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1.  "Sleepiness" is serious in adolescence: Two surveys of 3235 Canadian students 
BMC Public Health  2006;6:116.
Background
Evidence is growing that sleep problems in adolescents are significant impediments to learning and negatively affect behaviour, attainment of social competence and quality of life. The objectives of the study were to determine the level of sleepiness among students in high school, to identify factors to explain it, and to determine the association between sleepiness and performance in both academic and extracurricular activities
Methods
A cross-sectional survey of 2201 high school students in the Hamilton Wentworth District School Board and the Near North District School Board in Ontario was conducted in 1998/9. A similar survey was done three years later involving 1034 students in the Grand Erie District School Board in the same Province. The Epworth Sleepiness Scale (ESS) was used to measure sleepiness and we also assessed the reliability of this tool for this population. Descriptive analysis of the cohort and information on various measures of performance and demographic data were included. Regression analysis, using the generalised estimating equation (GEE), was utilized to investigate factors associated with risk of sleepiness (ESS>10).
Results
Seventy per cent of the students had less than 8.5 hours weeknight sleep. Bedtime habits such as a consistent bedtime routine, staying up late or drinking caffeinated beverages before bed were statistically significantly associated with ESS, as were weeknight sleep quantity and gender. As ESS increased there was an increase in the proportion of students who felt their grades had dropped because of sleepiness, were late for school, were often extremely sleepy at school, and were involved in fewer extracurricular activities. These performance measures were statistically significantly associated with ESS. Twenty-three percent of the students felt their grades had dropped because of sleepiness. Most students (58–68%) reported that they were "really sleepy" between 8 and 10 A.M.
Conclusion
Sleep deprivation and excessive daytime sleepiness were common in two samples of Ontario high school students and were associated with a decrease in academic achievement and extracurricular activity. There is a need to increase awareness of this problem in the education and health communities and to translate knowledge already available to strategies to address it.
doi:10.1186/1471-2458-6-116
PMCID: PMC1464124  PMID: 16670019
2.  Sleep complaints and daytime sleepiness among pharmaceutical students in Tripoli 
The Libyan Journal of Medicine  2012;7:10.3402/ljm.v7i0.18930.
Background
The effect of sleep difficulties has achieved a great deal of attention recently, with university students considered as a homogenized population, particularly affected by sleep habits.
Aim
The objective of this study was to investigate whether Libyan college students experience sleep disturbance during their academic programmes.
Methods
A cross-sectional survey was conducted in the college of Pharmacy, Tripoli University, during February 2010. A total of 201 students, including 179 females (89.05%) and 22 males (10.95%), were recruited from different academic levels. Data were collected using a structured questionnaire and included a number of life-style variables. Epworth Sleepiness Scale (ESS) was used for the assessment of daytime sleepiness.
Results
This study showed that the total sleep time (TST) on a weeknight was 6.40 h and 67 students reported napping during daytime. The TST plus naps totalled 7.39 h. Out of eight possible dozing situations, we found that the mean score for ESS was 8.78. In addition, 79 students showed an ESS score of >10. Furthermore, our results showed that the majority of students (>92%) reported poor sleep satisfaction with quality and duration of sleep hours. Thinking about difficulty of study but not increasing education programs or tea/coffee consumption is associated with sleep difficulties reported. Moreover, 77.6% of students reported an irregular sleep–wake schedule.
Conclusion
These findings indicate that students experienced excessive daytime sleepiness. The TST of pharmaceutical students in Libya, as in other developing countries, is less than those reported by Western students. Students experienced various environmental demands during their college years and, their quality of sleep was negatively affected.
doi:10.3402/ljm.v7i0.18930
PMCID: PMC3485400  PMID: 23118811
college students; sleep habits; sleep disorders; Epworth Sleepiness Scale
3.  Sleep patterns and habits in high school students in Iran 
Background
Sleep patterns and habits in high school students in Iran have not been well studied to date. This paper aims to re-address this balance and analyse sleep patterns and habits in Iranian children of high school age.
Methods
The subjects were 1,420 high school students randomly selected by stratified cluster sampling. This was a self-report study using a questionnaire which included items about usual sleep/wake behaviours over the previous month, such as sleep schedule, falling asleep in class, difficulty falling asleep, tiredness or sleepiness during the day, difficulty getting up in the morning, nightmares, and taking sleeping pills.
Results
The mean duration of night sleep was 7.7 h, with no difference between girls, boys, and school year (grade). The mean time of waking in the morning was not different between genders. About 9.9% of the girls and 4.6% of the boys perceived their quality of sleep as being bad, and 58% of them reported sleepiness during the day. About 4.2% of the subjects had used medication to enhance sleep. The time of going to bed was associated with grade level and gender. Sleep latency was not associated with gender and grade leve, l and 1.4% experienced bruxism more than four times a week.
Conclusion
Our results are in contrast with that of previous studies that concluded sleep duration is shorter in Asia than in Europe, that boys woke-up significantly later than girls, and that the frequency of sleep latency category was associated with gender and grade level. The magnitude of the daytime sleepiness, daytime sleepiness during classes, sleep latency, and incidences of waking up at night represent major public health concerns for Iran.
doi:10.1186/1744-859X-7-5
PMCID: PMC2292723  PMID: 18339201
4.  Study of Sleep Habits and Sleep Problems Among Medical Students of Pravara Institute of Medical Sciences Loni, Western Maharashtra, India 
Background:
Good quality sleep and adequate amount of sleep are important in order to have better cognitive performance and avoid health problems and psychiatric disorders.
Aim:
The aim of this study was to describe sleep habits and sleep problems in a population of undergraduates, interns and postgraduate students of Pravara Institute of Medical Sciences (Deemed University), Loni, Maharashtra, India.
Subject and Methods:
Sleep habits and problems were investigated using a convenience sample of students from Pravara Institute of Medical Sciences (Deemed University), Loni, Maharashtra, India. The study was carried out during Oct. to Dec. 2011 with population consisted of total 150 medical students. A self-administered questionnaire developed based on Epworth Daytime Sleepiness Scale and Pittsburgh Sleep Quality Index was used. Data was analyzed by using Statistical Package of Social Sciences (SPSS) version 16.0.
Results:
In this study, out of 150 medical students, 26/150 (17.3%) students had abnormal levels of daytime sleepiness while 20/150 (13.3%) were border line. Sleep quality in females was better than the male.
Conclusion:
Disorders related to poor sleep qualities are significant problems among medical students in our institution. Caffeine and alcohol ingestion affected sleep and there was high level of daytime sleepiness. Sleep difficulties resulted in irritability and affected lifestyle and interpersonal relationships.
doi:10.4103/2141-9248.109488
PMCID: PMC3634224  PMID: 23634330
Medical students; Sleep disorders; Sleep habits; Sleep quality
5.  Circadian Preference and Sleep-Wake Regularity: Associations With Self-Report Sleep Parameters in Daytime-Working Adults 
Chronobiology international  2011;28(9):802-809.
The aim of this study was to explore how interindividual differences in circadian type (morningness) and sleep timing regularity might be related to subjective sleep quality and quantity. Self-report circadian phase preference, sleep timing, sleep quality, and sleep duration were assessed in a sample of 62 day-working adults (33.9% male, age 23–48 yrs). The Pittsburgh Sleep Quality Index (PSQI) measured subjective sleep quality and the Sleep Timing Questionnaire (STQ) assessed habitual sleep latency and minutes awake after sleep onset. The duration, timing, and stability of sleep were assessed using the STQ separately for work-week nights (Sunday–Thursday) and for weekend nights (Friday and Saturday). Morningness-eveningness was assessed using the Composite Scale of Morningness (CSM). Daytime sleepiness was measured using the Epworth Sleepiness Scale (ESS). A morning-type orientation was associated with longer weekly sleep duration, better subjective sleep quality, and shorter sleep-onset latency. Stable weekday rise-time correlated with better self-reported sleep quality and shorter sleep-onset latency. A more regular weekend bedtime was associated with a shorter sleep latency. A more stable weekend rise-time was related to longer weekday sleep duration and lower daytime sleepiness. Increased overall regularity in rise-time was associated with better subjective sleep quality, shorter sleep-onset latency, and higher weekday sleep efficiency. Finally, a morning orientation was related to increased regularity in both bedtimes and rise-times. In conclusion, in daytime workers, a morning-type orientation and more stable sleep timing are associated with better subjective sleep quality.
doi:10.3109/07420528.2011.613137
PMCID: PMC4143130  PMID: 22080786
Chronotype; Human; Regularity; Sleep
6.  Effects of an irregular bedtime schedule on sleep quality, daytime sleepiness, and fatigue among university students in Taiwan 
BMC Public Health  2009;9:248.
