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Introduction: Among all patients with hypertension, those with resistant hypertension (RH) have the highest rates of subclinical organ damage (SOD). The prevalence of obstructive sleep apnea (OSA) is high in RH patients, and it could contribute to SOD. We aimed to investigate how OSA and its treatment are related to SOD in a large cohort of RH patients., Methods: This is an ancillary analysis to the SARAH study, a multicentre observational cohort aiming to evaluate the impact of OSA on RH. Individuals with RH who were undergoing a sleep study and have information on at least one of the SOD variables (vascular, cardiac or renal damage) were selected. Patients were followed-up for three years., Results: In total, 503 subjects were included. The participants were predominantly male, obese, and the median (IQR) apnea-hypopnea index (AHI) was 15.5 (7.90-31.5)events/h. No differences in the presence of vascular or cardiac damage were observed between OSA and non-OSA patients. A lower estimated glomerular filtration rate (eGFR) was observed in participants with OSA than in those without OSA, with an adjusted effect of -8.69mL/min/1.73m 2 (-13.59, -3.79; p value<0.001). Kidney damage was also greater in subjects with OSA, with an adjusted OR (95% CI) of 1.77 (1.09, 2.87; p value=0.02). The eGFR showed a linear dose-response relationship with OSA severity. Among patients treated with CPAP, lower eGFR values were observed in noncompliant subjects., Conclusions: OSA could contribute to worsening renal function in patients with RH. No compliance with CPAP was associated with lower values of eGFR., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Background: There is a close relationship between obstructive sleep apnoea (OSA) and resistant hypertension (RH). However, studies assessing the long-term effect of diagnosing and treating OSA on blood pressure (BP) control in these patients are lacking., Methods: To address this gap, we recruited 478 RH patients from hypertension units and followed them prospectively after they were screened for OSA through a sleep study. By performing 24-h ambulatory BP monitoring (ABPM) annually, the effect of OSA management was assessed., Results: The patients had a median (interquartile range (IQR)) age of 64.0 (57.2-69.0) years, 67% were males and most were nonsleepy, with a median (IQR) apnoea-hypopnoea index (AHI) of 15.8 (7.9-30.7) events·h -1 . The median (IQR) follow-up time was 3.01 (2.93-3.12) years. At baseline, severe OSA was associated with uncontrolled BP, nocturnal hypertension and a nondipper circadian BP pattern. Moreover, these patients had higher BP values during follow-up than did patients in the other groups. However, among patients with moderate and severe OSA, the management of sleep disordered breathing, including the implementation of continuous positive airway pressure treatment, was associated with a reduction in 24-h ABPM parameters, especially night-time BP values, at the 1-year follow-up. These benefits were attenuated over time and only subjects with severe OSA maintained an ABPM night-time reduction at 3 years. Furthermore, clinical variables such as uncontrolled BP, sex and age showed a predictive value for the BP response at 1 year of follow-up., Conclusion: A favourable long-term decrease in BP was detected by diagnosing and treating OSA in a cohort of RH patients from hypertension units, but over time this decrease was only partially maintained in severe OSA patients., Competing Interests: Conflict of interest: F. Barbé received research grants from Philips Respironics Inc. and ResMed (companies that develop products related to sleep apnoea), the Health Research Fund, the Spanish Ministry of Health, and the Spanish Respiratory Society to develop the SARAH study. Philips Respironics Inc. and ResMed partly funded the SARAH study but did not participate in nor were they involved in decisions regarding study development or the present manuscript. The remaining authors declare no competing interests., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Objectives: To investigate the sleep and circadian health of critical survivors 12 months after hospital discharge and to evaluate a possible effect of the severity of the disease within this context., Design: Observational, prospective study., Setting: Single-center study., Patients: Two hundred sixty patients admitted to the ICU due to severe acute respiratory syndrome coronavirus 2 infection., Interventions: None., Measurements and Main Results: The cohort was composed of 260 patients (69.2% males), with a median (quartile 1-quartile 3) age of 61.5 years (52.0-67.0 yr). The median length of ICU stay was 11.0 days (6.00-21.8 d), where 56.2% of the patients required invasive mechanical ventilation (IMV). The Pittsburgh Sleep Quality Index (PSQI) revealed that 43.1% of the cohort presented poor sleep quality 12 months after hospital discharge. Actigraphy data indicated an influence of the disease severity on the fragmentation of the circadian rest-activity rhythm at the 3- and 6-month follow-ups, which was no longer significant in the long term. Still, the length of the ICU stay and the duration of IMV predicted a higher fragmentation of the rhythm at the 12-month follow-up with effect sizes (95% CI) of 0.248 (0.078-0.418) and 0.182 (0.005-0.359), respectively. Relevant associations between the PSQI and the Hospital Anxiety and Depression Scale (rho = 0.55, anxiety; rho = 0.5, depression) as well as between the fragmentation of the rhythm and the diffusing lung capacity for carbon monoxide (rho = -0.35) were observed at this time point., Conclusions: Our findings reveal a great prevalence of critical survivors presenting poor sleep quality 12 