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Heliyon Dec 2019The aim of the present systematic review was to examine the scientific evidence for the efficacy of stabilized stannous fluoride (SnF) dentifrice in relation to dental... (Review)
Review
OBJECTIVES
The aim of the present systematic review was to examine the scientific evidence for the efficacy of stabilized stannous fluoride (SnF) dentifrice in relation to dental calculus, dental plaque, gingivitis, halitosis and staining.
DATA AND SOURCES
Medline OVID, Embase.com, and the Cochrane Library were searched from database inception until June 2017. Six researchers independently selected studies, extracted data, and assessed methodological quality. A meta-analysis of the 6-month gingivitis studies was done. Risk of bias was estimated using a checklist from the Swedish Agency for Health Technology Assessment (SBU, 2018).
STUDY SELECTION
Two studies on dental calculus, 21 on dental plaque and gingivitis, 4 on halitosis, and 5 on stain met the inclusion criteria. Risk of bias was high for the studies on dental calculus, halitosis, and stain, and varied for the dental plaque and gingivitis studies. Significant reductions in dental calculus and in halitosis were reported for the SnF dentifrice; no differences in stain reduction were noted. A meta-analysis on gingivitis found better results for the SnF dentifrice compared to other dentifrices, though the results of the individual trials in the meta-analyses showed a substantial heterogeneity.
CONCLUSIONS
The present review found that stabilized SnF toothpaste had a positive effect on the reduction of dental calculus build-up, dental plaque, gingivitis, stain and halitosis. A tendency towards a more pronounced effect than using toothpastes not containing SnF2 was found. However, a new generation of well conducted randomized trials are needed to further support these findings.
CLINICAL RELEVANCE
Adding a SnF toothpaste to the daily oral care routine is an easy strategy that may have multiple oral health benefits.
PubMed: 31872105
DOI: 10.1016/j.heliyon.2019.e02850 -
The Cochrane Database of Systematic... Apr 2019Good oral hygiene is thought to be important for oral health. This review is to determine the effectiveness of flossing in addition to toothbrushing for preventing gum... (Review)
Review
BACKGROUND
Good oral hygiene is thought to be important for oral health. This review is to determine the effectiveness of flossing in addition to toothbrushing for preventing gum disease and dental caries in adults.
OBJECTIVES
To assess the effects of flossing in addition to toothbrushing, as compared with toothbrushing alone, in the management of periodontal diseases and dental caries in adults.
SEARCH METHODS
We searched the following electronic databases: the Cochrane Oral Health Group Trials Register (to 17 October 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 4), MEDLINE via OVID (1950 to 17 October 2011), EMBASE via OVID (1980 to 17 October 2011), CINAHL via EBSCO (1980 to 17 October 2011), LILACS via BIREME (1982 to 17 October 2011), ZETOC Conference Proceedings (1980 to 17 October 2011), Web of Science Conference Proceedings (1990 to 17 October 2011), Clinicaltrials.gov (to 17 October 2011) and the metaRegister of Controlled Clinical Trials (to 17 October 2011). We imposed no restrictions regarding language or date of publication. We contacted manufacturers of dental floss to identify trials.
SELECTION CRITERIA
We included randomised controlled trials conducted comparing toothbrushing and flossing with only toothbrushing, in adults.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed risk of bias for the included studies and extracted data. We contacted trial authors for further details where these were unclear. The effect measure for each meta-analysis was the standardised mean difference (SMD) with 95% confidence intervals (CI) using random-effects models. We examined potential sources of heterogeneity, along with sensitivity analyses omitting trials at high risk of bias.
