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Background: Single-night disease misclassification of OSA due to night-to-night variability may contribute to inconsistent findings in OSA trials., Research Question: Does multinight quantification of OSA severity provide more precise estimates of associations with incident hypertension?, Study Design and Methods: A total of 3,831 participants without hypertension at baseline were included in simulation analyses. Included participants had ≥ 28 days of nightly apnea-hypopnea index (AHI) recordings via an under-mattress sensor and ≥ three separate BP measurements over a 3-month baseline period followed by ≥ three separate BP measurements 6 to 9 months postbaseline. Incident hypertension was defined as a mean systolic BP ≥ 140 mm Hg or a mean diastolic BP ≥ 90 mm Hg. Simulated trials (1,000) were performed, using bootstrap methods to investigate the effect of variable numbers of nights (x = 1-56 per participant) to quantify AHI and the ability to detect associations between OSA and incident hypertension via logistic regression adjusted for age, sex, and BMI., Results: Participants were middle-aged (mean ± SD, 52 ± 12 y), mostly male (91%), and overweight (BMI, 28 ± 5 kg/m 2 ). Single-night quantification of OSA failed to detect an association with hypertension risk in 42% of simulated trials (α = .05). Conversely, 100% of trials detected an association when AHI was quantified over ≥ 28 nights. Point estimates of hypertension risk were also 50% higher and uncertainty was five times lower during multinight vs single-night simulation trials., Interpretation: Multinight monitoring of OSA allows for better estimates of hypertension risk and potentially other adverse health outcomes associated with OSA. These findings have important implications for clinical care and OSA trial design., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Insomnia and obstructive sleep apnea commonly co-occur (co-morbid insomnia and sleep apnea), and their co-occurrence has been associated with worse cardiometabolic and mental health. However, it remains unknown if people with co-morbid insomnia and sleep apnea are at a heightened risk of incident cardiovascular events. This study used longitudinal data from the Sleep Heart Health Study (N = 5803) to investigate potential associations between co-morbid insomnia and sleep apnea and cardiovascular disease prevalence at baseline and cardiovascular event incidence over ~11 years follow-up. Insomnia was defined as self-reported difficulties initiating and/or maintaining sleep AND daytime impairment. Obstructive sleep apnea was defined as an apnea-hypopnea index ≥ 15 events per hr sleep. Co-morbid insomnia and sleep apnea was defined if both conditions were present. Data from 4160 participants were used for this analysis. The prevalence of no insomnia/obstructive sleep apnea, insomnia only, obstructive sleep apnea only and co-morbid insomnia and sleep apnea was 53.2%, 3.1%, 39.9% and 1.9%, respectively. Co-morbid insomnia and sleep apnea was associated with a 75% (odd ratios [95% confidence interval]; 1.75 [1.14, 2.67]) increase in likelihood of having cardiovascular disease at baseline after adjusting for pre-specified confounders. In the unadjusted model, co-morbid insomnia and sleep apnea was associated with a twofold increase (hazard ratio, 95% confidence interval: 2.00 [1.33, 2.99]) in risk of cardiovascular event incidence. However, after adjusting for pre-specified covariates, co-morbid insomnia and sleep apnea was not significantly associated with incident cardiovascular events (hazard ratio 1.38 [0.92, 2.07]). Comparable findings were obtained when an alternative definition of insomnia (difficulties initiating and/or maintaining sleep without daytime impairment) was used., (© 2022 European Sleep Research Society.)

Background: Increased mortality has been reported in people with insomnia and in those with obstructive sleep apnoea (OSA). However, these conditions commonly co-occur and the combined effect of comorbid insomnia and sleep apnoea (COMISA) on mortality risk is unknown. This study used Sleep Heart Health Study (SHHS) data to assess associations between COMISA and all-cause mortality risk., Methods: Insomnia was defined as difficulties falling asleep, maintaining sleep and/or early morning awakenings from sleep ≥16 times per month, and daytime impairments. OSA was defined as an apnoea-hypopnoea index ≥15 events·h -1 . COMISA was defined if both conditions were present. Multivariable adjusted Cox proportional hazards models were used to determine the association between COMISA and all-cause mortality (n=1210) over 15 years of follow-up., Results: 5236 participants were included. 2708 (52%) did not have insomnia/OSA (reference group), 170 (3%) had insomnia-alone, 2221 (42%) had OSA-alone and 137 (3%) had COMISA. COMISA participants had a higher prevalence of hypertension (OR 2.00, 95% CI 1.39-2.90) and cardiovascular disease (CVD) (OR 1.70, 95% CI 1.11-2.61) compared with the reference group. Insomnia-alone and OSA-alone were associated with higher risk of hypertension but not CVD compared with the reference group. Compared with the reference group, COMISA was associated with a 47% (hazard ratio 1.47, 95% CI 1.06-2.07) increased risk of mortality. The association between COMISA and mortality was consistent across multiple definitions of OSA and insomnia., Conclusions: COMISA was associated with higher rates of hypertension and CVD at baseline, and an increased risk of all-cause mortality compared with no insomnia/OSA., Competing Interests: Conflict of interest: B. Lechat has nothing to disclose. Conflict of interest: S. Appleton has nothing to disclose. Conflict of interest: Y.A. Melaku has nothing to disclose. Conflict of interest: K. Hansen reports grants from the Australian Research Council, during the conduct of the study. Conflict of interest: R.D. McEvoy reports grants from the National Health and Medical Research Council, during the conduct of the study. Conflict of interest: R. Adams reports grants from The Hospital Research Foundation, National Health and Medical Research Council, ResMed Foundation, Phillips Foundation and Sleep Health Foundation, during the conduct of the study. Conflict of interest: P. Catcheside reports grants from the National Health and Medical Research Council, Defence Science and Technology, and the Flinders Foundation, outside the submitted work. Conflict of interest: L. Lack reports grants, personal fees and nonfinancial support from Re-time Pty Ltd, outside the submitted work. Conflict of interest: D.J. Eckert reports grants from the National Health and Medical Research Council of Australia, during the conduct of the study; grants and personal fees from Apnimed, and Bayer, grants from the Collaborative Research Centre (CRC-P), outside the submitted work; and has a patent “Methods for estimating key phenotypic traits for obstructive sleep apnoea and simplified clinical tools to direct targeted therapy”, PCT patent application pending. Conflict of interest: A. Sweetman has nothing to disclose., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Rationale: Primary care clinicians may be well placed to play a greater role in obstructive sleep apnea (OSA) management. Objectives: To evaluate the outcomes and cost-effectiveness of sleep apnea management in primary versus specialist care, using an individual-participant data meta-analysis to determine whether age, sex, severity of OSA, and daytime sleepiness impacted outcomes. Methods: Data sources were the Cumulative Index to Nursing and Allied Health Literature (CINAHL) database, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid SP, Scopus, ProQuest, U.S. National Institutes of Health Ongoing Trials Register, and ISRCTN registry (inception until 09-25-2019). Hand searching was undertaken. Two authors independently assessed articles and included trials that randomized adults with a suspected diagnosis of sleep apnea to primary versus specialist management within the same study and reported daytime sleepiness using the Epworth Sleepiness Scale (range 0-24; >10 indicates pathological sleepiness; minimum clinically important difference 2 units) at baseline and follow-up. Results: The primary analysis combined data from 970 (100%) participants (four trials). Risk of bias was assessed (Cochrane Tool). One-stage intention-to-treat analysis showed a slightly smaller decrease in daytime sleepiness (0.8; 0.2 to 1.4), but greater reduction in diastolic blood pressure in primary care (-1.9; -3.2 to -0.6 mm Hg), with similar findings in the per-protocol analysis. Primary care-based within-trial healthcare system costs per participant were lower (-$448.51 U.S.), and quality-adjusted life years and daytime sleepiness improvements were less expensive. Similar primary outcome results were obtained for subgroups in both management settings. Conclusions: Similar outcomes in primary care at a lower cost provide strong support for implementation of primary care-based management of sleep apnea.

Rationale: Recent studies suggest that obstructive sleep apnea (OSA) severity can vary markedly from night to night, which may have important implications for diagnosis and management. Objectives: This study aimed to assess OSA prevalence from multinight in-home recordings and the impact of night-to-night variability in OSA severity on diagnostic classification in a large, global, nonrandomly selected community sample from a consumer database of people that purchased a novel, validated, under-mattress sleep analyzer. Methods: A total of 67,278 individuals aged between 18 and 90 years underwent in-home nightly monitoring over an average of approximately 170 nights per participant between July 2020 and March 2021. OSA was defined as a nightly mean apnea-hypopnea index (AHI) of more than 15 events/h. Outcomes were multinight global prevalence and likelihood of OSA misclassification from a single night's AHI value. Measurements and Main Results: More than 11.6 million nights of data were collected and analyzed. OSA global prevalence was 22.6% (95% confidence interval, 20.9-24.3%). The likelihood of misdiagnosis in people with OSA based on a single night ranged between approximately 20% and 50%. Misdiagnosis error rates decreased with increased monitoring nights (e.g., 1-night F1-score = 0.77 vs. 0.94 for 14 nights) and remained stable after 14 nights of monitoring. Conclusions: Multinight in-home monitoring using novel, noninvasive under-mattress sensor technology indicates a global prevalence of moderate to severe OSA of approximately 20%, and that approximately 20% of people diagnosed with a single-night study may be misclassified. These findings highlight the need to consider night-to-night variation in OSA diagnosis and management.

