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.     

Association between severity of untreated sleep apnoea and postoperative complications following major cardiac surgery: a prospective observational cohort study

ObjectiveTo examine whether untreated sleep apnoea is associated with prolonged Intensive Care Unit (ICU) stay and increased frequency of postoperative ICU complications, in patients undergoing major cardiac surgery.Patients/methodsAdult patients, undergoing elective coronary artery bypass grafting with or without cardiac valve surgery, between March 2013 and July 2014, were considered. We excluded patients participating in other interventional studies, those who had a tracheostomy before surgery, required emergency surgery or were due to be admitted on the day of surgery. Patients underwent inpatient overnight oximetry on the night prior to their surgery to assess for the presence of sleep apnoea. Since oximetry alone cannot differentiate obstructive from central apnoea, the results are reported as sleep apnoea which was diagnosed in patients with an arterial oxygen desaturation index (ODI) ≥ 5/h.ResultsThe primary outcome measure was length of stay (LoS) in ICU in days. The secondary outcome was a composite measure of postoperative complications in ICU. Multivariate models were developed to assess associations between ODI and the primary and secondary outcome measures, adjusting for preselected predictor variables, relative to primary and secondary outcomes. There was no significant association between ODI and ICU LoS, HR 1.0, 95% CI 0.99–1.02; p = 0.12. However we did find a significant association between ODI and postoperative complications in the ICU, OR = 1.1; 95% CI 1.02–1.17; p = 0.014. The probability of developing complications rose with higher ODI, reflecting sleep apnoea severity.ConclusionsAcknowledging the limitations of this prospective study, untreated sleep apnoea did not predict an increased length of stay in ICU but we do report an association with postoperative complications in patients undergoing major cardiac surgery.     

The effect of sleep duration and sleep quality on hypertension in middle-aged and older Chinese: the Dongfeng-Tongji Cohort Study

ObjectiveTo examine the independent and combined associations of sleep duration and sleep quality with hypertension in a middle-aged and older Chinese population.MethodsWe included 21,912 individuals aged 62.2 years at baseline from September 2008 to June 2010, and they were followed until October 2013. Sleep duration was self-reported and sleep quality was evaluated with questions designed according to the Pittsburgh Sleep Quality Index. Hypertension was defined as blood pressure ≥140/90 mmHg, or self-reported physician diagnosis of hypertension, or self-reported current use of antihypertensive medication.ResultsIn the cross-sectional analyses, the odds ratio of hypertension prevalence was significantly elevated (OR = 1.13, 95% CI = 1.03–1.24) in those who slept less than 7 h after adjusting for sex, age, body mass index, midday napping, cigarette smoking and sleep quality. It was particularly evident among males (OR = 1.19, 95% CI = 1.01–1.40) and individuals who were thin (OR = 2.00, 95% CI = 1.01–3.93) with full adjustment. The association was also found for sleep duration of 9∼<10 h after adjusting various covariates (OR = 1.14, 95% CI = 1.04–1.27). In addition, impaired sleep quality was only associated with hypertension in obese individuals (OR = 1.25, 95% CI = 1.02–1.50), not in other subgroups. However, no significant association was detected in any category of sleep duration or sleep quality in all models in the prospective analyses, and the results remained unchanged in the subgroup analyses of sex, age and body mass index.ConclusionsThe results of this study provide limited support for association of sleep duration and sleep quality with hypertension in middle-aged and older Chinese. Further studies are needed to confirm the results.     

Restless legs syndrome after high-risk TIA and minor stroke: association with reduced quality of life

