Cristina Embid

Emerging risk factors and the dose-response relationship between physical activity and lone atrial fibrillation: a prospective case-control study.

Abstract Aims The role of high-intensity exercise and other emerging risk factors in lone atrial fibrillation (Ln-AF) epidemiology is still under debate. The aim of this study was to analyse the contribution of each of the emerging risk factors and the impact of physical activity dose in patients with Ln-AF. Methods and results Patients with Ln-AF and age- and sex-matched healthy controls were included in a 2:1 prospective case–control study. We obtained clinical and anthropometric data transthoracic echocardiography, lifetime physical activity questionnaire, 24-h ambulatory blood pressure monitoring, Berlin questionnaire score, and, in patients at high risk for obstructive sleep apnoea (OSA) syndrome, a polysomnography. A total of 115 cases and 57 controls were enrolled. Conditional logistic regression analysis associated height [odds ratio (OR) 1.06 [1.01–1.11]], waist circumference (OR 1.06 [1.02–1.11]), OSA (OR 5.04 [1.44–17.45]), and 2000 or more hours of cumulative high-intensity endurance training to a higher AF risk. Our data indicated a U-shaped association between the extent of high-intensity training and AF risk. The risk of AF increased with an accumulated lifetime endurance sport activity ≥2000 h compared with sedentary individuals (OR 3.88 [1.55–9.73]). Nevertheless, a history of <2000 h of high-intensity training protected against AF when compared with sedentary individuals (OR 0.38 [0.12–0.98]). Conclusion A history of ≥2000 h of vigorous endurance training, tall stature, abdominal obesity, and OSA are frequently encountered as risk factors in patients with Ln-AF. Fewer than 2000 total hours of high-intensity endurance training associates with reduced Ln-AF risk.

A Bayesian cost-effectiveness analysis of a telemedicine-based strategy for the management of sleep apnoea: a multicentre randomised controlled trial

Background Compliance with continuous positive airway pressure (CPAP) therapy is essential in patients with obstructive sleep apnoea (OSA), but adequate control is not always possible. This is clinically important because CPAP can reverse the morbidity and mortality associated with OSA. Telemedicine, with support provided via a web platform and video conferences, could represent a cost-effective alternative to standard care management. Aim To assess the telemedicine impact on treatment compliance, cost-effectiveness and improvement in quality of life (QoL) when compared with traditional face-to-face follow-up. Methods A randomised controlled trial was performed to compare a telemedicine-based CPAP follow-up strategy with standard face-to-face management. Consecutive OSA patients requiring CPAP treatment, with sufficient internet skills and who agreed to participate, were enrolled. They were followed-up at 1, 3 and 6 months and answered surveys about sleep, CPAP side effects and lifestyle. We compared CPAP compliance, cost-effectiveness and QoL between the beginning and the end of the study. A Bayesian cost-effectiveness analysis with non-informative priors was performed. Results We randomised 139 patients. At 6 months, we found similar levels of CPAP compliance, and improved daytime sleepiness, QoL, side effects and degree of satisfaction in both groups. Despite requiring more visits, the telemedicine group was more cost-effective: costs were lower and differences in effectiveness were not relevant. Conclusions A telemedicine-based strategy for the follow-up of CPAP treatment in patients with OSA was as effective as standard hospital-based care in terms of CPAP compliance and symptom improvement, with comparable side effects and satisfaction rates. The telemedicine-based strategy had lower total costs due to savings on transport and less lost productivity (indirect costs). Trial register number NCT01716676.

Effect of CPAP on Cognition, Brain Function, and Structure Among Elderly Patients With OSA: A Randomized Pilot Study

BACKGROUND Despite the increasing aging population and the high prevalence of OSA in elderly adults, little is known about cognitive effects of OSA and the effectiveness of CPAP treatment. Therefore, this study investigated whether elderly patients with OSA present cognitive deficits and functional and structural alterations of the brain that could be improved by CPAP treatment. METHODS This randomized, evaluator-blinded, parallel-group, single-center pilot study involved patients aged ≥ 65 years with newly-diagnosed severe OSA syndrome. Thirty-three patients were assigned to receive either conservative care (CC) or CPAP plus CC for 3 months. At baseline and 3 months after treatment, patients underwent a neuropsychologic evaluation and a functional and structural MRI study of connectivity within the default mode network (DMN) and of cortical thickness. RESULTS Neuropsychologic evaluation revealed no differences in cognitive performance between OSA groups at baseline. By contrast, after CPAP treatment, patients showed a significant improvement in episodic (between-group difference in change, 7.60; 95% CI, 1.66-13.55; P = .014) and short-term memory (between-group difference in change, 1.06; 95% CI, 0.10-2.01; P = .032) and in executive function (speed of mental processing, 5.74; 95% CI, 1.69-9.79; P = .007; mental flexibility, -47.64; 95% CI, -81.83 to -13.45; P = .008), whereas no changes were observed in the CC group. Neuroimaging revealed an increase in the connectivity in the right middle frontal gyrus after 3 months of CPAP treatment and a higher percentage of cortical thinning in the CC group. No association was seen between cognition and brain functional connectivity changes within the DMN. CONCLUSIONS Elderly patients with severe OSA who present with cognitive difficulties could benefit from CPAP treatment. Moreover, CPAP treatment increases the connectivity of the DMN and attenuates cortical thinning. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT01826032; URL: www.clinicaltrials.gov.

