & Oztas, 2015 [69] English x Guler & Yilmaz 2013 [70] English x Chen & Liu, 2013 [71] English x Ulusu et al., 2012 [72] English x Dhar & Chen, 2012 [73] English x Antonson et al., 2012 [74] English x Sly et al., 2010 [75] English x Molina et al., 2014 [76] English x Falbo et al., 2002 [77] Spanish x Moraes et al., 2004 [78] Portuguese x Oliveira et al., 2009 [79] Portuguese x Silva et al., 2005 [80] Portuguese x Bresciani et al., 2002 [81] Portuguese x Peres et al., 2005 [82] Portuguese x Coelho & Ribeiro, 2002 [83] Portuguese x Ewoldsen et al., 1999 [84] Spanish x Oliveira, 2000 [85] Portuguese x Bustamante et al., 2004 [86] Spanish x Edelberg & Basso, 2000 [87] Spanish x Figueiredo et al., 1999 [88] Portuguese x Carvalho et al., 2011 [89] Portuguese x Pesaressi-Torres et al., 2013 [90] Spanish x Raggio, 2012 [91] Portuguese x Santos, 2010 [92] Portuguese x Zhang & Jin, 2015 [93] Chinese x Wan et al., 2007 [94] Chinese x Caoetal.,2011[95] Chinese x Guan & Chen, 2005 [96] Chinese x Ding et al., 2001 [97] Chinese x Ling et al., 2006 [98] Chinese x Feng et al., 2003 [99] Chinese x Yang, 2011 [100] Chinese x Miao et al., 2008 [101] Chinese x Hu & Xiao, 2008 [102] Chinese x Wang, 2006 [103] Chinese x

5 Clin Oral Invest (2018) 22: Table 1 (continued) Publication Language Survival <1 year Non-graduated dentist/nongraduated dental therapist Incorrect statistical survival analysis Non- HVGIC ART with rotary instruments Followed up by a publication of longer duration Leng et al., 2011 [104] Chinese x Hu et al., 2015 [105] Chinese x Yan et al., 2016 [106] Chinese x Wu & Li, 2012 [107] Chinese x Wang & Sun, 2007 [108] Chinese x Gao et al., 2004 [109] Chinese x Pu, 2014 [110] Chinese x Han et al., 2008 [111] Chinese x Ling & Wang, 2003 [112] Chinese x Li & Dou, 2005 [113] Chinese x Chen, 2010 [114] Chinese x meta-analysis is shown in Figs. 1, 2, and3. By the time the literature search was carried out, three English submittedmanuscriptshadbecomeknowntotheauthors(personal communication) and were included. Two of these manuscripts [12, 115] presented follow-up results of previous publications ([76, 41], respectively); the other [116] presented results published for the first time. Main characteristics of the included studies are presented in Table 2. Investigator agreement For English publications up to 1 June 2005, two investigators (MVH and JF) independently extracted the data related to the outcomes, as seen in the first published meta-analysis of the ART approach [2]. For English publications between 1 June 2005 and 1 February 2010, two investigators (RGA and JF) were independently responsible for the data extraction, as seen in the updated metaanalysis published in 2012 [3]. The data extraction for the current meta-analysis was performed by a group of six investigators. RGA and JF independently analysed studies published in English between 1 February 2010 and 1 February 2017 and extracted the survival percentages and corresponding standard errors or confidence intervals (CI) of the included studies. SL and DR independently analysed studies published in Portuguese and Spanish between 1 February 2010 and 1 February XH and XC independently analysed studies published in Chinese up to 1 February In case of a disagreement about extracted data between the investigators, consensus was reached through discussion without the need for external consultation. One investigator (JF) took part in all three versions of the meta-analysis. Quality of the included publications The quality assessment of the included publications took into account information related to methodological aspects that should be part of any clinical trial that aims to test the efficacy of the ART approach. Nine main quality criteria were examined: (1) generation of randomisation sequence, (2) allocation concealment, (3) training of operators in the ART technique, (4) independency of evaluators, (5) calibration of evaluators, (6) blinding of evaluators, (7) drop-out rate, (8) implementation of a prevention programme in combination with the performance of ART restorations and ART sealants and (9) report of the sample baseline caries experience. The quality assessment was performed qualitatively by classifying each of the study criteria as yes (low risk of bias), no (high risk of bias) or unclear (information not precisely reported or uncertainty about the potential of bias). A drop-out rate up to 30% was considered a low risk of bias and a drop-out rate not reported or more than 30% a high risk of bias. Two investigators (RGA and SL) were responsible for extracting data related to the quality assessment of the English publications. Statistical analysis The analyses were carried out by a statistician. If only survival percentages and number of sealants/restorations had been presented in the included publications, the 95% confidence interval (CI) had to be obtained from the statistical tables. CIs were used to calculate the standard error (SE) for the survival percentages according to the following equation: SE = (upper lower CI) / 4. Survival percentages per year within selected groups were combined by meta-analysis. If survival percentages showed homogeneity, a fixed-effect model was applied. In case

