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Frontiers in Immunology 2022A correlation between sleep and systemic lupus erythematosus (SLE) has been observed in a number of prior investigations. However, little is known regarding the...
A correlation between sleep and systemic lupus erythematosus (SLE) has been observed in a number of prior investigations. However, little is known regarding the potential causative relationship between them. In this study, we selected genetic instruments for sleep traits from pooled data from published genome-wide association studies (GWAS). Independent genetic variants associated with six sleep-related traits (chronotype, sleep duration, short sleep duration, long sleep duration, insomnia, and daytime sleepiness) were selected as instrumental variables. A two-sample Mendelian randomization (TSMR) study was first conducted to assess the causal relationship between sleep traits and SLE (7219 cases versus 15,991 controls). The reverse MR analysis was then used to infer the causal relationship between SLE and sleep traits. Inverse variance weighted (IVW), MR Egger, Weighted median, and Weighted mode were applied to perform the primary MR analysis. MR Egger regression and the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test were used to detect horizontal pleiotropy, and Cochran's was used to detect heterogeneity. In studies of the effect of sleep traits on SLE risk, the IVW method demonstrated no causal relationship between chronotype, sleep duration, short sleep duration, long sleep duration, insomnia, daytime sleepiness and SLE risk. The remaining three methods agreed with the results of IVW. In studies of the effect of SLE on the risk of sleep traits, neither IVW, MR Egger, Weighted median, nor Weighted mode methods provided evidence of a causal relationship between SLE and the risk of sleep traits. Overall, our study found no evidence of a bidirectional causal relationship between genetically predicted sleep traits and SLE.
Topics: Disorders of Excessive Somnolence; Genome-Wide Association Study; Humans; Lupus Erythematosus, Systemic; Mendelian Randomization Analysis; Sleep; Sleep Initiation and Maintenance Disorders
PubMed: 35784289
DOI: 10.3389/fimmu.2022.918749 -
Annals of the American Thoracic Society May 2021Many patients with obstructive sleep apnea (OSA) experience excessive daytime sleepiness (EDS), which can negatively affect daily functioning, cognition, mood, and other... (Review)
Review
Many patients with obstructive sleep apnea (OSA) experience excessive daytime sleepiness (EDS), which can negatively affect daily functioning, cognition, mood, and other aspects of well-being. Although EDS can be reduced with primary OSA treatment, such as continuous positive airway pressure (CPAP) therapy, a significant proportion of patients continue to experience EDS despite receiving optimized therapy for OSA. This article reviews the pathophysiology and clinical evaluation and management of EDS in patients with OSA. The mechanisms underlying EDS in CPAP-treated patients remain unclear. Experimental risk factors include chronic intermittent hypoxia and sleep fragmentation, which lead to oxidative injury and changes in neurons and brain circuit connectedness involving noradrenergic and dopaminergic neurotransmission in wake-promoting regions of the brain. In addition, neuroimaging studies have shown alterations in the brain's white matter and gray matter in patients with OSA and EDS. Clinical management of EDS begins with ruling out other potential causes of EDS and evaluating its severity. Tools to evaluate EDS include objective and self-reported assessments of sleepiness, as well as cognitive assessments. Patients who experience residual EDS despite primary OSA therapy may benefit from wake-promoting pharmacotherapy. Agents that inhibit reuptake of dopamine or of dopamine and norepinephrine (modafinil/armodafinil and solriamfetol, respectively) have demonstrated efficacy in reducing EDS and improving quality of life in patients with OSA. Additional research is needed on the effects of wake-promoting treatments on cognition in these patients and to identify individual or disorder-specific responses.
Topics: Continuous Positive Airway Pressure; Disorders of Excessive Somnolence; Humans; Modafinil; Quality of Life; Sleep Apnea, Obstructive
PubMed: 33621163
DOI: 10.1513/AnnalsATS.202006-696FR -
The Cochrane Database of Systematic... Jan 2022Although combination formulas containing antihistamines, decongestants, and/or analgesics are sold over-the-counter in large quantities for the common cold, the evidence... (Review)
Review
BACKGROUND
Although combination formulas containing antihistamines, decongestants, and/or analgesics are sold over-the-counter in large quantities for the common cold, the evidence for their effectiveness is limited. This is an update of a review first published in 2012.
