Towards a common European ethical and legal framework for conducting clinical research: the GATEKEEPER experience.

This paper examines the ethical and legal challenges encountered during the GATEKEEPER Project and how these challenges informed the development of a comprehensive framework for future Large-Scale Pilot (LSP) projects. GATEKEEPER is a LSP Project with 48 partners conducting 30 implementation studies across Europe with 50,000 target participants grouped into 9 Reference Use Cases. The project underscored the complexity of obtaining ethical approval across various jurisdictions with divergent regulations and procedures. Through a detailed analysis of the issues faced and the strategies employed to navigate these challenges, this study proposes an ethical and legal framework. This framework, derived from a comparative analysis of ethical application forms and regulations, aims to streamline the ethical approval process for future LSP research projects. By addressing the hurdles encountered in GATEKEEPER, the proposed framework offers a roadmap for more efficient and effective project management, ensuring smoother implementation of similar projects in the future.

Heterogeneous Effects of CPAP in Non-Sleepy OSA on CVD Outcomes: Post-hoc Machine Learning Analysis of the ISAACC Trial (ECSACT Study).

RATIONALE: Randomized controlled trials of continuous positive airway pressure (CPAP) therapy for cardiovascular disease (CVD) prevention among patients with obstructive sleep apnea (OSA) have been largely neutral. However, given OSA is a heterogeneous disease, there may be unidentified subgroups demonstrating differential treatment effects. OBJECTIVES: Apply a novel data-drive approach to identify non-sleepy OSA subgroups with heterogeneous effects of CPAP on CVD outcomes within the ISAACC study. METHODS: Participants were randomly partitioned into two datasets. One for training (70%) our machine learning model and a second (30%) for validation of significant findings. Model-based recursive partitioning was applied to identify subgroups with heterogeneous treatment effects. Survival analysis was conducted to compare treatment (CPAP versus usual care [UC]) outcomes within subgroups. RESULTS: A total of 1,224 non-sleepy OSA participants were included. Of fifty-five features entered into our model only two appeared in the final model (i.e., average OSA event duration and hypercholesterolemia). Among participants at or below the model-derived average event duration threshold (19.5 seconds), CPAP was protective for a composite of CVD events (training Hazard Ratio [HR] 0.46, p=0.002). For those with longer event duration (>19.5 seconds), an additional split occurred by hypercholesterolemia status. Among participants with longer event duration and hypercholesterolemia, CPAP resulted in more CVD events compared to UC (training HR 2.24, p=0.011). The point estimate for this harmful signal was also replicated in the testing dataset (HR 1.83, p=0.118). CONCLUSIONS: We discovered subgroups of non-sleepy OSA participants within the ISAACC study with heterogeneous effects of CPAP. Among the training dataset, those with longer OSA event duration and hypercholesterolemia had nearly 2.5-times more CVD events with CPAP compared to UC, while those with shorter OSA event duration had roughly half the rate of CVD events if randomized to CPAP.

Global mortality and readmission rates following COPD exacerbation-related hospitalisation: a meta-analysis of 65 945 individual patients.

Background: Exacerbations of COPD (ECOPD) have a major impact on patients and healthcare systems across the world. Precise estimates of the global burden of ECOPD on mortality and hospital readmission are needed to inform policy makers and aid preventive strategies to mitigate this burden. The aims of the present study were to explore global in-hospital mortality, post-discharge mortality and hospital readmission rates after ECOPD-related hospitalisation using an individual patient data meta-analysis (IPDMA) design. Methods: A systematic review was performed identifying studies that reported in-hospital mortality, post-discharge mortality and hospital readmission rates following ECOPD-related hospitalisation. Data analyses were conducted using a one-stage random-effects meta-analysis model. This study was conducted and reported in accordance with the PRISMA-IPD statement. Results: Data of 65 945 individual patients with COPD were analysed. The pooled in-hospital mortality rate was 6.2%, pooled 30-, 90- and 365-day post-discharge mortality rates were 1.8%, 5.5% and 10.9%, respectively, and pooled 30-, 90- and 365-day hospital readmission rates were 7.1%, 12.6% and 32.1%, respectively, with noticeable variability between studies and countries. Strongest predictors of mortality and hospital readmission included noninvasive mechanical ventilation and a history of two or more ECOPD-related hospitalisations <12 months prior to the index event. Conclusions: This IPDMA stresses the poor outcomes and high heterogeneity of ECOPD-related hospitalisation across the world. Whilst global standardisation of the management and follow-up of ECOPD-related hospitalisation should be at the heart of future implementation research, policy makers should focus on reimbursing evidence-based therapies that decrease (recurrent) ECOPD.