months after hospital discharge. Actigraphy data indicated the persistence of circadian alterations and a possible impact of the disease severity on the fragmentation of the circadian rest-activity rhythm, which was attenuated at the 12-month follow-up. This altogether highlights the relevance of considering the sleep and circadian health of critical survivors in the long term., Competing Interests: Dr. Labarca received support for article research from the National Research and Development Agency; he acknowledges receiving financial support from the Agencia Nacional de Investigación y Desarrollo (COVID 1005), Chile. Drs. Targa and de Gonzalo-Calvo have received financial support from Instituto de Salud Carlos III (Miguel Servet 2023: CP23/00095 and Miguel Servet 2020: CP20/00041, respectively), co-funded by Fondo Social Europeo Plus. Dr. Barbé is supported by the Institució Catalana de Recerca I Estudis Avançats Academia program. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Current core cerebrospinal fluid (CSF) AD biomarkers, widely employed for diagnosis, require a lumbar puncture to be performed, making them impractical as screening tools. Considering the role of sleep disturbances in AD, recent research suggests quantitative sleep electroencephalography features as potential non-invasive biomarkers of AD pathology. However, quantitative analysis of comprehensive polysomnography (PSG) signals remains relatively understudied. PSG is a non-invasive test enabling qualitative and quantitative analysis of a wide range of parameters, offering additional insights alongside other biomarkers. Machine Learning (ML) gained interest for its ability to discern intricate patterns within complex datasets, offering promise in AD neuropathology detection. Therefore, this study aims to evaluate the effectiveness of a multimodal ML approach in predicting core AD CSF biomarkers., Methods: Mild-moderate AD patients were prospectively recruited for PSG, followed by testing of CSF and blood samples for biomarkers. PSG signals underwent preprocessing to extract non-linear, time domain and frequency domain statistics quantitative features. Multiple ML algorithms were trained using four subsets of input features: clinical variables (CLINVAR), conventional PSG parameters (SLEEPVAR), quantitative PSG signal features (PSGVAR) and a combination of all subsets (ALL). Cross-validation techniques were employed to evaluate model performance and ensure generalizability. Regression models were developed to determine the most effective variable combinations for explaining variance in the biomarkers., Results: On 49 subjects, Gradient Boosting Regressors achieved the best results in estimating biomarkers levels, using different loss functions for each biomarker: least absolute deviation (LAD) for the A β 42, least squares (LS) for p -tau and Huber for t -tau. The ALL subset demonstrated the lowest training errors for all three biomarkers, albeit with varying test performance. Specifically, the SLEEPVAR subset yielded the best test performance in predicting A β 42, while the ALL subset most accurately predicted p -tau and t -tau due to the lowest test errors., Conclusions: Multimodal ML can help predict the outcome of CSF biomarkers in early AD by utilizing non-invasive and economically feasible variables. The integration of computational models into medical practice offers a promising tool for the screening of patients at risk of AD, potentially guiding clinical decisions., 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 © 2024 Gaeta, Quijada-López, Barbé, Vaca, Pujol, Minguez, Sánchez-de-la-Torre, Muñoz-Barrutia and Piñol-Ripoll.)

Background: Previous studies challenge the impact of obstructive sleep apnea (OSA) once patients are diagnosed with Alzheimer's disease (AD). Nevertheless, OSA recognizably disrupts sleep, and relevant associations between sleep, AD pathological markers, and cognition have been demonstrated. We aimed to further explore this, evaluating the associations between each breathing cessation event that compose the apnea-hypopnea index (AHI) and the sleep structure to finally investigate whether this was related to increased levels of AD markers and higher cognitive decline., Methods: Observational, prospective study, including consecutive patients diagnosed with mild-moderate AD. The participants were submitted to overnight polysomnography followed by a cerebrospinal fluid collection for AD pathological markers levels determination. Neuropsychological assessment was performed at baseline and after 12 months of follow-up., Results: The cohort was composed of 116 patients (55.2% females) with a median [p25;p75] age of 76.0 [72.0;80.0] years and an AHI of 25.9 [15.1;48.5], which was mainly defined by the presence of hypopneas and obstructive apneas. These were distinctively associated with the sleep structure, with obstructive apneas being related to arousals and sleep lightening and hypopneas being related to an increased number of arousals only. Despite having a lower frequency, mixed and central apneas also presented associations with the sleep structure, particularly increasing the time spent in the lighter sleep stages. In relation to AD pathological markers, obstructive and mixed apneas were related to an augment in neurofilament light levels while hypopneas were associated with a higher phosphorylated-tau/amyloid-beta protein ratio. Hypopneas were the most important event for an increased cognitive decline at the 12-month follow-up., Conclusions: Our findings highlight the importance of a patient-centered approach, with a comprehensive and detailed analysis of the AHI to effectively predict the different outcomes and tailor the appropriate therapeutic strategies., (© 2023. The Author(s).)

