Search

Resumen: Introducción: El síndrome de apneas-hipopneas del sueño (SAHS) y la obesidad infantil son dos entidades con alta prevalencia que constituyen un problema de salud pública. Objetivo: Analizar la interacción entre ambas, comparando grupos de niños que presentaban o no ambas condiciones. Pacientes y metodología: Estudio prospectivo en niños (3-14 años), remitidos a la «Unidad Multidisciplinar de Sueño» por sospecha de SAHS, entre el 1/11/2015 y el 1/08/2017. Se evaluaron los siguientes parámetros: antropometría, síntomas, tensión arterial, exploración otorrinolaringológica, polisomnografía (PSG nocturna) y estudio analítico. Resultados: Se valoraron 67 niños, 64% no obesos y 36% obesos.Se observó que los obesos tenían más edad (p

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

Sleep is considered an essential part of life and plays a vital role in good health and well-being. Equally important as a balanced diet and adequate exercise, quality and quantity of sleep are essential for maintaining good health and quality of life. Sleep-disordered breathing is one of the most prevalent conditions that compromises the quality and duration of sleep, with obstructive sleep apnea (OSA) being the most prevalent disorder among these conditions. OSA is a chronic and highly prevalent disease that is considered to be a true public health problem. OSA has been associated with increased cardiovascular, neurocognitive, metabolic and overall mortality risks, and its management is a challenge facing the health care system. To establish the main future lines of research in sleep respiratory medicine, the Spanish Sleep Network (SSN) promoted the 1st World Café experts' meeting. The overall vision was established by consensus as "Sleep as promoter of health and the social impact of sleep disturbances". Under this leitmotiv and given that OSA is the most prevalent sleep disorder, five research lines were established to develop a new comprehensive approach for OSA management: (1) an integrated network for the comprehensive management of OSA; (2) the biological impact of OSA on comorbidities with high mortality, namely, cardiovascular and metabolic diseases, neurocognitive diseases and cancer; (3) Big Data Analysis for the identification of OSA phenotypes; (4) personalized medicine in OSA; and (5) OSA in children: current needs and future perspectives.

The main methods for dating ballpoint pen inks in questioned documents used up to day are based mainly on the analysis of ink volatile components. These methods have some limitations still unresolved, such as the impossibility for dating documents older than two to five years and the destruction in part or totally of the questioned document after the analysis. This study aims to overcome these drawbacks by exploring the feasibility of dating inks based on their spectroscopic UV–vis-NIR diffuse reflectance spectra monitoring combined with a Partial Least-Squares (PLS) multivariate modelling. Inoxcrom® ink samples were exposed to artificial aging, their reflectance spectra were measured and a multivariate calibration was applied. Mathematical pretreatments of the spectroscopic data were carried out to enhance the prediction ability of the models and the qualitative interpretation of the spectra. The best PLS model was obtained after SNV spectral filter. Accurate predictions (RSD of 25%) were obtained for two of the five pen inks analysed and a correlation between the natural aging and the accelerated artificial aging could be established. Moreover, the spectra region more closely related to the ink aging process could be delimited, in which younger inks were characterized by modifications in the visible and NIR spectra region, while after aging the most influential region was the NIR spectrum. The mismatch with the other three pen inks tested could be attributed to consistent differences in ink formulations. Inks sharing a common chromatographic profile proved to fit correctly in the predictive model indicating that the methodology shows a great potential for future applications in the field of questioned documents dating.

This work reports the development and validation of an ultra-high-performance liquid chromatography method to separate 11 different cardiovascular drugs: acenocoumarol, amiloride, bisoprolol, fluvastatin, furosemide, glibenclamide, hydrochlorothiazide, rosiglitazone (internal standard), valsartan, verapamil and warfarin. Detection of the analytes was carried out by means of photodiode array and fluorescence detection. Initially, the most significant variables in liquid chromatography (pH of the mobile phase, nature of the organic modifier and stationary phase type) were studied simultaneously in a systematic way. Taking into account the resolution obtained for the different chromatographic separations, pH 4.5, methanol and C18 were chosen as mobile phase pH, organic modifier and stationary phase, respectively. The method was validated and applied to the analysis of real human plasma samples using a solid phase extraction sample treatment, and the robustness of the chromatographic separation was studied by experimental design. The reported method allows the separation of all the analytes and the IS in less than 6 min, and, furthermore, it simplifies the analysis of drugs used in combined cardiovascular therapy by applying a fast and simple methodology.

