Psychomotor Vigilance Performance in Participants with Excessive Daytime Sleepiness in Obstructive Sleep Apnea or Narcolepsy Compared with SAFTE-FAST Model Predictions.

INTRODUCTION: Excessive daytime sleepiness (EDS) associated with narcolepsy or obstructive sleep apnea (OSA) can impair vigilance/attention. Solriamfetol, a dopamine/norepinephrine reuptake inhibitor, is approved to treat EDS associated with narcolepsy (75-150 mg/day) or OSA (37.5-150 mg/day). The analysis reported here explored the use of the Sleep, Activity, Fatigue, and Task Effectiveness (SAFTE) model (used in transport industries to model performance based on accumulated sleep and circadian variability) as a substitute for healthy controls using psychomotor vigilance task (PVT) data collected during clinical studies. METHODS: Data were analyzed from two phase 2 studies of solriamfetol in adults with OSA (NCT02806895, EudraCT 2015-003930-28) or narcolepsy (NCT02806908, EudraCT 2015-003931-36). Participants were randomly assigned 1:1 to solriamfetol 150 mg/day (3 days) followed by 300 mg/day (4 days), or placebo (7 days), then crossed over to the other treatment. Actual task effectiveness scores were calculated from average PVT inverse reaction time (pre-dose; 2 h post-dose; 6 h post-dose). Actigraphy-derived sleep intervals were used in SAFTE to determine modeled healthy control task effectiveness scores. RESULTS: In participants with OSA (N = 31) on placebo or solriamfetol, actual and modeled healthy control task effectiveness did not differ at any time point. In participants with narcolepsy (N = 20) on placebo, actual task effectiveness at 2 h post-dose was lower than modeled healthy control task effectiveness (nominal P = 0.03), a difference not present with solriamfetol. There was no main effect of solriamfetol on actual or modeled healthy control task effectiveness across time points. CONCLUSION: This study represents a novel application of the SAFTE biomathematical model to approximate healthy controls in sleep disorder research and provides valuable lessons that may optimize future research. Future studies should perform a priori power analyses for model-tested outcomes and use sleep measures that capture sleep fragmentation characteristic of sleep disorders for sleep input (e.g., total sleep time rather than time in bed). TRIAL REGISTRATION: NCT02806895, EudraCT 2015-003930-28: A Randomized, Double-Blind, Placebo-Controlled, Crossover On-Road Driving Study Assessing the Effect of JZP-110 on Driving Performance in Subjects With Excessive Sleepiness Due to Obstructive Sleep Apnea. NCT02806908, EudraCT 2015-003931-36: A Randomized, Double-Blind, Placebo-Controlled, Crossover On-Road Driving Study Assessing the Effect of JZP-110 on Driving Performance in Subjects With Excessive Sleepiness Due to Narcolepsy.

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.

Effects of solriamfetol on on-the-road driving performance in participants with excessive daytime sleepiness associated with obstructive sleep apnoea.

OBJECTIVE: To evaluate the impact of solriamfetol, a dopamine and norepinephrine reuptake inhibitor, on on-the-road driving in participants with excessive daytime sleepiness (EDS) associated with obstructive sleep apnoea (OSA). METHODS: Eligible participants were aged 21-75 years with OSA and EDS (Maintenance of Wakefulness Test mean sleep latency <30 minutes and Epworth Sleepiness Scale score ≥10). Participants were randomised 1:1 to solriamfetol (150 mg/day [3 days], then 300 mg/day [4 days]) or placebo for 7 days, before crossover to the other treatment paradigm. On Day 7 of each period, standardised on-road driving tests occurred (2 and 6 hours postdose). Standard deviation of lateral position (SDLP) was the primary endpoint. RESULTS: Solriamfetol significantly reduced SDLP at 2 (n = 34; least squares mean difference, -1.1 cm; 95% CI, -1.85, -0.32; p = 0.006) and 6 hours postdose (n = 32; least squares mean difference, -0.8 cm; 95% CI, -1.58, -0.03; p = 0.043). Two hours postdose, 4 placebo-treated and 1 solriamfetol-treated participants had incomplete driving tests; 6 hours postdose, 7 and 3 participants, respectively, had incomplete tests. Common treatment-emergent adverse events included headache, nausea, and insomnia. CONCLUSIONS: Solriamfetol 300 mg/day significantly improved on-the-road driving performance in participants with EDS associated with OSA.