Background
An irregular bedtime schedule is a prevalent problem in young adults, and could be a factor detrimentally affecting sleep quality. The goal of the present study was to explore the association between an irregular bedtime schedule and sleep quality, daytime sleepiness, and fatigue among undergraduate students in Taiwan.
Methods
A total of 160 students underwent a semi-structured interview and completed a survey comprising 4 parts: Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), and a rating of irregular bedtime frequency. Participants were grouped into 3 groups in terms of irregular bedtime frequency: low, intermediate, or high according to their 2-week sleep log. To screen for psychological disorders or distress that may have affected responses on the sleep assessment measures, the Chinese health questionnaire-12 (CHQ-12) was also administered.
Results
We found an increase in bedtime schedule irregularity to be significantly associated with a decrease in average sleep time per day (Spearman r = -0.22, p = 0.05). Multivariate regression analysis revealed that irregular bedtime frequency and average sleep time per day were correlated with PSQI scores, but not with ESS or FSS scores. A significant positive correlation between irregular bedtime frequency and PSQI scores was evident in the intermediate (partial r = 0.18, p = 0.02) and high (partial r = 0.15, p = 0.05) frequency groups as compared to low frequency group.
Conclusion
The results of our study suggest a high prevalence of both an irregular bedtime schedule and insufficient sleep among university students in Taiwan. Students with an irregular bedtime schedule may experience poor sleep quality. We suggest further research that explores the mechanisms involved in an irregular bedtime schedule and the effectiveness of interventions for improving this condition.
doi:10.1186/1471-2458-9-248
PMCID: PMC2718885  PMID: 19615098
7.  Longitudinal Change in Sleep and Daytime Sleepiness in Postpartum Women 
PLoS ONE  2014;9(7):e103513.
Sleep disruption strongly influences daytime functioning; resultant sleepiness is recognised as a contributing risk-factor for individuals performing critical and dangerous tasks. While the relationship between sleep and sleepiness has been heavily investigated in the vulnerable sub-populations of shift workers and patients with sleep disorders, postpartum women have been comparatively overlooked. Thirty-three healthy, postpartum women recorded every episode of sleep and wake each day during postpartum weeks 6, 12 and 18. Although repeated measures analysis revealed there was no significant difference in the amount of nocturnal sleep and frequency of night-time wakings, there was a significant reduction in sleep disruption, due to fewer minutes of wake after sleep onset. Subjective sleepiness was measured each day using the Karolinska Sleepiness Scale; at the two earlier time points this was significantly correlated with sleep quality but not to sleep quantity. Epworth Sleepiness Scores significantly reduced over time; however, during week 18 over 50% of participants were still experiencing excessive daytime sleepiness (Epworth Sleepiness Score ≥12). Results have implications for health care providers and policy makers. Health care providers designing interventions to address sleepiness in new mothers should take into account the dynamic changes to sleep and sleepiness during this initial postpartum period. Policy makers developing regulations for parental leave entitlements should take into consideration the high prevalence of excessive daytime sleepiness experienced by new mothers, ensuring enough opportunity for daytime sleepiness to diminish to a manageable level prior to reengagement in the workforce.
doi:10.1371/journal.pone.0103513
PMCID: PMC4117520  PMID: 25078950
8.  Association between the melanopsin gene polymorphism OPN4*Ile394Thr and sleep/wake timing in Japanese university students 
Background
In our previous studies, we found that the Ile394Thr SNP in the melanopsin gene (OPN4) was functionally associated with the pupillary light reflex. This indicates the possibility that OPN4*Ile394Thr is associated with other non-image forming responses. The aim of this study was therefore to determine whether OPN4*Ile394Thr is associated with sleep/wake timing.
Methods
A total of 348 healthy Japanese university students participated in this study. Scalp hair was used to genotype the Ile394Thr SNP of OPN4. Sleep habits, including bedtime, wake time and sleep duration, were assessed separately for weekdays and weekends. A total of 328 samples, including 223 samples with TT genotype, 91 with TC genotype and 14 with CC genotype, were used for statistical analysis. No significant difference in age or male/female distribution was found among the three genotype groups.
Results
There was no significant difference in circadian preference among the genotype groups. During weekdays, bedtime, wake time and midpoint of sleep for CC subjects were significantly later than those for TT and TC subjects. However, there was no difference between TT and TC subjects in any of their sleep habits. During weekends, bedtime of CC subjects was significantly later than those of TT and TC subjects, and the midpoint of sleep of CC subjects was significantly later than that of TC subjects.
Conclusions
Our findings demonstrated that OPN4*Ile394Thr is associated with sleep/wake timing. We also found that the sleep/wake timing of subjects with the CC genotype was later than that of subjects with the TT or TC genotype.
doi:10.1186/1880-6805-33-9
PMCID: PMC4048048  PMID: 24887407
Genotype; Human; Melanopsin gene (OPN4); Single nucleotide polymorphism (SNP); Non-image forming responses; Sleep
9.  Obstructive Sleep Apnea and Risk of Cardiovascular Events and All-Cause Mortality: A Decade-Long Historical Cohort Study 
PLoS Medicine  2014;11(2):e1001599.
Tetyana Kendzerska and colleagues explore the association between physiological measures of obstructive sleep apnea other than the apnea-hypopnea index and the risk of cardiovascular events.
Please see later in the article for the Editors' Summary
Background
Obstructive sleep apnea (OSA) has been reported to be a risk factor for cardiovascular (CV) disease. Although the apnea-hypopnea index (AHI) is the most commonly used measure of OSA, other less well studied OSA-related variables may be more pathophysiologically relevant and offer better prediction. The objective of this study was to evaluate the relationship between OSA-related variables and risk of CV events.
Methods and Findings
A historical cohort study was conducted using clinical database and health administrative data. Adults referred for suspected OSA who underwent diagnostic polysomnography at the sleep laboratory at St Michael's Hospital (Toronto, Canada) between 1994 and 2010 were followed through provincial health administrative data (Ontario, Canada) until May 2011 to examine the occurrence of a composite outcome (myocardial infarction, stroke, congestive heart failure, revascularization procedures, or death from any cause). Cox regression models were used to investigate the association between baseline OSA-related variables and composite outcome controlling for traditional risk factors. The results were expressed as hazard ratios (HRs) and 95% CIs; for continuous variables, HRs compare the 75th and 25th percentiles. Over a median follow-up of 68 months, 1,172 (11.5%) of 10,149 participants experienced our composite outcome. In a fully adjusted model, other than AHI OSA-related variables were significant independent predictors: time spent with oxygen saturation <90% (9 minutes versus 0; HR = 1.50, 95% CI 1.25–1.79), sleep time (4.9 versus 6.4 hours; HR = 1.20, 95% CI 1.12–1.27), awakenings (35 versus 18; HR = 1.06, 95% CI 1.02–1.10), periodic leg movements (13 versus 0/hour; HR = 1.05, 95% CI 1.03–1.07), heart rate (70 versus 56 beats per minute [bpm]; HR = 1.28, 95% CI 1.19–1.37), and daytime sleepiness (HR = 1.13, 95% CI 1.01–1.28).The main study limitation was lack of information about continuous positive airway pressure (CPAP) adherence.
