Management and Treatment of Patients With Obstructive Sleep Apnea Using an Intelligent Monitoring System Based on Machine Learning Aiming to Improve Continuous Positive Airway Pressure Treatment Compliance: Randomized Controlled Trial.

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. TRIAL REGISTRATION: ClinicalTrials.gov NCT03116958; https://clinicaltrials.gov/ct2/show/NCT03116958.

Longitudinal Analysis of Causes of Mortality in Continuous Positive Airway Pressure-treated Patients at the Population Level.

Rationale: Randomized controlled trials do not support a role for continuous positive airway pressure (CPAP) in preventing major cardiovascular events or mortality in patients with obstructive sleep apnea (OSA). However, these trials' setting does not apply to most CPAP-treated patients. Objectives: We aimed to assess the effect of CPAP on mortality in real-world patients. Methods: We performed a population-based longitudinal observational study including all patients with OSA prescribed CPAP during 2011 in Catalonia, Spain, and non-OSA control subjects matched (1:2) by sex, 5-year age group, and region who were followed from 2011 to 2016. Results: A total of 9,317 CPAP-treated patients with OSA and 18,370 control subjects without OSA were included (median age, 67 [57-72] years; 74% male). During a median follow-up of 5.5 years, 2,301 deaths were recorded. After adjustment by a composite of diagnosed comorbidities and previous use of healthcare resources, CPAP-treated patients showed a lower risk of death than control subjects (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.61-0.74), with the association not being statistically significant in women. Cancer-related deaths were the main drivers of this association (men: HR, 0.44; 95% CI, 0.36-0.54; women: HR, 0.44; 95% CI, 0.28-0.68). No significant associations were found for cardiovascular-related deaths. CPAP-treated women had an increased risk of respiratory-related death (HR, 2.41; 95% CI, 1.37-4.23). Conclusions: CPAP-treated patients had a lower mortality rate than control subjects. This relationship was driven by cancer-related, but not cardiovascular-related, deaths. Results suggest a role for sex when prescribing CPAP, especially considering respiratory-related deaths, and foster a debate on the relationship between OSA and cardiovascular outcomes.

European Respiratory Society statement on sleep apnoea, sleepiness and driving risk.

Obstructive sleep apnoea (OSA) is highly prevalent and is a recognised risk factor for motor vehicle accidents (MVA). Effective treatment with continuous positive airway pressure has been associated with a normalisation of this increased accident risk. Thus, many jurisdictions have introduced regulations restricting the ability of OSA patients from driving until effectively treated. However, uncertainty prevails regarding the relative importance of OSA severity determined by the apnoea-hypopnoea frequency per hour and the degree of sleepiness in determining accident risk. Furthermore, the identification of subjects at risk of OSA and/or accident risk remains elusive. The introduction of official European regulations regarding fitness to drive prompted the European Respiratory Society to establish a task force to address the topic of sleep apnoea, sleepiness and driving with a view to providing an overview to clinicians involved in treating patients with the disorder. The present report evaluates the epidemiology of MVA in patients with OSA; the mechanisms involved in this association; the role of screening questionnaires, driving simulators and other techniques to evaluate sleepiness and/or impaired vigilance; the impact of treatment on MVA risk in affected drivers; and highlights the evidence gaps regarding the identification of OSA patients at risk of MVA.

A new postural device for the treatment of positional obstructive sleep apnea. A pilot study.

BACKGROUND: Approximately 60% of obstructive sleep apnea (OSA) diagnoses are position-dependent, and avoidance of the supine position could represent an effective treatment. Nevertheless, the majority of the available anti-supine treatments result in discomfort and low adherence. This study evaluated the effectiveness of a new vibrating supine avoidance device in reducing time spent in the supine position and the apnea-hypopnea index (AHI) without affecting sleep structure. Furthermore, the tolerability and satisfaction were also scored. METHODS: Observational prospective study of patients suffering from positional OSA. They were treated with a vibrating device and followed up at the first and fourth weeks after starting the treatment, and further polysomnographic studies were conducted while patients' wore the device. The comparison of the results was carried out through non-parametric tests. Significance level was 5%. RESULTS: Twelve patients had complete data. The device reduced time spent in the supine position (from 51.5 ±â€¯14.8% to 25.2 ±â€¯21.0%, p = 0.005), median AHI (from 30.7 (23.2-38.2) at baseline to 21.5 (12.4-24.3) at the fourth week, p = 0.002). Also an improvement in the minimum SaO2 (from 82.2 ±â€¯7.5 to 87.2 ±â€¯3.6 at the 4th week) was also observed. No variations in sleep quality or quantity were identified. All patients evaluated the device positively. CONCLUSION: Our device was effective in reducing the time spent in the supine position and improving AHI, SaO2 variables and sleep architecture. The device was well tolerated by the patients.

