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Rationale: Primary care clinicians may be well placed to play a greater role in obstructive sleep apnea management. Objectives: To evaluate the outcomes and cost-effectiveness of sleep apnea manage...

Background More than 20% of hospitalized patients with COVID-19 demonstrate ARDS requiring ICU admission. The long-term respiratory sequelae in such patients remain unclear. Research Question What are the major long-term pulmonary sequelae in critical patients who survive COVID-19? Study Design and Methods Consecutive patients with COVID-19 requiring ICU admission were recruited and evaluated 3 months after hospitalization discharge. The follow-up comprised symptom and quality of life, anxiety and depression questionnaires, pulmonary function tests, exercise test (6-min walking test [6MWT]), and chest CT imaging. Results One hundred twenty-five patients admitted to the ICU with ARDS secondary to COVID-19 were recruited between March and June 2020. At the 3-month follow-up, 62 patients were available for pulmonary evaluation. The most frequent symptoms were dyspnea (46.7%) and cough (34.4%). Eighty-two percent of patients showed a lung diffusing capacity of less than 80%. The median distance in the 6MWT was 400 m (interquartile range, 362-440 m). CT scans showed abnormal results in 70.2% of patients, demonstrating reticular lesions in 49.1% and fibrotic patterns in 21.1%. Patients with more severe alterations on chest CT scan showed worse pulmonary function and presented more degrees of desaturation in the 6MWT. Factors associated with the severity of lung damage on chest CT scan were age and length of invasive mechanical ventilation during the ICU stay. Interpretation Three months after hospital discharge, pulmonary structural abnormalities and functional impairment are highly prevalent in patients with ARDS secondary to COVID-19 who required an ICU stay. Pulmonary evaluation should be considered for all critical COVID-19 survivors 3 months after discharge.

Pulmonary hypertension (PH) is prevalent in obesity hypoventilation syndrome (OHS). However, there is a paucity of data assessing pathogenic factors associated with PH. Our objective is to assess risk factors that may be involved in the pathogenesis of PH in untreated OHS.

Purpose: The COVID-19 outbreak witnessed in the first months of 2020 has led to unprecedented changes in society’s lifestyle. In the current study, we aimed to investigate the effect of this unexpected context on sleep.Methods: During the COVID-19 outbreak, we performed an online survey with individuals formerly recruited for validation of the Spanish version of the sleep questionnaire Satisfaction, Alertness, Timing, Efficiency, and Duration (SATED). In the current survey, we asked the participants to complete the previously answered questionnaires, including the Pittsburgh Sleep Quality Index (PSQI), a modified version of the Epworth Sleepiness Scale (ESS), and the SATED questionnaire. We also assessed mood using the Profile of Mood States (POMS) questionnaire.Results: The 71 participants were mostly women (75%), with a mean (±SD) age of 40.7 ± 11.9 years. Comparing the previous PSQI score to that during the COVID-19 outbreak, we observed worsening sleep quality (5.45 ± 3.14 to 6.18 ± 3.03 points, p = 0.035). In parallel, there was an increase in the negative mood (p = 0.002). Accordingly, the decrease in sleep quality was substantially correlated with negative mood (p < 0.001). There were no differences in the ESS or SATED.Conclusions: The COVID-19 outbreak-associated events correlate with decreased sleep quality in association with an increase in negative mood. Considering the importance of sleep for a healthy life, and in particular for immune function, efforts should be made to improve awareness of this matter and to offer psychological assistance to affected individuals.

Background Noninvasive ventilation (NIV) is an effective form of treatment in obesity hypoventilation syndrome (OHS) with severe OSA. However, there is paucity of evidence in patients with OHS without severe OSA phenotype. Research Question Is NIV effective in OHS without severe OSA phenotype? Study Design and Methods In this multicenter, open-label parallel group clinical trial performed at 16 sites in Spain, we randomly assigned 98 stable ambulatory patients with untreated OHS and apnea-hypopnea index Results Forty-nine patients in the NIV group and 49 in the control group were randomized, and 48 patients in each group were analyzed. During a median follow-up of 4.98 years (interquartile range, 2.98-6.62), the mean hospitalization days per year ± SD was 2.60 ± 5.31 in the control group and 2.71 ± 4.52 in the NIV group (adjusted rate ratio, 1.07; 95% CI, 0.44-2.59; P = .882). NIV therapy, in contrast with the control group, produced significant longitudinal improvement in Paco2, pH, bicarbonate, quality of life (Medical Outcome Survey Short Form 36 physical component), and daytime sleepiness. Moreover, per-protocol analysis showed a statistically significant difference for the time until the first ED visit favoring NIV. In the subgroup with high NIV adherence, the time until the first event of hospital admission, ED visit, and mortality was longer than in the low adherence subgroup. Adverse events were similar between arms. Interpretation In stable ambulatory patients with OHS without severe OSA, NIV and lifestyle modification had similar long-term hospitalization days per year. A more intensive program aimed at improving NIV adherence may lead to better outcomes. Larger studies are necessary to better determine the long-term benefit of NIV in this subgroup of OHS. Trial Registry ClinicalTrials.gov; No.: NCT01405976; URL: www.clinicaltrials.gov

Rationale: Sleep constitutes a fundamental pillar of health in individuals and is an indicator of the health of a population.Objectives: Aiming to develop an easy-to-use tool to measure sleep healt...

Spanish Sleep Network., [Rationale] Obesity hypoventilation syndrome (OHS) has been associated with cardiac dysfunction. However, randomized trials assessing the impact of long-term noninvasive ventilation (NIV) or continuous positive airway pressure (CPAP) on cardiac structure and function assessed by echocardiography are lacking. Rationale: Obesity hypoventilation syndrome (OHS) has been associated with cardiac dysfunction. However, randomized trials assessing the impact of long-term noninvasive ventilation (NIV) or continuous positive airway pressure (CPAP) on cardiac structure and function assessed by echocardiography are lacking., [Objectives] In a prespecified secondary analysis of the largest multicenter randomized controlled trial of OHS (Pickwick Project; N = 221 patients with OHS and coexistent severe obstructive sleep apnea), we compared the effectiveness of three years of NIV and CPAP on structural and functional echocardiographic changes., [Methods] At baseline and annually during three sequential years, patients underwent transthoracic two-dimensional and Doppler echocardiography. Echocardiographers at each site were blinded to the treatment allocation. Statistical analysis was performed using a linear mixed-effects model with a treatment group and repeated measures interaction to determine the differential effect between CPAP and NIV. Measurements and Main Results: A total of 196 patients were analyzed: 102 were treated with CPAP and 94 were treated with NIV. Systolic pulmonary artery pressure decreased from 40.5 ± 1.47 mm Hg at baseline to 35.3 ± 1.33 mm Hg at three years with CPAP, and from 41.5 ± 1.56 mm Hg to 35.5 ± 1.42 with NIV (P, [Conclusions] In patients with OHS who have concomitant severe obstructive sleep apnea, long-term treatment with NIV and CPAP led to similar degrees of improvement in pulmonary hypertension and left ventricular diastolic dysfunction.