Obese children are at increased risk for developing obstructive sleep apnea (OSA), and both of these conditions are associated with an increased risk for end-organ morbidities. Both OSA and obesity (OB) have been associated with increased risk for Alzheimer disease (AD). This study aimed to assess whether OSA and OB lead to increased plasma levels of 2 AD markers amyloid β protein 42 (Aβ42) and pre-senilin 1 (PS1).Fasting morning plasma samples from otherwise healthy children with a diagnosis of OB, OSA, or both (OSA+OB), and controls, and in a subset of children with OSA after adenotonsillectomy (TA) were assayed for Aβ42 and PS1 levels using commercial enzyme-linked immunosorbent assay kits.286 children (mean age of 7.2 ± 2.7 y) were evaluated. Compared to control subjects, OB children had similar Aβ42 (108.3 ± 31.7 pg/mL versus 83.6 ± 14.6 pg/mL) and PS1 levels (0.89 ± 0.44 ng/mL versus 0.80 ± 0.29 pg/mL). However, OSA children (Aβ42: 186.2 ± 66.7 pg/mL; P0.001; PS1: 3.42 ± 1.46 ng/mL; P0.001), and particularly OSA+OB children had significant elevations in both Aβ42 (349.4 ± 112.9 pg/mL; P0.001) and PS1 (PS1: 4.54 ± 1.16 ng/mL; P0.001) circulating concentrations. In a subset of 24 children, TA resulted in significant reductions of Aβ42 (352.0 ± 145.2 versus 151.9 ± 81.4 pg/mL; P0.0001) and PS1 (4.82 ± 1.09 versus 2.02 ± 1.18 ng/mL; P0.0001).Thus, OSA, and particularly OSA+OB, are associated with increased plasma levels of AD biomarkers, which decline upon treatment of OSA in a representative, yet not all- encompassing subset of patients, suggesting that OSA may accelerate AD-related processes even in early childhood. However, the cognitive and overall health-related implications of these findings remain to be defined.

Background: Noninvasive ventilation (NIV) and continuous positive airway pressure (CPAP) are the habitual treatments for obesity hypoventilation syndrome (OHS). Despite differences in cost and complexity between them, there are no long-term effectiveness studies comparing both treatments. Objectives: We performed a large multicenter randomized open-labell controlled study to determine the comparative long-term effectiveness of NIV and CPAP using hospitalization days as the primary outcome measure. Methods: Sequentially screened OHS patients with severe sleep apnea were randomized into the above-mentioned arms for at least 3 years of follow-up. Hospital resources utilization, mortality, cardiovascular events incidence, dropouts, compliance and side effects were evaluated. Statistical analysis was performed using intention-to-treat protocol evaluating event/year per patient and incidence by negative binomial, logistic and Cox regressions models and survival analysis. A secundary analysis by compliance subgroups was performed. Results: 215 patients were randomized and 202 were available for primary analysis. The median follow-up was 5.42 years. The hospital days/year was 2.19±5.65 for CPAP and 1.44±3.07 for NIV (adjusted p=0.12). Other hospital resources utilization, cardiovascular events incidence, mortality, dropouts, compliance and side effects were similar between arms. The better compliance subgroup had lower hospital resources utilization and mortality regardless of the treatment used. Conclusion: NIV and CPAP have similar long-term effectiveness. Because CPAP has economical advantages and simplicity, CPAP should be the preferable treatment for OHS patients with severe OSA.

There are no randomized controlled trials assessing the impact of noninvasive ventilation (NIV) and continuous positive airway pressure (CPAP) on cardiac function in obesity hypoventilation syndrome (OHS). Objective: To determine the efficacy of 2 months of NIV, CPAP or lifestyle modification (control) on echocardiographic changes. Method: OHS patients (n=302) were sequentially randomized by: 1) severe obstructive sleep apnea (OSA), into NIV, CPAP or control; 2) non-severe OSA, into NIV or control. ABG, spirometry, six-minute walk distance, Epworth sleepiness scale, polysomnography and transthoracic echocardiogram were evaluated. Results: We analyzed 2 groups: 1) with or without severe OSA and NIV or control treatments (entire OHS group; n=222); 2) with severe OSA and NIV, CPAP or control treatments (severe OSA subgroup; n=221). In the entire OHS group, NIV improved the left ventricular (LV) hypertrophy (mass index: -6.6 g/m2; 95%CI -11/-2.1 vs 3.6; 95%CI -1.1/8.3; adjusted p Conclusion: Medium-term NIV therapy is more effective than CPAP and lifestyle modification in improving PAP and LV hypertrophy in OHS

