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Awareness of signs and symptoms of oral cancer is important to every dental provider. However, oral cancer can produce features that hamper its recognition, which can lead to a delay in diagnosis and treatment. This report describes two cases of gingival squamous cell carcinoma masquerading as periodontal disease. The clinical and radiographic features of these two cases illustrate that a thorough evaluation for potentially underlying malignant process should be performed on patients whose conditions are refractory to standard therapy.

Objectives To determine the effectiveness of systemic pharmacotherapeutic interventions compared to placebo in burning mouth syndrome (BMS) randomized controlled trials (RCTs) based on the core outcome domains recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT). Methods A systematic literature review of RCTs, concerning systemic pharmacotherapeutic interventions for BMS, published from January 1994 through October 2019, and meta-analysis was performed. Results Fourteen RCTs (n = 734 participants) were included. Of those, nine were eligible for the quantitative assessment due to the availability/homogeneity of data for at least one of the IMMPACT domains. Pain intensity was the only domain reported in all RCTs. Weighted mean changes in pain intensity, based on visual analogue scale (ΔVAS), were reported in three RCTs at 6 ± 2 weeks and only one RCT at 10+ weeks follow-ups. Quantitative assessment, based on ΔVAS, yielded very low evidence for the effectiveness of alpha-lipoic acid and clonazepam, low evidence for effectiveness of trazodone and melatonin, and moderate evidence for herbal compounds. Conclusions Based on the RCTs studied, variable levels of evidence exist that suggest that select pharmacological interventions are associated with improved symptoms. However, the underreporting of IMMPACT domains in BMS RCTs restricts the multidimensional assessment of systemic interventions outcomes. Standardized outcome measures need to be applied to future RCTs to improve understanding of intervention outcomes.

Translational animal models for oral mucositis (OM) are necessary to simulate and assess the bioclinical effects and response in humans. These models should simulate high levels of radiation exposure that leads to oxidative stress and inflammatory‐initiated tissue changes. Hamster models have been extensively studied to observe pathological effects of radiation exposure and help in the development of effective treatments. To successfully evaluate the potential for treatment regimens with consistency and relevance, a radiation‐induced OM hamster model was developed using a clinical linear accelerator utilized by cancer patients daily. The dose exposure to the isolated, everted cheek pouch of a hamster, as well as the progression of injury, pro‐inflammatory marker, histological, and elasticity analyses of the buccal pouch were conducted to verify replicability and reproducibility of the injury model. The findings from this model demonstrated its ability to consistently induce injury and resolution over 28 days using an acute dose of 60 Gy. This model was developed to enhance clinical relevance when evaluating potential efficacious treatments and can now be utilized in efficacy studies to better evaluate developed therapeutics in a preclinical model that is easy to translate to clinical studies..

Background: Leptin and adiponectin, two adipokines involved in glucose and lipid metabolism, have been linked to regulation of growth in early infancy, energy balance, and metabolic disorders in childhood. The aim of this study was to determine if concentrations of leptin and adiponectin could be measured reliably in infants’ saliva, to evaluate the degree of agreement with infant serum levels, and to explore their association with infant feeding status. Methods: A total of 34 infants were recruited after birth and followed for 20 weeks. After log-transformation of the values, a Bland-Altman graphical approach was used to summarize the direction of the difference between the serum and saliva values. Repeated measures mixed modeling was used to evaluate differences over time in these outcomes by feeding status. Results: Mean concentration of salivary leptin and adiponectin in infants was 3.7 ( SD = .8) ng/mL and 2.9 ( SD = 0.7) ng/mL, respectively. The degree of agreement between serum and saliva for log-transformed leptin and adiponectin values were relatively robust, albeit with a non-zero bias between the two methods, given that serum values were greater than corresponding saliva values for both adipokines in all infants. Each of the four repeated measures mixed models (one for each adipokine measure) had a significant main effect; however, the interaction between time and feeding status was not significant in any of the models. Conclusion: This study demonstrated that leptin and adiponectin can be measured in infant saliva, but in some cases leptin concentrations may be more difficult to detect.

AIM Salivary biomarkers can help in assessment of periodontitis; however, concentrations may be altered in the presence of diabetes. Hence, the ability of salivary biomarkers to discriminate periodontally healthy type II diabetics (T2DM) from T2DM who have periodontitis was examined. METHODS Ninety-two participants (29 with T2DM with chronic periodontitis, DWP; 32 T2DM without chronic periodontitis, DWoP; and 31 Not Periodontitis, NP) provided saliva and clinical parameters of periodontal health were recorded. Salivary concentrations of interleukin (IL)-1β, IL-6, matrix metalloproteinase-8 (MMP-8), macrophage inflammatory protein-1α (MIP-1α), adiponectin and resistin were measured by immunoassay. RESULTS Salivary analyte concentrations for IL-1β, MMP-8 and resistin correlated with clinical parameters of periodontitis, with MMP-8 demonstrating the strongest positive correlation with PD ≥5 mm (p

Objectives This literature review was performed to assess the risk of bleeding in dental implantation procedures in patients taking antiplatelet drugs (APs), oral anticoagulants (OACs) and direct oral anticoagulants (DOACs). Study Design MEDLINE and SCOPUS databases were searched for English language publications through October 2019, using the keywords “dental implants,” “dental implantation,” “anticoagulants,” “platelet aggregation inhibitors,” and “hemorrhage.” Reference lists of relevant articles were also hand searched. Collected data regarding dental implantation procedures, type of medications (APs, OACs and DOAC), and postoperative bleeding episodes were analyzed. Results Nine studies were included in the review. Postoperative bleeding occurred in 10 (2.2%) of 456 of cases involving dental implant placements; in all of those cases, bleeding was controlled with the use of local hemostatic agents. The bleeding incidence in patients on antiplatelet medications was 0.4% (range 1 of 253 to 1 of 261). Among those taking oral anticoagulants, the bleeding incidence was 5.7% (range 6 of 105 to 6 of 113), and among those on direct oral anticoagulants, the bleeding incidence was 3.3% (3 of 90). The numbers of more extensive surgical procedures (i.e., sinus lift and bone augmentation procedures) were small, and additional information regarding the surgery, the specific antithrombotic used, or bleeding was often not provided, so further analysis was not possible. Conclusions Evidence supports continuing OACs, DOACs, or APs during dental implant surgery.

