J Clin Periodontol 2013; 40: 5364 doi: 10.1111/jcpe.

12011

In-ofce treatment for dentin hypersensitivity: a systematic review and network meta-analysis
Lin P-Y, Cheng Y-W, Chu C-Y, Chien K-L, Lin C-P, Tu Y-K. In-ofce treatment for dentin hypersensitivity: a systematic review and network meta-analysis. J Clin Periodontol 2013; 40: 5364. doi: 10.1111/jcpe.12011.

Po-Yen Lin1,3, Ya-Wen Cheng1, Chia-Yi Chu1,3, Kuo-Liong Chien2, Chun-Pin Lin1 and Yu-Kang Tu2
1

Department of Dentistry, School of Dentistry, National Taiwan University and National Taiwan University Hospital, Taipei, Taiwan; 2 Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; 3 Department of Dentistry, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

Abstract Aim: Dentin hypersensitivity, caused by the exposure and patency of dentinal tubules, can affect patients quality of life. The aim of this study was to undertake a systematic review and a network meta-analysis, comparing the effectiveness in resolving dentin hypersensitivity among different in-ofce desensitizing treatments. Materials and Methods: A literature search was performed with electronic databases and by hand until December 2011. The included trials were divided into six treatment groups as placebo, physical occlusion, chemical occlusion, nerve desensitization, laser therapy and combined treatments. The treatment effects between groups were estimated with standardized mean differences by using a Bayesian network meta-analysis. Results: Forty studies were included. The standardized mean difference between placebo and physical occlusion was 2.57 [95% credible interval (CI): 4.24 to 0.94]; placebo versus chemical occlusion was 2.33 (95% CI: 3.65 to 1.04); placebo versus nerve desensitization was 1.72 (95% CI: 4.00 to 0.52); placebo versus laser therapy was 2.81 (95% CI: 4.41 to 1.24); placebo versus combined treatment was 3.47 (95% CI: 5.99 to 0.96). The comparisons of the ve active treatments showed no signicant differences. Conclusions: The results from network meta-analysis showed that most active treatment options had signicantly better treatment outcome than placebo.

Key words: dentin hypersensitivity; in-ofce treatment; network meta-analysis; randomized controlled trials; systematic review Accepted for publication 21 August 2012

Dentin hypersensitivity (DH) is dened as short, sharp pain arising from exposed dentin in response to
Conict of interest and source of funding statement No external funding, apart from the support of the authors institution, was available for this study. The authors declare that there are no conicts of interest in this study.
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stimuli typically thermal, evaporative, tactile, osmotic or chemical and which cannot be ascribed to any other form of dental defect or pathology (Holland et al. 1997). Clinical surveys showed the prevalence of DH ranged from 2.8% to 74%, depending on the population studied, study setting and study design (Orchardson & Collins 1987, Liu et al. 1998, Taani & Awartani 2002, Rees et al. 2003, Rees & Addy

2004, Shen et al. 2009, Que et al. 2010). It mostly affects individuals at their fourth and fth decade of life (Liu et al. 1998, Rees et al. 2003, Que et al. 2010), causing patient discomforts during eating or even breathing. The mechanism of dentin hypersensitivity had not been fully elucidated. The most accepted hypothesis is the hydrodynamic theory proposed by Brannstrom (1963). According to this theory, most pain-

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Lin et al.
large, pair-wise comparisons may be inefcient or not feasible (Tu et al. 2010, 2012, Hoaglin et al. 2011, Jansen et al. 2011). Network metaanalysis is a methodology for the statistical synthesis of direct and indirect comparisons of different treatments and had been used in dental research (Tu et al. 2010, 2012). The aim of this study was therefore to undertake a systematic review and a network meta-analysis, comparing the effectiveness in resolving dentin hypersensitivity among different in-ofce desensitizing treatments.
Material and Methods
Literature search

