Cluster Analysis of Home Mechanical Ventilation in COPD Patients: A Picture of the Real World and Its Impact on Mortality

Background: Treatment of chronic hypercapnic failure in COPD patients with home noninvasive ventilation (HNIV) remains unclear.Aim: To create a curated cohort of all COPD patients on HNIV in Catalonia, perform a cluster analysis, and evaluate mortality evolution.Study design and methods: This study was a multicenter, observational study including all COPD patients on HNIV on 1st January of 2018. Patients were selected through the Catalan Health Service, and administrative and clinical data were obtained in the previous four years. Principal component analysis of mixed data and hierarchical clustering were performed to identify clusters of patients. Mortality was evaluated from 1 January 2018 until 31 December 2020.Results: A total of 247 patients were enrolled. They were mostly male (78.1%), with a median (SD) age of 70.4 (9.4) years old. In 60%, 55% and 29% of patients, obesity, sleep apnea and heart failure coexisted, respectively. Cluster analysis identified four well-differentiated groups labeled for their clinical characteristics: (1) obese smokers, (2) very severe COPD, (3) sleep apnea and (4) older comorbid males. Patients belonging to Clusters (2) and (4) had a worse prognosis than patients in Clusters (1) and (3).Interpretation: A high heterogeneity in the prescription of HNIV was demonstrated. Cluster analysis identifies four different groups, of which only one had COPD as the main cause of ventilation, while the other three clusters showed a predominance of other comorbidities. This leads to different survival outcomes, including an overlapping phenotype of obesity-related disease and sleep apnea with better survival. (AU)

Cluster Analysis of Home Mechanical Ventilation in COPD Patients: A Picture of the Real World and Its Impact on Mortality.

BACKGROUND: Treatment of chronic hypercapnic failure in COPD patients with home noninvasive ventilation (HNIV) remains unclear. AIM: To create a curated cohort of all COPD patients on HNIV in Catalonia, perform a cluster analysis, and evaluate mortality evolution. STUDY DESIGN AND METHODS: This study was a multicenter, observational study including all COPD patients on HNIV on 1st January of 2018. Patients were selected through the Catalan Health Service, and administrative and clinical data were obtained in the previous four years. Principal component analysis of mixed data and hierarchical clustering were performed to identify clusters of patients. Mortality was evaluated from 1 January 2018 until 31 December 2020. RESULTS: A total of 247 patients were enrolled. They were mostly male (78.1%), with a median (SD) age of 70.4 (9.4) years old. In 60%, 55% and 29% of patients, obesity, sleep apnea and heart failure coexisted, respectively. Cluster analysis identified four well-differentiated groups labeled for their clinical characteristics: (1) obese smokers, (2) very severe COPD, (3) sleep apnea and (4) older comorbid males. Patients belonging to Clusters (2) and (4) had a worse prognosis than patients in Clusters (1) and (3). INTERPRETATION: A high heterogeneity in the prescription of HNIV was demonstrated. Cluster analysis identifies four different groups, of which only one had COPD as the main cause of ventilation, while the other three clusters showed a predominance of other comorbidities. This leads to different survival outcomes, including an overlapping phenotype of obesity-related disease and sleep apnea with better survival.

Role of respiratory intermediate care units during the SARS-CoV-2 pandemic.

RATIONALE: The SARS-CoV2 pandemic increased exponentially the need for both Intensive (ICU) and Intermediate Care Units (RICU). The latter are of particular importance because they can play a dual role in critical and post-critical care of COVID-19 patients. Here, we describe the setup of 2 new RICUs in our institution to face the SARS-CoV-2 pandemic and discuss the clinical characteristics and outcomes of the patients attended. METHODS: Retrospective analysis of the characteristics and outcomes of COVID-19 patients admitted to 2 new RICUs built specifically in our institution to face the first wave of the SARS-CoV-2 pandemic, from April 1 until May 30, 2020. RESULTS: During this period, 106 COVID-19 patients were admitted to these 2 RICUs, 65 of them (61%) transferred from an ICU (step-down) and 41 (39%) from the ward or emergency room (step-up). Most of them (72%) were male and mean age was 66 ± 12 years. 31% of them required support with oxygen therapy via high-flow nasal cannula (HFNC) and 14% non-invasive ventilation (NIV). 42 of the 65 patients stepping down (65%) had a previous tracheostomy performed and most of them (74%) were successfully decannulated during their stay in the RICU. Length of stay was 7 [4-11] days. 90-day mortality was 19% being significantly higher in stepping up patients than in those transferred from the ICU (25 vs. 10% respectively; p < 0.001). CONCLUSIONS: RICUs are a valuable hospital resource to respond to the challenges of the SARS-CoV-2 pandemic both to treat deteriorating and recovering COVID-19 patients.