Background: Obstructive sleep apnea (OSA) is a common disease caused by repeated episodes of collapse of the upper airway during sleep and is associated with the development of cardiovascular disease (CVD). However, there is high heterogeneity in the impact of OSA on patients. Until now, the profile of OSA patients at risk of developing CVD has not been defined, including the measurable variables that could be used to predict the CVD risk of a patient with OSA. Objective: The aim of this study was to identify the microRNA (mi­RNA) profile associated with CVD in patients with OSA. Method: This is an observational, cross-sectional study that included 132 male patients. Three groups were defined as OSA patients, OSA patients with hypertension, and OSA patients who developed a major cardiovascular event. Polysomnography and ambulatory blood pressure measurements were performed. The expression profiling of 188 miRNAs in plasma was performed in 21 subjects (matched by BMI and age) by the TaqMan low density array (TLDA). miRNAs differentially expressed in the different subgroups of patients and miRNAs that correlated with the cardiovascular risk SCORE were selected for validation by RT-qPCR in the 111 remaining patients. Results: From the TLDA analysis, 7 miRNAs were selected for validation. Differential expression was not confirmed in any of the miRNAs. miR-143 was associated with nocturnal systolic blood pressure. miR-107 correlated with 24-h blood pressure parameters and with nocturnal hypertension. miR-486 was associated with the cardiovascular risk SCORE. Conclusions: The circulating profile of miRNAs does not seem to be different in any of the subgroups of patients with OSA and different cardiovascular risk factors. Nevertheless, miR-107 and miR-143 are associated with specific blood pressure parameters in patients with OSA and miR-486 is associated with the cardiovascular risk SCORE.

Introduction: Obstructive sleep apnea (OSA) is a chronic, heterogeneous and multicomponent disorder with associated cardiovascular and metabolic alterations. Despite being the most common sleep-disordered breathing, it remains a significantly undiagnosed condition. Objective: We examined the plasma metabolome and lipidome of patients with suspected OSA, aiming to identify potential diagnosis biomarkers and to provide insights into the pathophysiological mechanisms underlying the disease. Additionally, we evaluated the impact of continuous positive airway pressure (CPAP) treatment on the circulating metabolomic and lipidomic profile. Material and methods: Observational-prospective-longitudinal study including 206 consecutive subjects referred to the sleep unit. OSA was defined as an apnea-hypopnoea index ≥ 15 events/h after polysomnography (PSG). Patients treated with CPAP were followed-up for 6 months. Untargeted plasma metabolomic and lipidomic profiling was performed using liquid chromatography coulpled to massspectrometry. Results: A plasma profile composed of 33 metabolites (mainly glycerophospholipids and bile acids) was identified in OSA vs. non-OSA patients. This profile correlated with specific PSG measures of OSA severity related to sleep fragmentation and hypoxemia. Machine learning analyses disclosed a 4-metabolites-signature that provided an accuracy (95% CI) of 0.98 (0.95-0.99) for OSA detection. CPAP treatment was associated with changes in 5 plasma metabolites previously altered by OSA. Conclusions: This analysis of the circulating metabolome and lipidome reveals a molecular fingerprint of OSA, which was modulated after effective CPAP treatment. Our results suggest blood-based biomarker candidates with potential application in the personalized management of OSA and suggest the activation of adaptive mechanisms in response to OSA-derived hypoxia. We thank the individuals who participated in this trial, their families, and the clinical and research team in the sleep department. LP is the recipient of a predoctoral fellowship from the Ministry of Universities of Spain (FPU19/01555). MJ is a “Serra Húnter” Fellow. MSdT has received financial support from the “Ramon ´ y Cajal” grant (RYC2019- 027831-I) from the “Ministerio de Ciencia e Innovacion ´ - Agencia Estatal de Investigacion´ ” cofunded by the European Social Fund (ESF) / “Investing in your future”

Aims Atrial fibrillation (AF) has been associated with intracellular calcium disturbances in human atrial myocytes, but little is known about the potential influence of sex and we here aimed to address this issue. Methods and results Alterations in calcium regulatory mechanisms were assessed in human atrial myocytes from patients without AF or with long-standing persistent or permanent AF. Patch-clamp measurements revealed that L-type calcium current (ICa) density was significantly smaller in males with than without AF (¿1.15¿±¿0.37 vs. ¿2.06¿±¿0.29 pA/pF) but not in females with AF (¿1.88¿±¿0.40 vs. ¿2.21¿±¿0.0.30 pA/pF). In contrast, transient inward currents (ITi) were more frequent in females with than without AF (1.92¿±¿0.36 vs. 1.10¿±¿0.19 events/min) but not in males with AF. Moreover, confocal calcium imaging showed that females with AF had more calcium spark sites than those without AF (9.8¿±¿1.8 vs. 2.2¿±¿1.9 sites/µm2) and sparks were wider (3.0¿±¿0.3 vs. 2.2¿±¿0.3 µm) and lasted longer (79¿±¿6 vs. 55¿±¿8 ms), favouring their fusion into calcium waves that triggers ITIs and afterdepolarizations. This was linked to higher ryanodine receptor phosphorylation at s2808 in women with AF, and inhibition of adenosine A2A or beta-adrenergic receptors that modulate s2808 phosphorylation was able to reduce the higher incidence of ITI in women with AF. Conclusion Perturbations of the calcium homoeostasis in AF is sex-dependent, concurring with increased spontaneous SR calcium release-induced electrical activity in women but not in men, and with diminished ICa density in men only., This work was supported by grants from The Spanish Ministry of Science Innovation and Universities [SAF2017-88019-C3-1-R MICIU /AEI/ FEDER /UE] to L.H.-M. [SAF2017-88019-C3-2-R MICIU /AEI/ FEDER /UE] to R.B. and [ SAF2017-87349-R MICIU /AEI/ FEDER /UE] to F.C.; and from the Spanish Ministry of Health and Consume, ISCIII, CIBERCV [CB16/11/00276] and Fondo Europeo de Desarrollo Regional (FEDER) to J.C., Fundació Marato TV3 [20152030/31] to L.H.-M./F.C. Also supported by ISC III [PIE14/00034] and IWT [SBO-140028] to F.C., a PhD grant [FPU/01250] to S.C., a PERIS grant from Generalitat de Catalunya to A.L. and [SGR2017-1769] to L.H.-M.