Insomnia and obstructive sleep apnea (OSA) commonly co-occur. Approximately 30-50% of patients with OSA report clinically significant insomnia symptoms, and 30-40% of patients with chronic insomnia fulfil diagnostic criteria for OSA. Compared to either insomnia or OSA alone, co-morbid insomnia and sleep apnea (COMISA) is associated with greater morbidity for patients, complex diagnostic decisions for clinicians, and reduced response to otherwise effective treatment approaches. Potential bi-directional causal relationships between the mechanisms and manifestations of insomnia and OSA could play an integral role in the development and management of COMISA. A greater understanding of these relationships is required to guide personalized diagnostic and treatment approaches for COMISA. This review summarizes the available evidence of bi-directional relationships between COMISA, including epidemiological research, case studies, single-arm treatment studies, randomized controlled treatment trials, and objective sleep study data. This evidence is integrated into a conceptual model of COMISA to help refine the understanding of potential bi-directional causal relationships between the two disorders. This theoretical framework is essential to help guide future research, improve diagnostic tools, determine novel therapeutic targets, and guide tailored sequenced and multi-faceted treatment approaches for this common, complex, and debilitating condition., Competing Interests: Conflicts of interest Financial conflicts of interest AS, LL and DMc report receiving research funding support from competitive grants from ResMed Australia; Philips Respironics USA. LL reports receiving research funding support and has shares in Re-time Pty Ltd (Adelaide, Australia). Outside the current study, DJE has a Cooperative Research Centre (CRC)-P grant (Industry partner Oventus Medical) and receives research income from Bayer and Apnimed and serves as a consultant. PC reports receiving grants from NHMRC and Defence Science and Technology outside this study. The remaining authors report no relevant financial conflicts of interest. Non-financial conflicts of interest Outside the current study DJE and PC report receiving equipment loan support from Philips. AS, LL, and DMc report receiving equipment support from Philips and ResMed. The remaining authors report no relevant non-financial conflicts of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: In this study, we sought to estimate the prevalence of concomitant sleep-disordered breathing (SDB) in patients with atrial fibrillation (AF) and to systematically evaluate how SDB is assessed in this population., Methods: We searched Medline, Embase and Cinahl databases through August 2020 for studies reporting on SDB in a minimum 100 patients with AF. For quantitative analysis, studies were required to have systematically assessed for SDB in consecutive AF patients. Pooled prevalence estimates were calculated with the use of the random effects model. Weighted mean differences and odds ratios were calculated when possible to assess the strength of association between baseline characteristics and SDB., Results: The search yielded 2758 records, of which 33 studies (n = 23,894 patients) met the inclusion criteria for qualitative synthesis and 13 studies (n = 2660 patients) met the meta-analysis criteria. The pooled SDB prevalence based on an SDB diagnosis cutoff of apnea-hypopnea index (AHI) ≥ 5/h was 78% (95% confidence interval [CI] 70%-86%; P < 0.001). For moderate-to-severe SDB (AHI ≥ 15/h), the pooled SDB prevalence was 40% (95% CI 32%-48%; P < 0.001). High degrees of heterogeneity were observed (I 2  = 96% and 94%, respectively; P < 0.001). Sleep testing with the use of poly(somno)graphy or oximetry was the most common assessment tool used (in 22 studies, 66%) but inconsistent diagnostic thresholds were used., Conclusions: SDB is highly prevalent in patients with AF. Wide variation exists in the diagnostic tools and thresholds used to detect concomitant SDB in AF. Prospective systematic testing for SDB in unselected cohorts of AF patients may be required to define the true prevalence of SDB in this population., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Study Objectives: Patients with comorbid insomnia and sleep apnea (COMISA) report increased severity of depression, anxiety, and stress symptoms compared to patients with either insomnia or sleep apnea alone. Although cognitive behavioral therapy for insomnia (CBTi) is an effective treatment for COMISA, previous research suggests a reduced response to CBTi by patients with insomnia and depression, anxiety, and stress symptoms. Therefore, we used randomized controlled trial data to investigate the impact of depression, anxiety, and stress symptoms before treatment on changes in insomnia after CBTi vs control in patients with COMISA., Methods: 145 patients with COMISA (insomnia as defined by the International Classification of Sleep Disorders, third edition and apnea-hypopnea index ≥ 15 events/h) were randomized to CBTi (n = 72) or no-treatment control (n = 73). One-week sleep diaries and standardized questionnaire measures of insomnia, sleepiness, fatigue, depression, anxiety, and stress were completed pretreatment and posttreatment. Mixed models were used to examine interactions between depression, anxiety, and stress symptoms before treatment, intervention-group (CBTi, control), and time (pretreatment, posttreatment) on insomnia symptoms., Results: Approximately half of this COMISA sample reported at least mild symptoms of depression (57%), anxiety (53%), and stress (48%) before treatment. Patients reporting greater depression, anxiety, and stress symptoms before treatment also reported increased severity of insomnia, daytime fatigue, and sleepiness. Improvements in questionnaire and diary-measured insomnia symptoms improved during CBTi and were not moderated by severity of depression, anxiety, or stress symptoms before treatment (all interaction P ≥ .11)., Conclusions: We found no evidence that symptoms of depression, anxiety, or stress impair the effectiveness of CBTi in improving insomnia symptoms in patients with COMISA. Patients with COMISA and comorbid symptoms of depression, anxiety, and stress should be referred for CBTi to treat insomnia and improve subsequent management of their obstructive sleep apnea., Clinical Trial Registration: Registry: Australian New Zealand Clinical Trials Registry; Name: Treating comorbid insomnia with obstructive sleep apnea (COMISA) study: A new treatment strategy for patients with combined insomnia and sleep apnea; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365184; Identifier: ACTRN12613001178730., (© 2021 American Academy of Sleep Medicine.)

Study Objectives: While cognitive and behavioral therapy for insomnia (CBTi) is an effective treatment in patients with comorbid moderate and severe obstructive sleep apnea (OSA), there is concern that the bedtime restriction component of CBTi might dangerously exacerbate daytime sleepiness in such patients. We examined randomized controlled trial data to investigate the effect of OSA severity, and pretreatment daytime sleepiness on week-to-week changes in daytime sleepiness and sleep parameters during CBTi and no-treatment control., Methods: One hundred and forty-five patients with untreated physician-diagnosed OSA (apnea-hypopnea index ≥15) and psychologist-diagnosed insomnia (ICSD-3) were randomized to a 4-week CBTi program (n = 72) or no-treatment control (n = 73). The Epworth sleepiness scale (ESS) and sleep diaries were completed during pretreatment, weekly CBTi sessions, and posttreatment. Effects of OSA severity, pretreatment daytime sleepiness, and intervention group on weekly changes in daytime sleepiness and sleep parameters were investigated., Results: The CBTi group reported a 15% increase in ESS scores following the first week of bedtime restriction (M change = 1.3 points, 95% CI = 0.1-2.5, p = 0.031, Cohen's d = 0.27) which immediately returned to pretreatment levels for all subsequent weeks, while sleep parameters gradually improved throughout CBTi. There were no differences in changes in daytime sleepiness during treatment between CBTi and control groups or OSA-severity groups. Higher pretreatment ESS scores were associated with a greater ESS reduction during CBTi., Conclusions: CBTi appears to be a safe and effective treatment in the presence of comorbid moderate and severe OSA. Nevertheless, patients living with comorbid insomnia and sleep apnea and treated with CBTi should be monitored closely for increased daytime sleepiness during the initial weeks of bedtime restriction therapy., Clinical Trial Registration: Treating comorbid insomnia with obstructive sleep apnoea (COMISA) study: A new treatment strategy for patients with combined insomnia and sleep apnoea, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id = 365184 Australian New Zealand Clinical Trials Registry: ACTRN12613001178730. Universal Trial Number: U1111-1149-4230., (© Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Introduction: Sleep-disordered breathing (SDB) in patients with motor neurone disease (MND) is normally attributed to hypoventilation due to muscle weakness. However, we have observed different patterns of SDB among MND patients referred for non-invasive ventilation, which do not appear to be explained by respiratory muscle weakness alone., Aim: The aim of this study was to examine the characteristics of SDB in MND., Methods: This is a retrospective analysis of sleep studies (using polysomnography [PSG]), pulmonary function tests, and arterial blood gases in MND patients referred to a tertiary sleep medicine service for clinical review. Sleep apnoeas were characterised as obstructive or central, and to further characterise the nature of SDB, hypopnoeas were classified as obstructive versus central., Results: Among 13 MND patients who had a diagnostic PSG, the mean ± SD age was 68.9 ± 9.8 years, BMI 23.0 ± 4.3 kg/m2, forced vital capacity 55.7 ± 20.9% predicted, and partial pressure of CO2 (arterial blood) 52.7 ± 12.1 mm Hg. A total of 38% of patients (5/13) showed evidence of sleep hypoventilation. The total apnoea/hypopnoea index (AHI) was (median [interquartile range]) 44.4(36.2-56.4)/h, with 92% (12/13) showing an AHI >10/h, predominantly due to obstructive events, although 8% (1/13) also showed frequent central apnoea/hypopnoeas., Conclusions: Patients with MND exhibit a wide variety of SDB. The prevalence of obstructive sleep apnoea (OSA) is surprising considering the normal BMI in most patients. A dystonic tongue and increased upper-airway collapsibility might predispose these patients to OSA. The wide variety of SDB demonstrated might have implications for ventilator settings and patients' outcomes., (© 2021 S. Karger AG, Basel.)