Spanish Society of Pulmonology and Thoracic Surgery positioning on the use of telemedine in sleep-disordered breathing and mechanical ventilation / Posicionamiento de la Sociedad Española de Neumología y Cirugía Torácica en el uso del la telemedicina en los trastornos respiratorios del sueño y ventilación mecánica

The rapid introduction of new information and communication technologies into medical practice has prompted the Spanish Society of Pulmonology and Thoracic Surgery to publish a position paper on sleep-disordered breathing, especially in relation to positive pressure treatment. It should be pointed out that the scientific literature is to some extent controversial due to a paucity of large randomized multicenter studies with long-term follow-up. Moreover, the telematics devices and systems on the market vary widely. As a result, the recommendations are based primarily on a consensus of expert professionals. Another very important aspect addressed extensively in this document is the obvious lack of regulations on telemedicine and the operations of commercial companies. The most important recommendations included in this position paper are that telemedicine is primarily advocated in subjects with travel problems or who live far from the hospital, in patients with poor CPAP compliance, and in most cases treated with non-invasive mechanical ventilation. A key element is patient individualization. It is imperative that the relevant technical, legal and ethical requirements (medical device regulations, data protection, and informed consent) are met. Finally, expert professionals from our society must contribute to and become involved in spearheading this technological change. (AU)

Como consecuencia de la rápida introducción de las nuevas tecnologías de información y comunicación (TIC) en la práctica médica, la Sociedad Española de Neumología y Cirugía Torácica ha promovido la elaboración de un documento de posicionamiento aplicado a los trastornos respiratorios del sueño, especialmente en relación con el tratamiento con presión positiva. Cabe mencionar que la literatura científica es en parte controvertida debido a que no existen suficientes estudios multicéntricos aleatorizados, con elevado número de pacientes y seguimiento a largo plazo. Además, los equipos y sistemas telemáticos en el mercado son diferentes. Como consecuencia, las recomendaciones se basan sobre todo en un consenso de profesionales expertos. Otros aspectos muy importantes son la clara ausencia de normativa o las funciones propias de las casas comerciales, que en este trabajo se abordan ampliamente. Las recomendaciones más importantes incluidas en el documento de posicionamiento son que la telemedicina se destina, básicamente, a sujetos con problemas de desplazamiento o con domicilio lejano, a aquellos que no cumplen de forma adecuada el tratamiento con CPAP y a la mayoría de los casos con ventilación mecánica no invasiva. Un elemento clave es la individualización de los pacientes. Es imperativo que se cumplan los requisitos técnicos, legales y deontológicos pertinentes (normativa de los productos sanitarios, protección de datos y consentimiento informado). Por último, los profesionales expertos de nuestra sociedad han de contribuir e implicarse en el liderazgo de este cambio tecnológico. (AU)

Spanish Society of Pulmonology and Thoracic Surgery positioning on the use of telemedine in sleep-disordered breathing and mechanical ventilation. / Posicionamiento de la Sociedad Española de Neumología y Cirugía Torácica en el uso de la telemedicina en los trastornos respiratorios del sueño y ventilación mecánica.

The rapid introduction of new information and communication technologies into medical practice has prompted Spanish Society of Pulmonology and Thoracic SurgeryR to publish a position paper on sleep-disordered breathing, especially in relation to positive pressure treatment. It should be pointed out that the scientific literature is to some extent controversial due to a paucity of large randomized multicenter studies with long-term follow-up. Moreover, the telematics devices and systems on the market vary widely. As a result, the recommendations are based primarily on a consensus of expert professionals. Another very important aspect addressed extensively in this document is the obvious lack of regulations on legal matters and the operations of commercial companies. The most important recommendations included in this position paper are that telemedicine is primarily advocated in subjects with travel problems or who live far from the hospital, in patients with poor CPAP compliance, and in most cases treated with non-invasive mechanical ventilation. A key element is patient individualization. It is imperative that the relevant technical, legal and ethical requirements (medical device regulations, data protection, and informed consent) are met. Finally, expert professionals from our society must contribute to and become involved in spearheading this technological change.

Improving home oxygen therapy in patients with interstitial lung diseases: application of a noninvasive ventilation device.

