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Circadian rhythms alter with ageing and may be aetiologically linked to neurodegeneration. This study explored the association between clinical markers and 1) dim light melatonin onset (DLMO) time and 2) phase angle derived from sleep midpoint, in older adults with varying dementia risks. Participants completed 14 days of actigraphy followed by in-lab measurement of salivary melatonin, from which DLMO time and phase angle were computed. Eighty participants (age = 65.5, SD = 9.6), 44 males (55%), MMSE (28.6, SD = 1.5) were included in the analysis. Sex (t = 2.15, p = .04), sleep onset (r = 0.49, p .001) and midpoint (r = 0.44, p .001) also correlated with DLMO time. Multiple linear regression showed chronotype, average actigraphy-derived light exposure during the DLMO window (window 2 h prior to DLMO to 2 h post), early biological day (6-10 h post DLMO time) and late biological day (10-14 h post DLMO time) were predictive of DLMO time (adjusted R

Background Poor sleep health is now recognised as a significant risk factor for chronic diseases and is associated with considerable comorbidity and mortality. Community pharmacists are primary care clinicians with an integral role in sleep health promotion and chronic sleep disorder management; however, it is unclear to what extent this is currently being undertaken or what the perspectives of Australian community pharmacists regarding their role in sleep health are. Objectives To explore community pharmacists’ current sleep health practice and perspectives on the potential future of sleep health care in community pharmacy. Methods Qualitative semi-structured interviews were carried out with a maximally varied, convenience-based purposive sample of community pharmacists. Interviews were audio-recorded, transcribed verbatim and subjected to, in sequence; an inductive analysis followed by a deductive approach where the inductively derived thematic structure was used as a framework. Results Twenty-five community pharmacists from two Australian states were interviewed. Insomnia and obstructive sleep apnea (OSA) were the most frequently encountered sleep disorders in community pharmacy presentations. Four key themes were derived from the data: 1) Preparedness, 2) Approach, 3) Capabilities and 4) What needs to change? All participants reported that their sleep health knowledge was insufficient and emphasized the need for more education and training. Although some were engaged in providing OSA services, none of the participants offered services for insomnia or other sleep disorders. Time/task pressures, low health system/health care professional sleep health recognition/awareness and the lack of standardised pharmacy-specific sleep health management guidelines were commonly cited barriers for sleep health service provision. Conclusion Community pharmacists commonly manage day-to-day sleep health; however, most expressed a need for increased sleep health recognition/awareness by the health system, targeted education/training for pharmacists and support for the future provision of community pharmacy-delivered sleep health services. With the appropriate implementation strategies, community pharmacists could utilise their availability and accessibility to improve the future of primary care sleep health management.

Reduced heart rate variability can be an early sign of autonomic dysfunction in neurodegenerative diseases and may be related to brain dysfunction in the central autonomic network. As yet, such autonomic dysfunction has not been examined during sleep—which is an ideal physiological state to study brain–heart interaction as both the central and peripheral nervous systems behave differently compared to during wakefulness. Therefore, the primary aim of the current study was to examine whether heart rate variability during nocturnal sleep, specifically slow wave (deep) sleep, is associated with central autonomic network functional connectivity in older adults ‘at-risk’ of dementia. Older adults (n = 78; age range = 50–88 years; 64% female) attending a memory clinic for cognitive concerns underwent resting-state functional magnetic resonance imaging and an overnight polysomnography. From these, central autonomic network functional connectivity strength and heart rate variability data during sleep were derived, respectively. High-frequency heart rate variability was extracted to index parasympathetic activity during distinct periods of sleep, including slow wave sleep as well as secondary outcomes of non-rapid eye movement sleep, wake after sleep onset, and rapid eye movement sleep. General linear models were used to examine associations between central autonomic network functional connectivity and high-frequency heart rate variability. Analyses revealed that increased high-frequency heart rate variability during slow wave sleep was associated with stronger functional connectivity (F = 3.98, P = 0.022) in two core brain regions within the central autonomic network, the right anterior insular and posterior midcingulate cortex, as well as stronger functional connectivity (F = 6.21, P = 0.005) between broader central autonomic network brain regions—the right amygdala with three sub-nuclei of the thalamus. There were no significant associations between high-frequency heart rate variability and central autonomic network connectivity during wake after sleep onset or rapid eye movement sleep. These findings show that in older adults ‘at-risk’ of dementia, parasympathetic regulation during slow wave sleep is uniquely linked to differential functional connectivity within both core and broader central autonomic network brain regions. It is possible that dysfunctional brain–heart interactions manifest primarily during this specific period of sleep known for its role in memory and metabolic clearance. Further studies elucidating the pathophysiology and directionality of this relationship should be conducted to determine if heart rate variability drives neurodegeneration, or if brain degeneration within the central autonomic network promotes aberrant heart rate variability.

