External proficiency testing improves inter-scorer reliability of polysomnography scoring.

PURPOSE: This study evaluated whether or not polysomnography (PSG) inter-scorer reliability (ISR) across sleep centres could be improved by external proficiency testing (EPT), or by EPT combined with method alignment training. METHODS: Experienced scorers form 15 sleep centres were randomised to the following: (1) a control group, (2) a group that received a self-directed intervention of EPT reports (EPTPassive) or (3) a group that received an active intervention of method alignment training and EPT reports (EPTActive). Respiratory, arousal and sleep scoring ISR from sixteen PSG fragments were compared between groups across time. RESULTS: Among 30 scorers, there were no ISR changes in controls between baseline (BL) and 6 months (6 m). Both EPT groups showed ISR improvement from BL to 6 m for respiratory, arousal and sleep scoring (p < 0.05). Respiratory scoring back-transformed mean (95CI) proportion of specific agreement (PSA) for the EPTPassive group improved from 0.78 (0.72-0.84) to 0.80 (0.74-0.86) and for the EPTActive group from 0.80 (0.74-0.85) to 0.82 (0.76-0.88). Arousal scoring PSA for the EPTPassive group improved from 0.72 (0.66-0.77) to 0.74 (0.69-0.79) and for the EPTActive group from 0.71 (0.65-0.76) to 0.77 (0.72-0.82). Sleep scoring kappa for the EPTPassive group improved from 0.64 (0.58-0.69) to 0.73 (0.68-0.77) and for the EPTActive group from = 0.75 (0.71-0.80) to 0.80 (0.76-0.85). Overall, poorer performers achieved greater improvement. CONCLUSION: External proficiency testing produced modest, statistically significant PSG inter-scorer reliability improvements among experienced scorers across sleep centres, with potential to improve clinical management of individual patients and increase research study statistical power.

Positive airway pressure for sleep-disordered breathing in acute quadriplegia: a randomised controlled trial.

RATIONALE: Highly prevalent and severe sleep-disordered breathing caused by acute cervical spinal cord injury (quadriplegia) is associated with neurocognitive dysfunction and sleepiness and is likely to impair rehabilitation. OBJECTIVE: To determine whether 3 months of autotitrating CPAP would improve neurocognitive function, sleepiness, quality of life, anxiety and depression more than usual care in acute quadriplegia. METHODS AND MEASUREMENTS: Multinational, randomised controlled trial (11 centres) from July 2009 to October 2015. The primary outcome was neurocognitive (attention and information processing as measure with the Paced Auditory Serial Addition Task). Daytime sleepiness (Karolinska Sleepiness Scale) was a priori identified as the most important secondary outcome. MAIN RESULTS: 1810 incident cases were screened. 332 underwent full, portable polysomnography, 273 of whom had an apnoea hypopnoea index greater than 10. 160 tolerated at least 4 hours of CPAP during a 3-day run-in and were randomised. 149 participants (134 men, age 46±34 years, 81±57 days postinjury) completed the trial. CPAP use averaged 2.9±2.3 hours per night with 21% fully 'adherent' (at least 4 hours use on 5 days per week). Intention-to-treat analyses revealed no significant differences between groups in the Paced Auditory Serial Addition Task (mean improvement of 2.28, 95% CI -7.09 to 11.6; p=0.63). Controlling for premorbid intelligence, age and obstructive sleep apnoea severity (group effect -1.15, 95% CI -10 to 7.7) did not alter this finding. Sleepiness was significantly improved by CPAP on intention-to-treat analysis (mean difference -1.26, 95% CI -2.2 to -0.32; p=0.01). CONCLUSION: CPAP did not improve Paced Auditory Serial Addition Task scores but significantly reduced sleepiness after acute quadriplegia. TRIAL REGISTRATION NUMBER: ACTRN12605000799651.

Pilot study of remote telemonitoring in COPD.

