Modeling longitudinal oral health status and pneumonia risk: secondary data analyses of an integrated dental-medical cohort.

BACKGROUND: Mounting evidence indicates potential associations between poor oral health status (OHS) and increased pneumonia risk. Relative pneumonia risk was assessed in the context of longitudinally documented OHS. METHODS: Electronic medical/dental patient data captured from 2007 through 2019 were retrieved from the integrated health records of Marshfield Clinic Health Systems. Participant eligibility initiated with an assessment of OHS, stratified into the best, moderate, or worst OHS groups, with the additional criterion of 'no pneumonia diagnosis in the past 90 days'. Pneumonia incidence was longitudinally monitored for up to 1 year from each qualifying dental visit. Models were assessed, with and without adjustment for prior pneumonia incidence, adjusted for smoking and subjected to confounding mitigation attributable to known pneumonia risk factors by applying propensity score analysis. Time-to-event analysis and proportional hazard modeling were applied to investigate relative pneumonia risk over time among the OHS groups. RESULTS: Modeling identified associations between any incident pneumonia subtype and 'number of missing teeth' (p < 0.001) and 'clinically assessed periodontal status' (p < 0.01), which remained significant following adjustment for prior pneumonia incidence and smoking. The hazard ratio (HR) for 'any incident pneumonia' in the best OHS group for 'number of missing teeth' was 0.65, 95% confidence interval (CI) [0.54 - 0.79] (unadjusted) and 0.744, 95% CI [0.61 - 0.91] (adjusted). The HR for 'any incident pneumonia' in the best 'clinically assessed periodontal status' group was 0.72, 95% CI [0.58 - 0.90] (unadjusted) and 0.78, 95% CI [0.62 - 0.97] (adjusted). CONCLUSION/CLINICAL RELEVANCE: Poor OHS increased pneumonia risk. Proactive attention of medical providers to patient OHS and health literacy surrounding oral-systemic disease association is vital, especially in high-risk populations.

World Workshop on Oral Medicine VII: Prognostic biomarkers in oral leukoplakia and proliferative verrucous leukoplakia-A systematic review of retrospective studies.

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.

ESTABLISHING A QUALITY IMPROVEMENT CULTURE WITHIN A LARGE INTEGRATED MEDICAL-DENTAL HEALTH SYSTEM WITH A POPULATION BASED FOCUS.

OBJECTIVES: 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.

KIAA1217: A novel candidate gene associated with isolated and syndromic vertebral malformations.

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.

Patient Awareness of Association of Diabetes and Periodontal Disease.

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 <.0001). While over 80% of respondents correctly answered questions about gum disease symptomology and contribution of oral health practices on diabetes prevention, only 51% knew that PD affected blood sugar control. Willingness to comply with medical screening conducted by dental providers for diseases affecting oral health was indicated by 44% of respondents (p < .0001). Study results indicated that knowledgeability levels among patients surrounding the effect of PD on DM needed improvement. Strategic educational interventions targeting improved health literacy among patients may further promote prevention of DM-PD complications. Health literacy gaps remain to be addressed in patient understanding of the importance of detecting and managing dysglycemia for maintenance of periodontal health, creating opportunities for patient education.

Updates from the Evidence Base Examining Association between Periodontal Disease and Type 2 Diabetes Mellitus: Current Status and Clinical Relevance.

PURPOSE OF THE REVIEW: 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. RECENT FINDINGS: 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.

World Workshop on Oral Medicine VII: Biomarkers predicting lymphoma in the salivary glands of patients with Sjögren's syndrome-A systematic review.

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, that is, 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.

World Workshop on Oral Medicine VII: Prognostic biomarkers in oral leukoplakia: A systematic review of longitudinal studies.

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.

Knowledgeability, Attitude and Behavior of Primary Care Providers Towards Oral Cancer: a Pilot Study.

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.

Integrating Medical-Dental Care for Diabetic Patients: Qualitative Assessment of Provider Perspectives.

Globally, periodontal disease and diabetes have achieved epidemic proportions and have become a top health care priority. Mutual bidirectional exacerbation of these conditions is promoting creation of cross-disciplinary integrated care delivery (ICD) models that bridge the traditionally siloed health care domains of dentistry and medicine. 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; were 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.

Patient awareness/knowledge towards oral cancer: a cross-sectional survey.

