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BACKGROUND: The evidence base supports effectiveness of dental sealants for prevention of childhood caries in school-aged children. OBJECTIVE: This study describes planning, development, usability testing and outcomes following implementation of DentaSeal, a web-based application designed to accurately track unique student data and generate reports for all Wisconsin school-based sealant placement (SP) programs. METHODS: Application software development was informed by a steering committee of representative stakeholders who were interviewed to inform design and provide feedback for design of DentaSeal during development and evaluation. Software development proceeded based on wireframes developed to build architectural design. Usability testing followed and informed any required adjustments to the application. The DentaSeal prototype was beta tested and fully implemented subsequently in the public health sector. RESULTS: The DentaSeal application demonstrated capacity to: 1) track unique student SP data and longitudinal encounter history, 2) generate reports and 3) support administrative tracking. In 2019, DentaSeal captured SP data of 47 school-based programs in Wisconsin that sponsored > 7,000 program visits for 184,000 children from 62 counties. Delivery of > 548,000 SP services were catalogued. CONCLUSIONS: For public health initiatives targeting reduction in caries incidence, web-based applications such as DentaSeal represent useful longitudinal tracking tools for cataloguing SP in school-based program participants.

Introduction Pneumonia is caused by microbes that establish an infectious process in the lungs. The gold standard for pneumonia diagnosis is radiologist-documented pneumonia-related features in radiology notes that are captured in electronic health records in an unstructured format. Objective The study objective was to develop a methodological approach for assessing validity of a pneumonia diagnosis based on identifying presence or absence of key radiographic features in radiology reports with subsequent rendering of diagnostic decisions into a structured format. Methods A pneumonia-specific natural language processing (NLP) pipeline was strategically developed applying Clinical Text Analysis and Knowledge Extraction System (cTAKES) to validate pneumonia diagnoses following development of a pneumonia feature–specific lexicon. Radiographic reports of study-eligible subjects identified by International Classification of Diseases (ICD) codes were parsed through the NLP pipeline. Classification rules were developed to assign each pneumonia episode into one of three categories: “positive,” “negative,” or “not classified: requires manual review” based on tagged concepts that support or refute diagnostic codes. Results A total of 91,998 pneumonia episodes diagnosed in 65,904 patients were retrieved retrospectively. Approximately 89% (81,707/91,998) of the total pneumonia episodes were documented by 225,893 chest X-ray reports. NLP classified and validated 33% (26,800/81,707) of pneumonia episodes classified as “Pneumonia-positive,” 19% as (15401/81,707) as “Pneumonia-negative,” and 48% (39,209/81,707) as “episode classification pending further manual review.” NLP pipeline performance metrics included accuracy (76.3%), sensitivity (88%), and specificity (75%). Conclusion The pneumonia-specific NLP pipeline exhibited good performance comparable to other pneumonia-specific NLP systems developed to date.

Background The International Classification of Disease (ICD) coding for pneumonia classification is based on causal organism or use of general pneumonia codes, creating challenges for epidemiological evaluations where pneumonia is standardly subtyped by settings, exposures, and time of emergence. Pneumonia subtype classification requires data available in electronic health records (EHRs), frequently in nonstructured formats including radiological interpretation or clinical notes that complicate electronic classification. Objective The current study undertook development of a rule-based pneumonia subtyping algorithm for stratifying pneumonia by the setting in which it emerged using information documented in the EHR. Methods Pneumonia subtype classification was developed by interrogating patient information within the EHR of a large private Health System. ICD coding was mined in the EHR applying requirements for “rule of two” pneumonia-related codes or one ICD code and radiologically confirmed pneumonia validated by natural language processing and/or documented antibiotic prescriptions. A rule-based algorithm flow chart was created to support subclassification based on features including symptomatic patient point of entry into the health care system timing of pneumonia emergence and identification of clinical, laboratory, or medication orders that informed definition of the pneumonia subclassification algorithm. Results Data from 65,904 study-eligible patients with 91,998 episodes of pneumonia diagnoses documented by 380,509 encounters were analyzed, while 8,611 episodes were excluded following Natural Language Processing classification of pneumonia status as “negative” or “unknown.” Subtyping of 83,387 episodes identified: community-acquired (54.5%), hospital-acquired (20%), aspiration-related (10.7%), health care–acquired (5%), and ventilator-associated (0.4%) cases, and 9.4% cases were not classifiable by the algorithm. Conclusion Study outcome indicated capacity to achieve electronic pneumonia subtype classification based on interrogation of big data available in the EHR. Examination of portability of the algorithm to achieve rule-based pneumonia classification in other health systems remains to be explored.

Introduction: To conduct a statewide survey among Wisconsin-based dental providers evaluating current knowledgeability, attitudes and practice behaviors surrounding management of patients with diabetes/prediabetes in the dental setting. The study explored perceptions on feasibility, value, barriers, and current status of integrated care model (ICM) adoption by dental practicesMaterials and Methods: A 32-question paper-based survey was mailed to all licensed dentists and dental hygienists practicing in Wisconsin. The study was conducted over a 4 week period in 2019. The survey instrument was adapted from a previous validated survey and was expanded to include questions on ICM adoption. Content and validity analyses and beta testing were conducted prior to dissemination of the survey. Descriptive statistics and chi-square tests were applied for data analyses. Thematic analyses was performed on open-ended questions.Results: Survey response rate was 12% (N = 854/7,356) representing 41% dentists and 59% dental hygienists. While 68% reported educating patients on oral health-diabetes association, only 18% reported medical consultations to inform dental treatment, and “frequent” (22%) or “occasional” (40%), medical triage. Knowledge-based questions were correctly answered by >70% of participants. While 50% valued chair-side glycemic screening and 85% supported non-invasive chair-side screening to identify at-risk patients,>88% relied on patient-reported diabetic status. Barriers to ICM adoption included time investment (70%), patient activation/cooperation (62%), cost (50%), insurance coverage (50%), infrequent interdisciplinary communication (46%), lack of equipment (33%) and provider (31%).Conclusion: Low rates of ICM adoption, chair-side testing, medical consultation and triage, and need for educational curricula reform were identified.

