Adherence to continuous positive airway pressure in adults with an intellectual disability

Study objectivesThis retrospective study evaluated the feasibility of continuous positive airway pressure (CPAP) therapy in adults with intellectual disabilities (ID).MethodsCPAP therapy of 24 obstructive sleep apnea syndrome (OSA) patients with ID were compared to age- and sex-matched adults with normal cognitive functioning. All ID patients received an intensive in-hospital training protocol to stimulate adherence. Good adherence was defined as a use of >70% of the nights and >4 h/night. Influencing factors were assessed.ResultsBaseline apnea-hypopnea index (AHI) was significantly higher in ID patients compared to controls (median 34/h (range 6–101) versus 17/h (range 5–50), p = 0.013). The required average duration of in-hospital training was four nights (range 1–8 days). At six weeks, 60% of the ID patients showed good adherence and 65% at six months, compared to 71% and 50% respectively in the control group. Mean CPAP use per night was equal in both groups both at six weeks (5 h in both groups) and six months (ID 6:30 h vs control 5 h (p = 0.18)). CPAP adherence correlated with baseline AHI in the control patients, but not in ID patients. There was no correlation between CPAP adherence and the level of ID or the degree of support at home.ConclusionsUsing an intensive training protocol it is very well feasible to apply CPAP therapy in OSA patients with any degree of ID. CPAP adherence in ID patients was comparable to the control patients in this study as well as to previously published adherence numbers.     

Comparisons of measures used to screen for obstructive sleep apnea in patients referred to a sleep clinic

Study objectivesObstructive Sleep Apnea (OSA) contributes to all-cause mortality. An American Academy of Sleep Medicine task force is focusing on improving detection and categorization of OSA symptoms and severity to promote screening, assessment, and diagnosis. The purpose of this study was to psychometrically compare measures used in OSA screening (Berlin, Epworth Sleepiness Scale (ESS), STOP Bang) and a portable sleep monitor (PSM) to apnea-hypopnea index (AHI) and levels from polysomnogram (PSG).MethodsAn observational, cross-sectional design was used. Patients referred to a sleep specialist were enrolled at initial sleep evaluation. Participants completed measures used in OSA screening, then sent home for one night using PSM. PSGs were ordered by the physician and AHI results were obtained from the medical record.ResultsParticipants (N = 170) were enrolled in the study. Almost all participants completed the OSA measures, approximately half-completed PSM measurement, and the majority completed laboratory PSG. The STOP Bang had the highest levels of sensitivity; the ESS had the lowest. The ESS had the highest specificity and reliability levels; the STOP Bang had the lowest. The PSM measure had the highest positive predictive value (PPV) and the strongest psychometric properties of the screening measures.ConclusionsThe STOP Bang was the preferred self-report OSA screening measure because of high levels of sensitivity. The ESS was the least desirable measure. PSM measurement consistently predicted the presence of OSA but at the expense of low sensitivity at AHI levels ≥30. This expands the knowledge of validity testing of screening measures used for OSA.     

Women with symptoms of sleep-disordered breathing are less likely to be diagnosed and treated for sleep apnea than men

BackgroundWomen are often underrepresented at sleep clinics evaluating sleep-disordered breathing (SDB). The aim of the present study was to analyze gender differences in sleep apnea diagnosis and treatment in men and women with similar symptoms of SDB.MethodsRespiratory Health in Northern Europe (RHINE) provided information about snoring, excessive daytime sleepiness (EDS), BMI and somatic diseases at baseline (1999–2001) and follow-up (2010–2012) from 4962 men and 5892 women. At follow-up participants were asked whether they had a diagnosis of and/or treatment for sleep apnea.ResultsAmong those with symptoms of SDB (snoring and EDS), more men than women had been given the diagnosis of sleep apnea (25% vs. 14%, p < 0.001), any treatment (17% vs. 11%, p = 0.05) and CPAP (6% vs. 3%, p = 0.04) at follow-up.Predictors of receiving treatment were age, BMI, SDB symptoms at baseline and weight gain, while female gender was related to a lower probability of receiving treatment (adj. OR 0.3, 95% CI 0.3–0.5).In both genders, the symptoms of SDB increased the risk of developing hypertension (adj OR, 95% CI: 1.5, 1.2–1.8) and diabetes (1.5, 1.05–2.3), independent of age, BMI, smoking and weight gain.ConclusionsSnoring females with daytime sleepiness may be under-diagnosed and under-treated for sleep apnea compared with males, despite running a similar risk of developing hypertension and diabetes.     