Analgesic prescribing patterns are influenced by internal and external factors. Understanding these factors could help improve prescribing practices.We conducted a retrospective analysis of electronic health records with regard to analgesic prescriptions written from 2013 through 2018 at the University of Kentucky College of Dentistry. Deidentified information (age, gender, dental procedures, analgesic drug, quantity, and refills) were recorded and studied with respect to national guidelines and recent state legislation using the χOpioids comprised 74.9% of the 17,099 analgesic prescriptions written. Extractions were most commonly associated with opioid prescriptions. Multivariate analysis showed that (1) older patients were more likely to receive an opioid prescription (P.01) but with fewer pills (P.01); (2) surgical extractions were associated with a lower opioid prescription rate (P.01) but more opioid pills per prescription compared with nonsurgical extractions (P.01); and (3) the odds of receiving an opioid prescription and the number of opioid pills prescribed decreased over year after release of the national guideline (P.01) and after enactment of state legislation (P.01).Regulations and guidelines were associated with reduction in opioid prescriptions.

The International Classification of Diseases (ICD-11) proposes revisions in the nomenclature, disease definition, and diagnostic criteria for "burning mouth syndrome" (BMS). This process could benefit from additional systematically collected expert input. Thus, the purpose of this study was to use the Delphi method to (1) determine whether revision in nomenclature and alternative names for "BMS" are warranted and (2) identify areas of consensus among experts for changes to the disease description and proposed diagnostic criteria of "BMS," as described in the ICD-11 (World Health Organization). From 31 international invited experts, 23 who expressed interest were sent the survey. The study used 4 iterative surveys, each with a response rate of ≥82%. Consensus was predefined as 70% of participants in agreement. Data were summarized using both descriptive statistics and qualitative thematic analysis. Consensus indicated that BMS should not be classified as a syndrome and recommended instead renaming to "burning mouth disorder." Consensus included deletion of 2 diagnostic criteria: (1) emotional distress or functional disability and (2) the number of hours symptoms occur per day. Additional items that reached consensus clarified the disease definition and proposed more separate diagnostic criteria, including a list of local and systemic factors to evaluate as potential secondary causes of oral burning. Experts in this study recommended and came to consensus on select revisions to the proposed ICD-11 BMS nomenclature, diagnostic criteria, and disease definition. The revisions recommended have the potential to improve clarity, consistency, and accuracy of diagnosis for this disorder.

Objective To examine postoperative bleeding in patients taking antiplatelet and anticoagulant medications after invasive periodontal procedures. Study Design This 6-year retrospective study collected data from the electronic health records of patients who underwent invasive periodontal procedures at the College of Dentistry, University of Kentucky Lexington, from January 1, 2011 through April 1, 2017. Records were included when the medical history was current, an invasive periodontal procedure was performed, an antiplatelet or anticoagulant medication was taken, and a postoperative visit was documented. Results Four hundred and fifty-six patients (age range 22–89 years; mean age 66.1 years; 58% male) met the inclusion criteria and underwent 867 invasive periodontal procedures. Antiplatelet medications, warfarin, a direct oral anticoagulant, or a combination of these drugs were taken during 484 scaling and root planing procedures, 218 implant placements, 53 open flap debridements, 16 gingival grafts, 15 lateral windows, and 71 other. Medications were continued in 99.6% of patients during the procedure. Postoperative bleeding occurred after three procedures (0.35%) and resolved with local hemostatic measures. Medications were temporarily discontinued in four instances (range 1–5 days); none of these patients experienced postoperative bleeding. Conclusions Postoperative bleeding was infrequent in patients who underwent an invasive periodontal procedure while taking an antiplatelet or anticoagulant drug.

There are few absolute contraindications to dental implant placement. Relative contraindications include cognitive decline, American Society of Anesthesiology patient status IV or higher categories, or medical conditions that may jeopardize the life or lifespan of the patient. Precautions for placing dental implants should be viewed with respect to the evidence-based exposures that can contribute to risk of failure, including but not limited to local, behavioral, and medical factors. Risk for dental implant failure increases in association with (1) past history of periodontal disease, (2) bruxism, (3) smoking, and (4) radiation therapy.

Objectives: To determine the frequency of use of the core outcome domains published by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) in burning mouth syndrome (BMS) randomized controlled trials (RCTs). Methods: This systematic review, conducted as part of the World Workshop on Oral Medicine VII (WWOM VII), was performed by searching the literature for studies published in PubMed, Web of Science, PsycINFO, Cochrane Database/Cochrane Central, and Google Scholar from January 1994 (when the first BMS definition came out) through October 2017. Results: A total of 36 RCTs (n = 2,175 study participants) were included and analyzed. The overall reporting of the IMMPACT core and supplemental outcome domains was low even after the publication of the IMMPACT consensus papers in 2003 and 2005 (mean before IMMPACT consensus publication = 2.6 out of 6; mean after IMMPACT publication = 3.8 out of 6). Use of validated assessment tools recommended by the IMMPACT consensus was scarce (1.9 out of 6). None of the RCTs reviewed cited the IMMPACT consensus papers. Conclusions: The underreporting of IMMPACT outcome domains in BMS RCTs is significant. Raising awareness regarding the existence of standardized outcome domains in chronic pain research is essential to ensure more accurate, comparable, and consistent interpretation of RCT findings that can be clinically translatable.

Background A core outcome set (COS) represents the agreed minimum set of domains and measurement instruments that should be measured and reported in any clinical trial for a given condition. In BMS randomized controlled trials (RCTs), the outcomes identified in the existing literature regarding the efficacy of therapeutic interventions are numerous and diverse. Although the standardized IMMPACT core outcome domains has been developed for measurement of outcomes in chronic pain RCTs, no BMS-specific COS have been adopted and validated. With the evolving landscape of BMS management end points and the development of new therapies, a consensus on a COS for use in future BMS trials is paramount to reduce heterogeneity in outcome reporting. The aim of this study was to reach a consensus for adopting the standardized Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) outcome domains, and their tools of assessment, for burning mouth syndrome (BMS) clinical trials and clinical practice. Methods A BMS-specific COS will be developed using the method recommended by the Core Outcome Measures in Effective Trials (COMET) initiative (Registration: http://www.comet-initiative.org/studies/details/1357). Selection of questionnaire outcome measures was informed by the IMMPACT consensus and previous systematic review of RCTs in BMS conducted by the consortium. An international group of clinicians and researchers will be invited to participate in several rounds of a Delphi survey. A consensus meeting will be held with the objective of ratifying the outcomes for inclusion in the COS. A finalized COS explanatory document will be drafted, including all outcomes and measurements as determined by the Delphi rounds and consensus meeting. Discussion A COS for the management of BMS will improve the quality of future RCTs, reduce outcome reporting heterogeneity, and facilitate more vigorous data synthesis of management interventions for systematic reviews and meta-analysis. This would ensure enhanced quality evidence for clinical management of the condition.

