Identification of Salivary Metabolic Signatures Associated with Primary Sjögren's Disease.

Sjögren's disease (SjD) is the second most prevalent autoimmune disorder that involves chronic inflammation of exocrine glands. Correct diagnosis of primary SjD (pSjD) can span over many years since disease symptoms manifest only in advanced stages of salivary and lachrymal glandular destruction, and consensus diagnostic methods have critical sensitivity and selectivity limitations. Using nuclear magnetic resonance (NMR) spectroscopy, we determined the composition of metabolites in unstimulated saliva samples from 30 pSjD subjects and 30 participants who do not have Sjögren's disease (non-Sjögren's control group, NS-C). Thirty-four metabolites were quantified in each sample, and analysis was conducted on both non-normalized (concentration) and normalized metabolomics data from all study participants (ages 23-78) and on an age-restricted subset of the data (ages 30-70) while applying false discovery rate correction in determining data significance. The normalized data of saliva samples from all study participants, and of the age-restricted subset, indicated significant increases in the levels of glucose, glycerol, taurine, and lactate, as well as significant decreases in the levels of 5-aminopentanoate, acetate, butyrate and propionate, in subjects with pSjD compared to subjects in the NS-C group. Additionally, a significant increase in choline was found only in the age-restricted subset, and a significant decrease in fucose was found only in the whole study population in normalized data of saliva samples from the pSjD group compared to the NS-C group. Metabolite concentration data of saliva samples from all study participants, but not from the age-restricted subset, indicated significant increases in the levels of glucose, glycerol, taurine, and lactate in subjects with pSjD compared to controls. The study showed that NMR metabolomics can be implemented in defining salivary metabolic signatures that are associated with disease status, and can contribute to differential analysis between subjects with pSjD and those who are not affected with this disease, in the clinic.

Examiner training and reliability in two randomized clinical trials of adult dental caries.

OBJECTIVES: This report describes the training of dental examiners participating in two dental caries clinical trials and reports the inter- and intra-examiner reliability scores from the initial standardization sessions. METHODS: Study examiners were trained to use a modified International Caries Detection and Assessment System II system to detect the visual signs of non-cavitated and cavitated dental caries in adult subjects. Dental caries was classified as no caries (S), non-cavitated caries (D1), enamel caries (D2), and dentine caries (D3). Three standardization sessions involving 60 subjects and 3,604 tooth surface calls were used to calculate several measures of examiner reliability. RESULTS: The prevalence of dental caries observed in the standardization sessions ranged from 1.4 percent to 13.5 percent of the coronal tooth surfaces examined. Overall agreement between pairs of examiners ranged from 0.88 to 0.99. An intra-class coefficient threshold of 0.60 was surpassed for all but one examiner. Inter-examiner unweighted kappa values were low (0.23-0.35), but weighted kappas and the ratio of observed to maximum kappas were more encouraging (0.42-0.83). The highest kappa values occurred for the S/D1 versus D2/D3 two-level classification of dental caries, for which seven of the eight examiners achieved observed to maximum kappa values over 0.90. Intra-examiner reliability was notably higher than inter-examiner reliability for all measures and dental caries classifications employed. CONCLUSION: The methods and results for the initial examiner training and standardization sessions for two large clinical trials are reported. Recommendations for others planning examiner training and standardization sessions are offered.

Long-term clinical observation of dental caries in salivary hypofunction patients using a supersaturated calcium-phosphate remineralizing rinse.

OBJECTIVE: One therapeutic approach to the management of xerostomia and its related oral sequelae is the use of a supersaturated Ca2+/PO4(3-) rinse in conjunction with fluoride. This study evaluated the use of the supersaturated rinse in high-risk patients from a single dental clinic. METHODS: Patients (n = 134) at high risk for caries due to xerostomia were prescribed the calcium phosphate rinse and 1.1% NaF for daily use, and were evaluated for caries incidence over an average observation period of five years. All patients were instructed to use the rinse three to four times a day, depending on the severity of dryness of the mouth and rate of salivary flow. Compliance, or regular use of the rinse, was determined through monitoring by staff at each visit, a self-administered clinic questionnaire pertaining to usage of the rinse, and records from a single hospital pharmacy that supplied the rinse to all participating patients. Those patients who were found to typically use the remineralizing solution at least once a day during the entire follow-up period were classified as compliant. All individual surfaces at risk for caries (SAR) were examined and recorded at each visit to determine changes in average SAR per patient RESULTS: Patients who regularly used the supersaturated rinse, along with commercially available prescription sodium fluoride, were found to experience a significant increase in reversals of caries, and a significant decrease in net coronal and root surface caries increment. The mean for the compliant group was 0.034 (SD 0.303), and the non-compliant mean was 0.315 (SD 0.735) with p > 0.0001 per surfaces/month. CONCLUSION: These observations suggest that long-term compliance with the daily supersaturated rinse was protective against caries progression in a high-risk population.