OBJECTIVES
To assess the effectiveness of antihistamine-decongestant-analgesic combinations compared with placebo or other active controls (excluding antibiotics) in reducing the duration of symptoms and alleviating symptoms (general feeling of illness, nasal congestion, rhinorrhoea, sneezing, and cough) in children and adults with the common cold.
SEARCH METHODS
We searched CENTRAL, MEDLINE via EBSCOhost, Embase, CINAHL via EBSCOhost, LILACS, and Web of Science to 10 June 2021. We searched the WHO ICTRP and ClinicalTrials.gov on 10 June 2021.
SELECTION CRITERIA
Randomised controlled trials investigating the effectiveness of antihistamine-decongestant-analgesic combinations compared with placebo, other active treatment (excluding antibiotics), or no treatment in children and adults with the common cold.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. We assessed the certainty of the evidence using the GRADE approach. We categorised the included trials according to the active ingredients.
MAIN RESULTS
We identified 30 studies (6304 participants) including 31 treatment comparisons. The control intervention was placebo in 26 trials and an active substance (paracetamol, chlorphenindione + phenylpropanolamine + belladonna, diphenhydramine) in six trials (two trials had placebo as well as active treatment arms). Reporting of methods was generally poor, and there were large differences in study design, participants, interventions, and outcomes. Most of the included trials involved adult participants. Children were included in nine trials. Three trials included very young children (from six months to five years), and five trials included children aged 2 to 16. One trial included adults and children aged 12 years or older. The trials took place in different settings: university clinics, paediatric departments, family medicine departments, and general practice surgeries. Antihistamine-decongestant: 14 trials (1298 participants). Eight trials reported on global effectiveness, of which six studies were pooled (281 participants on active treatment and 284 participants on placebo). The odds ratio (OR) of treatment failure was 0.31 (95% confidence interval (CI) 0.20 to 0.48; moderate certainty evidence); number needed to treat for an additional beneficial outcome (NNTB) 3.9 (95% CI 3.03 to 5.2). On the final evaluation day (follow-up: 3 to 10 days), 55% of participants in the placebo group had a favourable response compared to 70% on active treatment. Of the two trials not pooled, one showed some global effect, whilst the other showed no effect. Adverse effects: the antihistamine-decongestant group experienced more adverse effects than the control group: 128/419 (31%) versus 100/423 (13%) participants suffered one or more adverse effects (OR 1.58, 95%CI 0.78 to 3.21; moderate certainty of evidence). Antihistamine-analgesic: four trials (1608 participants). Two trials reported on global effectiveness; data from one trial were presented (290 participants on active treatment and 292 participants on ascorbic acid). The OR of treatment failure was 0.33 (95% CI 0.23 to 0.46; moderate certainty evidence); NNTB 6.67 (95% CI 4.76 to 12.5). Forty-three per cent of participants in the control group and 70% in the active treatment group were cured after six days of treatment. The second trial also showed an effect in favour of the active treatment. Adverse effects: there were not significantly more adverse effects in the active treatment group compared to placebo (drowsiness, hypersomnia, sleepiness 10/152 versus 4/120; OR 1.64 (95 % CI 0.48 to 5.59; low certainty evidence). Analgesic-decongestant: seven trials (2575 participants). One trial reported on global effectiveness: 73% of participants in the analgesic-decongestant group reported a benefit compared with 52% in the control group (paracetamol) (OR of treatment failure 0.28, 95% CI 0.15 to 0.52; moderate certainty evidence; NNTB 4.7). Adverse effects: the decongestant-analgesic group experienced significantly more adverse effects than the control group (199/1122 versus 75/675; OR 1.62 95% CI 1.18 to 2.23; high certainty evidence; number needed to treat for an additional harmful outcome (NNTH 17). Antihistamine-analgesic-decongestant: six trials (1014 participants). Five trials reported on global effectiveness, of which two studies in adults could be pooled: global effect reported with active treatment (52%) and placebo (34%) was equivalent to a difference of less than one point on a four- or five-point scale; the OR of treatment failure was 0.47 (95% CI 0.33 to 0.67; low certainty evidence); NNTB 5.6 (95% CI 3.8 to 10.2). One trial in children aged 2 to 12 years, and two trials in adults found no beneficial effect. Adverse effects: in one trial 5/224 (2%) suffered adverse effects with the active treatment versus 9/208 (4%) with placebo. Two other trials reported no differences between treatment groups.