Background Nonopioids provide sufficient analgesia with less risk after most dental procedures, but opioid prescriptions are still common. This study analyzed opioid prescribing characteristics on the basis of patient demographics and procedure types. Methods The authors conducted a secondary analysis of an existing data set of opioid prescriptions issued from 2013 through 2018 from a college of dentistry in central Appalachia. Opioid prescriptions for young children or liquids were excluded. The authors analyzed prescriptions according to patient age group and sedation level required for surgical procedures. Results Of 12,464 opioid prescriptions analyzed, 70% were written after extractions or surgical procedures. More than one-half (57.3%) were written for patients younger than 45 years. Adolescent and young adult (AYA) patients received prescriptions of higher quantities (mean [standard deviation], 20.9 [6.4] pills; 95% confidence interval, 20.6 to 21.1) and of longer durations (mean [standard deviation], 3.3 [1.5] days; 95% confidence interval, 3.2 to 3.4) than other groups (P Conclusions AYA patients received more opioids than older patients after dental procedures, which is concerning given the high risk associated with AYA opioid exposure. Faculty in colleges of dentistry should educate students and residents on the risks and benefits of opioid therapy as well as alternative analgesics and via exemplifying appropriate prescribing behavior. Practical Implications AYA patients represent a seemingly unidentified high-risk age group for dentists. Dentists who perform invasive procedures must examine carefully opioid prescription necessity and prescribe in a manner consistent with best practices.

OBJECTIVE To investigate biological markers of peri-implantitis (PIP) in crevicular fluid before and after surgical and antimicrobial therapy. MATERIAL AND METHODS Forty-eight participants (24 healthy implants and 24 PIP) were clinically evaluated, and peri-implant crevicular fluid (PICF) samples were collected at baseline for both groups, and at 3-months after surgical and antimicrobial treatment (ie, n = 21 PIP completers). Samples were analyzed for interleukin-1β (IL-1β), matrix metalloproteinase-8 (MMP-8), and macrophage inflammatory protein-1α (MIP-1α) using immunoassay and the results compared between groups. RESULTS Peri-implantitis sites at baseline demonstrated significantly higher mean periodontal probing depths, percentage bleeding on probing (P ≤ 0.001), and mean IL-1β concentration in PICF compared to healthy implant sites (17.9 vs 1.7 pg/μL; P = 0.02). Three months after treatment, periodontal probing depths, bleeding on probing, suppuration (P

Objective: To conduct a systematic review analyzing disease definitions and diagnostic criteria used in randomized controlled trials (RCTs) involving burning mouth syndrome (BMS). Methods: A systematic search conducted in PubMed, Web of Science, PsycINFO, Cochrane Database/Cochrane Central, and Google Scholar that included RCTs on BMS published between 1994 and 2017 was performed. Results: Considerable variability in BMS disease definitions and diagnostic criteria used created substantial heterogeneity in the selection of participants and weakened the rigor of the 36 RCTs identified. The analyzed RCTs routinely under-reported the methods used to rule in or out study participants and the number of individuals excluded from BMS RCTs. Conclusions: Our findings indicate that a large proportion of participants enrolled in these studies may have had an underlying condition that could have explained their BMS symptoms. Thus, outcomes of therapeutic interventions from these BMS RCTs should be interpreted with caution due to heterogeneous disease definitions and diagnostic criteria. In order to improve the quality of clinical trials, future research should focus on establishing consensus for a single definition of BMS that includes specific inclusion and exclusion criteria that should be used to select study participants for clinical trials.

Background and Objective Adiponectin is produced by adipose cells and is considered an anti-inflammatory molecule. In contrast, C-reactive protein (CRP) has been identified as a hallmark of systemic inflammation and used as a risk marker of cardiovascular disease (CVD). Of interest was the relationship of these two biomarkers to oral health and CVD risk. Material and Methods This investigation examined these two molecules in serum and unstimulated whole saliva of patients within 48 h of an acute myocardial infarction (AMI) compared to control subjects. We hypothesized a differential response in these biomolecules resulting from the heart attack that would be affected by both the body mass index and oral health characteristics of the individuals. Results Significantly lower adiponectin levels were observed in the serum of patients with AMI. Serum adiponectin in both groups and salivary adiponectin in patients with AMI decreased with increasing body mass index. Oral health was significantly worse in patients with AMI, and both serum and salivary adiponectin were elevated with better oral health in control subjects. Serum CRP levels were increased in patients with AMI regardless of their oral health, and both serum and salivary CRP were significantly elevated in S-T wave elevated patients with MI. Conclusions These initial data provide evidence relating obesity and oral health to salivary and serum analyte levels that occur in association with cardiac events. Relationships have been described between CVD risk and periodontal disease. Additionally, various systemic inflammatory biomarkers appear to reflect both the CVD risk and the extent/severity of periodontitis. Our findings indicated that oral health and obesity contribute to altering levels of these salivary and serum analytes in association with cardiac events. The potential that serum and/or salivary biomarkers could aid in evaluating CVD risk requires knowledge regarding how the oral health of the individual would impact the effectiveness of these biological measures.

