Region-specific changes in brain activity and memory after continuous positive airway pressure therapy in obstructive sleep apnea: a pilot high-density electroencephalography study.

STUDY OBJECTIVES: Limited channel electroencephalography (EEG) investigations in obstructive sleep apnea (OSA) have revealed deficits in slow wave activity (SWA) and spindles during sleep and increased EEG slowing during resting wakefulness. High-density EEG (Hd-EEG) has also detected local parietal deficits in SWA (delta power) during NREM. It is unclear whether effective continuous positive airway pressure (CPAP) treatment reverses regional SWA deficits, and other regional sleep and wake EEG abnormalities, and whether any recovery relates to improved overnight memory consolidation. METHODS: A clinical sample of men with moderate-severe OSA underwent sleep and resting wake recordings with 256-channel Hd-EEG before and after 3 months of CPAP. Declarative and procedural memory tasks were administered pre- and post-sleep. Topographical spectral power maps and differences between baseline and treatment were compared using t-tests and statistical nonparametric mapping (SnPM). RESULTS: In 11 compliant CPAP users (5.2 ±â€…1.1 hours/night), total sleep time did not differ after CPAP but N1 and N2 sleep were lower and N3 was higher. Centro-parietal gamma power during N3 increased and fronto-central slow spindle activity during N2 decreased (SnPM < 0.05). No other significant differences in EEG power were observed. When averaged specifically within the parietal region, N3 delta power increased after CPAP (p = 0.0029) and was correlated with the change in overnight procedural memory consolidation (rho = 0.79, p = 0.03). During resting wakefulness, there were trends for reduced delta and theta power. CONCLUSIONS: Effective CPAP treatment of OSA may correct regional EEG abnormalities, and regional recovery of SWA may relate to procedural memory improvements in the short term.

Giving weight to incretin-based pharmacotherapy for obesity-related sleep apnea: a revolution or a pipe dream?

Obesity is a chronic disease affecting over 670 million adults globally, with multiple complications including obstructive sleep apnea (OSA). Substantial weight loss in patients with obesity-related OSA can reduce or even eliminate OSA as well as reduce sleepiness and improve cardio-metabolic health. Evidence suggests that these improvements exceed those that occur with device-based OSA therapies like continuous positive airway pressure which continue to be the first-line of therapy. Resistance to weight management as a first-line strategy to combat OSA could arise from the complexities in delivering and maintaining adequate weight management, particularly in sleep clinic settings. Recently, incretin-based pharmacotherapies including glucagon-like peptide 1 (GLP-1) receptor agonists alone or combined with glucose-dependent insulinotropic polypeptide (GIP) receptor agonists have been developed to target glycemic control in type 2 diabetes. These medications also slow gastric emptying and reduce energy intake. In randomized, placebo-controlled trials of these medications in diabetic and non-diabetic populations with obesity, participants on active medication lost up to 20% of their body weight, with corresponding improvements in blood pressure, lipid levels, physical functioning, and fat mass loss. Their adverse effects are predominantly gastrointestinal-related, mild, and transient. There are trials currently underway within individuals with obesity-related OSA, with a focus on reduction in weight, OSA severity, and cardio-metabolic outcomes. These medications have the potential to substantially disrupt the management of OSA. Pending coming data, we will need to consider pharmacological weight loss as a first-line therapy and how that influences training and management guidelines.

The Relationship between Anxiety, Subjective and Objective Sleep, Chronotype and Circadian Rhythms with Depressive Symptoms in Insomnia Disorder.