Prevalence and characteristics of positional sleep apnea in the HypnoLaus population-based cohort

Objective/BackgroundTo determine the prevalence of positional obstructive sleep apnea (POSA) and exclusive POSA (ePOSA) in the general population and to assess the factors independently associated with POSA and ePOSA according to gender and menopausal status.Patients/MethodsParticipants of the population-based HypnoLaus Sleep Cohort underwent full polysomnography at home. POSA was defined as an apnea-hypopnea index (AHI) ≥5/h, and supine/non-supine AHI ratio (sAHI/nsAHI) ≥2 (ePOSA when non-supine AHI was normalized).ResultsIn this study, 1719 subjects (40-85y.o. 46% men) with at least 30 min spent in both the supine and non-supine positions were included. OSA was present in 1224 subjects (71%) (AHI >5/H). POSA was present in 53% of all subjects, and in 75% of OSA subjects. ePOSA was present in 26% of all subjects and in 36% of OSA subjects. In multivariate analyses, lower AHI and lower BMI were both associated with POSA and ePOSA in males. In premenopausal females, no single factor was associated with POSA while a lower AHI and an Epworth sleepiness scale >10 were associated with ePOSA. In postmenopausal women, a lower BMI was associated with POSA and a lower AHI and a lower Mallampati score with ePOSA.ConclusionsIn this large population-based study, we found that POSA is present in 53% of the middle-to-older age general population, and in 75% of OSA subjects. ePOSA was present in 36% of OSA subjects, suggesting that a large proportion of them could be treated with positional therapy. AHI and BMI were differently associated with POSA in men, and pre or post-menopausal women.     

The effects of continuous positive airway pressure therapy on Troponin-T and N-terminal pro B-type natriuretic peptide in patients with obstructive sleep apnoea: a randomised controlled trial

IntroductionUntreated obstructive sleep apnoea (OSA) is associated with increased risk of coronary artery disease (CAD) and heart failure. High-sensitivity cardiac troponin (hs Trop-T) and B-type natriuretic peptide (NT-pro-BNP) are sensitive biomarkers for myocardial injury and heart failure respectively. No randomised controlled trials have examined the treatment effect of continuous positive airway pressure (CPAP) in patients with OSA on these biomarkers.MethodPatients >21 years old with apnoea-hypopnoea index (AHI) ≥25/h by overnight polysomnography were recruited. Main exclusion criteria were previous CPAP use and any significant comorbidities including CAD and heart failure. Eligible subjects were randomised to receive CPAP or sham CPAP for eight weeks each in a crossover design with a wash out period of one month between the treatments. Blood samples were collected at 8pm, 3am, and 8am during sleep studies conducted at the end of each eight-week treatment period.ResultsOf the 37 patients who were randomised, 28 patients had stored frozen samples available for analysis. In comparison to sham treatment, CPAP significantly lowered the NT-pro-BNP level by 0.91 pmol/L (p = 0.0002). The reduction of 0.235 ng/L in hs Trop-T on CPAP therapy was not statistically significant (p = 0.052). There were no overnight changes, across the three time points, in either biomarker with either treatment.ConclusionOur study confirms CPAP therapy in patients with moderate-severe OSA reduces NT-pro-BNP, but we did not confirm a significant effect on hs Trop-T. Future larger studies of longer duration incorporating biomarkers and cardiac functional measures are needed to better establish the benefit of OSA treatment.     

