Metrology of two wearable sleep trackers against polysomnography in patients with sleep complaints.

Sleep trackers are used widely by patients with sleep complaints, however their metrological validation is often poor and relies on healthy subjects. We assessed the metrological validity of two commercially available sleep trackers (Withings Activité/Fitbit Alta HR) through a prospective observational monocentric study, in adult patients referred for polysomnography (PSG). We compared the total sleep time (TST), REM time, REM latency, nonREM1 + 2 time, nonREM3 time, and wake after sleep onset (WASO). We report absolute and relative errors, Bland-Altman representations, and a contingency table of times spent in sleep stages with respect to PSG. Sixty-five patients were included (final sample size 58 for Withings and 52 for Fitbit). Both devices gave a relatively accurate sleep start time with a median absolute error of 5 (IQR -43; 27) min for Withings and -2.0 (-12.5; 4.2) min for Fitbit but both overestimated TST. Withings tended to underestimate WASO with a median absolute error of -25.0 (-61.5; -8.5) min, while Fitbit tended to overestimate it (median absolute error 10 (-18; 43) min. Withings underestimated light sleep and overestimated deep sleep, while Fitbit overestimated light and REM sleep and underestimated deep sleep. The overall kappas for concordance of each epoch between PSG and devices were low: 0.12 (95%CI 0.117-0.121) for Withings and VPSG indications 0.07 (95%CI 0.067-0.071) for Fitbit, as well as kappas for each VPSG indication 0.07 (95%CI 0.067-0.071). Thus, commercially available sleep trackers are not reliable for sleep architecture in patients with sleep complaints/pathologies and should not replace actigraphy and/or PSG.

Continuous positive airway pressure as an accurate marker for non-24-hour sleep-wake rhythm disorder.

Non-24-h sleep-wake rhythm disorder is quite rare in sighted patients and frequently associated with psychiatric disorders. We report the case of a 46-year-old man with autism spectrum disorder (ASD) and agoraphobia who had been referred for a suspicion of obstructive sleep apnea syndrome (OSAS). Polysomnography and arterial blood gas confirmed moderate OSAS associated with hypoventilation. Continuous positive airway pressure (CPAP) was started on fixed mode with excellent results. At follow-up, his CPAP report data revealed an irregular sleep-wake rhythm with a progressive offset of sleep schedule and wake time delayed from 1 h from day to day. Melatonin (or agonist) is efficacious and safe for long-term treatment in ASD and circadian rhythm sleep-wake disorder (CRSWD) with light therapy and wakefulness promoting medication. This case underlines the importance to sensitise psychiatrists to sleep and CRSWD, and also that CPAP data offer a possible objective alternative to sleep diary.

Factors associated with insomnia symptoms: A cross-sectional study during a Covid-19 fully restrictive lockdown.

Insomnia is the most frequent sleep disorder and a public health concern that increased during the Covid 19 pandemic. Fully restrictive lockdowns during Covid are interesting periods to examine the impact of environmental and behavioural changes on the emergence of insomnia symptoms. In this cross-sectional study we aimed to (1) determine the main factors associated with insomnia symptoms during a Covid-19 fully restrictive lockdown examining the associated daily life alterations and (2) create a predictive model of insomnia symptoms. We used the data drawn from the "Covid-RythmE" study that reached volunteers from the general French population through an online survey during the last 2 weeks of the 2 month full lockdown. Associations with insomnia symptoms were tested and significant associations were entered in a Backward Stepwise Logistic Regression (BSLR) to assess the best combination to classify individuals with or without insomnia symptoms. From the 1624 participants, 50.64% suffered from mild to severe insomnia symptoms as assessed by the ISI. The best combination for explaining insomnia symptoms with 74.26% of accuracy included: age (OR = 1.15), females (OR = 1.26), smaller home sizes (OR = 0.77), environmental noises (OR = 1.59), anxiety symptoms (OR = 1.24), depressive symptoms (OR = 1.15), regularity of sleep-wake schedules (OR = 1.25), exposure to screen during the morning (OR = 1.13), and LED light during the evening (OR = 1.17). Thus, lifestyle schedule and exposure to natural synchronizers such as light, are primordial in considering in insomnia physiopathology, prevention and treatment, as well as the associated mental health status.