Background: Continuous positive airway pressure (CPAP) is an effective treatment for obstructive sleep apnea (OSA), but treatment compliance is often unsatisfactory. Objective: The aim of this study was to assess the effectiveness and cost-effectiveness of an intelligent monitoring system for improving CPAP compliance. Methods: This is a prospective, open label, parallel, randomized controlled trial including 60 newly diagnosed patients with OSA requiring CPAP (Apnea–Hypopnea Index [AHI] >15) from Lleida, Spain. Participants were randomized (1:1) to standard management or the MiSAOS intelligent monitoring system, involving (1) early compliance detection, thus providing measures of patient’s CPAP compliance from the very first days of usage; (2) machine learning–based prediction of midterm future CPAP compliance; and (3) rule-based recommendations for the patient (app) and care team. Clinical and anthropometric variables, daytime sleepiness, and quality of life were recorded at baseline and after 6 months, together with patient’s compliance, satisfaction, and health care costs. Results: Randomized patients had a mean age of 57 (SD 11) years, mean AHI of 50 (SD 27), and 13% (8/60) were women. Patients in the intervention arm had a mean (95% CI) of 1.14 (0.04-2.23) hours/day higher adjusted CPAP compliance than controls (P=.047). Patients’ satisfaction was excellent in both arms, and up to 88% (15/17) of intervention patients reported willingness to keep using the MiSAOS app in the future. No significant differences were found in costs (control: mean €90.2 (SD 53.14) (US $105.76 [SD 62.31]); intervention: mean €96.2 (SD 62.13) (US $112.70 [SD 72.85]); P=.70; €1=US $1.17 was considered throughout). Overall costs combined with results on compliance demonstrated cost-effectiveness in a bootstrap-based simulation analysis. Conclusions: A machine learning–based intelligent monitoring system increased daily compliance, reported excellent patient satisfaction similar to that reported in usual care, and did not incur in a substantial increase in costs, thus proving cost-effectiveness. This study supports the implementation of intelligent eHealth frameworks for the management of patients with CPAP-treated OSA and confirms the value of patients’ empowerment in the management of chronic diseases. This work is part of the myOSA project (RTC-2014-3138-1), funded by the Spanish Ministry of Economy, Industry and Competitiveness (Ministerio de Economía, Industria y Competitividad) and Agencia Estatal de Investigación, under the framework “Retos-Colaboración”, State Scientific and Technical Research and Innovation Plan 2013-2016. The work was cofunded by the European Regional Development Fund (ERDF), “A way to make Europe”. JdB acknowledges receiving financial support from the Catalan Health Department (Pla Estratègic de Recerca i Innovació en Salut [PERIS] 2016: SLT002/16/00364) and Instituto de Salud Carlos III (ISCIII; Miguel Servet 2019: CP19/00108), co-funded by the European Social Fund (ESF), “Investing in your future”. Funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Background: Recent studies have suggested that the population with a first event of acute coronary syndrome (ACS) is susceptible to the deleterious effects of obstructive sleep apnea (OSA)(Zapater, A. et al. Am J Respir Crit Care Med 2020; 202:1698-1706). Aim and objectives: We explore respiratory polygraphy parameters that are associated with an increased risk of recurrence cardiovascular events in this subgroup of patients with ACS. Methods: Post-hoc analysis of the ISAACC study, including 723 patients admitted for a first ACS (NCT01335087). A principal component analysis (PCA) was performed using six respiratory polygraphy parameters: apnea-hypopnea index (AHI), oxygen desaturation index, mean and minimum oxygen saturation (SaO2), average duration of events and percentage of time with SaO2 Results: PCA showed that two respiratory polygraphy patterns accounted for 70% of variance. A first pattern was mainly characterized by low mean SaO2 and events with severe desaturation (High Time with SaO2 Conclusions: A sleep apnea pattern, mainly characterized by high mean SaO2 and longer duration events with severe desaturation, is associated with a high risk of recurrent cardiovascular events in patients who have suffered a first ACS.

Background Alterations in circadian rhythms are present in the presymptomatic stage of Alzheimer’s disease (AD), possibly contributing to its pathogenesis. However, it is unknown whether such alterations are associated with worse outcomes once individuals are diagnosed with symptomatic disease. We aimed to evaluate the association between the circadian rest-activity pattern and AD-related features in patients with mild-moderate AD. Methods We assessed the circadian rest-activity pattern of consecutive patients with mild-moderate AD through actigraphy for 14 days. Cerebrospinal fluid was obtained to determine the levels of important pathological markers including amyloid-beta protein (Aβ42), phosphorylated tau (P-tau), total tau (T-tau), and neurofilament light (NF-L). Neuropsychological evaluation was conducted at the beginning of the study and after 12 months of follow-up. Linear regression models were performed considering the global population and Aβ42+ patients only. Results The cohort included 100 patients with mild-moderate AD. The median age [p25;p75] was 76.0 [73.0;80.0] years and 63.0% were female. Older age (effect size [SE] of 0.324 [0.096]; p = 0.001) and male sex (0.780 [0.193]; p = 0.001) were associated with increased fragmentation and decreased synchronization of the rhythm, respectively. After adjusting for age, sex, and season of the year, increased levels of T-tau (effect size [95% CI] of 0.343 [0.139 to 0.547]; p = 0.001) and NF-L (0.444 [0.212 to 0.676]; p = 0.001) were associated with a higher amplitude of the rest-activity rhythm. Increased fragmentation of the rhythm at baseline was associated with greater cognitive decline after one year of follow-up independent of age, sex, T-tau/Aβ42 ratio, educational level, and season of the year (− 0.715 [− 1.272 to − 0.157]; p = 0.013). Similar findings were obtained considering only the Aβ42+ patients. Conclusions Our results suggest a potential role of the circadian rest-activity pattern in predicting the cognitive decline of patients with mild-moderate AD. Further studies are warranted to confirm these findings and to elucidate whether there is causality among the observed associations.

Rationale: Obstructive sleep apnea (OSA) is associated with poor blood pressure (BP) control and resistant hypertension (RH). Nevertheless, studies assessing its prevalence, characteristics, and association with BP control in patients with RH are limited. Objectives: The aim of this multicenter study was to assess the prevalence of OSA in a large cohort of subjects with RH and to evaluate the association of OSA with BP control. Methods: We recruited consecutive subjects with RH from three countries. A formal sleep test and blood pressure measurements, including 24-hour ambulatory blood pressure monitoring, were performed in all participants. Results: In total, 284 subjects with RH were included in the final analysis. Of these, 83.5% (95% confidence interval [CI], 78.7-87.3%) had OSA (apnea-hypopnea index >= 5 events/h); 31.7% (95% CI 26.5-37.3%) had mild OSA, 25.7% (95% CI, 21-31.1%) had moderate OSA, and 26.1% (95% CI, 21.3-31.5%) had severe OSA. Patients with severe OSA had higher BP values than subjects with mild to moderate or no OSA. A greater effect was observed on the average nighttime BP, with an adjusted effect of 5.72 mm Hg (95% CI, 1.08-10.35 mm Hg) in severe OSA compared with participants without OSA. A dose-response association between the severity of OSA and BP values was observed. The prevalence of severe OSA was slightly higher in uncontrolled participants (adjusted odds ratio, 1.69; 95% CI, 0.97-2.99) but was not statistically significant. Conclusions: The present study confirms the high prevalence of OSA in participants with RH. Furthermore, it shows a dose-response association between OSA severity and BP measurements, especially in the nighttime.

