We report the case of a 79-year-old female with a complex medical history, presenting with recurrent gingival swelling, progressive gingival hyperplasia, and osteonecrosis of the jaw potentially associated with tocilizumab. Oral complications developed in close proximity to diagnosis of chronic myelomonocytic leukemia, complicating diagnosis and management.

This systematic analysis assesses the total and risk-attributable burden of lip and oral cavity cancer and other pharyngeal cancer for 204 countries and territories and by Socio-demographic Index using 2019 Global Burden of Diseases, Injuries, and Risk Factors Study estimates.

Importance:Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning. Objective:To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates. Evidence Review:The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019. Findings:In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia. Conclusions and Relevance:In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts.

Objectives Mechanisms underlying burning mouth syndrome (BMS) remain unclear. Evidence of changes in oral mucosal epithelial cells has been found in patients with BMS. This case-control study aimed to investigate whether BMS cases have evidence of impaired mucosal barrier function compared with controls without BMS, focusing on the role of salivary mucins as a first line of defense for oral epithelial cells. Study Design A total of 50 women (22 BMS cases and 28 healthy controls) age 50 years or older were included in this study. Participants attended a clinical visit including assessment of BMS symptoms, salivary sample collection, oral examination, swab for candida detection, and DNA collection using the DNA•SAL device. Total protein concentration was measured using the bicinchoninic acid assay. MUC1 protein concentration in saliva samples was quantified by sandwich enzyme-linked immunosorbent assay (Invitrogen). Salivary glycosylation was assessed by protein-normalized dot blot against 3 lectins (Maackia Amurensis Lectin II; WGA: wheat germ agglutinin; UEA: ulex europeus agglutinin (MAL-II), WGA, and UEA). H antigen, the precursor of ABO antigens, secretor status was predicted by performing Sanger DNA sequencing of the FUT2 gene. Results The average salivary protein concentration was 1.30 mg/mL in BMS cases vs 0.94 mg/mL in controls (P = .15). Mann-Whitney U test showed a trend toward lower levels of MUC1 in BMS cases (n = 20, sum of ranks = 392.50) compared with controls (n = 24, sum of ranks = 597.50; P = .17). UEA, MALII, and WGA reactivities were each quantitatively lower in cases compared with controls but varied widely (P = NS). The percentage of nonsecretors was 23% among cases vs 38% among controls (P = .28). Genotype-predicted secretors had significantly higher UEA reactivity compared with nonsecretors (P < .001). Conclusions Our study overall found trends consistent with higher salivary protein concentration, lower salivary MUC1 levels, and salivary hypoglycosylation in BMS cases compared with controls, although no findings were statistically significant. Study limitations include subject heterogeneity and sample size. As expected, UEA levels were significantly higher in secretors compared with nonsecretors. Other aspects of the oral epithelial barrier, including the quantity of other mucins and glycosylation, remain to be examined.

Objectives: Conditioned pain modulation (CPM) is a psychophysical parameter that is used to reflect the efficacy of endogenous pain inhibition. CPM reliability is important for research and potential clinical applications. The aim of this systematic review and meta-analysis was to evaluate the reliability of CPM tests in healthy individuals and chronic pain patients. Methods: We searched three databases for peer-reviewed studies published from inception to October 2020: EMBASE, Web of Science and NCBI. Risk of bias and the quality of the included studies were assessed. A meta-analysis with a random effects model was conducted to estimate intraclass correlation coefficients (ICCs). Results: Meta-analysis was performed on 25 papers that examined healthy participants (k=21) or chronic pain patients (k=4). The highest CPM intra-session reliability was with pressure as test stimulus (TS) and ischemic pressure (IP) or cold pressor test (CPT) as conditioning stimulus (CS) in healthy individuals (ICC 0.64, 95% CI 0.45-0.77), and pressure as TS with CPT as CS in patients (ICC 0.77, 95% CI 0.70-0.82). The highest inter-session ICC was with IP as TS and IP or CPT as CS (ICC 0.51, 95% CI 0.42-0.59) in healthy subjects. The only data available in patients for inter-session reliability were with pressure as TS and CPT as CS (ICC 0.44, 95% CI 0.11-0.69). Quality ranged from very good to excellent using the QACMRR checklist. The majority of the studies (24 out of 25) scored inadequate in Kappa coefficient reporting item of the COSMIN-ROB checklist. Conclusions: Pressure and CPT were the TS and CS most consistently associated with good to excellent intra-session reliability in healthy volunteers and chronic pain patients. The inter-session reliability was fair or less for all modalities, both in healthy volunteers and chronic pain patients.

