Using Artificial Intelligence to Improve the Accuracy of a Wrist-Worn, Noninvasive Glucose Monitor: A Pilot Study.

BACKGROUND: Self-monitoring of glucose is important to the successful management of diabetes; however, existing monitoring methods require a degree of invasive measurement which can be unpleasant for users. This study investigates the accuracy of a noninvasive glucose monitoring system that analyses spectral variations in microwave signals. METHODS: An open-label, pilot design study was conducted with four cohorts (N = 5/cohort). In each session, a dial-resonating sensor (DRS) attached to the wrist automatically collected data every 60 seconds, with a novel artificial intelligence (AI) model converting signal resonance output to a glucose prediction. Plasma glucose was measured in venous blood samples every 5 minutes for Cohorts 1 to 3 and every 10 minutes for Cohort 4. Accuracy was evaluated by calculating the mean absolute relative difference (MARD) between the DRS and plasma glucose values. RESULTS: Accurate plasma glucose predictions were obtained across all four cohorts using a random sampling procedure applied to the full four-cohort data set, with an average MARD of 10.3%. A statistical analysis demonstrates the quality of these predictions, with a surveillance error grid (SEG) plot indicating no data pairs falling into the high-risk zones. CONCLUSIONS: These findings show that MARD values approaching accuracies comparable to current commercial alternatives can be obtained from a multiparticipant pilot study with the application of AI. Microwave biosensors and AI models show promise for improving the accuracy and convenience of glucose monitoring systems for people with diabetes.

Diagnosis and management of heparin-induced thrombocytopenia: third edition

This guideline updates and widens the scope of the previ-ous British Society for Haematology (BSH) Clinical guide-lines for Diagnosis and Management of Heparin-Induced Thrombocytopenia: Second Edition1 to include functional assays in the diagnosis of heparin-induced thrombocytope-nia (HIT), when to use direct-acting oral anti-coagulants, and the role of intravenous (IV) immunoglobulins and plasma exchange in the management of HIT and spontane-ous HIT.HIT is an immune-mediated, highly pro-thrombotic dis-order of platelet activation caused by pathogenic antibodies against a platelet factor 4 (PF4)­heparin complex. It is the most frequent drug-induced immune thrombocytopenia and may lead to life-threatening thrombosis. There are two distinct forms of HIT: type I, also known as heparin-asso-ciated thrombocytopenia, which is a non-immunological response to heparin treatment, mediated by a direct interac-tion between heparin and circulating platelets causing plate-let clumping or sequestration, and type II, which is immune mediated.

An interim oral appliance as a screening tool during drug-induced sleep endoscopy to predict treatment success with a mandibular advancement device for obstructive sleep apnea.

PURPOSE: Previous studies have shown a wide range of efficacy (29 to 71%) of a mandibular advancement device (MAD) in the treatment of obstructive sleep apnea (OSA). Currently, the ability to preselect suitable patients for MAD therapy based on individual characteristics related to upper airway collapsibility is limited. We investigated if the use of non-custom interim MAD during drug-induced sleep endoscopy (DISE) could be a valuable screening tool to predict MAD treatment outcome. METHODS: In a single-center prospective study including a consecutive series of patients with OSA, we compared DISE outcomes with a MAD in situ with polysomnography results after 3 months of using the same MAD that was used during DISE. RESULTS: Of 41 patients who completed the study, the median apnea-hypopnea index (AHI) was 16.0 events/h [IQR 7.4-23.4]. Respiratory outcomes on polysomnography, including apnea index (AI), total AHI, AHI in supine position, and oxygen desaturation index, all significantly improved after 3 months of MAD treatment. With complete improvement of the upper airway obstruction with the MAD in situ during DISE in supine position, patients were 6.3 times more likely to be a responder to MAD treatment compared to patients with a persisting complete obstruction, although not statistically significant (OR 6.3; 95%CI 0.9-42.7; p = 0.060). CONCLUSION: The potential predictive value with regard to MAD therapy outcomes of the use of an interim MAD during DISE would be an important finding, since the prediction of MAD therapy outcome is of great clinical and scientific interest. A study with a larger cohort should be performed to further investigate our findings.

Using digital interventions to reduce digitalization-related stress: does it work?