Insomnia is a highly prevalent sleep disorder with strong bidirectional associations with depressive symptoms. The circadian preference for eveningness has been shown to be associated with depressive symptoms in insomnia and other mental health conditions. However, there is a lack of studies in insomnia investigating whether objective measures, such as dim light melatonin onset (DLMO) or polysomnographic (PSG) sleep, are associated with depressive symptoms. Therefore, we investigated the associations between subjective measures (questionnaires assessing anxiety, sleep quality and circadian preference, and sleep diary) and depressive symptoms and whether the addition of objective measures (DLMO, PSG parameters) would strengthen the associations with depressive symptoms. In 115 insomnia disorder patients we found that anxiety was strongly associated with depressive symptoms in a model including circadian preference, dysfunctional beliefs of sleep, and self-reported previous depressive symptoms (R2 = 0.496, p < 0.001). The addition of sleep diary measures did not strengthen the model. We also found that the addition of objective measures (DLMO, PSG parameters) did not improve the subjective associations with depressive symptoms. Our data suggest that objective circadian markers are less important in the prediction of depressive symptoms in insomnia compared to subjective measures.

Young Adults' Perceptions of 2 Publicly Available Digital Resources for Self-injury: Qualitative Study of a Peer Support App and Web-Based Factsheets.

BACKGROUND: Digital resources have the potential to bridge the gaps in mental health services for young people who self-injure. Most research on digital resources for this population has involved observational studies of content in web-based communities or formative studies focused on the design and early evaluation of new interventions. Far less research has sought to understand young people's experiences with publicly available digital resources or to identify specific components of these resources that are perceived to be of value in their recovery. OBJECTIVE: This study aimed to understand young people's experiences with 2 publicly available digital resources for self-injury-a peer support app and web-based factsheets-and to disentangle potential explanatory mechanisms associated with perceived benefits and harms. METHODS: Participants were 96 individuals (aged 16-25 years) with nonsuicidal self-injury behavior in the past month, who recently completed a pilot randomized controlled trial designed to assess the efficacy of a peer support app as compared with web-based factsheets to reduce self-injury behavior. The trial showed that participants using the peer support app reported less self-injury behavior relative to those receiving the web-based factsheets over 8 weeks. In this study, we used a conventional approach to content analysis of responses to 2 open-ended questions delivered at the end of the trial with the aims of exploring participants' overall experiences with these resources and identifying the qualities of these resources that were perceived to be beneficial to or harmful for participants' recovery. RESULTS: Overall, participants were more likely to report benefits than harms. Participants who used the peer support app reported more harms than those who received the web-based factsheets. In the open coding phase, clear benefits were also derived from repeated weekly surveys about self-injury. Key benefits across digital resources included enhanced self-knowledge, reduction in self-injury activity, increased outreach or informal conversations, improved attitudes toward therapy, improved mood, and feeling supported and less alone. Key challenges included worsened or unchanged self-injury activity, diminished mood, and increased barriers to outreach. The most prominent benefit derived from the web-based factsheets and weekly surveys was improved self-understanding. However, the way this manifested differed, with factsheets providing insight on why participants engage in self-injury and the function it serves them and surveys making the frequency and severity of participants' behaviors more apparent. The benefits perceived from using the peer support app were general improvements in mood and feeling less alone. CONCLUSIONS: Findings contribute a nuanced understanding of young people's experiences with these digital resources and have implications for the optimization of existing platforms and the design of novel resources to support individuals who self-injure.

Cediranib in Combination with Olaparib in Patients without a Germline BRCA1/2 Mutation and with Recurrent Platinum-Resistant Ovarian Cancer: Phase IIb CONCERTO Trial.

PURPOSE: The efficacy, safety, and tolerability of cediranib plus olaparib (cedi/ola) were investigated in patients with nongermline-BRCA-mutated (non-gBRCAm) platinum-resistant recurrent ovarian cancer. PATIENTS AND METHODS: PARP inhibitor-naïve women aged ≥18 years with platinum-resistant non-gBRCAm ovarian cancer, ECOG performance status of 0-2, and ≥3 prior lines of therapy received cediranib 30 mg once daily plus olaparib 200 mg twice daily in this single-arm, multicenter, phase IIb trial. The primary endpoint was objective response rate (ORR) by independent central review (ICR) using RECIST 1.1. Progression-free survival (PFS), overall survival (OS), and safety and tolerability were also examined. RESULTS: Sixty patients received cedi/ola, all of whom had confirmed non-gBRCAm status. Patients had received a median of four lines of chemotherapy; most (88.3%) had received prior bevacizumab. ORR by ICR was 15.3%, median PFS was 5.1 months, and median OS was 13.2 months. Forty-four (73.3%) patients reported a grade ≥3 adverse event (AE), with one patient experiencing a grade 5 AE (sepsis), considered unrelated to the study treatment. Dose interruptions, reductions, and discontinuations due to AEs occurred in 55.0%, 18.3%, and 18.3% of patients, respectively. Patients with high global loss of heterozygosity (gLOH) had ORR of 26.7% [4/15; 95% confidence interval (CI), 7.8-55.1], while ORR was 12.5% (4/32; 95% CI, 3.5-29.0) in the low gLOH group. CONCLUSIONS: Clinical activity was shown for the cedi/ola combination in heavily pretreated, non-gBRCAm, platinum-resistant patients with ovarian cancer despite failing to meet the target ORR of 20%, highlighting a need for further biomarker studies.