Objectives Neurotoxin injection into muscles to reduce movement or pain has seen increasing use and study. For orofacial pain, however, patient selection factors and long-term efficacy are not well characterized. The objective of the present study was to describe the clinical characteristics and effects in a series of patients with temporomandibular disorder [TMD] pain who had received multiple masseter neurotoxin injections over the course of years. Methods Patients referred for tertiary/quaternary care within the oral medicine clinical services from April 2015 to December 2019 were investigated. At least 40 patients with TMD pain were treated with botulinum toxin over this time period. Extensive baseline questionnaires along with pain drawings were used to characterize the patients, including graded chronic pain and related Pain, Enjoyment of Life and General Activity [PEG] scales. Symptom Checklist 90 Revised [SCL-90 R], General Anxiety Disorder 7-item [GAD-7], and Patient Health Questionnaire 9 [PHQ-9] psychological measures were also administered. Diagnostic Criteria for Temporomandibular Disorders [DC-TMD] examinations were done at each visit, along with standardized assessments of neurosensory abnormalities, with masseter and temporalis estimated volume. Fifty units of incobotulinum toxin A were injected into superior and inferior masseters bilaterally in each patient. Returning patients were seen in follow-up from 1 to 4.5 years later in the clinic with extensive metrics. Results Of 40 patients with TMD treated with at least 1 encounter with neurotoxin, 4 were located who had received at least 3 injection procedures over 12 months or longer and reported 50% or greater reduction in average pain intensity and pain impact. These patients’ ages were 27, 29, 29, and 32 years; 3 were female. All reported having TMD pain for more than 5 years, and all were diagnosed with masseter myalgia, masseteric hypertrophy, definite sleep bruxism, migraine or tension-type headache, and mild to moderate psychological distress. All 4 were treated initially with self-care, nonsteroidal anti-inflammatory drugs, muscle relaxants, and occlusal appliances with some success, but they desired more reduction of pain and pain impact. All patients reported pain reduction after neurotoxin within 2-3 weeks, with effective (50-100%) pain relief for up to 6 months. Total injection visits ranged from 3 to 9 over the course of 1 to 4.5 years. Conclusions For a subset of patients with subacute TMD masseter pain, botulinum toxin injections resulted in substantial reductions in orofacial pain intensity and impact that could be sustained with repeated injections. Neurotoxin injection into muscles to reduce movement or pain has seen increasing use and study. For orofacial pain, however, patient selection factors and long-term efficacy are not well characterized. The objective of the present study was to describe the clinical characteristics and effects in a series of patients with temporomandibular disorder [TMD] pain who had received multiple masseter neurotoxin injections over the course of years. Patients referred for tertiary/quaternary care within the oral medicine clinical services from April 2015 to December 2019 were investigated. At least 40 patients with TMD pain were treated with botulinum toxin over this time period. Extensive baseline questionnaires along with pain drawings were used to characterize the patients, including graded chronic pain and related Pain, Enjoyment of Life and General Activity [PEG] scales. Symptom Checklist 90 Revised [SCL-90 R], General Anxiety Disorder 7-item [GAD-7], and Patient Health Questionnaire 9 [PHQ-9] psychological measures were also administered. Diagnostic Criteria for Temporomandibular Disorders [DC-TMD] examinations were done at each visit, along with standardized assessments of neurosensory abnormalities, with masseter and temporalis estimated volume. Fifty units of incobotulinum toxin A were injected into superior and inferior masseters bilaterally in each patient. Returning patients were seen in follow-up from 1 to 4.5 years later in the clinic with extensive metrics. Of 40 patients with TMD treated with at least 1 encounter with neurotoxin, 4 were located who had received at least 3 injection procedures over 12 months or longer and reported 50% or greater reduction in average pain intensity and pain impact. These patients’ ages were 27, 29, 29, and 32 years; 3 were female. All reported having TMD pain for more than 5 years, and all were diagnosed with masseter myalgia, masseteric hypertrophy, definite sleep bruxism, migraine or tension-type headache, and mild to moderate psychological distress. All 4 were treated initially with self-care, nonsteroidal anti-inflammatory drugs, muscle relaxants, and occlusal appliances with some success, but they desired more reduction of pain and pain impact. All patients reported pain reduction after neurotoxin within 2-3 weeks, with effective (50-100%) pain relief for up to 6 months. Total injection visits ranged from 3 to 9 over the course of 1 to 4.5 years. For a subset of patients with subacute TMD masseter pain, botulinum toxin injections resulted in substantial reductions in orofacial pain intensity and impact that could be sustained with repeated injections.