AUTHORS' CONCLUSIONS
We found a lack of data on the effectiveness of antihistamine-analgesic-decongestant combinations for the common cold. Based on these scarce data, the effect on individual symptoms is probably too small to be clinically relevant. The current evidence suggests that antihistamine-analgesic-decongestant combinations have some general benefit in adults and older children. These benefits must be weighed against the risk of adverse effects. There is no evidence of effectiveness in young children. In 2005, the US Food and Drug Administration issued a warning about adverse effects associated with the use of over-the-counter nasal preparations containing phenylpropanolamine.
Topics: Adolescent; Adult; Analgesics; Child; Child, Preschool; Common Cold; Cough; Histamine Antagonists; Humans; Nasal Decongestants; United States
PubMed: 35060618
DOI: 10.1002/14651858.CD004976.pub4 -
The Cochrane Database of Systematic... Nov 2020Obstructive sleep apnoea (OSA) is a syndrome characterised by episodes of apnoea (complete cessation of breathing) or hypopnoea (insufficient breathing) during sleep.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Obstructive sleep apnoea (OSA) is a syndrome characterised by episodes of apnoea (complete cessation of breathing) or hypopnoea (insufficient breathing) during sleep. Classical symptoms of the disease - such as snoring, unsatisfactory rest and daytime sleepiness - are experienced mainly by men; women report more unspecific symptoms such as low energy or fatigue, tiredness, initial insomnia and morning headaches. OSA is associated with an increased risk of occupational injuries, metabolic diseases, cardiovascular diseases, mortality, and being involved in traffic accidents. Continuous positive airway pressure (CPAP) - delivered by a machine which uses a hose and mask or nosepiece to deliver constant and steady air pressure- is considered the first treatment option for most people with OSA. However, adherence to treatment is often suboptimal. Myofunctional therapy could be an alternative for many patients. Myofunctional therapy consists of combinations of oropharyngeal exercises - i.e. mouth and throat exercises. These combinations typically include both isotonic and isometric exercises involving several muscles and areas of the mouth, pharynx and upper respiratory tract, to work on functions such as speaking, breathing, blowing, sucking, chewing and swallowing.
OBJECTIVES
To evaluate the benefits and harms of myofunctional therapy (oropharyngeal exercises) for the treatment of obstructive sleep apnoea.
SEARCH METHODS
We identified randomised controlled trials (RCTs) from the Cochrane Airways Trials Register (date of last search 1 May 2020). We found other trials at web-based clinical trials registers.
SELECTION CRITERIA
We included RCTs that recruited adults and children with a diagnosis of OSA.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. We assessed our confidence in the evidence by using GRADE recommendations. Primary outcomes were daytime sleepiness, morbidity and mortality.
