Multi-ancestry Genome-Wide Association Study of Early Childhood Caries.

Early childhood caries (ECC) is the most common non-communicable childhood disease. It is an important health problem with known environmental and social/behavioral influences that lacks evidence for specific associated genetic risk loci. To address this knowledge gap, we conducted a genome-wide association study of ECC in a multi-ancestry population of U.S. preschool-age children (n=6,103) participating in a community-based epidemiologic study of early childhood oral health. Calibrated examiners used ICDAS criteria to measure ECC with the primary trait using the dmfs index with decay classified as macroscopic enamel loss (ICDAS ≥3). We estimated heritability, concordance rates, and conducted genome-wide association analyses to estimate overall genetic effects; the effects stratified by sex, household water fluoride, and dietary sugar; and leveraged the combined gene/gene-environment effects using the 2-degree-of-freedom (2df) joint test. The common genetic variants explained 24% of the phenotypic variance (heritability) of the primary ECC trait and the concordance rate was higher with a higher degree of relatedness. We identified 21 novel non-overlapping genome-wide significant loci for ECC. Two loci, namely RP11-856F16 . 2 (rs74606067) and SLC41A3 (rs71327750) showed evidence of association with dental caries in external cohorts, namely the GLIDE consortium adult cohort (n=∼487,000) and the GLIDE pediatric cohort (n=19,000), respectively. The gene-based tests identified TAAR6 as a genome-wide significant gene. Implicated genes have relevant biological functions including roles in tooth development and taste. These novel associations expand the genomics knowledge base for this common childhood disease and underscore the importance of accounting for sex and pertinent environmental exposures in genetic investigations of oral health.

Multiple Imputation for Partial Recording Periodontal Examination Protocols.

AIM: Partial-mouth recording protocols often result in underestimation of population prevalence and extent of periodontitis. We posit that multiple imputation of measures such as clinical attachment loss for nonselected tooth sites in partial-mouth samples can reduce bias in periodontitis estimates. METHODS: Multiple imputation for correlated site-level dichotomous outcomes in a generalized estimating equations framework is used to impute site-level binary indicators for clinical attachment loss exceeding a fixed threshold in partial-mouth samples. Periodontitis case definitions are applied to the imputed "complete" dentitions, enabling estimation of prevalence and other summaries of periodontitis for partial-mouth samples as if for full-mouth examinations. A multiple imputation-bootstrap procedure is described and applied for point and variance estimation of these periodontitis measures. The procedure is evaluated with pseudo-partial-mouth samples based on random site selection protocols of 28 to 84 periodontal sites repeatedly generated from full-mouth periodontal examinations of 3,621 participants in the 2013 to 2014 National Health and Nutrition Examination Survey (NHANES) survey. RESULTS: Multiple imputation applied to partial-mouth samples overestimated periodontitis mean extent, defined as the number of sites with clinical attachment loss 3 mm or greater, by 9.5% in random site selection protocols with 84 sites and overestimated prevalence by 5% to 10% in all the evaluated protocols. CONCLUSIONS: In the 2013 to 2014 NHANES data, multiple imputation of site-level periodontal indicators provides less biased estimates of periodontitis prevalence and extent than has been reported from estimates based on the direct application of full-mouth case definitions to partial-mouth samples. Multiple imputation provides a promising solution to the longstanding, vexing problem of estimation bias in partial-mouth recording, with potential application to a wide array of case definitions, periodontitis measures, and partial recording protocols. KNOWLEDGE TRANSFER STATEMENT: Partial-mouth sampling, while a resource-efficient strategy for obtaining oral disease estimates, often results in underestimation of periodontitis metrics. Multiple imputation for nonselected periodontal sites produces pseudo-full-mouth data sets that may be analyzed and combined to produce estimates with small bias.

Edentulism Predicts Cognitive Decline in the US Health and Retirement Cohort Study.