BACKGROUND: Proper adjustment of arterial oxygen saturation (SaO2) during daily activities in patients with interstitial lung disease (ILD) requiring long-term oxygen therapy is challenging. Given the multifactorial nature of the limited exercise tolerance in patients with ILDs, the isolated use of oxygen therapy may not be enough. As demonstrated previously in patients with chronic obstructive pulmonary disease, the use of a noninvasive ventilation (NIV) device combined with oxygen therapy may prevent the falling of oxygen saturation during exercise, due to an improvement of the ventilation-perfusion ratio and a reduction of the respiratory work, thus enhancing exercise tolerance. We sought to assess in patients diagnosed with ILD who are in need of oxygen therapy, the effect of associating an NIV to improve oxygen parameters and the distance covered during the 6 min walking test (6MWT). METHODS: We conducted a prospective observational study in patients with ILDs. After a clinical characterization, we performed a 6MWT in two different situations: using a portable oxygen concentrator with the regular flow used by the patient during their daily life activities and afterwards adding the additional support of a NIV. The oxygen saturation parameters were registered with a portable oximeter. RESULTS: We included 16 patients with different ILDs who have oxygen therapy prescribed. The use of NIV associated with oxygen therapy in comparison with the use of oxygen therapy alone showed an increase of the average SaO2 [91% (88-93) versus 88% (86-90%); p = 0.0005] and a decrease in the percentage of time with oxygen saturation <90%: 36% (6-56%) versus 58% (36-77%); p < 0.0001. There were no changes in the 6MWT distance: 307 m (222-419 m) versus 316 m (228-425 m); p = 0.10. CONCLUSIONS: In our study the use of a NIV system associated with long-term oxygen therapy during exercise showed beneficial effects, especially improvement of oxygen saturation.The reviews of this paper are available via the supplemental material section.

Integrated Care Intervention Supported by a Mobile Health Tool for Patients Using Noninvasive Ventilation at Home: Randomized Controlled Trial.

BACKGROUND: Home-based noninvasive ventilation has proven cost-effective. But, adherence to therapy still constitutes a common clinical problem. We hypothesized that a behavioral intervention supported by a mobile health (mHealth) app could enhance patient self-efficacy. It is widely accepted that mHealth-supported services can enhance productive interactions among the stakeholders involved in home-based respiratory therapies. OBJECTIVE: This study aimed to measure changes in self-efficacy in patients with chronic respiratory failure due to diverse etiologies during a 3-month follow-up period after the intervention. Ancillary objectives were assessment of usability and acceptability of the mobile app as well as its potential contribution to collaborative work among stakeholders. METHODS: A single-blind, single-center, randomized controlled trial was conducted between February 2019 and June 2019 with 67 adult patients with chronic respiratory failure undergoing home-based noninvasive ventilation. In the intervention group, a psychologist delivered a face-to-face motivational intervention. Follow-up was supported by a mobile app that allowed patients to report the number of hours of daily noninvasive ventilation use and problems with the therapy. Advice was automatically delivered by the mobile app in case of a reported problem. The control group received usual care. The primary outcome was the change in the Self Efficacy in Sleep Apnea questionnaire score. Secondary outcomes included app usability, app acceptability, continuity of care, person-centered care, and ventilatory parameters. RESULTS: Self-efficacy was not significantly different in the intervention group after the intervention (before: mean 3.4, SD 0.6; after: mean 3.4, SD 0.5, P=.51). No changes were observed in adherence to therapy nor quality of life. Overall, the mHealth tool had a good usability score (mean 78 points) and high acceptance rate (mean score of 7.5/10 on a Likert scale). It was considered user-friendly (mean score of 8.2/10 on a Likert scale) and easy to use without assistance (mean score of 8.5/10 on a Likert scale). Patients also scored the perception of continuity of care and person-centered care as high. CONCLUSIONS: The integrated care intervention supported by the mobile app did not improve patient self-management. However, the high acceptance of the mobile app might indicate potential for enhanced communication among stakeholders. The study identified key elements required for mHealth tools to provide effective support to collaborative work and personalized care. TRIAL REGISTRATION: ClinicalTrials.gov NCT03932175; https://clinicaltrials.gov/ct2/show/NCT03932175.

Characterization of the sleep disorder of anti-IgLON5 disease.