Management of sleep apnea without high pretest probability or with comorbidities by three nights of portable sleep monitoring.

STUDY OBJECTIVES Obstructive sleep apnea (OSA) diagnosis using simplified methods such as portable sleep monitoring (PM) is only recommended in patients with a high pretest probability. The aim is to determine the diagnostic efficacy, consequent therapeutic decision-making, and costs of OSA diagnosis using polysomnography (PSG) versus three consecutive studies of PM in patients with mild to moderate suspicion of sleep apnea or with comorbidity that can mask OSA symptoms. DESIGN AND SETTING Randomized, blinded, crossover study of 3 nights of PM (3N-PM) versus PSG. The diagnostic efficacy was evaluated with receiver operating characteristic (ROC) curves. Therapeutic decisions to assess concordance between the two different approaches were performed by sleep physicians and respiratory physicians (staff and residents) using agreement level and kappa coefficient. The costs of each diagnostic strategy were considered. PATIENTS AND RESULTS Fifty-six patients were selected. Epworth Sleepiness Scale was 10.1 (5.3) points. Bland-Altman plot for apnea-hypopnea index (AHI) showed good agreement. ROC curves showed the best area under the curve in patients with PSG AHI ≥ 5 [0.955 (confidence interval = 0.862-0.993)]. For a PSG AHI ≥ 5, a PM AHI of 5 would effectively exclude and confirm OSA diagnosis. For a PSG AHI ≥ 15, a PM AHI ≥ 22 would confirm and PM AHI < 7 would exclude OSA. The best agreement of therapeutic decisions was achieved by the sleep medicine specialists (81.8%). The best cost-diagnostic efficacy was obtained by the 3N-PM. CONCLUSIONS Three consecutive nights of portable monitoring at home evaluated by a qualified sleep specialist is useful for the management of patients without high pretest probability of obstructive sleep apnea or with comorbidities. CLINICAL TRIAL REGISTRATION http://www.clinicaltrials.gov, registration number: NCT01820156. CITATION Guerrero A, Embid C, Isetta V, Farre R, Duran-Cantolla J, Parra O, Barbé F, Montserrat JM, Masa JF. Management of sleep apnea without high pretest probability or with comorbidities by three nights of portable sleep monitoring.

Effectiveness of three sleep apnea management alternatives.

RATIONALE Home respiratory polygraphy (HRP) may be a cost-effective alternative to polysomnography (PSG) for diagnosis and treatment election in patients with high clinical probability of obstructive sleep apnea (OSA), but there is conflicting evidence on its use for a wider spectrum of patients. OBJECTIVES To determine the efficacy and cost of OSA management (diagnosis and therapeutic decision making) using (1) PSG for all patients (PSG arm); (2) HRP for all patients (HRP arm); and (3) HRP for a subsample of patients with high clinical probability of being treated with continuous positive airway pressure (CPAP) and PSG for the remainder (elective HRP arm). METHODS Multicentric study of 366 patients with intermediate-high clinical probability of OSA, randomly subjected to HRP and PSG. We explored the diagnostic and therapeutic decision agreements between the PSG and both HRP arms for several HRP cutoff points and calculated costs for equal diagnostic and/or therapeutic decision efficacy. RESULTS For equal diagnostic and therapeutic decision efficacy, PSG arm costs were 18% higher than HRP arm costs and 20% higher than elective HRP arm costs. HRP arm costs tended to be lower than elective HRP arm costs, and both tended to be lower than PSG arm costs if patient costs were omitted. CONCLUSION Home respiratory polygraphy is a less costly alternative than polysomnography for the diagnosis and therapeutic decision making for patients with suspected obstructive sleep apnea. We found no advantage in cost terms, however, in using home respiratory polygraphy for all patients or home respiratory polygraphy for the most symptomatic patients and polysomnography for the rest.

