The Contribution of Insomnia and Obstructive Sleep Apnea on the Transition from Acute to Chronic Painful Temporomandibular Disorders and their Persistence: A Prospective 3-Month Cohort Study.

Background: Insomnia, and Excessive Daytime Sleepiness (EDS), a surrogate marker of Obstructive Sleep Apnea (OSA), are common sleep-related conditions among painful temporomandibular disorders (TMD) patients. OSA was found to increase the risk of chronic painful TMD. Aims: This prospective cohort study aims to determine the contribution of insomnia and EDS on acute to chronic painful TMD transition as well as its persistence when chronic pain is defined by: (i) duration (> 3 months), and (ii) dysfunction (Graded Chronic Pain Scale [GCPS II-IV]). Methods: From 456 patients recruited between 2015 to 2021, through four locations in Canada, 378 completed the follow-up. A diagnosis was obtained using the Research Diagnostic Criteria or the Diagnostic Criteria for TMD. Insomnia was assessed with the Insomnia Severity Scale (ISS), and OSA was assessed using the Epworth Sleepiness Scale (ESS) which measures EDS, both at baseline. Patients completed the GCPS form at baseline and 3-month follow-up. Results: Borderline associations were found between EDS and the transition or persistence of chronic painful TMD when chronic pain was defined by pain duration (RR adjusted_duration = 1.11, P = 0.07) and dysfunction (RRadjusted_dysfunction =1.40, P = 0.051). Furthermore, EDS was specifically associated with persistent painful TMD when chronic pain was defined by pain duration (RR = 1.13, 95%CI: 1.00-1.26, P = 0.04). Insomnia was not related to the study outcomes (RRadjusted_duration = 0.94, P = 0.27, RRadjusted_dysfunction =1.00, P = 0.99). Conclusion: Results indicate that EDS contrary to insomnia predicted the persistence of chronic painful TMD at a 3-month follow-up.

Contexte: L'insomnie et la somnolence excessive en journée, un marqueur substitut de l'apnée du sommeil obstructive, sont des affections courantes liées au sommeil chez les patients souffrant de troubles temporo-mandibulaires douloureux. On a découvert que l'apnée obstructive du sommeil augmentait le risque de troubles temporo-mandibulaires douloureux chroniques.Objectifs: Cette étude de cohorte prospective vise à déterminer la contribution de l'insomnie et de la somnolence excessive en journée à la transition des troubles temporo-mandibulaires douloureux aigus à chroniques, ainsi qu'à leur persistance lorsque la douleur chronique est définie par : (i) la durée (> 3 mois), et (ii) la dysfonction (Échelle de douleur chronique graduée [GCPS II-IV]).Méthodes: Sur 456 patients recrutés entre 2015 et 2021 dans quatre endroits au Canada, 378 ont terminé le suivi. Un diagnostic a été établi en utilisant les Critères de diagnostic pour la recherche ou les Critères de diagnostic pour les troubles temporo-mandibulaires douloureux. L'insomnie a été évaluée à l'aide de l'Indice de sévérité de l'insomnie (ISI) et l'apnée obstructive du sommeil a été évaluée à l'aide de l'Échelle de somnolence d'Epworth (ESS), qui mesure la somnolence excessive en journée, tous deux au début de l'étude. Les patients ont rempli le formulaire GCPS au début de l'étude et lors du suivi à trois mois.Résultats: Des associations marginales ont été trouvées entre la somnolence excessive en journée et la transition ou la persistance des troubles temporo-mandibulaires douloureux chroniques lorsque la douleur chronique était définie par la durée de la douleur (RR ajusté pour la durée = 1,11, P = 0,07) et la dysfonction (RR ajusté pour la dysfonction = 1,40, P = 0,051). De plus, la somnolence excessive en journée était spécifiquement associée à la persistance des troubles temporo-mandibulaires douloureux lorsque la douleur chronique était définie par la durée de la douleur (RR = 1,13, IC à 95 % : 1,00-1,26, P = 0,04). L'insomnie n'était pas liée aux résultats de l'étude (RR ajusté pour la durée = 0,94, P = 0,27, RR ajusté pour la dysfonction = 1,00, P = 0,99).Conclusion: Les résultats indiquent que la somnolence excessive en journée, contrairement à l'insomnie, prédisait la persistance des troubles temporo-mandibulaires douloureux chroniques lors du suivi de trois mois.

The contribution of pain and disability on the transition from acute to chronic pain-related TMD: A 3-month prospective cohort study.