Stridor combined with other sleep breathing disorders in multiple system atrophy: a tailored treatment?

ObjectivesTo determine the frequency of sleep breathing disorders in multiple systemic atrophy (MSA, combining Parkinsonism, cerebellar syndrome, and dysautonomia) and evaluate the benefit/tolerance of various modes of ventilation.MethodsWe retrospectively analyzed 45 patients with MSA having undergone a videopolysomnography. Their sleep characteristics were compared to those of 45 patients with Parkinson's disease and 45 healthy controls, matched for age and sex. Patients with MSA received fixed continuous positive airway pressure (CPAP) when stridor was isolated, auto-adjusting CPAP when it was combined with obstructive sleep apnea, and adaptive servo-ventilation (ASV) when combined with central sleep apnea.ResultsHigher periodic leg movements index and more frequent REM sleep behavior disorder were observed in MSA patients, compared to patients with Parkinson's disease and healthy controls. In MSA, 28/45 (62.2%) patients had sleep breathing disorders, including (overlapping samples) stridor (n = 17, 38%), obstructive sleep apnea (n = 14, 31%), central sleep apnea (n = 4, 9%), and ataxic breathing (n = 1). Except for three initial refusals and two yet untreated patients, fixed CPAP (n = 9), auto-adjusting CPAP (n = 8) and ASV (n = 2) were well-tolerated (limited leaks and good compliance) and successfully controlled stridor plus sleep apnea. Treated patients had survival times similar to those of patients without any sleep breathing disorder.ConclusionIn this small group, tailored management of stridor in MSA as an independent issue or combined with obstructive and central sleep apnea, yields a survival similar to survival in patients without sleep breathing disorders.     

Spontaneous improvement in both obstructive sleep apnea and cognitive impairment after stroke

BackgroundKnowledge available about the relationship between obstructive sleep apnea (OSA) and cognitive impairment after stroke is limited. The evolution of OSA and cognitive performance after stroke is not sufficiently described.MethodsWe prospectively enrolled and examined acute stroke patients without previously diagnosed OSA. The following information was collected: (1) demographics, (2) sleep cardio-respiratory polygraphy (PG) at 72 h, day seven, month three, and month 12 after stroke, (3) post-stroke functional disability tests at entry and at months three and 12, and (4) cognition (attention and orientation, memory, verbal fluency, language, and visual-spatial abilities) using the revised Addenbrooke's Cognitive Examination (ACE-R) at months three and 12.ResultsOf 68 patients completing the study, OSA was diagnosed in 42 (61.8%) patients. The mean apnea/hypopnea index (AHI) at study entry of 21.0 ± 13.7 spontaneously declined to 11.6 ± 11.2 at month 12 in the OSA group (p < 0.0005). The total ACE-R score was significantly reduced at months three (p = 0.005) and 12 (p = 0.004) in the OSA group. Poorer performance on the subtests of memory at months 3 (p = 0.039) and 12 (p = 0.040) and verbal fluency at months 3 (p < 0.005) and 12 (p < 0.005) were observed in the OSA group compared to non-OSA group. Visual-spatial abilities in both the OSA (p = 0.001) and non-OSA (p = 0.046) groups and the total ACE-R score in the OSA (p = 0.005) and non-OSA (p = 0.002) groups improved.ConclusionsA high prevalence of OSA and cognitive decline were present in patients after an acute stroke. Spontaneous improvements in both OSA and cognitive impairment were observed.     

