Impact of cystic fibrosis multidisciplinary virtual clinics on patient experience, time commitments and costs.

BACKGROUND AND AIMS: The experience of outpatient care may differ for select patient groups. This prospective study evaluates the adult patient experience of multidisciplinary outpatient cystic fibrosis (CF) care with videoconferencing through telehealth compared with face-to-face care the year prior. METHODS: People with CF without a lung transplant were recruited. Patient-reported outcomes were obtained at commencement and 12 months into the study, reflecting both their face-to-face and telehealth through videoconferencing experience, respectively. Three patient cohorts were analysed: (i) participants with a regional residence, (ii) participants with a nonregional including metropolitan residence and (iii) participants with colonised multiresistant microbiota. RESULTS: Seventy-four patients were enrolled in the study (mean age, 37 ± 11 years; 50% male; mean forced expiratory volume in the first second of expiration, 60% [standard deviation, 23]) between February 2020 and May 2021. No differences between models were observed in the participants' rating of the health care team, general and mental health rating, and their confidence in handling treatment plans at home. No between-group differences in the Cystic Fibrosis Questionnaire - Revised (CFQ-R) were observed. Travel duration and the cost of attending a clinic was significantly reduced, particularly for the regional group (4 h, AU$108 per clinic; P < 0.05). A total of 93% respondents preferred to continue with a hybrid approach. CONCLUSION: In this pilot study, participants' experience of care and quality of life were no different with face-to-face and virtual care between the groups. Time and cost-savings, particularly for patients living in regional areas, were observed. Most participants preferred to continue with a hybrid model for outpatient care.

Region-specific changes in brain activity and memory after continuous positive airway pressure therapy in obstructive sleep apnea: a pilot high-density electroencephalography study.

STUDY OBJECTIVES: Limited channel electroencephalography (EEG) investigations in obstructive sleep apnea (OSA) have revealed deficits in slow wave activity (SWA) and spindles during sleep and increased EEG slowing during resting wakefulness. High-density EEG (Hd-EEG) has also detected local parietal deficits in SWA (delta power) during NREM. It is unclear whether effective continuous positive airway pressure (CPAP) treatment reverses regional SWA deficits, and other regional sleep and wake EEG abnormalities, and whether any recovery relates to improved overnight memory consolidation. METHODS: A clinical sample of men with moderate-severe OSA underwent sleep and resting wake recordings with 256-channel Hd-EEG before and after 3 months of CPAP. Declarative and procedural memory tasks were administered pre- and post-sleep. Topographical spectral power maps and differences between baseline and treatment were compared using t-tests and statistical nonparametric mapping (SnPM). RESULTS: In 11 compliant CPAP users (5.2 ±â€…1.1 hours/night), total sleep time did not differ after CPAP but N1 and N2 sleep were lower and N3 was higher. Centro-parietal gamma power during N3 increased and fronto-central slow spindle activity during N2 decreased (SnPM < 0.05). No other significant differences in EEG power were observed. When averaged specifically within the parietal region, N3 delta power increased after CPAP (p = 0.0029) and was correlated with the change in overnight procedural memory consolidation (rho = 0.79, p = 0.03). During resting wakefulness, there were trends for reduced delta and theta power. CONCLUSIONS: Effective CPAP treatment of OSA may correct regional EEG abnormalities, and regional recovery of SWA may relate to procedural memory improvements in the short term.

Armodafinil to reduce the sleepiness related side-effects of sleep restriction therapy being used to treat insomnia disorder: An open label clinical trial pilot study compared with historical controls.

