Salivary inflammatory biomarkers as a predictor of post-traumatic stress disorder and depressive symptom severity in trauma patients: A prospective study.

BACKGROUND: Although post-traumatic stress disorder (PTSD) and depression screening are recommended for traumatic injury patients, routine screening is still uncommon. Salivary inflammatory biomarkers have biological plausibility and potential feasibility and acceptability for screening. This study tested prospective associations between several salivary inflammatory biomarkers (proinflammatory cytokines interleukin-1ß, interleukin-6, tumor necrosis factor-α; and C-reactive protein), collected during hospitalization and PTSD and depressive symptoms at 5-month follow-up. METHODS: Adult traumatic injury patients (N = 696) at a major urban Level 1 trauma center provided salivary samples and completed PTSD and depressive symptom measures during days 0-13 of inpatient hospitalization. At 5-month follow-up, 368 patients (77 % male, 23 % female) completed the Clinician-Administered PTSD Scale for DSM-IV and the Self-rated Inventory of Depressive Symptomatology. Analyses focused on a latent inflammatory cytokine factor and C-reactive protein at baseline predicting 5-month PTSD and depression symptom outcomes and included baseline symptom levels as covariates. RESULTS: A latent factor representing proinflammatory cytokines was not related to 5-month PTSD or depressive symptom severity. Higher salivary CRP was related to greater PTSD symptom severity (ß = .10, p = .03) at 5-month follow-up and more severity in the following depressive symptoms: changes in weight and appetite, bodily complaints, and constipation/diarrhea (ß's from .14 to .16, p's from .004 -.03). CONCLUSION: In a primarily Latine and Black trauma patient sample, salivary CRP measured after traumatic injury was related to greater PTSD symptom severity and severity in several depressive symptom clusters. Our preliminary findings suggest that salivary or systemic CRP may be useful to include in models predicting post-trauma psychopathology.

Inter-observer agreement among specialists in the diagnosis of oral potentially malignant disorders and oral cancer using store-and-forward technology.

OBJECTIVES: Oral cancer is a leading cause of morbidity and mortality. Screening and mobile Health (mHealth)-based approach facilitates early detection remotely in a resource-limited settings. Recent advances in eHealth technology have enabled remote monitoring and triage to detect oral cancer in its early stages. Although studies have been conducted to evaluate the diagnostic efficacy of remote specialists, to our knowledge, no studies have been conducted to evaluate the consistency of remote specialists. The aim of this study was to evaluate interobserver agreement between specialists through telemedicine systems in real-world settings using store-and-forward technology. MATERIALS AND METHODS: The two remote specialists independently diagnosed clinical images (n=822) from image archives. The onsite specialist diagnosed the same participants using conventional visual examination, which was tabulated. The diagnostic accuracy of two remote specialists was compared with that of the onsite specialist. Images that were confirmed histopathologically were compared with the onsite diagnoses and the two remote specialists. RESULTS: There was moderate agreement (k= 0.682) between two remote specialists and (k= 0.629) between the onsite specialist and two remote specialists in the diagnosis of oral lesions. The sensitivity and specificity of remote specialist 1 were 92.7% and 83.3%, respectively, and those of remote specialist 2 were 95.8% and 60%, respectively, each compared with histopathology. CONCLUSION: The diagnostic accuracy of the two remote specialists was optimal, suggesting that "store and forward" technology and telehealth can be an effective tool for triage and monitoring of patients. CLINICAL RELEVANCE: Telemedicine is a good tool for triage and enables faster patient care in real-world settings.

Methamphetamine use and oral health-related quality of life.