A randomized controlled study to evaluate an experimental moisturizing mouthwash formulation in participants experiencing dry mouth symptoms.

OBJECTIVE: The aim of this study was to evaluate the efficacy and tolerability of an experimental moisturizing mouthwash versus water only in participants experiencing dry mouth symptoms, including those with Sjögren syndrome (n = 28). STUDY DESIGN: Participants were randomized to the experimental mouthwash group (n = 53) or the water-only group (n = 47). For 8 days, the mouthwash group used 1 to 2 doses/day at home; both groups could sip water, as needed. Supervised treatment occurred on days 1, 3, and 8, and during this treatment, before and after administration, participants completed the Product Performance and Attributes Questionnaire parts 1 through 4. RESULTS: Significant between-treatment differences on all Product Performance and Attributes Questionnaire questions were shown at most time points. On day 8, at 120 minutes, there was a significant difference on Product Performance and Attributes Questionnaire 3-Question 1 ("Relieves the discomfort of dry mouth"; the predefined primary efficacy variable) in favor of mouthwash versus water (0.63 [95% confidence interval 0.17-1.10]; P = .0084). Subgroup analysis found a significant difference that favored mouthwash in participants without Sjögren syndrome (0.67 [0.11,1.23]; P = .0203) but not with Sjögren syndrome (0.52 [-0.35,1.38; P = .2272). Eight, non-serious, oral treatment-related adverse events were reported by the mouthwash group. CONCLUSIONS: The findings of a subjective questionnaire showed that an experimental moisturizing mouthwash provided greater relief than water only from dry mouth symptoms over 8 days.

A study to assess the safety and tolerability of three toothbrushes.

This study evaluated the oral soft tissue safety and tolerability of an experimental powered toothbrush (Crest SpinBrush Pro) compared to two leading manual toothbrushes: an advanced-design manual toothbrush (Oral-B CrossAction) and a flat-trimmed toothbrush (Oral-B 40 Indicator). Manual brushes are generally viewed as safe for use, and as such are appropriate controls. A total of 140 subjects was enrolled in this single-center, randomized, examiner-blind parallel study over a four-week test period. Subjects were instructed to brush in their normal manner, twice per day for 60 seconds per use. An oral soft tissue interview and examination were conducted by a trained dentist examiner at baseline, as well as three days and four weeks after baseline to assess clinical signs and symptoms of oral irritation associated with use of the toothbrushes. Overall, there were 19 adverse events reported for 18 subjects (13% of the population). The adverse events were distributed across test groups with five subjects in the experimental powered brush group, eight in the advanced design manual toothbrush group and five in the flat-trimmed toothbrush group experiencing at least one adverse event. The most frequently reported adverse event was localized irritation/inflammation of the gingiva. All adverse events were mild in severity except for one report of severe hyperesthesia (tooth sensitivity) in the advanced-design manual toothbrush group. There were no statistically significant differences between the groups for the proportion of subjects reporting adverse events at either three days or four weeks of product use. The results of this study indicate that daily use with the Crest SpinBrush Pro powered toothbrush is at least as safe as two leading manual toothbrushes.

Oral implications of polypharmacy in the elderly.

One of the major side effects of medications prescribed to elderly patients is the qualitative and quantitative alteration of saliva (salivary hypofunction). Saliva plays a pivotal role in the homeostasis of the oral cavity because of its protective and functional properties, including facilitating speech, swallowing, enhancing taste, buffering and neutralizing intrinsic and extrinsic acid, remineralizing teeth, maintaining the oral mucosal health, preventing overgrowth of noxious microorganisms, and xerostomia. With salivary hypofunction, a plethora of complications arise, resulting in decreased quality of life. The anticholinergic effects of medications can be overcome, and the oral cavity can be restored to normalcy.