The nightmare severity index (NSI): A short new multidimensional tool for assessing nightmares.

This psychometric pilot study aims to evaluate a new multidimensional simple scale, named the nightmare severity index (NSI) - close to the existing insomnia (ISI) and hypersomnia (HSI) severity indexes. The NSI encompasses all main dimensions of nightmare disorder, evaluating four subdimensions: frequency, emotional impact, diurnal impact, and nocturnal impact of nightmares. The NSI was completed by a total of 102 patients. The majority of the population consisted of women (64%) and outpatient individuals (76%) diagnosed with mood disorders such as depression (31%) and bipolar disorder (41%). Comorbidity with post-traumatic stress disorder (PTSD) was prevalent (44%), and psychotropic medications were commonly used (47%). Internal validity analyses indicated that the NSI was well suited for exploratory factor analysis. All items demonstrated satisfactory correlations with the factors, and the questionnaire exhibited good internal consistency (Cronbach's alpha >0.7). Higher NSI scores were observed among individuals experiencing nightmare symptoms considering the DSM-5/ICSD-3 criteria. In summary, the NSI proves to be a promising and valuable tool for clinical practice, demonstrating good acceptability, internal validity, and the ability to assess nightmare severity.

Adaptive servo ventilation for sleep apnoea in heart failure: the FACE study 3-month data.

RATIONALE: Adaptive servo ventilation (ASV) is contraindicated in patients with systolic heart failure (HF) who have a left ventricular ejection fraction (LVEF) below 45% and predominant central sleep apnoea (CSA). However, the effects of ASV in other HF subgroups have not been clearly defined. OBJECTIVE: The European, multicentre, prospective, observational cohort trial, FACE, evaluated the effects of ASV therapy on morbidity and mortality in patients with HF with sleep-disordered breathing (SDB); 3-month outcomes in patient subgroups defined using latent class analysis (LCA) are presented. METHODS: Consecutive patients with HF with predominant CSA (±obstructive sleep apnoea) indicated for ASV were included from 2009 to 2018; the non-ASV group included patients who refused/were noncompliant with ASV. The primary endpoint was time to composite first event (all-cause death, lifesaving cardiovascular intervention or unplanned hospitalisation for worsening of chronic HF). MEASUREMENTS AND MAIN RESULTS: Baseline assessments were performed in 503 patients, and 482 underwent 3-month follow-up. LCA identified six discrete patient clusters characterised by variations in LVEF, SDB type, age, comorbidities and ASV acceptance. The 3- month rate of primary outcome events was significantly higher in cluster 1 patients (predominantly men, low LVEF, severe HF, CSA; 13.9% vs 1.5%-5% in other clusters, p<0.01). CONCLUSION: For the first time, our data identified homogeneous patient clusters representing clinically relevant subgroups relating to SDB management in patients with HF with different ASV usage, each with a different prognosis. This may improve patient phenotyping in clinical practice and allow individualisation of therapy.

Sleep and circadian rhythm characteristics in individuals from the general population during the French COVID-19 full lockdown.

