Transcutaneous electrical stimulation in obstructive sleep apnoea: current developments and concepts of the TESLA-home programme.

PURPOSE OF REVIEW: Obstructive sleep apnoea (OSA) is a highly prevalent condition affecting about 1 billion people worldwide. The first line therapy for most patients with OSA is continuous positive airway pressure (CPAP) therapy. However, there are significant limitations with long-term adherence to CPAP therapy, which may be as low as 30-60%. RECENT FINDING: Electrical stimulation of the hypoglossal nerve has been studied in recent years. It achieves upper airway patency by causing a contraction of the genioglossus muscle, the strongest dilator of the upper airway, and by maintaining its neuromuscular tone in the asleep patient with OSA. Electrical stimulation can be delivered invasively, hypoglossal nerve stimulation (HNS), and noninvasively, transcutaneous electrical stimulation in OSA (TESLA). However, randomised controlled trials, the STAR and the TESLA trial, have provided promising results on efficacy and safety of the methods. SUMMARY: Patient and public involvement underlines the interest in TESLA and HNS and highlights the need to provide non-CPAP therapeutic options to those who may find it difficult to cope with first line therapies. The relatively low costs and the favourable safety profile of the TESLA approach provide the chance to offer this treatment to patients with OSA following further development of the evidence.

Validation of a New Contactless and Continuous Respiratory Rate Monitoring Device Based on Ultra-Wideband Radar Technology.

Respiratory rate (RR) is typically the first vital sign to change when a patient decompensates. Despite this, RR is often monitored infrequently and inaccurately. The Circadia Contactless Breathing Monitor™ (model C100) is a novel device that uses ultra-wideband radar to monitor RR continuously and un-obtrusively. Performance of the Circadia Monitor was assessed by direct comparison to manually scored reference data. Data were collected across a range of clinical and non-clinical settings, considering a broad range of user characteristics and use cases, in a total of 50 subjects. Bland-Altman analysis showed high agreement with the gold standard reference for all study data, and agreement fell within the predefined acceptance criteria of ±5 breaths per minute (BrPM). The 95% limits of agreement were -3.0 to 1.3 BrPM for a nonprobability sample of subjects while awake, -2.3 to 1.7 BrPM for a clinical sample of subjects while asleep, and -1.2 to 0.7 BrPM for a sample of healthy subjects while asleep. Accuracy rate, using an error margin of ±2 BrPM, was found to be 90% or higher. Results demonstrate that the Circadia Monitor can effectively and efficiently be used for accurate spot measurements and continuous bedside monitoring of RR in low acuity settings, such as the nursing home or hospital ward, or for remote patient monitoring.

Video polysomnographic findings in non-rapid eye movement parasomnia.

Although video polysomnography (vPSG) is not routinely recommended for the evaluation of typical cases of non-rapid eye movement (NREM) parasomnias, it can aid diagnosis of unusual cases, other sleep disorders and complicated cases with REM behaviour disorder (RBD), and in differentiating parasomnias from epilepsy. In this study, we aimed to assess vPSG findings in consecutive patients with a clinical diagnosis of NREM-parasomnia covering the whole phenotypic spectrum. Five hundred and twelve patients with a final diagnosis of NREM parasomnia who had undergone vPSG were retrospectively identified. vPSGs were analysed for features of NREM parasomnia and for the presence of other sleep disorders. Two hundred and six (40.0%) patients were clinically diagnosed with sleepwalking, 72 (14.1%) with sleep terrors, 39 (7.6%) with confusional arousals, 15 (2.9%) with sexsomnia, seven (1.4%) with sleep-related eating disorder, 122 (23.8%) with mixed phenotype, and 51 (10.0%) with parasomnia overlap disorder (POD). The vPSG supported the diagnosis of NREM parasomnia in 64.4% of the patients and of POD in 98%. In 28.9% of the patients, obstructive sleep apnea (OSA) or/and periodic limb movements during sleep (PLMS) were identified, most commonly in older, male, sleepy and obese patients. vPSG has a high diagnostic yield in patients with NREM parasomnia and should be routinely performed when there is diagnostic doubt, or in patients where there is a suspicion of OSA and PLMS.