inducing stimuli increase centrifugal uid ow within the dentinal tubules, giving rise to a pressure change throughout the entire dentin. Based on this mechanism, two phases must coincide to produce DH, the exposure of dentin and the opening of the dentinal tubular system. Therefore, the ideal treatment of DH should be able to reduce uid ow in dentinal tubules or block pulpal nerve response or both (Holland et al. 1997, Canadian Advisory Board on Dentin Hypersensitivity 2003). A large number of desensitizing methods such as dentifrices containing potassium salts and in-ofce topical desensitizing agents have been offered to the market to solve the problem. It has been suggested that the treatment of DH is to begin with an at-home method, such as a desensitizing dentifrice (Sowinski et al. 2001, Poulsen et al. 2006, Orsini et al. 2010); this alone may alleviate the condition. If at-home methods do not satisfactorily resolve the problem, an in-ofce treatment may be indicated. When DH is localized to one or two teeth, an in-ofce method may be the rst choice of treatment (Orchardson & Gillam 2006). There is a wide range of in-ofce treatments for DH, including dentin adhesives (Ide et al. 1998, Schwarz et al. 2002, Kakaboura et al. 2005, Tengrungsun & Sangkla 2008), resin emulsions (Prati et al. 2001, Erdemir et al. 2010), copal varnishes (Olusile et al. 2008), glutaraldehyde-based adhesives (Duran & Sengun 2004, Kakaboura et al. 2005, Polderman & Frencken 2007, Ishihata et al. 2012), oxalates (Gillam et al. 2004, Merika et al. 2006, Assis et al. 2011), uorides (Tarbet et al. 1979, McBride et al. 1991, Merika et al. 2006, Ritter et al. 2006, Fiocchi et al. 2007), potassium nitrates (Frechoso et al. 2003, Sicilia et al. 2009) and laser therapies (Gerschman et al. 1994, Lier et al. 2002, Schwarz et al. 2002, Tengrungsun & Sangkla 2008), so it can be a challenge for selecting the most appropriate treatment for patients, and the relative effectiveness of those treatments remains uncertain. Traditional meta-analysis undertakes pair-wise comparisons between treatments, but when the number of available treatments is

because it involves a wider area of dentin, and it was used most often than tactile test or cold stimuli test in clinical trials on DH. Moreover, air test was usually recorded by response-based methods, which can be used to calculate mean differences for our meta-analysis. Trials using tactile test or cold stimuli test only would therefore be excluded in this review.
Treatment group classication

The literature search within MEDLINE (via PubMed), ScienceDirect, ISI web of science, Ovid and Cochrane Central Register of Controlled Trials (CENTRAL) databases up to December 2011 was undertaken. To identify relevant studies, we used the following term (dentin* OR tooth OR teeth) AND (hypersensit* OR desensiti* OR desensitize*) NOT (toothpaste OR dentifrice), limited to clinical trials and humans; no language restrictions were imposed. The reference lists of previously published reviews (Canadian Advisory Board on Dentin Hypersensitivity 2003, Orchardson & Gillam 2006, West 2008, Al-Sabbagh et al. 2009, Porto et al. 2009, Cunha-Cruz et al. 2011, He et al. 2011, Sgolastra et al. 2011) were crosschecked. The literature search and data extractions (Fig. 1) were undertaken in duplicate, and quality assessment of included studies, such as randomization, allocation concealment, blinding, intention to treat and sample size calculation, was carried out independently by three authors (PY Lin, YW Cheng, CY Chu). Disagreements on study inclusions and quality assessment were resolved by discussions among the three authors. Tactile, cold and evaporative air stimuli were commonly used in outcome assessment for DH. In this systematic review, we chose articles which used evaporative air test for further meta-analysis to minimize the heterogeneity of methods used to assess DH. Air test is a more accurate method for evaluating DH

Treatments used by the included trials were divided into six groups according to the underlying mechanisms proposed by a recent review (Porto et al. 2009): group I: placebo; group II: physical occlusion of dentinal tubules; group III: chemical occlusion of dentinal tubules; group IV: nerve desensitization; group V: photobiomodulating action (Laser therapy); and group VI: combined treatment (any combination of groups IIV) (Table 1).
Data extraction and statistical analysis

Three authors (PY Lin, YW Cheng, CY Chu) performed data extraction. Most of the literatures used visual analogue scales (VAS) or verbal rating scales (VRS) for pain assessment of DH (Holland et al. 1997). The number of participants, means and standard deviations of treatment effects were extracted from the reports or using a pooled estimation formula which assumed a correlation coefcient of baseline and outcome measurement equal to 0.5 (Tu et al. 2005). When multiple teeth were treated within one patient, the standard error of means for treatment effects were derived from the standard deviation by using the number of patients as the unit of analysis. If the number of patients in each group was not available, we contacted the corresponding authors by email for requesting more detailed information, or assumed that the numbers of participants were equal for all treatment groups. Both VAS and VRS were used for evaluating treatment effects of DH products in clinical trials, but the scales of them differed. VAS consists of a straight line that is 10 cm in length, the ends of which are dened with the words: no
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DH network meta-analysis

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Fig. 1. Flowchart for literature search and identications of articles for review.

