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Background: This study aims to (i) evaluate the association between anxiety and depressive symptoms and health-related quality of life (HRQoL); and (ii) identify the effect modifiers of this relationship in patients with chronic obstructive pulmonary disease (COPD).Methods: A total of 337 clinically stable COPD patients answered the St. George's Respiratory Questionnaire (SGRQ) (assessing HRQoL) and the Hospital Anxiety and Depression Scale (HADS). Socio-demographic information, lung function, and other clinical data were collected.Results: Most patients (93%) were male; they had a mean (SD) age of 68 (9) years and mild to very severe COPD (post-bronchodilator FEV1 52 (16)% predicted). Multivariate analyses showed that anxiety, depression, or both conditions were associated with poor HRQoL (for all SGRQ domains). The association between anxiety and total HRQoL score was 6.7 points higher (indicating a worse HRQoL) in current workers than in retired individuals. Estimates for patients with "both anxiety and depression" were 5.8 points lower in stage I-II than in stage III-IV COPD, and 10.2 points higher in patients with other comorbidities than in those with only COPD.Conclusions: This study shows a significant association between anxiety, depression, or both conditions and impaired HRQoL. Clinically relevant factors affecting the magnitude of this association include work status, COPD severity, and the presence of comorbidities. [ABSTRACT FROM AUTHOR]