OBJECTIVE To conduct systematic review applying "preferred reporting items for systematic reviews and meta-analyses statement" and "prediction model risk of assessment bias tool" to studies examining the performance of predictive models incorporating oral health-related variables as candidate predictors for projecting undiagnosed diabetes mellitus (Type 2)/prediabetes risk. MATERIALS AND METHODS Literature searches undertaken in PubMed, Web of Science, and Gray literature identified eligible studies published between January 1, 1980 and July 31, 2018. Systematically reviewed studies met inclusion criteria if studies applied multivariable regression modeling or informatics approaches to risk prediction for undiagnosed diabetes/prediabetes, and included dental/oral health-related variables modeled either independently, or in combination with other risk variables. RESULTS Eligibility for systematic review was determined for seven of the 71 studies screened. Nineteen dental/oral health-related variables were examined across studies. "Periodontal pocket depth" and/or "missing teeth" were oral health variables consistently retained as predictive variables in models across all systematically reviewed studies. Strong performance metrics were reported for derived models by all systematically reviewed studies. The predictive power of independently modeled oral health variables was marginally amplified when modeled with point-of-care biological glycemic measures in dental settings. Meta-analysis was precluded due to high inter-study variability in study design and population diversity. CONCLUSIONS Predictive modeling consistently supported "periodontal measures" and "missing teeth" as candidate variables for predicting undiagnosed diabetes/prediabetes. Validation of predictive risk modeling for undiagnosed diabetes/prediabetes across diverse populations will test the feasibility of translating such models into clinical practice settings as noninvasive screening tools for identifying at-risk individuals following demonstration of model validity within the defined population.

Dr. David Satcher issued the first Surgeon General Report on oral health in the United States in 2000, drawing attention to a prevailing oral health access crisis. Dr. Satcher's report resonated in Wisconsin where a statewide growing dental access crisis was in progress and inspired grassroots efforts by a Family Health Center to establish a practice-based multi-site dental infrastructure that was integrated into a large regional multi-specialty medical clinic serving a largely rural population. An overview is provided of fundamental elements and relationships that supported establishment of the infrastructure, services, outreach and expanded access offered inclusively to all patients. Further, this community action report presents a blueprint that delineates key dimensions critical to planning and establishing a regionalized infrastructure offering access to all patients. Feasibility of establishing inclusive dental care is documented, and our model is proposed as a potentially replicable prototype for increasing dental access across other federally qualified health centers. Finally, this report is responsive to Dr. Jerome Adam's solicitations for feedback that will inform his plan for issuing a new Surgeon General report that updates status of oral health in America and progress in reversing oral health access disparities.

Background In this study, the authors sought to explore the receptivity, preparedness, and rates of adoption of integrated medical-dental models of care (MOCs) in the practice setting among primary care providers (PCPs) treating patients with diabetes mellitus (DM). Methods The authors conducted an anonymous statewide survey targeting PCPs across a range of Wisconsin-based practice settings to evaluate knowledgeability, attitude, practice behaviors, and perceived barriers to oral health screening in a medical setting. Qualitative analytical approaches included thematic analyses applied to evaluate the status of and barriers to integrated medical-dental MOC adoption. Results The integrated medical-dental MOC adoption rate was 34%. Top perceived barriers to integrated medical-dental MOC adoption included insurance coverage (71%) and care access (70%). A total of 39% indicated competency for educating patients about the association between DM and periodontitis. Although 72% of PCPs indicated optimal periodicity for oral health assessment as frequent, 39% reported frequently conducting such assessments. Conclusions Although PCPs indicate receptivity to integrated medical-dental MOCs, PCPs identify suboptimal education, lack of adequate training in oral-systemic disease assessment, and barriers to oral health care access as barriers to integrated medical-dental MOC adoption. Practical Implications Integrated medical-dental MOC adoption in care delivery to patients with DM remains below average. Interdisciplinary efforts and education are needed to address identified barriers to care integration.

OBJECTIVE: To conduct a systematic review of studies exploring potential biomarkers for development, course and efficacy of treatment of lymphomas in salivary glands of patients with Sjögren's syndrome.MATERIAL AND METHODS: Eligible studies were identified through a comprehensive search of two databases, i.e. PubMed and EMBASE. Quality of included articles was assessed with the 'Quality In Prognosis Studies' (QUIPS) tool. The 'CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies' (CHARMS) was used to facilitate data extraction.RESULTS: Fifty-eight studies met the inclusion criteria. Only one study assessed the progression of lymphoma. Moderate risk of bias was detected in 'outcome measurement', 'study participation' and 'study confounding' domains. Parotid gland enlargement, mixed monoclonal cryoglobulins and low C4 levels represented strongest predictors of lymphoma development. The role of histological biomarkers, and specifically germinal centers, remains controversial. Clinical and methodological heterogeneity across studies precluded conduct of a meta-analysis.CONCLUSIONS: Specific biomarkers in combination with clinical manifestations represent potential candidates for advancing precision medicine approaches to lymphoma prediction in patients with Sjögren's syndrome. Current focus has increasingly been on genetic and epigenetic markers as candidate predictors. Predictive accuracy of key biomarker candidates remains to be tested in well-designed prospectively-followed Sjögren's syndrome cohorts. This article is protected by copyright. All rights reserved.