Use of a Mobile Peer Support App Among Young People With Nonsuicidal Self-injury: Small-scale Randomized Controlled Trial.

BACKGROUND: Nonsuicidal self-injury (NSSI) is a widespread behavior among adolescents and young adults. Although many individuals who self-injure do not seek treatment, there is evidence for web-based help-seeking through web-based communities and mobile peer support networks. However, few studies have rigorously tested the efficacy of such platforms on outcomes relevant for NSSI recovery. OBJECTIVE: The aim of this small-scale preregistered randomized controlled trial is to provide preliminary insight into the shorter- and longer-term efficacy of the use of a peer support app, TalkLife, in reducing NSSI frequency and urges and increasing readiness to change. In addition, we explore contact with informal support, interest in therapy, and attitudes toward professional help-seeking. METHODS: Individuals aged 16-25 years with current (within 3 months) and chronic (>6 episodes in the past year) NSSI history were eligible to participate in this study. After baseline assessments, the intervention group was instructed to use the app actively (eg, post or comment at least three times per week) and the control group received weekly psychoeducational materials through email, for 8 weeks. Follow-up was assessed at 1 month and 2 months. Linear mixed modeling was used to evaluate condition and time point effects for the primary outcomes of NSSI frequency and urges, readiness to change, contact with informal support, interest in therapy, and attitudes toward professional help-seeking. RESULTS: A total of 131 participants were included in the analysis. We evidenced a significant effect of condition on NSSI frequency such that the participants using the peer support app self-injured less over the course of the study (mean 1.30, SE 0.18) than those in the control condition (mean 1.62, SE 0.18; P=.02; η2=0.02). We also evidenced a significant condition effect of readiness to change such that the treatment participants reported greater confidence in their ability to change their NSSI behavior (mean 6.28, SE 0.41) than the control participants (mean 5.67, SE 0.41; P=.04; η2=0.02). No significant differences were observed for contact with informal support, interest in therapy, or attitudes toward professional help-seeking. CONCLUSIONS: Use of the peer support app was related to reduced NSSI frequency and greater confidence in one's ability to change NSSI behavior over the course of the study period, but no effects on NSSI urges, contact with informal support, interest in therapy, or attitudes toward professional help-seeking were observed. The findings provide preliminary support for considering the use of mobile peer support apps as a supplement to NSSI intervention and point to the need for larger-scale trials. TRIAL REGISTRATION: Open Science Foundation; https://osf.io/3uay9.

Safety of higher doses of melatonin in adults: A systematic review and meta-analysis.