The full 2-month lockdown to fight the coronavirus disease 2019 (COVID-19) pandemic in 2020 led to substantial disruption of daily life and routines. The present study aimed to comprehensively identify the lockdown's effects on sleep, daily rhythms and emotions of the French population. A survey was published online during the last week of the 2-month full lockdown and 1,627 individuals completed the online survey. The survey was self-administered and included standardised questionnaires. Sleep schedules were delayed during lockdown in more than half of the participants. New severe delayed sleep phase affected 10% of participants with sleep schedules delayed by ≥3 hr during the lockdown compared to before. A significant decrease in exposure to morning (p < 0.001) and evening natural light (p < 0.001), a significant increase in screen exposure time (with a significant screen exposure >3 hr during the evening for 45% of the participants during lockdown versus 18% before lockdown, p < 0.001), an increase in substance use for one-quarter of participants, a poorer sleep quality in 56% of participants, and less regular sleep schedules in 48% of participants were observed. We also found a poorer sleep quality in women than men during lockdown (p = 0.004). The French full lockdown had a severe impact on sleep quality, sleep-wake rhythms, and sleep behaviours. The implementation of public health strategies for the prevention and care of sleep-wake cycles during lockdown are therefore essential.

Effect of adaptive servo ventilation on central sleep apnea and sleep structure in systolic heart failure patients: polysomnography data from the SERVE-HF major sub study.

This SERVE-HF (Treatment of Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients With Heart Failure) sub study analysis evaluated polysomnography (PSG) data in patients with heart failure with reduced ejection fraction (HFrEF) and predominant central sleep apnea (CSA) randomised to guideline-based medical therapy, with or without adaptive servo ventilation (ASV). Patients underwent full overnight PSG at baseline and at 12 months. All PSG recordings were analysed by a core laboratory. Only data for patients with baseline and 3- or 12-month values were included. The sub study included 312 patients; the number with available PSG data differed for each variable (94-103 in the control group, 77-99 in the ASV group). After 12 months, baseline-adjusted respiratory measures were significantly better in the ASV group versus control. Although some between-group differences in sleep measures were seen at 12 months (e.g., better sleep efficiency in the ASV group), these were unlikely to be clinically significant. The number of periodic leg movements during sleep (PLMS) increased in the ASV group (p = 0.039). At 12 months, the respiratory arousal index was significantly lower in the ASV versus control group (p < 0.001), whilst the PLMS-related arousal index was significantly higher in the ASV group (p = 0.04 versus control). ASV attenuated the respiratory variables characterising sleep apnea in patients with HFrEF and predominant CSA in SERVE-HF. Sleep quality improvements during ASV therapy were small and unlikely to be clinically significant. The increase in PLMS and PLMS-related arousals during ASV warrants further investigation, particularly relating to their potential association with increased cardiovascular risk.

Obstructive Apneas in a Mouse Model of Congenital Central Hypoventilation Syndrome.

Rationale: Congenital central hypoventilation syndrome (CCHS) is characterized by life-threatening sleep hypoventilation and is caused by PHOX2B gene mutations, most frequently the PHOX2B27Ala/+ mutation, with patients requiring lifelong ventilatory support. It is unclear whether obstructive apneas are part of the syndrome. Objectives: To determine if Phox2b27Ala/+ mice, which present the main symptoms of CCHS and die within hours after birth, also express obstructive apneas, and to investigate potential underlying mechanisms. Methods: Apneas were classified as central, obstructive, or mixed by using a novel system combining pneumotachography and laser detection of abdominal movement immediately after birth. Several respiratory nuclei involved in airway patency were examined by immunohistochemistry and electrophysiology in brainstem-spinal cord preparations. Measurements and Main Results: The median (interquartile range) of obstructive apnea frequency was 2.3 (1.5-3.3)/min in Phox2b27Ala/+ pups versus 0.6 (0.4-1.0)/min in wild types (P < 0.0001). Obstructive apnea duration was 2.7 seconds (2.3-3.9) in Phox2b27Ala/+ pups versus 1.7 seconds (1.1-1.9) in wild types (P < 0.0001). Central and mixed apneas presented similar significant differences. In Phox2b27Ala/+ preparations, the hypoglossal nucleus had fewer (P < 0.05) and smaller (P < 0.01) neurons, compared with wild-type preparations. Importantly, coordination of phrenic and hypoglossal motor activities was disrupted, as evidenced by the longer and variable delay of hypoglossal activity with respect to phrenic activity onset (P < 0.001). Conclusions: The Phox2b27Ala/+ mutation predisposed pups not only to hypoventilation and central apneas, but also to obstructive and mixed apneas, likely because of hypoglossal dysgenesis. These results thus demand attention toward obstructive events in infants with CCHS.