GATEKEEPER's Strategy for the Multinational Large-Scale Piloting of an eHealth Platform: Tutorial on How to Identify Relevant Settings and Use Cases.

BACKGROUND: The World Health Organization's strategy toward healthy aging fosters person-centered integrated care sustained by eHealth systems. However, there is a need for standardized frameworks or platforms accommodating and interconnecting multiple of these systems while ensuring secure, relevant, fair, trust-based data sharing and use. The H2020 project GATEKEEPER aims to implement and test an open-source, European, standard-based, interoperable, and secure framework serving broad populations of aging citizens with heterogeneous health needs. OBJECTIVE: We aim to describe the rationale for the selection of an optimal group of settings for the multinational large-scale piloting of the GATEKEEPER platform. METHODS: The selection of implementation sites and reference use cases (RUCs) was based on the adoption of a double stratification pyramid reflecting the overall health of target populations and the intensity of proposed interventions; the identification of a principles guiding implementation site selection; and the elaboration of guidelines for RUC selection, ensuring clinical relevance and scientific excellence while covering the whole spectrum of citizen complexities and intervention intensities. RESULTS: Seven European countries were selected, covering Europe's geographical and socioeconomic heterogeneity: Cyprus, Germany, Greece, Italy, Poland, Spain, and the United Kingdom. These were complemented by the following 3 Asian pilots: Hong Kong, Singapore, and Taiwan. Implementation sites consisted of local ecosystems, including health care organizations and partners from industry, civil society, academia, and government, prioritizing the highly rated European Innovation Partnership on Active and Healthy Aging reference sites. RUCs covered the whole spectrum of chronic diseases, citizen complexities, and intervention intensities while privileging clinical relevance and scientific rigor. These included lifestyle-related early detection and interventions, using artificial intelligence-based digital coaches to promote healthy lifestyle and delay the onset or worsening of chronic diseases in healthy citizens; chronic obstructive pulmonary disease and heart failure decompensations management, proposing integrated care management based on advanced wearable monitoring and machine learning (ML) to predict decompensations; management of glycemic status in diabetes mellitus, based on beat to beat monitoring and short-term ML-based prediction of glycemic dynamics; treatment decision support systems for Parkinson disease, continuously monitoring motor and nonmotor complications to trigger enhanced treatment strategies; primary and secondary stroke prevention, using a coaching app and educational simulations with virtual and augmented reality; management of multimorbid older patients or patients with cancer, exploring novel chronic care models based on digital coaching, and advanced monitoring and ML; high blood pressure management, with ML-based predictions based on different intensities of monitoring through self-managed apps; and COVID-19 management, with integrated management tools limiting physical contact among actors. CONCLUSIONS: This paper provides a methodology for selecting adequate settings for the large-scale piloting of eHealth frameworks and exemplifies with the decisions taken in GATEKEEPER the current views of the WHO and European Commission while moving forward toward a European Data Space.

Key Factors Associated With Pulmonary Sequelae in the Follow-Up of Critically Ill COVID-19 Patients.