Melatonin is commonly used for sleep and jetlag at low doses. However, there is less documentation on the safety of higher doses, which are being increasingly used for a wide variety of conditions, including more recently COVID-19 prevention and treatment. The aim of this review was to investigate the safety of higher doses of melatonin in adults. Medline, Scopus, Embase and PsycINFO databases from inception until December 2019 with convenience searches until October 2020. Randomised controlled trials investigating high-dose melatonin (≥10 mg) in human adults over 30 years of age were included. Two investigators independently abstracted articles using PRISMA guidelines. Risk of bias was assessed by a committee of three investigators. 79 studies were identified with a total of 3861 participants. Studies included a large range of medical conditions. The meta-analysis was pooled data using a random effects model. The outcomes examined were the number of adverse events (AEs), serious adverse events (SAEs) and withdrawals due to AEs. A total of 29 studies (37%) made no mention of the presence or absence of AEs. Overall, only four studies met the pre-specified low risk of bias criteria for meta-analysis. In that small subset, melatonin did not cause a detectable increase in SAEs (Rate Ratio = 0.88 [0.52, 1.50], p = .64) or withdrawals due to AEs (0.93 [0.24, 3.56], p = .92), but did appear to increase the risk of AEs such as drowsiness, headache and dizziness (1.40 [1.15, 1.69], p < .001). Overall, there has been limited AE reporting from high-dose melatonin studies. Based on this limited evidence, melatonin appears to have a good safety profile. Better safety reporting in future long-term trials is needed to confirm this as our confidence limits were very wide due to the paucity of suitable data.

Development and validation of a model for diagnosis of obstructive sleep apnoea in primary care.

BACKGROUND AND OBJECTIVE: Use of in-laboratory polysomnography (PSG) to diagnose obstructive sleep apnoea (OSA) is cost and resource intensive. Questionnaires, physical measurements and home monitors have been studied as potential simpler alternatives. This study aimed to develop a diagnostic model for OSA for use in primary care. METHODS: Primary care practitioners were trained to recognize symptoms of sleep apnoea and recruited patients based on the clinical need to investigate OSA. Assessment was by symptom questionnaires, anthropomorphic measurements, digital facial photography, and a single-channel nasal flow monitor (Flow Wizard©, DiagnoseIT, Sydney, Australia) worn at home for 3 nights. The in-laboratory PSG was the reference test, with OSA defined as apnoea-hypopnoea index (AHI) ≥10 events/h. RESULTS: In the model development phase, 25 primary care practitioners studied 315 patients in whom they suspected OSA, of which 57% had AHI≥10 and 22% had AHI≥30. Published OSA questionnaires provided low to moderate prediction of OSA (area under the curve [AUC] 0.53-0.73). The nasal flow monitor alone yielded high accuracy for predicting OSA with AUC of 0.87. Sensitivity was 0.87 and specificity 0.77 at a threshold respiratory event index (REI) of 18 events/h. A model adding age, gender, symptoms and BMI to the nasal flow monitor REI only modestly improved OSA prediction (AUC 0.89), with similar AUC (0.88) confirmed in the validation population of 114 patients. CONCLUSION: Sleep apnoea can be diagnosed in the primary care setting with a combination of clinical judgement and portable monitor test outcomes.

Feasibility of 3-month melatonin supplementation for brain oxidative stress and sleep in mild cognitive impairment: protocol for a randomised, placebo-controlled study.

INTRODUCTION: Melatonin has multiple proposed therapeutic benefits including antioxidant properties, synchronisation of the circadian system and lowering of blood pressure. In this protocol, we outline a randomised controlled trial to assess the feasibility, acceptability and tolerability of higher dose (25 mg) melatonin to target brain oxidative stress and sleep disturbance in older adults with mild cognitive impairment (MCI). METHODS AND ANALYSIS: The study design is a randomised double-blind, placebo-controlled, parallel group trial. Forty individuals with MCI will be recruited from the Healthy Brain Ageing Clinic, University of Sydney and from the community, and randomised to receive either 25 mg oral melatonin or placebo nightly for 12 weeks. The primary outcomes are feasibility of recruitment, acceptability of intervention and adherence to trial medication at 12 weeks. Secondary outcomes will include the effect of melatonin on brain oxidative stress as measured by magnetic resonance spectroscopy, blood pressure, blood biomarkers, mood, cognition and sleep. Outcomes will be collected at 6 and 12 weeks. The results of this feasibility trial will inform a future conclusive randomised controlled trial to specifically test the efficacy of melatonin on modifiable risk factors of dementia, as well as cognition and brain function. This will be the first trial to investigate the effect of melatonin in the population with MCI in this way, with the future aim of using this approach to reduce progression to dementia. ETHICS AND DISSEMINATION: This protocol has been approved by the Sydney Local Health District Ethics Committee (X18-0077). This randomised controlled trial will be conducted in compliance with the protocol published in the registry, the International Conference for Harmonisation on Good Clinical Practice and all other applicable regulatory requirements. The findings of the trial will be disseminated via conferences, publications and media, as applicable. Participants will be informed of results of the study at the conclusion of the trial. Eligible authors will include investigators who are involved in the conception and design of the study, the conduct of the trial, the analysis of the results, and reporting and presentation of study findings. TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trials Registry (ANZCTRN 12619000876190). PROTOCOL VERSION: V.8 15 October 2020.