Conclusion
OSA-related factors other than AHI were shown as important predictors of composite CV outcome and should be considered in future studies and clinical practice.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder, particularly among middle-aged and elderly people. It is characterized by apnea—a brief interruption in breathing that lasts at least 10 seconds—and hypopnea—a decrease of more than 50% in the amplitude of breathing that lasts at least 10 seconds or clear but smaller decrease in amplitude associated with either oxygen desaturation or an arousal. Patients with OSA experience numerous episodes of apnea and hypopnea during the night; severe OSA is defined as having 30 or more episodes per hour (an apnea-hypopnea index [AHI] of >30). These breathing interruptions occur when relaxation of the upper airway muscles decreases the airflow, which lowers the amount of oxygen in the blood. As a result, affected individuals frequently wake from deep sleep as they struggle to breathe. Symptoms of OSA include loud snoring and daytime sleepiness. Treatments include lifestyle changes such as losing weight (excess fat around the neck increases airway collapse) and smoking cessation. For severe OSA, doctors recommend continuous positive airway pressure (CPAP), in which a machine blows pressurized air through a face mask into the airway to keep it open.
Why Was This Study Done?
OSA can be life-threatening. Most directly, daytime sleepiness can cause accidents, but OSA is also associated with an increased risk of developing cardiovascular disease (CVD, disease that affects the heart and the circulation). To date, studies that have investigated the association between OSA and the risk of myocardial infarction (heart attack), congestive heart failure, stroke, and other CVDs have used the AHI to diagnose and categorize the severity of OSA. However, by focussing on AHI, clinicians and researchers may be missing opportunities to improve their ability to predict which patients are at the highest risk of CVD. In this historical cohort study, the researchers investigate the association between other OSA-related variables (for example, blood oxygen saturation and sleep fragmentation) and the risk of cardiovascular events and all-cause mortality (death). A historical cohort study examines the medical records of groups of individuals who have different characteristics at baseline for the subsequent occurrence of specific outcomes.
What Did the Researchers Do and Find?
The researchers used administrative data (including hospitalization records and physicians' claims for services supplied to patients) to follow up adults referred for suspected OSA who underwent diagnostic polysomnography (a sleep study) at a single Canadian hospital between 1994 and 2010. A database of the polysomnography results provided information on OSA-related variables for all the study participants. Over an average follow-up of about 6 years, 11.5% of the 10,149 participants were hospitalized for a myocardial infarction, stroke, or congestive heart failure, underwent a revascularization procedure (an intervention that restores the blood supply to an organ or tissue after CVD has blocked a blood vessel), or had died from any cause. After adjusting for multiple established risk factors for CVD such as smoking and age in Cox regression models (a statistical approach that examines associations between patient variables and outcomes), several OSA-related variables (but not AHI) were significant predictors of CVD. The strongest OSA-related predictor of cardiovascular events or all-cause mortality was total sleep time spent with oxygen saturation below 90%, which increased the risk of a cardiovascular event or death by 50%. Other statistically significant OSA-related predictors (predictors that were unlikely to be associated with the outcome through chance) of cardiovascular events or death included total sleep time, number of awakenings, frequency of periodic leg movements, heart rate, and daytime sleepiness.
What Do These Findings Mean?
These findings indicate that OSA-related factors other than AHI are important predictors of the composite outcome of a cardiovascular event or all-cause mortality. Indeed, although AHI was significantly associated with the researchers' composite outcome in an analysis that did not consider other established risk factors for CVD (“confounders”), the association became non-significant after controlling for potential confounders. The accuracy of these findings, which need to be confirmed in other settings, is likely to be limited by the lack of information available about the use of CPAP by study participants and by the lack of adjustment for some important confounders. Importantly, however, these findings suggest that OSA-related factors other than AHI should be considered as predictors of CVD in future studies and in clinical practice.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001599.
The US National Heart Lung and Blood Institute has information (including several videos) about obstructive sleep apnea (in English and Spanish), sleep studies, heart disease, and other cardiovascular diseases (some information in English and Spanish)
The UK National Health Service Choices website provides information (including personal stories) about sleep apnea and about cardiovascular disease
The not-for-profit American Sleep Apnea Association provides detailed information about sleep apnea for patients and health-care professionals, including personal stories about the condition
The MedlinePlus encyclopedia has pages on obstructive sleep apnea and on polysomnography; MedlinePlus provides links to further information and advice about obstructive sleep apnea, heart diseases, and vascular diseases (in English and Spanish)
doi:10.1371/journal.pmed.1001599
PMCID: PMC3913558  PMID: 24503600
10.  Circadian melatonin rhythm and excessive daytime sleepiness in Parkinson’s disease 
JAMA neurology  2014;71(4):463-469.
Importance
Diurnal fluctuations of motor and non-motor symptoms and high prevalence of sleep/wake disturbances in Parkinson’s disease (PD) suggest a role of the circadian system in the modulation of these symptoms. Yet, surprisingly little is known regarding circadian function in PD, and whether circadian dysfunction is involved in the development of sleep/wake disturbances in PD.
Objective
The objective of this study was to determine the relationship between the timing and amplitude of the 24-hour melatonin rhythm, a marker of endogenous circadian rhythmicity, with self-reported sleep quality, the severity of daytime sleepiness and disease metrics.
Design
A cross-sectional study, (2009–2012).
Setting
PD and Movement Disorders Center, Northwestern University, Chicago.
Participants
Twenty PD patients on stable dopaminergic therapy and 15 age-matched controls underwent blood sampling for the measurement of serum melatonin levels at 30-minute intervals for 24 hours under modified constant routine conditions.
Main Outcome Measure(s)
Clinical and demographic data, self-reported measures of sleep quality (Pittsburgh Sleep Quality Index (PSQI)) and daytime sleepiness (Epworth Sleepiness Scale (ESS)), circadian markers of the melatonin rhythm, including the amplitude, area-under-the-curve (AUC), and phase of the 24-hour rhythm.
Results
Participants with PD had a blunted circadian rhythms of melatonin secretion compared to controls; both the amplitude of the melatonin rhythm and the 24-hour AUC for circulating melatonin levels were significantly lower in PD participants compared with controls (p<0.001). Markers of circadian phase were not significantly different between the two groups. Among PD participants, those with excessive daytime sleepiness (ESS score ≥10) had a significantly lower amplitude of the melatonin rhythm and the 24-hour melatonin AUC compared with PD participants without excessive sleepiness (p=0.001). Disease duration, UPDRS scores, levodopa equivalent dose and global PSQI scores in the PD group were not significantly related to measures of the melatonin circadian rhythm.
Conclusion and Relevance
These results indicate that circadian dysfunction may underlie excessive sleepiness in PD. The nature of this association needs to be further explored in longitudinal studies. Approaches aimed to strengthen circadian function, such as timed bright light and exercise, might potentially serve as complementary therapies for the non-motor manifestations of PD.
doi:10.1001/jamaneurol.2013.6239
PMCID: PMC4078989  PMID: 24566763
11.  Depressive Symptoms and Subjective And Objective Sleep In Community-Dwelling Older Women 
Objectives
To examine the relationship between depressive symptoms and subjective and objective sleep in older women.
Design
Cross-sectional.
Setting
Four US clinical centers.
Participants
3045 community-dwelling women ≥70 years.
Measurements
Depressive symptoms were assessed with the Geriatric Depression Scale categorizing participants as “normal” (0–2, referent), “some depressive symptoms” (3–5), or “depressed” (≥6). Subjective sleep quality and daytime sleepiness were assessed using the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). Objective sleep measures were assessed with wrist actigraphy.
Results
In multivariable-adjusted models, there were graded associations between increased level of depressive symptoms and both worse subjective sleep quality and more subjective daytime sleepiness (p-trends <0.001). Women with some depressive symptoms (OR 1.82, CI 1.48–2.24) and depressed (OR 2.84, CI 2.08–3.86) women had greater odds of reporting poor sleep (PSQI>5). Women with some depressive symptoms (OR 1.97, CI 1.47–2.64) and depressed women (OR 1.70, CI 1.12–2.58) had greater odds of reporting excessive daytime sleepiness (ESS>10). There were also graded associations between increased level of depressive symptoms and objectively measured wake after sleep onset (WASO) (p-trend = 0.030) and long wake episodes >5 minutes (p-trend 0.006). Depressed women had modestly increased odds of WASO ≥1 hour (OR 1.37, CI 1.03–1.83). Women with some depressive symptoms (OR 1.49, CI 1.19–1.86) and depressed women (OR 2.04, CI 1.52–2.74) had greater odds of being in the highest quartile for number of nap episodes >5 minutes. No associations between depressive symptom level and prolonged sleep latency, reduced sleep efficiency, or reduced or increased total sleep time were found.