Table 1. Grouping of the included articles for network meta-analysis Group Group I Placebo No treatment Water Not specied placebo Desensitizing toothpaste Group II Physical occlusion of dentinal tubules Pumice paste Sodium bicarbonate Hydroxyapatites Bioglasses Glass ionomers Dentin bonding agents Resins Group III Chemical occlusion of dentinal tubules Fluorides Oxalates Glutaraldehyde-based agents Calcium compounds Group IV Nerve desensitization Potassium nitrates Guanethidine Group V Photobiomodulating action Laser therapy Group VI Combined treatment Any combination of Groups IIV

Treatment option

pain and severe pain (Scott & Huskisson 1976). The scale of VAS is usually 010 or 0100. VRS uses word descriptors as a scaling technique to describe variations of pain. The scale is usually 03 as follows: 0, no discomfort; 1, discomfort or mild pain; 2, severe pain during stimulation; 3, severe pain which persisted for some time after stimulation (Holland et al. 1997). If the study had more than one follow-up period, we would use the nal assessment for data extraction. To combine data from different scales, it has been suggested that dividing the mean difference in each study by that studys standard deviation to create a standardized mean difference which would be comparable across studies (Glass 1976). The standardized mean difference can be viewed as the mean difference that
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would have been obtained if all data were transformed into a scale where the standard deviation within-group was equal to 1.0. Twelve articles were excluded (Kielbassa et al. 1997, Prati et al. 2001, Marsilio et al. 2003, Singal et al. 2005, Merika et al. 2006, Ritter et al. 2006, Fiocchi et al. 2007, Azarpazhooh et al. 2009, Dilsiz et al. 2009, Banerjee et al. 2010, Jalali & Lindh 2010, Sethna et al. 2011) because they tested the treatments classied as the same group. For example, Dilsiz et al. (2009) compared two types of lasers, the Nd:YAG laser and the 685-nm diode laser, for treating DH. Network meta-analysis, for multiple treatments comparisons by incorporating direct and indirect evidence, was undertaken using the Bayesian hierarchical random-effects modelling. Because the included studies

reported treatment outcomes with different lengths of follow-ups, the length of follow-up was stratied into two categories using 1 month as the cut-off value. The study design was divided into parallel group and split-mouth design to account for the heterogeneity in treatment effects. The authors assumed a within-patient correlation coefcient equal to 0.25 for splitmouth trials. Standard pair-wise meta-analyses of direct comparisons among each group were carried out and compared to results from the network meta-analysis. Meta-regressions with covariates such as study design, length of follow-ups, multiple treatment courses and interaction terms among them were also conducted to explore if they could explain the heterogeneity. In addition, the number of times the same desensitizing treatment

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Table 2. Summary of studies included in the network meta-analysis Treatment agent VRS (03) Parallel Parallel Split mouth Parallel Parallel Split mouth Split mouth Split mouth 6 months Immediate 8 weeks 1 week 84 days 3 months Immediate 1 1 1 4 1 3 1 14 days 1 VRS (04) VRS (03) VAS (010) VAS (0.100) VAS (0.100) VAS (010) VAS (0100) Subject number Treatment effect SD Pain score type Study design Follow-up period Treatment courses OHI No N/A N/A N/A Yes No N/A N/A

Lin et al.

Study, year, country

Group

Tarbet et al. (1979), NY

McBride et al. (1991), UK

I III I III

20 20 48 47

patients patients patients patients

0.11 0.01 0.31 2.11 1.08 1.43 0.83 0.61

Dondi dallOrologio & Malferrari (1993), Italy

Dunne & Hannington-Kiff (1993), UK Gerschman et al. (1994), Denmark Ide et al. (1998), UK

Yates et al. (1998), UK 16 teeth 16 teeth 32.00 33.40 19.30 21.90 VAS (010) VRS (14) VRS (03) VRS (03) VRS (03)

I III III I IV I V I II I III

34 40 42 20 19 28 21 16 16 36 36

teeth teeth teeth patients patients patients patients patients patients patients patients

2.16 2.26 0.29 1.20 3.80 0.80 3.90 8.10 25.30 3.88 3.91 0.60 0.53 0.42 2.10 2.60 1.65 1.85 27.91 27.89 1.99 1.73