The association of insomnia disorder characterised by objective short sleep duration with hypertension, diabetes and body mass index: A systematic review and meta-analysis.

Insomnia disorder with objective short sleep duration (less than 6 h of objective sleep or sleep efficiency less than 85%) has been considered as a biologically severe subtype of insomnia associated with a higher risk of cardiometabolic disease morbidity. This systematic review and meta-analysis firstly compared insomnia disorder with objective short and normal sleep duration, and subsequently, objective short sleep duration with and without insomnia disorder, and their associations with hypertension, type 2 diabetes and body mass index. A systematic search of five databases yielded 2345 non-duplicated articles, of which 11 individual studies were used for the qualitative review and 10 individual studies for the meta-analysis. The sample size varied from 30 to 4994 participants. A higher risk of hypertension (RR 1.54, 95% CI: [1.30; 1.82] p < 0.0001) and type 2 diabetes (RR 1.63 [1.37; 1.94], p < 0.0001) was associated with insomnia disorder with objective short sleep compared to normal sleep duration, but not for body mass index. Comparisons between insomnia disorder with objective short sleep and objective short sleep without insomnia disorder showed no significant differences. However, the majority of these studies were cross-sectional, and there is a need for more cohort study data.

Pharmacokinetics of exogenous melatonin in relation to formulation, and effects on sleep: A systematic review.

There is conflicting evidence on the clinical efficacy of exogenous melatonin for the treatment of sleep disorders. This may be due to differences in the pharmacokinetic (PK) properties of melatonin formulations used in clinical trials. The aim of this systematic review was to understand the relationship between melatonin formulations and PK parameters and, where possible, the effects on sleep outcomes. To this purpose, we conducted a systematic review and nineteen papers were included. The studies included three melatonin transdermal formulation, thirteen oral formulations, one topical, two buccal, two intravenous and two nasogastric formulations. Seven studies investigated the effect of the melatonin formulation on sleep and six of them found a significant improvement in one or more sleep parameters. The potential for an improved controlled release formulation that delays maximum concentration (Cmax) was identified. The different formulations and doses affect melatonin PK, suggesting that treatment efficacy maybe affected. Based on the current evidence, we are unable to provide recommendations of specific melatonin formulations and PK parameters for specific sleep disorders. Future studies should systematically investigate how different PK parameters of melatonin formulations affect efficacy treatment of sleep as well as circadian disorders.

Disparities in ovarian cancer survival at the only NCI-designated cancer center in Kansas.

BACKGROUND: This study examined the impact of geographic distance on survival outcomes for patients receiving treatment for ovarian cancer at the only NCI-designated cancer center (NCI-CC) in Kansas. METHODS: We identified ovarian cancer patients treated at the University of Kansas Cancer Center between 2010 and 2015. Demographic factors and clinical characteristics were abstracted. The main outcome measure was overall survival according to geographic distance from the institution. Kaplan Meier survival curves and Cox proportional hazard models were generated using SAS v9.4. RESULTS: 220 patients were identified. Survival analysis based on distance from the institution demonstrated that patients who lived ≤10 miles from the institution had worse overall survival (p = 0.0207) and were more likely to have suboptimal cytoreductive surgery (p = 0.0276). Lower estimated median income was also associated with a 1.54 increased risk of death, 95% CI (1.031-2.292), p = 0.0347. CONCLUSIONS: We determined that ovarian cancer survival disparities exist in our patient population. Lower rates of optimal cytoreductive surgery has been identified as a possible driver of poor prognosis for patients who lived in proximity to our institution.