Although most cases of pain-related temporomandibular disorders (TMD) are mild and self-limiting, about 10% of TMD patients develop severe disorders associated with chronic pain and disability. It has been suggested that pain intensity contributes to the transition from acute to chronic pain-related TMD. Therefore, the aims of this current prospective cohort study were to assess if pain intensity, pain always being present, pain or stiffness on awakening, jaw activities, and interference, were associated with the transition from acute to chronic pain-related TMD at 3 months of follow-up. One hundred and nine participants, recruited from four clinics in Montreal and Ottawa, received examinations and completed the required instruments at baseline and at the 3rd month of follow-up. In a multivariable analysis including sex, age, characteristic pain index (CPI) (OR = 1.03, 95%CI = 1.01-1.06, P = 0.005), moderate to severe average pain intensity (OR = 3.51, 95%CI = 1.24-9.93, P = 0.02), disability points score (OR = 1.29, 95%CI = 1.06-1.57, P = 0.01), interferences (ORs = 1.30-1.32, P = 0.003-0.005), screening score (OR = 1.37, 95%CI = 1.08-1.76, P = 0.01), and pain always present (OR = 2.55, 95%CI = 1.08-6.00, P = 0.03) assessed at first-visit were related to the transition outcome at the 3rd month of follow-up. Further, we found that if 4 patients with acute pain-related TMD on average were exposed to these risk factors at baseline, 1 would have the transition from acute to chronic pain at 3 months of follow-up. Results indicate that these factors are associated with the transition from acute to chronic pain-related TMD, and therefore should be considered as important factors when evaluating and developing treatment plans for patients with pain-related TMD.

Back and neck pain: A comparison between acute and chronic pain-related Temporomandibular Disorders.

Background: Temporomandibular disorders (TMDs) are common and cause persistent pain. Comorbidities are associated with TMDs and can affect the effectiveness of their treatments. The literature is lacking enough evidence on the difference between acute and chronic pain, particularly in TMDs. Investigating this difference could highlight potential risk factors for the transition from acute to chronic pain-related TMDs. Aim: To compare the likelihood of back and neck pain (BP, NP) between acute and chronic pain-related TMDs (AP-TMD, CP-TMD) as defined by pain duration and pain-related disability. . Methods: Participants with AP-TMDs (≤3 months) and CP-TMDs (>3 months) were recruited according to the diagnostic criteria and research diagnostic criteria of TMD. BP and NP were assessed using a self-reported checklist. CP-TMDs defined by disability (chronic disability) and depression and anxiety symptoms were assessed using validated instruments. Logistic regression analyses were employed. Results: This study enrolled 487 adults with AP-TMD (n = 118) and CP-TMD (n = 369). Relative to AP-TMD, participants with CP-TMD had twice the odds of reporting NP (odds ratio [OR] = 2.17 , 95% CI 1.27-3.71) but not BP (OR = 0.96, 95% CI 0.57-1.64). Participants with chronic disability were twice as likely to report NP (OR = 1.95 , 95% CI 1.20-3.17 ) but not BP (OR = 1.13, 95% CI 0.69-1.82) compared to those without. All analyses were adjusted for age, sex, and anxiety and depression symptoms. Conclusions: Within the limitations of this study, results suggest that central dysregulation or trigeminocervical convergence mechanisms are implicated in the process of pain-related TMD chronification and highlight the relevance of considering disability when defining CP-TMDs.

Contexte : Les troubles temporo-mandibulaires (TTM) sont fréquents et provoquent des douleurs persistantes. Des comorbidités sont associées aux TTM et peuvent affecter l'efficacité de leur traitement. Il n'y a pas suffisamment de données probantes dans la litt\érature sur la différence entre la douleur aiguë et la douleur chronique, en particulier dans les TTM. L'étude de cette différence pourrait mettre en évidence les facteurs de risque potentiels pour la transition des TTM liés à la douleur aiguë aux TTM liés à la douleur chronique.Objectif : Comparer la probabilité de douleur au dos et de douleur cervicale (DD, DC) entre les TTM liés à la douleur aiguë et les TTM liés à la douleur chronique (TTM-DA, TTM-DC), telles que définis par la durée de la douleur et l'incapacité liée à la douleur.Méthodes : Les participants atteints de TTM-DA (≤3 mois) et de TTM-DC (>3 mois) ont été recrutés selon les critères diagnostiques et les critères diagnostiques pour la recherche en matière de TTM. La douleur au dos et la douleur cervicale ont été évaluées à l'aide d'une liste de contrôle autodéclarée. Les TTM-DC définis par l'invalidité (invalidité chronique) et les symptômes de dépression et d'anxiété ont été évalués à l'aide d'instruments validés. Des analyses de régression logistique ont été utilisées.Résultats : Cette étude a inclus 487 adultes atteints de TTM-DA (n = 118) et de TTM-DC (n = 369). Comparativement aux patients atteints de TTM-DA, les participants atteints de TTM-DC étaient deux fois plus susceptibles de déclarer de la douleur cervicale (rapport de cotes [RC] = 2,17, IC à 95 % 1,27-3,71) mais pas de douleur au dos (RC = 0,96, IC à 95 % 0,57-1,64). Les participants ayant une incapacité chronique étaient deux fois plus susceptibles de déclarer de la douleur cervicale (RC = 1,95, IC à 95 % 1,20-3,17), mais pas de douleur au dos (RC = 1,13, IC à 95 % 0,69-1,82) que ceux n'en ayant pas. Toutes les analyses ont été ajustées en fonction de l'âge, du sexe, de l'anxiété et des symptômes de dépression.Conclusions : Dans les limites de cette étude, les résultats indiquent que la dysrégulation centrale ou les mécanismes de convergence trigéminocervicale sont impliqués dans le processus de chronicisation des TTM liés à la douleur et soulignent la pertinence de tenir compte de l'incapacité au moment de définir les TTM-DC.