OBJECTIVE: To identify the prognostic biomarker candidates for stratification and long-term surveillance of oral leukoplakia progressing to cancer via a systematic literature review.MATERIALS AND METHODS: Systematic searches with no date restrictions were conducted on March 29, 2018, targeting the databases PubMed (Ovid), EMBASE (Ovid), EBM (Ovid), and Web of Science (ISI). Bias was assessed using the Quality in Prognosis Studies tool. Biomarkers were stratified based on hallmarks of cancer.RESULTS: Inclusion criteria were met by 25 of 3,415 studies. A range of biomarkers were evaluated experimentally for risk stratification, prognosis, and surveillance of oral leukoplakia in tissue, blood, and saliva. However, the studies were highly heterogeneous and require further validation. Biomarkers reported in these studies included inflammatory or oxidative markers, growth factors, ion channels, genetic and cellular regulatory factors, and epigenetic biomarkers. Studies tended to include small sample sizes, under-reported or variably reported histopathological data, did not address potential confounding, reported limited/variable follow-up data, or lacked a control group. Inclusion of subsets from chemoprevention trials may have introduced bias regarding reported malignant transformation rates and accuracy of prognostic biomarkers.CONCLUSIONS: This review identified insufficient longitudinal evidence to support validated prognostic biomarkers for oral leukoplakia. Further studies are needed to identify molecular targets with the potential to mitigate risk of malignant transformation.

Objective Health education interventions during pregnancy can influence maternal oral health (OH), maternal OH-behaviors and children’s OH. Interventions that can be delivered at anytime and anywhere, for example mobile-health (mHealth) provides an opportunity to address challenges of health education and support activation of women in underserved and rural communities to modify their health behavior. This pilot study was undertaken as a part of a mHealth initiative to determine knowledge, attitudes, and behaviors related to pregnancy and ECC prevention among women attending obstetrics/gynecology (OB/GYN) practices at a large rurally-based clinic. Methods A cross-sectional survey study was voluntarily engaged by women (n = 191) aged 18 to 59 years attending OB/GYN visits, over a 3-week period from 12/2019 to 1/2020. Survey results were analyzed applying descriptive statistics, X2 and Fisher’s Exact tests. The significance level was set at P Results Approximately half of respondents were between 18 and 29 years (53%), had a college degree (55%), and 100% reported cell phone use. Whereas 53% and 31%, respectively, indicated that they were “somewhat” or “very” sure of how to prevent ECC in their children, only 9% recognized evidence of early decay and 30% did not know the purpose of fluoride. Overall, only 27% of participants correctly answered the knowledge-based questions. Further, only 57% reported their provider explained things in a way that was easy to understand. Only 24% reported seeing a dentist during their current pregnancy. Conclusions Study results suggested potential gaps in knowledge and behaviors related to ECC prevention and provided baseline data to inform future interventions to improve ECC prevention practices. Notably, majority of participants used their cell phones for making medical/dental appointments and reported using their phones to look up health-related information. This demographic represents a potentially receptive target for mHealth approaches to improve understanding of oral health maintenance during pregnancy and ECC prevention.

Background Aberrant DNA methylation has been firmly established as a factor contributing to the pathogenesis of colorectal cancer (CRC) via its capacity to silence tumour suppressor genes. However, the methylation status of multiple tumour suppressor genes and their roles in promoting CRC metastasis are not well characterised. Methods We explored the methylation and expression profiles of CPEB1 (the gene encoding cytoplasmic polyadenylation element-binding protein 1), a candidate CRC tumour suppressor gene, using The Cancer Genome Atlas (TCGA) database and validated these results in both CRC cell lines and cells from Han Chinese CRC patients (n = 104). The functional role of CPEB1 in CRC was examined in experiments performed in vitro and in vivo. A candidate transcription factor capable of regulating CPEB1 expression was predicted in silico and validated by luciferase reporter, DNA pull-down, and electrophoretic mobility shift assays. Results Hypermethylation and decreased expression of CPEB1 in CRC tumour tissues were revealed by TCGA database. We also identified a significant inverse correlation (Pearson’s R = − 0.43, P CPEB1 expression. We validated these results in CRC samples and two CRC cell lines. We also demonstrated that up-regulation of CPEB1 resulted in significantly decreased tumour growth, migration, invasion, and tumorigenicity and promoted tumour cell apoptosis both in vitro and in vivo. We identified the transcription factors CCAAT enhancer-binding protein beta (CEBPB) and transcription factor CP2 (TFCP2) as critical regulators of CPEB1 expression. Hypermethylation of the CPEB1 promoter resulted in a simultaneous increase in the capacity for TFCP2 binding and a decreased likelihood of CEBPB binding, both of which led to diminished expression of CPEB1. Conclusions Our results identified a novel tumour-suppressive role of CPEB1 in CRC and found that hypermethylation of the CPEB1 promoter may lead to diminished expression due to decreased chromatin accessibility and transcription factor binding. Collectively, these results suggest a potential role for CPEB1 in the diagnosis and treatment of CRC.

Background Quality improvement strategies have been an integral part of healthcare to attain improved care delivery and effective health outcomes. The dental quality initiative improvement (DQII) presented in this manuscript represents a case study of successful implementation of a quality improvement culture within a large integrated-medical-dental health system serving a largely rural population. Methods The key elements of DQII included steering committee establishment, definition or dental quality measures and development/implementation of a dental quality analytics dashboard (DQAD) that provides relevant data on dental quality measures. Qualitative metrics were applied to look at the improvement in performance for the various measures relative to quality benchmarks. Results DQII facilitated improved oversight of care continuity and provider performance surrounding quality measures at granular and/or institutional level. Improvement associated with care delivery performance relative to benchmarks was observed. Conclusions DQII further advanced the quality improvement culture prevalent in our learning healthcare environment with its focus on value-based care delivery. DQII initiative and establishment of DQAD provided ability to track performance in operational care delivery for dental providers in a clinical setting in real time.