MAIN RESULTS
We found nine studies eligible for inclusion in this review and nine ongoing studies. The nine included RCTs analysed a total of 347 participants, 69 of them women and 13 children. The adults' mean ages ranged from 46 to 51, daytime sleepiness scores from eight to 14, and severity of the condition from mild to severe OSA. The studies' duration ranged from two to four months. None of the studies assessed accidents, cardiovascular diseases or mortality outcomes. We sought data about adverse events, but none of the included studies reported these. In adults, compared to sham therapy, myofunctional therapy: probably reduces daytime sleepiness (Epworth Sleepiness Scale (ESS), MD (mean difference) -4.52 points, 95% Confidence Interval (CI) -6.67 to -2.36; two studies, 82 participants; moderate-certainty evidence); may increase sleep quality (MD -3.90 points, 95% CI -6.31 to -1.49; one study, 31 participants; low-certainty evidence); may result in a large reduction in Apnoea-Hypopnoea Index (AHI, MD -13.20 points, 95% CI -18.48 to -7.93; two studies, 82 participants; low-certainty evidence); may have little to no effect in reduction of snoring frequency but the evidence is very uncertain (Standardised Mean Difference (SMD) -0.53 points, 95% CI -1.03 to -0.03; two studies, 67 participants; very low-certainty evidence); and probably reduces subjective snoring intensity slightly (MD -1.9 points, 95% CI -3.69 to -0.11 one study, 51 participants; moderate-certainty evidence). Compared to waiting list, myofunctional therapy may: reduce daytime sleepiness (ESS, change from baseline MD -3.00 points, 95% CI -5.47 to -0.53; one study, 25 participants; low-certainty evidence); result in little to no difference in sleep quality (MD -0.70 points, 95% CI -2.01 to 0.61; one study, 25 participants; low-certainty evidence); and reduce AHI (MD -6.20 points, 95% CI -11.94 to -0.46; one study, 25 participants; low-certainty evidence). Compared to CPAP, myofunctional therapy may result in little to no difference in daytime sleepiness (MD 0.30 points, 95% CI -1.65 to 2.25; one study, 54 participants; low-certainty evidence); and may increase AHI (MD 9.60 points, 95% CI 2.46 to 16.74; one study, 54 participants; low-certainty evidence). Compared to CPAP plus myofunctional therapy, myofunctional therapy alone may result in little to no difference in daytime sleepiness (MD 0.20 points, 95% CI -2.56 to 2.96; one study, 49 participants; low-certainty evidence) and may increase AHI (MD 10.50 points, 95% CI 3.43 to 17.57; one study, 49 participants; low-certainty evidence). Compared to respiratory exercises plus nasal dilator strip, myofunctional therapy may result in little to no difference in daytime sleepiness (MD 0.20 points, 95% CI -2.46 to 2.86; one study, 58 participants; low-certainty evidence); probably increases sleep quality slightly (-1.94 points, 95% CI -3.17 to -0.72; two studies, 97 participants; moderate-certainty evidence); and may result in little to no difference in AHI (MD -3.80 points, 95% CI -9.05 to 1.45; one study, 58 participants; low-certainty evidence). Compared to standard medical treatment, myofunctional therapy may reduce daytime sleepiness (MD -6.40 points, 95% CI -9.82 to -2.98; one study, 26 participants; low-certainty evidence) and may increase sleep quality (MD -3.10 points, 95% CI -5.12 to -1.08; one study, 26 participants; low-certainty evidence). In children, compared to nasal washing alone, myofunctional therapy and nasal washing may result in little to no difference in AHI (MD 3.00, 95% CI -0.26 to 6.26; one study, 13 participants; low-certainty evidence).
AUTHORS' CONCLUSIONS
Compared to sham therapy, myofunctional therapy probably reduces daytime sleepiness and may increase sleep quality in the short term. The certainty of the evidence for all comparisons ranges from moderate to very low, mainly due to lack of blinding of the assessors of subjective outcomes, incomplete outcome data and imprecision. More studies are needed. In future studies, outcome assessors should be blinded. New trials should recruit more participants, including more women and children, and have longer treatment and follow-up periods.
Topics: Apnea; Child; Continuous Positive Airway Pressure; Disorders of Excessive Somnolence; Exercise; Female; Humans; Isotonic Contraction; Male; Middle Aged; Myofunctional Therapy; Oropharynx; Randomized Controlled Trials as Topic; Sleep Apnea, Obstructive; Snoring; Therapeutic Irrigation; Waiting Lists
PubMed: 33141943
DOI: 10.1002/14651858.CD013449.pub2 -
The Cochrane Database of Systematic... Nov 2020Sleep disturbances, including reduced nocturnal sleep time, sleep fragmentation, nocturnal wandering, and daytime sleepiness are common clinical problems in dementia,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sleep disturbances, including reduced nocturnal sleep time, sleep fragmentation, nocturnal wandering, and daytime sleepiness are common clinical problems in dementia, and are associated with significant carer distress, increased healthcare costs, and institutionalisation. Although non-drug interventions are recommended as the first-line approach to managing these problems, drug treatment is often sought and used. However, there is significant uncertainty about the efficacy and adverse effects of the various hypnotic drugs in this clinically vulnerable population.