Burning mouth syndrome (BMS) is a chronic pain condition that most commonly affects postmenopausal women older than 50 years of age. Xerostomia is a common complaint among BMS patients. However, previous studies showed inconsistent findings regarding saliva flow rate reduction. This study examined saliva flow rates, degree of mucosal hydration, xerostomia, and clinical characteristics in BMS patients compared with healthy controls. Unstimulated whole saliva (USWS) was collected through passive drooling; residual mucosal saliva (RMS) was collected using filter paper strips. Stimulated whole saliva (SWS) was collected while chewing on gum base. Oral exam and self-report data were collected. A total of 50 women (22 BMS cases and 28 healthy controls) aged 50 years or older were included in the analysis of this study. Mean age was 62 years for cases and 56 years for controls (P=0.05). Compared with controls, cases had significantly lower USWS flow rates (P<0.001) and had a higher prevalence of xerostomia (P=0.001), gastrointestinal disease (P<0.001), and vaginal dryness (P=0.01). These data show that oral and vaginal dryness are common among BMS patients. Further studies are needed to investigate potential pathophysiological mechanisms related to the quality of saliva and mucosal barrier status among these patients.

s Committee: Chair: Kentaro Ikeda, DDS, MPH Co-Chair: Bhavik Desai, DMD, PhD 1:00PM #1: Whole Saliva And Residual Mucosal Saliva In Patients With Burning Mouth Syndrome: A Case-Control Study *Sumeia Gamal Werfalli, Mark Drangsholt, Michael Martin, Linda LeResche University of Washington, USA Objectives: Burning Mouth Syndrome (BMS) is a chronic pain condition. Xerostomia is a common complaint among BMS patients. However, previous studies showed inconsistent findings regarding saliva flow rate reduction among these patients. The aim of this study was to examine unstimulated (UWS) and stimulated (SWS) whole saliva flow rates, degree of mucosal hydration and xerostomia in female BMS patients compared with controls. Methods: Cases were female patients at a university oral medicine clinic diagnosed with BMS (ICD-10 code K14.6). Controls were similarly-aged women without BMS. Collection of salivary samples and other data took place during a 1-hour session between 9:00am and 12:00pm. UWS was collected under resting conditions by passive drooling into a plastic tube for 10 minutes; to assess mucosal hydration, residual mucosal saliva (RMS) was collected using filter paper strips from four mucosal sites-anterior hard palate, buccal mucosa, anterior tongue and lower lip. Strips were placed in a microcentrifuge tube and weighed. SWS was collected while chewing on gum base for 5 minutes. Low UWS was defined as ≤ 0.1 ml/min and low SWS as ≤ 0.7 ml/min. Participants completed the Short-form of the Xerostomia Inventory (SXI-D). We used chi square to assess association between UWS, SWS and BMS and t-tests to assess differences in RMS levels. Results: 56 women (27 cases and 29 controls) participated in this study. Mean age was 61 years for cases and 58 for controls (n.s.); the majority in each group were post-menopausal. 66% of cases vs. 38% of controls had low UWS (p =0.03). 48% of cases vs. 34% of controls had low SWS (p=0.06). Compared to controls, BMS cases had lower mean levels of tongue RMS (0.007 gm vs. 0.01gm, p=0.03). 55% of the cases vs. 7% of controls reported xerostomia (p < 0.001). UWS and SWS were not related to xerostomia report, but RMS on the tongue was significantly lower among women with xerostomia (p=0.002). Conclusions: BMS patients had statistically significant reductions in UWS, tongue RMS, and a higher prevalence of xerostomia. Low hydration of the tongue should be further investigated as a possible trigger of xerostomia sensation. #2: Mandibular And Palatal Tori Exposed By Trauma Are Risk Factors For Medication Related Osteonecrosis Of The Jaws. A Report From The Copenhagen ONJ Cohort *Morten Schiødt Copenhagen University Hospital, Aarhus University Hospital, Denmark Objectives: Mandibular and palatal tori are usually considered anatomical risk factors for the development of medication related osteonecrosis of the jaws (MRONJ/ONJ). However, trauma may also be involved in the pathogenesis. To examine the prevalence and characteristics of MRONJ related to tori within the Copenhagen ONJ cohort and to evaluate trauma as a possible risk factor.