Sleep disturbances in early clinical stages of psychotic and bipolar disorders: A meta-analysis.

OBJECTIVE: To provide a qualitative view and quantitative measure of sleep disturbances across and between early stages - clinical ultra high-risk and first episode - of psychotic and bipolar disorders. METHODS: Electronic databases (PubMed, Cochrane, Embase, PsychINFO) were searched up to March 2021 for studies comparing sleep measures between individuals with an early stage and controls. Standard mean deviations (Cohen's d effect sizes) were calculated for all comparisons and pooled with random-effects models. Chi-square tests were used for direct between-subgroups (ultra high-risk vs first episode) comparisons of standard mean deviations. The effects of age, sex ratio, symptoms and treatment were examined in meta-regression analyses. RESULTS: A database search identified 13 studies that contrasted sleep measures between individuals with an early stage (N = 537) and controls (N = 360). We observed poorer subjective sleep quality (standard mean deviation = 1.32; 95% confidence interval, [1.01, 1.62]), shorter total sleep time (standard mean deviation =-0.44; 95% confidence interval, [-0.67, -0.21]), lower sleep efficiency (standard mean deviation = -0.72; 95% confidence interval, [-1.08, -0.36]), longer sleep onset latency (standard mean deviation = 0.75; 95% confidence interval, [0.45, 1.06]) and longer duration of wake after sleep onset (standard mean deviation = 0.49; 95% confidence interval, [0.21, 0.77]) were observed in early stages compared to controls. No significant differences were observed for any of the reported electroencephalographic parameters of sleep architecture. No significant between-subgroups differences were observed. Meta-regressions revealed a significant effect of the age and the antipsychotic status on subjective measures of sleep. CONCLUSION: The early stage population presents with significant impairments of subjective sleep quality continuity, duration and initiation. Systematic assessments of sleep in early intervention settings may allow early identification and treatment of sleep disturbances in this population.

Association of Standard Electroencephalography Findings With Mortality and Command Following in Mechanically Ventilated Patients Remaining Unresponsive After Sedation Interruption.

CONTEXT: Delayed awakening after sedation interruption is frequent in critically ill patients receiving mechanical ventilation. OBJECTIVES: We aimed to investigate the association of standard electroencephalography with mortality and command following in this setting. DESIGN, SETTING, AND PATIENTS: In a single-center study, we retrospectively analyzed standard electroencephalography performed in consecutive mechanically ventilated patients remaining unresponsive (comatose/stuporous or unable to follow commands) after sedation interruption. Standard electroencephalography parameters (background activity, continuity, and reactivity) were reassessed by neurophysiologists, blinded to patients' outcome. Patients were categorized during follow-up into three groups based on their best examination as: 1) command following, 2) unresponsive, or 3) deceased. Cause-specific models were used to identify independent standard electroencephalography parameters associated with main outcomes, that is, mortality and command following. Follow-up was right-censored 30 days after standard electroencephalography. MEASUREMENTS AND MAIN RESULTS: Main standard electroencephalography parameters recorded in 121 unresponsive patients (median time between sedation interruption and standard electroencephalography: 2 d [interquartile range, 1-4 d]) consisted of a background frequency greater than 4 Hz in 71 (59%), a discontinuous background in 19 (16%), and a preserved reactivity in 98/120 (82%) patients. At 30 days, 66 patients (55%) were command following, nine (7%) were unresponsive, and 46 (38%) had died. In a multivariate analysis adjusted for nonneurologic organ failure, a reactive standard electroencephalography with a background frequency greater than 4 Hz was independently associated with a reduced risk of death (cause-specific hazard ratio, 0.38; CI 95%, 0.16-0.9). By contrast, none of the standard electroencephalography parameters were independently associated with command following. Sensitivity analyses conducted after exclusion of 29 patients with hypoxic brain injury revealed similar findings. CONCLUSIONS: In patients remaining unresponsive after sedation interruption, a pattern consisting of a reactive standard electroencephalography with a background frequency greater than 4 Hz was associated with decreased odds of death. None of the standard electroencephalography parameters were independently associated with command following.