Effectiveness and side-effect profile of stimulant therapy as monotherapy and in combination in the central hypersomnias in clinical practice.

Effectiveness and side-effect profile data on pharmacotherapy for daytime sleepiness in central hypersomnias are based largely upon randomized controlled trials. Evidence regarding the use of combination therapy is scant. The aim of this study was to examine the effectiveness and occurrence of drug-related side effects of these drugs in routine clinical practice. Adult patients diagnosed with a central hypersomnia during a 54-month period at a tertiary sleep disorders centre were identified retrospectively. Side effects were recorded at every follow-up visit. A total of 126 patients, with 3275 patient-months of drug exposure, were categorized into narcolepsy type 1 (n = 70), narcolepsy type 2 (n = 47) and idiopathic hypersomnia (n = 9). Modafinil was the most common drug used as a first-line treatment (93%) and in combination therapy (70%). Thirty-nine per cent of the patients demonstrated a complete, 25% partial and 36% a poor response to treatment. Combination treatment improved daytime sleepiness in 55% of the patients with residual symptoms despite monotherapy. Sixty per cent of patients reported side effects, and 30% reported treatment-limiting side effects. Drugs had similar side-effect incidence (P = 0.363) and their side-effect profile met those reported in the literature. Twenty-seven per cent of the patients received combination treatment and had fewer side effects compared to monotherapy (29.4% versus 60%, respectively, P = 0.001). Monotherapy appears to achieve satisfactory symptom control in most patients with central hypersomnia, but significant side effects are common. Combination therapy appears to be a useful and safe option in patients with refractory symptoms.

Sleep apps: what role do they play in clinical medicine?

PURPOSE OF REVIEW: Today's smartphones boast more computing power than the Apollo Guidance Computer. Given the ubiquity and popularity of smartphones, are we already carrying around miniaturized sleep labs in our pockets? RECENT FINDINGS: There is still a lack of validation studies for consumer sleep technologies in general and apps for monitoring sleep in particular. To overcome this gap, multidisciplinary teams are needed that focus on feasibility work at the intersection of software engineering, data science and clinical sleep medicine. SUMMARY: To date, no smartphone app for monitoring sleep through movement sensors has been successfully validated against polysomnography, despite the role and validity of actigraphy in sleep medicine having been well established. Missing separation of concerns, not methodology, poses the key limiting factor: The two essential steps in the monitoring process, data collection and scoring, are chained together inside a black box due to the closed nature of consumer devices. This leaves researchers with little room for influence nor can they access raw data. Multidisciplinary teams that wield complete power over the sleep monitoring process are sorely needed.

The relationship between pulmonary hypertension and obstructive sleep apnea.

PURPOSE OF REVIEW: Although obstructive sleep apnea (OSA)-associated pulmonary hypertension is not uncommon and carries a worse prognosis if left untreated, it is less well recognized by clinicians. This review provides information on prevalence, pathophysiology, clinical presentation, treatment, and prognosis of pulmonary hypertension in OSA. RECENT FINDINGS: The prevalence of pulmonary hypertension in OSA ranges from 17 to 53%. The underlying pathophysiology is complex and yet to be fully understood. Continuous positive airway pressure has been proven to be efficacious in the treatment of OSA-associated pulmonary hypertension. SUMMARY: There is still lack of research in this field. We look forward to more well designed studies to help us understand this disease entity better.

Sleep-stage sequencing of sleep-onset REM periods in MSLT predicts treatment response in patients with narcolepsy.

