Air pollution, weather and positive airway pressure treatment adherence in adults with sleep apnea: a retrospective community-based repeated-measures longitudinal study.

We assessed the relation between air pollution, weather, and adherence to positive airway pressure (PAP) therapy in a retrospective community-based repeated-measures study of adults with obstructive sleep apnea who purchased PAP devices from a registered provider between 2013 and 2017 (Ottawa, Ontario, Canada) and had at least one day of data. Daily PAP-derived data, air pollution, and weather databases were linked using postal code. The exposures were mean nocturnal (8:00 p.m. to 8:00 a.m.) (i) residential concentrations of nitrogen dioxide (NO2 ), fine particulate matter <=2.5 µm (PM2.5 ), ozone (O3 ), and Air Quality Health Index (AQHI), and (ii) temperature, relative humidity, and barometric pressure. Covariates in the main model were demographics, season, exposure year, and PAP therapy mode. We analysed 8148 adults (median age of 54 years and 61% men) and 2,071,588 days of data. Based on daily data, the median (interquartile range) daily PAP usage was 416 (323-487) min. Using mixed-effect regression analyses to incorporate daily data and clustering by individuals, we found a statistically significant decrease in adherence for increased levels of NO2 , PM2.5 , and AQHI. The largest effect was for NO2 : a decrease in daily PAP use while comparing the highest versus lowest quartiles (Qs) was 3.4 (95% confidence interval [CI] 2.8-3.9) min. Decreased PAP adherence was also associated with increased temperature (Q4 versus Q1: 2.6 [95% CI: 1.5-3.7] min) and decreased barometric pressure (Q1 versus Q4: 2.0 [95% CI 1.5-2.5] min). We observed modest but statistically significant acute effects of air pollution and weather on daily PAP adherence.

Moving toward Equitable Care for Sleep Apnea in the United States: Positive Airway Pressure Adherence Thresholds: An Official American Thoracic Society Policy Statement.

Background: Positive airway pressure (PAP) is a highly effective treatment for obstructive sleep apnea (OSA), but adherence limits its efficacy. In addition, coverage of PAP by CMS (Centers for Medicare & Medicaid Services) and other insurers in the United States depends on adherence. This leaves many beneficiaries without PAP, disproportionally impacting non-white and low socioeconomic position patients with OSA and exacerbating sleep health disparities. Methods: An inter-professional, multidisciplinary, international committee with various stakeholders was formed. Three working groups (the historical policy origins, impact of current policy, and international PAP coverage models) met and performed literature reviews and discussions. Using surveys and an iterative discussion-based consensus process, the policy statement recommendations were created. Results: In this position paper, we advocate for policy change to CMS PAP coverage requirements to reduce inequities and align with patient-centered goals. We specifically call for eradicating repeat polysomnography, eliminating the 4-hour rule, and focusing on patient-oriented outcomes such as improved sleepiness and sleep quality. Conclusions: Modifications to the current policies for PAP insurance coverage could improve health disparities.

Causes, Consequences, and Treatments of Sleep and Circadian Disruption in the ICU: An Official American Thoracic Society Research Statement.

Background: Sleep and circadian disruption (SCD) is common and severe in the ICU. On the basis of rigorous evidence in non-ICU populations and emerging evidence in ICU populations, SCD is likely to have a profound negative impact on patient outcomes. Thus, it is urgent that we establish research priorities to advance understanding of ICU SCD. Methods: We convened a multidisciplinary group with relevant expertise to participate in an American Thoracic Society Workshop. Workshop objectives included identifying ICU SCD subtopics of interest, key knowledge gaps, and research priorities. Members attended remote sessions from March to November 2021. Recorded presentations were prepared and viewed by members before Workshop sessions. Workshop discussion focused on key gaps and related research priorities. The priorities listed herein were selected on the basis of rank as established by a series of anonymous surveys. Results: We identified the following research priorities: establish an ICU SCD definition, further develop rigorous and feasible ICU SCD measures, test associations between ICU SCD domains and outcomes, promote the inclusion of mechanistic and patient-centered outcomes within large clinical studies, leverage implementation science strategies to maximize intervention fidelity and sustainability, and collaborate among investigators to harmonize methods and promote multisite investigation. Conclusions: ICU SCD is a complex and compelling potential target for improving ICU outcomes. Given the influence on all other research priorities, further development of rigorous, feasible ICU SCD measurement is a key next step in advancing the field.

Acute hypoxia elicits lasting reductions in the sympathetic action potential transduction of arterial blood pressure in males.

