Privacy-preserving analysis of time-to-event data under nested case-control sampling.

Analyses of distributed data networks of rare diseases are constrained by legitimate privacy and ethical concerns. Analytical centers (e.g. research institutions) are thus confronted with the challenging task of obtaining data from recruiting sites that are often unable or unwilling to share personal records of participants. For time-to-event data, recently popularized disclosure techniques with privacy guarantees (e.g., Differentially Private Generative Adversarial Networks) are generally computationally expensive or inaccessible to applied researchers. To perform the widely used Cox proportional hazards regression, we propose an easy-to-implement privacy-preserving data analysis technique by pooling (i.e. aggregating) individual records of covariates at recruiting sites under the nested case-control sampling framework before sharing the pooled nested case-control subcohort. We show that the pooled hazard ratio estimators, under the pooled nested case-control subsamples from the contributing sites, are maximum likelihood estimators and provide consistent estimates of the individual level full cohort HRs. Furthermore, a sampling technique for generating pseudo-event times for individual subjects that constitute the pooled nested case-control subsamples is proposed. Our method is demonstrated using extensive simulations and analysis of the National Lung Screening Trial data. The utility of our proposed approach is compared to the gold standard (full cohort) and synthetic data generated using classification and regression trees. The proposed pooling technique performs to near-optimal levels comparable to full cohort analysis or synthetic data; the efficiency improves in rare event settings when more controls are matched on during nested case-control subcohort sampling.

Development and internal validation of a prognostic model for loss of balance and falls in mid- to late-stage Parkinson's disease.

BACKGROUND: Mid- to late-stage Parkinson's disease (PD) is often linked with worsened and significant impairment of motor activities, but existing prognostic markers do not adequately capture the risk of loss of balance in PD patients. This study aims to develop a risk prognostic model for mid- to late-stage PD and identify prognostic factors that are indicative of impending loss of balance and falls. METHODS: The study included 307 participants of which 75 were diagnosed with idiopathic PD and 232 were neurological or non-neurological controls. Among the PD group, 46 were early-stage (Hoehn and Yahr [H&Y] = 1,2) with no significant loss of balance while 29 were mid- to late-stage (H&Y = 3,4,5) which is characterized by loss of balance and falls. Multivariable logistic regression (MLR) was used to develop a prognostic model for mid- to late-stage PD. Model discrimination was assessed by ROC curves. The model was internally validated through bootstrapping and calibration plots. RESULTS: The relevant factors identified and included in the final MLR model were shortness of breath, age, swollen joints, heme oxygenase-1 (HO-1) protein, and total salivary protein. The model had an AUC of 0.82 (95% CI = 0.71-0.92) and was well calibrated (calibration slope = 0.77, intercept = 0.03). The likelihood of shortness of breath (OR = 7.91, 95% CI = 1.63-45.12) was significantly higher among mid- to late-stage PD than early-stage. Age and total salivary protein were also significantly higher among mid- to late-stage PD. CONCLUSION: The MLR prognostic model for mid- to late-stage PD may assist physicians in identifying patients at high risk for loss of balance and falls.

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.

Salivary microR-153 and microR-223 Levels as Potential Diagnostic Biomarkers of Idiopathic Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is the most common movement disorder among adults, affecting 2% of the world population older than 65 years of age. No diagnostic biomarker for routine use in clinical settings currently exists. Dysregulation of microRNAs (miRNAs) has been implicated in various neurodegenerative conditions, including PD. Distinct miRNAs have been demonstrated to be involved in the regulation of α-synuclein, a key player in PD pathogenesis; miR-153 and miR-223 are downregulated in the brain and serum of parkinsonian GFAP.HMOX1 transgenic mice where they directly regulate α-synuclein. OBJECTIVE: To ascertain whether salivary miR-153 and miR-223 are similarly downmodulated in, and may serve as diagnostic biomarkers of, idiopathic PD. METHODS: Using reverse transcriptase quantitative polymerase chain reaction, miR-153 and miR-223 levels were evaluated in the saliva of 77 non-neurological controls and 83 PD patients. Levels of heme oxygenase-1 and α-synuclein were measured using enzyme-linked immunosorbent assay. Analyses were adjusted by age, sex, medication exposure, disease duration, and relevant comorbidities. RESULTS: Log-transformed expression levels of miR-153 and miR-223 were significantly decreased in the saliva of human PD patients in comparison with nonneurological controls. The miRNA expression levels did not change as a function of disease progression (Hoehn and Yahr staging). The area under the receiver operating characteristic curve separating controls from PD patients was 79% (95% confidence interval, 61%-96%) for miR-153 and 77% (95% confidence interval, 59%-95%) for miR-223. The ratios of miRNAs to oligomeric α-synuclein, total α-synuclein, or heme oxygenase-1 protein did not improve accuracy of the test. CONCLUSION: Salivary miR-153 and miR-223 levels may serve as useful, noninvasive, and relatively inexpensive diagnostic biomarkers of idiopathic PD. © 2019 International Parkinson and Movement Disorder Society.