Digitalization entails positive and negative consequences for employees. In a longitudinal, randomized control group design over 14 days (N = 95 participants), we piloted and expected each of three app-based interventions to positively influence general well-being, well-being related to information and communication technology (ICT) and recovery compared to the control group with no intervention. The meditation intervention significantly increased general well-being (satisfaction) and recovery (detachment) compared to the control group but did not reduce general stress. The cognitive-behavioural intervention significantly increased general well-being (less stress). The informational intervention, however, increased the general stress level. No intervention changed the level of ICT-specific well-being. Thus, classic stress interventions conveyed via ICTs (app-based) may be effective for addressing classic stress symptoms, but not yet for new forms of stress. Future research should investigate structural differences between classic stressors and new kinds of ICT-related stressors to identify starting points for new types of interventions.

Implementation of 3D Multi-Color Fluorescence Microscopy in a Quadruple Trap Optical Tweezers System.

Recent advances in the design and measurement capabilities of optical tweezers instruments, and especially the combination with multi-color fluorescence detection, have accommodated a dramatic increase in the versatility of optical trapping. Quadruple (Q)-trap optical tweezers are an excellent example of such an advance, by providing three-dimensional control over two constructs and thereby enabling for example DNA-DNA braiding. However, the implementation of fluorescence detection in such a Q-trapping system poses several challenges: (1) since typical samples span a distance in the order of tens of micrometers, it requires imaging of a large field of view, (2) in order to capture fast molecular dynamics, fast imaging with single-molecule sensitivity is desired, (3) in order to study three-dimensional objects, it could be needed to detect emission light at different axial heights while keeping the objective lens and thus the optically trapped microspheres in a fixed position. In this chapter, we describe design guidelines for a fluorescence imaging module on a Q-trap system that overcomes these challenges and provide a step-by-step description for construction and alignment of such a system. Finally, we present detailed instructions for proof-of-concept experiments that can be used to validate and highlight the capabilities of the instruments.

Equal effect of a noncustom vs a custom mandibular advancement device in treatment of obstructive sleep apnea.

STUDY OBJECTIVES: Numerous types of mandibular advancement devices (MADs) are available to treat patients with obstructive sleep apnea, varying from noncustom to custom devices. Only a limited number of studies have been performed to determine whether a noncustom MAD could be used to predict treatment success of a custom MAD. In this study, we investigated the potential of a new-generation noncustom MAD, by comparing its effectiveness with a custom MAD. We hypothesized that the effectiveness of the devices is similar with regard to both objective (polysomnography) and self-reported (questionnaires, adherence, and patient satisfaction) outcomes. METHODS: This was a single-center prospective randomized crossover study including a consecutive series of patients with obstructive sleep apnea. Patients were randomized to start either with the noncustom or custom MAD. Both MADs were applied for 12 weeks, followed by polysomnography with MAD in situ and questionnaires. After the first 12 weeks of follow-up, a washout period of 1 week was applied. Equal effectiveness was defined as no significant differences in both objective and self-reported outcomes between both devices. RESULTS: Fifty-eight patients were included; 40 completed the full follow-up. The median apnea-hypopnea index significantly decreased from 16.3 (7.7, 24.8) events/h to 10.7 (5.6, 16.6) events/h with the custom MAD (P = .010) and to 7.8 (2.9, 16.1) events/h with the noncustom MAD (P < .001). Self-reported outcomes significantly improved in both groups. No significant differences were found between both devices. CONCLUSIONS: The effectiveness of a noncustom and custom MAD is comparable, which suggests that a noncustom MAD can be used as a selection tool for MAD treatment eligibility to improve MAD treatment outcome. CLINICAL TRIAL REGISTRATION: Registry: Netherlands Trial Register; Name: The Use of a Boil and Bite Mandibular Advancement Device vs a Custom Mandibular Advancement Device in Obstructive Sleep Apnea Management; URL: https://www.trialregister.nl/trial/7249; Identifier: NL64738.100.18. CITATION: Bosschieter PFN, Uniken Venema JAM, Vonk PE, et al. Equal effect of a noncustom vs a custom mandibular advancement device in treatment of obstructive sleep apnea. J Clin Sleep Med. 2022;18(9):2155-2165.

Duplex DNA and BLM regulate gate opening by the human TopoIIIα-RMI1-RMI2 complex.