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.

Position-dependent obstructive sleep apnea and its influence on treatment success of mandibular advancement devices.

PURPOSE: Depending on the severity of pre-treatment obstructive sleep apnea (OSA) and the criteria used to define treatment success, the efficacy of mandibular advancement devices (MADs) ranges from 30 to 69%. Identifying suitable candidates is the key to increasing the efficacy of a MAD. Positive predictors include a low body mass index, a low apnea-hypopnea index (AHI), and low age. Another consideration is whether or not a patient's OSA is position dependent. To evaluate the effect of such dependency on MAD treatment success, we studied the following: treatment success across the patient's total AHI and in the supine and non-supine sleeping positions; the influence of pre-treatment position dependency on MAD treatment success; and the effect of MAD treatment on post-treatment shifts in position dependency. METHODS: This is a single-center retrospective study of patients with OSA. Patients were diagnosed through an overnight polysomnography and treated with a MAD between February 2015 and January 2018. They were defined as being positional if the AHI in supine sleeping position was at least twice as high as in the non-supine position. RESULTS: Complete treatment success was achieved in 32% of study population (n = 96) and partial success in 54%. Complete treatment success was significantly higher (p = 0.004) when a patient was sleeping in the non-supine position. Treatment success did not differ significantly between patients who were position dependent and those who were not. When treated with a MAD, patients did not spend significantly more time in supine position. Neither did we find any post-treatment shifts in position dependency. CONCLUSION: A MAD is an effective treatment modality that may significantly reduce the total AHI, supine, and non-supine AHI. Since position dependency has no impact on MAD treatment success, it does not determine whether or not a patient is a suitable candidate for MAD treatment.

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.

The influence of position dependency on surgical success in patients with obstructive sleep apnea undergoing maxillomandibular advancement.

STUDY OBJECTIVES: (1) To evaluate surgical success in patients with obstructive sleep apnea undergoing maxillomandibular advancement (MMA) stratifying for the reduction of both the total apnea-hypopnea index (AHI) and the AHI in the supine and nonsupine position; (2) to evaluate the influence of position dependency on surgical outcome; and (3) to analyze the prevalence of residual position-dependent obstructive sleep apnea (OSA) in nonresponders after MMA. METHODS: A single-center retrospective study including a consecutive series of patients with OSA undergoing MMA between August 2011 and February 2019. RESULTS: In total, 57 patients were included. The overall surgical success was 52.6%. No significant difference in surgical success between nonpositional patients (NPP) and positional patients (PP) with OSA was found. Surgical success of the supine AHI was not significantly different between NPP and PP, but surgical success of the nonsupine AHI was significantly greater in NPP than in PP. Of the 17 preoperative NPP, 13 of them moved to being PP with less severe OSA postoperatively. In total, 21 out of 27 nonresponders (77.8%) were PP postoperatively. CONCLUSIONS: No significant difference in surgical success between NPP and PP undergoing MMA was found. However, the improvement of total and nonsupine AHI in NPP was significantly greater compared to PP. In nonresponders, a postoperative shift from severe OSA in NPP to less severe OSA in PP was found, caused by a greater reduction of the nonsupine AHI than the supine AHI postoperatively. In patients with residual OSA in the supine position after MMA, additional treatment with positional therapy can be indicated.

Perioperative Care of Patients With Obstructive Sleep Apnea Undergoing Upper Airway Surgery: A Review and Consensus Recommendations.