Conclusion
Greater depressive symptom levels were associated with more subjective sleep disturbance and objective evidence of sleep fragmentation and napping.
doi:10.1111/j.1532-5415.2012.03908.x
PMCID: PMC3517685  PMID: 22428562
Depression; sleep; actigraphy; elderly; age
12.  Genome-wide association of sleep and circadian phenotypes 
BMC Medical Genetics  2007;8(Suppl 1):S9.
Background
Numerous studies suggest genetic influences on sleepiness and circadian rhythms. The Sleep Heart Health Study collected questionnaire data on sleep habits and sleepiness from 2848 Framingham Heart Study Offspring Cohort participants. More than 700 participants were genotyped using the Affymetrix 100K SNP GeneChip, providing a unique opportunity to assess genetic linkage and association of these traits.
Methods
Sleepiness (defined as the Epworth Sleepiness Scale score), usual bedtime and usual sleep duration were assessed by self-completion questionnaire. Standardized residual measures adjusted for age, sex and BMI were analyzed. Multipoint variance components linkage analysis was performed. Association of SNPs to sleep phenotypes was analyzed with both population-based and family-based association tests, with analysis limited to 70,987 autosomal SNPs with minor allele frequency ≥10%, call rate ≥80%, and no significant deviation from Hardy-Weinberg equilibrium (p ≥ 0.001).
Results
Heritability of sleepiness was 0.29, bedtime 0.22, and sleep duration 0.17. Both genotype and sleep phenotype data were available for 749 subjects. Linkage analysis revealed five linkage peaks of LOD >2: four to usual bedtime, one to sleep duration. These peaks include several candidate sleep-related genes, including CSNK2A2, encoding a known component of the circadian molecular clock, and PROK2, encoding a putative transmitter of the behavioral circadian rhythm from the suprachiasmatic nucleus. Association tests identified an association of usual bedtime with a non-synonymous coding SNP in NPSR1 that has been shown to encode a gain of function mutation of the neuropeptide S receptor, whose endogenous ligand is a potent promoter of wakefulness. Each copy of the minor allele of this SNP was associated with a 15 minute later mean bedtime. The lowest p value was for association of sleepiness with a SNP located in an intron of PDE4D, which encodes a cAMP-specific phosphodiesterase widely expressed in human brain. Full association results are posted at .
Conclusion
This analysis confirms prior reports of significant heritability of sleepiness, usual bedtime, and usual sleep duration. Several genetic loci with suggestive linkage to these traits are identified, including linkage peaks containing circadian clock-related genes. Association tests identify NPSR1 and PDE4D as possible mediators of bedtime and sleepiness.
doi:10.1186/1471-2350-8-S1-S9
PMCID: PMC1995620  PMID: 17903308
13.  Sleep Deficiency and Sleep Health Problems in Chinese Adolescents 
A survey of sleep schedules, sleep health, and the impact on school performance was conducted in 585 adolescents in a high school in China. A high level of early and circadian-disadvantaged sleep/wake schedules during weekdays was observed. Significantly shorter sleep duration on weekdays was reported (P < 0.0001). Older teenagers slept significantly less than the younger teenagers (P < 0.0001). Complaints of inadequate sleep and sleepiness during weekdays were prevalent. Night awakenings were reported in 32.2% of students. Students with a sleep length of less than 7 hours, complaint of inadequate sleep, or excessive daytime sleepiness during weekdays were more likely to report an adverse effect of poor sleep on performance. The present observations are qualitatively similar to those reported in our study in American adolescents, particularly with respect to Chinese adolescents exhibiting a similar sleep deficiency on weekdays. We concluded that sleep deficiency and sleep health problems were prevalent in the participating adolescents in China, and were perceived to adversely affect school performance.
doi:10.4137/CMPed.S8407
PMCID: PMC3620771  PMID: 23641162
sleep deprivation; sleep health problem; adolescents; school performance
14.  The Association between the Phenotype of Excessive Daytime Sleepiness and Blood Pressure in Patients with Obstructive Sleep Apnea-Hypopnea Syndrome 
Objective Investigate the clinical features and the blood pressure (BP) pattern of the phenotype of excessive daytime sleepiness (EDS) in OSAHS.
Methods A total of 508 Chinese adults with suspected OSAHS were referred to our sleep laboratory from October 2009 to May 2012. On the same night of polysomnography (PSG), the levels of blood pressure were measured before sleeping (bedtime BP) and immediately after waking up in the next morning (morning BP). EDS was recognized as Epworth Sleepiness Scale (ESS)≥9. Subjects were classified into four groups based on the apnea-hypopnea index (AHI) from PSG as follows: control (simple snoring) group (control, n=104) with AHI<5; mild group (mild, n=89) with AHI≥5 and <15; moderate group (moderate, n=70) with AHI≥15 and<30; and severe group (severe, n=245) with AHI ≥30. The differences and correlations between BP and PSG parameters in EDS and non-EDS group of OSAHS patients were analyzed.
Results In all subjects, ESS was positively correlated with morning diastolic blood pressure (DBP), Mean arterial pressure (MAP) and bedtime DBP (r=0.144, 0.102 and 0.114, respectively, each P value<0.05). In OSAHS patients, ESS was only positively correlated with morning DBP (r=0.137, P<0.05). OSAHS patients with EDS phenotype were younger and were more likely to have the symptom of waking up feeling tired (36.1% vs. 23.2%, p=0.023), who had lower MSaO2, longer SIT90 (the ratio of time of SpO2 below 90% in total sleep time) and higher DBP (bedtime as well as morning). In patients with AHI≥15, ESS was correlated positively with both bedtime and morning DBP after controlling the confounding effects of age, sex, BMI, AHI and nadir nocturnal oxygen saturation( r=0.126,0.143, respectively, both P values<0.05). And in OSAHS patients of EDS phenotype, the bedtime DBP, bedtime MAP, morning DBP, and morning MAP were 3~5 mm Hg higher than that in patients of non-EDS phenotype(P<0.05). In the moderate and severe OSAHS group, patients with EDS phenotype were younger and had a lower mean blood oxygen saturation (MSaO2), longer time of SpO2 below 90% and higher SIT90 than patients with non-EDS phenotype (P<0.05). In hypertensive OSAHS patients, patients with EDS were also younger and had higher micro-arousal index (MiI), as well as higher morning DBP, morning MAP and bedtime DBP than that in non-EDS group (P<0.05).
Conclusions EDS in OSAHS patients is a special phenotype, which was characterized by younger age, higher DBP and more severe hypoxic load. This feature is mainly manifested in moderate and severe OSAHS patients. It is very important to identify the phenotype of EDS in patients with OSAHS, who may meet more benefits from effective treatment of OSAHS by correcting the intermittent nocturnal hypoxia and sleep fragmentation.
doi:10.7150/ijms.7487
PMCID: PMC4025171  PMID: 24843321
Obstructive sleep apnea hypopnea syndrome (OSAHS); Epworth sleepiness scale (ESS); excessive daytime sleepiness (EDS); Blood pressure (BP); AHI; Chinese adults.
15.  Sleep Patterns Among Rural Chinese Twin Adolescents 
Sleep medicine  2008;10(4):479-489.
Objective
To examine sleep patterns and influencing factors (age, gender, Tanner Stage, weekday vs. weekend, and pre-sleep activity) among rural Chinese adolescents.
Methods
This is a prospective study among 621 adolescents aged 11–20 years (341 males) using both a questionnaire and sleep diary to obtain bedtime, wake-up time, sleep latency, and total sleep time (TST).
Results
The median TST was 8.6 hours on weekdays and 9.4 hours on weekends. Despite absence of late night social pressure and computers, a U-shaped TST pattern was observed across age and Tanner stage, with a nadir around age 15–16 years or Tanner IV. Bedtimes became progressively later with age and Tanner Stage, while wake-up time was considerably earlier for school students or up to Tanner IV. Later wake-up times and longer TST on weekends were seen in school students, but not in non-school adolescents (>17 years). Pre-sleep activity, like reading or studying, was related to later bedtime, earlier wake-up time, and shorter TST in both genders.