This longitudinal cohort study examines if 1) cognitive decline varies by birth cohort, adjusting for covariates, and 2) edentulism and nonuse of dental care predict 10-y cognitive decline (2008-2018). The Health and Retirement Study (HRS) features a representative sample of US adults over age 50. Eligibility criteria included having cognitive interview data available and responding to the question, "Have you lost all of your upper and lower natural permanent teeth?" at 2+ time points between 2006 and 2018. Use of dental care in the past 2 y was assessed. Linear mixed models for repeated measures estimated the trajectories of mean cognition over time for the birth cohorts, adjusted for baseline cognition, dentition status, dental care use, and covariates (demographic characteristics, health behaviors, and medical conditions). Cohort-by-time interaction terms were included to assess if cognitive decline varied by birth cohort. Ten-year change in cognition status (measured by HRS Cogtot27)-categorized as dementia (<7); cognitive impairment, not demented (7-11) 7≤Cogtot27<12; and normal (≥12)-was also investigated according to birth cohort, dentition status, and dental care use. Mean (SD) baseline age was 63.4 (10.1) y (n = 22,728). Older birth cohorts had greater cognitive decline than younger cohorts. Linear mixed-model estimates and 95% confidence intervals for protective factors for cognitive decline included higher baseline cognition (HRS Cogtot27) (0.49; 0.48-0.50), use of dental care in the past 2 y (0.17; 0.10-0.23), and covariates such as greater household wealth and being married. Risk increased with being edentulous (-0.42; -0.56 to -0.28), history of stroke or diabetes, less education, Medicaid recipient, current smoker, loneliness, and poor/fair self-rated health. Edentulism and irregular dental care are among important predictors of cognitive decline. Tooth retention and regular dental care throughout life appear to be important for maintaining oral and cognitive health.

Prediction Model Development and Validation of 12-Year Incident Edentulism of Older Adults in the United States.

INTRODUCTION: Edentulism affects health and quality of life. OBJECTIVES: Identify factors that predict older adults becoming edentulous over 12 y in the US Health and Retirement Study (HRS) by developing and validating a prediction model. METHODS: The HRS includes data on a representative sample of US adults aged >50 y. Selection criteria included participants in 2006 and 2018 who answered, "Have you lost all of your upper and lower natural permanent teeth?" Persons who answered "no" in 2006 and "yes" in 2018 experienced incident edentulism. Excluding 2006 edentulous, the data set (n = 4,288) was split into selection (70%, n = 3,002) and test data (30%, n = 1,286), and Monte Carlo cross-validation was applied to 500 random partitions of the selection data into training (n = 1,716) and validation (n = 1,286) data sets. Fitted logistic models from the training data sets were applied to the validation data sets to obtain area under the curve (AUC) for 32 candidate models. Six variables were included in all models (age, race/ethnicity, gender, education, smoking, last dental visit) while all combinations of 5 variables (income, alcohol use, self-rated health, loneliness, cognitive status) were considered for inclusion. The best parsimonious model based on highest mean AUC was fitted to the selection data set to obtain a final prediction equation. It was applied to the test data to estimate AUC and 95% confidence interval using 1,000 bootstrap samples. RESULTS: From 2006 to 2018, 9.7% of older adults became edentulous. The 2006 mean (SD) age was 66.7 (8.7) for newly edentulous and 66.3 (8.4) for dentate (P = 0.31). The baseline 6-variable model mean AUC was 0.740. The 7-variable model with cognition had AUC = 0.749 and test data AUC = 0.748 (95% confidence interval, 0.715-0.781), modestly improving prediction. Negligible improvement was gained from adding more variables. CONCLUSION: Cognition information improved the 12-y prediction of becoming edentulous beyond the modifiable risk factors of smoking and dental care use, as well as nonmodifiable demographic factors. KNOWLEDGE TRANSFER STATEMENT: This prediction modeling and validation study identifies cognition as well as modifiable (dental care use, smoking) and nonmodifiable factors (race, ethnicity, gender, age, education) associated with incident complete tooth loss in the United States. This information is useful for the public, dental care providers, and health policy makers in improving approaches to preventive care, oral and general health, and quality of life for older adults.