Post-hypoxia sympathoexcitation does not elicit corresponding changes in vascular tone, suggesting diminished sympathetic signalling. Blunted sympathetic transduction following acute hypoxia, however, has not been confirmed and the effects of hypoxia on the sympathetic transduction of mean arterial pressure (MAP) as a function of action potential (AP) activity is unknown. We hypothesized that MAP changes would be blunted during acute hypoxia but restored in recovery and asynchronous APs would elicit smaller MAP changes than synchronous APs. Seven healthy males (age: 24 (3) years; BMI: 25 (3) kg/m2 ) underwent 20 min isocapnic hypoxia (PET O2 : 47 (2) mmHg) and 30 min recovery. Multi-unit microneurography (muscle sympathetic nerve activity; MSNA) and continuous wavelet transform with matched mother wavelet was used to detect sympathetic APs during baseline, hypoxia, early (first 7 min) and late (last 7 min) recovery. AP groups were classified as synchronous APs, asynchronous APs (occurring outside an MSNA burst) and no AP activity. Sympathetic transduction of MAP was quantified using signal-averaging, with ΔMAP tracked following AP group cardiac cycles. Following synchronous APs, ΔMAP was reduced in hypoxia (+1.8 (0.9) mmHg) and early recovery (+1.5 (0.7) mmHg) compared with baseline (+3.1 (2.2) mmHg). AP group-by-condition interactions show that at rest asynchronous APs attenuate MAP reductions compared with no AP activity (-0.4 (1.1) vs. -2.2 (1.2) mmHg, respectively), with no difference between AP groups in hypoxia, early or late recovery. Sympathetic transduction of MAP is blunted in hypoxia and early recovery. At rest, asynchronous sympathetic APs contribute to neural regulation of MAP by attenuating nadir pressure responses. KEY POINTS: Acute isocapnic hypoxia elicits lasting sympathoexcitation that does not correspond to parallel changes in vascular tone, suggesting blunted sympathetic transduction. Signal-averaging techniques track the magnitude and temporal cardiovascular responses following integrated muscle sympathetic nerve activity (MSNA) burst and non-burst cardiac cycles. However, this does not fully characterize the effects of sympathetic action potential (AP) activity on blood pressure control. We show that hypoxia blunts the sympathetic transduction of mean arterial pressure (MAP) following synchronous APs that form integrated MSNA bursts and that sympathetic transduction of MAP remains attenuated into early recovery. At rest, asynchronous APs attenuate the reduction in MAP compared with cardiac cycles following no AP activity, thus asynchronous sympathetic APs appear to contribute to the neural regulation of blood pressure. The results advance our understanding of sympathetic transduction of arterial pressure during and following exposure to acute isocapnic hypoxia in humans.

Association of clinically significant obstructive sleep apnoea with risks of contracting COVID-19 and serious COVID-19 complications: a retrospective population-based study of health administrative data.

RATIONALE/OBJECTIVES: Despite plausible pathophysiological mechanisms, more research is needed to confirm the relationship between obstructive sleep apnoea (OSA) and the risk of COVID-19 infection or COVID-19-related serious complications. METHODS: We conducted a retrospective population-based cohort study using provincial health administrative data (Ontario, Canada). Adults with physician-diagnosed OSA who received positive airway pressure therapy in the 5 years prepandemic (OSA group) were propensity score matched by baseline characteristics to individuals in the general population at low risk of OSA (non-OSA group) using inverse probability of treatment weighting. Weighted HRs of (1) a positive COVID-19 test and (2) COVID-19-related emergency department (ED) visits, hospitalisations, intensive care unit (ICU) admissions and mortality, within 12 months of pandemic onset, were compared between groups. We also evaluated the impact of comorbid cardiometabolic or chronic airways disease. RESULTS: We identified and matched 324 029 individuals in the OSA group to 4 588 200 individuals in the non-OSA group. Compared with the non-OSA group, those in the OSA group were at a greater hazard of testing positive for COVID-19 (HR=1.17, 95% CI 1.13 to 1.21), having a COVID-19-related ED visit (HR=1.62, 95% CI 1.51 to 1.73), hospitalisation (HR=1.50, 95% CI 1.37 to 1.65) or ICU admission (HR=1.53, 95% CI 1.27 to 1.84). COVID-19-related 30-day mortality was not different (HR=0.98, 95% CI 0.82 to 1.16).We found that for the OSA group, comorbid airways disease but not cardiometabolic conditions increased the hazards of COVID-19-related outcomes, including mortality. CONCLUSION: In this large population-based study, we demonstrated that a recent diagnosis of OSA requiring treatment was associated with an increased hazard of testing positive for COVID-19 and serious COVID-19-related complications, particularly in those with co-existing chronic airways disease.