To determine the influence of age on sleepiness-related driving performance in individuals with obstructive sleep apnea (OSA).Extended wakefulness protocol comparing simulated driving performance in younger and older individuals with OSA.Fifty-two individuals with OSA (15 female) were median split into younger (≤55 years, n = 26) and older (55 years, n = 26) groups.Participants underwent polysomnography to derive sleep parameters and confirm OSA diagnosis. One-to-2 weeks following polysomnography, participants completed a 60-minute driving simulation 4 hours prior to their habitual bedtime. Participants remained awake to 3 hours post habitual bedtime before repeating the task.Median age was 44.5 years (25th, 75th centiles = 37.0, 48.0) for the younger group and 64.5 years (60.0, 70.0) for the older group. When comparing the performance change between baseline and extended wakefulness, the younger patients had greater deterioration on all driving simulator parameters (crashes, standard deviation of lateral position, speed deviation and braking reaction time, all p.05), compared to the older group. Linear regression found a 10-year age increase was associated with an a ∼30%-41% reduction in crash occurrence when accounting for covariates (p = .023). Age also predicted standard deviation of lateral position deviation, but not when sleep efficiency and self-reported sleepiness were included as covariates.Older participants with OSA were less vulnerable than younger participants to sleepiness-related driving simulator impairment when assessed at night-time following extended wakefulness. Future work should assess naturalistic on-road driving to determine if this extends to a variety of challenging driving scenarios.

The first-line treatment for insomnia is cognitive-behavioral therapy. However, there is persistent use of pharmacotherapy, particularly, sedative-hypnotics. Consultant pharmacists can provide medication review services for people using multiple medications. Therefore, they are well placed to provide sleep health/insomnia care with regard to sedative-hypnotic use and behavioral treatment recommendations/sleep health education. However, this avenue is, as yet, unexplored.To explore consultant pharmacists' current sleep health-related provisions and what their perspectives are around developing/implementing a consultant pharmacist-led behavioral service for insomnia.Qualitative semi-structured interviews were conducted with a convenience-based sample of consultant pharmacists. Interviews were audio-recorded, transcribed, and inductively analyzed.Twenty-four consultant pharmacists were interviewed. Three themes were gauged: 1)Insomnia/sleep health concerns are growing. Primary health professionals need to scale up their sleep health-care provisions to accommodate for this health demand. Consultant pharmacists are interested/willing to expand their sleep-related practice and provide evidence-based insomnia therapies; however, factors such as education/training, service configuration support, and patient attitudes should be addressed.

Objective This pilot trial aimed to provide evidence for whether the integration of a wearable device with digital behavioral therapy for insomnia (dBTi) improves treatment outcomes and engagement. Participants and methods One hundred and twenty-eight participants with insomnia symptoms were randomized to a 3-week dBTi program (SleepFix®) with a wearable device enabling sleep data synchronization (dBTi+wearable group; n = 62) or dBTi alone (n = 66). Participants completed the Insomnia Severity Index (ISI) and modified Pittsburgh Sleep Quality Index (PSQI) parameters: wake-after-sleep-onset (WASO), sleep-onset-latency (SOL), and total sleep time (TST) at baseline and weeks 1, 2, 3, and primary endpoint of week 6 and follow-up at 12 weeks. Engagement was measured by the number of daily sleep diaries logged in the app. Results There was no difference in ISI change scores between the groups from pre- to post-treatment (Cohen's d= 0.7, p= .061). The dBTi+wearable group showed greater improvements in WASO (d= 0.8, p = .005) and TST (d= 0.3, p= .049) compared to the dBTi group. Significantly greater engagement (sleep diary entries) was observed in the dBTi+wearable group (mean = 22.4, SD = 10.0) compared to the dBTi group (mean = 14.1, SD = 14.2) (p = .010). Conclusions This pilot trial found that integration of wearable device with a digital insomnia therapy enhanced user engagement and led to improvements in sleep parameters compared to dBTi alone. These findings suggest that adjunctive wearable technologies may improve digital insomnia therapy effectiveness.

This integrative review aimed to draw conclusions from evidence on how registered nurses are measuring respiratory rates for acute care patients.Despite the growing research supporting respiratory rate as an early indicator for clinical deterioration, respiratory rate has consistently been the least frequently measured and accurately documented vital sign.An integrative review.A systematic literature search was conducted in June 2022 in four databases: CINAHL, PubMed, Medline and Scopus. Quality appraisal was undertaken using the Joanna Briggs Institute's Checklist. PRISMA guidelines were followed to ensure explicit reporting and reported in the PRISMA checklist.Overall, 9915 records were identified, and 19 met the inclusion criteria. Of these 19 articles, seven themes emerged: estimation and digit preference, lack of understanding and knowledge, not valuing the clinical significance of respiratory rate, oxygen saturation substitute, interobserver agreement, subjective concern and count duration. A high prevalence of bias, estimation and incorrect technique was evident. A total of 15 articles reported specifically on how registered nurses are measuring respiratory rates on general medical and surgical wards.Despite its importance, this integrative review has determined that respiratory rates are not being assessed correctly by nursing staff in the acute care environment. Evidence of using estimation, value bias or quick count and multiply techniques are emerging themes which urgently require further research. No patient or public contribution.

To determine the effects of repeated physical activity on iron and zinc homeostases in a living system, we quantified blood and tissue levels of these two metals in sedentary and physically active Long-Evans rats. At post-natal day (PND) 22, female rats were assigned to either a sedentary or an active treatment group (n=10/group). The physically active rats increased their use of a commercially-constructed stainless steel wire wheel so that, by the end of the study (PND 101), they were running an average of 512.8 ± 31.9 (mean ± standard error) minutes/night. After euthanization, plasma and aliquots of liver, lung, heart, and gastrocnemius muscle were obtained. Following digestion, non-heme iron and zinc concentrations in plasma and tissues were measured using inductively coupled plasma optical emission spectroscopy. Concentrations of both non-heme iron and zinc in plasma and liver were significantly decreased among the physically active rats relative to the sedentary animals. In the lung, both metals were increased in concentration among the physically active animals but the change in zinc did not reach significance. Similarly, tissue non-heme iron and zinc levels were both increased in heart and muscle from the physically active group. It is concluded that repeated physical activity in an animal model can be associated with a translocation of both iron and zinc from sites of storage (e.g. liver) to tissues with increased metabolism (e.g. the lung, heart, and skeletal muscle).

