Respiratory internal kinematics of the tongue base and soft palate in obese minipigs with obstructive sleep apnea.

It is largely unknown how the tongue base and soft palate deform to alter the configuration of the oropharyngeal airway during respiration. This study is to address this important gap. After live sleep monitoring of five Yucatan and two Panepinto minipigs to verify obstructive sleep apnea (OSA), eight and four ultrasonic crystals were implanted into the tongue base and soft palate to circumscribe a cubic and square region, respectively. The 3D and 2D deformational changes of the circumscribed regions were measured simultaneously with electromyographic activity of the oropharyngeal muscles during spontaneous respiration under sedated sleep. The results indicated that both obese Yucatan and Panepinto minipigs presented spontaneous OSA, but not in three nonobese Yucatan minipigs. During inspiration, the tongue base showed elongation in both dorsal and ventral regions but thinning and thickening in the anterior and posterior regions, respectively. The widths showed opposite directions, widening in the dorsal but narrowing in the ventral regions. The soft palate expanded in both length and width. Compared to normal controls, obese/OSA ones showed similar directions of deformational changes, but the magnitude of change was two times larger in the tongue base and soft palate, and obese/OSA Panepinto minipigs presented 10 times larger changes in all dimensions of both the tongue base and the soft palate. The distance changes between the dorsal surface of tongue base and soft palate during inspiration increased in normal but decreased in obese OSA minipigs.

Sleep apnea multi-level surgery trial: long-term observational outcomes.

STUDY OBJECTIVES: The sleep apnea multi-level surgery (SAMS) randomized clinical trial showed surgery improved outcomes at 6 months compared to ongoing medical management in patients with moderate or severe obstructive sleep apnea (OSA) who failed continuous positive airway pressure therapy. This study reports the long-term outcomes of the multi-level surgery as a case series. METHODS: Surgical participants were reassessed >2 years postoperatively with the same outcomes reported in the main SAMS trial. Primary outcomes were apnea-hypopnea index (AHI) and Epworth sleepiness scale (ESS), with secondary outcomes including other polysomnography measures, symptoms, quality of life, and adverse events. Long-term effectiveness (baseline to long-term follow-up [LTFU]) and interval changes (6 month to LTFU) were assessed using mixed effects regression models. Control participants were also reassessed for rate of subsequent surgery and outcomes. RESULTS: 36/48 (75%) of surgical participants were reevaluated (mean (standard deviation)) 3.5 (1.0) years following surgery, with 29 undergoing polysomnography. AHI was 41/h (23) at preoperative baseline and 21/h (18) at follow-up, representing persistent improvement of -24/h (95% CI -32, -17; p < 0.001). ESS was 12.3 (3.5) at baseline and 5.5 (3.9) at follow-up, representing persistent improvement of -6.8 (95% CI -8.3, -5.4; p < 0.001). Secondary outcomes were improved long term, and adverse events were minor. Interval change analysis suggests stability of outcomes. 36/43 (84%) of the control participants were reevaluated, with 25 (69%) reporting subsequent surgery, with symptom and quality of life improvements. CONCLUSION: Multi-level upper airway surgery improves OSA burden with long-term maintenance of treatment effect in adults with moderate or severe OSA in whom conventional therapy failed. CLINICAL TRIAL: Multi-level airway surgery in patients with moderate-severe obstructive sleep apnea (OSA) who have failed medical management to assess change in OSA events and daytime sleepiness; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366019&isReview=true; ACTRN12614000338662.

Mean disease alleviation between surgery and continuous positive airway pressure in matched adults with obstructive sleep apnea.