Conclusions
Age, Tanner stage, and pre-sleep activity affected sleep patterns in this sample of rural Chinese adolescents. Later bedtime coupled with earlier wake-up time associated with academic demand appear to be important contributors to sleep loss among school students.
doi:10.1016/j.sleep.2008.04.011
PMCID: PMC2753967  PMID: 18752997
Age; gender; puberty; Tanner stages; sleep patterns; wake-up time; bedtime; total sleep time
16.  Predictors of poor sleep quality among Lebanese university students: association between evening typology, lifestyle behaviors, and sleep habits 
Adequate, good night sleep is fundamental to well-being and is known to be influenced by myriad biological and environmental factors. Given the unavailability of sleep data about Lebanon, the cultural shifts and socioeconomic pressures that have affected many aspects of society, particularly for students and working adults, as well as our understanding of sleep in university students in other countries, we conducted a national study to assess sleep quality and factors contributing to sleep and general health in a culture-specific context. A self-filled questionnaire, inquiring about sociodemographics, health-risk behaviors, personal health, and evaluating sleep quality and chronotype using standard scales was completed by 540 students at private and public universities in Lebanon. Overall, they reported sleeping 7.95±1.34 hours per night, although 12.3% reported sleeping <6.5 hours and more than half scored in the poor-sleeper category on the Pittsburgh Sleep Quality Index (PSQI). Sleep timing differed markedly between weekdays and weekends, with bedtimes and wake-up times delayed by 1.51 and 2.43 hours, respectively, on weekends. While most scored in the “neither type” category on the Morningness–Eveningness Questionnaire (MEQ), 24.5% were evening types and 7.3% were morning types. MEQ score was significantly correlated with smoking behavior and daily study onset, as well as with PSQI score, with eveningness associated with greater number of cigarettes, later study times, and poor sleep. We conclude that the prevalence of poor sleep quality among Lebanese university students is associated with reduced sleep duration and shifts in sleep timing between weekdays and weekends, especially among evening types. While chronotype and certain behavioral choices interact to affect sleep dimensions and quality, raising awareness about the importance of obtaining adequate nighttime sleep on daily performance and avoiding risky behaviors may help Lebanese students make better choices in school and work schedules.
doi:10.2147/NSS.S55538
PMCID: PMC3894960  PMID: 24470782
bedtime irregularities; chronotype; Lebanon; PSQI; sleep duration; behavioral habits
17.  Daytime Sleepiness in Parkinson’s Disease: A Reappraisal 
PLoS ONE  2014;9(9):e107278.
Background
Excessive daytime sleepiness is a frequent complaint in Parkinson’s disease (PD); however the frequency and risk factors for objective sleepiness remain mostly unknown. We investigated both the frequency and determinants of self-reported and objective daytime sleepiness in patients with Parkinson’s disease (PD) using a wide range of potential predictors.
Methods
One hundred and thirty four consecutive patients with PD, without selection bias for sleep complaint, underwent a semi-structured clinical interview and a one night polysomnography followed by a multiple sleep latency test (MSLT). Demographic characteristics, medical history, PD course and severity, daytime sleepiness, depressive and insomnia symptoms, treatment intake, pain, restless legs syndrome, REM sleep behaviour disorder, and nighttime sleep measures were collected. Self-reported daytime sleepiness was defined by an Epworth Sleepiness Scale (ESS) score above 10. A mean sleep latency on MSLT below 8 minutes defined objective daytime sleepiness.
Results
Of 134 patients with PD, 46.3% had subjective and only 13.4% had objective sleepiness with a weak negative correlation between ESS and MSLT latency. A high body mass index (BMI) was associated with both ESS and MSLT, a pain complaint with ESS, and a higher apnea/hypopnea index with MSLT. However, no associations were found between both objective and subjective sleepiness, and measures of motor disability, disease onset, medication (type and dose), depression, insomnia, restless legs syndrome, REM sleep behaviour disorder and nighttime sleep evaluation.
Conclusion
We found a high frequency of self-reported EDS in PD, a finding which is however not confirmed by the gold standard neurophysiological evaluation. Current treatment options for EDS in PD are very limited; it thus remains to be determined whether decreasing pain and BMI in association with the treatment of sleep apnea syndrome would decrease significantly daytime sleepiness in PD.
doi:10.1371/journal.pone.0107278
PMCID: PMC4157859  PMID: 25198548
18.  Prostatic hyperplasia is highly associated with nocturia and excessive sleepiness: a cross-sectional study 
BMJ Open  2012;2(3):e000505.
Objectives
The objective of this study is to assess the impact of nocturia on sleep in patients with lower urinary tract symptoms (LUTS)/benign prostatic enlargement (BPE) (nocturia≥2).
Design
Cross-sectional survey.
Setting
798 urologists and general practitioners randomly selected from the overall population of urologists and general practitioners of every French region.
Participants
A total of 2179 LUTS/BPE men (aged 67.5±7.5 years old) were recruited.
Primary and secondary outcome measures
Validated patients' self-administered questionnaires were used to assess the severity of LUTS/BPE (the International Prostate Symptom Score), sleep characteristics (sleep log) and sleep disorders (the International Classification of Sleep Disorders (ICSD-2) and the DSM-IV). Sleepiness was assessed with the Epworth Sleepiness Scale (ESS). The volume of 24 h diuresis (1500 ml) was measured.
Results
Participants had on average 2.9±0.9 nocturia episodes (three or more episodes in 67%) and the International Prostate Symptom Score of 15.8±5.7; 60.9% complained of insomnia according to the ICSD-2, 7.9% of restless leg syndrome and 6.4% of obstructive sleep apnoea. 32.3% had excessive sleepiness (ESS >10) and 3.1% severe excessive sleepiness (ESS >16). Insomnia was mainly nocturnal awakenings with an average wake after sleep onset of 89±47 min. The number of episodes of nocturia per night correlated significantly with wake after sleep onset and ESS but not with total sleep time and sleep latency.
Conclusion
Nocturia is significantly associated with sleep maintenance insomnia and sleepiness in men with BPE.
Article summary
Article focus
Complaint of nocturia and its links with excessive sleepiness.
Assessment of the impact of nocturia on sleep.
Key messages
By being disruptive to sleep, the nocturia episodes affected sleep efficiency and quality.
The number of nocturia episodes was associated with an increased sleepiness in men with benign prostatic hyperplasia.
Strengths and limitations of this study
This is a cross-sectional study. It would have been more convincing to compare our subjects to a similar group of older people with no benign prostatic hyperplasia. However, our study focused on the frequency of insomnia and on the correlates between benign prostatic hyperplasia and insomnia.
doi:10.1136/bmjopen-2011-000505
PMCID: PMC3367152  PMID: 22649170
19.  Sleep Insufficiency, Sleep Health Problems and Performance in High School Students 
A survey on sleep schedule, sleep health, school performance and school start times was conducted in 1,941 adolescents. A high level of early and circadian-disadvantaged sleep/wake schedules during weekdays was observed. Shorter sleep duration on weekdays was reported, especially in upper classmen. Complaints of inadequate sleep and sleepiness during weekdays, alarm clock use, and napping were prevalent. Night awakening and prolonged sleep onset were common and associated with poor school performance. Students with a sleep length of less than 7 hours on both weekdays and weekends exhibited poorer performance, while those who made up this sleep loss on weekends did not. The total number of poor sleep factors in an individual also correlated with poor school performance. Earlier school start times were associated with a perception of poor sleep quality, shorter sleep duration and more sleep health problems. We conclude that sleep inadequacies and sleep health problems were prevalent in this population, especially in those who started school earlier in the morning, and that these poor sleep factors were associated with school performance.
doi:10.4137/CCRPM.S7955
PMCID: PMC3212860  PMID: 22084618
sleep deprivation; sleep health problem; adolescents; performance; school start time
20.  Polysomnography in Patients With Obstructive Sleep Apnea 
Executive Summary
Objective
The objective of this health technology policy assessment was to evaluate the clinical utility and cost-effectiveness of sleep studies in Ontario.
Clinical Need: Target Population and Condition
Sleep disorders are common and obstructive sleep apnea (OSA) is the predominant type. Obstructive sleep apnea is the repetitive complete obstruction (apnea) or partial obstruction (hypopnea) of the collapsible part of the upper airway during sleep. The syndrome is associated with excessive daytime sleepiness or chronic fatigue. Several studies have shown that OSA is associated with hypertension, stroke, and other cardiovascular disorders; many researchers believe that these cardiovascular disorders are consequences of OSA. This has generated increasing interest in recent years in sleep studies.