BackgroundThis systematic review aimed to investigate whether the administration of hypnotic medicines, z-drugs, melatonin or benzodiazepines, reduced pain intensity postoperatively.MethodsMedline, Embase, Cinahl, Psych info, Central and PubMed databases were searched, from inception to February 2020 to identify relevant trials. The search was extended, post hoc, to include meta-Register of Controlled Trials, the Web of Science and the conference booklets for the 14th, 15th, and 16th International Association for the Study of Pain conferences. Two independent reviewers screened titles and abstracts and cross-checked the extracted data.ResultsThe search retrieved 5546 articles. After full-text screening, 15 trials were included, which had randomised 1252 participants. There is moderate-quality evidence that in the short-term [WMD − 1.06, CI − 1.48 to − 0.64,p≤ .01] and low-quality evidence that in the medium-term [WMD − 0.90, CI − 1.43 to − 0.37,p≤ .01] postoperative period oral zolpidem 5/10 mg with other analgesic medicines reduced pain intensity compared to the same analgesic medicines alone.There is low-quality evidence that melatonin was not effective on postoperative pain intensity compared to placebo. The results of benzodiazepines on pain intensity were mixed. The authors reported no significant adverse events.ConclusionsThere is promising evidence that the hypnotic medicine zolpidem, adjuvant to other analgesics, is effective at achieving a minimally clinically important difference in pain intensity postoperatively. There is no consistent effect of melatonin or benzodiazepines on postoperative pain intensity. Readers should interpret these results with some caution due to the lack of data on safety, the small number of trials included in the pooled effects and their sample sizes.Systematic review registrationThe protocol for this systematic review was registered with PROSPERO ID=CRD42015025327.

Social prescribing, also known as “community referral”, is a means of referring individuals living in the community to existing local non-clinical health, welfare, and social support services. International evidence demonstrates that social prescribing improves biopsychosocial quality of life, and burden on health services. Australia’s first social prescribing pilot program for individuals with mental illness (mood and psychotic spectrum disorders) was implemented in Sydney in 2016/2017; this study evaluates that program. Participants included 13 adults who were assessed at baseline and six-month follow-up. Outcomes included self-perceived quality of life, welfare needs, health status, loneliness, social participation, and economic participation. Results indicate significant improvements in quality of life and health status. This pilot program demonstrates that social prescribing may improve participant outcomes. It fits well within Australian health policy and funding models which focus on bolstering community care, and may be scalable, particularly in geographically isolated communities.

Chronic low back pain (LBP) shares a bidirectional relationship with sleep disturbance. Analgesics are often used for chronic LBP management however, the effects on sleep have not been thoroughly reviewed. This systematic review and meta-analysis assessed the effect of opioid and non-opioid medications on sleep in people with chronic LBP. Electronic databases were searched for randomized controlled trials which resulted in 16 eligible articles (14 studies). Sleep measures were secondary outcomes, with one study assessing sleep objectively and all other studies reporting subjective sleep. Twelve studies assessed opioid therapies whilst two studies examined non-opioid therapies. Eight studies (all opioid) were included in meta-analyses of sleep quality and sleep disturbance comparing opioid therapies with placebo-controls. Opioid therapies significantly improved sleep quality (SMD = 0.27, 95% CI: 0.17-0.36) and reduced sleep disturbance (SMD = 0.32, 95% CI: 0.25-0.40) compared to placebo-control. These findings show a clear improvement in subjective sleep associated with opioid therapies however, future studies should examine objective sleep outcomes which remain largely unexplored in chronic LBP. Addressing both pain and sleep together is important for effective management of comorbid conditions of chronic LBP and sleep disturbance due to their bidirectional relationship.

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.

A palladium-catalysed flow chemistry protocol to selectively mediate Nβ side-chain Cbz-lysis from extended peptide sequences in the presence of trityl, t-butyl and Nα-Fmoc protecting groups.

Insomnia disorder (ID) is a heterogeneous disorder with proposed subtypes based on objective sleep duration. We speculated that insomnia subtyping with additional power spectral analysis and measurement of response to acute sleep restriction may be informative in overall assessment of ID. To explore alternative classifications of ID subtypes, insomnia patients (n = 99) underwent two consecutive overnight sleep studies: (i) habitual sleep opportunity (polysomnography, PSG) and, (ii) two hours less sleep opportunity (electroencephalography, EEG), with the first night compared to healthy controls (n = 25). ID subtypes were derived from data-driven classification of PSG, EEG spectral power and interhemispheric EEG asymmetry index. Three insomnia subtypes with different sleep duration and NREM spectral power were identified. One subtype (n = 26) had shorter sleep duration and lower NREM delta power than healthy controls (short-sleep delta-deficient; SSDD), the second subtype (n = 51) had normal sleep duration but lower NREM delta power than healthy controls (normal-sleep delta-deficient; NSDD) and a third subtype showed (n = 22) no difference in sleep duration or delta power from healthy controls (normal neurophysiological sleep; NNS). Acute sleep restriction improved multiple objective sleep measures across all insomnia subtypes including increased delta power in SSDD and NSDD, and improvements in subjective sleep quality for SSDD (p = 0.03), with a trend observed for NSDD (p = 0.057). These exploratory results suggest evidence of novel neurophysiological insomnia subtypes that may inform sleep state misperception in ID and with further research, may provide pathways for personalised care.