MAIN RESULTS
Twelve trials were included in this review, with a total of 582 participants in flossing plus toothbrushing (intervention) groups and 501 participants in toothbrushing (control) groups. All included trials reported the outcomes of plaque and gingivitis. Seven of the included trials were assessed as at unclear risk of bias and five were at high risk of bias.Flossing plus toothbrushing showed a statistically significant benefit compared to toothbrushing in reducing gingivitis at the three time points studied, the SMD being -0.36 (95% CI -0.66 to -0.05) at 1 month, SMD -0.41 (95% CI -0.68 to -0.14) at 3 months and SMD -0.72 (95% CI -1.09 to -0.35) at 6 months. The 1-month estimate translates to a 0.13 point reduction on a 0 to 3 point scale for Loe-Silness gingivitis index, and the 3 and 6 month results translate to 0.20 and 0.09 reductions on the same scale.Overall there is weak, very unreliable evidence which suggests that flossing plus toothbrushing may be associated with a small reduction in plaque at 1 or 3 months.None of the included trials reported data for the outcomes of caries, calculus, clinical attachment loss, or quality of life. There was some inconsistent reporting of adverse effects.
AUTHORS' CONCLUSIONS
There is some evidence from twelve studies that flossing in addition to toothbrushing reduces gingivitis compared to toothbrushing alone. There is weak, very unreliable evidence from 10 studies that flossing plus toothbrushing may be associated with a small reduction in plaque at 1 and 3 months. No studies reported the effectiveness of flossing plus toothbrushing for preventing dental caries.
PubMed: 31013348
DOI: 10.1002/14651858.CD008829.pub3 -
The Cochrane Database of Systematic... Dec 2018Many dentists or hygienists provide scaling and polishing for patients at regular intervals, even for those at low risk of developing periodontal disease. There is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many dentists or hygienists provide scaling and polishing for patients at regular intervals, even for those at low risk of developing periodontal disease. There is debate over the clinical and cost effectiveness of 'routine scaling and polishing' and the optimal frequency at which it should be provided for healthy adults.A 'routine scale and polish' treatment is defined as scaling or polishing, or both, of the crown and root surfaces of teeth to remove local irritational factors (plaque, calculus, debris and staining), which does not involve periodontal surgery or any form of adjunctive periodontal therapy such as the use of chemotherapeutic agents or root planing. Routine scale and polish treatments are typically provided in general dental practice settings. The technique may also be referred to as prophylaxis, professional mechanical plaque removal or periodontal instrumentation.This review updates a version published in 2013.
OBJECTIVES
1. To determine the beneficial and harmful effects of routine scaling and polishing for periodontal health.2. To determine the beneficial and harmful effects of routine scaling and polishing at different recall intervals for periodontal health.3. To determine the beneficial and harmful effects of routine scaling and polishing for periodontal health when the treatment is provided by dentists compared with dental care professionals (dental therapists or dental hygienists).
SEARCH METHODS
Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 10 January 2018), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2017, Issue 12), MEDLINE Ovid (1946 to 10 January 2018), and Embase Ovid (1980 to 10 January 2018). The US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.
SELECTION CRITERIA
Randomised controlled trials of routine scale and polish treatments, with or without oral hygiene instruction, in healthy dentate adults without severe periodontitis. We excluded split-mouth trials.