Back to sleep or not: the effect of the supine position on pediatric OSA: Sleeping position in children with OSA

BackgroundIn both adults and children, obstructive sleep apnea (OSA) has significant adverse cardiovascular consequences. In adults, sleeping position has a marked effect on the severity of OSA; however, the limited number of studies conducted in children have reported conflicting findings. We aimed to evaluate the effect of sleeping position on OSA severity and the cardiovascular consequences in preschool-aged children.MethodsThis was a retrospective analysis of children (3–5 years of age) diagnosed with OSA (n = 75) and nonsnoring controls (n = 25). Sleeping position was classified as supine, semi-supine, left lateral, right lateral, prone, and semi-prone by using video recordings during one night of attended polysomnography. OSA severity and cardiovascular parameters were compared between the positions.ResultsAll children spent significantly more sleep time in the supine position than in any other position. The obstructive apnea-hypopnea index was higher in the supine position than in the other sleeping positions during NREM (p < 0.05), higher in the moderate/severe OSA group when sleeping in the supine position than when sleeping in the left and right lateral positions (p < 0.05 for both) and prone position (p = 0.007) during REM. Sympathovagal balance was decreased in children with OSA in the supine and lateral positions (p < 0.05).ConclusionsThis study identified that preschool-aged children, whether nonsnoring controls or children with OSA, predominately sleep in the supine position, and OSA was more severe in the supine position. We suggest that to avoid the supine sleep position, positional therapy has the potential to ameliorate OSA severity, and the known cardiovascular consequences.     

Does comorbid obstructive sleep apnea impair the effectiveness of cognitive and behavioral therapy for insomnia?

AimsComorbid insomnia and obstructive sleep apnea (OSA) represents a highly prevalent and debilitating condition; however, physicians and researchers are still uncertain about the most effective treatment approach. Several research groups have suggested that these patients should initially receive treatment for their insomnia before the sleep apnea is targeted. The current study aims to determine whether Cognitive and Behavioral Therapy for Insomnia (CBT-i) can effectively treat insomnia in patients with comorbid OSA and whether its effectiveness is impaired by the presence of OSA.MethodsA retrospective chart review was conducted to examine 455 insomnia patients entering a CBT-i treatment program in a hospital out-patient setting. Three hundred and fourteen patients were diagnosed with insomnia alone and 141 with insomnia and comorbid OSA. Improvements in average sleep diary parameters, global insomnia severity, and several daytime functioning questionnaires from baseline, to post-treatment, to 3-month follow-up were compared between insomnia patients with and without comorbid OSA.ResultsInsomnia patients with comorbid OSA experienced significant improvements in insomnia symptoms, global insomnia severity, and other daytime functioning measures during and following treatment. Furthermore, improvements were no different between patients with or without comorbid OSA. Sleep apnea presence and severity were not related to rates of insomnia-remission or treatment-resistance following treatment.ConclusionsCBT-i is an effective treatment in the presence of comorbid OSA. This information offers support for the suggestion that patients with comorbid insomnia and OSA should be treated with CBT-i prior to the treatment of the OSA.     

Awareness and knowledge of obstructive sleep apnea among the general population

BackgroundObstructive sleep apnea (OSA) is an increasingly prevalent condition that remains largely undiagnosed. We aimed to assess the level of awareness and knowledge of OSA among the general population.MethodsThe Singapore Health 2 was a population-based study that comprised interview and health screening components. Out of 2720 subjects who completed the interview component, 2080 subjects gave consent for further health surveys. We contacted these subjects and conducted a structured telephone interview.ResultsWe completed 1306 telephone interviews (response rate 62.8%). Two hundred and eighty-one (21.5%) respondents were aware of OSA, but only 170 (13.0%) respondents could define OSA correctly. A total of 77 (5.9%), 158 (12.1%), 150 (11.5%) and 110 (8.4%) respondents were able to correctly list at least one risk factor, symptom, health consequence and treatment options for OSA, respectively. The most common sources of information about OSA were traditional media such as newspapers (42.0%), internet (14.2%) or relatives and friends (14.6%). On multivariate analysis, respondents were more likely to define OSA correctly if they were older (≥61years), (odds ratio of 2.99, 95% Confidence Interval [CI]: 1.66–5.41), were Chinese as compared to Indians (odds ratio 2.63, 95% CI: 1.46–4.72), had higher levels of income (odds ratio 2.18, 95% CI 1.16–4.10) and post-secondary education (odds ratio 2.87, 95% CI: 1.28–6.45).ConclusionAwareness and knowledge of OSA among the general population is currently poor. The effectiveness of ongoing health education campaigns to increase awareness should be monitored by examining temporal trends in public knowledge of sleep apnea.     