Rationale: Although obstructive sleep apnea (OSA) is a prevalent condition among patients with acute coronary syndrome (ACS), the impact of OSA on cardiovascular event (CVE) recurrence is not homogeneous. We previously defined a specific phenotype of first-ACS patients without previous cardiovascular disease who are at increased risk of OSA-related CVE recurrence. However, the pathobiological mechanisms whereby OSA leads to adverse cardiovascular outcomes in this singular ACS phenotype remain to be investigated., Objective: To characterize the molecular pathways that relate OSA with CVE recurrence., Methods: This post hoc analysis of the ISAACC study (NCT01335087) included subjects without previous cardiovascular disease who were hospitalized for a first ACS and developed a recurrent CVE during the follow-up. Patients underwent respiratory polygraphy and fasting blood extraction during hospitalization. Two study groups were established on the basis of the apnea-hypopnea index (AHI): untreated severe OSA (AHI≥30events/h) and non-OSA (AHI<15events/h) groups. Proteomic profiling analysis included 276 cardiovascular and inflammatory-related plasma proteins via Olink® technology., Results: Proteomics was performed in 58 patients (77.6% male, median [p25;p75] age 58.0 [51.2;65.8] years, and median BMI 28.6 [25.8;31.2]kg/m 2 ). Thirty patients had severe OSA, and 28 subjects were considered non-OSA controls. A total of 24 plasma proteins were differentially expressed between the groups. Among these proteins, 18 were significantly associated with OSA severity parameters derived from respiratory polygraphy. Further bioinformatic analyses of OSA-related proteins revealed their involvement in several molecular pathways, mostly related to immune function, cell signaling, and inflammatory processes., Conclusion: A specific proteomic profile related to OSA presence and severity was identified in the plasma of ACS patients who developed recurrent CVEs. This analysis suggests the activation of key OSA-mediated molecular pathways with potential implications for cardiovascular prognosis., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Randomized controlled trials (RCT) have not demonstrated a role for continuous positive airway pressure (CPAP) on the secondary prevention of major cardiovascular events in obstructive sleep apnea (OSA) patients. However, participants in RCTs are substantially different from real-world patients. Therefore, we aimed to assess the effect of CPAP treatment on major cardiovascular events in real-world OSA patients., Methods: Population-based longitudinal observational study including all OSA patients with an active CPAP prescription at the beginning of 2011 in Catalonia, Spain, that terminated CPAP treatment during 2011 and did not have CPAP prescriptions between 2012-2015; and propensity-score-matched OSA patients that continued CPAP treatment until the end of 2015 or death. Adjusted hazard ratios were used to assess the association between CPAP treatment and overall and cardiovascular mortality, cardiovascular hospitalizations, or major adverse cardiovascular events (MACEs)., Results: 3638 CPAP terminators and 10,914 propensity-score-matched continuators were included (median age 67 [57-77] years, 71.4% male). During a median follow-up of 47.9 months CPAP continuators showed a lower risk of cardiovascular death than terminators (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.50-0.75) after adjusting by age, sex and key comorbidities. Similar results were found for cardiovascular hospitalizations (HR: 0.87; 95% CI: 0.76-0.99) and MACEs (HR: 0.84; 95% CI: 0.75-0.95)., Conclusion: CPAP treatment continuation could be associated with a significantly lower risk of major cardiovascular events in real-world OSA patients. This result highlights the importance of including real-world patients in studies on OSA., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Healthy lifestyle interventions have a positive impact on multiple disease trajectories, including cancer-related outcomes. Specifically, appropriate habitual physical activity, adequate sleep, and a regular wholesome diet are of paramount importance for the wellness and supportive care of survivors of cancer. Mobile health (mHealth) apps have the potential to support novel tailored lifestyle interventions., Objective: This observational pilot study aims to assess the feasibility of mHealth multidimensional longitudinal monitoring in survivors of cancer. The primary objective is to test the compliance (user engagement) with the monitoring solution. Secondary objectives include recording clinically relevant subjective and objective measures collected through the digital solution., Methods: This is a monocentric pilot study taking place in Bangor, Wales, United Kingdom. We plan to enroll up to 100 adult survivors of cancer not receiving toxic anticancer treatment, who will provide self-reported behavioral data recorded via a dedicated app and validated questionnaires and objective data automatically collected by a paired smartwatch over 16 weeks. The participants will continue with their normal routine surveillance care for their cancer. The primary end point is feasibility (eg, mHealth monitoring acceptability). Composite secondary end points include clinically relevant patient-reported outcome measures (eg, the Edmonton Symptom Assessment System score) and objective physiological measures (eg, step counts). This trial received a favorable ethical review in May 2023 (Integrated Research Application System 301068)., Results: This study is part of an array of pilots within a European Union funded project, entitled "GATEKEEPER," conducted at different sites across Europe and covering various chronic diseases. Study accrual is anticipated to commence in January 2024 and continue until June 2024. It is hypothesized that mHealth monitoring will be feasible in survivors of cancer; specifically, at least 50% (50/100) of the participants will engage with the app at least once a week in 8 of the 16 study weeks., Conclusions: In a population with potentially complex clinical needs, this pilot study will test the feasibility of multidimensional remote monitoring of patient-reported outcomes and physiological parameters. Satisfactory compliance with the use of the app and smartwatch, whether confirmed or infirmed through this study, will be propaedeutic to the development of innovative mHealth interventions in survivors of cancer., International Registered Report Identifier (irrid): PRR1-10.2196/52957., (©Pasquale F Innominato, Jamie H Macdonald, Wendy Saxton, Laura Longshaw, Rachel Granger, Iman Naja, Carlo Allocca, Ruth Edwards, Solah Rasheed, Frans Folkvord, Jordi de Batlle, Rohit Ail, Enrico Motta, Catherine Bale, Claire Fuller, Anna P Mullard, Christian P Subbe, Dawn Griffiths, Nicholas I Wreglesworth, Leandro Pecchia, Giuseppe Fico, Alessio Antonini. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 30.04.2024.)

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., (© 2024. The Author(s).)