OBJECTIVE The objective of this study was to determine the efficacy of a novel point-of-care immunoflow device (POCID) for detecting matrix metalloproteinase (MMP)-8 concentrations in oral fluids in comparison with a gold standard laboratory-based immunoassay. METHODS Oral rinse fluid and whole expectorated saliva samples were collected from 41 participants clinically classified as periodontally healthy or diseased. Samples were analyzed for MMP-8 by Luminex immunoassay and POCID. Photographed POCID results were assessed by optical scan and visually by two examiners. Data were analyzed by Pearson's correlation and receiver-operating characteristics. RESULTS MMP-8 was readily detected by the POCID, and concentrations correlated well with Luminex for both saliva and rinse fluids (r = 0.57-0.93). Thresholds that distinguished periodontitis from health were delineated from both the optical scans and visual reads of the POCID (sensitivity: 0.7-0.9, specificity: 0.5-0.7; P

We developed a Cardiac ScoreCard based on a multivariate index assay.Using a single chip for multiple cardiac applications reduces cost and time.Lasso logistic regression performs shrinkage and selection in multimarker models.Biomarkers and traditional risk factors predict cardiac wellness and heart failure. Clinical decision support systems (CDSSs) have the potential to save lives and reduce unnecessary costs through early detection and frequent monitoring of both traditional risk factors and novel biomarkers for cardiovascular disease (CVD). However, the widespread adoption of CDSSs for the identification of heart diseases has been limited, likely due to the poor interpretability of clinically relevant results and the lack of seamless integration between measurements and disease predictions. In this paper we present the Cardiac ScoreCard-a multivariate index assay system with the potential to assist in the diagnosis and prognosis of a spectrum of CVD. The Cardiac ScoreCard system is based on lasso logistic regression techniques which utilize both patient demographics and novel biomarker data for the prediction of heart failure (HF) and cardiac wellness. Lasso logistic regression models were trained on a merged clinical dataset comprising 579 patients with 6 traditional risk factors and 14 biomarker measurements. The prediction performance of the Cardiac ScoreCard was assessed with 5-fold cross-validation and compared with reference methods. The experimental results reveal that the ScoreCard models improved performance in discriminating disease versus non-case (AUC=0.8403 and 0.9412 for cardiac wellness and HF, respectively), and the models exhibit good calibration. Clinical insights to the prediction of HF and cardiac wellness are provided in the form of logistic regression coefficients which suggest that augmenting the traditional risk factors with a multimarker panel spanning a diverse cardiovascular pathophysiology provides improved performance over reference methods. Additionally, a framework is provided for seamless integration with biomarker measurements from point-of-care medical microdevices, and a lasso-based feature selection process is described for the down-selection of biomarkers in multimarker panels.

In a recent publication in Science Translational Medicine 9:1-9, Aran et al (2017) provide a series of elegant experiments that present an innovative noninvasive intraoral method for vaccination that uses a device termed MucoJet (Aran et al, 2017). Their findings delineate an easy to use system involving jet velocity to penetrate buccal mucosa and deliver a vaccine to underlying immune cells. This technology provides a launching pad for several potential innovations for healthcare. This article is protected by copyright. All rights reserved.

Aim To investigate the synergistic role of biologic markers from saliva, serum and plaque in modelling periodontitis disease progression. Material and methods This longitudinal study evaluated characteristics of disease progression in 114 patients with generalized moderate to severe periodontitis. The primary outcome was detection of sites with progressing attachment loss sites over 6 months in patients who received scaling and root planing or oral hygiene only. The predictive potential of 27 biomarkers in serum, whole saliva and subgingival plaque was evaluated using three classification algorithms (Support Vector Machines; Naive Bayes Classifier; and Linear Discriminant Analysis) within an ensemble predictive modelling framework. Results Disease progression occurred in 24.6% of subjects (28/114). Predictive modelling using Naive Bayes Classifier identified progressors best with sensitivity of ~89%. The use of the three classification algorithms revealed the concerted role of salivary matrix metalloproteinase-8, serum biomarkers (serum amyloid P, matrix metalloproteinase 1, bactericidal permeability-increasing protein, isoprostane) along with levels of Porphryomonas gingivalis and Tannerella forsythia in plaque in predicting progressors. Conclusions Synergistic utility of baseline bacterial and inflammatory biomarkers from saliva, serum and plaque predicted disease progression.

Persistent pain is a major health problem and is a primary reason that many people seek health care services.1,2 Persistent pain conditions are challenging to live with and are often associated with high levels of stress for the individual.3,4 These conditions are characterized by complex interactions between cognitive, emotional, and physiologic disturbances that bring about significant coping challenges for patients. Each of these disturbances requires that individuals exert effort toward regulating their behavior in multiple domains while enduring and subsequently managing the persistent pain condition.4 The successful management of persistent pain mediated by the trigeminal nerve is the goal of orofacial pain patients and clinicians alike. It is not surprising that persistent orofacial pain taxes personal resources and has been associated with self-regulatory deficits in patients. Self-regulation involves the capacity to exert control over cognition, emotions, and behaviors.5-7 It is defined as one's ability to alter his/her own responses by overriding one response in favor of a less common but more desired response.4,8 Self-regulation is also related to executive functioning, including the ability to make choices. Research in human populations indicates that performing an initial self-regulatory task may cause fatigue that results in poorer subsequent performance on executive tasks.9,10 Thus, self-regulatory fatigue and executive capacity covary inversely in a way that can lead to a potential downward spiral where repeated responses to demands leads to self-regulatory fatigue, which in turn reduces executive cognitive resources.4 This pattern increases the difficulty for an individual to meet further demands such as those associated with persistent intractable pain in structures mediated by the trigeminal nerve. Although self-regulation has been implicated as important in the management of persistent pain conditions, research outcomes show that persistent pain itself can interfere with the ability to self-regulate.11 In the one human study on pain and self-regulation found in the literature, patients with persistent pain conditions, ie, fibromyalgia and temporomandibular disorders, had less capacity to persist on a persistence task following an initial self-regulation task than persons without persistent pain.11 These findings suggest that the presence of persistent pain leaves one vulnerable to self-regulatory fatigue because of the significant demands required for coping with persistent pain. In the past, many researchers have argued that self-regulation occurs only in humans; however, a recent animal study has shown that it is possible to examine these effects in other species.12 In that study, dogs in a self-regulatory condition (ie, dogs commanded to sit and stay for a short period of time) performed worse on a persistence task (ie, attempting to retrieve food from a toy) than dogs that had not been required to self-regulate prior to exposure to the persistence task. These findings suggest that self-regulatory capacity may be a finite resource across species and is involved in guiding and directing a broad spectrum of behaviors. Although past research on self-regulation has been primarily conducted with human participants,13-15 it would be beneficial to study the effects of persistent pain on self-regulation in a rodent model. A rodent model of persistent pain allows for greater experimental control and fewer threats to internal validity. For example, in human populations with persistent pain, both physical and psychological comorbid conditions are common.16,17 Studying persistent pain conditions with animals in a controlled setting allows investigators to limit the variables affecting the relationship between persistent pain and self-regulation. Additionally, animal models allow for investigation of physiological pathways responsible for self-regulatory deficits as well as possible pharmacological treatments. The aims of the current study were to determine (1) whether self-regulation can be studied successfully in a rodent model and (2) whether persistent facial pain influences self-regulatory behavior. It was hypothesized that animals experiencing persistent neuropathic pain would perform more poorly on a persistence task that immediately followed an initial self-regulatory depletion task than naive animals that were not experiencing pain. Specifically, it was expected that as a result of increased fatigue following the self-regulation task, animals that underwent surgery to induce a chronic constriction injury of the infraorbital nerve (CCI-ION) would press a lever during the persistence task for a shorter period of time as well as a fewer number of times than naive animals.