BACKGROUND: Remote in-home monitoring (RM) of symptoms and physiological variables may allow early detection and treatment of exacerbations of chronic obstructive pulmonary disease (COPD). It is unclear whether RM improves patient outcomes or healthcare resource utilization. This study determined whether RM is feasible in patients with COPD and if RM reduces hospital admissions or length of stay (LOS) or improves health-related quality of life (HRQOL). SUBJECTS AND METHODS: Forty-four patients were randomized to standard best practice care (SBP) (n=22) or SBP+RM (n=22). RM involved daily recording of physiological variables, symptoms, and medication usage. RESULTS: There were no differences (mean±SD, SBP versus SBP+RM) in age (68±8 versus 70±9 years), gender (male:female 10:12 in both groups), or previous computer familiarity (59% versus 50%) between groups. The SBP group had a lower forced expiratory volume in 1 s (0.66±0.24 versus 0.91±0.34 L, p<0.01) and more current smokers (six versus none, p<0.05). There were no differences in number of COPD-related admissions/year (1.5±1.8 versus 1.3±1.7, p=0.76), COPD-related LOS days/year (15.6±19.4 versus 11.4±19.6, p=0.66), total admissions/year (2.2±2.1 versus 2.0±2.3, p=0.86), total LOS days/year (22.1±29.9 versus 21.6±30.4, p=0.88), or HRQOL between the two groups. CONCLUSIONS: The addition of RM to SBP was feasible but did not reduce healthcare utilization or improve quality of life in this group of patients already receiving comprehensive respiratory care.

The new AASM criteria for scoring hypopneas: impact on the apnea hypopnea index.

STUDY OBJECTIVES: To compare apnea-hypopnea indices (AHIs) derived using 3 standard hypopnea definitions published by the American Academy of Sleep Medicine (AASM); and to examine the impact of hypopnea definition differences on the measured prevalence of obstructive sleep apnea (OSA). DESIGN: Retrospective review of previously scored in-laboratory polysomnography (PSG). SETTING: Two tertiary-hospital clinical sleep laboratories. PATIENTS OR PARTICIPANTS: 328 consecutive patients investigated for OSA during a 3-month period. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: AHIs were originally calculated using previous AASM hypopnea scoring criteria (AHI(Chicago)), requiring either >50% airflow reduction or a lesser airflow reduction with associated >3% oxygen desaturation or arousal. AHIs using the "recommended" (AHI(Rec)) and the "alternative" (AHI(Alt)) hypopnea definitions of the AASM Manual for Scoring of Sleep and Associated Events were then derived in separate passes of the previously scored data. In this process, hypopneas that did not satisfy the stricter hypopnea definition criteria were removed. For AHI(Rec), hypopneas were required to have > or =30% airflow reduction and > or =4% desaturation; and for AHI(Alt), hypopneas were required to have > or =50% airflow reduction and > or =3% desaturation or arousal. The median AHI(Rec) was approximately 30% of the median AHI(Chicago), whereas the median AHI(Alt), was approximately 60% of the AHI(Chicago), with large, AHI-dependent, patient-specific differences observed. Equivalent cut-points for AHI(Rec) and AHI(Alt), compared to AHI(Chicago) cut-points of 5, 15, and 30/h were established with receiver operator curves (ROC). These cut-points were also approximately 30% of AHI(Chicago) using AHI(Rec) and 60% of AHI(Chicago) using AHI(Alt). Failure to adjust cut-points for the new criteria would result in approximately 40% of patients previously classifled as positive for OSA using AHI(Chicago) being negative using AHI(Rec) and 25% being negative using AHI(Alt). CONCLUSIONS: This study demonstrates that using different published standard hypopnea definitions leads to marked differences in AHI. These results provide insight to clinicians and researchers in interpreting results obtained using different published standard hypopnea definitions, and they suggest that consideration should be given to revising the current scoring recommendations to include a single standardized hypopnea definition.

Genioglossus muscle responses to resistive loads in severe OSA patients and healthy control subjects.