BackgroundRestless legs syndrome (RLS) is a movement disorder that is associated with poor quality of life and depressive symptoms in the general population. Emerging evidence suggests that RLS is closely associated with cerebrovascular disease. We assessed the effect of RLS on quality of life after stroke and transient ischemic attack (TIA).MethodsIn this single-center prospective study, we recruited patients within 14 days of high-risk TIA or minor stroke. Patients were diagnosed with RLS using a questionnaire based on the 2003 International RLS Study Group criteria, and diagnoses were confirmed by a sleep neurologist. Follow-up assessments were conducted within 2–6 months of recruitment. The outcome of quality of life was measured using the Stroke-specific Quality of Life (SS-QoL).ResultsOf the 94 patients recruited into the study, 23 (24.4%) were diagnosed with RLS: 11 were newly diagnosed with RLS and 12 had RLS preceding the index stroke/TIA. There were no significant differences in baseline characteristics between those with or without RLS. Median SS-QoL in patients with RLS was lower at baseline (p = 0.008) and at follow-up (p = 0.002). RLS patients had more depressive symptoms at follow-up (p = 0.007). Ordinal logistic regression demonstrated that RLS was negatively associated with quality of life at baseline (OR = 0.28; p = 0.010) and at follow-up (OR = 0.14; p = 0.029), independent of functional outcome and depressive symptoms.ConclusionsRLS is common after stroke or TIA and negatively affects the quality of life. Screening for RLS after cerebrovascular events may be warranted, and future research should assess whether treatment of RLS can improve post-stroke quality of life.     

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.     

Characterizing the Mechanisms of Central and Peripheral Forms of Neurostimulation in Chronic Dysphagic Stroke Patients

BackgroundSwallowing problems following stroke may result in increased risk of aspiration pneumonia, malnutrition, and dehydration.Objective/hypothesisOur hypothesis was that three neurostimulation techniques would produce beneficial effects on chronic dysphagia following stroke through a common brain mechanism that would predict behavioral response.MethodsIn 18 dysphagic stroke patients (mean age: 66 ± 3 years, 3 female, time-post-stroke: 63 ± 15 weeks [±SD]), pharyngeal electromyographic responses were recorded after single-pulse transcranial magnetic stimulation (TMS) over the pharyngeal motor cortex, to measure corticobulbar excitability before, immediately, and 30 min, after real and sham applications of neurostimulation. Patients were randomized to a single session of either: pharyngeal electrical stimulation (PES), paired associative stimulation (PAS) or repetitive TMS (rTMS). Penetration-aspiration scores and bolus transfer timings were assessed before and after both real and sham interventions using videofluoroscopy.ResultsCorticobulbar excitability of pharyngeal motor cortex was beneficially modulated by PES, PAS and to a lesser extent by rTMS, with functionally relevant changes in the unaffected hemisphere. Following combining the results of real neurostimulation, an overall increase in corticobulbar excitability in the unaffected hemisphere (P = .005, F_1,17 = 10.6, ANOVA) with an associated 15% reduction in aspiration (P = .005, z = −2.79) was observed compared to sham.ConclusionsIn this mechanistic study, an increase in corticobulbar excitability the unaffected projection was correlated with the improvement in swallowing safety (P = .001, rho = −.732), but modality-specific differences were observed. Paradigms providing peripheral input favored change in neurophysiological and behavioral outcome measures in chronic dysphagia patients. Further larger cohort studies of neurostimulation in chronic dysphagic stroke are imperative.     

Sleep duration on workdays or nonworkdays and cardiac–cerebral vascular diseases in Southern China

ObjectivesThis study aimed to assess the relationship between sleep duration on work or nonworkdays and myocardial infarction (MI) and stroke in Southern China.MethodsA cross-sectional survey was conducted among 15,364 participants of age ≥15 years in Southern China from November 2013 to August 2014. Data on self-reported duration of sleep on workdays or nonworkdays as well as history of MI and stroke were collected in the questionnaire. The subjects were examined for weight, height, waist circumference, and blood pressure. Multivariate logistic regression analyses were performed to evaluate the association of sleep duration with MI and stroke.ResultOverall, compared with a sleep duration of 6–8 h, individuals who slept <6 h on workdays and nonworkdays were associated with increased risk for MI (odds ratio [OR] = 3.17, 2.04). Furthermore, individuals who slept >8 h on workdays and nonworkdays were associated with an increased risk for stroke (OR = 1.86, 1.54). Although this association persisted in men and subjects aged <65 years, we also observed that long sleep duration on workdays was associated with MI, especially among women, and short sleep duration on nonworkdays was associated with stroke among those aged 65 years or older. Participants with abnormal sleep duration and hypertension had higher risk of MI and stroke. Sleep debt was independently associated with MI risk, but not stroke (OR = 1.40; 95% confidence interval [CI]: 1.06–1.86), specifically among men aged <65 years.ConclusionsCompared with a sleep duration of 6–8 h, both short and long sleep duration were associated with the prevalence of MI and stroke and these associations were more pronounced among hypertensive persons, and tended to vary by age and sex. Moreover, sleep debt was linked to greater MI risk among men aged <65 years. These findings suggest that we should develop a healthy biological clock.     