Transitional care from skilled nursing facilities to home: study protocol for a stepped wedge cluster randomized trial.

BACKGROUND: Skilled nursing facility (SNF) patients are medically complex with multiple, advanced chronic conditions. They are dependent on caregivers and have experienced recent acute illnesses. Among SNF patients, the rate of mortality or acute care use is over 50% within 90 days of discharge, yet these patients and their caregivers often do not receive the quality of transitional care that prepares them to manage serious illnesses at home. METHODS: The study will test the efficacy of Connect-Home, a successfully piloted transitional care intervention targeting seriously ill SNF patients discharged to home and their caregivers. The study setting will be SNFs in North Carolina, USA, and, following discharge, in patients' home. Using a stepped wedge cluster randomized trial design, six SNFs will transition at randomly assigned intervals from standard discharge planning to the Connect-Home intervention. The SNFs will contribute data for patients (N = 360) and their caregivers (N = 360), during both the standard discharge planning and Connect-Home time periods. Connect-Home is a two-step intervention: (a) SNF staff create an individualized Transition Plan of Care to manage the patient's illness at home; and (b) a Connect-Home Activation RN visits the patient's home to implement the written Transition Plan of Care. A key feature of the trial includes training of the SNF and Home Care Agency staff to complete the transition plan rather than using study interventionists. The primary outcomes will be patient preparedness for discharge and caregiver preparedness for caregiving role. With the proposed sample and using a two-sided test at the 5% significance level, we have 80% power to detect a 18% increase in the patient's preparedness for discharge score. We will employ linear mixed models to compare observations between intervention and usual care periods to assess primary outcomes. Secondary outcomes include (a) patients' quality of life, functional status, and days of acute care use and (b) caregivers' burden and distress. DISCUSSION: Study results will determine the efficacy of an intervention using existing clinical staff to (a) improve transitional care for seriously ill SNF patients and their caregivers, (b) prevent avoidable days of acute care use in a population with persistent risks from chronic conditions, and (c) advance the science of transitional care within end-of-life and palliative care trajectories of SNF patients and their caregivers. While this study protocol was being implemented, the COVID-19 pandemic occurred and this protocol was revised to mitigate COVID-related risks of patients, their caregivers, SNF staff, and the study team. Thus, this paper includes additional material describing these modifications. TRIAL REGISTRATION: ClinicalTrials.gov NCT03810534 . Registered on January 18, 2019.

Flossing Is Associated with Improved Oral Health in Older Adults.

The effect of preventive oral habits is largely unexplored in older individuals. The purpose of this study was to evaluate the associations between home use of flossing and prevalence of periodontal disease and caries in older adults. Five-year incident tooth loss was also evaluated. Data on 686 individuals ≥65 y-old from the Piedmont 65+ Dental Study were examined including: 1) interproximal clinical attachment level (iCAL), 2) interproximal probing depth (iPD), 3) numbers of caries, and 4) missing teeth. Flossing behavior was evaluated according to the Periodontal Profile Class (PPC) system. Five-year follow-up data (n = 375) was evaluated for incident tooth loss. Dichotomous and categorical variables were analyzed using Pearson chi-square tests as well as covariate-adjusted Cochran-Mantel-Haenszel tests. Multiple linear regression compared clinical parameters based on flossing behavior. Elderly flossers had lower (mean, SE) %iCAL≥3 mm (38.2, 2.38 vs. 48.8, 1.56) and %iPD≥4 mm (8.70, 1.41 vs. 14.4, 0.93) compared to nonflossers (P ≤ 0.005). Flossers showed less coronal caries compared to nonflossers (P = 0.02). Baseline number of missing teeth (mean, SE) was 11.5 (0.35) in nonflossers compared to 8.6 (0.53) in flossers (P < 0.0001). Regular dental visitors had lower oral disease levels compared to episodic dental users. The majority of flossers classified into PPC-Stage I (health) whereas nonflossers classified as PPC-Stages V, VI, and VII (disease). At the 5-y follow-up visit, the average tooth loss for flossers was ~1 tooth compared to ~4 teeth lost for nonflossers (P < 0.0001). Among all teeth, molars showed the highest benefit (>40%) for flossing behavior (P = 0.0005). In conclusion, the extent of oral disease for older individuals was significantly less in flossers than in nonflossers. Flossers showed less periodontal disease, fewer dental caries, and loss of fewer teeth over a 5-y period. These findings further support flossing as an important oral hygiene behavior to prevent oral disease progression in older adults.