Painful and non-painful comorbidities associated with short- and long-term painful temporomandibular disorders: A cross-sectional study among adolescents from Brazil, Canada and France.

BACKGROUND: Temporomandibular disorder (TMD) pain is common among adolescents. The association between painful TMD and other comorbidities has been demonstrated. However, the difference between short-term (<6 months) and long-term (≥ 6 months) painful TMD is not yet clear. OBJECTIVE: The aim of this study was to assess the association between comorbidities and short- and long-term painful TMD among adolescents. METHODS: In this cross-sectional study, adolescents were recruited from Montreal (Canada), Nice (France) and Arceburgo (Brazil). Self-reported painful TMD, comorbidities, school absence and analgesic intake were assessed using reliable instruments. Multivariable logistic regression analyses were conducted to assess the study aims. RESULTS: The prevalence of short- and long-term painful TMD was estimated at 22.29% and 9.93% respectively. The number of comorbidities was associated with short- (OR = 1.71, 95%CI = 1.53-1.90) and long-term painful TMD (OR = 1.79, 95%CI = 1.55-2.08) compared to controls. Frequent headaches (ORshort-term  = 4.39, 95%CI = 3.23-5.98, ORlong-term  = 3.69, 95%CI = 2.45-5.57) and back pain (ORshort-term  = 1.46, 95%CI = 1.06-2.03, ORlong-term  = 1.69, 95%CI = 1.11-2.59) were associated with both painful TMD groups. Frequent neck pain (OR = 2.23, 95%CI = 1.53-3.26) and allergies were only associated with short-term painful TMD (OR = 1.54, 95%CI = 1.13-2.10). Frequent stomach pain was related to long-term (OR = 2.01, 95%CI = 1.35-3.26), and it was the only comorbidity significantly more frequent among the long than short-term TMD (OR = 1.82, 95%CI: 1.14-2.90). These analyses were adjusted by sex, age and city. CONCLUSION: In this multi-centre study, both short- and long-term painful TMD are associated with frequent headaches and back pain, whereas frequent neck pain and allergies are related to only short-term and frequent stomach pain with long-term painful TMD.

Acute and Chronic Temporomandibular Disorder Pain: A critical review of differentiating factors and predictors of acute to chronic pain transition.

AIMS: The aims of this critical review were to: (i) assess the factors that differentiate acute from chronic temporomandibular disorders (TMD) pain; (ii) assess the risk factors associated with the transition from acute to chronic TMD pain; and (iii) summarize and appraise the studies. METHOD: The databases used were MEDLINE, Embase, and Cochrane Database of Systematic Reviews. Eligible studies included articles comparing acute to chronic TMD pain, and cohort studies assessing the risk factors implicated in the transition from acute to chronic TMD pain. RESULTS: Seven articles were selected: one case-control study, three cross-sectional studies, and three cohort studies. These studies found that psychological factors were more common in chronic than acute TMD pain patients; however, these factors did not increase the transition risk in the multivariable model. Myofascial and baseline pain intensity were associated with the transition from acute to chronic TMD pain at a 6-month follow-up. Due to methodological weaknesses in the available literature, more research is required to establish the risk factors implicated in the transition from acute to chronic TMD pain. CONCLUSION: This review found some evidence that myofascial pain is associated with the transition risk from acute to chronic TMD pain at a 6-month follow-up and that pain intensity at baseline is associated with more intense TMD pain 6 months later. There is insufficient evidence to draw conclusions about the role of demographics and psychological disorders as independent risk factors.

Salivary Heme Oxygenase-1: A Potential Biomarker for Central Neurodegeneration.

