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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
Background
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.
Conclusions
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
Background
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 http://dx.doi.org/10.1371/journal.pmed.1001762.
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)
doi:10.1371/journal.pmed.1001762
PMCID: PMC4244041  PMID: 25423175
2.  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
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.
doi:10.1007/s11325-006-0084-8
PMCID: PMC1794626  PMID: 17136406
Continuous positive airway pressure; Sleep apnea; Oral appliance
5.  Sleep apnea and occupational accidents: Are oral appliances the solution? 
Background:
Dental practitioners have a key role in the quality of life and prevention of occupational accidents of workers with Obstructive Sleep Apnea Syndrome (OSAS).
Aim:
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.
Results:
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.
Conclusion:
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.
doi:10.4103/0019-5278.146887
PMCID: PMC4280775  PMID: 25568596
Continuous positive air pressure; obstructive sleep apnea; occupational accidents; oral appliances; review
6.  Modified Interim Mandibular Advancement (MIMA) Appliance for Symptomatic Correction of Obstructive Sleep Apnea 
Obstructive Sleep Apnea (OSA) is a chronic, progressive, multifactorial, life-threatening disorder that causes significant impact on patient’s life. Patients with OSA [Apnea/Hypopnea Index (AHI)>30] who cannot tolerate Continuous Positive Airway Pressure (CPAP) therapy or are not surgical candidates may benefit from oral appliances. This paper describes interim appliance devised from existing Hawley’s retainer in patients with OSA. A 38-year-old man of athletic built with history of orthodontic treatment six months back due to esthetic concerns and wearing upper Hawley’s retainer, reported with chief complaint of frequent nocturnal awakening along with excessive daytime somnolence. Based on diagnostic aids, he was diagnosed with Class II Division 1 malocclusion with severe mandibular retrusion. Sleep test revealed AHI score of 34, suggestive of severe OSA. With ENT and Oral surgeon concurrence, mandibular advancement of 7mm with Bilateral Sagital Split Osteotomy (BSSO) with distraction was contemplated as a viable functional and curative stable treatment plan. Because of non-adherence and non-compliance with CPAP therapy and on request of patient, an interim anterior positioning appliance was devised to facilitate comfortable sound sleep till the time surgery is impending. After three months of wearing this customized appliance, improved quality of sleep was discernible; both subjectively as reported by patient and objectively using sleep test (AHI=9.8).
doi:10.7860/JCDR/2016/19177.8238
PMCID: PMC5028426  PMID: 27656589
Mandibular advancement devices; Severe sleep apnoea; Skeletal Class II
7.  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
8.  Oral Appliance for the Treatment of Severe Obstructive Sleep Apnea in Edentulous Patient 
Oral appliances have attracted interest for the treatment of mild and moderate obstructive sleep apnea (OSA) and the mandibular repositioning device (MRD) or a tongue-retainer device (TRD) is usually indicated to increase the upper air space. Describes a combination of MRD (with 60 % maximum mandibular protrusion) and TRD to treat severe OSA. Polysomnography (PSG) and two questionnaires: the Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI) evaluated the sleep pattern in two times (after and before the use of oral appliance). The initial PSG exam was compatible with diagnoses severe OSA and the Apnea–Hypopnea Index was 40.4, and 54 % oxygen saturation −spO2. The ESS and PSQI scores were 11 and 6, respectively. After she began wearing the device she stopped snoring, her Apnea–Hypopnea Index decreased to 17.6, presented a sleep efficiency of 81.6 % and had a 77 % spO2. The ESS and PSQI scores dropped to three. MRD in association with the tongue-retainer was effective in reducing the severity of the apnea for this edentulous patient.
doi:10.1007/s13191-013-0312-4
PMCID: PMC4501976  PMID: 26199526
Sleep apnea; Oral appliance; Sleep disturbance
9.  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
10.  Oral appliance treatment in moderate and severe obstructive sleep apnoea patients non‐adherent to CPAP  
Journal of Oral Rehabilitation  2015;43(4):249-258.