Comparative analysis of predictive methods for early assessment of compliance with continuous positive airway pressure therapy.

BACKGROUND: Patients suffering obstructive sleep apnea are mainly treated with continuous positive airway pressure (CPAP). Although it is a highly effective treatment, compliance with this therapy is problematic to achieve with serious consequences for the patients' health. Unfortunately, there is a clear lack of clinical analytical tools to support the early prediction of compliant patients. METHODS: This work intends to take a further step in this direction by building compliance classifiers with CPAP therapy at three different moments of the patient follow-up, before the therapy starts (baseline) and at months 1 and 3 after the baseline. RESULTS: Results of the clinical trial shows that month 3 was the time-point with the most accurate classifier reaching an f1-score of 87% and 84% in cross-validation and test. At month 1, performances were almost as high as in month 3 with 82% and 84% of f1-score. At baseline, where no information of patients' CPAP use was given yet, the best classifier achieved 73% and 76% of f1-score in cross-validation and test set respectively. Subsequent analyzes carried out with the best classifiers of each time point revealed baseline factors (i.e. headaches, psychological symptoms, arterial hypertension and EuroQol visual analog scale) closely related to the prediction of compliance independently of the time-point. In addition, among the variables taken only during the follow-up of the patients, Epworth and the average nighttime hours were the most important to predict compliance with CPAP. CONCLUSIONS: Best classifiers reported high performances after one month of treatment, being the third month when significant differences were achieved with respect to the baseline. Four baseline variables were reported relevant for the prediction of compliance with CPAP at each time-point. Two characteristics more were also highlighted for the prediction of compliance at months 1 and 3. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT03116958 . Retrospectively registered on 17 April 2017.

Cardiac Troponin Values in Patients With Acute Coronary Syndrome and Sleep Apnea: A Pilot Study.

BACKGROUND: An analysis of cardiac injury markers in patients with OSA who sustain an episode of acute coronary syndrome (ACS) may contribute to a better understanding of the interactions and impact of OSA in subjects with ACS. We compared peak cardiac troponin I (cTnI) levels in patients with OSA and patients without OSA who were admitted for ACS. METHODS: Blood samples were collected every 6 hours from the time of admission until two consecutive assays showed a downward trend in the cTnI assay. The highest value obtained defined the peak cTnI value, which provides an estimate of infarct size. RESULTS: We included 89 patients with OSA and 38 patients without OSA with an apnea-hypopnea index of a median of 32 (interquartile range [IQR], 20.8-46.6/h and 4.8 [IQR, 1.6-9.6]/h, respectively. The peak cTnI value was significantly higher in patients without OSA than in patients with OSA (median, 10.7 ng/mL [IQR, 1.78-40.1 ng/mL] vs 3.79 ng/mL [IQR, 0.37-24.3 ng/mL]; P = .04). The multivariable linear regression analysis of the relationship between peak cTnI value and patient group, age, sex, and type of ACS showed that the presence or absence of OSA significantly contributed to the peak cTnI level, which was 54% lower in patients with OSA than in those without OSA. CONCLUSIONS: The results of this study suggest that OSA has a protective effect in the context of myocardial infarction and that patients with OSA may experience less severe myocardial injury. The possible role of OSA in cardioprotection should be explored in future studies.

Blood pressure response to CPAP treatment in subjects with obstructive sleep apnoea: the predictive value of 24-h ambulatory blood pressure monitoring.

The reduction in blood pressure (BP) with continuous positive airway pressure (CPAP) is modest and highly variable. In this study, we identified the variables that predict BP response to CPAP.24-h ambulatory BP monitoring (ABPM), C-reactive protein (CRP), leptin, adiponectin and 24-h urinary catecholamine were measured before and after 6 months of CPAP in obstructive sleep apnoea (OSA) patients.Overall, 88 middle-aged, obese male patients with severe OSA (median apnoea-hypopnoea index 42 events·h-1) were included; 28.4% had hypertension. 62 patients finished the study, and 60 were analysed. The daytime diastolic BP (-2 mmHg) and norepinephrine (-109.5 nmol·day-1) were reduced after CPAP, but no changes in the 24-h BP, night-time BP, dopamine, epinephrine, CRP, leptin or adiponectin were detected. The nocturnal normotension was associated with an increased night-time-BP (+4 mmHg) after CPAP, whereas nocturnal hypertension was associated with a reduction of 24-h BP (-3 mmHg). A multivariate linear regression model showed differential night-time BP changes after CPAP. Specifically, low night-time heart rate (<68 bpm) and BP dipper profile were associated with increased night-time BP and new diagnosis of nocturnal hypertension.Our results suggest that nocturnal hypertension, circadian BP pattern and night-time heart rate could be clinical predictors of BP response to CPAP and support the usefulness of 24-h ABPM for OSA patients before treatment initiation. These results need to be confirmed in further studies.