Morris et al. (1999), USA

I III

Lier et al. (2002), Norway

Split mouth Split mouth Split mouth Parallel Split mouth

16 weeks 6 months 30 days 14 days 3 months

1 1 5 1 1

No Yes N/A Yes N/A

Schwarz et al. (2002), Germany

Corona et al. (2003), Brazil

Frechoso et al. (2003), Spain

Zhang (2003), China

III I V I II V III V I IV IV II II II II II II III 12 patients 10 patients 0.92 0.67 0.83 0.82

18 teeth 17 patients 17 patients 30 patients 30 patients 30 patients 12 patients 12 patients 15 patients 15 patients 15 patients 10 patients 11 patients 11 patients 9 patients 8 patients 12 patients 10 patients

36.20 2.99 2.72 0.20 0.30 1.90 1.17 1.37 1.46 1.40 1.66 1.67 1.00 1.75 1.08 1.25 0.58 1.00 28.80 2.33 2.15 0.36 0.40 0.44 0.80 0.70 0.74 0.98 1.11 0.74 0.80 0.74 0.83 0.74 0.83 0.96

III

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III

No treatment NaF Deionized water Iontophoresis with 2% NaF No treatment Gluma three Primer Gluma 2000 Conditioner Distil water Guanethidine No treatment GaAlAs laser No treatment Dentin bonding agent Water Amorphous calcium phosphate Distil water Oxalate-containing resin solution 0.7% uoride solution Placebo Nd:YAG laser No treatment Resin adhesives Er:YAG laser Fluoride varnish GaAlAs laser Placebo 5% NK 10% NK Dentin bonding (occlusal) Enamel bonding (occlusal) Dentin bonding (cervical) Enamel bonding (cervical) Dentin bonding (root) Enamel bonding (root) 75% of NaF glycerine paste (occlusal) 75% of NaF glycerine paste (cervical) 75% of NaF glycerine paste (root)

Table 2. (Continued) Treatment agent SD 2.61 2.05 2.21 VAS (010) Split mouth 3 months 1 Pain score type Study design Follow-up period Treatment courses 44 teeth 59 teeth 76 teeth 1.71 1.97 3.12 Subject number Treatment effect OHI N/A

Study, year, country

Group

Duran & Sengun (2004), Turkey

II III VI

2012 John Wiley & Sons A/S VAS (010) Parallel Split mouth Split mouth 4 weeks 9 months 6 weeks VAS (010) VRS (03) 6 1 1 Yes N/A Yes 42 56 16 16 13 13 40 40 40 16 teeth 28 teeth 30 teeth 32 teeth VAS (0100) VRS (03) VRS (03) VRS (03) VRS (14) 4.20 0.27 Split mouth Split mouth Split mouth Parallel Parallel 1 week 3 months 30 days Immediate 6 months 1 1 1 1 1 N/A N/A N/A N/A Yes 26.50 24.90 0.91 1.26 0.46 0.76 0.51 0.51 27.40 26.90 2.78 1.36 1.85 0.71 0.35 1.19 3.10 3.30 0.30 0.30 0.50 0.36 VAS (010) Split mouth 8 weeks teeth teeth patients patients patients patients teeth teeth teeth 1.38 1.29 4.42 3.91 0.72 0.30 0.24 0.63 0.99 4.96 1.37 2.68 2.69 0.75 0.72 0.14 0.15 0.14 I 1 No 72 72 14 14 70 70 23 22 patients patients patients patients patients patients patients patients VAS (010) VAS (0100) Parallel Parallel 4 weeks 7 days 1 1 Yes Yes 10 10 10 10 10 10 10 13 13 patients patients patients patients patients patients patients patients patients 0.75 1.94 1.87 1.99 1.98 5.05 4.62 1.62 48.10 0.59 0.47 0.64 0.55 0.50 0.90 0.92 8.40 6.14 13 13 36 32 patients patients patients patients 15 patients 15 patients 15 patients 51.50 57.40 2.70 2.73 0.67 0.73 1.53 8.85 6.07 0.34 0.34 0.82 1.10 0.74 VRS (03) VRS (03) Parallel Parallel 12 weeks 60 days 1 1 Yes Yes Dentin bonding agent HEMA + NaF Dentin bonding agent + Fluoride Liner Glutaraldehyde-based agent Sodium & calcium uoride Curing light GaAlas laser Placebo Ferric oxalate Water Dentin bonding agent Glutaraldehyde-based agent Desensitizer-free bio-adhesive gel Prompt L-pop 2% NaF bio-adhesive gel 5% Potassium nitrate bio-adhesive gel Placebo Potassium uoride varnish Glass ionomer Glutaraldehyde-based agent Dentin bonding agent GaAlAs laser Pumice paste 8% arginine and calcium carbonate 2% NaF 2% NaF + CO2 laser 2% NaF + Er:YAG laser CO2 laser Er:YAG laser Fluoride varnish Nd:YAG laser Water Glutaraldehyde-based agent Fluoride varnish NK gel Pumice paste 8% arginine and calcium carbonate Placebo 10% NK Diode laser