PURPOSE: Methamphetamine (MA) is associated with adverse health effects, including the rampant tooth decay condition called "Meth Mouth." However, the impact of MA use on oral health-related quality of life (OHRQOL) is unknown. This study assessed the relationship between MA use and self-reported OHRQOL. METHODS: This cross-sectional study uses information from 545 MA-using participants recruited from Los Angeles County, California. Dental examinations were performed by three calibrated dentists using National Health and Nutrition Examination Survey (NHANES) protocols. Data on socio-demographic, behavioral, and drug-use history were recorded using questionnaires. Participants were categorized as 'light' or 'moderate/heavy' users based on reported frequency of MA use in the past 30 days. Route of MA administration was categorized as 'smoking' or 'other.' Self-reported OHRQOL was based on the Oral Health Impact Profile scale. RESULTS: Majority of the participants were male (80.9%). Median age was 45.0 years (IQR-13.0). Median number of days of MA use was 10.0 (IQR-12.0). Smoking was the preferred route of MA use (70.2%). Root caries in ≥ 3 teeth were reported in 78% of MA users. More than half of the participants reported having painful aching in mouth, avoidance of particular food items, feeling embarrassed, and discomfort while eating in the last 12 months. In unadjusted logistic models, moderate/heavy MA users were more likely to report an affected sense of taste [OR = 1.58, 95% CI (1.10-2.27)] and avoidance of particular foods [OR = 1.45, 95% CI (1.02-2.01)] than light users. Among individuals preferring other MA administration routes, moderate/heavy MA users were 3.09 times as likely to report an affected sense of taste than light users [OR = 3.09, 95% CI (1.52-6.27)]. CONCLUSION: Oral health and OHRQOL appear to be worse among Methamphetamine users than in the US general population.

Soda Consumption Among Methamphetamine Users in the USA: Impact on Oral Health.

PURPOSE: Dental disease is associated with methamphetamine (MA) use and partly attributed to excessive consumption of sugared sodas. Hence, the purpose of this study was to verify patterns of sugared soda intake and their relationship to oral health. MATERIALS AND METHODS: Detailed assessments with 541 MA users at two dental clinics were conducted. Assessment included a lifetime history of methamphetamine use, sugared soda consumption and a dental exam. RESULTS: Subjects were predominantly male (80.8%; mean age 44.4 years), on average had used MA for 11.6 years and drank an average of 35.3 sodas per month. Number of days of MA use over the past 30 days was significantly associated with soda consumption. Increased years of MA use was associated with the likelihood of users reporting less overall satisfaction with life because of their teeth, specifically difficulty eating, and dry mouth. This is the first study to show a statistically significant association between MA use and sugared soda consumption. CONCLUSIONS: MA users' consumption of sugared sodas is higher than in the adult general population, and this is the first study to show a statistically significant association between MA use and sugared soda consumption. In addition, increased soda consumption was associated with more dental problems among MA users.

Disposable collection kit for rapid and reliable collection of saliva.

OBJECTIVES: To describe and evaluate disposable saliva collection kit for rapid, reliable, and reproducible collection of saliva samples. METHODS: The saliva collection kit comprised of a saliva absorbent swab and an extractor unit was used to retrieve whole saliva samples from 10 subjects. The accuracy and precision of the extracted volumes (3, 10, and 30 µl) were compared to similar volumes drawn from control samples obtained by passive drool. Additionally, the impact of kit collection method on subsequent immunoassay results was verified by assessing salivary cortisol levels in the samples and comparing them to controls. RESULTS: The recovered volumes for the whole saliva samples were 3.85 ± 0.28, 10.79 ± 0.95, and 31.18 ± 1.72 µl, respectively (CV = 8.76%) and 2.91 ± 0.19, 9.75 ± 0.43, and 29.64 ± 0.91 µl, respectively, (CV = 6.36%) for the controls. There was a close correspondence between the salivary cortisol levels from the saliva samples obtained by the collection kit and the controls (R(2) > 0.96). CONCLUSIONS: The disposable saliva collection kit allows accurate and repeatable collection of fixed amounts of whole saliva and does not interfere with subsequent measurements of salivary cortisol. The simple collection process, lack of elaborate specimen recovery steps, and the short turnaround time (<3 min) should render the kit attractive to test subjects and researchers alike.

Performance of a quality assurance program for assessing dental health in methamphetamine users.