Background: Atrial fibrillation (AF) management guidelines recommend screening for symptoms of sleep-disordered breathing (SDB). We aimed to assess the role of self-reported daytime sleepiness in detection of patients with SDB and AF., Methods: A total of 442 consecutive ambulatory patients with AF who were considered candidates for rhythm control and underwent polysomnography comprised the study population. The utility of daytime sleepiness (quantified by the Epworth Sleepiness Scale [ESS]) to predict any (apnea-hypopnea index [AHI] ≥ 5), moderate-to-severe (AHI ≥ 15), and severe (AHI ≥ 30) SDB on polysomnography was tested., Results: Mean age was 60 ± 11 years and 69% patients were men. SDB was present in two-thirds of the population with 33% having moderate-to-severe SDB. Daytime sleepiness was low (median ESS = 8/24) and the ESS poorly predicted SDB, regardless of the degree of SDB tested (area under the curve: 0.48-0.56). Excessive daytime sleepiness (ESS ≥ 11) was present in 11.9% of the SDB population and had a negative predictive value of 43.1% and a positive predictive value of 67.5% to detect moderate-to-severe SDB. Male gender (odds ratio [OR]: 2.3, 95% confidence interval [CI]: 1.4-3.8, P = 0.001), obesity (OR: 3.5, 95% CI: 2.3-5.5, P < 0.001), diabetes (OR: 2.3, 95% CI: 1.2-4.4, P = 0.08), and stroke (OR: 4.6, 95% CI: 1.7-12.3, P = 0.002) were independently associated with an increased likelihood of moderate-to-severe SDB., Conclusions: In an ambulatory AF population, SDB was common but most patients reported low daytime sleepiness levels. Clinical features, rather than daytime sleepiness, were predictive of patients with moderate-to-severe SDB. Lack of excessive daytime sleepiness should not preclude patients from being investigated for the potential presence of concomitant SDB., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to determine night-to-night variability in the severity of sleep-disordered breathing (SDB) and the dynamic intraindividual relationship to daily risk of incident atrial fibrillation (AF) by using simultaneous long-term day-by-day SDB and AF monitoring., Background: Night-to-night variability in SDB severity may result in a dynamic exposure to SDB related conditions impacting the timing and extent of cardiovascular responses., Methods: This study was an observational cohort study. Daily data for AF burden and average respiratory disturbance index (RDI) were extracted from pacemakers capable of monitoring nightly SDB and daily AF burden in 72 patients. Nightly RDI values were grouped into quartiles of severity within each patient. AF burdens of >5 min, >1 h, and >12 h were the outcome variables., Results: A total of 32% of patients had a mean RDI of ≥20/h, indicative of overall severe SDB. There was significant night-to-night variation in RDI reflected by an absolute SD of ±6.3 events/h (range 2 to 14 events/h) within any given patient. Within each patient, the nights with the highest RDI (in their highest quartile) conferred a 1.7-fold (1.2 to 2.2; p < 0.001), 2.3-fold (1.6 to 3.5; p < 0.001), and 10.2-fold (3.5 to 29.9; p < 0.001) increase risk of having at least 5 min, 1 h, and 12 h, respectively, of AF during the same day compared with the best sleep nights (in their lowest quartiles)., Conclusions: There is considerable night-to-night variability in SDB severity which cannot be detected by 1 single overnight sleep study. SDB burden may be a better metric with which to assess the extent of dynamic SDB related cardiovascular responses such as daily AF risk than the categorical diagnosis of SDB. (Night-to-Night Variability in Severity of Sleep Apnea and Daily Dynamic Atrial Fibrillation Risk [VARIOSA-AF]; ACTRN 12618000757213)., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Background: Sleep-disordered breathing (SDB) is highly prevalent in patients with atrial fibrillation (AF) and its treatment can improve rhythm control. Polysomnography (PSG) is the gold standard for the diagnosis of SDB but its high cost and limited availability constrain its role as a standard SDB screening tool. We sought to assess the diagnostic utility of overnight oximetry in predicting SDB in AF patients., Methods: We analyzed prospectively collected data on 439 patients with documented AF (62% paroxysmal AF) who underwent PSG. Overnight oximetry was used to determine the oxygen desaturation index (ODI, number of desaturation/h) by a novel automated computer algorithm. ODI was validated against PSG derived apnea-hypopnea index (AHI)., Results: The sample consisted of 69% men with a mean age of 59.9 ± 11.3 years and body mass index of 30 ± 5 kg/m 2 . The median AHI was 9.5 [3.6-21.0]/h and the prevalence of moderate (AHI 15-29/h) and severe SDB (AHI ≥ 30/h) was 17.3% and 16.6% respectively. The ODI was able to detect moderate-to-severe SDB (AHI ≥ 15/h; area under the receiver-operating-characteristic curve (AUC): 0.951, 95% CI: 0.929-0.972) and severe SDB (AHI ≥ 30/h; 0.932, 95% CI: 0.895-0.968) with high diagnostic accuracy. An ODI cut-off of 4.1/h resulted in a 91% sensitivity and 83% specificity in discriminating between patients with and without AHI ≥ 15/h. An ODI of 7.6/h yielded a sensitivity and specificity for AHI ≥ 30/h of 89% and 83%, respectively., Conclusions: ODI derived from a simple and low-cost overnight oximetry can be used as an accessible and reliable screening tool, particularly to rule out SDB., (Copyright © 2018 Elsevier B.V. All rights reserved.)

There is mounting evidence for an association between sleep disorders and hypertension. In obstructive sleep apnea (OSA), there are plausible biological reasons for the development of hypertension, and treatment of OSA results in modest (2-3 mm Hg), adherence-dependent decreases in blood pressure, with larger effects evident in those with resistant hypertension. However, prospective, population-based cohort studies have not yet convincingly demonstrated a link between OSA and incident hypertension, and adequately powered controlled trials of CPAP for the prevention or treatment or hypertension are lacking. While associations have been identified between short sleep duration, insomnia, restless legs syndrome (RLS), shift work, and hypertension, the causative role of these conditions/circumstances is not proven, and further well-designed pathophysiological and/or interventional studies are needed. Particular emphasis should be placed on defining subgroups of hypertensive OSA patients that stand to benefit most from OSA treatment and in understanding the link between sleep apnea and hypertensive disorders of pregnancy. Well-controlled intervention studies are needed in populations with short sleep duration, insomnia, shift work sleep disorder, and RLS to confirm their putative links with hypertension.

Emerging research highlights the complex interrelationships between sleep-disordered breathing and cardiovascular disease, presenting clinical and research opportunities as well as challenges. Patients presenting to cardiology clinics have a high prevalence of obstructive and central sleep apnea associated with Cheyne-Stokes respiration. Multiple mechanisms have been identified by which sleep disturbances adversely affect cardiovascular structure and function. Epidemiological research indicates that obstructive sleep apnea is associated with increases in the incidence and progression of coronary heart disease, heart failure, stroke, and atrial fibrillation. Central sleep apnea associated with Cheyne-Stokes respiration predicts incident heart failure and atrial fibrillation; among patients with heart failure, it strongly predicts mortality. Thus, a strong literature provides the mechanistic and empirical bases for considering obstructive sleep apnea and central sleep apnea associated with Cheyne-Stokes respiration as potentially modifiable risk factors for cardiovascular disease. Data from small trials provide evidence that treatment of obstructive sleep apnea with continuous positive airway pressure improves not only patient-reported outcomes such as sleepiness, quality of life, and mood but also intermediate cardiovascular end points such as blood pressure, cardiac ejection fraction, vascular parameters, and arrhythmias. However, data from large-scale randomized controlled trials do not currently support a role for positive pressure therapies for reducing cardiovascular mortality. The results of 2 recent large randomized controlled trials, published in 2015 and 2016, raise questions about the effectiveness of pressure therapies in reducing clinical end points, although 1 trial supported the beneficial effect of continuous positive airway pressure on quality of life, mood, and work absenteeism. This review provides a contextual framework for interpreting the results of recent studies, key clinical messages, and suggestions for future sleep and cardiovascular research, which include further consideration of individual risk factors, use of existing and new multimodality therapies that also address adherence, and implementation of trials that are sufficiently powered to target end points and to support subgroup analyses. These goals may best be addressed through strengthening collaboration among the cardiology, sleep medicine, and clinical trial communities., (© 2017 American Heart Association, Inc.)