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.

Dentist Practice Patterns and Therapeutic Confidence in the Treatment of Pain Related to Temporomandibular Disorders in a Dental Practice-Based Research Network.

AIMS: To quantify the practice patterns of Japanese dentists in the management of pain related to temporomandibular disorders (TMD) and to identify specific characteristics that are significantly associated with the decision to perform occlusal adjustment for TMD-related pain. METHODS: A cross-sectional study was conducted consisting of a questionnaire survey of dentists affiliated with the Dental Practice-Based Research Network Japan (JDPBRN) (n = 148). Participants were asked how they diagnosed and treated TMD-related pain. Associations between dentist characteristics and the decision to perform occlusal adjustment were analyzed via multiple logistic regression. RESULTS: A total of 113 clinicians responded to the questionnaire (76% response rate), and 81% of them (n = 89) had treated TMD during the previous year. Dentists treated an average of 1.9 ± 1.8 (mean ± SD) patients with TMD-related pain per month. Most JDPBRN dentists used similar diagnostic protocols, including questions and examinations. The most frequent treatments were splints or mouthguards (96.5%), medications (84.7%), and self-care (69.4%). Occlusal adjustment for TMD-related pain was performed by 58% of the participants. Multiple logistic regression analysis identified two factors significantly associated with the decision to perform occlusal adjustment: dentist lack of confidence in curing TMD-related acute pain (odds ratio [OR] 5.60; 95% confidence interval [CI] 1.260 to 24.861) and proportion of patients with severe TMD-related pain (OR 0.95; 95% CI 0.909 to 0.999). CONCLUSION: The most common treatments for TMD-related pain were reversible treatments; however, over half of the dentists performed occlusal adjustment for TMD-related pain. The results of this study suggest that an evidence-practice gap exists for occlusal adjustment for TMD-related pain.

Effectiveness of school-based dental sealant programs among children from low-income backgrounds: a pragmatic randomized clinical trial with a follow-up of 3 years.

AIM: A split-mouth randomized clinical trial was carried out to assess the effectiveness of a school-based dental sealant (SBDS) program for French children from low-income backgrounds within 3 years of follow-up. The secondary objectives were to determine the risk factors for the occurrence of new carious lesions (ICDAS 3-6) on first permanent molars, to evaluate the effectiveness of the program according to risk factors and to assess sealant retention. METHODS: The study included 276 6- to 7-year old pupils (457 pairs of first permanent molars) from Nice. The sealing was performed in first- or second-grade children. The first permanent molars were randomized into two groups: One received resin-based sealant and the other formed a nontreatment group. Carious lesions ICDAS 3-6 on permanent and primary teeth, visible plaque, streptococcus mutans and/or lactobacillus counts were recorded at baseline to assess individual caries risk (ICR). The putative confounders recorded at baseline were sex, grade level, and characteristics of first permanent molars. An intent-to-treat analysis was performed, where the study outcome was the occurrence of new carious lesions within 3 years of follow-up. Univariate and multivariate Cox proportional hazards models (hazard risk, HR) using the procedure PHREG with the option of Covsandwich were performed in SAS to assess the effectiveness of the SBDS program. RESULTS: At 3 years of follow-up, 228 children (378 tooth pairs) remained in the analysis. The survival analysis showed that first permanent molars that received sealants had 67% (adjusted HR: 0.33; 95% CI: 0.24-0.46) less risk of developing new carious lesions during all the follow-up than molars without sealant. In addition, children with carious lesions ICDAS 3-6 on permanent and primary teeth, that is, high ICR, had three times the risk of having a new carious lesion than others without, independently of the sealant treatment (adjusted HR: 3.00; 95% CI: 1.55-5.75). Effectiveness of the SBDS program at 3 years of follow-up depended on the presence of carious lesions ICDAS 3-6 (HR in 173 children with carious lesions: 0.32; 95% CI: 0.23-0.46) at baseline (HR in 103 children without carious lesions: 0.42; 95% CI: 0.16-1.12). Finally, the overall retention rate was 32.3%. CONCLUSION: The effectiveness of the SBDS program was demonstrated in low socioeconomic areas. Selection of schoolchildren according to the presence of carious lesions ICDAS 3-6 should be considered in a SBDS program.