STUDY OBJECTIVE: To characterize the sleep disorder of anti-IgLON5 disease. METHODS: We reviewed 27 video-polysomnographies (V-PSG), 6 multiple sleep latency tests (MSLT), 2 videsomnoscopies with dexmedetomidine, and 10 actigraphies recorded during the disease course of five patients. Due to severe sleep architecture abnormalities, we used a novel modified sleep scoring system combining conventional stages with a descriptive approach in which two additional stages were identified: undifferentiated-NREM (UN-NREM) and poorly structured N2 (P-SN2) sleep that were characterized by abnormal motor activation and absence or sparse elements of conventional NREM sleep. RESULTS: Sleep-related vocalizations, movements, behaviors, and respiratory abnormalities were reported by bed-partners. In all patients, NREM sleep onset and sleep reentering after an awakening occurred as UN-NREM (median: 29.8% of total sleep time [TST]) and P-SN2 sleep (14.5% TST) associated with vocalizations and simple and quasi-purposeful movements. Sleep initiation was normalized in one patient with a high dose of steroids, but NREM sleep abnormalities reappeared in subsequent V-PSG. In all patients, if sleep continued uninterrupted, there was a progressive normalization with normal N2 (11.7% TST) and N3 (22.3% TST) sleep but stridor and obstructive apnea emerged. REM sleep behavior disorder (RBD) occurred in four patients. Sleep initiation was also altered in MSLT and dexmedetomidine-induced sleep. Actigraphy showed a 10-fold increase of nocturnal activity compared with controls. Sleep abnormalities remained stable during the disease. CONCLUSIONS: The sleep disorder of anti-IgLON5 disease presents as a complex sleep pattern characterized by abnormal sleep initiation with undifferentiated NREM sleep, RBD, periods of normal NREM sleep, stridor, and obstructive apnea.

Effects of a Combined Community Exercise Program in Obstructive Sleep Apnea Syndrome: A Randomized Clinical Trial.

Physical activity is associated with a decreased prevalence of obstructive sleep apnea and improved sleep efficiency. Studies on the effects of a comprehensive exercise program in a community setting remain limited. Our objective was to investigate the effects of a combined physical and oropharyngeal exercise program on the apnea-hypopnea index in patients with moderate to severe obstructive sleep apnea. This was a randomized clinical trial where the intervention group followed an eight-week urban-walking program, oropharyngeal exercises, and diet and sleep recommendations. The control group followed diet and sleep recommendations. A total of 33 patients were enrolled and randomized and, finally, 27 patients were included in the study (IG, 14; CG, 13) Obstructive sleep apnea patients were analyzed with a median age of 67 (52⁻74) and median apnea-hypopnea index of 32 events/h (25⁻41). The apnea-hypopnea index did not differ between groups pre- and post-intervention. However, in intervention patients younger than 60 (n = 6) a reduction of the apnea-hypopnea index from 29.5 (21.8⁻48.3) to 15.5 (11⁻34) events/h (p = 0.028) was observed. While a comprehensive multimodal program does not modify the apnea-hypopnea index, it could reduce body weight and increase the walking distance of patients with moderate to severe obstructive sleep apnea. Patients younger than 60 may also present a decreased apnea-hypopnea index after intervention.

A New mHealth application to support treatment of sleep apnoea patients.

Introduction Continuous positive airway pressure (CPAP) is the first-choice treatment for obstructive sleep apnoea (OSA), but adherence is frequently suboptimal. Innovative, patient-centred interventions are, therefore, needed to enhance compliance. Due to its low cost and ubiquity, mobile health (mHealth) technology seems particularly suited for this purpose. We endeavoured to develop an mHealth application called "APPnea," aimed at promoting patient self-monitoring of CPAP treatment. We then assessed the feasibility and acceptability of APPnea in a group of OSA patients. Methods Consecutive OSA patients used APPnea for six weeks. APPnea gave patients daily reminders to answer three questions about their OSA treatment (CPAP use, physical activity, and diet) and prompted them to upload their body weight weekly. Answers were saved to a secure server for further analysis. After completing the study, patients gave their anonymous opinions about APPnea. Results We enrolled 60 patients with OSA receiving CPAP treatment. The mean age was 56 ± 10 years and the apnoea-hypopnea index was 47 ± 25 events/hour. In total, 63% of participants completed the daily questionnaire for more than 66% of the study period. Objective CPAP compliance was generally high (5.3 ± 1.6 hours/night). In a subset of 38 patients naïve to CPAP, those who used APPnea regularly had significantly higher CPAP compliance. Satisfaction levels were high for the majority of users. Conclusion This mHealth intervention is not only feasible but also satisfactory to patients. Although larger randomized trials and cost-effectiveness studies should be performed, this study shows that APPnea could promote participation and improve compliance among patients with OSA, thereby improving outcomes.

Emerging risk factors and the dose-response relationship between physical activity and lone atrial fibrillation: a prospective case-control study.