Objectives Impact of implementing data-driven performance metric-tracking across a 10-dental center infrastructure established by Family Heath Center of Marshfield (FHC-M) was examined for relative impact on achieving value-based care delivery in serving a patient population characterized by 88% Medicaid representation. Methods To track progress toward national benchmarks for preventive care delivery, dental quality analytics dashboard tracking was implemented in real time with sharing of performance metrics across centers. Compliance rate with Uniform Data Systems reporting requirements for sealant placement on permanent first molars in children aged 6-9 years of age at moderate-to-high risk of caries was targeted at FHC-M dental centers for comparison with those of other community health centers statewide and nationally. Hygienist-to-dentist ratio to support robust sealant placement capacity was further examined. Results Uniform Data Systems data for rate of sealant placement between 2016-2018 revealed that FHC-M consistently exceeded rates reported statewide and nationally. For this quality indicator, performance across all dental practices in 27 states reported by Centers for Medicare and Medicaid Services in 2018 achieved 23% in 2017 compared to 73% and 52% placement rates reported by FHC-M and community health centers, respectively. A 1:1 hygienist-to-dentist was documented across FHC-M dental centers compared to 0.5:1 reported nationally. Conclusions Implementation of quality metric dashboard and a 1:1 dentist-to-hygienist ratio supported realization of value-based dental care delivery relative to caries prevention in a moderate-to-high risk pediatric Medicaid population through achievement of robust sealant placement. Importance of adequate hygienist staffing, "same day" sealant placement and performance feedback supported by technology are highlighted.

Objective To systematically review retrospective studies examining prognostic potentials of candidate biomarkers to stratify malignant progression of oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL). Materials and methods A systematic literature search of PubMed, EMBASE, Evidence-Based Medicine and Web of Science databases targeted literature published through 29 March 2018. Inter-rater agreement was ascertained during title, abstract and full-text reviews. Eligibility evaluation and data abstraction from eligible studies were guided by predefined PICO questions and bias assessment by the Quality in Prognosis Studies tool. Reporting followed Preferred Reporting Items for Systematic Review and Meta-Analysis criteria. Biomarkers were stratified based on cancer hallmarks. Results Eligible studies (n = 54/3,415) evaluated 109 unique biomarkers in tissue specimens from 2,762 cases (2,713 OL, 49 PVL). No biomarker achieved benchmarks for clinical application to detect malignant transformation. Inter-rater reliability was high, but 65% of included studies had high "Study Confounding" bias risk. Conclusion There was no evidence to support translation of candidate biomarkers predictive of malignant transformation of OL and PVL. Systematically designed, large, optimally controlled, collaborative, prospective and longitudinal studies with a priori-specified methods to identify, recruit, prospectively follow and test for malignant transformation are needed to enhance feasibility of prognostic biomarkers predicting malignant OL or PVL transformation.

Oral cavity cancer (OCC) is associated with high morbidity and mortality rates when diagnosed at late stages. Early detection of increased risk provides an opportunity for implementing prevention strategies surrounding modifiable risk factors and screening to promote early detection and intervention. Historical evidence identified a gap in the training of primary care providers (PCPs) surrounding the examination of the oral cavity. The absence of clinically applicable analytical tools to identify patients with high-risk OCC phenotypes at point-of-care (POC) causes missed opportunities for implementing patient-specific interventional strategies. This study developed an OCC risk assessment tool prototype by applying machine learning (ML) approaches to a rich retrospectively collected data set abstracted from a clinical enterprise data warehouse. We compared the performance of six ML classifiers by applying the 10-fold cross-validation approach. Accuracy, recall, precision, specificity, area under the receiver operating characteristic curve, and recall–precision curves for the derived voting algorithm were: 78%, 64%, 88%, 92%, 0.83, and 0.81, respectively. The performance of two classifiers, multilayer perceptron and AdaBoost, closely mirrored the voting algorithm. Integration of the OCC risk assessment tool developed by clinical informatics application into an electronic health record as a clinical decision support tool can assist PCPs in targeting at-risk patients for personalized interventional care.

This cross-sectional study sought to assess the current awareness, knowledge, and behavior regarding diabetes mellitus (DM) and periodontal disease (PD) association among a convenience sample of patients from a large Wisconsin-based integrated medical-dental health care organization serving largely rurally based communities. An anonymous 10-question survey was distributed at regional medical and dental centers of dental and medical clinics of a single health care institution over a 4-week period, to achieve a cross-sectional sampling of patients aged 18 to 80 years. Among 946 respondents, 616 were female. Patient-reported periodicity for dental visits was highest between 6 months and 1 year (56.4%). Respondents reporting “poor-fair” knowledgeability surrounding DM–PD association correlated with highest interest in learning more about DM–PD relationship ( p

