Predicting neurodegeneration from sleep related biofluid changes.

Sleep-wake disturbances are common in neurodegenerative diseases and may occur years before the clinical diagnosis, potentially either representing an early stage of the disease itself or acting as a pathophysiological driver. Therefore, discovering biomarkers that identify individuals with sleep-wake disturbances who are at risk of developing neurodegenerative diseases will allow early diagnosis and intervention. Given the association between sleep and neurodegeneration, the most frequently analyzed fluid biomarkers in people with sleep-wake disturbances to date include those directly associated with neurodegeneration itself, such as neurofilament light chain, phosphorylated tau, amyloid-beta and alpha-synuclein. Abnormalities in these biomarkers in patients with sleep-wake disturbances are considered as evidence of an underlying neurodegenerative process. Levels of hormonal sleep-related biomarkers such as melatonin, cortisol and orexin are often abnormal in patients with clinical neurodegenerative diseases, but their relationships with the more standard neurodegenerative biomarkers remain unclear. Similarly, it is unclear whether other chronobiological/circadian biomarkers, such as disrupted clock gene expression, are causal factors or a consequence of neurodegeneration. Current data would suggest that a combination of fluid biomarkers may identify sleep-wake disturbances that are most predictive for the risk of developing neurodegenerative disease with more optimal sensitivity and specificity.

Hypoxemia during rapid eye movement sleep mediates memory impairment in older adults at risk for dementia via CA1 hippocampal volume loss.

BACKGROUND AND PURPOSE: Obstructive sleep apnea is associated with increased dementia risk. Nocturnal hypoxemia, which can be more severe during rapid eye movement (REM) sleep, may be a key mechanism. This study examines how REM hypoxemia affects memory and explores whether hippocampal vulnerability to hypoxemia mediates this effect in older adults at risk for dementia. METHODS: Older adults aged ≥50 years (N = 338) with subjective or mild cognitive impairment (i.e., objective impairment) underwent neuropsychological, mood, and medical assessment, magnetic resonance imaging scanning (n = 135), and overnight polysomnography. Verbal learning and memory were assessed with the Rey Auditory Verbal Learning Test. REM sleep hypoxemia was measured using the Oxygen Desaturation Index-3% (REM-ODI). Hippocampal subfield (CA1, CA3, subiculum, and dentate gyrus) volumes were derived from T1 and high-resolution hippocampus T2 scans. We determined whether the relationship between REM-ODI and learning and memory was mediated by hippocampal subfield volume. Analyses were repeated in non-REM sleep to determine whether the effects were REM-specific. RESULTS: Although there was not a direct effect of REM-ODI on verbal learning (p > 0.05) or memory (p > 0.05), mediation analyses showed a significant indirect effect of high REM-ODI on poorer verbal learning (ß = -0.09, 95% confidence interval [CI] = -0.238 to -0.005) and memory (ß = -0.100, 95% CI = -0.255 to -0.005), which was mediated by CA1 volume. These associations were absent in non-REM sleep (p > 0.05). CONCLUSIONS: Hypoxemia during REM sleep may impair memory in people at risk for dementia by reducing CA1 hippocampal volume. Research is needed to explore whether interventions targeting REM sleep hypoxemia are protective against memory decline.

Effectiveness of interventions for the prevention or management of workplace violence in student nurses during clinical placement: A systematic review.