Current treatment recommendations for narcolepsy suggest that modafinil should be used as a first-line treatment ahead of conventional stimulants or sodium oxybate. In this study, performed in a tertiary sleep disorders centre, treatment responses were examined following these recommendations, and the ability of sleep-stage sequencing of sleep-onset rapid eye movement periods in the multiple sleep latency test to predict treatment response. Over a 3.5-year period, 255 patients were retrospectively identified in the authors' database as patients diagnosed with narcolepsy, type 1 (with cataplexy) or type 2 (without) using clinical and polysomnographic criteria. Eligible patients were examined in detail, sleep study data were abstracted and sleep-stage sequencing of sleep-onset rapid eye movement periods were analysed. Response to treatment was graded utilizing an internally developed scale. Seventy-five patients were included (39% males). Forty (53%) were diagnosed with type 1 narcolepsy with a mean follow-up of 2.37 ± 1.35 years. Ninety-seven percent of the patients were initially started on modafinil, and overall 59% reported complete response on the last follow-up. Twenty-nine patients (39%) had the sequence of sleep stage 1 or wake to rapid eye movement in all of their sleep-onset rapid eye movement periods, with most of these diagnosed as narcolepsy type 1 (72%). The presence of this specific sleep-stage sequence in all sleep-onset rapid eye movement periods was associated with worse treatment response (P = 0.0023). Sleep-stage sequence analysis of sleep-onset rapid eye movement periods in the multiple sleep latency test may aid the prediction of treatment response in narcoleptics and provide a useful prognostic tool in clinical practice, above and beyond their classification as narcolepsy type 1 or 2.

Residual excessive sleepiness in patients with obstructive sleep apnea on treatment with continuous positive airway pressure.

PURPOSE OF REVIEW: One of the most common causes of excessive daytime sleepiness in clinical practice is obstructive sleep apnea syndrome (OSAS). So far, continuous positive airway pressure (CPAP) is the most effective treatment for OSA. Some of the patients do not improve on CPAP and remain sleepy despite using CPAP.This review provides updated information about the possible causes of residual sleepiness whilst using the CPAP in patients with OSAS. RECENT FINDINGS: Prevalence of OSAS has increased recently to 23.4% in women and 49.7% in men. Periodic limb movement, behaviorally induced insufficient sleep syndrome and depression are the most common causes of persistent sleepiness on CPAP. Residual sleepiness after exclusion of all possible causes is 6%. SUMMARY: There is still lack of sufficient evidence about the accurate characteristics and possible causes of this residual sleepiness and how to address this in large prospective studies.

Detecting early signs of deterioration and preventing hospitalizations in skilled nursing facilities using remote respiratory monitoring.

An increase in respiratory rate (RR) can be an early indicator of clinical deterioration, yet it remains an often-neglected vital sign. The most common way of measuring RR is by manually counting chest-wall movements, a time-consuming and error-prone process. Staffing and funding shortages, particularly in post-acute and long-term care, mean these RR measurements are often infrequent, potentially leading to missed diagnoses and preventable readmissions. Here we present a case series from skilled nursing facilities, highlighting how continuous respiratory monitoring using a contactless remote patient monitoring (RPM) system can support clinicians in initiating timely interventions, potentially reducing preventable hospitalizations, mortality, and associated financial implications.

Sleep stage sequence analysis of sleep onset REM periods in the hypersomnias.

BACKGROUND: The Multiple Sleep Latency Test (MSLT) remains an important diagnostic tool in the diagnosis of hypersomnias. However, a positive MSLT may be found in other sleep disorders, such as behaviourally induced inadequate sleep syndrome (BIISS). It has been demonstrated that in sleep onset rapid eye movement (SOREM) periods in BIISS, REM sleep tends to arise from stage 2 sleep (non-REM (NREM) 2), rather than stage 1 sleep (NREM1), as in narcolepsy. METHODS: We performed sleep stage sequence analysis on 127 patients with nocturnal polysomnography and MSLT, including 25 with narcolepsy with cataplexy (N+C), 41 with narcolepsy without cataplexy (N-C), 21 with idiopathic hypersomnia with long sleep time (IHL), 20 with BIISS and 20 with periodic limb movement disorder (PLMD). 537 naps were recorded, containing 176 SOREM periods. RESULTS: All SOREM periods in the IHL, BIISS and PLMD groups arose from NREM2 sleep, 75% of those in N+C arose from NREM1 and in N-C only 52% arose from NREM1. Within the N-C group, those with SOREM periods all arising from stage 1 had a shorter MSL (p=0.02). CONCLUSIONS: These results suggest that SOREM periods arising from NREM1 have high sensitivity for the diagnosis of narcolepsy and that SOREM periods from NREM1 are a marker of severity, either of sleepiness or REM instability. Sleep stage sequence analysis of SOREM periods may also aid more accurate phenotyping of the hypersomnias and in particular clarify heterogeneity among patients with narcolepsy without cataplexy.