DATA COLLECTION AND ANALYSIS
Two review authors screened the results of the searches against inclusion criteria, extracted data and assessed risk of bias independently and in duplicate. We calculated mean differences (MDs) (or standardised mean differences (SMDs) when different scales were reported) and 95% confidence intervals (CIs) for continuous data. We calculated risk ratios (RR) and 95% CIs for dichotomous data. We used a fixed-effect model for meta-analyses. We contacted study authors when necessary to obtain missing information. We rated the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included two studies with 1711 participants in the analyses. Both studies were conducted in UK general dental practices and involved adults without severe periodontitis who were regular attenders at dental appointments. One study measured outcomes at 24 months and the other at 36 months. Neither study measured adverse effects, changes in attachment level, tooth loss or halitosis.Comparison 1: routine scaling and polishing versus no scheduled scaling and polishingTwo studies compared planned, regular interval (six- and 12-monthly) scale and polish treatments versus no scheduled treatment. We found little or no difference between groups over a two- to three-year period for gingivitis, probing depths, oral health-related quality of life (all high-certainty evidence) and plaque (low-certainty evidence). The SMD for gingivitis when comparing six-monthly scale and polish treatment versus no scheduled treatment was -0.01 (95% CI -0.13 to 0.11; two trials, 1087 participants), and for 12-monthly scale and polish versus no scheduled treatment was -0.04 (95% CI -0.16 to 0.08; two trials, 1091 participants).Regular planned scale and polish treatments produced a small reduction in calculus levels over two to three years when compared with no scheduled scale and polish treatments (high-certainty evidence). The SMD for six-monthly scale and polish versus no scheduled treatment was -0.32 (95% CI -0.44 to -0.20; two trials, 1088 participants) and for 12-monthly scale and polish versus no scheduled treatment was -0.19 (95% CI -0.31 to -0.07; two trials, 1088 participants). The clinical importance of these small reductions is unclear.Participants' self-reported levels of oral cleanliness were higher when receiving six- and 12-monthly scale and polish treatments compared to no scheduled treatment, but the certainty of the evidence is low.Comparison 2: routine scaling and polishing at different recall intervalsTwo studies compared routine six-monthly scale and polish treatments versus 12-monthly treatments. We found little or no difference between groups over two to three years for the outcomes of gingivitis, probing depths, oral health-related quality of life (all high-certainty evidence) and plaque (low-certainty evidence). The SMD for gingivitis was 0.03 (95% CI -0.09 to 0.15; two trials, 1090 participants; I = 0%). Six- monthly scale and polish treatments produced a small reduction in calculus levels over a two- to three-year period when compared with 12-monthly treatments (SMD -0.13 (95% CI -0.25 to -0.01; 2 trials, 1086 participants; high-certainty evidence). The clinical importance of this small reduction is unclear.The comparative effects of six- and 12-monthly scale and polish treatments on patients' self-reported levels of oral cleanliness were uncertain (very low-certainty evidence).Comparison 3: routine scaling and polishing provided by dentists compared with dental care professionals (dental therapists or hygienists)No studies evaluated this comparison.The review findings in relation to costs were uncertain (very low-certainty evidence).
AUTHORS' CONCLUSIONS
For adults without severe periodontitis who regularly access routine dental care, routine scale and polish treatment makes little or no difference to gingivitis, probing depths and oral health-related quality of life over two to three years follow-up when compared with no scheduled scale and polish treatments (high-certainty evidence). There may also be little or no difference in plaque levels over two years (low-certainty evidence). Routine scaling and polishing reduces calculus levels compared with no routine scaling and polishing, with six-monthly treatments reducing calculus more than 12-monthly treatments over two to three years follow-up (high-certainty evidence), although the clinical importance of these small reductions is uncertain. Available evidence on the costs of the treatments is uncertain. The studies did not assess adverse effects.
Topics: Adult; Dental Calculus; Dental Plaque; Dental Polishing; Dental Prophylaxis; Dental Scaling; Gingivitis; Humans; Patient Satisfaction; Periodontal Diseases; Quality of Life; Randomized Controlled Trials as Topic; Time Factors
PubMed: 30590875
DOI: 10.1002/14651858.CD004625.pub5 -
The Cochrane Database of Systematic... Jan 2018Periodontitis is a bacterially-induced, chronic inflammatory disease that destroys the connective tissues and bone that support teeth. Active periodontal treatment aims... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Periodontitis is a bacterially-induced, chronic inflammatory disease that destroys the connective tissues and bone that support teeth. Active periodontal treatment aims to reduce the inflammatory response, primarily through eradication of bacterial deposits. Following completion of treatment and arrest of inflammation, supportive periodontal therapy (SPT) is employed to reduce the probability of re-infection and progression of the disease; to maintain teeth without pain, excessive mobility or persistent infection in the long term, and to prevent related oral diseases.According to the American Academy of Periodontology, SPT should include all components of a typical dental recall examination, and importantly should also include periodontal re-evaluation and risk assessment, supragingival and subgingival removal of bacterial plaque and calculus, and re-treatment of any sites showing recurrent or persistent disease. While the first four points might be expected to form part of the routine examination appointment for periodontally healthy patients, the inclusion of thorough periodontal evaluation, risk assessment and subsequent treatment - normally including mechanical debridement of any plaque or calculus deposits - differentiates SPT from routine care.Success of SPT has been reported in a number of long-term, retrospective studies. This review aimed to assess the evidence available from randomised controlled trials (RCTs).