Does craniofacial morphology relate to sleep apnea severity reduction following weight loss intervention? A patient-level meta-analysis.

STUDY OBJECTIVES: Obesity is a common and reversible risk factor for obstructive sleep apnea (OSA). However, there is substantial unexplained variability in the amount of OSA improvement for any given amount of weight loss. Facial photography is a simple, inexpensive, and radiation-free method for craniofacial assessment. Our aims were (1) to determine whether facial measurements can explain OSA changes, beyond weight loss magnitude and (2) whether facial morphology relates to how effective weight loss will be for OSA improvement. METHODS: We combined data from three weight loss intervention trials in which participants had standardized pre-intervention facial photography (N = 91; 70.3% male, mean ± SD weight loss 10.4 ± 9.6% with 20.5 ± 51.2% apnea-hypopnea index [AHI] reduction). Three skeletal-type craniofacial measurements (mandibular length, lower face height, and maxilla-mandible relationship angle) were assessed for relationship to AHI change following weight loss intervention. RESULTS: Weight and AHI changes were moderately correlated (rho = 0.3, p = 0.002). In linear regression, an increased maxilla-mandible relationship angle related to AHI improvement (ß [95% CI] -1.7 [-2.9, -0.5], p = 0.004). Maxilla-mandible relationship angle explained 10% in the variance in AHI over the amount predicted by weight loss amount (20%). The relationship between weight change and AHI was unaffected by the maxilla-mandible relationship angle (interaction term p > 0.05). CONCLUSIONS: Regardless of facial morphology, weight loss is similarly moderately predictive of OSA improvement. Increased maxilla-mandible relationship angle, suggestive of retrognathia, was weakly predictive of OSA response to weight loss. Although this is unlikely to be clinically useful, exploration in other ethnic groups may be warranted.

Objective measurement of sleep in mild cognitive impairment: A systematic review and meta-analysis.

Older adults with mild cognitive impairment (MCI) are at-risk of developing dementia, particularly Alzheimer's disease. While some research suggests that alterations in sleep architecture may mediate cognitive decline, the nature and magnitude of changes to sleep macro- (sleep stages) and micro-architecture (electroencephalography (EEG) oscillations) in MCI is not yet clear. This study aimed to systematically review and meta-analyse case-control studies objectively measuring sleep in MCI. A systematic search was conducted using PubMed, Scopus, Web of Science, Embase and Psycinfo databases and after review, a total of 10 studies met inclusion criteria. Of these, all reported sleep macro-architecture and four reported micro-architecture outcomes. A combined total of 430 participants (209 with and 221 without MCI) underwent objective sleep assessments in the included full text articles. Findings show that compared to healthy controls, those with MCI have pronounced changes in sleep macro-architecture with greater wake after sleep onset, reduced total sleep time, lower sleep efficiency, longer sleep onset latency, longer rapid eye movement sleep (REM) latency, reduced REM sleep, greater N1 sleep, and worse severity of hypoxemia. Pooling of sleep micro-architecture EEG measures was not possible due to limited studies, however reduced spindles in non-REM sleep and greater EEG slowing in REM sleep were reported.

The Production of Listeriolysin O and Subsequent Intracellular Infections by Listeria monocytogenes Are Regulated by Exogenous Short Chain Fatty Acid Mixtures.

Listeria monocytogenes is a foodborne pathogen capable of secreting listeriolysin O (LLO), a pore-forming toxin encoded by the hly gene. While the functions of LLO have been studied extensively, how the production of LLO is modulated by the intestinal environment, devoid of oxygen and enriched in short chain fatty acids (SCFAs), is not completely understood. Using L. monocytogenes strain 10403s, we found that hly transcription was moderately decreased by aerobic SCFA exposures but significantly increased by anaerobic SCFA exposures. Moreover, aerobic, but not anaerobic, exposure to low levels of SCFAs resulted in a significantly higher LLO activity. These results demonstrated that transcriptional and post-transcriptional regulations of LLO production were separately modulated by SCFAs and were responsive to oxygen levels. Examining isogenic mutants revealed that PrfA and SigB play a role in regulating LLO production in response to SCFAs. Effects of SCFAs were also present in the cardiotropic strain 07PF0776 but distinctly different from those in strain 10403s. For both strains, prior exposures to SCFAs altered intracellular infections in Caco-2 and RAW264.7 cells and the plaque sizes in L fibroblasts, a result confirming the ability of L. monocytogenes to adapt to SCFAs in ways that impact its subsequent infection outcomes.