This study aimed to determine whether there is impairment of genioglossus neuromuscular responses to small negative pressure respiratory stimuli, close to the conscious detection threshold, in obstructive sleep apnea (OSA). We compared genioglossus electromyogram (EMGgg) responses to midinspiratory resistive loads of varying intensity (≈1.2-6.2 cmH2O·L-1·s), delivered via a nasal mask, between 16 severe OSA and 17 control participants while the subjects were awake and in a seated upright position. We examined the relationship between stimulus intensity and peak EMGgg amplitude in a 200-ms poststimulus window and hypothesized that OSA patients would have an increased activation threshold and reduced sensitivity in the relationship between EMGgg activation and stimulus intensity. There was no significant difference between control and OSA participants in the threshold (P = 0.545) or the sensitivity (P = 0.482) of the EMGgg amplitude vs. stimulus intensity relationship, where change in epiglottic pressure relative to background epiglottic pressure represented stimulus intensity. These results do not support the hypothesis that deficits in neuromuscular response to negative upper airway pressure exist in OSA during wakefulness; however, the results are likely influenced by a counterintuitive and novel genioglossus muscle suppression response observed in a significant proportion of both OSA and healthy control participants. This suppression response may relate to the inhibition seen in inspiratory muscles such as the diaphragm in response to sudden-onset negative pressure, and its presence provides new insight into the upper airway neuromuscular response to the collapsing force of negative pressure.NEW & NOTEWORTHY Our study used a novel midinspiratory resistive load stimulus to study upper airway neuromuscular responses to negative pressure during wakefulness in obstructive sleep apnea (OSA). Although no differences were found between OSA and healthy groups, the study uncovered a novel and unexpected suppression of neuromuscular activity in a large proportion of both OSA and healthy participants. The unusual response provides new insight into the upper airway neuromuscular response to the collapsing force of negative pressure.

SMART-COP: a tool for predicting the need for intensive respiratory or vasopressor support in community-acquired pneumonia.

BACKGROUND: Existing severity assessment tools, such as the pneumonia severity index (PSI) and CURB-65 (tool based on confusion, urea level, respiratory rate, blood pressure, and age >or=65 years), predict 30-day mortality in community-acquired pneumonia (CAP) and have limited ability to predict which patients will require intensive respiratory or vasopressor support (IRVS). METHODS: The Australian CAP Study (ACAPS) was a prospective study of 882 episodes in which each patient had a detailed assessment of severity features, etiology, and treatment outcomes. Multivariate logistic regression was performed to identify features at initial assessment that were associated with receipt of IRVS. These results were converted into a simple points-based severity tool that was validated in 5 external databases, totaling 7464 patients. RESULTS: In ACAPS, 10.3% of patients received IRVS, and the 30-day mortality rate was 5.7%. The features statistically significantly associated with receipt of IRVS were low systolic blood pressure (2 points), multilobar chest radiography involvement (1 point), low albumin level (1 point), high respiratory rate (1 point), tachycardia (1 point), confusion (1 point), poor oxygenation (2 points), and low arterial pH (2 points): SMART-COP. A SMART-COP score of >or=3 points identified 92% of patients who received IRVS, including 84% of patients who did not need immediate admission to the intensive care unit. Accuracy was also high in the 5 validation databases. Sensitivities of PSI and CURB-65 for identifying the need for IRVS were 74% and 39%, respectively. CONCLUSIONS: SMART-COP is a simple, practical clinical tool for accurately predicting the need for IRVS that is likely to assist clinicians in determining CAP severity.

The etiology of community-acquired pneumonia in Australia: why penicillin plus doxycycline or a macrolide is the most appropriate therapy.