The Effect of Physician Oral Health Services on Dental Use and Expenditures under General Anesthesia.

BACKGROUND: Despite early evidence touting the effectiveness of physician-provided oral health services (POHS), recent evidence suggests these services might have little impact on caries-related outcomes in children. General anesthesia (GA) is often used to treat early childhood caries and may be considered the most extreme utilization outcome. We sought to assess the impact of POHS utilization on dental GA utilization and expenditures. METHODS: We used the Medicaid claims of a birth cohort of children born in 2008 in North Carolina (N = 32,558) to determine the impact of POHS on dental utilization and expenditures under GA for individual children. Children were followed until their eighth birthday. We analyzed the association of the number of prior POHS visits with visit-specific outcomes of dental treatment under GA using population-averaged models fit with generalized estimating equations with exchangeable working correlation structure. RESULTS: Children with 2 or more previous POHS visits had reduced odds of GA (odds ratio [OR] = 0.93; confidence interval [CI], 0.87-0.99; P = 0.029) and expenditures ($114; CI,-$152.61 to -$75.19; P < 0.001) compared to those without physician-provided oral health visits, adjusting for age, sex, race/ethnicity, and geographic residence. Dental expenditures did not differ between POHS and non-POHS subjects at non-GA visits. CONCLUSIONS: POHS decreased the odds of having dental GA treatment and dental expenditures at GA visits. The role of physicians in oral health care can reduce the impact on the most severe outcome-treatment under general anesthesia. KNOWLEDGE TRANSFER STATEMENT: The results of this study have important financial implications for state Medicaid programs and disease management programs trying to mitigate the costs of treating early childhood caries under general anesthesia. Children who receive physician oral health care are less likely to use and more likely to save money on general anesthesia to complete dental treatment.

Interdental Cleaning Is Associated with Decreased Oral Disease Prevalence.

The purpose of this study was to evaluate the associations between interdental cleaning behavior and the prevalence of caries and periodontal disease and numbers of missing teeth, with data from the National Health and Nutrition Examination Survey (2011 to 2012 and 2013 to 2014). Analysis included the following parameters: interproximal clinical attachment level (iCAL) ≥3 mm, interproximal probing depth (iPD) ≥4 mm, number of coronal and interproximal caries, number of missing teeth, ≥1 surfaces with coronal caries, and periodontal profile classes (PPCs). Chi-square was used for bivariate associations. Associations of interdental cleaning with outcomes were assessed with multiple linear regression and generalized logit regression, adjusting for age, race, sex, diabetes, smoking, education, dental visits, and sugar consumption. Nonusers had a significantly higher percentage of sites with iCAL ≥3 mm and iPD ≥4 mm as compared with individuals who used interdental cleaning devices ( P < 0.0001). Individuals with a higher frequency of cleaning (4 to 7×/wk) had a significantly lower extent of sites with iCAL ≥3 mm as compared with lower-frequency cleaning (1 to 3×/wk; P ≤ 0.05). Interdental cleaning users showed lower numbers of coronal caries, interproximal coronal caries, and missing teeth as compared with nonusers ( P < 0.0001). Nonusers had 1.73-times (95% confidence interval, 1.53 to 1.94) higher odds for having ≥1 surfaces of coronal caries as compared with interdental cleaning users, regardless of the weekly frequency. Individuals were less likely to be in diseased PPCs if they were interdental cleaning users. Low-frequency cleaners (1 to 3×/wk) had significantly greater odds (1.43; 95% confidence interval, 1.08 to 1.88) to have severe disease (PPC-G) versus health (PPC-A) than were high-frequency cleaners (4 to 7×/wk). Interdental cleaning users showed lower levels of periodontal disease and caries and lower numbers of missing teeth. Higher frequency of interdental cleaning was correlated with increased periodontal health. Individuals with severe periodontal disease could show additional oral health benefits by increasing cleaning frequency. The data support the use of interdental cleaning devices as an oral hygiene behavior for promoting health.