6 2708 Clin Oral Invest (2018) 22: Fig. 1 Flowchart of retrieved English publications to included publications reporting survival results of ART sealants and ART restorations Pubmed Embase Total number of publica ons retrieved on search strategy 722 Excluded publica ons, by reading abstracts, for the following reasons: - ART publica ons without survival results - ART survival results obtained from retrospec ve studies - ART men oned in general den stry publica ons - ART men oned in non-dental publica ons - ART related le ers - ART publica ons in non-traceable journals - Survival results repeated in other journal/language - Survival results using resin composite - Survival results on root surfaces - Survival results on anterior teeth - Survival results followed up by a publica on of longer dura on - Survival results the same in two publica ons 104 Number of eligible publica ons selected for full reading Added publica ons: - personal communica on 12,13,16 (n=3) 107 Number of publica ons before applica on of exclusion criteria Excluded publica ons (n=65) (Table 1) 42 Included publica ons for the meta-analysis of heterogeneity, a random-effect model was used. The decision criterion was the p value for the homogeneity test. I 2 values were used to grade the level of heterogeneity of the survival percentages per survival year. Categorisation of the level of heterogeneity followed the suggestion presented by the Cochrane Research Group [155]. The meta-analyses were performed in R version using the survcomp package [156]. Results The complete database used for the meta-analysis comprised a total of 43 included publications from 22 countries and regions: Argentina, Brazil, China, Ecuador, Egypt, Hong Kong, India, Iraq, Kuwait, Latvia, Malaysia, Mexico, Nigeria, Panama, Pakistan, South Africa, Suriname, Syria, Tanzania, Turkey, Uruguay and Zimbabwe.

7 Clin Oral Invest (2018) 22: Fig. 2 Flowchart of retrieved Portuguese/Spanish publications to included publications reporting survival results of ART sealants and ART restorations BBO LILACS Total number of publica ons retrieved on search strategy 319 Excluded publica ons, by reading abstracts, for the following reasons: - ART publica ons without survival results - ART publica ons in non-traceable journals/theses - Survival results repeated in other journal/language - ART publica ons mee ng at least one of the exclusion criteria 16 Number of eligible publica ons selected for full reading Excluded publica ons (n=16) (Table 1) 0 Included publica ons for the meta-analysis Homogeneity of survival results The level of heterogeneity for ART restorations and ART sealants by survival year, using I 2 as a guide, is presented in Table 3. Heterogeneity was substantial or higher for most of the weighted mean survival percentages of all types of ART restorations and sealant retention, whereas the level of heterogeneity for the weighted mean survival percentages for the dentine-cariouslesion-preventive effect of ART sealants was much lower, even showing full homogeneity (survival years 1 and 3). ART restorations The survival percentages and standard errors of single- and multiple-surface ART restorations in primary posterior teeth are presented in Tables 4 and 5, respectively.theweighted mean annual failure rates of single- and multiple-surface ART restorations in primary posterior teeth over the first 3 years were 5 and 17%, respectively. The survival percentages and standard errors of single- and multiple-surface ART restorations in permanent posterior teeth are presented in Tables 6 and 7, respectively. The weighted mean annual failure rate of single-surface ART restorations in permanent posterior teeth over the first 5 years was 4.1%. The weighted mean annual failure rate of multiple-surface ART restorations in permanent posterior teeth was 7.3% over the first year and 10.9% over the first 2 years. ART sealants The survival percentages and standard errors of fully and partially retained ART sealants in permanent posterior teeth are presented in Table 8. The weighted mean annual failure rates of completely lost ART sealants in permanent posterior teeth over the first 3 and 4 years were 10.7 and 9.6%, respectively. The survival percentages and standard errors of dentinecarious-lesion-free previously sealed pits and fissures using ART sealants in permanent posterior teeth are presented in Table 9. The weighted mean annual dentine-carious-lesionfailure rates of previously sealed pits and fissures using ART sealants in permanent posterior teeth over the first 3 and 5 years were 0.9 and 1.9%, respectively. Quality assessment Table 10 shows the quality assessment for the included studies. Only one trial, which was published as two study reports [115, 153], presented a low risk of bias for all