Sleep medicine catalogue of knowledge and skills - Revision.

The 'catalogue of knowledge and skills' for sleep medicine presents the blueprint for a curriculum, a textbook, and an examination on sleep medicine. The first catalogue of knowledge and skills was presented by the European Sleep Research Society in 2014. It was developed following a formal Delphi procedure. A revised version was needed in order to incorporate changes that have occurred in the meantime in the International Classification of Sleep Disorders, updates in the manual for scoring sleep and associated events, and, most important, new knowledge in sleep physiology and pathophysiology. In addition, another major change can be observed in sleep medicine: a paradigm shift in sleep medicine has taken place. Sleep medicine is no longer a small interdisciplinary field in medicine. Sleep medicine has increased in terms of recognition and importance in medical care. Consequently, major medical fields (e.g. pneumology, cardiology, neurology, psychiatry, otorhinolaryngology, paediatrics) recognise that sleep disorders become a necessity for education and for diagnostic assessment in their discipline. This paradigm change is considered in the catalogue of knowledge and skills revision by the addition of new chapters.

Association of serious adverse events with Cheyne-Stokes respiration characteristics in patients with systolic heart failure and central sleep apnoea: A SERVE-Heart Failure substudy analysis.

BACKGROUND AND OBJECTIVE: Increases in Cheyne-Stokes respiration (CSR) cycle length (CL), lung-to-periphery circulation time (LPCT) and time to peak flow (TTPF) may reflect impaired cardiac function. This retrospective analysis used an automatic algorithm to evaluate baseline CSR-related features and then determined whether these could be used to identify patients with systolic heart failure (HF) who experienced serious adverse events in the Treatment of Sleep-Disordered Breathing with Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients with Heart Failure (SERVE-HF) substudy. METHODS: A total of 280 patients had overnight diagnostic polysomnography data available; an automated algorithm was applied to quantify CSR-related features. RESULTS: Median baseline CL, LPCT and TTPF were similar in the control (n = 152) and adaptive servo-ventilation (ASV, n = 156) groups. In both groups, CSR-related features were significantly longer in patients who did (n = 129) versus did not (n = 140) experience a primary endpoint event (all-cause death, life-saving cardiovascular intervention or unplanned hospitalization for worsening HF): CL, 61.1 versus 55.1 s (P = 0.002); LPCT, 36.5 versus 31.5 s (P < 0.001); TTPF, 15.20 versus 13.35 s (P < 0.001), respectively. This finding was independent of treatment allocation. CONCLUSION: Patients with systolic HF and central sleep apnoea who experienced serious adverse events had longer CSR CL, LPCT and TTPF. Future studies should examine an independent role for CSR-related features to enable risk stratification in systolic HF.

Early EEG for Prognostication Under Venoarterial Extracorporeal Membrane Oxygenation.