Differential Misclassification of Disease under Partial-Mouth Sampling.

AIM:: The effect of misclassification of a cluster-level dichotomous outcome (disease) due to partial-cluster sampling on its association with a dichotomous exposure is investigated. METHODS:: Disease (e.g., chronic periodontitis) is deemed to exist in a cluster (e.g., full mouth) when a condition of interest (e.g., pocket depth or clinical attachment loss exceeding an established threshold) is present in number and pattern across observations (e.g., tooth sites) in the cluster according to a specific criterion. When a subset of observations within each cluster is selected (i.e., partial-mouth sampling), specificity of disease is 100% (in the absence of site-level measurement error), whereas sensitivity is imperfect and generally unknown. Using conditional probability arguments, we investigate disease misclassification under partial-cluster sampling and its impact on the estimated disease-exposure association when the exposure is cluster level and measured without error. RESULTS:: When the probability of disease varies by exposure status, outcome misclassification at the cluster level is differential under partial-cluster sampling and depends on 1) the partial recording protocol, including the number of observations sampled and the particular sites selected in a cluster; 2) the joint probability structure of the condition within clusters; and 3) the criterion for disease. A numeric example demonstrates that disease-exposure odds ratios under partial-cluster random sampling can be biased in either direction (toward or away from the null) relative to gold-standard odds ratios under full-cluster sampling. CONCLUSIONS:: In general, misclassification of disease is differential under partial-cluster sampling. In particular, sensitivity and negative predictive values depend on exposure status, which leads to biased inference. KNOWLEDGE TRANSFER STATEMENT:: Partial-mouth sampling causes disease misclassification probabilities, including sensitivity, to vary by exposure groups when disease prevalence differs between groups. As a result, disease-exposure associations may be under- or overestimated by standard analysis procedures for periodontal data relative to full-mouth estimates. Procedures that address bias are needed for partial-recording protocols.

Early Head Start, Pediatric Dental Use, and Oral Health-Related Quality of Life.

The objective of the study was to examine the mediating effect of child dental use on the effectiveness of North Carolina Early Head Start (EHS) in improving oral health-related quality of life (OHRQoL). In total, 479 parents of children enrolled in EHS and 699 parents of Medicaid-matched children were interviewed at baseline when children were approximately 10 mo old and 24 mo later. In this quasi-experimental study, mediation analysis was performed using the counterfactual framework analysis, which employed 2 logit models with random effects: 1) for the mediator as a function of the treatment and covariates and 2) for the outcome as a function of the treatment, mediator, and covariates. The covariates were baseline dental OHRQoL, dental need, survey language, and a propensity score. We used in-person computer-assisted, structured interviews to collect information on demographic characteristics and dental use and to administer the Early Childhood Oral Health Impact Scale, a measure of OHRQoL. Dental use had a mediation effect in the undesired direction with a 2-percentage point increase in the probability of any negative impact to OHRQoL (95% confidence interval [CI], 0.3%-3.9%). Even with higher dental use by EHS participants, the probability of any negative impact to OHRQoL was approximately 8 percentage points lower if an individual were moved from the non-EHS group to the EHS group (95% CI, -13.9% to -1.2%). EHS increases child dental use, which worsens family OHRQoL. However, EHS is associated with improved OHRQoL overall. Knowledge Transfer Statement: Study results can inform policy makers that comprehensive early childhood education programs improve oral health-related quality of life (OHRQoL) for disadvantaged families with young children in pathways outside of clinical dental care. This awareness and its promotion can lead to greater resource investments in early childhood education programs. Information about the negative impacts of dental use on OHRQoL should lead to the development and testing of strategies in dentistry and Early Head Start to improve dental care experiences.

