Realizing the clinical utility of saliva for monitoring oral diseases.

In the era of personalized/precision health care, additional effort is being expended to understand the biology and molecular mechanisms of disease processes. How these mechanisms are affected by individual genetics, environmental exposures, and behavioral choices will encompass an expanding role in the future of optimally preventing and treating diseases. Considering saliva as an important biological fluid for analysis to inform oral disease detection/description continues to expand. This review provides an overview of saliva as a diagnostic fluid and the features of various biomarkers that have been reported. We emphasize the use of salivary biomarkers in periodontitis and transport the reader through extant literature, gaps in knowledge, and a structured approach toward validating and determine the utility of biomarkers in periodontitis. A summation of the findings support the likelihood that a panel of biomarkers including both host molecules and specific microorganisms will be required to most effectively identify risk for early transition to disease, ongoing disease activity, progression, and likelihood of response to standard periodontal therapy. The goals would be to develop predictive algorithms that serve as adjunctive diagnostic tools which provide the clinician and patient important information for making informed clinical decisions.

Prevalence of Decay and Tooth Condition Changes Adjacent to Restored Dental Implants: A Retrospective Radiographic Study.

This study examined the association between a dental implant and changes in adjacent teeth over time. Electronic health records of 1818 patients who received a dental implant were retrospectively evaluated over 14 years (2005-2019) in a university setting. The status of the adjacent tooth and vertical and horizontal distance from the implant platform to adjacent teeth were determined using digital intraoral radiographs taken at baseline and the last follow-up visit (1-14 years, median four years). In total, 1085 dental implants were evaluated. There were 234 instances of a change in the adjacent tooth. Decay was observed in 83 (7.6%) of adjacent teeth; the mean time to development was four years (range 1 to 14 years). Approximately 9% of adjacent teeth received direct restorations, 4.8% received indirect restorations, 1% received endodontic root canal treatment (RCT), and 5.6% were extracted. The mean horizontal distance between the implant platform and the adjacent teeth was 3.56 mm; the mean vertical distance from the contact point to the alveolar crest on the tooth side was 6.2 mm at the 1st time of the reported decay on x-ray. These distances did not significantly influence the occurrence of caries. The prevalence of interproximal contact loss (ICL) was higher on the mesial of the implant crown at 63% compared to 20% on the distal side. This large retrospective analysis identified that teeth adjacent to a dental implant were at risk of decay and changes in their condition. In addition, the implant-to-tooth distance and inadequate emergence profile may contribute as caries risk factors in addition to hygiene and a high sugar level diet. These findings appear essential for clinicians when making treatment decisions and discussing outcomes with patients.

Alternatives to dental opioid prescribing after tooth extraction (ADOPT): protocol for a stepped wedge cluster randomized trial.

BACKGROUND: Dentists and oral surgeons are leading prescribers of opioids to adolescents and young adults (AYA), who are at high risk for developing problematic opioid use after an initial exposure. Most opioids are prescribed after tooth extraction, but non-opioid analgesics provide similar analgesia and are recommended by multiple professional organizations. METHODS: This multi-site stepped wedge cluster-randomized trial will assess whether a multicomponent behavioral intervention can influence opioid prescribing behavior among dentists and oral surgeons compared to usual practice. Across up to 12 clinical practices (clusters), up to 33 dentists/oral surgeons (provider participants) who perform tooth extractions for individuals 12-25 years old will be enrolled. After enrollment, all provider participants will receive the intervention at a time based on the sequence to which their cluster is randomized. The intervention consists of prescriber education via academic detailing plus provision of standardized patient post-extraction instructions and blister packs of acetaminophen and ibuprofen. Provider participants will dispense the blister packs and distribute the patient instructions at their discretion to AYA undergoing tooth extraction, with or without additional analgesics. The primary outcome is a binary, patient-level indicator of electronic post-extraction opioid prescription. Data for the primary outcome will be collected from the provider participant's electronic health records quarterly throughout the study. Provider participants will complete a survey before and approximately 3 months after transitioning into the intervention condition to assess implementation outcomes. AYA patients undergoing tooth extraction will be offered a survey to assess pain control and satisfaction with pain management in the week after their extraction. Primary analyses will use generalized estimating equations to compare the binary patient-level indicator of being prescribed a post-extraction opioid in the intervention condition compared to usual practice. Secondary analyses will assess provider participants' perceptions of feasibility and appropriateness of the intervention, and patient-reported pain control and satisfaction with pain management. Analyses will adjust for patient-level factors (e.g., sex, number of teeth extracted, etc.). DISCUSSION: This real-world study will address an important need, providing information on the effectiveness of a multicomponent intervention at modifying dental prescribing behavior and reducing opioid prescriptions to AYA. CLINICALTRIALS: GOV: NCT06275191.