Objectives Burning mouth syndrome (BMS) is a chronic pain condition. Xerostomia is a common complaint among patients with BMS. However, previous studies have reported inconsistent findings regarding salivary flow rate reduction among these patients. The aim of this study was to examine unstimulated whole saliva (UWS) and stimulated whole saliva (SWS) flow rates, degree of mucosal hydration, and xerostomia in female patients with BMS compared with controls. Study Design The study included female patients diagnosed with BMS (ICD-10 code K14.6) at a university oral medicine clinic. Controls were similarly aged women without BMS. Collection of salivary samples and other data took place during a 1-hour session between 9:00 a.m. and 12:00 noon. UWS was collected under resting conditions by passive drooling into a plastic tube for 10 minutes; to assess mucosal hydration, residual mucosal saliva (RMS) was collected by using filter paper strips, from 4 mucosal sites—anterior hard palate, buccal mucosa, anterior tongue, and lower lip. The strips were then placed in a microcentrifuge tube and weighed. SWS was collected while the patient chewed on gum base for 5 minutes. Low UWS was defined as 0.1 mL/min or less and low SWS as 0.7 mL/min or less. Participants completed the Short Form of the Xerostomia Inventory (SXI-D). We used the χ2 test to assess the association between UWS, SWS, and BMS and t tests to assess the differences in residual mucosal saliva (RMS) levels. Results Fifty-six women (27 cases and 29 controls) participated in this study. Mean age was 61 years for cases and 58 for controls (n.s.). Most participants in each group were postmenopausal; 66% of cases versus 38% of controls had low UWS (P = .03; and 48% of cases versus 34% of controls had low SWS (P =.06). Compared with controls, BMS cases had lower mean levels of tongue RMS (0.007 g vs 0.01 g; P = .03); 55% of the cases versus 7% of controls reported xerostomia (P < .001). UWS and SWS were not related to reporting of xerostomia, but RMS on the tongue was significantly lower in women with xerostomia (P = .002). Conclusions Patients with BMS had statistically significant reductions in UWS and tongue RMS and a higher prevalence of xerostomia. Low hydration of the tongue should be further investigated as a possible trigger of xerostomia sensation. Burning mouth syndrome (BMS) is a chronic pain condition. Xerostomia is a common complaint among patients with BMS. However, previous studies have reported inconsistent findings regarding salivary flow rate reduction among these patients. The aim of this study was to examine unstimulated whole saliva (UWS) and stimulated whole saliva (SWS) flow rates, degree of mucosal hydration, and xerostomia in female patients with BMS compared with controls. The study included female patients diagnosed with BMS (ICD-10 code K14.6) at a university oral medicine clinic. Controls were similarly aged women without BMS. Collection of salivary samples and other data took place during a 1-hour session between 9:00 a.m. and 12:00 noon. UWS was collected under resting conditions by passive drooling into a plastic tube for 10 minutes; to assess mucosal hydration, residual mucosal saliva (RMS) was collected by using filter paper strips, from 4 mucosal sites—anterior hard palate, buccal mucosa, anterior tongue, and lower lip. The strips were then placed in a microcentrifuge tube and weighed. SWS was collected while the patient chewed on gum base for 5 minutes. Low UWS was defined as 0.1 mL/min or less and low SWS as 0.7 mL/min or less. Participants completed the Short Form of the Xerostomia Inventory (SXI-D). We used the χ2 test to assess the association between UWS, SWS, and BMS and t tests to assess the differences in residual mucosal saliva (RMS) levels. Fifty-six women (27 cases and 29 controls) participated in this study. Mean age was 61 years for cases and 58 for controls (n.s.). Most participants in each group were postmenopausal; 66% of cases versus 38% of controls had low UWS (P = .03; and 48% of cases versus 34% of controls had low SWS (P =.06). Compared with controls, BMS cases had lower mean levels of tongue RMS (0.007 g vs 0.01 g; P = .03); 55% of the cases versus 7% of controls reported xerostomia (P < .001). UWS and SWS were not related to reporting of xerostomia, but RMS on the tongue was significantly lower in women with xerostomia (P = .002). Patients with BMS had statistically significant reductions in UWS and tongue RMS and a higher prevalence of xerostomia. Low hydration of the tongue should be further investigated as a possible trigger of xerostomia sensation.