A Potential Biofilm Metabolite Signature for Caries Activity - A Pilot Clinical Study.

BACKGROUND: This study's aim was to compare the dental biofilm metabolite-profile of caries-active (N=11) or caries-free (N=4) children by gas chromatography-mass spectrometry (GC/MS) analyses. METHODS: Samples collected after overnight fasting, with or without a previous glucose rinse, were combined for each child based on the caries status of the site, re-suspended in ethanol and analyzed by GC/MS. RESULTS: Biofilm from caries-active sites exhibited a different chromatographic profile compared to caries-free sites. Qualitative and quantitative analysis suggested a special cluster of branched alcohols and esters present at substantially higher intensity in biofilms of caries-active sites. CONCLUSIONS: This pilot study indicates that there are metabolites present in the biofilm which have the potential to provide a characteristic metabolomics signature for caries activity.

Regression analysis of correlated ordinal data using orthogonalized residuals.

Semi-parametric regression models for the joint estimation of marginal mean and within-cluster pairwise association parameters are used in a variety of settings for population-averaged modeling of multivariate categorical outcomes. Recently, a formulation of alternating logistic regressions based on orthogonalized, marginal residuals has been introduced for correlated binary data. Unlike the original procedure based on conditional residuals, its covariance estimator is invariant to the ordering of observations within clusters. In this article, the orthogonalized residuals method is extended to model correlated ordinal data with a global odds ratio, and shown in a simulation study to be more efficient and less biased with regards to estimating within-cluster association parameters than an existing extension to ordinal data of alternating logistic regressions based on conditional residuals. Orthogonalized residuals are used to estimate a model for three correlated ordinal outcomes measured repeatedly in a longitudinal clinical trial of an intervention to improve recovery of patients' perception of altered sensation following jaw surgery.

Preventive Services by Medical and Dental Providers and Treatment Outcomes.

OBJECTIVE: Nearly all state Medicaid programs reimburse nondental primary care providers (PCPs) for providing preventive oral health services to young children; yet, little is known about how treatment outcomes compare with children visiting dentists. This study compared the association between the provider of preventive services (PCP, dentist, or both) with Medicaid-enrolled children before their third birthday and subsequent dental caries-related treatment (CRT) and CRT payment. METHODS: We conducted a retrospective study of young children enrolled in North Carolina Medicaid during 2000 to 2006. The annual number of CRT and CRT payments per child between the ages of 3 and 5 yr were estimated with a zero-inflated negative binomial regression and a hurdle model, respectively. Models were adjusted for relevant child- and county-level characteristics and used propensity score weighting to address observed confounding. RESULTS: We examined 41,453 children with > 1 preventive oral health visit from a PCP, dentist, or both before their third birthday. Unadjusted annual mean CRT and payments were lowest among children who had only PCP visits (CRT = 0.87, payment = $172) and higher among children with only dentist visits (CRT = 1.48, payment = $234) and both PCP and dentist visits (CRT = 1.52, payment = $273). Adjusted results indicated that children who had dentist visits (with or without PCP visits) had significantly more CRT and higher CRT payments per year during the ages of 3 and 4 yr than children who had only PCP visits. However, these differences attenuated each year after age 3 yr. CONCLUSIONS: Because of children's increased opportunity to receive multiple visits in medical offices during well-child visits, preventive oral health services provided by PCPs may lead to a greater reduction in CRT than dentist visits alone. This study supports guidelines and reimbursement policies that allow preventive dental visits based on individual needs.