A novel approach using actigraphy to quantify the level of disruption of sleep by in-home polysomnography: the MrOS Sleep Study: Sleep disruption by polysomnography

BackgroundThe “first-night effect” of polysomnography (PSG) has been previously studied; however, the ability to quantify the sleep disruption level has been confounded with the use of PSG on all nights. We used actigraphy to quantify disruption level and examined characteristics associated with disruption.MethodsTotally, 778 older men (76.2 ± 5.4 years) from a population-based study at six US centers underwent one night of in-home PSG. Actigraphy was performed on the PSG night and three subsequent nights. Actigraphically measured total sleep time (TST), sleep efficiency (SE), wake after sleep onset (WASO), and sleep onset latency (SOL) from the PSG night and subsequent nights were compared. Linear regression models were used to examine the association of characteristics and sleep disruption.ResultsOn average, sleep on the PSG night was worse than the following night (p < 0.05, TST 21 ± 85 min less, SE 2.3 ± 11.3% less, WASO 4.9 ± 51.8 min more, SOL 6.6 ± 56.2 min more). Sleep on the PSG night was significantly worse than that two and three nights later. Characteristics associated with greater sleep disruption on the PSG night included older age, higher apnea–hypopnea index, worse neuromuscular function, and more depressive symptoms. Minorities and men with excessive daytime sleepiness slept somewhat better on the PSG night.ConclusionsAmong older men, there was sleep disruption on the PSG night, which may lead to sleep time underestimation. The increase of sleep on the night after the PSG suggests that data from the second monitoring may overestimate sleep.     

Sleep disorders,sleepiness, and near-miss accidents among long-distance highway drivers in the summertime

ObjectiveWe aimed to investigate sleepiness, sleep hygiene, sleep disorders, and driving risk among highway drivers.MethodsWe collected data using cross-sectional surveys, including the Epworth Sleepiness Scale (ESS) questionnaire, Basic Nordic Sleep Questionnaire (BNSQ), and a travel questionnaire; we also obtained sleep data from the past 24 h and information on usual sleep schedules. Police officers invited automobile drivers to participate.ResultsThere were 3051 drivers (mean age, 46 ± 13 y; 75% men) who completed the survey (80% participation rate). Eighty-seven (2.9%) drivers reported near-miss sleepy accidents (NMSA) during the trip; 8.5% of NMSA occurred during the past year and 2.3% reported sleepiness-related accidents occurring in the past year. Mean driving time was 181 ± 109 min and mean sleep duration in the past 24 h was 480 ± 104 min; mean sleep duration during workweeks was 468 ± 74 min. Significant risk factors for NMSA during the trip were NMSA in the past year, nonrestorative sleep and snoring in the past 3 months, and sleepiness during the interview. Neither sleep time in the past 24 h nor acute sleep debt (sleep time difference between workweeks and the past 24 h) correlated with the occurrence of near misses.ConclusionsUnlike previous studies, acute sleep loss no longer explains sleepiness at the wheel. Sleep-related breathing disorders or nonrestorative sleep help to explain NMSA more adequately than acute sleep loss.     