Persistence of bovine tuberculosis (bTB) in cattle herd remains a major challenge in disease elimination due to the ineffectual removal of all infected animals in a bTB breakdown. Characterization of herds with a higher probability of experiencing further bTB breakdowns can help to implement specific risk-based policies for disease control and eradication. Here, our aim was to identify herd- and breakdown-level risk factors in bTB infected herds in Castilla y Leon, Spain, associated with a decreased time to recurrence and an increased risk of recurrence using a mixed effects Cox proportional hazards model and a multivariable logistic regression model, respectively. Results revealed that location (province), herd size and number of incoming animals/contacts were good predictors of a decreased time to bTB recurrence and an increased risk of becoming a recurrent herd. Additionally, the duration of the previous outbreak and the number of IFN-γ herd-tests applied in it were associated with increased odds of (an early) recurrence. Risk factors identified here can be used for early identification of herds in which bTB eradication may be more challenging and that should thus be subjected to increased control efforts. The characterization of high-risk herds may help to minimize the risk of reinfection and emphasize early detection and removal of bTB positive animals in the herd., Competing Interests: Declaration of Competing Interest None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of the paper. Ethical review and approval were not required for the animal study because all data was collected as part of authorized regulatory surveillance in the framework of the Spanish National Eradication Program for Bovine Tuberculosis. Written informed consent for participation was not obtained from the owners because approval from premises owners was not required for this study., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We characterized the polysomnography (PSG) parameters associated with alterations in the circadian blood pressure (BP) pattern aiming to identify the main contributors to explain the nondipper profile in obstructive sleep apnea (OSA). This is an observational prospective-multicenter study that included participants referred to the sleep unit for suspected OSA. Following a PSG study, subjects with an apnea-hypopnea index (AHI) ≥5 events/hr were included. Two groups were established based on the 24-hr ambulatory blood pressure monitoring dipping ratio (DR; night/day BP ratio): dippers (DR ≤ 0.9) and nondippers (DR > 0.9). The cohort consisted of 299 patients: 131 (43.8%) dippers and 168 (56.2%) nondippers. A significant increase in the risk of presenting a nondipper BP pattern was found along with AHI gain [odds ratio (OR) (95% CI) = 1.71 (1.28 to 2.28)]. The best AHI cutoff for predicting nondipper status was 25.2 events/hr, increasing the OR (95% CI) to 3.50 (2.02 to 6.07). The hypopnea index [OR (95% CI) = 1.70 (1.27 to 2.26)], TSat90 [OR (95% CI) = 1.41 (1.06 to 1.87)], and respiratory arousal index [OR (95% CI) = 1.74 (1.30 to 2.34)] were individually associated with the risk of a nondipping pattern. Multivariate variable selection processes identified the respiratory arousal index as the most relevant risk factor for the nondipper profile, beyond classical clinical risk factors and usual PSG metrics., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.)

Objectives: To evaluate the sleep and circadian rest-activity pattern of critical COVID-19 survivors 3 months after hospital discharge., Design: Observational, prospective study., Setting: Single-center study., Patients: One hundred seventy-two consecutive COVID-19 survivors admitted to the ICU with acute respiratory distress syndrome., Interventions: Seven days of actigraphy for sleep and circadian rest-activity pattern assessment; validated questionnaires; respiratory tests at the 3-month follow-up., Measurements and Main Results: The cohort included 172 patients, mostly males (67.4%) with a median (25th-75th percentile) age of 61.0 years (52.8-67.0 yr). The median number of days at the ICU was 11.0 (6.00-24.0), and 51.7% of the patients received invasive mechanical ventilation (IMV). According to the Pittsburgh Sleep Quality Index (PSQI), 60.5% presented poor sleep quality 3 months after hospital discharge, which was further confirmed by actigraphy. Female sex was associated with an increased score in the PSQI (p < 0.05) and IMV during ICU stay was able to predict a higher fragmentation of the rest-activity rhythm at the 3-month follow-up (p < 0.001). Furthermore, compromised mental health measured by the Hospital Anxiety and Depression Scale was associated with poor sleep quality (p < 0.001)., Conclusions: Our findings highlight the importance of considering sleep and circadian health after hospital discharge. Within this context, IMV during the ICU stay could aid in predicting an increased fragmentation of the rest-activity rhythm at the 3-month follow-up. Furthermore, compromised mental health could be a marker for sleep disruption at the post-COVID period., Competing Interests: Dr. Labarca has received financial support from Agencia Nacional de Investigacion y Desarrollo, Chile, grant COVID 1005. Dr. de Gonzalo-Calvo has received financial support from Instituto de Salud Carlos III (Miguel Servet 2020: CP20/00041), co-funded by the European Social Fund/“Investing in your future.” Drs. de Gonzalo-Calvo and Barbé disclosed work for hire. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Introduction: Contagious agalactia (CA) is a disease affecting small ruminants with worldwide distribution and caused by several mycoplasmas, especially M. agalactiae . The main option for systematic diagnosis under monitoring control programmes is the enzyme-linked immunosorbent assay (ELISA) test., Material and Methods: This study was designed to appraise the performance of two commercial indirect ELISA tests using M. agalactiae p48 protein and one using total protein, for antibody detection in small ruminants after natural infection with different M. agalactiae strains. We carried out the test evaluation using sera of confirmed M. agalactiae -positive goats with clinical signs. In addition, test agreement was assessed by kappa between the three commercial ELISA tests., Results: All three ELISA tests showed high validity scores (Youden's J: 72.9-84%). The sensitivity values for the P48 protein-based tests were 76.9% and 84.6%, and was 79% for the total protein-based test. The specificity of all tests was 100%. In addition, between the total protein-based ELISA test and the other two ELISA tests based on the P48 protein, the agreement was substantial (kappa: 0.762-0.763) and the agreement between the latter two tests was almost perfect (kappa: 0.93)., Conclusion: The validity parameters for all tests allowed their application for diagnostic purposes in lactating goats excreting M. agalactiae in milk and presenting clinical signs. The agreements show that any of these ELISA tests could be equally well used for diagnosis in programmes against CA., Competing Interests: Conflict of Interest Conflict of Interest Statement: The authors declare that there is no conflict of interests regarding the publication of this article., (© 2022 A. Sánchez et al., published by Sciendo.)

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).)

Study Objectives: To investigate the association between sleep and cognitive decline of patients with mild-moderate Alzheimer's disease., Methods: Observational, prospective study, including consecutive patients diagnosed with mild-moderate Alzheimer's disease. Cerebrospinal fluid was collected for amyloid-beta, total-tau, and phospho-tau levels determination. Also, overnight polysomnography was performed, followed by neuropsychological evaluations at baseline and after 12 months of follow-up. Principal component analysis revealed two profiles of patients in terms of sleep: one with a propensity to deepen the sleep (deep sleepers) and the other with a propensity to spend most of the time in the lighter sleep stage (light sleepers)., Results: The cohort included 125 patients with a median [IQR] of 75.0 [72.0;80.0] years. Deep and light sleepers did not present differences in relation to the cerebrospinal fluid pathological markers and to the cognitive function at the baseline. However, there was a significant difference of -1.51 (95% CI: -2.43 to -0.59) in the Mini-mental state examination after 12 months of follow-up. Accordingly, sleep depth and cognitive decline presented a dose-response relationship (p-for-trend = 0.02). Similar outcomes were observed in relation to the processing speed (Stroop words test, p-value = 0.016) and to the executive function (Verbal fluency test, p-value = 0.023)., Conclusions: Considering the increased cognitive decline presented by light sleepers, the sleep profile may have a predictive role in relation to the cognitive function of patients with mild-moderate Alzheimer's disease. The modifiable nature of sleep sets this behavior as a possible useful intervention to prevent a marked cognitive decline., Clinical Trial Information: Role of Hypoxia Ans Sleep Fragmentation in Alzheimer's Disease. and Sleep Fragmentation. Completed. NCT02814045., (© Sleep Research Society 2021. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Alterations in circadian rhythms are present in the presymptomatic stage of Alzheimer's disease (AD), possibly contributing to its pathogenesis. However, it is unknown whether such alterations are associated with worse outcomes once individuals are diagnosed with symptomatic disease. We aimed to evaluate the association between the circadian rest-activity pattern and AD-related features in patients with mild-moderate AD., Methods: We assessed the circadian rest-activity pattern of consecutive patients with mild-moderate AD through actigraphy for 14 days. Cerebrospinal fluid was obtained to determine the levels of important pathological markers including amyloid-beta protein (Aβ42), phosphorylated tau (P-tau), total tau (T-tau), and neurofilament light (NF-L). Neuropsychological evaluation was conducted at the beginning of the study and after 12 months of follow-up. Linear regression models were performed considering the global population and Aβ42+ patients only., Results: The cohort included 100 patients with mild-moderate AD. The median age [p 25 ;p 75 ] was 76.0 [73.0;80.0] years and 63.0% were female. Older age (effect size [SE] of 0.324 [0.096]; p = 0.001) and male sex (0.780 [0.193]; p = 0.001) were associated with increased fragmentation and decreased synchronization of the rhythm, respectively. After adjusting for age, sex, and season of the year, increased levels of T-tau (effect size [95% CI] of 0.343 [0.139 to 0.547]; p = 0.001) and NF-L (0.444 [0.212 to 0.676]; p = 0.001) were associated with a higher amplitude of the rest-activity rhythm. Increased fragmentation of the rhythm at baseline was associated with greater cognitive decline after one year of follow-up independent of age, sex, T-tau/Aβ42 ratio, educational level, and season of the year (- 0.715 [- 1.272 to - 0.157]; p = 0.013). Similar findings were obtained considering only the Aβ42+ patients., Conclusions: Our results suggest a potential role of the circadian rest-activity pattern in predicting the cognitive decline of patients with mild-moderate AD. Further studies are warranted to confirm these findings and to elucidate whether there is causality among the observed associations., (© 2021. The Author(s).)