OBJECTIVES
To determine the effects of supportive periodontal therapy (SPT) in the maintenance of the dentition of adults treated for periodontitis.
SEARCH METHODS
Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 8 May 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2017, Issue 5), MEDLINE Ovid (1946 to 8 May 2017), and Embase Ovid (1980 to 8 May 2017). The US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.
SELECTION CRITERIA
Randomised controlled trials (RCTs) evaluating SPT versus monitoring only or alternative approaches to mechanical debridement; SPT alone versus SPT with adjunctive interventions; different approaches to or providers of SPT; and different time intervals for SPT delivery.We excluded split-mouth studies where we considered there could be a risk of contamination.Participants must have completed active periodontal therapy at least six months prior to randomisation and be enrolled in an SPT programme. Trials must have had a minimum follow-up period of 12 months.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened search results to identify studies for inclusion, assessed the risk of bias in included studies and extracted study data. When possible, we calculated mean differences (MDs) and 95% confidence intervals (CIs) for continuous variables. Two review authors assessed the quality of evidence for each comparison and outcome using GRADE criteria.
MAIN RESULTS
We included four trials involving 307 participants aged 31 to 85 years, who had been previously treated for moderate to severe chronic periodontitis. Three studies compared adjuncts to mechanical debridement in SPT versus debridement only. The adjuncts were local antibiotics in two studies (one at high risk of bias and one at low risk) and photodynamic therapy in one study (at unclear risk of bias). One study at high risk of bias compared provision of SPT by a specialist versus general practitioner. We did not identify any RCTs evaluating the effects of SPT versus monitoring only, or of providing SPT at different time intervals, or that compared the effects of mechanical debridement using different approaches or technologies.No included trials measured our primary outcome 'tooth loss'; however, studies evaluated signs of inflammation and potential periodontal disease progression, including bleeding on probing (BoP), clinical attachment level (CAL) and probing pocket depth (PPD).There was no evidence of a difference between SPT delivered by a specialist versus a general practitioner for BoP or PPD at 12 months (very low-quality evidence). This study did not measure CAL or adverse events.Due to heterogeneous outcome reporting, it was not possible to combine data from the two studies comparing mechanical debridement with or without the use of adjunctive local antibiotics. Both studies found no evidence of a difference between groups at 12 months (low to very low-quality evidence). There were no adverse events in either study.The use of adjunctive photodynamic therapy did not demonstrate evidence of benefit compared to mechanical debridement only (very low-quality evidence). Adverse events were not measured.The quality of the evidence is low to very low for these comparisons. Future research is likely to change the findings, therefore the results should be interpreted with caution.
AUTHORS' CONCLUSIONS
Overall, there is insufficient evidence to determine the superiority of different protocols or adjunctive strategies to improve tooth maintenance during SPT. No trials evaluated SPT versus monitoring only. The evidence available for the comparisons evaluated is of low to very low quality, and hampered by dissimilarities in outcome reporting. More trials using uniform definitions and outcomes are required to address the objectives of this review.
Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Chronic Periodontitis; Dental Plaque; Humans; Middle Aged; Periodontal Debridement; Periodontics; Photochemotherapy; Randomized Controlled Trials as Topic; Tooth Loss
PubMed: 29291254
DOI: 10.1002/14651858.CD009376.pub2 -
The Cochrane Database of Systematic... Mar 2017Dental plaque associated gingivitis is a reversible inflammatory condition caused by accumulation and persistence of microbial biofilms (dental plaque) on the teeth. It... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dental plaque associated gingivitis is a reversible inflammatory condition caused by accumulation and persistence of microbial biofilms (dental plaque) on the teeth. It is characterised by redness and swelling of the gingivae (gums) and a tendency for the gingivae to bleed easily. In susceptible individuals, gingivitis may lead to periodontitis and loss of the soft tissue and bony support for the tooth. It is thought that chlorhexidine mouthrinse may reduce the build-up of plaque thereby reducing gingivitis.