Association between nighttime sleep duration,midday naps,and glycemic levels in Japanese patients with type 2 diabetes

ObjectivesTo clarify the relationship between nighttime sleep duration, midday naps, and glycemic control in Japanese patients diagnosed with type 2 diabetes (n = 355) or impaired glucose tolerance (n = 43).MethodsA total of 398 patients completed a self-administered questionnaire on sleep duration/quality and were divided into five groups according to their self-reported nighttime sleep duration: <5 h, 5–6 h, 6–7 h, 7–8 h, and >8 h. Each group was further divided into two subgroups each according to the presence or absence of midday naps. Poor glycemic control was defined as HbA1c ≥ 7.0%.ResultsShort nighttime sleep (<5 h), poor sleep induction, daytime sleepiness, and low sleep satisfaction were associated with high HbA1c levels. HbA1c was higher in the short nighttime sleep/no nap group than in non-nappers with different nighttime sleep duration, whereas the short nighttime sleep/nap group showed similar HbA1c levels to the other nap subgroups. In multivariate logistic regression models, after adjusting for a number of potential confounders, short (<5 h) nighttime sleep without nap was significantly associated with poor glycemic control compared with 6–7 h nighttime sleep without nap (OR [95% CI]: 7.14 [2.20–23.20]). However, taking naps reduced this risk for poor glycemic control in short sleepers. Other risk factors for poor glycemic control were low sleep satisfaction (1.73 [1.10–2.70]) and poor sleep induction (1.69 [1.14–2.50]).ConclusionsPoor sleep quality and quantity could aggravate glycemic control in type 2 diabetes. Midday naps could mitigate the deleterious effects of short nighttime sleep on glycemic control.Clinical trials registrationUMIN 000017887.     

Hearing loss mediates executive function impairment in sleep-disordered breathing

BackgroundSleep-disordered breathing (SDB) is often co-morbid with conductive hearing loss in early childhood due to a shared aetiology of adenotonsillar hypertrophy. Hearing loss is independently associated with impairment of executive function and behavioural difficulties. We hypothesised that these impairments in children with SDB may be mediated through hearing loss.MethodsFifty-eight children including 37 snorers awaiting adenotonsillectomy and 21 healthy non-snoring controls, aged 3–5 years, were assessed with pure tone audiometry, Strengths and Difficulties (SDQ), Behaviour Rating of Executive Function (BRIEF-P), and Childhood Middle Ear Disease and Hearing questionnaires. Polysomnography in snoring children generated an obstructive apnoea/hypopnea index (OAHI). Two regression models examined the effect of SDB and the mediating impact of hearing loss on BRIEF and SDQ.ResultsSnoring children had significantly poorer hearing, greater past exposure to hearing loss, and higher total SDQ and BRIEF-P scores than non-snoring controls. The first regression model, including all children, demonstrated that the impact of snoring on BRIEF_P, but not SDQ, was entirely mediated by a history of hearing loss exposure but not same-day audiometry. The second model examined snoring children only, categorising the group into 12 with obstructive sleep apnoea (OSA) (OAHI ≥ 5) and 25 without OSA. OSA had a direct effect on SDQ scores, but this was not mediated by a history of hearing loss.ConclusionIn early childhood, conductive hearing loss mediates the relationship between SDB, irrespective of severity, and parent report of executive function but not behaviour. Treatment of hearing loss in pre-school SDB might improve executive function.     

Prevalence and predictors of obstructive sleep apnoea in young children with Down syndrome

BackgroundChildren with Down syndrome (DS) are vulnerable to obstructive sleep apnoea (OSA) because of their unique craniofacial anatomy and hypotonia. Understanding the predictors of OSA in DS may enable targeted screening.MethodsChildren with DS (n = 202) aged from six months to below six years (110 boys) were recruited from three UK children's hospitals. The clinical assessment included height, weight and tonsillar size. The parents either set up cardiorespiratory polygraphy at home or chose laboratory studies. Studies with less than four hours of interpretable data were repeated where possible. American Academy of Sleep Medicine (AASM) 2012 scoring criteria were used to derive an obstructive apnoea/hypopnoea index (OAHI). Predictors of moderate to severe OSA were examined.ResultsIn total, 188/202 (93%) participants were successfully studied. Of these, 169 studies were completed at home and 19 in a sleep laboratory. Moderate to severe OSA, defined by an OAHI of >5/h, was found in 14% and mild to moderate OSA (1/h≥OAHI <5/h) was found in 59% of the children. Male gender and habitual snoring predicted OSA but did not have independent predictive power in the presence of the other factors. Age in months, body mass index (BMI) centile and tonsillar size did not predict OSA.ConclusionsModerate to severe OSA is common in very young children with DS. Examination of tonsillar size did not predict OSA severity. Population-based screening for OSA is recommended in these children, and domiciliary cardiorespiratory polygraphy is an acceptable screening approach. Further research is required to understand the natural history, associated morbidity, optimal screening methodology and treatment modality for OSA in these children.     