Sleep restriction therapy (SRT) is an effective stand-alone behavioural intervention for insomnia disorder. However, its daytime side effects, particularly sleepiness, may be troubling for patients and/or may be a necessary part of the patient's treatment journey. This pilot trial aims to explore the potential benefit of armodafinil, a wakefulness promoter. Patients were treated with SRT with open label adjunctive armodafinil (150 mg/day). Thirty-three patients from previous studies that have undergone exactly the same SRT intervention acted as controls. The primary outcome measure was the insomnia severity index (ISI), and secondary outcomes were the Epworth sleepiness scale, sleep restriction adherence scale (SRAS), and safety from baseline through to 12 weeks. We recruited 25 patients into the trial. Data for the primary end point (ISI at 12 weeks) was available for 20 of the participants. The baseline insomnia severity index was 20.2 (SD 3.3) and decreased to 9.1 (SE 1.1), with no change, to 10.2 and 11.2 at weeks 6 and 12 respectively (all p > 0.05 compared with baseline). The insomnia severity index values for armodafinil patients were statistically inferior to historical controls at the primary time point of 12 weeks (11.2 vs. 6.7, p < 0.01). Sleep restriction therapy plus armodafinil treatment was associated with frequent minor side effects but was generally safe and acceptable to patients. Sleep restriction therapy was associated with a robust clinical response in the insomnia severity index values for insomnia patients. Based upon historical control data, armodafinil does not appear to have beneficial adjunctive effects in addition to sleep restriction therapy alone.

Daily Inhaled Corticosteroids Treatment Abolishes Airway Hyperresponsiveness to Mannitol in Defence and Police Recruits.

Background: Airway hyperresponsiveness (AHR) is a key pathophysiological feature of asthma and causes exercise-induced bronchoconstriction (EIB). Indirect bronchial provocation tests (BPTs) (e.g., exercise, mannitol) aid to diagnose asthma and identify EIB. Daily inhaled corticosteroids (ICS) can abolish AHR caused by indirect stimuli. Where strenuous physical exertion is integral to an occupation, identification of those at risk of EIB is important and documentation of inhibition of AHR with ICS is required before recruitment. Methods/Objectives: A retrospective analysis was performed on 155 potential recruits with AHR to mannitol who underwent follow-up assessment after daily ICS treatment to determine the proportion that can abolish AHR using ICS and to determine any predictors of the persistence of AHR. Results: Airway hyperresponsiveness was abolished in the majority (84%, n = 130) over the treatment period (mean ± SD 143 ± 72days), and it was defined as the provoking dose of mannitol to cause a 15% fall in FEV1 (cumulative inhaled dose of mannitol to cause 15% fall in FEV1, PD15) improved from (GeoMean) 183 to 521 mg. Compared with recruits in whom AHR was abolished with daily ICS (i.e., no 15% fall in FEV1 to the maximum cumulative dose of mannitol of 635 mg), in those where AHR remained (16%, n = 25), baseline AHR was more severe (PD15: 85 mg vs. 213 mg, P < 0.001), baseline FEV1% was lower (89 vs. 96%; 95%CI:2-12, P=0.004), and they had a longer follow-up duration (180 vs. 136 days; 13-74, P = 0.006). Baseline FEV1% (adjusted odds ratio 0.85; 95%CI:0.77-0.93), FEV1/FVC (0.78; 0.67-0.90), FEF25-75% (1.15; 1.06-1.25), and airway reactivity to mannitol (%Fall/cumulative dose of mannitol multiplied by 100) (1.07; 1.03-1.11) predicted AHR remaining after daily ICS. Conclusion: Airway hyperresponsiveness to mannitol can be abolished after 20 weeks of daily treatment with ICS. Inhibition of AHR is likely due to attenuation of airway inflammation in response to ICS treatment. Increased airway reactivity and lower spirometry variables predicted the persistence of AHR. Thus, those with a slower response to daily ICS on AHR can potentially be identified at the commencement of monitoring ICS using inhaled mannitol.

The emerging role of the lung microbiome and its importance in non-small cell lung cancer diagnosis and treatment.

Over the last 10 years, with the development of culture-free bacterial identification techniques, understanding of how the microbiome influences diseases has increased exponentially and has highlighted potential opportunities for its use as a diagnostic biomarker and interventional target in many diseases including malignancy. Initial research focused on the faecal microbiome since it contains the densest bacterial populations and many other mucosal sites, such as the lungs, were until recently thought to be sterile. However, in recent years, it has become clear that the lower airways are home to a dynamic bacterial population sustained by the migration and elimination of microbes from the gastrointestinal and upper airway tracts. As in the gut, the lung microbiome plays an important role in regulating mucosal immunity and maintaining the balance between immune tolerance and inflammation. Studies to date have all shown that the lung microbiome undergoes significant changes in the setting of pulmonary disease. In lung cancer, animal models and small patient cohort studies have suggested that microbiome dysbiosis may not only impact tumour progression and response to therapy, particularly immunotherapy, but also plays a key role in cancer pathogenesis by influencing early carcinogenic pathways. These early results have led to concerted efforts to identify microbiome signatures that represent diagnostic biomarkers of early-stage disease and to consider modulation of the lung microbiome as a potential therapeutic strategy. Lung microbiome research is in its infancy and studies to date have been small, single centre with significant methodological variation. Large, multicentre longitudinal studies are needed to establish the clinical potential of this exciting field.