AIMS: The role of high-intensity exercise and other emerging risk factors in lone atrial fibrillation (Ln-AF) epidemiology is still under debate. The aim of this study was to analyse the contribution of each of the emerging risk factors and the impact of physical activity dose in patients with Ln-AF. METHODS AND RESULTS: Patients with Ln-AF and age- and sex-matched healthy controls were included in a 2:1 prospective case-control study. We obtained clinical and anthropometric data transthoracic echocardiography, lifetime physical activity questionnaire, 24-h ambulatory blood pressure monitoring, Berlin questionnaire score, and, in patients at high risk for obstructive sleep apnoea (OSA) syndrome, a polysomnography. A total of 115 cases and 57 controls were enrolled. Conditional logistic regression analysis associated height [odds ratio (OR) 1.06 [1.01-1.11]], waist circumference (OR 1.06 [1.02-1.11]), OSA (OR 5.04 [1.44-17.45]), and 2000 or more hours of cumulative high-intensity endurance training to a higher AF risk. Our data indicated a U-shaped association between the extent of high-intensity training and AF risk. The risk of AF increased with an accumulated lifetime endurance sport activity ≥ 2,000 h compared with sedentary individuals (OR 3.88 [1.55-9.73]). Nevertheless, a history of <2000 h of high-intensity training protected against AF when compared with sedentary individuals (OR 0.38 [0.12-0.98]). CONCLUSION: A history of ≥ 2,000 h of vigorous endurance training, tall stature, abdominal obesity, and OSA are frequently encountered as risk factors in patients with Ln-AF. Fewer than 2000 total hours of high-intensity endurance training associates with reduced Ln-AF risk.

A Bayesian cost-effectiveness analysis of a telemedicine-based strategy for the management of sleep apnoea: a multicentre randomised controlled trial.

BACKGROUND: Compliance with continuous positive airway pressure (CPAP) therapy is essential in patients with obstructive sleep apnoea (OSA), but adequate control is not always possible. This is clinically important because CPAP can reverse the morbidity and mortality associated with OSA. Telemedicine, with support provided via a web platform and video conferences, could represent a cost-effective alternative to standard care management. AIM: To assess the telemedicine impact on treatment compliance, cost-effectiveness and improvement in quality of life (QoL) when compared with traditional face-to-face follow-up. METHODS: A randomised controlled trial was performed to compare a telemedicine-based CPAP follow-up strategy with standard face-to-face management. Consecutive OSA patients requiring CPAP treatment, with sufficient internet skills and who agreed to participate, were enrolled. They were followed-up at 1, 3 and 6 months and answered surveys about sleep, CPAP side effects and lifestyle. We compared CPAP compliance, cost-effectiveness and QoL between the beginning and the end of the study. A Bayesian cost-effectiveness analysis with non-informative priors was performed. RESULTS: We randomised 139 patients. At 6 months, we found similar levels of CPAP compliance, and improved daytime sleepiness, QoL, side effects and degree of satisfaction in both groups. Despite requiring more visits, the telemedicine group was more cost-effective: costs were lower and differences in effectiveness were not relevant. CONCLUSIONS: A telemedicine-based strategy for the follow-up of CPAP treatment in patients with OSA was as effective as standard hospital-based care in terms of CPAP compliance and symptom improvement, with comparable side effects and satisfaction rates. The telemedicine-based strategy had lower total costs due to savings on transport and less lost productivity (indirect costs). TRIAL REGISTER NUMBER: NCT01716676.

Effect of CPAP on Cognition, Brain Function, and Structure Among Elderly Patients With OSA: A Randomized Pilot Study.

BACKGROUND: Despite the increasing aging population and the high prevalence of OSA in elderly adults, little is known about cognitive effects of OSA and the effectiveness of CPAP treatment. Therefore, this study investigated whether elderly patients with OSA present cognitive deficits and functional and structural alterations of the brain that could be improved by CPAP treatment. METHODS: This randomized, evaluator-blinded, parallel-group, single-center pilot study involved patients aged ≥ 65 years with newly-diagnosed severe OSA syndrome. Thirty-three patients were assigned to receive either conservative care (CC) or CPAP plus CC for 3 months. At baseline and 3 months after treatment, patients underwent a neuropsychologic evaluation and a functional and structural MRI study of connectivity within the default mode network (DMN) and of cortical thickness. RESULTS: Neuropsychologic evaluation revealed no differences in cognitive performance between OSA groups at baseline. By contrast, after CPAP treatment, patients showed a significant improvement in episodic (between-group difference in change, 7.60; 95% CI, 1.66-13.55; P = .014) and short-term memory (between-group difference in change, 1.06; 95% CI, 0.10-2.01; P = .032) and in executive function (speed of mental processing, 5.74; 95% CI, 1.69-9.79; P = .007; mental flexibility, -47.64; 95% CI, -81.83 to -13.45; P = .008), whereas no changes were observed in the CC group. Neuroimaging revealed an increase in the connectivity in the right middle frontal gyrus after 3 months of CPAP treatment and a higher percentage of cortical thinning in the CC group. No association was seen between cognition and brain functional connectivity changes within the DMN. CONCLUSIONS: Elderly patients with severe OSA who present with cognitive difficulties could benefit from CPAP treatment. Moreover, CPAP treatment increases the connectivity of the DMN and attenuates cortical thinning. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01826032; URL: www.clinicaltrials.gov.