Background The authors aimed to determine whether electrical dental devices would interfere with the function of cardiac pacemakers or implantable cardioverter defibrillators (ICDs) in humans. Methods The authors exposed asymptomatic nonpacemaker-dependent patients to commonly used electrical dental equipment (for example, battery-operated curing lights, ultrasonic baths, ultrasonic scalers, electric pulp testers, and electric toothbrushes) in an outpatient cardiology clinic. The authors operated dental devices at various distances and programmed cardiac devices to sense and pace. The authors obtained cardiac tracings using a cardiac programming unit and a cardiac provider who noted any interference interpreted the results in real time. Results The authors enrolled 32 consecutive patients and tested 12 pacemakers and 20 ICDs. They did not observe any significant clinical interference in sensing and pacing functions in any patient; however, they noted minor interference without clinical impact in the telemetry from the cardiac programming unit during use of the ultrasonic scaler and bath. Conclusions The findings of this prospective study suggest that electrical devices commonly used in dental practices do not interfere with the sensing and pacing of contemporary cardiac patients’ pacemakers or ICDs. However, they do interfere with the telemetry from the cardiac programming unit, without any clinical impact on patient safety. These findings should help in the development of clinical guidelines regarding dental management of patients with pacemakers or ICDs. Practical Implications Electrical dental devices (for example, ultrasonic baths, ultrasonic scalers) induced minor interference with programmers that interrogate cardiac devices implanted in patients; however, overall, dental devices do not appear to interfere with pacemakers’ and defibrillators’ pacing and sensing function.

Objective To examine the effects of direct oral anticoagulants (DOACs) on bleeding complications following dental surgeries. Subjects and methods This 6-year retrospective study collected data from records of patients undergoing oral surgical procedures within a university setting. An electronic health record database was searched using current procedural terminology codes for oral surgical procedures. Information regarding patient, procedural factors, and postoperative complications were extracted. Data were analyzed by Fisher's exact test. Results Of patients who had a procedural code associated with oral surgery, only 0.11% (12/11,320) took a DOAC. Twelve patients (10 males, age ranging from 44 to 90 years) underwent 17 surgeries by nine different practitioners involving 98 extractions, 14 alveoloplasties, two tuberosity reductions, and two tori removals. In nine cases, the DOAC was discontinued a mean of 52.5 hrs prior to surgery (range 12-120 hrs). Bleeding complications were not reported for patients whose drug was discontinued or continued. Documentation of drug continuation/discontinuation was poor. Conclusions Bleeding was not observed with direct oral anticoagulation use in this oral surgery cohort. Drug discontinuation/continuation was not a factor in bleeding outcomes, and direct oral anticoagulation interruption was variable and poorly documented.

Background The authors conducted medical laboratory screenings in a dental setting to determine the relationships between the laboratory test results and self-reported medical health findings.

Salivary biomarkers are potentially important for determining the presence, risk, and progression of periodontal disease. However, clinical translation of biomarker technology from lab to chairside requires studies that identify biomarkers associated with the transitional phase between health and periodontal disease (i.e., gingivitis).Eighty participants (40 with gingivitis, 40 healthy) provided saliva at baseline and 7 to 30 days later. An additional sample was collected from gingivitis participants 10 to 30 days after dental prophylaxis. Clinical parameters of gingival disease were recorded at baseline and the final visit. Salivary concentrations of interleukin (IL)-1β, IL-6, matrix metalloproteinase (MMP)-8, macrophage inflammatory protein (MIP)-1α, and prostaglandin E2 (PGE2) were measured.Clinical features of health and gingivitis were stable at both baseline visits. Participants with gingivitis demonstrated significantly higher bleeding on probing (BOP), plaque index (PI), and gingival index (GI) (P ≤0.002) and a significant drop in BOP, PI, and GI post-treatment (P ≤0.001). Concentrations of MIP-1α and PGE2 were significantly higher (2.8 times) in the gingivitis group than the healthy group (P ≤0.02). After dental prophylaxis, mean biomarker concentrations did not decrease significantly from baseline in the gingivitis group, although concentrations of IL-1β, IL-6, and MMP-8 approached healthy levels, whereas MIP-1α and PGE2 concentrations remained significantly higher than in the healthy group (P ≤0.04). Odds ratio analyses showed that PGE2 concentrations, alone and in combination with MIP-1α, readily discriminated gingivitis from health.Salivary PGE2 and MIP-1α discriminate gingivitis from health, and patients with gingivitis who return to clinical health continue to produce inflammatory mediators for weeks after dental prophylaxis.

The comparative utility of serum and saliva as diagnostic fluids for identifying biomarkers of acute myocardial infarction (AMI) was investigated. The goal was to determine if salivary biomarkers could facilitate a screening diagnosis of AMI, especially in cases of non-ST elevation MI (NSTEMI), since these cases are not readily identified by electrocardiogram (ECG). Serum and unstimulated whole saliva (UWS) collected from 92 AMI patients within 48 hours of chest pain onset and 105 asymptomatic healthy control individuals were assayed for 13 proteins relevant to cardiovascular disease, by Beadlyte technology (Luminex®) and enzyme immunoassays. Data were analyzed with concentration cut-points, ECG findings, logistic regression (LR) (adjusted for matching for age, gender, race, smoking, number of teeth, and oral health status), and classification and regression tree (CART) analysis. A sensitivity analysis was conducted by repetition of the CART analysis in 58 cases and 58 controls, each matched by age and gender. Serum biomarkers demonstrated AMI sensitivity and specificity superior to that of saliva, as determined by LR and CART. The predominant discriminators in serum by LR were troponin I (TnI), B-type natriuretic peptide (BNP), and creatine kinase-MB (CK-MB), and TnI and BNP by CART. In saliva, LR identified C-reactive protein (CRP) as the biomarker most predictive of AMI. A combination of smoking tobacco, UWS CRP, CK-MB, sCD40 ligand, gender, and number of teeth identified AMI in the CART decision trees. When ECG findings, salivary biomarkers, and confounders were included, AMI was predicted with 80.0% sensitivity and 100% specificity. These analyses support the potential utility of salivary biomarker measurements used with ECG for the identification of AMI. Thus, saliva-based tests may provide additional diagnostic screening information in the clinical course for patients suspected of having an AMI.