Pulmonary Function and Sleep Breathing: Two New Targets for Type 2 Diabetes Care.

Population-based studies showing the negative impact of type 2 diabetes (T2D) on lung function are overviewed. Among the well-recognized pathophysiological mechanisms, the metabolic pathways related to insulin resistance (IR), low-grade chronic inflammation, leptin resistance, microvascular damage, and autonomic neuropathy are emphasized. Histopathological changes are exposed, and findings reported from experimental models are clearly differentiated from those described in humans. The accelerated decline in pulmonary function that appears in patients with cystic fibrosis (CF) with related abnormalities of glucose tolerance and diabetes is considered as an example to further investigate the relationship between T2D and the lung. Furthermore, a possible causal link between antihyperglycemic therapies and pulmonary function is examined. T2D similarly affects breathing during sleep, becoming an independent risk factor for higher rates of sleep apnea, leading to nocturnal hypoxemia and daytime sleepiness. Therefore, the impact of T2D on sleep breathing and its influence on sleep architecture is analyzed. Finally, the effect of improving some pathophysiological mechanisms, primarily IR and inflammation, as well as the optimization of blood glucose control on sleep breathing is evaluated. In summary, the lung should be considered by those providing care for people with diabetes and raise the central issue of whether the normalization of glucose levels can improve pulmonary function and ameliorate sleep-disordered breathing. Therefore, patients with T2D should be considered a vulnerable group for pulmonary dysfunction. However, further research aimed at elucidating how to screen for the lung impairment in the population with diabetes in a cost-effective manner is needed.

Characterization of the CPAP-treated patient population in Catalonia.

There are different phenotypes of obstructive sleep apnoea (OSA), many of which have not been characterised. Identification of these different phenotypes is important in defining prognosis and guiding the therapeutic strategy. The aim of this study was to characterise the entire population of continuous positive airway pressure (CPAP)-treated patients in Catalonia and identify specific patient profiles using cluster analysis. A total of 72,217 CPAP-treated patients who contacted the Catalan Health System (CatSalut) during the years 2012 and 2013 were included. Six clusters were identified, classified as "Neoplastic patients" (Cluster 1, 10.4%), "Metabolic syndrome patients" (Cluster 2, 27.7%), "Asthmatic patients" (Cluster 3, 5.8%), "Musculoskeletal and joint disorder patients" (Cluster 4, 10.3%), "Patients with few comorbidities" (Cluster 5, 35.6%) and "Oldest and cardiac disease patients" (Cluster 6, 10.2%). Healthcare facility use and mortality were highest in patients from Cluster 1 and 6. Conversely, patients in Clusters 2 and 4 had low morbidity, mortality and healthcare resource use. Our findings highlight the heterogeneity of CPAP-treated patients, and suggest that OSA is associated with a different prognosis in the clusters identified. These results suggest the need for a comprehensive and individualised approach to CPAP treatment of OSA.

Predictors of obstructive sleep apnoea in patients admitted for acute coronary syndrome.

Identifying undiagnosed obstructive sleep apnoea (OSA) patients in cardiovascular clinics could improve their management. Aiming to build an OSA predictive model, a broad analysis of clinical variables was performed in a cohort of acute coronary syndrome (ACS) patients.Sociodemographic, anthropometric, life-style and pharmacological variables were recorded. Clinical measures included blood pressure, electrocardiography, echocardiography, blood count, troponin levels and a metabolic panel. OSA was diagnosed using respiratory polygraphy. Logistic regression models and classification and regression trees were used to create predictive models.A total of 978 patients were included (298 subjects with apnoea-hypopnoea index (AHI) <15 events·h-1 and 680 with AHI ≥15 events·h-1). Age, BMI, Epworth sleepiness scale, peak troponin levels and use of calcium antagonists were the main determinants of AHI ≥15 events·h-1 (C statistic 0.71; sensitivity 94%; specificity 24%). Age, BMI, blood triglycerides, peak troponin levels and Killip class ≥II were determinants of AHI ≥30 events·h-1 (C statistic of 0.67; sensitivity 31%; specificity 86%).Although a set of variables associated with OSA was identified, no model could successfully predict OSA in patients admitted for ACS. Given the high prevalence of OSA, the authors propose respiratory polygraphy as a to-be-explored strategy to identify OSA in ACS patients.