Insomnia is one of the most common sleep disorders which can dramatically impair life quality and negatively affect an individual's physical and mental health. Recently, various deep learning based methods have been proposed for automatic and objective insomnia detection, owing to the great success of deep learning techniques. However, due to the scarcity of public insomnia data, a deep learning model trained on a dataset with a small number of insomnia subjects may compromise the generalization capacity of the model and eventually limit the performance of insomnia detection. Meanwhile, there have been a number of public EEG datasets collected from a large number of healthy subjects for various sleep research tasks such as sleep staging. Therefore, to utilize such abundant EEG datasets for addressing the data scarcity issue in insomnia detection, in this paper we propose a domain adaptation based model to better extract insomnia related features of the target domain by leveraging stage annotations from the source domain. For each domain, two pairs of common encoder and private encoder are firstly trained to extract sleep related features and sleep irrelevant features, respectively. In order to further discriminate source domain and target domain, a domain classifier is introduced. Then, the common encoder of the target domain will be used together with the Long Short Term Memory (LSTM) network for insomnia detection. To the best of our knowledge, this is the first deep learning based domain adaptation model using single channel raw EEG signals to detect insomnia at subject level. We use the Montreal Archive of Sleep Studies (MASS) dataset which contains only healthy subjects as source domain and two datasets which contain both healthy and insomnia subjects as target domain to validate our model's generalizability. Experimental results on the two target domain datasets (a public one and an in-house one) demonstrate that our model generalizes well on two target domain datasets with different sampling rates. In particular, our proposed method is able to improve insomnia detection performance from 50.0% to 90.9% and 66.7%-79.2% in terms of accuracy on the two target domain datasets, respectively.

The authors provide an interdisciplinary investigation of student videography for assessment in higher education. Video is becoming a dominant communication modality in our world; school students a...

Background The popularity of biofeedback as a non-pharmacological treatment option for insomnia has increased in recent times despite inconsistent empirical evidence for its therapeutic efficacy. Objective The purpose of the current review was to systematically assess the efficacy of using biofeedback to treat insomnia. Methods and results A search of electronic databases (PubMED, MEDLINE, OvidSP, Ovid EMBASE, PsychInfo, The Cochrane Library including Cochrane Reviews), clinical trials databases and registries (Clinical Trials Database [US], Australian New Zealand Clinical Trials Registry [ANZCTR]) and online journal (eg, SLEEP, Sleep Medicine) identified 92 studies. Of these, 50 publications were descriptive or review papers about use of biofeedback for the treatment of insomnia, while an additional 37 did not meet the detailed inclusion criteria (ie not original research, participants do not meet the diagnostic criteria for insomnia). Six full-text articles met inclusion criteria and were included in this review. Methodological flaws including poor study design (small sample size, lack of control group) limit the validity of the body of work in this field to date and fail adequately to account for other unspecified factors likely to drive the observed changes, such as care and attention of those administering the treatment, as well as the expectations and motivations of the patient. Conclusion There is an urgent need for future studies to clarify the role of unspecific placebo effects when reporting biofeedback effects for the treatment of insomnia.

Summary The comparative efficacy of various approaches of digital cognitive behavioral therapy for insomnia (CBTi) is still unclear. This network meta-analysis explored the comparative efficacy of digital CBTi approaches in adults with insomnia. Four electronic databases were searched from inception to June 27, 2020. Primary outcomes were self-reported total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), sleep efficiency (SE), and insomnia symptoms; these were measured using sleep diaries or valid questionnaires. A random-effects network meta-analysis in a frequentist framework was used. Fifty-four randomized controlled trials comprising 11,815 participants were included. Compared with usual care, web-based CBTi with a therapist demonstrated significantly longer TST (mean difference [MD]: 23.19 min, 95% confidence interval [CI]: 18.98 to 27.39 min), shorter SOL (MD: −18.76 min, 95% CI −24.20 to –13.31 min), lower WASO (MD: −31.40 min, 95% CI: −36.26 to −26.55 min), and greater SE (MD: 10.37%, 95% CI: 8.08% to 12.65%). The surface under the cumulative ranking curve indicates that web-based CBTi with therapists is most likely to be ranked the highest among all treatments, and thus, this network meta-analysis suggests that such a treatment is the optimal intervention for improving sleep duration and SE as well as the reductions in SOL and WASO. PROSPERO registration number CRD42020171134.

IntroductionMelatonin 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 analysisThe 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 disseminationThis 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 numberAustralian and New Zealand Clinical Trials Registry (ANZCTRN 12619000876190).Protocol versionV.8 15 October 2020.

Objectives Insomnia is diagnosed using clinical interview but actigraphy is often used as a consecutive multi-day measurement of activity-rest cycles to quantify sleep-wake periods. However, discrepancies between subjective complaints of insomnia and objective actigraphy measurement exist. The aims of the current study were to (i) predict subjective sleep quality using actigraphic data and, (ii) identify features of actigraphy that are associated with poor subjective sleep quality. Methods Actigraphy data were collected for 14-consecutive days with corresponding subjective sleep quality ratings from participants with Insomnia Disorder and healthy controls. We fitted multiple machine learning algorithms to determine the best performing method with the highest accuracy of predicting subjective quality rating using actigraphic data. Results We analysed a total of 1278 days of actigraphy and corresponding subjective sleep quality ratings from 86 insomnia disorder patients and 20 healthy controls. The k-neighbors classifier provided the best performance in predicting subjective sleep quality with an overall accuracy, sensitivity and specificity of 83%, 74% and 87% respectively, and an average AUC-ROC of 0.88. We also found that activity recorded in the early morning (04:00-08:00) and overnight periods (00:00-04:00) had the greatest influence on sleep quality scores, with poor sleep quality related to these periods.. Conclusions A machine learning model based on actigraphy time-series data successfully predicted self-reported sleep quality. This approach could facilitate clinician’s diagnostic capabilities and provide an objective marker of subjective sleep disturbance.