INTRODUCTION: Critical COVID-19 survivors have a high risk of respiratory sequelae. Therefore, we aimed to identify key factors associated with altered lung function and CT scan abnormalities at a follow-up visit in a cohort of critical COVID-19 survivors. METHODS: Multicenter ambispective observational study in 52 Spanish intensive care units. Up to 1327 PCR-confirmed critical COVID-19 patients had sociodemographic, anthropometric, comorbidity and lifestyle characteristics collected at hospital admission; clinical and biological parameters throughout hospital stay; and, lung function and CT scan at a follow-up visit. RESULTS: The median [p25-p75] time from discharge to follow-up was 3.57 [2.77-4.92] months. Median age was 60 [53-67] years, 27.8% women. The mean (SD) percentage of predicted diffusing lung capacity for carbon monoxide (DLCO) at follow-up was 72.02 (18.33)% predicted, with 66% of patients having DLCO<80% and 24% having DLCO<60%. CT scan showed persistent pulmonary infiltrates, fibrotic lesions, and emphysema in 33%, 25% and 6% of patients, respectively. Key variables associated with DLCO<60% were chronic lung disease (CLD) (OR: 1.86 (1.18-2.92)), duration of invasive mechanical ventilation (IMV) (OR: 1.56 (1.37-1.77)), age (OR [per-1-SD] (95%CI): 1.39 (1.18-1.63)), urea (OR: 1.16 (0.97-1.39)) and estimated glomerular filtration rate at ICU admission (OR: 0.88 (0.73-1.06)). Bacterial pneumonia (1.62 (1.11-2.35)) and duration of ventilation (NIMV (1.23 (1.06-1.42), IMV (1.21 (1.01-1.45)) and prone positioning (1.17 (0.98-1.39)) were associated with fibrotic lesions. CONCLUSION: Age and CLD, reflecting patients' baseline vulnerability, and markers of COVID-19 severity, such as duration of IMV and renal failure, were key factors associated with impaired DLCO and CT abnormalities.

Proteomic profiling for prediction of recurrent cardiovascular event in patients with acute coronary syndrome and obstructive sleep apnea: A post-hoc analysis from the ISAACC study.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with a recurrent cardiovascular event (CVE) risk in patients with a first acute coronary syndrome (ACS). However, the pathological pathways by which OSA promotes this deleterious role are unknown. We aim to explore the proteomic profile associated with OSA that promote the recurrent CVE risk in severe OSA patients with ACS without previous cardiovascular diseases. METHODS: This post-hoc analysis from the ISAACC study (NCT01335087) included 86 patients admitted for ACS. Patients underwent respiratory polygraphy for the first 24-72 h to OSA diagnosis. We analyzed of 276 cardiovascular and inflammatory related proteins in baseline fasting plasma samples using proximity expression assay technology (Olink®, Sweden). Protein levels were compared between severe OSA patients with/without recurrent CVEs during follow-up. Random forest was conducted to select relevant proteins and generate a predictive model of recurrent CVE. RESULTS: We included 86 patients (median age: 61 years, median BMI: 29.4 kg/m2 and 86 % males) admitted for ACS with severe OSA (56 without recurrent CVE/30 with recurrent CVE). The plasma levels of 38 proteins were differentially expressed between groups. Additionally, 12 proteins had a significant association with respiratory polygraphy parameters. Three proteins discriminate with an AUC of 0.81 (95 % CI of 0.71-0.9) between severe OSA patients with and without recurrent CVE. These proteins were implicated in cell proliferation, communication and apoptosis, and regulation/response to the inflammatory and immune systems. CONCLUSION: In ACS patients with severe OSA, a proteomic profile was associated with recurrent CVEs. This proteomic profile was correlated with specific OSA parameters from respiratory polygraphy. Proteomic profiling may provide an new direction for patient risk stratification and clinical management.

One Year Overview and Follow-Up in a Post-COVID Consultation of Critically Ill Patients.

The long-term clinical management and evolution of a cohort of critical COVID-19 survivors have not been described in detail. We report a prospective observational study of COVID-19 patients admitted to the ICU between March and August 2020. The follow-up in a post-COVID consultation comprised symptoms, pulmonary function tests, the 6-minute walking test (6MWT), and chest computed tomography (CT). Additionally, questionnaires to evaluate the prevalence of post-COVID-19 syndrome were administered at 1 year. A total of 181 patients were admitted to the ICU during the study period. They were middle-aged (median [IQR] of 61 [52;67]) and male (66.9%), with a median ICU stay of 9 (5-24.2) days. 20% died in the hospital, and 39 were not able to be included. A cohort of 105 patients initiated the follow-up. At 1 year, 32.2% persisted with respiratory alterations and needed to continue the follow-up. Ten percent still had moderate/severe lung diffusion (DLCO) involvement (<60%), and 53.7% had a fibrotic pattern on CT. Moreover, patients had a mean (SD) number of symptoms of 5.7 ± 4.6, and 61.3% met the criteria for post-COVID syndrome at 1 year. During the follow-up, 46 patients were discharged, and 16 were transferred to other consultations. Other conditions, such as emphysema (21.6%), COPD (8.2%), severe neurocognitive disorders (4.1%), and lung cancer (1%) were identified. A high use of health care resources is observed in the first year. In conclusion, one-third of critically ill COVID-19 patients need to continue follow-up beyond 1 year, due to abnormalities on DLCO, chest CT, or persistent symptoms.