Tooth-surface-specific effects of xylitol: randomized trial results.

The Xylitol for Adult Caries Trial was a three-year, double-blind, multi-center, randomized clinical trial that evaluated the effectiveness of xylitol vs. placebo lozenges in the prevention of dental caries in caries-active adults. The purpose of this secondary analysis was to investigate whether xylitol lozenges had a differential effect on cumulative caries increments on different tooth surfaces. Participants (ages 21-80 yrs) with at least one follow-up visit (n = 620) were examined at baseline, 12, 24, and 33 months. Negative binomial and zero-inflated negative binomial regression models were used to estimate incidence rate ratios (IRR) for xylitol's differential effect on cumulative caries increments on root and coronal surfaces and, among coronal surfaces, on smooth (buccal and lingual), occlusal, and proximal surfaces. Participants in the xylitol arm developed 40% fewer root caries lesions (0.23 D2FS/year) than those in the placebo arm (0.38 D2FS/year; IRR = 0.60; 95% CI [0.44, 0.81]; p < .001). There was no statistically significant difference between xylitol and control participants in the incidence of smooth-surface caries (p = .100), occlusal-surface caries (p = .408), or proximal-surface caries (p = .159). Among these caries-active adults, xylitol appears to have a caries-preventive effect on root surfaces (ClinicalTrials.gov NCT00393055).

Surface-specific efficacy of fluoride varnish in caries prevention in the primary dentition: results of a community randomized clinical trial.

OBJECTIVES: Fluoride varnish (FV) is efficacious in caries prevention although its effects among different tooth surfaces are poorly understood. This study sought to determine the extent to which caries-preventive effects of a community intervention that included FV application among preschool-aged children varied according to primary tooth anatomy and baseline tooth pathology. METHODS: Secondary analysis was undertaken of data from a community-randomized controlled trial among 543 3- to 5-year-old Aboriginal children in 30 Northern Territory Australian communities. Children in intervention communities received community health promotion and FV application once every 6 months. Net caries (d(3)mfs) risk and 95% confidence limits (CL) were estimated for the control and intervention arms, and stratified according to tooth anatomy/location and baseline pathology (sound, enamel opacity, hypoplastic defect or precavitated carious lesion). The intervention's efficacy was quantified using generalized estimating equation modeling accounting for study design and clustering. The assumption of efficacy homogeneity was tested using a Wald χ(2) test with a p < 0.2 criterion and post hoc pairwise comparisons. RESULTS: The intervention resulted in a 25% reduction (relative risk, RR = 0.75; 95% CL = 0.71, 0.80) in the 2-year surface-level caries risk. There was substantial heterogeneity in FV efficacy by baseline surface pathology: RRs were 0.73 for sound, 0.77 for opaque, 0.90 for precavitated, and 0.92 for hypoplastic surfaces. Among sound surfaces, maxillary anterior facials received significantly more benefit (RR = 0.62) compared to pits and fissures (RR = 0.78). CONCLUSION: The intervention had greatest efficacy on surfaces that were sound at baseline. Among those sound surfaces, maxillary anterior facials received most caries-preventive benefit.

Review and recommendations for zero-inflated count regression modeling of dental caries indices in epidemiological studies.

Over the past 5-10 years, zero-inflated (ZI) count regression models have been increasingly applied to the analysis of dental caries indices (e.g. DMFT, dfms). The main reason for that is linked to the broad decline in children's caries experience, such that dmf and DMF indices more frequently generate low or even zero counts. This article specifically reviews the application of ZI Poisson and ZI negative binomial regression models to dental caries, with emphasis on the description of the models and the interpretation of fitted model results given the study goals. The review finds that interpretations provided in the published caries research are often imprecise or inadvertently misleading, particularly with respect to failing to discriminate between inference for the class of susceptible persons defined by such models and inference for the sampled population in terms of overall exposure effects. Recommendations are provided to enhance the use as well as the interpretation and reporting of results of count regression models when applied to epidemiological studies of dental caries.