BACKGROUND: Available data on the etiology of community-acquired pneumonia (CAP) in Australia are very limited. Local treatment guidelines promote the use of combination therapy with agents such as penicillin or amoxycillin combined with either doxycycline or a macrolide. METHODS: The Australian CAP Study (ACAPS) was a prospective, multicenter study of 885 episodes of CAP in which all patients underwent detailed assessment for bacterial and viral pathogens (cultures, urinary antigen testing, serological methods, and polymerase chain reaction). Antibiotic agents and relevant clinical outcomes were recorded. RESULTS: The etiology was identified in 404 (45.6%) of 885 episodes, with the most frequent causes being Streptococcus pneumoniae (14%), Mycoplasma pneumoniae (9%), and respiratory viruses (15%; influenza, picornavirus, respiratory syncytial virus, parainfluenza virus, and adenovirus). Antibiotic-resistant pathogens were rare: only 5.4% of patients had an infection for which therapy with penicillin plus doxycycline would potentially fail. Concordance with local antibiotic recommendations was high (82.4%), with the most commonly prescribed regimens being a penicillin plus either doxycycline or a macrolide (55.8%) or ceftriaxone plus either doxycycline or a macrolide (36.8%). The 30-day mortality rate was 5.6% (50 of 885 episodes), and mechanical ventilation or vasopressor support were required in 94 episodes (10.6%). Outcomes were not compromised by receipt of narrower-spectrum beta-lactams, and they did not differ on the basis of whether a pathogen was identified. CONCLUSIONS: The vast majority of patients with CAP can be treated successfully with narrow-spectrum beta-lactam treatment, such as penicillin combined with doxycycline or a macrolide. Greater use of such therapy could potentially reduce the emergence of antibiotic resistance among common bacterial pathogens.

The effect of acute sleep deprivation on visual evoked potentials in professional drivers.

STUDY OBJECTIVES: Previous studies have demonstrated that as little as 18 hours of sleep deprivation can cause deleterious effects on performance. It has also been suggested that sleep deprivation can cause a "tunnel-vision" effect, in which attention is restricted to the center of the visual field. The current study aimed to replicate these behavioral effects and to examine the electrophysiological underpinnings of these changes. DESIGN: Repeated-measures experimental study. SETTING: University laboratory. PATIENTS OR PARTICIPANTS: Nineteen professional drivers (1 woman; mean age = 45.3 +/- 9.1 years). INTERVENTIONS: Two experimental sessions were performed; one following 27 hours of sleep deprivation and the other following a normal night of sleep, with control for circadian effects. MEASUREMENTS & RESULTS: A tunnel-vision task (central versus peripheral visual discrimination) and a standard checkerboard-viewing task were performed while 32-channel EEG was recorded. For the tunnel-vision task, sleep deprivation resulted in an overall slowing of reaction times and increased errors of omission for both peripheral and foveal stimuli (P < 0.05). These changes were related to reduced P300 amplitude (indexing cognitive processing) but not measures of early visual processing. No evidence was found for an interaction effect between sleep deprivation and visual-field position, either in terms of behavior or electrophysiological responses. Slower processing of the sustained parvocellular visual pathway was demonstrated. CONCLUSIONS: These findings suggest that performance deficits on visual tasks during sleep deprivation are due to higher cognitive processes rather than early visual processing. Sleep deprivation may differentially impair processing of more-detailed visual information. Features of the study design (eg, visual angle, duration of sleep deprivation) may influence whether peripheral visual-field neglect occurs.

Estimating the prevalence of sleep-disordered breathing in community-based, long-term stroke survivors using a validated predictive model.

BACKGROUND: Assessing sleep-disordered breathing (SDB) in aged or disabled populations is difficult. AIMS: To validate a multivariable apnea risk prediction index (MAPI) in stroke survivors and estimate SDB prevalence (apnea-hypopnea index >or=10) in a community-based stroke cohort. METHODS: Self-reported sleep apnea symptoms, demographic and anthropometric data were obtained from a hospital-based (SCOPES II, n = 152) and a community-based (NEMESIS, n = 431) cohort at about 3 years after stroke. Logistic regression models for prediction of SDB using the MAPI were validated with home-based nocturnal polygraphic data recordings obtained in 74 SCOPES II participants. RESULTS: NEMESIS subjects (median age 76, females 45%) were older than SCOPES II subjects (median age 70, females 42%). SDB prevalence was 44.9% in the nocturnal polygraphy subset, and estimated as 44.1% (SCOPES II) and 50.6% (NEMESIS) using a modified MAPI. CONCLUSION: The MAPI can be reliably used in stroke cohorts and SDB affects about half of chronic stroke survivors.