The Technology Being Reviewed
There is no ‘gold standard’ for the diagnosis of OSA, which makes it difficult to calibrate any test for diagnosis. Traditionally, polysomnography (PSG) in an attended setting (sleep laboratory) has been used as a reference standard for the diagnosis of OSA. Polysomnography measures several sleep variables, one of which is the apnea-hypopnea index (AHI) or respiratory disturbance index (RDI). The AHI is defined as the sum of apneas and hypopneas per hour of sleep; apnea is defined as the absence of airflow for ≥ 10 seconds; and hypopnea is defined as reduction in respiratory effort with ≥ 4% oxygen desaturation. The RDI is defined as the sum of apneas, hypopneas, and abnormal respiratory events per hour of sleep. Often the two terms are used interchangeably. The AHI has been widely used to diagnose OSA, although with different cut-off levels, the basis for which are often unclear or arbitrarily determined. Generally, an AHI of more than five events per hour of sleep is considered abnormal and the patient is considered to have a sleep disorder. An abnormal AHI accompanied by excessive daytime sleepiness is the hallmark for OSA diagnosis. For patients diagnosed with OSA, continuous positive airway pressure (CPAP) therapy is the treatment of choice. Polysomnography may also used for titrating CPAP to individual needs.
In January 2005, the College of Physicians and Surgeons of Ontario published the second edition of Independent Health Facilities: Clinical Practice Parameters and Facility Standards: Sleep Medicine, commonly known as “The Sleep Book.” The Sleep Book states that OSA is the most common primary respiratory sleep disorder and a full overnight sleep study is considered the current standard test for individuals in whom OSA is suspected (based on clinical signs and symptoms), particularly if CPAP or surgical therapy is being considered.
Polysomnography in a sleep laboratory is time-consuming and expensive. With the evolution of technology, portable devices have emerged that measure more or less the same sleep variables in sleep laboratories as in the home. Newer CPAP devices also have auto-titration features and can record sleep variables including AHI. These devices, if equally accurate, may reduce the dependency on sleep laboratories for the diagnosis of OSA and the titration of CPAP, and thus may be more cost-effective.
Difficulties arise, however, when trying to assess and compare the diagnostic efficacy of in-home PSG versus in-lab. The AHI measured from portable devices in-home is the sum of apneas and hypopneas per hour of time in bed, rather than of sleep, and the absolute diagnostic efficacy of in-lab PSG is unknown. To compare in-home PSG with in-lab PSG, several researchers have used correlation coefficients or sensitivity and specificity, while others have used Bland-Altman plots or receiver operating characteristics (ROC) curves. All these approaches, however, have potential pitfalls. Correlation coefficients do not measure agreement; sensitivity and specificity are not helpful when the true disease status is unknown; and Bland-Altman plots measure agreement (but are helpful when the range of clinical equivalence is known). Lastly, receiver operating characteristics curves are generated using logistic regression with the true disease status as the dependent variable and test values as the independent variable. Thus, each value of the test is used as a cut-point to measure sensitivity and specificity, which are then plotted on an x-y plane. The cut-point that maximizes both sensitivity and specificity is chosen as the cut-off level to discriminate between disease and no-disease states. In the absence of a gold standard to determine the true disease status, ROC curves are of minimal value.
At the request of the Ontario Health Technology Advisory Committee (OHTAC), MAS has thus reviewed the literature on PSG published over the last two years to examine new developments.
Methods
Review Strategy
There is a large body of literature on sleep studies and several reviews have been conducted. Two large cohort studies, the Sleep Heart Health Study and the Wisconsin Sleep Cohort Study, are the main sources of evidence on sleep literature.
To examine new developments on PSG published in the past two years, MEDLINE, EMBASE, MEDLINE In-Process & Other Non-Indexed Citations, the Cochrane Database of Systematic Reviews and Cochrane CENTRAL, INAHTA, and websites of other health technology assessment agencies were searched. Any study that reported results of in-home or in-lab PSG was included. All articles that reported findings from the Sleep Heart Health Study and the Wisconsin Sleep Cohort Study were also reviewed.
Diffusion of Sleep Laboratories
To estimate the diffusion of sleep laboratories, a list of sleep laboratories licensed under the Independent Health Facility Act was obtained. The annual number of sleep studies per 100,000 individuals in Ontario from 2000 to 2004 was also estimated using administrative databases.
Summary of Findings
Literature Review
A total of 315 articles were identified that were published in the past two years; 227 were excluded after reviewing titles and abstracts. A total of 59 articles were identified that reported findings of the Sleep Heart Health Study and the Wisconsin Sleep Cohort Study.
Prevalence
Based on cross-sectional data from the Wisconsin Sleep Cohort Study of 602 men and women aged 30 to 60 years, it is estimated that the prevalence of sleep-disordered breathing is 9% in women and 24% in men, on the basis of more than five AHI events per hour of sleep. Among the women with sleep disorder breathing, 22.6% had daytime sleepiness and among the men, 15.5% had daytime sleepiness. Based on this, the prevalence of OSA in the middle-aged adult population is estimated to be 2% in women and 4% in men.
Snoring is present in 94% of OSA patients, but not all snorers have OSA. Women report daytime sleepiness less often compared with their male counterparts (of similar age, body mass index [BMI], and AHI). Prevalence of OSA tends to be higher in older age groups compared with younger age groups.
Diagnostic Value of Polysomnography
It is believed that PSG in the sleep laboratory is more accurate than in-home PSG. In the absence of a gold standard, however, claims of accuracy cannot be substantiated. In general, there is poor correlation between PSG variables and clinical variables. A variety of cut-off points of AHI (> 5, > 10, and > 15) are arbitrarily used to diagnose and categorize severity of OSA, though the clinical importance of these cut-off points has not been determined.
Recently, a study of the use of a therapeutic trial of CPAP to diagnose OSA was reported. The authors studied habitual snorers with daytime sleepiness in the absence of other medical or psychiatric disorders. Using PSG as the reference standard, the authors calculated the sensitivity of this test to be 80% and its specificity to be 97%. Further, they concluded that PSG could be avoided in 46% of this population.
Obstructive Sleep Apnea and Obesity
Obstructive sleep apnea is strongly associated with obesity. Obese individuals (BMI >30 kg/m2) are at higher risk for OSA compared with non-obese individuals and up to 75% of OSA patients are obese. It is hypothesized that obese individuals have large deposits of fat in the neck that cause the upper airway to collapse in the supine position during sleep. The observations reported from several studies support the hypothesis that AHIs (or RDIs) are significantly reduced with weight loss in obese individuals.
Obstructive Sleep Apnea and Cardiovascular Diseases
Associations have been shown between OSA and comorbidities such as diabetes mellitus and hypertension, which are known risk factors for myocardial infarction and stroke. Patients with more severe forms of OSA (based on AHI) report poorer quality of life and increased health care utilization compared with patients with milder forms of OSA. From animal models, it is hypothesized that sleep fragmentation results in glucose intolerance and hypertension. There is, however, no evidence from prospective studies in humans to establish a causal link between OSA and hypertension or diabetes mellitus. It is also not clear that the associations between OSA and other diseases are independent of obesity; in most of these studies, patients with higher values of AHI had higher values of BMI compared with patients with lower AHI values.
A recent meta-analysis of bariatric surgery has shown that weight loss in obese individuals (mean BMI = 46.8 kg/m2; range = 32.30–68.80) significantly improved their health profile. Diabetes was resolved in 76.8% of patients, hypertension was resolved in 61.7% of patients, hyperlipidemia improved in 70% of patients, and OSA resolved in 85.7% of patients. This suggests that obesity leads to OSA, diabetes, and hypertension, rather than OSA independently causing diabetes and hypertension.
Health Technology Assessments, Guidelines, and Recommendations
In April 2005, the Centers for Medicare and Medicaid Services (CMS) in the United States published its decision and review regarding in-home and in-lab sleep studies for the diagnosis and treatment of OSA with CPAP. In order to cover CPAP, CMS requires that a diagnosis of OSA be established using PSG in a sleep laboratory. After reviewing the literature, CMS concluded that the evidence was not adequate to determine that unattended portable sleep study was reasonable and necessary in the diagnosis of OSA.