Evaluation of microRNAs (miRNAs) could allow characterization of the obstructive sleep apnea (OSA) and help diagnose it more accurately. We aimed to examine circulating miRNA profiles to establish the differences between non-OSA and OSA patients. Additionally, we aimed to analyse the effect of continuous positive airway pressure (CPAP) treatment on the miRNA profile. This observational, longitudinal study included 230 subjects referred to the Sleep Unit due to suspected OSA. Expression profiling of 188 miRNAs in plasma was performed in 27 subjects by TaqMan-Low-Density-Array. OSA-related miRNAs were selected for validation by RT-qPCR in 203 patients. Prediction models were built to discriminate between non-OSA and OSA: 1) NoSAS-score, 2) differentially expressed miRNAs, and 3) combination of NoSAS-score plus miRNAs. The differentially expressed miRNAs were measured after 6 months of follow-up. From the 14 miRNAs selected for validation, 6 were confirmed to be differentially expressed. The areas under the curve were 0.73 for the NoSAS-score, 0.81 for the miRNAs and 0.86 for the combination. After 6 months of CPAP treatment, miRNA levels in the OSA group seem to approximate to non-OSA levels. A cluster of miRNAs was identified to differentiate between non-OSA and OSA patients. CPAP treatment was associated with changes in the circulating miRNA profile. The founding sources have no role in the writing, data collection, analysis or interpretation of the study. The project is supported by PI 14/01266 and PI 18/00449 from the Instituto de Salud Carlos III (ISCIII), Fondo Europeo de Desarrollo Regional (FEDER), Sociedad Española de Neumología y Cirugía Torácica (SEPAR) and Societat Catalana de Pneumologia (SOCAP). The work is supported by IRBLleida Biobank (B.0000682) and PLATAFORMA BIOBANCOS PT17/0015/0027”. F.S.-M. is the recipient of a predoctoral fellowship from “AGAUR-University of Lleida” and Convocatòria d’Ajuts 2018 de Promoció a la Recerca en Salut

Background A close relationship between obstructive sleep apnoea (OSA) and Alzheimer's disease (AD) has been described in recent years. OSA is a risk factor for AD, but the diagnosis and clinical characteristics of OSA in patients with AD is not well understood. This study evaluated the clinical utility of two screening questionnaires, the STOP-Bang questionnaire (SBQ) and the Berlin questionnaire (BQ), to identify which patients with mild AD are at higher risk of having OSA and to determine the clinical predictors of OSA in this population. Methods In this study, 91 consecutive outpatients with mild AD were prospectively evaluated with the SBQ and the BQ. All patients underwent level 1 in-laboratory polysomnography. The predictive performance of the questionnaires were calculated for different apnoea-hypopnoea index (AHI) cut-offs. Results The median age of the patients was 76.0 (73.0; 80.0) years, and 58 (63.7%) were female. Of those, 81 patients (89.02%) were found to have OSA defined by an AHI > 5 events/h. Comparing the predictive performances of the SBQ and the BQ, the SBQ was found to have a higher diagnostic sensitivity (85% vs 4%), a lower specificity (35% vs. 96%), a higher positive predictive value (PPV) (44% vs 33%) and negative predictive value (NPV) (80% vs 65%) for detecting severe OSA at an AHI cut-off of 30 events/h. None of the items alone in the two questionnaires predicted the risk of OSA. A modified version of the SBQ, with new cut-off points for several variables according to the characteristics of AD patients, showed a slightly greater AUC than the standard SBQ (AUC 0.61 vs 0.72). Conclusion There is a high prevalence of OSA among patients with mild AD. The SBQ and the BQ are not good screening tools for detecting OSA in patients with AD. A modified version of SBQ could increase the detection of these patients.

Rationale: Evidence suggests that the physiopathologic consequences of obstructive sleep apnea (OSA) resemble those induced by aging. Some studies report that the deleterious effects associated wit...

[Rationale] Obesity hypoventilation syndrome (OHS) with concomitant severe obstructive sleep apnea (OSA) is treated with CPAP or noninvasive ventilation (NIV) during sleep. NIV is costlier, but may be advantageous because it provides ventilatory support. However, there are no long-term trials comparing these treatment modalities based on OHS severity., [Objective] To determine if CPAP have similar effectiveness when compared to NIV according to OHS severity subgroups., [Methods] Post hoc analysis of the Pickwick randomized clinical trial in which 215 ambulatory patients with untreated OHS and concomitant severe OSA, defined as apnoea-hypopnea index (AHI) ≥ 30 events/h, were allocated to NIV or CPAP. In the present analysis, the Pickwick cohort was divided in severity subgroups based on the degree of baseline daytime hypercapnia (PaCO2 of 45–49.9 or ≥50 mmHg). Repeated measures of PaCO2 and PaO2 during the subsequent 3 years were compared between CPAP and NIV in the two severity subgroups. Statistical analysis was performed using linear mixed-effects model., [Results] 204 patients, 97 in the NIV group and 107 in the CPAP group were analyzed. The longitudinal improvements of PaCO2 and PaO2 were similar between CPAP and NIV based on the PaCO2 severity subgroups., [Conclusion] In ambulatory patients with OHS and concomitant severe OSA who were treated with NIV or CPAP, long-term NIV therapy was similar to CPAP in improving awake hypercapnia, regardless of the severity of baseline hypercapnia. Therefore, in this patient population, the decision to prescribe CPAP or NIV cannot be solely based on the presenting level of PaCO2., [Introducción] El síndrome de hipoventilación-obesidad (SHO) con apnea obstructiva del sueño (AOS) grave concomitante se trata con CPAPo ventilación no invasiva (VNI) durante el sueño. La VNI es más costosa, pero puede ser beneficiosa porque proporciona soporte ventilatorio; sin embargo, no existen estudios a largo plazo que comparen estas modalidades de tratamiento basándose en la gravedad del SHO., [Objetivo] Determinar si la CPAP tiene una eficacia similar a la VNI según los subgrupos de gravedad del SHO., [Métodos] Análisis a posteriori del ensayo clínico aleatorizado Pickwick en el que 215 pacientes ambulatorios con SHO sin tratar y con AOS grave concomitante (definida como un índice de apnea-hipopnea [IAH] ≥ 30 episodios/hora) recibieron tratamiento con VNI o CPAP. En el presente análisis, la cohorte Pickwick se dividió en subgrupos según la gravedad basándose en el grado de hipercapnia diurna al inicio del estudio (PaCO2 de 45-49.9 mm Hg o ≥ 50 mm Hg). Se compararon las mediciones periódicas de PaCO2 y PaO2 durante los 3 años siguientes entre la CPAP y la VNI entre los dos subgrupos de gravedad. Se realizó un análisis estadístico utilizando un modelo lineal mixto., [Resultados] Se analizaron 204 pacientes, 97 en el grupo de VNI y 107 en el grupo de CPAP. Las mejoras lineales de PaCO2 y PaO2 fueron similares entre la CPAP y la NIV según los subgrupos de gravedad en función de la PaCO2., [Conclusión] En los pacientes ambulatorios con SHO y AOS grave concomitante a los que se trató con VNI o CPAP, el tratamiento a largo plazo con VNI resultó similar a la CPAP, en cuanto a la mejora de la hipercapnia en vigilia, independientemente de la gravedad de la hipercapnia de inicio. Por lo tanto, en esta población de pacientes la decisión de prescribir CPAP o VNI no puede basarse exclusivamente en el nivel de partida de PaCO2., Instituto de Salud Carlos III (Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo, Madrid, Spain) PI050402, Spanish Respiratory Foundation 2005 (FEPAR) and Air Liquide Spain.

