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1.  Effect of Treatment of Obstructive Sleep Apnea on Depressive Symptoms: Systematic Review and Meta-Analysis 
PLoS Medicine  2014;11(11):e1001762.
In a meta-analysis of randomized controlled trials, Matthew James and colleagues investigate the effects of continuous positive airway pressure or mandibular advancement devices on depression.
Please see later in the article for the Editors' Summary
Obstructive sleep apnea (OSA) is associated with increased morbidity and mortality, and decreased quality of life. Treatment with continuous positive airway pressure (CPAP) or mandibular advancement devices (MADs) is effective for many symptoms of OSA. However, it remains controversial whether treatment with CPAP or MAD also improves depressive symptoms.
Methods and Findings
We performed a systematic review and meta-analysis of randomized controlled trials that examined the effect of CPAP or MADs on depressive symptoms in patients with OSA. We searched Medline, EMBASE, the Cochrane Central Registry of Controlled Trials, and PsycINFO from the inception of the databases until August 15, 2014, for relevant articles.
In a random effects meta-analysis of 19 identified trials, CPAP treatment resulted in an improvement in depressive symptoms compared to control, but with significant heterogeneity between trials (Q statistic, p<0.001; I2 = 71.3%, 95% CI: 54%, 82%). CPAP treatment resulted in significantly greater improvement in depressive symptoms in the two trials with a higher burden of depression at baseline (meta-regression, p<0.001). The pooled standardized mean difference (SMD) in depressive symptoms with CPAP treatment in these two trial populations with baseline depression was 2.004 (95% CI: 1.387, 2.621), compared to 0.197 (95% CI: 0.059, 0.334) for 15 trials of populations without depression at baseline. Pooled estimates of the treatment effect of CPAP were greater in parallel arm trials than in crossover trials (meta-regression, p = 0.076). Random effects meta-analysis of five trials of MADs showed a significant improvement in depressive symptoms with MADs versus controls: SMD = 0.214 (95% CI: 0.026, 0.401) without significant heterogeneity (I2 = 0%, 95% CI: 0%, 79%). Studies were limited by the use of depressive symptom scales that have not been validated specifically in people with OSA.
CPAP and MADs may be useful components of treatment of depressive symptoms in individuals with OSA and depression. The efficacy of CPAP and MADs compared to standard therapies for depression is unknown.
Please see later in the article for the Editors' Summary
Editors' Summary
Obstructive sleep apnea (OSA) is a sleep-related breathing disorder that is particularly common among middle-aged and elderly people, although most are unaware that they have the condition. It is characterized by the occurrence of numerous brief (ten seconds or so) breathing interruptions during sleep. These “apneas” occur when relaxation of the upper airway muscles decreases airflow, which lowers the level of oxygen in the blood. Consequently, affected individuals are frequently aroused 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. Mild to moderate OSA can also be treated using a mandibular advancement device (MAD), a “splint” that fits inside the mouth and pushes the jaw and tongue forward to increase the space at the back of the throat and reduce airway narrowing. For severe OSA, doctors recommend continuous positive airway pressure (CPAP), in which a machine blows pressurized air into the airway through a facemask to keep it open.
Why Was This Study Done?
OSA is a serious condition that is associated with an increased risk of illness and death. Clinical depression (long-lasting, overwhelming feelings of sadness and hopelessness), for example, is common among people with OSA. The interaction between these frequently co-morbid (co-existing) conditions is complex. The sleep disruption and weight gain that are often associated with depression could cause or worsen OSA. Conversely, OSA could trigger depression by causing sleep disruption and by inducing cognitive changes (changes in thinking) by intermittently starving the brain of oxygen. If the latter scenario is correct, then treating OSA with CPAP or MADs might improve depressive symptoms. Several trials have investigated this possibility, but their results have been equivocal. Here, the researchers undertake a systematic review and meta-analysis of randomized controlled trials that have examined the effect of CPAP or MADs on depressive symptoms in patients with OSA to find out whether treating co-morbid OSA in patients with depression can help to treat depression. A randomized controlled trial compares the outcomes of individuals chosen to receive different interventions through the play of chance, a systematic review uses predefined criteria to identify all the research on a given topic, and meta-analysis uses statistical methods to combine the results of several studies.
What Did the Researchers Do and Find?
The researchers identified 22 trials that investigated the effects of CPAP or MAD treatment in patients with OSA and that measured depressive symptoms before and after treatment. Meta-analysis of the results of 19 trials that provided information about the effect of CPAP on depressive symptoms indicated that CPAP improved depressive symptoms compared to the control intervention (usually sham CPAP) but revealed considerable heterogeneity (variability) between trials. Notably, CPAP treatment resulted in a greater improvement in depressive symptoms in trials in which there was a high prevalence of depression at baseline than in trials in which there was a low prevalence of depression at baseline. Moreover, the magnitude of this improvement in depressive symptoms in trials with a high prevalence of depression at baseline was large enough to be clinically relevant. Meta-analysis of five trials that provided information about the effect of MADs on depressive symptoms indicated that MADs also improved depressive symptoms compared to the control intervention (sham MAD).
What Do These Findings Mean?
These findings suggest that both CPAP and MAD treatment for OSA can result in modest improvements in depressive symptoms and that populations with high initial levels of depressive symptoms may reap the greatest benefits of CPAP treatment. These findings give no indication of the efficacy of CPAP and MADs compared to standard treatments for depression such as antidepressant medications. Moreover, their accuracy may be limited by methodological limitations within the trials included in the meta-analyses reported here. For example, the questionnaires used to measure depression in these trials were not validated for use in people with OSA. Further high-quality randomized controlled trials are therefore needed to confirm the findings of this systematic review and meta-analysis. For now, however, these findings suggest that the use of CPAP and MADs may help improve depressive symptoms among people with OSA.