Management of continuous positive airway pressure treatment compliance using telemonitoring in obstructive sleep apnoea.

Continuous positive airway pressure (CPAP) is an effective treatment for obstructive sleep apnoea (OSA), but treatment compliance is often unsatisfactory. This study investigated the efficacy and cost-effectiveness of telemonitoring for improving CPAP compliance.100 newly diagnosed OSA patients requiring CPAP (apnoea-hypopnoea index >15 events·h-1) were randomised to standard management or a telemonitoring programme that collected daily information about compliance, air leaks and residual respiratory events, and initiated patient contact to resolve issues. Clinical/anthropometric variables, daytime sleepiness and quality of life were recorded at baseline and after 3 months. Patient satisfaction, additional visits/calls, side-effects and total costs were assessed.There were no significant differences between the standard and telemedicine groups in terms of CPAP compliance (4.9±2.2 versus 5.1±2.1 h·night-1), symptoms, clinical variables, quality of life and unwanted effects. Telemedicine was less expensive than standard management (EUR123.65 versus EUR170.97; p=0.022) and was cost-effective (incremental cost-effectiveness ratio EUR17 358.65 per quality-adjusted life-year gained). Overall patient satisfaction was high, but significantly more patients rated satisfaction as high/very high in the standard management versus telemedicine group (96% versus 74%; p=0.034).Telemonitoring did not improve CPAP treatment compliance and was associated with lower patient satisfaction. However, it was more cost-effective than traditional follow-up.

Effects of Ethnicity on the Prevalence of Obstructive Sleep Apnoea in Patients with Acute Coronary Syndrome: A Pooled Analysis of the ISAACC Trial and Sleep and Stent Study.

BACKGROUND: Obstructive sleep apnoea (OSA) is an emerging risk factor for acute coronary syndrome (ACS). We sought to determine the effects of ethnicity on the prevalence of OSA in patients presenting with ACS who participated in an overnight sleep study. METHODS: A pooled analysis using patient-level data from the ISAACC Trial and Sleep and Stent Study was performed. Using the same portable diagnostic device, OSA was defined as an apnoea-hypopnoea index of ≥15 events per hour. RESULTS: A total of 1961 patients were analysed, including Spanish (53.6%, n=1050), Chinese (25.5%, n=500), Indian (12.0%, n=235), Malay (6.1%, n=119), Brazilian (1.7%, n=34) and Burmese (1.2%, n=23) populations. Significant differences in body mass index (BMI) were found among the various ethnic groups, averaging from 25.3kg/m2 for Indians and 25.4kg/m2 for Chinese to 28.6kg/m2 for Spaniards. The prevalence of OSA was highest in the Spanish (63.1%), followed by the Chinese (50.2%), Malay (47.9%), Burmese (43.5%), Brazilian (41.2%), and Indian (36.1%) patients. The estimated odds ratio of BMI on OSA was highest in the Chinese population (1.17; 95% confidence interval: 1.10-1.24), but was not significant in the Spanish, Burmese or Brazilian populations. The area under the curve (AUC) for the Asian patients (ranging from 0.6365 to 0.6692) was higher than that for the Spanish patients (0.5161). CONCLUSION: There was significant ethnic variation in the prevalence of OSA in patients with ACS. The magnitude of the effect of BMI on OSA was greater in the Chinese population than in the Spanish patients.

H-Prune through GSK-3ß interaction sustains canonical WNT/ß-catenin signaling enhancing cancer progression in NSCLC.

H-Prune hydrolyzes short-chain polyphosphates (PPase activity) together with an hitherto cAMP-phosphodiesterase (PDE), the latest influencing different human cancers by its overexpression. H-Prune promotes cell migration in cooperation with glycogen synthase kinase-3 (Gsk-3ß). Gsk-3ß is a negative regulator of canonical WNT/ß-catenin signaling. Here, we investigate the role of Gsk-3ß/h-Prune complex in the regulation of WNT/ß-catenin signaling, demonstrating the h-Prune capability to activate WNT signaling also in a paracrine manner, through Wnt3a secretion. In vivo study demonstrates that h-Prune silencing inhibits lung metastasis formation, increasing mouse survival. We assessed h-Prune levels in peripheral blood of lung cancer patients using ELISA assay, showing that h-Prune is an early diagnostic marker for lung cancer. Our study dissects out the mechanism of action of h-Prune in tumorigenic cells and also sheds light on the identification of a new therapeutic target in non-small-cell lung cancer.