Summary
The aim of this retrospective study was to evaluate the effect of individually adjusted custom‐made mandibular advancement device/oral appliance (OA) in treatment of patients with moderate and severe obstructive sleep apnoea (OSA), who were non‐adherent to continuous positive airway pressure (CPAP) therapy. During 2007‐2013, 116 patients with moderate (n = 82) and severe (n = 34) OSA non‐adherent to CPAP treatment were referred for dental management with an individually adjusted OA at a specialist sleep clinic. Ten of the participants (8·6%) were lost to follow‐up, leaving the data set to consist of 106 patients (71 men/35 women, mean age 57 year, range 28‐90). Nocturnal respiratory polygraphic recordings were performed at baseline and follow‐up. Average time between baseline polygraphy and follow‐up was 12 months. A successful OA treatment outcome was based on polygraphy at the follow‐up and divided into three groups: 1 = AHI <5; 2 = 5 ≤ AHI <10 and >50% reduction in baseline AHI; and 3. >50% reduction in baseline AHI. If there was a ≤ 50% reduction in baseline AHI at the follow‐up, the treatment was considered as a failure. The overall treatment success rate was 75%. There was no significant difference in success rates between patients in the moderate and severe categories (69% and 77%, respectively). Low oxygen saturation (SpO2 nadir) had a high predictive value for OA treatment failure. OA treatment of patients non‐adherent to CPAP is efficient and especially promising for the severe OSA group who are at greatest risks for developing serious comorbidities, if left untreated.
doi:10.1111/joor.12376
PMCID: PMC4834725  PMID: 26707632
continuous positive airway pressure; mandibular advancement; medical device; obstructive sleep apnoea; oximetry; somnography
11.  Sleep apnoea 
BMJ Clinical Evidence  2009;2009:2301.
Introduction
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).
Results
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.
Conclusions
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
12.  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.
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1186/1471-2466-14-188
PMCID: PMC4258250  PMID: 25433468
Obstructive sleep apnea; Continuous positive airway pressure therapy; Compliance; Side effects; Pakistan
13.  Treatments for Obstructive Sleep Apnea 
Objective
To review the efficacy of current treatment options for adults with obstructive sleep apnea (OSA).
Methods
Review of the literature.
Results
OSA, characterized by repetitive ≥ 10-second interruptions (apnea) or reductions (hypopnea) in airflow, is initiated by partial or complete collapse in the upper airway despite respiratory effort. When left untreated, OSA is associated with comorbid conditions, such as cardiovascular and metabolic diseases. The current “gold standard” treatment for OSA is continuous positive air pressure (CPAP), which pneumatically stabilizes the upper airways. CPAP has proven efficacy and potential cost savings via decreases in health comorbidities and/or motor-vehicle crashes. However, CPAP treatment is not well-tolerated due to various side effects, and adherence among OSA subjects can be as low as 50% in certain populations. Other treatment options for OSA include improving CPAP tolerability, increasing CPAP adherence through patient interventions, weight loss/exercise, positional therapy, nasal expiratory positive airway pressure, oral pressure therapy, oral appliances, surgery, hypoglossal nerve stimulation, drug treatment, and combining 2 or more of the aforementioned treatments. Despite the many options available to treat OSA, none of them are as efficacious as CPAP. However, many of these treatments are tolerable, and adherence rates are higher than those of the CPAP, making them a more viable treatment option for long-term use.
Conclusion
Patients need to weigh the benefits and risks of available treatments for OSA. More large randomized controlled studies on treatments or combination of treatments for OSA are needed that measure parameters such as treatment adherence, apnea-hypopnea index, oxygen desaturation, subjective sleepiness, quality of life, and adverse events.
PMCID: PMC4847952  PMID: 27134515
14.  Use of CPAP to reduce arterial stiffness in moderate-to-severe obstructive sleep apnoea, without excessive daytime sleepiness (STIFFSLEEP): an observational cohort study protocol 
BMJ Open  2016;6(7):e011385.
Introduction
Sleepiness is a cardinal symptom in obstructive sleep apnoea (OSA) but most patients have unspecific symptoms. Arterial stiffness, evaluated by pulse wave velocity (PWV), is related to atherosclerosis and cardiovascular (CV) risk. Arterial stiffness was reported to be higher in patients with OSA, improving after treatment with continuous positive airway pressure (CPAP). This study aims to assess whether the same effect occurs in patients with OSA and without sleepiness.