Rationale: Evidence suggests that the physiopathologic consequences of obstructive sleep apnea (OSA) resemble those induced by aging. Some studies report that the deleterious effects associated with OSA might be age dependent. Objectives: To evaluate the association of OSA with the aging process and to determine whether this association is maintained across different age groups. Methods: This was an observational, prospective study including 599 patients with suspected OSA. Five hallmarks of aging were evaluated: alteration of cellular communication (serum CRP [C-reactive protein] concentration), deregulation of nutrient sensing (insulin resistance), telomere attrition (leukocyte telomeric length), mitochondrial dysfunction (leukocyte mitochondrial DNA copy number), and genomic instability (urinary 8-hydroxy-2-deoxyguanosine concentration). For age-stratified analyses, subjects were divided into four groups according to the apnea-hypopnea index (AHI) and the median age (50 yr): young patients without OSA (age < 50 yr old, AHI < 15 events/h), young patients with OSA (age < 50 yr old, AHI ⩾ 15 events/h), older patients without OSA (age ⩾ 50 yr old, AHI < 15 events/h), and older patients with OSA (age ⩾ 50 yr old, AHI ⩾ 15 events/h). Results: A dose-response relationship was found between the AHI, arousal index, and time during the night spent with an oxygen saturation less than 90% and the following hallmarks: alteration of cellular communication, deregulation of nutrient sensing, mitochondrial dysfunction, and genomic instability. Considering age-stratified analyses, OSA was associated with an increase in several hallmarks of aging in young patients, but no significant association of OSA was identified in older patients. Conclusions: In subjects under 50 years of age, OSA is associated with an increase in specific hallmarks of aging, independent of several known confounding factors.

Post-mortem inspection (PMI) of routinely slaughtered cattle in abattoirs is an extremely valuable tool for detecting bovine tuberculosis (bTB) infected herds that can supplement active surveillance activities. However, its true performance is difficult to assess due to the multiple factors that may affect it. Here, we determined relative efficiencies in the detection of bTB-compatible lesions and probabilities of subsequent laboratory confirmation of abattoirs located in Castilla y Leon, one of the regions with the largest cattle population in Spain, between 2010 and 2017. The slaughtered animal population was split based on the results of the ante-mortem tests (reactors or non-reactors), and two generalized linear multivariable mixed models were fitted to each subpopulation to calculate the risk of lesion detection and laboratory confirmation per abattoir while accounting for the effect of potential confounding variables. Throughout the 8-year period, ∼30,000 reactors and >2.8 million non-reactor animals in the ante-mortem tests were culled in the abattoirs under study. Bovine TB compatible lesions were detected in 4,710 (16%) reactors and 828 (0.03%) non-reactor animals, of which >95% were confirmed as infected through bacteriology. The probability of disclosure of bTB-like lesions was associated with the animal subpopulation, type of source unit, the herd size, the year of slaughter, the breed and age of the animal, and/or the season of slaughter. The probabilities of detection of bTB-like lesions varied largely depending on the abattoir in both subpopulations, ranging from 603 to 3,070 per 10,000 animals for the reactors and 0.2-16.1 per 10,000 animals for the non-reactor animals. Results obtained here will help to quantify the performance of PMI in abattoirs in Castilla y Leon and the between-abattoir variability, and to identify animals at increased risk of having bTB-like lesions detected during PMI based on animal- and farm-related factors., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: During the long wait and the global anxiety for a vaccine against COVID-19, impressively high-safety and effective vaccines were invented by multiple pharmaceutical companies., Aim: We aimed to assess the attitudes of healthcare providers and evaluate their intention to advocate for the vaccine., Methods: This was a cross-sectional study conducted in a tertiary private hospital where an electronic survey was distributed among healthcare providers (HCPs). The survey contained two sections: socio-demographic characteristics and Likert-scale perception, with 72% internal consistency., Results: The response rate to the email survey was 37% (n = 236). In addition, 169 (71.6%) of respondents were women, with more than half (134, 56.8%) aged ≤35 years. A total of 110 (46.6%) had over 10 years of experience, and most of them were nurses (146, 62%). Univariate analysis revealed that older participants significantly accepted and advocated for the new vaccine more than the younger ones. In the multivariate analysis, men were significantly more likely than women to accept and advocate for the new vaccine, as were those with chronic illnesses. Participants with allergy were significantly less likely to accept the vaccine than others. odds ratio (OR) and p -values were 2.5, 0.003; 2.3, 0.04; and 0.4, 0.01, respectively., Conclusion: The acceptance rate for the newly-developed COVID-19 vaccines was average among HCPs. Sex, age, presence of chronic illnesses, and allergy were significant predictors of accepting the vaccine.