BACKGROUND: Systematic characterization of the dental consequences of methamphetamine (MA) abuse presupposes a rigorous quality assurance (QA) program to ensure the credibility of the data collected and the scientific integrity and validity of the clinical study. In this report we describe and evaluate the performance of a quality assurance program implemented in a large cross-sectional study of the dental consequences of MA use. METHODS: A large community sample of MA users was recruited over a 30 month period during 2011-13 and received comprehensive oral examinations and psychosocial assessments by site examiners based at two large community health centers in Los Angeles. National Health and Nutrition Examination Survey (NHANES) protocols for oral health assessments were utilized to characterize dental disease. Using NHANES oral health quality assurance guidelines, examiner reliability statistics such as Cohen's Kappa coefficients and inter-class correlation coefficients were calculated to assess the magnitude of agreement between the site examiners and a reference examiner to ensure conformance and comparability with NHANES practices. RESULTS: Approximately 9% (n = 49) of the enrolled 574 MA users received a repeat dental caries and periodontal examination conducted by the reference examiner. There was high concordance between the reference examiner and the site examiners for identification of untreated dental disease (Kappa statistic values: 0.57-0.75, percent agreement 83-88%). For identification of untreated caries on at least 5 surfaces of anterior teeth, the Kappas ranged from 0.77 to 0.87, and percent agreement from 94 to 97%. The intra-class coefficients (ICCs) ranged from 0.87 to 89 for attachment loss across all periodontal sites assessed and the ICCs ranged from 0.79 to 0.81 for pocket depth. For overall gingival recession, the ICCs ranged from 0.88 to 0.91. When Kappa was calculated based on the CDC/AAP case definitions for severe periodontitis, inter-examiner reliability for site examiners was low (Kappa 0.27-0.67). CONCLUSION: Overall, the quality assurance program confirmed the procedural adherence of the quality of the data collected on the distribution of dental caries and periodontal disease in MA-users. Examiner concordance was higher for dental caries but lower for specific periodontal assessments.

A Remote Oral Self-Care Behaviors Assessment System in Vulnerable Populations: Usability and Feasibility Study.

BACKGROUND: Preventative self-care can reduce dental disease that disproportionately burdens vulnerable populations. Personalized digital oral self-care behavioral interventions offer a promising solution. However, the success of these digital interventions depends on toothbrushing data collection e-platforms attuned to the needs and preferences of vulnerable communities. OBJECTIVE: The aim of this study is to assess the usability and feasibility of the Remote Oral Behaviors Assessment System (ROBAS), which has been adapted to address the unique requirements of socioeconomically disadvantaged minority individuals. METHODS: A cohort of 53 community-clinic participants, including 31 (58%) Latino and 22 (42%) Black individuals with no prior experience using electric toothbrushes, were recruited to use ROBAS, with planned assessments at baseline, 2 months, and 4 months. Beyond evaluating ROBAS's technical performance, extensive feedback was gathered to gauge users' experiences, viewpoints, and overall contentment. The System Usability Scale (SUS) served as a primary metric for assessing user satisfaction and acceptability. RESULTS: ROBAS exhibited largely reliable and consistent data-gathering capabilities. SUS scores (mean 75.6, SD 14.5) reflected participant contentment within a range of values for other commonly used digital devices and technologies. Among participants who answered questions about willingness to pay for ROBAS, 97% (30/31) indicated that they were willing to pay for ROBAS either as a one-time payment or as a subscription-based service. Additionally, 87.5% of participants expressed that they would endorse it to acquaintances. Most participants expressed no reservations about privacy; among those who expressed privacy concerns (n=20, 50%), the concerns included exposure of information (n=18, 45%), monitoring of brushing habits (n=12, 30%), and collection of information (n=14, 35%), although these concerns did not significantly correlate with specific participant traits. In qualitative terms, users valued ROBAS's ability to monitor brushing habits but called for refinements, especially in Wi-Fi and application connectivity. Recommendations for system improvements encompassed enhanced app functionality, individualized coaching, more comprehensive brushing data, and the addition of flossing activity tracking. CONCLUSIONS: The research highlights ROBAS's promise as a digital platform for unobtrusively tracking daily oral self-care activities in marginalized communities. The system proved to be both feasible, as evidenced by its stable and accurate data capture of brushing behaviors, and user-friendly, as reflected by strong SUS scores and positive user feedback. Influential factors for its uptake included ease of learning and operation, and the feedback provided.