Background and aims: Conditioned Pain Modulation (CPM) is a measure of pain inhibition-facilitation in humans that may elucidate pain mechanisms and potentially serve as a diagnostic test. In laboratory settings, the difference between two pain measures [painful test stimulus (TS) without and with the conditioning stimulus (CS) application] reflects the CPM magnitude. Before the CPM test can be used as a diagnostic tool, its reliability on the same day (intra-session) and across multiple days (inter-session) needs to be known. Furthermore, it is important to determine the most reliable anatomical sites for both the TS and the CS. This study aimed to measure the intra-session and inter-session reliability of the CPM test paradigm in healthy subjects with the TS ( pressure pain threshold-PPT) applied to three test sites: the face, hand, and dorsum of the foot, and the CS (cold pressor test-CPT) applied to the contralateral hand. Methods: Sixty healthy participants aged 18-65 were tested by the same examiner on 3 separate days, with an interval of 2-7 days. On each day, testing was comprised of two identical experimental sessions in which the PPT test was performed on each of the three dominant anatomical sites in randomized order followed by the CPM test (repeating the PPT with CPT on the non-dominant hand). CPM magnitude was calculated as the percent change in PPT. The Intraclass Correlation Coefficient (ICC), Coefficient of Variation (CV), and Bland-Altman analyses were used to assess reliability. Results: PPT relative reliability ranged from good to excellent at all three sites; the hand showed an intra-session ICC of 0.90 (0.84, 0.94) before CPT and ICC of 0.89 (0.83, 0.92) during CPT. The PPT absolute reliability was also high, showing a low bias and small variability when performed on all three sites; for example, CV of the hand intra-session was 8.0 before CPT and 8.1 during CPT. The relative reliability of the CPM test, although only fair, was most reliable when performed during the intra-session visits on the hand; ICC of 0.57 (0.37, 0.71) vs. 0.20 (0.03, 0.39) for the face, and 0.22 (0.01, 0.46) for the foot. The inter-session reliability was lower in all three anatomical sites, with the best reliability on the hand with an ICC of 0.40 (0.23, 0.55). The pattern of absolute reliability of CPM was similar to the relative reliability findings, with the reliability best on the hand, showing lower intra-session and inter-session variability (CV% = 43.5 and 51.5, vs. 70.1 and 73.1 for the face, and 75.9 and 78.9 for the foot). The CPM test was more reliable in women than in men, and in older vs. younger participants. Discussion: The CPM test was most reliable when the TS was applied to the dominant hand and CS performed on the contralateral hand. These data indicate that using the CS and TS in the same but contralateral dermatome in CPM testing may create the most reliable results.