We evaluated the influence of untreated obstructive sleep apnoea (OSA) on the magnitude of cognitive decline and on several cognitive subdomains in patients with mild-to-moderate Alzheimer's disease.In this single-centre study, 144 patients were recruited prospectively from a cognitive impairment unit and underwent overnight polysomnography.The mean±sd change in the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) score at 12 months was 3.19±5.61 in the non-OSA group and 0.08±5.62 in the OSA group, with an intergroup difference of -3.36 (95% CI 0.19-0.16; p=0.002). We did not observe a significant difference in any cognitive subdomains at 12 months. Regarding Mini-Mental State Examination scores at 36 months, the mean change was 1.69 (95% CI -1.26-4.64; p=0.445). No significant differences were found among different OSA severity groups.We observed that ADAS-cog scores were better in the OSA group than in the non-OSA group by a statistically but not clinically significant margin. We did not find differences in the different cognitive subdomains after 1 year or in global cognition after 3 years of follow-up., Competing Interests: Conflict of interest: C. Jorge has nothing to disclose. Conflict of interest: A. Targa has nothing to disclose. Conflict of interest: I.D. Benítez has nothing to disclose. Conflict of interest: F. Dakterzada has nothing to disclose. Conflict of interest: G. Torres has nothing to disclose. Conflict of interest: O. Minguez has nothing to disclose. Conflict of interest: A. Carnes has nothing to disclose. Conflict of interest: M. Pujol has nothing to disclose. Conflict of interest: A. Gibert has nothing to disclose. Conflict of interest: R. López has nothing to disclose. Conflict of interest: A.M. Gaeta has nothing to disclose. Conflict of interest: M. Dalmases has nothing to disclose. Conflict of interest: R. Farré has nothing to disclose. Conflict of interest: M. Sánchez-de-la-Torre has nothing to disclose. Conflict of interest: F. Barbé has nothing to disclose. Conflict of interest: G. Piñol-Ripoll has nothing to disclose., (Copyright ©ERS 2020.)

The persistence of bovine tuberculosis (bTB) in certain cattle herds is a major concern in countries pursuing disease eradication worldwide. The chronic nature of the disease, the lack of performance of diagnostic tools, and the presence of wildlife reservoirs may lead infected herds to require longer periods to achieve the officially tuberculosis-free (OTF) status. Here, we evaluated the impact of farm and breakdown characteristics on the probability of disease persistence in infected farms in Castilla y Leon, a bTB-endemic region of Spain, using survival and logistic regression models. Data from bTB breakdowns occurring in 3,550 bTB-positive herds detected in 2010-2017 were analyzed. A multivariable Cox proportional hazards model was fitted using time to recover OTF status as the response variable, and a multivariable logistic regression model using the chronic status (yes/no) for herds experiencing particularly long breakdowns as the outcome variable was also used. Both analyses revealed that county-level bTB herd prevalence, herd size, number of incoming animals in the previous 3 years, number of skin test reactors in the disclosing test, and number of days between the disclosing and follow-up tests were associated with increased breakdown duration. Production type was not consistently associated with chronic infection, suggesting that once infected, it is not a significant predictor of outbreak duration beyond the initial stages of the breakdown. Province-level location and number of animals that are bacteriology-positive also affected significantly the expected herd breakdown duration, but their effect became less significant over time. Risk factors identified in this study may help to identify herds more prone to suffer chronic bTB infection that may require additional control measures early on in a breakdown., (Copyright © 2020 Pozo, Romero, Bezos, Grau, Nacar, Saez, Minguez and Alvarez.)