Respiratory Polygraphy Patterns and Risk of Recurrent Cardiovascular Events in Patients With Acute Coronary Syndrome.

Introduction: Obstructive sleep apnea (OSA) severity is based on the apnea-hypopnea index (AHI). The AHI is a simplistic measure that is inadequate for capturing disease severity and its consequences in cardiovascular diseases (CVDs). Deleterious effects of OSA have been suggested to influence the prognosis of specific endotypes of patients with acute coronary syndrome (ACS). We aim to identify respiratory polygraphy (RP) patterns that contribute to identifying the risk of recurrent cardiovascular events in patients with ACS. Methods: Post hoc analysis of the ISAACC study, including 723 patients admitted for a first ACS (NCT01335087) in which RP was performed. To identify specific RP patterns, a principal component analysis (PCA) was performed using six RP parameters: AHI, oxygen desaturation index, mean and minimum oxygen saturation (SaO2), average duration of events and percentage of time with SaO2 < 90%. An independent HypnoLaus population-based cohort was used to validate the RP components. Results: From the ISAACC study, PCA showed that two RP components accounted for 70% of the variance in the RP data. These components were validated in the HypnoLaus cohort, with two similar RP components that explained 71.3% of the variance in the RP data. The first component (component 1) was mainly characterized by low mean SaO2 and obstructive respiratory events with severe desaturation, and the second component (component 2) was characterized by high mean SaO2 and long-duration obstructive respiratory events without severe desaturation. In the ISAACC cohort, component 2 was associated with an increased risk of recurrent cardiovascular events in the third tertile with an adjusted hazard ratio (95% CI) of 2.44 (1.07 to 5.56; p-value = 0.03) compared to first tertile. For component 1, no significant association was found for the risk of recurrent cardiovascular events. Conclusion: A RP component, mainly characterized by intermittent hypoxemia, is associated with a high risk of recurrent cardiovascular events in patients without previous CVD who have suffered a first ACS.

Prognostic implications of comorbidity patterns in critically ill COVID-19 patients: A multicenter, observational study.

Background: The clinical heterogeneity of COVID-19 suggests the existence of different phenotypes with prognostic implications. We aimed to analyze comorbidity patterns in critically ill COVID-19 patients and assess their impact on in-hospital outcomes, response to treatment and sequelae. Methods: Multicenter prospective/retrospective observational study in intensive care units of 55 Spanish hospitals. 5866 PCR-confirmed COVID-19 patients had comorbidities recorded at hospital admission; clinical and biological parameters, in-hospital procedures and complications throughout the stay; and, clinical complications, persistent symptoms and sequelae at 3 and 6 months. Findings: Latent class analysis identified 3 phenotypes using training and test subcohorts: low-morbidity (n=3385; 58%), younger and with few comorbidities; high-morbidity (n=2074; 35%), with high comorbid burden; and renal-morbidity (n=407; 7%), with chronic kidney disease (CKD), high comorbidity burden and the worst oxygenation profile. Renal-morbidity and high-morbidity had more in-hospital complications and higher mortality risk than low-morbidity (adjusted HR (95% CI): 1.57 (1.34-1.84) and 1.16 (1.05-1.28), respectively). Corticosteroids, but not tocilizumab, were associated with lower mortality risk (HR (95% CI) 0.76 (0.63-0.93)), especially in renal-morbidity and high-morbidity. Renal-morbidity and high-morbidity showed the worst lung function throughout the follow-up, with renal-morbidity having the highest risk of infectious complications (6%), emergency visits (29%) or hospital readmissions (14%) at 6 months (p<0.01). Interpretation: Comorbidity-based phenotypes were identified and associated with different expression of in-hospital complications, mortality, treatment response, and sequelae, with CKD playing a major role. This could help clinicians in day-to-day decision making including the management of post-discharge COVID-19 sequelae. Funding: ISCIII, UNESPA, CIBERES, FEDER, ESF.