STUDY OBJECTIVES: Polysomnography parameters measure treatment efficacy for obstructive sleep apnea (OSA), such as reduction in apnea-hypopnea index (AHI). However, for continuous positive airway pressure (CPAP) therapy, polysomnography measures do not factor in adherence and thus do not measure effectiveness. Mean disease alleviation (MDA) corrects polysomnography measures for CPAP adherence and was used to compare treatment effectiveness between CPAP and multilevel upper airway surgery. METHODS: This retrospective cohort study consisted of a consecutive sample of 331 patients with OSA managed with multilevel airway surgery as second-line treatment (N = 97) or CPAP (N = 234). Therapeutic effectiveness (MDA as % change or as corrected change in AHI) was calculated as the product of therapeutic efficacy (% or absolute change in AHI) and adherence (% time on CPAP of average nightly sleep). Cardinality and propensity score matching was utilized to manage confounding variables. RESULTS: Surgery patients achieved greater MDA % than CPAP users (67 ± 30% vs. 60 ± 28%, p = 0.04, difference 7 ± 3%, 95% confidence interval 4% to 14%) in an unmatched comparison, despite a lower therapeutic efficacy seen with surgery. Cardinality matching demonstrated comparable MDA % in surgery (64%) and CPAP (57%) groups (p = 0.14, difference 8 ± 5%, 95% confidence interval -18% to 3%). MDA measured as corrected change in AHI showed similar results. CONCLUSIONS: In adult patients with OSA, multilevel upper airway surgery and CPAP provide comparable therapeutic effectiveness on polysomnography. For patients with inadequate CPAP use, surgery should be considered.

Barriers and communication behaviors impacting referral to sleep surgery: qualitative patient perspectives.

STUDY OBJECTIVES: Physician-patient interactions influence the immediate encounter and leave lasting impressions for future health care encounters. We aimed to understand patient experiences and decision-making for considering sleep surgery, in terms of barriers and communication behaviors that facilitate or hinder referral for consideration of sleep surgery management of obstructive sleep apnea (OSA) when continuous positive airway pressure (CPAP) therapy has failed. METHODS: We employed qualitative methods, using semistructured interviews of adults with OSA who presented for sleep surgery consultation after unsatisfactory therapy with CPAP. Open-ended questions traced symptoms and progression of sleep apnea burden, trials of noninvasive OSA therapies, outcomes, and patient expectations and concerns. The interviews were audio-recorded, transcribed, and analyzed using content analysis to identify themes. RESULTS: Ten adult patients with OSA were enrolled March through April 2021 and reached predominant thematic saturation. Barriers to sleep surgery consultation included: (1) delays in OSA diagnosis due to limited OSA awareness among patients or primary providers and patients' perceived inconvenience of sleep testing, (2) patients faulted for slow progress, (3) patient-reported lack of urgency by providers in troubleshooting noninvasive management options, (4) scheduling delays and waitlists, and (5) cost. Patients were receptive to noninvasive treatment options, but inadequate improvement led to frustration after multiple encounters. Patients appreciated empathetic providers who shared information through transparent and understandable explanations and who presented multiple treatment options. CONCLUSIONS: Experiences of patients with OSA highlight the need for shared decision-making through improved communication of unresolved concerns and alternative management options, including timely referral for sleep surgery consultation when indicated. CITATION: Ikeda AK, McShay C, Marsh R, et al. Barriers and communication behaviors impacting referral to sleep surgery: qualitative patient perspectives. J Clin Sleep Med. 2023;19(1):111-117.

Patient Factors and Preferences in Choosing Sleep Surgery for Obstructive Sleep Apnea: A Qualitative Study.

OBJECTIVE: There are several obstructive sleep apnea (OSA) treatment options available to patients, including surgery and less invasive therapies. Little is known about the factors that influence patient preferences for treatment. We aimed to understand factors influencing patient experience and decision making for undergoing sleep surgery. STUDY DESIGN: Retrospective qualitative study. SETTING: Tertiary sleep surgery clinic. METHODS: We conducted semistructured interviews with adults who previously underwent any nasal and/or pharyngeal sleep surgery. We asked open-ended questions about their decision-making process within a preconceived thematic framework of chief OSA symptoms, expectations for recovery, and sources of information. The interviews were audio recorded and transcribed, and content was analyzed for defined, emergent, and prevalent themes. RESULTS: Ten patients were interviewed from December 11, 2020 through January 29, 2021. Six patients underwent nasal surgery, 1 underwent pharyngeal surgery, and 3 underwent staged nasal and pharyngeal procedures. All patients were beyond the acute recovery phase. Reasons for pursuing surgical consultation varied from sleep apnea burden to external factors, such as recommendations from significant others. Duration of sleep surgery consideration varied from months to years. Major concerns about sleep surgery involved anesthesia and postoperative pain. External factors influencing patients' decisions to pursue sleep surgery included family and friend support. Postoperative outcomes of surgery included patient satisfaction with decision for surgery, given OSA improvements. CONCLUSION: Understanding patient factors that influence decision making for sleep surgery may guide clinicians in patient-centered counseling that engages patients in decision making, aligning with clinical symptoms and patient preferences.