Background The study objective was to evaluate the workflow of dental providers who use the existing electronic dental record (EDR) system at a large regional health care system to establish a diagnostic-centric culture as part of their dental practice. A further goal focused on identifying when improvements to the workflow and design of the EDR may be indicated. Methods Dental procedures performed on patients and corresponding International Classification of Diseases , Ninth Revision, Clinical Modification (ICD-9-CM) diagnoses were retrospectively mined from Marshfield Clinic's enterprise data warehouse. All dental procedures performed were selected and paired with corresponding diagnostic codes documented by dental providers. Frequency of documented diagnosis was further analyzed by characterizing correspondence with their ranking order in the diagnosis column with and without a scroll bar within the EDR user interface (UI). Accuracy of selecting appropriate ICD-9-CM for the corresponding Code on Dental Procedure and Nomenclature (CDT) was checked for 10% (n = 6,187) of the procedure-diagnosis pairs. Results Of the 61,511 unique procedures documented using 147 CDTs, 11% (6,914 procedures) had a corresponding "not available" option associated under the diagnoses column, whereas 89% (54,597) of dental procedures were associated with a corresponding ICD-9-CM diagnostic code. Overall tendency of dental providers to select the first or last options from the diagnostic list with a scroll bar was noted. Appropriateness of documenting corresponding ICD-9-CM to CDT procedures indicated 98% accuracy. Conclusion EDR UI design greatly affected documentation process. Redesigning the EDR UI from the results will increase both the quality and utility of clinical documentation.

Globally, periodontal disease and diabetes have achieved epidemic proportions and have become a top healthcare priority. Mutual bidirectional exacerbation of these conditions driven by underlying inflammatory processes has been demonstrated. Creation of cross-disciplinary integrated care delivery (ICD) models that bridge the traditionally-siloed healthcare domains of dentistry and medicine are being advanced to improve management of both conditions. By engaging focus groups inclusive of both medical and dental providers and one-on-one interviews, this qualitative study investigated provider knowledgeability, receptiveness, and readiness to engage ICD and sought input from the medical/dental primary care practitioner participants on perceived opportunities, benefits, and challenges to achieving ICD models for patients with diabetes/prediabetes. Statewide regional representation and inclusivity of diverse practice settings were emphasized in soliciting participants. Thematic analysis of focus group and interview transcripts was undertaken to establish current state-of-the-art, gauge receptivity to alternative ICD models, and seek insights from practitioners surrounding opportunities and barriers to ICD achievement. Forty providers participated, and thematic analyses achieved saturation. Providers were well informed regarding disease interaction, receptive to ICD, including implementation of better screening and referral processes, and favored improving interdisciplinary communication inclusive of access to integrated electronic health records. Perceived barriers and opportunities communicated by participants for advancing ICD were documented.

BACKGROUND: Inflammation is intimately involved in the pathogenesis of atherosclerosis and is accurately measured by high sensitivity C-reactive protein (hs-CRP), a sensitive marker for future risk of cardiovascular disease. The Correlation between Oral Health and Systemic Inflammation (COHESION) trial was designed to test the hypothesis that PlaqueHD, a plaque identifying toothpaste, reduces hs-CRP. METHODS: COHESION was designed initially to enroll 132 subjects with hs-CRP between 2.0 and 10.0 milligrams per liter but randomized 112 between 0.5 and 10.0, of which 103 had baseline and follow up data and comprise the intention to treat sample. Of these, a pre-specified subgroup analysis included 40 with baseline hs-CRP > 2.0 and all hs-CRP < 10. Since the distribution of hs-CRP was skewed toward higher values, to achieve normality assumptions, the significance of changes in hs-CRP between groups over time was tested on log-transformed data using a mixed effects analysis of variance. RESULTS: The intention-to-treat analysis showed no significant differences between the PlaqueHD and placebo group (p=0.615). The pre-specified subgroup analysis showed a significant difference between the PlaqueHD and placebo group (p=0.047). This finding resulted from a reduction in hs-CRP at follow up of 0.58 in the PlaqueHD and an increase of 0.55 in the placebo group. CONCLUSIONS: These findings are compatible with those of a prior pilot trial which also suggested benefits only in subjects with baseline elevations. These findings suggest that future trials targeting reductions of hs-CRP levels should randomize subjects with baseline hs-CRP between 2.0 and 10.0.

Epidemiological surveillance documents an escalating epidemic prevalence of both type 2 diabetes (T2DM) and periodontal disease (PD). The principal goals of this review are to: 1) re-examine the clinical significance of associations between PD and T2DM, based on strength of collective evidence as determined by systematic review and meta-analysis, and 2) review findings of the systematic reviews and meta-analyses in light of the current understanding of PD-associated pathophysiology and intersection with T2DM pathophysiology. Tooth loss predicts risk for chronic disease and mortality. PD is significantly associated with complications of diabetes, including retinopathy. Based on systematic reviews and meta-analyses, the adjunctive use of certain antibiotics enhances non-surgical periodontal treatment (NSPT) in patients with T2DM. Systematic reviews and meta-analyses support NSPT efficacy in achieving metabolic control. Systematic reviews and meta-analyses support the association between PD and T2DM, albeit the effect size may be modest. PD-T2DM interactions have important clinical implications.

Vertebral malformations (VMs) are caused by alterations in somitogenesis and may occur in association with other congenital anomalies. The genetic etiology of most VMs remains unknown and their identification may facilitate the development of novel therapeutic and prevention strategies. Exome sequencing was performed on both the discovery cohort of nine unrelated probands from the USA with VMs and the replication cohort from China (Deciphering Disorders Involving Scoliosis & COmorbidities study). The discovery cohort was analyzed using the PhenoDB analysis tool. Heterozygous and homozygous, rare and functional variants were selected and evaluated for their ClinVar, HGMD, OMIM, GWAS, mouse model phenotypes, and other annotations to identify the best candidates. Genes with candidate variants in three or more probands were selected. The replication cohort was analyzed by another in-house developed pipeline. We identified rare heterozygous variants in KIAA1217 in four out of nine probands in the discovery cohort and in five out of 35 probands in the replication cohort. Collectively, we identified 11 KIAA1217 rare variants in 10 probands, three of which have not been described in gnomAD and one of which is a nonsense variant. We propose that genetic variations of KIAA1217 may contribute to the etiology of VMs.

