Randomized clinical trials of dental bleaching – Compliance with the CONSORT Statement: a systematic review

LOGUERCIO, Alessandro Dourado; MARAN, Bianca Medeiros; HANZEN, Taíse Alessandra; PAULA, Alexandra Mara de; PERDIGÃO, Jorge; REIS, Alessandra

doi:10.1590/1807-3107BOR-2017.vol31.0060

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Critical Review • Braz. oral. res. 31 (suppl 1) • Aug 2017 • https://doi.org/10.1590/1807-3107BOR-2017.vol31.0060 linkcopy

Randomized clinical trials of dental bleaching – Compliance with the CONSORT Statement: a systematic review

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

We reviewed the literature to evaluate: a) The compliance of randomized clinical trials (RCTs) on bleaching with the CONSORT; and b) the risk of bias of these studies using the Cochrane Collaboration risk of bias tool (CCRT). We searched the Cochrane Library, PubMed and other electronic databases, to find RCTs focused on bleaching (or whitening). The articles were evaluated in compliance with CONSORT in a scale: 0 = no description, 1 = poor description and 2 = adequate description. Descriptive analyses of the number of studies by journal, follow-up period, country and quality assessments were performed with CCRT for assessing risk of bias in RCTs. 185 RCTs were included for assessment. More than 30% of the studies received score 0 or 1. Protocol, flow chart, allocation concealment and sample size were more critical items, as 80% of the studies scored 0. The overall CONSORT score for the included studies was 16.7 ± 5.4 points, which represents 52.2% of the maximum CONSORT score. A significant difference among journal, country and period of time was observed (p < 0.02). Only 7.6% of the studies were judged at “low” risk; 62.1% were classified as “unclear”; and 30.3% as “high” risk of bias. The adherence of RCTs evaluating bleaching materials and techniques to the CONSORT is still low with unclear/high risk of bias.

Tooth Bleaching; Dental Sensitivity

Pubmed
#1 (((((((((((((((((((tooth discoloration[MeSH Terms]) OR dentition, permanent[MeSH Terms]) OR color[MeSH Terms]) OR color[Title/Abstract]) OR colour[Title/Abstract]) OR “tooth discoloration”[Title/Abstract]) OR “tooth discolouration”[Title/Abstract]) OR “teeth discoloration”[Title/Abstract]) OR “teeth discolouration”[Title/Abstract]) OR “discolored tooth”[Title/Abstract]) OR “discoloured tooth”[Title/Abstract]) OR “discolored teeth”[Title/Abstract]) OR “discoloured teeth”[Title/Abstract]) OR “dental discoloration”[Title/Abstract]) OR “dental discolouration”[Title/Abstract]) OR “tooth staining”[Title/Abstract]) OR “teeth staining”[Title/Abstract]) OR “stained tooth”[Title/Abstract]) OR “stained teeth”[Title/Abstract]) OR “dental staining”[Title/Abstract]	#2 ((((((((((((((((((tooth bleaching[MeSH Terms]) OR tooth bleaching agents[MeSH Terms]) OR peroxides[MeSH Terms]) OR hydrogen peroxide[MeSH Terms]) OR carbamide peroxide[Supplementary Concept]) OR peroxides[Title/Abstract]) OR “hydrogen peroxide”[Title/Abstract]) OR “carbamide peroxide”[Title/Abstract]) OR bleaching[Title/Abstract]) OR whitening[Title/Abstract]) OR “in office”[Title/Abstract]) OR “at home”[Title/Abstract]) OR “light activation”[Title/Abstract]) OR “light activated”[Title/Abstract]) OR “laser assisted”[Title/Abstract]) OR “dentist-supervised”[Title/Abstract]) OR nightguard[Title/Abstract]) OR “tray-delivered”[Title/Abstract]) OR “jump-start”[Title/Abstract]		#3 (randomized controlled trial[pt] OR controlled clinical trial[pt] OR randomized controlled trials[mh] OR random allocation[mh] OR double-blind method[mh] OR single-blind method[mh] OR clinical trial[pt] OR clinical trials[mh] OR (“clinical trial”[tw]) OR ((singl[tw] OR doubl[tw] OR trebl[tw] OR tripl[tw]) AND (mask[tw] OR blind[tw])) OR (placebos[mh] OR placebo[tw] OR random[tw] OR research design[mh:noexp] OR comparative study[pt] OR evaluation studies as topic[mh] OR follow-up studies[mh] OR prospective studies[mh] OR control[tw] OR prospective[tw] OR volunteer*[tw]) NOT (animals[mh] NOT humans[mh]))
#1 AND #2 AND #3
Cochrane Library
#1 MeSH descriptor: [Tooth Discoloration] explode all trees		#8 MeSH descriptor: [Tooth Bleaching Agents] explode all trees
#2 MeSH descriptor: [Dentition, Permanent] explode all trees		#9 MeSH descriptor: [Peroxides] explode all trees
#3 MeSH descriptor: [Color] explode all trees		#10 MeSH descriptor: [Hydrogen Peroxide] explode all trees