Use of computational fluid dynamics (CFD) to model observed nasal nitric oxide levels in human subjects.

BACKGROUND: Upper airway nitric oxide (NO) is physiologically important in airway regulation and defense, and nasal NO (nNO) levels typically exceed those in exhaled breath (fractional exhaled NO [FeNO]). Elevated concentrations of NO sampled from the nose, in turn, reflect even higher concentrations in the paranasal sinuses, suggesting a "reservoir" role for the latter. However, the dynamics of NO flux within the sinonasal compartment are poorly understood. METHODS: Data from 10 human subjects who had previously undergone both real-time nNO sampling and computed tomography (CT) scanning of the sinuses were analyzed using computational fluid dynamics (CFD) methods. Modeled and observed nNO values during the initial 2-s transient ("spike") during nasal exhalation were then compared. RESULTS: Examining the initial 2-s transient spike for each subject (as well as the pooled group), there was a statistically significant correlation between modeled and observed nNO levels, with r values ranging from 0.43 to 0.89 (p values ranging from <0.05 to <0.0001). Model performance varied between subjects, with weaker correlations evident in those with high background (FeNO) levels. In addition, the CFD simulation suggests that ethmoid sinuses (>60%) and diffusion process (>54%) contributed most to total nasal NO emissions. CONCLUSION: Analysis of this dataset confirms that CFD is a valuable modeling tool for nNO dynamics, and highlights the importance of the ethmoid sinuses, as well as the role of diffusion as an initiating step in sinonasal NO flux. Future model iterations may apply more generally if baseline FeNO is taken into account.

Association of Laryngeal Botulinum Neurotoxin Injection With Work Productivity for Patients With Spasmodic Dysphonia.

Importance: A disordered voice can affect an individual across both work and non-work-related life domains. There is insufficient research on the effect of spasmodic dysphonia or its treatment with botulinum neurotoxin (BoNT) injections on work productivity. Objective: To assess whether employed patients with spasmodic dysphonia experience voice-related work productivity impairment before BoNT injection, and had a 10% or greater improvement in productivity 1 month after treatment with BoNT injection. Design, Setting, and Particpants: This prospective case series carried out in 2 laryngology outpatient clinics from November 1, 2015, to August 30, 2018 included a consecutive sample of adult employed patients diagnosed with spasmodic dysphonia. Analysis was conducted between November 1, 2015, to July 31, 2018. Exposures: Treatment with BoNT injection into the intrinsic laryngeal musculature. Main Outcomes and Measures: Eligible participants completed the following validated outcomes instruments immediately before and 1 month after outpatient laryngeal BoNT injection: the Work Productivity and Activity Impairment instrument (WPAI), Voice Handicap Index (VHI), and WorkHoarse. Demographic, comorbidity, and occupational voice use data were also collected at baseline. The changes in outcome measures (primary, WPAI Work Productivity Impairment domain) were tested using a paired 2-tailed t test. Exploratory subgroup analyses were analyzed with multivariable linear regression, adjusting for demographic, comorbidity, and voice use variables. Results: Of the 101 patients enrolled, 75 completed the study. The mean (SD) age of the 75 completing participants was 55.7 (11.8) years and 53 (71%) were women. The participants who completed the study had mean (SD) voice-related work productivity impairment of 43% (27%) at baseline and 22% (23%) at 1 month after BoNT injection (difference, 20% [27%] improvement; 95% CI, 14%-27%; effect size, 0.74). Conclusions and Relevance: This case series study found that employed patients with spasmodic dysphonia reported voice-related work productivity impairment, which improved significantly 1 month after treatment with BoNT injection. The association of spasmodic dysphonia with voice-related work productivity appeared greater in women than men with comparable outcomes with BoNT treatment, but this exploratory sex-associated difference requires independent validation.

Computational modeling of nasal nitric oxide flux from the paranasal sinuses: Validation against human experiment.