BACKGROUND/OBJECTIVES: Tools for prognostication of neurologic outcome of adult patients under venoarterial ECMO (VA-ECMO) have not been thoroughly investigated. We aimed to determine whether early standard electroencephalography (stdEEG) can be used for prognostication in adults under VA-ECMO. METHODS: Prospective single-center observational study conducted in two intensive care units of a university hospital, Paris, France. Early stdEEG was performed on consecutive adult patients treated with VA-ECMO for refractory cardiogenic shock or refractory cardiac arrest. The association between stdEEG findings and unfavorable outcome was investigated. The primary endpoint was 28-day mortality. The secondary endpoint was severe disability or death at 90 days, defined by a score of 4-6 on the modified Rankin scale. RESULTS: A total of 122 patients were included, of whom 35 (29%) received cardiopulmonary resuscitation before VA-ECMO cannulation. Main stdEEG findings included low background frequency ≤ 4 Hz (n = 27, 22%) and background abnormalities, i.e., a discontinuous (n = 20, 17%) and/or an unreactive background (n = 12, 10%). Background abnormalities displayed better performances for prediction of unfavorable outcomes, as compared to clinical parameters at time of recording. An unreactive stdEEG background in combination with a background frequency ≤ 4 Hz had a false positive rate of 0% for prediction of unfavorable outcome at 28 days and 90 days, with sensitivities of 8% and 6%, respectively. After adjustment for confounders, a lower background frequency was independently associated with unfavorable outcome at 28 days (adjusted odds ratio per 1-Hz increment, 95% CI 0.71, 0.52-0.97), whereas no such independent association was observed at 90 days. CONCLUSION: Standard EEG abnormalities recorded at time of VA-ECMO initiation are predictive of unfavorable outcomes. However, the low sensitivity of these parameters highlights the need for a multimodal evaluation for improving management of care and prognostication.

Sex differences in mandibular repositioning device therapy effectiveness in patients with obstructive sleep apnea syndrome.

PURPOSE: Mandibular repositioning devices (MRDs) are an effective treatment option for obstructive sleep apnea syndrome (OSAS), particularly in patients who refuse or cannot tolerate continuous positive airway pressure (CPAP). However, sex differences in the response to therapy and predictors of response are not clearly defined. This analysis of data from the long-term prospective ORCADES trial compared MRD efficacy in men and women with OSAS. METHODS: The ORCADES study included patients with newly diagnosed mild-to-moderate or severe OSAS who refused or were non-compliant with CPAP. MRD therapy was titrated over 3-6 months. The primary endpoint was treatment success (≥ 50% decrease in apnea-hypopnea index (AHI)). Complete response was defined using a range of AHI cut-off values (< 5/h, < 10/h, < 15/h). RESULTS: Overall treatment success rates were 89% in women and 76% in men (p = 0.019); corresponding rates in those with severe OSAS (AHI > 30/h) were 100% and 68% (p = 0.0015). In women vs. men, overall complete response rates at AHI cut-off values of < 5/h, <10/h, and < 15/h were 49 vs. 34% (p = 0.0052), 78 vs. 62% (p = 0.016), and 92 vs. 76% (p = 0.0032). On multivariate analysis, significant predictors of MRD treatment success were overbite and baseline apnea index in men, and neck circumference and no previous CPAP therapy in women. There were sex differences in the occurrence of side effects. Temporomandibular joint pain was the most common reason for stopping MRD therapy. CONCLUSIONS: MRD therapy was effective in women with OSA of any severity, with significantly higher response rates compared with men especially in severe OSAS. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT01326143).

The parapharyngeal adipose corpus: anatomic and radiologic study.

PURPOSE: Although the morphology of the parapharyngeal adipose corpus (PAC) has been already described, the clinical interest of its volume and weight in the genesis of obstructive sleep apnea syndrome (OSAS) is still controversial. The volume of the PAC has been determined in OSAS patients but not in a normal population. The aim of our study was to investigate the morphology of the PAC by dissection and MRI in a normal population and to determine if there is a relation between the dimensions and volume of the PAC and the Body Mass Index (BMI). METHODS: Thirty hemifaces of 15 fresh cadavers have been dissected after silicone injection with dissection of the external carotid artery and its main branches, with harvesting of the PAC. The PAC has been measured and weighed. Twenty-nine MRI of healthy subjects have been examined to determine the volume of the PAC, the palate-pharynx distance, and epiglottis-pharynx distance. RESULTS: In dissection study the weight of the PAC was 18.57 g ± 2.24, the vertical dimension (height) was 4.61 cm ± 0.51, the frontal dimension (width) was 1.62 cm ± 0.24. The blood supply of the PAC constituted of branches coming from the ascending palatal and ascending pharyngeal arteries. The volume of the PAC on the right side was 1.56 cm3 ± 0.38, on the left side 1.54 cm3 ± 0.37. Its horizontal greater dimension was 1.70 cm ± 0.07. CONCLUSIONS: There is a correlation between the volume of the PAC and the BMI in a normal population. A surgical resection of the PAC in OSAS patients by transoral robotic-assisted surgery can be proposed with preservation of the ascending palatal and ascending pharyngeal arteries.