Long-Term Effect of Obstructive Sleep Apnea and Continuous Positive Airway Pressure Treatment on Blood Pressure in Patients with Acute Coronary Syndrome: A Clinical Trial.

Rationale: Obstructive sleep apnea (OSA) is prevalent in patients with acute coronary syndrome (ACS) and is a cause of secondary hypertension. Objectives: To explore the long-term effects of OSA and continuous positive airway pressure (CPAP) treatment on blood pressure (BP) in patients with ACS. Methods: Post hoc analysis of the ISAACC study (Continuous Positive Airway Pressure in Patients with Acute Coronary Syndrome and Obstructive Sleep Apnea; NCT01335087) included 1,803 patients admitted for ACS. Patients with OSA (apnea-hypopnea index [AHI], ⩾15 events/h) were randomly assigned to receive either CPAP or usual care and were seen in follow-up for 1-5 years. Office BP was determined at each visit. Results: We included 596 patients without OSA, 978 patients in the usual care or poor CPAP adherence group, and 229 patients in the good CPAP adherence group. At baseline, 52% of the patients were diagnosed with hypertension. Median (25th to 75th percentile) age and body mass index were 59 (52.0 to 67.0) years and 28.2 (25.6 to 31.2) kg/m2, respectively. After a median (25th to 75th percentile) follow-up of 41.2 (18.3 to 59.6) months, BP changes were similar in the OSA and non-OSA groups. However, we observed an increase in BP in the third tertile of the AHI (AHI, >40 events/h), with a maximum difference in mean BP of +3.3 mm Hg at 30 months. Patients with OSA with good CPAP adherence (⩾4 h/night) reduced mean BP after 18 months compared with patients with usual care/poor CPAP adherence, with a maximum mean difference (95% confidence interval) of -4.7 (-6.7 to -2.7) mm Hg. In patients with severe OSA, we observed a maximum mean difference of -7.1 (-10.3 to -3.8) mm Hg. Conclusions: In patients with ACS, severe OSA is associated with a long-term increase in BP, which is reduced by good CPAP adherence. Clinical trial registered with www.clinicaltrials.gov (NCT01335087).

Impact of time to intubation on mortality and pulmonary sequelae in critically ill patients with COVID-19: a prospective cohort study.

QUESTION: We evaluated whether the time between first respiratory support and intubation of patients receiving invasive mechanical ventilation (IMV) due to COVID-19 was associated with mortality or pulmonary sequelae. MATERIALS AND METHODS: Prospective cohort of critical COVID-19 patients on IMV. Patients were classified as early intubation if they were intubated within the first 48 h from the first respiratory support or delayed intubation if they were intubated later. Surviving patients were evaluated after hospital discharge. RESULTS: We included 205 patients (140 with early IMV and 65 with delayed IMV). The median [p25;p75] age was 63 [56.0; 70.0] years, and 74.1% were male. The survival analysis showed a significant increase in the risk of mortality in the delayed group with an adjusted hazard ratio (HR) of 2.45 (95% CI 1.29-4.65). The continuous predictor time to IMV showed a nonlinear association with the risk of in-hospital mortality. A multivariate mortality model showed that delay of IMV was a factor associated with mortality (HR of 2.40; 95% CI 1.42-4.1). During follow-up, patients in the delayed group showed a worse DLCO (mean difference of - 10.77 (95% CI - 18.40 to - 3.15), with a greater number of affected lobes (+ 1.51 [95% CI 0.89-2.13]) and a greater TSS (+ 4.35 [95% CI 2.41-6.27]) in the chest CT scan. CONCLUSIONS: Among critically ill patients with COVID-19 who required IMV, the delay in intubation from the first respiratory support was associated with an increase in hospital mortality and worse pulmonary sequelae during follow-up.

Benzodiazepine and Z-Drug Use and the Risk of Developing Dementia.

