In-home mandibular repositioning during sleep using MATRx plus predicts outcome and efficacious positioning for oral appliance treatment of obstructive sleep apnea.

STUDY OBJECTIVES: Oral appliance therapy is not commonly used to treat obstructive sleep apnea due to inconsistent efficacy and lack of established configuration procedures. Both problems may be overcome by information gathered while repositioning the mandible during sleep. The purpose of this investigation was to determine if an unattended sleep study with a mandibular positioner can predict therapeutic success and efficacious mandibular position, assess the contribution of artificial intelligence analytics to such a system, and evaluate symptom resolution using an objective titration approach. METHODS: Fifty-eight individuals with obstructive sleep apnea underwent an unattended sleep study with an auto-adjusting mandibular positioner followed by fitting of a custom oral appliance. Therapeutic outcome was assessed by the 4% oxygen desaturation index with therapeutic success defined as oxygen desaturation index < 10 h-1. Outcome was prospectively predicted by an artificial intelligence system and a heuristic, rule-based method. An efficacious mandibular position was also prospectively predicted by the test. Data on obstructive sleep apnea symptom resolution were collected 6 months following initiation of oral appliance therapy. RESULTS: The artificial intelligence method had significantly higher predictive accuracy (sensitivity: 0.91, specificity: 1.00) than the heuristic method (P = .016). The predicted efficacious mandibular position was associated with therapeutic success in 83% of responders. Appliances titrated based on oxygen desaturation index effectively resolved obstructive sleep apnea symptoms. CONCLUSIONS: The MATRx plus device provides an accurate means for predicting outcome to oral appliance therapy in the home environment and offers a replacement to blind titration of oral appliances. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Predictive Accuracy of MATRx plus in Identifying Favorable Candidates for Oral Appliance Therapy; Identifier: NCT03217383; URL: https://clinicaltrials.gov/ct2/show/NCT03217383. CITATION: Mosca EV, Bruehlmann S, Zouboules SM, et al. In-home mandibular repositioning during sleep using MATRx plus predicts outcome and efficacious positioning for oral appliance treatment of obstructive sleep apnea. J Clin Sleep Med. 2022;18(3):911-919.

Validation of a new unattended sleep apnea monitor using two methods for the identification of hypopneas.

STUDY OBJECTIVES: The objective of the present study was to evaluate the accuracy of a home sleep apnea test (HSAT), MATRx plus (Zephyr Sleep Technologies, Calgary, Alberta, Canada), in identifying apneas and hypopneas and estimating indices of obstructive sleep apnea (OSA). METHODS: Individuals with suspected OSA underwent a one-night study wearing both HSAT and polysomnogram (PSG) sensors. The results provided by the overnight HSAT were compared with those from the simultaneously recorded PSG. The PSG data were scored manually, and the HSAT data were analyzed automatically using both preceding peak (PP) and moving average window (MW) methods for determining the reference oxyhemoglobin saturation (O2 Sat). Accuracy of the HSAT in detecting individual apneic and hypopneic events was evaluated on an epoch-by-epoch basis. The apnea-hypopnea indices from the two recording systems were compared. RESULTS: Agreement analysis for the individual apneic and hypopneic events yielded median values for sensitivity and specificity of 0.89 and 0.98 and positive and negative likelihood ratios of 37.35 and 0.11, respectively. Comparison of OSA indices between the two systems yielded correlation coefficients in the range of 0.95-0.96 and intraclass correlation coefficients ranging from 0.92-0.96. Bland-Altman analyses showed 0-2 cases lying outside the ± 2 standard deviation (SD) band and biases ranging from 2.1 to 5.3 events/h. The biases were larger for MW than PP. CONCLUSIONS: The MATRx plus HSAT identifies apneic and hypopneic events and estimates OSA indices with accuracy suitable for clinical purposes but not in children, patients with underlying lung disease, and habitual mouth-breathers. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: PSG Validation of MATRx plus AHI; Identifier: NCT03627169.

A Feedback-Controlled Mandibular Positioner Identifies Individuals With Sleep Apnea Who Will Respond to Oral Appliance Therapy.