Importance: Sleep apnea (obstructive and central) is associated with adverse cardiovascular risk factors and increased risks of cardiovascular disease. Positive airway pressure (PAP) provides symptomatic relief, whether delivered continuously (CPAP) or as adaptive servo-ventilation (ASV), but the associations with cardiovascular outcomes and death are unclear., Objective: To assess the association of PAP vs control with cardiovascular events and death in patients with sleep apnea., Data Sources and Study Selection: MEDLINE, EMBASE, and the Cochrane Library were systematically searched from inception date to March 2017 for randomized clinical trials that included reporting of major adverse cardiovascular events or deaths., Data Extraction and Synthesis: Two authors independently extracted data using standardized forms. Summary relative risks (RRs), risk differences (RDs) and 95% CIs were obtained using random-effects meta-analysis., Main Outcomes and Measures: The main outcomes were a composite of acute coronary syndrome (ACS) events, stroke, or vascular death (major adverse cardiovascular events); cause-specific vascular events; and death., Results: The analyses included data from 10 trials (9 CPAP; 1 ASV) of patients with sleep apnea (N = 7266; mean age, 60.9 [range, 51.5 to 71.1] years; 5847 [80.5%] men; mean [SD] body mass index, 30.0 [5.2]. Among 356 major adverse cardiovascular events and 613 deaths recorded, there was no significant association of PAP with major adverse cardiovascular events (RR, 0.77 [95% CI, 0.53 to 1.13]; P = .19 and RD, -0.01 [95% CI, -0.03 to 0.01]; P = .23), cardiovascular death (RR, 1.15 [95% CI, 0.88 to 1.50]; P = .30 and RD -0.00 [95% CI, -0.02 to 0.02]; P = .87), or all-cause death (RR, 1.13 [95% CI, 0.99 to 1.29]; P = .08 and RD, 0.00 [95% CI, -0.01 to 0.01]; P = .51). The same was true for ACS, stroke, and heart failure. There was no evidence of different associations for CPAP vs ASV (all P value homogeneity >.24), and meta-regressions identified no associations of PAP with outcomes for different levels of apnea severity, follow-up duration, or adherence to PAP (all P values > .13)., Conclusions and Relevance: The use of PAP, compared with no treatment or sham, was not associated with reduced risks of cardiovascular outcomes or death for patients with sleep apnea. Although there are other benefits of treatment with PAP for sleep apnea, these findings do not support treatment with PAP with a goal of prevention of these outcomes.

Study Objectives: The use of opioid medication for chronic pain has been increasing. The main aim of this study was to assess how many patients on opioids for chronic pain had sleep disordered breathing (SDB) and the type of SDB. The impact of these medications on daytime arterial blood gas (ABG) measurements and psychomotor vigilance was also studied., Methods: Twenty-four patients (aged 18-75 years) on long-term opioids were prospectively recruited. Patients underwent home polysomnogram (PSG), psychomotor vigilance testing (PVT), and awake daytime ABG. Overnight PSG findings were compared to those of patients matched for age, sex, and BMI referred to our sleep service for evaluation of SDB. PVT results in the patient cohort were compared to PVT in healthy controls., Results: Forty-six percent of opioid patients had severe SDB as defined by an apnea hypopnea index (AHI) > 30/h. The severity of SDB was similar in opioid-treated pain clinic patients and sleep clinic patients (mean ± SD AHI: Opioid-treated patients 32.7 ± 25.6; Sleep Study comparator group 28.9 ± 24.6, p = 0.6). Opioid patients had a higher frequency of central apneas and a lower arousal index (CAI: 3.9 ± 8.3 vs. 0.3 ± 0.5 events/h; p = 0.004, AI 8.0 ± 4.1 vs. 20.1 ± 13.8, p < 0.001). Pain clinic patients had impaired gas exchange during sleep and wakefulness. Nine of 20 (45%) had daytime hypercapnia, indicating a surprising number were in chronic respiratory failure. Morphine equivalent doses correlated with the severity of SDB. PVT was impaired when compared to a healthy PVT comparator group (RT: Opioid-treated patients 0.43 ± 0.27: Healthy PVT comparator group 0.28 ± 0.03 sec; p < 0.001)., Conclusions: Patients on long-term opioids frequently have severe SDB, which in part is central in origin. PVT was markedly impaired. Half of the patients studied have evidence of chronic ventilatory failure., Commentary: A commentary on this article appears in this issue on page 853

Objective: Patients with primary Sjögren's syndrome (pSS) have higher fatigue levels and also suffer from excessive day time sleepiness. The underlying mechanisms for this are not fully understood. Knowing that these patients have higher salivary surface tension, we postulated that sleep disordered breathing (SDB) would be more common and would be a contributor to these symptoms amongst pSS patients. We investigated the prevalence of SDB in pSS patients and its relationship to their symptoms of fatigue and excessive daytime sleepiness., Methods: This was an observational study of 28 pSS patients (mean±SEM age, 58.7±1.9) and 18 healthy subjects (mean±SEM age, 55.8±3.4) matched for age, sex, and BMI. All the participants underwent an overnight polysomnography. The two groups were compared for fatigue, sleepiness, anxiety, and depression scores, and for the frequency of obstructive apneas and hypopneas during sleep. Correlation analyses were used to explore relationships between sleep study variables and excess sleepiness and fatigue., Results: Fatigue, sleepiness, anxiety and depression symptoms, and sleep onset latency were significantly greater in pSS patients than controls. pSS patients had twice the frequency of obstructive apneas and hypopneas compared with control subjects (median[IQR],18.6/h [10.4-40.1] vs. 9.9/h [6.5-23.4]; p=0.032) and OSA defined as an apnea-hypopnea index >15 events/h of sleep was more prevalent amongst pSS patients than controls (64% vs. 28%; p=0.033). While no significant correlations were found between parameters of sleep disordered breathing and sleepiness scores or fatigue scores in the pSS group, CPAP treatment in a small subset of the pSS who were more severely affected by OSA suggested significant symptomatic benefit., Conclusion: OSA appears to be increased in pSS and may be a useful therapeutic target to improve the quality of life of these patients., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Obese obstructive sleep apnea (OSA) patients potentially defend end-expiratory lung volume (EELV) during wakefulness via increased expiratory diaphragmatic activity (eEMG(dia)). A reduction in eEMG(dia) and EELV at sleep onset could, therefore, increase upper airway collapsibility via reduced tracheal traction. The aim of this study was to establish if eEMG(dia) is greater in obese OSA patients vs. healthy-weight controls during wakefulness, and to compare eEMG(dia) and EELV changes at sleep onset between groups as a function of stable breathing, hypopnea vs. apnea events developing within the first few breaths after sleep onset. Eight obese men with OSA and eight healthy-weight men without OSA were studied in the supine position while instrumented with an intraesophageal catheter to measure eEMG(dia) and magnetometer coils to assess changes in EELV. While eEMG(dia) expressed as %maximal activity was not significantly different between groups during wakefulness, OSA patients experienced a greater fall in eEMG(dia) following sleep onset (group × breath, P < 0.001) and a greater decrease when respiratory events accompanied sleep onsets (category × breath, P < 0.001). The decrease in EELV by the third postsleep onset breath was small (OSA, 61.4 ± 8.0 ml, P < 0.001; controls, 34.0 ± 4.2 ml, P < 0.001), with the decrease significantly greater in OSA patients over time (group × breath, P = 0.007). There was a greater decrease with more severe events (category × breath, P < 0.001), with EELV decreasing by 89.6 ± 14.2 ml (P < 0.001) at the onset of apneas in the OSA group. These data support that diaphragm tone and EELV frequently decrease following sleep onset, with greater falls at transitions accompanied by respiratory events. In addition to decrements in upper airway dilator muscle activity, decreasing lung volume potentially contributes to an increased propensity for upper airway collapse in OSA patients at sleep onset.

Objectives: To describe the growth in the use of state-funded (Medicare) polysomnography (PSG) in Australia since 1990 and to compare PSG growth to other common diagnostic procedures and growth in total Medicare payments., Methods: Interrogation of online database of historical census-level data routinely collected by Medicare., Results: There has been a steady rise in the number of PSGs performed in Australia since 1990; the growth has been faster than overall Medicare-spending growth and faster than growth in comparable diagnostic procedures. However, there are marked interstate differences in growth. Per capita data, available only for 1995 to 2004, shows that nationwide PSG provision has risen from 123 to 308 per 100,000 people enrolled in Medicare., Conclusions: The provision of PSG in Australia has been growing steadily since publicly funded reimbursement began in 1990. This growth has been faster than the overall population growth and faster than the growth in Medicare funding for other diagnostic procedures and classes of medical interventions. However, the provision of PSG might be expected to continue to increase because the per capita provision (308 per 100,000) is still less than recent estimates from Canada and the United States (370.4 and 427.0 per 100,000, respectively).

Breathing effort is important to quantify to understand mechanisms underlying central and obstructive sleep apnea, respiratory-related arousals, and the timing and effectiveness of invasive or noninvasive mechanically assisted ventilation. Current quantitative methods to evaluate breathing effort rely on inspiratory esophageal or epiglottic pressure swings or changes in diaphragm electromyographic (EMG) activity, where units are problematic to interpret and compare between individuals and to measured ventilation. This paper derives a novel method to quantify breathing effort in units directly comparable with measured ventilation by applying respiratory mechanics first principles to convert continuous transpulmonary pressure measurements into "attempted" airflow expected to have arisen without upper airway obstruction. The method was evaluated using data from 11 subjects undergoing overnight polysomnography, including six patients with obesity with severe obstructive sleep apnea (OSA), including one who also had frequent central events, and five healthy-weight controls. Classic respiratory mechanics showed excellent fits of airflow and volume to transpulmonary pressures during wake periods of stable unobstructed breathing (means ± SD, r2 = 0.94 ± 0.03), with significantly higher respiratory system resistance in patients compared with healthy controls (11.2 ± 3.3 vs. 7.1 ± 1.9 cmH2O·L−1·s, P = 0.032). Subsequent estimates of attempted airflow from transpulmonary pressure changes clearly highlighted periods of acute and prolonged upper airway obstruction, including within the first few breaths following sleep onset in patients with OSA. This novel technique provides unique quantitative insights into the complex and dynamically changing interrelationships between breathing effort and achieved airflow during periods of obstructed breathing in sleep. NEW & NOTEWORTHY: Ineffective breathing efforts with snoring and obstructive sleep apnea (OSA) are challenging to quantify. Measurements of esophageal or epiglottic pressure swings and diaphragm electromyography are useful, but units are problematic to interpret and compare between individuals and to measured ventilation. This paper derives a novel method that uses esophageal pressure and respiratory mechanics first principles to quantify breathing effort as "attempted" flow and volume in units directly comparable with measured airflow, volume, and ventilation. [ABSTRACT FROM AUTHOR]