OBJECTIVES
To assess the effects, including common adverse effects, of any drug treatment versus placebo for sleep disorders in people with dementia.
SEARCH METHODS
We searched ALOIS (www.medicine.ox.ac.uk/alois), the Cochrane Dementia and Cognitive Improvement Group's Specialized Register, on 19 February 2020, using the terms: sleep, insomnia, circadian, hypersomnia, parasomnia, somnolence, rest-activity, and sundowning.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared a drug with placebo, and that had the primary aim of improving sleep in people with dementia who had an identified sleep disturbance at baseline.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data on study design, risk of bias, and results. We used the mean difference (MD) or risk ratio (RR) with 95% confidence intervals (CI) as the measures of treatment effect, and where possible, synthesised results using a fixed-effect model. Key outcomes to be included in our summary tables were chosen with the help of a panel of carers. We used GRADE methods to rate the certainty of the evidence.
MAIN RESULTS
We found nine eligible RCTs investigating: melatonin (5 studies, n = 222, five studies, but only two yielded data on our primary sleep outcomes suitable for meta-analysis), the sedative antidepressant trazodone (1 study, n = 30), the melatonin-receptor agonist ramelteon (1 study, n = 74, no peer-reviewed publication), and the orexin antagonists suvorexant and lemborexant (2 studies, n = 323). Participants in the trazodone study and most participants in the melatonin studies had moderate-to-severe dementia due to Alzheimer's disease (AD); those in the ramelteon study and the orexin antagonist studies had mild-to-moderate AD. Participants had a variety of common sleep problems at baseline. Primary sleep outcomes were measured using actigraphy or polysomnography. In one study, melatonin treatment was combined with light therapy. Only four studies systematically assessed adverse effects. Overall, we considered the studies to be at low or unclear risk of bias. We found low-certainty evidence that melatonin doses up to 10 mg may have little or no effect on any major sleep outcome over eight to 10 weeks in people with AD and sleep disturbances. We could synthesise data for two of our primary sleep outcomes: total nocturnal sleep time (TNST) (MD 10.68 minutes, 95% CI -16.22 to 37.59; 2 studies, n = 184), and the ratio of day-time to night-time sleep (MD -0.13, 95% CI -0.29 to 0.03; 2 studies; n = 184). From single studies, we found no evidence of an effect of melatonin on sleep efficiency, time awake after sleep onset, number of night-time awakenings, or mean duration of sleep bouts. There were no serious adverse effects of melatonin reported. We found low-certainty evidence that trazodone 50 mg for two weeks may improve TNST (MD 42.46 minutes, 95% CI 0.9 to 84.0; 1 study, n = 30), and sleep efficiency (MD 8.53%, 95% CI 1.9 to 15.1; 1 study, n = 30) in people with moderate-to-severe AD. The effect on time awake after sleep onset was uncertain due to very serious imprecision (MD -20.41 minutes, 95% CI -60.4 to 19.6; 1 study, n = 30). There may be little or no effect on number of night-time awakenings (MD -3.71, 95% CI -8.2 to 0.8; 1 study, n = 30) or time asleep in the day (MD 5.12 minutes, 95% CI -28.2 to 38.4). There were no serious adverse effects of trazodone reported. The small (n = 74), phase 2 trial investigating ramelteon 8 mg was reported only in summary form on the sponsor's website. We considered the certainty of the evidence to be low. There was no evidence of any important effect of ramelteon on any nocturnal sleep outcomes. There were no serious adverse effects. We found moderate-certainty evidence that an orexin antagonist taken for four weeks by people with mild-to-moderate AD probably increases TNST (MD 28.2 minutes, 95% CI 11.1 to 45.3; 1 study, n = 274) and decreases time awake after sleep onset (MD -15.7 minutes, 95% CI -28.1 to -3.3: 1 study, n = 274) but has little or no effect on number of awakenings (MD 0.0, 95% CI -0.5 to 0.5; 1 study, n = 274). It may be associated with a small increase in sleep efficiency (MD 4.26%, 95% CI 1.26 to 7.26; 2 studies, n = 312), has no clear effect on sleep latency (MD -12.1 minutes, 95% CI -25.9 to 1.7; 1 study, n = 274), and may have little or no effect on the mean duration of sleep bouts (MD -2.42 minutes, 95% CI -5.53 to 0.7; 1 study, n = 38). Adverse events were probably no more common among participants taking orexin antagonists than those taking placebo (RR 1.29, 95% CI 0.83 to 1.99; 2 studies, n = 323).