BACKGROUND: Nitric oxide (NO) is important in respiratory physiology and airway defense. Although the paranasal sinuses are the major source of nasal NO, transport dynamics between the sinuses and nasal cavities are poorly understood. METHODS: Exhaled nasal NO tracings were measured in two non-asthmatic subjects (one with allergic rhinitis, one without) using NO analyzer connected via face mask. We subsequently performed computational fluid dynamics NO emission simulations based on individual CT scans and compared to the experimental data. RESULTS: Simulated exhaled NO tracings match well with experimental data (r > 0.84, p < 0.01) for both subjects, with measured peaks reaching 319.6 ppb in one subject (allergic-rhinitis), and 196.9 ppb in the other. The CFD simulation accurately captured the peak differences, even though the initial sinus NO concentration for both cases was set to the same 9000 ppb based on literature value. Further, the CFD simulation suggests that ethmoid sinuses contributed the most (>67%, other sinuses combined <33%) to total nasal NO emission in both cases and that diffusion contributes more than convective transport. By turning off diffusion (setting NO diffusivity to ~0), the NO emission peaks for both cases were reduced by >70%. CONCLUSION: Historically, nasal NO emissions were thought to be contributed mostly by the maxillary sinuses (the largest sinuses) and active air movement (convection). Here, we showed that the ethmoid sinuses and diffusive transport dominate the process. These findings may have a substantial impact on our view of nasal NO emission mechanisms and sinus physiopathology in general.

Improving outcomes of hypoglossal nerve stimulation therapy: current practice, future directions, and research gaps. Proceedings of the 2019 International Sleep Surgery Society Research Forum.

Hypoglossal nerve stimulation (HGNS) has evolved as a novel and effective therapy for patients with moderate-to-severe obstructive sleep apnea. Despite positive published outcomes of HGNS, there exist uncertainties regarding proper patient selection, surgical technique, and the reporting of outcomes and individual factors that impact therapy effectiveness. According to current guidelines, this therapy is indicated for select patients, and recommendations are based on the Stimulation Therapy for Apnea Reduction or STAR trial. Ongoing research and physician experiences continuously improve methods to optimize the therapy. An understanding of the way in which airway anatomy, obstructive sleep apnea phenotypes, individual health status, psychological conditions, and comorbid sleep disorders influence the effectiveness of HGNS is essential to improve outcomes and expand therapy indications. This article presents discussions on current evidence, future directions, and research gaps for HGNS therapy from the 10th International Surgical Sleep Society expert research panel. CITATION: Suurna MV, Jacobowitz O, Chang J, et al. Improving outcomes of hypoglossal nerve stimulation therapy: current practice, future directions and research gaps. Proceedings of the 2019 International Sleep Surgery Society Research Forum. J Clin Sleep Med. 2021;17(12):2477-2487.

Volumetric magnetic resonance imaging analysis of multilevel upper airway surgery effects on pharyngeal structure.

STUDY OBJECTIVES: The Sleep Apnea Multilevel Surgery (SAMS) trial found that modified uvulopalatopharyngoplasty with tonsillectomy (if tonsils present) combined with radiofrequency tongue ablation reduced obstructive sleep apnea (OSA) severity and daytime sleepiness in moderate-severe OSA. This study aimed to investigate mechanisms of effect on apnea-hypopnea index (AHI) reduction by assessing changes in upper airway volumes (airway space, soft palate, tongue, and intra-tongue fat). METHODS: This is a case series analysis of 43 participants of 51 randomized to the surgical arm of the SAMS trial who underwent repeat magnetic resonance imaging (MRI). Upper airway volume, length, and cross-sectional area, soft palate and tongue volumes, and tongue fat were measured. Relationships between changes in anatomical structures and AHI were assessed. RESULTS: The participant sample was predominantly male (79%); mean ± SD age 42.7 ± 13.3 years, body mass index 30.8 ± 4.1 kg/m2, and AHI 47.0 ± 22.3 events/hour. There were no, or minor, overall volumetric changes in the airway, soft palate, total tongue, or tongue fat volume. Post-surgery there was an increase in the minimum cross-sectional area by 0.1 cm2 (95% confidence interval 0.04-0.2 cm2) in the pharyngeal airway, but not statistically significant on corrected analysis. There was no association between anatomical changes and AHI improvement. CONCLUSIONS: This contemporary multilevel upper airway surgery has been shown to be an effective OSA treatment. The current anatomical investigation suggests there are not significant post-operative volumetric changes associated with OSA improvement 6-month post-surgery. This suggests that effect on OSA improvement is achieved without notable deformation of airway volume. Reduced need for neuromuscular compensation during wake following anatomical improvement via surgery could explain the lack of measurable volume change. Further research to understand the mechanisms of action of multilevel surgery is required. CLINICAL TRIAL: This manuscript presents a planned image analysis of participants randomized to the surgical arm or the clinical trial multilevel airway surgery in patients with moderate-severe obstructive sleep apnea (OSA) who have failed medical management to assess change in OSA events and daytime sleepiness. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=266019&isReview=true%20Australian%20New%20Zealand%20Clinical%20Trials%20Registry%20ACTRN12514000338662, prospectively registered on March 31, 2014.