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., Competing Interests: Conflict of interest: K. Waeijen-Smit, M. Crutsen, S. Keene, T.J. Ringbæk, F. Fabbian, C-t. Lun, B. Ergan, C. Estebam, J.M. Quintana Lopez, C.L. Chang, R.J. Hancox, E. Shafuddin, H. Ellis, C. Janson, G. Gudmundsson, D. Epstein, A. Lacoma, C. Osadnik, I. Alia, F. Spannella, Z. Karakurt, H. Mehravaran, C. Utens, M.D. de Kruif, F.W.S. Ko, S.P. Trethewey, K. Vermeersch, S. Zilberman-Itskovich, C. Echevarria, R.T.M. Sprooten, P. Faverio, H.J. Prins and S. Houben-Wilke have no grants or personal fees to report. Conflict of interest: M. Miravitlles has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Kamada, Takeda, Zambon, CSL Behring, Specialty Therapeutics, Janssen, Grifols and Novartis, consulting fees from AstraZeneca, Atriva Therapeutics, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, CSL Behring, Inhibrx, Ferrer, Menarini, Mereo Biopharma, Spin Therapeutics, ONO Pharma, Palobiofarma SL, Takeda, Novartis, Novo Nordisk, Sanofi and Grifols and research grants from Grifols. Conflict of interest: E. Crisafulli has received honoraria for lecturing, scientific advisory boards and participation in clinical studies for AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Menarini, Novartis, Qbgroup and Sanofi. Conflict of interest: A. Torres reports speaker/consulting honoraria from Pfizer, MSD, Janssen and Biomerieux. Conflict of interest: C. Mueller has received research support from the Swiss National Science Foundation, the Swiss Heart Foundation, the University of Basel, the University Hospital Basel, the KTI, Abbott, Beckman Coulter, BRAHMS, Idorsia, LSI-Medience, Ortho Diagnostics, Novartis, Roche, Siemens, SpinChip and Singulex, as well as speaker/consulting honoraria from Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Daiichi Sankyo, Idorsia, Novartis, Osler, Roche, SpinChip and Sanofi, all outside the submitted work. Conflict of interest: P. Schuetz has received grants from Nestle, Abbot, bioMerieux and Thermofisher outside the submitted work. Conflict of interest: E. Mekov has received grants and personal fees from Chiesi, and speaker or consulting fees from AstraZeneca and Chiesi. Conflict of interest: T.H. Harries is supported by a National Institute for Health and Care Research Academic Clinical Lectureship. Conflict of interest: J.L. López-Campos has received honoraria during the last 3 years for lecturing, scientific advice, participation in clinical studies or writing for publications for (alphabetical order): AstraZeneca, Bial, Boehringer, Chiesi, CSL Behring, Faes, Ferrer, Gebro, Grifols, GSK, Megalabs, Menarini and Novartis. Conflict of interest: C.S. Ulrik has received personal fees and grants from AstraZeneca, Chiesi, Boehringer Ingelheim, GSK, Novartis, Sanofi, Menarini, TEVA, ALK-Abello, Takeda, Orion Pharma, TFF Pharmaceuticals and Covis Pharma outside the submitted work. Conflict of interest: J. Dominguez has received honoraria for lectures from Oxford Immunotec (UK) and received payments for license transference from GenID (Germany), and grants from La Fundació La Marató TV3, Instituto de Salud Carlos III (CP03/00112), Catalan Pulmonology Society (SOCAP), Catalan Pulmonology Foundation (FUCAP) and Spanish Society of Pulmonology and Thoracic Surgery (SEPAR). Conflict of interest: A.M. Turner reports research grants outside the submitted work from AstraZeneca, Resmed, Phillips, Chiesi, Grifols, CSL Behring and NIHR, and honoraria from GSK and Boehringer Ingelheim. Conflict of interest: D. Bumbacea has received grants and personal fees in the last 3 years from AstraZeneca, Eli Lilly, Novartis, Sanofi and Synairgen outside of the submitted work. Conflict of interest: PBM has received grants and personal fees from Philips, ResMed, Breas, Chiesi, Fischer & Paykel and, Sanofi outside the submitted work. Conflict of interest: J. Steer has received grants and honoraria, outside the submitted work, from Chiesi, Menarini Group, AstraZeneca and Pfizer. Conflict of interest: S.C. Bourke has received research grants from GSK (BEC COPD IRAS 285200), and additional support from Radiometer for an NIHR-funded study (NIVOW IRAS 313485), Philips, ResMed, and Pfizer Open Air, took part in clinical advisory boards with Philips and AstraZeneca, and has received honoraria from Boehringer Ingelheim, Chiesi, GSK, and AstraZeneca. Conflict of interest: N. Lane reports research grants from Bright Northumbria and The ResMed Foundation; and nonfinancial support from Chiesi and BREAS outside the submitted work. Conflict of interest: J. de Batlle acknowledges receiving financial support from Instituto de Salud Carlos III (Miguel Servet 2019: CP19/00108), co-funded by the European Social Fund, “Investing in your future”. Conflict of interest: R. Russell has received personal fees, outside of the submitted work, from AstraZeneca, Chiesi, Covis, GlaxoSmithKline and Boehringer Ingelheim. Conflict of interest: J.L. Cross has received grants from National Institute of Health Research. Conflict of interest: M.A. Spruit has received grants from the Netherlands Lung Foundation, Stichting Asthma Bestrijding, AstraZeneca, Boehringer Ingeheim, TEVA and CHIESI outside the submitted work. Conflict of interest: S.O. Simons has received grants and personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Chiesi outside the submitted work. Conflict of interest: F.M.E. Franssen has received grants and personal fees from AstraZeneca, Chiesi, Boehringer Ingelheim, Glaxosmithkline, Novartis and MSD outside the submitted work. Conflict of interest: All authors declare no conflicts of interest in relation to the present study., (Copyright ©The authors 2024.)