Founded in 1916, Marshfield Clinic has expanded to become one of the largest private multispecialty group practices in the United States. This integrated and comprehensive care system comprises of Marshfield Clinic, Marshfield Clinic Hospital, Marshfield Clinic Research Institute, Marshfield Clinic Education Foundation, Security Health Plan, its health maintenance organization and Family Health Center of Marshfield, its partnering federally qualified health center. Through a network of 50 electronically integrated satellite medical and dental clinics, Marshfield Clinic Health System (MCHS) serves a largely rural-dwelling population with a median low to mid-level income range in an expansive service area that encompasses Central, Western, and Northern Wisconsin. The current infrastructure represents century-long cumulative efforts whose stated mission from inception of Marshfield Clinic was stated as: serving patients through accessible, high quality healthcare, research and education. MCHS has been active in crafting effectiveness in integrating medical and dental care. This chapter provides an overview of how integrated health care delivery was achieved and supported through multifaceted approaches including development and training of integrated medical-dental healthcare delivery teams, inter-professional training and practice implementation. Achievement of improvement in clinical outcome through integrated healthcare delivery efforts is reviewed.

In this study, the authors sought to explore the receptivity, preparedness, and rates of adoption of integrated medical-dental models of care (MOCs) in the practice setting among primary care providers (PCPs) treating patients with diabetes mellitus (DM).The authors conducted an anonymous statewide survey targeting PCPs across a range of Wisconsin-based practice settings to evaluate knowledgeability, attitude, practice behaviors, and perceived barriers to oral health screening in a medical setting. Qualitative analytical approaches included thematic analyses applied to evaluate the status of and barriers to integrated medical-dental MOC adoption.The integrated medical-dental MOC adoption rate was 34%. Top perceived barriers to integrated medical-dental MOC adoption included insurance coverage (71%) and care access (70%). A total of 39% indicated competency for educating patients about the association between DM and periodontitis. Although 72% of PCPs indicated optimal periodicity for oral health assessment as frequent, 39% reported frequently conducting such assessments.Although PCPs indicate receptivity to integrated medical-dental MOCs, PCPs identify suboptimal education, lack of adequate training in oral-systemic disease assessment, and barriers to oral health care access as barriers to integrated medical-dental MOC adoption.Integrated medical-dental MOC adoption in care delivery to patients with DM remains below average. Interdisciplinary efforts and education are needed to address identified barriers to care integration.

Background This cross-sectional retrospective study utilized Natural Language Processing (NLP) to extract tobacco-use associated variables from clinical notes documented in the Electronic Health Record (EHR). Objecitve To develop a rule-based algorithm for determining the present status of the patient's tobacco-use. Methods Clinical notes (n= 5,371 documents) from 363 patients were mined and classified by NLP software into four classes namely: "Current Smoker", "Past Smoker", "Nonsmoker" and "Unknown". Two coders manually classified these documents into above mentioned classes (document-level gold standard classification (DLGSC)). A tobacco-use status was derived per patient (patient-level gold standard classification (PLGSC)), based on individual documents' status by the same two coders. The DLGSC and PLGSC were compared to the results derived from NLP and rule-based algorithm, respectively. Results The initial Cohen's kappa (n= 1,000 documents) was 0.9448 (95% CI = 0.9281-0.9615), indicating a strong agreement between the two raters. Subsequently, for 371 documents the Cohen's kappa was 0.9889 (95% CI = 0.979-1.000). The F-measures for the document-level classification for the four classes were 0.700, 0.753, 0.839 and 0.988 while the patient-level classifications were 0.580, 0.771, 0.730 and 0.933 respectively. Conclusions NLP and the rule-based algorithm exhibited utility for deriving the present tobacco-use status of patients. Current strategies are targeting further improvement in precision to enhance translational value of the tool.

We thank Professor Warnakulasuriya for his letter (Warnakulasuriya, 2019) and comments in relation to our systematic review of prospective studies assessing the prognostic biomarkers of oral leukoplakia (Villa et al., 2019). We agree that identifying prognostic biomarkers for oral leukoplakia is an important topic for oral medicine specialists. Hence our commitment to addressing such a diverse and scientifically challenging area as a component of World Workshop of Oral Medicine VII. This article is protected by copyright. All rights reserved.

The study objective was to evaluate the workflow of dental providers who use the existing electronic dental record (EDR) system at a large regional health care system to establish a diagnostic-centric culture as part of their dental practice. A further goal focused on identifying when improvements to the workflow and design of the EDR may be indicated.Dental procedures performed on patients and corresponding International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnoses were retrospectively mined from Marshfield Clinic's enterprise data warehouse. All dental procedures performed were selected and paired with corresponding diagnostic codes documented by dental providers. Frequency of documented diagnosis was further analyzed by characterizing correspondence with their ranking order in the diagnosis column with and without a scroll bar within the EDR user interface (UI). Accuracy of selecting appropriate ICD-9-CM for the corresponding Code on Dental Procedure and Nomenclature (CDT) was checked for 10% (n = 6,187) of the procedure-diagnosis pairs.Of the 61,511 unique procedures documented using 147 CDTs, 11% (6,914 procedures) had a corresponding "not available" option associated under the diagnoses column, whereas 89% (54,597) of dental procedures were associated with a corresponding ICD-9-CM diagnostic code. Overall tendency of dental providers to select the first or last options from the diagnostic list with a scroll bar was noted. Appropriateness of documenting corresponding ICD-9-CM to CDT procedures indicated 98% accuracy.EDR UI design greatly affected documentation process. Redesigning the EDR UI from the results will increase both the quality and utility of clinical documentation.