Adaptive Servo-Ventilation for Central Sleep Apnea in Systolic Heart Failure.

BACKGROUND: Central sleep apnea is associated with poor prognosis and death in patients with heart failure. Adaptive servo-ventilation is a therapy that uses a noninvasive ventilator to treat central sleep apnea by delivering servo-controlled inspiratory pressure support on top of expiratory positive airway pressure. We investigated the effects of adaptive servo-ventilation in patients who had heart failure with reduced ejection fraction and predominantly central sleep apnea. METHODS: We randomly assigned 1325 patients with a left ventricular ejection fraction of 45% or less, an apnea-hypopnea index (AHI) of 15 or more events (occurrences of apnea or hypopnea) per hour, and a predominance of central events to receive guideline-based medical treatment with adaptive servo-ventilation or guideline-based medical treatment alone (control). The primary end point in the time-to-event analysis was the first event of death from any cause, lifesaving cardiovascular intervention (cardiac transplantation, implantation of a ventricular assist device, resuscitation after sudden cardiac arrest, or appropriate lifesaving shock), or unplanned hospitalization for worsening heart failure. RESULTS: In the adaptive servo-ventilation group, the mean AHI at 12 months was 6.6 events per hour. The incidence of the primary end point did not differ significantly between the adaptive servo-ventilation group and the control group (54.1% and 50.8%, respectively; hazard ratio, 1.13; 95% confidence interval [CI], 0.97 to 1.31; P=0.10). All-cause mortality and cardiovascular mortality were significantly higher in the adaptive servo-ventilation group than in the control group (hazard ratio for death from any cause, 1.28; 95% CI, 1.06 to 1.55; P=0.01; and hazard ratio for cardiovascular death, 1.34; 95% CI, 1.09 to 1.65; P=0.006). CONCLUSIONS: Adaptive servo-ventilation had no significant effect on the primary end point in patients who had heart failure with reduced ejection fraction and predominantly central sleep apnea, but all-cause and cardiovascular mortality were both increased with this therapy. (Funded by ResMed and others; SERVE-HF ClinicalTrials.gov number, NCT00733343.).

Early Electroencephalography Findings in Cardiogenic Shock Patients Treated by Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: We aimed to assess early electroencephalography findings in patients treated by venoarterial extracorporeal membrane oxygenation and their association with neurologic outcome. DESIGN: Single-center observational study. SETTING: Medical ICU of a university hospital. PATIENTS: An early standardized electroencephalography assessment, that is, standard electroencephalography followed by continuous electroencephalography, was performed in consecutive cardiogenic shock patients requiring venoarterial extracorporeal membrane oxygenation. Associations between electroencephalography findings and outcome, defined as a composite of acute brain injury or death at 14 days, were investigated. MEASUREMENTS AND MAIN RESULTS: Twenty-two patients with a median Full Outline of Unresponsiveness score of 4 (interquartile range, 3-6) were studied. Pupillary light reflex, corneal reflex, and cough reflex were preserved in 20 (90%), 17 (77%), and 17 (77%) patients, respectively. Overall, standard electroencephalography findings consisted of diffuse slowing in 21 patients (95%) and severe background abnormalities in 13 patients (59%) (i.e., a discontinuous [n = 5; 23%] and/or an unreactive background [n = 9; 41%]). Severe background abnormalities on standard electroencephalography (poor outcome rate: 69% vs 22%; p = 0.03) and absence of sleep transients on continuous electroencephalography (poor outcome rate: 67% vs 14%; p = 0.02) were associated with a poor outcome, whereas neurologic findings and doses of sedation were not. Patients without sleep transients on continuous electroencephalography tended to have lower Full Outline of Unresponsiveness scores than patients with preserved sleep transients-appearing patterns. CONCLUSIONS: In patients treated by venoarterial extracorporeal membrane oxygenation, early severe background abnormalities on standard electroencephalography provide important information on neurologic outcome. The lack of sleep transients on continuous electroencephalography reflects the severity of brain dysfunction and might represent an additional prognostic marker.