#4 color:ti,ab,kw or tth next discoloration:ti,ab,kw or discolored next tth:ti,ab,kw or dental next discoloration:ti,ab,kw or t*th next staining:ti,ab,kw (Word variations have been searched)		#11”carbamide peroxide”:ti,ab,kw or peroxides:ti,ab,kw or “hydrogen peroxide”:ti,ab,kw or bleaching:ti,ab,kw or whitening:ti,ab,kw (Word variations have been searched)
#5 stained next t*th:ti,ab,kw or dental next staining:ti,ab,kw (Word variations have been searched)		#12 “in office”:ti,ab,kw or “at home”:ti,ab,kw or light next activat*:ti,ab,kw or laser next assisted:ti,ab,kw or dentist supervised:ti,ab,kw (Word variations have been searched)
#6 #1 or #2 or #3 or #4 or #5		#13 nightguard:ti,ab,kw or tray delivered:ti,ab,kw or jump start:ti,ab,kw (Word variations have been searched)
#7 MeSH descriptor: [Tooth Bleaching] explode all trees		#14 #7 or #8 or #9 or #10 or #11 or #12 or #13
#15 #6 AND #14
Lilacs and BBO
#1 (MH: “tooth discoloration” OR MH: “permanent dentition” OR MH:color OR color OR cor OR colour OR “tooth discoloration” OR “descoloração do dente” OR “decoloración del diente” OR “descoloración del diente” OR “tooth discolouration” OR “teeth discoloration” OR “descoloração dos dentes” OR “decoloración de los dientes” OR “descoloración de los dientes” OR “teeth discolouration” OR “discolored tooth” OR “dente descolorido” OR “discoloured tooth” OR “discolored teeth” OR “dentes descoloridos” OR “diente pigmentado” OR “dientes pigmentados” OR “dentes pigmentados” OR “dente pigmentado” OR “discoloured teeth” OR “dental discoloration” OR “descoloração dental” OR “decoloración dental” OR “decoloración dentaria” OR “descoloración dental” OR “descoloración dentaria” OR “dental discolouration” OR “tooth staining” OR “manchamento dental” OR “tinción dental” OR “tinción dentaria” OR “pigmentación dental” OR “pigmentación dentaria” OR “teeth staining” OR “dentes manchados” OR “stained tooth” OR “dente manchado” OR “stained teeth” OR “mancha nos dentes” OR “mancha en los dientes” OR “dental staining” OR “mancha en lo diente” OR “mancha no dente”)		#2 (MH:”tooth bleaching” OR MH:”tooth bleaching agents” OR MH:peroxides OR MH:”hydrogen peroxide” OR peroxides OR peróxidos OR “hydrogen peroxide” OR “peróxido de hidrogênio” OR “carbamide peroxide” OR “peróxido de carbamida” OR bleaching OR branqueamento OR blanqueo OR whitening OR clareamento OR blanqueamiento OR clareamiento OR “in-office” OR “em consultório” OR “en ambulatorio” OR “at home” OR caseiro OR “casero” OR “light activation” OR fotoativação OR “activación por luz” OR “light activated” OR “ativado por luz” OR “activado por luz” OR “laser assisted” OR “a laser” OR “con láser” OR “dentist-supervised” OR “superviosionado por dentista” OR “supervisado por el dentista” OR nightguard OR “tray-delivered” OR moldeira OR cubeta OR “jump-start” OR associado OR combinado)
#1 AND #2
Web of science
#1Tópico: (“tth discoloration”) OR Tópico: (“permanent dentition”) OR Tópico: (colo$r) OR Tópico: (“discolored tth”) OR Tópico: (“dental discoloration”) OR Tópico: (“tth staining”) OR Tópico: (“stained t*th”) OR Tópico:(“dental staining”)		#2 Tópico:(“tth bleaching”) OR Tópico:(peroxides) OR Tópico: (“hydrogen peroxide”) OR Tópico: (“carbamide peroxide”) OR Tópico: (bleaching) ORTópico: (whitening) OR Tópico: (“in-office”) OR Tópico: (“at home”) ORTópico: (“light activat”) OR Tópico:(“laser assisted”) OR Tópico:(“dentist-supervised”) OR Tópico:(nightguard) OR Tópico: (“tray-delivered”) OR Tópico: (“jump-start”)
#1 AND #2
Scopus
#1 (TITLE-ABS-KEY (“tth discoloration”) OR TITLE-ABS-KEY (“permanent dentition”) OR TITLE-ABS-KEY (color) OR TITLE-ABS-KEY (“tth discolouration”) OR TITLE-ABS-KEY (“discolored tth”) OR TITLE-ABS-KEY (“discoloured tth”) OR TITLE-ABS-KEY (“dental discoloration”) OR TITLE-ABS-KEY (“tth staining”) OR TITLE-ABS-KEY (“stained tth”) OR TITLE-ABS-KEY (“dental staining”))		#2 (TITLE-ABS-KEY (“tth bleaching”) OR TITLE-ABS-KEY (peroxides) OR TITLE-ABS-KEY (“hydrogen peroxide”) OR TITLE-ABS-KEY (“carbamide peroxide”) OR TITLE-ABS-KEY (bleaching) OR TITLE-ABS-KEY (whitening) OR TITLE-ABS-KEY (“in office”) OR TITLE-ABS-KEY (“at home”) OR TITLE-ABS-KEY (“light activat”) OR TITLE-ABS-KEY (“laser assisted”) OR TITLE-ABS-KEY (“dentist-supervised”) OR TITLE-ABS-KEY (nightguard) OR TITLE-ABS-KEY (“tray-delivered”) OR TITLE-ABS-KEY (“jump-start”))
#1 AND #2