WITHDRAWN: Update in Sleep 2021.

Ahead of Print article withdrawn by publisher.

The rs579459 ABO gene polymorphism and risk of incident cardiovascular events in obstructive sleep apnea: a pilot study.

PURPOSE: We have previously shown that the TT genotype (rs579459 location of the ABO gene) is significantly associated with circulating levels of e-selectin in patients with suspected obstructive sleep apnea (OSA). We hypothesized that this genotype would be associated with incident cardiovascular disease (CVD). METHODS: Patients with suspected OSA who had a full diagnostic polysomnogram from 2003 to 2011 were recruited; CV events occurring within 8 years of polysomnography were identified by linkage to provincial health databases. Cox proportional hazards models were used to evaluate the incidence of first CV events as a function of the rs579459 genotype. RESULTS: In this targeted study, 408 patients were studied, and 39 incident events were identified. A larger proportion of patients with the TT genotype had an event (31/247; 12.6%) than the CT and CC genotypes (8/161; 5.0%); in univariate analysis, the TT genotype was significantly associated with CV events (HR = 2.53; 95% CI = 1.16-5.51, p = 0.02). After adjustment for age, AHI, sex, smoking, diabetes, statin use, and BMI, the TT genotype remained a significant predictor (HR = 2.35; 95% CI = 1.02-5.42, p = 0.046). No events were found in patients with an absence of both OSA and the TT genotype (N = 30). The effect of the SNP was partially (16.2%) mediated by e-selectin levels. CONCLUSION: This is the first study to examine genetic variants as a risk factor for incident CVD in the context of OSA. Although these results are preliminary and in need of replication, it suggests that genetic markers may become useful in helping to guide precision clinical care.

Vascular and renal telomere shortening in mice exposed to chronic intermittent hypoxia.

Obstructive sleep apnea (OSA) is a chronic condition characterized by chronic intermittent hypoxia (IH) and is associated with cardiovascular (CVD) and chronic kidney diseases (CKD). Patients with OSA have increased biomarkers of aging such as telomere shortening. We used PCR to report shortened telomere lengths in aortic and renal tissues from mice exposed to 8 weeks of IH. Our data indicate that IH, a hallmark of OSA, accelerates vascular and renal aging that may contribute to OSA-induced CVD and CKD.

Perioperative myocardial injury risk after elective knee and hip arthroplasty in patients with a high risk of obstructive sleep apnea.

BACKGROUND: Myocardial injury after non-cardiac surgery (MINS) occurs in approximately 8-13% of patients and has significant 30-day mortality. Patients with obstructive sleep apnea (OSA) suffer recurrent hypoxemia during sleep and surgical patients with OSA are known to have increased risk of cardiorespiratory complications. We hypothesized that patients at high risk for OSA may have an increased risk of MINS. As a secondary analysis, we assessed rates of postoperative cardiopulmonary complications. METHODS: Adult patients undergoing elective knee or hip arthroplasty with STOPBANG score ≥ 5 were recruited. MINS was determined by measuring troponin-I on postoperative days 1 and 2. RESULTS: A total of 82 patients were studied. Only one patient had a positive troponin (MINS rate of 1.2%). The rate of cardiopulmonary complications was low (4.9%) and the 30-day mortality rate for these patients was 0. CONCLUSION: The incidence of MINS and postoperative cardiopulmonary complications in patients with elective arthroplasty and a high risk of OSA were low.

Acute intermittent hypercapnic hypoxia and sympathetic neurovascular transduction in men.