Catathrenia,a REM predominant disorder of arousal?

ObjectivesCatathrenia is an uncommon and poorly understood disorder, characterized by groaning during sleep occurring in tandem with prolonged expiration. Its classification, pathogenesis, and clinical relevance remain debated, substantially due to the limited number of cases reported to date. We report a series of consecutive cases of catathrenia, their clinical and polysomnographic characteristics, and their subsequent management.MethodsConsecutive patients with catathrenia who had undergone full polysomnography in our institution over a 5.5-year period were included. Catathrenia events (CEs) were examined in clusters, which formulated catathrenia periods (CPs). The relationships between CPs, sleep stage distribution, electroencephalogram (EEG) arousals, and other sleep parameters were assessed, along with the clinical presentation and management of catathrenic patients.ResultsA total of 427 CPs were identified in 38 patients, 81% arising from rapid eye movement (REM) sleep. EEG arousals preceded or coincided with the onset of 84% of CPs, which were of longer duration than those not associated with an arousal (57.3 ± 56.8 vs. 32.2 ± 29.4 s, p < 0.001). Each CE had a characteristic airflow signal, with inspiration preceding a protracted expiration and a brief more rapid exhalation, followed by deep inspiration. Although the majority of patients were referred on the basis of bed partner complaints, 44.7% complained of daytime sleepiness. Continuous positive airway pressure therapy and sleep-consolidating pharmacotherapy led to subjective improvement, but were limited by poor long-term adherence.ConclusionsIn the largest series of catathrenia patients reported to date, we found that this rare disorder is characterized by a distinct breathing pattern and arises predominantly from REM sleep, with arousals almost uniformly preceding or coinciding with the onset of CPs.     

Efficacy and safety of almorexant in adult chronic insomnia: a randomized placebo-controlled trial with an active reference

Background and objectivesThe orally active dual OX₁R and OX₂R antagonist, almorexant, targets the orexin system for the treatment of primary insomnia. This clinical trial assessed the effect of almorexant on sleep maintenance and other sleep endpoints, and its safety and tolerability in adults.Patients and methodsProspective, randomized, double-blind, placebo-controlled, active referenced trial in male and female adults aged 18–64 years with chronic, primary insomnia. Patients were randomized 1:1:1:1 to receive placebo, almorexant 100 mg, almorexant 200 mg, or zolpidem 10 mg (active reference) for 16 days. Primary efficacy assessments were objective (polysomnography-measured) and subjective (patient-recorded) wake time after sleep onset (WASO). Further sleep variables were also evaluated.ResultsFrom 709 randomized patients, 707 (mean age 45.4 years; 61.7% female) received treatment and 663 (93.8%) completed the study. A significant decrease versus placebo in median objective WASO was observed with almorexant 200 mg at the start and end of randomized treatment (−26.8 min and −19.5 min, respectively; both p < 0.0001); subjective WASO also decreased over the two-week treatment period (p = 0.0006). Objective and subjective total sleep time (TST) were increased with almorexant 200 mg (p < 0.0001). Almorexant 200 mg significantly reduced objective and subjective latency to persistent sleep and latency to sleep onset at initiation of therapy, and provided longer duration of sleep stages with no suppression of slow-wave sleep. No impaired next-day performance, rebound insomnia, or withdrawal effects were observed. Adverse events were similar with almorexant and placebo.ConclusionAlmorexant reduced time to sleep onset and maintained sleep without residual effects on next-day performance or safety concerns. This study provides further support for the role of the endogenous orexin system in insomnia disorder.ClinicalTrials.gov registrationNCT00608985.     