Inclusion criteria	Exclusion criteria
Parallel and Split-mouth RCTs published in 1996 or later	Laboratory studies
	Conference abstracts
Different types of bleaching systems (in-office, at home and jump-start) (bleaching strips, gels, dentifrices, use of light) regarding.	Thesis
Studies that evaluate color change, toxicity, postoperative sensitivity and application technique	Reports published in any media other than peer-reviewed journals
The studies included patients of any age group	Reported cases

CONSORT item	Sub-item	Score	Adherence to the methods and results items of the consort statement

			Description
Trial design		Positive [2]	The trial design is clearly written in the text (split mouth, cross-over, factorial, cluster).
		Negative [0]	This information is not reported.
		Poor [1]	1. Information can be obtained during reading the manuscript, although this is not explicity reported by the authors. 2. There is lack of consistence between sections of the article (examples - abstract does not match the material and methods section; the presentation of the results does not match the description of the trial design; flow diagram presents different information, etc.).
Participants	Eligibility criteria	Positive [2]	The inclusion and exclusion criteria is clear, so that readers can know exactly which population the data can be extrapolated to.
		Negative [0]	The information is not reported.
		Poor [1]	1. Incomplete information of eligibility criteria compared to most of the studies on the field. 2. Presence of inconsistencies in the inclusion/exclusion criteria that prevents the readers from knowing the population at which the intervention/control groups were performed.
	Settings and location	Positive [2]	Clear description of the setting (academic, practice-based research, university, private clinics, etc.) as well as the date at which the intervention was implemented.
		Negative [0]	The setting and/or the location is not reported in the text.
		Poor [1]	1. Authors describe either the setting or the date but never both. 2. This information can be obtained indirectly in the text
Interventions		Positive [2]	The interventions for each group are described with sufficient details to allow replication, including how they were actually administered.
		Negative [0]	There is no description.
		Poor [1]	There are missing information that prevents the replication of the interventions/comparators.
Outcomes		Positive [2]	At least the primary outcomes were defined in details, including how and when they were assessed. Consider it as clear when the details are clear, but the authors did not use the term “primary outcome” or related synonyms.
		Negative [0]	There is no definition of the primary outcome and/or secondary outcomes.
		Poor [1]	1. The authors only report they have used a specific criteria without detailing the most important outcomes of such criteria. 2. The description of the primary outcome and/or secondary outcomes is very superficial and does not allow replication of the method.
Sample size		Positive [2]	Method of sample size calculation is described in a way to allow replication. It should be identified the primary outcome for each the sample size was calculated for. Elements of the sample size calculation are (1) the estimated outcomes in each group (which implies the clinically important target difference between the intervention groups); (2) the α (type I) error level; (3) the statistical power (or the β (type II) error level); and (4), for continuous outcomes, the standard deviation of the measurements should be reported. For equivalence trials, the equivalence limit, instead of the effect size should be reported.
		Negative [0]	There is no description in the article.
		Poor [1]	The sample size is described but some parameters are missing so that it prevents replication.
Randomization	Sequence generation	Positive [2]	1. Clear description of the random sequence generation. 2. or clear description of a non-random sequence method.
		Negative [0]	There is no information in the text.
		Poor [1]	The authors only provide a very superficial description (such as the “groups were randomly allocated”) or do not provide sufficient information to allow replication of the randomization process.
	Allocation concealment	Positive [2]	Clear description of the allocation concealment. See next columns for evaluation of the Risk of Bias.
		Negative [0]	There is no information in the text.
		Poor [1]	not applicable
Blinding		Positive [2]	1) The authors describe who is blinded in the study. 2. In single-blind studies (when this is clearly reported by the authors), just the description of participant or evaluator (the one blinded) is enough; however when the study is double blind or triple blind all blinded people should be described. 2) The study describes just the participant or examiner blinded but one of these people cannot be blinded by intrinsic features of the study design.
		Negative [0]	There is no description of the blinding.
		Poor [1]	Insufficient/partial information. For instance, (1) the authors describe examiners’ blinding or participants’ blinding, but never both. (2) The authors describe the study was blind or double-blind but does not specify who was blinded.
Statistical methods	Hypothesis testing	Positive [2]	Statistical methods are described with enough detail to enable a knowledgeable reader with access to the original data to verify the reported results. Additionally, statistical tests employed by the authors seem to be adequate for the type of trial design and nature of the data collected.
		Negative [0]	Statistical methods are not described.
		Poor [1]	1) There is not enough information to evaluate the statistical method used by the authors and/or the type of statistical tests employed by the authors are inadequate for the trial design and/or nature of the data (for instance, tests that do not take into account the paired nature of the data when this is the case). 2) The authors describe several statistical tests but does not specify for each outcome they were applied.
	Estimated effect size	Positive [2]	Authors report at least for the primary outcome the effect size and its precision (such as 95% confidence interval). Odds ratio, risk ratio, risk difference, mean difference, etc.
		Negative [0]	There is no description of the effect size and 95% confidence interval
		Poor [1]	There is incomplete information.
Participant flow	Flow diagram	Positive [2]	For each group, the numbers of participants who were randomly assigned, received intended treatment and were analyzed for the primary outcome is described in the flow chart CONSORT diagram.
		Negative [0]	The flow-chart is not presented in the article.
		Poor [1]	1. There are inconsistencies between the numbers described in the flow-chart and other parts of the manuscript. 2. Incomplete diagram with missing information
	Losses/Exclusions	Positive [2]	1. For each group, losses and exclusions after randomization are described with reasons. 2. During reading, reviewer observes that there is no loss to follow-up.
		Negative [0]	1. There is no description of losses and exclusions.
		Poor [1]	Incomplete information. For instance, 1. the authors describe the overall percentage of losses but this information is not specified per group. 2. The authors describe the losses and exclusions but does not specify the reasons
Baseline data		Positive [2]	A table/text description containing baseline demographic and clinical characteristics of each group are presented in the article.
		Negative [0]	There is no table/text description with baseline data or description in the body of the text.
		Poor [1]	1. A table/ text description with baseline data is presented but the data is not distributed between the study groups and/or given in percentages instead of raw numbers. 2. Insufficient information about participants is provided; 3. Inconsistencies in the data presented can be observed.
Numbers analysed		Positive [2]	For each group and for each outcome, the number or participants (denominator) included in the analysis are clear.
		Negative [0]	Authors do not report the numbers analyzed.
		Poor [1]	There is no clear description of the number of participants (denominator) included in the analysis of at least one of the outcomes. 2. Instead of reporting the raw number of participants, the authors report their data in percentages. 3. The authors fail to report the baseline number of patients included in each analysis. 4. Data can be obtained indirectly in the study.
Registration and protocol		Positive [2]	The study was registered in a trial registry and the protocol number is provided.
		Negative [0]	This information is not available in the manuscript. Registration in an Ethics Committee is valid as trial registry
		Poor [1]	The authors describe that the study was registered but does not provide the registration number and/or the number provided does not link to the study.

Characteristics	Categories	Number of studies	Percentage (%)
Journal	Clin Oral Investig	5	2.7
	J Clin Dent	10	5.4
	J Esthet Restor Dent	11	5.9
	J Dent	12	6.5
	JADA	12	6.5
	Quintessence Int	13	7.0
	Am J Dent	14	7.6
	Comp Cont Educ Dent	21	11.4
	Oper Dent	33	17.8
	Others*	54	29.2
Country	UK	6	3.2
	Italy	7	3.8
	Germany	14	7.6
	Brazil	52	28.1
	USA	75	40.5
	Others**	31	16.8
Period of time	1996 to 2000	17	9.2
	2001 to 2005	48	25.9
	2006 to 2010	52	28.1
	2011 to 2016	68	36.8
Follow-up period (days)	0	5	2.7
	7	12	6.5
	14	42	22.7
	21	10	5.4
	28	19	10.3
	30	6	3.2
	42	5	2.7
	168	12	6.5
	Others***	74	40.0