Standardized guidelines for the oral health management of patients with rare diseases exhibiting morphologic anomalies are currently lacking. This review considers Bardet-Biedl syndrome (BBS), a monogenic autosomal recessive nonmotile ciliopathy, as an archetypal condition. Dental anomalies are present in a majority of individuals affected by BBS due to abnormal embryonic orofacial and tooth development. Genetically encoded intrinsic oral structural anomalies and heterogeneous BBS clinical phenotypes and consequent oral comorbidities confound oral health management. Since the comorbid spectrum of BBS phenotypes spans diabetes, renal disease, obesity, sleep apnea, cardiovascular disease, and cognitive disorders, a broad spectrum of collateral oral disease may be encountered. The genetic impact of BBS on the anatomic development of oral components and oral pathology encountered in the context of various BBS phenotypes and their associated comorbidities are reviewed herein. Challenges encountered in managing patients with BBS are highlighted, emphasizing the spectrum of oral pathology associated with heterogeneous clinical phenotypic expression. Guidelines for provision of care across the spectrum of BBS clinical phenotypes are considered. Establishment of integrated medical-dental delivery models of oral care in the context of rare diseases is emphasized, including involvement of caregivers in the context of managing these patients with special needs.

Escalating prevalence of both diabetes and periodontal disease, two diseases associated with bi-directional exacerbation, has been reported. Periodontal disease represents a modifiable risk factor that may reduce diabetes onset or progression, and integrated models of cross-disciplinary care are needed to establish and manage glycemic control in affected patients. An ad-hoc environmental scan of current literature and media sought to characterize factors impacting status of integrated care models based on review of the existing evidence base in literature and media surrounding: (1) current cross-disciplinary practice patterns, (2) epidemiological updates, (3) status on risk assessment and screening for dysglycemia in the dental setting, (4) status on implementation of quality metrics for oral health, (5) care model pilots, and (6) public health perspectives. The survey revealed: escalating prevalence of diabetes and periodontitis globally; greater emphasis on oral health assessment for diabetic patients in recent medical clinical practice guidelines; high knowledgeability surrounding oral-systemic impacts on diabetes and growing receptivity to medical-dental integration among medical and dental providers; increasing numbers of programs/studies reporting on positive impact of emerging integrated dental-medical care models on diabetic patient healthcare access and health outcomes; a growing evidence base for clinically significant rates of undiagnosed dysglycemia among dental patients reported by point-of-care pilot studies; no current recommendation for population-based screening for dysglycemia in dental settings pending a stronger evidence base; improved definition of true periodontitis prevalence in (pre)/diabetics; emerging recognition of the need for oral health quality indicators and tracking; evidence of persistence in dental access disparity; updated status on barriers to integration. The potential benefit of creating clinically-applicable integrated care models to support holistic management of an escalating diabetic population by targeting modifiable risk factors including periodontitis is being recognized by the health industry. Cross-disciplinary efforts supported by high quality research are needed to mitigate previously- and newly-defined barriers of care integration and expedite development and implementation of integrated care models in various practice settings. Implementation of quality monitoring in the dental setting will support definition of the impact and efficacy of interventional clinical care models on patient outcomes.

Objectives: Calumenin, a molecular chaperone, exerts a regulatory effect on the vitamin K-dependent γ-carboxylation redox cycle that inhibits transfer of the reduced vitamin K from VKORC1, the pharmacological target of warfarin, to the γ-carboxylase. Because of its polymorphic structure and central role in the warfarin metabolic pathway, a contributory role for calumenin to warfarin dose variability has been posited. The current study sought to validate modulation of therapeutic dosing requirements by a single nucleotide polymorphisms (SNP) occurring in the calumenin gene (CALU) reported in previous studies. The CALU SNP was further modeled to detect interaction with SNPs occurring in VKORC1, CYP2C9, and CYP4F2 genes and characterize any additional contribution to variability in therapeutic warfarin dose requirement. Setting: The study was undertaken in an established, well-characterized cohort of subjects treated with warfarin in the Anticoagulation Clinic of Marshfield Clinic in Marshfield, Wisconsin. Methods: Subjects (N=491) previously genotyped for SNPS known to contribute variability to therapeutic warfarin dose requirement were genotyped for CALU SNP rs1043550, using TaqMan assays. Contribution of CALU SNP rs1043550 was modeled relative to other genotypic and phenotypic characteristics including gender, diagnosis, age, body surface area, underlying indication for warfarin, comorbidities, and pharmacological exposures. Interaction between SNPs impacting on warfarin dose requirements and calumenin SNPs was also modeled. Results: Small differences in warfarin dosing requirements detected among individuals encoding the mutant G allele in the calumenin SNP were not statistically or clinically significant relative to therapeutic warfarin dose requirement and did not independently contribute significantly to the warfarin dosing model. Interaction between calumenin and VKORC1 SNPs contributed only minor additional variability to that ascribed to the wild type VKORC1 genotype. Conclusions: The impact of the CALU SNP on warfarin dose variability was minor and did not contribute significantly to therapeutic warfarin dose requirement in our study cohort. While no contribution was noted for the SNP examined in the present study, further examination of interaction between genetic elements contributing major impact on therapeutic warfarin dose requirements and genes exhibiting a lesser contribution is warranted.