8 2710 Clin Oral Invest (2018) 22: Fig. 3 Flowchart of retrieved Chinese publications to included publications reporting survival results of ART sealants and ART restorations CNKI VIP Total number of publica ons retrieved on search strategy 775 Excluded publica ons, by reading abstracts, for the following reasons: - ART publica ons without survival results - ART publica ons in non-traceable journals/theses - Survival results repeated in other journal/language - ART publica ons mee ng at least one of the exclusion criteria - Survival results followed up by a publica on of longer dura on - Survival results using resin composite - Survival results of wedge-shaped defects ART restora ons - Survival results of ART sealants in primary teeth 22 Number of eligible publica ons selected for full reading Excluded publica ons (n=22) (Table 1) 0 Included publica ons for the meta-analysis assessed criteria. None presented a high risk of bias for all assessed criteria. The criterion that was classified as indicating a low risk of bias more often was drop-out rate. Twenty-three trials reported a loss to follow-up rate of less than 30%, one trial [140, 141] did not mention the loss to follow-up rate, and 10 presented a rate of higher than 30%. Training of operators, independency of evaluators and calibration of evaluators (crucial aspects of trials that report on the longevity of ART restorations and sealants) were classified as having a low risk of bias in 24, 22 and 26 trials, respectively. Discussion Methodological aspects Compared to the 2012 ART meta-analysis, the number of included studies on ART restorations in primary teeth, as well as on ART sealants in permanent teeth, had almost doubled, particularly in the first two evaluation years. This substantial increase in the number of eligible studies was not observed in ART studies for restorations in permanent teeth. It seems that the ART approach has found in paediatric dentistry its greater acceptance, which can be easily explained by its potential to cause less pain and anxiety and to be less invasive to dental tissues [7, 8, 10]. Publications were excluded largely because of incorrect statistical survival analysis, followedby non-graduated dentist/non-graduated dental therapist and the use of non-hvgic restorative materials. Incorrect statistical survival analysis referred mainly to two situations: (1) the use of simple descriptive analysis instead of an appropriate survival analysis to obtain the studied outcome and (2) the report of a unique survival rate for a combination of different types of restorations (single and multiple surfaces), different types of teeth (anterior and posterior) and different types of dentition

9 Clin Oral Invest (2018) 22: Table 2 Main characteristics of the included studies Publication Age (years) Type of dentition Study environment Glass-ionomer cement used Evaluation criteria Honkala et al., 2003 [117] 2 9 (mean 5.7) Primary Dental clinic ChemFlex ART and USPHS Louw et al., 2002 [118] 6 9 (mean 7.3) Primary Field Fuji IX ART Luo et al., 1999 [119] and Lo et al., 2001 [120] 6 14 Primary and permanent Field ChemFlex and Fuji IX GP ART and USPHS Taifour et al., 2002 [121] 6 7 Primary Dental clinic Fuji IX and KetacMolar ART Yip et al., 2002 [122] and Yu et al., 2004 [123] 7 9 Primary Dental clinic Fuji IX GP and KetacMolar Aplicap Ersin et al., 2006 [124] 6 10 (mean 8.07) Primary Field Fuji IX GP USPHS Van Gemert-Schriks et al., 2007 [125] Mean 6.09 Primary and permanent ART Field Ketac-Molar ART Menezes et al., 2006 [126] 4 6 Primary Dental clinic Ketac-Molar Specific for the study indirect assessment (photographs) Yassen, 2009 [127] 6 7 (6.7) Primary Field Ionofil ART Deepa & Shobha, 2010 [128] 4 9 (mean 5.3) Primary Dental clinic Fuji IX and Amalgomer CR ART Hilgert et al., 2014 [129] and Hilgertetal.,2015[130] and Hilgert et al., 2017 [116] 6 7 (mean 6.8) Primary and permanent Molina et al., 2017 [12] 3 39 (mean 13.6) / all patients with disability Primary and