Alcohol and sleep I: effects on normal sleep.

This review provides a qualitative assessment of all known scientific studies on the impact of alcohol ingestion on nocturnal sleep in healthy volunteers. At all dosages, alcohol causes a reduction in sleep onset latency, a more consolidated first half sleep and an increase in sleep disruption in the second half of sleep. The effects on rapid eye movement (REM) sleep in the first half of sleep appear to be dose related with low and moderate doses showing no clear trend on REM sleep in the first half of the night whereas at high doses, REM sleep reduction in the first part of sleep is significant. Total night REM sleep percentage is decreased in the majority of studies at moderate and high doses with no clear trend apparent at low doses. The onset of the first REM sleep period is significantly delayed at all doses and appears to be the most recognizable effect of alcohol on REM sleep followed by the reduction in total night REM sleep. The majority of studies, across dose, age and gender, confirm an increase in slow wave sleep (SWS) in the first half of the night relative to baseline values. The impact of alcohol on SWS in the first half of night appears to be more robust than the effect on REM sleep and does not appear to be an epiphenomenon REM sleep reduction. Total night SWS is increased at high alcohol doses across gender and age groups.

Volume targeted versus pressure support non-invasive ventilation in patients with super obesity and chronic respiratory failure: a randomised controlled trial.

INTRODUCTION: Automatic titration modes of non-invasive ventilation, including average volume assured pressure support (AVAPS), are hybrid technologies that target a set volume by automated adjustment of pressure support (PS). These automated modes could offer potential advantages over fixed level PS, in particular, in patients who are super obese. METHODS: Consecutive patients with obesity hypoventilation syndrome were enrolled in a two-centre prospective single-blind randomised controlled trial of AVAPS versus fixed-level PS using a strict protocolised setup. MEASUREMENTS: The primary outcome was change in daytime arterial PCO(2) (PaCO(2)) at 3 months. Body composition, physical activity (7-day actigraphy) and health-related quality of life (severe respiratory insufficiency questionnaire, SRI) were secondary outcome measures. RESULTS: 50 patients (body mass index 50±7 kg/m(2); 55±11 years; 53% men) were enrolled with a mean PaCO(2) of 6.9±0.8 kPa and SRI of 53±17. 46 patients (23 AVAPS and 23 PS) completed the trial. At 3 months, improvements in PaCO(2) were observed in both groups (AVAPS 0.6 kPa, 95% CI 0.2 to 1.1, p<0.01 vs PS 0.6 kPa, 95% CI 0.1 to 1.1, p=0.02) but no between-group difference (-0.1 kPa, 95% CI -0.7 to 0.6, p=0.87). SRI also improved in both groups (AVAPS 11, 95% CI 6 to 17, p<0.001 vs PS 7, 95% CI 1 to 12, p=0.02; between groups 5, 95% CI -3 to 12, p=0.21). Secondary analysis of both groups combined showed improvements in daytime physical activity that correlated with reduction in fat mass (r=0.48; p=0.01). CONCLUSION: The study demonstrated no differences between automated AVAPS mode and fixed-level PS mode using a strict protocolised setup in patients who were super obese. The data suggest that the management of sleep-disordered breathing may enhance daytime activity and promote weight loss in super-obese patients.

Performance Evaluation of the Circadia Contactless Breathing Monitor and Sleep Analysis Algorithm for Sleep Stage Classification.