The objective of this study was to assess current knowledgeability, attitudes, and practice behaviors of primary care providers (PCPs) towards oral cancer screening. Applying a cross-sectional design, a 14-question survey was emailed to 307 PCPs practicing at a large, multi-specialty, rurally based healthcare system. Survey data were collected and managed using REDCap and analyzed applying descriptive statistics. A 20 % response rate (n = 61/307) was achieved for survey completion. Approximately 70 % of respondents were physicians, 16 % were nurse practitioners, and 13 % were physician assistants. Nearly 60 % of respondents were family medicine practitioners. Limited training surrounding oral cancer screening during medical training was reported by 64 %. Although 78 % of respondents reported never performing oral cancer screening on patients in their practice, >90 % answered knowledge-based questions correctly. Frequency rate for specialist referral for suspicious lesions by PCPs was 56 % “frequently”. Optimal periodicity for oral cancer screening on all patients selected by respondents was 61 % “annually”, 3 % “every 6 months”, 3 % “every visit”, 2 % “not at all”, and 31 % “unsure”. This study established a baseline surrounding current knowledgeability, practice patterns, and opinions of PCPs towards oral cancer screening at a single, large, regional healthcare system. In the absence of evidence-based support for population-based cancer screening, this study result suggests a need for better integration of oral cancer surveillance into the medical setting, supplemented by education and training with emphasis on assessment of high-risk patients to achieve early detection. Prospectively, larger studies are needed to validate these findings.

Introduction The epidemiology of tamoxifen and venous thromboembolism (VTE) is not well understood, and most data on tamoxifen toxicity are from adjuvant clinical trials. This study examined the relationship between the duration of tamoxifen use in female patients with breast cancer and the risk of VTE in a large population-based setting. Materials and Methods Retrospective electronic data extraction on tamoxifen utilization was undertaken among a cohort of 3572 women with breast cancer seen at Marshfield Clinic between January 1, 1994 and June 31, 2009. Observational follow-up extended until February, 2010. Results On initial exposure to tamoxifen, women had a clustering of VTE events. Cox proportional hazards regression, adjusting for multiple clinically-important covariates including age, body mass index, cancer stage, and concurrent diabetes, demonstrated that as use of tamoxifen continued in those without earlier VTE events, risk of subsequent VTE gradually increased, albeit at a lower rate (hazard ratio per year of tamoxifen duration=1.225, P Conclusions In our study population, initiating tamoxifen coincided with an initial clustering of VTE events, with risks due specifically to tamoxifen, increasing during continued exposure. Evidence suggested that the VTE clustering occurred in high risk individuals at initiation of tamoxifen therapy. Careful selection of patients for whom tamoxifen therapy is appropriate based on susceptibility to VTE is thus required prior to initiation of therapy.

Type 2 diabetes mellitus (DM) and cancer are common diseases that are frequently diagnosed in the same individual. An association between the two conditions has long been postulated. Here, we review the epidemiological evidence for increased risk of cancer, decreased cancer survival, and decreased rates of cancer screening in diabetic patients. The risk for several cancers, including cancers of the pancreas, liver, colorectum, breast, urinary tract, and endometrium, is increased in patients with DM. In a pooled risk analysis weighting published meta-analytic relative risk (RR) for individual cancer by differences in their incidence rates, we found a population RR of 0.97 (95 % CI, 0.75-1.25) in men and 1.29 (95 % CI, 1.16-1.44) in women. All meta-analyses showed an increased relative risk for cancer in diabetic men, except studies of prostate cancer, in which a protective effect was observed. The relationship between diabetes and cancer appears to be complex, and at present, a clear temporal relationship between the two conditions cannot be defined. DM also impacts negatively on cancer-related survival outcomes and cancer screening rates. The overwhelming evidence for lower cancer screening rates, increased incidence of certain cancers, and poorer prognosis after cancer diagnosis in diabetic patients dictates a need for improved cancer care in diabetic individuals through improved screening measures, development of risk assessment tools, and consideration of cancer prevention strategies in diabetic patients. Part two of this review focuses on the biological and pharmacological mechanisms that may account for the association between DM and cancer.

An association between type 2 diabetes mellitus (DM) and cancer has long been postulated, but the biological mechanism responsible for this association has not been defined. In part one of this review, we discussed the epidemiological evidence for increased risk of cancer, decreased cancer survival, and decreased rates of cancer screening in diabetic patients. Here we review the risk factors shared by cancer and DM and how DM medications play a role in altering cancer risk. Hyperinsulinemia stands out as a major factor contributing to the association between DM and cancer, and modulation of circulating insulin levels by DM medications appears to play an important role in altering cancer risk. Drugs that increase circulating insulin, including exogenous insulin, insulin analogs, and insulin secretagogues, are generally associated with an increased cancer risk. In contrast, drugs that regulate insulin signaling without increasing levels, especially metformin, appear to be associated with a decreased cancer risk. In addition to hyperinsulinemia, the effect of DM medications on other shared risk factors including hyperglycemia, obesity, and oxidative stress as well as demographic factors that may influence the use of certain DM drugs in different populations are described. Further elucidation of the mechanisms behind the association between DM, cancer, and the role of DM medications in modulating cancer risk may aid in the development of better prevention and treatment options for both DM and cancer. Additionally, incorporation of DM medication use into cancer prediction models may lead to the development of improved risk assessment tools for diabetic patients.

Periodontal disease and diabetes, two diseases that have achieved epidemic status, share a bidirectional relationship driven by micro-inflammatory processes. The present review frames the current understanding of the pathological processes that appear to link these diseases and advances the hypothesis that reversal of the epidemic is possible through application of interdisciplinary intervention and advancement of oral-systemic personalized medicine. An overview of how Marshfield Clinic's unique clinical, informatics and bio-repository resources and infrastructures are being aligned to advance oral-systemic personalized medicine is presented as an interventional model with the potential to reverse the epidemic trends seen for these two chronic diseases over the past several decades. The overall vision is to engineer a transformational shift in paradigm from 'personalized medicine' to 'personalized health'.