Topoisomerase IIIα is a type 1A topoisomerase that forms a complex with RMI1 and RMI2 called TRR in human cells. TRR plays an essential role in resolving DNA replication and recombination intermediates, often alongside the helicase BLM. While the TRR catalytic cycle is known to involve a protein-mediated single-stranded (ss)DNA gate, the detailed mechanism is not fully understood. Here, we probe the catalytic steps of TRR using optical tweezers and fluorescence microscopy. We demonstrate that TRR forms an open gate in ssDNA of 8.5 ± 3.8 nm, and directly visualize binding of a second ssDNA or double-stranded (ds)DNA molecule to the open TRR-ssDNA gate, followed by catenation in each case. Strikingly, dsDNA binding increases the gate size (by ~16%), while BLM alters the mechanical flexibility of the gate. These findings reveal an unexpected plasticity of the TRR-ssDNA gate size and suggest that TRR-mediated transfer of dsDNA may be more relevant in vivo than previously believed.

Cardiovascular and metabolic effects of a mandibular advancement device and continuous positive airway pressure in moderate obstructive sleep apnea: a randomized controlled trial.

STUDY OBJECTIVES: It has been suggested that treatment for obstructive sleep apnea (OSA) reduces cardiovascular risk. So far, knowledge is limited about the difference in the reduction of this risk between mandibular advancement device (MAD) and continuous positive airway pressure (CPAP) therapy. The aim of this study was to compare the cardiovascular effects of MAD vs CPAP therapy in patients with moderate OSA. METHODS: Patients with an apnea-hypopnea index of 15-30 events/h were randomized to either MAD or CPAP therapy. At baseline and after 12-month follow-up, 24-hour ambulant blood pressure measurements and laboratory measurements were performed. Ambulant blood pressure measurements consisted of 24-hour, daytime and night-time systolic and diastolic blood pressure and heart rate measurements. Laboratory measurements consisted of serum lipid values, creatinine, high-sensitivity C-reactive protein, plasma glucose, hemoglobin A1c glycated hemoglobin, proinflammatory cytokines, soluble receptor for advanced glycation end-products, chemokines, and adhesion molecules. RESULTS: Of the 85 randomized patients with moderate OSA, data were available for 54 patients (n = 24 MAD, n = 30 CPAP) at 12-month follow-up and showed that apnea-hypopnea index significantly decreased with either therapy. In the MAD group, soluble receptor for advanced glycation end-products and glycated hemoglobin were significantly higher after 12 months' follow-up compared to baseline. No significant changes were found between MAD and CPAP treatments for all outcomes. CONCLUSIONS: Treatment of patients with moderate OSA with either MAD or CPAP therapy had no profound effects on major cardiovascular risk factors after 12 months. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: MRA Therapy vs CPAP Therapy in Moderate OSAS; Identifier: NCT01588275; URL: https://clinicaltrials.gov/ct2/show/NCT01588275. CITATION: Uniken Venema JAM, Knol-de Vries GE, van Goor H, Westra J, Hoekema A, Wijkstra PJ. Cardiovascular and metabolic effects of a mandibular advancement device and continuous positive airway pressure in moderate obstructive sleep apnea: a randomized controlled trial. J Clin Sleep Med. 2022;18(6)1547-1555.

When and why telepressure and technostress creators impair employee well-being.

Objectives. This article describes the effects of two specific information and communication technology (ICT) demands (telepressure, technostress creators) on employee well-being, and investigates a mediating effect of detachment (Study 1) and moderating effects of technostress inhibitors on the effects of ICT demands on well-being (Study 2) and detachment (Study 3). Methods. Three quantitative studies with employees (Study 1, N = 296; Study 2, N = 142; Study 3, N = 316) were conducted. Results. The results support the negative effect of ICT demands on several well-being indicators. They also show how detachment mediates the effect of telepressure on well-being (Study 1) and how technostress inhibitors moderate the effect of technostress creators on well-being (Study 2). Technostress inhibitors further buffer negative effects of technostress creators on detachment (Study 3). Conclusion. Interventions to reduce negative consequences of ICTs by increasing the level of technostress inhibitors (e.g., technical support) or facilitating employee detachment (e.g., through communication policies) are derived. The findings confirm that general models explaining stress and well-being are applicable to new forms of job demands and extend existing empirical support for the effect of ICT demands on well-being. Future research should investigate the interplay between the studied variables within a moderated mediation model.