Whole unstimulated salivary flow rate decreases during acute stressful condition.

OBJECTIVE: To examine the influence of acute stress on salivary flow using a validated stressor paradigm. STUDY DESIGN: This uniform crossover study consisted of 40 healthy adults who underwent the Trier Social Stress Test, consisting of a 5-minute mental arithmetic task (MAT), and a nonstressful task (NST), consisting of a 5-minute free speech task. The order of the tasks was counterbalanced and unstimulated whole saliva (UWS) was measured in 2 groups of 20 participants during each 5-minute task condition, with a 10-minute washout period between tasks. At baseline, mathematical ability was self-reported and psychological distress was measured using the Symptom Checklist-90-Revised. Heart rate (HR) and breathing rate (BR) were recorded during each task. RESULTS: Age, sex, HR, BR, and psychological distress were similar between groups at baseline (P > .05). During the MAT, HR increased significantly and mean UWS flow rate decreased significantly compared with the NST (P < .001). CONCLUSIONS: An acute psychobiological stressor task was associated with a rapid decrease in salivary flow in adults. Thus, stress can contribute to reduced salivary flow and should be considered as a factor during the diagnostic workup of patients who complain of a dry mouth.

A review of animal models for burning mouth syndrome: Mechanistic insights and knowledge gaps.

OBJECTIVES: The underlying mechanisms of burning mouth syndrome (BMS) remain unclear leading to challenges and unsatisfactory management. Current treatments focus primarily on symptom relief, with few consistently achieving a 50% reduction in pain. This review aims to explore animal models of BMS to gain a better understanding of the underlying mechanisms and to discuss potential and existing knowledge gaps. METHODS: A comprehensive review of PubMed® , Google Scholar, and Scopus was performed to assess advances and significant gaps of existing rodent models that mimic BMS-related symptoms. RESULTS: Rodent models of BMS involve reproduction of dry-tongue, chorda tympani transection, or overexpression of artemin protein. Existing preclinical models tend to highlight one specific etiopathogenesis and often overlook sex- and hormone-specific factors. CONCLUSION: Combining aspects from various BMS models could prove beneficial in developing comprehensive experimental designs and outcomes encompassing the multifaceted nature of BMS.

Imaging Evaluation of the Temporomandibular Joint.

This article describes the anatomy and function of the temporomandibular joint (TMJ), provides an overview of the various imaging modalities available for evaluating the TMJ, and discusses a variety of miscellaneous diseases that affect the TMJ.

Xerostomia, reduced salivary flow, and oral burning: Associations from a cross-sectional study.

