Search

Introduction: Efficacy of oral appliance therapy is variable, limiting its potential as first-line therapy. Site and severity of pharyngeal collapse are known determinants of success/failure with oral appliance therapy. Specifically, risk factors for an incomplete response to oral appliances include a more collapsible upper-airway, complete concentric collapse of the palate (CCCp), and collapse at oropharyngeal lateral walls. Collapsibility can be estimated from clinical polysomnography, but site of collapse detection remains limited. We recently developed a method for differentiating patients with CCCp and lateral wall collapse from those with tongue-base or epiglottic collapse using airflow from polysomnography (Op de Beeck et al World Sleep 2022). In the current study, we applied this method to investigate the utility of including polysomnographic site of collapse with collapsibility for predicting oral appliance treatment responses. Method(s): Eighty-one patients with OSA (median[IQR] apnea-hypopnea index, AHI: 34[22,54]events/h, age: 50[45,56]years, 20 women, BMI: 30[27,34]kg/m2) were assessed via polysomnography at baseline and on oral appliance treatment. From the baseline study, collapsibility was estimated using the average reduction in ventilation per respiratory event ("event depth"). For site of collapse, a continuous variable describing the probability of CCCp and lateral walls versus tongue base and epiglottis was estimated; briefly, six recognizable flow-shape characteristics (including greater inspiratory scoopiness, skewness, earlier peak flow) calculated from breaths within scored hypopneas were combined using linear regression (trained to predict results of drug-induced sleep endoscopy: cross-validated OR=4.3[1.6-11.8], pseudo-R2=0.33). We tested the hypothesis that a complete response to oral appliance therapy (>50% reduction in AHI and treatment AHI<10 events/h) is associated with absence of predicted CCCp or lateral wall collapse, adjusting for

Study Objectives: Oral appliance therapy is an increasingly common option for treating obstructive sleep apnea (OSA) in patients who are intolerant to continuous positive airway pressure (CPAP). Clinically applicable tools to identify patients who could respond to oral appliance therapy are limited. Method(s): Data from three studies (N = 81) were compiled, which included two sleep study nights, on and off oral appliance treatment. Along with clinical variables, airflow features were computed that included the average drop in airflow during respiratory events (event depth) and flow shape features, which, from previous work, indicates the mechanism of pharyngeal collapse. A model was developed to predict oral appliance treatment response (>50% reduction in apnea-hypopnea index [AHI] from baseline plus a treatment AHI <10 events/h). Model performance was quantified using (1) accuracy and (2) the difference in oral appliance treatment efficacy (percent reduction in AHI) and treatment AHI between predicted responders and nonresponders. Result(s): In addition to age and body mass index (BMI), event depth and expiratory "pinching" (validated to reflect palatal prolapse) were the airflow features selected by the model. Nonresponders had deeper events, "pinched" expiratory flow shape (i.e. associated with palatal collapse), were older, and had a higher BMI. Prediction accuracy was 74% and treatment AHI was lower in predicted responders compared to nonresponders by a clinically meaningful margin (8.0 [5.1 to 11.6] vs. 20.0 [12.2 to 29.5] events/h, p < 0.001). Conclusion(s): A model developed with airflow features calculated from routine polysomnography, combined with age and BMI, identified oral appliance treatment responders from nonresponders. This research represents an important application of phenotyping to identify alternative treatments for personalized OSA management.Copyright © Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep

Introduction: We recently demonstrated that patients with "deep" respiratory events (i.e., complete apneas, suggesting a more collapsible pharynx) were less likely to respond to oral appliance therapy. However, event depth, which requires accurate airflow measurements, can be difficult to determine due to movement of the nasal cannula or oral breathing. Oxygen saturation is an alternative signal for potentially characterizing respiratory event depth that is not impacted by these challenges in airflow measurement. In general, the reduction in ventilation during a respiratory event is proportional to the rate of change in oxygen saturation; deeper events cause a more rapid drop in oxygen saturation per unit time. Therefore, the aim of this abstract was to demonstrate that the slope of the oxygen desaturation curve is proportional to event depth and can be similarly associated with oral appliance treatment efficacy. Method(s): Eighty-one OSA patients (AHI>10 events/hr) were assessed via polysomnography during one night off and one night on treatment with oral appliance. Event depth and desaturation slope were measured from the "average" ventilatory and saturation profiles, respectively, as follows. The time-series signal (e.g. oxygen saturation) from all respiratory events were aligned at event termination and ensemble averaged to output a signal profile of the average respiratory event. Event depth was calculated as the mean reduction in ventilation from the ventilatory profile of the average respiratory event. Desaturation slope was measured as the change in oxygen saturation from the 10th (i.e. event start) to the 90th (i.e. event end) percentile of the saturation profile of the average respiratory event, divided by time between these points. Correlation between event depth and desaturation slope was assessed using Pearson's correlation. Bivariate logistic regression tested differences in both variables between oral appliance responders (>50% reduction in AHI from b