The interactive effects of extended wakefulness and low-dose alcohol on simulated driving and vigilance.

OBJECTIVES: Sleep deprivation and alcohol both impair driving performance. This study assessed the interactive effect of low-dose alcohol and extended wakefulness. DESIGN: Repeated-measures, crossover design evaluating psychomotor and driving function in a non-sleep-deprived state and after extended wakefulness with and without low-dose alcohol. SETTING: Teaching hospital sleep laboratory. PARTICIPANTS: Nineteen volunteer professional drivers. INTERVENTION & MEASUREMENTS: Driving simulation (AusEd) and the Psychomotor Vigilance Task (PVT) were measured in a rested state (12-15 hours awake) and after extended wakefulness (18-21 hours awake) during two sessions. Alcohol was administered during one session, with performance measured at blood alcohol concentrations (BAC) of 0.00%, 0.03%, and 0.05% in a non-sleep-deprived state, and at 0.03% after extended wakefulness (at 01:00 and 03:00). During the second session, tests were performed at the same times without alcohol. RESULTS: The combination of extended wakefulness and low-dose alcohol had significant deleterious effects on reaction time and lapses (PVT) and variation in lane position and speed (AusEd). Extended wakefulness (18-21 hours awake) combined with low-dose alcohol (0.03% BAC) resulted in more lapses (t = -2.75, P < 0.05) and greater variation in lane position (t = -3.94, P < 0.01) and speed (t = -2.79, P < 0.05) than did a BAC of 0.05% in a rested state. CONCLUSION: The combination of legal low-dose alcohol and extended wakefulness results in impairment worse than that at an alcohol level known to increase accident risk. Avoiding alcohol when driving after extended wakefulness may reduce accident risk.

Sensory detection of threshold intensity resistive loads in severe obstructive sleep apnoea.

Respiratory related evoked potentials (RREPs) were used to investigate whether sensory detection of small mid-inspiratory resistive loads (≈1.2-6.2 cmH2OL-1s), delivered during wakefulness, was impaired in obstructive sleep apnoea (OSA). It was reasoned that impaired detection of minor airway patency challenge may lead to difficult-to-remedy further collapse. There was a significant reduction in OSA (n=16) vs. control (n=17) participants in the slope of the relationship between the P1 RREP component amplitude, which reflects arrival of somatosensory information at the cortex, and stimulus intensity, expressed as change in epiglottic pressure (mean [95% confidence intervals]: -0.50 [-0.97, -0.03] vs. -1.78 [-2.54, -1.02]; P=0.004), suggesting a reduction in sensitivity to small respiratory loads. However there was no significant difference in sensitivity after background Pepi was taken into account (P=0.268). Additionally, there were no significant group differences in the threshold of the P1 amplitude/stimulus intensity relationship, or in the P1 latency. These results indicate a reduced sensitivity to detection of small upper airway negative pressure stimuli in OSA related to a reduction in mechanoreceptor activation (likely related to increased airway resistance in OSA vs. controls; P=0.002) rather than defective mechanosensory function.

Inhomogeneity of ventilation leads to unpredictable errors in measured D(L)CO.

We evaluated the effects of inhomogeneity of ventilation on single-breath (SB), rebreathing (RB) and open circuit (OC) D(L)CO using a mathematical model consisting of two alveolar compartments and a common dead space. Inhomogeneity in ventilation was studied by altering inspired volume, initial alveolar volume and compartment size independently. When distribution of inspired volume between alveolar compartments was inhomogeneous (9:1), D(L)CO was underestimated by 35% for SB, 25% for RB, and 16% for OC, and there was an underestimation in V(A) of 9%, 15% and 9%, respectively. With inhomogeneity in initial alveolar volume there was an overestimation in D(L)CO of 13%, 7% and 11% for SB, RB and OC techniques and an underestimation of V(A) of 7%, 12% and 9%. Finally inhomogeneity of compartment size led to an underestimation of D(L)CO of 18%, 35% and 36% with no change in measured V(A). These results suggest D(L)CO measurements are sensitive to inhomogeneity of ventilation, and importantly, all techniques were at times, significantly in error.

