Sleep-disordered breathing-do we have to change gears in heart failure?

The majority of patients with heart failure have sleep-disordered breathing (SDB)-with central (rather than obstructive) sleep apnoea becoming the predominant form in those with more severe disease. Cyclical apnoeas and hypopnoeas are associated with sleep disturbance, hypoxaemia, haemodynamic changes, and sympathetic activation. Such patients have a worse prognosis than those without SDB. Mask-based therapies of positive airway pressure targeted at SDB can improve measures of sleep quality and partially normalise the sleep and respiratory physiology, but recent randomised trials of cardiovascular outcomes in central sleep apnoea have been neutral or suggested the possibility of harm, likely from increased sudden death. Further randomised outcome studies (with cardiovascular mortality and hospitalisation endpoints) are required to determine whether mask-based treatment for SDB is appropriate for patients with chronic systolic heart failure and obstructive sleep apnoea, for those with heart failure with preserved ejection fraction, and for those with decompensated heart failure. New therapies for sleep apnoea-such as implantable phrenic nerve stimulators-also require robust assessment. No longer can the surrogate endpoints of improvement in respiratory and sleep metrics be taken as adequate therapeutic outcome measures in patients with heart failure and sleep apnoea

Sleep apnoea and metabolic dysfunction.

Obstructive sleep apnoea (OSA) is a highly prevalent condition often associated with central obesity. In the past few years, several studies have analysed the potential independent contribution of OSA to the pathogenesis of metabolic abnormalities, including type 2 diabetes, the metabolic syndrome and nonalcoholic fatty liver disease. New perspectives in OSA patient care have been opened by the promotion of lifestyle interventions, such as diet and exercise programmes that could improve both OSA and the metabolic profile. The rich clinical literature on this subject, together with the growing amount of data on pathophysiological mechanisms provided by animal studies using the chronic intermittent hypoxia model, urged the organising Committee of the Sleep and Breathing meeting to organise a session on sleep apnoea and metabolic dysfunction, in collaboration with the European Association for the Study of Diabetes. This review summarises the state-of-the-art lectures presented in the session, more specifically the relationship between OSA and diabetes, the role of OSA in the metabolic consequences of obesity, and the effects of lifestyle interventions on nocturnal respiratory disturbances and the metabolic profile in OSA patient

Dabigatran and Warfarin for Stroke Prevention in Atrial Fibrillation: Use, Switching, and Clinical Effects Following New Market Entry in Real-World Patients

Patients with atrial fibrillation frequently benefit from anticoagulation to prevent stroke and systemic embolism. For decades, warfarin was the primary oral anticoagulant option despite its narrow therapeutic index requiring monitoring and drug-drug interactions. Dabigatran’s recent availability provides practical advantages including no monitoring and fewer interactions; however, it lacks a convenient reversal agent for bleeding events. Currently, it is unclear what factors have driven anticoagulant utilization since dabigatran’s introduction, and little real-world evidence on the agents’ comparative effectiveness and safety is available. The objectives were to describe dabigatran and warfarin’s utilization and switching patterns and assess their comparative effectiveness and safety. A cohort of non-valvular atrial fibrillation patients initiating anticoagulation from a large US database of commercial and Medicare supplement claims from 2009-2012 was extracted. We first examined factors associated with anticoagulant selection using a retrospective cohort design and multivariable regression. We then evaluated the effectiveness and safety of dabigatran compared with warfarin using multivariable Cox proportional hazards regression and propensity score weighting. Finally, we evaluated the clinical effects of switching anticoagulants compared with non-switching using a time-varying exposure design and multivariable Cox proportional hazards regression. Of the 64,935 patients included in the cohort, 32.5% used dabigatran. Dabigatran users were less likely to have high ischemic stroke or bleeding risk or other clinical comorbidities. Switching anticoagulation was also less frequent among patients with higher ischemic stroke or bleeding risk. Dabigatran was associated with a lower risk of ischemic stroke or venous thromboembolism, and no relation was seen between anticoagulant and harmful outcomes including bleeding events or acute myocardial infarction. However, dabigatran was also associated with a higher risk of gastrointestinal bleeding. Compared with non-switchers, no relation was seen between switching anticoagulants and an increased risk of stroke, systemic embolism, bleeding events, or myocardial infarction. Despite the rapid uptake of dabigatran, these results highlight that patients initiating dabigatran were generally healthier than those initiating warfarin. Dabigatran may be considered a safe and possibly more effective alternative to warfarin in patients with atrial fibrillation; despite encouraging results from the observed lack of increased adverse outcomes from switching anticoagulants, caution is still recommended

An empirical method to cluster objective nebulizer adherence data among adults with cystic fibrosis

Background: The purpose of using preventative inhaled treatments in cystic fibrosis is to improve health outcomes. Therefore, understanding the relationship between adherence to treatment and health outcome is crucial. Temporal variability, as well as absolute magnitude of adherence affects health outcomes, and there is likely to be a threshold effect in the relationship between adherence and outcomes. We therefore propose a pragmatic algorithm-based clustering method of objective nebulizer adherence data to better understand this relationship, and potentially, to guide clinical decisions. Methods to cluster adherence data: This clustering method consists of three related steps. The first step is to split adherence data for the previous 12 months into four 3-monthly sections. The second step is to calculate mean adherence for each section and to score the section based on mean adherence. The third step is to aggregate the individual scores to determine the final cluster (“cluster 1” = very low adherence; “cluster 2” = low adherence; “cluster 3” = moderate adherence; “cluster 4” = high adherence), and taking into account adherence trend as represented by sequential individual scores. The individual scores should be displayed along with the final cluster for clinicians to fully understand the adherence data. Three illustrative cases: We present three cases to illustrate the use of the proposed clustering method. Conclusion: This pragmatic clustering method can deal with adherence data of variable duration (ie, can be used even if 12 months’ worth of data are unavailable) and can cluster adherence data in real time. Empirical support for some of the clustering parameters is not yet available, but the suggested classifications provide a structure to investigate parameters in future prospective datasets in which there are accurate measurements of nebulizer adherence and health outcomes