A novel gradient reverse phase high performance liquid chromatography tandem mass spectrometry (HPLC/MS-MS) was performed as a method for the determination of dobutamine hydrochloride (DOB) in newborn pig plasma samples. It was developed and validated after optimization of sample treatment and various chromatographic and mass spectrometric conditions. Trimethoxydobutamine (TMD) was used as internal standard. Heptafluorobutyric acid (HFBA) and ethyl acetate were used for the treatment of plasma samples. The separation of dobutamine and internal standard was done using a Kinetex F5 (50×2.1mm, 2.6μm, 100A) analytical column. The mobile phase was a mixture of acetonitrile and HCOOH 0.01%. The column oven temperature was optimized at 40° C and the flow rate was 0.25mL/min. DOB and TMD were detected by multiple reaction monitoring (MRM) mode in ESI+, using a cone voltage (CV) of 25V and a collision energy (CE) of 25eV. The weighted calibration curve (1/x2) was found to be linear over the concentration range of 1-100ng/mL (r2>0.999). The limit of quantification (LLOQ) of the method was 1ng/mL. The values of selectivity, carryover, LLOQ, linearity, accuracy, precision, matrix effect, stability and recovery obtained meet the acceptable range according to European Medicines Agency (EMA) and Food and Drug Administration (FDA) guidelines. The method was efficiently applied to quantify DOB in plasma samples from a pharmacokinetic/pharmacodynamic study in a disease model of newborn piglet.

A pilot study for the investigation of the maturation grade of children has been carried out using plasma samples already analyzed in a previous pharmacokinetic study. By using a meticulous data treatment, possible confounding factors that may hinder the obtained results were identified. By doing so, it was possible to obtain enough evidence to support the feasibility of performing a larger study eluding some unwanted variability and minimizing not only the number of subjects involved but also the time and money spent on the study. In the pilot study the metabolic profiles obtained using UHPLC-TOF-MS technique of plasma samples from 14 newborn piglets (

Copyright © 2017 by the American Thoracic Society, Rationale: The vast majority of children around the world undergoing adenotonsillectomy for obstructive sleep apnea-hypopnea syndrome (OSA) are not objectively diagnosed by nocturnal polysomnography because of access availability and cost issues. Automated analysis of nocturnal oximetry (nSpO2), which is readily and globally available, could potentially provide a reliable and convenient diagnostic approach for pediatric OSA. Methods: Deidentified nSpO2 recordings from a total of 4,191 children originating from 13 pediatric sleep laboratories around the world were prospectively evaluated after developing and validating an automated neural network algorithm using an initial set of single-channel nSpO2 recordings from 589 patients referred for suspected OSA. Measurements and main results: The automatically estimated apnea-hypopnea index (AHI) showed high agreement with AHI from conventional polysomnography (intraclass correlation coefficient, 0.785) when tested in 3,602 additional subjects. Further assessment on the widely used AHI cutoff points of 1, 5, and 10 events/h revealed an incremental diagnostic ability (75.2, 81.7, and 90.2% accuracy; 0.788, 0.854, and 0.913 area under the receiver operating characteristic curve, respectively). Conclusions: Neural network-based automated analyses of nSpO2 recordings provide accurate identification of OSA severity among habitually snoring children with a high pretest probability of OSA. Thus, nocturnal oximetry may enable a simple and effective diagnostic alternative to nocturnal polysomnography, leading to more timely interventions and potentially improved outcomes.