KEY POINTS: Intermittent hypoxia leads to long-lasting increases in muscle sympathetic nerve activity and blood pressure, contributing to increased risk for hypertension in obstructive sleep apnoea patients. We determined whether augmented vascular responses to increasing sympathetic vasomotor outflow, termed sympathetic neurovascular transduction (sNVT), accompanied changes in blood pressure following acute intermittent hypercapnic hypoxia in men. Lower body negative pressure was utilized to induce a range of sympathetic vasoconstrictor firing while measuring beat-by-beat blood pressure and forearm vascular conductance. IH reduced vascular shear stress and steepened the relationship between diastolic blood pressure and sympathetic discharge frequency, suggesting greater systemic sNVT. Our results indicate that recurring cycles of acute intermittent hypercapnic hypoxia characteristic of obstructive sleep apnoea could promote hypertension by increasing sNVT. ABSTRACT: Acute intermittent hypercapnic hypoxia (IH) induces long-lasting elevations in sympathetic vasomotor outflow and blood pressure in healthy humans. It is unknown whether IH alters sympathetic neurovascular transduction (sNVT), measured as the relationship between sympathetic vasomotor outflow and either forearm vascular conductance (FVC; regional sNVT) or diastolic blood pressure (systemic sNVT). We tested the hypothesis that IH augments sNVT by exposing healthy males to 40 consecutive 1 min breathing cycles, each comprising 40 s of hypercapnic hypoxia ( PETCO2 : +4 ± 3 mmHg above baseline; PETO2 : 48 ± 3 mmHg) and 20 s of normoxia (n = 9), or a 40 min air-breathing control (n = 7). Before and after the intervention, lower body negative pressure (LBNP; 3 min at -15, -30 and -45 mmHg) was applied to elicit reflex increases in muscle sympathetic nerve activity (MSNA, fibular microneurography) when clamping end-tidal gases at baseline levels. Ventilation, arterial pressure [systolic blood pressure, diastolic blood pressure, mean arterial pressure (MAP)], brachial artery blood flow ( Q̇BA ), FVC ( Q̇BA /MAP) and MSNA burst frequency were measured continuously. Following IH, but not control, ventilation [5 L min-1 ; 95% confidence interval (CI) = 1-9] and MAP (5 mmHg; 95% CI = 1-9) were increased, whereas FVC (-0.2 mL min-1  mmHg-1 ; 95% CI = -0.0 to -0.4) and mean shear rate (-21.9 s-1 ; 95% CI = -5.8 to -38.0; all P < 0.05) were reduced. Systemic sNVT was increased following IH (0.25 mmHg burst-1  min-1 ; 95% CI = 0.01-0.49; P < 0.05), whereas changes in regional forearm sNVT were similar between IH and sham. Reductions in vessel wall shear stress and, consequently, nitric oxide production may contribute to heightened systemic sNVT and provide a potential neurovascular mechanism for elevated blood pressure in obstructive sleep apnoea.

Outcomes of Critically Ill Patients Who Have Serotype 5 Invasive Pneumococcal Disease.

PURPOSE: To determine whether invasive pneumococcal disease (IPD) due to serotype 5, which occurred as a local outbreak in 2006 to 2007, is associated with intensive care unit (ICU) admission, hospital mortality, or organ supports in those who are critically ill. MATERIALS AND METHODS: Retrospective review of patients who presented with IPD to 2 tertiary hospitals in Vancouver, Canada, from July 2004 to June 2007. We compared patient characteristics, interventions, and outcomes between patients who had serotype 5 and other serotypes using bivariate and multivariate analyses. RESULTS: A total of 149 patients had serotype 5 and 106 had nonserotype 5. Patients with serotype 5 were younger, had lower prevalence of comorbid diseases, and had higher rates of substance use than patients with nonserotype 5. There were no differences in chest tube placement for complications of pneumonia or in ICU admission. Frequency of necrotizing pneumonia and hospital mortality were lower in the serotype 5 group. For the 71 patients with IPD who were admitted to ICU, there was no difference in severity of illness, ICU length of stay, or ICU mortality between the groups. There was also no difference in organ supports except that the serotype 5 group was more likely to receive vasopressors. CONCLUSION: Serotype 5 in patients who have IPD is associated with no difference in ICU admission but with increased use of vasopressors and lower hospital mortality.

Obstructive Sleep Apnea Severity and the Risk of Occupational Injury: A Prospective Observational Cohort.

OBJECTIVE: To determine whether patients with obstructive sleep apnea (OSA) are at increased risk of occupational injury (OI) METHODS: Working patients (aged 18 to 65 who reported more than 10 h of work per week) who were referred to the University of British Columbia Sleep Laboratory for suspected OSA for polysomnogram (PSG) were recruited from 2003 to 2011. Patients completed an extensive survey the night of their PSG. Validated OI was obtained by linking patient data to Workers Compensation Board Claims Data. RESULTS: 1109 workers were studied; mean age was 47.1 years, median AHI was 15.0/h, median BMI was 30 kg/m2, 70.2% were male and 29% of patients worked in physical or manual related occupations. 78 patients (7.03%) suffered 140 OI in the 5 years after PSG. In a multivariate logistic regression model, OSA severity [defined as a log(AHI + 1)] was a significant predictor of OI (p = 0.04) after controlling for age, sex, BMI, and physical or manual related occupations. Patients with moderate and severe OSA had approximately two times the odds of an OI compared to patients without OSA (OR 1.99, 95% CI 0.96-4.44 and 2.00, 95% CI 0.96-4.49 for moderate and severe OSA groups, respectively). CONCLUSIONS: In this prospective study, OSA severity was independently associated with an increased risk of OI.