Gentile & Greghi (2004), Brazil Gillam et al. (2004), UK

Kakaboura et al. (2005), Greece

III III I V I III I II III

Pamir et al. (2005), Turkey

II III

IV

Zantner et al. (2006), Germany Polderman & Frencken (2007), the Netherlands Tengrungsun & Sangkla (2008), Thailand Hamlin et al. (2009), USA

I III II III II V II III

Ipci et al. (2009), Turkey

Kara & Orbak (2009), Turkey Ozen et al. (2009), Turkey

III VI VI V V III V I III

Schiff et al. (2009), USA

III IV II III

DH network meta-analysis

Sicilia et al. (2009), Spain

I IV V

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Table 2. (Continued) Treatment agent SD VAS (010) Parallel Split mouth Parallel 60 days 60 days 1 3 3 months 4 VAS (010) VAS (010) N/A Yes N/A Pain score type Study design Follow-up period Treatment courses Subject number Treatment effect OHI

Study, year, country

Group

Lin et al.

Vieira et al. (2009), Brazil

Dilsiz et al. (2010b), Turkey

I III V I V

8 patients 8 patients 8 patients 26 teeth 26 teeth

3.84 3.88 4.09 3.89 6.00 2.72 2.78 2.59 1.01 0.68

Dilsiz et al. (2010a), Turkey

Eitner et al. (2010), Germany VAS (010) Split mouth

VAS (010) Parallel

1 month 4 weeks

1 1

Yes N/A

Erdemir et al. (2010), Turkey 44 patient 45 patients 45 patients 45 patients 45 patients 24.12 0.54 VAS (010) Parallel 23.79 24.12 23.12 0.51 0.68 0.57 VAS (010) + VRS(03) 4.34 2.65

I V V V I III III II VI

24 24 24 24 21 20 21 44 43

teeth teeth teeth teeth patients patients patients patients patients

0.25 5.37 7.25 4.04 1.60 2.86 2.27 2.16 3.37 1.12 1.51 0.97 0.91 1.31 1.90 1.79 2.31 2.77

III

Shetty et al. (2010), India

I I II

Split mouth

8 weeks

15

Yes

II

Aranha & De Paula Eduardo (2012), Brazil

1 month

Yes

Assis et al. (2011), Brazil

I V V V I III III

7 patients 7 patients 7 patients 7 patients 13 patients 13 patients 13 patients

2.46 3.16 2.26 1.67 0.70 0.80 0.70 2.36 2.30 0.85 1.27 1.00 1.00 1.00

VRS (03)

Split mouth

4 weeks

N/A

VAS (0100) VAS (0100) VAS (0100)

Parallel Parallel Parallel

7 days 7 days 7 days

1 1 6 (laser)

N/A N/A Yes

Castillo et al. (2011), Lima, Peru Castillo et al. (2011), Cusco, Peru Orhan et al. (2011), Turkey

Yilmaz et al. (2011a), Turkey

VAS (010) VAS (010) VAS (010)

Split mouth Split mouth Split mouth

3 months 3 months 6 months 1

1 1

Yes Yes Yes

Yilmaz et al. (2011c), Turkey

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Yilmaz et al. (2011b), Turkey

I III I III I I III V I V I V V I I III V

Placebo 3% potassium oxalate GaAlAs laser Desensitizing toothpaste Desensitizing toothpaste + diode laser No treatment Er:YAG laser Nd:YAG laser Diode laser No treatment Gluma Fluoride Resin emulsion Oxalic acid + dentin bonding agent Fluoride containing adhesives Water No treatment Duraphat + Hydroxyapatite-dry powder Duraphat + Hydroxyapatite precipitate No treatment Er:YAG laser 0.25W Er,Cr:YSGG laser 0.5W Er,Cr: YSGG laser Placebo 3% potassium oxalate Calcium and uoride compounds Water Diammine silver uoride Water Diammine silver uoride No treatment Water Glutaraldehyde-based agent GaAlAs laser No treatment Er,Cr:YSGG laser No treatment Er,Cr:YSGG laser GaAlAs laser Saline (NaF control) No treatment (Laser control) NaF GaAlAs laser 34 patients 37 patients 29 patients 26 patients 4 patients 4 patients 4 patients 4 patients 42 patients 42 patients 51 patients 51 patients 51 patients 48 patients 48 patients 48 patients 48 patients 0.40 35.80 5.50 23.40 2.25 0.00 55.30 59.00 0.79 5.67 0.50 6.20 6.00 0.06 0.17 3.35 5.16 16.20 27.70 18.10 21.00 11.99 4.02 8.89 11.68 1.84 1.58 1.40 1.28 1.21 1.13 1.40 1.77 1.45