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., (©Jordi de Batlle, Ivan D Benítez, Anna Moncusí-Moix, Odysseas Androutsos, Rosana Angles Barbastro, Alessio Antonini, Eunate Arana, Maria Fernanda Cabrera-Umpierrez, Gloria Cea, George Ε Dafoulas, Frans Folkvord, Ane Fullaondo, Francesco Giuliani, Hsiao-Ling Huang, Pasquale F Innominato, Przemyslaw Kardas, Vivian W Q Lou, Yannis Manios, Maria Matsangidou, Franco Mercalli, Mounir Mokhtari, Silvio Pagliara, Julia Schellong, Lisa Stieler, Konstantinos Votis, Paula Currás, Maria Teresa Arredondo, Jorge Posada, Sergio Guillén, Leandro Pecchia, Ferran Barbé, Gerard Torres, Giuseppe Fico, the GATEKEEPER project. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 28.06.2023.)

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 [p 25 -p 75 ] 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 (D LCO ) at follow-up was 72.02 (18.33)% predicted, with 66% of patients having D LCO <80% and 24% having D LCO <60%. CT scan showed persistent pulmonary infiltrates, fibrotic lesions, and emphysema in 33%, 25% and 6% of patients, respectively. Key variables associated with D LCO <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 D LCO and CT abnormalities., (Published by Elsevier España, S.L.U.)

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/m 2 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., Competing Interests: Conflict of interest statement FB received a research grant from ResMed (an Australian company that develops products related to sleep apnea), the Health Research Fund, the Spanish Ministry of Health, the Spanish Respiratory Society, the Catalonian Cardiology Society, Esteve-Teijin (Spain), Oxigen Salud (Spain), and ALLER to develop the ISAACC trial. ResMed partly funded the ISAACC study but did not participate in nor was involved in decisions regarding study development or the present manuscript. All other authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 González, Zuil, Benítez, de Gonzalo-Calvo, Aguilar, Santisteve, Vaca, Minguez, Seck, Torres, de Batlle, Gómez, Barril, Moncusí-Moix, Monge, Gort-Paniello, Ferrer, Ceccato, Fernández, Motos, Riera, Menéndez, Garcia-Gasulla, Peñuelas, Labarca, Caballero, Barberà, Torres and Barbé.)

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 (SaO 2 ), average duration of events and percentage of time with SaO 2 < 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 SaO 2 and obstructive respiratory events with severe desaturation, and the second component (component 2) was characterized by high mean SaO 2 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zapater, Solelhac, Sánchez-de-la-Torre, Gracia-Lavedan, Benitez, Torres, De Batlle, Haba-Rubio, Berger, Abad, Duran-Cantolla, Urrutia, Mediano, Masdeu, Ordax-Carbajo, Masa, De la Peña, Mayos, Coloma, Montserrat, Chiner, Mínguez, Pascual, Cortijo, Martínez, Dalmases, Lee, McEvoy, Barbé, Heinzer and Sánchez-de-la-Torre.)

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/m 2 (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 (e β (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., (Copyright © 2021 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

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., Competing Interests: None declared., (© 2022 The Author(s).)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of CINP.)

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 [p 25 ;p 75 ] 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., (© 2022. The Author(s).)

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., Competing Interests: NO authors have competing interests The authors have declared that no competing interests exist.