Additional Information
Please access these websites via the online version of this summary at
The US National Heart, Lung, and Blood Institute has information (including several videos) about sleep apnea (in English and Spanish)
The UK National Health Service Choices website provides information and personal stories about obstructive sleep apnea and depression
The not-for-profit American Sleep Apnea Association provides detailed information about sleep apnea for patients and healthcare professionals, including personal stories about the condition
The US National Institute of Mental Health provides information on all aspects of depression (in English and Spanish)
The Anxiety and Depression Association of America provides information about sleep disorders
The MedlinePlus encyclopedia has a page on obstructive sleep apnea; MedlinePlus provides links to further information and advice about obstructive sleep apnea and about depression (in English and Spanish)
PMCID: PMC4244041  PMID: 25423175
2.  Polysomnography in Patients With Obstructive Sleep Apnea 
Executive Summary
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.
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.
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.
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
3.  A short-term controlled trial of an adjustable oral appliance for the treatment of mild to moderate obstructive sleep apnoea 
Thorax  1997;52(4):362-368.
BACKGROUND: Although oral appliances are effective in some patients with obstructive sleep apnoea (OSA), they are not universally effective. A novel anterior mandibular positioner (AMP) has been developed with an adjustable hinge that allows progressive advancement of the mandible. The objective of this prospective crossover study was to compare efficacy, side effects, patient compliance, and preference between AMP and nasal continuous positive airway pressure (nCPAP) in patients with symptomatic mild to moderate OSA. METHODS: Twenty four patients of mean (SD) age 44.0 (10.6) years were recruited with a mean (SD) body mass index of 32.0 (8.2) kg/m2, Epworth sleepiness score 10.7 (3.4), and apnoea/hypopnoea index 26.8 (11.9)/hour. There was a two week wash-in and a two week wash-out period and two treatment periods (AMP and nCPAP) each of four months. Efficacy, side effects, compliance, and preference were evaluated by a questionnaire and home sleep monitoring. RESULTS: One patient dropped out early in the study and three refused to cross over so treatment results are presented on the remaining 20 patients. The apnoea/hypopnoea index (AHI) was lower with nasal CPAP 4.2 (2.2)/hour than with the AMP 13.6 (14.5)/hour (p < 0.01). Eleven of the 20 patients (55%) who used the AMP were treatment successes (reduction of AHI to < 10/hour and relief of symptoms), one (5%) was a compliance failure (unable or unwilling to use the treatment), and eight (40%) were treatment failures (failure to reduce AHI to < 10/hour and/or failure to relieve symptoms). Fourteen of the 20 patients (70%) who used nCPAP were treatment successes, six (30%) were compliance failures, and there were no treatment failures. There was greater patient satisfaction with the AMP (p < 0.01) than with nCPAP but no difference in reported side effects or compliance. CONCLUSIONS: AMP is an effective treatment in some patients with mild to moderate OSA and is associated with greater patient satisfaction than nCPAP. 

PMCID: PMC1758547  PMID: 9196520
4.  Review of oral appliances for treatment of sleep-disordered breathing 
Between 1982 and 2006, there were 89 distinct publications dealing with oral appliance therapy involving a total of 3,027 patients, which reported results of sleep studies performed with and without the appliance. These studies, which constitute a very heterogeneous group in terms of methodology and patient population, are reviewed and the results summarized. This review focused on the following outcomes: sleep apnea (i.e. reduction in the apnea/hypopnea index or respiratory disturbance index), ability of oral appliances to reduce snoring, effect of oral appliances on daytime function, comparison of oral appliances with other treatments (continuous positive airway pressure and surgery), side effects, dental changes (overbite and overjet), and long-term compliance. We found that the success rate, defined as the ability of the oral appliances to reduce apnea/hypopnea index to less than 10, is 54%. The response rate, defined as at least 50% reduction in the initial apnea/hypopnea index (although it still remained above 10), is 21%. When only the results of randomized, crossover, placebo-controlled studies are considered, the success and response rates are 50% and 14%, respectively. Snoring was reduced by 45%. In the studies comparing oral appliances to continuous positive airway pressure (CPAP) or to uvulopalatopharyngoplasty (UPPP), an appliance reduced initial AHI by 42%, CPAP reduced it by 75%, and UPPP by 30%. The majority of patients prefer using oral appliance than CPAP. Use of oral appliances improves daytime function somewhat; the Epworth sleepiness score (ESS) dropped from 11.2 to 7.8 in 854 patients. A summary of the follow-up compliance data shows that at 30 months, 56–68% of patients continue to use oral appliance. Side effects are relatively minor but frequent. The most common ones are excessive salivation and teeth discomfort. Efficacy and side effects depend on the type of appliance, degree of protrusion, vertical opening, and other settings. We conclude that oral appliances, although not as effective as CPAP in reducing sleep apnea, snoring, and improving daytime function, have a definite role in the treatment of snoring and sleep apnea.
PMCID: PMC1794626  PMID: 17136406
Continuous positive airway pressure; Sleep apnea; Oral appliance
5.  Sleep apnea and occupational accidents: Are oral appliances the solution? 
Dental practitioners have a key role in the quality of life and prevention of occupational accidents of workers with Obstructive Sleep Apnea Syndrome (OSAS).
The aim of this study was to review the impact of OSAS, the Continuous Positive Airway Pressure (CPAP) therapy, and the evidence regarding the use of oral appliances (OA) on the health and safety of workers.
Materials and Methods:
Searches were conducted in MEDLINE (PubMed), Lilacs and Sci ELO. Articles published from January 1980 to June 2014 were included.
The research retrieved 2188 articles and 99 met the inclusion criteria. An increase in occupational accidents due to reduced vigilance and attention in snorers and patients with OSAS was observed. Such involvements were related to excessive daytime sleepiness and neurocognitive function impairments. The use of OA are less effective when compared with CPAP, but the results related to excessive sleepiness and cognitive performance showed improvements similar to CPAP. Treatments with OA showed greater patient compliance than the CPAP therapy.
OSAS is a prevalent disorder among workers, leads to increased risk of occupational accidents, and has a significant impact on the economy. The CPAP therapy reduces the risk of occupational accidents. The OA can improve the work performance; but there is no scientific evidence associating its use with occupational accidents reduction. Future research should focus on determining the cost-effectiveness of OA as well as its influence and efficacy in preventing occupational accidents.