BACKGROUND: Benzodiazepines (BZDs) and Z-drugs (BZDRs) are among the most prescribed medications for anxiety and insomnia, especially among older adults. Our objective was to investigate the association between the use of BZDRs and the risk of dementia. METHODS: A community-based retrospective cohort study was conducted based on the data available from 2002 to 2015 in Catalan Health Service. This cohort included all BZDR users (N = 83 138) and nonusers (N = 84 652) older than 45 years. A minimum 5-year lag window and an adjustment for psychiatric problems were applied for the data analysis. RESULTS: The hazard ratio (HR) for the risk of incident dementia among BZDR users was 1.22 (95% CI = 1.15 to 1.31). This risk was not significant after adjusting the data confounding factors (HR = 1.01; 95% CI = 0.94 to 1.08). We observed a higher risk with short-to-intermediate half-life BZDs (HR = 1.11; 95% CI = 1.04 to 1.20) and Z-drugs (HR = 1.20; 95% CI = 1.07 to 1.33) than for intermediate-to-long half-life BZDs (HR = 1.01; 95% CI = 0.94 to 1.08). We demonstrated a higher risk of incident dementia (HR = 1.23; 95% CI = 1.07 to 1.41 and odds ratio = 1.38; 95% CI = 1.27 to 1.50, respectively) in patients who received 91 to 180 defined daily doses (DDDs) and >180 DDDs compared with patients who received <90 DDD. Regarding patient sex, the risk of dementia was higher in women than in men. CONCLUSION: We found that the incidence of dementia was not higher among all BZDR users. Short half-life BZDs and Z-drugs increased the risk of dementia at the highest doses, especially in female patients, showing a dose-response relationship.

Prevalence of Obstructive Sleep Apnoea and Its Association With Atherosclerotic Plaques in a Cohort of Subjects With Mild-Moderate Cardiovascular Risk.

INTRODUCTION: Classic cardiovascular risk factors do not explain all the cardiovascular events. Obstructive sleep apnoea (OSA) has been proposed as a potential and prevalent cardiovascular risk factor. Our study aimed to describe the prevalence of OSA in a middle-aged cohort with mild-moderate cardiovascular risk and evaluate its association with atherosclerotic disease. METHODS: This is an observational cross-sectional ancillary study of the ILERVAS project which was aimed to study subclinical arterial disease in a cohort with mild-moderate cardiovascular risk. In a sample of consecutive subjects, we performed a sleep study and evaluate OSA prevalence and its association with carotid and femoral atheroma plaques and atherosclerotic burden. RESULTS: Overall, 966 subjects with a median age of 57 years (25-75th percentile; 52-62) and a body mass index (BMI) of 28.5kg/m2 (25.6-31.6) were included. Of these, 72.6% (69.7%-75.3%) had OSA (apnoea-hypopnoea index (AHI)≥5/h); 35.7% (32.8%-38.8%) had mild OSA (AHI 5-14.9/h) and 36.9% (33.9%-39.9%) had moderate/severe OSA (AHI≥15/h). Mean oxygen saturation and the percentage of time with oxygen saturation<90% (CT90) were associated with atherosclerotic burden (eß (95%CI) 0.932 (0.892, 0.974); 1.005 (1.002, 1.009), respectively) and total plaque (OR (95%CI) 0.88 (0.797,0.971); 1.013 (1.004,1.021), respectively). No association with the AHI or oxygen desaturation index was found. CONCLUSIONS: This study confirms a high prevalence of OSA in patients with mild-moderate cardiovascular risk and shows an association between atherosclerotic burden, total and femoral plaque with CT90 and mean oxygen saturation, suggesting the importance of OSA-related hypoxaemia in the induction of atherosclerotic disease.

Multidimensional sleep health is associated with mental well-being in Australian adults.