AIM: To systematically investigate the effectiveness of interventions for managing workplace violence experienced by registered nursing students during clinical placement. DESIGN: A systematic review of experimental studies. METHODS: The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The key search concepts such as "Nursing students", "Education", "workplace violence", "clinical placement" and "clinical study" were inspected to identify relevant articles (Appendix A). Two independent reviewers completed screening, critical appraisal and data extraction. Due to heterogeneity among the included studies, results were synthesized narratively. DATA SOURCES: MEDLINE (Ovid), CINAHL (EBSCOhost), Web of Science Core Collection (Clarivate Analytics), Scopus (Elsevier), Embase (Ovid), Cochrane CENTRAL, ERIC (ProQuest), ProQuest Central and ProQuest Social Science Premium Collection were searched from inception to 27th February 2023. RESULTS: A total of 13 studies were included in this review. The predominant intervention for managing workplace violence experienced by registered nursing students during clinical placements was education. Approaches varied among studies and included didactic teaching, e-learning, role-playing and simulation practice. The included studies showed uncertain improvements in registered nursing students' confidence, coping skills, knowledge, competence and self-efficacy in dealing with workplace violence during clinical placements. Only one study assessed the incidence rate of workplace violence and found that a multi-faceted intervention involving both staff and students decreased the incidence. CONCLUSION: Given the heterogeneity of educational interventions, the effect of interventions for managing workplace violence during students' clinical placement is uncertain. To address this gap, high-quality, proactive and combined interventions at both institutional and organizational levels are needed.

Nursing students' experience of workplace violence in clinical practice: A qualitative systematic review.

AIMS: To systematically identify, appraise and synthesise qualitative studies investigating Registered Nurse students' (RNS) experiences of workplace violence (WPV) while on clinical placement. It is expected that the literature review findings will guide the development of targeted programs and policies to address WPV against RNS. BACKGROUND: WPV affects RNS during clinical placements as they are vulnerable to violence due to their limited experience and skills to challenge abusive behaviour. In this review, RNS are students enrolled in a Bachelor of Nursing program to become registered nurses and exclude students who are enrolled in nursing program that does not lead to registration as a registered nurse. For example, enrolled in nursing programs and postgraduate nursing programs. RNS are chosen for their scope of practice and the training requirements. RNS reported experiencing WPV mainly from colleagues, staff, teachers, doctors and supervisors, which resulted in leaving nursing practice, impacting students' progression and healthcare systems. This review examines all types of violence RNS face irrespective of the abuser. METHODS: A qualitative systematic review of existing literature was conducted through a comprehensive database search of eight databases MEDLINE, CINAHL, Web of Science, Scopus, Embase, Cochrane Central and ProQuest. Furthermore, reference lists of included studies were searched to identify further research. English language qualitative primary studies of any study design were searched from inception to 6th June 2022 and included if they met the inclusion criteria. Double review process utilised from screening until data synthesis reported according to PRISMA. JBI critical appraisal tools were used to assess the studies, and data extraction utilised JBI QARI tool and screened for credibility and confidence in findings. RESULTS: A total of 18 studies met the inclusion criteria, and the studies were conducted in nine countries. Five main themes relating to RNS experiences of WPV while on clinical placement were identified, including: 'Types of workplace violence', 'Perpetrators', 'Causes', 'Consequences' and 'Management of workplace violence'. CONCLUSIONS: This qualitative systematic review provides new and significant knowledge in understanding the phenomenon of WPV experienced by RNS while on clinical placement. RELATIVE TO CLINICAL PRACTICE: This review highlights the unwillingness of RNS to reach out to instructors or clinical placement leaders in many situations and identifies avenues of support and awareness that are crucial to empower and enabling students to seek support.

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.

Predictors of weight loss in obese patients with obstructive sleep apnea.