Obstructive Sleep Apnea Severity, Body Mass Index, and Circulating Levels of Cellular Adhesion Molecules.

PURPOSE: To investigate the relationship between obstructive sleep apnea (OSA) severity, body mass index (BMI), and circulating levels of inflammatory adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin). METHODS: A cross-sectional clinical cohort study on all consecutive adults referred to the University of British Columbia (UBC) Sleep Laboratory for a polysomnogram (PSG) for suspected OSA provided a morning blood sample. Samples were analyzed with multiplex immune assay (MilliporeSigma, CA) to assess the levels of adhesion molecules. RESULTS: 488 patients were studied; the majority were male (68%) with a mean age of 50 yrs, mean AHI of 23 events/hour, and mean BMI of 32 kg/m2. In multivariable linear regression models, all three adhesion molecules were significantly associated with BMI (E-selectin p < 0.0001; ICAM-1 p = 0.0007; VCAM-1 p = 0.0003). However, only E-selectin was independently associated with AHI (p = 0.02); there was no significant interaction between AHI and BMI for E-selectin (p = 0.33). CONCLUSIONS: Although all three adhesion molecules were associated with BMI, only E-selectin was independently associated with OSA severity. Future studies are needed to determine the clinical significance of the relationship between E-selectin and OSA.

Association of intensive care unit occupancy during admission and inpatient mortality: a retrospective cohort study.

PURPOSE: There is conflicting evidence regarding the influence of intensive care unit (ICU) occupancy at the time of admission on important patient outcomes such as mortality. The objective of this analysis was to characterize the association between ICU occupancy at the time of ICU admission and subsequent mortality. METHODS: This single-centre, retrospective cohort study included all patients admitted to the ICU at the Vancouver General Hospital between 4 January 2010 and 8 October 2017. Intensive care unit occupancy was defined as the number of ICU bed hours utilized in a day divided by the total amount of ICU bed hours available for that day. We constructed mixed-effects logistic regression models controlling for relevant covariates to assess the impact of admission occupancy quintiles on total inpatient (ICU and ward) and early (72-hr) ICU mortality. RESULTS: This analysis included 10,365 ICU admissions by 8,562 unique patients. Compared with ICU admissions in the median occupancy quintile, admissions in the highest and second highest occupancy quintile were associated with a significant increase in the odds of inpatient mortality (highest: odds ratio [OR], 1.33; 95% confidence interval [CI], 1.12 to 1.59; P value < 0.001; second highest: OR, 1.21; 95% CI, 1.02 to 1.44; P value < 0.03). No association between admission occupancy and 72-hr ICU mortality was observed. CONCLUSIONS: Admission to the ICU on days of high occupancy was associated with increased inpatient mortality, but not with increased 72-hr ICU mortality. Capacity strain on the ICU may result in significant negative consequences for patients, but further research is needed to fully characterize the complex effects of capacity strain.

Association between intensive care unit occupancy at discharge, afterhours discharges, and clinical outcomes: a historical cohort study.

PURPOSE: There is a paucity of evidence evaluating whether intensive care unit (ICU) discharge occupancy is associated with clinical outcomes. It is unknown whether increased discharge occupancy leads to greater afterhours discharges and downstream consequences. We explore the association between ICU discharge occupancy and afterhours discharges, 72-hr readmission, and 30-day mortality. METHODS: This single-centre, historical cohort study included all patients discharged from the Vancouver General Hospital ICU between 5 April 2010 and 13 September 2017. Data were obtained from the British Columbia Critical Care Database. Occupancy was defined as the number of ICU bed hours utilized divided by the available bed hours for that day. Any discharge between 22:00 and 6:59 was considered afterhours. Logistic regression models adjusting for important covariates were constructed. RESULTS: We included 8,862 ICU discharges representing 7,288 individual patients. There were 1,180 (13.3%) afterhours discharges, 408 (4.6%) 72-hr readmissions, and 574 (6.5%) 30-day post-discharge deaths. Greater discharge occupancy was associated with afterhours discharges (per 10% increase: adjusted odds ratio [aOR], 1.12; 95% confidence interval [CI], 1.03 to 1.20; P = 0.005). Discharge occupancy was not associated with 72-hr readmission (per 10% increase: aOR, 0.97; 95% CI, 0.87 to 1.09; P = 0.62) or 30-day mortality (per 10% increase: aOR, 1.05; 95% CI, 0.95 to 1.16; P = 0.32). Afterhours discharge was not associated with 72-hr readmission (aOR, 1.15; 95% CI, 0.86 to 1.54; P = 0.34) or 30-day mortality (aOR, 1.05; 95% CI, 0.82 to 1.36; P = 0.69). CONCLUSIONS: Greater ICU discharge occupancy was associated with a significant increase in afterhours discharges. Nevertheless, neither discharge occupancy nor afterhours discharge were associated with 72-hr readmission or 30-day mortality.

