Faculty Bibliography

OBJECTIVE/UNASSIGNED:Current approaches to school-based caries prevention can increase access to oral healthcare, but are often limited by costs and other logistical challenges. Evidence from large pragmatic trials support the use of silver diamine fluoride (SDF) to prevent and control caries in school dental programs. In this pilot, we developed implementation strategies and integrated SDF into an existing school-based dental program, Smiles For Students (SFS). METHODS/UNASSIGNED:This was a single-group observational pilot. Using a school-based SDF implementation toolkit, SFS clinicians received training in clinical protocols as well as ongoing interactive technical assistance to support SDF integration. SDF was then implemented into existing clinical workflows. RESULTS/UNASSIGNED:Following training and implementation, the Smiles For Students program saw a 23 % increase in the number of patients served, a 53 % decrease in the per-child treatment time, a 45 % decrease in labor costs despite increased enrollment, and a 24 % decrease in supply costs. Qualitative feedback indicated strong support for simplified clinical protocols, reduction in cumbersome supplies and materials, and increased flexibility with space and resources. CONCLUSIONS/UNASSIGNED:In a pilot implementation project in which SDF was integrated into an existing school-based dental program serving 16 schools, multiple logistical and economic challenges were mitigated and program clinicians utilized both sealants and SDF to meet the needs of participating children.

INTRODUCTION/BACKGROUND:Teledentistry, also known as "virtual" dental examinations, is an innovative approach to increasing access to care. The objective of this study was to evaluate the diagnostic inter-rater reliability between virtual and in-person examinations for patients seeking emergency dental care (sick call) at a military dental treatment facility. MATERIALS AND METHODS/METHODS:One hundred subjects received both virtual and in-person examinations on the same day, in random order. The virtual examiner and subject were stationed in separate rooms and used only a laptop equipped with a camera, microphone, and speaker to complete the virtual exam. In contrast, the in-person examiner had access to all standard care modalities in a dental treatment room. After the first encounter, the subject proceeded to the corresponding virtual or in-person exam, and both examiners determined a diagnosis. Inter-rater agreement was determined between the two encounters for both diagnosis specialty category and diagnostic code using the Kappa coefficient. RESULTS:The results of the inter-rater analyses showed a Kappa score of 0.644 for the diagnosis specialty category (P < .001) and a Kappa score of 0.714 for diagnostic codes (P < .001). Both analyses indicated "substantial" agreement. CONCLUSIONS:We conclude that teledentistry can be an effective tool for determining a diagnosis and improving access to care for dental emergencies at military dental treatment facilities.

Sodium-glucose transporter-2 inhibitor (SGLT2i) drugs are widely used for lowering blood glucose levels independent of insulin. Beyond this, these drugs induce various metabolic changes, including weight loss and impaired bone integrity. There is a significant gap in understanding SGLT2i-induced skeletal changes, as SGLT2 is not expressed in osteoblasts or osteocytes, which use glucose to remodel the bone matrix. We studied the impact of 1, 3, or 6 months of canagliflozin (CANA), an SGLT2i treatment, on the skeleton of 6-month-old genetically heterogeneous UM-HET3 mice. Significant metabolic adaptations to CANA were evident as early as 1.5 months post-treatment, specifically in male mice. CANA-treated male mice exhibited notable reductions in body weight and decreased proinflammatory and bone remodeling markers associated with reduced cortical bone remodeling indices. Bone tissue metabolome indicated enrichment in metabolites related to amino acid transport and tryptophan catabolism in CANA-treated male mice. In contrast, CANA-treated female mice showed increases in nucleic acid metabolism. An integrOmics approach of source-matched bone tissue metabolome and bone marrow RNAseq indicated a positive correlation between the two omics data sets in male mice. Three clusters of transcripts and metabolites involved in energy metabolism, oxidative stress response, and cellular proliferation and differentiation were reduced in CANA-treated male mice. In conclusion, CANA affects bone metabolism mainly via the 'glucose restriction state' it induces and impacts bone cell proliferation and differentiation. These findings underline the effects of SGLT2i on bone health and highlight the need to consider sex-specific responses when developing clinical treatments that alter substrate availability.