Sleep disordered breathing in chronic stroke survivors. A study of the long term follow-up of the SCOPES cohort using home based polysomnography.

Prevalence of sleep-disordered breathing (SDB) (apnea-hypopnea index [AHI] > or = 5) in acute stroke patients ranges between 44% and 95%, compared to the community prevalence, 9 to 35% for women and 8 to 57% for men [age range 30-60 years]. Limited data exists beyond 3 months following stroke. We assessed the prevalence of SDB amongst stroke survivors at 3 years and compared results to data reported in normal and elderly populations. 90/143 eligible stroke survivors from an existing cohort underwent a home based sleep study. Mean age of the 78 subjects with a valid sleep study was 64 years (SD 15). Prevalence of SDB (AHI > or = 5) was 81% (95% CI 72% to 90%) and sleep apnoea syndrome (AHI > or = 5 plus ESS score > or =11) was 20% (95% CI 11% to 29%). Important predictors for AHI > or = 15 were haemorrhagic stroke (aOR12.06 [1.42-102.74]) and stroke severity at 1 month (aOR4.15 [1.05-16.38]). Large case-control studies are needed.

The maintenance of wakefulness test in normal healthy subjects.

STUDY OBJECTIVES: The Maintenance of Wakefulness Test (MWT) examines an individual's ability to stay awake in an environment of decreased sensory stimulation. Only 1 previous study has systematically examined the MWT in normal healthy subjects. SETTING: Sleep disorders unit laboratory PARTICIPANTS AND DESIGN: 31 subjects (mean age 48.5 years, SD 9.6; 8 women) were randomly selected via the telephone directory within a 30-km radius of the test centers. They answered a general screen for health complaints (respiratory, cardiovascular, and psychiatric disorders) and sleep difficulties (snoring). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Overnight polysomnography and a 40-minute MWT the following day were performed on all subjects. Mean sleep latency to the first epoch of unequivocal sleep during the 40-minute trial MWT was 36.9 +/- 5.4 (SD) minutes. The lower normal limit, defined as 2 SD below the mean, was therefore 26.1 minutes. Mean sleep latency for the first 20 minutes of the trial (with sleep latency defined as time to the first appearance of 1 epoch of stage 1 sleep or a 10-second microsleep) was 18.6 +/- 2.3 minutes, with a lower normal limit of 14.0 minutes. CONCLUSIONS: The mean results are consistent with previously published normative data. However, the SDs found in this study are smaller, and, thus, the lower normal limit suggested here is 4 to 6 minutes longer. The subjects in this study were randomly selected from the general population and may, therefore, be a truer representation of the normal population than in the previous study in which subjects were recruited via hospital advertisements and word of mouth.

Severe gastroesophageal reflux is associated with reduced carbon monoxide diffusing capacity.

OBJECTIVE: To assess whether severe gastroesophageal reflux (GER) is associated with abnormalities in lung function including measures of lung volume and gas diffusion. METHODS: Data from 147 patients with obesity (body mass index [BMI] range, 31.7 to 70 kg/m(2)) who presented for obesity surgery was analyzed retrospectively. A questionnaire was completed preoperatively that included a history of GER, frequency and severity of symptoms, investigations, and medications used. A history of lung disease, sleep-disordered breathing, and smoking also was obtained. A physician who was blinded to lung function graded GER severity prospectively by the results of pH monitoring and/or gastroscopy, and medication use. Spirometry, lung volumes, and gas transfer were measured preoperatively. RESULTS: Patients with severe GER had reduced levels of the diffusing capacity of the lung for carbon monoxide (DLCO) [21.1 mL/min/mm Hg; 95% confidence interval (CI), 18.9 to 23.2], as measured by CO transfer, compared with those patients without GER (26.3 mL/min/mm Hg; 95% CI, 24.4 to 28.2; p = 0.001). This remained significant after adjusting for age, gender, BMI, and smoking history. Gas transfer corrected for lung volume also was reduced in the group with severe GER (4.6 mL/min/mm Hg per L; 95% CI, 4.3 to 4.9) compared to the group without GER (5.3 mL/min/mm Hg per L; 95% CI, 5.1 to 5.5; p = 0.001). There was no significant difference in other measures of lung function. CONCLUSIONS: Severe GER is associated with an impairment of gas exchange. This may be due to microaspiration of gastric acid or fluid into the airways.