Magnesium supplementation for the treatment of restless legs syndrome and periodic limb movement disorder: A systematic review.

Magnesium supplementation is often suggested for restless legs syndrome (RLS) or period limb movement disorder (PLMD) based on anecdotal evidence that it relieves symptoms and because it is also commonly recommended for leg cramps. We aimed to review all articles reporting the effects of magnesium supplementation on changes in RLS and/or PLMD. We conducted a systematic search looking for all relevant articles and then two reviewers read all article titles and abstracts to identify relevant studies. Eligible studies were scored for their quality as interventional trials. We found 855 abstracts and 16 of these could not be definitively excluded for not addressing all aspects of our research question. Seven full-text articles were unlocatable and one was ineligible which left eight studies with relevant data. One was a randomised placebo-controlled trial, three were case series and four were case studies. The RCT did not find a significant treatment effect of magnesium but may have been underpowered. After quality appraisal and synthesis of the evidence we were unable to make a conclusion as to the effectiveness of magnesium for RLS/PLMD. It is not clear whether magnesium helps relieve RLS or PLMD or in which patient groups any benefit might be seen.

A review of psychosocial factors and personality in the treatment of obstructive sleep apnoea.

Effective treatment of obstructive sleep apnoea (OSA) is primarily determined by adherence to the selected intervention. The most common treatment pathways are mechanical devices such as continuous positive airway pressure (CPAP) or a mandibular advancement device, often combined with weight loss therapy. Weight reduction is usually an adjunct therapy but may be used as a secondary treatment in mild-to-moderate OSA when mechanical treatments cannot be tolerated. To enhance the uptake and adherence to treatment, clinicians may assess patient's personality profiles and psychological readiness. There is a paucity of evidence related to these aspects of patient care and this article outlines the current research in relation to patient presentation, treatment uptake and barriers, and methods to enhance treatment adherence.This article disseminates personality traits observed in patients with OSA and identifies vulnerable groups who may require additional support to increase treatment adherence. It summarises the current evidence for treatment barriers in patients with OSA. Low self-efficacy in relation to CPAP and weight loss adherence will be explored as well as the potential to predict treatment responders and enhance therapeutic uptake and adherence. Extending personality traits into research and clinical practice could potentially result in more successful CPAP therapy and weight loss treatment outcomes.

Parsing the craniofacial phenotype: effect of weight change in an obstructive sleep apnoea population.

PURPOSE: Craniofacial structure is an important risk factor in the development of obstructive sleep apnoea. Most craniofacial imaging methods are not feasible for large-scale studies or the clinic. Craniofacial photography is a high-throughput technique for facial phenotyping; however, derived measurements are a composite of skeletal and soft tissue craniofacial information. Weight change is a paradigm to help determine which facial measurements most relate to regional soft tissue (i.e. change with weight) versus skeletal structure (i.e. stable with weight changes). We aimed to assess the association between weight change and changes in key facial measurements from facial photography. METHODS: Calibrated frontal and profile photographs were taken of participants in weight loss studies (N = 106). Univariate linear regression was used to assess whether weight change explained changes in facial dimensions. RESULTS: Patients lost 11.7 ± 10.8 kg body weight and 2.0 ± 2.0 cm of neck circumference. Weight changes influenced face width (r = 0.3, p < 0.001), mandibular width (r = 0.4, p < 0.001) and cervicomental angle (r = 0.3, p = 0.001). Facial angles, facial heights and mandibular length were not influenced by weight change. CONCLUSIONS: A weight loss paradigm suggests that face and mandibular width and cervicomental angle most strongly reflect regional adiposity. Facial angles and heights are insensitive to weight change and could be more representative of craniofacial skeletal structure. This study informs the interpretation of facial phenotype assessed by this craniofacial photographic method which can be applied to future studies of craniofacial phenotype in OSA.