Several mouse lines with congenital growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis disruption have shown improved health and extended lifespan. The current study investigated how inactivating this axis, specifically during aging, impacts the healthspan. We used a tamoxifen-inducible global GH receptor (GHR) knockout mouse model starting at 12 months and followed the mice until 24 months of age (iGHRKO_12-24 mice). We found sex- and tissue-specific effects, with some being pro-aging and others anti-aging. Measuring an array of cytokines in serum revealed that inactivation of the GH/IGF-1 axis at 12 months did not affect systemic inflammation during aging. On the other hand, hypothalamic inflammation was significantly reduced in iGHRKO_12-24 mice, evidenced by GFAP⁺ (glial fibrillary acidic protein, a marker of astrocytes) and Iba-1⁺ (a marker for microglia). Liver RNAseq analysis indicated feminization of the male transcriptome, with significant changes in the expression of monooxygenase, sulfotransferase, and solute-carrier-transporter gene clusters. Finally, we found impaired bone morphology, more pronounced in male iGHRKO_12-24 mice and correlated with GH/IGF-1 inactivation onset age. We conclude that inhibiting the GH/IGF-1 axis during aging only partially preserves the beneficial healthspan effects observed with congenital GH deficiency.

BACKGROUND:The sustainability of school-based oral health programs depends on the utilization of effective, efficient treatments and the availability of a trained clinical workforce. The objective of this study was to determine whether registered nurses are comparable to dental hygienists in the application and effectiveness of silver diamine fluoride (SDF) and fluoride varnish (FV) for the prevention of dental caries. METHODS:CariedAway was a school-based study of SDF and FV versus dental sealants and atraumatic restorations. Within the SDF + FV arm, participants were treated by either a licensed dental hygienist or a registered nurse, both under the supervision of a paediatric dentist. Although initial treatment assignment in CariedAway was randomized, assignment to provider was not. The proportion of children who remained caries free after 2 years was assessed for non-inferiority using two-group proportion tests, adjusting for the clustering effect of schools. RESULTS:A total of 417 children with no untreated caries at baseline were analysed including 298 treated by hygienists and 119 by nurses. The proportion of children who remained caries free after 2 years was 0.81 and 0.80 for those treated by hygienists and nurses, respectively, for a difference of 0.01 (95% CI = -0.07, 0.098) and within the pre-determined non-inferiority margin. CONCLUSIONS:Nurses may be effective in treating children with silver diamine fluoride and other fluoride varnishes in school-based oral health programs.

BACKGROUND/UNASSIGNED:Dental caries is the world's most prevalent noncommunicable disease, disproportionately affecting children from low-income rural areas. This study assessed the effectiveness of using silver diamine fluoride (SDF) for school-based caries prevention. METHODS/UNASSIGNED:The CariedAway 3.0 study was a cluster-randomized pragmatic non-inferiority trial comparing SDF to sealants and atraumatic restorations (ART) for the prevention and control of dental caries. All participants also received fluoride varnish. Analysis consisted of multilevel mixed-effects logistic and negative binomial regression for the prevalence and incidence of dental caries, respectively, and a non-inferiority margin of 10% for the difference between groups was used. Dental caries was defined as an ICDAS score of four or greater. RESULTS/UNASSIGNED:A total of 3345 children were enrolled in the trial, however there was a large proportion of children who were noncompliant and received external dental care. In adjusted analyses of compliant participants (n=1083, consisting of 543 in the SDF group and 540 in the sealant and ART group), there was no difference in the weighted risk difference between treatment groups (B=0.003, 95% CI = -0.0001, 0.0008). The odds of caries was elevated in the SDF group in longitudinal analyses (OR = 1.35, 95% CI = 0.86, 2.11) but was not significant and was below the non-inferiority margin. There were no significant differences between groups for caries incidence in adjusted models (IRR = 1.19, 95% CI = 0.81, 1.74). Results for intent to treat analyses were similar to that of per-protocol. DISCUSSION/UNASSIGNED:In this school-based clinical trial, the prevalence of dental caries in children treated with SDF and fluoride varnish was non-inferior compared to those treated with sealants, ART, and fluoride varnish, although the overall risk was slightly higher. Unfortunately, a high rate of dropout and participant noncompliance was observed, likely due to the impacts of COVID-19 on study procedures. As a result, observed effects may be unreliable beyond the short-term. TRIAL REGISTRATION/UNASSIGNED:NCT03448107.