BACKGROUND: Parkinson disease (PD) is the second most common neurodegenerative disease, affecting 2% of the population over 65 years of age. PD diagnosis is based on clinical examination and can only be confirmed during autopsy. In 2018, we reported that heme oxygenase-1 (HO-1), an inducible stress response protein important for heme catabolism and implicated in PD pathology, was higher in PD saliva relative to healthy controls, suggesting that salivary HO-1 may serve as a potential biomarker of PD. OBJECTIVES: To ascertain whether HO-1 protein levels are elevated in PD saliva relative to degenerative neurological, non-degenerative neurological and healthy controls. METHODOLOGY: The study included 307 participants comprising 75 participants with idiopathic PD and 3 control groups: 162 non-neurological, 37 non-PD degenerative neurological, and 33 non-degenerative neurological participants. Salivary HO-1 and total protein concentrations were measured using ELISA and BCA assay, respectively. Receiver operating characteristic (ROC) curves were used to estimate model discrimination. Analyses were adjusted by age, sex, total protein, and relevant comorbidities. RESULTS: Elevated HO-1 concentrations were observed in the PD group and other neurodegenerative conditions compared to subjects with no neurological or non-degenerative neurological conditions. ROC curves using HO-1 levels and covariates yielded areas under the curve above 85% in models for PD or neurodegenerative conditions versus controls. CONCLUSIONS: Salivary HO-1 concentrations in combination with covariates may provide a biomarker signature that distinguishes patients with neurodegenerative conditions from persons without. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that salivary HO-1 multivariable models can distinguish neurodegenerative conditions.

Heme oxygenase-1 in blood and saliva during acute psychosis: A pilot study.

Despite the extensive prevalence of psychosis and schizophrenia spectrum disorders, their biological underpinnings remain largely unexplained. Recently, the overproduction of heme oxygenase-1 (HO-1), an enzyme that catalyzes the degradation of heme, was associated with oxidative stress and a neurologic phenotype similar to schizophrenia in transgenic mice. We sought to evaluate, by comparing patients experiencing an acute psychotic episode, and age/sex-matched healthy control participants, whether there was an association between HO-1 overexpression and psychosis. This cross-sectional pilot study included 16 patients and 17 control participants. Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction were used to quantify HO-1 expression in blood and saliva. Four psychiatric questionnaires were used to measure psychiatric symptoms in participants. Higher levels of salivary HO-1 expression were detected in patients experiencing an acute psychotic episode when compared to control participants (84.01 vs. 61.26 ng/ml, p = 0.026), but plasma and lymphocyte HO-1 expression did not significantly differ between groups. Overexpression of HO-1 in saliva specimens was also positively associated with psychiatric symptom severity and disability. The overexpression of HO-1 in the saliva of patients with psychosis suggests that it may serve as a potential biomarker for this symptom which should be explored in larger clinical trials.

Characterization and heme oxygenase-1 content of extracellular vesicles in human biofluids.

Heme oxygenase-1 (HO-1), a highly inducible stress protein that degrades heme to biliverdin, carbon monoxide, and free ferrous iron, is increased in blood and other biofluids of subjects with various systemic and neurological disorders. HO-1 does not contain an N-terminal signal peptide and the mechanism responsible for its secretion remains unknown. Extracellular vesicles (EVs) are membrane-bound inclusions that transport microRNAs, messenger RNAs, lipids, and proteins among diverse cellular and extracellular compartments. The objective of the current study was to determine whether EVs in human biofluids contain HO-1, and whether the latter may be transported in EVs from brain to periphery. Total, L1 cell adhesion molecule protein (L1CAM)-enriched (neuron-derived), and glutamate aspartate transporter 1 (GLAST)-enriched (astrocyte-derived) EVs were purified from five different human biofluids (saliva [n = 40], plasma [n = 14], serum [n = 10], urine [n = 10], and cerebrospinal fluid [n = 11]) using polymer precipitation and immuno-affinity-based capture methods. L1CAM-enriched, GLAST-enriched, and L1CAM/GLAST-depleted (LGD) EV, along with EV-depleted (EVD), fractions were validated by nanoparticle tracking analysis, enzyme-linked immunosorbent assay (ELISA), and western blot. HO-1 was assayed in all fractions using ELISA and western blot. The majority of HO-1 protein was localized to LGD, L1CAM-enriched, and GLAST-enriched EVs of all human biofluids surveyed after adjusting for age and sex, with little HO-1 protein detected in EVD fractions. HO-1 protein in human biofluids is predominantly localized to EV compartments. A substantial proportion of EV HO-1 in peripheral human biofluids is derived from the central nervous system and may contribute to the systemic manifestations of various neurological conditions.