Evaluating axial alignment and knee phenotypes in a young Indian population, using X-rays converted to three-dimensional bone models, and their relevance in total knee arthroplasty.

PURPOSE: The standard principle of total knee arthroplasty (TKA) targeted by most orthopaedicians is the alignment of the lower limb in a neutral mechanical axis. However, for several patients the neutral mechanical alignment is not normal. Aligning these patients to a neutral mechanical axis may not result in desirable outcomes as it may feel unnatural. This study aimed to discover what percentage of the young healthy Indian population have a neutral hip-knee-ankle angle (HKA = 180°) and what percentage of this population have a deviation from the neutral HKA. We also studied the distribution of knee phenotypes in this non-arthritic population. SUBJECTS AND METHODS: A total of 196 lower limbs were evaluated from 100 subjects, between the ages of 20 and 35 years, without any history of lower limb pathology, of which 50 were males and 50 were females. All volunteers were subjected to full-leg standing anteroposterior and lateral digital radiographs on which various alignment parameters were analysed. Three-dimensional bone models were generated using a validated software. RESULTS: 125 limbs (63.7%) from the total population lay in the range of 180 ± 3°; 7.14% (14/196) of the total limbs had an HKA angle of 180°; 29.5% (58/196) of the total population had a varus alignment, i.e., HKA angle of ≤176° and 6.6% (13/196) had knees in valgus alignment, i.e., HKA angle of ≥184°. Thirty-four percent (33/96) of limbs in men and 25% (25/100) of limbs in women had constitutional varus knees with an alignment of ≤176°; 5.2% (5) of limbs in men and 8% (8) of limbs in women had constitutional valgus knees with an alignment of ≥184°; 67/96 knees in males and 58 knees in females were in the range of 180 ± 3°. CONCLUSIONS: A significant portion of the normal population had limbs that deviated from the neutral HKA. If these subjects were to need TKA in the future, it would not be desirable to restore their alignment to its neutral.

Reference gene evaluation for normalization of gene expression studies with lymph tissue and node­derived stromal cells of patients with oral squamous cell carcinoma.

Profiling studies using reverse transcription quantitative PCR (RT-qPCR) require reliable normalization to reference genes to accurately interpret the results. A stable reference gene panel was established to profile metastatic and non-metastatic lymph nodes in patients with oral squamous cell carcinoma. The stability of 18S ribosomal RNA (18SrRNA), ribosomal Protein Lateral Stalk Subunit P0 (RPLP0), ribosomal Protein L27 (RPL27), TATA-box binding protein (TBP), hypoxanthine phosphoribosyl-transferase 1 (HPRT1), beta-actin (ACTB), glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) and vimentin (VIM) was evaluated, as reference genes for profiling patient-derived lymph node stromal cells (LNSCs; N=8; N0:6, N+:2) and lymph node tissues (Patients:14, Nodes=20; N0:7; N+:13). The genes were initially assessed based on their expression levels, specificity, and stability rankings to identify the best combination of reference genes. VIM was excluded from the final analysis because of its low expression (high quantification cycle >32) and multiple peaks in the melting curve. The stability analysis was performed using Reffinder, which utilizes four tools; geNorm, NormFinder, BestKeeper and Comparative ∆Ct methods, thereby enabling the computing of a comprehensive ranking. Evaluation of the gene profiles indicated that while RPLP0 and 18SrRNA were stable in both lymph node tissues and LNSCs, HPRT1, RPL27 were uniquely stable in these tissues whereas ACTB and TBP were most stable in LNSCs. The present study identified the most stable reference gene panel for the RT-qPCR profiling of lymph node tissues and patient-derived LNSCs. The observation that the gene panel differed between the two model systems further emphasized the need to evaluate the reference gene subset based on the disease and cellular context.