BACKGROUND:Primary osteoarthritis (OA) occurs without identifiable underlying causes such as previous injuries or specific medical conditions. Age is a major contributing factor to OA, and as one ages, various joint tissues undergo gradual change, including degeneration of the articular cartilage, alterations in subchondral bone (SCB) morphology, and inflammation of the synovium. METHODS:We investigated the prevalence of primary OA in aged, genetically diverse UM-HET3 mice. Articular cartilage (AC) integrity and SCB morphology were assessed in 182 knee joints of 22-25 months old mice using the Osteoarthritis Research Society International (OARSI) scoring system and micro-CT, respectively. Additionally, we explored the effects of methylene blue (MB) and mitoquinone (MitoQ), two agents that affect mitochondrial function, on the prevalence and progression of OA during aging. RESULTS:Aged UM-HET3 mice showed a high prevalence of primary OA in both sexes. Significant positive correlations were found between cumulative AC (cAC) scores and synovitis in both sexes, and osteophyte formation in female mice. Ectopic chondrogenesis did not show significant correlations with cAC scores. Significant direct correlations were found between AC scores and inflammatory markers in chondrocytes, including matrix metalloproteinase-13, inducible nitric oxide synthase, and the NLR family pyrin domain containing-3 inflammasome in both sexes, indicating a link between OA severity and inflammation. Additionally, markers of cell cycle arrest, such as p16 and β-galactosidase, also correlated with AC scores. In male mice, no significant correlations were found between SCB morphology traits and cAC scores, while in female mice, significant correlations were found between cAC scores and tibial SCB plate bone mineral density. Notably, MB and MitoQ treatments influenced the disease's progression in a sex-specific manner. MB treatment significantly reduced cAC scores at the medial knee joint, while MitoQ treatment reduced cAC scores, but these did not reach significance. CONCLUSIONS:Our study provides comprehensive insights into the prevalence and progression of primary OA in aged UM-HET3 mice, highlighting the sex-specific effects of MB and MitoQ treatments. The correlations between AC scores and various pathological factors underscore the multifaceted nature of OA and its association with inflammation and subchondral bone changes.

BACKGROUND:Dental caries (tooth decay) is the world's most prevalent noncommunicable disease and can lead to pain, infection, and edentulism. Many children with caries lack access to traditional dental services. School-based caries prevention can increase access to care and reduce health inequities. Disruptions in school-based care due to pandemic control policies may result in children losing access to their primary dental care option. METHODS:The CariedAway project was a school-based caries prevention program in operation from 2019 to 2023 in urban schools with a high proportion of low-income, minority students. Program operations were suspended for 2 years due to the COVID-19 pandemic. We estimated the prevalence of untreated decay, swelling, fistula, and pulpal involvement in participants at baseline and again after restrictions were lifted. RESULTS:A total of 2998 children between the ages of 5 and 13 years were enrolled and received preventive care prior to pandemic shutdowns, and 1398 (47%) completed a follow-up observation after 2 years. At baseline, approximately 30% had untreated caries on any dentition, 11% of children presented with evidence of dental sealants, and no participants had swelling, fistula, or pulpal involvement. After 24 months, 12% of participants had swelling fistula, or pulpal involvement that was not treated during the pandemic period. CONCLUSION:There are considerable unmet dental needs in high-risk children that may be further exacerbated by a lack of access to care during disease outbreaks.