Identifying predictive factors for neuropathic pain after breast cancer surgery using machine learning.

INTRODUCTION: Neuropathic pain (NP) remains a major debilitating condition affecting more than 26% of breast cancer survivors worldwide. NP is diagnosed using a validated 10-items Douleur Neuropathique - 4 screening questionnaire which is administered 3 months after surgery and requires patient-doctor interaction. To develop an effective prognosis model admissible soon after surgery, without the need for patient-doctor interaction, we sought to [1] identify specific pain characteristics that can help determine which patients may be susceptible to NP after BC surgery, and 2) assess the utility of machine learning models developed in objective [1] as a knowledge discovery tool for downstream analysis. METHODS: The dataset is from a prospective cohort study of female patients scheduled to undergo breast cancer surgery for the first time at the Jewish General Hospital, Montreal, Canada between November 2014 and March 2019. NP was assessed at 3 months after surgery using Douleur Neuropathique - 4 interview scores (in short, DN4-interview; range: 0-7). For the primary analysis, we constructed six ML algorithms (least square, ridge, elastic net, random forest, gradient boosting, and neural net) to identify the most relevant predictors for DN4-interview score; and compared model performance based on root mean square error (RMSE). For the secondary analysis, we built a logistic classification model for neuropathic pain (DN4-interview score ≥ 3 versus DN4-interview score < 3) using the relevant-consensus-predictors from the primary analysis. RESULTS: Anxiety, type of surgery, preoperative baseline pain and acute pain on movement were identified as the most relevant predictors for DN4 - interview score. The least square regression model (RMSE = 1.43) is comparable in performance with random forest (RMSE = 1.39) and neural network model (RMSE = 1.50). The Gradient boosting model (RMSE = 1.16) outperformed the models compared including the penalized regression models (ridge regressions, RMSE = 1.28; and elastic net, RMSE = 1.31). In the secondary analysis, the preferred logistic regression classier for NP had an area under the curve (AUC) of 0.68 (95% CI = 0.57 to 0.79). Anxiety was significantly associated with the likelihood of NP (odds ratio = 2.18; 95% CI = 1.05-4.49). In comparison to their counterparts, the odds of NP were higher in participants with acute pain on movement or with present preoperative baseline pain or participants who performed total mastectomy surgery, but the differences were not statistically significant. CONCLUSIONS: Modern machine learning models show improvements over traditional least square regression in predicting of DN4-interview score. Penalized regression methods and the Gradient boosting model out-perform other models. As a predictor discovery tool, machine learning algorithms identify relevant predictors for DN4-interview score that remain statistically significant indicators of neuropathic pain in the classification model. Anxiety, type of surgery and acute pain on movement remain the most useful predictors for neuropathic pain.

Comorbid conditions associated with painful temporomandibular disorders in adolescents from Brazil, Canada and France: A cross-sectional study.

BACKGROUND: Painful temporomandibular disorder (TMD) is common among adolescents. Presence of painful comorbidities may worsen painful TMD and impact treatment effectiveness. OBJECTIVE: The aim of this study was to assess the association between painful TMD and comorbidities. METHODOLOGY: In this cross-sectional study, adolescents were recruited in Montreal (Canada), Nice (France) and Arceburgo (Brazil). Reliable instruments were used to assess painful TMD and comorbidities. Multivariable logistic and linear regression analyses were conducted to assess the study aims. RESULTS: The prevalence of self-reported painful TMD was estimated at 31.6%; Arceburgo (31.6%), Montreal (23.4%) and Nice (31.8%). Painful TMD was more common among girls than boys (OR = 1.96). Painful TMD was associated with a higher number of comorbidities (OR = 1.77); Arceburgo (OR = 1.81), Montreal (OR = 1.80) and Nice (OR = 1.72). A stronger association was found between painful TMD and headaches (OR = 4.09) and a weaker one with stomach pain (OR = 1.40). Allergies were also related to painful TMD (OR = 1.43). CONCLUSION: Painful TMD was associated with comorbidities. Headaches were consistently associated with painful TMD. Other associations were modified by sex and/or covariates related to the cities where participants were recruited.

Greater palatine block for V2 trigeminal neuralgia: Case report.