SD, standard deviation; OHI, oral hygiene instruction; VRS, verbal rating scales; VAS, visual analogue scales; N/A, not available.

DH network meta-analysis
being given to each patient in the study and any oral hygiene instruction given to patients after treatments were also recorded. If the patients were instructed to maintain the same habits during the trial, it was recorded as no oral hygiene instruction being given. The oral hygiene instruction included toothbrush types, brushing methods and frequency, and eating habits. The Bayesian random-effects network meta-analysis was performed using the statistical software WinBUGS (version 14.3, MRC Biostatistics Unit, Cambridge, UK) with 50,000 simulations. Non-informative priors were used throughout the analysis. The standard pair-wise random-effects meta-analysis, heterogeneity between studies and metaregressions were performed using statistical software STATA (version 11.2, StataCorp LP, College Station, TX, USA). The statistical signicance level was set at 5%.
Results
Study selection

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Yilmaz et al. 2011b). Seven studies (Dondi dallOrologio & Malferrari 1993, Morris et al. 1999, Duran & Sengun 2004, Kakaboura et al. 2005, Pamir et al. 2005, Dilsiz et al. 2010a, b) reported their treatment effects by the number of teeth as the unit, so we estimated the numbers of participants were equal in each group of these trials. Adverse events were not observed during these studies.
Quality of studies

Figure 1 summarized the details of the study selection process and the reasons for exclusion. A total of 290 potential relevant titles, abstracts and articles were found electronically, plus reference lists of reviews and related articles, of which 194 were screened for further evaluation by retrieving full texts. Finally, we identied 40 trials that met all inclusion criteria. The characteristics of these included trials were listed in Table 2.
Study description

Appendix S1 shows the quality of the included trials. Thirty-seven studies described as randomized; of them, 21 studies clearly described the allocation process. Triple blinding (patient, caregiver and examiner blinding) was performed in ve of the 44 trials (Frechoso et al. 2003, Zantner et al. 2006, Sicilia et al. 2009, Castillo et al. 2011, Orhan et al. 2011). The masking system used was clearly described in nine trials (Dunne & Hannington-Kiff 1993, Ide et al. 1998, Ozen et al. 2009, Sicilia et al. 2009, Castillo et al. 2011, Orhan et al. 2011, Yilmaz et al. 2011a, b, c), and the remaining were unclear about it. Seven of the included trials reported sample size and statistical power calculations (Morris et al. 1999, Zantner et al. 2006, Sicilia et al. 2009, Castillo et al. 2011, Yilmaz et al. 2011a, b, c).
Network meta-analysis

The overall results from network meta-analysis showed that most active treatment options including physical occlusion group, chemical occlusion group, laser therapy group and combined treatment group had signicantly better treatment outcome than placebo group except nerve desensitization group (Appendix S2). The standardized mean difference between placebo group versus physical occlusion group was 2.57 [95% credible interval (CI): 4.24, 0.94]; placebo group versus chemical occlusion group was 2.33 (95% CI: 3.65, 1.04); placebo group versus nerve desensitization group was 1.72 (95% CI: 4.00, 0.52); placebo group versus laser therapy group was 2.81 (95% CI: 4.41, 1.24); placebo group versus combined treatment group was 3.47 (95% CI: 5.99, 0.96). However, comparisons of the ve active treatment groups showed no signicant differences. The combined treatment group had better outcomes than the other groups (0.90 compared with physical occlusion group, 1.14 compared with chemical occlusion group, 1.75 compared with nerve desensitization group, 0.65 compared with laser therapy group) although the differences were not signicant either. The study designs including split-mouth-designed trials versus parallel-designed trials, followup periods, and multiple treatment courses versus single treatment showed no signicant differences.
Pair-wise meta-analysis, heterogeneity and meta-regression

Forty studies were grouped into six different kinds of treatments in the network meta-analysis, yielding 15 possible pairs of comparisons (Fig. 2). Evidence of direct comparisons was only available in 9 of 15 pairs (Figs 2 and 3).