IMPORTANCE/UNASSIGNED:Dental caries is the world's most prevalent noncommunicable disease and a source of health inequity; school dental sealant programs are a common preventive measure. Silver diamine fluoride (SDF) may provide an alternative therapy to prevent and control caries if shown to be noninferior to sealant treatment. OBJECTIVE/UNASSIGNED:To determine whether school-based application of SDF is noninferior to dental sealants and atraumatic restorative treatment (ART) in the prevalence of dental caries. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:The Silver Diamine Fluoride Versus Therapeutic Sealants for the Arrest and Prevention of Dental Caries in Low-Income Minority Children (CariedAway) study was a pragmatic noninferiority cluster-randomized clinical trial conducted from February 2018 to June 2023 to compare silver diamine fluoride vs therapeutic sealants for the arrest and prevention of dental caries. Children at primary schools in New York, New York, with at least 50% of the student population reporting as Black or Hispanic and at least 80% receiving free or reduced lunch were included. This population was selected as they are at the highest risk of caries in New York. Students were randomized to receive either SDF or sealant with ART; those aged 5 to 13 years were included in the analysis. Treatment was provided at every visit based on need, and the number of visits varied by child. Schools with preexisting oral health programs were excluded, as were children who did not speak English. Of 17 741 students assessed for eligibility, 7418 were randomized, and 4100 completed follow-up and were included in the final analysis. INTERVENTIONS/UNASSIGNED:Participants were randomized at the school level to receive either a 38% concentration SDF solution or glass ionomer sealants and ART. Each participant also received fluoride varnish. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Primary study outcomes were the prevalence and incidence of dental caries. RESULTS/UNASSIGNED:A total of 7418 children (mean [SD] age, 7.58 [1.90] years; 4006 [54.0%] female; 125 [1.7%] Asian, 1246 [16.8%] Black, 3648 [49.2%] Hispanic, 153 [2.1%] White, 114 [1.5%] multiple races or ethnicities, 90 [1.2%] other [unspecified], 2042 [27.5%] unreported) were enrolled and randomized to receive either SDF (n = 3739) or sealants with ART (n = 3679). After initial treatment, 4100 participants (55.0%) completed at least 1 follow-up observation. The overall baseline prevalence of dental caries was approximately 27.2% (95% CI, 25.7-28.6). The odds of decay prevalence decreased longitudinally (odds ratio [OR], 0.79; 95% CI, 0.75-0.83) and SDF was noninferior compared to sealants and ART (OR, 0.94; 95% CI, 0.80-1.11). The crude incidence of dental caries in children treated with SDF was 10.2 per 1000 tooth-years vs 9.8 per 1000 tooth-years in children treated with sealants and ART (rate ratio, 1.05; 95% CI, 0.97-1.12). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this school-based pragmatic randomized clinical trial, application of SDF resulted in nearly identical caries incidence compared to dental sealants and ART and was noninferior in the longitudinal prevalence of caries. These findings suggest that SDF may provide an effective alternative for use in school caries prevention. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT03442309.

Methylene blue (MB) is a well-established antioxidant that has been shown to improve mitochondrial function in both in vitro and in vivo settings. Mitoquinone (MitoQ) is a selective antioxidant that specifically targets mitochondria and effectively reduces the accumulation of reactive oxygen species. To investigate the effect of long-term administration of MB on skeletal morphology, we administered MB to aged (18 months old) female C57BL/J6 mice, as well as to adult male and female mice with a genetically diverse background (UM-HET3). Additionally, we used MitoQ as an alternative approach to target mitochondrial oxidative stress during aging in adult female and male UM-HET3 mice. Although we observed some beneficial effects of MB and MitoQ in vitro, the administration of these compounds in vivo did not alter the progression of age-induced bone loss. Specifically, treating 18-month-old female mice with MB for 6 or 12 months did not have an effect on age-related bone loss. Similarly, long-term treatment with MB from 7 to 22 months or with MitoQ from 4 to 22 months of age did not affect the morphology of cortical bone at the mid-diaphysis of the femur, trabecular bone at the distal-metaphysis of the femur, or trabecular bone at the lumbar vertebra-5 in UM-HET3 mice. Based on our findings, it appears that long-term treatment with MB or MitoQ alone, as a means to reduce skeletal oxidative stress, is insufficient to inhibit age-associated bone loss. This supports the notion that interventions solely with antioxidants may not provide adequate protection against skeletal aging.