Diabetes mellitus is independently associated with more severe cognitive impairment in Parkinson disease

BackgroundThere is increasing interest in interactions between metabolic syndromes and neurodegeneration. Diabetes mellitus (DM) contributes to cognitive impairment in the elderly but its effect in Parkinson disease (PD) is not well studied.ObjectiveTo investigate effects of comorbid DM on cognition in PD independent from PD-specific primary neurodegenerations.MethodsCross-sectional study. Patients with PD (n = 148); age 65.6 ± 7.4 years, Hoehn and Yahr stage 2.4 ± 0.6, with (n = 15) and without (n = 133) comorbid type II DM, underwent [¹¹C]methyl-4-piperidinyl propionate (PMP) acetylcholinesterase (AChE) PET imaging to assess cortical cholinergic denervation, [¹¹C]dihydrotetrabenazine (DTBZ) PET imaging to assess nigrostriatal denervation, and neuropsychological assessments. A global cognitive Z-score was calculated based on normative data. Analysis of covariance was performed to determine cognitive differences between subjects with and without DM while controlling for nigrostriatal denervation, cortical cholinergic denervation, levodopa equivalent dose and education covariates.ResultsThere were no significant differences in age, gender, Hoehn and Yahr stage or duration of disease between diabetic and non-diabetic PD subjects. There was a non-significant trend toward lower years of education in the diabetic PD subjects compared with non-diabetic PD subjects. PD diabetics had significantly lower mean (±SD) global cognitive Z-scores (−0.98 ± 1.01) compared to the non-diabetics (−0.36 ± 0.91; F = 7.78, P = 0.006) when controlling for covariate effects of education, striatal dopaminergic denervation, and cortical cholinergic denervation (total model F = 8.39, P < 0.0001).ConclusionDiabetes mellitus is independently associated with more severe cognitive impairment in PD likely through mechanisms other than disease-specific neurodegenerations.     

Sleep in women undergoing in vitro fertilization: a pilot study

ObjectiveSleep disturbances are thought to be frequent in women undergoing IVF despite minimal research of this hypothesis. Our goal was to longitudinally assess sleep duration and disturbances in women undergoing IVF and assess impact of habitual sleep duration on oocytes retrieved, an important outcome in IVF.MethodsActigraphy and questionnaire batteries containing sleep and psychometric instruments were performed prior to and throughout 24 IVF cycles.ResultsTST <7 h was present in 46%, 57%, 69%, and 42% of baseline, stimulation, post-oocyte retrieval, and post-embryo transfer recordings. ESS >10 was noted in 24%, 33%, and 36% of cycles during baseline, stimulation, and post-embryo transfer. PSQI >5 was noted in 57%, 43%, and 29% of cycles during baseline, stimulation, and post-embryo transfer. TST (F = 2.95, p = 0.04) and ESS (F = 4.36, p = 0.02) were the only sleep metrics in which a significant main effect of time was found by mixed models analysis.The final linear regression model chosen by stepwise selection to best explain the variability in oocytes retrieved included anti-mullerian hormone, day three follicle stimulating hormone, and baseline TST and explained 40% of the variance in oocytes retrieved (adjusted R² = 0.40, p = 0.03). Although not statistically significant, a trend towards a linear association between baseline TST and oocytes retrieved was seen with an increase of oocytes retrieved by 1.5 for every hour increase in TST (p = 0.09).ConclusionsThis is the first study to describe, with subjective and objective measures, sleep disturbances present throughout the IVF cycle. Importantly, a trend towards a linear relationship between TST and oocytes retrieved was found in this pilot study. Sleep may be a modifiable target to improve outcomes in women undergoing IVF and further investigations are needed.