Item	Examples
Trial design
	Example 1: “This study was a randomized, single-blind, controlled trial with a parallel group and an allocation rate of 1:1.”56
	Example 2: “This was a randomized, parallel, placebo-controlled, triple-masked clinical trial, in which the patient, operator, and evaluator were masked to the group assignment. A third researcher, not involved in the evaluation process, was responsible for the randomization process, and delivery and guidance on the administration of the drugs.”57
Participants
Eligibility criteria	The authors judged that it was not necessary to add some examples, because this item showed an adequate reporting as seen in Figure 2.
Settings and locations	Example 1: “The study took place in the clinics of the dentistry schools at the State University of Ponta Grossa, Paraná, and the University of São Paulo, São Paulo, from June 2010 to June 2012.”58
Settings and locations	Example 2: “This study was performed from February 2011 to March 2012 in the city of Guarapuava (Paraná, Brazil).”12
Interventions	The authors judged that it was not necessary to add some examples, because this item showed an adequate reporting as seen in Figure 2.
Outcomes	The authors judged that it was not necessary to add some examples, because this item showed an adequate reporting as seen in Figure 2.
Sample size
For Tooth sensitivity	For superiority trial: “The primary outcome of this study was the absolute risk of TS. The absolute risk of TS (that is, the number of patients [percent] who reported pain at some point during dental bleaching) was reported to be approximately 87% (4,8) for the bleaching product Whiteness HP Maxx (FGM Dental Products). Thus, a minimum sample size of 56 participants was required to have a 90% chance of detecting, as significant at the 2-sided 5% level, a decrease in the primary outcome measure from 86% in the control group to 50% in the experimental group.”57
For Tooth sensitivity	For equivalent trial: We selected the absolute risk of TS as the primary study outcome. Considering the absolute risk of TS to be approximately 90% (19, 40) participants were required to be 90% (study power) sure that the limits of a two-sided 90% confidence interval will exclude a difference between the standard and experimental group of more than 30% (equivalence limit).”59
For Color evaluation	For superiority trial: “The primary outcome of this study was color change of the participants’ teeth. A previous study (34) reported that two bleaching sessions with the product Whiteness HP Maxx 35% (FGM Dental Products, Joinville, SC, Brazil) without light activation produced a whitening effect of about 7 ± 2 SGUs. To detect a difference of 2 SGUs between the means of any pair of the study groups, with a power of 80% and an alpha of 5%, a minimum sample size of 17 patients per group was required. This threshold of perceptibility was based on the fact that ‘‘untrained’’ people, such as the patients, do not detect easily changes of one shade guide unit at the lighter end of the vita classical guide.”58
For Color evaluation	For equivalent trial: We based the sample size calculation on the color change measured with the spectrophotometer (DE), the primary outcome of the study. One hundred eighteen participants were required to exclude a difference of means of 2.0 units of DE at 1 week and 1 month (equivalence limit) with a power of 90 % and a of 5 %. With these calculations, we took into consideration a standard deviation of 3.3 in the DE. The equivalence limit we chose was lower than the DE threshold of 3.0, above which color differences become clinically perceptible (24-26).”60
Randomisation
Sequence generation, allocation concealment and implementation	Example 1: “The randomization process was performed by coin toss immediately before the bleaching procedure to provide adequate allocation concealment.”61
	Example 2: “Participants were randomly divided into four groups according to the combination of the main factors: HP (20% or 35%) and light activation (with or without). A third person who was not involved in the research protocol performed the randomization procedure by using computer-generated tables. We used blocked randomization (block sizes of 2 and 4) with an equal allocation ratio (www.sealedenvelope.com). Opaque and sealed envelopes containing the identification of the groups were prepared by a third party not involved in the study intervention.”58
Blinding	Example 1: “The participant and the operator could not be blinded to the procedure, as the application of bleaching gel for different times could not be masked. However, the examiners who evaluated the color changes were not aware of which group the participant was assigned to.”62
Blinding	Example 2: “Neither the participant nor the operator knew the group allocation, both being blinded to the protocol.” “The two examiners, blinded to the allocation assignment, scheduled these patients for bleaching and evaluated their teeth against the shade guide at baseline and 30 days after the procedure.”63
Statistical methods
Hypothesis testing	The authors judged that it was not necessary to add some examples, because this item showed an adequate reporting as seen in Figure 2.
Estimated effect size	Two examples of how to report an effect size can be seen in Tables 6 and 7.
Participants
Flow diagram	Please see the following link to have access templates of the CONSORT flow diagram available in MS Word (http://www.consort-statement.org/consort-statement/flow-diagram)
Losses and exclusions	The authors judged that it was not necessary to add some examples, because this item showed an adequate reporting as seen in Figure 2.
Baseline data	Two examples of how to report an effect size can be seen in Tables 8 and 9.
Numbers analysed	The authors judged that it was not necessary to add some examples, because this item showed an adequate reporting as seen in Figure 2.
Registration and protocol	Example 1: “The ClinicalTrials.gov identification number was NCT02017873.”4
Registration and protocol	Example 2: “The clinical investigation was approved (protocol number 172.988) by the scientific review committee and by the committee for the protection of human participants of the local university. It was registered in the Brazilian clinical trials registry under the identification number RBR-6pt2n3.”57

Characteristics	Smokers	Non-smokers
Age (years; mean ± SD)
Brazil	26.3 ± 6.5	24.1 ± 6.8
Chile	29.3 ± 9.4	25.5 ± 6.6
Male (%)
Brazil	46.7	53.3
Chile	63.3	36.7
Baseline color (L*; mean ± SD)
Brazil	82.4 ± 4.9	82.3 ± 4.3
Chile	83.2 ± 4.0	84.9 ± 3.8
Baseline color (b*; mean ± SD)
Brazil	22.6 ± 3.6	23.2 ± 3.6
Chile	22.2 ± 3.1	21.7 ± 2.5
Baseline color (a*; mean ± SD)
Brazil	-1.0 ± 1.0	-0.5 ± 1.0
Chile	-0.0 ± 0.7	-0.2 ± 0.6
Baseline color (SGU; mean ± SD)
Brazil	6.8 ± 2.3	7.4 ± 2.5
Chile	7.2 ± 1.7	8.4 ± 2.9
Smoking time (years; mean ± SD)
Brazil	8 ± 5.9	-
Chile	11.8 ± 9.1	-
Number cigarettes/day (mean ± SD)
Brazil	13.2 ± 4.0	-
Chile	12.8 ± 3.8	-