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 evolution of racial, ethnic, and gender diversity in US otolaryngology residency programs.

OBJECTIVE: To examine the evolution of racial, ethnic, and gender diversity in US otolaryngology-head and neck surgery residency programs and compare these figures with other residency programs. DESIGN: Retrospective database review. SETTING: US residency programs. METHODS: Information concerning minority and female representation in US residency programs was obtained from annually published graduate medical education reports by the Journal of the American Medical Association from 1975 to 2010. Minority representation among US population and university students was obtained from the US Census Bureau. The racial, ethnic, and gender diversity of otolaryngology residents was then compared with other medical fields (general surgery, family medicine, and internal medicine). RESULTS: Underrepresentation in otolaryngology-head and neck surgery is particularly disconcerting for African Americans (-2.3%/y, P = .09) and Native Americans (1.5%/y, P = .11) given their nonsignificant annual growth rates. Hispanic representation (17.3%/y, P < .0001) is growing in otolaryngology but is half the rate of growth of the Hispanic American population (32.8%/y, P < .0001). There is nonetheless promise for women (70.6%/y, P < .0001) and Asian Americans (63.0%/y, P < .0001), who demonstrated statistically significant growth trends. CONCLUSION: To our knowledge, this is the first study to describe the evolution of female and minority representation among US otolaryngology residents. Despite increasing gender, ethnic, and racial diversity among medical residents in general, female and certain minority group representation in US otolaryngology residency programs is lagging. These findings are in contrast to rising trends of diversity within other residency programs including general surgery.

The feasibility of a clinical trial of pain related to temporomandibular muscle and joint disorders: the results of a survey from the Collaboration on Networked Dental and Oral Research dental practice-based research networks.

BACKGROUND: The authors conducted a survey to characterize the strategies used by general dentists to manage pain related to temporomandibular muscle and joint disorders (TMJDs) and to assess the feasibility of conducting a randomized controlled trial (RCT) to determine the effectiveness of these strategies. METHODS: Dentists from three dental practice-based research networks (PBRNs) (The Dental Practice-Based Research Network, Practitioners Engaged in Applied Research and Learning Network and Northwest Practice-based REsearch Collaborative in Evidence-based DENTistry) agreed to participate in this survey. RESULTS: Of 862 dentists surveyed, 654 were general dentists who treated TMJDs; among these, 80.3 percent stated they would participate in a future RCT. Dentists treated an average of three patients with TMJD-related pain per month. Splints or mouthguards (97.6 percent), self-care (85.9 percent) and over-the-counter or prescribed medications (84.6 percent) were the treatments most frequently used. The treatments dentists preferred to compare in an RCT were splint or mouthguard therapy (35.8 percent), self-care (27.4 percent) and medication (17.0 percent). CONCLUSIONS: Most general dentists treat TMJD-related pain, and initial reversible care typically is provided. It is feasible to conduct an RCT in a dental PBRN to assess the effectiveness of splint or mouthguard therapy, self-care or medication for the initial management of painful TMJD. CLINICAL IMPLICATIONS: There is an opportunity to do an RCT in a dental PBRN, which could lead to the development of evidence-based treatment guidelines for the initial treatment of TMJD-related pain by primary care dentists.

Effectiveness of school-based dental sealant programs among children from low-income backgrounds in France: a pragmatic randomized clinical trial.