Obstructive sleep apnea in obese minipigs.

OBJECTIVE: Obesity has reached epidemic proportions and is a strong risk factor for obstructive sleep apnea (OSA). However, the underlying mechanisms are poorly understood and current treatment strategies for OSA and obesity have critical limitations. Thus, establishment of an obesity-related large animal model with spontaneous OSA is imperative. MATERIALS AND METHODS: Natural and sedated sleep were monitored and characterized in 4 obese (body mass index - BMI>48) and 3 non-obese (BMI<40) minipigs. These minipigs were instrumented with the BioRadio system under sedation for the wireless recording of respiratory airflow, snoring, abdominal and chest respiratory movements, electroencephalogram, electrooclulogram, electromyogram, and oxygen saturation. After instrumentation, the minipigs were placed in a dark room with a remote night-vision camera for monitoring all behaviors. Wakefulness and different sleep stages were classified, and episodes of apneas and/or hypopneas were identified during natural and/or sedated sleep. RESULTS: No hypopnea episodes were observed in two of the non-obese minipigs, but one non-obese minipig had 5 hypopnea events. Heavy snoring and 27-58 apnea and/or hypopnea episodes were identified in all 4 obese minipigs. Most of these episodes occurred in the rapid eye movement stage during natural sleep and/or sedated sleep in Yucatan minipigs. CONCLUSIONS: Obese minipigs can experience naturally occurring OSA, thus are an ideal large animal model for obese-related OSA studies.

Effect of Multilevel Upper Airway Surgery vs Medical Management on the Apnea-Hypopnea Index and Patient-Reported Daytime Sleepiness Among Patients With Moderate or Severe Obstructive Sleep Apnea: The SAMS Randomized Clinical Trial.

Importance: Many adults with obstructive sleep apnea (OSA) use device treatments inadequately and remain untreated. Objective: To determine whether combined palatal and tongue surgery to enlarge or stabilize the upper airway is an effective treatment for patients with OSA when conventional device treatment failed. Design, Setting, and Participants: Multicenter, parallel-group, open-label randomized clinical trial of upper airway surgery vs ongoing medical management. Adults with symptomatic moderate or severe OSA in whom conventional treatments had failed were enrolled between November 2014 and October 2017, with follow-up until August 2018. Interventions: Multilevel surgery (modified uvulopalatopharyngoplasty and minimally invasive tongue volume reduction; n = 51) or ongoing medical management (eg, advice on sleep positioning, weight loss; n = 51). Main Outcomes and Measures: Primary outcome measures were the apnea-hypopnea index (AHI; ie, the number of apnea and hypopnea events/h; 15-30 indicates moderate and >30 indicates severe OSA) and the Epworth Sleepiness Scale (ESS; range, 0-24; >10 indicates pathological sleepiness). Baseline-adjusted differences between groups at 6 months were assessed. Minimal clinically important differences are 15 events per hour for AHI and 2 units for ESS. Results: Among 102 participants who were randomized (mean [SD] age, 44.6 [12.8] years; 18 [18%] women), 91 (89%) completed the trial. The mean AHI was 47.9 at baseline and 20.8 at 6 months for the surgery group and 45.3 at baseline and 34.5 at 6 months for the medical management group (mean baseline-adjusted between-group difference at 6 mo, -17.6 events/h [95% CI, -26.8 to -8.4]; P < .001). The mean ESS was 12.4 at baseline and 5.3 at 6 months in the surgery group and 11.1 at baseline and 10.5 at 6 months in the medical management group (mean baseline-adjusted between-group difference at 6 mo, -6.7 [95% CI, -8.2 to -5.2]; P < .001). Two participants (4%) in the surgery group had serious adverse events (1 had a myocardial infarction on postoperative day 5 and 1 was hospitalized for observation following hematemesis of old blood). Conclusions and Relevance: In this preliminary study of adults with moderate or severe OSA in whom conventional therapy had failed, combined palatal and tongue surgery, compared with medical management, reduced the number of apnea and hypopnea events and patient-reported sleepiness at 6 months. Further research is needed to confirm these findings in additional populations and to understand clinical utility, long-term efficacy, and safety of multilevel upper airway surgery for treatment of patients with OSA. Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12614000338662.