Results from standard pair-wise meta-analysis of overall studies showed that physical occlusion group, chemical occlusion group,

The 40 trials included in the nal meta-analysis were full reports published between 1979 and 2011, and 36 of them were published after 2000. Table 2 showed the summary of grouping and intervention. Of all 40 studies, 22 were split-mouth trials and the others were parallel trials. Follow-up periods were somewhat diverse in these studies, ranged from immediate (McBride et al. 1991, Dunne & Hannington-Kiff 1993, Hamlin et al. 2009) to 69 months (Dondi dallOrologio & Malferrari 1993, Schwarz et al. 2002, Kakaboura et al. 2005, Ipci et al. 2009,
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Figure 2. Network for the comparisons among different in-ofce treatments for dentin hypersensitivity. Dotted lines refer to those comparisons that have not been tested directly in clinical trials. The width of the solid lines is in proportion to the amount of evidence available in the literatures.

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Lin et al.

Fig. 3. Forest plot of the standard pair-wise meta-analysis for different in-ofce treatments for dentin hypersensitivity.
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DH network meta-analysis
laser therapy group and combined treatment group had signicantly better treatment outcomes than placebo group (Appendix S2 and Fig. 3), which was similar to the result of network meta-analysis. The comparisons of active treatment groups showed that laser therapy group had signicant better treatment outcome than physical occlusion group; however, only one study provided the data (Tengrungsun & Sangkla 2008). It also showed that combined treatment group had signicant better outcome than physical occlusion group and chemical occlusion group, with three trials providing the data (Duran & Sengun 2004, Ipci et al. 2009, Erdemir et al. 2010). The statistical heterogeneity of these comparisons was high (I-squared = 88.6% ~96.7%, Fig. 3) except the comparison between physical occlusion group and combined treatment group (I-squared = 0.0%, p = 0.71). Meta-regressions with covariates including the length of follow-ups, study design, multiple treatment courses and interaction terms among them were tested and none of the results was signicant (p > 0.05).
Discussion

61

The current systematic review attempted to analyse all published clinical trials to assess evidence for different in-ofce desensitizing agents of DH treatments. After review and critiques, 40 studies were included into the nal analysis (Fig. 1). With network meta-analysis, the result could provide clinical researchers some useful information. The results from network metaanalysis and standard pair-wise metaanalysis were in general consistent: physical occlusion group, chemical occlusion group, laser therapy group and combined treatment group had signicantly better treatment outcomes than placebo group (Appendix S2). Among the comparisons of active treatments, the pair-wise meta-analysis showed that laser therapy group achieved better treatment outcome than physical occlusion group while the network meta-analysis showed little differences. Although ve studies directly compared placebo and physical occlusion group and 13 directly compared placebo and laser therapy group, only one study
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directly compared physical occlusion and laser (Tengrungsun & Sangkla 2008) (Fig. 3). In Tengrungsuns study, they directly compared the clinical efcacy of the 30-mW GaAlAs laser for 1 min and dentin bonding agent in treating DH and concluded that the GaAlAs laser had less desensitizing efcacy then the dentin bonding agent. The network meta-analysis incorporated both direct and indirect evidence within the whole network and also included all different types of lasers as one group. The inconsistency in results between direct and indirect evidence may be due to chance alone, as only one study provided direct evidence, but it may also indicate the treatment effects of different types of lasers are not the same. In this study, the network metaanalysis showed that regarding the treatment efcacy of dentin hypersensitivity, in-ofce products was more effective than the placebo, which indicated that the active in-ofce agent could overcome the placebo effect and demonstrated their efcacy. Although the current study did not show any preference for the ve groups of active agents included, both network and standard meta-analyses indicated that these active treatments achieved better outcomes to relieve patients DH symptoms than the placebo group (Appendix S2 and Fig. 3), demonstrating that the treatments were more helpful than placebo effect or the Hawthorne effect. So far, there was not enough evidence to show that toothpastes containing potassium is effective in relieving symptoms of DH (Poulsen et al. 2006), but after considering patients costeffectiveness, Orchardson & Gillam (2006) and the Canadian Advisory Board on Dentin Hypersensitivity (Canadian Advisory Board on Dentin Hypersensitivity 2003) suggested the treatment protocol of DH is to begin with home-care method, such as a desensitizing dentifrice. If the symptom persists, an in-ofce treatment is then indicated. This strategy was much more conservative and logical. Grossman suggested that the ideal desensitizing agent should not irritate or endanger the integrity of the pulp, should be relatively painless on application or shortly after-