Single subject research design, also known as N-of-1 research, is a scientific method in which an individual person serves as the research subject. We treat “N-of-1” and “single subject” as synonyms encompassing all scientific practice which focuses on observations made about a single person. Other names for similar and overlapping approaches include: single case experiments [1–3] single case research [4, 5], single case designs [6], and single patient trials [7]. Some authors distinguish between single subject research in general, which may be descriptive and exploratory in character, and single subject experiments that are prospectively planned and use formal methods such as randomization, blinding, or crossover comparisons. Here, we use N-of-1 and single subject research as synonymous, high level general terms for research focused on an individual rather than a group. N-of-1 research is common in applied fields of psychology, education, and human behavior where it has benefited from extensive methodical research and practical guidance for practitioners [8, 9]. However, over a half-century of study and advocacy, including pioneering publications by Guyatt et al., Larson et al., Mahon et al., and others, have failed to establish single subject science as central to research and practice in medicine [10–13]. A systematic review of 122 eligible N-of-1 studies published between 1985 and 2013 showed wide variation in methodology and reporting, reducing the power of these studies to influence practice [14]. Researchers advocating N-of-1 techniques have noted that the practical obstacles to design, conduct, analyze and apply the results for single subjects have simply been too high [15, 16]. Nevertheless the rise of personalized medicine and patient-centered research create new opportunities for using N-of-1 methods [17, 18]. Recent key publications include an extensive and comprehensive user guide for the design and implementation of N-of-1 trials [19], an update of the standard (CONSORT) for reporting N-of-1 trials [20, 21], and a special issue of the Journal of Clinical Epidemiology devoted to individual patients as the primary source and target of clinical research [22]. General public interest in gathering data about health is also growing. A Pew Internet study conducted in 2013 found that 1 in 5 Americans use some form of technology to track their health [23]. In 2016, the number of consumers in the United States who use mobile health apps increased from 16 percent in 2014 to 33 percent and the number of consumers who use health wearables increased from 9 percent to 21 percent [24]. According to data from the International Data Corporation (IDC), 104.3 million wearable devices were shipped in 2016, a number that is likely to be almost doubled by 2021 [25]. The increasing availability of home blood testing kits, wearable glucose monitors, and heart rate monitors, among other consumer health tools and services, suggest a large scale transformation of the measurement context for N-of-1 research. The combination of increased public interest and reliable measurement technologies broadly available may reduce the barriers to application of N-of-1 methodology [16, 26]. These consumer technologies have already attracted research attention. For instance, activity trackers made by Fitbit, Inc, have been deployed as instrumentation in over 450 public scientific studies [27]. Of course, application of wearables for clinical or research practice requires the technology to be valid and reliable. Research has found considerable variation of accuracy in different consumer wearables, including activity trackers [28–30], sleep trackers [31, 32], and wrist worn heart rate monitors [33, 34]. Despite this variation, there have been some notable successes. For instance, in an innovative two year study published in 2017, Li et al. demonstrated that measurement of heart rate and skin temperature using consumer wearables could predict inflammatory response as revealed by laboratory blood work showing elevated hs-CRP and onset of symptoms [35]. In presenting the articles in this focus theme, we aim to encourage attention to single subject research from from both scholars and researchers in health and biomedical informatics who may play a key role in advancing its practical methods and resolving doubts about its power and validity.