Background Insomnia is a highly prevalent sleep disorder and the first-line recommended treatment is cognitive behavioural therapy. However, there is persistent use of pharmacotherapy, mainly, sedative-hypnotics. Consultant pharmacists can provide medication review services for patients on polypharmacy, and are therefore well placed to educate patients and provide sleep health/insomnia care with regards to pharmacotherapy and behavioural therapy use. Objectives To explore consultant pharmacists’ current sleep health-related practice and what their perspectives are around developing/implementing a consultant pharmacist-led behavioural service for insomnia. Methods Qualitative semi-structured interviews were conducted with a convenience-based sample of consultant pharmacists. Interviews were audio-recorded, transcribed and thematically analysed. Results Twenty-four consultant pharmacists were interviewed. Three themes were gauged: 1) Trivializing insomnia and sleep health, 2) Patients – an integral piece of the treatment puzzle, 3) Making it work. Participants commonly dealt with older patients and frequently encountered patients with sleep complaints/consuming sleep aids. Generally, it was believed that sleep health was considered a ‘non-priority’, with other comorbidities taking precedence in health provisions. While interested in expanding their sleep health/insomnia practice, participants expressed the need for appropriate education/training, funding and collaborative treatment configurations. Further, patients’ attitudes towards treatment approaches were regarded critical to future service developments. Conclusion Insomnia/sleep health concerns are growing. Primary health professionals need to scale up their sleep health care provisions to accommodate for this health demand. Consultant pharmacists are interested/willing to expand their sleep-related practice and provide evidence-based insomnia therapies, however factors such as education/training, service configuration support and patient attitudes should be addressed.

Introduction While Very Low Energy Diets (VLEDs) have been proven to reduce weight in patients with obstructive sleep apnoea (OSA) and co-morbid obesity, they can also result in excessive loss of muscle mass which adversely impacts health. Concurrent exercise training is considered an effective method of preventing muscle mass loss. Methods This prospective randomised controlled trial will recruit 30 overweight and obese men with untreated moderate-to-severe OSA to undergo a 12-week VLED with or without high-intensity functional exercise (HIFE) training. HIFE will be delivered through a commercially available supervised exercise program and incorporates interval training with a combination of progressively graded aerobic and anaerobic exercise. The primary outcome measures are changes in body composition, assessed by dual x-ray absorptiometry (DEXA), and OSA severity (measured by apnoea hypopnea index). Secondary outcomes include glucose tolerance, ventilatory response, and peak oxygen uptake. Data will be analysed on an intention-to-treat basis. Paired T-tests will be used to test the treatment effect of exercise compared to control. Confidence intervals will be used to analyse change in muscle mass and other secondary outcomes. Results Only one participant has completed the protocol to date. No results are available at this time. Discussion The results of this pilot study will look to confirm whether HIFE can protect against muscle mass loss, and additively benefit OSA severity during VLED, compared to VLED alone. It will also inform estimation of feasibility for a larger definitive study.

Background Mobile health (mHealth) apps offer a scalable option for treating sleep disturbances at a population level. However, there is a lack of clarity about the development and evaluation of evidence-based mHealth apps. Objective The aim of this systematic review was to provide evidence for the design engineering and clinical implementation and evaluation of mHealth apps for sleep disturbance. Methods A systematic search of studies published from the inception of databases through February 2020 was conducted using 5 databases (MEDLINE, Embase, Cochrane Library, PsycINFO, and CINAHL). Results A total of 6015 papers were identified using the search strategy. After screening, 15 papers were identified that examined the design engineering and clinical implementation and evaluation of 8 different mHealth apps for sleep disturbance. Most of these apps delivered cognitive behavioral therapy for insomnia (CBT-I, n=4) or modified CBT-I (n=2). Half of the apps (n=4) identified adopting user-centered design or multidisciplinary teams in their design approach. Only 3 papers described user and data privacy. End-user acceptability and engagement were the most frequently assessed implementation metrics. Only 1 app had available evidence assessing all 4 implementation metrics (ie, acceptability, engagement, usability, and adherence). Most apps were prototype versions (n=5), with few matured apps. A total of 6 apps had supporting papers that provided a quantitative evaluation of clinical outcomes, but only 1 app had a supporting, adequately powered randomized controlled trial. Conclusions This is the first systematic review to synthesize and examine evidence for the design engineering and clinical implementation and evaluation of mHealth apps for sleep disturbance. The minimal number of apps with published evidence for design engineering and clinical implementation and evaluation contrasts starkly with the number of commercial sleep apps available. Moreover, there appears to be no standardization and consistency in the use of best practice design approaches and implementation assessments, along with very few rigorous efficacy evaluations. To facilitate the development of successful and evidence-based apps for sleep disturbance, we developed a high-level framework to guide researchers and app developers in the end-to-end process of app development and evaluation.