Background The purpose of this systematic review was to determine the potential effect of dental treatment before cardiac valve surgery (CVS) or left ventricular assist device (LVAD) implantation on morbidity and mortality. Types of Studies Reviewed The authors included relevant studies from MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, including randomized controlled trials and cohort studies, published from 1998 through 2019 and involving adults who received dental treatment before CVS or LVAD implantation. The authors assessed bias by using the Newcastle-Ottawa Quality Assessment Scale and evidence certainty by using the Grading of Recommendations Assessment, Development and Evaluation approach. The authors used a meta-analysis with a random-effects model to estimate dichotomous and continuous outcomes, expressed as relative risk (RR) and weighted mean difference. Results Six studies met the inclusion criteria for CVS but none for LVAD implantation. Very low certainty in the evidence suggested uncertainty as to whether health outcomes for patients undergoing dental treatment before CVS differed from those who did not. Postsurgical outcomes included all-cause mortality (RR, 1.00; 95% confidence interval [CI], 0.53 to 1.91), infective endocarditis (RR, 1.30; 95% CI, 0.51 to 3.35), postsurgical infection (RR, 1.01; 95% CI, 0.76 to 1.33), and length of stay in the hospital (weighted mean difference, 2.9; 95% CI, −2.3 to 8.1). Conclusions and Practical Implications From the available evidence, it is unclear whether postoperative outcomes differ in patients receiving dental treatment before CVS compared with outcomes in those who do not. Dentists and medical care professionals should collaborate on an appropriate course of action for each patient, weighing any potentially relevant care considerations.

Background— The prognosis and treatment of patients with low-flow (LF) severe aortic stenosis are controversial. Methods and Results— The Placement of Aortic Transcatheter Valves (PARTNER) trial randomized patients with severe aortic stenosis to medical management versus transcatheter aortic valve replacement (TAVR; inoperable cohort) and surgical aortic valve replacement versus TAVR (high-risk cohort). Among 971 patients with evaluable echocardiograms (92%), LF (stroke volume index ≤35 mL/m 2 ) was observed in 530 (55%); LF and low ejection fraction (P =0.006). In the inoperable cohort, patients with LF had higher mortality than those with normal flow, but both groups improved with TAVR (46% versus 76% with LF and 38% versus 53% with normal flow; P P =0.02). LF was an independent predictor of mortality in all patient cohorts (hazard ratio, ≈1.5), whereas ejection fraction and gradient were not. Conclusions— LF is common in severe aortic stenosis and independently predicts mortality. Survival is improved with TAVR compared with medical management and similar with TAVR and surgical aortic valve replacement. A measure of flow (stroke volume index) should be included in the evaluation and therapeutic decision making of patients with severe aortic stenosis. Clinical Trial Registration— URL: http://www.clinicaltrial.gov . Unique identifier: NCT0053089.4.

Objectives Factors influencing xerostomia during intensity-modulated radiation therapy (IMRT) were assessed. Methods A 6-week study of 32 head and neck cancer (HNC) patients was performed. Subjects completed the Xerostomia Inventory (XI) and provided stimulated saliva (SS) at baseline, week 2 and at end of IMRT. Influence of SS flow rate (SSFR), calcium and mucin 5b (MUC5b) concentrations and radiation dose on xerostomia was determined. Results HNC subjects experienced mean SSFR decline of 36% by visit 2 ( N = 27; P = .012) and 57% by visit 3 ( N = 20; P = .0004). Concentrations of calcium and MUC5b increased, but not significantly during IMRT ( P > .05). Xerostomia correlated most with decreasing salivary flow rate as determined by Spearman correlations ( P P Conclusions Although IMRT is sparing to the parotid glands, it has an early effect on SSFR and the constituents in saliva in a manner that is associated with the perception of xerostomia.

Background The authors performed a systematic search of the literature to identify the frequency of, risk of experiencing and factors associated with adrenal crises in dental patients. Methods The authors searched PubMed and Ovid MEDLINE (1947-June 20, 2012) and Embase (1974-2012) for English-language articles related to cases of adrenal crisis in dentistry and extracted and analyzed data from the articles. The six authors determined whether the cases identified met a consensus definition of adrenal crisis. Results Of 148 articles identified in the initial screening, 34 articles were included in the final review, from which six cases met the criteria of adrenal crisis. The authors categorized four cases as “suggestive of adrenal crisis” and two cases as “consistent with adrenal crisis.” Risk factors were significant adrenal insufficiency, pain, infection, having undergone an invasive procedure, having received a barbiturate general anesthetic, and poor health status and stability at the time of presentation. The authors estimated risk to be less than one in 650,000 in patients with adrenal insufficiency. Conclusions Adrenal crisis is rare in dental patients, with only six reports of it having been published in the past 66 years. Risk is associated with unrecognized adrenal insufficiency, poor health status and stability at the time of treatment, pain, infection, having undergone an invasive procedure and having received a barbiturate general anesthetic. Clinical Implications Risk of adrenal crisis is reduced through proper evaluation of the patient, identification of risk factors and following appropriate preventive measures.

