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Barloese M.,Danish Headache Center | Jennum P.,Danish Center for Sleep Medicine | Knudsen S.,Glostrup University Hospital | Jensen R.,Danish Headache Center

Purpose of review: Sleep and the chronobiological disease cluster headache are believed to be interconnected. Despite efforts, the precise nature of the relationship remains obscured. A better understanding of this relation may lead to more effective therapeutic regimes for patients suffering from this debilitating disease. This review aims to evaluate the existing literature on the subject of cluster headache and sleep.Latest findings: Several previous studies describe an association between episodic cluster headache and distinct macrostructural sleep phases. This association was not confirmed in a recent study of seven episodic cluster headache patients, but it was suggested that further studies into the correlation between cluster headache attacks and the microstructure of sleep are relevant. The connection between cluster headache and the hypocretins is currently under investigation.Summary: There is evidence in favour of an association between episodic cluster headache and REM sleep whereas no such relation to chronic cluster headache has been reported. Particular features in the microstructure of sleep and arousal mechanisms could play a role in the pathogenesis of cluster headache. Reports indicate that cluster headache and obstructive sleep apnoea are associated. Single cases show improvement upon treatment of sleep apnoea, but the causal relationship remains in question. © International Headache Society 2012 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav. Source

Tonnesen P.,Danish Center for Sleep Medicine
Progress in Respiratory Research

The basic principles in quitting smoking are to set a target quit day and try to cut down to zero cigarettes in a few weeks-but best at target quit day-and then use one of the primary drugs for smoking cessation for 2-3 months. In this period, the ex-smoker has to break the psychological addiction as well as the nicotine dependence. Using one of the primary drugs reduces the withdrawal symptoms. Any support will increase quit rate and counselling should be used in combination with one of the primary drugs, i.e. varenicline, nicotine replacement treatment (NRT) and bupropion SR. Varenicline and the combination of two NRT formulations is equally effective, while varenicline is more effective than either single NRT or bupropion SR. NRTs are especially safe. All three drugs have also been shown to be especially effective in patients with chronic obstructive pulmonary disease and in patients with cardiovascular disorders; the main reason for the larger effect in this subgroup is the low quit rate among placebo-treated subjects. There is extensive and solid scientific proof that underlines the efficacy of these three primary drugs in smoking cessation as well as the very high cost-effectiveness of smoking cessation. Vaccines against nicotine have not been effective until now. © 2015 S. Karger AG, Basel. Source

Boyko Y.,Vejle Hospital | Ording H.,Vejle Hospital | Ording H.,University of Southern Denmark | Jennum P.,Danish Center for Sleep Medicine | Jennum P.,Copenhagen University
Acta Anaesthesiologica Scandinavica

Sleep disturbances in the intensive care unit (ICU) seem to lead to development of delirium, prolonged ICU stay, and increased mortality. That is why sufficient sleep is important for good outcome and recovery in critically ill patients. A variety of small studies reveal pathological sleep patterns in critically ill patients including abnormal circadian rhythm, high arousal and awakening index, reduced Slow Wave Sleep, and Rapid Eye Movement sleep. The purpose of this study is to summarise different aspects of sleep-awake disturbances, causes and handling methods in critically ill patients by reviewing the underlying literature. There are no studies of level 1 evidence proving the positive impact of the tested interventions on the critically ill patients' sleep pattern. Thus, disturbed sleep in critically ill patients with all the severe consequences remains an unresolved problem and needs further investigation. © 2012 The Authors. Source

Jennum P.,Danish Center for Sleep Medicine | Ibsen R.,itracks | Kjellberg J.,Danish National Institute for Local and Regional Government Research
Journal of Clinical Sleep Medicine

Background: Sleep-disordered breathing (SDB) causes burden to the sufferer, the healthcare system and society. Most studies have focused on cardiovascular diseases (CVDs) after a diagnosis of obstructive sleep apnea (OSA) or obesity hypoventilation syndrome (OHS); however, the overall morbidity prior to an SDB diagnosis has not been evaluated. The aim of this study was to identify morbidity prior to a SDB diagnosis to identify patients at risk for having/developing SDB. Methods: Using data from the Danish National Patient Registry (1998-2006), we identified all patients nationwide given a diagnosis of OSA (19,438) or OHS (755) in all hospitals and clinics. For each patient, we randomly selected 4 citizens matched for age, sex, and socioeconomic status from the Danish Civil Registration System Statistics. Results: Patients with OSA or OHS presented with increased morbidity at least 3 years prior to their SDB diagnosis. The most common contacts with the health system (odds ratio [OR]/confidence interval [CI]) for OSA/OHS were due to musculoskeletal system (1.36[1.29-1.42]/1.35[1.05-1.74]); CVD (1.38[1.30-1.46]/1.80[1.38-2.34]); endocrine, nutritional, and metabolic diseases (1.62[1.50-1.76]/4.10[2.90-5.78]) ; diseases of the nervous system (1.62[1.0-1.76]/3.54[2.56-4.88]); respiratory system (1.84[1.73-1.96]/2.83[2.07-3.89]); skin and subcutaneous tissue (1.18[1.07-1.30]/2.12[1.33-3.38]); gastrointestinal (1.17[1.10-1.24]/NS); infections (1.20[1.08-1.33]/NS); genitourinary system (1.21[1.13-1.30]/NS); and ear, nose, and throat (1.44[1.32-1.56]/NS). Conclusions: Patients with SDB show significant morbidities several years prior to a diagnosis of OSA or OHS. OSA should be considered in all medical specialties as an important comorbidity. In our study, evidence points to particular emphasis for considering this diagnosis in endocrinology and metabolic specialties. Source

De La Herran-Arita A.K.,Stanford University | Kornum B.R.,Stanford University | Kornum B.R.,Danish Center for Sleep Medicine | Mahlios J.,Stanford University | And 11 more authors.
Science Translational Medicine

Narcolepsy, a disorder strongly associated with human leukocyte antigen (HLA)-DQA1*01:02/DQB1*06:02 (DQ0602), is characterized by excessive daytime sleepiness, cataplexy, and rapid eyemovement sleep abnormalities. It is caused by the loss of ∼70,000 posterior hypothalamic neurons that produce the wake-promoting neuropeptide hypocretin (HCRT) (orexin). We identified two DQ0602-binding HCRT epitopes, HCRT56-68 and HCRT87-99, that activated a subpopulation of CD4+ T cells in narcolepsy patients but not in DQ0602-positive healthy control subjects. Because of the established association of narcolepsy with the 2009 H1N1 influenza A strain (pH1N1), we administered a seasonal influenza vaccine (containing pH1N1) to patients with narcolepsy and found an increased frequency of circulating HCRT56-68- and HCRT87-99-reactive T cells. We also identified a hemagglutinin (HA) pHA1 epitope specific to the 2009 H1N1 strain, pHA1275-287, with homology to HCRT56-68 and HCRT87-99. In vitro stimulation of narcolepsy CD4+ T cells with pH1N1 proteins or pHA1 275-287 increased the frequency of HCRT56-68- and HCRT87-99-reactive T cells. Our data indicate the presence of CD4+ T cells that are reactive to HCRT in narcolepsy patients and possible molecular mimicry between HCRT and a similar epitope in influenza pH1N1, pHA1275-287. Source

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