Optimizing an adaptive digital oral health intervention for promoting oral self-care behaviors: Micro-randomized trial protocol.

Dental disease continues to be one of the most prevalent chronic diseases in the United States. Although oral self-care behaviors (OSCB), involving systematic twice-a-day tooth brushing, can prevent dental disease, this basic behavior is not sufficiently practiced. Recent advances in digital technology offer tremendous potential for promoting OSCB by delivering Just-In-Time Adaptive Interventions (JITAIs)- interventions that leverage dynamic information about the person's state and context to effectively prompt them to engage in a desired behavior in real-time, real-world settings. However, limited research attention has been given to systematically investigating how to best prompt individuals to engage in OSCB in daily life, and under what conditions prompting would be most beneficial. This paper describes the protocol for a Micro-Randomized Trial (MRT) to inform the development of a JITAI for promoting ideal OSCB, namely, brushing twice daily, for two minutes each time, in all four dental quadrants (i.e., 2x2x4). Sensors within an electric toothbrush (eBrush) will be used to track OSCB and a matching mobile app (Oralytics) will deliver on-demand feedback and educational information. The MRT will micro-randomize participants twice daily (morning and evening) to either (a) a prompt (push notification) containing one of several theoretically grounded engagement strategies or (b) no prompt. The goal is to investigate whether, what type of, and under what conditions prompting increases engagement in ideal OSCB. The results will build the empirical foundation necessary to develop an optimized JITAI that will be evaluated relative to a suitable control in a future randomized controlled trial.

Contrasting clinical outcomes and socio-economic impact of young versus elderly-onset oral squamous cell carcinoma, a novel health economic analysis.

OBJECTIVES: The incidence of young-onset oral squamous cell carcinoma (OSCC) is growing, even among non-smokers/drinkers. The effects of adverse histopathological features on long-term oncologic outcomes between the young and old are controversial and confounded by significant heterogeneity. Few studies have evaluated the socio-economic impact of premature mortality from OSCC. Our study seeks to quantify these differences and their economic impact on society. MATERIALS AND METHODS: Four hundred and seventy-eight young (<45 years) and 1660 old patients (≥45 years) with OSCC were studied. Logistic regression determined predictors of recurrence and death. Survival analysis was calculated via the Kaplan-Meier method. A separate health economic analysis was conducted for India and Singapore. Years of Potential Productive Life Lost (YPPLL) were estimated with the Human Capital Approach, and premature mortality cost was derived using population-level data. RESULTS: Adverse histopathological features were seen more frequently in young OSCC: PNI (42.9% vs. 35%, p = 0.002), LVI (22.4% vs. 17.3%, p = 0.013) and ENE (36% vs. 24.5%, p < 0.001). Although 5-year OS/DSS were similar, the young cohort had received more intensive adjuvant therapy (CCRT 26.9% vs. 16.6%, p < 0.001). Among Singaporean males, the premature mortality cost per death was US $396,528, and per YPPLL was US $45,486. This was US $397,402 and US $38,458 for females. Among Indian males, the premature mortality cost per death was US $30,641, and per YPPLL was US $595. This was US $ 21,038 and US $305 for females. CONCLUSION: Young-onset OSCC is an aggressive disease, mitigated by the ability to receive intensive adjuvant treatment. From our loss of productivity analysis, the socio-economic costs from premature mortality are substantial. Early cancer screening and educational outreach campaigns should be tailored to this cohort. Alongside, more funding should be diverted to genetic research, developing novel biomarkers and improving the efficacy of adjuvant treatment in OSCC.

Improving accuracy in nodal staging of oral cancer: Proposal of a new system.