Deterioration in driving performance during sleep deprivation is similar in professional and nonprofessional drivers.

OBJECTIVE: There is some suggestion in the literature that professional drivers might self-select to be more resistant to the effects of sleep deprivation; however, this question has not been directly examined. The current laboratory study aimed to compare performance changes during acute sleep deprivation between professional and nonprofessional drivers. METHODS: Twenty volunteer male professional drivers and 20 nonprofessional drivers performed a simulated driving task (AusEd) and the Psychomotor Vigilance Task (PVT) during 24 hours of continuous wakefulness. Ratings of subjective sleepiness were also examined. RESULTS: There was a progressive and significant increase in lateral lane position and speed variability on the simulated driving task and an increase in PVT reaction times and lapses after participants had been awake for 17 to 24 hours (Ps < .01). There was no difference in performance changes between the professional and nonprofessional drivers. CONCLUSIONS: Professional drivers in this study had the same susceptibility to sleep deprivation as nonprofessional drivers. This finding does not support the concept that professional drivers are resistant to sleep loss.

Auto-titrating continuous positive airway pressure treatment for obstructive sleep apnoea after acute quadriplegia (COSAQ): study protocol for a randomized controlled trial.

BACKGROUND: Quadriplegia is a severe, catastrophic injury that predominantly affects people early in life, resulting in lifelong physical disability. Obstructive sleep apnoea is a direct consequence of quadriplegia and is associated with neurocognitive deficits, sleepiness and reduced quality of life. The usual treatment for sleep apnoea is nasal continuous positive airway pressure (CPAP); however, this is poorly tolerated in quadriplegia. To encourage patients to use this therapy, we have to demonstrate that the benefits outweigh the inconvenience. We therefore propose a prospective, multinational randomized controlled trial of three months of CPAP for obstructive sleep apnoea after acute quadriplegia. METHODS/DESIGN: Specialist spinal cord injury centres across Australia, New Zealand, the UK and Canada will recruit medically stable individuals who have sustained a (new) traumatic quadriplegia (complete or incomplete second cervical to first thoracic level lesions). Participants will be screened for obstructive sleep apnoea using full, portable sleep studies. Those with an apnoea hypopnoea index greater than 10 per hour will proceed to an initial three-night trial of CPAP. Those who can tolerate CPAP for at least 4 hours on at least one night of the initial trial will be randomized to either usual care or a 3-month period of auto-titrating CPAP. The primary hypothesis is that nocturnal CPAP will improve neuropsychological functioning more than usual care alone. The secondary hypothesis is that the magnitude of improvement of neuropsychological function will be predicted by the severity of baseline sleepiness measures, sleep fragmentation and sleep apnoea. Neuropsychological tests and full polysomnography will be performed at baseline and 3 months with interim measures of sleepiness and symptoms of autonomic dysfunction measured weekly. Spirometry will be performed monthly. Neuropsychological tests will be administered by blinded assessors. Recruitment commenced in July 2009. DISCUSSION: The results of this trial will demonstrate the effect of nocturnal CPAP treatment of obstructive sleep apnoea in acute quadriplegia. If CPAP can improve neurocognitive function after injury, it is likely that rehabilitation and subsequent community participation will be substantially improved for this group of predominantly young and severely physically disabled people. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ACTRN12605000799651.

Magnetic resonance spectroscopy and neurocognitive dysfunction in obstructive sleep apnea before and after CPAP treatment.