permanent Field Ketac Molar Easymix ART; presence of caries (dentinal lesion); sealant retention (partial/full/not present) Dental clinic Equia system and Chemfil Rock ART with the addition of one code for pulpal involvement Cefaly et al., 2007 [131] 9-16 Permanent Field Ketac Molar and Fuji VIII ART Ercan et al., 2009 [132] 7 12 Permanent Field Ketac Molar ART and USPHS Farag et al., 2011 [133] (mean 14.6) Permanent Dental clinic ART modified and FDI indirect assessment (die stone replicas and photographs) Frencken et al., 1998 [134] Mean 14.1 Permanent Field Fuji IX ART Frencken et al., 2006 [135] 6 9 Permanent Dental clinic Fuji IX and KetacMolar ART Ho et al., 1999 [27] Adults (mean 25.9 yrs. for Fuji IX group and 27.4 yrs. for ChemFil Superior group) Permanent Dental clinic Fuji IX and ChemFil Superior Specific for the study indirect assessment (radiographs, photographs and die stone replicas) and direct assessment (looking for fractures, caries and wear) Kikwilu et al., 2001 [136] 8 15 (mean 10.8) Permanent Field Fuji IX ART Lo et al., 2007 [137] (mean 12.5) Permanent Field Ketac-Molar ART and USPHS Loh, 2003 [138] Mean 8.2 Permanent Field Fuji IX ART modified Mickenautsch et al., 1999 [139] 6 11 (mean 10.5) Permanent Dental clinic Fuji IX and KetacMolar ART 7 9 Permanent Field Not reported USPHS PAHO, 2006 [140] and Estupiñán-Day et al., 2013 [141] Rahimtoola & Van Amerongen, 2002 [142] 6 16 (mean 11.4) Permanent Field Fuji IX Specific for the study

10 2712 Clin Oral Invest (2018) 22: Table 2 (continued) Publication Age (years) Type of dentition Study environment Glass-ionomer cement used Evaluation criteria Yip et al., 2002 [143] and Gao et al., 2003 [144] Adults (mean 34.6) Permanent Dental clinic Fuji IX GP and Ketac-Molar Aplicap Ziraps & Honkala, 2002 [145] 8 14 (mean 11) Permanent Dental clinic ChemFlex and Fuji IX ART Ibiyemietal.,2011[146, 147] 8 19 (mean 13.1) Permanent Field Fuji IX GP ART modified Permanent Dental clinic Fuji IX ART and USPHS Zanata et al., 2011 [148] Pregnant women (mean 19) Specific for the study indirect assessment (radiographs, photographs and die stone replicas) and direct assessment (looking for fractures, pain of pulpal origin and caries) Vieira et al., 2006 [149] 6 8 Permanent Field ChemFlex Presence of caries (dentinal lesion); sealant retention (partial/full/not present) Holmgren et al., 2013 [150] Permanent Field Ketac-Molar Presence of caries (dentinal lesion); sealant retention (partial/full/not present) Luengas-Quintero et al., 2013 [151] 6 13 Permanent (only sealants were included in this meta-analysis) Field Ketac Molar Easymix ART Liu et al., 2014 [152] 7 9 (mean 7.8) Permanent Field Ketac-Molar Easymix Presence of caries (ICDAS codes 4 6); sealant retention (partial/full/not present) Zhang et al., 2014 [153] and Zhang et al., 2017 [115] 7 9 (mean 8) Permanent Field Ketac Molar Easymix Specific for the study (regarding sealant retention) and presence of caries (dentinal lesion) Beiruti et al., 2006 [154] Mean 7.8 Permanent Dental clinic Fuji IX Presence of caries (dentinal lesion); sealant retention (partial/full)

11 Clin Oral Invest (2018) 22: Table 3 Level of heterogeneity (I 2 square) of survival results by dentition, type of cavity and survival year Dentition Type of cavity Survival year Heterogeneity p value I 2 Level Restorations Primary Single Substantial Substantial Quite high Primary Multiple Substantial Substantial Quite high Permanent Single Substantial Substantial Quite high Substantial Moderate Low/unimportant 10 n/a n/a n/a Permanent Multiple Substantial Substantial 3 n/a n/a n/a 5 n/a n/a n/a 10 n/a n/a n/a Sealants Permanent Retention Quite high Quite high Substantial Substantial 5 n/a n/a n/a 6 n/a n/a n/a Permanent Caries No prevention Substantial No Moderate Substantial 6 n/a n/a n/a n/a not applicable (primary and permanent). It is important to highlight that, although the unit of the statistical analysis (the tooth) and the unit of randomisation (usually the patient or the school) were different in several included publications, the fact was not considered an exclusion criterion. A form of statistical correction was performed only in a few studies but should be regarded as an important aspect for future randomised clinical trials (RCTs) that aim to assess the longevity of dental restorations. A large number of ART studies had dental students as operators. It should be highlighted that as students they are in the process of learning skills and, therefore, cannot be the prime operators in invasive medical treatment whose efficacy is under study. Moreover, given the known fact that the operator, even among dentists [121, 142, 157], is