Producción Científica, Untreated paediatric obstructive sleep apnoea syndrome (OSAS) can severely affect the development and quality of life of children. In-hospital polysomnography (PSG) is the gold standard for a definitive diagnosis though it is relatively unavailable and particularly intrusive. Nocturnal portable oximetry has emerged as a reliable technique for OSAS screening. Nevertheless, additional evidences are demanded. Our study is aimed at assessing the usefulness of multiscale entropy (MSE) to characterise oximetric recordings. We hypothesise that MSE could provide relevant information of blood oxygen saturation (SpO2) dynamics in the detection of childhood OSAS. In order to achieve this goal, a dataset composed of unattended SpO2 recordings from 50 children showing clinical suspicion of OSAS was analysed. SpO2 was parameterised by means of MSE and conventional oximetric indices. An optimum feature subset composed of five MSE-derived features and four conventional clinical indices were obtained using automated bidirectional stepwise feature selection. Logistic regression (LR) was used for classification. Our optimum LR model reached 83.5% accuracy (84.5% sensitivity and 83.0% specificity). Our results suggest that MSE provides relevant information from oximetry that is complementary to conventional approaches. Therefore, MSE may be useful to improve the diagnostic ability of unattended oximetry as a simplified screening test for childhood OSAS., Sociedad Española de Neumología y Cirugía Torácica (SEPAR) project 153/2015, Junta de Castilla y León (Consejería de Educación) y el Fondo Europeo de Desarrollo Regional (FEDER), projects (RTC-2015-3446-1) y (TEC2014-53196-R), Ministerio de Economía y Competitividad (MINECO) y FEDER, y el proyecto POCTEP 0378_AD_EEGWA_2_P de la Comisión Europea. L., National Institutes of Health (NIH) grant 1R01HL130984-01, Ministerio de Asuntos Económicos y Transformación Digital, grant IJCI-2014-22664

Obese children are at increased risk for developing obstructive sleep apnea (OSA), and both of these conditions are associated with an increased risk for endothelial dysfunction (ED) in children, an early risk factor for atherosclerosis and cardiovascular disease. Although weight loss and treatment of OSA by adenotonsillectomy improve endothelial function, not every obese child or child with OSA develops ED. Exosomes are circulating extracellular vesicles containing functional mRNA and microRNA (miRNA) that can be delivered to other cells, such as endothelial cells.To investigate whether circulating exosomal miRNAs of children with OSA differentiate based on endothelial functional status.Obese children (body mass index z score1.65) and nonobese children were recruited and underwent polysomnographic testing (PSG), and fasting endothelial function measurements and blood draws in the morning after PSG. Plasma exosomes were isolated from all subjects. Isolated exosomes were then incubated with confluent endothelial cell monolayer cultures. Electric cell-substrate impedance sensing systems were used to determine the ability of exosomes to disrupt the intercellular barrier formed by confluent endothelial cells. In addition, immunofluorescent assessments of zonula occludens-1 tight junction protein cellular distribution were conducted to examine endothelial barrier dysfunction. miRNA and mRNA arrays were also applied to exosomes and endothelial cells, and miRNA inhibitors and mimics were transfected for mechanistic assays.Plasma exosomes isolated from either obese children or nonobese children with OSA were primarily derived from endothelial cell sources and recapitulated ED, or its absence, in naive human endothelial cells and also in vivo when injected into mice. Microarrays identified a restricted signature of exosomal miRNAs that readily distinguished ED from normal endothelial function. Among the miRNAs, expression of exosomal miRNA-630 was reduced in children with ED and normalized after therapy along with restoration of endothelial function. Conversely, transfection of exosomes from subjects without ED with an miRNA-630 inhibitor induces the ED functional phenotype. Gene target discovery experiments further revealed that miRNA-630 regulates 416 gene targets in endothelial cells that include the Nrf2, AMP kinase, and tight junction pathways.These observations elucidate a novel role of exosomal miRNA-360 as a putative key mediator of vascular function and cardiovascular disease risk in children with underlying OSA and/or obesity, and identify therapeutic targets.