Objective: To assess the prevalence of obstructive sleep apnea (OSA) in patients with mild-moderate Alzheimer's Disease (AD) and to evaluate cognitive characteristics according to the severity of OSA., Methods: Patients with mild-moderate AD, recruited prospectively from a cognitive impairment unit, underwent overnight polysomnography. OSA was defined as an apnea-hypopnea index > 5/h. AD severity was assessed using the Mini-Mental State Examination and extensive neuropsychological battery. Epworth Sleepiness Scale and APOE status were analyzed., Results: The cohort included 128 patients with a median [IQR] age of 75.0 [72.0;79.2] years and 57.8% were women. OSA was diagnosed in 116 subjects (90.6%). The distribution of mild, moderate and severe severity of OSA was 29 (22.7%), 37 (28.9%) and 50 (39.1%), respectively. Regarding sleep symptoms, the cohort showed normal values of daytime sleepiness (median EES score 5 [3, 8]), while nycturia (89.1%) and snoring (71.1%) were the most common symptoms. Participants with severe OSA included a higher proportion of older men, were associated with snoring and sedentariness. No significant differences in cognitive assessment were found between patients with and without severe OSA in any of the domains. The prevalence of APOE ε4 was not significantly different between patients with and without severe OSA., Conclusion: There was a high prevalence of OSA in patients with mild-moderate AD. OSA was not associated with sleepiness or worse cognitive function. APOE ε4 was not related to the presence or severity of OSA. Further longitudinal studies will be required to evaluate whether OSA impairs cognitive evolution in AD patients.

In spite of the efforts invested to eradicate bovine tuberculosis (bTB) in cattle, the disease is still present in several developed countries, including Spain. Among the factors related with disease persistence in high prevalence areas, the lack of sensitivity of the screening test for detection of infected herds [single intradermal tuberculin (SIT) test] can play a major role. Here, a scenario tree model mimicking the diagnostic test scheme in place in the region of Castilla y Leon (Spain) was developed to estimate the probability of detecting bTB in an infected-non detected officially tuberculosis free (OTF) herd (herd sensitivity, HSe). In order to do so the probability of detecting at least one positive animal in the SIT test with/without post-mortem (detection of lesions and culture) confirmation in an infected herd was estimated using Monte Carlo simulation through @RISK (Palisade Co, NY, USA). Uncertainty on the accuracy of the diagnostic tests was introduced in the model using distributions based on the literature. The performance of the model was evaluated by comparing the predicted number of SIT/post-mortem positive animals in infected herds with those observed in newly detected bTB-infected herds in the region in 2011-2015. The estimated HSe of the SIT test was 76.2% (95% probability interval: 19.8-97.6). According to the model, bTB infection would be then confirmed through culture in 65.3% (95% PI: 50.0-82.3) of the herds detected through the SIT test, so that overall the proportion of infected-non detected OTF herds in which the infection could be confirmed after the initial SIT test was 49.6% (95% PI: 9.75-80.3). The predicted HSe of both SIT test and culture was directly correlated with herd size. Results from the model suggest a moderate but highly variable HSe of the current surveillance system in place for bTB detection in OTF herds located in high prevalence areas, that could be maximized by performing multiple tests within a year as indicated in the Spanish eradication program (with a median SIT HSe of 87% when two consecutive tests were considered). In addition, these results highlight the usefulness of performing subsequent SIT tests to rule out infection in SIT-positive herds even when the causative agent cannot be isolated., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: A close relationship between obstructive sleep apnoea (OSA) and Alzheimer's disease (AD) has been described in recent years. OSA is a risk factor for AD, but the diagnosis and clinical characteristics of OSA in patients with AD is not well understood. This study evaluated the clinical utility of two screening questionnaires, the STOP-Bang questionnaire (SBQ) and the Berlin questionnaire (BQ), to identify which patients with mild AD are at higher risk of having OSA and to determine the clinical predictors of OSA in this population., Methods: In this study, 91 consecutive outpatients with mild AD were prospectively evaluated with the SBQ and the BQ. All patients underwent level 1 in-laboratory polysomnography. The predictive performance of the questionnaires were calculated for different apnoea-hypopnoea index (AHI) cut-offs., Results: The median age of the patients was 76.0 (73.0; 80.0) years, and 58 (63.7%) were female. Of those, 81 patients (89.02%) were found to have OSA defined by an AHI > 5 events/h. Comparing the predictive performances of the SBQ and the BQ, the SBQ was found to have a higher diagnostic sensitivity (85% vs 4%), a lower specificity (35% vs. 96%), a higher positive predictive value (PPV) (44% vs 33%) and negative predictive value (NPV) (80% vs 65%) for detecting severe OSA at an AHI cut-off of 30 events/h. None of the items alone in the two questionnaires predicted the risk of OSA. A modified version of the SBQ, with new cut-off points for several variables according to the characteristics of AD patients, showed a slightly greater AUC than the standard SBQ (AUC 0.61 vs 0.72)., Conclusion: There is a high prevalence of OSA among patients with mild AD. The SBQ and the BQ are not good screening tools for detecting OSA in patients with AD. A modified version of SBQ could increase the detection of these patients., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Between-farm transmission of bovine tuberculosis (bTB) occurs mostly through fence-to-fence contact between neighbouring farms, endemic infected wildlife or movement of infected animals. Unfortunately, bTB detection is frequently delayed and identification of the source of introduction is often difficult, particularly in endemic regions. Here, we characterized the cattle movement network of Castilla y Leon, a high bTB-prevalence (1.9% at the farm level in 2015) region in Spain, over six years and analysed the distribution of bTB to ultimately assess the likelihood of spatial and movement-mediated transmission. We analysed movement and bTB data from 27,633 units located in the region, of which 87% were involved in ~1.4 million movements of ~8.8 million animals. Network-level connectivity was low, although a few highly connected units were identified. Up to 15% of the herds became bTB-positive at some point during the study, with the highest percentage found in bullfighting and beef herds. Although bTB-positive herds had a significantly higher degree and moved more cattle than negative herds. Results of the k-test, a permutation-based procedure, suggested that positive farms were not significantly clustered in the movement network. Location was a likely risk factor as bTB-positive farms tended to be located within 5 km from each other. Results suggested that movements may be a source of bTB in cattle in Castilla y Leon, although local factors may be more influential in determining risk of disease at the farm level. The description of the movement network in Castilla y Leon may be valuable for bTB surveillance in Spain. Moreover, results are useful to assess the movement-associated risk for multiple diseases., (© 2018 Blackwell Verlag GmbH.)