an important variable in the survival percentage of ART restorations, a decision was made to exclude trials in which ART restorations were performed by dental students. So far, studies have reported lower survival results for dental students than for dentists [50, 54, 59]. The exclusion of studies that had used non-hvgic restorative materials with the ART approach was based on the outcomes of the 2006 ART meta-analysis, which concluded significantly higher weighted mean survival percentages for ART restorations and sealants that had used HVGIC than for those that had used low- or mediumviscosity glass-ionomer [2]. The quality assessment of publications was not used as an exclusion criterion nor as an attempt to perform sensitivity or subgroup analyses. Instead of using a quality score for each

12 2714 Clin Oral Invest (2018) 22: Table 4 Overview of survival results (in %) and standard error (SE) of single-surface ART restorations using high-viscosity glass-ionomer cements in primary posterior teeth by year of survival Study Country Year of survival Survival SE Survival SE Survival SE Honkala et al., 2003 [117] Kuwait Louw et al., 2002 [118] South Africa Luo et al., 1999 [119] and Lo et al., 2001 [120] China Taifour et al., 2002 [121] Syria Yip et al., 2002 [122] a and Yu et al., 2004 [123] a China Yip et al., 2002 [122] b andyuetal.,2004[123] b China Ersin et al., 2006 [124] Turkey Van Gemert-Schriks et al., 2007 [125] Suriname Menezes et al., 2006 [126] Brazil Yassen, 2009 [127] Iraq Deepa & Shobha, 2010 [128] a India Deepa & Shobha, 2010 [128] b India Hilgert et al., 2014 [129] Brazil Molina et al., 2017 [12] Argentina Weighted mean score a,b Same study but different glass-ionomer cement included publication as a weight for cumulative meta-analysis or meta-regression, the quality assessment was incorporated only qualitatively in this systematic review. Many quality scales and checklists have been proposed in the literature, but it is still difficult to accept that a generic quality assessment tool can be equally successfully applied Table 5 Overview of survival results (in %) and standard error (SE) of multiple-surface ART restorations using high-viscosity glass-ionomer cements in primary posterior teeth by year of survival Study Country Year of survival Survival SE Survival SE Survival SE Ersin et al., 2006 [124] Turkey Van Gemert-Schriks et al., 2007 [125] Suriname Honkala et al., 2003 [117] Kuwait Louw et al., 2002 [118] South Africa Luo et al., 1999 [119] and Lo et al., 2001 [120] China Menezes et al., 2006 [126] Brazil Taifour et al., 2002 [121] Syria Yip et al., 2002 [122] a and Yu et al., 2004 [123] a China Yip et al., 2002 [122] b andyuetal.,2004[123] b China Deepa & Shobha, 2010 [128] a India Deepa & Shobha, 2010 [128] b India Hilgert et al., 2014 [129] Brazil Molina et al., 2017 [12] Argentina Weighted mean score a, b Same study but different glass-ionomer cement

13 Clin Oral Invest (2018) 22: Table 6 Overview of survival results (in %) and standard error (SE) of single-surface ART restorations using high-viscosity glass-ionomer cements in permanent posterior teeth by year of survival Study Country Year of survival Survival SE Survival SE Survival SE Survival SE Survival SE Survival SE Survival SE Cefaly et al., 2007 [131] Brazil Ercan et al., 2009 [132] Turkey Farag et al., 2011 [133] Egypt Frencken et al., 1998 [134] Zimbabwe Frencken et al., 2006 [135] Syria Van Gemert-Schriks et al., 2007 [125] Suriname Ho et al., 1999 [27] Hong Kong Kikwilu et al., 2001 [136] Tanzania Lo et al., 2007 [137] China Loh, 2003 [138] Malaysia Luo et al., 1999 [119] and Lo et al., 2001 [120] China Mickenautsch et al., 1999 [139] South Africa PAHO, 2006 [140] a and Estupiñán-Day et al., 2013 [141] Ecuador PAHO, 2006 [140] b and Estupiñán-Day et al., 2013 [141] Uruguay PAHO, 2006 [140] c and Estupiñán-Day et al., 2013 [141] Panama Rahimtoola & Van Amerongen, 2002 [142] Pakistan Yip et al., 2002 [143] and Gao et al., 2003 [144] China Ziraps & Honkala, 2002 [145] Latvia Ibiyemietal.,2011[146, 147] Nigeria Zanata et al., 2011 [148] Brazil Molina et al., 2017 [12] Argentina Weighted mean score a, b, c Same study but carried out in different countries