PMCID: PMC4280775  PMID: 25568596
Continuous positive air pressure; obstructive sleep apnea; occupational accidents; oral appliances; review
6.  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
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.
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
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
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)
PMCID: PMC3913558  PMID: 24503600
7.  Position paper by Canadian dental sleep medicine professionals regarding the role of different health care professionals in managing obstructive sleep apnea and snoring with oral appliances 
The present Canadian position paper contains recommendations for the management by dentists of sleep-disordered breathing in adults with the use of oral appliances (OAs) as a treatment option for snoring and obstructive sleep apnea (OSA). The recommendations are based on literature reviews and expert panel consensus. OAs offer an effective, first-line treatment option for patients with mild to moderate OSA who prefer an OA to continuous positive airway pressure (CPAP) therapy, or for severe OSA patients who cannot tolerate CPAP, are inappropriate candidates for CPAP or who have failed CPAP treatment attempts. The purpose of the present position paper is to guide interdisciplinary teamwork (sleep physicians and sleep dentists) and to clarify the role of each professional in the management of OA therapy. The diagnosis of OSA should always be made by a physician, and OAs should be fitted by a qualified dentist who is trained and experienced in dental sleep medicine. Follow-up assessment by the referring physician and polysomnography or sleep studies are required to verify treatment efficacy. The present article emphasizes the need for a team approach to OA therapy and provides treatment guidelines for dentists trained in dental sleep medicine. Many of the dentists and sleep physicians who contributed to the preparation of the present article are members of the Canadian Sleep Society and the authors reached a consensus based on the current literature.
PMCID: PMC3473005  PMID: 23061075
Bruxism; Dental sleep medicine; Obstructive sleep apnea; Oral appliances; Position paper; Sleep-disordered breathing; Snoring
8.  Sleep apnoea 
BMJ Clinical Evidence  2009;2009:2301.
Sleep apnoea is the popular term for obstructive sleep apnoea-hypopnoea syndrome (OSAHS). OSAHS is abnormal breathing during sleep that causes recurrent arousals, sleep fragmentation, excessive daytime sleepiness, and nocturnal hypoxaemia. Apnoea may be "central", in which there is cessation of inspiratory effort, or "obstructive", in which inspiratory efforts continue but are ineffective because of upper airway obstruction. OSAHS affects up to 4% of men and 2% of women in the USA, with obesity being a major determinant.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatment for severe obstructive sleep apnoea-hypopnoea syndrome? What are the effects of treatment for non-severe obstructive sleep apnoea-hypopnoea syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
We found 43 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
In this systematic review we present information relating to the effectiveness and safety of the following interventions: nasal continuous positive airway pressure (CPAP); measures aimed at improving compliance with CPAP; oral appliances; and weight loss.
Key Points
Sleep apnoea is the popular term for obstructive sleep apnoea-hypopnoea syndrome (OSAHS). OSAHS is abnormal breathing during sleep that causes recurrent arousals, sleep fragmentation, daytime sleepiness, and nocturnal hypoxaemia. Apnoea may be "central", in which there is cessation of inspiratory effort, or "obstructive", in which inspiratory efforts continue but are ineffective because of upper airway obstruction.OSAHS affects up to 4% of men and 2% of women in the USA, with obesity being a major determinant.
In people with severe OSAHS, nasal CPAP has been shown to reduce daytime sleepiness compared with control treatments. Although effective, it can be difficult getting people to comply with the prescribed CPAP regimen. Compliance seems no better with variations of CPAP, such as automatically titrated CPAP, bi-level positive airway pressure, patient-titrated CPAP, or CPAP plus humidification. We don't know whether educational or psychological interventions may improve compliance with CPAP.
Oral appliances that produce anterior advancement of the mandible seem to be effective in improving sleep-disordered breathing in people with OSAHS (either severe or non-severe). Oral appliances are probably not as effective as CPAP, and we don't know how well they work in the long term.
We found no sufficient evidence judging the effectiveness of weight loss on OSAHS (either severe or non-severe), although there is consensus that advice about weight reduction is an important component of management of OSAHS.
Nasal CPAP also seems beneficial to people suffering from non-severe OSAHS. Nasal CPAP is less acceptable in people with non-severe OSAHS, and we don't know whether measures aimed at improving compliance effectively increase usage.
PMCID: PMC2907765  PMID: 21726484
9.  Compliance with continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea among privately paying patients- a cross sectional study 
BMC Pulmonary Medicine  2014;14:188.
To evaluate the compliance, benefits and side effects associated with continuous positive airway pressure (CPAP) therapy among Pakistani patients treated for obstructive sleep apnea (OSA) in private sector.
Patients diagnosed to have OSA based on overnight study who were recommended for CPAP therapy, between 1998 and 2003, were evaluated by telephonic survey and review of hospital notes. Compliance, benefits and side effects associated with CPAP therapy were assessed.
Out of 135 patients who were prescribed CPAP therapy, 75 could be contacted. Sixty (80%) started using CPAP within one month of diagnosis and 46 (61%) continued to use it long-term (beyond one year). Compliance with CPAP therapy was associated with higher body mass index, higher Epworth sleepiness scale score, history of witnessed apnea, and reduction in daytime sleepiness with CPAP therapy. OSA severity as assessed by apnea-hypopnea index did not affect compliance with CPAP therapy. Use of anti-depressants and CPAP induced sleep disturbances were associated with poor compliance with CPAP therapy.
Obesity, excessive daytime sleepiness, witnessed apnea and improvement of daytime symptoms following use of CPAP were predictors of improved compliance. Use of antidepressants and CPAP induced sleep disturbances were predictors of poor compliance.
PMCID: PMC4258250  PMID: 25433468
Obstructive sleep apnea; Continuous positive airway pressure therapy; Compliance; Side effects; Pakistan
10.  Comparison of Titratable Oral Appliance and Mandibular Advancement Splint in the Treatment of Patients with Obstructive Sleep Apnea 
ISRN Dentistry  2011;2011:581692.