wards, should be easily applied, rapid in action, permanently effective and nally should not discolour tooth structure (Grossman 1935). Unfortunately, no such treatment has been identied to date. However, in the current study, we found that none of the included trials reported any adverse effects or pulp damages during the study periods, so these in-ofce treatment options are relatively safe and met the rst criteria of the ideal desensitizing agent, and some authors still regard laser therapies as relatively invasive considering their potential damage to pulp, though (Launay et al. 1987, Schwarz et al. 2008). Erosion is currently believed to be the major factor involved in tooth wear and subsequent dentinal tubules exposure (Dababneh et al. 1999). Therefore, reducing dietary acids intake and oral hygiene instruction to patients with DH should be included as part of standard management of dentin hypersensitivity (Canadian Advisory Board on Dentin Hypersensitivity 2003). Among the included trials in the present study, only three of them mentioned the instruction of avoiding excessive dietary acids or providing dietary counselling (Ipci et al. 2009, Shetty et al. 2010, Aranha & De Paula Eduardo 2012). If this predisposing factor was not removed or modied, the treatment may provide only shortterm success (Canadian Advisory Board on Dentin Hypersensitivity 2003), which may partly contribute to limited efcacy of currently available desensitizing therapies. The objectives of the desensitizing therapy are to alleviate the symptoms of pain or discomfort and to improve the life quality of the patients with DH, while evaluating patients response to clinical stimuli may be viewed as a surrogate endpoint (Holland et al. 1997). In the current study, we reviewed 40 clinical trials using in-ofce desensitizing agents, and these trials used controlled clinical stimuli, such as evaporative air, tactile and thermal, to evaluate the baseline and posttreatment response of the patients; only two evaluated how the efcacy of treatment affects the patients everyday life (Frechoso et al. 2003, Sicilia et al. 2009), which should be

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References
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the most important clinical outcome but was often neglected. To minimize the differences between the trials, we used standardized mean difference and only included trials with evaporative air test. However, the result of pairwise meta-analysis still showed relatively high statistical heterogeneity, with I-squared = 88.6% ~ 96.7% (Fig. 3). We explored the heterogeneity by undertaking meta-regression with covariates such as length of follow-ups, study design and multiple treatment courses, but both network and standard metaregressions showed no signicant impact of these covariates. Finally, this systematic review has several limitations. Firstly, most trials did not report how randomization was undertaken and whether treatment allocations were unknown to caregivers, although treatment allocations sometimes become recognizable owing to materials and devices used. Secondly, due to insufcient reporting of the results in the included studies, some assumptions such like the number of participants in each group were made in the data extraction procedure. Thirdly, the trials that did not use evaporative air test to evaluate DH or the treatments categorized within the same group were excluded, and this might lose some important information. Finally, although we divided the studies into six groups in the network meta-analysis, we did not conduct any test for further within treatment group comparisons.

Conclusion

In conclusion, the results from network meta-analysis showed that most active treatment options including physical occlusion, chemical occlusion, laser therapy and combined therapy had signicantly better treatment outcome than placebo. The comparisons of the ve active treatment groups showed no signicant differences.
Acknowledgements

The authors thank Renee Tseng (Medical library of Taiwan Adventist Hospital) for her contribution to the literature search.

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DH network meta-analysis
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Appendix S1. Quality assessment of the included articles for network meta-analysis. Appendix S2. Results of network and standard meta-analysis.

Supporting Information

Additional Supporting Information may be found in the online version of this article:

Address: Yu-Kang Tu Institute of Epidemiology and Preventive Medicine College of Public Health, National Taiwan University Room 539, 17 Xu-Zhou Road Taipei Taiwan E-mail: yukangtu@ntu.edu.tw

Clinical Relevance

Scientic rationale for the study: A large number of in-ofce desensitizing agents are available for treating dentin hypersensitivity (DH), and this study used the network metaanalysis to compare the relative

effectiveness among those agents in resolving DH. Principal ndings: Most active agents achieved better treatment outcome than placebo group, but there was no substantial difference between active agents.

Practical implications: Although currently there is no gold-standard treatment for DH, commonly used in-ofce desensitizing agents for DH seemed to be effective.

2012 John Wiley & Sons A/S