PURPOSE: Consistent predictors of weight loss outcomes with very low-energy diets (VLEDs) in obstructive sleep apnea (OSA) have not been identified. This study aimed to identify variables predictive of weight loss success in obese patients with OSA undertaking an intensive weight loss programme. METHODS: We analysed biological, psychological, and behavioural variables as potential predictors of weight loss in obese patients with OSA after a 2-month VLED followed by one of two 10-month weight loss maintenance diets. Actigraphy, in-lab polysomnography, urinary catecholamines, and various psychological and behavioural variables were measured at baseline, 2, and 12 months. Spearman's correlations analysed baseline variables with 2-month weight loss, and 2-month variables with 2-12 month-weight change. RESULTS: Forty-two patients completed the VLED and thirty-eight completed the maintenance diets. Actigraphy data revealed that late bedtime (rs = - 0.45, p = < 0.01) was correlated with 2-month weight loss. The change in the time that participants got out of bed (rise-time) from baseline to two months was also correlated with 2-month weight loss (rs = 0.36, p = 0.03). The Impact of Weight on Quality of Life-Lite questionnaire (IWQOL) Public Distress domain (rs = - 0.54, p = < 0.01) and total (rs = - 0.38, p = 0.02) scores were correlated with weight loss maintenance from 2 to 12 months. CONCLUSIONS: Results from this small patient sample reveal correlations between actigraphy characteristics and weight loss in obese patients with OSA. We suggest the IWQOL may also be a useful clinical tool to identify OSA patients at risk of weight regain after initial weight loss. CLINICAL TRIAL REGISTRATION: This clinical trial was prospectively registered on 18/02/2013 with the Australia and New Zealand Clinical Trials Registry (ACTRN12613000191796). PUBLIC REGISTRY TITLE: Sleep, Lifestyle, Energy, Eating, Exercise Program for the management of sleep apnea patients indicated for weight loss treatment: A randomised, controlled pilot study. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363680.

Assessing mother-infant bonding: reliability of the recorded interaction task.

OBJECTIVE: This study examined the intra- and inter-rater reliability of the Recorded Interaction Task (RIT); a novel tool to assess mother-infant bonding via observational methods. BACKGROUND: Mother-infant bonding describes the reciprocal early emotional connection between mother and infant. Whilst various tools exist to assess mother-infant bonding, many incorrectly confuse this construct with mother-infant attachment. Further, available tools are limited to those that employ self-report methods, thus may reflect perceived behaviour, rather than actual behaviour. The RIT is a novel tool for observational assessment of mother-infant bonding. A standard interaction between mother and infant is recorded, and later assessed against specified bonding-related behaviours. Before its use in research, reliability testing must be undertaken to ensure the RIT may be used consistently. METHODS: The RIT was administered to 15 mother-infant dyads. Participant recordings were assessed by three trained raters at two time points, using the RIT observation scoring sheet. Intra-rater reliability was determined by comparing scores at each time point for each rater. Inter-rater reliability was determined by assessing reliability of scores at the first time point. RESULTS: Strong intra-rater reliability (ICC >0.86) and fair inter-rater reliability (ICC = 0.55) were observed. CONCLUSION: The current findings support the RIT's potential to reliably assess mother-infant bonding.

Approaches for estimating benefits and costs of interventions in plant biosecurity across invasion phases.

Nonnative plant pests cause billions of dollars in damages. It is critical to prevent or reduce these losses by intervening at various stages of the invasion process, including pathway risk management (to prevent pest arrival), surveillance and eradication (to counter establishment), and management of established pests (to limit damages). Quantifying benefits and costs of these interventions is important to justify and prioritize investments and to inform biosecurity policy. However, approaches for these estimations differ in (1) the assumed relationship between supply, demand, and prices, and (2) the ability to assess different types of direct and indirect costs at invasion stages, for a given arrival or establishment probability. Here we review economic approaches available to estimate benefits and costs of biosecurity interventions to inform the appropriate selection of approaches. In doing so, we complement previous studies and reviews on estimates of damages from invasive species by considering the influence of economic and methodological assumptions. Cost accounting is suitable for rapid decisions, specific impacts, and simple methodological assumptions but fails to account for feedbacks, such as market adjustments, and may overestimate long-term economic impacts. Partial equilibrium models consider changes in consumer and producer surplus due to pest impacts or interventions and can account for feedbacks in affected sectors but require specialized economic models, comprehensive data sets, and estimates of commodity supply and demand curves. More intensive computable general equilibrium models can account for feedbacks across entire economies, including capital and labor, and linkages among these. The two major considerations in choosing an approach are (1) the goals of the analysis (e.g., consideration of a single pest or intervention with a limited range of impacts vs. multiple interventions, pests or sectors), and (2) the resources available for analysis such as knowledge, budget and time.