Brain tissue hypoxia and oxidative stress induced by obstructive apneas is different in young and aged rats.

STUDY OBJECTIVES To test the hypotheses that brain oxygen partial pressure (PtO2) in response to obstructive apneas changes with age and that it might lead to different levels of cerebral tissue oxidative stress. DESIGN Prospective controlled animal study. SETTING University laboratory. PARTICIPANTS Sixty-four male Wistar rats: 32 young (3 mo old) and 32 aged (18 mo). INTERVENTIONS Protocol 1: Twenty-four animals were subjected to obstructive apneas (50 apneas/h, lasting 15 sec each) or to sham procedure for 50 min. Protocol 2: Forty rats were subjected to obstructive apneas or sham procedure for 4 h. MEASUREMENTS AND RESULTS Protocol 1: Real-time PtO2 measurements were performed using a fast-response oxygen microelectrode. During successive apneas cerebral cortex PtO2 presented a different pattern in the two age groups; there was a fast increase in young rats, whereas it remained without significant changes between the beginning and the end of the protocol in the aged group. Protocol 2: Brain oxidative stress assessed by lipid peroxidation increased after apneas in young rats (1.34 ± 0.17 nmol/mg of protein) compared to old ones (0.63 ± 0.03 nmol/mg), where a higher expression of antioxidant enzymes was observed. CONCLUSIONS The results suggest that brain oxidative stress in aged rats is lower than in young rats in response to recurrent apneas, mimicking obstructive sleep apnea. This could be due to the different PtO2 response observed between age groups and the increased antioxidant expression in aged rats. CITATION Dalmases M, Torres M, Márquez-Kisinousky L, Almendros I, Planas AM, Embid C, Martínez-Garcia MA, Navajas D, Farré R, Montserrat JM. Brain tissue hypoxia and oxidative stress induced by obstructive apneas is different in young and aged rats.

Optimizing screening of severe obstructive sleep apnea in patients undergoing bariatric surgery

BACKGROUND Obstructive sleep apnea is common in patients waiting for bariatric surgery (BS). International consensuses have recommended assessment of obstructive sleep apnea in the preoperative evaluation to avoid perioperative complications. Polysomnography is the standard diagnostic method but is expensive and time-consuming. The aim of our study was to detect those patients who merit treatment before BS using a simple predictor model. The study was conducted at 3 university hospitals (Hospital de Bellvitge, Hospital de la Santa Creu i Sant Pau, Hospital Clinic de Barcelona). METHODS A prospective cross-sectional study was conducted of 136 consecutive bariatric subjects. The outcome variable was severe obstructive sleep apnea, defined as an apnea-hypoapnea index of ≥30 events/hr by polysomnography. The predictors evaluated were anthropometric and clinical in the first model, with an oxygen desaturation index of ≥3% added to the second model. Predictive models were constructed using multivariate logistic regression analysis. The best model was selected according to the area under the receiver operating characteristic curve. RESULTS The first model identified 4 independent factors: age, waist circumference, systolic blood pressure, and witnessed apnea episodes, with a sensitivity of 78%, specificity of 68%, and area under the receiver operating characteristic curve of .83 (95% confidence interval .76-.90, P < .001). The second model identified 2 independent factors (witness apnea episodes, oxygen desaturation index of ≥3%), with a sensitivity of 91%, specificity of 85%, and area under the receiver operating characteristic curve of .94 (95% confidence interval .89-.98, P < .001). The 2-step model predictive values were sensitivity of 90%, specificity of 91%, and accuracy of 90% (95% confidence interval 84-94%). After applying the first model and then the second, 45% of subjects would have been ruled out (15% and 30%, respectively) and 55% would require additional sleep management before BS. CONCLUSION The proposed model could be useful for improving the management of complex patients before BS and optimizing limited polysomnography resources.

A New mHealth application to support treatment of sleep apnoea patients.