Improvements in cognitive function and quantitative sleep electroencephalogram in obstructive sleep apnea after six months of continuous positive airway pressure treatment.

STUDY OBJECTIVES: Untreated obstructive sleep apnea (OSA) is associated with cognitive deficits and altered brain electrophysiology. We evaluated the effect of continuous positive airway pressure (CPAP) treatment on quantitative sleep electroencephalogram (EEG) measures and cognitive function. METHODS: We studied 167 patients with OSA (age 50 ±â€…13, AHI 35.0 ±â€…26.8) before and after 6 months of CPAP. Cognitive tests assessed working memory, sustained attention, visuospatial scanning, and executive function. All participants underwent overnight polysomnography at baseline and after CPAP. Power spectral analysis was performed on EEG data (C3-M2) in a sub-set of 90 participants. Relative delta EEG power and sigma power in NREM and EEG slowing in REM were calculated. Spindle densities (events/min) in N2 were also derived using automated spindle event detection. All outcomes were analysed as change from baseline. RESULTS: Cognitive function across all cognitive domains improved after six months of CPAP. In our sub-set, increased relative delta power (p < .0001) and reduced sigma power (p = .001) during NREM were observed after the 6-month treatment period. Overall, fast and slow sleep spindle densities during N2 were increased after treatment. CONCLUSIONS: Cognitive performance was improved and sleep EEG features were enhanced when assessing the effects of CPAP. These findings suggest the reversibility of cognitive deficits and altered brain electrophysiology observed in untreated OSA following six months of treatment.

Predictors of weight loss in obese patients with obstructive sleep apnea.

PURPOSE: Consistent predictors of weight loss outcomes with very low-energy diets (VLEDs) in obstructive sleep apnea (OSA) have not been identified. This study aimed to identify variables predictive of weight loss success in obese patients with OSA undertaking an intensive weight loss programme. METHODS: We analysed biological, psychological, and behavioural variables as potential predictors of weight loss in obese patients with OSA after a 2-month VLED followed by one of two 10-month weight loss maintenance diets. Actigraphy, in-lab polysomnography, urinary catecholamines, and various psychological and behavioural variables were measured at baseline, 2, and 12 months. Spearman's correlations analysed baseline variables with 2-month weight loss, and 2-month variables with 2-12 month-weight change. RESULTS: Forty-two patients completed the VLED and thirty-eight completed the maintenance diets. Actigraphy data revealed that late bedtime (rs = - 0.45, p = < 0.01) was correlated with 2-month weight loss. The change in the time that participants got out of bed (rise-time) from baseline to two months was also correlated with 2-month weight loss (rs = 0.36, p = 0.03). The Impact of Weight on Quality of Life-Lite questionnaire (IWQOL) Public Distress domain (rs = - 0.54, p = < 0.01) and total (rs = - 0.38, p = 0.02) scores were correlated with weight loss maintenance from 2 to 12 months. CONCLUSIONS: Results from this small patient sample reveal correlations between actigraphy characteristics and weight loss in obese patients with OSA. We suggest the IWQOL may also be a useful clinical tool to identify OSA patients at risk of weight regain after initial weight loss. CLINICAL TRIAL REGISTRATION: This clinical trial was prospectively registered on 18/02/2013 with the Australia and New Zealand Clinical Trials Registry (ACTRN12613000191796). PUBLIC REGISTRY TITLE: Sleep, Lifestyle, Energy, Eating, Exercise Program for the management of sleep apnea patients indicated for weight loss treatment: A randomised, controlled pilot study. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363680.