BACKGROUND: Despite introduction of extranodal extension (ENE) into the AJCC 8th edition of oral cancer staging, previous criticisms persist, such as limited discrimination between sub-stages and doubtful prognostic value of contralateral nodal disease. The purpose of this study was to compare our novel nodal staging system, based on the number of positive nodes and ENE, to the AJCC staging system in surgically treated patients. METHODS: Retrospective analysis of 4710 patients with oral squamous cell carcinoma (OSCC) treated with surgery±adjuvant therapy in 8 institutions in Australia, North America and Asia. With overall survival (OS) and disease specific survival (DSS) as endpoint, the prognostic performance of AJCC 8th and 7th editions were compared using hazard consistency, hazard discrimination, likelihood difference and balance. RESULTS: Our new nodal staging system (PN) a progressive and linear increase in hazard ratio (HR) from pN0 to pN3, with good separation of Kaplan Meier curves. Using the predetermined criteria for evaluation of a staging system, our proposed staging model outperformed AJCC 8th and 7th editions in prediction of OS and DSS. CONCLUSION: PN was the lymph node staging system that provided the most accurate prediction of OS and DSS for patients in our cohort of OSCC. Additionally, it can be easily adopted, addresses the shortcomings of the existing systems and should be considered for future editions of the TNM staging system.

Saliva sampling method affects performance of a salivary α-amylase biosensor.

OBJECTIVES: Prompted by the discordance between a standardized salivary alpha-amylase (sAA) biosensor applied in clinical settings and a reference laboratory analyzer, we examined the impact of the saliva sampling method on the analytic performance of the biosensor. METHODS: Direct mouth readings using the biosensor from 31 normal, healthy volunteers were compared to biosensor and conventional assay readings obtained from saliva samples collected concurrently by passive drool and processed in three different ways (unprocessed, thawed, and thawed and centrifuged). RESULTS: The direct readings from the mouth showed consistently lower sAA values (Ps < 0.01) compared to all other combinations of sample processing and quantification platforms (biosensor vs. conventional assay). Readings obtained from passive drool saliva were strongly correlated with one another, and Bland-Altman plots of agreement indicated a smaller discrepancy between conventional and biosensor readings obtained with passive drool when compared to the direct mouth readings. CONCLUSIONS: Our study indicates that the analytical performance of the sAA biosensor is influenced significantly by the saliva sampling method. In contrast to the relatively imprecise direct mouth measurements, biosensor sAA levels established indirectly from passive drool saliva samples provide more accurate estimation of sAA levels, even after intermediary processing steps (e.g., freezing, thawing, centrifugation).

Developing Message Strategies to Engage Racial and Ethnic Minority Groups in Digital Oral Self-Care Interventions: Participatory Co-Design Approach.

BACKGROUND: The prevention of oral health diseases is a key public health issue and a major challenge for racial and ethnic minority groups, who often face barriers in accessing dental care. Daily toothbrushing is an important self-care behavior necessary for sustaining good oral health, yet engagement in regular brushing remains a challenge. Identifying strategies to promote engagement in regular oral self-care behaviors among populations at risk of poor oral health is critical. OBJECTIVE: The formative research described here focused on creating messages for a digital oral self-care intervention targeting a racially and ethnically diverse population. Theoretically grounded strategies (reciprocity, reciprocity-by-proxy, and curiosity) were used to promote engagement in 3 aspects: oral self-care behaviors, an oral care smartphone app, and digital messages. A web-based participatory co-design approach was used to develop messages that are resource efficient, appealing, and novel; this approach involved dental experts, individuals from the general population, and individuals from the target population-dental patients from predominantly low-income racial and ethnic minority groups. Given that many individuals from racially and ethnically diverse populations face anonymity and confidentiality concerns when participating in research, we used an approach to message development that aimed to mitigate these concerns. METHODS: Messages were initially developed with feedback from dental experts and Amazon Mechanical Turk workers. Dental patients were then recruited for 2 facilitator-mediated group webinar sessions held over Zoom (Zoom Video Communications; session 1: n=13; session 2: n=7), in which they provided both quantitative ratings and qualitative feedback on the messages. Participants interacted with the facilitator through Zoom polls and a chat window that was anonymous to other participants. Participants did not directly interact with each other, and the facilitator mediated sessions by verbally asking for message feedback and sharing key suggestions with the group for additional feedback. This approach plausibly enhanced participant anonymity and confidentiality during the sessions. RESULTS: Participants rated messages highly in terms of liking (overall rating: mean 2.63, SD 0.58; reciprocity: mean 2.65, SD 0.52; reciprocity-by-proxy: mean 2.58, SD 0.53; curiosity involving interactive oral health questions and answers: mean 2.45, SD 0.69; curiosity involving tailored brushing feedback: mean 2.77, SD 0.48) on a scale ranging from 1 (do not like it) to 3 (like it). Qualitative feedback indicated that the participants preferred messages that were straightforward, enthusiastic, conversational, relatable, and authentic. CONCLUSIONS: This formative research has the potential to guide the design of messages for future digital health behavioral interventions targeting individuals from diverse racial and ethnic populations. Insights emphasize the importance of identifying key stimuli and tasks that require engagement, gathering multiple perspectives during message development, and using new approaches for collecting both quantitative and qualitative data while mitigating anonymity and confidentiality concerns.