Population pharmacokinetic model of subcutaneous fentanyl in older acute care patients.

PURPOSE: Subcutaneous fentanyl injection is commonly prescribed to manage acute pain in older patients; however, there is a gap in the literature describing the pharmacokinetic parameters for this route of administration in this population. The aim of this study was to develop and evaluate a population pharmacokinetic model for subcutaneous fentanyl injection in older patients. METHODS: Twenty-one patients who received subcutaneous fentanyl injections (50 to 75 µg) were recruited. Fentanyl concentrations were determined using a validated liquid chromatography/tandem mass spectrometry method. A population pharmacokinetic model was developed using non-linear mixed-effects modelling. A base model was selected based on the Akaike information criterion. Age, sex, body weight, number of previous fentanyl doses, number of prescribed medications, creatinine clearance, Charlson Comorbidity Index, Identification of Seniors at Risk score and concurrent use of CYP3A4 inhibitors were covariates considered for inclusion. A p value of < 0.05 was considered statistically significant for inclusion of covariates in the final model by stepwise addition. The simulation performance of the model was assessed by visual predictive check. RESULTS: A one-compartment, first-order absorption with lag time and linear elimination model was the best to fit to the fentanyl concentration data. The absorption rate constant was 0.136 h-1 (between subject variability (BSV), 46%), lag time 0.66 h (BSV 51%), apparent volume of distribution 6.28 L (BSV 30%), and apparent clearance 16.3 L.h-1 (BSV 54%). The Charlson Comorbidity Index was the only covariate included in the final model, where a higher value of the index increased fentanyl exposure and Cmax. CONCLUSION: This is the first report of subcutaneous fentanyl population pharmacokinetic model to evaluate fentanyl pharmacokinetic in older patients. The between subject variability in clearance and subcutaneous absorption rate was relatively high, and some patients recorded high fentanyl concentrations in the context of their titration to effect.

Dose-dependent effects of continuous positive airway pressure for sleep apnea on weight or metabolic function: Individual patient-level clinical trial meta-analysis.

Therapeutic-continuous positive airway pressure seems to increase weight compared with placebo-continuous positive airway pressure. It is not known whether weight gain with therapeutic-continuous positive airway pressure dose is dependent or whether it causes metabolic dysfunction. Data synthesis of three randomised placebo-continuous positive airway pressure-controlled trials (2-3 months) was performed to test whether there is a dose-dependent effect of continuous positive airway pressure on weight. Fasting glucose, insulin, insulin resistance (homeostatic model assessment), lipids and visceral abdominal fat were also tested to determine any effect on metabolic function. Mixed-model analysis of variance was used to quantify these effects. One-hundred and twenty-eight patients were analysed. Overall there was a small increase in weight with therapeutic-continuous positive airway pressure use compared with placebo-continuous positive airway pressure (difference: 1.17 kg; 0.37-1.97, p = 0.005), which was greater with high-use therapeutic-continuous positive airway pressure compared with high-use placebo-continuous positive airway pressure (1.45 kg; 0.10-2.80, p = 0.04). Continuous positive airway pressure use as a continuous variable was also significantly associated with weight change in continuous positive airway pressure users (0.30 kg hr-1  night-1 ; 0.04-0.56, p = 0.001), but not in placebo users (0.04 kg hr-1  night-1 ; -0.22 to 0.26, p = 0.76). Neither therapeutic-continuous positive airway pressure nor the dose of therapeutic-continuous positive airway pressure caused any changes to metabolic outcomes. The weight gain effects of medium-term therapeutic-continuous positive airway pressure appear modest and are not accompanied by any adverse metabolic effects.