AIMS: This study describes a novel nerve block directed at the maxillary (V2) division of the fifth cranial nerve as treatment for medication-refractory trigeminal neuralgia (TN). METHODS AND RESULTS: The authors present three cases of TN treated with V2 nerve block using commonly available local anesthetics injected through the greater palatine foramen. Patients' medications were noted before and after the procedure. Following the injection, patients were followed over time and outcome was assessed. Patients experienced rapid and long-lasting pain relief allowing for significant reduction in antineuralgia medications. This was done with the objective of breaking the pain cycle with subsequent discontinuation or reduction of analgesic medications. CONCLUSION: This technique may be an effective treatment for medication-refractory V2 TN. By interrupting the pain cycle, this renders the condition amenable to long-term control using diminished doses of standard antineuralgia pharmaceuticals. The practical implications of the described procedure are that it is simple, safe, and well-tolerated with few or no adverse effects. This novel technique is a diagnostic feature for the dentist to differentiate between sources of facial pain.

Evaluation of salivary heme oxygenase-1 as a potential biomarker of early Parkinson's disease.

BACKGROUND AND HYPOTHESIS: To date, there are no chemical analytes, including biochemical indices of oxidative stress, metabolites of α-synuclein protein, and differential protein expression patterns on proteomic profiling, for use in clinics as a diagnostic biomarker of idiopathic PD. OBJECTIVES: Heme oxygenase-1 has been implicated in the pathogenesis of PD. The objective of this study is to ascertain whether salivary heme oxygenase-1 may serve as a biomarker for early idiopathic PD. METHODS: Fifty-eight PD patients and 59 non-neurological disease controls were recruited. Levels of heme oxygenase-1 expression were assayed using enzyme-linked immunosorbent assay and western blot analysis of whole, unstimulated saliva. Analyses were adjusted by sex, l-dopa exposure, and relevant comorbidities. RESULTS: We documented: (1) the presence of 32-kDa heme oxygenase-1 protein in human saliva; (2) significantly higher mean heme oxygenase-1 protein concentrations in saliva of PD patients relative to control values; (3) no variability in salivary heme oxygenase-1 levels with sex, age, l-dopa equivalence, or comorbidities; and (4) significantly higher mean salivary heme oxygenase-1 concentrations in patients with H & Y stage 1 PD (early) than control subjects and stage 2 and stage 3 PD patients. The area under the receiver operating characteristic curve that separated controls from PD H & Y stage 1 was 76% (95% confidence interval: 63-90). CONCLUSIONS: Salivary heme oxygenase-1 concentrations may provide a useful, noninvasive, and relatively inexpensive biomarker of early idiopathic PD. © 2018 International Parkinson and Movement Disorder Society.

Relationship Between Disease Characteristics and Oral Radiologic Findings in Systemic Sclerosis: Results From a Canadian Oral Health Study.

OBJECTIVE: Systemic sclerosis (SSc; scleroderma) is associated with a wide periodontal ligament (PDL) and mandibular erosions. We investigated the clinical correlates of SSc with these radiologic abnormalities. METHODS: Subjects from the Canadian Scleroderma Research Group cohort underwent detailed radiologic examinations. Associations between radiologic abnormalities and clinical manifestations of SSc were examined with univariate and multivariate analyses. RESULTS: The study included 159 subjects; 90.6% were women, the mean ± SD age was 56 ± 10 years, diffuse disease was present in 28.3%, and mean ± SD disease duration was 13.7 ± 8.4 years. Widening of the PDL involving at least 1 tooth was present in 38% of subjects, and 14.5% had at least 1 site in the mandible with an erosion. In analyses adjusting for age, disease duration, sex, smoking, and education, we found significant associations between the number of teeth with widening of the PDL and disease severity assessed by the physician global assessment (PGA) (relative risk [RR] 1.19, 95% confidence interval [95% CI] 1.02-1.39, P = 0.028). Analyses replacing the PGA with the skin score, disease subset, or anti-topoisomerase I antibodies confirmed the relationship with indices of disease severity. There was no relationship between either the number of teeth with periodontal disease or the number of missing teeth, and the number of teeth with wide PDL. A smaller interdental distance (RR 0.89, 95% CI 0.82-0.97, P = 0.006), but not disease severity, facial skin score, or ischemia was associated with a larger number of erosions. CONCLUSION: In SSc, a wide PDL may reflect generalized overproduction of collagen, and mandibular erosions are related to local factors in the oral cavity.

The Canadian Systemic Sclerosis Oral Health Study IV: oral radiographic manifestations in systemic sclerosis compared with the general population.