Sleep in children with type 1 diabetes and their parents in the T1D Exchange

ObjectivesSleep has physiological and behavioral impacts on diabetes outcomes, yet little is known about the impact of sleep disturbances in children with type 1 diabetes. The current study sought to characterize sleep in children with type 1 diabetes and in their parents and to examine the associations between child sleep, glycemic control and adherence, parent sleep and well-being, parental fear of hypoglycemia, and nocturnal caregiving behavior.MethodsSurveys were emailed to parents of 2- to 12-year-old participants in the Type 1 Diabetes (T1D) Exchange clinic registry. Clinical data were obtained from the registry for the 515 respondents.ResultsIn our sample, 67% of children met criteria for poor sleep quality. Child sleep quality was related to glycemic control (HbA1c of 7.9% [63 mmol/mol] in children with poor sleep quality vs 7.6% [60 mmol/mol] in children with non-poor sleep quality; P < 0.001) but not mean frequency of blood glucose monitoring (BGM) (7.6 times/day vs 7.4 in poor/non-poor quality; P = 0.56). Associations were similar for sleep duration. Children with poor sleep quality were more likely to experience severe hypoglycemia (4% in children with poor sleep quality vs 1% in children with non-poor sleep quality; P = 0.05) and more likely to experience DKA (7% vs 4%, respectively; P < 0.001). Poorer child sleep quality was associated with poorer parental sleep quality, parental well-being, and fear of hypoglycemia (P < 0.001 for all). Child sleep was not related to the use of diabetes-related technology (CGM, insulin pump).ConclusionsSleep may be a modifiable factor to improve glycemic control and reduce parental distress.     

Will daytime occupational noise exposures induce nighttime sleep disturbance?

BackgroundNighttime environmental noise affects sleep quality. However, the effects of daytime occupational noise remain unclear.MethodsA quasi-experiment of 48 participants who had been employed for at least six months in two hospital cafeterias. The participants were randomly designated to be assessed on high- and low-noise workdays for 8 h or low- and high-noise workdays, separated by a washout period of 14 days. Subsequently, pure tone audiometry, autonomic nervous system (ANS) function tests, serum cortisol tests, and polysomnography were conducted.ResultsFor the 40 participants in the study, the 8-h time-weighted average of personal noise exposed on high- and low-noise workdays was 76.8 dBA (standard deviation, SD: 6.2) and 61.0 dBA (SD: 7.1), respectively. Participants with higher personal noise exposure during the day were found to have a lower percentage of slow wave sleep (percent change of mean value: −1.287%; 95% CI: −2.602%, −0.037%) and lower sleep efficiency (−0.267%; 95% CI: −0.525%, −0.008%). In addition, after work, personal noise exposure was revealed to be related to increased serum cortisol levels (1.698%; 95% CI: 0.887%, 2.528%), and sympathetic activity as measured by low frequency/high frequency (3.000%; 95% CI: 1.294%, 4.706%) and blood pressures by cold pressor test (systolic: 5.163%; 95% CI: 2.780%, 7.537%) (diastolic: 3.109%; 95% CI: 1.604%, 4.614%).ConclusionsDaytime occupational noise exposure had sustained effects on nighttime sleep quality, specifically on slow wave sleep and sleep efficiency. These disturbances could be partially explained by post-shift elevated cortisol and ANS activity. The psychosocial and metabolic consequences of poorer sleep quality induced by occupational noise exposure warrant further investigation.     