The Barcelona Sleepiness Index: A New Instrument to Assess Excessive Daytime Sleepiness in Sleep Disordered Breathing.

STUDY OBJECTIVES: To develop the Barcelona Sleepiness Index (BSI), an interviewer-administered instrument for assessing excessive daytime sleepiness (EDS) in sleep-disordered breathing (SDB) that correlates well with objective measures of EDS and which is sensitive to change with treatment. METHODS: (1) Generation of a preliminary item list: Fifty-three consecutive SDB patients complaining of EDS and their bed partners were interviewed using a focus group methodology to generate a list of situations prone to cause sleepiness. Sixty different consecutive SDB patients were then evaluated using cognitive interviews to refine this list. (2) Construct validity: The maintenance of wakefulness test (MWT), the multiple sleep latency test (MSLT) and the sustained attention to response task (SART) test were used in an additional 98 consecutive SDB patients with and without EDS. The item combination that best correlated with the objective tests constituted the BSI. Cutoff values were determined to differentiate between patients with and without EDS. (3) Sensitivity to change: Thirty patients requiring continuous positive airway pressure (CPAP) were evaluated after satisfactory treatment. RESULTS: A combination of two items, "in the morning, when relaxing" and "in the afternoon, standing inactive, in a public place," presented the highest correlations with the MWT (r: -0.50, p < 0.001), the MSLT (r: -0.21, p = 0.07), and the SART (r: 0.27, p < 0.02) and constituted the BSI. The BSI significantly correlated with oxyhemoglobin saturation measures (nadir SpO2: r: -0.28, p = 0.01; CT 85: r: 0.23, p = 0.04) and showed a high sensitivity to change with CPAP treatment (t: 3.4, p = 0.002). A score of 2 or more identified patients with objective EDS (sensitivity = 64.9%, specificity = 72.1%). CONCLUSION: The Barcelona Sleepiness Index is a simple, brief instrument for measuring subjective EDS in SDB.

Mutual information measures applied to EEG signals for sleepiness characterization.

Excessive daytime sleepiness (EDS) is one of the main symptoms of several sleep related disorders with a great impact on the patient lives. While many studies have been carried out in order to assess daytime sleepiness, the automatic EDS detection still remains an open problem. In this work, a novel approach to this issue based on non-linear dynamical analysis of EEG signal was proposed. Multichannel EEG signals were recorded during five maintenance of wakefulness (MWT) and multiple sleep latency (MSLT) tests alternated throughout the day from patients suffering from sleep disordered breathing. A group of 20 patients with excessive daytime sleepiness (EDS) was compared with a group of 20 patients without daytime sleepiness (WDS), by analyzing 60-s EEG windows in waking state. Measures obtained from cross-mutual information function (CMIF) and auto-mutual-information function (AMIF) were calculated in the EEG. These functions permitted a quantification of the complexity properties of the EEG signal and the non-linear couplings between different zones of the scalp. Statistical differences between EDS and WDS groups were found in ß band during MSLT events (p-value < 0.0001). WDS group presented more complexity than EDS in the occipital zone, while a stronger nonlinear coupling between occipital and frontal zones was detected in EDS patients than in WDS. The AMIF and CMIF measures yielded sensitivity and specificity above 80% and AUC of ROC above 0.85 in classifying EDS and WDS patients.

Effectiveness of home single-channel nasal pressure for sleep apnea diagnosis.