Objective. To compare the effect of two intraoral devices (titratable oral appliance-Klearway (KW) and mandibular advancement splint (MAS)) in mild and moderate obstructive sleep apnea (OSA) patients. Method and Materials. The study group was comprised of twenty-four adult volunteer patients with OSA. Twelve subjects were fitted with a titratable oral appliance (group KW) protruding the mandible (85% of maximum protrusion). The other 12 subjects received MAS with 75% protrusion of the mandible (group MAS). Baseline, (“0.PSG”), first week (K1.PSG for KW group and M1.PSG for MAS group), and after the first month (K2.PSG for KW group and M2′. PSG for MAS group). Results. Both groups produced similar reduction in apnea-hypopnea index (AHI) from baseline till the end of the first week and first month (P < .05). However, the success rate of both groups at the end of the first month was found to be statistically different from the success rate of the first week (P < .05). The reduction in mean AHI of group KW-moderate (KW-mo) was significantly different from the mean AHI of group MAS-moderate (MAS-mo) at the end of the first month (P < .05). Conclusion. This study suggests that Klearway appliance was more effective in treating moderate OSA patients than MAS appliance. It was concluded that an appliance that provides 85% mandibular advancement to open the upper airway was more effective in reducing the number of high apneic events during sleep in comparison to the one which provides 75%.
PMCID: PMC3169918  PMID: 21991480
11.  Reconstructive procedures for disturbed functions within the upper airway: pharyngeal breathing/snoring 
Breathing disorders which have their origin within the pharynx mainly occur during sleep. These so-called obstructive sleep-related breathing disorders include three different disturbances which have to be distinguished properly: simple snoring, upper airway resistance syndrome (UARS) and obstructive sleep apnea (OSA). Each disturbance requires a different treatment.
Simple snoring does not affect the physical health of the snorer himself, but often leads to social problems due to the annoying character of the breathing sounds. Appropriate treatment modalities are oral devices and transcutaneous or ttransmucosal electrical stimulation of the muscles of the floor of the mouth via surface electrodes. As reconstructive surgical procedures adenotomies, tonsillectomies, tonsillotomies, or adenotonsillectomies are successfully used in children. Moreover, in adults radiofrequency treatments of the tonsils, the soft palate and of the base of tongue, as well as uvulopalatopharyngoplasty (UPPP), laser-assisted uvulopalatoplasty (LAUP) and palatal implants are adequate treatments for simple snoring.
Adequate therapies for UARS and mild OSA (less than 20 breathing events per hour of sleep) are oral appliances. Nasal continuos positive airway pressure (NCPAP) ventilation is a very successful treatment modality, but shows low compliance in these patients, as daytime symptoms like excessive sleepiness or or impaired cognitive functions are often unincisive in patients with mild OSA. Reconstructive procedures like UPPP, radiofrequency surgery of the tonsils or the base of tongue, hyoid suspension, mandibular osteotomy with genioglossus advancement (MO) are successful treatment options either as isolated procedures or in combination within so-called multi-level surgery concepts.
Goldstandard for the treatment of moderate to severe OSA is the nCPAP ventilation. All patients should at least try this treatment modality. Only in the rare cases of nCPAP failure (2%) and in the relatively frequent cases of nCPAP incompliance (30%) reconstructive surgical procedures become necessary as second choice treatments. These are adenectomies, tonsillectomies, tonsillotomies in children and hyoid suspension, MO, multi-level surgery concepts, or maxillomandibular advancement osteotomies in adults.
PMCID: PMC3201014  PMID: 22073056
12.  Evaluation of an auto-CPAP device for treatment of obstructive sleep apnoea 
Thorax  1998;53(8):643-648.
BACKGROUND—Auto-CPAP machines used in the treatment of obstructive sleep apnoea (OSA) are designed to vary the treatment pressure automatically in order always to apply the actually needed pressure. Consequently they should be able to achieve at least identical therapeutic effects as conventional constant pressure CPAP with a lower mean treatment pressure. The present study was designed to evaluate the therapeutic efficacy and the treatment pressure of an auto-CPAP machine (REM+auto®, SEFAM) in comparison with a conventional CPAP device.
METHODS—Following CPAP titration, 16 patients with OSA were allocated to receive conventional CPAP and auto-CPAP treatment under polysomnographic control in a randomised order. After each treatment the patients were asked to assess the therapy using a questionnaire; a vigilance test was also carried out and subjective daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS).
RESULTS—The mean (SD) apnoea/hypopnoea index (AHI) during auto-CPAP treatment was comparable with that during conventional CPAP treatment (4.2 (5.1) versus 3.6 (4.0)). Neither an analysis of sleep architecture nor the arousal index (7.4 (4.1) versus 7.0 (4.3)) revealed any significant differences. Daytime sleepiness measured with the ESS was also comparable (5.3 (3.4) versus 6.5 (4.2)). The vigilance test showed normal values after both treatments in all patients with no significant differences. The mean pressure during auto-CPAP treatment (8.1 (2.9) mbar), however, was significantly higher than that employed in conventional CPAP treatment (7.6 (2.7) mbar; mean difference 0.5 mbar; 95% CI 0.1 to 0.9 mbar; p<0.05).
CONCLUSIONS—Auto-CPAP was equally as effective as conventional CPAP with respect to therapeutic efficacy. The aim of reducing the treatment pressure with auto-CPAP, however, was not achieved.

PMCID: PMC1745298  PMID: 9828849
13.  An empirical continuous positive airway pressure trial for suspected obstructive sleep apnea 
Standard practice in obstructive sleep apnea (OSA) management requires that a positive diagnostic, overnight polysomnography (PSG) test be obtained before initiating treatment. However, long waiting times due to lack of access to PSG testing facilities may delay the initiation of definitive treatment for OSA.
To evaluate the response of patients who had a high clinical suspicion for OSA and who were waiting for a PSG test to an empirical continuous positive airway pressure (CPAP) trial.