Association between dopaminergic dysfunction and anxiety in de novo Parkinson's disease

ObjectivesTo explore the relationships between nigrostriatal dysfunction and neuropsychiatric symptoms (including anxiety, depression and apathy) in a large cohort of newly diagnosed, drug-naïve Parkinson disease (PD) patients compared to a cohort of healthy controls (HC).MethodsThis is a cross-sectional analysis of the Parkinson's Progression Markers Initiative (PPMI) cohort at baseline, including 405 PD patients and 187 HC. Nigrostriatal degeneration was evaluated by means of SPECT DAT scan. Relationships between neuropsychiatric symptoms and DAT uptakes were analysed by means of stepwise multiple regression analysis.ResultsIn the PD group, lower DAT uptake in the right caudate was associated with higher STAI trait subscore (β = −2.939, 95%CI: −4.634 to −1.254, p = 0.001). Depression and apathy scores were not related with DAT uptakes. No associations were found in the HC group.ConclusionsOur cross-sectional analysis of the PPMI data shows that lower caudate DAT uptake is associated with higher level of anxiety. The data strengthens the relationship between dopaminergic dysfunction and neuropsychiatric symptoms in early PD.     

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.     

Intraindividual sleep variability and its association with insomnia identity and poor sleep

ObjectiveInsomnia identity refers to the conviction that one has insomnia, which can occur independently of poor sleep. Night-to-night variability in sleep (termed intraindividual variability [IIV]) may contribute to insomnia identity yet remain undetected via conventional mean analyses. This study compared sleep IIV across four subgroups: noncomplaining good sleepers (NG), complaining poor sleepers (CP), complaining good sleepers (CG), and noncomplaining poor sleepers (NP).MethodsThis study analyzed 14 days of sleep diary data from 723 adults. Participants were classified according to presence/absence of a sleep complaint and presence/absence of poor sleep. A 2 × 2 multivariate analysis of covariance (MANCOVA) was performed to explore differences on five measures of sleep IIV: intraindividual standard deviation in total sleep time (iSD TST), sleep onset latency (iSD SOL), wake after sleep onset (iSD WASO), number of nightly awakenings (iSD NWAK), and sleep efficiency (iSD SE).ResultsMANCOVA revealed significant main effects of poor sleep, sleep complaint, and their interaction on sleep IIV. Poor sleepers exhibited greater IIV across all sleep parameters compared to good sleepers. Similarly, individuals with a sleep complaint exhibited greater IIV compared to individuals with no complaint. The interaction revealed that iSD SOL was significantly greater among CP than NP, and iSD NWAK was significantly greater among CG than NG.ConclusionsGreater night-to-night variability in specific sleep parameters was present among complaining versus noncomplaining sleepers in good and poor sleep subgroups. These findings suggest certain aspects of sleep consistency may be salient for treatment-seeking individuals based on their quantitative sleep status.     

Differences in sleep problems between Japanese and Chinese preschoolers: a cross-cultural comparison within the Asian region

Study objectivesPrevious studies have performed cross-cultural comparisons of differences in childhood sleep problems between Asian and Western countries. However, whether such differences can be observed among Asian countries remains unclear. The present study aimed to investigate differences in the pattern of sleep problems between Japanese and Chinese preschoolers.MethodsData were collected from one city in Japan and 10 cities in China. The present study recruited 438 Japanese and 1020 Chinese preschoolers aged four and five years. Sleep problems and patterns were assessed on the basis of parental reports using the Children's Sleep Habits Questionnaire (CSHQ).ResultsAnalysis of covariance revealed no significant difference in total CSHQ scores between Japanese and Chinese preschoolers, thus indicating that the total severity of sleep problems did not differ between the groups. Japanese preschoolers exhibited higher scores on the bedtime resistance subscale of the CSHQ than Chinese preschoolers. Conversely, Chinese preschoolers exhibited higher subscale scores for night wakings and sleep-disordered breathing. In addition, Japanese preschoolers exhibited earlier bedtimes and wake times and shorter total sleep times than Chinese preschoolers.ConclusionsOur findings indicate that the patterns of sleep problems in preschoolers differ between Japan and China and that such differences may be due to differences in cosleeping practices, bedtime routines, and/or environmental conditions. Thus, investigators studying sleep in preschoolers should consider regional differences in the pattern of sleep problems, even among Asian countries.     