Changes of vitamin D levels and bone turnover markers after CPAP therapy: a randomized sham-controlled trial.

The aim was to investigate whether continuous positive airway pressure treatment could modulate serum vitamin D (25-hydroxyvitamin D) and bone turnover markers (collagen-type 1 cross-linked C-telopeptide, osteocalcin and N-terminal propeptide of type 1 collagen) in secondary analysis from a randomized controlled trial. Sixty-five continuous positive airway pressure-naïve male patients with obstructive sleep apnea (age = 49 ± 12 years, apnea-hypopnea index = 39.9 ± 17.7 events h-1 , body mass index = 31.3 ± 5.2 kg m-2 ) were randomized to receive either real (n = 34) or sham (n = 31) continuous positive airway pressure for 12 weeks. At 12 weeks, all participants received real continuous positive airway pressure for an additional 12 weeks. After 12 weeks of continuous positive airway pressure (real versus sham), there were no between-group differences for any of the main outcomes [Δ25-hydroxyvitamin D: -0.80 ± 5.28 ng mL-1 (mean ± SE) versus 3.08 ± 3.66 ng mL-1 , P = 0.42; Δcollagen-type 1 cross-linked C-telopeptide: 0.011 ± 0.014 ng mL-1 versus -0.004 ± 0.009 ng mL-1 , P = 0.48; Δosteocalcin: 1.13 ± 1.12 ng mL-1 versus 0.46 ± 0.75 ng mL-1 , P = 0.80; ΔN-terminal propeptide of type 1 collagen: 2.07 ± 3.05 µg L-1 versus -1.05 ± 2.13 µg L-1 , P = 0.48]. There were no further differences in subgroup analyses (continuous positive airway pressure-compliant patients, patients with severe obstructive sleep apnea or sleepy patients). However, after 24 weeks irrespective of initial randomization, vitamin D increased in patients with severe obstructive sleep apnea (9.56 ± 5.51 ng mL-1 , P = 0.045) and in sleepy patients (14.0 ± 4.69 ng mL-1 , P = 0.007). Also, there was a significant increase in osteocalcin at 24 weeks (3.27 ± 1.06 ng mL-1 , P = 0.01) in compliant patients. We conclude that 12 weeks of continuous positive airway pressure did not modulate vitamin D or modulate any of the bone turnover markers compared with sham. However, it is plausible that continuous positive airway pressure may have late beneficial effects on vitamin D levels and bone turnover markers in selected groups of patients with obstructive sleep apnea.

Maintenance diets following rapid weight loss in obstructive sleep apnea: a pilot 1-year clinical trial.

Very low energy diets (VLED) appear to be the most efficacious dietary-based obesity reduction treatments in obstructive sleep apnea (OSA); however, effective weight loss maintenance strategies remain untested in this condition. Our study aimed to assess the feasibility, tolerability and efficacy of two common maintenance diets during a 10-month follow-up period after rapid weight loss using a 2-month VLED. In this two-arm, single-centre, open-label pilot trial, obese adult OSA patients received a 2-month VLED before being allocated to either the Australian Guide to Healthy Eating diet (AGHE) or a low glycaemic index high-protein diet (LGHP). Outcomes were measured at 0, 2 and 12 months. We recruited 44 patients [113.1 ± 19.5 kg, body mass index (BMI): 37.2 ± 5.6 kg m-2 , 49.3 ± 9.2 years, 12 females]. Twenty-four patients were on continuous positive airway pressure (CPAP) or mandibular advancement splint (MAS) therapy for OSA. Forty-two patients completed the VLED. The primary outcome of waist circumference was reduced by 10.6 cm at 2 months [95% confidence interval (CI): 9.2-12.1], and patients lost 12.9 kg in total weight (95% CI: 11.2-14.6). There were small but statistically significant regains in waist circumference between 2 and 12 months [AGHE = 3.5 cm (1.3-5.6) and LGHP = 2.8 cm (0.6-5.0]. Other outcomes followed a similar pattern of change. After weight loss with a 2-month VLED in obese patients with OSA, a structured weight loss maintenance programme incorporating commonly used diets was feasible, tolerable and efficacious for 10 months. This programme may be deployed easily within sleep clinics; however, future research should first test its translation within general clinical practice.