STUDY OBJECTIVES: Mandibular protruding oral appliances represent a potentially important therapy for obstructive sleep apnea (OSA). However, their clinical utility is limited by a less-than-ideal efficacy rate and uncertainty regarding an efficacious mandibular position, pointing to the need for a tool to assist in delivery of the therapy. The current study assesses the ability to prospectively identify therapeutic responders and determine an efficacious mandibular position. METHODS: Individuals (n = 202) with OSA participated in a blinded, 2-part investigation. A system for identifying therapeutic responders was developed in part 1 (n = 149); the predictive accuracy of this system was prospectively evaluated on a new population in part 2 (n = 53). Each participant underwent a 2-night, in-home feedback-controlled mandibular positioner (FCMP) test, followed by treatment with a custom oral appliance and an outcome study with the oral appliance in place. A machine learning classification system was trained to predict therapeutic outcome on data obtained from FCMP studies on part 1 participants. The accuracy of this trained system was then evaluated on part 2 participants by examining the agreement between prospectively predicted outcome and observed outcome. A predicted efficacious mandibular position was derived from each FCMP study. RESULTS: Predictive accuracy was as follows: sensitivity 85%; specificity 93%; positive predictive value 97%; and negative predictive value 72%. Of participants correctly predicted to respond to therapy, the predicted mandibular protrusive position proved efficacious in 86% of cases. CONCLUSIONS: An unattended, in-home FCMP test prospectively identifies individuals with OSA who will respond to oral appliance therapy and provides an efficacious mandibular position. CLINICAL TRIAL REGISTRATION: The trial that this study reports on is registered on www.clinicaltrials.gov, ID NCT03011762, study name: Feasibility and Predictive Accuracy of an In-Home Computer Controlled Mandibular Positioner in Identifying Favourable Candidates for Oral Appliance Therapy.

In situ cell-matrix mechanics in tendon fascicles and seeded collagen gels: implications for the multiscale design of biomaterials.

Designing biomaterials to mimic and function within the complex mechanobiological conditions of connective tissues requires a detailed understanding of the micromechanical environment of the cell. The objective of our study was to measure the in situ cell-matrix strains from applied tension in both tendon fascicles and cell-seeded type I collagen scaffolds using laser scanning confocal microscopy techniques. Tendon fascicles and collagen gels were fluorescently labelled to simultaneously visualise the extracellular matrix and cell nuclei under applied tensile strains of 5%. There were significant differences observed in the micromechanics at the cell-matrix scale suggesting that the type I collagen scaffold did not replicate the pattern of native tendon strains. In particular, although the overall in situ tensile strains in the matrix were quite similar (∼2.5%) between the tendon fascicles and the collagen scaffolds, there were significant differences at the cell-matrix boundary with visible shear across cell nuclei of >1 µm measured in native tendon which was not observed at all in the collagen scaffolds. Similarly, there was significant non-uniformity of intercellular strains with relative sliding observed between cell rows in tendon which again was not observed in the collagen scaffolds where the strain environment was much more uniform. If the native micromechanical environment is not replicated in biomaterial scaffolds, then the cells may receive incorrect or mixed mechanical signals which could affect their biosynthetic response to mechanical load in tissue engineering applications. This study highlights the importance of considering the microscale mechanics in the design of biomaterial scaffolds and the need to incorporate such features in computational models of connective tissues.

Remotely controlled mandibular protrusion during sleep predicts therapeutic success with oral appliances in patients with obstructive sleep apnea.

STUDY OBJECTIVES: The present study addresses the need for a validated tool that prospectively identifies favorable candidates for oral appliance therapy in treatment of obstructive sleep apnea. The objective of the study was to evaluate the ability of a mandibular titration study, performed with a remotely controlled mandibular positioner (RCMP), to predict treatment outcome with a mandibular repositioning appliance (MRA) and to predict an effective target protrusive position (ETPP). DESIGN: A prospective, blinded, outcome study. SETTING: Standard clinical care with tests performed in the polysomnographic laboratory. PARTICIPANTS: Consecutive patients (n = 67) recruited from a sleep center or a dental practice using broad inclusion criteria (age 21-80 years; AHI > 10/h; BMI < 40 kg/m(2)). INTERVENTIONS: Therapeutic outcome with a mandibular protruding oral appliance was predicted following a mandibular protrusive titration study in the polysomnographic laboratory using a remotely controlled positioner and prospectively established predictive rules. An ETPP was also prospectively determined for participants predicted to be therapeutically successful with MRA therapy. All participants were blindly treated with a MRA, at either the predicted ETPP or a sham position, and therapeutic outcome was compared against prediction. MEASUREMENTS AND RESULTS: At the final protrusive position, standard predictive parameters (sensitivity, specificity, positive and negative predictive values) showed statistically significant predictive accuracy (P < 0.05) in the range of 83% to 94%. The predicted ETPP provided an efficacious protrusive position in 87% of participants predicted to be therapeutically successful with MRA therapy (P < 0.05). CONCLUSIONS: Using prospectively established rules for interpreting the polysomnographic data, the mandibular titration study predicted mandibular repositioning appliance therapeutic outcome with significant accuracy, particularly with regard to accurately predicting therapeutic success. As well, among the participants predicted to be therapeutically successful with mandibular repositioning appliance therapy, the effective target protrusive position provided efficacious mandibular protrusion in the majority.