Intra-individual stability of NREM sleep quantitative EEG measures in obstructive sleep apnea.

Electroencephalography is collected routinely during clinical polysomnography, but is often utilised to simply determine sleep time to calculate apnea-hypopnea indices. Quantitative analysis of these data (quantitative electroencephalogram) may provide trait-like information to predict patient vulnerability to sleepiness. Measurements of trait-like characteristics need to have high test-retest reliability. We aimed to investigate the intra-individual stability of slow-wave (delta power) and spindle frequency (sigma power) activity during non-rapid eye movement sleep in patients with obstructive sleep apnea. We recorded sleep electroencephalograms during two overnight polysomnographic recordings in 61 patients with obstructive sleep apnea (median days between studies 47, inter-quartile range 53). Electroencephalograms recorded at C3-M2 derivation were quantitatively analysed using power spectral analysis following artefact removal. Relative delta (0.5-4.5 Hz) and sigma (12-15 Hz) power during non-rapid eye movement sleep were calculated. Intra-class correlation coefficients and Bland-Altman plots were used to assess agreement between nights. Intra-class correlation coefficients demonstrated good-to-excellent agreement in the delta and sigma frequencies between nights (intra-class correlation coefficients: 0.84, 0.89, respectively). Bland-Altman analysis of delta power showed a mean difference close to zero (-0.4, 95% limits of agreement -9.4, 8.7) and no heteroscedasticity with increasing power. Sigma power demonstrated heteroscedasticity, with reduced stability as sigma power increased. The mean difference of sigma power between nights was close to zero (0.1, 95% limits -1.6, 1.8). We have demonstrated the stability of slow-wave and spindle frequency electroencephalograms during non-rapid eye movement sleep within patients with obstructive sleep apnea. The electroencephalogram profile during non-rapid eye movement sleep may be a useful biomarker for predicting vulnerability to daytime impairment in obstructive sleep apnea and responsiveness to treatment.

Is Metabolic Rate Increased in Insomnia Disorder? A Systematic Review.

Background: Insomnia disorder is a highly prevalent health condition, affecting ~10-15% of the adult population worldwide. A central feature of insomnia is hyperarousal characterized as persistent and increased somatic, cognitive and cortical stimulation. Hyperarousal leads to a state of conditioned arousal that disrupts both sleep and daytime function. Research studies have shown increases in body temperature, heart rate, electroencephalographic activity, catecholamines, and oxygen consumption as a measure of metabolic rate. These findings provide evidence of increased physiological activation in insomnia however results are not consistent. The aim of the systematic review was to determine if metabolic rate in patients with insomnia is increased in keeping with the hyperarousal hypothesis. Methods: We searched Pubmed, Web of Science, CINAHL, PsycINFO, EMBASE, and Scopus databases for observational and interventional studies that have measured metabolic rate in insomnia. Study characteristics were extracted and summarized and a risk of bias was performed for each of the studies. Results: Two reviewers screened 963 abstracts with 35 articles of interest for full-text review. Four articles evaluating 75 participants were included in this systematic review. Two studies showed increased oxygen consumption across 24 h in insomnia patients compared with good-sleeping controls. One study which measured oxygen consumption at only a single timepoint showed no difference between insomnia patients and good-sleeping controls. A further study evaluating the effect of lorazepam on oxygen consumption in patients with chronic insomnia showed that lorazepam reduced metabolic rate during the night time only. Conclusions: These findings show that metabolic rate appears to be increased across 24 h in line with the hyperarousal model of insomnia. However, these increases in metabolic rate in insomnia were minor compared to good-sleeping controls and the clinical significance is unclear. Larger, methodologically robust studies are required to confirm these findings and the effect of any increase in metabolic rate on sleep-wake disturbances or pathophysiology.