BACKGROUND: Oral cancer (OC) is associated with multiple risk factors and high mortality rates and substantially contributes to the global cancer burden despite being highly preventable. This cross-sectional study sought to assess current knowledge, awareness, and behaviors of patients in rural communities surrounding OC risk. METHODS: An anonymous 21-question survey was distributed to patients in waiting rooms of a large integrated medical-dental health system serving north-central Wisconsin. Survey results were summarized via descriptive statistics. Odds ratios surrounding health literacy on OC risk factors were obtained using unconditional univariate logistic regression analysis. RESULTS: Of 504 dental and 306 medical patients completing the survey, 62.2% were female, Caucasian/White (92%) with 41% having a ≤ high school diploma/equivalent. Current smoker/smokeless tobacco use was reported by 34%, while 39% reported former tobacco exposure. Alcohol use was reported by 54% of respondents at the following frequencies: < once/week, (35%); 1-2 times/week, (16%); 3-4 times/week, (6%); 5-6 times/week, (2%); and daily, (23%). Knowledge about tobacco and alcohol use and increased OC risk was reported by 94 and 40%, respectively. About 50% reported knowledgeability regarding cancer-associated symptomology. Tobacco cessation was reported by 20% of responders. Receipt of education on OC from healthcare providers and human papilloma virus links to OC causation was reported by 38 and 21%, respectively. CONCLUSION: Patients who smoked > 20+ cigarettes per day were more knowledgeable about tobacco and OC risk compared to non-smokers and those who smoked ≤ 19 cigarettes/day (p = 0.0647). Patients who were alcohol consumers exhibited higher knowledgeability surrounding increased OC risk with alcohol and tobacco exposures compared to alcohol abstainers (p = 0.06). We concluded that patients recognized links between tobacco and OC risk but demonstrated lower knowledge of other causal factors. Strategic patient education by providers could increase awareness of OC risk.

Status Update on Translation of Integrated Primary Dental-Medical Care Delivery for Management of Diabetic Patients.

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.

Medical Providers' Oral Health Knowledgeability, Attitudes, and Practice Behaviors: An Opportunity for Interprofessional Collaboration.

OBJECTIVE: Evaluation of current knowledgeability, attitudes, and practice behaviors of medical providers from a large health care system toward oral health was undertaken as a pilot effort to better understand and integrate oral health into the overall health care delivery. METHODS: Invitations to complete a 28-question survey, designed in a web-based platform (SurveyMonkey(®)), were emailed to 1407 medical multispecialty physicians, residents, and nurses within the health system. The questionnaire included sections on provider demographics, oral health knowledgeability and attitudes, and current practice conducting oral health screenings. RESULTS: A 14% (n = 199/1407) response rate was achieved for survey completion. There were 16% who reported good coverage of oral/dental health topics in their medical training curriculum. Competency level was <30% for identifying tooth decay and oral pathology. There were 95% who reported never applying fluoride varnish in their practice, while >80% answered knowledge-based questions correctly. Frequency rates for dental referral by the medical providers were 32% 'frequently' and 68% 'infrequently.' Perceptions of optimal frequency for conducting oral health assessment in their professional practices ranged from 69% indicating 'frequently' to 25% indicating 'infrequently.' CONCLUSION: Overall, positive attitudes were observed toward incorporation of oral health examination into medical practice. The study identified lack of oral health treatment and infrequent referral by medical providers to dental providers. Results support likelihood for acceptance of care models that incorporate a medical/dental team-based approach complemented by oral health training for medical providers to enhance holistic health care delivery. Limitations of this pilot study include potential selection bias and lack of generalizability beyond our institution; further studies are planned in additional settings statewide to validate findings.

Does CALU SNP rs1043550 contribute variability to therapeutic warfarin dosing requirements?

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.

Tamoxifen-induced venothromboembolic events: exploring validation of putative genetic association.