A retrospective study of all patients who had been offered empirical CPAP therapy for suspected OSA was conducted. After outpatient assessment, 183 patients with a high pretest probability of having OSA began empirical CPAP testing using an arbitrary CPAP pressure. The presence of OSA, the accuracy of empirical CPAP pressure prescription, the adherence to empirical CPAP and the improvement in daytime somnolence were evaluated at the time of PSG.
Of 183 patients on a CPAP trial, 91% had OSA, which was at least moderate (more than 15 apneas and hypopneas per hour of sleep) in 75% of the patients. Eighty per cent of the patients had significant daytime somnolence (Epworth Sleepiness Scale [ESS] greater than 10, mean ± SD ESS 14±5), which improved with CPAP (ESS 9.0±5, P<0.01). In 40% of the patients, the arbitrary CPAP pressure was lower than that determined by manual titration. Adherence to a trial of CPAP (longer than 2 h/night) predicted OSA with a sensitivity of 82% and a specificity of 41%; the positive and negative predictive values were 92% and 22%, respectively.
At the time of PSG testing, OSA was present in 91% of the patients who had received empirical CPAP. An empirical CPAP provided satisfactory interim treatment for excessive somnolence, despite the fact that the CPAP pressure was suboptimal in 40% of the patients.
PMCID: PMC2676837  PMID: 17464380
Continuous positive airway pressure; CPAP responsiveness; CPAP trial; Empirical CPAP; Obstructive sleep apnea
14.  Efficacy of custom made oral appliance for treatment of obstructive sleep apnea 
Contemporary Clinical Dentistry  2015;6(3):341-347.
oral appliance for the treatment of OSA is considered as an effective, low-risk alternative to CPAP. Demand for oral appliance increases as an alternative for those who cannot tolerate CPAP and refuse surgery. Oral appliances uses the traditional methods to advance the mandible thus modify the posture and their by enlarge the airway or otherwise reduce the collapsibility.
Aims and Objectives:
The main objective of this study was to evaluate the efficacy of custom made oral appliance on sleep characteristics of OSA patients. Materials and Methods: Polysomnography was done on 15 patients of 24-60 years of age before (T1), and after the delivery of the custom made oral appliance (T2).
Statistical Analysis:
Paired t tests were performed to determine the significance of change in the polysomnographic and cephalometric variables. P < 0.05 was considered as significant. Results: All patients with oral appliance showed an improvement in sleep parameters with an increase in sleep efficiency, and desaturation index with the use of oral appliance. ESS and cephalometric findings showed improvement in the sleep apnea in concordance with the sleep parameters.
Custom made oral appliance is a useful treatment option for improving quality of sleep and can be considered as an alternative treatment modality.
PMCID: PMC4549985  PMID: 26321833
Continuous positive airway pressure; obstructive sleep apnea; obstructive sleep apnea appliance
15.  Continuous positive airway pressure reduces daytime sleepiness in mild to moderate obstructive sleep apnoea: a meta‐analysis 
Thorax  2006;61(5):430-434.
Obstructive sleep apnoea syndrome (OSAS) affects an estimated 2–4% of the middle aged population. Meta‐analyses of randomised controlled trials have shown that the severe presentation of the syndrome (apnoea hypopnoea index (AHI) >30/hour) is effectively treated with continuous positive airway pressure (CPAP). Until recently there have been insufficient data to determine whether CPAP improves sleepiness in the larger subgroup with mild to moderate OSAS (AHI 5–30/hour).
A systematic search of Medline and a hand search identified seven randomised controlled trials where CPAP was compared with either a placebo or with conservative management in the treatment of mild to moderate OSAS (AHI 5–30/hour). All trials used the Epworth Sleepiness Scale (ESS), four used the Multiple Sleep Latency Test (MSLT), and three used the Maintenance of Wakefulness Test (MWT) to measure sleepiness.
Meta‐analyses indicated that CPAP significantly reduced subjective daytime sleepiness (ESS) by 1.2 points (95% CI 0.5 to 1.9, p = 0.001), improved objective daytime wakefulness (MWT) by 2.1 minutes (95% CI 0.5 to 3.7, p = 0.011), but did not affect objective daytime sleepiness (MSLT, mean benefit −0.2 minutes, 95% CI −1.0 to 0.6, p = 0.6). The two significant effects were small (effect size <0.30).
CPAP elicits small improvements in subjective sleepiness and objective wakefulness in people with mild to moderate OSAS. However, the effects on sleepiness are of limited clinical significance.
PMCID: PMC2111183  PMID: 16467072
continuous positive airway pressure; obstructive sleep apnoea; meta‐analysis
16.  Randomised study of three non‐surgical treatments in mild to moderate obstructive sleep apnoea 
Thorax  2006;62(4):354-359.
Patients with mild to moderate obstructive sleep apnoea (OSA) may be managed with different treatment options. This study compared the effectiveness of three commonly used non‐surgical treatment modalities.
Subjects with mild to moderate OSA were randomised to one of three treatment groups for 10 weeks: conservative measures (sleep hygiene) only, continuous positive airways pressure (CPAP) in addition to conservative measures or an oral appliance in addition to conservative measures. All overweight subjects were referred to a weight‐reduction class. OSA was assessed by polysomnography. Blood pressure was recorded in the morning and evening in the sleep laboratory. Daytime sleepiness was assessed with the Epworth Sleepiness Scale. Health‐related quality of life (HRQOL) was assessed with the 36‐Item Short‐Form Health Survey (SF‐36) and Sleep Apnoea Quality of Life Index (SAQLI).
101 subjects with a mean (SEM) apnoea–hypopnoea index (AHI) of 21.4 (1.1) were randomised to one of the three groups. The severity of sleep‐disordered breathing was decreased in the CPAP and oral appliance groups compared with the conservative measures group, and the CPAP group was significantly better than the oral appliance group. Relief from sleepiness was significantly better in the CPAP group. CPAP was also better than the oral appliance or conservative measures in improving the “bodily pain” domain, and better than conservative measures in improving the “physical function” domain of SF‐36. Both CPAP and the oral appliance were more effective than conservative measures in improving the SAQLI, although no difference was detected between the CPAP and oral appliance groups. CPAP and the oral appliance significantly lowered the morning diastolic blood pressure compared with baseline values, but there was no difference in the changes in blood pressure between the groups. There was also a linear relationship between the changes in AHI and body weight.