AUTHORS' CONCLUSIONS
We discovered a distinct lack of evidence to guide decisions about drug treatment of sleep problems in dementia. In particular, we found no RCTs of many widely prescribed drugs, including the benzodiazepine and non-benzodiazepine hypnotics, although there is considerable uncertainty about the balance of benefits and risks for these common treatments. We found no evidence for beneficial effects of melatonin (up to 10 mg) or a melatonin receptor agonist. There was evidence of some beneficial effects on sleep outcomes from trazodone and orexin antagonists and no evidence of harmful effects in these small trials, although larger trials in a broader range of participants are needed to allow more definitive conclusions to be reached. Systematic assessment of adverse effects in future trials is essential.
Topics: Alzheimer Disease; Azepines; Caregiver Burden; Cognition; Humans; Indenes; Melatonin; Pyridines; Pyrimidines; Randomized Controlled Trials as Topic; Sleep; Sleep Wake Disorders; Time Factors; Trazodone; Triazoles
PubMed: 33189083
DOI: 10.1002/14651858.CD009178.pub4 -
The Neuroscientist : a Review Journal... Aug 2020Advances in neuroimaging open up the possibility for new powerful tools to be developed that potentially can be applied to clinical populations to improve the diagnosis... (Review)
Review
Advances in neuroimaging open up the possibility for new powerful tools to be developed that potentially can be applied to clinical populations to improve the diagnosis of neurological disorders, including sleep disorders. At present, the diagnosis of narcolepsy and primary hypersomnias is largely limited to subjective assessments and objective measurements of behavior and sleep physiology. In this review, we focus on recent neuroimaging findings that provide insight into the neural basis of narcolepsy and the primary hypersomnias Kleine-Levin syndrome and idiopathic hypersomnia. We describe the role of neuroimaging in confirming previous genetic, neurochemical, and neurophysiological findings and highlight studies that permit a greater understanding of the symptoms of these sleep disorders. We conclude by considering some of the remaining challenges to overcome, the existing knowledge gaps, and the potential role for neuroimaging in understanding the pathogenesis and clinical features of narcolepsy and primary hypersomnias.
Topics: Animals; Disorders of Excessive Somnolence; Humans; Kleine-Levin Syndrome; Narcolepsy; Nervous System Diseases; Neuroimaging; Sleep
PubMed: 32111133
DOI: 10.1177/1073858420905829 -
Nature Communications May 2023Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with...
Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix®.
Topics: Humans; Autoimmunity; Influenza, Human; Influenza A Virus, H1N1 Subtype; Autoimmune Diseases; Influenza Vaccines; Narcolepsy
PubMed: 37188663
DOI: 10.1038/s41467-023-36120-z -
American Journal of Respiratory and... Sep 2022Randomized controlled trials of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) have not demonstrated protection against... (Randomized Controlled Trial)
Randomized Controlled Trial
Randomized controlled trials of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) have not demonstrated protection against adverse cardiovascular outcomes. Recently, observational studies revealed that OSA-related cardiovascular risk is concentrated in patients with an elevated pulse rate response to respiratory events (ΔHR). Here, in this analysis of a prospective clinical trial, we test the hypothesis that a greater pretreatment ΔHR is associated with greater CPAP-related protection against adverse cardiovascular outcomes. ΔHR was measured from baseline polysomnography of the RICCADSA (Randomized Intervention with CPAP in CAD and OSA) randomized controlled trial (patients with coronary artery disease [CAD] and OSA [apnea-hypopnea index ⩾ 15 events/h] with Epworth Sleepiness Scale score < 10; : = 113:113; male, 85%; age, 66 ± 8 [mean ± SD] yr). The primary outcome was a composite of repeat revascularization, myocardial infarction, stroke, and cardiovascular mortality. Multivariable Cox regression assessed whether the effect of CPAP was moderated by ΔHR (treatment-by-ΔHR interaction). The CPAP-related reduction in risk increased progressively with increasing pretreatment ΔHR (interaction hazard ratio [95% confidence interval], 0.49 [0.27 to 0.90] per SD increase in ΔHR; < 0.05). This means that in patients with a ΔHR of 1 SD above the mean (i.e., 10 beats/min), CPAP was estimated to reduce cardiovascular risk by 59% (6% to 82%) ( < 0.05), but no significant risk reduction was estimated in patients with a mean ΔHR (6 beats/min; CPAP risk reduction, 16% [-53% to 54%]; = 0.6). The protective effect of CPAP in patients with CAD and OSA without excessive sleepiness was modified by the ΔHR. Specifically, patients with higher ΔHR exhibit greater cardiovascular benefit from CPAP therapy.