IMPORTANCE: To date, no consensus exists regarding optimal perioperative care of patients with obstructive sleep apnea (OSA) undergoing upper airway (UA) surgery. These patients are at risk related to anesthesia and postoperative analgesia, among other risks associated with difficult airway control, and may require intensified perioperative management. OBJECTIVE: To provide a consensus-based guideline by reviewing available literature and collecting expert opinion during an international consensus meeting with experts from relevant speciliaties. EVIDENCE REVIEW: In a consensus meeting conducted on April 4, 2018, a total of 47 questions covering preoperative, intraoperative, and postoperative care were formulated by 12 international experts with extensive clinical experience in the field of UA surgery for OSA. Systematic literature searches were performed by an independent information specialist and 6 researchers according to the Oxford and GRADE systems, and 164 articles published on or before December 31, 2011, were included in the analysis. Two moderators chaired the meeting according to the Amsterdam Delphi Method, including iteration of literature conclusions, expert discussion, and voting rounds. Consensus was reached when there was 70% or more agreement among experts. FINDINGS: Of 47 questions, 35 led to a recommendation or statement. The remaining 12 questions provided no additional information and were excluded in the judgment of experts. Consensus was reached for 32 recommendations. For 1 question there was less than 70% agreement among experts; therefore, consensus was not achieved. Highlights of these recommendations include (1) postoperative bleeding is a complication described for all types of UA surgery; (2) OSA is a relative risk factor for difficult mask ventilation and intubation, and plans for difficult airway management should be considered and implemented; (3) safe perioperative care should be provided, with aspects such as OSA severity, adherent use of positive airway pressure, type of surgery, and comorbidities taken into account; (4) although there is no direct evidence to date, in patients undergoing UA surgery, preoperative treatment with positive airway pressure may reduce the risk of postoperative airway complications; and (5) alternative pain management options perioperatively to reduce opioid use should be considered. CONCLUSIONS AND RELEVANCE: This consensus contains 35 recommendations and statements on the perioperative care of patients with OSA undergoing UA surgery and may be used as a guideline in daily practice.

[Hypoglossal nerve stimulation for obstructive sleep apnoea; technique, indication and future prospects]. / Stimulatie van tongzenuw bij obstructieve slaapapneu.

Hypoglossal nerve stimulation for obstructive sleep apnoea; technique, indication and future prospects Continuous positive airway pressure (CPAP) is the treatment of first choice in patients with moderate to severe obstructive sleep apnoea (OSA); however, 1 in 3 patients does not tolerate CPAP. Upper airway stimulation (UAS) is an alternative for CPAP. This is a new treatment, intended for patients with CPAP intolerance or failure. The muscles responsible for protrusion of the tongue are activated by unilateral stimulation of the hypoglossal nerve, resulting in opening up of the pharynx. Since April 2017, UAS treatment has been reimbursed for a select group of patients by the National Healthcare Institute in the Netherlands, leading to an increase in demand for UAS.

Drug-induced sleep endoscopy: new insights in lateral head rotation compared to lateral head and trunk rotation in (non)positional obstructive sleep apnea patients.

OBJECTIVE: To compare the effect of lateral head rotation to lateral head and trunk rotation on upper airway patency during drug-induced sleep endoscopy (DISE) in nonpositional obstructive sleep apnea (OSA) patients (NPP) and positional OSA patients (PP). METHODS: Prospective cohort study. RESULTS: In total 92 patients were included. Seventy-five patients were male (82%) with a mean age of 47.2 ± 11.3 years, a body mass index of 27.0 ± 3.3 kg/m2 , and a median apnea-hypopnea index of 16.7 per hour (8.7, 26,5). Of all patients, 75% were PP. Lateral head rotation and lateral head and trunk rotation findings are similar in NPP at each possible level of obstruction, with exception of the oropharynx but not in PP. In PP, lateral head rotation and both lateral head and trunk observations were different at every possible obstruction site. CONCLUSION: The effect of lateral head rotation and lateral head and trunk rotation on upper airway patency during DISE is significantly different in PP. In NPP, similar results regarding the degree of upper airway obstruction were found at the level of the velum, tongue base, and epiglottis. LEVEL OF EVIDENCE: 2b Laryngoscope, 129:2430-2435, 2019.