Association of Allergic Rhinitis With Change in Nasal Congestion in New Continuous Positive Airway Pressure Users.

Importance: Nasal congestion occurring after continuous positive airway pressure (CPAP) treatment initiation impairs CPAP adherence. Allergic rhinitis is associated with worsening nasal congestion in patients who are exposed to nonallergic triggers. Use of CPAP presents potential nonallergic triggers (eg, humidity, temperature, pressure, and airflow). Objective: To compare nasal congestion among CPAP users with allergic rhinitis, nonallergic rhinitis, and no rhinitis. We hypothesize that CPAP patients with baseline allergic rhinitis are more likely to experience a worsening of nasal congestion (or less improvement in nasal congestion) compared with patients with no baseline rhinitis. Design, Setting, and Participants: This prospective cohort study included consecutive patients newly diagnosed with obstructive sleep apnea in a tertiary sleep center who were using CPAP therapy 3 months after diagnosis. Baseline rhinitis status was assigned as allergic rhinitis, nonallergic rhinitis, or no rhinitis, based on questionnaire responses and past allergy testing. Data were collected from 2004 to 2008 and analyzed from July 2019 to February 2020. Main Outcomes and Measures: At baseline before CPAP exposure and again 3 months later, subjective nasal congestion was measured with the Nasal Obstruction Symptom Evaluation (NOSE) scale and a visual analog scale (VAS), each scored from 0 to 100 (100 = worst congestion). Changes in nasal congestion were tested over 3 months for the whole cohort, within each rhinitis subgroup (paired t test), and between rhinitis subgroups (multivariate linear regression). Results: The study cohort comprised 102 participants, of whom 61 (60%) were male and the mean (SD) age was 50 (13). The study included 23 (22.5%) participants with allergic rhinitis, 67 (65.7%) with nonallergic rhinitis, and 12 (11.8%) with no rhinitis. Nasal congestion improved from baseline to 3 months in the whole cohort (mean [SD] NOSE score, 38 [26] to 27 [23], mean [SD] change, -10 [23]; 95% CI, -15 to -6; mean [SD] VAS score, 41 [27] to 32 [28]; mean [SD] change, -10 [26]; 95% CI, [-15 to -4]) and in each rhinitis subgroup. Adjusted improvement in nasal congestion at 3 months was significantly less in the allergic rhinitis subgroup compared with the no rhinitis subgroup (positive difference means less improvement) compared with baseline: NOSE score 14 (95% CI, 1 to 28) and VAS score 15 (95% CI, 0 to 30). Conclusions and Relevance: Initiation of CPAP was associated with improved subjective nasal congestion, but less improvement in patients with baseline allergic rhinitis. Baseline allergic rhinitis may predict which patients are more vulnerable to potential congestive effects of CPAP.

The Association of Sleep Apnea and Cancer in Veterans.

OBJECTIVE: To test the association between preexisting obstructive sleep apnea (OSA) and subsequent cancer in a large long-term cohort of veteran patients. STUDY DESIGN: Retrospective matched cohort study. SETTING: The Veterans Affairs Health Care System. SUBJECTS AND METHODS: All veteran patients diagnosed with OSA between 1993 and 2013 by International Classification of Diseases, Ninth Revision (ICD-9) codes in any Veterans Affairs facility and veteran patients without an OSA diagnosis, matched to patients with OSA by age and index year. Cancer diagnoses were identified by ICD-9 codes for the time period at least 2 years after OSA diagnosis or index date. We tested the association between OSA and cancer using multivariate Cox regression with time since cohort entry as the time axis, adjusting for potential confounders. RESULTS: The cohort included 1,377,285 patients (726,008 with and 651,277 without an OSA diagnosis) with mean age of 55 years, predominantly male (94%), a minority obese (32%), and median follow-up of 7.4 years (range, 2.0-25.2). The proportion of patients diagnosed with cancer was higher in those with vs without an OSA diagnosis (8.3% vs 3.6%; mean difference 4.8%; 95% confidence interval [CI], 4.7%-4.8%; P < .001). After adjusting for age, sex, year of cohort entry, smoking status, alcohol use, obesity, and comorbidity, the hazard of incident cancer was nearly double in patients with vs without an OSA diagnosis (hazard ratio, 1.97; 95% CI, 1.94-2.00; P < .001). CONCLUSION: Preexisting OSA was strongly associated with subsequent cancer in this veteran cohort, independent of several known cancer risk factors. These findings suggest that OSA may be a strong, independent risk factor for subsequent cancer development.