STUDY OBJECTIVES: To determine whether cerebral metabolite changes may underlie abnormalities of neurocognitive function and respiratory control in OSA. DESIGN: Observational, before and after CPAP treatment. SETTING: Two tertiary hospital research institutes. PARTICIPANTS: 30 untreated severe OSA patients, and 25 age-matched healthy controls, all males free of comorbidities, and all having had detailed structural brain analysis using voxel-based morphometry (VBM). MEASUREMENTS AND RESULTS: Single voxel bilateral hippocampal and brainstem, and multivoxel frontal metabolite concentrations were measured using magnetic resonance spectroscopy (MRS) in a high resolution (3T) scanner. Subjects also completed a battery of neurocognitive tests. Patients had repeat testing after 6 months of CPAP. There were significant differences at baseline in frontal N-acetylaspartate/choline (NAA/Cho) ratios (patients [mean (SD)] 4.56 [0.41], controls 4.92 [0.44], P = 0.001), and in hippocampal choline/creatine (Cho/Cr) ratios (0.38 [0.04] vs 0.41 [0.04], P = 0.006), (both ANCOVA, with age and premorbid IQ as covariates). No longitudinal changes were seen with treatment (n = 27, paired t tests), however the hippocampal differences were no longer significant at 6 months, and frontal NAA/Cr ratios were now also significantly different (patients 1.55 [0.13] vs control 1.65 [0.18] P = 0.01). No significant correlations were found between spectroscopy results and neurocognitive test results, but significant negative correlations were seen between arousal index and frontal NAA/Cho (r = -0.39, corrected P = 0.033) and between % total sleep time at SpO(2) < 90% and hippocampal Cho/Cr (r = -0.40, corrected P = 0.01). CONCLUSIONS: OSA patients have brain metabolite changes detected by MRS, suggestive of decreased frontal lobe neuronal viability and integrity, and decreased hippocampal membrane turnover. These regions have previously been shown to have no gross structural lesions using VBM. Little change was seen with treatment with CPAP for 6 months. No correlation of metabolite concentrations was seen with results on neurocognitive tests, but there were significant negative correlations with OSA severity as measured by severity of nocturnal hypoxemia.

The 2007 AASM recommendations for EEG electrode placement in polysomnography: impact on sleep and cortical arousal scoring.

STUDY OBJECTIVE: To examine the impact of using American Academy of Sleep Medicine (AASM) recommended EEG derivations (F4/M1, C4/M1, O2/M1) vs. a single derivation (C4/M1) in polysomnography (PSG) on the measurement of sleep and cortical arousals, including inter- and intra-observer variability. DESIGN: Prospective, non-blinded, randomized comparison. SETTING: Three Australian tertiary-care hospital clinical sleep laboratories. PATIENTS OR PARTICIPANTS: 30 PSGs from consecutive patients investigated for obstructive sleep apnea (OSA) during December 2007 and January 2008. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: To examine the impact of EEG derivations on PSG summary statistics, 3 scorers from different Australian clinical sleep laboratories each scored separate sets of 10 PSGs twice, once using 3 EEG derivations and once using 1 EEG derivation. To examine the impact on inter- and intra-scorer reliability, all 3 scorers scored a subset of 10 PSGs 4 times, twice using each method. All PSGs were de-identified and scored in random order according to the 2007 AASM Manual for the Scoring of Sleep and Associated Events. Using 3 referential EEG derivations during PSG, as recommended in the AASM manual, instead of a single central EEG derivation, as originally suggested by Rechtschaffen and Kales (1968), resulted in a mean ± SE decrease in N1 sleep of 9.6 ± 3.9 min (P = 0.018) and an increase in N3 sleep of 10.6 ± 2.8 min (P = 0.001). No significant differences were observed for any other sleep or arousal scoring summary statistics; nor were any differences observed in inter-scorer or intra-scorer reliability for scoring sleep or cortical arousals. CONCLUSION: This study provides information for those changing practice to comply with the 2007 AASM recommendations for EEG placement in PSG, for those using portable devices that are unable to comply with the recommendations due to limited channel options, and for the development of future standards for PSG scoring and recording. As the use of multiple EEG derivations only led to small changes in the distribution of derived sleep stages and no significant differences in scoring reliability, this study calls into question the need to use multiple EEG derivations in clinical PSG as suggested in the AASM manual.