Introduction Continuous positive airway pressure (CPAP) is the first-choice treatment for obstructive sleep apnoea (OSA), but adherence is frequently suboptimal. Innovative, patient-centred interventions are, therefore, needed to enhance compliance. Due to its low cost and ubiquity, mobile health (mHealth) technology seems particularly suited for this purpose. We endeavoured to develop an mHealth application called “APPnea,” aimed at promoting patient self-monitoring of CPAP treatment. We then assessed the feasibility and acceptability of APPnea in a group of OSA patients. Methods Consecutive OSA patients used APPnea for six weeks. APPnea gave patients daily reminders to answer three questions about their OSA treatment (CPAP use, physical activity, and diet) and prompted them to upload their body weight weekly. Answers were saved to a secure server for further analysis. After completing the study, patients gave their anonymous opinions about APPnea. Results We enrolled 60 patients with OSA receiving CPAP treatment. The mean age was 56 ± 10 years and the apnoea–hypopnea index was 47 ± 25 events/hour. In total, 63% of participants completed the daily questionnaire for more than 66% of the study period. Objective CPAP compliance was generally high (5.3 ± 1.6 hours/night). In a subset of 38 patients naïve to CPAP, those who used APPnea regularly had significantly higher CPAP compliance. Satisfaction levels were high for the majority of users. Conclusion This mHealth intervention is not only feasible but also satisfactory to patients. Although larger randomized trials and cost-effectiveness studies should be performed, this study shows that APPnea could promote participation and improve compliance among patients with OSA, thereby improving outcomes.

Significance of Including a Surrogate Arousal for Sleep Apnea-Hypopnea Syndrome Diagnosis by Respiratory Polygraphy

RATIONALE Respiratory polygraphy is an accepted alternative to polysomnography (PSG) for sleep apnea/hypopnea syndrome (SAHS) diagnosis, although it underestimates the apnea-hypopnea index (AHI) because respiratory polygraphy cannot identify arousals. OBJECTIVES We performed a multicentric, randomized, blinded crossover study to determine the agreement between home respiratory polygraphy (HRP) and PSG, and between simultaneous respiratory polygraphy (respiratory polygraphy with PSG) (SimultRP) and PSG by means of 2 AHI scoring protocols with or without hyperventilation following flow reduction considered as a surrogate arousal. METHODS We included suspected SAHS patients from 8 hospitals. They were assigned to home and hospital protocols at random. We determined the agreement between respiratory polygraphy AHI and PSG AHI scorings using Bland and Altman plots and diagnostic agreement using receiver operating characteristic (ROC) curves. The agreement in therapeutic decisions (continuous positive airway pressure treatment or not) between HRP and PSG scorings was done with likelihood ratios and post-test probability calculations. RESULTS Of 366 randomized patients, 342 completed the protocol. AHI from HRP scorings (with and without surrogate arousal) had similar agreement with PSG. AHI from SimultRP with surrogate arousal scoring had better agreement with PSG than AHI from SimultRP without surrogate arousal. HRP with surrogate arousal scoring had slightly worse ROC curves than HRP without surrogate arousal, and the opposite was true for SimultRP scorings. HRP with surrogate arousal showed slightly better agreement with PSG in therapeutic decisions than for HRP without surrogate arousal. CONCLUSION Incorporating a surrogate arousal measure into HRP did not substantially increase its agreement with PSG when compared with the usual procedure (HRP without surrogate arousal).

Effects of heated humidification on nasal inflammation in a CPAP rat model.

BACKGROUND Rhinitis is a potential side effect of nasal continuous positive airway pressure (nCPAP). Heated Humidification (HH) is applied to treat rhinitic symptoms, but its usefulness is controversial. Confounding factors such as previous rhinitis or nasal obstruction make it difficult to draw definitive conclusions. Animal models could therefore be useful. OBJECTIVES To study the effects of HH as a mechanism that may reduce nasal inflammation during nCPAP application in the presence or absence of an oral leak (OL). METHODS Prospective controlled animal study. Setting I: Sixty Sprague-Dawley rats were distributed into noCPAP (naïve), sham-CPAP with HH, 5 and 10cm H(2)O nCPAP, and 10cm H(2)O nCPAP with HH for 5h. Setting II: Thirty-three rats were exposed to nCPAP, nCPAP with a controlled OL, and nCPAP with controlled OL and HH (n=11 each). The degree of nasal inflammation was assessed by directly evaluating the percentage of neutrophils in the nasal mucosa. RESULTS Percentage of neutrophils was higher after 5h of 10cm nCPAP compared to the control group (0.96+/-0.26% vs. 0.18+/-0.05%; p=0.001). When HH was applied, the percentage of neutrophils did not differ from that observed in the nCPAP group. The addition of a controlled OL, did not show significant differences in the neutrophils count compared to nCPAP alone (0.75+/-0.19% vs. 0.83+/-0.29%; p=0.70). Moreover, the application of HH to the rat with OL did not change the percentage of neutrophils. CONCLUSIONS HH applied to an acute rat model of nCPAP with and without a controlled OL does not seem to reduce nasal inflammation.