Impact of obstructive sleep apnoea and experiences of using positive airway pressure

The aim of this thesis was to explore the impact of the common sleep-related breathing disorder, obstructive sleep apnoea (OSA); specifically for people with a bipolar disorder (BD) diagnosis but also the wider experience of the first-line treatment for OSA, positive airway pressure (PAP). Chapter 1 is a systematic literature review and thematic synthesis of experiences using PAP to treat OSA. Twenty-five papers were reviewed and included in the thematic synthesis. The quality of each paper was appraised and considered in relation to contribution to the resultant analytical themes. The metasynthesis gave voice to user experiences of PAP and revealed barriers to PAP use at a healthcare service level. The findings highlight the need for a biopsychosocial approach and long-term person-centred support to enhance PAP use. Chapter 2 is a primary empirical research paper on an investigation as to whether people with suspected-OSA and a BD diagnosis experience more sleep and affect instability when “inter-episode” compared to people with a BD diagnosis alone. Ecological momentary assessment was utilised. Eighteen participants (twelve with suspected-OSA) wore an acitgraph for two weeks whilst completing an affect questionnaire twice daily. Measures of instability were calculated using the mean squared successive difference and probability of acute change indices. The groups were not found to significantly differ other than reduced sleep efficiency in the suspected-OSA group. However, only 48% of the intended sample was successfully recruited due to the COVID-19 pandemic. Important avenues for further research are highlighted. Chapter 3 is a critical appraisal of the thesis. Salient issues relevant to future research and clinical practice are discussed, in addition to the under recognised clinical issue of sleep which inspired this thesis

Sleep homeostasis in the European jackdaw (<i>Coloeus monedula</i>):Sleep deprivation increases NREM sleep time and EEG power while reducing hemispheric asymmetry

Introduction: Sleep is a wide-spread phenomenon that is thought to occur in all animals. Yet, the function of it remains an enigma. Conducting sleep experiments in different species may shed light on the evolution and functions of sleep. Therefore, we studied sleep architecture and sleep homeostatic responses to sleep deprivation in the European jackdaw (Coloeus monedula).Methods: A total of nine young adult birds were implanted with epidural electrodes and equipped with miniature data loggers for recording movement activity (accelerometery) and electroencephalogram (EEG). Individually-housed jackdaws were recorded under controlled conditions with a 12:12-h light-dark cycle.Results: During baseline, the birds spent on average 48.5% of the time asleep (39.8% non-rapid eye movement (NREM) sleep and 8.7% rapid eye movement (REM) sleep). Most of the sleep occurred during the dark phase (dark phase: 75.3% NREM sleep and 17.2% REM sleep; light phase 4.3% NREM sleep and 0.1% REM sleep). After sleep deprivation of 4 and 8 h starting at lights off, the birds showed a dose-dependent increase in NREM sleep time. Also, NREM sleep EEG power in the 1.5–3 Hz frequency range, which is considered to be a marker of sleep homeostasis in mammals, was significantly increased for 1-2 h after both 4SD and 8SD. While there was little true unihemispheric sleep in the Jackdaws, there was a certain degree of hemispheric asymmetry in NREM sleep EEG power during baseline, which reduced after sleep deprivation in a dose-dependent manner.Conclusion: In conclusion, jackdaws display homeostatic regulation of NREM sleep and sleep pressure promotes coherence in EEG power

The Laboratory-Based Intermountain Validated Exacerbation (LIVE) Score Identifies Chronic Obstructive Pulmonary Disease Patients at High Mortality Risk.

Background: Identifying COPD patients at high risk for mortality or healthcare utilization remains a challenge. A robust system for identifying high-risk COPD patients using Electronic Health Record (EHR) data would empower targeting interventions aimed at ensuring guideline compliance and multimorbidity management. The purpose of this study was to empirically derive, validate, and characterize subgroups of COPD patients based on routinely collected clinical data widely available within the EHR. Methods: Cluster analysis was used in 5,006 patients with COPD at Intermountain to identify clusters based on a large collection of clinical variables. Recursive Partitioning (RP) was then used to determine a preferred tree that assigned patients to clusters based on a parsimonious variable subset. The mortality, COPD exacerbations, and comorbidity profile of the identified groups were examined. The findings were validated in an independent Intermountain cohort and in external cohorts from the United States Veterans Affairs (VA) and University of Chicago Medicine systems. Measurements and Main Results: The RP algorithm identified five LIVE Scores based on laboratory values: albumin, creatinine, chloride, potassium, and hemoglobin. The groups were characterized by increasing risk of mortality. The lowest risk, LIVE Score 5 had 8% 4-year mortality vs. 56% in the highest risk LIVE Score 1 (p &lt; 0.001). These findings were validated in the VA cohort (n = 83,134), an expanded Intermountain cohort (n = 48,871) and in the University of Chicago system (n = 3,236). Higher mortality groups also had higher COPD exacerbation rates and comorbidity rates. Conclusions: In large clinical datasets across different organizations, the LIVE Score utilizes existing laboratory data for COPD patients, and may be used to stratify risk for mortality and COPD exacerbations