The COVID-19 emergency pandemic resulting from infection with SARS-CoV-2 represents a major threat to public health worldwide. There is an urgent clinical demand for easily accessible tools to address weaknesses and gaps in the management of COVID-19 patients. In this context, transcriptomic profiling of liquid biopsies, especially microRNAs (miRNAs), has recently emerged as a robust source of potential clinical indicators for medical decision-making. Nevertheless, the analysis of the circulating miRNA signature and its translation to clinical practice requires strict control of a wide array of methodological details. In this review, we indicate the main methodological aspects that should be addressed when evaluating the circulating miRNA profiles in COVID-19 patients, from preanalytical and analytical variables to the experimental design, impact of confounding, analysis of the data and interpretation of the findings, among others. Additionally, we provide practice points to ensure the rigour and reproducibility of miRNA-based biomarker investigations of this condition. Abbreviations: ACE: angiotensin-converting enzyme; ARDS: acute respiratory distress syndrome; COVID-19: coronavirus disease 2019; ERDN: early Detection Research Network; LMWH: low molecular weight heparin; miRNA: microRNA; ncRNA: noncoding RNA; SARS-CoV-2: severe acute respiratory syndrome coronavirus-2; SOP: standard operating procedure.

Study Objectives Chronic intermittent hypoxia (CIH) is a major determinant in obstructive sleep apnea cardiovascular morbidity and this effect is influenced by age. The objective of the present study was to assess the differential molecular mechanisms at gene-level expression involved in the cardiovascular remodeling induced by CIH according to chronological age. Methods Two- and 18-month-old mice (N = 8 each) were subjected to CIH or normoxia for 8 weeks. Total messenger RNA (mRNA) was extracted from left ventricle myocardium and aortic arch, and gene expression of 46 intermediaries of aging, oxidative stress, and inflammation was measured by quantitative real-time polymerase chain reaction. Results Cardiac gene expression of Nrf2 (2.05-fold increase, p < 0.001), Sod2 (1.9-fold increase, p = 0.035), Igf1r (1.4-fold increase, p = 0.028), Mtor (1.8-fold increase, p = 0.06), Foxo3 (1.5-fold increase, p = 0.020), Sirt4, Sirt6, and Sirt7 (1.3-fold increase, p = 0.012; 1.1-fold change, p = 0.031; 1.3-fold change, p = 0.029) was increased after CIH in young mice, but not in old mice. In aortic tissue, endothelial isoform of nitric oxide synthase was reduced in young mice (p < 0.001), Nrf2 was reduced in 80% (p < 0.001) in young mice and 45% (p = 0.07) in old mice, as its downstream antioxidant target Sod2 (82% reduced, p < 0.001). IL33 Conclusions CIH effect in gene expression is organ-dependent, and is modulated by age. CIH increased transcriptional expression of genes involved in cardioprotection and cell survival in young, but not in old mice. In aortic tissue, CIH reduced gene expression related to an antioxidant response in both young and old mice, suggesting vascular oxidative stress and a proaging process.

The objective was to describe the clinical characteristics and outcomes of hospitalized COVID-19 patients during the two different epidemic periods. Prospective, observational, cohort study of hospitalized COVID-19. A total of 421 consecutive patients were included, 188 during the first period (March-May 2020) and 233 in the second wave (July-December 2020). Clinical, epidemiological, prognostic and therapeutic data were compared. Patients of the first outbreak were older and more comorbid, presented worse PaO2/FiO2 ratio and an increased creatinine and D-dimer levels at hospital admission. The hospital stay was shorter (14.5[8;29] vs 8[6;14] days, p

STUDY OBJECTIVES: The majority of studies investigating the association between sleep and Alzheimer's disease (AD) biomarkers have been performed in healthy participants. Our objective was to investigate the association between sleep and several biomarkers that reflect distinct aspects of AD physiopathology. METHODS: The cohort included 104 individuals with mild-moderate AD. The participants were submitted to one-night polysomnography, and cerebrospinal fluid was collected in the following morning to measure the selected biomarkers associated with amyloid deposition, tau pathology, neurodegeneration, axonal damage, synaptic integrity, neuroinflammation, and oxidative damage. RESULTS: There was a positive correlation between neurofilament light (NF-L) and the time spent in stage 1 of non-rapid eyes movement (NREM) (N1) sleep and a negative correlation between this marker and the time spent in stage 3 of NREM (N3) sleep. Accordingly, we observed that deep sleep was associated with lower levels of NF-L, whereas light sleep increased the probability of having higher levels of this marker. Furthermore, chitinase-3-like-1 (YKL-40) was negatively correlated with sleep efficiency, the time spent in stage 2 of NREM (N2) sleep, and the time spent in N3 sleep. Conversely, there was a positive correlation between N3 sleep and the oxidative protein damage markers N-ε-(carboxyethyl)lysine and N-ε-(malondialdehyde)lysine. CONCLUSIONS: There were significant correlations between sleep parameters and AD biomarkers related to axonal damage and neuroinflammation, such as NF-L and YKL-40. A lack of deep sleep was associated with higher levels of NF-L. This highlights a potential role for NF-L as a biomarker of sleep disruption in patients with mild-moderate AD in addition to its role in predicting neurodegeneration and cognitive decline. This study was supported by the Generalitat of Catalonia, Department of Health (PERIS 2019 SLT008/18/00050) and “Fundació La Marató TV3” (464/C/2014) to G.P.R.; by the Spanish Ministry of Economy and Competitiveness, Institute of Health Carlos III (grant number P114/00328), the Spanish Ministry of Science, Innovation and University (RTI 2018–099) of Catalonia, and Agency for Management of University and Research grants (2017 SGR696) to R.P. This study has been co-financed by FEDER funds from the European Union (“A way to build Europe”). IRBLleida is a CERCA Programme/Generalitat of Catalonia. F.D. was supported by the Agency for Management of University and Research grants (FI_B100153).