Cardiopulmonary coupling and serum cardiac biomarkers in obesity hypoventilation syndrome and obstructive sleep apnea with morbid obesity.

STUDY OBJECTIVES: The main cause of death in patients with obesity hypoventilation syndrome (OHS) is cardiac rather than respiratory failure. Here, we investigated autonomic-respiratory coupling and serum cardiac biomarkers in patients with OHS and obstructive sleep apnea (OSA) with comparable body mass index and apnea-hypopnea index. METHODS: Cardiopulmonary coupling (CPC) and cyclic variation of heart rate analysis was performed on the electrocardiogram signal from the overnight polysomnogram. Cardiac serum biomarkers were obtained in patients with OHS and OSA with a body mass index > 40 kg/m2. Samples were obtained at baseline and after 3 months of positive airway pressure (PAP) therapy in both groups. RESULTS: Patients with OHS (n = 15) and OSA (n = 36) were recruited. No group differences in CPC, cyclic variation of heart rate, and serum biomarkers were observed at baseline and after 3 months of PAP therapy. An improvement in several CPC metrics, including the sleep apnea index, unstable sleep (low-frequency coupling and elevated low-frequency coupling narrow band), and cyclic variation of heart rate were observed in both groups with PAP use. However, distinct differences in response characteristics were noted. Elevated low-frequency coupling narrow band coupling correlated with highly sensitive troponin-T (P < .05) in the combined cohort. Baseline highly sensitive troponin-T inversely correlated with awake oxygen saturation in the OHS group (P < .05). CONCLUSIONS: PAP therapy can significantly improve CPC stability in patients with obesity with OSA or OHS, with key differences. Elevated low-frequency coupling narrow band may function as a surrogate biomarker for early subclinical cardiac disease. Low awake oxygen saturation could also increase this biomarker in OHS. CLINICAL TRIAL REGISTRATION: Registry: Australian New Zealand Clinical Trials Registry; Name: Obesity Hypoventilation Syndrome and Neurocognitive Dysfunction; URL: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367492; Identifier: ACTRN12615000122550. CITATION: Sivam S, Wang D, Wong KKH, et al. Cardiopulmonary coupling and serum cardiac biomarkers in obesity hypoventilation syndrome and obstructive sleep apnea with morbid obesity. J Clin Sleep Med. 2022;18(4):1063-1071.

Development and validation of a model for diagnosis of obstructive sleep apnoea in primary care.

BACKGROUND AND OBJECTIVE: Use of in-laboratory polysomnography (PSG) to diagnose obstructive sleep apnoea (OSA) is cost and resource intensive. Questionnaires, physical measurements and home monitors have been studied as potential simpler alternatives. This study aimed to develop a diagnostic model for OSA for use in primary care. METHODS: Primary care practitioners were trained to recognize symptoms of sleep apnoea and recruited patients based on the clinical need to investigate OSA. Assessment was by symptom questionnaires, anthropomorphic measurements, digital facial photography, and a single-channel nasal flow monitor (Flow Wizard©, DiagnoseIT, Sydney, Australia) worn at home for 3 nights. The in-laboratory PSG was the reference test, with OSA defined as apnoea-hypopnoea index (AHI) ≥10 events/h. RESULTS: In the model development phase, 25 primary care practitioners studied 315 patients in whom they suspected OSA, of which 57% had AHI≥10 and 22% had AHI≥30. Published OSA questionnaires provided low to moderate prediction of OSA (area under the curve [AUC] 0.53-0.73). The nasal flow monitor alone yielded high accuracy for predicting OSA with AUC of 0.87. Sensitivity was 0.87 and specificity 0.77 at a threshold respiratory event index (REI) of 18 events/h. A model adding age, gender, symptoms and BMI to the nasal flow monitor REI only modestly improved OSA prediction (AUC 0.89), with similar AUC (0.88) confirmed in the validation population of 114 patients. CONCLUSION: Sleep apnoea can be diagnosed in the primary care setting with a combination of clinical judgement and portable monitor test outcomes.

Sleep spindle activity correlates with implicit statistical learning consolidation in untreated obstructive sleep apnea patients.