In May 2005, the Canadian Coordinating Office of Health Technology Assessment (CCOHTA) published a review of guidelines for referral of patients to sleep laboratories. The review included 37 guidelines and associated reviews that covered 18 applications of sleep laboratory studies. The CCOHTA reported that the level of evidence for many applications was of limited quality, that some cited studies were not relevant to the recommendations made, that many recommendations reflect consensus positions only, and that there was a need for more good quality studies of many sleep laboratory applications.
Diffusion
As of the time of writing, there are 97 licensed sleep laboratories in Ontario. In 2000, the number of sleep studies performed in Ontario was 376/100,000 people. There was a steady rise in sleep studies in the following years such that in 2004, 769 sleep studies per 100,000 people were performed, for a total of 96,134 sleep studies. Based on prevalence estimates of the Wisconsin Sleep Cohort Study, it was estimated that 927,105 people aged 30 to 60 years have sleep-disordered breathing. Thus, there may be a 10-fold rise in the rate of sleep tests in the next few years.
Economic Analysis
In 2004, approximately 96,000 sleep studies were conducted in Ontario at a total cost of ~$47 million (Cdn). Since obesity is associated with sleep disordered breathing, MAS compared the costs of sleep studies to the cost of bariatric surgery. The cost of bariatric surgery is $17,350 per patient. In 2004, Ontario spent $4.7 million per year for 270 patients to undergo bariatric surgery in the province, and $8.2 million for 225 patients to seek out-of-country treatment. Using a Markov model, it was concluded that shifting costs from sleep studies to bariatric surgery would benefit more patients with OSA and may also prevent health consequences related to diabetes, hypertension, and hyperlipidemia. It is estimated that the annual cost of treating comorbid conditions in morbidly obese patients often exceeds $10,000 per patient. Thus, the downstream cost savings could be substantial.
Considerations for Policy Development
Weight loss is associated with a decrease in OSA severity. Treating and preventing obesity would also substantially reduce the economic burden associated with diabetes, hypertension, hyperlipidemia, and OSA. Promotion of healthy weights may be achieved by a multisectorial approach as recommended by the Chief Medical Officer of Health for Ontario. Bariatric surgery has the potential to help morbidly obese individuals (BMI > 35 kg/m2 with an accompanying comorbid condition, or BMI > 40 kg/m2) lose weight. In January 2005, MAS completed an assessment of bariatric surgery, based on which OHTAC recommended an improvement in access to these surgeries for morbidly obese patients in Ontario.
Habitual snorers with excessive daytime sleepiness have a high pretest probability of having OSA. These patients could be offered a therapeutic trial of CPAP to diagnose OSA, rather than a PSG. A majority of these patients are also obese and may benefit from weight loss. Individualized weight loss programs should, therefore, be offered and patients who are morbidly obese should be offered bariatric surgery.
That said, and in view of the still evolving understanding of the causes, consequences and optimal treatment of OSA, further research is warranted to identify which patients should be screened for OSA.
PMCID: PMC3379160  PMID: 23074483
21.  Adolescent Sleep Patterns and Night-Time Technology Use: Results of the Australian Broadcasting Corporation's Big Sleep Survey 
PLoS ONE  2014;9(11):e111700.
Introduction
Electronic devices in the bedroom are broadly linked with poor sleep in adolescents. This study investigated whether there is a dose-response relationship between use of electronic devices (computers, cellphones, televisions and radios) in bed prior to sleep and adolescent sleep patterns.
Methods
Adolescents aged 11–17 yrs (n = 1,184; 67.6% female) completed an Australia-wide internet survey that examined sleep patterns, sleepiness, sleep disorders, the presence of electronic devices in the bedroom and frequency of use in bed at night.
Results
Over 70% of adolescents reported 2 or more electronic devices in their bedroom at night. Use of devices in bed a few nights per week or more was 46.8% cellphone, 38.5% computer, 23.2% TV, and 15.8% radio. Device use had dose-dependent associations with later sleep onset on weekdays (highest-dose computer adjOR  = 3.75: 99% CI  = 2.17–6.46; cellphone 2.29: 1.22–4.30) and weekends (computer 3.68: 2.14–6.32; cellphone 3.24: 1.70–6.19; TV 2.32: 1.30–4.14), and later waking on weekdays (computer 2.08: 1.25–3.44; TV 2.31: 1.33–4.02) and weekends (computer 1.99: 1.21–3.26; cellphone 2.33: 1.33–4.08; TV 2.04: 1.18–3.55). Only ‘almost every night’ computer use (: 2.43: 1.45–4.08) was associated with short weekday sleep duration, and only ‘almost every night’ cellphone use (2.23: 1.26–3.94) was associated with wake lag (waking later on weekends).
Conclusions
Use of computers, cell-phones and televisions at higher doses was associated with delayed sleep/wake schedules and wake lag, potentially impairing health and educational outcomes.
doi:10.1371/journal.pone.0111700
PMCID: PMC4229101  PMID: 25390034
22.  Actual and Perceived Sleep: Associations with Daytime Functioning among Postpartum Women 
Physiology & behavior  2010;102(2):234-238.
Sleep and wake have a homeostatic relation that influences most aspects of physiology and waking behavior. Sleep disturbance has a detrimental effect on sleepiness and psychomotor vigilance. The purpose of this study was to identify which actual or perceived sleep characteristics accounted for the most variance in daytime functioning among postpartum mothers. Seventy first-time postpartum mothers' actual sleep (actigraphically estimated: total sleep time, number of wake bouts, length of nocturnal wake, and sleep efficiency) and perceived sleep (self-reported: number of awakenings, wake time, and sleep quality) was measured along with their daytime functioning (Stanford Sleepiness Scale [SSS], Epworth Sleepiness Scale [ESS], Visual Analogue of Fatigue Scale [VAFS], and morning Psychomotor Vigilance Test [PVT]). Data were repeatedly collected from the same sample during postpartum weeks 2, 7, and 13. Four stepwise linear regressions were calculated for each postpartum week to examine which objective and/or subjective variable(s) accounted for the most variance in daytime functioning. The SSS and VAFS were both most consistently associated with perceived sleep quality. The ESS was most consistently associated with actual total sleep time. PVT performance was most consistently associated with estimates of actual and perceived sleep efficiency. Actual and perceived sleep profiles were differentially associated with specific daytime functions. These results from postpartum mothers may indicate that populations who experience specific forms of sleep disturbance (e.g. fragmentation, deprivation) may also experience specific daytime conditions.
doi:10.1016/j.physbeh.2010.11.017
PMCID: PMC3010463  PMID: 21095200
Actual; actigraphy; subjective; objective; perceived; sleep; sleepiness; fatigue; performance; behavior; postpartum; maternal
23.  Sleep-Disordered Breathing and Mortality: A Prospective Cohort Study 
PLoS Medicine  2009;6(8):e1000132.
In a cohort of 6,441 volunteers followed over an average of 8.2 years, Naresh Punjabi and colleagues find sleep-disordered breathing to be independently associated with mortality and identify predictive characteristics.
Background
Sleep-disordered breathing is a common condition associated with adverse health outcomes including hypertension and cardiovascular disease. The overall objective of this study was to determine whether sleep-disordered breathing and its sequelae of intermittent hypoxemia and recurrent arousals are associated with mortality in a community sample of adults aged 40 years or older.