14 2716 Clin Oral Invest (2018) 22: Table 7 Overview of survival results (in %) and standard error (SE) of multiple-surface ART restorations using high-viscosity glass-ionomers cements in permanent posterior teeth by year of survival Study Country Year of survival Survival SE Survival SE Survival SE Survival SE Survival SE Cefaly et al., 2007 [131] Brazil Ercan et al., 2009 [132] Turkey Farag et al., 2011 [133] Egypt Zanata et al., 2011 [148] Brazil Molina et al., 2017 [12] Argentina Weighted mean score to all different types of studies. Since prospective one-arm trials were also included, our decision was to assess single quality components that were relevant to the longevity of ART restorations and sealants (Table 10) rather than use a formal scale developed only for RCTs. Regarding the component blinding of evaluators, it is worth noting that whilst this is considered extremely important for preventing bias in any drug medical trial, it seems inappropriate for assessing the quality of dental clinical trials that compare visible different restorative materials or deal with one type of restorative material only. In the present meta-analysis, three of nine studies in which blinding of evaluators would be possible did not perform the blinding properly (Table 10). Despite not being possible for all dental clinical trials, blinding should not be neglected in those trials that compare visible similar restorative materials in order to reduce the risk of detection bias. For the 18 included RCTs in which the component generation of randomisation sequence was considered to have been undertaken (Table 10), all but four failed to report on adequate allocation concealment, which shows a high risk of selection bias in these included publications. Taking additionally into account that 19 of 43 included publications presented a high risk of bias (or at least uncertainty about the potential of bias) for more than half of the quality assessment criteria (Table 10), the results of the current meta-analysis should be interpreted with caution. Even though these results are based on the best available evidence, their validity is to a certain extent compromised by the lack of more methodologically refined trials. In order to improve the level of scientific evidence regarding the survival of different restorative treatments, two new RCTs comparing ART to conventional treatments have been conducted using a superior design according to the guidelines of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) [158, 159]. Although the methodological aspects of both trials have been published in detail as study protocols, it should be highlighted that one of the trials [158] does not make clear if operators in charge of providing restorative treatment are graduated professionals. In Table 8 survival Overview of survival results (in %) and standard error (SE) of partially and fully retained ART sealants in permanent posterior teeth by year of Study Country Year of survival Survival SE Survival SE Survival SE Survival SE Survival SE Survival SE Frencken et al., 1998 [134] Zimbabwe Vieira et al., 2006 [149] Brazil Holmgren et al., 2013 [150] a China Luengas-Quintero et al., 2013 [151] Mexico Liu et al., 2014 [152] China Zhang et al., 2017 [115] China Hilgert et al., 2017 [116] Brazil Weighted mean score a Additional information extracted from Holmgren et al. [18] and personal communication

15 Clin Oral Invest (2018) 22: Table 9 Overview of survival results (in %) and standard error (SE) of caries-free previously sealed pits and fissures using ART sealants in permanent posterior teeth by year of survival Study Country Year of survival Survival SE Survival SE Survival SE Survival SE Survival SE Survival SE Frencken et al., 1998 [134] Zimbabwe Vieira et al., 2006 [149] Brazil Holmgren et al., 2013 [150] a China Luengas-Quintero et al., 2013 [151] Mexico Liu et al., 2014 [152] China Zhang et al., 2014 [153] China Hilgert et al., 2015 [130] Brazil Beiruti et al., 2006 [154] Syria Weighted mean score a Additional information extracted from Holmgren et al. [18] and personal communication case of them being students, the trial may not give such a strong contribution to the question whether ART restorations survive as long as conventional restorative treatments. The results of the meta-analyses gain in quality even more if a high level of homogeneity is obtained. Its level is dependent on the power of the homogeneity test which is dependent on the number of studies and the respective results and confidence intervals. A low p value is usually associated with a high I 2 percentage. In the present meta-analyses that included a number of studies from a total of 22 countries and regions, all with different study backgrounds, the level of heterogeneity of the weighted mean survival percentages for the ART restorations was at least substantial. Heterogeneity for the weighted survival percentages of ART sealants was much lower and even reached the level of homogeneity. Overall, it is fair to conclude that the required methodological aspects for performing a meta-analysis have been met to the highest