OBJECTIVE/BACKGROUND: The aim of this study was to examine the relationship between overnight consolidation of implicit statistical learning with spindle frequency EEG activity and slow frequency delta power during non-rapid eye movement (NREM) sleep in obstructive sleep apnea (OSA). PATIENTS/METHODS: Forty-seven OSA participants completed the experiment. Prior to sleep, participants performed a reaction time cover task containing hidden patterns of pictures, about which participants were not informed. After the familiarisation phase, participants underwent overnight polysomnography. 24 h after the familiarisation phase, participants performed a test phase to assess their learning of the hidden patterns, expressed as a percentage of the number of correctly identified patterns. Spindle frequency activity (SFA) and delta power (0.5-4.5 Hz), were quantified from NREM electroencephalography. Associations between statistical learning and sleep EEG, and OSA severity measures were examined. RESULTS: SFA in NREM sleep in frontal and central brain regions was positively correlated with statistical learning scores (r = 0.41 to 0.31, p = 0.006 to 0.044). In multiple regression, greater SFA and longer sleep onset latency were significant predictors of better statistical learning performance. Delta power and OSA severity were not significantly correlated with statistical learning. CONCLUSIONS: These findings suggest spindle activity may serve as a marker of statistical learning capability in OSA. This work provides novel insight into how altered sleep physiology relates to consolidation of implicitly learnt information in patients with moderate to severe OSA.

The effect of acute morphine on sleep in male patients suffering from sleep apnea: Is there a genetic effect? An RCT Study.

Questionnaire-based studies have suggested genetic differences in sleep symptoms in chronic opioid users. The present study aims to investigate if there is a genetic effect on sleep architecture and quantitative electroencephalogram (EEG) in response to acute morphine. Under a randomized, double-blind, placebo-controlled, crossover design, 68 men with obstructive sleep apnea undertook two overnight polysomnographic studies conducted at least 1 week apart. Each night they received either 40 mg of controlled-release morphine or placebo. Sleep architecture and quantitative EEG were compared between conditions. Blood was sampled before sleep and on the next morning for genotyping and pharmacokinetic analyses. We analysed three candidate genes (OPRM1 [rs1799971, 118 A > G], ABCB1[rs1045642, 3435 C > T] and HTR3B [rs7103572 C > T]). We found that morphine decreased slow wave sleep and rapid eye movement sleep and increased stage 2 sleep. Those effects were less in subjects with HTR3B CT/TT than in those with CC genotype. Similarly, sleep onset latency was shortened in the ABCB1 CC subgroup compared with the CT/TT subgroup. Total sleep time was significantly increased in ABCB1 CC but not in CT/TT subjects. Sleep apnea and plasma morphine and metabolite concentration were not confounding factors for these genetic differences in sleep. With morphine, patients had significantly more active/unstable EEG (lower delta/alpha ratio) during sleep. No genetic effects on quantitative EEG were detected. In summary, we identified two genes (HTR3B and ABCB1) with significant variation in the sleep architecture response to morphine. Morphine caused a more active/unstable EEG during sleep. Our findings may have relevance for a personalized medicine approach to targeted morphine therapy.

Does craniofacial morphology relate to sleep apnea severity reduction following weight loss intervention? A patient-level meta-analysis.

STUDY OBJECTIVES: Obesity is a common and reversible risk factor for obstructive sleep apnea (OSA). However, there is substantial unexplained variability in the amount of OSA improvement for any given amount of weight loss. Facial photography is a simple, inexpensive, and radiation-free method for craniofacial assessment. Our aims were (1) to determine whether facial measurements can explain OSA changes, beyond weight loss magnitude and (2) whether facial morphology relates to how effective weight loss will be for OSA improvement. METHODS: We combined data from three weight loss intervention trials in which participants had standardized pre-intervention facial photography (N = 91; 70.3% male, mean ± SD weight loss 10.4 ± 9.6% with 20.5 ± 51.2% apnea-hypopnea index [AHI] reduction). Three skeletal-type craniofacial measurements (mandibular length, lower face height, and maxilla-mandible relationship angle) were assessed for relationship to AHI change following weight loss intervention. RESULTS: Weight and AHI changes were moderately correlated (rho = 0.3, p = 0.002). In linear regression, an increased maxilla-mandible relationship angle related to AHI improvement (ß [95% CI] -1.7 [-2.9, -0.5], p = 0.004). Maxilla-mandible relationship angle explained 10% in the variance in AHI over the amount predicted by weight loss amount (20%). The relationship between weight change and AHI was unaffected by the maxilla-mandible relationship angle (interaction term p > 0.05). CONCLUSIONS: Regardless of facial morphology, weight loss is similarly moderately predictive of OSA improvement. Increased maxilla-mandible relationship angle, suggestive of retrognathia, was weakly predictive of OSA response to weight loss. Although this is unlikely to be clinically useful, exploration in other ethnic groups may be warranted.