OBJECTIVES
To assess the effectiveness of chlorhexidine mouthrinse used as an adjunct to mechanical oral hygiene procedures for the control of gingivitis and plaque compared to mechanical oral hygiene procedures alone or mechanical oral hygiene procedures plus placebo/control mouthrinse. Mechanical oral hygiene procedures were toothbrushing with/without the use of dental floss or interdental cleaning aids and could include professional tooth cleaning/periodontal treatment.To determine whether the effect of chlorhexidine mouthrinse is influenced by chlorhexidine concentration, or frequency of rinsing (once/day versus twice/day).To report and describe any adverse effects associated with chlorhexidine mouthrinse use from included trials.
SEARCH METHODS
Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 28 September 2016); the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8) in the Cochrane Library (searched 28 September 2016); MEDLINE Ovid (1946 to 28 September 2016); Embase Ovid (1980 to 28 September 2016); and CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1937 to 28 September 2016). We searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.
SELECTION CRITERIA
We included randomised controlled trials assessing the effects of chlorhexidine mouthrinse used as an adjunct to mechanical oral hygiene procedures for at least 4 weeks on gingivitis in children and adults. Mechanical oral hygiene procedures were toothbrushing with/without use of dental floss or interdental cleaning aids and could include professional tooth cleaning/periodontal treatment. We included trials where participants had gingivitis or periodontitis, where participants were healthy and where some or all participants had medical conditions or special care needs.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the search results extracted data and assessed the risk of bias of the included studies. We attempted to contact study authors for missing data or clarification where feasible. For continuous outcomes, we used means and standard deviations to obtain the mean difference (MD) and 95% confidence interval (CI). We combined MDs where studies used the same scale and standardised mean differences (SMDs) where studies used different scales. For dichotomous outcomes, we reported risk ratios (RR) and 95% CIs. Due to anticipated heterogeneity we used random-effects models for all meta-analyses.
MAIN RESULTS
We included 51 studies that analysed a total of 5345 participants. One study was assessed as being at unclear risk of bias, with the remaining 50 being at high risk of bias, however, this did not affect the quality assessments for gingivitis and plaque as we believe that further research is very unlikely to change our confidence in the estimate of effect. Gingivitis After 4 to 6 weeks of use, chlorhexidine mouthrinse reduced gingivitis (Gingival Index (GI) 0 to 3 scale) by 0.21 (95% CI 0.11 to 0.31) compared to placebo, control or no mouthrinse (10 trials, 805 participants with mild gingival inflammation (mean score 1 on the GI scale) analysed, high-quality evidence). A similar effect size was found for reducing gingivitis at 6 months. There were insufficient data to determine the reduction in gingivitis associated with chlorhexidine mouthrinse use in individuals with mean GI scores of 1.1 to 3 (moderate or severe levels of gingival inflammation). Plaque Plaque was measured by different indices and the SMD at 4 to 6 weeks was 1.45 (95% CI 1.00 to 1.90) standard deviations lower in the chlorhexidine group (12 trials, 950 participants analysed, high-quality evidence), indicating a large reduction in plaque. A similar large reduction was found for chlorhexidine mouthrinse use at 6 months. Extrinsic tooth staining There was a large increase in extrinsic tooth staining in participants using chlorhexidine mouthrinse at 4 to 6 weeks. The SMD was 1.07 (95% CI 0.80 to 1.34) standard deviations higher (eight trials, 415 participants analysed, moderate-quality evidence) in the chlorhexidine mouthrinse group. There was also a large increase in extrinsic tooth staining in participants using chlorhexidine mouthrinse at 7 to 12 weeks and 6 months. Calculus Results for the effect of chlorhexidine mouthrinse on calculus formation were inconclusive. Effect of concentration and frequency of rinsing There were insufficient data to determine whether there was a difference in effect for either chlorhexidine concentration or frequency of rinsing. Other adverse effects The adverse effects most commonly reported in the included studies were taste disturbance/alteration (reported in 11 studies), effects on the oral mucosa including soreness, irritation, mild desquamation and mucosal ulceration/erosions (reported in 13 studies) and a general burning sensation or a burning tongue or both (reported in nine studies).