CO2 inhalation has been previously reported as a treatment for central sleep apnea both when associated with heart failure or where the cause is unknown. Here, we evaluated a novel CO2 supply system using a novel open mask capable of comfortably delivering a constantly inspired fraction of CO2 (FICO2 ) during sleep. We recruited 18 patients with central sleep apnea (13 patients with cardiac disease, and 5 patients idiopathic) diagnosed by diaphragm electromyogram (EMG) recordings made during overnight full polysomnography (PSG) (night 1). In each case, the optimal FICO2 was determined by an overnight manual titration with PSG (night 2). Titration commenced at 1% CO2 and increased by 0.2% increments until central sleep apnea (CSA) disappeared. Patients were then treated on the third night (night 3) with the lowest therapeutically effective concentration of CO2 derived from night 2. Comparing night 1 and night 3, both apnea-hypopnea index (AHI; 31 ± 14 vs. 6 ± 3 events/h, P < 0.01) and arousal index (22 ± 8 vs. 15 ± 8 events/h, P < 0.01) were significantly improved during CO2 treatment. Sleep efficiency improved from 71 ± 18 to 80± 11%, P < 0.05, and sleep latency was shorter (23 ± 18 vs. 10 ± 10 min, P < 0.01). Heart rate was not different between night 1 and night 3. Our data confirm the feasibility of our CO2 delivery system and indicate that individually titrated CO2 supplementation with a novel device including a special open mask can reduce sleep disordered breathing severity and improve sleep quality. Randomized controlled studies should now be undertaken to assess therapeutic benefit for patients with CSA. NEW & NOTEWORTHY A novel device using a special mask was developed and proved that CO2 therapy using the device could eliminate central sleep apnea (CSA) events and improve sleep quality including reducing arousal index in patients with heart failure. The device would become a useful clinical treatment for heart failure patients with CSA. [ABSTRACT FROM AUTHOR]

Continuous positive airway pressure (CPAP) is the first-line treatment for obstructive sleep apnea (OSA). Although CPAP improves symptoms (e.g., daytime sleepiness), there is a lack of high-quality evidence that CPAP prevents many long-term outcomes, including cognitive impairment, myocardial infarction, and stroke. Observational studies suggest that patients with symptoms may be particularly likely to experience these preventive benefits with CPAP, but ethical and practical concerns limited the participation of such patients in prior long-term randomized trials. As a result, there is uncertainty about the full benefits of CPAP, and resolving this uncertainty is a key priority for the field. This workshop assembled clinicians, researchers, ethicists, and patients to identify strategies to understand the causal effects of CPAP on long-term clinically important outcomes among patients with symptomatic OSA. Quasi-experimental designs can provide valuable information and are less time and resource intensive than trials. Under specific conditions and assumptions, quasi-experimental studies may be able to provide causal estimates of CPAP's effectiveness from generalizable observational cohorts. However, randomized trials represent the most reliable approach to understanding the causal effects of CPAP among patients with symptoms. Randomized trials of CPAP can ethically include patients with symptomatic OSA, as long as there is outcome-specific equipoise, adequate informed consent, and a plan to maximize safety while minimizing harm (e.g., monitoring for pathologic sleepiness). Furthermore, multiple strategies exist to ensure the generalizability and practicality of future randomized trials of CPAP. These strategies include reducing the burden of trial procedures, improving patient-centeredness, and engaging historically excluded and underserved populations. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA) severity can vary markedly from night-to-night. However, the impact of night-to-night variability in OSA severity on key cardiovascular outcomes such as hypertension is unknown. Thus, the primary aim of this study is to determine the effects of night-to-night variability in OSA severity on hypertension likelihood. This study uses in-home monitoring of 15,526 adults with ~180 nights per participant with an under-mattress sleep sensor device, plus ~30 repeat blood pressure measures. OSA severity is defined from the mean estimated apnea–hypopnoea index (AHI) over the ~6-month recording period for each participant. Night-to-night variability in severity is determined from the standard deviation of the estimated AHI across recording nights. Uncontrolled hypertension is defined as mean systolic blood pressure ≥140 mmHg and/or mean diastolic blood pressure ≥90 mmHg. Regression analyses are performed adjusted for age, sex, and body mass index. A total of 12,287 participants (12% female) are included in the analyses. Participants in the highest night-to-night variability quartile within each OSA severity category, have a 50–70% increase in uncontrolled hypertension likelihood versus the lowest variability quartile, independent of OSA severity. This study demonstrates that high night-to-night variability in OSA severity is a predictor of uncontrolled hypertension, independent of OSA severity. These findings have important implications for the identification of which OSA patients are most at risk of cardiovascular harm. [ABSTRACT FROM AUTHOR]

It is challenging to determine which patients with obstructive sleep apnea (OSA) have impaired driving ability. Vulnerability to this neurobehavioral impairment may be explained by lower brain metabolites levels involved in mitochondrial metabolism. This study compared markers of brain energy metabolism in OSA patients identified as vulnerable vs resistant to driving impairment following extended wakefulness. 44 patients with moderate‐severe OSA underwent 28hr extended wakefulness with three 90min driving simulation assessments. Using a two‐step cluster analysis, objective driving data (steering deviation and crashes) from the 2nd driving assessment (22.5 h awake) was used to categorise patients into vulnerable (poor driving, n = 21) or resistant groups (good driving, n = 23). 1H magnetic resonance spectra were acquired at baseline using two scan sequences (short echo PRESS and longer echo‐time asymmetric PRESS), focusing on key metabolites, creatine, glutamate, N‐acetylaspartate (NAA) in the hippocampus, anterior cingulate cortex and left orbito‐frontal cortex. Based on cluster analysis, the vulnerable group had impaired driving performance compared with the resistant group and had lower levels of creatine (PRESS p = ns, APRESS p = 0.039), glutamate, (PRESS p < 0.01, APRESS p < 0.01), NAA (PRESS p = 0.038, APRESS p = 0.035) exclusively in the left orbito‐frontal cortex. Adjusted analysis, higher glutamate was associated with a 21% (PRESS) and 36% (APRESS) reduced risk of vulnerable classification. Brain mitochondrial bioenergetics in the frontal brain regions are impaired in OSA patients who are vulnerable to driving impairment following sleep loss. These findings provide a potential way to identify at risk OSA phenotype when assessing fitness to drive, but this requires confirmation in larger future studies. [ABSTRACT FROM AUTHOR]

Background: The high and increasing demand for obstructive sleep apnea (OSA) care has exceeded the capacity of specialist sleep services prompting consideration of whether general practitioners could have an enhanced role in service delivery. However, little is known about the current involvement, experiences and attitudes of Australian general practitioners towards OSA. The purpose of this study was to provide an in-depth analysis of Australian general practitioners' experiences and opinions regarding their care of patients with OSA to inform the design and implementation of new general practice models of care.Methods: Purposive sampling was used to recruit participants with maximum variation in age, experience and location. Semi-structured interviews were conducted and were analysed using Thematic Analysis.Results: Three major themes were identified: (1) General practitioners are important in recognising symptoms of OSA and facilitating a diagnosis by others; (2) Inequities in access to the assessment and management of OSA; and (3) General practitioners currently have a limited role in the management of OSA.Conclusions: When consulting with patients with symptoms of OSA, general practitioners see their primary responsibility as providing a referral for diagnosis by others. General practitioners working with patients in areas of greater need, such as rural/remote areas and those of socio-economic disadvantage, demonstrated interest in being more involved in OSA management. Inequities in access to assessment and management are potential drivers for change in future models of care for OSA in general practice. [ABSTRACT FROM AUTHOR]

Objective: Co-morbid insomnia and sleep apnea (COMISA) is a common and debilitating condition that is more difficult to treat compared to insomnia or sleep apnea-alone. Emerging evidence suggests that cognitive behavioral therapy for insomnia (CBTi) is effective in patients with COMISA, however, those with more severe sleep apnea and evidence of greater objective sleep disturbance may be less responsive to CBTi. Polysomnographic sleep study data has been used to predict treatment response to CBTi in patients with insomnia-alone, but not in patients with COMISA. We used randomized controlled trial data to investigate polysomnographic predictors of insomnia improvement following CBTi, versus control in participants with COMISA. Methods: One hundred and forty five participants with insomnia (ICSD-3) and sleep apnea [apnea-hypopnea index (AHI) ≥ 15] were randomized to CBTi (n = 72) or no-treatment control (n = 73). Mixed models were used to investigate the effect of pre-treatment AHI, sleep duration, and other traditional (AASM sleep macrostructure), and novel [quantitative electroencephalography (qEEG)] polysomnographic predictors of between-group changes in Insomnia Severity Index (ISI) scores from pre-treatment to post-treatment. Results: Compared to control, CBTi was associated with greater ISI improvement among participants with; higher AHI (interaction p = 0.011), less wake after sleep onset (interaction p = 0.045), and less N3 sleep (interaction p = 0.005). No quantitative electroencephalographic, or other traditional polysomnographic variables predicted between-group ISI change (all p > 0.09). Discussion: Among participants with COMISA, higher OSA severity predicted a greater treatment-response to CBTi, versus control. People with COMISA should be treated with CBTi, which is effective even in the presence of severe OSA and objective sleep disturbance. [ABSTRACT FROM AUTHOR]