OBJECTIVE: Determine the association between xerostomia, salivary flow, and oral burning. STUDY DESIGN: A cross-sectional retrospective study involving consecutive patients with an oral burning complaint during a 6-year period. Treatments including a dry mouth management protocol (DMP) along with other therapies were implemented. Study variables included xerostomia, unstimulated whole salivary flow rate (UWSFR), pain intensity, and medication use. Statistical analyses included Pearson correlations, linear regression, and Analysis of Variance. RESULTS: Among the 124 patients meeting the inclusion criteria, 99 were female, with a mean age of 63.1 (range 26-86) years. The baseline UWSFR was low (0.24 ± 0.29 mL/min) and 46% experienced hyposalivation (<0.1 mL/min). Xerostomia was reported by 77.7%, and 82.8% had coexistence of xerostomia and hyposalivation. DMP resulted in significant pain reduction between visits (P < .001). CONCLUSIONS: Hyposalivation and xerostomia were highly prevalent in patients with oral burning. A DMP proved beneficial to these patients.

Biomarker panel discriminates diabetics with and without periodontitis pre- and post-therapy.

BACKGROUND AND OBJECTIVE: Biological regulators of periodontal inflammation, collagen degradation, and insulin resistance have not been determined in association with severity of periodontitis and response to periodontal treatment in diabetics. Our objective was to determine whether type 2 diabetes (T2DM) patients with periodontal disease present a distinct salivary biomarker profile compared with T2DM patients without periodontal disease and healthy subjects (without diabetes and periodontitis) pre- and post-nonsurgical therapy. METHODS: Clinical parameters of periodontal health and whole unstimulated saliva were collected from 92 participants (31 Not Periodontitis, NP; 32 T2DM without periodontitis, DWoP; and 29 with T2DM with periodontitis, DWP) at baseline. The T2DM groups received scaling and root planning (SRP) and provided saliva at 6-week follow-up. Salivary concentrations of interleukin (IL)-1ß, IL-6, matrix metalloproteinase-8 (MMP-8), and resistin were measured by immunoassay. RESULTS: The DWP group had significantly more disease and higher salivary concentrations at baseline for IL-1ß, MMP-8, and resistin (p's < .01) compared with DWoP and NP. SRP resulted in significant improvement in periodontal parameters for the T2DM groups; however, more disease persisted (p < .001), and IL-1ß, MMP-8, and resistin concentrations remained significantly higher in the DWP than the DWoP group (p < .01) at 6 weeks post-treatment. Principal component analysis demonstrated the DWoP group appeared more biologically similar to the NP group than the DWP group. Concentrations of these salivary biomarkers increased with increasing periodontal disease severity (p < .05) in this study population. CONCLUSION: Salivary concentrations of IL-1ß, MMP-8, and resistin appear to serve as biomarkers of periodontal status pre- and post-treatment, irrespective of diabetes status.

Dental opioid prescription patterns in academic and community settings.

OBJECTIVES: Reports of interventions to improve dental opioid prescribing have come primarily from academic settings, but most opioid prescriptions are written by community dentists. This analysis compares prescription characteristics between these two groups to inform interventions to improve dental opioid prescribing in community settings. METHODS: State prescription drug monitoring program data from 2013 to 2020 were used to compare opioid prescriptions from dentists at academic institutions (PDAI) to prescriptions from dentists in non-academic settings (PDNS). Linear regression was used to assess daily morphine milligram equivalents (MME), total MME, and days' supply, adjusting for year, age, sex, and rurality. RESULTS: Prescriptions from dentists at the academic institution accounted for less than 2% of over 2.3 million dental opioid prescriptions analyzed. Over 80% of prescriptions in both groups were written for <50 MME per day and for ≤3 days' supply. On average, in the adjusted models, prescriptions from the academic institution were written for about 75 additional MME per prescription and nearly a full day longer duration. Compared to adults, adolescents were the only age group who received both higher daily doses and longer days' supply. CONCLUSIONS: Prescriptions from dentists at academic institutions accounted for small percentage of opioid prescriptions, but prescription characteristics were clinically comparable between groups. Interventional targets to reduce opioid prescribing in academic institutions could be applied to community settings.

WWOM VII: Effectiveness of topical interventions in the management of burning mouth syndrome: A systematic review.