Background In anti-phospholipase A2 receptor (PLA2R) membranous nephropathy (MN) there is controversy whether spontaneous remission (SR) can be predicted using a single titre or by assessing the dynamic changes in anti-PLA2R antibody (ab) titres. The study objective was to identify the optimal dynamics of anti-PLA2Rab titres to predict SR in MN. Methods A total of 127 nephrotic patients with anti-PLA2R-MN were prospectively followed up for 6 months under conservative treatment. Anti-PLA2Rabs and proteinuria were assessed at diagnosis and monthly thereafter. The primary endpoint (PEP) was a reduction of proteinuria ≥50% at 6 months. Logistic models with baseline and evolutive anti-PLA2Rab titres were developed to predict the PEP. Results A total of 28 patients (22%) reached the PEP. These patients were more frequently female and had significantly lower baseline proteinuria and anti-PLA2Rab titres. An anti-PLA2R titre ≤97.5 RU/mL at diagnosis had a sensitivity of 71% and a specificity of 81% to predict the PEP. The model including baseline anti-PLA2Rabs and a reduction ≥15% at 3 months predicted the PEP with a sensitivity of 93% and a specificity of 80%, with an area under the curve that was significantly greater than that obtained with relative changes of proteinuria in the same period of time {odds ratio [OR] 0.95 [95% confidence interval (CI) 0.91–0.98 versus OR 0.79 [95% CI 0.70–0.88], respectively; P = 0.0013}. Conclusions Combining the baseline anti-PLA2Rab titres with their relative changes at 3 months after diagnosis gives the earliest prediction for achieving a reduction of urinary protein excretion ≥50% at 6 months in MN, thereby shortening the observation period currently recommended to make individualized decisions to start immunosuppressive therapy., Graphical Abstract Graphical Abstract

We aimed to examine the circulating microRNA (miRNA) profile of hospitalized COVID-19 patients and evaluate its potential as a source of biomarkers for the management of the disease. This was an observational and multicenter study that included 84 patients with a positive nasopharyngeal swab Polymerase chain reaction (PCR) test for SARS-CoV-2 recruited during the first pandemic wave in Spain (March-June 2020). Patients were stratified according to disease severity: hospitalized patients admitted to the clinical wards without requiring critical care and patients admitted to the intensive care unit (ICU). An additional study was completed including ICU nonsurvivors and survivors. Plasma miRNA profiling was performed using reverse transcription polymerase quantitative chain reaction (RT-qPCR). Predictive models were constructed using least absolute shrinkage and selection operator (LASSO) regression. Ten circulating miRNAs were dysregulated in ICU patients compared to ward patients. LASSO analysis identified a signature of three miRNAs (miR-148a-3p, miR-451a and miR-486-5p) that distinguishes between ICU and ward patients [AUC (95% CI) = 0.89 (0.81-0.97)]. Among critically ill patients, six miRNAs were downregulated between nonsurvivors and survivors. A signature based on two miRNAs (miR-192-5p and miR-323a-3p) differentiated ICU nonsurvivors from survivors [AUC (95% CI) = 0.80 (0.64–0.96)]. The discriminatory potential of the signature was higher than that observed for laboratory parameters such as leukocyte counts, C-reactive protein (CRP) or D-dimer [maximum AUC (95% CI) for these variables = 0.73 (0.55–0.92)]. miRNA levels were correlated with the duration of ICU stay. Specific circulating miRNA profiles are associated with the severity of COVID-19. Plasma miRNA signatures emerge as a novel tool to assist in the early prediction of vital status deterioration among ICU patients. Supported by ISCIII (CIBERESUCICOVID, COV20/00110), co-funded by ERDF, “Una manera de hacer Europa”. DdGC acknowledges receiving financial support from Instituto de Salud Carlos III (ISCIII), Miguel Servet 2020 (CP20/00041), co-funded by the European Social Fund (ESF), “Investing in your future”. LP is the recipient of a predoctoral fellowship from the Ministry of Universities of Spain (FPU19/03526). This work partially supported by IRBLleida Biobank (B.0000682) and “Plataforma Biobancos PT17/0015/0027/”. Peer Reviewed "Article signat per 33 autors/es: David de Gonzalo-Calvo, Iván D. Benítez, Lucía Pinilla, Amara Carratalá, Anna Moncusí-Moix, Clara Gort-Paniello, Marta Molinero, Jessica González, Gerard Torres, María Bernal, Silvia Pico, Raquel Almansa, Noelia Jorge, Alicia Ortega, Elena Bustamante-Munguira, José Manuel Gómez, Milagros González-Rivera, Dariela Micheloud, Pablo Ryan, Amalia Martinez, Luis Tamayo, César Aldecoa, Ricard Ferrer, Adrián Ceccato, Laia Fernández-Barat, Ana Motos, Jordi Riera, Rosario Menéndez, Dario Garcia-Gasulla, Oscar Peñuelas, Antoni Torres, Jesús F. Bermejo-Martin, Ferran Barbé on behalf of the Ciberesucicovid Project (Cov20/00110, Isciii)"

Study Objectives To investigate the association between sleep and cognitive decline of patients with mild-moderate Alzheimer’s disease. Methods Observational, prospective study, including consecutive patients diagnosed with mild-moderate Alzheimer’s disease. Cerebrospinal fluid was collected for amyloid-beta, total-tau, and phospho-tau levels determination. Also, overnight polysomnography was performed, followed by neuropsychological evaluations at baseline and after 12 months of follow-up. Principal component analysis revealed two profiles of patients in terms of sleep: one with a propensity to deepen the sleep (deep sleepers) and the other with a propensity to spend most of the time in the lighter sleep stage (light sleepers). Results The cohort included 125 patients with a median [IQR] of 75.0 [72.0;80.0] years. Deep and light sleepers did not present differences in relation to the cerebrospinal fluid pathological markers and to the cognitive function at the baseline. However, there was a significant difference of −1.51 (95% CI: −2.43 to −0.59) in the Mini-mental state examination after 12 months of follow-up. Accordingly, sleep depth and cognitive decline presented a dose–response relationship (p-for-trend = 0.02). Similar outcomes were observed in relation to the processing speed (Stroop words test, p-value = 0.016) and to the executive function (Verbal fluency test, p-value = 0.023). Conclusions Considering the increased cognitive decline presented by light sleepers, the sleep profile may have a predictive role in relation to the cognitive function of patients with mild-moderate Alzheimer’s disease. The modifiable nature of sleep sets this behavior as a possible useful intervention to prevent a marked cognitive decline. Clinical Trial Information Role of Hypoxia Ans Sleep Fragmentation in Alzheimer’s Disease. and Sleep Fragmentation. Completed. NCT02814045

Rationale: Noninvasive ventilation (NIV) is an effective treatment in obesity hypoventilation syndrome (OHS) with severe obstructive sleep apnoea (OSA) but there is paucity of evidence in OHS patients without severe OSA phenotype. Methods: In this multicentre (16 sites in Spain), open-label parallel group clinical trial, we randomly assigned 98 stable ambulatory patients with untreated OHS and apnoea-hypopnoea index Results:49 patients were randomised in each group and 48 patients were analysed in each one of them. During a median [IQR] follow-up of 4.98 [2.98; 6.62] years, mean (SD) hospitalization days/year was 2.60 (5.31) in the control group and 2.71 (4.52) in the NIV group [adjusted rate ratio (95% CI) 1.07 (0.44; 2.59) (p = 0.882)]. Cardiovascular events occurred in 11 (23%) participants in the control group and 10 (21%) in the NIV group (hazard ratio (95% CI) 0.96 (0.40;2.30), p=0.927). Similar results were observed in the per-protocol analysis [rate ratio (95% CI) 1.21 (0.43;3.41) (p=0.717)]. Death occurred in 9 (19%) participants in both arms (adjusted hazard ratio (95% CI) 1.07 (0.41;2.82), p=0.893). Similar results were found in the per-protocol analysis [rate ratio (95% CI) 1.38 (0.50;3.79) (p=0.529)]. Conclusion: In stable ambulatory patients with OHS without severe OSA, NIV and lifestyle modification had similar long-term hospitalization days-year. Larger studies are necessary to better determine the long-term benefit of NIV in this subgroup of OHS.