Chronotherapy for hypertension in obstructive sleep apnoea (CHOSA): a randomised, double-blind, placebo-controlled crossover trial.

BACKGROUND: Obstructive sleep apnoea (OSA) is an important cause of secondary hypertension. Nocturnal hypertension is particularly prevalent in OSA and is a strong predictor of cardiovascular mortality. Studies in patients with essential hypertension have suggested that nocturnal administration of antihypertensives improves nocturnal blood pressure (BP) without elevating daytime BP. We evaluated the efficacy of this technique in patients with OSA with stage I/II hypertension, both before and after the addition of CPAP. METHODS: In this double-blind randomised placebo-controlled crossover trial, patients with moderate-to-severe OSA and hypertension received 6 weeks each of evening or morning perindopril with opposing time-matched placebo. CPAP therapy was subsequently added for 8 weeks in addition to either morning or evening perindopril. The primary outcome was sleep systolic BP (SBP) using 24-hour BP monitoring, analysed using linear mixed models. RESULTS: Between March 2011 and January 2015, 85 patients were randomised, 79 completed both dosing times, 78 completed the CPAP phase. Sleep SBP reduced significantly from baseline with both evening (-6.9 mm Hg) and morning (-8.0 mm Hg) dosing, but there was no difference between dosing times (difference: 1.1 mm Hg, 95% CI -0.3 to 2.5). However, wake SBP reduced more with morning (-9.8 mm Hg) than evening (-8.0 mm Hg) dosing (difference: 1.8 mm Hg, 95% CI 1.1 to 2.5). Addition of CPAP to either evening or morning dosing further reduced sleep SBP, but by a similar amount (evening: -3.2 mm Hg, 95% CI -5.1 to -1.3; morning: -3.3 mm Hg, 95% CI -5.2 to 1.5). CONCLUSIONS: Our findings support combining OSA treatment with morning administration of antihypertensives. Unlike in essential hypertension, our results do not support evening administration of antihypertensives, at least with perindopril. Further research is required before this strategy can be widely adopted into hypertension guidelines and clinical practice. TRIAL REGISTRATION NUMBER: ACTRN12611000216910, Results.

Pre-registration paid employment practices of undergraduate nursing students: A scoping review.

OBJECTIVES: This article presents findings from a scoping review that sought to highlight what is known about pre-registration paid employment practices of undergraduate nursing students. BACKGROUND: Researchers have identified large numbers of undergraduate nursing students engaging in paid employment. This review was prompted by our interest in the different employment choices that students make and whether these choices have any impact on transition to practice. DESIGN: A scoping review was designed to map the existing evidence base on undergraduate student nurse employment practices. Scoping reviews support the identification of a broad range of literature, which encompasses all types of study design. DATA SOURCES: Utilising key search terms, databases searched included MEDLINE, CINAHL, Psych INFO, EMBASE, SCOPUS, SCIRUS, Joanna Briggs Institute, Web of Science, Informit Health and the Cochrane database. REVIEW METHOD: We utilised Arksey and O'Malley's five-stage approach: identifying the research question; identifying relevant studies; study selection; charting the data; and collating, summarising and reporting the results. Based on the research question, relevant literature was selected which was reported in accordance with Arksey and O'Malley's framework. RESULTS: The scoping review identified 40 articles that explored the nature of undergraduate student nurse paid employment activity. Highlighted themes included: reasons for engaging in paid employment; specific paid employment models; paid employment and academic performance, and paid employment choice and transition to graduate practice. CONCLUSION: The review highlighted a lack of studies detailing the relationship between paid employment and transition to graduate nurse practice, particularly those studies situated within the hospitality sector.