CPAP produced the best improvement in terms of physiological, symptomatic and HRQOL measures, while the oral appliance was slightly less effective. Weight loss, if achieved, resulted in an improvement in sleep parameters, but weight control alone was not uniformly effective.
PMCID: PMC2092459  PMID: 17121868
17.  Long-term oral appliance therapy in obstructive sleep apnea syndrome: a controlled study on dental side effects 
Clinical Oral Investigations  2012;17(2):475-482.
This study aimed to assess possible dental side effects associated with long-term use of an adjustable oral appliance compared with continuous positive airway pressure (CPAP) in patients with the obstructive sleep apnea syndrome and to study the relationship between these possible side effects and the degree of mandibular protrusion associated with oral appliance therapy.
Materials and methods
As part of a previously conducted RCT, 51 patients were randomized to oral appliance therapy and 52 patients to CPAP therapy. At baseline and after a 2-year follow-up, dental plaster study models in full occlusion were obtained which were thereupon analyzed with respect to relevant variables.
Long-term use of an oral appliance resulted in small but significant dental changes compared with CPAP. In the oral appliance group, overbite and overjet decreased 1.2 (±1.1) mm and 1.5 (±1.5) mm, respectively. Furthermore, we found a significantly larger anterior–posterior change in the occlusion (−1.3 ± 1.5 mm) in the oral appliance group compared to the CPAP group (−0.1 ± 0.6 mm). Moreover, both groups showed a significant decrease in number of occlusal contact points in the (pre)molar region. Linear regression analysis revealed that the decrease in overbite was associated with the mean mandibular protrusion during follow-up [regression coefficient (β) = −0.02, 95 % confidence interval (−0.04 to −0.00)].
Oral appliance therapy should be considered as a lifelong treatment, and there is a risk of dental side effects to occur.
Clinical relevance
Patients treated with the oral appliance need a thorough follow-up by a dentist or dental-specialist experienced in the field of dental sleep medicine.
PMCID: PMC3579417  PMID: 22562077
CPAP; Obstructive sleep apnea syndrome; Oral appliance; Side effects; Study models; Therapy
18.  Randomised controlled crossover trial of humidified continuous positive airway pressure in mild obstructive sleep apnoea 
Thorax  2005;60(5):427-432.
Background: It is unclear whether continuous positive airway pressure (CPAP), the treatment of choice for severe obstructive sleep apnoea (OSA), is effective at improving outcomes in mild OSA.
Methods: To help define the role of humidified CPAP in mild OSA, a randomised crossover study was undertaken of patients with an apnoea hypopnoea index (AHI) of 5–30/hour. Subjective sleepiness, objective wakefulness, mood, reaction time, and quality of life were measured at baseline, after 3 weeks treatment with humidified CPAP and 3 weeks sham CPAP (2 week washout).
Results: Twenty nine of 31 enrolled patients (age 25–67 years, seven women, mean (SD) body mass index 31.5 (6) kg/m2) completed the protocol. Humidified CPAP improved polysomnographic indices of OSA and Epworth Sleepiness Scale (2.4 points (95% CI 0.6 to 4.2)). Objective wakefulness (modified maintenance of wakefulness test) showed a trend towards improvement (5.2 minutes (95% CI –0.6 to 11)). Mood (Hospital Anxiety and Depression Scale), quality of life (SF 36, Functional Outcomes of Sleep Questionnaire), and reaction times (Psychomotor Vigilance Task) were not improved more than sham CPAP. Compliance with humidified and sham CPAP both averaged 4.9 hours/night. Placebo effects were evident in many outcomes and there was no clear treatment preference.
Conclusions: Humidified CPAP improves subjective sleepiness and possibly objective wakefulness but not reaction times, quality of life, or mood. These results do not support the routine use of CPAP in all patients with mild OSA, but offers some support for the trialling of CPAP in those with severe sleepiness.
PMCID: PMC1758913  PMID: 15860720
19.  Health effects of identifying patients with undiagnosed obstructive sleep apnea in the preoperative clinic: a follow-up study 
Canadian Journal of Anaesthesia  2012;59(6):544-555.
Undiagnosed obstructive sleep apnea (OSA) is a highly prevalent breathing disorder. The purpose of this study was to determine the effects of preoperative screening and subsequent treatment for OSA on the health of patients.
We conducted a two-year follow-up study of patients previously enrolled in a large prospective study in which patients were given the STOP questionnaire for OSA screening (n = 2,467). All patients who underwent a polysomnography were considered eligible (n = 211) and were asked to complete a paper-based mailed questionnaire. The severity of OSA, comorbidities, and treatment modalities and their effects were evaluated from the returned questionnaire. Research ethics board approval was obtained and returning the questionnaire implied informed patient consent.
The response rate was 67%. One hundred twenty-eight (82%) of the 156 patients who responded had OSA established by polysomnography. Among these 128 patients with OSA, 88 (69%) were prescribed continuous positive airway pressure (CPAP) therapy and 40 (31%) were prescribed other (non-CPAP) treatment. Among those 88 patients receiving CPAP, 40 (45%) were compliant and 48 (55%) were non-compliant. The CPAP compliant patients had a greater reduction in medication for comorbidities than the CPAP non-compliant or the other treatment group (38% vs 3% vs 0%, respectively; P < 0.001). A significant improvement in snoring, sleep quality, and daytime sleepiness was reported by CPAP compliant users compared with CPAP non-compliant or other treatment groups (P < 0.001).
The preoperative patients who were identified to have OSA and were compliant with CPAP use may have health benefits in terms of improved snoring, sleep quality, and daytime sleepiness. Timely diagnosis and treatment compliance may reduce symptoms of OSA and severity of associated comorbidities along with a reduction in medications.