OBJECTIVE: A pilot study to examine accrual rates, efficiency of data capture approaches, study design and genotyping capacity for a future genetic validation study was undertaken. DESIGN: The process pilot evaluated feasibility of applying a matched case-control design to validate association of two candidate estrogen receptor (ER) single nucleotide polymorphisms (SNPs) with incidence of venothromboembolic events (VTE) in breast cancer patients treated with tamoxifen where criteria included frequency matching by age, number of years diagnosed with breast cancer within 4-year intervals, and geographic residency. SETTING: The study was conducted at Marshfield Clinic, in central Wisconsin. PARTICIPANTS: Study-eligible cases with a breast cancer diagnosis between 1994 and 2006 who experienced a VTE within 5 years of last tamoxifen exposure were matched at a ratio of 1:4 to controls with a breast cancer diagnosed between 1994 and 2006 with no VTE history following tamoxifen exposure for ≥2 years. METHODS: Feasibility of enrolling, phenotyping, and genotyping 20% of the total number of validated eligible cases and controls was tested in order to project enrollment rates and assess probability of enrolling the projected sample size for the prospective validation study and adequacy of planned data capture. Conditional logistic regression analysis was conducted for the matched case-control study design. RESULTS: Enrollment accruals included 19 of 24 targeted cases (79%), and 74 of 96 (77%) targeted controls. Electronic data capture for most variables was nearly 100%. No unexpected statistically significant differences were observed between cases and controls. Capacity to conduct in-house screening for rs2234689 (ER1 PvuII), rs9340799 (ER1 XbaI), rs13146272 (CYP4V2), rs2227589 (SERPINC 1) and rs1613662 (GP6) was successfully established. Association of GP6 with VTE was further validated (P=0.0403; OR, 0.19). CONCLUSION: Accrual rates to the larger prospective study will require a multi-center design to ensure enrollment of adequate numbers of cases and controls for achieving the projected sample size required to validate association of the ER SNPs. To prevent study failure due to poor accrual, the importance of conducting feasibility studies before launching large scale validation studies of genetic association and adverse drug events, is discussed.

Prostate cancer risk in pre-diabetic men: a matched cohort study.

BACKGROUND: Diagnosis and duration of type 2 diabetes mellitus (DM) appear to be associated with decreased prostate cancer risk. Limitations of previous studies include methods of subject selection and accurate definition of DM diagnosis. We examined the temporal relationship between DM and prostate cancer risk exploring the period of greatest risk starting from the prediabetic to the post-diabetic period using clinical and administrative data to accurately define the date of DM diagnosis. METHODS: We identified 5,813 men who developed DM between January 1, 1995 and December 31, 2009 (reference date, date of DM onset or matched date for non-diabetic cohort) and 28,019 non-diabetic men matched by age, smoking history, residence, and reference date. Prostate cancer incidence before and after the reference date was assessed using Cox regression modeling adjusted for matching variables, body mass index, insurance status, and comorbidities. Primary outcomes included hazard ratio (HR) and number needed to be exposed to DM for one additional person to be harmed (NNEH) or benefit (NNEB) with respect to prostate cancer risk. RESULTS: After full adjustment, the HR for prostate cancer before DM diagnosis was 0.96 (95% CI 0.85-1.08; P=0.4752), and the NNEB was 974 at DM diagnosis. After the reference date, the fully-adjusted HR for prostate cancer in diabetic men was 0.84 (95% CI 0.72-0.97, P=0.0167), and the NNEB 3 years after DM onset was 425. The NNEB continued to decrease over time, reaching 63 at 15 years after DM onset, suggesting an increasing protective effect of DM on prostate cancer risk over time. No significant difference between the diabetic and non-diabetic cohort was found prior to reference date. CONCLUSION: Prostate cancer risk is not reduced in pre-diabetic men but decreases after DM diagnosis and the protective effect of DM onset on prostate cancer risk increases with DM duration.

DentaSeal: A school-based dental sealant efficiency assessment tool to support statewide monitoring and reporting: A field report.

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.

A database of annotated promoters of genes associated with common respiratory and related diseases.

Many genes have been implicated in the pathogenesis of common respiratory and related diseases (RRDs), yet the underlying mechanisms are largely unknown. Differential gene expression patterns in diseased and healthy individuals suggest that RRDs affect or are affected by modified transcription regulation programs. It is thus crucial to characterize implicated genes in terms of transcriptional regulation. For this purpose, we conducted a promoter analysis of genes associated with 11 common RRDs including allergic rhinitis, asthma, bronchiectasis, bronchiolitis, bronchitis, chronic obstructive pulmonary disease, cystic fibrosis, emphysema, eczema, psoriasis, and urticaria, many of which are thought to be genetically related. The objective of the present study was to obtain deeper insight into the transcriptional regulation of these disease-associated genes by annotating their promoter regions with transcription factors (TFs) and TF binding sites (TFBSs). We discovered many TFs that are significantly enriched in the target disease groups including associations that have been documented in the literature. We also identified a number of putative TFs/TFBSs that appear to be novel. The results of our analysis are provided in an online database that is freely accessible to researchers at http://www.respiratorygenomics.com. Promoter-associated TFBS information and related genomic features, such as histone modification sites, microsatellites, CpG islands, and SNPs, are graphically summarized in the database. Users can compare and contrast underlying mechanisms of specific RRDs relative to candidate genes, TFs, gene ontology terms, micro-RNAs, and biological pathways for the conduct of metaanalyses. This database represents a novel, useful resource for RRD researchers.

Diabetes and cancer II: role of diabetes medications and influence of shared risk factors.

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.