Reward Design For An Online Reinforcement Learning Algorithm Supporting Oral Self-Care.

While dental disease is largely preventable, professional advice on optimal oral hygiene practices is often forgotten or abandoned by patients. Therefore patients may benefit from timely and personalized encouragement to engage in oral self-care behaviors. In this paper, we develop an online reinforcement learning (RL) algorithm for use in optimizing the delivery of mobile-based prompts to encourage oral hygiene behaviors. One of the main challenges in developing such an algorithm is ensuring that the algorithm considers the impact of current actions on the effectiveness of future actions (i.e., delayed effects), especially when the algorithm has been designed to run stably and autonomously in a constrained, real-world setting characterized by highly noisy, sparse data. We address this challenge by designing a quality reward that maximizes the desired health outcome (i.e., high-quality brushing) while minimizing user burden. We also highlight a procedure for optimizing the hyperparameters of the reward by building a simulation environment test bed and evaluating candidates using the test bed. The RL algorithm discussed in this paper will be deployed in Oralytics. To the best of our knowledge, Oralytics is the first mobile health study utilizing an RL algorithm designed to prevent dental disease by optimizing the delivery of motivational messages supporting oral self-care behaviors.

CD44-SNA1 integrated cytopathology for delineation of high grade dysplastic and neoplastic oral lesions.

The high prevalence of oral potentially-malignant disorders exhibits diverse severity and risk of malignant transformation, which mandates a Point-of-Care diagnostic tool. Low patient compliance for biopsies underscores the need for minimally-invasive diagnosis. Oral cytology, an apt method, is not clinically applicable due to a lack of definitive diagnostic criteria and subjective interpretation. The primary objective of this study was to identify and evaluate the efficacy of biomarkers for cytology-based delineation of high-risk oral lesions. A comprehensive systematic review and meta-analysis of biomarkers recognized a panel of markers (n: 10) delineating dysplastic oral lesions. In this observational cross sectional study, immunohistochemical validation (n: 131) identified a four-marker panel, CD44, Cyclin D1, SNA-1, and MAA, with the best sensitivity (>75%; AUC>0.75) in delineating benign, hyperplasia, and mild-dysplasia (Low Risk Lesions; LRL) from moderate-severe dysplasia (High Grade Dysplasia: HGD) along with cancer. Independent validation by cytology (n: 133) showed that expression of SNA-1 and CD44 significantly delineate HGD and cancer with high sensitivity (>83%). Multiplex validation in another cohort (n: 138), integrated with a machine learning model incorporating clinical parameters, further improved the sensitivity and specificity (>88%). Additionally, image automation with SNA-1 profiled data set also provided a high sensitivity (sensitivity: 86%). In the present study, cytology with a two-marker panel, detecting aberrant glycosylation and a glycoprotein, provided efficient risk stratification of oral lesions. Our study indicated that use of a two-biomarker panel (CD44/SNA-1) integrated with clinical parameters or SNA-1 with automated image analysis (Sensitivity >85%) or multiplexed two-marker panel analysis (Sensitivity: >90%) provided efficient risk stratification of oral lesions, indicating the significance of biomarker-integrated cytopathology in the development of a Point-of-care assay.