Falls-related hospitalization and injury rates are steadily increasing globally due to a growth in the aging population, and the associated health problems that increase risk of falls. One such associated health problem is sleep disturbances and disorders. Recent cohort studies have shown that subjectively reported poor quality sleep is associated with an increased risk of falls. Obstructive sleep apnea (OSA) is a common sleep disorder characterized by the repetitive reductions, or cessation, of airflow. Some studies have shown that OSA impairs posture/balance and gait with nocturnal hypoxemia the likely main cause. Emerging evidence suggests that treating OSA by continuous positive airway pressure (CPAP) can improve gait, but no studies to date have examined the effect of CPAP on posture/balance. The overall control of balance relies on a complex interaction between several physiological functions including vestibular, muscle, visual, and cognitive functions. We postulate that OSA impacts balance by affecting these different systems to various degrees, with the nocturnal hypoxic burden likely playing an important role. Importantly, these impairments in balance/posture and possible falls risk may be alleviated by OSA treatment. Larger mechanistic studies are needed to properly elucidate how OSA affects falls risk and future large-scale randomized control trials are needed to determine the effectiveness of OSA treatment in reducing the risk of falls. [ABSTRACT FROM AUTHOR]

Background: Traditional methods for the quantification of OSA severity may not encapsulate potential relationships between hypoxemia in OSA and cardiovascular risk.Research Question: Do novel nocturnal oxygen saturation (Spo2) metrics have prognostic value in patients with OSA and high cardiovascular event risk?Study Design and Methods: We conducted post hoc analyses of the Sleep Apnea Cardiovascular Endpoints (SAVE) trial. In 2687 individuals, Cox proportional hazards models that were stratified for treatment allocation were used to determine the associations between clinical characteristics, pulse oximetry-derived metrics that were designed to quantify sustained and episodic features of hypoxemia, and cardiovascular outcomes. Metrics included oxygen desaturation index, time <90% Spo2, average Spo2 for the entire recording (mean Spo2), average Spo2 during desaturation events (desaturation Spo2), average baseline Spo2 interpolated across episodic desaturation events (baseline Spo2), episodic desaturation event duration and desaturation/resaturation-time ratio, and mean and SD of pulse rate.Results: Neither apnea-hypopnea index, oxygen desaturation index, nor any of the novel Spo2 metrics were associated with the primary SAVE composite cardiovascular outcome. Mean and baseline Spo2 were associated with heart failure (hazard ratio [HR], 0.81; 95% CI, 0.69-0.95; P = .009; and HR, 0.78; 95% CI, 0.67-0.90; P = .001, respectively) and myocardial infarction (HR, 0.86; 95% CI, 0.77-0.95; P = .003; and HR, 0.81; 95% CI, 0.73-0.90; P < .001, respectively). Desaturation duration and desaturation/resaturation time ratio, with established risk factors, predicted future heart failure (area under the curve, 0.86; 95% CI, 0.79-0.93).Interpretation: Apnea-hypopnea index and oxygen desaturation index were not associated with cardiovascular outcomes. In contrast, the pattern of oxygen desaturation was associated with heart failure and myocardial infarction. However, concomitant risk factors remained the predominant determinants for secondary cardiovascular events and thus deserve the most intensive management. [ABSTRACT FROM AUTHOR]

Background: The relation of snoring to risks of stroke and other major cardiovascular (CV) events is uncertain.Research Question: We aimed to determine associations of snoring patterns and major CV events in relation to OSA among participants of the international Sleep Apnea cardiovascular Endpoints (SAVE) trial.Study Design and Methods: Post hoc analyses of the SAVE trial, which involved 2,687 patients with coexisting moderate-to-severe OSA and established coronary or cerebral CV disease, who were randomly allocated to CPAP treatment plus usual care or usual care alone, and followed-up for a median 3.5 years. Associations of self-reported snoring patterns (frequency and loudness) and breathing pauses collected on the Berlin questionnaire at baseline and multiple times during follow-up, and adjudicated composites of CV outcomes (primary, CV death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for unstable angina, heart failure, or transient ischemic attack; and separately of cardiac and cerebral events), were evaluated in time-dependent Cox proportional hazards models adjusted for various confounders including the apnea-hypopnea index.Results: Increase (per category) of snoring frequency (adjusted hazard ratio [HR], 1.10; 95% CI, 1.02-1.20; P = .015), loudness (HR, 1.16; 95% CI, 1.06-1.27; P = .001), and breathing pauses (HR, 1.16; 95% CI, 1.08-1.25; P < .001) at any time point during follow-up were each associated with the primary composite CV outcome. These associations were driven by significant associations for cerebral rather than cardiac events, and positive interactions between the three snoring patterns for cerebral events. There was no significant interaction between CPAP treatment and snoring variables for cerebral events.Interpretation: Snoring in patients with OSA with established CV disease is associated with greater risks of cerebral but not cardiac events, independent of CPAP treatment and frequency of apnea and hypopnea events.Trial Registry: ClinicalTrials.gov; No.: NCT00738179; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Background: Although recent evidence suggests that OSA treatment may cause weight gain, the long-term effects of CPAP on weight are not well established.Methods: This study was a post hoc analysis of the Sleep Apnea Cardiovascular Endpoints (SAVE) study, a multicenter, randomized trial of CPAP plus standard care vs standard care alone in adults with a history of cardiac or cerebrovascular events and moderate to severe OSA. Participants with weight, BMI, and neck and waist circumferences measured at baseline and during follow-up were included. Linear mixed models were used to examine sex-specific temporal differences, and a sensitivity analysis compared high CPAP adherers (≥ 4 h per night) with propensity-matched control participants.Results: A total of 2,483 adults (1,248 in the CPAP group and 1,235 in the control group) were included (mean 6.1 ± 1.5 measures of weight available). After a mean follow-up of 3.78 years, there was no difference in weight change between the CPAP and control groups, for male subjects (mean [95% CI] between-group difference, 0.07 kg [-0.40 to 0.54]; P = .773) or female subjects (mean [95% CI] between-group difference, -0.14 kg [-0.37 to 0.09]; P = .233). Similarly, there were no significant differences in BMI or other anthropometric measures. Although male participants who used CPAP ≥ 4 h per night gained slightly more weight than matched male control subjects without CPAP (mean difference, 0.38 kg [95% CI, 0.04 to 0.73]; P = .031), there were no between-group differences in other anthropometric variables, nor were there any differences between female high CPAP adherers and matched control subjects.Conclusions: Long-term CPAP use in patients with comorbid OSA and cardiovascular disease does not result in clinically significant weight change.Trial Registry: ClinicalTrials.gov; No.: NCT00738179; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

There is mounting evidence for an association between sleep disorders and hypertension. In obstructive sleep apnea (OSA), there are plausible biological reasons for the development of hypertension, and treatment of OSA results in modest (2–3 mm Hg), adherence-dependent decreases in blood pressure, with larger effects evident in those with resistant hypertension. However, prospective, population-based cohort studies have not yet convincingly demonstrated a link between OSA and incident hypertension, and adequately powered controlled trials of CPAP for the prevention or treatment or hypertension are lacking. While associations have been identified between short sleep duration, insomnia, restless legs syndrome (RLS), shift work, and hypertension, the causative role of these conditions/circumstances is not proven, and further well-designed pathophysiological and/or interventional studies are needed. Particular emphasis should be placed on defining subgroups of hypertensive OSA patients that stand to benefit most from OSA treatment and in understanding the link between sleep apnea and hypertensive disorders of pregnancy. Well-controlled intervention studies are needed in populations with short sleep duration, insomnia, shift work sleep disorder, and RLS to confirm their putative links with hypertension. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and objective Obstructive sleep apnoea ( OSA) and insomnia coexist in clinical populations but prevalence in the community and risk factors remain largely unknown. We examined the prevalence and profile of previously undiagnosed co-morbid OSA and insomnia symptoms ( COMISA) in community-dwelling men. Methods Men ( n = 700, aged 58.5 ± 11.0 (mean ± SD) years) without a prior diagnosis of OSA completed full at-home unattended polysomnography, the Pittsburgh Sleep Quality Index and 36-item short form ( SF-36) survey (2007-2012). Insomnia symptoms included difficulty initiating/maintaining sleep in the presence of daytime fatigue ( DIMS-F). Depressive symptoms were assessed using the Beck Depression Inventory- 1A, Centre for Epidemiological Studies Depression Scale and Patient Health Questionnaire-9 ( PHQ-9) (2007-2010). Univariate ( χ2 and analysis of variance ( ANOVA)) and multiple linear regressions were used to compare data from four groups of individuals: neither disorder; previously undiagnosed OSA (apnoea-hypopnoea index ≥ 10) or DIMS-F alone; and COMISA. Results COMISA prevalence was 6.7%. Depression prevalence ( COMISA, 42.6%; DIMS-F, 21.6%; OSA, 8.4%, χ2 = 71.6, P < 0.00) and symptom scale scores (e.g. PHQ-9 mean ± SD: 16.1 ± 5.5 c.f. DIMS-F: 14.0 ± 4.9, P < 0.01 and OSA: 11.4 ± 3.0, P = 0.01) were highest in men with COMISA. In COMISA, respiratory and arousal indices were similar to those observed in OSA whilst reductions in subjective sleep and day dysfunction scores were similar to DIMS-F. After adjustment, predicted mean depression scores were all higher in DIMS-F and COMISA using linear regression (e.g. PHQ-9 β (95% CI): DIMS-F: 2.3 (1.2, 3.5); COMISA: 4.1 (3.0, 5.1)). Conclusion Men with COMISA have a greater prevalence, and severity, of depression than men with only one disorder. [ABSTRACT FROM AUTHOR]