OBJECTIVE: The aim of this study was to compare oral radiologic abnormalities associated with systemic sclerosis (SSc) against abnormalities in the general population. STUDY DESIGN: Patients with SSc and healthy controls were enrolled in a multi-site cross-sectional study. Included in the radiology examination were a panoramic radiograph, four bitewings, and an anterior mandibular periapical radiograph. Radiographs were evaluated by two oral and maxillofacial radiologists tested for interobserver and intraobserver reliability. Chi-squared tests, Fisher exact tests, and Mann Whitney U tests were used to summarize the radiologic manifestations of patients and controls. RESULTS: We assessed 163 SSc patients and 231 controls. Widening of the periodontal ligament space (PLS) (P < .001), with higher percentage of teeth with PLS widening (P < .001), was significantly more frequent in patients with SSc than in controls. The most significant differences between the two groups were found in the molars and premolars (P < .001). Moreover, 26% of the patients with SSc had a periapical PLS greater than 0.19 mm compared with 13% of the controls (P = .003). Patients with SSc had significantly more erosions compared with controls (14.5% vs. 3.6%; P < .001), mostly in the condyles (P = .022), coronoid processes (P = .005) and other locations (P = .012). CONCLUSION: Patients with SSc had more teeth with PLS widening and erosions of the mandible compared with controls.

Salivary biomarkers of oxidative stress: A critical review.

Human saliva is an increasingly attractive medium for biomarker discovery due to its amenability to noninvasive and repeated sampling, ease of collection and processing, and suitability for single analyte or metabolomic measurements. Salivary biomarkers of oxidative stress reflect local and systemic pathologies and may inform on the diagnosis, prognosis, and therapeutic responsiveness of numerous human diseases. However, for many of the disorders investigated, data reporting on alterations in salivary redox homeostasis are often highly conflicted across studies. We surveyed the available biomedical literature on this topic and noted significant discrepancies in the study designs, target populations, and operating procedures which likely contribute to the discordant data sets reported. Based on these observations, guidelines are provided to minimize interlaboratory variability in redox biomarker discovery based on human saliva.

The Canadian systemic sclerosis oral health study II: the relationship between oral and global health-related quality of life in systemic sclerosis.

OBJECTIVE: Both oral and global health-related quality of life (HRQoL) are markedly impaired in SSc. In this study we aimed to determine the degree of association between oral HRQoL and global HRQoL in SSc. METHODS: Subjects were recruited from the Canadian Scleroderma Research Group registry. Global HRQoL was measured using the Medical Outcomes Trust 36-item Short Form Health Survey (SF-36) and oral HRQoL with the Oral Health Impact Profile (OHIP). The Medsger Disease Severity Score was used to determine organ involvement. Multivariate regression models determined the independent association of the OHIP with the SF-36 after adjusting for confounders. RESULTS: This study included 156 SSc subjects. The majority (90%) were women, with a mean age of 56 years, mean disease duration 13.8 years (s.d. 8.5) and 29% of the subjects had dcSSc. Mean total OHIP score was 40.8 (s.d. 32.4). Mean SF-36 mental component summary (MCS) score was 49.7 (s.d. 11.1) and physical component summary (PCS) score was 37.0 (s.d. 10.7). In adjusted analyses, the total OHIP score was significantly associated with the SF-36 MCS and PCS, accounting for 9.7% and 5.6% of their respective variances. Measures of disease severity were not related to OHIP score. CONCLUSION: Oral HRQoL in SSc is independently associated with global HRQoL. Oral HRQoL, however, is not related to physician-assessed disease severity. This suggests that physicians may be disregarding issues related to oral health. HRQoL is an additional dimension of HRQoL not captured by generic instruments such as the SF-36.

Relationship between disease characteristics and orofacial manifestations in systemic sclerosis: Canadian Systemic Sclerosis Oral Health Study III.

OBJECTIVE: Systemic sclerosis (SSc; scleroderma) is associated with decreased saliva production and interincisal distance, more missing teeth, and periodontal disease. We undertook this study to determine the clinical correlates of SSc with these oral abnormalities. METHODS: Subjects were recruited from the Canadian Scleroderma Research Group cohort. Detailed dental and clinical examinations were performed according to standardized protocols. Associations between dental abnormalities and selected clinical and serologic manifestations of SSc were examined. RESULTS: One hundred sixty-three SSc subjects were included: 90% women, mean ± SD age 56 ± 11 years, mean ± SD disease duration 14 ± 8 years, 72% with limited cutaneous disease, and 28% with diffuse cutaneous disease. Decreased saliva production was associated with Sjögren's syndrome-related autoantibodies (ß = -43.32; 95% confidence interval [95% CI] -80.89, -5.75), but not with disease severity (ß = -2.51; 95% CI -8.75, 3.73). Decreased interincisal distance was related to disease severity (ß = -1.02; 95% CI -1.63, -0.42) and the modified Rodnan skin thickness score (ß = -0.38; 95% CI -0.53, -0.23). The number of missing teeth was associated with decreased saliva production (relative risk [RR] 0.97; 95% CI 0.94, 0.99), worse hand function (RR 1.52; 95% CI 1.13, 2.02), and the presence of gastroesophageal reflux disease (GERD; RR 1.68 [95% CI 1.14, 2.46]). No clinical or serologic variables were correlated with periodontal disease. CONCLUSION: In SSc, diminished interincisal distance is related to overall disease severity. Decreased saliva production is related to concomitant Sjögren's syndrome antibodies. Tooth loss is associated with poor upper extremity function, GERD, and decreased saliva. The etiology of excess periodontal disease is likely multifactorial and remains unclear.