Interpersonal synchrony when singing in a choir.

Singing in a choir has long been known to enhance well-being and protect mental health. Clearly, the experience of a uniquely harmonious social activity is very satisfying for the singers. How might this come about? One of the important factors positively associated with well-being is interpersonal action coordination allowing the choir to function as a whole. This review focuses on temporal coordination dynamics of physiological systems and/or subsystems forming part or the core of the functional substrate of choir singing. These coordination dynamics will be evaluated with respect to the concept of a superordinate system, or superorganism, based on the principles of self-organization and circular causality. We conclude that choral singing is a dynamic process requiring tight interpersonal action coordination that is characterized by coupled physiological systems and specific network topology dynamics, representing a potent biomarker for social interaction.

Mandibular advancement device design: A systematic review on outcomes in obstructive sleep apnea treatment.

Obstructive Sleep Apnea (OSA) is often treated with Mandibular Advancement Devices (MADs). It is unclear whether particular design features are superior to others in terms of OSA alleviation. In order to facilitate clinical decision-making, this systematic review summarizes the objective and subjective outcomes of different available MAD designs. Studies comparing different MAD designs in OSA treatment were searched. After screening 1887 titles and abstracts, 20 original RCTs and six cohort studies were included. 14 articles were systematically reviewed in a meta-analysis. The decrease in AHI was significantly different between some of the MAD designs. The clinical relevance of the observed differences was however limited. Monoblock appliances performed more favorable, compared to bilateral thrust (effect size:-0.37; CI:-1.81 to 0.07). Midline traction appliances performed more favorable, compared to other designs. Custom appliances performed more favorable, compared to thermoplastic appliances (effect size:0.86; CI:-0.62 to 2.35). Furthermore, there were no clinically relevant differences between MAD designs in reduction of ESS, compliance, preference, side effects, and cost effectiveness. With respect to the included trials, presently there is not one superior custom MAD design in OSA treatment regarding the effect on AHI reduction, ESS improvement, compliance, preference, side effects, cost effectiveness, and other disease-related outcomes. We confirm custom MAD designs perform superior to thermoplastic MAD designs.

Unravelling the mechanisms of Type 1A topoisomerases using single-molecule approaches.

Topoisomerases are essential enzymes that regulate DNA topology. Type 1A family topoisomerases are found in nearly all living organisms and are unique in that they require single-stranded (ss)DNA for activity. These enzymes are vital for maintaining supercoiling homeostasis and resolving DNA entanglements generated during DNA replication and repair. While the catalytic cycle of Type 1A topoisomerases has been long-known to involve an enzyme-bridged ssDNA gate that allows strand passage, a deeper mechanistic understanding of these enzymes has only recently begun to emerge. This knowledge has been greatly enhanced through the combination of biochemical studies and increasingly sophisticated single-molecule assays based on magnetic tweezers, optical tweezers, atomic force microscopy and Förster resonance energy transfer. In this review, we discuss how single-molecule assays have advanced our understanding of the gate opening dynamics and strand-passage mechanisms of Type 1A topoisomerases, as well as the interplay of Type 1A topoisomerases with partner proteins, such as RecQ-family helicases. We also highlight how these assays have shed new light on the likely functional roles of Type 1A topoisomerases in vivo and discuss recent developments in single-molecule technologies that could be applied to further enhance our understanding of these essential enzymes.

Microsleep disturbances are associated with noradrenergic dysfunction in Parkinson's disease.

STUDY OBJECTIVES: Parkinson's disease (PD) commonly involves degeneration of sleep-wake regulating brainstem nuclei; likewise, sleep-wake disturbances are highly prevalent in PD patients. As polysomnography macroparameters typically show only minor changes in PD, we investigated sleep microstructure, particularly cyclic alternating pattern (CAP), and its relation to alterations of the noradrenergic system in these patients. METHODS: We analyzed 27 PD patients and 13 healthy control (HC) subjects who underwent overnight polysomnography and 11C-MeNER positron emission tomography for evaluation of noradrenaline transporter density. Sleep macroparameters, as well as CAP metrics, were evaluated according to the consensus statement from 2001. Statistical analysis comprised group comparisons and correlation analysis of CAP metrics with clinical characteristics of PD patients as well as noradrenaline transporter density. RESULTS: PD patients and HC subjects were comparable in demographic characteristics (age, sex, body mass index) and polysomnography macroparameters. CAP rate as well as A index differed significantly between groups, with PD patients having a lower CAP rate (46.7 ± 6.6% versus 38.0 ± 11.6%, p = 0.015) and lower A index (49.0 ± 8.7/hour versus 40.1 ± 15.4/hour, p = 0.042). In PD patients, both CAP metrics correlated significantly with diminished noradrenaline transporter density in arousal prompting brainstem nuclei (locus coeruleus, raphe nuclei) as well as arousal propagating brain structures like thalamus and bitemporal cortex. CONCLUSIONS: Sleep microstructure is more severely altered than sleep macrostructure in PD patients and is associated with widespread dysfunction of the noradrenergic arousal system.