Although polysomnography (PSG) remains the gold standard for studying sleep in the lab, the development of wearable and 'nearable' non-EEG based sleep monitors has the potential to make long-term sleep monitoring in a home environment possible. However, validation of these novel technologies against PSG is required. The current study aims to evaluate the sleep staging performance of the radar-based Circadia Contactless Breathing Monitor (model C100) and proprietary Sleep Analysis Algorithm, both in a home and sleep lab environment, on cohorts of healthy sleepers. The C100 device was initially used to record 17 nights of sleep data from 9 participants alongside PSG, with a subsequent 24 nights of PSG data for validation purposes. Respiration and body movement features were extracted from sensor data, and a machine learning algorithm was developed to perform sleep stage prediction. The algorithm was trained using PSG data obtained in the initial dataset (n=17), and validated using leave- one-subject-out cross-validation. An epoch-by-epoch recall (true positive rate) of 75.0 %, 59.9 %, 74.8 % and 57.1 %, was found for 'Deep', 'Light', 'REM' and 'Wake' respectively. Highly similar results were obtained in the independent validation dataset (n=24), indicating robustness of results and generalizability of the sleep staging model, at least in the healthy population. The device was found to outperform both a consumer and medical grade wrist-worn monitoring device (Fitbit Alta HR and Philips Respironics Actiwatch) on sleep metric estimation accuracy. These results indicate that the developed non-contact monitor forms a viable alternative to existing clinically used wrist-worn methods, and that longitudinal monitoring of sleep stages in a home environment becomes feasible.

NREM parasomnias: a treatment approach based upon a retrospective case series of 512 patients.

BACKGROUND: Non-REM parasomnias are not uncommon conditions in the general population. Current treatment options are based on small case series and reports. In this study, we aimed to present the clinical experience from a large cohort of patients. PATIENTS: Five hundred and twelve patients with Non-REM parasomnia or parasomnia overlap disorder (POD), who had undergone a video polysomnography and were exposed to treatment, were retrospectively identified. Treatment outcome was assessed based on patients' reports, and treatment approach on a locally accepted hierarchy of interventions. RESULTS: Forty percent of patients were diagnosed with sleepwalking, 23.8% with mixed-phenotype and 10% with POD. Ultimately, 97.2% reported adequate control of their symptoms. Moreover, 60.1% were treated with pharmacotherapy and 32.0% without, consistent across all phenotypes (p = 0.09). Benzodiazepines were the most common drugs prescribed (47.1%, p < 0.05). In the end, 37.7% of our patients were receiving a benzodiazepine as part of their successful treatment, 11.7% an antidepressant, 9.2% a z-drug, and 10.7% melatonin. Finally, 13.2%, 12.1%, and 5.8% of our patients reported good control of their symptoms with sleep hygiene, management of sleep-disordered breathing, and psychological interventions (cognitive behavioral therapy [CBT] or mindfulness-based stress reduction [MBSR]), as monotherapy, respectively. CONCLUSION: The treatment approach to effective treatment of the patients with Non-REM parasomnias or POD offering first sleep hygiene advice, next treatment of concurrent sleep disorders and management of other priming factors like stress and anxiety, and lastly pharmacotherapy for Non-REM parasomnia is supported by our results. Non pharmacological interventions were effective in one third of our patients, and CBT/MBSR and melatonin appeared promising new treatments.

Domiciliary use of transcutaneous electrical stimulation for patients with obstructive sleep apnoea: a conceptual framework for the TESLA home programme.

Obstructive sleep apnoea (OSA) is a global health problem of increasing prevalence. Effective treatments are available with continuous positive airway pressure (CPAP) therapy and mandibular advancement devices (MAD). However, there is limited long-term adherence to therapy, as CPAP and MAD require permanent usage to avoid recurrence of the symptoms and adverse ill health. Alternative treatments would aid in the treatment cascade to manage OSA effectively whenever standard therapy has been trialled and failed. Hypoglossal nerve stimulation (HNS), an invasive approach to stimulate the pharyngeal dilator muscles of the upper airway during sleep, has been approved for the treatment of OSA by several healthcare systems in recent years. In parallel to the development of HNS, a non-invasive approach has been developed to deliver electrical stimulation. Transcutaneous electrical stimulation in obstructive sleep apnoea (TESLA) uses non-invasive electrical stimulation to increase neuromuscular tone of the upper airway dilator muscles of patients with OSA during sleep. Data from previous feasibility studies and randomised controlled trials have helped to identify a subgroup of patients who are "responders" to this treatment. However, further investigations are required to assess usability, functionality and task accomplishment of this novel treatment. Consideration of these factors in the study design of future clinical trials will strengthen research methodology and protocols, improve patient related outcome measures and assessments, to optimise this emerging therapeutical option. In this review, we will introduce a conceptual framework for the TESLA home programme highlighting qualitative aspects and outcomes.