Feature	20%	20% + light	35%	35% + light
Age (mean ± SD)	22.9 ± 4.0	22.0 ± 4.4	23.0 ± 3.4	22.0 ± 3.6
Female (n, %)	13 (68)	12 (63)	13 (68)	12 (60)
Baseline SGU (median, 25 and 75 percentil)	12 (11 – 14)	12 (11 – 12)	12 (10,5 – 15)	11 (9 – 12)

Color evaluation tools	Groups		p-value	Mean difference (95%CI)

	Placebo	Dexamethasone
Vita Classical	3.1 ± 2.6	3.4 ± 2.3	0.642	- 0.3 (-9.9–10.5)
Dexamethasone	2.8 ± 2.2	2.7 ± 1.6	0.775	- 0.6 (-9.4–10.6)
p-value	6.0 ± 4.7	6.6 ± 4.0	0.582	- 0.6 (-11.4–12.6)

Periods	Group	Number of patients with TS		Absolute risk (95%CI)	Risk ratio (95%CI)	p-value*

		Yes	No
During in-office session	HP35%	17	3	85.0 (64.0–95.0)	1.8 (1.1– 3.2)	0.02
During in-office session	HP20%	7	8	47.0 (25.0–69.0)	1.8 (1.1– 3.2)	0.02
Up to 48 h after in-office session	HP35%	13	7	65.0 (43.2–81.9)	2.0 (0.9–4.3)	0.09
Up to 48 h after in-office session	HP20%	5	10	33.3 (15.2–58.3)	2.0 (0.9–4.3)	0.09
During at-home bleaching	HP35%	5	15	25.0 (11.2–46.9)	1.3 (0.5–3.8)	0.71
During at-home bleaching	HP20%	5	10	33.3 (15.2–58.3)	1.3 (0.5–3.8)	0.71

Characteristics	Categories	Mean ± SD	Median (interquartile range)	p-value*
Journal	Clin Oral Investig	19.60 ± 6.58 A	18 (18–22)	< 0.0001
	J Clin Dent	16.30 ± 1.42 A,B	16 (15–17)
	J Esthet Restor Dent	15.27 ± 3.04 A,B	14 (13–17.5)
	J Dent	21.75 ± 6.50 A	20 (17.5–28.25)
	JADA	19.33 ± 5.28 A	19.5 (13–22.5)
	Quintessence Int	15.54 ± 4.33 A,B	14 (13–16)
	Am J Dent	18.36 ± 4.22 A,B	18.5 (16.25–19.75)
	Comp Cont Educ Dent	15.24 ± 3.06 A,B	15 (13–18)
	Oper Dent	19.94 ± 6.32 A	18 (15–25)
	Others	13.80 ± 4.99 B	13 (11–16)
Country	UK	14.83 ± 2.99 B	15 (12.5–17.5)	0.02
	Italy	14.29 ± 6.80 B	13 (9.5–19)
	Germany	16.71 ± 4.05 A,B	17 (14.25–18)
	Brazil	19.48 ± 6.93 A	20.5 (13.75–25)
	USA	15.25 ± 3.13 B	15 (13.5–18)
	Others	16.10 ± 4.99 A,B	14.5 (12.25–18)
Period of time	1996 to 2000	13.47 ± 4.03 B	14 (11–16)	0.004
	2001 to 2005	15.54 ± 2.81 A,B	16 (14–18)
	2006 to 2010	15.75 ± 4.01 A,B	15 (13–19)
	2011 to 2016	19.03 ± 6.87 A	18 (13.75–25)