Rationale: Obesity hypoventilation syndrome (OHS) has been associated with cardiac dysfunction. However, randomized trials have assessing the impact of long-term noninvasive ventilation (NIV) or CPAP on cardiac structure and function assessed by echocardiography are lacking. Methods: In a pre-specified secondary analysis of the largest multicenter randomized controlled trial of OHS〔Pickwick project, n=221 patient with OHS and coexistent severe obstructive sleep apnea (OSA)〕, we compared the effectiveness of 3 years of NIV and CPAP on structural and functional echocardiographic changes. At baseline and annually during 3 sequential years patients underwent transthoracic two-dimensional and doppler echocardiography. Echocardiographers were blinded to the treatment allocation. Statistical analysis was performed using a linear mixed-effects model with a treatment group/repeated measures interaction to determine the differential effect between CPAP and NIV. Results:196 patients were analyzed, 102 treated with CPAP and 94 treated with NIV. Systolic pulmonary artery pressure decreased from 40.5±1.47 mmHg at baseline to 35.3±1.33 mmHg at 3 years with CPAP and from 41.5±1.56 mmHg to 35.5±1.42 with NIV (p Conclusion: In patients with OHS and concomitant severe OSA, long-term treatment with NIV and CPAP led to similar degrees of improvement in pulmonary hypertension and LVDF.

BACKGROUND AND PURPOSE: The COVID-19 epidemic is affecting almost all individuals worldwide, and patients with Alzheimer's disease (AD) and amnesic mild cognitive impairment (MCI) are particularly at risk due to their characteristics and age. We analysed the impact of the pandemic on these patients' neuropsychiatric symptoms and their quality of life after 5 weeks of lockdown in Spain. METHODS: A total of 40 patients with a diagnosis of MCI (n = 20) or mild AD (n = 20) from the Cognitive Stimulation Program of the Cognitive Disorders Unit were evaluated. All patients had undergone a previous evaluation during the month before the lockdown, and were re-evaluated after 5 weeks of lockdown. The Neuropsychiatric Inventory (NPI) and EuroQol-5D questionnaire (EQ-5D) were used to assess neuropsychiatric symptoms in patients and the quality of life in patients as well in caregivers. RESULTS: The mean (SD) total baseline NPI score was 33.75 (22.28), compared with 39.05 (27.96) after confinement (P = 0.028). The most frequently affected neuropsychiatric symptoms were apathy [4.15 (3.78) vs. 5.75 (4.02); P = 0.002] and anxiety [3.95 (3.73) vs. 5.30 (4.01); P = 0.006] in patients with MCI, and apathy [2.35 (2.70) vs. 3.75 (3.78); P = 0.036], agitation [0.45 (1.14) vs. 1.50 (2.66); P = 0.029] and aberrant motor behaviour [1.25 (2.86) vs. 2.00 (2.93); P = 0.044] in patients with AD. We did not observe differences in EQ-5D scores during the re-evaluation. The 30% of patients and 40% of caregivers reported a worsening of the patients' health status during confinement. CONCLUSIONS: The results of this study show the worsening of neuropsychiatric symptoms in patients with AD and MCI during 5 weeks of lockdown, with agitation, apathy and aberrant motor activity being the most affected symptoms.

The diagnosis of obstructive sleep apnea (OSA) in Alzheimer’s disease (AD) by polysomnography (PSG) is challenging due to the required collaboration of the patients. In addition, screening questionnaires have demonstrated limited usefulness with this subpopulation. Considering this, we investigated the circulating microRNA (miRNA) profile associated with OSA in AD patients. This study included a carefully selected cohort of females with mild-moderate AD confirmed by biological evaluation (n = 29). The individuals were submitted to one-night PSG to diagnose OSA (apnea-hypopnea index ≥ 15/h) and the blood was collected in the following morning. The plasma miRNA profile was evaluated using RT-qPCR. The patients had a mean (SD) age of 75.8 (5.99) years old with a body mass index of 28.6 (3.83) kg m−2. We observed a subset of 15 miRNAs differentially expressed between OSA and non-OSA patients, of which 10 were significantly correlated with the severity of OSA. Based on this, we built a prediction model that generated an AUC (95% CI) of 0.95 (0.88–1.00) including 5 of the differentially expressed miRNAs that correlated with OSA severity: miR-26a-5p, miR-30a-3p, miR-374a-5p, miR-377-3p, and miR-545-3p. Our preliminary results suggest a plasma miRNA signature associated with the presence of OSA in AD patients. Further studies will be necessary to validate these findings.

We evaluated the influence of untreated obstructive sleep apnoea (OSA) on the magnitude of cognitive decline and on several cognitive subdomains in patients with mild-to-moderate Alzheimer's disease.In this single-centre study, 144 patients were recruited prospectively from a cognitive impairment unit and underwent overnight polysomnography.The mean±sd change in the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) score at 12 months was 3.19±5.61 in the non-OSA group and 0.08±5.62 in the OSA group, with an intergroup difference of −3.36 (95% CI 0.19–0.16; p=0.002). We did not observe a significant difference in any cognitive subdomains at 12 months. Regarding Mini-Mental State Examination scores at 36 months, the mean change was 1.69 (95% CI −1.26–4.64; p=0.445). No significant differences were found among different OSA severity groups.We observed that ADAS-cog scores were better in the OSA group than in the non-OSA group by a statistically but not clinically significant margin. We did not find differences in the different cognitive subdomains after 1 year or in global cognition after 3 years of follow-up.