Importance: Sleep apnea (obstructive and central) is associated with adverse cardiovascular risk factors and increased risks of cardiovascular disease. Positive airway pressure (PAP) provides symptomatic relief, whether delivered continuously (CPAP) or as adaptive servo-ventilation (ASV), but the associations with cardiovascular outcomes and death are unclear.Objective: To assess the association of PAP vs control with cardiovascular events and death in patients with sleep apnea.Data Sources and Study Selection: MEDLINE, EMBASE, and the Cochrane Library were systematically searched from inception date to March 2017 for randomized clinical trials that included reporting of major adverse cardiovascular events or deaths.Data Extraction and Synthesis: Two authors independently extracted data using standardized forms. Summary relative risks (RRs), risk differences (RDs) and 95% CIs were obtained using random-effects meta-analysis.Main Outcomes and Measures: The main outcomes were a composite of acute coronary syndrome (ACS) events, stroke, or vascular death (major adverse cardiovascular events); cause-specific vascular events; and death.Results: The analyses included data from 10 trials (9 CPAP; 1 ASV) of patients with sleep apnea (N = 7266; mean age, 60.9 [range, 51.5 to 71.1] years; 5847 [80.5%] men; mean [SD] body mass index, 30.0 [5.2]. Among 356 major adverse cardiovascular events and 613 deaths recorded, there was no significant association of PAP with major adverse cardiovascular events (RR, 0.77 [95% CI, 0.53 to 1.13]; P = .19 and RD, -0.01 [95% CI, -0.03 to 0.01]; P = .23), cardiovascular death (RR, 1.15 [95% CI, 0.88 to 1.50]; P = .30 and RD -0.00 [95% CI, -0.02 to 0.02]; P = .87), or all-cause death (RR, 1.13 [95% CI, 0.99 to 1.29]; P = .08 and RD, 0.00 [95% CI, -0.01 to 0.01]; P = .51). The same was true for ACS, stroke, and heart failure. There was no evidence of different associations for CPAP vs ASV (all P value homogeneity >.24), and meta-regressions identified no associations of PAP with outcomes for different levels of apnea severity, follow-up duration, or adherence to PAP (all P values > .13).Conclusions and Relevance: The use of PAP, compared with no treatment or sham, was not associated with reduced risks of cardiovascular outcomes or death for patients with sleep apnea. Although there are other benefits of treatment with PAP for sleep apnea, these findings do not support treatment with PAP with a goal of prevention of these outcomes. [ABSTRACT FROM AUTHOR]

Background: The clinical utility of limited-channel sleep studies (which are increasingly conducted at home) versus laboratory polysomnography (PSG) for diagnosing obstructive sleep apnea (OSA) is unclear.Objective: To compare patient outcomes after PSG versus limited-channel studies.Design: Multicenter, randomized, noninferiority study. (Australian New Zealand Clinical Trials Registry: ACTRN12611000926932).Setting: 7 academic sleep centers.Participants: Patients (n = 406) aged 25 to 80 years with suspected OSA.Intervention: Sleep study information disclosed to sleep physicians comprised level 1 (L1) PSG data (n = 135); level 3 (L3), which included airflow, thoracoabdominal bands, body position, electrocardiography, and oxygen saturation (n = 136); or level 4 (L4), which included oxygen saturation and heart rate (n = 135).Measurements: The primary outcome was change in Functional Outcomes of Sleep Questionnaire (FOSQ) score at 4 months. Secondary outcomes included the Epworth Sleepiness Scale (ESS), the Sleep Apnea Symptoms Questionnaire (SASQ), continuous positive airway pressure (CPAP) compliance, and physician decision making.Results: Change in FOSQ score was not inferior for L3 (mean difference [MD], 0.01 [95% CI, -0.47 to 0.49; P = 0.96]) or L4 (MD, -0.46 [CI, -0.94 to 0.02; P = 0.058]) versus L1 (noninferiority margin [NIM], -1.0). Compared with L1, change in ESS score was not inferior for L3 (MD, 0.08 [CI, -0.98 to 1.13; P = 0.89]) but was inconclusive for L4 (MD, 1.30 [CI, 0.26 to 2.35; P = 0.015]) (NIM, 2.0). For L4 versus L1, there was less improvement in SASQ score (-17.8 vs. -24.7; P = 0.018), less CPAP use (4.5 vs. 5.3 hours per night; P = 0.04), and lower physician diagnostic confidence (P = 0.003).Limitation: Limited-channel studies were simulated by extracting laboratory PSG data and were not done in the home.Conclusion: The results support manually scored L3 testing in routine practice. Poorer outcomes with L4 testing may relate, in part, to reduced physician confidence.Primary Funding Source: National Health and Medical Research Council and Repat Foundation. [ABSTRACT FROM AUTHOR]

Background Obstructive sleep apnea is associated with an increased risk of cardiovascular events; whether treatment with continuous positive airway pressure (CPAP) prevents major cardiovascular events is uncertain. Methods After a 1-week run-in period during which the participants used sham CPAP, we randomly assigned 2717 eligible adults between 45 and 75 years of age who had moderate-to-severe obstructive sleep apnea and coronary or cerebrovascular disease to receive CPAP treatment plus usual care (CPAP group) or usual care alone (usual-care group). The primary composite end point was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for unstable angina, heart failure, or transient ischemic attack. Secondary end points included other cardiovascular outcomes, health-related quality of life, snoring symptoms, daytime sleepiness, and mood. Results Most of the participants were men who had moderate-to-severe obstructive sleep apnea and minimal sleepiness. In the CPAP group, the mean duration of adherence to CPAP therapy was 3.3 hours per night, and the mean apnea-hypopnea index (the number of apnea or hypopnea events per hour of recording) decreased from 29.0 events per hour at baseline to 3.7 events per hour during follow-up. After a mean follow-up of 3.7 years, a primary end-point event had occurred in 229 participants in the CPAP group (17.0%) and in 207 participants in the usual-care group (15.4%) (hazard ratio with CPAP, 1.10; 95% confidence interval, 0.91 to 1.32; P=0.34). No significant effect on any individual or other composite cardiovascular end point was observed. CPAP significantly reduced snoring and daytime sleepiness and improved health-related quality of life and mood. Conclusions Therapy with CPAP plus usual care, as compared with usual care alone, did not prevent cardiovascular events in patients with moderate-to-severe obstructive sleep apnea and established cardiovascular disease. (Funded by the National Health and Medical Research Council of Australia and others; SAVE ClinicalTrials.gov number, NCT00738179 ; Australian New Zealand Clinical Trials Registry number, ACTRN12608000409370 .). [ABSTRACT FROM AUTHOR]

Background: Evidence linking OSA with hypertension in population studies is conflicting. We examined longitudinal and cross-sectional associations of previously unrecognized OSA, including OSA occurring in rapid eye movement (REM) sleep, with hypertension.Methods: The Men Androgens Inflammation Lifestyle Environment and Stress (MAILES) study is a longitudinal study of community-dwelling men in Adelaide, South Australia. Biomedical assessments at baseline (2002-2006) and follow-up (2007-2010) identified hypertension (systolic ≥ 140 mm Hg and/or diastolic ≥ 90 mm Hg, or medication) and risk factors. In 2010 to 2011, 837 men without a prior diagnosis of OSA underwent full in-home unattended polysomnography of whom 739 recorded ≥ 30 min of REM sleep. Hypertension at follow-up (concomitant with OSA status) was defined as prevalent hypertension. Recent-onset hypertension was defined as hypertension at biomedical follow-up (56 months mean follow-up [range, 48-74]) in men free of hypertension at baseline.Results: Severe REM OSA (apnea hypopnea index ≥30/h) showed independent adjusted associations with prevalent (OR, 2.40, 95% CI, 1.42-4.06), and recent-onset hypertension (2.24 [1.04-4.81]). Significant associations with non-REM AHI were not seen. In men with AHI < 10, REM OSA (apnea hypopnea index) ≥ 20/h was significantly associated with prevalent hypertension (2.67 [1.33-5.38]) and the relationship with recent-onset hypertension was positive but not statistically significant (2.32 [0.79-6.84]). Similar results were seen when analyses were confined to men with non-REM AHI < 10.Conclusions: In men not considered to have OSA (AHI < 10), hypertension was associated with OSA during REM sleep. REM OSA may need consideration as an important clinical entity requiring treatment but further systematic assessment and evidence is needed. [ABSTRACT FROM AUTHOR]

The high prevalence of obstructive sleep apnoea ( OSA) and increasing awareness of its potential health consequences has placed significant pressure on laboratory-based sleep services leading to growing waiting lists and delays in diagnosis and treatment. Consequently, there has been increasing interest in the use of simplified, ambulatory models of care involving clinical prediction tools, portable sleep monitoring and home autotitrating continuous positive airway pressure. Researchers are also exploring the potential role for a wider range of health-care providers, including trained nurses and general practitioners, in the primary management of OSA. Recent randomized, controlled studies evaluating the clinical effectiveness of ambulatory management strategies versus traditional laboratory-based care for patients with OSA have consistently demonstrated that comparable patient outcomes can be achieved. The cost-effectiveness of these strategies is currently being debated, and further research examining the long-term economic implications of ambulatory models of care is needed. [ABSTRACT FROM AUTHOR]