HYPOTHESIS:It has been hypothesized that high fungiform papillae density may be a risk factor for developing the taste and pain alterations characteristic of burning mouth syndrome. OBJECTIVE:Evaluate whether fungiform papillae density, taste sensitivity, and mechanical pain sensitivity differ between burning mouth syndrome cases and controls. STUDY DESIGN:This case-control study compared cases diagnosed with primary burning mouth syndrome with pain-free controls. METHODS:Participants (17 female cases and 23 female controls) rated the intensity of sucrose, sodium chloride, citric acid, and quinine applied separately to each side of the anterior tongue and sampled whole mouth. Mechanical pain sensitivity was assessed separately for each side of the tongue using weighted pins. Digital photographs of participants' tongues were used to count fungiform papillae. RESULTS:Burning mouth syndrome cases had increased whole mouth taste intensity. Cases also had increased sensitivity to quinine on the anterior tongue, as well as increased mechanical pain sensitivity on the anterior tongue. Fungiform papillae density did not differ significantly between cases and controls. Fungiform papillae density on the left and right sides of the tongue were correlated in controls; however, there was no left/right side correlation in cases. CONCLUSION:Cases had increased pain and taste perception on the anterior tongue. The lack of correlation between left and right fungiform papillae density in cases may be an indication of asymmetrical lingual innervation in these patients. LEVEL OF EVIDENCE:3b. Laryngoscope, 128:841-846, 2018.

Squamous cell carcinoma (SCC) is the most common type of cancer seen in the oropharynx. Early diagnosis & management is of utmost importance in these cancers because the spread of unrecognized disease is often fatal. Symptoms after oropharyngeal cancer treatment can lead to delayed or misdiagnosis. Analysis of a recent oropharyngeal cancer case with symptoms that mimicked other orofacial pain conditions leading to diagnostic delay, is presented to help prevent poor outcomes and delays in similar cases.

Aims: The original Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis I diagnostic algorithms have been demonstrated to be reliable. However, the Validation Project determined that the RDC/TMD Axis I validity was below the target sensitivity of ≥ 0.70 and specificity of ≥ 0.95. Consequently, these empirical results supported the development of revised RDC/TMD Axis I diagnostic algorithms that were subsequently demonstrated to be valid for the most common pain-related TMD and for one temporomandibular joint (TMJ) intra-articular disorder. The original RDC/TMD Axis II instruments were shown to be both reliable and valid. Working from these findings and revisions, two international consensus workshops were convened, from which recommendations were obtained for the finalization of new Axis I diagnostic algorithms and new Axis II instruments. Methods: Through a series of workshops and symposia, a panel of clinical and basic science pain experts modified the revised RDC/TMD Axis I algorithms by using comprehensive searches of published TMD diagnostic literature followed by review and consensus via a formal structured process. The panel’s recommendations for further revision of the Axis I diagnostic algorithms were assessed for validity by using the Validation Project’s data set, and for reliability by using newly collected data from the ongoing TMJ Impact Project—the follow-up study to the Validation Project. New Axis II instruments were identified through a comprehensive search of the literature providing valid instruments that, relative to the RDC/TMD, are shorter in length, are available in the public domain, and currently are being used in medical settings. Results: The newly recommended Diagnostic Criteria for TMD (DC/TMD) Axis I protocol includes both a valid screener for detecting any pain-related TMD as well as valid diagnostic criteria for differentiating the most common pain-related TMD (sensitivity ≥ 0.86, specificity ≥ 0.98) and for one intra-articular disorder (sensitivity of 0.80 and specificity of 0.97). Diagnostic criteria for other common intra-articular disorders lack adequate validity for clinical diagnoses but can be used for screening purposes. Inter-examiner reliability for the clinical assessment associated with the validated DC/TMD criteria for pain-related TMD is excellent (kappa ≥ 0.85). Finally, a comprehensive classification system that includes both the common and less common TMD is also presented. The Axis II protocol retains selected original RDC/TMD screening instruments augmented with new instruments to assess jaw function as well as behavioral and additional psychosocial factors. The Axis II protocol is divided into screening and comprehensive selfreport instrument sets. The screening instruments' 41 questions assess pain intensity, pain-related disability, psychological distress, jaw functional limitations, and parafunctional behaviors, and a pain drawing is used to assess locations of pain. The comprehensive instruments, composed of 81 questions, assess in further detail jaw functional limitations and psychological distress as well as additional constructs of anxiety and presence of comorbid pain conditions. Conclusion: The recommended evidence-based new DC/TMD protocol is appropriate for use in both clinical and research settings. More comprehensive instruments augment short and simple screening instruments for Axis I and Axis II. These validated instruments allow for identification of patients with a range of simple to complex TMD presentations. J Oral Facial Pain Headache 2014;28:6–27. doi: 10.11607/jop.1151