Sleep EEG microstructure is associated with neurobehavioural impairment after extended wakefulness in obstructive sleep apnea.

PURPOSE: Using quantitative EEG (qEEG) analysis, we investigated sleep EEG microstructure as correlates of neurobehavioural performance after 24 h of extended wakefulness in untreated OSA. METHODS: Eight male OSA patients underwent overnight polysomnography (PSG) at baseline followed by 40 h awake with repeated performance testing (psychomotor vigilance task [PVT] and AusEd driving simulator). EEG slowing during REM and spindle density during NREM sleep were calculated using power spectral analysis and a spindle detection algorithm at frontal and central electrode sites. Correlations between sleep EEG microstructure measures and performance after 24-h awake were assessed. RESULTS: Greater EEG slowing during REM sleep was associated with slower PVT reaction times (rho = - 0.79, p = 0.02), more PVT lapses (rho = 0.87, p = 0.005) and more AusEd crashes (rho = 0.73, p = 0.04). Decreased spindle density in NREM sleep was also associated with slower PVT reaction times (rho = 0.89, p = 0.007). Traditional PSG measures of disease severity were not consistent correlates of neurobehavioural performance in OSA. CONCLUSIONS: Sleep EEG microstructure measures recorded during routine PSG are associated with impaired vigilance in OSA patients after sleep deprivation. SIGNIFICANCE: Quantitative brain oscillatory (or EEG)-based measures of sleep may better reflect the deleterious effects of untreated OSA than traditional PSG metrics in at-risk individuals. Trial Registration ACTRN12606000066583.

Prevalence of chronic kidney disease in obesity hypoventilation syndrome and obstructive sleep apnoea with severe obesity.

PURPOSE: Chronic kidney disease (CKD) is common in severe obstructive sleep apnoea (OSA), however prevalence in obesity hypoventilation syndrome (OHS) is not known. This study sought to compare prevalence of CKD in OHS and equally obese OSA patients with comparable apnoea hypopnoea indexes (AHI), and secondarily examine the impact of positive airway pressure (PAP) therapy on CKD parameters. METHODS: Estimated Glomerular Filtration Rate (eGFR) and spot urine protein creatinine ratio (PCR) were obtained in patients with OHS (Partial pressure of carbon dioxide, PaCO2 > 45 mmHg) and OSA (AHI > 20 events per hour, PaCO2 < 45 mmHg) with a body mass index (BMI) > 40 kg/m2. Samples were obtained at baseline and after three months of PAP in both groups. RESULTS: Patients with OHS (n = 15, PaCO2 49 mmHg; daytime oxygen saturation, SpO2 94%; total sleep time with SpO2<90%, T90 308min) and OSA (n = 36, PaCO2 40 mmHg, SpO2 96%, T90 140min) were recruited. Stage 1-3 kidney function was present in 7 (46%) and 8 (22%) patients with OHS and OSA respectively (p = 0.08). Mean PCR was higher in OHS than OSA (23 ± 29 v 10 ± 6 mg/mmol; p = 0.03), while the prevalence of proteinuria was not different (40% v 19%, p = 0.19). Proteinuria was not significantly altered by three months of PAP. Moderate associations were demonstrated between eGFR, PaCO2, awake SpO2 and/or HbA1c (r > 0.5, p < 0.05) in OHS. CONCLUSION: The prevalence of CKD, primarily early-stage with proteinuria, is at least as frequent in OHS as it is in OSA, if not worse. Markers of CKD were not significantly impacted by PAP therapy.