Background and Purpose: The exact prevalence of sleep disorders following stroke or transient ischemic attack (TIA) remains unclear. We aimed to determine the prevalence of sleep-disordered breathing, insomnia, periodic leg movement during sleep, and restless leg syndrome following stroke or TIA in acute, subacute, and chronic phases and examine the moderating effects of patient characteristics (eg, age) and methodological features (eg, study quality) on the prevalence. Methods: We performed a systematic review and meta-analysis. Embase and PubMed were searched from inception to December 18, 2019. We included 64 047 adults in 169 studies (prospective, retrospective, case-control, and cross-sectional study designs) reporting the prevalence of sleep disorders following stroke or TIA. Results: In the acute phase, the overall prevalence of mild, moderate, and severe sleep-disordered breathing was 66.8%, 50.3%, and 31.6% (95% CIs, 63.8–69.7, 41.9–58.7, and 24.9–39.1). In the subacute phase, the prevalence of mild, moderate, and severe sleep-disordered breathing was 65.5%, 44.3%, and 36.1% (95% CIs, 58.9–71.5, 36.1–52.8, and 22.2–52.8). In the chronic phase, the summary prevalence of mild, moderate, and severe sleep-disordered breathing was 66.2%, 33.1%, and 25.1% (95% CIs, 58.6–73.1, 24.8–42.6, and 10.9–47.6). The prevalence rates of insomnia in the acute, subacute, and chronic phases were 40.7%, 42.6%, and 35.9% (95% CIs, 31.8–50.3, 31.7–54.1, and 28.6–44.0). The pooled prevalence of periodic leg movement during sleep in the acute, subacute, and chronic phases was 32.0%, 27.3%, and 48.2% (95% CIs, 7.4–73.5, 11.6–51.7, and 33.1–63.5). The summary prevalence of restless leg syndrome in the acute and chronic phases was 10.4% and 13.7% (95 CIs, 6.4–16.4 and 2.3–51.8). Age, sex, comorbidities, smoking history, and study region had significant moderating effects on the prevalence of sleep disorders. Conclusions: Sleep disorders following stroke or TIA are highly prevalent over time. Our findings indicate the importance of early screening and treating sleep disorders following stroke or TIA.

Alkaline electrolyzed water (AEW) and walking are strongly recommended for ameliorating oxidative stress and inflammation. Nevertheless, there is a lack of information on the combination of both on alleviating inflammation, oxidative stress, and improving the quality of life (QoL). We investigated the synergistic effects of drinking AEW and walking on advanced glycation end products (AGEs), advanced oxidation protein products (AOPPs), malondialdehyde (MDA), white blood cells (WBCs), neutrophil-lymphocyte ratio (NLR) and QoL. In total, 81 eligible patients with type 2 diabetes (T2DM) were randomly allocated via single blind to four groups: consumed 2 L/day of AEW (n = 20), instructed to walk for 150 min/week (n = 20), received a combination of AEW and walking (n = 20), and continue their habitual diet and activity (n = 21). Data were collected and analyzed before and after 8 weeks of intervention. Our results showed a significant interaction between the group and time, with both AEW and walking independently and synergistically ameliorating AGEs, AOPPs, MDA, NLR and WBCs levels. Moreover, the AEW group had a higher physical and total QoL score. The walking group and the combined group had higher scores in physical, mental and total QoL compared to the control group. The synergistic effect of AEW and regular walking are an advisable treatment for patients with T2DM.

We examined whether a polymorphism of the PERIOD3 gene (PER3; rs57875989) modulated the sleep promoting effects of melatonin in Delayed Sleep-Wake Phase Disorder (DSWPD). One hundred and four individuals (53 males; 29.4±10.0 years) with DSWPD and a delayed dim light melatonin onset (DLMO) collected buccal swabs for genotyping (PER34/4 n=43; PER3 5 allele [heterozygous and homozygous] n=60). Participants were randomised to placebo or 0.5mg melatonin taken 1 hour before desired bedtime (or ~ 1.45 h before DLMO), with sleep attempted at desired bedtime (4 weeks; 5-7 nights/week). We assessed sleep (diary and actigraphy), Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Patient-Reported Outcomes Measurement Information System (PROMIS: Sleep Disturbance, Sleep-Related Impairment), Sheehan Disability Scale (SDS), and Patient- and Clinician-Global Improvement (PGI-C, CGI-C). Melatonin treatment response on actigraphic sleep onset time did not differ between genotypes. For PER34/4 carriers, self-reported sleep onset time was advanced by a larger amount and sleep onset latency (SOL) was shorter in melatonin-treated patients compared to those receiving placebo (P=0.008), while actigraphic sleep efficiency in the first third of the sleep episode (SE T1) did not differ. For PER3 5 carriers, actigraphic SOL and SE T1 showed a larger improvement with melatonin (P

Secondhand smoke (SHS) and physical inactivity are thought to be associated with type 2 diabetes mellitus (T2DM), but the synergistic effect of SHS with physical inactivity and their relationships with T2DM&ndash, associated inflammation biomarkers have not been estimated. We investigated the roles of SHS exposure and physical inactivity and their synergistic effect on T2DM risk and their relationships with T2DM associated inflammation biomarkers, neutrophil&ndash, lymphocyte ratio (NLR) and white blood cells (WBCs). A case&ndash, control study was conducted in total 588 participants (294 case T2DM and 294 healthy controls) from five community clinics in Indonesia. Participants completed a standardized questionnaire on demographic information, smoking status, physical activity habits and food consumption. WBCs and NLR levels were determined using an automated hematology analyzer. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were analyzed using multiple logistic regression model. The synergistic effect was analyzed using additive interaction for logistic regression. Physical inactive people exposed to SHS exhibited a synergistically increased 7.78-fold risk of T2DM compared with people who were not exposed to SHS and who were physically active. SHS is significantly correlated with a high NLR, WBCs and has a synergistic effect with physical inactivity on increasing susceptibility to T2DM.