PMCID: PMC3345111  PMID: 22461134
Medicine & Public Health; Pediatrics; Cardiology; Anesthesiology; Pain Medicine; Pneumology/Respiratory System; Intensive / Critical Care Medicine
20.  Two months follow up of auto-CPAP treatment in patients with obstructive sleep apnoea 
Thorax  1999;54(2):147-149.
BACKGROUND—Continuous positive airway pressure (CPAP) with fixed mask pressure is the current standard treatment for obstructive sleep apnoea (OSA). Auto-CPAP devices apply at any time the minimally required pressure to normalise breathing and may improve patient comfort and compliance. We present an open descriptive study of auto-CPAP treatment at home in patients previously managed with conventional CPAP.
METHODS—Fifteen patients with obstructive sleep apnoea (OSA), previously treated for at least one year with standard CPAP, were followed prospectively for a two month period on auto-CPAP. Outcome measures were both subjective evaluation by the patients and objective (polysomnographic) data obtained at one and two months of follow up.
RESULTS—The Epworth sleepiness score did not change significantly between baseline and follow up after one and two months and no systematic changes in CPAP related side effects were reported. Compared with the baseline polysomnographic values without treatment, a significant improvement in both respiratory and sleep parameters was observed during auto-CPAP. These results were not significantly different from those obtained with standard CPAP. A significant correlation was found between the effective CPAP pressure (Peff) and the amount of time spent below Peff during auto-CPAP treatment (r = 0.6,p = 0.01).
CONCLUSION—Long term auto-CPAP treatment in these patients with severe OSA appears to provide comparable efficacy to that of standard CPAP treatment.

PMCID: PMC1745422  PMID: 10325921
21.  Insulin Resistance in Moderate to Severe Obstructive Sleep Apnea in Nondiabetics and Its Response to Continuous Positive Airway Pressure Treatment 
The effects of nasal continuous positive airway pressure (CPAP) on insulin resistance (IR) in obstructive sleep apnea (OSA) are still under discussion especially in nondiabetics. Trials have found conflicting results in this regard.
The study was to measure IR in nondiabetic patients with moderate to severe OSA and to evaluate the effect of nasal CPAP on IR in these patients.
Materials and Methods:
A total of 30 consecutively newly diagnosed patients with moderate to severe OSA was enrolled in the study. OSA was diagnosed by doing an overnight polysomnography. Plasma glucose and insulin levels were measured at baseline and after 1 month of CPAP treatment. IR was calculated by homeostasis model assessment (HOMA) method.
Of 30 OSA patients, 21 were males, and 9 were females. The mean age of the subjects was 49.9 years, and mean body mass index (BMI) was 29.33. All 30 patients had moderate to severe OSA with a mean apnea and hypopnea index (AHI) of 80.46/h. The Epworth sleepiness score (ESS) showed a significant change with 1 month of treatment with CPAP from baseline of 13 to 9.7 (P ≤ 0.0001). There was a significant reduction in fasting insulin levels from 21.75 to 19.39 (P = 0.009). There was a small fall in fasting glucose, but it was not significant. The HOMA IR also reduced from 5.78 to 4.82 which was significant (P = 0.024) without any significant change in BMI (P = 0.916). The HOMA IR did not showed any positive correlation with different variables of OSA severity, ESS (r = 0.156) (P = 0.410), AHI (r = 0.177) (P = 0.349), and percentage of test time <90% saturation (r = −0.296) (P = 0.112).
Moderate to severe OSA is associated with an increase in IR and effective treatment with CPAP rapidly improves the insulin sensitivity in nondiabetic patients with OSA without any change in BMI.
PMCID: PMC4215486  PMID: 25489561
Continuous positive airway pressure; Insulin resistance; Obstructive sleep apnea
22.  A multicenter evaluation of oral pressure therapy for the treatment of obstructive sleep apnea 
Sleep medicine  2013;14(9):830-837.
We aimed to evaluate the impact of a novel noninvasive oral pressure therapy (OPT) (Winx®, ApniCure) system on polysomnographic measures of sleep-disordered breathing, sleep architecture, and sleep stability in obstructive sleep apnea (OSA).
Subjects and methods
A 4-week, multicenter, prospective, open-label, randomized, crossover, first-night order of control vs treatment, single-arm trial was conducted in five American Academy of Sleep Medicine (AASM) – accredited sleep clinics and one research laboratory. Sixty-three subjects (analysis cohort) were studied from a screening cohort of 367 subjects. The analysis cohort was 69.8% men, ages 53.6 ± 8.9 years (mean ± SD), body mass index of 32.3 ± 4.5 kg/m2, with mild to severe OSA. At treatment initiation, subjects received random assignment to one night with and one without (control) treatment, and they were assessed again following 28 nights of treatment. Breathing and sleep architecture were assessed each night based on blind scoring by a single centralized scorer using AASM criteria.
Average nightly usage across the take-home period was 6.0 ± 1.4 h. There were no severe or serious device-related adverse events (AEs). Median apnea–hypopnea index (AHI) was 27.5 events per hour on the control night, 13.4 events per hour on the first treatment night, and 14.8 events per hour after 28 days of treatment. A clinically significant response (treatment AHI ≤10/h and ≤50% of control values) was seen in 20 of the 63 subjects evaluated. Rapid eye movement percentage (REM%) was significantly increased, and N1%, stage shifts to N1 sleep, overall stage shifts, total awakenings, and arousals per hour were all significantly reduced at both treatment nights compared to controls. Mean Epworth sleepiness scale (ESS) was significantly reduced from 12.1 to 8.6 (Cohen d effect size, 0.68) in those untreated for two or more weeks prior to OPT study participation and remained unchanged in subjects who directly switched from continuous positive airway pressure (CPAP) therapy to OPT.
Clinically significant improvements in sleep quality and continuity, AHI, ODI, ESS, and overall clinical status were achieved in an easily identified subgroup. OPT was safe and well-tolerated and nightly usage was high.