INTRODUCTION: Home single-channel nasal pressure (HNP) may be an alternative to polysomnography (PSG) for obstructive sleep apnea (OSA) diagnosis, but no cost studies have yet been carried out. Automatic scoring is simpler but generally less effective than manual scoring. OBJECTIVES: To determine the diagnostic efficacy and cost of both scorings (automatic and manual) compared with PSG, taking as a polysomnographic OSA diagnosis several apnea-hypopnea index (AHI) cutoff points. METHODS: We included suspected OSA patients in a multicenter study. They were randomized to home and hospital protocols. We constructed receiver operating characteristic (ROC) curves for both scorings. Diagnostic efficacy was explored for several HNP AHI cutoff points, and costs were calculated for equally effective alternatives. RESULTS: Of 787 randomized patients, 752 underwent HNP. Manual scoring produced better ROC curves than automatic for AHI < 15; similar curves were obtained for AHI ≥ 15. A valid HNP with manual scoring would determine the presence of OSA (or otherwise) in 90% of patients with a polysomnographic AHI ≥ 5 cutoff point, in 74% of patients with a polysomnographic AHI ≥ 10 cutoff point, and in 61% of patients with a polysomnographic AHI ≥ 15 cutoff point. In the same way, a valid HNP with automatic scoring would determine the presence of OSA (or otherwise) in 73% of patients with a polysomnographic AHI ≥ 5 cutoff point, in 64% of patients with a polysomnographic AHI ≥ 10 cutoff point, and in 57% of patients with a polysomnographic AHI ≥ 15 cutoff point. The costs of either HNP approaches were 40% to 70% lower than those of PSG at the same level of diagnostic efficacy. Manual HNP had the lowest cost for low polysomnographic AHI levels (≥ 5 and ≥ 10), and manual and automatic scorings had similar costs for higher polysomnographic cutoff points (AHI ≥ 15) of diagnosis. CONCLUSION: Home single-channel nasal pressure (HNP) is a cheaper alternative than polysomnography for obstructive sleep apnea diagnosis. HNP with manual scoring seems to have better diagnostic accuracy and a lower cost than automatic scoring for patients with low apnea-hypopnea index (AHI) levels, although automatic scoring has similar diagnostic accuracy and cost as manual scoring for intermediate and high AHI levels. Therefore, automatic scoring can be appropriately used, although diagnostic efficacy could improve if we carried out manual scoring on patients with AHI < 15. CLINICAL TRIALS INFORMATION: Clinicaltrials.gov identifier: NCT01347398.

Management of sleep apnea without high pretest probability or with comorbidities by three nights of portable sleep monitoring.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) diagnosis using simplified methods such as portable sleep monitoring (PM) is only recommended in patients with a high pretest probability. The aim is to determine the diagnostic efficacy, consequent therapeutic decision-making, and costs of OSA diagnosis using polysomnography (PSG) versus three consecutive studies of PM in patients with mild to moderate suspicion of sleep apnea or with comorbidity that can mask OSA symptoms. DESIGN AND SETTING: Randomized, blinded, crossover study of 3 nights of PM (3N-PM) versus PSG. The diagnostic efficacy was evaluated with receiver operating characteristic (ROC) curves. Therapeutic decisions to assess concordance between the two different approaches were performed by sleep physicians and respiratory physicians (staff and residents) using agreement level and kappa coefficient. The costs of each diagnostic strategy were considered. PATIENTS AND RESULTS: Fifty-six patients were selected. Epworth Sleepiness Scale was 10.1 (5.3) points. Bland-Altman plot for apnea-hypopnea index (AHI) showed good agreement. ROC curves showed the best area under the curve in patients with PSG AHI ≥ 5 [0.955 (confidence interval = 0.862-0.993)]. For a PSG AHI ≥ 5, a PM AHI of 5 would effectively exclude and confirm OSA diagnosis. For a PSG AHI ≥ 15, a PM AHI ≥ 22 would confirm and PM AHI < 7 would exclude OSA. The best agreement of therapeutic decisions was achieved by the sleep medicine specialists (81.8%). The best cost-diagnostic efficacy was obtained by the 3N-PM. CONCLUSIONS: Three consecutive nights of portable monitoring at home evaluated by a qualified sleep specialist is useful for the management of patients without high pretest probability of obstructive sleep apnea or with comorbidities. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov, registration number: NCT01820156. CITATION: Guerrero A, Embid C, Isetta V, Farre R, Duran-Cantolla J, Parra O, Barbé F, Montserrat JM, Masa JF. Management of sleep apnea without high pretest probability or with comorbidities by three nights of portable sleep monitoring.

Brain tissue hypoxia and oxidative stress induced by obstructive apneas is different in young and aged rats.