Background Bioscience in nursing education covers a broad range of disciplinary areas (anatomy, physiology, pathophysiology and pharmacology) and underpins clinical assessment and critical thinking in nursing practice. This is imperative for patient safety and favourable patient outcomes. In nursing programs for registration, most bioscience content is taught during the early phases of the program and little incorporated into postgraduate nursing programs. Objectives The aim of this study was to explore student's perceived relationship between clinical relevance and engagement (attention and time) with bioscience content, by surveying undergraduates and postgraduate nursing students. Design This sequential mixed methods study included two phases. Methods The first phase comprised of focus group interviews from one Australian University. Thematic analysis of these data, coupled with existing literature, informed the second study phase; a quantitative questionnaire. Participants Focus group interviews included N = 30 students from one tertiary site; 10 from each year level. The questionnaire was administered to nursing students undertaking undergraduate nursing studies (1st, 2nd & 3rd years), and postgraduate nursing studies. Results Nursing students (n = 406) across three Australian universities (four programmes) completed the questionnaire. The clinical relevance of bioscience was widely appreciated; 91.6% of undergraduate nursing students and 98.5% of postgraduate nursing students indicated that every nurse must have a good understanding of bioscience. However, there was an inverse relationship between engagement with bioscience and timing in the curriculum, as 50% of undergraduate nursing students indicated that bioscience content took up too much of their time, compared to only 20% of postgraduate nurses (odds ratio 0.27 [0.16–0.46], p Conclusion Nursing students' perceptions of the clinical relevance of bioscience for their career strongly corresponds with their progression through their studies. Unfortunately, as students progress to the later years of their nursing education, their engagement with formal bioscience education decreases. This poses the question ‘Are we delivering bioscience content to nursing students at the appropriate time?’

Introduction Insomnia is a highly prevalent and costly condition that is associated with increased health risks and healthcare utilisation. Anecdotally, cannabis use is frequently reported by consumers to promote sleep. However, there is limited research on the effects of cannabis on sleep and daytime function in people with insomnia disorder using objective measures. This proof-of-concept study will evaluate the effects of a single dose of an oral cannabis-based medicine on sleep and daytime function in participants with chronic insomnia disorder. Methods and analysis A randomised, crossover, placebo-controlled, single-dose study design will be used to test the safety and efficacy of an oral oil solution (‘ETC120’) containing 10 mg Δ9-tetrahydrocannabinol (THC) and 200 mg cannabidiol (CBD) in 20 participants diagnosed with chronic insomnia disorder. Participants aged 35–60 years will be recruited over an 18-month period commencing August 2019. Each participant will receive both the active drug and matched placebo, in a counterbalanced order, during two overnight study assessment visits, with at least a 1-week washout period between each visit. The primary outcomes are total sleep time and wake after sleep onset assessed via polysomnography. In addition, 256-channel high-density electroencephalography and source modelling using structural brain MRI will be used to comprehensively examine brain activation during sleep and wake periods on ETC120 versus placebo. Next-day cognitive function, alertness and simulated driving performance will also be investigated. Ethics and dissemination Ethics approval was received from Bellberry Human Research Ethics Committee (2018-04-284). The findings will be disseminated in a peer-reviewed open-access journal and at academic conferences. Trial registration number ANZCTRN12619000714189.

IntroductionInsomnia is a highly prevalent and costly condition that is associated with increased health risks and healthcare utilisation. Anecdotally, cannabis use is frequently reported by consumers to promote sleep. However, there is limited research on the effects of cannabis on sleep and daytime function in people with insomnia disorder using objective measures. This proof-of-concept study will evaluate the effects of a single dose of an oral cannabis-based medicine on sleep and daytime function in participants with chronic insomnia disorder.Methods and analysisA randomised, crossover, placebo-controlled, single-dose study design will be used to test the safety and efficacy of an oral oil solution (‘ETC120’) containing 10 mg Δ9-tetrahydrocannabinol (THC) and 200 mg cannabidiol (CBD) in 20 participants diagnosed with chronic insomnia disorder. Participants aged 35–60 years will be recruited over an 18-month period commencing August 2019. Each participant will receive both the active drug and matched placebo, in a counterbalanced order, during two overnight study assessment visits, with at least a 1-week washout period between each visit. The primary outcomes are total sleep time and wake after sleep onset assessed via polysomnography. In addition, 256-channel high-density electroencephalography and source modelling using structural brain MRI will be used to comprehensively examine brain activation during sleep and wake periods on ETC120 versus placebo. Next-day cognitive function, alertness and simulated driving performance will also be investigated.Ethics and disseminationEthics approval was received from Bellberry Human Research Ethics Committee (2018-04-284). The findings will be disseminated in a peer-reviewed open-access journal and at academic conferences.Trial registration numberANZCTRN12619000714189.