Safety and efficacy of long-term use of sodium oxybate for narcolepsy with cataplexy in routine clinical practice.

BACKGROUND: Sodium oxybate is licensed in Europe for the treatment of narcolepsy with cataplexy in adults. The aim of this study was to assess the efficacy and safety of sodium oxybate in clinical practice in patients with narcolepsy and cataplexy refractory to other treatments. MATERIALS AND METHODS: This was a retrospective single centre study including patients with severe narcolepsy with cataplexy refractory to other treatments, who were initiated on sodium oxybate between 2009 and 2015. Patients were allowed to be on other stimulants or/and anti-cataplectic agents. Epworth sleepiness scale (ESS) and weekly cataplexy events were recorded. Side effects (SEs) were recorded at every follow-up visit. RESULTS: 90 patients were prescribed sodium oxybate, with a total of 3116 patient-months of drug exposure. ESS and weekly cataplexy events were significantly reduced by sodium oxybate for all patients (ΔESS = 4.3 ± 4.4 and Δcataplexy = 21.8 ± 18.5 events/week; p < 0.0001, respectively). The required maintenance dose could not be predicted based upon gender, body mass index, or clinical factors. 60% of patients were able to reduce or come off other medications. Half of the patients experienced at least one SE, and 26.6% had to stop treatment due to limiting SEs. Nausea, mood swings and enuresis were the most commonly reported SEs. SEs that led to drug discontinuation, particularly psychosis, were associated with increasing age and were observed early after the initiation of the drug. CONCLUSIONS: Sodium oxybate provides a good clinical efficacy and acceptable safety profile in routine clinical practice for the treatment of patients suffering from narcolepsy with cataplexy. A quarter of patients experience SEs requiring withdrawal of the drug with older patients being more vulnerable to the more serious SEs.

Catathrenia, a REM predominant disorder of arousal?

OBJECTIVES: Catathrenia is an uncommon and poorly understood disorder, characterized by groaning during sleep occurring in tandem with prolonged expiration. Its classification, pathogenesis, and clinical relevance remain debated, substantially due to the limited number of cases reported to date. We report a series of consecutive cases of catathrenia, their clinical and polysomnographic characteristics, and their subsequent management. METHODS: Consecutive patients with catathrenia who had undergone full polysomnography in our institution over a 5.5-year period were included. Catathrenia events (CEs) were examined in clusters, which formulated catathrenia periods (CPs). The relationships between CPs, sleep stage distribution, electroencephalogram (EEG) arousals, and other sleep parameters were assessed, along with the clinical presentation and management of catathrenic patients. RESULTS: A total of 427 CPs were identified in 38 patients, 81% arising from rapid eye movement (REM) sleep. EEG arousals preceded or coincided with the onset of 84% of CPs, which were of longer duration than those not associated with an arousal (57.3 ± 56.8 vs. 32.2 ± 29.4 s, p < 0.001). Each CE had a characteristic airflow signal, with inspiration preceding a protracted expiration and a brief more rapid exhalation, followed by deep inspiration. Although the majority of patients were referred on the basis of bed partner complaints, 44.7% complained of daytime sleepiness. Continuous positive airway pressure therapy and sleep-consolidating pharmacotherapy led to subjective improvement, but were limited by poor long-term adherence. CONCLUSIONS: In the largest series of catathrenia patients reported to date, we found that this rare disorder is characterized by a distinct breathing pattern and arises predominantly from REM sleep, with arousals almost uniformly preceding or coinciding with the onset of CPs.