Ethics, consent and blinding: lessons from a placebo/sham controlled CPAP crossover trial.

INTRODUCTION: Performing rigorously designed clinical trials in device-based treatments is challenging. Continuous positive airway pressure (CPAP) is the most effective device-based treatment for obstructive sleep apnoea. We performed a randomised crossover trial of CPAP versus placebo therapy and did not disclose the presence of placebo. We assessed rates of staff unblinding, the likelihood of patient unblinding and obtained patient perceptions on lack of full disclosure. METHODS: All patients (n=30) underwent a semi-structured exit interview. Prior to full disclosure patients were asked questions to ascertain whether they suspected one therapy was ineffective. The use of placebo was then disclosed and additional questions were administered to indicate the likelihood of unblinding had full disclosure occurred during consent. Staff unblinding was determined by means of a questionnaire that was completed after each patient encounter. RESULTS: While the lack of full disclosure prevented patient unblinding during the trial, patients revealed a clear preference for active CPAP. After disclosing the presence of placebo, 73% (n=22) felt they would have been unblinded had they known at the start of the trial. Only one patient described unease about the lack of full disclosure. Staff thought they were unblinded in 6% (n=16/282) of encounters. They correctly identified the treatment device in 69% of cases (n=11/16, p<0.001). CONCLUSIONS: Successful patient blinding was achieved, however this was probably reliant on the lack of full disclosure. Staff unblinding occurred and highlights the difficulty with investigator blinding in device-based trials. Ethical challenges in this type of study are likely to compromise research feasibility. TRIAL REGISTRATION NUMBER: This clinical trial is registered with the Australian and New Zealand Clinical Trials Registry at http://www.anzctr.org.au (ACTRN 12605000066684).

Effects of 8 weeks of CPAP on lipid-based oxidative markers in obstructive sleep apnea: a randomized trial.

Dyslipidaemia and increased oxidative stress have been reported in severe obstructive sleep apnea, and both may be related to the development of cardiovascular disease. We have previously shown in a randomized crossover study in patients with moderate to severe obstructive sleep apnea that therapeutic continuous positive airway pressure treatment for 8 weeks improved postprandial triglycerides and total cholesterol when compared with sham continuous positive airway pressure. From this study we have now compared the effect of 8 weeks of therapeutic continuous positive airway pressure and sham continuous positive airway pressure on oxidative lipid damage and plasma lipophilic antioxidant levels. Unesterified cholesterol, esterified unsaturated fatty acids (cholesteryl linoleate: C18:2; and cholesteryl arachidonate: C20:4; the major unsaturated and oxidizable lipids in low-density lipoproteins), their corresponding oxidized products [cholesteryl ester-derived lipid hydroperoxides and hydroxides (CE-O(O)H)] and antioxidant vitamin E were assessed at 20:30 hours before sleep, and at 06:00 and 08:30 hours after sleep. Amongst the 29 patients completing the study, three had incomplete or missing [CE-O(O)H] data. The mean apnea -hypopnoea index, age and body mass index were 38 per hour, 49 years and 32 kg m(-2) , respectively. No differences in lipid-based oxidative markers or lipophilic antioxidant levels were observed between the continuous positive airway pressure and sham continuous positive airway pressure arms at any of the three time-points [unesterified cholesterol 0.01 mm, P > 0.05; cholesteryl linoleate: C18:2 0.05 mm, P > 0.05; cholesteryl arachidonate: C20:4 0.02 mm, P = 0.05; CE-O(O)H 2.5 nm, P > 0.05; and lipid-soluble antioxidant vitamin E 0.03 µm, P > 0.05]. In this study, accumulating CE-O(O)H, a marker of lipid oxidation, does not appear to play a role in oxidative stress in obstructive sleep apnea.