Importance: Due to increasing demand for sleep services, there has been growing interest in ambulatory models of care for patients with obstructive sleep apnea. With appropriate training and simplified management tools, primary care physicians are ideally positioned to take on a greater role in diagnosis and treatment.Objective: To compare the clinical efficacy and within-trial costs of a simplified model of diagnosis and care in primary care relative to that in specialist sleep centers.Design, Setting, and Patients: A randomized, controlled, noninferiority study involving 155 patients with obstructive sleep apnea that was treated at primary care practices (n=81) in metropolitan Adelaide, 3 rural regions of South Australia or at a university hospital sleep medicine center in Adelaide, Australia (n = 74), between September 2008 and June 2010.Interventions: Primary care management of obstructive sleep apnea vs usual care in a specialist sleep center; both plans included continuous positive airway pressure, mandibular advancement splints, or conservative measures only.Main Outcome and Measures: The primary outcome was 6-month change in Epworth Sleepiness Scale (ESS) score, which ranges from 0 (no daytime sleepiness) to 24 points (high level of daytime sleepiness). The noninferiority margin was -2.0. Secondary outcomes included disease-specific and general quality of life measures, obstructive sleep apnea symptoms, adherence to using continuous positive airway pressure, patient satisfaction, and health care costs.Results: There were significant improvements in ESS scores from baseline to 6 months in both groups. In the primary care group, the mean baseline score of 12.8 decreased to 7.0 at 6 months (P < .001), and in the specialist group, the score decreased from a mean of 12.5 to 7.0 (P < .001). Primary care management was noninferior to specialist management with a mean change in ESS score of 5.8 vs 5.4 (adjusted difference, -0.13; lower bound of 1-sided 95% CI, -1.5; P = .43). There were no differences in secondary outcome measures between groups. Seventeen patients (21%) withdrew from the study in the primary care group vs 6 patients (8%) in the specialist group.Conclusions and Relevance: Among patients with obstructive sleep apnea, treatment under a primary care model compared with a specialist model did not result in worse sleepiness scores, suggesting that the 2 treatment modes may be comparable. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12608000514303. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnoea (OSA) is characterised by repetitive closure of the upper airway, repetitive oxygen desaturations and sleep fragmentation. The prevalence of adult OSA is increasing because of a worldwide increase in obesity and the ageing of populations. OSA presents with a variety of symptoms the most prominent of which are snoring and daytime tiredness. Interestingly though, a significant proportion of OSA sufferers report little or no daytime symptoms. OSA has been associated with an increased risk of cardiovascular disease, cognitive abnormalities and mental health problems. Randomised controlled trial evidence is awaited to confirm a causal relationship between OSA and these various disorders. The gold standard diagnostic investigation for OSA is overnight laboratory-based polysomnography (sleep study), however, ambulatory models of care incorporating screening questionnaires and home sleep studies have been recently evaluated and are now being incorporated into routine clinical practice. Patients with OSA are very often obese and exhibit a range of comorbidities, such as hypertension, depression and diabetes. Management, therefore, needs to be based on a multidisciplinary and holistic approach which includes lifestyle modifications. Continuous positive airway pressure (CPAP) is the first-line therapy for severe OSA. Oral appliances should be considered in patients with mild or moderate disease, or in those unable to tolerate CPAP. New, minimally invasive surgical techniques are currently being developed to achieve better patient outcomes and reduce surgical morbidity. Successful long-term management of OSA requires careful patient education, enlistment of the family's support and the adoption of self-management and patient goal-setting principles. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare metropolitan on-road driving performance in patients with severe obstructive sleep apnea (OSA) and healthy age-matched controls. A driving assessor-based on-road driving test was performed at 2.00 pm in severe OSA patients and age-matched healthy controls. Main outcomemeasures included passing or failing the test, occurrence of minor traffic faults (e.g. not indicating, late braking, mirror checking) and traffic law infringements (e.g. failing to stop or give way, speeding). Compared to controls, there was no evidence of gross driving impairment or higher driving test failure rate in OSA patients. However, OSA patients demonstrated 60% more traffic law infringements (11.0 ± 1.8 versus 6.8 ± 1.0% of general driving tasks, p = 0.024), primarily reflecting repeated failure to stop at stop signs and/or traffic lights (p = 0.037). Patients with severeOSA break road laws more frequently than age-matched controls during a short city driving test,suggesting greater inattention and thus potentially higher motor vehicle accident risk. Further studies are needed to extend these early findings, which raise serious clinical and road safety concerns. [ABSTRACT FROM AUTHOR]

Background: Because of previous sleep disturbance and sleep hypoxia, patients with obstructive sleep apnea (OSA) might be more vulnerable to the effects of alcohol and sleep restriction than healthy persons. Objective: To compare the effects of sleep restriction and alcohol on driving simulator performance in patients with OSA and agematched control participants. Design: Driving simulator assessments in 2 groups under 3 different conditions presented in random order. Setting: Adelaide Institute for Sleep Health, Sleep Laboratory, Adelaide, Australia. Participants: 38 untreated patients with OSA and 20 control participants. Measurements: Steering deviation, crashes, and braking reaction time. Intervention: Unrestricted sleep, sleep restricted to a maximum of 4 hours, and ingestion of an amount of 40% vodka calculated to achieve a blood alcohol level of 0.05 g/dL. Results: Patients with OSA demonstrated increased steering deviation compared with control participants (mean, 50.5 cm [95% CI, 46.1 to 54.9 cm] in the OSA group and 38.4 cm [CI, 32.4 to 44.4 cm] in the control group; P < 0.01) and significantly greater steering deterioration over time (group by time interaction, P = 0.02). The increase in steering deviation after sleep restriction and alcohol was approximately 40% greater in patients with OSA than in control participants (group by condition interaction, P = 0.04). Patients with OSA crashed more frequently than control participants (1 vs. 24 participants; odds ratio [OR], 25.4; P = 0.03) and crashed more frequently after sleep restriction (OR, 4.0; P < 0.01) and alcohol consumption (OR, 2.3; P = 0.02) than after normal sleep. In patients with OSA, prolonged eye closure (>2 seconds) and microsleeps (> 2 seconds of theta activity on electroencephalography) were significant crash predictors (OR, 19.2 and 7.2, respectively; P < 0.01). Braking reaction time was slower after sleep restriction than after normal sleep (mean, 1.39 [SD, 0.06] seconds vs. 1.22 [SD, 0.04] seconds; P < 0.01) but not after alcohol consumption. No group differences were found. Limitation: Simulated driving was assessed rather than on-road driving. Conclusion: Patients with OSA are more vulnerable than healthy persons to the effects of alcohol consumption and sleep restriction on various driving performance variables. Primary Funding Source: Australian National Health and Medical Research Council. [ABSTRACT FROM AUTHOR]

Hypoxia can depress ventilation, respiratory load sensation, and the cough reflex, and potentially other protective respiratory reflexes such as respiratory muscle responses to increased respiratory load. In sleep-disordered breathing, increased respiratory load and hypoxia frequently coexist. This study aimed to examine the effects of hypoxia on the reflex responses of 1) the genioglossus (the largest upper airway dilator muscle) and 2) the scalene muscle (an obligatory inspiratory muscle) to negative-pressure pulse stimuli during wake- fulness and sleep. We hypothesized that hypoxia would impair these reflex responses. Fourteen healthy men, 19-42 yr old, were studied on two separate occasions, - I wk apart. Bipolar fine-wire electrodes were inserted orally into the genioglossus muscle, and surface elec- trodes were placed overlying the left scalene muscle to record EMG activity. In random order, participants were exposed to mild overnight hypoxia (arterial oxygen saturation -85%) or medical air. Respiratory muscle reflex responses were elicited via negative-pressure pulse stimuli (approximately -10 cmH2O at the mask, 250-ms duration) delivered in early inspiration during wakefulness and sleep. Negative- pressure pulse stimuli resulted in a short-latency activation followed by a suppression of the genioglossus EMG that did not alter with hypoxia. Conversely, the predominant response of the scalene EMG to negative-pressure pulse stimuli was suppression followed by acti- vation with more pronounced suppression during hypoxia compared with normoxia (mean ± SE suppression duration 64 ± 6 vs. 38 ± 6 ms, P = 0.006). These results indicate differential sensitivity to the depressive effects of hypoxia in the reflex responsiveness to sudden respiratory loads to breathing between these two respiratory muscles. [ABSTRACT FROM AUTHOR]

Prader-Willi Syndrome (PWS) is a rare genetic disorder characterized by a range of physical, psychological, and physiological abnormalities. It is also distinguished by the high prevalence of obstructive sleep apnea syndrome (OSAS), i.e., repetitive upper airway collapse during sleep resulting in hypoxia and sleep fragmentation. In non-PWS populations, OSAS is associated with a range of neurocognitive and psychosocial deficits. Importantly, these deficits are at least partly reversible following treatment. Given the findings in non-PWS populations, it is possible that OSAS may contribute to neurocognitive and psychosocial deficits in PWS. The present review examines this possibility. While acknowledging a primary contribution from the primary genetic abnormality to central neural dysfunction in PWS, we conclude that OSAS may be an important secondary contributing factor to reduced neurocognitive and psychosocial performance. Treatment of OSAS may have potential benefits in improving neurocognitive performance and behavior in PWS, but this awaits confirmatory investigation. [ABSTRACT FROM AUTHOR]