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., (©Cecilia Turino, Ivan D Benítez, Xavier Rafael-Palou, Ana Mayoral, Alejandro Lopera, Lydia Pascual, Rafaela Vaca, Anunciación Cortijo, Anna Moncusí-Moix, Mireia Dalmases, Eloisa Vargiu, Jordi Blanco, Ferran Barbé, Jordi de Batlle. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 18.10.2021.)

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., (©Jordi Colomina, Reis Drudis, Montserrat Torra, Francesc Pallisó, Mireia Massip, Eloisa Vargiu, Nuria Nadal, Araceli Fuentes, Marta Ortega Bravo, Felip Miralles, Ferran Barbé, Gerard Torres, Jordi de Batlle, The CONNECARE-Lleida Group. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 02.09.2021.)

Background: Integrated care can generate health and social care efficiencies through the defragmentation of care and adoption of patient-centered preventive models. eHealth can be a key enabling technology for integrated care., Objective: The aim of this study was to assess the effectiveness and cost-effectiveness of the implementation of a mobile health (mHealth)-enabled integrated care model for complex chronic patients., Methods: As part of the CONNECARE Horizon 2020 project, a prospective, pragmatic, two-arm, parallel implementation trial was held in a rural region of Catalonia, Spain. During 3 months, elderly patients with chronic obstructive pulmonary disease or heart failure and their carers experienced the combined benefits of the CONNECARE organizational integrated care 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. We assessed changes in health status with the 12-Item Short-Form Survey (SF-12), unplanned visits and admissions during a 6-month follow up, and the incremental cost-effectiveness ratio (ICER)., Results: A total of 48 patients were included in the integrated care arm and 28 patients receiving usual care were included in the control arm (mean age 82 years, SD 7 years; mean Charlson index 7, SD 2). Integrated care patients showed a significant increase in the SF-12 physical domain with a mean change of +3.7 (SD 8.4) (P=.004) and total SF-12 score with a mean change of +5.8 (SD 12.8) (P=.003); however, the differences in differences between groups were not statistically significant. Integrated care patients had 57% less unplanned visits (P=.004) and 50% less hospital admissions related to their main chronic diseases (P=.32). The integrated care program generated savings in different cost scenarios and the ICER demonstrated the cost-effectiveness of the program., Conclusions: The implementation of a patient-centered mHealth-enabled integrated care model empowering the patient, and connecting primary, hospital, and social care professionals reduced unplanned contacts with the health system and health costs, and was cost-effective. These findings support the notion of system-wide cross-organizational care pathways supported by mHealth as a successful way to implement integrated care., (©Jordi de Batlle, Mireia Massip, Eloisa Vargiu, Nuria Nadal, Araceli Fuentes, Marta Ortega Bravo, Felip Miralles, Ferran Barbé, Gerard Torres, CONNECARE-Lleida Group. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 14.01.2021.)

Proton pump inhibitors (PPIs) are among the most prescribed medications. Previous epidemiological studies have presented contradictory results about PPIs and the risk of dementia. Our objective was to investigate the association between the use of PPIs and an increasing risk of incident AD or non-AD dementias. A community-based retrospective cohort study was conducted based on the data available from 1st January 2002 to 31st December 2015 in the Catalan health service (CatSalut) system. This cohort included all PPI users (N = 36,360) and non-users (N = 99,362). A lag window of 5 years was considered between the beginning of the PPI treatment and the diagnosis of dementia. PPI use was not associated with the risk of AD (adjusted odds ratio (OR) 1.06) (95% CI 0.93-1.21; p = 0.408). A weakly but significantly increased risk of non-AD dementias was observed among PPI users (adjusted OR 1.20, 95% CI 1.05-1.37; p = 0.007). A higher dose of PPIs was not associated with an increased risk of either AD or non-AD dementias (OR 1.20; 95% CI 0.91-1.61 and OR 0.95; 95% CI 0.74-1.22, respectively). Regarding the number of PPIs used, we observed an increased risk of AD (OR 1.47; 95% CI 1.18-1.83) and non-AD dementias (OR 1.38; 95% CI 1.12-1.70) in users of two types of PPIs compared with those who used only one type. We did not find a higher incidence of AD among PPI users, but a weak increase in the risk of non-AD dementias among PPI users was observed.