OBJECTIVES: To assess the effectiveness of topical interventions in the management of burning mouth syndrome (BMS), 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 on topical interventions for the management of BMS, published in PubMed, Web of Science, PsycInfo, Cochrane Database/Central, and Google Scholar through May 2021 was performed. RESULTS: Eight RCTs (n = 358 study participants) were included in this study. Due to underreporting of IMMPACT domains, publication bias, high degree of heterogeneity between studies, meta-analysis was not undertaken. Based on changes in visual analogue pain scores (ΔVAS), the most reported outcome, the effectiveness of the topical interventions was demonstrated; however, it is low level of evidence. CONCLUSIONS: High levels of variability (interventions, outcomes, outcome measurement tools, and intervention effects evaluated), heterogeneity, publication bias, and underreporting of IMMPACT domains were observed across the RCTs. This systematic review highlights the need for application of standardized outcome measures to future RCTs. At the present time, there is lack of moderate-strong evidence on short- and long-term outcomes to support or refute the use of any particular topical intervention in managing BMS. Future RCTs with standardized outcome measures are needed.

Low-dose naltrexone for treatment of burning mouth syndrome.

OBJECTIVE: The International Classification of Disease defines burning mouth syndrome (BMS) as a chronic intraoral burning sensation, with no identifiable local or systemic cause. Since current management is often unsatisfactory, the aim of this report is to describe a new treatment modality (i.e., low-dose naltrexone [LDN]). STUDY DESIGN: A 62-year-old woman presented with the complaint of burning on the tongue of 3 years' duration. Existing comorbidities were fibromyalgia, irritable bowel syndrome, headache, and interstitial cystitis. Her reported pain intensity ranged from 2/10 (morning) to 8/10 (evening) on a numeric rating scale. With the diagnosis of BMS and hyposalivation, and in light of her current clonazepam use and fibromyalgia, a dry mouth protocol and LDN (3 mg) were prescribed. RESULTS: After 1 month, her pain intensity decreased by 50%, with no pain upon awakening. After 2 months, the widespread pain associated with her chronic morbidities also reduced by 50%, and her headache disappeared. After adjusting LDN dose to 4.5 mg, the patient was stable at 6 months, with 50% reduction of widespread pain and 2/10 BMS pain, and no reported side effects. CONCLUSIONS: These preliminary results suggest that LDN may be a feasible and effective treatment for BMS, especially in patients' refractory to traditional treatment.

Myeloperoxidase: A Circulating Marker of Inflammation and Tooth Infection.

BACKGROUND: Atherosclerotic cardiovascular disease and tooth infection are common in primary care, and both significantly reduce quality of life. Our study aimed to examine signs of vascular inflammation associated with loss of tooth vitality before and after a single tooth extraction. METHODS: An observational cohort study was performed with adults who had a nonvital tooth and an indicated desire for tooth extraction. Concentrations of total cholesterol, high-density lipoprotein-cholesterol, high-sensitivity C-reactive protein (hs-CRP), myeloperoxidase (MPO), and troponin T were measured in venous blood serum or plasma at baseline and 6-weeks after tooth extraction. RESULTS: Circulating hs-CRP levels were > 3 mg/dL in 15 participants (68.2%) and MPO levels were > 350 pmol/L in 9 (40.9%) of 22 participants at baseline. After tooth extraction (n = 18), MPO levels decreased significantly compared with baseline (P < .00006) and hs-CRP levels moved directionally downward. The response rate for MPO was 88.9% (confidence interval: 65.1%-98.6%) from visit 1 to visit 2. Those with high MPO levels at baseline demonstrated larger reductions in MPO levels by visit 2 than those with lower baseline MPO levels (r = .81; P < .0001). A total of 13 individuals (72.2%) achieved MPO levels < 350 pmol/L and 11 (61.1%) achieved hs-CRP levels < 3 mg/dL at visit 2. Total cholesterol, high-density lipoprotein-cholesterol, and troponin T levels did not significantly change from visit 1 to visit 2. CONCLUSION: A link between dental infection and circulating levels of inflammation was observed, suggesting that oral infection could be a risk factor for atherosclerotic cardiovascular disease.