possible level considering the data available. Main findings The weighted mean survival percentages of single-surface ART/HVGIC restorations in both the 2012 and 2017 metaanalyses were very high. The weighted mean 3-year survival percentage of single-surface ART/HVGIC restorations in primary posterior teeth in 2017 (85%) was different from that in 2012 (66%), but the difference was not statistically significant. It is fair to conclude that ART can safely be used to restore single-surface cavities in primary teeth. Non-significant differences were found in weighted mean survival percentage for multiple-surface ART/HVGIC restorations in primary posterior teeth over the first 3 years between the 2012 and 2017 ART meta-analyses. The first year weighted mean survival percentage of multiple-surface ART restorations in the 2017 meta-analysis was fairly high, but the survival percentages at years 2 and 3, although higher than in 2010, were insufficiently high. Unfortunately, the metaanalyses did not include a category of cavity size, which would otherwise have made it possible to recommend the use of ART/HVGIC restorations in certain sizes of multiplesurface cavities. After all, it is known that large multiplesurface ART/HVGIC restorations fail more frequently than smaller ones [128, 160]. It is fair to conclude that ART/ HVGIC can be used as an alternative method for restoring multiple-surface cavities in posterior primary teeth, but that particularly the larger cavities should not be attempted. Such cavities can be treated perhaps through an application regime of silver diamine fluoride [161] or with the ultra-conservative treatment (UCT) approach, in which large cavities are brushed plaque free with a toothbrush and fluoridated toothpaste [162], or with the Hall technique [163]. The number of included ART studies that investigated the survival of restorations in single-surface cavities in permanent posterior teeth at the first 3 years was high to very high. After 3 years, however, the number was much lower and the survival outcomes were less reliable, although the standard error was not very high. The only long-term (10 years) ART/HVGIC survival study in single-surface restorations in posterior teeth in adults resulted in a survival percentage of 87% [148]. This finding is very high and exceeds the weighted mean annual failure percentage of 4.1% over the first 5 years found in the present meta-analysis. Different from the recommendation that the ART approach can be safely used to restore singlesurface cavities in posterior permanent teeth, insufficient data make it impossible to give an informed opinion about its use in multiple-surface cavities in posterior permanent teeth. The weighted mean annual failure rate of fully and partially retained ART/HVGIC sealants over the first 3 years was

16 2718 Clin Oral Invest (2018) 22: Table 10 Quality assessment of included studies Study Quality assessment criteria Generation of randomisation sequence Allocation concealment Training of operators Independency of evaluators Calibration of evaluators Blinding of evaluators Completeness of follow up Implementation of a preventive programme Sample baseline caries experience Honkala et al., 2003 [117] Yes No Yes No Unclear NP/NA Yes No No Louw et al., 2002 [118] Yes No Yes Yes Yes NP/NA Yes Yes No Luo et al., 1999 [119] and Lo et al., 2001 Yes No Yes Yes Yes Unclear Yes No No [120] Taifour et al., 2002 [121] Yes No Yes Yes Yes NP/NA Yes Yes No Yip et al., 2002 [122] and Yu et al., 2004 Unclear No Yes Unclear No NP/NA No a No No [123] Ersin et al., 2006 [124] Yes No No Yes Yes NP/NA Yes No Unclear b Van Gemert-Schriks et al., 2007 [125] Unclear No Yes No Yes NP/NA Yes No Yes Menezes et al., 2006 [126] Yes Yes No Yes Yes Yes Yes No No Yassen, 2009 [127] Yes No No Yes Yes Yes Yes No No Deepa & Shobha, 2010 [128] Yes No Yes Yes Yes Yes Yes No No Hilgert et al., 2014 [129] and Hilgert et al., Yes No Yes Yes Yes NP/NA Yes Yes Yes 2015 [130] and Hilgert et al., 2017 [116] Molina et al., 2017 [12] No No No Yes Yes NP/NA Yes No Unclear c Cefaly et al., 2007 [131] Unclear No Yes Yes Yes Unclear Yes Yes Yes Ercan et al., 2009 [132] Yes No Yes No Yes NP/NA Yes No Unclear b Farag et al., 2011 [133] No No No Yes Yes NP/NA No a Yes Yes Frencken et al., 1998 [134] No No Yes Yes No NP/NA No a Yes Unclear b Frencken et al., 2006 [135] Yes No Yes Yes Yes NP/NA No a Yes Yes Ho et al., 1999 [27] Unclear Unclear No Unclear Unclear NP/NA Yes No No Kikwilu et al., 2001 [136] No No Unclear Unclear Unclear NP/NA Yes No No Lo et al., 2007 [137] No No Yes No Yes NP/NA No a No Yes Loh, 2003 [138] No No Yes No Yes NP/NA No a No Unclear b Mickenautsch et al., 1999 [139] Unclear No Unclear Yes Unclear Unclear No a No Unclear b PAHO, 2006 [140] and Estupiñán-Day et al., 2013 [141] Yes Yes Yes Yes Yes NP/NA No No No Rahimtoola & Van Amerongen, 2002 [142] Yes No Yes No Yes NP/NA Yes No Yes No No Unclear Unclear Unclear NP/NA Yes No No Yip et al., 2002 [143] and Gao et al., 2003 [144] Ziraps & Honkala, 2002 [145] Yes No No Yes Unclear Yes Yes No No Ibiyemietal.,2011[146, 147] Yes Yes Yes Yes Yes Yes Yes Yes No Zanata et al., 2011 [148] Unclear No Yes Yes Yes NP/NA No a Yes Yes Vieira et al., 2006 [149] Unclear Unclear Yes Yes Yes Yes Yes Yes Yes