Saliva is an oral fluid, composed mainly of water, produced and secreted in large part from the acinar and ductal cells of the major and minor salivary glands. Whole saliva derives additional constituents from serum, gingival crevicular fluid and oral mucosal transudate, making it appealing as a potential diagnostic fluid reflective of circulating levels in blood.1 Several studies report systemic biomarkers appearing in saliva including electrolytes,2, 3 blood products,4 enzymes and tissue destruction molecules,5–9 inflammatory markers,10–16 as well as proteins putatively associated with deadly diseases.17–21 However, the clinical utility of salivary diagnostics for the assessment of systemic disease remains elusive.20, 22–27 Cardiovascular disease (CVD) is a major cause of mortality in the U.S. and worldwide. More than 17 million people died from CVD in 2008, with the majority due to atherosclerotic events including myocardial infarction.28, 29 With the extend and importance of this disease, easy, noninvasive and low cost screening methods for the detection of myocardial infarction continue to be sought. One such potential screening fluid is saliva.30 Support for the use of saliva for the detection of CVD and myocardial infarction is built upon the framework that many serum biomarkers associated with inflammation, atherosclerosis, plaque stability and myocardial damage are known and appear in oral fluids.4, 9, 31–35 However, only a limited number of studies have demonstrated correlations between serum and salivary biomarkers of CVD.14, 33, 36 Thus, additional research is required if we are to gain a greater understanding of the clinical utility of saliva compared to serum with respect to CVD and myocardial infarction assessment. This is particularly important for finding new diagnostics for situations where acquisition, processing or analysis of blood is problematic. In this research investigation, we hypothesized that select salivary biomarkers would correlate with serum biomarkers of CVD in patients with pre-existing heart disease and could yield important diagnostic information regarding the evolution and progression of myocardial necrosis. To test this hypothesis we employed a unique model of myocardial infarction in patients with a pre-existing CVD (i.e., hypertrophic cardiomyopathy [HCM]) who were scheduled to undergo alcohol septal ablation (ASA). This procedure results in a controlled myocardial infarction and subsequent remodeling processes that permit improved hemodynamics and improved patient outcomes.37, 38 Together, the pre-existing CVD and subsequent kinetic course of myocardial necrosis allowed us to predict that a spectrum of myocardial damage, inflammation and tissue remodeling biomarkers would appear in serum and saliva at baseline, and significant spikes would occur in these biomarker levels during the post-operative phase consistent with myocardial infarction.39–43 Here this unique study design permitted us to report the novel findings that salivary levels of troponin (Tn)I and C-reactive protein (CRP) reflected changes in serum consistent with myocardial damage, and select salivary biomarkers correlate with serum biomarkers of CVD.

The aim of this study was to identify factors associated with death in relation to dental care.A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Dental and Oral Sciences Source, Web of Science, and the Cochrane database were searched, and the references of all retrieved articles were analyzed. Studies were included if death had occurred within 90 days of the dental appointment, and if the patient's age, procedure, and information regarding cause or time of death were provided. Factors associated with death were assessed by multivariate analyses and logistic regression.Fifty-six publications, including retrospective studies and case reports/series that reported 148 fatalities, were analyzed. On average, 2.6 deaths were reported per year. The leading cause of deaths was anesthesia/sedation/medication-related complications (n = 70). Other causes were cardiovascular events (n = 31), infection (n = 19), airway-respiratory complications (n = 18), bleeding (n = 5), and others (n = 5). Age (P .0001), disease severity (P .02), disease stability (P .006), dental provider characteristics (P .05), level of consciousness/sedation (P .02), and drug effects (P .03) had significant associations with death.Reports of death were rare; however, specific risk factors associated with dentistry were identified. A better understanding of these factors is important for the development of guidelines that help prevent fatalities in dentistry.

Oral medicine (stomatology) is a recognized and increasingly important dental specialty in many parts of the world that recognizes and fosters the interplay between medical health and oral health. Its dental activities rely greatly on the underlying biology of disease and evidence-based outcomes. However, full recognition of the importance of oral medicine to patient care, research, and education is not yet totally universally acknowledged. To address these shortcomings, we outline the birth, growth, and future of oral medicine globally, and record identifiable past contributions to the development of the specialty, providing an accurate, unique, and valuable resource on oral medicine. Although it was challenging to gather the data, we present this information as a review that endeavors to summarize the salient points about oral medicine, based on MEDLINE, other internet searches, communication with oral medicine and stomatological societies across the world, the web page http://en.wikipedia.org/wiki/List_of_dental_organizations, and discussions with a wide range of key senior persons in the specialty.

Sexton WM, Lin Y, Kryscio RJ, Dawson III DR, Ebersole JL, Miller CS. Salivary biomarkers of periodontal disease in response to treatment. J Clin Periodontol 2011; 38: 434–441. doi: 10.1111/j.1600-051X.2011.01706.x Abstract Background: Salivary biomarkers of periodontitis were assessed longitudinally to determine response to therapy. Methods: A 6-month case-controlled study of adults with chronic periodontitis was performed, with 33 participants receiving oral hygiene instructions (OHI) alone and 35 with scaling and root planing (SRP) combined with OHI. Saliva samples collected at week 0, 16 and 28 were analysed for interleukin (IL)-1β, IL-8, macrophage inflammatory protein (MIP)-1α, matrix metalloproteinase-8 (MMP-8), osteoprotegerin (OPG), and tumour necrosis factor-α (TNF)-α. Clinical measures of periodontal disease were recorded at each visit. Results: All parameters of periodontal health improved significantly in both groups by week 16 (p

Oral Diseases (2011) 17 (Suppl. 1), 58–72 Objectives: Human papillomavirus (HPV) in oral carcinoma (OSCC) and potentially malignant disorders (OPMD) is controversial. The primary aim was to calculate pooled risk estimates for the association of HPV with OSCC and OPMD when compared with healthy oral mucosa as controls. We also examined the effects of sampling techniques on HPV detection rates. Methods: Systematic review was performed using PubMed (January 1966–September 2010) and EMBASE (January 1990–September 2010). Eligible studies included randomized controlled, cohort and cross-sectional studies. Pooled data were analysed by calculating odds ratios, using a random effects model. Risk of bias was based on characteristics of study group, appropriateness of the control group and prospective design. Results: Of the 1121 publications identified, 39 cross-sectional studies met the inclusion criteria. Collectively, 1885 cases and 2248 controls of OSCC and 956 cases and 675 controls of OPMD were available for analysis. Significant association was found between pooled HPV-DNA detection and OSCC (OR = 3.98; 95% CI: 2.62–6.02) and even for HPV16 only (OR = 3.86; 95% CI: 2.16–6.86). HPV was also associated with OPMD (OR = 3.87; 95% CI: 2.87–5.21). In a subgroup analysis of OPMD, HPV was also associated with oral leukoplakia (OR = 4.03; 95% CI: 2.34–6.92), oral lichen planus (OR = 5.12; 95% CI: 2.40–10.93), and epithelial dysplasia (OR = 5.10; 95% CI: 2.03–12.80). Conclusions: The results suggest a potentially important causal association between HPV and OSCC and OPMD.