Interpretable and Reliable Oral Cancer Classifier with Attention Mechanism and Expert Knowledge Embedding via Attention Map.

Convolutional neural networks have demonstrated excellent performance in oral cancer detection and classification. However, the end-to-end learning strategy makes CNNs hard to interpret, and it can be challenging to fully understand the decision-making procedure. Additionally, reliability is also a significant challenge for CNN based approaches. In this study, we proposed a neural network called the attention branch network (ABN), which combines the visual explanation and attention mechanisms to improve the recognition performance and interpret the decision-making simultaneously. We also embedded expert knowledge into the network by having human experts manually edit the attention maps for the attention mechanism. Our experiments have shown that ABN performs better than the original baseline network. By introducing the Squeeze-and-Excitation (SE) blocks to the network, the cross-validation accuracy increased further. Furthermore, we observed that some previously misclassified cases were correctly recognized after updating by manually editing the attention maps. The cross-validation accuracy increased from 0.846 to 0.875 with the ABN (Resnet18 as baseline), 0.877 with SE-ABN, and 0.903 after embedding expert knowledge. The proposed method provides an accurate, interpretable, and reliable oral cancer computer-aided diagnosis system through visual explanation, attention mechanisms, and expert knowledge embedding.

Inter-observer agreement among specialists in the diagnosis of Oral Potentially Malignant Disorders and Oral Cancer using Store-and-Forward technology.

Oral Cancer is one of the most common causes of morbidity and mortality. Screening and mobile Health (mHealth) based approach facilitates remote early detection of Oral cancer in a resource-constrained settings. The emerging eHealth technology has aided specialist reach to rural areas enabling remote monitoring and triaging to downstage Oral cancer. Though the diagnostic accuracy of the remote specialist has been evaluated, there are no studies evaluating the consistency among the remote specialists, to the best of our knowledge. The purpose of the study was to evaluate the interobserver agreement between the specialists through telemedicine systems in real-world settings using store and forward technology. Two remote specialists independently diagnosed the clinical images from image repositories, and the diagnostic accuracy was compared with onsite specialist and histopathological diagnosis when available. Moderate agreement (k = 0.682) between two remote specialists and (k = 0.629) between the onsite specialist and two remote specialists in diagnosing oral lesions. The sensitivity and specificity of remote specialist 1 were 92.7% and 83.3%, whereas remote specialist 2 was 95.8% and 60%, respectively, compared to histopathology. The store and forward technology and telecare can be effective tools in triaging and surveillance of patients.

Utility of a salivary biosensor for objective assessment of surgery-related stress.

PURPOSE: To evaluate the clinical utility of a salivary α-amylase (sAA) biosensor for assessing oral surgery-related stress responses and the differential effect of the personality trait of pain catastrophizing. PATIENTS AND METHODS: A prospective cohort study was conducted in 76 healthy subjects who underwent elective removal of their third molars. Along with subjects' self-reports of anxiety and pain, biosensor-facilitated measurements of sAA levels were obtained at multiple time points during the preoperative consult, surgery, and postsurgical follow-up visits. In addition, subjects completed the Pain Catastrophizing Scale at baseline. Mixed-effect regression models examined changes in sAA levels and self-report ratings within and across visits and the contribution of pain catastrophizing. RESULTS: The sAA levels were lower during surgery and postsurgical follow-up compared with the consult visit (P < .01). The sAA levels decreased during the surgery visit (P < .05) and did not change during the consult or follow-up visits. Individuals who reported greater helplessness to pain manifested higher sAA levels during the surgery visit (P < .05). Self-reported anxiety ratings were highest during the surgery visit, and pain ratings were highest during the follow-up visit. CONCLUSIONS: The sAA levels did not show the predicted increases during the surgery visit compared with the consult and postsurgical follow-up visits or increases during the surgery visit. However, individuals who reported responding to pain with helplessness had higher sAA levels in anticipation of surgery, providing proof of concept for the value of point-of-care assessments of surgery-induced stresses and the differential effect of personality traits.