Methods and analysis
This observational study assesses the CV effect of CPAP therapy on a cohort of patients with moderate-to-severe OSA; the effect on the subcohorts of sleepy and non-sleepy patients will be compared. A systematic and consecutive sample of patients advised CPAP therapy will be recruited from a single outpatient sleep clinic (Centro Hospitalar de Lisboa Central—CHLC, Portugal). Eligible patients are male, younger than 65 years, with confirmed moderate-to-severe OSA and apnoea–hypopnea index (AHI) above 15/hour. Other sleep disorders, diabetes or any CV disease other than hypertension are exclusion criteria. Clinical evaluation at baseline includes Epworth Sleepiness Scale (ESS), and sleepiness is defined as ESS above 10. OSA will be confirmed by polygraphic study (cardiorespiratory, level 3). Participants are advised to undertake an assessment of carotid-femoral PWV (cf-PWV) and 24 hours evaluation of ambulatory blood pressure monitoring (ABPM), at baseline and after 4 months of CPAP therapy. Compliance and effectiveness of CPAP will be assessed. The main outcome is the variation of cf-PWV over time.
Ethics and dissemination
This protocol was approved by the Ethics Committees of CHLC (reference number 84/2012) and NOVA Medical School (number36/2014/CEFCM), Lisbon. Informed, written consent will be obtained. Its results will be presented at conferences and published in peer-reviewed journals.
Trial registration number
NCT02273089; Pre-results.
doi:10.1136/bmjopen-2016-011385
PMCID: PMC4947760  PMID: 27406645
Obstructive sleep apnea; Sleepiness; Pulse wave velocity; Arterial stiffness
15.  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%.
doi:10.5402/2011/581692
PMCID: PMC3169918  PMID: 21991480
16.  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
17.  Changes in Neurocognitive Architecture in Patients with Obstructive Sleep Apnea Treated with Continuous Positive Airway Pressure 
EBioMedicine  2016;7:221-229.
Background
Obstructive sleep apnea (OSA) is a chronic, multisystem disorder that has a bidirectional relationship with several major neurological disorders, including Alzheimer's dementia. Treatment with Continuous Positive Airway Pressure (CPAP) offers some protection from the effects of OSA, although it is still unclear which populations should be targeted, for how long, and what the effects of treatment are on different organ systems. We investigated whether cognitive improvements can be achieved as early as one month into CPAP treatment in patients with OSA.
Methods
55 patients (mean (SD) age: 47.6 (11.1) years) with newly diagnosed moderate–severe OSA (Oxygen Desaturation Index: 36.6 (25.2) events/hour; Epworth sleepiness score (ESS): 12.8 (4.9)) and 35 matched healthy volunteers were studied. All participants underwent neurocognitive testing, neuroimaging and polysomnography. Patients were randomized into parallel groups: CPAP with best supportive care (BSC), or BSC alone for one month, after which they were re-tested.
Findings
One month of CPAP with BSC resulted in a hypertrophic trend in the right thalamus [mean difference (%): 4.04, 95% CI: 1.47 to 6.61], which was absent in the BSC group [− 2.29, 95% CI: − 4.34 to − 0.24]. Significant improvement was also recorded in ESS, in the CPAP plus BSC group, following treatment [mean difference (%): − 27.97, 95% CI: − 36.75 to − 19.19 vs 2.46, 95% CI: − 5.23 to 10.15; P = 0.012], correlated to neuroplastic changes in brainstem (r = − 0.37; P = 0.05), and improvements in delayed logical memory scores [57.20, 95% CI: 42.94 to 71.46 vs 23.41, 95% CI: 17.17 to 29.65; P = 0.037].
Interpretation
One month of CPAP treatment can lead to adaptive alterations in the neurocognitive architecture that underlies the reduced sleepiness, and improved verbal episodic memory in patients with OSA. We propose that partial neural recovery occurs during short periods of treatment with CPAP.
Highlights
•One month of CPAP treatment leads to adaptive alterations in the neuroanatomy and neurocognition in patients with OSA.•Improvements in sleepiness and verbal episodic memory were demonstrable following only one month of treatment with CPAP.•Our findings support the clinical rationale for the use of CPAP treatment to relieve sleepiness, even for a short duration.
Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder that has been linked with dementia, stroke and increased risks of cardiovascular disease. Continuous positive airway pressure (CPAP) treatment has been shown to be effective in reducing sleepiness in moderate to severe OSA. However, the evidence for its use to reverse or slow the rate of cognitive decline is unclear. Our findings show that one month of CPAP treatment in patients with moderate to severe OSA leads to adaptive alterations in the brain networks associated with reduced sleepiness and improved memory.
doi:10.1016/j.ebiom.2016.03.020
PMCID: PMC4909326  PMID: 27322475
Obstructive sleep apnea; Continuous Positive Airway Pressure; Neuroimaging; Cognition
18.  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
19.  Efficacy of custom made oral appliance for treatment of obstructive sleep apnea 
Contemporary Clinical Dentistry  2015;6(3):341-347.
Introduction:
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.
Conclusions:
Custom made oral appliance is a useful treatment option for improving quality of sleep and can be considered as an alternative treatment modality.
doi:10.4103/0976-237X.161881
PMCID: PMC4549985  PMID: 26321833
Continuous positive airway pressure; obstructive sleep apnea; obstructive sleep apnea appliance
20.  An empirical continuous positive airway pressure trial for suspected obstructive sleep apnea 
BACKGROUND:
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.
OBJECTIVES:
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.
METHODS:
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.
RESULTS:
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.
CONCLUSIONS:
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
21.  Continuous positive airway pressure reduces daytime sleepiness in mild to moderate obstructive sleep apnoea: a meta‐analysis 
Thorax  2006;61(5):430-434.
Background
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).
Methods
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.
Results
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).
Conclusions
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.
doi:10.1136/thx.2005.050583
PMCID: PMC2111183  PMID: 16467072
continuous positive airway pressure; obstructive sleep apnoea; meta‐analysis
22.  Therapeutic outcomes of mandibular advancement devices as an initial treatment modality for obstructive sleep apnea 
Medicine  2016;95(46):e5265.
Abstract
Although continuous positive airway pressure (CPAP) is a highly efficacious treatment for obstructive sleep apnea (OSA), there is a need for alternative treatment options, such as sleep surgeries and mandibular advancement devices (MADs), to overcome the limitations of CPAP.
This study aimed to analyze the therapeutic outcomes of OSA subjects who were treated with a MAD, and to estimate the clinical impact of MAD as a first-line treatment for OSA.
Forty-seven patients diagnosed with OSA received an adjustable MAD as an initial treatment. Drug-induced sleep endoscopic findings and sleep parameters (both pre-MAD and post-MAD treatment), such as apnea index, oxygen saturation, and degree of daytime sleepiness, were assessed retrospectively.
The MAD treatment resulted in a significant reduction in apnea–hypopnea index, and also a significant elevation in lowest oxygen saturation. Satisfactory results of MAD treatment as a first treatment modality were observed in 27 patients, and a successful outcome was reached in approximately 72% of patients. The OSA patients who had lower body mass index and upper airway narrowing at the level of palate and tongue base showed relatively higher rates of a satisfactory outcome even in cases of moderate or severe OSA.
These results suggest that the use of a MAD may be an alternative treatment option in OSA patients with retropalatal and retroglossal area narrowing regardless of disease severity. Additionally, MADs can be recommended as an initial treatment modality, and the effectiveness of MADs in achieving success may not be inferior to CPAP.
doi:10.1097/MD.0000000000005265
PMCID: PMC5120906  PMID: 27861349
initial treatment modality; mandibular advancement device; obstructive sleep apnea; therapeutic outcome
23.  Continuous positive airway pressure therapy in non-sleepy patients with obstructive sleep apnea: results of a meta-analysis 
Journal of Thoracic Disease  2016;8(10):2738-2747.
Background
Although continuous positive airway pressure (CPAP) has become the first line of therapy for obstructive sleep apnea (OSA), it remains controversial whether non-sleepy patients could benefit from CPAP treatment.
Methods
We searched the online databases Medline, Embase, the Cochrane library and the Cochrane Central Registry of Controlled Trials to select eligible control trials, including non-sleepy OSA patients and those patients treated by CPAP or either sham CPAP or no CPAP.
Results
Seven eligible studies (1,541 patients) were included. The pooled estimates of the mean changes after CPAP treatment for the systolic blood pressure (SBP) and diastolic blood pressure (DBP) were −0.51 mmHg (95% CI, −3.39 to 2.38 mmHg; P=0.73) and −0.92 mmHg (95% CI, −1.39 to −0.46 mmHg; P<0.001), respectively. CPAP should not improve subjective sleepiness in the minimally symptomatic OSA patients, as the change in the Epworth sleepiness scale (ESS) was −0.51 (95% CI, −1.68 to 0.67; P=0.397). However, CPAP can effectively reduce AHI or ODI by 15.57 events/h (95% CI, −29.32 to −1.82; P=0.026) compared to controls. However, the risk of cardiovascular events did not significantly decrease [odds ratio (OR), 0.80; 95% CI, 0.50 to 1.26; P=0.332] in the end.