ISSLS prize winner: Collagen fibril sliding governs cell mechanics in the anulus fibrosus: an in situ confocal microscopy study of bovine discs.

STUDY DESIGN: In situ investigation of collagen and cell mechanics in bovine caudal discs using novel techniques of confocal microscopy. OBJECTIVE: To measure simultaneously the in situ intercellular and collagen matrix mechanics in the inner and outer anulus fibrosus of the intervertebral disc subjected to flexion. SUMMARY OF BACKGROUND DATA: Mechanobiology studies, both in vivo and in vitro, clearly demonstrate that mechanical factors can influence the metabolic activity of disc cells, altering the expression of key extracellular matrix molecules. Essential to elucidating the mechanotransduction mechanisms is a detailed understanding of the in situ mechanical environment of disc cells in response to whole-body mechanical loads. METHODS: Confocal microscopy was used to simultaneously track and capture in situ images of fluorescently labeled cells and matrix during an applied flexion. The position of the nuclear centroids was calculated before and after applied flexion to quantify the in situ intercellular mechanics of both lamellar and interlamellar cells. The deflection patterns of lines photobleached into the extracellular matrix were used to quantify collagen fibril sliding and collagen fibril strains in situ. RESULTS: The extracellular matrix was observed to deflect nonuniformly due to the relative sliding of the collagen fibrils. Intercellular displacements within the lamellar layers were also nonuniform, both along a cell row and between adjacent rows. Within a cell row, the intercellular displacements were small (<1%). CONCLUSIONS: The in situ cell mechanics of anular cells was found to be strongly influenced by collagen fibril sliding in the extracellular matrix and could not be inferred directly from applied tissue loads.

In situ intercellular mechanics of the bovine outer annulus fibrosus subjected to biaxial strains.

In situ intercellular strains in the outer annulus fibrosus of bovine caudal discs were determined under two states of biaxial strain. Confocal microscopy was used to track and capture images of fluorescently labelled nuclei at applied Lagrangian strains in the axial direction (E(A)(S)) of 0%, 7.5% and 15% while the circumferential direction (E(C)(S)) was constrained to either 0% or -2.5%. The position of the nuclear centroids were calculated in each image and used to investigate the in situ intercellular mechanics of both lamellar and interlamellar cells. The intercellular Lagrangian strains measured in situ were non-uniform and did not correspond with the biaxial Lagrangian strains applied to the tissue. A row-oriented analysis of intercellular unit displacements within the lamellar layers found that the magnitudes of unit displacements between cells along a row (delta;(II)) were small (|delta;(IIavg)|=1.6% at E(C)(S)=0%, E(A)(S)=15%; |delta;(IIavg)|=3.0% at E(C)(S)=-2.5%, E(A)(S)=15%) with negative unit displacements occurring greater than one-third of the time. Evidence of interlamellar shear and increased intercellular Lagrangian strains among the cells within the interlamellar septa suggested that their in situ mechanical environment may be more complex. The in situ intercellular strains of annular cells were strongly dependent upon the local structure and behaviour of the extracellular matrix and did not correspond with applied tissue strains. This knowledge has immediate relevance for in vitro investigations of disc mechanobiology, and will also provide a base to investigate the mechanical implications of disc degeneration at the cellular level.

Regional variations in the cellular matrix of the annulus fibrosus of the intervertebral disc.

The three-dimensional architecture of cells in the annulus fibrosus was studied by a systematic, histological examination using antibodies to cytoskeletal components, in conjunction with confocal microscopy. Variations in cell shape, arrangement of cellular processes and cytoskeletal architecture were found both within and between the defined zones of the outer and inner annulus. The morphology of three, novel annulus fibrosus cells is described: extended cordlike cells that form an interconnected network at the periphery of the disc; cells with extensive, sinuous processes in the inner region of the annulus fibrosus; and cells with broad, branching processes specific to the interlamellar septae of the outer annulus. The complex, yet seemingly deliberate arrangement of various cell shapes and their processes suggests multiple functional roles. Regional variations in the organization of the actin and vimentin cytoskeletal networks is reported across all regions of the annulus. Most notable is the continuous, strand arrangement of the actin label at the disc's periphery in contrast to its punctate appearance in all other regions. The gap junction protein connexin 43 was found within cells from all regions of the annulus, including those which did not form physical connections with surrounding cells. These observations of the cellular matrix in the healthy intervertebral disc should contribute to a better understanding of site-specific changes in tissue architecture, biochemistry and mechanical properties during degeneration, injury and healing.