OBJECTIVESWe investigated general dentists' reasons for recommending removal or retention of third molars and whether patients adhered to dentists' recommendations.METHODSIn a 2-year prospective cohort study (2009-2011) in the Pacific Northwest, we followed 801 patients aged 16 to 22 years from 50 general dental practices. Generalized estimating equations logistic regressions related patient and dentist characteristics to dentists' recommendations to remove third molars and to patient adherence.RESULTSGeneral dentists recommended removal of 1683 third molars from 469 (59%) participants, mainly to prevent future problems (79%) or because a third molar had an unfavorable orientation or was unlikely to erupt (57%). Dentists recommended retention and monitoring of 1244 third molars from 366 (46%) participants, because it was too early to decide (73%), eruption path was favorable (39%), or space for eruption was sufficient (26%). When dentists recommended removal, 55% of participants adhered to this recommendation during follow-up, and the main reason was availability of insurance (88%).CONCLUSIONSGeneral dentists frequently recommended removal of third molars for reasons not related to symptoms or pathology, but rather to prevent future problems.

The reliability of comprehensive intra-oral quantitative sensory testing (QST) protocol has not been examined systematically in patients with chronic oro-facial pain. The aim of the present multicentre study was to examine test-retest and interexaminer reliability of intra-oral QST measures in terms of absolute values and z-scores as well as within-session coefficients of variation (CV) values in patients with atypical odontalgia (AO) and healthy pain-free controls. Forty-five patients with AO and 68 healthy controls were subjected to bilateral intra-oral gingival QST and unilateral extratrigeminal QST (thenar) on three occasions (twice on 1 day by two different examiners and once approximately 1 week later by one of the examiners). Intra-class correlation coefficients and kappa values for interexaminer and test-retest reliability were computed. Most of the standardised intra-oral QST measures showed fair to excellent interexaminer (9-12 of 13 measures) and test-retest (7-11 of 13 measures) reliability. Furthermore, no robust differences in reliability measures or within-session variability (CV) were detected between patients with AO and the healthy reference group. These reliability results in chronic orofacial pain patients support earlier suggestions based on data from healthy subjects that intra-oral QST is sufficiently reliable for use as a part of a comprehensive evaluation of patients with somatosensory disturbances or neuropathic pain in the trigeminal region.

OBJECTIVES:We investigated outcomes of third molar removal or retention in adolescents and young adults.METHODS:We recruited patients aged 16 to 22 years from a dental practice-based research network in the Pacific Northwest from May 2009 through September 2010 who had at least 1 third molar present and had never undergone third molar removal. Data were acquired via questionnaire and clinical examination at baseline, periodic online questionnaires, and clinical examination at 24 months.RESULTS:A total of 801 patients participated. Among patients undergoing third molar removal, rates of paresthesia and jaw joint symptoms lasting more than 1 month were 6.3 and 34.3 per 100 person-years, respectively. Among patients not undergoing removal, corresponding rates were 0.7 and 8.8. Periodontal attachment loss at distal sites of second molars did not significantly differ by third molar removal status. Incident caries at the distal surfaces of second molars occurred in fewer than 1% of all sites.CONCLUSIONS:Rates of paresthesia and temporomandibular joint disorder were higher after third molar removal. Periodontal attachment loss and incident caries at the distal sites of second molars were not affected by extraction status.