Adaptive servo ventilation for central sleep apnoea in heart failure: SERVE-HF on-treatment analysis.

This on-treatment analysis was conducted to facilitate understanding of mechanisms underlying the increased risk of all-cause and cardiovascular mortality in heart failure patients with reduced ejection fraction and predominant central sleep apnoea randomised to adaptive servo ventilation versus the control group in the SERVE-HF trial.Time-dependent on-treatment analyses were conducted (unadjusted and adjusted for predictive covariates). A comprehensive, time-dependent model was developed to correct for asymmetric selection effects (to minimise bias).The comprehensive model showed increased cardiovascular death hazard ratios during adaptive servo ventilation usage periods, slightly lower than those in the SERVE-HF intention-to-treat analysis. Self-selection bias was evident. Patients randomised to adaptive servo ventilation who crossed over to the control group were at higher risk of cardiovascular death than controls, while control patients with crossover to adaptive servo ventilation showed a trend towards lower risk of cardiovascular death than patients randomised to adaptive servo ventilation. Cardiovascular risk did not increase as nightly adaptive servo ventilation usage increased.On-treatment analysis showed similar results to the SERVE-HF intention-to-treat analysis, with an increased risk of cardiovascular death in heart failure with reduced ejection fraction patients with predominant central sleep apnoea treated with adaptive servo ventilation. Bias is inevitable and needs to be taken into account in any kind of on-treatment analysis in positive airway pressure studies.

Obstructive sleep apnoea and related comorbidities in incident idiopathic pulmonary fibrosis.

The objectives of this prospective study were: 1) to determine the prevalence and determinants of obstructive sleep apnoea (OSA) in patients with newly diagnosed idiopathic pulmonary fibrosis (IPF); 2) to determine whether OSA was associated with cardiovascular disease (CVD) as well as increased oxidative stress and levels of IPF biomarkers in the blood.A group of 45 patients with newly diagnosed IPF attended polysomnography. The prevalence of CVD and the severity of coronary artery calcification were investigated by high-resolution computed tomography. The levels of 8-hydroxydeoxyguanosine (8-OH-DG) and various IPF biomarkers in the blood were compared between patients with no or mild OSA (apnoea-hypopnoea index (AHI) <15 events·h-1), with moderate OSA (15 ≤AHI <30 events·h-1) and with severe OSA (AHI ≥30 events·h-1).The prevalence of moderate-to-severe OSA and severe OSA was 62% and 40%, respectively. AHI did not correlate with demographic or physiological data. All patients with severe OSA had a medical history of CVD, versus 41.2% and 40% of those with no or mild OSA, or with moderate OSA, respectively (p<0.0001). Ischaemic heart disease (IHD) and moderate-to-severe coronary artery calcifications were strongly associated with severe OSA. The 8-OH-DG and matrix metalloproteinase-7 serum levels were significantly increased in the severe OSA group.Moderate-to-severe OSA is highly prevalent in incident IPF and severe OSA is strongly associated with the presence of CVD, particularly IHD.