Study identification	Year	Journal	Average CONSORT score	Risk of bias tool

				random sequence	allocation concealment	participant blinding	examiner blinding	incomplete outcome data	selective reporting
Acosta Gómez et al.³⁴	1999	Univ Odontol	11	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Al Shethri et al.⁶⁵	2003	Oper Dent	18	LOW	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Almeida et al.⁶⁶	2012	Int J Periodontics Restorative Dent	16	UNCLEAR	UNCLEAR	HIGH	HIGH	LOW	HIGH
Alomari, El Daraa⁶⁷	2010	J Contemp Dent Pract	13	UNCLEAR	UNCLEAR	LOW	LOW	LOW	LOW
Alonso de la Peña, Balboa Cabrita⁶⁸	2006	Quintessence Int	14	UNCLEAR	HIGH	HIGH	HIGH	HIGH	LOW
Alonso de la Peña, Lopez Ranton⁶⁹	2014	Oper Dent	18	LOW	UNCLEAR	HIGH	HIGH	LOW	LOW
Auschill et al.⁷⁰	2005	Oper Dent	18	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW	LOW
Auschill et al.⁷¹	2012	Quintessence Int	26	LOW	LOW	UNCLEAR	LOW	LOW	LOW
Barlow et al.⁷²	2009	Int J Dent	21	LOW	UNCLEAR	UNCLEAR	LOW	LOW	LOW
Barnes et al.⁷³	1998	Comp Cont Educ Dent	15	HIGH	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Basting et al.⁷⁴	2012	Oper Dent	21	LOW	LOW	UNCLEAR	LOW	LOW	LOW
Berga-Caballero et al.⁷⁵	2006	Med Oral Patol Oral Cir Bucal	13	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW
Bernardon et al.⁷⁶	2010	Oper Dent	16	LOW	UNCLEAR	UNCLEAR	LOW	LOW	LOW
Bernardon et al.⁷⁷	2015	J Prosthet Dent	12	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	HIGH
Bernardon et al.⁷⁸	2016	J Prosthet Dent	10	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Bizhang et al.⁷⁹	2007	Am J Dent	20	UNCLEAR	HIGH	UNCLEAR	UNCLEAR	LOW	HIGH
Bizhang et al.⁸⁰	2009	Oper Dent	18	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Bonafé et al.⁸¹	2014	Clin Oral Investig	22	LOW	UNCLEAR	LOW	LOW	LOW	LOW
Bortolatto et al.⁸²	2016	Lasers Med Sci	26	LOW	LOW	LOW	LOW	LOW	LOW
Braun et al.⁸³	2007	Dent Mater	15	HIGH	UNCLEAR	LOW	LOW	LOW	LOW
Browning et al.⁸⁴	2012	J Esthet Restor Dent	17	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Browning et al.⁸⁵	2004	Oper Dent	13	UNCLEAR	UNCLEAR	LOW	LOW	UNCLEAR	LOW
Bruhn et al.⁸⁶	2012	Int J Dent Hyg	16	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Callan et al.⁸⁷	2008	Am J Dent	12	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Cardoso et al.⁸⁸	2011	JADA	17	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Carvalho et al.⁸⁹	2005	Rev Assoc Paul Cir Dent	6	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW
Cerqueira et al.⁹⁰	2013	Rev Assoc Paul Cir Dent	19	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Cibirka et al.⁹¹	1999	J Esthet Dent	15	LOW	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW
Collins et al.⁹²	2004	J Dent	19	HIGH	UNCLEAR	UNCLEAR	LOW	UNCLEAR	LOW
Corbella et al.⁹³	2009	Dent Cadmos	8	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	HIGH
Cronin et al.⁹⁴	2005	Comp Cont Educ Dent	16	UNCLEAR	UNCLEAR	UNCLEAR	LOW	UNCLEAR	HIGH
da Costa et al.⁹⁵	2010	Oper Dent	19	LOW	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
da Costa et al.⁹⁶	2011	J Esthet Restor Dent	22	LOW	LOW	UNCLEAR	LOW	LOW	LOW
Dawson et al.⁹⁷	2011	Oper Dent	19	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
de Almeida et al.⁹⁸	2014	Photomed Laser Surg	20	UNCLEAR	UNCLER	LOW	LOW	LOW	LOW
de Freitas et al.⁹⁹	2016	Quintessence Int	17	LOW	UNCLEAR	UNCLEAR	LOW	UNCLEAR	LOW
de Geus et al.¹⁰⁰	2015	JADA	29	LOW	LOW	UNCLEAR	LOW	LOW	LOW
de Geus et al.⁴	2015	J Dent	28	LOW	LOW	UNCLEAR	UNCLEAR	LOW	LOW
de Geus et al.⁶⁴	2015	Oper Dent	25	LOW	LOW	LOW	LOW	LOW	LOW
de Paula et al.⁶³	2013	Clin Oral Invest	29	LOW	LOW	LOW	LOW	LOW	LOW
de Paula et al.⁵⁹	2015	J Dent	29	LOW	LOW	UNCLEAR	LOW	LOW	LOW
de Paula et al.¹²	2014	Oper Dent	30	LOW	LOW	LOW	LOW	LOW	LOW
Delgado et al.¹⁰¹	2007	P R Health Sci J	16	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR
Deliperi et al.¹⁰²	2004	JADA	17	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Donly et al.¹⁰³	2002	Comp Cont Educ Dent	14	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Donly et al.¹⁰⁴	2005	Pediatr Dent	17	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW
Donly et al.¹⁰⁵	2006	Gen Dent	15	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW
Donly et al.¹⁰⁶	2007	Gen Dent	21	HIGH	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Donly et al.¹⁰⁷	2010	Am J Dent	19	HIGH	UNCLEAR	UNCLEAR	LOW	LOW	LOW
Farrel et al.¹⁰⁸	2006	J Clin Dent	18	HIGH	UNCLEAR	LOW	LOW	LOW	LOW
Fernandez et al.¹⁰⁹	2016	Oper Dent	30	LOW	LOW	LOW	LOW	LOW	LOW
Ferrari et al.¹¹⁰	2004	Am J Dent	17	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Gallagher et al.¹¹¹	2002	J Clin Dent	15	UNCLEAR	UNCLEAR	HIGH	LOW	LOW	LOW
Gallo et al.¹¹²	2009	Quintessence Int	14	UNCLEAR	UNCLEAR	LOW	LOW	UNCLEAR	LOW
Garcia-Godoy et al.¹¹³	2004	Comp Cont Educ Dent	17	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Gerlach et al.¹¹⁴	2000	Comp Cont Educ Dent	20	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW	LOW
Gerlach et al.¹¹⁵	2001	Am J Dent	18	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW	LOW
Gerlach et al.¹¹⁶	2002	Comp Cont Educ Dent	16	HIGH	UNCLEAR	LOW	LOW	LOW	HIGH
Gerlach et al.¹¹⁷	2004	J Clin Dent	15	HIGH	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Gerlach et al.¹¹⁸	2005	Comp Cont Educ Dent	15	HIGH	UNCLEAR	LOW	LOW	LOW	LOW