Producción Científica, Study Objectives: Nocturnal oximetry has emerged as a simple, readily available, and potentially useful diagnostic tool of childhood obstructive sleep apnea-hypopnea syndrome (OSAHS). However, at-home respiratory polygraphy (HRP) remains the preferred alternative to polysomnography (PSG) in unattended settings. The aim of this study was two-fold: (1) to design and assess a novel methodology for pediatric OSAHS screening based on automated analysis of at-home oxyhemoglobin saturation (SpO2), and (2) to compare its diagnostic performance with HRP. Methods: SpO2 recordings were parameterized by means of time, frequency, and conventional oximetric measures. Logistic regression (LR) models were optimized using genetic algorithms (GAs) for 3 cutoffs for OSAHS: 1, 3, and 5 events per hour (e/h). The diagnostic performance of LR models, manual obstructive apnea-hypopnea index (OAHI) from HRP, and the conventional oxygen desaturation index ≥3% (ODI3) were assessed. Results: For a cutoff of 1 e/h, the optimal LR model significantly outperformed both conventional HRP-derived ODI3 and OAHI: 85.5% Accuracy (HRP 74.6%; ODI3 65.9%) and 0.97 AUC (HRP 0.78; ODI3 0.75) were reached. For a cutoff of 3 e/h, the LR model achieved 83.4% Accuracy (HRP 85.0%; ODI3 74.5%) and 0.96 AUC (HRP 0.93; ODI3 0.85) whereas using a cutoff of 5 e/h, oximetry reached 82.8% Accuracy (HRP 85.1%; ODI3 76.7) and 0.97 AUC (HRP 0.95; ODI3 0.84). Conclusions: Automated analysis of at-home SpO2 recordings provide accurate detection of children with high pre-test probability of OSAHS. Thus, unsupervised nocturnal oximetry may enable a simple and effective alternative to HRP and PSG in unattended settings., This research has been partially supported by the project 153/2015 of the Sociedad Española de Neumología y Cirugía Torácica (SEPAR), the project RTC-2015-3446-1 from the Ministerio de Economía y Competitividad and the European Regional Development Fund (FEDER), and the project VA037U16 from the Consejería de Educación de la Junta de Castilla y León and FEDER. L. Kheirandish-Gozal is supported by NIH grant 1R01HL130984-01. D. Álvarez was in receipt of a Juan de la Cierva grant from the Ministerio de Economía y Competitividad.

Background Obesity hypoventilation syndrome (OHS) is associated with a high burden of cardiovascular morbidity (CVM) and mortality. The majority of patients with OHS have concomitant OSA, but there is a paucity of data on the association between CVM and OSA severity in patients with OHS. The objective of our study was to assess the association between CVM and OSA severity in a large cohort of patients with OHS. Methods In a cross-sectional analysis, we examined the association between OSA severity based on tertiles of oxygen desaturation index (ODI) and CVM in 302 patients with OHS. Logistic regression models were constructed to quantify the independent association between OSA severity and prevalent CVM after adjusting for various important confounders. Results The prevalence of CVM decreased significantly with increasing severity of OSA based on ODI as a continuous variable or ODI tertiles. This inverse relationship between OSA severity and prevalence of CVM was seen in the highest ODI tertile and it persisted despite adjustment for multiple confounders. Chronic heart failure had the strongest negative association with the highest ODI tertile. No significant CVM risk change was observed between the first and second ODI tertiles. Patients in the highest ODI tertile were younger, predominantly male, more obese, more hypersomnolent, had worse nocturnal and daytime gas exchange, lower prevalence of hypertension, better exercise tolerance, and fewer days hospitalized than patients in the lowest ODI tertile. Conclusions In patients with OHS, the highest OSA severity phenotype was associated with reduced risk of CVM. This finding should guide the design of future clinical trials assessing the impact of interventions aimed at decreasing cardiovascular morbidity and mortality in patients with OHS. Trial Registry Clinicaltrial.gov; No.: NCT01405976 ; URL: www.clinicaltrials.gov

La Sociedad Espanola de Sueno tiene como uno de sus principales objetivos la promocion de un sueno saludable en la poblacion general y profesionales de la salud. El presente documento pretende realizar una revision de la literatura cientifica actual sobre habitos de sueno que sirva de fundamento para establecer unas recomendaciones generales y utiles para la poblacion general espanola, en el contexto de un sueno saludable, e identificar aquellos principales retos en la investigacion sobre habitos de sueno. El desarrollo del documento se ha realizado por un equipo multidisciplinar de miembros de la Sociedad Espanola de Sueno integrado por expertos en medicina pediatrica del sueno, neurofisiologia clinica, neumologia, neurologia, cronobiologia, fisiologia y psicologia. Se ha procedido a una revision de la bibliografia cientifica existente sobre habitos de sueno en poblacion general, y se han abordado los siguientes aspectos: estado actual de los habitos de sueno en la poblacion espanola; revision generica de la cantidad optima de horas de sueno; impacto del entorno ambiental (ruido, temperatura, iluminacion...), horarios de sueno, alimentacion y deporte; y apartados especificos para ninos y adolescentes, trabajadores a turnos y conduccion de vehiculos. De todos los aspectos abordados a lo largo de este documento, se concluyen unas recomendaciones generales finales que serviran de guia a la poblacion general y profesionales de la salud, asi como se discuten los principales retos ambientales y futuras direcciones de investigacion.