There is growing interest in understanding how maternal diet might affect the sensitivity of offspring to environmental exposures. Previous studies demonstrated that adult rat offspring (approximately 6-months-old) from dams given a high-fat diet (HFD) prior to, during, and after pregnancy displayed elevated pulmonary responses to an acute ozone (O3) exposure. The aim of this study was to examine the influence of maternal and perinatal HFD on pulmonary and metabolic responses to O3 in male and female young-adult offspring (approximately 3-month old). One-month-old F0 female Long-Evans rats commenced HFD (60% kcal from fat) or control diet (CD; 10.5% kcal from fat) and were bred on PND 72. Offspring were maintained on respective HFD or CD until PND 29 when all groups were switched to CD. The 3-months-old female and male offspring (n = 10/group) were exposed to air or 0.8 ppm O3 for 5hr/day for 2 consecutive days. Maternal and perinatal HFD significantly increased body weight and body fat % in offspring regardless of gender. Ozone exposure, but not maternal and perinatal diet, induced hyperglycemia and glucose intolerance in the offspring. Ozone-induced alterations in pulmonary function were exacerbated by maternal and perinatal HFD in both offspring genders. Pulmonary injury/inflammation markers in response to O3 exposure such as bronchoalveolar lavage fluid total protein, lactate dehydrogenase, total cells, and neutrophils were further augmented in offspring (males>females) from dams fed the HFD. Data suggest that maternal and perinatal HFD may enhance the susceptibility of offspring to O3-induced pulmonary injury and that these effects may be sex-specific.

Background Depression is common in older people and is associated with underlying brain change increasing the risk of dementia. Sleep disturbance is frequently reported by those with lifetime depression, however whether circadian misalignment also exists is unclear. We aimed to examine circadian rhythms and sleep associations in older patients with and without lifetime depression. Methods Thirty-four older people meeting DSM-IV criteria for lifetime major depression (mean age = 63.9 years), and 30 healthy controls (mean age = 65.7 years) were recruited. Participants underwent 2-weeks of actigraphy followed by a 3-night protocol including dim light melatonin onset (DLMO) assessment and overnight polysomnography (PSG) for sleep architecture. DLMO and phase angle of entrainment were computed. Results Compared to controls, participants with depression had a significantly longer phase angle of entrainment (6.82 h ± 1.45 vs. 5.87 h ± 1.60, p = 0.02, Cohens-d = 0.62). A small to moderate yet non-significant difference in DLMO times, with earlier DLMO (34 ± 27 min) observed in depression (20:36 ± 1:48 vs. 21:10 ± 1:48, p = 0.22, Cohens-d = 0.32). Individuals with depression had longer sleep latency and latency to rapid eye movement sleep than controls (all p Conclusion Circadian advancement and alterations to the timing of sleep and REM onset are evident in older people with lifetime major depression, despite having only mild residual symptoms. Further research examining the prognostic significance of these changes is warranted as well as chronotherapeutic treatment studies.

The influence of maternal high-fat diet (HFD) on metabolic response to ozone was examined in Long-Evans rat offspring. F0 females were fed control diet (CD; 10%kcal from fat) or HFD (60%kcal from fat) starting at post-natal day (PND) 30. Rats were bred on PND 72. Dietary regimen was maintained until PND 30 when all offspring were switched to CD. On PND 40, F1 offspring (n = 10/group/sex) were exposed to air or 0.8 ppm ozone for 5 h. Serum samples were collected for global metabolomic analysis (n = 8/group/sex). Offspring from HFD dams had increased body fat and weight relative to CD. Metabolomic analysis revealed significant sex-, diet-, and exposure-related changes. Maternal HFD increased free fatty acids and decreased phospholipids (male > female) in air-exposed rats. Microbiome-associated histidine and tyrosine metabolites were increased in both sexes, while 1,5-anhydroglucitol levels decreased in males indicating susceptibility to insulin resistance. Ozone decreased monohydroxy fatty acids and acyl carnitines and increased pyruvate along with TCA cycle intermediates in females (HFD > CD). Ozone increased various amino acids, polyamines, and metabolites of gut microbiota in HFD female offspring indicating gut microbiome alterations. Collectively, these data suggest that maternal HFD increases offspring susceptibility to metabolic alterations in a sex-specific manner when challenged with environmental stressors.

Study Objectives Cardiovascular autonomic dysfunction, as measured by short-term diurnal heart rate variability (HRV), has been reported in older adults with mild cognitive impairment (MCI). However, it is unclear whether this impairment also exists during sleep in this group. We, therefore, compared overnight HRV during sleep in older adults with MCI and those with subjective cognitive impairment (SCI). Methods Older adults (n = 210) underwent overnight polysomnography. Eligible participants were characterized as multi-domain MCI or SCI. The multi-domain MCI group was comprised of amnestic and non-amnestic subtypes. Power spectral analysis of HRV was conducted on the overnight electrocardiogram during non-rapid eye movement (NREM), rapid eye movement (REM), N1, N2, N3 sleep stages, and wake periods. High-frequency HRV (HF-HRV) was employed as the primary measure to estimate parasympathetic function. Results The MCI group showed reduced HF-HRV during NREM sleep (p = 0.018), but not during wake or REM sleep (p > 0.05) compared to the SCI group. Participants with aMCI compared to SCI had the most pronounced reduction in HF-HRV across all NREM sleep stages—N1, N2, and N3, but not during wake or REM sleep. The naMCI sub-group did not show any significant differences in HF-HRV during any sleep stage compared to SCI. Conclusions Our study showed that amnestic MCI participants had greater reductions in HF-HRV during NREM sleep, relative to those with SCI, suggesting potential vulnerability to sleep-related parasympathetic dysfunction. HF-HRV, especially during NREM sleep, may be an early biomarker for dementia detection.