Digitalisation anxiety: development and validation of a new scale.

The increasing spread of digital technologies and respective consequences for the way we live, work, and communicate can evoke feelings of tension and discomfort. This so-called digitalisation anxiety is related to existing and future technologies, includes the process of digitalisation in everyday life, and refers to multiple levels (the individual, organisations, and society). Existing scales measuring technology-related fears due not adequately reflect these features. Therefore, we developed the German version of the Digitalisation Anxiety Scale (DAS). Having generated items based on a qualitative interview study (Study 1, n = 26), we demonstrated the DAS's factor structure, internal consistency and construct validity in Study 2a (n = 109) and test-retest reliability in Study 2b (n = 30). In Study 3 (n = 223), the scale's structure was confirmed and correlates of digitalisation anxiety were examined. The final version of the DAS consists of 35 items with a four-factor structure (societal triggers for digitalisation anxiety, triggers related to interaction and leadership, triggers within oneself and triggers resulting from the digitalisation implementation process). Digitalisation Anxiety had negative relationships with well-being and performance. The scale allows practitioners and researchers to measure and benchmark individuals' levels of digitalisation anxiety, and to track changes over time. The scale can inform interventions aiming at reducing digitalisation anxiety and stress resulting from digitalisation.

Stretching DNA to twice the normal length with single-molecule hydrodynamic trapping.

Single-molecule force spectroscopy has brought many new insights into nanoscale biology, from the functioning of molecular motors to the mechanical response of soft materials within the cell. To expand the single-molecule toolbox, we have developed a surface-free force spectroscopy assay based on a high-speed hydrodynamic trap capable of applying extremely high tensions for long periods of time. High-speed single-molecule trapping is enabled by a rigid and gas-impermeable microfluidic chip, rapidly and inexpensively fabricated out of glass, double-sided tape and UV-curable adhesive. Our approach does not require difficult covalent attachment chemistries, and enables simultaneous force application and single-molecule fluorescence. Using this approach, we have induced a highly extended state with twice the contour length of B-DNA in regions of partially intercalated double-stranded (dsDNA) by applying forces up to 250 pN. This highly extended state resembles the hyperstretched state of dsDNA, which was initially discovered as a structure fully intercalated by dyes under high tension. It has been hypothesized that hyperstretched DNA could also be induced without the aid of intercalators if high-enough forces were applied, which matches our observation. Combining force application with single-molecule fluorescence imaging is critical for distinguishing hyperstretched DNA from single-stranded DNA that can result from peeling. High-speed hydrodynamic trapping is a powerful yet accessible force spectroscopy method that enables the mechanics of biomolecules to be probed in previously difficult to access regimes.

Eyelid squinting during food pecking in pigeons.

The visual control of pecking by pigeons (Columba livia) has latterly been thought to be restricted to the fixation stops interrupting their downward head movements because these stops prevent interference by motion blur. Pigeons were also assumed to close their eyes during the final head thrust of the peck. Here, we re-examined their pecking motions using high-speed video recordings and supplementary provisions that permitted a three-dimensional spatial analysis of the movement, including measurement of pupil diameter and eyelid slit width. The results confirm that pigeons do not close their eyes completely during the presumed optically ballistic phase of pecking. Instead, their eyelids are narrowed to a slit. The width of this slit is sensitive to both the ambient illumination level and the visual background against which seed targets have to be detected and grasped. There is also evidence of some interaction between pupil diameter and eyelid slit width. We surmise that besides being an eye-protecting reflex, the partial covering of the pupil with the eyelids may increase the depth of focus, enabling pigeons to obtain sharp retinal images of peck target items at very close range and during the beak-gape 'handling' of food items and occasional grit particles.