PMCID: PMC3932027  PMID: 23871259
Oral pressure therapy; Obstructive sleep apnea; AHI; ODI; Compliance; Epworth sleepiness scale
23.  Prevalence of Obstructive Sleep Apnea Syndrome and CPAP Adherence in the Elderly Chinese Population 
PLoS ONE  2015;10(3):e0119829.
This study assessed the prevalence of obstructive sleep apnea syndrome (OSAS) and CPAP adherence in the elderly Chinese in Hong Kong.
We conducted a sleep questionnaire survey among the elders aged ≥60 years in the community centres followed by level 3 home sleep study (Embletta). Subjects with an apnea hypopnea index (AHI) ≥ 15/hr alone and those with AHI ≥ 5/hr plus either cardiovascular risk factors or Epworth Sleepiness Score (ESS) ≥ 10 were offered CPAP treatment.
Altogether 819 subjects were interviewed with mean (SD) age of 73.9 (7.5) years, BMI 24.2 (3.6) kg/m2, neck circumference 34.9 (3.4) cm and ESS 6.6 (5.2). Daytime sleepiness was reported by 72.4%, snoring loudly 5.1% and witnessed apnea 4%. Among 234 subjects who underwent home sleep study, 156 (66.7%), 102 (43.6%), 70 (29.9%) and 45 (19.2%) had AHI ≥ 5, ≥ 10, ≥ 15 and ≥ 20/hr respectively, with the prevalence increasing with age and BMI. In the sample, 149 subjects (63.7%) were classified as having OSAS, as defined by an AHI ≥ 5/hr with associated symptoms, involving 81 men (74.3%) and 68 women (54.4%). Neck circumference and snoring frequency were the only positive independent factors associated with the AHI and the diagnosis of OSAS. Among 141 subjects who were offered CPAP treatment, 30 accepted CPAP prescription with improvement of ESS and cognitive function over 12 months with CPAP usage of 4.2 (2.2) h/night.
This study showed a high prevalence of OSAS among the community elders in Hong Kong. Home CPAP acceptance was low but there was significant improvement of subjective sleepiness and cognitive function among those on CPAP treatment.
PMCID: PMC4361659  PMID: 25774657
24.  Long-term compliance with continuous positive airway pressure in patients with obstructive sleep apnea 
Continuous positive airway pressure (CPAP) is an effective treatment for obstructive sleep apnea (OSA). However, compliance is a significant problem and has been incompletely assessed in long-term studies.
To assess the long-term compliance of OSA patients with CPAP therapy.
Eighty patients who had had a diagnosis of OSA at least four years previously and received a written prescription for CPAP were evaluated.
Subjects were identified by reviewing sleep laboratory records. Participants were contacted by telephone and were asked to quantitate their CPAP use (hours per night, nights per week) and to evaluate whether there had been improvement in symptoms. Those who commenced but subsequently abandoned therapy and those who never initiated treatment were questioned about their reasons for noncompliance.
Patient demographics included mean (± SD) age (58±11 years), male sex (70 of 80 patients [88%]) and mean apnea-hypopnea index (70±44 events/h). At the time of the interview (64.0±3.7 months after diagnosis), 43 of 80 patients (54%) were still using CPAP and most reported an improvement in symptoms. Twelve of 80 patients (15%) had abandoned CPAP after using it for 10.1±15.5 months, and 25 of 80 patients (31%) had never commenced therapy after initial diagnosis and CPAP titration. Analysis of scores reflecting initial patient sleepiness revealed a significant association of this symptom with subsequent CPAP compliance.
Although many patients with OSA derive subjective benefit from, and adhere to treatment with CPAP, a significant proportion of those so diagnosed either do not initiate or eventually abandon therapy. Initial experience with CPAP appears to be important, reinforcing the need for early education and support in these patients.
PMCID: PMC2679572  PMID: 18949106
CPAP; CPAP compliance; Obstructive sleep apnea
25.  The correlation of anxiety and depression with obstructive sleep apnea syndrome 
Obstructive sleep apnea syndrome (OSAS) is a common sleep disorder characterized by repeated upper airway obstruction during sleep. While respiratory pauses followed by loud snoring and daytime sleepiness are the main symptoms of OSAS, the patients may complain from sleep disruption, headache, mood disturbance, irritability, and memory impairment. However, the association of sleep apnea with anxiety and depression is not completely understood. Adherence to continuous positive airway pressure (CPAP), the treatment of choice for OSAS, may be influenced by psychological conditions, especially claustrophobia. The aim of this study was to evaluate the association of OSAS with anxiety and depression symptoms. This study also investigated the association of anxiety with body mass index (BMI) and the severity of OSAS.
Materials and Methods:
We conducted a cross-sectional study on 178 adult individuals diagnosed with OSAS at the sleep laboratory between September 2008 and May 2012. The participants were interviewed according to a checklist regarding both their chief complaints and other associated symptoms. The psychological status was assessed according to Beck anxiety inventory (BAI) and Beck depression inventory (BDI) scoring. The severity of breathing disorder was classified as mild, moderate, and severe based on apnea–hypopnea index (AHI) which was ascertained by overnight polysomnography. Daytime sleepiness was assessed by Epworth sleepiness scale (ESS).
The mean (SD) age of participants was 50.33 years. In terms of sex, 85.5% of the study population were males and14.4% were females. We found no relation between sex and the symptoms of OSAS. Regarding the frequency of anxiety and depression symptoms, 53.9% of the individuals had some degree of anxiety, while 46.1% demonstrated depressive symptoms. In terms of OSAS severity, this study showed that OSAS severity was associated with the frequency of anxiety, chocking, and sleepiness (P : 0.001). According to polysomnographic results, we found that the majority of patients suffering from anxiety and chocking (66.7% and 71.4%, respectively) had severe OSAS, while only 23.1% of patients with sleepiness had severe OSAS.
Our study showed that the frequency of anxiety in OSAS patients is higher than in the general population regardless of the gender. Furthermore, it is more likely that OSAS patients present with anxiety and depression than the typical symptoms.
PMCID: PMC4061640  PMID: 24949026
Anxiety; depression; obstructive sleep apnea syndrome

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