The Canadian systemic sclerosis oral health study: orofacial manifestations and oral health-related quality of life in systemic sclerosis compared with the general population.

OBJECTIVE: The aim of this study was to compare oral abnormalities and oral health-related quality of life (HRQoL) of patients with SSc with the general population. METHODS: SSc patients and healthy controls were enrolled in a multisite cross-sectional study. A standardized oral examination was performed. Oral HRQoL was measured with the Oral Health Impact Profile (OHIP). Multivariate regression analyses were performed to identify associations between SSc, oral abnormalities and oral HRQoL. RESULTS: We assessed 163 SSc patients and 231 controls. SSc patients had more decayed teeth (SSc 0.88, controls 0.59, P = 0.0465) and periodontal disease [number of teeth with pocket depth (PD) >3 mm or clinical attachment level (CAL) ≥5.5 mm; SSc 5.23, controls 2.94, P < 0.0001]. SSc patients produced less saliva (SSc 147.52 mg/min, controls 163.19 mg/min, P = 0.0259) and their interincisal distance was smaller (SSc 37.68 mm, controls 44.30 mm, P < 0.0001). SSc patients had significantly reduced oral HRQoL compared with controls (mean OHIP score: SSc 41.58, controls 26.67, P < 0.0001). Multivariate regression analyses confirmed that SSc was a significant independent predictor of missing teeth, periodontal disease, interincisal distance, saliva production and OHIP scores. CONCLUSION: Subjects with SSc have impaired oral health and oral HRQoL compared with the general population. These data can be used to develop targeted interventions to improve oral health and HRQoL in SSc.

Periodontal disease is not associated with preeclampsia in Canadian pregnant women.

BACKGROUND: The findings from the studies on the relationship between periodontal disease and preeclampsia are inconsistent. The objective of this study is to examine the relationship between periodontal disease and preeclampsia. METHODS: A multicenter case-control study was conducted in Quebec, Canada. Preeclampsia was defined as blood pressure ≥140/90 mm Hg and ≥1+ proteinuria after 20 weeks of gestation. Periodontitis was defined as the presence of ≥4 sites with a probing depth ≥5 mm and a clinical attachment loss ≥3 mm at the same sites. RESULTS: A total of 92 preeclamptic women and 245 controls were analyzed. The percentage of periodontal disease was 18.5% in preeclamptic women and 19.2% in normotensive women (crude odds ratio [OR] = 0.96, 95% confidence interval [CI] = 0.52 to 1.77). After adjusting for confounding variables, periodontitis remained not associated with preeclampsia (adjusted OR = 1.13, 95% CI = 0.59 to 2.17). CONCLUSION: This study does not support the hypothesis of an association between periodontal disease and preeclampsia.

Altered redox homeostasis in human diabetes saliva.

BACKGROUND: Oxidative stress has been implicated in the pathogenesis of diabetes mellitus (DM). Levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-epi-prostaglandin-F(2α) (8-epi-PGF2α), and total protein carbonyls were measured to assess whether DM is associated with altered salivary redox homeostasis. METHODS: A total of 215 patients with diabetes and 481 healthy controls were recruited from the Department of Endocrinology at the Jewish General Hospital in Montreal. Levels of oxidative biomarkers were assayed using enzyme-linked immunosorbent assay (ELISA) in whole unstimulated saliva. Associations of the redox data with exposure to insulin, metformin and dietary control were assessed by logistic regression analyses. RESULTS: We observed (i) significantly higher mean levels of 8-OHdG and protein carbonyls in whole unstimulated saliva of patients with diabetes compared to controls, (ii) higher mean levels of protein carbonyls in type 1 diabetes as well as higher mean levels of 8-OHdG and protein carbonyls in type 2 diabetes compared to controls, (iii) elevated levels of protein carbonyls in diet-controlled patients and in patients with diabetes on insulin and metformin, (iv) elevated levels of 8-OHdG in patients on metformin, and (v) significant associations between subjects with DM and salivary 8-OHdG and protein carbonyls. CONCLUSION: DM is associated with increased oxidative modification of salivary DNA and proteins. Salivary redox homeostasis is perturbed in DM and may inform on the presence of the disease and efficacy of therapeutic interventions.