Does CPAP treat depressive symptoms in individuals with OSA? An analysis of two 12-week randomized sham CPAP-controlled trials.

BACKGROUND: Depression is common in patients with obstructive sleep apnea (OSA). Whether treating OSA with continuous positive airway pressure (CPAP) improves depressive symptoms remains inconclusive. We examined the impact of CPAP on depressive symptoms in OSA patients compared to sham CPAP. METHODS: A sub-analysis of two previous randomized sham-controlled trials was conducted. 126 male OSA patients (age = 51 ± 11 years; BMI = 32.0 ± 5.1 kg/m2; apnea hypopnea index = 42.4 ± 22.6 events/hour) were randomised either to therapeutic CPAP (n = 65) or sham CPAP (n = 61). Depressive symptoms were measured using the Depression, Anxiety and Stress Scale (DASS). The main outcome was the change in the DASS depression score (DASSD) after three months between the therapeutic and sham CPAP arms. RESULTS: The change in DASSD at three months did not differ between therapeutic and sham CPAP (mean difference: 0.5, 95% CI -3.6 to 4.6, p = 0.80). There was no significant between-group differences within the sub-groups of adherent users (device usage≥4hrs/day), or those with baseline depression (DASSD>9). In a secondary analysis of patients with baseline depression, adherent therapeutic CPAP use was associated with a greater reduction in DASSD scores compared to non-adherers (-10.0, 95% CI -18.3 to -1.8, p = 0.019). CONCLUSIONS: Overall, three months of CPAP did not significantly improve depression scores in OSA patients. Adherent use of therapeutic CPAP in patients with baseline depressive symptoms was associated with a reduction in symptom score. Future trials involving OSA patients with higher depressive symptoms will enable us to understand the complex interaction between OSA and depression.

Comparing treatment effects of a convenient vibratory positional device to CPAP in positional OSA: a crossover randomised controlled trial.

OBJECTIVES: Up to 77% of patients with obstructive sleep apnoea (OSA) have positional OSA (POSA) but traditional positional therapy (PT) methods have failed as they were poorly tolerated. New convenient vibratory PT devices have been invented but while recent studies suggest high treatment efficacy and adherence, there are no published data comparing these devices directly with continuous positive airway pressure (CPAP). Our objective is to evaluate if a convenient vibratory PT device is non-inferior to CPAP in POSA treatment. METHODS: In this crossover randomised controlled trial, we enrolled patients with POSA with significant daytime sleepiness (Epworth Sleepiness Scale (ESS)≥10). POSA diagnosis was based on: (1) total Apnoea/Hypopnoea Index (AHI)>10/hour and non-supine AHI<10/hour (2) supine AHI≥2 × non-supine AHI. Patients used their initial allocated devices (PT or CPAP) for 8 weeks before crossing to the alternative intervention after a 1 week washout. The primary aim is to measure changes in ESS between the two treatments. Secondary outcomes include sleep study parameters and patient treatment preference (ClinicalTrials.gov: NCT03125512). RESULTS: 40 patients completed the trial between April 2017 and December 2018. Difference in ESS after 8 weeks of device use (PT minus CPAP) was 2.0 (95% CI 0.68 to 3.32), exceeding our predetermined non-inferiority margin of 1.5. AHI on CPAP was lower than with PT (4.0±3.2 vs 13.0±13.8 events/hour, respectively, p=0.001), although both were lower than at baseline. Time spent supine was significantly lower with PT than CPAP (p<0.001). 60% of patients preferred CPAP, 20% preferred PT, while 20% preferred neither device. CONCLUSIONS: The non-inferiority ESS endpoint for PT compared with CPAP was not met and the results were inconclusive. Future trials with larger sample sizes or in less symptomatic patients are warranted to provide further insight into the role of these new vibratory PT devices.

Slow-frequency electroencephalography activity during wake and sleep in obesity hypoventilation syndrome.