RéSUMé: OBJECTIF: Il n'existe que peu de données probantes évaluant si le taux d'occupation de l'unité de soins intensifs (USI) au moment du congé est associé aux devenirs cliniques. Nous ne savons pas si un taux d'occupation plus élevé au moment du congé entraîne davantage de congés pendant la nuit et si cette situation a des conséquences. Nous avons exploré l'association entre le taux d'occupation de l'USI au moment du congé et les congés donnés pendant la nuit, la réadmission dans les premières 72 h, et la mortalité à 30 jours. MéTHODE: Cette étude de cohorte historique et monocentrique a englobé tous les patients ayant reçu leur congé de l'USI de l'Hôpital général de Vancouver entre le 5 avril 2010 et le 13 septembre 2017. Les données ont été tirées de la Base de données des soins intensifs de Colombie-Britannique (British Columbia Critical Care Database). Le taux d'occupation était défini comme le nombre d'heures d'occupation de lit de l'USI utilisées divisé par le nombre d'heures d'occupation de lit disponibles pour ladite journée. Tout congé reçu entre 22 h et 6 h 59 était considéré comme survenant pendant la nuit. Des modèles de régression logistique ont été élaborés afin de tenir compte des covariables importantes. RéSULTATS: Nous avons inclus 8862 congés de l'USI, représentant 7288 patients individuels. Au total, il y a eu 1180 (13,3 %) congés donnés pendant la nuit, 408 (4,6 %) réadmissions dans les 72 h suivantes, et 574 (6,5 %) décès à 30 jours après le congé. Un taux d'occupation plus élevé au moment du congé était associé à des congés pendant la nuit (par augmentation de 10 % : rapport de cotes ajusté [RCA], 1,12; intervalle de confiance [IC] 95 %, 1,03 à 1,20; P = 0,005). Le taux d'occupation lors du congé n'a pas été associé à une réadmission dans les premières 72 h (par augmentation de 10 % : RCA, 0,97; IC 95 %, 0,87 à 1,09; P = 0,62) ou à une mortalité à 30 jours (par augmentation de 10 % : RCA, 1,05; IC 95 %, 0,95 à 1,16; P = 0,32). Les congés pendant la nuit n'ont pas été associés à une réadmission dans les 72 h suivantes (RCA, 1,15; IC 95 %, 0,86 à 1,54; P = 0,34) ou à une mortalité à 30 jours (RCA, 1,05; IC 95 %, 0,82 à 1,36; P = 0,69). CONCLUSION: Un taux d'occupation de l'USI plus élevé au moment du congé était associé à une augmentation significative des congés donnés pendant la nuit. Cependant, ni le taux d'occupation lors du congé, ni le congé donné pendant la nuit, n'étaient associés à une réadmission à 72 h ou une mortalité à 30 jours.

Sleep Quality and Nocturnal Symptoms in a Community-Based COPD Cohort.

Small studies have suggested that patients with chronic obstructive pulmonary disease (COPD) have poor sleep quality. Our aim was to examine the prevalence of subjective sleep-related complaints and predictors of poor sleep quality in a large community-based COPD cohort. We analyzed cross-sectional data on sleep questionnaire responses from the Canadian Cohort of Obstructive Lung Disease (CanCOLD) study, a population-based, prospective longitudinal cohort study across Canada. The cohort comprises a COPD group and two matched non-COPD (never-smokers and ever-smokers) groups. Sleep-related symptoms were assessed using questionnaires including Pittsburgh Sleep Quality Index (PSQI). A total score of PSQI > 5 is indicative of poor sleep quality. Health-related quality of life measures and the presence of mood disturbance were assessed using Short Form-36™ Health Survey (SF-36) multi-item questionnaires and Hospital Anxiety and Depression Scale (HADS), respectively. Predictors of poor sleep quality were analyzed using multivariable logistic regression analysis. Of the 1123 subjects, 263 were healthy controls, 323 at-risk controls, and 537 had COPD (297 had mild, 240 with moderate to severe disease). The mean PSQI score was not significantly different between groups. COPD patients with poor sleep quality had lower diffusion capacity, higher HADS anxiety and depression scores and lower SF-36 mental and physical component summary scores than COPD patients classified as good sleepers. The presence of restless legs and obstructive sleep apnea symptoms, waist circumference, predicted diffusion capacity and HADS anxiety and depression scores were identified as independent predictors of poor sleep quality.