Gerlach, Barker¹¹⁹	2003	Am J Dent	20	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW	LOW
Gerlach, Sagel¹²⁰	2004	JADA	15	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Gerlach et al.¹²¹	2002	Am J Dent	20	HIGH	UNCLEAR	UNCLEAR	LOW	LOW	LOW
Gerlach, Zhou¹²¹	2004	Comp Cont Educ Dent	20	HIGH	UNCLEAR	UNCLEAR	LOW	LOW	LOW
Giachetti et al.¹²²	2010	JADA	23	LOW	LOW	UNCLEAR	UNCLEAR	LOW	LOW
Giniger et al.¹²³	2005	J Clin Dent	15	HIGH	UNCLEAR	UNCLEAR	LOW	LOW	LOW
Giniger et al.¹²⁴	2005	JADA	21	HIGH	UNCLEAR	LOW	LOW	LOW	LOW
Gomes et al.¹³	2008	R Dent Press Estet	10	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	HIGH
Goodson et al.¹²⁵	2005	J Clin Dent	11	LOW	UNCLEAR	LOW	LOW	UNCLEAR	HIGH
Grobler et al.¹²⁶	2011	Int J Dent	13	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Guênes et al.¹²⁷	2015	RFO UPF		UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW	LOW
Guerrero et al.¹²⁸	2007	Am J Dent	20	UNCLEAR	UNCLEAR	LOW	LOW	LOW	LOW
Gurgan et al.¹²⁹	2010	Lasers Med Sci	14	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Hanning et al.¹³⁰	2007	Clin Oral Investig	18	UNCLEAR	UNCLEAR	LOW	LOW	LOW	HIGH
Henry et al.¹³¹	2013	Int J Dent Hyg	18	UNCLEAR	UNCLEAR	LOW	HIGH	LOW	LOW
Hyland et al.¹³²	2015	Clin Oral Investig	11	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	HIGH
Ishikawa-Nagai et al.¹³³	2004	J Esthet Restor Dent	13	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW
Jadad et al.¹³⁴	2011	Am J Orthod Dentofacial Orthop	9	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW
Javaheri, Janis¹³⁵	2000	Oper Dent	6	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	HIGH
Karpina et al.¹³⁶	2002	Am J Dent	14	UNCLEAR	UNCLEAR	LOW	LOW	LOW	LOW
Karpina et al.¹³⁷	2003	J Prosthodont	14	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	HIGH
Kihn et al.¹³⁸	2000	JADA	17	HIGH	UNCLEAR	LOW	LOW	LOW	LOW
Kihn et al.¹³⁹	2002	Comp Cont Educ Dent	12	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Knosel et al.¹⁴⁰	2007	Angle Orthod	10	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW
Knosel et al.¹⁴¹	2008	Quintessence Int	12	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW
Kose et al.¹⁴²	2011	Am J Dent	20	LOW	UNCLEAR	LOW	LOW	LOW	LOW
Kose et al.⁶²	2016	Oper Dent	28	LOW	LOW	LOW	LOW	LOW	LOW
Kossatz et al.¹⁴³	2011	Oper Dent	17	LOW	UNCLEAR	LOW	LOW	LOW	LOW
Kossatz et al.¹⁴⁴	2012	JADA	25	LOW	UNCLEAR	LOW	LOW	LOW	LOW
Kozlovsky et al.¹⁴⁵	1996	Oral Health	10	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	HIGH	LOW
Krause et al.¹⁴⁶	2008	Quintessence Int	13	HIGH	UNCLEAR	LOW	LOW	UNCLEAR	LOW
Kugel et al.¹⁴⁷	2002	Comp Cont Educ Dent	11	HIGH	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW
Kugel et al.¹⁴⁸	2006	Comp Cont Educ Dent	12	UNCLEAR	UNCLEAR	LOW	LOW	LOW	LOW
Kugel et al.¹⁴⁹	2004	Comp Cont Educ Dent	19	UNCLEAR	UNCLEAR	LOW	LOW	LOW	LOW
Kugel et al.¹⁵⁰	2009	J Esthet Restor Dent	19	HIGH	UNCLEAR	LOW	LOW	LOW	LOW
Kugel, Kastali¹⁵¹	2000	Comp Cont Educ Dent	18	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Leonard et al.¹⁵²	1999	J Esthet Restor Dent	13	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW	LOW
Leonard et al.¹⁵³	2001	J Esthet Restor Dent	18	HIGH	UNCLEAR	LOW	UNCLEAR	LOW	LOW
Leonard et al.¹⁵⁴	2004	J Esthet Restor Dent	12	UNCLEAR	UNCLEAR	HIGH	LOW	UNCLEAR	LOW
Lewgoy et al.¹⁵⁵	2011	Rev ABO Nac	6	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW
Li et al.¹⁵⁶	2003	Comp Cont Educ Dent	18	HIGH	UNCLEAR	LOW	LOW	LOW	LOW
Lo et al.¹⁵⁷	2007	Am J Dent	21	UNCLEAR	UNCLEAR	LOW	LOW	LOW	HIGH
Lo Giudice et al.¹⁵⁸	2016	Open Dent J	6	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW
Loguercio et al.¹⁵⁹	2015	Braz Oral Res	30	LOW	LOW	LOW	LOW	LOW	LOW
Loyola-Rodriguez et al.¹⁶⁰	2003	J Clin Pediatr Dent	12	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW
Luo et al.¹⁶¹	2007	J Dent	16	HIGH	UNCLEAR	UNCLEAR	LOW	LOW	LOW
Machado et al.¹⁶²	2013	Quintessence Int	13	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW
Machado et al.¹⁶³	2016	Int J Periodontics Restorative Dent	16	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Maghaireh et al.¹⁶⁴	2014	Oper Dent	16	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Marson et al.¹⁶⁵	2008	Oper Dent	13	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Martín et al.¹⁶⁶	2015	J Dent	30	LOW	UNCLEAR	LOW	LOW	LOW	LOW
Martins et al.¹⁶⁷	2011	Rev Assoc Paul Cir Dent	12	LOW	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW
Matis et al.¹⁶⁸	1998	Quintessence Int	15	HIGH	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Matis et al.¹⁶⁹	2000	Quintessence Int	17	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Matis et al.¹⁷⁰	2002	Oper Dent	17	LOW	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Matis et al.¹⁷¹	2002	Quintessence Int	14	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Matis et al.¹⁷²	2005	Oper Dent	15	UNCLEAR	UNCLEAR	LOW	LOW	UNCLEAR	UNCLEAR
Matis et al.¹⁷³	2006	Oper Dent	14	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Matis et al.¹⁷⁴	2007	Oper Dent	11	UNCLEAR	UNCLEAR	LOW	LOW	UNCLEAR	LOW
Matis et al.¹⁷⁵	2009	Oper Dent	15	LOW	UNCLEAR	LOW	LOW	LOW	LOW
Medeiros, de Lima¹⁷⁶	2008	J Can Dent Assoc	17	LOW	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Mehta et al.¹⁷⁷	2013	Eur J Oral Sci	14	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Meireles et al.¹⁷⁸	2008	J Dent	22	LOW	UNCLEAR	LOW	LOW	LOW	LOW