OBJECTIVES: A split-mouth randomized clinical trial was carried out to assess the effectiveness of a school-based dental sealant (SBDS) program for French children from low-income backgrounds. The secondary objectives were to determine the effectiveness of the program according to the baseline individual caries risk (ICR) and to assess the sealant retention. METHODS: The study included 276 pupils from Nice. The sealing was performed in the first or second grades. The permanent first molars were randomized into two groups: one received resin-based sealant and the other no treatment. Active caries on permanent and temporary teeth, visible plaque, Streptococcus mutans (SM) and Lactobacillus counts were recorded at baseline to assess ICR. An intent-to-treat analysis was performed based on the occurrence of new caries at 1 year of follow-up (study outcome). Univariate and multivariable conditional tooth-matched logistic regression analyses (Proc phreg; SAS) were used to assess the effectiveness of the SBDS program. RESULTS: At 1 year of follow-up, 253 children (421 pairs) remained in the analysis. In the adjusted analysis, first permanent molars that received sealants were less at risk of developing new caries at 1 year of follow-up compared with those from the control group (OR = 0.26, 95% CI: 0.14-0.49). Independently of the treatment, SM count, and all other covariates, only the variable 'active caries at baseline' remained related to new caries on first molars at 1 year (OR = 3.11, 95% CI: 1.27-7.62). The effect of the sealants was significant only when the analyses included subjects with active caries (OR = 0.25; 95% CI: 0.12-0.50) or with a high SM count (>10(5) , OR = 0.20; 95% CI: 0.10-0.41) at baseline. At the 1-year follow-up, total retention was recorded in 52.7% (n = 222) of the treated teeth. CONCLUSION: The 1-year effectiveness of the SBDS program was demonstrated in low socio-economic areas. Selection of schoolchildren according to individual caries risk factors should be considered in a SBDS program.

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.

Age is associated with self-reported sleep bruxism, independently of tooth loss.

PURPOSE: The aim of this study was to investigate whether the association between self-reported sleep bruxism (SB) and age is modified by the presence of tooth loss. METHODS: A cross-sectional study was done involving 1,930 residents, ranging from 18 to 89 years of age, who underwent health checkups at the rural health center in Japan. The data collection included oral examinations and self-administrated questionnaires. RESULTS: The prevalence of self-reported SB was 8% (n = 152). It was higher in the groups ranging from 30 to 39 and 40 to 49 years of age in comparison to the groups composed of individuals older than 60 years of age. In the crude analyses, the prevalence of self-reported SB was associated with tooth loss, male, smoking, snoring, sleep talking and a history of childhood teeth grinding. A multiple logistic regression confirmed a significant relationship between self-reported SB and the groups of 30-39 years of age (OR: 2.78, P = 0.003) and 40-49 years of age (OR: 2.31, P = 0.005). Snoring (OR: 2.58, P = 0.001) and known (OR: 8.09, P < 0.001) or unknown (OR: 3.03 P < 0.001%) childhood teeth grinding also showed to be related to self-reported SB. CONCLUSIONS: The present study demonstrates that self-reported SB is associated with age, independently of tooth loss. The associations between SB and age will await further physiological investigations.

Altered salivary redox homeostasis in patients with systemic sclerosis.

OBJECTIVE: Oxidative stress has been implicated in the pathogenesis of systemic sclerosis (SSc). Our objective was to determine whether SSc is associated with altered redox homeostasis in human saliva. METHODS: Study participants were 70 women with SSc and 120 female controls. 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-epi-prostaglandin F 2alpha (8-epi-PGF2alpha), and total protein carbonyls were assayed by ELISA to quantify oxidative damage to nucleic acids, lipids, and proteins, respectively, in whole nonstimulated saliva. RESULTS: We observed a significantly positive association between salivary log protein carbonyls and SSc in a crude statistic (OR 9.06, p < 0.0001), and multivariable model adjusted for log 8-OHdG, log 8-epi-PGF2alpha, and antioxidant exposure (OR 9.26, p < 0.0001). No significant association was noted between SSc and salivary log 8-epi-PGF2alpha or log 8-OHdG. CONCLUSION: Salivary redox homeostasis is perturbed in patients with SSc and may inform on the pathophysiology and presence of the disease (biomarkers) and efficacy of therapeutic interventions.