Intermittent hypoxia impairs uterine artery function in pregnant mice.

KEY POINTS: Obstructive sleep apnoea (OSA) is a chronic condition characterized by intermittent hypoxia that induces oxidative stress and inflammation leading to cardiovascular disease. Women can develop OSA during late pregnancy, which is associated with adverse maternal and fetal outcomes. However, the effects of OSA throughout pregnancy on fetoplacental outcomes are unknown. Using a mouse model of intermittent hypoxia, we evaluated main uterine artery function, spiral artery remodelling, circulating angiogenic and anti-angiogenic factors, and placental hypoxia and oxidative stress at gestational day 14.5 in pregnant mice. Gestational intermittent hypoxia increased placental weight but decreased fetal weight, impaired uterine artery function, increased circulating angiogenic and anti-angiogenic factors, and induced placental hypoxia and oxidative stress, but had no impact on spiral artery remodelling. Our results suggest that pregnant women experiencing OSA during pregnancy could be at risk of maternal and fetal complications. ABSTRACT: Obstructive sleep apnoea (OSA) is characterized by chronic intermittent hypoxia (IH) and is associated with increased inflammation, oxidative stress and endothelial dysfunction. OSA is a common sleep disorder and remains under-diagnosed; it can increase the risk of adverse maternal and fetal outcomes in pregnant women. We investigated the effects of gestational IH (GIH) on uterine artery function, spiral artery remodelling and placental circulating angiogenic and anti-angiogenic factors in pregnant female mice. WT C57BL/6 mice (8 weeks) were exposed to either GIH ( FIO2 12%) or intermittent air ( FIO2 21%) for 14.5 days of gestation. Exposure to GIH reduced fetal weight but increased placental weight. GIH dams had higher plasma levels of oxidative stress (8-isoprostane) and inflammatory markers (tumour necrosis factor-α). GIH significantly reduced uterine artery function as indicated by reduced endothelium-dependent vasodilatation and enhanced vasoconstriction. Plasma levels of placental angiogenic and anti-angiogenic markers (soluble fms-like tyrosine kinase-1, soluble endoglin, angiogenic placental growth factor-2 and vascular endothelial growth factor) were higher in pregnant mice exposed to GIH. There was no evidence of impaired spiral artery remodelling based on immunostaining with α-smooth muscle actin and cytokeratin-7, and also by measurements of lumen area. Immunostaining for markers of hypoxia (pimonidazole) and oxidative stress (4-hydroxynonenal) were higher in mice exposed to GIH. Our data show that GIH adversely affects uterine vascular function and may be a mechanism by which gestational OSA leads to adverse maternal and fetal outcomes.

Gestational intermittent hypoxia induces endothelial dysfunction, reduces perivascular adiponectin and causes epigenetic changes in adult male offspring.

KEY POINTS: Obstructive sleep apnoea (OSA) is characterized by intermittent hypoxia, which causes oxidative stress and inflammation and increases the risk of cardiovascular disease. OSA during pregnancy causes adverse maternal and fetal outcomes. The effects of pre-existing OSA in pregnant women on cardiometabolic outcomes in the offspring are unknown. We evaluated basic metabolic parameters, as well as aortic vascular and perivascular adipose tissue (PVAT) function in response to adiponectin, and examined DNA methylation of adiponectin gene promoter in PVAT in 16-week-old adult offspring exposed to gestational intermittent hypoxia (GIH). GIH decreased body weights at week 1 in both male and female offspring, and caused subsequent increases in body weight and food consumption in male offspring only. Adult female offspring had normal levels of lipids, glucose and insulin, with no endothelial dysfunction. Adult male offspring exhibited dyslipidaemia, insulin resistance and hyperleptinaemia. Decreased endothelial-dependent vasodilatation, loss of anti-contractile activity of PVAT and low circulating PVAT adiponectin levels, as well as increased pro-inflammatory gene expression and DNA methylation of adiponectin gene promoter, occurred in adult male offspring. Our results suggest that male offspring of women with OSA could be at risk of developing cardiometabolic disease during adulthood. ABSTRACT: Perturbations during pregnancy can program the offspring to develop cardiometabolic diseases later in life. Obstructive sleep apnoea (OSA) is a chronic condition that frequently affects pregnancies and leads to adverse fetal outcomes. We assessed the offspring of female mice experiencing gestational intermittent hypoxia (GIH), a hallmark of OSA, for changes in metabolic profiles, aortic nitric oxide (NO)-dependent relaxations, perivascular adipose tissue (PVAT) anti-contractile activities and the responses to adiponectin, and DNA methylation of the adiponectin gene promoter in PVAT tissue. Pregnant mouse dams were exposed to intermittent hypoxic cycles ( FIO2 21-12%) for 18 days. GIH resulted in lower body weights of pups at week 1, followed by significant weight gain by week 16 of age in male but not female offspring. Plasma lipids, leptin and insulin resistance were higher in GIH male adult offspring. Endothelium-dependent relaxation in response to ACh and the anti-contractile activity of PVAT in the abdominal aorta was reduced in GIH adult male offspring. Incubation of arteries from GIH adult male offspring with adiponectin restored the anti-contractile activity of PVAT. Both circulating and PVAT tissue homogenate levels of adiponectin, as well as gene expression of adiponectin in PVAT, were lower in GIH male offspring, along with an increased gene expression of inflammatory cytokines. Pyrosequencing of adiponectin gene promoter in PVAT showed increased DNA methylation in GIH male offspring. Our results indicate that GIH leads to vascular disease in adult male offspring through PVAT dysfunction, which was associated with low adiponectin levels and epigenetic modifications on the adiponectin gene promoter.