Meireles et al.¹⁷⁹	2008	Oper Dent	21	LOW	UNCLEAR	LOW	LOW	LOW	LOW
Meireles et al.¹⁸⁰	2009	JADA	21	LOW	UNCLEAR	LOW	LOW	LOW	LOW
Meireles et al.¹⁸¹	2010	J Dent	21	LOW	UNCLEAR	LOW	LOW	LOW	LOW
Meireles et al.¹⁸²	2014	J Dent	22	LOW	UNCLEAR	LOW	LOW	LOW	LOW
Mena Serrano et al.⁵⁸	2016	Oper Dent	30	LOW	LOW	LOW	LOW	LOW	LOW
Miller et al.¹⁸³	2000	Pract Proced Aesthet Dent	4	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR
Moghadam et al.¹⁸⁴	2013	Eur J Dent	20	LOW	UNCLEAR	LOW	LOW	LOW	LOW
Mohan et al.¹⁸⁵	2008	J Dent	19	HIGH	UNCLEAR	LOW	LOW	LOW	LOW
Mokhlis et al.¹⁸⁶	2000	JADA	16	HIGH	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Mondelli et al.¹⁸⁷	2012	J Appl Oral Sci	13	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Montenegro-Arana et al.¹⁸⁸	2016	Oper Dent	25	LOW	LOW	LOW	UN	LOW	LOW
Morgan et al.¹⁸⁹	2015	Br Dent J	12	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW
Myers et al.¹⁹⁰	2003	J Esthet Restor Dent	14	LOW	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW
Nathoo et al.¹⁹¹	2001	Comp Cont Educ Dent	13	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Nathoo et al.¹⁹²	2003	J Clin Dent	17	HIGH	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	HIGH
Navarra et al.¹⁹³	2014	Int J Dent Hyg	11	LOW	LOW	UNCLEAR	UNCLEAR	UNCLEAR	HIGH
Nutter et al.¹⁹⁴	2013	J Dent	14	LOW	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Ontiveros, Paravina¹⁹⁵	2009	J Dent	13	LOW	UNCLEAR	LOW	LOW	LOW	LOW
Palé et al.¹⁹⁶	2014	Odontology	14	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Paphatanasiou et al.¹⁹⁷	2001	Comp Cont Educ Dent	13	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Paphatanasiou et al.¹⁹⁸	2002	Comp Cont Educ Dent	17	UNCLEAR	UNCLEAR	LOW	UNCLEAR	LOW	LOW
Perry et al.¹⁹⁹	2013	Comp Cont Educ Dent	9	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	HIGH	LOW
Polydorou et al.²⁰⁰	2013	Oper Dent	15	UNCLEAR	UNCLEAR	LOW	UNCLEAR	LOW	LOW
Posso Moreno et al.²⁰¹	2010	Univ Odontol	15	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	HIGH
Reis et al.²⁰²	2011	Oper Dent	24	LOW	LOW	LOW	LOW	LOW	LOW
Reis et al.²⁰³	2011	Oper Dent	24	LOW	LOW	LOW	LOW	LOW	LOW
Reis et al.²⁰⁴	2013	Oper Dent	31	LOW	LOW	LOW	LOW	LOW	LOW
Rezende et al.²⁰⁵	2014	Rev Assoc Paul Cir Dent	13	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Rezende et al.²⁰⁶	2013	Oper Dent	23	UNCLEAR	UNCLEAR	LOW	UNCLEAR	LOW	LOW
Rezende et al.²⁰⁷	2016	Oper Dent	25	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW	LOW
Rezende et al.⁶¹	2016	Oper Dent	30	LOW	LOW	LOW	LOW	LOW	LOW
Rosenstiel et al.²⁰⁸	1996	Quintessence Int	11	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	HIGH
Santana et al.²⁰⁹	2014	Braz Dent Journal	24	UNCLEAR	UNCLEAR	LOW	LOW	LOW	LOW
Shahidi et al.²¹⁰	2005	J Clin Dent	17	HIGH	UNCLEAR	LOW	LOW	LOW	LOW
Shanbhag et al.²¹¹	2013	J Contemp Dent Pract	14	HIGH	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Sielski et al.²¹²	2003	Comp Cont Educ Dent	18	HIGH	UNCLEAR	LOW	LOW	LOW	HIGH
Silva et al.²¹³	2012	Rev Odontol Bras Central	10	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	HIGH	HIGH
Simon et al.²¹⁴	2014	J Clin Dent	16	HIGH	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW
Soares et al.²¹⁵	2006	Rev Odont UNESP	8	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	HIGH	LOW
Strobl et al.²¹⁶	2010	Lasers Med Sci	14	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Sundfeld et al.²¹⁷	2015	Indian J Dent Res	12	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Swift et al.²¹⁸	1997	J Esthet Restor Dent	15	UNCLEAR	UNCLEAR	LOW	UNCLEAR	LOW	LOW
Swift et al.²¹⁹	1999	J Esthet Restor Dent	14	UNCLEAR	UNCLEAR	LOW	UNCLEAR	LOW	LOW
Swift et al.²²⁰	2004	Comp Cont Educ Dent	18	UNCLEAR	UNCLEAR	LOW	UNCLEAR	LOW	LOW
Swift et al.²²¹	2009	J Dent	19	UNCLEAR	UNCLEAR	LOW	LOW	LOW	LOW
Tavares et al.²²²	2003	JADA	19	LOW	UNCLEAR	LOW	LOW	LOW	LOW
Tay et al.⁶	2009	JADA	24	LOW	LOW	LOW	LOW	LOW	LOW
Tay et al.²²³	2012	Am J Dent	29	LOW	LOW	LOW	LOW	LOW	LOW
Tsubura²²⁴	2010	Odontology	10	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Tsubura ,Yamaguchi²²⁵	2005	Odontology	12	UNCLEAR	UNCLEAR	UNCLEAR	LOW	HIGH	LOW
Türkün et al.²²⁶	2010	J Esthet Restor Dent	12	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	HIGH	LOW
Vano et al.²²⁷	2015	Int J Dent Hyg	24	UNCLEAR	LOW	UNCLEAR	LOW	LOW	LOW
Ward, Felix²²⁸	2012	Comp Cont Educ Dent	13	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Wetter et al.²²⁹	2009	Lasers Med Sci	14	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Xu et al.²³⁰	2007	Am J Dent	17	UNCLEAR	UNCLEAR	LOW	LOW	LOW	LOW
Yudhira et al.²³¹	2007	Am J Dent	22	HIGH	LOW	LOW	LOW	LOW	LOW
Zantner et al.²³²	2006	Quintessence Int	23	LOW	UNCLEAR	LOW	LOW	LOW	LOW
Zekonis et al.²³³	2003	Oper Dent	18	LOW	UNCLEAR	UNCLEAR	LOW	LOW	LOW
Zhao et al.²³⁴	2013	Quintessence Int	15	LOW	LOW	UNCLEAR	UNCLEAR	LOW	LOW
Ziebolz et al.²³⁵	2007	Clin Oral Investig	18	HIGH	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW
Ziemba et al.²³⁶	2005	J Clin Dent	19	LOW	LOW	UNCLEAR	UNCLEAR	LOW	LOW

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[TFN1] *Representing 37 different journals; **Representing 18 different countries; ***Representing 33 different follow-up period (days).