BACKGROUND: It is well established that parity and use of oral contraceptives reduce the risk of ovarian cancer, but the associations with other reproductive variables are less clear. METHODS: We examined the associations of oral contraceptive use and reproductive factors with ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 327 396 eligible women, 878 developed ovarian cancer over an average of 9 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models stratified by centre and age, and adjusted for smoking status, body mass index, unilateral ovariectomy, simple hysterectomy, menopausal hormone therapy, and mutually adjusted for age at menarche, age at menopause, number of full-term pregnancies and duration of oral contraceptive use. RESULTS: Women who used oral contraceptives for 10 or more years had a significant 45% (HR, 0.55; 95% CI, 0.41-0.75) lower risk compared with users of 1 year or less (P-trend, <0.01). Compared with nulliparous women, parous women had a 29% (HR, 0.71; 95% CI, 0.59-0.87) lower risk, with an 8% reduction in risk for each additional pregnancy. A high age at menopause was associated with a higher risk of ovarian cancer (>52 vs <= 45 years: HR, 1.46; 95% CI, 1.06-1.99; P-trend, 0.02). Age at menarche, age at first full-term pregnancy, incomplete pregnancies and breastfeeding were not associated with risk. CONCLUSION: This study shows a strong protective association of oral contraceptives and parity with ovarian cancer risk, a higher risk with a late age at menopause, and no association with other reproductive factors. British Journal of Cancer (2011) 105, 1436-1442. doi:10.1038/bjc.2011.371 www.bjcancer.com Published online 13 September 2011 (C) 2011 Cancer Research UK

Obstructive Sleep Apnea (OSA) is a condition in which the patient repeatedly stops breathing during sleep due to the collapse of the upper airway. The upper airway collapse is caused by a relaxation of the upper airway muscles, combined with a decrease in intraluminal pressure and hence an increase in external pressure from the surrounding tissue. A possible treatment that is becoming more and more popular, due to its reversibility, is the oral intervention like a Mandibular Advancement Device. This device brings the mandibula forward in order to increase the upper airway volume and prevent total upper airway collapse during sleep. The patient only uses the device during the night. However the efficiency of the MAD can vary significantly from patient to patient. The use of Computational Fluid Dynamics allows for a prediction of the outcome of a treatment with an MAD. This makes it possible to compare upper airway volume and to determine the upper airway resistance (UAR) through finite volume flow simulations for both cases. Boundary conditions for the model are obtained from the patient during a sleep study. Therefore the flow modelling is based on patient specific geometry and patient specific boundary conditions. A mesh dependency and turbulence dependency study was performed. Whenever the simulations showed a decrease in upper airway resistance, also a clinical improvement was observed. Clinical improvements are measured by looking at the apnea-hypopnea index (AHI) which indicates the number of events (upper airway closures or near closures) per hour and the snoring index quantifying the degree of snoring. In conclusion, one can say that the combination of advanced imaging and functional analysis shows a large potential for future medical treatments.

The resin-dentin interdiffusion zone produced by a dentin-adhesive system that removes the smear layer and concurrently decalcifies superficial dentin was morphologically examined by both scanning and transmission electron microscopy. Cross-sectioned resin-bonded dentin discs were etched with an argon-ion beam to make the resin-dentin interface observable by SEM. For the TEM examination, the sections were partly decalcified by an aqueous EDTA solution to facilitate ultramicrotomy and to disclose the ultrastructure of the interdiffusion zone. Both SEM and TEM confirmed the presence of the resin-dentin interdiffusion zone as the junction between the deep unaltered dentin structure and the restorative resin. Within the interdiffusion zone, three sublayers with characteristic ultrastructure and staining were identified by TEM. An upper diffuse black layer contained few structural features. Underneath, partially-altered collagen fibrils were closely packed, mostly running parallel with the interface and perpendicular to the dentinal tubules. Their outline was electron-dense, forming tunnel-like structures. At the base of the upper layer, several stained projections were found to bulge out into the underlying collagen network and appeared to be confined by obstructive, parallel-running collagen fibrils. Finally, the third dense layer, containing hydroxyapatite crystals, demarcated the superficially demineralized dentin layer from the deeper unaltered dentin. Resin diffusion into the decalcified dentin surface layer was evident, but diminished with depth, presumably reducing deeper resin impregnation into the interfibrillar spaces. The citric acid dentin-pretreatment probably caused denaturation of the superficial collagen fibrils. Its decalcifying effect gradually weakened with depth, leaving behind hydroxyapatite crystals at the base of the interdiffusion zone. These crystals appeared to have been resistant to the EDTA TEM-sample decalcification procedure, which suggests