WWOM VII: Effectiveness of systemic pharmacotherapeutic interventions in the management of BMS: A systematic review and meta-analysis.

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.

Effect of chewing gum containing Xylitol and blackberry powder on oral bacteria: A randomized controlled crossover trial.

OBJECTIVE: The aim was to determine the effect of chewing gum containing xylitol and freeze-dried blackberry powder on oral bacteria. DESIGN: This was a randomized, controlled, cross-over study (RCT #: NCT05133557). Fifty participants chewed gum over an 8 h period, four times for 20 min at 2-hour intervals, containing 700 mg xylitol (CG) with or without 50 mg blackberry powder (BG), while wearing a stent containing a sterile enamel chip. After a 1 week washout, participants chewed gum from the other group following the same protocol. The primary outcome was the amount of nine oral bacteria in saliva as determined by quantitative PCR. The secondary outcome was bacteria formed on enamel chips. RESULTS: Chewing BG for four twenty-minute intervals reduced mean total bacteria load and the relative abundance of six of the nine bacteria studied in saliva (p < 0.05). In comparison, only four bacteria were reduced in abundance in the CG group. After gum chewing and regardless of group, S. sanguinis and A. naeslundii were the predominant bacteria adherent to enamel, with S. mutans representing < 1 % of the total bacteria on enamel. CONCLUSION: Bacterial loads in saliva were rapidly, differentially, and significantly reduced after one day of chewing BG.

Factors influencing opioid prescribing after tooth extraction.

BACKGROUND: Tooth extractions account for most opioid prescriptions from dentists, but specific characteristics that influence likelihood are less established. Improving understanding can facilitate development of tailored interventions to reduce unnecessary opioid prescribing. METHODS: The authors performed a retrospective review of patients 12 years and older undergoing tooth extraction at the College of Dentistry at the University of Kentucky from 2013 through 2020. The primary end point was issuance of an opioid prescription related to the encounter. RESULTS: In 44,387 eligible records analyzed, 10,628 (23.9%) patients received an opioid prescription. Results of multivariable logistic regression found that the factors associated with an opioid prescription included receipt of a nonopioid analgesic prescription (adjusted odds ratio [aOR], 11.36; 95% CI, 10.37 to 12.44), receipt of an antibiotic prescription (aOR, 8.29; 95% CI, 7.57 to 9.08), procedural sedation (aOR, 2.11; 95% CI, 1.93 to 2.31), surgical extraction (aOR, 1.96; 95% CI, 1.84 to 2.10), and third molar extractions (1 tooth: aOR, 1.14; 95% CI 1.04 to 1.25; 2 teeth: aOR, 2.09; 95% CI, 2.87 to 2.34; 3 teeth: aOR, 2.73; 95% CI, 2.36 to 3.15; 4 teeth: aOR, 3.45; 95% CI, 3.10 to 3.83). Factors that decreased risk included having an appointment in 2018 or later (aOR, 0.31; 95% CI, 0.29 to 0.33), in a student (aOR, 0.57; 95% CI, 0.51 to 0.65) or resident (aOR, 0.33; 95% CI, 0.31 to 0.36) clinic, and on any day other than Friday (Monday: aOR, 0.83; 95% CI, 0.76 to 0.91; Tuesday: aOR, 0.90; 95% CI, 0.83 to 0.99; Wednesday: aOR, 0.89; 95% CI, 0.81 to 0.97; Thursday: aOR, 0.88; 95% CI 0.81 to 0.97). CONCLUSIONS: Opioid prescriptions after tooth extraction were common in patients undergoing more extensive procedures. Provider perceptions, habits, and several clinical factors appeared to influence prescribing patterns. PRACTICAL IMPLICATIONS: The decision to prescribe an opioid appears to be associated with habits and factors perceived to modulate postoperative pain, which may serve as targets for opioid reduction strategies.