One-Year Outcomes in Caregivers of Critically Ill Patients.

BACKGROUND: Few resources are available to support caregivers of patients who have survived critical illness; consequently, the caregivers' own health may suffer. We studied caregiver and patient characteristics to determine which characteristics were associated with caregivers' health outcomes during the first year after patient discharge from an intensive care unit (ICU). METHODS: We prospectively enrolled 280 caregivers of patients who had received 7 or more days of mechanical ventilation in an ICU. Using hospital data and self-administered questionnaires, we collected information on caregiver and patient characteristics, including caregiver depressive symptoms, psychological well-being, health-related quality of life, sense of control over life, and effect of providing care on other activities. Assessments occurred 7 days and 3, 6, and 12 months after ICU discharge. RESULTS: The caregivers' mean age was 53 years, 70% were women, and 61% were caring for a spouse. A large percentage of caregivers (67% initially and 43% at 1 year) reported high levels of depressive symptoms. Depressive symptoms decreased at least partially with time in 84% of the caregivers but did not in 16%. Variables that were significantly associated with worse mental health outcomes in caregivers were younger age, greater effect of patient care on other activities, less social support, less sense of control over life, and less personal growth. No patient variables were consistently associated with caregiver outcomes over time. CONCLUSIONS: In this study, most caregivers of critically ill patients reported high levels of depressive symptoms, which commonly persisted up to 1 year and did not decrease in some caregivers. (Funded by the Canadian Institutes of Health Research and others; ClinicalTrials.gov number, NCT00896220.).

Positive airway pressure for sleep-disordered breathing in acute quadriplegia: a randomised controlled trial.

RATIONALE: Highly prevalent and severe sleep-disordered breathing caused by acute cervical spinal cord injury (quadriplegia) is associated with neurocognitive dysfunction and sleepiness and is likely to impair rehabilitation. OBJECTIVE: To determine whether 3 months of autotitrating CPAP would improve neurocognitive function, sleepiness, quality of life, anxiety and depression more than usual care in acute quadriplegia. METHODS AND MEASUREMENTS: Multinational, randomised controlled trial (11 centres) from July 2009 to October 2015. The primary outcome was neurocognitive (attention and information processing as measure with the Paced Auditory Serial Addition Task). Daytime sleepiness (Karolinska Sleepiness Scale) was a priori identified as the most important secondary outcome. MAIN RESULTS: 1810 incident cases were screened. 332 underwent full, portable polysomnography, 273 of whom had an apnoea hypopnoea index greater than 10. 160 tolerated at least 4 hours of CPAP during a 3-day run-in and were randomised. 149 participants (134 men, age 46±34 years, 81±57 days postinjury) completed the trial. CPAP use averaged 2.9±2.3 hours per night with 21% fully 'adherent' (at least 4 hours use on 5 days per week). Intention-to-treat analyses revealed no significant differences between groups in the Paced Auditory Serial Addition Task (mean improvement of 2.28, 95% CI -7.09 to 11.6; p=0.63). Controlling for premorbid intelligence, age and obstructive sleep apnoea severity (group effect -1.15, 95% CI -10 to 7.7) did not alter this finding. Sleepiness was significantly improved by CPAP on intention-to-treat analysis (mean difference -1.26, 95% CI -2.2 to -0.32; p=0.01). CONCLUSION: CPAP did not improve Paced Auditory Serial Addition Task scores but significantly reduced sleepiness after acute quadriplegia. TRIAL REGISTRATION NUMBER: ACTRN12605000799651.