STUDY OBJECTIVES: To test the hypotheses that brain oxygen partial pressure (PtO2) in response to obstructive apneas changes with age and that it might lead to different levels of cerebral tissue oxidative stress. DESIGN: Prospective controlled animal study. SETTING: University laboratory. PARTICIPANTS: Sixty-four male Wistar rats: 32 young (3 mo old) and 32 aged (18 mo). INTERVENTIONS: Protocol 1: Twenty-four animals were subjected to obstructive apneas (50 apneas/h, lasting 15 sec each) or to sham procedure for 50 min. Protocol 2: Forty rats were subjected to obstructive apneas or sham procedure for 4 h. MEASUREMENTS AND RESULTS: Protocol 1: Real-time PtO2 measurements were performed using a fast-response oxygen microelectrode. During successive apneas cerebral cortex PtO2 presented a different pattern in the two age groups; there was a fast increase in young rats, whereas it remained without significant changes between the beginning and the end of the protocol in the aged group. Protocol 2: Brain oxidative stress assessed by lipid peroxidation increased after apneas in young rats (1.34 ± 0.17 nmol/mg of protein) compared to old ones (0.63 ± 0.03 nmol/mg), where a higher expression of antioxidant enzymes was observed. CONCLUSIONS: The results suggest that brain oxidative stress in aged rats is lower than in young rats in response to recurrent apneas, mimicking obstructive sleep apnea. This could be due to the different PtO2 response observed between age groups and the increased antioxidant expression in aged rats. CITATION: Dalmases M, Torres M, Márquez-Kisinousky L, Almendros I, Planas AM, Embid C, Martínez-Garcia MA, Navajas D, Farré R, Montserrat JM. Brain tissue hypoxia and oxidative stress induced by obstructive apneas is different in young and aged rats.

A novel non-rapid-eye movement and rapid-eye-movement parasomnia with sleep breathing disorder associated with antibodies to IgLON5: a case series, characterisation of the antigen, and post-mortem study.

BACKGROUND: Autoimmunity might be associated with or implicated in sleep and neurodegenerative disorders. We aimed to describe the features of a novel neurological syndrome associated with prominent sleep dysfunction and antibodies to a neuronal antigen. METHODS: In this observational study, we used clinical and video polysomnography to identify a novel sleep disorder in three patients referred to the Sleep Unit of Hospital Clinic, University of Barcelona, Spain, for abnormal sleep behaviours and obstructive sleep apnoea. These patients had antibodies against a neuronal surface antigen, which were also present in five additional patients referred to our laboratory for antibody studies. These five patients had been assessed with polysomnography, which was done in our sleep unit in one patient and the recording reviewed in a second patient. Two patients underwent post-mortem brain examination. Immunoprecipitation and mass spectrometry were used to characterise the antigen and develop an assay for antibody testing. Serum or CSF from 298 patients with neurodegenerative, sleep, or autoimmune disorders served as control samples. FINDINGS: All eight patients (five women; median age at disease onset 59 years [range 52-76]) had abnormal sleep movements and behaviours and obstructive sleep apnoea, as confirmed by polysomnography. Six patients had chronic progression with a median duration from symptom onset to death or last visit of 5 years (range 2-12); in four the sleep disorder was the initial and most prominent feature, and in two it was preceded by gait instability followed by dysarthria, dysphagia, ataxia, or chorea. Two patients had a rapid progression with disequilibrium, dysarthria, dysphagia, and central hypoventilation, and died 2 months and 6 months, respectively, after symptom onset. In five of five patients, video polysomnography showed features of obstructive sleep apnoea, stridor, and abnormal sleep architecture (undifferentiated non-rapid-eye-movement [non-REM] sleep or poorly structured stage N2, simple movements and finalistic behaviours, normalisation of non-REM sleep by the end of the night, and, in the four patients with REM sleep recorded, REM sleep behaviour disorder). Four of four patients had HLA-DRB1*1001 and HLA-DQB1*0501 alleles. All patients had antibodies (mainly IgG4) against IgLON5, a neuronal cell adhesion molecule. Only one of the 298 controls, who had progressive supranuclear palsy, had IgLON5 antibodies. Neuropathology showed neuronal loss and extensive deposits of hyperphosphorylated tau mainly involving the tegmentum of the brainstem and hypothalamus in the two patients studied. INTERPRETATION: IgLON5 antibodies identify a unique non-REM and REM parasomnia with sleep breathing dysfunction and pathological features suggesting a tauopathy. FUNDING: Fondo de Investigaciones Sanitarias, Centros de Investigación Biomédica en Red de enfermedades neurodegenerativas (CIBERNED) and Respiratorias (CIBERES), Ministerio de Economía y Competitividad, Fundació la Marató TV3, and the National Institutes of Health.