17 Clin Oral Invest (2018) 22: Table 10 (continued) Study Quality assessment criteria Sample baseline caries experience Implementation of a preventive programme Completeness of follow up Blinding of evaluators Calibration of evaluators Independency of evaluators Training of operators Allocation concealment Generation of randomisation sequence Holmgren et al., 2013 [150] No No Yes No Yes NP/NA No a Yes Yes Luengas-Quintero et al., 2013 [151] No No Yes Yes Yes NP/NA Yes Yes No Liu et al., 2014 [152] Yes Unclear Yes No Yes NP/NA Yes Yes No Zhang et al., 2014 [153] andzhangetal., Yes Yes Yes Yes Yes NP/NA Yes Yes Yes 2017 [115] Beiruti et al., 2006 [154] Yes No Yes Yes Yes NP/NA No a Yes Yes NP = not possible (restorative materials used were different in visual assessment); NA = not applicable (1 treatment group only) a Loss to follow-up more than 30% b dfmt/dmft provided did not refer to treatment groups, but to the whole sample examined before application of inclusion criteria c dfmt/dmft provided did not refer to each treatment group, but to all treated subjects substantial but not significantly different from that reported in the 2012 meta-analysis: 10.7 versus 9.3%. The difference was due to the inclusion of one extra study in 2017 [116]thathada lower survival percentage for 3 years of follow-up when compared to those from The 5-year weighted mean survival percentage of dentine-carious-lesion-free pits and fissures that had been sealed was very high and was equal to the comparable survival percentage reported in the previous metaanalysis because no additional study with 5 years of followup was included in this update. With four more studies in the database, the present meta-analysis ensures that the efficacy of ART/HVGIC sealants in controlling dentine-carious-lesion development in pits and fissures is well established. Comparing survival results of ART/HVGIC with traditional restorations and sealants On the basis of three studies, no significant difference in the 2- year survival percentages between single- and multiplesurface ART/HVGIC and amalgam restorations in primary molars was reported [164]. For single-surface cavities in primary molars, this finding is supported by a 3-year study that compared ART with amalgam restorations [129]. For multiple-surface cavities in primary molars, a systematic review performed with only RCTs concluded that ART/HVGIC restorations have similar survival percentages to conventional treatment of amalgam and resin composite restorations [165]. The 2017 Cochrane review on ART could not conclude about ART/HVGIC restorations against amalgam/composite restorations in both primary and permanent teeth because of insufficient information. It, however, compared ART/HVGIC treatment against a treatment that consists of cleaning the cavity with rotating instruments and restoring it with the same HVGIC in multiple surfaces in primary teeth. On the basis of three studies, of which two were carried out with dental students and one with also dental hygienists as operators, the difference between the two treatments was of borderline significance, favouring the rotating excavation treatment [166]. Although the weighted mean survival percentages of ART/ HVGIC restorations in multiple-surface cavities in posterior primary teeth in the present meta-analysis were not high, evidence shows that these survival percentages do not differ significantly from those calculated for conventionally produced restorations using amalgam or resin composite. It appears that it is difficult to achieve high restoration survival percentages in multiple-surface cavities in primary posterior teeth, independent of the treatment approach and restorative material used. In comparison with traditional amalgam restorations of the same size, type of dentition and follow-up period, a systematic review [164] concluded that ART/HVGIC restorations in permanent teeth appear to be equally successful and that their survival percentages may even exceed those of amalgam restorations. This finding was corroborated by an updated systematic