Objective: To assess the effectiveness and cost-effectiveness of primary care (PC) and sleep unit (SU) models for the management of subjects with suspected obstructive sleep apnoea (OSA)., Methods: Multicentre, open-label, two-arm, parallel-group, non-inferiority randomised controlled trial. A total of 302 subjects with suspected OSA and/or resistant hypertension were consecutively enrolled, 149 were treated at 11 PC units and 153 patients at a SU. The primary outcomes were a 6-month change in the Epworth Sleepiness Scale (ESS) score and Health Utilities Index (HUI). The non-inferiority margin for the ESS score was -2.0., Results: A total of 80.2% and 70.6% of the PC and SU patients were diagnosed with OSA, respectively, and 59.3% and 60.4% of those were treated with CPAP in PC and SU units, respectively. The Apnoea-Hypopnoea Index was similar between the groups (PC vs SU (median (IQR); 23.1 (26.8) events/h vs 21.8 (35.2) events/h), and the baseline ESS score was higher in the PC than in the SU group (10.3 (6.6) vs 9 (7.2)). After 6 months, the ESS score of the PC group decreased from a mean of 10.1 to 7.6 (-2.49; 95% CI -3.3 to -1.69), and that of the SU group decreased from 8.85 to 5.73 (-3.11; 95% CI -3.94 to 2.28). The adjusted difference between groups for the mean change in the ESS score was -1.25 (one-sided 95% CI -1.88; p=0.025), supporting the non-inferiority of PC management. We did not observe differences in the HUI between groups. The cost analysis showed a median savings of €558.14/patient for the PC setting compared with the SU setting., Conclusions: Among patients with suspected OSA, the PC model did not result in a worse ESS score or HUI than the specialist model and generated savings in terms of management cost. Therefore, the PC model was more cost-efficient than the SU model., Trial Registration: Results; >>NCT02234765, Clinical Trials.gov., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

In Spain, the national bovine tuberculosis (bTB) eradication program is based on yearly skin testing of every ≥6 weeks old animal using the single or comparative tuberculin test and parallel use of the interferon-gamma (IFN-γ) assay as an ancillary diagnostic test in infected herds. There are several versions of the latter. Recently, a new commercial IDvet IFN-γ assay has been authorized for use in the program, but there is limited scientific evidence about its performance in different epidemiological settings. Therefore, two studies to evaluate the performance of the IDvet assay were conducted. In study 1, a concordance analysis between the new IDvet and the Bovigam IFN-γ assay in use in Spain for over 10 years was conducted. In study 2, results from the IDvet assay when applied in tandem with a single intradermal tuberculin (SIT) test were used to evaluate the concordance between both tests and to estimate their sensitivity (Se) and specificity (Sp) using a Bayesian latent-class model. Field data from cattle herds located in Madrid and Castilla y Leon (Spain) were collected. For study 1, herd selection was based on a high expected prevalence of reactors to the IFN-γ assay, while herds were selected at random to estimate Se and Sp of the new IDvet assay in study 2. Agreement between the results obtained with both kits for IFN-γ assay was poor (Kappa = 0.20), and a receiver operating characteristic (ROC) analysis indicated a low Se of the new IDvet relative to the Bovigam in a heavily bTB infected population. The Bayesian latent-class analysis estimated the Se of the IDvet assay to be 36.7% [95% probability posterior interval (PPI) 14.7-78.8%] with estimated Sp close to 100% when the cut-off recommended by the manufacturer (35) was applied. At the alternative cut-off values of 16 and 4, the estimated Se of the IDvet assay increased to 49.0% (PPI: 24.8-94.1%) and 56.0% (PPI: 30.8-96.3%), respectively, while maintaining a high specificity. The results suggest that the new IDvet assay may have lower sensitivity than the Bovigam for diagnosis of bTB in cattle herds in Spain, and that adjusting its cut-off might be considered.