Development of a Sleep Apnea-Specific Health State Utility Algorithm.

Importance: With the increasing emphasis on economic evaluations, there is a need for additional methods of measuring patient utility in the obstructive sleep apnea population. Objective: To develop and validate a utility scoring algorithm for a sleep apnea-specific quality-of-life instrument. Design, Setting, and Participants: Development and validation were conducted at 2 tertiary referral sleep centers and associated sleep clinics and included patients with newly diagnosed obstructive sleep apnea from a randomized clinical trial and an associated observational cohort study. Baseline participants were randomly divided into a model development group (60%) and a cross-validation group (40%). Main Outcomes and Measures: Utility scoring of the Symptoms of Nocturnal Obstruction and Related Events (SNORE-25) was mapped from the SF-6D utility index through multiple linear regression in the development sample using the Akaike information criterion to determine the best model. Results: A total of 500 participants (development, n = 300; validation, n = 200) were enrolled; the analyzed sample of 500 participants included 295 men (59%), and the mean (SD) age was 48.6 (12.8) years, with a range of 18 to 90 years. The mean (SD) SF-6D utility among participants with untreated sleep apnea was 0.61 (0.08; range, 0.40-0.85) with similar utility across sleep apnea severity groups. The best-fit model (the SNORE Utility Index) was the natural log conversion of the instrument subscales (r2 = 0.32 in the development sample). The SNORE Utility Index retained this association within the validation sample (r2 = 0.33). Conclusions and Relevance: The SNORE Utility Index provides a validated, disease-specific, preference-weighted utility instrument that can be used in future studies of patients with obstructive sleep apnea.

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.

Sleep Apnea Multilevel Surgery (SAMS) trial protocol: a multicenter randomized clinical trial of upper airway surgery for patients with obstructive sleep apnea who have failed continuous positive airway pressure.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a serious and costly public health problem. The main medical treatment, continuous positive airway pressure, is efficacious when used, but poorly tolerated in up to 50% of patients. Upper airway reconstructive surgery is available when medical treatments fail but randomized trial evidence supporting its use is limited. This protocol details a randomized controlled trial designed to assess the clinical effectiveness, safety, and cost-effectiveness of a multilevel upper airway surgical procedure for OSA. METHODS: A prospective, parallel-group, open label, randomized, controlled, multicenter clinical trial in adults with moderate or severe OSA who have failed or refused medical therapies. Six clinical sites in Australia randomly allocated participants in a 1:1 ratio to receive either an upper airway surgical procedure consisting of a modified uvulopalatopharyngoplasty and minimally invasive tongue volume reduction, or to continue with ongoing medical management, and followed them for 6 months. RESULTS: Primary outcomes: difference between groups in baseline-adjusted 6 month OSA severity (apnea-hypopnea index) and subjective sleepiness (Epworth Sleepiness Scale). Secondary outcomes: other OSA symptoms (e.g. snoring and objective sleepiness), other polysomnography parameters (e.g. arousal index and 4% oxygen desaturation index), quality of life, 24 hr ambulatory blood pressure, adverse events, and adherence to ongoing medical therapies (medical group). CONCLUSIONS: The Sleep Apnea Multilevel Surgery (SAMS) trial is of global public health importance for testing the effectiveness and safety of a multilevel surgical procedure for patients with OSA who have failed medical treatment. CLINICAL TRIAL REGISTRATION: Multilevel airway surgery in patients with moderate-severe Obstructive Sleep Apnea (OSA) who have failed medical management to assess change in OSA events and daytime sleepiness. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366019&isReview=true Australian New Zealand Clinical Trials Registry ACTRN12614000338662, prospectively registered on 31 March 2014.