Topics: Adult; Aged; Continuous Positive Airway Pressure; Coronary Artery Disease; Disorders of Excessive Somnolence; Female; Humans; Male; Middle Aged; Prospective Studies; Sleep Apnea, Obstructive; Sleepiness; Treatment Outcome
PubMed: 35579605
DOI: 10.1164/rccm.202111-2608OC -
Sleep Feb 2022Rapid eye movement (REM) sleep behavior disorder (RBD) and other sleep disturbances are frequent in leucine-rich, glioma inactivated protein 1-IgG (LGI1) and...
STUDY OBJECTIVES
Rapid eye movement (REM) sleep behavior disorder (RBD) and other sleep disturbances are frequent in leucine-rich, glioma inactivated protein 1-IgG (LGI1) and contactin-associated protein 2-IgG (CASPR2) autoimmunity, yet polysomnographic analyses of these disorders remain limited. We aimed to characterize clinical presentations and analyze polysomnographic manifestations, especially quantitative REM sleep without atonia (RSWA) in LGI1/CASPR2-IgG seropositive (LGI/CASPR2+) patients.
METHODS
We retrospectively analyzed clinical and polysomnographic features and quantitative RSWA between LGI1+/CASPR2+ patients and age-sex matched controls. Groups were compared with Wilcoxon rank-sum and chi-square tests. Combined submentalis and anterior tibialis (SM + AT) RSWA was the primary outcome.
RESULTS
Among 11 (LGI1+, n = 9; CASPR2+, n = 2) patients, Morvan syndrome sleep features were present in seven (63.6%) LGI1+/CASPR2+ patients, with simultaneous insomnia and dream enactment behavior (DEB) in three (27.3%), and the most common presenting sleep disturbances were DEB (n = 5), insomnia (n = 5), and sleep apnea (n = 8; median apnea-hypopnea index = 15/hour). Median Epworth Sleepiness Scale was nine (range 3-24; n = 10), with hypersomnia in four (36.4%). LGI1+/CASPR2+ patients had increased N1 sleep (p = .02), decreased REM sleep (p = .001), and higher levels of SM + AT any RSWA (p < .001). Eight of nine (89%) LGI1+ exceeded RBD RSWA thresholds (DEB, n = 5; isolated RSWA, n = 3). RSWA was greater in AT than SM. All 10 LGI1+/CASPR2+ patients treated with immunotherapy benefitted, and 5/10 had improved sleep disturbances.
CONCLUSIONS
LGI1/CASPR2-IgG autoimmunity is associated with prominent dream enactment, insomnia, RSWA, sleep apnea, and shallower sleep. Polysomnography provides objective disease markers in LGI1+/CASPR2+ autoimmunity and immunotherapy may benefit associated sleep disturbances.
Topics: Autoimmunity; Humans; Intracellular Signaling Peptides and Proteins; Membrane Proteins; Nerve Tissue Proteins; Polysomnography; REM Sleep Behavior Disorder; Retrospective Studies; Sleep, REM
PubMed: 34953167
DOI: 10.1093/sleep/zsab297