Methods and Findings
We prospectively examined whether sleep-disordered breathing was associated with an increased risk of death from any cause in 6,441 men and women participating in the Sleep Heart Health Study. Sleep-disordered breathing was assessed with the apnea–hypopnea index (AHI) based on an in-home polysomnogram. Survival analysis and proportional hazards regression models were used to calculate hazard ratios for mortality after adjusting for age, sex, race, smoking status, body mass index, and prevalent medical conditions. The average follow-up period for the cohort was 8.2 y during which 1,047 participants (587 men and 460 women) died. Compared to those without sleep-disordered breathing (AHI: <5 events/h), the fully adjusted hazard ratios for all-cause mortality in those with mild (AHI: 5.0–14.9 events/h), moderate (AHI: 15.0–29.9 events/h), and severe (AHI: ≥30.0 events/h) sleep-disordered breathing were 0.93 (95% CI: 0.80–1.08), 1.17 (95% CI: 0.97–1.42), and 1.46 (95% CI: 1.14–1.86), respectively. Stratified analyses by sex and age showed that the increased risk of death associated with severe sleep-disordered breathing was statistically significant in men aged 40–70 y (hazard ratio: 2.09; 95% CI: 1.31–3.33). Measures of sleep-related intermittent hypoxemia, but not sleep fragmentation, were independently associated with all-cause mortality. Coronary artery disease–related mortality associated with sleep-disordered breathing showed a pattern of association similar to all-cause mortality.
Conclusions
Sleep-disordered breathing is associated with all-cause mortality and specifically that due to coronary artery disease, particularly in men aged 40–70 y with severe sleep-disordered breathing.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
About 1 in 10 women and 1 in 4 men have a chronic condition called sleep-disordered breathing although most are unaware of their problem. Sleep-disordered breathing, which is commonest in middle-aged and elderly people, is characterized by numerous, brief (10 second or so) interruptions of breathing during sleep. These interruptions, which usually occur when relaxation of the upper airway muscles decreases airflow, lower the level of oxygen in the blood and, as a result, affected individuals are frequently aroused from deep sleep as they struggle to breathe. Symptoms of sleep-disordered breathing include loud snoring and daytime sleepiness. Treatments include lifestyle changes such as losing weight (excess fat around the neck increases airway collapse) and smoking cessation. Affected people can also use special devices to prevent them sleeping on their backs, but for severe sleep-disordered breathing, doctors often recommend continuous positive airway pressure (CPAP), a machine that pressurizes the upper airway through a face mask to keep it open.
Why Was This Study Done?
Sleep-disordered breathing is a serious condition. It is associated with several adverse health conditions including coronary artery disease (narrowing of the blood vessels that supply the heart, a condition that can cause a heart attack) and daytime sleepiness that can affect an individual's driving ability. In addition, several clinic- and community-based studies suggest that sleep-disordered sleeping may increase a person's risk of dying. However, because these studies have been small and have often failed to allow for other conditions and characteristics that affect an individual's risk of dying (“confounding factors”), they provide inconsistent or incomplete information about the potential association between sleep-disordered breathing and the risk of death. In this prospective cohort study (part of the Sleep Heart Health Study, which is researching the effects of sleep-disordered breathing on cardiovascular health), the researchers examine whether sleep-disordered breathing is associated with all-cause mortality (death from any cause) in a large community sample of adults. A prospective cohort study is one in which a group of participants is enrolled and then followed forward in time (in this case for several years) to see what happens to them.
What Did the Researchers Do and Find?
At enrollment, the study participants—more than 6,000 people aged 40 years or older, none of whom were being treated for sleep-disordered breathing—had a health examination. Their night-time breathing, sleep patterns, and blood oxygen levels were also assessed and these data used to calculate each participant's apnea-hypopnea index (AHI)—the number of apneas and hypopneas per hour. During the study follow-up period, 1,047 participants died. Compared to participants without sleep-disordered sleeping, participants with severe sleep-disordered breathing (an AHI of ≥30) were about one and a half times as likely to die from any cause after adjustment for potential confounding factors. People with milder sleep-disordered breathing did not have a statistically significant increased risk of dying. After dividing the participants into subgroups according to their age and sex, men aged 40–70 years with severe sleep-disordered breathing had a statistically increased risk of dying from any cause (twice the risk of men of a similar age without sleep-disordered breathing). Finally, death from coronary artery disease was also associated with sleep-disordered breathing in men but not in women.
What Do These Findings Mean?
These findings indicate that sleep-disordered breathing is associated with an increased risk of all-cause mortality, particularly in men aged 40–70 years, even after allowing for known confounding factors. They also suggest that the increased risk of death is specifically associated with coronary artery disease although further studies are needed to confirm this finding because it was based on the analysis of a small subgroup of study participants. Although this study is much larger than previous investigations into the association between sleep-disordered breathing and all-cause mortality, it has several limitations including its reliance on a single night's measurements for the diagnosis of sleep-disordered breathing. Nevertheless, these findings suggest that clinical trials should now be started to assess whether treatment can reduce the increased risk of death that seems to be associated with this common disorder.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000132.
The US National Heart Lung and Blood Institute has information (including a video) about sleep-disordered breathing (sleep apnea) (in English and Spanish)
The UK National Heath Service also provides information for patients about sleep apnea
MedlinePlus provides links to further information and advice about sleep-disordered breathing (in English and Spanish)
More information on the Sleep Heart Health Study is available
doi:10.1371/journal.pmed.1000132
PMCID: PMC2722083  PMID: 19688045
24.  Causes and consequences of sleepiness among college students 
Daytime sleepiness, sleep deprivation, and irregular sleep schedules are highly prevalent among college students, as 50% report daytime sleepiness and 70% attain insufficient sleep. The consequences of sleep deprivation and daytime sleepiness are especially problematic to college students and can result in lower grade point averages, increased risk of academic failure, compromised learning, impaired mood, and increased risk of motor vehicle accidents. This article reviews the current prevalence of sleepiness and sleep deprivation among college students, contributing factors for sleep deprivation, and the role of sleep in learning and memory. The impact of sleep and sleep disorders on academics, grade point average, driving, and mood will be examined. Most importantly, effective and viable interventions to decrease sleepiness and sleep deprivation through sleep education classes, online programs, encouragement of naps, and adjustment of class time will be reviewed. This paper highlights that addressing sleep issues, which are not often considered as a risk factor for depression and academic failure, should be encouraged. Promotion of university and college policies and class schedules that encourage healthy and adequate sleep could have a significant impact on the sleep, learning, and health of college students. Future research to investigate effective and feasible interventions, which disseminate both sleep knowledge and encouragement of healthy sleep habits to college students in a time and cost effective manner, is a priority.
doi:10.2147/NSS.S62907
PMCID: PMC4075951  PMID: 25018659
grade point average; GPA; sleep deprivation; academic performance; adolescence; sleep education programs
25.  Sleepiness, Quality of Life, and Sleep Maintenance in REM versus non-REM Sleep-disordered Breathing 
Rationale: The impact of REM-predominant sleep-disordered breathing (SDB) on sleepiness, quality of life (QOL), and sleep maintenance is uncertain.
Objective: To evaluate the association of SDB during REM sleep with daytime sleepiness, health-related QOL, and difficulty maintaining sleep, in comparison to their association with SDB during non-REM sleep in a community-based cohort.
Methods: Cross-sectional analysis of 5,649 Sleep Heart Health Study participants (mean age 62.5 [SD = 10.9], 52.6% women, 22.6% ethnic minorities). SDB during REM and non-REM sleep was quantified using polysomnographically derived apnea-hypopnea index in REM (AHIREM) and non-REM (AHINREM) sleep. Sleepiness, sleep maintenance, and QOL were respectively quantified using the Epworth Sleepiness Scale (ESS), the Sleep Heart Health Study Sleep Habit Questionnaire, and the physical and mental composites scales of the Medical Outcomes Study Short Form (SF)-36.
Measurements and Main Results: AHIREM was not associated with the ESS scores or the physical and mental components scales scores of the SF-36 after adjusting for demographics, body mass index, and AHINREM. AHIREM was not associated with frequent difficulty maintaining sleep or early awakening from sleep. AHINREM was associated with the ESS score (β = 0.25; 95% confidence interval [CI], 0.16 to 0.34) and the physical (β = −0.12; 95% CI, −0.42 to −0.01) and mental (β = −0.20; 95% CI, −0.20 to −0.01) components scores of the SF-36 adjusting for demographics, body mass index, and AHIREM.
Conclusions: In a community-based sample of middle-aged and older adults, REM-predominant SDB is not independently associated with daytime sleepiness, impaired health-related QOL, or self-reported sleep disruption.
doi:10.1164/rccm.200908-1304OC
PMCID: PMC3269234  PMID: 20093641
epidemiology; sleep apnea syndromes; sleep, REM; hypersomnia

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