Development of a clinician-administered National Institutes of Health-Brief Fatigue Inventory: A measure of fatigue in the context of depressive disorders

ObjectiveFatigue is a complex, multidimensional condition. Although it is often associated with depression, it is not known whether it has a distinct network from depression or whether it can be clinically evaluated, separately. This study describes preliminary findings in the development of a brief, clinician-administered instrument to measure fatigue in the context of depressive disorders using items from existing clinician-administered depression and mania scales.MethodsBased on items from prior fatigue measurements, items were selected from the Hamilton Depression Rating Scale (HDRS), Montgomery–Asberg Depression Rating Scale (MADRS), Young Mania Rating Scale, and Structured Interview Guide for HDRS with Atypical Depression. The final items composed the NIH-Brief Fatigue Inventory (NIH-BFI). Responses from 89 depressed adults collected pre- and post-antidepressant therapy (ADT) determined the reliability and consistency of the NIH-BFI using Cronbach's alpha and principal components analysis (PCA). Correlations of the NIH-BFI and fatigue items from other scales before and after ADT explored validity.ResultsThe 7-item NIH-BFI had Cronbach alphas ranging from 0.81 to 0.88 and PCA indicating a single dimension. The NIH-BFI score was strongly correlated (r = 0.73, p < 0.001) with fatigue items from Beck Depression Index, with MADRS without fatigue items (r = 0.77, p < 0.001), and HDRS without fatigue items (pre: r = 0.69, p < 0.001).ConclusionsPreliminary findings show support for internal consistency reliability and validity of the NIH-BFI, a clinician-administered measure of fatigue. Further testing in other clinical populations is recommended to obtain additional information on reliability and validity. The NIH-BFI provides a method for clinician-rated fatigue that may be a separate from depression.     

Slow-wave sleep and androgens: selective slow-wave sleep suppression affects testosterone and 17α-hydroxyprogesterone secretion

ObjectivesLevels of steroid hormones such as androgens and cortisol exhibit circadian variation, and their fluctuations are related to the sleep-wake cycle. Currently, the functional role of different stages of sleep in steroid hormone secretion remains unclear. The present study aims to explore the effect of slow-wave sleep (SWS) suppression on morning levels of cortisol and androgens.MethodsTwelve healthy male volunteers participated in two experimental sessions: a session with selective SWS suppression during night sleep and a session with regular night sleep (control). SWS suppression was achieved by stimulation using an acoustic tone. Salivary samples were collected in the morning immediately after awakening and again 40 min later. The samples were analysed by liquid chromatography-tandem mass spectrometry for testosterone, androstenedione (Ad), dehydroepiandrosterone (DHEA), 17α-hydroxyprogesterone (17-OHP), and cortisol.ResultsSWS suppression reduced overall SWS duration by 54.2% without significant changes in total sleep time and sleep efficiency. In the session with selective SWS suppression, the average level of morning testosterone was lower than in the control session (p = 0.017). Likewise, 17-OHP was lower in the SWS suppression condition (p = 0.011) whereas the ratio of DHEA/Ad was higher (p = 0.025). There were no significant differences between sessions in cortisol, Ad, or DHEA concentrations.ConclusionsThe effect of selective SWS suppression on morning levels of testosterone and 17-OHP points to the importance of SWS for the synthesis and secretion of androgens. These results suggest that chronic sleep problems, which lead to reduced SWS, increase the risk for the development of androgen deficiency in the long term.     

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.     

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.     

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.     

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.     

Recurrence of suicide attempt in adolescents lost to contact early by clinicians: The 10-year REPEATERS cohort of French adolescents

Losing contact with adult suicide attempters in the year after the suicide attempt (SA) increases the risk of recurrence. The situation with adolescents is unknown. We aimed to determine whether being lost to contact early (LCE) by clinicians is a risk factor of long-term SA recurrence among adolescents and the associated factors. Data were collected 10 years after an index SA and a Cox model was used for analysis. Among the 249 SA patients included, 59 (24%) were LCE, the most important risk factor of SA recurrence up to 10 years (hazard ratio [HR] = 2.8 [95% confidence interval (95% CI) 1.4–5.5]; p = .016). Risk factors of being LCE were female sex (odds ratio [OR] = 2.9 [95% CI 1.1–8.2]; p = .009), a psychiatric comorbidity (OR = 2.2 [1.1–4.3]; p = .023) and no family history of suicide (OR = 2.1 [1.1–4.3]; p = .047). These results support the development of preventive actions early after an SA in an adolescent to maintain contact and care.