Background The authors conducted a study to determine if electromagnetic interference of cardiac pacemaker and implantable cardioverter-defibrillator (ICD) activity occurs during the operation of electronic dental devices. Methods The authors tested nine electronic dental devices in vitro to assess their ability to interfere with the function of two pacemakers and two ICDs as determined by electrocardiographic telemetry. Results The pacing activity of both pacemakers and the dual-chamber ICD were inhibited during operation of the battery-operated composite curing light at between 2 and 10 centimeters from the generator or leads. The use of the ultrasonic scaler interfered with the pacing activity of the dual-chamber pacemaker at between 17 and 23 cm from the generator or leads, the single-chamber pacemaker at 15 cm from the generator or leads and both ICDs at 7 cm from the leads. The operation of the ultrasonic cleaning system interfered with the activity of the dual-chamber pacemaker at between 15 and 23 cm from the generator or leads, and of the single-chamber pacemaker at 12 cm. Operation of the electric toothbrush, electrosurgical unit, electric pulp tester, high- and low-speed handpieces, and an amalgamator did not alter pacing function. Conclusion Select electronic dental devices interfere with pacemakers' and ICDs' sensing and pacing activity in vitro. Clinical Implications Use of the ultrasonic scaler, ultrasonic cleaning system and battery-operated composite curing light may produce deleterious effects in patients who have pacemakers or ICDs.

Background Tetracyclines are broad-spectrum antibiotics used by dental practitioners in the treatment of periodontal disease. They generally are safe in adults. However, caution is advised in patients who have pre-existing kidney disease. Case Description A 42-year-old woman with polycystic kidney disease received a prescription for tetracycline (250 milligrams, four times daily) after undergoing tooth extractions. She developed nausea, vomiting and diarrhea within days and end-stage renal disease within two weeks of taking the antibiotic. Hemodialysis was required to stabilize the patient's condition. Use of the Naranjo nomogram demonstrated an association between the two events. Clinical Implications This case illustrates the importance of obtaining a thorough medical history and understanding potential adverse drug effects before prescribing a common antibiotic.

Generally, clinical parameters are used in dental practice for periodontal disease, yet several drawbacks exist with the clinical standards for addressing the needs of the public at large in determining the current status/progression of the disease, and requiring a significant amount of damage before these parameters can document disease. Therefore, a quick, easy and reliable method of assessing and monitoring periodontal disease should provide important diagnostic information that improves and speeds treatment decisions and moves the field closer to individualized point-of-care diagnostics. Objective: This report provides results for a saliva-based diagnostic approach for periodontal health and disease based upon the abundance of salivary analytes coincident with disease, and the significant progress already made in the identification of discriminatory salivary biomarkers of periodontitis. Methods: We evaluated biomarkers representing various phases of periodontitis initiation and progression (IL-1ß, IL-6, MMP-8, MIP-1α) in whole saliva from 209 subjects categorized with periodontal health, gingivitis, and periodontitis. Results: Evaluation of the salivary analytes demonstrated utility for individual biomarkers to differentiate periodontitis from health. Inclusion of gingivitis patients into the analyses provided a more robust basis to estimate the value of each of these analytes. Various clinical and statistical approaches showed that pairs or panels of the analytes were able to increase the sensitivity and specificity for the identification of disease. Conclusions: Salivary concentrations of IL-1ß, IL-6, MMP-8, MIP-1α alone and in combination are able to distinguish health from gingivitis and periodontitis. The data clearly demonstrated a heterogeneity in response profiles of these analytes that supports the need for refinement of the standard clinical classifications if we are to move toward precision/personalized dentistry for the twenty-first century.

The pathophysiology of burning mouth disorder (BMD) is not clearly understood, but central neuropathic mechanisms are thought to be involved. The aim of this study was to gain insight into the pathophysiology associated with BMD by using functional magnetic resonance imaging (fMRI). Areas of brain activation following thermal stimulation of the trigeminal nerve of eight female patients with BMD (mean age 49.1+/-10.1) were mapped using fMRI and compared with those of eight matched pain-free volunteers (mean age 50.3+/-12.3). Qualitative and quantitative differences in brain activation patterns between the two study groups were demonstrated. BMD patients displayed greater fractional signal changes in the right anterior cingulate cortex (BA 32/24) and bilateral precuneus than did controls (p0.005). The control group showed larger fractional signal changes in the bilateral thalamus, right middle frontal gyrus, right pre-central gyrus, left lingual gyrus, and cerebellum than did the BMD patients (p0.005). In addition, BMD patients had less volumetric activation throughout the entire brain compared to the control group. Overall, BMD patients displayed brain activation patterns similar to those of patients with other neuropathic pain conditions and appear to process thermal painful stimulation to the trigeminal nerve qualitatively and quantitatively different than pain-free individuals. These findings suggest that brain hypoactivity may be an important feature in the pathophysiology of BMD.

Background The authors conducted a study to determine if salivary biomarkers specific for three aspects of periodontitis—inflammation, collagen degradation and bone turnover—correlate with clinical features of periodontal disease. Methods The relationship between periodontal disease and the levels of interleukin-1 beta (IL-1β), matrix metalloproteinase (MMP)-8, and osteoprotegerin (OPG) in whole saliva of 57 adults (28 “case” subjects with moderate-to-severe periodontal disease and 29 healthy control subjects) was examined in a case-control trial. Results Mean levels of IL-1β and MMP-8 in saliva were significantly higher in case subjects than in controls. Both analytes correlated with periodontal indexes, whereas, after adjustment for confounders, OPG did not. Elevated salivary levels of MMP-8 or IL-1β (more than two standard deviations above the mean of the controls) significantly increased the risk of periodontal disease (odds ratios in the 11.3–15.4 range ). Combined elevated salivary levels of MMP-8 and IL-1β increased the risk of experiencing periodontal disease 45-fold, and elevations in all three biomarkers correlated with individual clinical parameters indicative of periodontal disease. Conclusion Salivary levels of MMP-8 and IL-1β appear to serve as biomarkers of periodontitis. Clinical Implications Qualitative changes in the composition of salivary biomarkers could have significance in the diagnosis and treatment of periodontal disease.