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Abstract Background Dental caries is one of the primary causes of tooth loss among adults. It is estimated to affect a majority of Americans aged 55 and older, with a disproportionately higher burden in disadvantaged populations. Although a number of treatments are currently in use for caries prevention in adults, evidence for their efficacy and effectiveness is limited. Methods/Design The Prevention of Adult Caries Study (PACS) is a multicenter, placebo-controlled, double-blind, randomized clinical trial of the efficacy of a chlorhexidine (10% w/v) dental coating in preventing adult caries. Participants (n = 983) were recruited from four different dental delivery systems serving four diverse communities, including one American Indian population, and were randomized to receive either chlorhexidine or a placebo treatment. The primary outcome is the net caries increment (including non-cavitated lesions) from baseline to 13 months of follow-up. A cost-effectiveness analysis also will be considered. Discussion This new dental treatment, if efficacious and approved for use by the Food and Drug Administration (FDA), would become a new in-office, anti-microbial agent for the prevention of adult caries in the United States. Trial Registration Number NCT00357877

Ianalumab, an afuscosylated monoclonal antibody, depletes B cells and blocks survival signals mediated by the B-cell activating factor receptor (BAFFR). Sjögren disease (SjD) is an autoimmune disorder with exocrine glandular and extraglandular manifestations, elevated BAFF, and autoantibodies to nuclear antigens. A phase 2b dose-finding trial of ianalumab (NCT02962895) in 190 patients with active SjD met its primary endpoint; 300 mg was clinically efficacious and improved whole salivary flow. Here, we explored changes in autoantibody and proteomic signatures with ianalumab treatment to characterize biomarkers associated with SjD disease activity. Patients with active SjD (N = 190) were randomized (1:1:1:1) to receive placebo or ianalumab (5/50/300 mg). Serum samples collected at baseline and week 24 were used for protein profiling and delineation of interferon protein signatures using the SomaScan(R) v4.1 platform. Autoantibodies and BAFF levels were assessed by Luminex-based enzyme-linked immunoassay assays. A linear mixed-effect model was used to identify longitudinal changes in protein concentration at week 24 versus baseline. Results were visualized using heatmaps and hierarchical clustering. At baseline, cluster analysis did not reveal significant correlations between European League Against Rheumatism Sjögren's Syndrome Disease Activity Index scores (including subdomains) and levels of autoantibodies or proteins of interest. Ianalumab led to marked changes in autoantibody and serum protein levels. The 300-mg dose showed increased numbers of significantly modulated serum proteins (42) with more pronounced expression modulation versus the 5-mg (9) and 50-mg (20) dose groups. Several B-cell surface proteins were consistently downregulated by ianalumab, including FcRL4, plausibly involved in the pathogenicity of SjD. The 50-mg and 300-mg doses induced downregulation of additional proteins: B-cell maturation antigen, specifically expressed by antibody-producing cells, or the chemokines CXCL13 and CCL21, associated with immune infiltration of glandular tissues. A trend for downregulation of interferon protein signatures was seen with 50-mg and 300-mg doses. No differential proteomic signatures related to baseline disease activity were identified. The dose response in clinical efficacy of ianalumab in patients with SjD observed in the phase 2b trial is also reflected at the protein level, with increased depth and breadth of proteomic changes by week 24, correlating with increasing dose. [ABSTRACT FROM AUTHOR]

Background: Dental caries is one of the primary causes of tooth loss among adults. It is estimated to affect a majority of Americans aged 55 and older, with a disproportionately higher burden in disadvantaged populations. Although a number of treatments are currently in use for caries prevention in adults, evidence for their efficacy and effectiveness is limited. Methods/Design: The Prevention of Adult Caries Study (PACS) is a multicenter, placebo-controlled, double-blind, randomized clinical trial of the efficacy of a chlorhexidine (10% w/v) dental coating in preventing adult caries. Participants (n = 983) were recruited from four different dental delivery systems serving four diverse communities, including one American Indian population, and were randomized to receive either chlorhexidine or a placebo treatment. The primary outcome is the net caries increment (including non-cavitated lesions) from baseline to 13 months of follow-up. A cost-effectiveness analysis also will be considered. Discussion: This new dental treatment, if efficacious and approved for use by the Food and Drug Administration (FDA), would become a new in-office, anti-microbial agent for the prevention of adult caries in the United States. Trial Registration Number: NCT00357877. [ABSTRACT FROM AUTHOR]

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.

Background: : Sjögren's syndrome is characterized by the presence of xerostomia and/or xerophthalmia. Pilocarpine, a muscarinic cholinergic agonist, has been proven to be efficacious in treating radiation-induced xerostomia (up to 30 mg/day) and symptoms of dry mouth in Sjögren's patients (up to 20 mg/day)., Objective: : To compare the safety and efficacy of oral pilocarpine (dose-adjusted) versus placebo in the treatment of dry eye and dry mouth symptoms in Sjögren's syndrome at 6 and 12 weeks., Methods: : In this 11-center, 256-patient placebo-controlled study, the safety and efficacy of oral pilocarpine (20 mg to 30 mg daily) for relief of Sjögren's-related dry mouth and dry eye symptoms was assessed. Changes in symptoms and salivary flow were measured over 12 weeks., Results: : Compared with placebo, salivary flow was significantly increased in the pilocarpine group (P

Objective: We hypothesize that androgen deficiency is a critical etiologic factor in the pathogenesis of aqueous-deficient and evaporative dry eye in Sjögren's syndrome (SS). We investigated whether women with SS have a deficiency in total androgens. We also examined whether these patients have elevated serum concentrations of estrogens., Methods: Blood was drawn from women with primary and secondary SS and age matched controls, and analyzed for steroid concentrations by gas and liquid chromatography-mass spectrometry., Results: Our results show that women with SS are androgen-deficient. Concentrations of 5-androstene-3beta,17beta-diol (5-diol), dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT), androsterone-glucuronide (ADT-G), and androstane-3a,17beta-diol-G (3alpha-diol-G) were all significantly reduced in SS sera relative to controls. In contrast, SS was not associated with significant alterations in the serum concentrations of testosterone, androstenedione, estrone, or 17beta-estradiol. These overall findings could not be attributed to the use of oral contraceptives or hormone replacement therapy, because the concentrations of 5-diol, DHEA, DHT, ADT-G and 3a-diol-G were also decreased in patients with SS compared to levels in control women who were not taking exogenous estrogens., Conclusion: Our results show that women with SS are androgen-deficient.

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.