Conclusions
CPAP treatment can reduce OSA severity in non-sleepy patients and minutely reduce the DBP, but CPAP seems to have no overall beneficial effects on subjective sleepiness, SBP, or cardiovascular risk.
doi:10.21037/jtd.2016.09.40
PMCID: PMC5107495  PMID: 27867549
Sleep apnea; obstructive/complications/therapy; continuous positive airway pressure/method (CPAP/method); hypertension; cardiovascular diseases
24.  Continuous Positive Airway Pressure Compliance in Patients with Obstructive Sleep Apnea 
Tanaffos  2016;15(1):25-30.
Background:
Obstructive sleep apnea (OSA) is a common condition in adults. In most cases, first-line therapy includes treatment with positive airway pressure devices. However, because of discomfort, continuous positive airway pressure (CPAP) compliance is often poor. To determine the willingness of patients to use CPAP device, the relationship of demographic and polysomnographic variables with tolerance and the willingness to use CPAP, was evaluated.
Materials and Methods:
In this cross-sectional study, 120 OSA patients who were treated with CPAP in Baqiyatallah Hospital, Tehran, Iran, were selected by convenience sampling. Polysomnographic variables, willingness to use CPAP for short and long periods of time and possible complications were evaluated.
Results:
One hundred-twenty cases with a mean age of 53±10.3 years were assessed. The mean Epworth Sleepiness Scale (ESS) score was 11.9 ± 6.2 in CPAP users versus 11.8±6.1 in patients who did not use CPAP. The willingness to use CPAP for short-term was significantly different between the two groups (P=0.008). The average minimum oxygen saturation rate of patients was 75.21% in CPAP users versus 71.63% in non CPAP users. Also, the average desaturation index was higher in CPAP users (54.5 vs. 44.98). The mean ESS was 14.03 ± 6.19 in those who accepted long-term treatment versus 8.85 ± 4.89 (P=0.003). Skin wounds and rhinitis were reported in 4.1% and 4.1% of patients, respectively.
Conclusion:
It is concluded that high CPAP compliance rates are achievable through comprehensive CPAP therapy.
PMCID: PMC4937758  PMID: 27403175
Sleep Apnea, Obstructive; Continuous Positive Airway Pressure; Compliance
25.  Effect of Acute Intermittent CPAP Depressurization during Sleep in Obese Patients 
PLoS ONE  2016;11(1):e0146606.
Background
Obstructive Sleep Apnea (OSA) describes intermittent collapse of the airway during sleep, for which continuous positive airway pressure (CPAP) is often prescribed for treatment. Prior studies suggest that discontinuation of CPAP leads to a gradual, rather than immediate return of baseline severity of OSA. The objective of this study was to determine the extent of OSA recurrence during short intervals of CPAP depressurization during sleep.
Methods
Nine obese (BMI = 40.4 ± 3.5) subjects with severe OSA (AHI = 88.9 ± 6.8) adherent to CPAP were studied during one night in the sleep laboratory. Nasal CPAP was delivered at therapeutic (11.1 ± 0.6 cm H20) or atmospheric pressure, in alternating fashion for 1-hour periods during the night. We compared sleep architecture and metrics of OSA during CPAP-on and CPAP-off periods.
Results
8/9 subjects tolerated CPAP withdrawal. The average AHI during CPAP-on and CPAP-off periods was 3.6 ± 0.6 and 15.8 ± 3.6 respectively (p<0.05). The average 3% ODI during CPAP-on and CPAP-off was 4.7 ± 2 and 20.4 ± 4.7 respectively (p<0.05). CPAP depressurization also induced more awake (p<0.05) and stage N1 (p<0.01) sleep, and less stage REM (p<0.05) with a trend towards decreased stage N3 (p = 0.064).
Conclusion
Acute intermittent depressurization of CPAP during sleep led to deterioration of sleep architecture but only partial re-emergence of OSA. These observations suggest carryover effects of CPAP.
doi:10.1371/journal.pone.0146606
PMCID: PMC4701426  PMID: 26731735

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