The few studies assessing the relationship between mental health and a multidimensional measure of sleep have been conducted in samples of almost exclusively women. In the present study, we therefore assessed associations of multidimensional sleep health with mental well-being in Australian adults. A cross-sectional, national online survey of sleep health was conducted in 2019 in 2,044 community dwelling adults aged 18-90 years. Composite scores of self-reported healthy sleep were based on Ru-SATED (R-SATED) dimensions of satisfaction, alertness, timing, efficiency and duration scored 0 (never/rarely), 1 (sometimes) or 2 (usually/always), and regularity (social jet lag) was scored 0 (≥1 hr) or 1 (<1 hr). Mental well-being was identified by a report of no problem on the EuroQol (European quality of life) five dimension five level scale (EQ-5D-5L) anxiety/depression scale, as well as absence of six chronic depressive symptoms. Ordinal logistic regression analyses determined associations of mental well-being with sleep dimensions, and total R-SATED (range 0-11) and SATED scores (0-10), adjusted for sociodemographic and health factors. In males and females, healthy categories of SATED dimensions (but not regularity) were associated with mental well-being. A 1 unit increase in the total SATED score (mean [SD] 6.6 [2.1]) was associated with less problems on the EQ-5D-5L (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.08-1.14) and fewer chronic depressive symptoms (OR 1.20, 95% CI 1.17-1.23). These estimates did not differ when the total R-SATED score was considered. Sleep health promotion focussing solely on traditional messaging around healthy sleep duration may limit mental health gains. Rather, a more holistic approach to public health messaging to improve sleep health literacy may be beneficial for mental well-being.

Clinical management and outcome differences between first and second waves among COVID-19 hospitalized patients: A regional prospective observational cohort.

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<0.001), ICU admissions (31.9% vs 13.3%, p<0.001) and the number of patients who required mechanical ventilation (OR = 0.12 [0.05-10.26]; p<0.001) were reduced. There were no significant differences in hospital and 30-day after discharge mortality (adjusted HR = 1.56; p = 0.1056) or hospital readmissions. New treatments and clinical strategies appear to improve hospital length, ICU admissions and the requirement for mechanical ventilation. However, we did not observe differences in mortality or readmissions.

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.

Implementing mHealth-Enabled Integrated Care for Complex Chronic Patients With Osteoarthritis Undergoing Primary Hip or Knee Arthroplasty: Prospective, Two-Arm, Parallel Trial.

BACKGROUND: Osteoarthritis is a disabling condition that is often associated with other comorbidities. Total hip or knee arthroplasty is an effective surgical treatment for osteoarthritis when indicated, but comorbidities can impair their results by increasing complications and social and economic costs. Integrated care (IC) models supported by eHealth can increase efficiency through defragmentation of care and promote patient-centeredness. OBJECTIVE: This study aims to assess the effectiveness and cost-effectiveness of implementing a mobile health (mHealth)-enabled IC model for complex chronic patients undergoing primary total hip or knee arthroplasty. METHODS: As part of the Horizon 2020 Personalized Connected Care for Complex Chronic Patients (CONNECARE) project, a prospective, pragmatic, two-arm, parallel implementation trial was conducted in the rural region of Lleida, Catalonia, Spain. For 3 months, complex chronic patients undergoing total hip or knee arthroplasty and their caregivers received the combined benefits of the CONNECARE organizational IC model and the eHealth platform supporting it, consisting of a patient self-management app, a set of integrated sensors, and a web-based platform connecting professionals from different settings, or usual care (UC). We assessed changes in health status (12-item short-form survey [SF-12]), unplanned visits and admissions during a 6-month follow-up, and the incremental cost-effectiveness ratio. RESULTS: A total of 29 patients were recruited for the mHealth-enabled IC arm, and 30 patients were recruited for the UC arm. Both groups were statistically comparable for baseline characteristics, such as age; sex; type of arthroplasty; and Charlson index, American Society of Anesthesiologists classification, Barthel index, Hospital Anxiety and Depression scale, Western Ontario and McMaster Universities Osteoarthritis Index, and Pfeiffer mental status questionnaire scores. Patients in both groups had significant increases in the SF-12 physical domain and total SF-12 score, but differences in differences between the groups were not statistically significant. IC patients had 50% fewer unplanned visits (P=.006). Only 1 hospital admission was recorded during the follow-up (UC arm). The IC program generated savings in different cost scenarios, and the incremental cost-effectiveness ratio demonstrated cost-effectiveness. CONCLUSIONS: Chronic patients undergoing hip or knee arthroplasty can benefit from the implementation of patient-centered mHealth-enabled IC models aimed at empowering patients and facilitating transitions from specialized hospital care to primary care. Such models can reduce unplanned contacts with the health system and reduce overall health costs, proving to be cost-effective. Overall, our findings support the notion of system-wide cross-organizational care pathways supported by mHealth as a successful way to implement IC for patients undergoing elective surgery.

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.