Background. MicroRNAs (miRNAs) are noncoding RNAs that are highly relevant as disease biomarkers. Several studies that explored the role of miRNAs in Alzheimer’s disease (AD) demonstrated their usefulness in clinical identification. Nevertheless, miRNAs that may act as endogenous controls (ECs) have not yet been established. The identification of ECs would contribute to the standardization of these biomarkers in AD. The objective of the study was to identify miRNAs that can be used as ECs in AD. Methods. We evaluated 145 patients divided into two different cohorts. One was a discovery cohort of 19 women diagnosed with mild to moderate AD (Mini-Mental State Examination (MMSE) score ≥ 20) and with confirmed pathologic levels of Aβ42 in CSF. The stability assessment cohort consisted of 126 individuals: 24 subjects without AD or any kind of dementia and negative for all core CSF biomarkers of AD, 25 subjects with MCI and negative for CSF biomarkers (MCI −), 22 subjects with MCI and positive for CSF biomarkers (MCI +), and 55 subjects with AD and positive for CSF biomarkers. In the discovery cohort, a profile of 384 miRNAs was determined in the plasma by TaqMan low-density array. The best EC candidates were identified by mean-centering and concordance correlation restricted normalization methods. The stability of the EC candidates was assessed using the GeNorm, BestKeeper, and NormFinder algorithms. Results. Nine miRNAs (hsa-miR-324-5p, hsa-miR-22-5p, hsa-miR-103a-2-5p, hsa-miR-362-5p, hsa-miR-425-3p, hsa-miR-423-5p, hsa-let-7i-3p, hsa-miR-532-5p, and hsa-miR-1301-3p) were identified as EC candidates in the discovery cohort. The validation results indicated that hsa-miR-103a-2-5p was the best EC, followed by hsa-miR-22-5p, hsa-miR-1301-3p, and hsa-miR-425-3p, which had similar stability values in all three algorithms. Conclusions. We identified a profile of four miRNAs as potential plasma ECs to be used for normalization of miRNA expression data in studies of subjects with cognitive impairment. Generalitat of Catalonia, Department of Health (PERIS 2019 SLT008/18/00050), and “Fundació La Marató TV3” (464/C/2014) to GPR. This study was cofinanced by FEDER funds from the European Union (“A way to build Europe”). IRBLleida is a CERCA Programme/Generalitat of Catalonia. FD was supported by the Agency for Management of University and Research Grants (FI_B100153). David de Gonzalo Calvo acknowledges receiving financial support from Instituto de Salud Carlos III (ISCIII); Miguel Servet 2020: CP20/00041, co-funded by the European Social Fund (ESF)/“Investing in your future”.

Background Obesity hypoventilation syndrome (OHS) is treated with either non-invasive ventilation (NIV) or CPAP, but there are no long-term cost-effectiveness studies comparing the two treatment modalities. Objectives We performed a large, multicentre, randomised, open-label controlled study to determine the comparative long-term cost and effectiveness of NIV versus CPAP in patients with OHS with severe obstructive sleep apnoea (OSA) using hospitalisation days as the primary outcome measure. Methods Hospital resource utilisation and within trial costs were evaluated against the difference in effectiveness based on the primary outcome (hospitalisation days/year, transformed and non-transformed in monetary term). Costs and effectiveness were estimated from a log-normal distribution using a Bayesian approach. A secondary analysis by adherence subgroups was performed. Results In total, 363 patients were selected, 215 were randomised and 202 were available for the analysis. The median (IQR) follow-up was 3.01 (2.91-3.14) years for NIV group and 3.00 (2.92-3.17) years for CPAP. The mean (SD) Bayesian estimated hospital days was 2.13 (0.73) for CPAP and 1.89 (0.78) for NIV. The mean (SD) Bayesian estimated cost per patient/year in the NIV arm, excluding hospitalisation costs, was €2075.98 (91.6), which was higher than the cost in the CPAP arm of €1219.06 (52.3); mean difference €857.6 (105.5). CPAP was more cost-effective than NIV (99.5% probability) because longer hospital stay in the CPAP arm was compensated for by its lower costs. Similar findings were observed in the high and low adherence subgroups. Conclusion CPAP is more cost-effective than NIV; therefore, CPAP should be the preferred treatment for patients with OHS with severe OSA. Trial registration number NCT01405976, Instituto de Salud Carlos III (Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo) PI050402, Spanish Respiratory Foundation 2005 (FEPAR) and Air Liquide Spain.

Background: Sleep-disordered breathing encompasses a group of diseases, of which obstructive sleep apnea (OSA) is most frequent. Alzheimer's disease (AD) is the most prevalent neurodegenerative disease; it is manifested as an initial deficit of episodic memory that evolves into global cognitive and psychosocial dysfunction, and its prevalence is increasing around the world. OSA has been described as a risk factor for AD, and its prevalence is higher in AD patients. However, little is known about the influence of OSA on cognition in the AD population.The aim of this study was to evaluate the impact of nontreated OSA on the cognitive evolution of patients with mild-moderate AD, to investigate whether the magnitude of the cognitive decline is associated with the severity of OSA and to evaluate the influence of OSA on several cognitive subdomains in AD patients. Methods: In this single-center study, patients with mild-moderate AD were recruited prospectively from a cognitive impairment unit and underwent overnight polysomnography. OSA was defined as an apnea-hypopnea index (AHI) >15/h. AD severity was assessed using the Mini-Mental State Examination (MMSE). The primary outcome was to measure the change in cognitive score on the Alzheimer’s Disease Assessment Scale-cognitive scale (ADAS-cog) from baseline to 12 months in patients with mild AD with and without OSA. An extensive battery of neuropsychological tests, including the Epworth Sleepiness Scale (ESS), were performed and APOE status was measured. Findings: The cohort included 144 patients with a mean (SD) age of 75.19 (5.30) years; 72 (57.6%) were women, and the mean MMSE score was 23.5 (2.24) points at baseline. The mean (SD) change in the ADAS-cog score at 12 months was 3.19 (5.61) in the non-OSA group and 0.08 (5.62) in the OSA group, with a difference between the groups of -3.36 (95%CI 0.19 to 0.16; p=0.002). Regarding the changes in the ADAS-cog subitems at 12 months, ideational praxis, remembering test instructions and commands showed a significant difference between the groups (p

ObjectiveTo assess the effectiveness and cost-effectiveness of primary care (PC) and sleep unit (SU) models for the management of subjects with suspected obstructive sleep apnoea (OSA).MethodsMulticentre, open-label, two-arm, parallel-group, non-inferiority randomised controlled trial. A total of 302 subjects with suspected OSA and/or resistant hypertension were consecutively enrolled, 149 were treated at 11 PC units and 153 patients at a SU. The primary outcomes were a 6-month change in the Epworth Sleepiness Scale (ESS) score and Health Utilities Index (HUI). The non-inferiority margin for the ESS score was −2.0.ResultsA total of 80.2% and 70.6% of the PC and SU patients were diagnosed with OSA, respectively, and 59.3% and 60.4% of those were treated with CPAP in PC and SU units, respectively. The Apnoea–Hypopnoea Index was similar between the groups (PC vs SU (median (IQR); 23.1 (26.8) events/h vs 21.8 (35.2) events/h), and the baseline ESS score was higher in the PC than in the SU group (10.3 (6.6) vs 9 (7.2)). After 6 months, the ESS score of the PC group decreased from a mean of 10.1 to 7.6 (−2.49; 95% CI −3.3 to −1.69), and that of the SU group decreased from 8.85 to 5.73 (−3.11; 95% CI −3.94 to 2.28). The adjusted difference between groups for the mean change in the ESS score was −1.25 (one-sided 95% CI −1.88; p=0.025), supporting the non-inferiority of PC management. We did not observe differences in the HUI between groups. The cost analysis showed a median savings of €558.14/patient for the PC setting compared with the SU setting.ConclusionsAmong patients with suspected OSA, the PC model did not result in a worse ESS score or HUI than the specialist model and generated savings in terms of management cost. Therefore, the PC model was more cost-efficient than the SU model.Trial registrationResults; >>NCT02234765, Clinical Trials.gov.