STUDY OBJECTIVE: Neurophysiological activity during wake and sleep states in obesity hypoventilation (OHS) and its relationship with neurocognitive function is not well understood. This study compared OHS with equally obese obstructive sleep apnea (OSA) patients, with similar apnea-hypopnea indices. METHODS: Resting wake and overnight sleep electroencephalography (EEG) recordings, neurocognitive tests, and sleepiness, depression and anxiety scores were assessed before and after 3 months of positive airway pressure (PAP) therapy in 15 OHS and 36 OSA patients. RESULTS: Pretreatment, greater slow frequency EEG activity during wake and sleep states (increased delta-alpha ratio during sleep, and theta power during awake) was observed in the OHS group compared to the OSA group. EEG slowing was correlated with poorer performance on the psychomotor vigilance task (slowest 10% of reciprocal reaction times, psychomotor vigilance test [PVT SRRT], primary outcome), and worse sleep-related hypoxemia measures in OHS. There was no between-group significant difference in PVT performance at pre or post-treatment. Similarly, despite both groups demonstrating improved sleepiness, anxiety and depression scores with PAP therapy, there were no differences in treatment response between the OSA and OHS groups. CONCLUSION: Patients with OHS have greater slow frequency EEG activity during sleep and wake than equally obese patients with OSA. Greater EEG slowing was associated with worse vigilance and lower oxygenation during sleep. CLINICAL TRIAL: This trial was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12615000122550).

The effect of acute exposure to morphine on breathing variability and cardiopulmonary coupling in men with obstructive sleep apnea: A randomized controlled trial.

Opioid-related deaths from respiratory depression are increasing but there is only limited information on the effect of morphine on breathing during sleep. This study aimed to detect and quantify opioid-induced cardiorespiratory pattern changes during sleep in obstructive sleep apnea (OSA) patients using novel automated methods and correlate these with conventional polysomnography (PSG) measures. Under a randomized double-blind placebo-controlled crossover design, 60 male OSA patients attended two one-night visits to the sleep laboratory, at least a week apart. Either a 40-mg controlled-release oral morphine dose or placebo was administered. Breathing during sleep was measured by standard in-laboratory PSG. We analysed the inter-breath interval (IBI) from the PSG flow channel to quantify breathing irregularity. Cardiopulmonary coupling (CPC) was analysed using the PSG electrocardiogram (ECG) channel. Following the consumption of morphine, the 60 OSA patients had fewer breaths (p = .0006), a longer inter-breath interval (p < .0001) and more irregular breathing with increased IBI coefficient of variation (CV) (p = .0015) compared to the placebo night. A higher CPC sleep quality index was found with morphine use. The change of key IBI and CPC parameters was significantly correlated with the change of key PSG sleep-disordered breathing parameters. In conclusion, 40 mg controlled-release morphine resulted in a longer breathing cycle and increased breathing irregularity but generally more stable sleep in OSA patients. The significant links between the IBI and CPC techniques and a range of PSG sleep-disordered breathing parameters may suggest a practical value as surrogate overnight cardiorespiratory measurements, because both respiratory flow and ECG can be detected by small portable devices.

Melatonin for rapid eye movement sleep behavior disorder in Parkinson's disease: A randomised controlled trial.

BACKGROUND: Melatonin may reduce REM-sleep behavior disorder (RBD) symptoms in Parkinson's disease (PD), though robust clinical trials are lacking. OBJECTIVE: To assess the efficacy of prolonged-release (PR) melatonin for RBD in PD. METHODS: Randomized, double-blind, placebo-controlled, parallel-group trial with an 8-week intervention and 4-week observation pre- and postintervention (ACTRN12613000648729). Thirty PD patients with rapid eye movement sleep behavior disorder were randomized to 4 mg of prolonged-release melatonin (Circadin) or matched placebo, ingested orally once-daily before bedtime. Primary outcome was the aggregate of rapid eye movement sleep behavior disorder incidents averaged over weeks 5 to 8 of treatment captured by a weekly diary. Data were included in a mixed-model analysis of variance (n = 15 per group). RESULTS: No differences between groups at the primary endpoint (3.4 events/week melatonin vs. 3.6 placebo; difference, 0.2; 95% confidence interval = -3.2 to 3.6; P = 0.92). Adverse events included mild headaches, fatigue, and morning sleepiness (n = 4 melatonin; n = 5 placebo). CONCLUSION: Prolonged-release melatonin 4 mg did not reduce rapid eye movement sleep behavior disorder in PD. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.