Jaw thrust versus the use of a boil-and-bite mandibular advancement device as a screening tool during drug-induced sleep endoscopy.

STUDY OBJECTIVES: The objectives of this study were to analyze agreement in degree of obstruction and configuration of the upper airway between jaw thrust and an oral device in situ during drug-induced sleep endoscopy and to evaluate clinical decision making using jaw thrust or a boil-and-bite mandibular advancement device (MAD; the MyTAP). METHODS: This was a single-center prospective cohort study in patients with obstructive sleep apnea who underwent drug-induced sleep endoscopy between January and July 2019. RESULTS: Sixty-three patients were included. Agreement among observations in the supine position for degree of obstruction was 60% (n = 36, κ = 0.41) at the level of the velum, 68.3% (n = 41, κ = 0.35) for oropharynx, 58.3% (n = 35, κ = 0.28) for tongue base, and 56.7% (n = 34, κ = 0.14) for epiglottis; agreement among observations in the lateral position were 81.7% (n = 49, κ = 0.32), 71.7% (n = 43, κ = 0.36), 90.0% (n = 54, κ = 0.23), and 96.7% (n = 58, κ = could not be determined), respectively. In the supine position, agreement for configuration of obstruction at the level of the velum was found in 20 of 29 patients (69.0%, κ = 0.41) and in the lateral position was 100%. Thirty patients would have been prescribed a MAD using jaw thrust and 34 using the boil-and-bite MAD as a screening instrument. The main reason for being labeled as nonsuitable was complete residual retropalatal collapse during jaw thrust. Using the boil-and-bite MAD, this was caused by complete retropalatal or hypopharyngeal collapse. CONCLUSIONS: There is only slight to moderate agreement in degree of obstruction for jaw thrust and a new-generation boil-and-bite MAD during drug-induced sleep endoscopy. Greater improvement of upper airway patency at the hypopharyngeal level was observed during jaw thrust, but this maneuver was less effective in improving upper airway obstruction at the retropalatal level.

Long-term obstructive sleep apnea therapy: a 10-year follow-up of mandibular advancement device and continuous positive airway pressure.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a sleep-related breathing disorder, commonly managed by either continuous positive airway pressure (CPAP) or a mandibular advancement device (MAD). Long-term follow-up and comparison regarding efficacy of these therapies is scarce. In this study the results of treatment, patient adherence, and satisfaction over a 10-year follow-up of these therapies are reported. METHODS: This is a longitudinal follow-up study taken from a subset of patients initially enrolled in a randomized controlled clinical trial of 103 patients with OSA (51 and 52 patients randomized for MAD and CPAP, respectively). After a 10-year follow-up period, 14 patients using MAD and 17 patients using CPAP could be evaluated for this longitudinal follow-up study. Data were analyzed at baseline, after 3 months and at 1-, 2-, and 10-year follow-up. All 31 patients with OSA underwent polysomnography and self-reported measurements. RESULTS: Polysomnography results showed a favorable outcome of both therapies at 10-year follow-up. At baseline, included patients in both groups did not significantly differ in apnea-hypopnea index (AHI) values. At 10-year follow-up, both the MAD and CPAP groups showed a significant reduction in AHI. At baseline the mean AHI in the MAD group was 31.7 ± 20.6 events/h whereas in the CPAP group it was 49.2 ± 26.1 events/h. At 10-year follow-up the mean AHI in the MAD group was 9.9 ± 10.3 events/h and in the CPAP group it was 3.4 ± 5.4 events/h. Both therapies resulted in a substantial improvement in self-reported neurobehavioral outcomes at 10-year follow-up. CONCLUSIONS: Both CPAP and MAD therapy demonstrate good and stable treatment effects after a 10-year follow-up period. Therefore, when indicated, both therapies are appropriate modalities for the long-term management of OSA. CLINICAL TRIAL REGISTRATION: Registry: Netherlands Trial Register; Name: Management of the Obstructive Sleep Apnea-Hypopnea Syndrome: Oral Appliance versus Continuous Positive Airway Pressure Therapy; Identifier: NL75; URL: https://www.trialregister.nl/trial/75.