Follicle-stimulating hormone and bioavailable estradiol are less important than weight and race in determining bone density in younger postmenopausal women.

UNLABELLED: The association between follicle-stimulating hormone (FSH) and bone density was tested in 111 postmenopausal women aged 50-64 years. In the multivariable analysis, weight and race were important determinants of bone mineral density. FSH, bioavailable estradiol, and other hormonal variables did not show statistically significant associations with bone density at any site. INTRODUCTION: FSH has been associated with bone density loss in animal models and longitudinal studies of women. Most of these analyses have not considered the effect of weight or race. METHODS: We tested the association between FSH and bone density in younger postmenopausal women, adjusting for patient-related factors. In 111 postmenopausal women aged 50-64 years, areal bone mineral density (BMD) was measured at the lumbar spine, femoral neck, total hip, and distal radius using dual-energy X-ray absorptiometry, and volumetric BMD was measured at the distal radius using peripheral quantitative computed tomography (pQCT). Height, weight, osteoporosis risk factors, and serum hormonal factors were assessed. RESULTS: FSH inversely correlated with weight, bioavailable estradiol, areal BMD at the lumbar spine and hip, and volumetric BMD at the ultradistal radius. In the multivariable analysis, no hormonal variable showed a statistically significant association with areal BMD at any site. Weight was independently associated with BMD at all central sites (p < 0.001), but not with BMD or pQCT measures at the distal radius. Race was independently associated with areal BMD at all sites (p ≤ 0.008) and with cortical area at the 33% distal radius (p = 0.004). CONCLUSIONS: Correlations between FSH and bioavailable estradiol and BMD did not persist after adjustment for weight and race in younger postmenopausal women. Weight and race were more important determinants of bone density and should be included in analyses of hormonal influences on bone.

Regression models for patient-reported measures having ordered categories recorded on multiple occasions.

OBJECTIVES: The article reviews proportional and partial proportional odds regression for ordered categorical outcomes, such as patient-reported measures, that are frequently used in clinical research in dentistry. METHODS: The proportional odds regression model for ordinal data is a generalization of ordinary logistic regression for dichotomous responses. When the proportional odds assumption holds for some but not all of the covariates, the lesser known partial proportional odds model is shown to provide a useful extension. RESULTS: The ordinal data models are illustrated for the analysis of repeated ordinal outcomes to determine whether the burden associated with sensory alteration following a bilateral sagittal split osteotomy procedure differed for those patients who were given opening exercises only following surgery and those who received sensory retraining exercises in conjunction with standard opening exercises. CONCLUSIONS: Proportional and partial proportional odds models are broadly applicable to the analysis of cross-sectional and longitudinal ordinal data in dental research.

Alteration of PTGS2 promoter methylation in chronic periodontitis.

Levels of prostaglandin E(2) and the prostaglandin-endoperoxide synthase-2 (PTGS2, or COX-2) increase in actively progressing periodontal lesions, but decrease in chronic disease. We hypothesized that chronic inflammation is associated with altered DNA methylation levels within the PTGS2 promoter, with effects on COX-2 mRNA expression. PTGS2 promoter methylation levels from periodontally inflamed gingival biopsies showed a 5.06-fold increase as compared with non-inflamed samples (p = 0.03), and the odds of methylation in a CpG site in the inflamed gingival group is 4.46 times higher than in the same site in the non-inflamed group (p = 0.016). The level of methylation at -458 bp was inversely associated with transcriptional levels of PTGS2 (RT-PCR) (p = 0.01). Analysis of the data suggests that, in chronically inflamed tissues, there is a hypermethylation pattern of the PTGS2 promoter in association with a lower level of PTGS2 transcription, consistent with a dampening of COX-2 expression in chronic periodontitis. These findings suggest that the chronic persistence of the biofilm and inflammation may be associated with epigenetic changes in local tissues at the biofilm-gingival interface.