AUTHORS' CONCLUSIONS
There is high-quality evidence from studies that reported the Löe and Silness Gingival Index of a reduction in gingivitis in individuals with mild gingival inflammation on average (mean score of 1 on the 0 to 3 GI scale) that was not considered to be clinically relevant. There is high-quality evidence of a large reduction in dental plaque with chlorhexidine mouthrinse used as an adjunct to mechanical oral hygiene procedures for 4 to 6 weeks and 6 months. There is no evidence that one concentration of chlorhexidine rinse is more effective than another. There is insufficient evidence to determine the reduction in gingivitis associated with chlorhexidine mouthrinse use in individuals with mean GI scores of 1.1 to 3 indicating moderate or severe levels of gingival inflammation. Rinsing with chlorhexidine mouthrinse for 4 weeks or longer causes extrinsic tooth staining. In addition, other adverse effects such as calculus build up, transient taste disturbance and effects on the oral mucosa were reported in the included studies.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Chemotherapy, Adjuvant; Child; Chlorhexidine; Dental Plaque; Dental Plaque Index; Dental Prophylaxis; Female; Gingivitis; Humans; Male; Middle Aged; Mouthwashes; Oral Hygiene; Publication Bias; Randomized Controlled Trials as Topic; Time Factors; Tooth Discoloration
PubMed: 28362061
DOI: 10.1002/14651858.CD008676.pub2 -
Advances in Nutrition (Bethesda, Md.) Nov 2015The aim of this systematic review was to identify and summarize evidence of the association between anthropometric measurements and periodontal status in children and... (Meta-Analysis)
Meta-Analysis Review
The aim of this systematic review was to identify and summarize evidence of the association between anthropometric measurements and periodontal status in children and adolescents. We searched PubMed, Institute for Scientific Information Web of Knowledge, Cochrane Library, and 7 additional databases, following the guidance of Preferred Reporting Items for Systematic Reviews and Meta-Analyses, up to December 2014. Observational studies reporting data on the association between anthropometric measurements and periodontal diseases in 2-18-y-old participants were included. An initial search identified 4191 papers; 278 potentially effective studies (k = 0.82) and 16 effective studies (k = 0.83) were included after screening. The mean quality of evidence among the studies was 20.3, according to the Strengthening the Reporting of Observational studies in Epidemiology checklist (k = 0.79). Meta-analyses showed that obesity (measured by body mass index) was significantly associated with visible plaque index (OR: 4.75; 95% CI: 2.42, 9.34), bleeding on probing (OR: 5.41; 95% CI: 2.75, 10.63), subgingival calculus (OR: 3.07; 95% CI: 1.10, 8.62), probing depth (OR: 14.15; 95% CI: 5.10, 39.25) and flow rate of salivary secretion (standardized mean difference: -0.89; 95% CI: -1.18, -0.61). However, various results were reported in the effective studies that were not included in meta-analyses. In conclusion, obesity is associated with some signs of periodontal disease in children and adolescents. Further studies with a comprehensive prospective cohort design and more potential variables are recommended.
Topics: Adolescent; Anthropometry; Body Mass Index; Child; Child, Preschool; Dental Plaque; Energy Intake; Gingivitis; Humans; Inflammation; Obesity; Periodontal Diseases; Periodontal Index; Salivation
PubMed: 26567204
DOI: 10.3945/an.115.010017