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1.  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
2.  Validation of the Malay version of Berlin questionaire to identify Malaysian patients for obstructive sleep apnea 
Objective:
To validate the Malay version of Berlin Questionnaire (BQ) as a tool to screen for patients at risk of obstructive sleep apnea (OSA) in primary care
Background:
Most patients with OSA are unrecognised and untreated. Thus, the BQ has been used as a tool to screen for patients at risk for OSA. However, this tool has not been validated in Malay version.
Materials and Methods:
A parallel back-to-back translation method was applied to produce the Malay version (Berlin-M). The Malay version was administered to 150 patients in a tertiary respiratory medical centre.  Concurrent validity of the Berlin-M was determined using the Apnea Hypopnea Index (AHI) as the gold standard measure.  The test-retest reliability and internal consistency of the Berlin-M were determined.
Results:
Most patients were males (64.0%) and majority of them were Malays (63.3%). Based on the sleep study test, 121 (84.0%) were classified as high risk while 23 (16.0%) as low risk using the Apnea Hypopnea Index (AHI) ≥5 as the cutoff point. The test–retest reliability Kappa value showed a good range between 0.864 – 1.000. The Cronbach’s alpha of BQ was 0.750 in category 1 and 0.888 in category 2. The sensitivity and specificity were 92% and 17% respectively.
Conclusion:
The BQ showed high sensitivity (92%) but low specificity (17%). Therefore, though the Berlin-M is useful as a screening tool, it is not a confirmatory diagnostic tool.
PMCID: PMC4170461  PMID: 25606261
obstructive sleep apnoea; Berlin questionnaire; reliability; validity; sensitivity; specificity
3.  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
4.  The Berlin questionnaire screens for obstructive sleep apnea in idiopathic intracranial hypertension 
Background
Obstructive sleep apnea (OSA) may be associated with idiopathic intracranial hypertension (IIH), a disorder most commonly occurring in young obese women. Because polysomnography, the standard test for diagnosing OSA, is expensive and time-consuming, questionnaires have been developed to identify persons with OSA. The Berlin questionnaire (BQ) reliably identifies middle-aged and older persons in the community who are at high-risk for OSA. We aimed to validate the BQ as a screening tool for OSA in IIH patients.
Methods
Patients with newly diagnosed IIH completed the BQ and then underwent diagnostic polysomnography. The BQ was scored as high- or low-risk for OSA, and the diagnosis of OSA was based on polysomnography findings. OSA was defined as an apnea-hypopnea index of ≥5 on polysomnography.
Results
Thirty patients were evaluated [24 women; 15 white, 15 black; age 16–54 years (median 32 years) and BMI 27.3–51.7 kg/m2 (median 39.8 kg/m2)]. Twenty patients (66.7%) had a high-risk BQ score and eighteen (60%) exhibited OSA. Fifteen of 20 (75%) with a high-risk BQ score had OSA, while 3 of 10 (30%) with a low-risk score had OSA (Fisher test, p=0.045). The sensitivity and specificity of the BQ for OSA in IIH patients were 83% and 58%, respectively, whereas the positive predictive value was 75%.
Conclusions
A low-risk BQ score identifies IIH patients who are unlikely to have OSA. Polysomnography should be considered in those with a high-risk score.
doi:10.1097/WNO.0b013e31821a4d54
PMCID: PMC3433717  PMID: 21537196
Idiopathic Intracranial Hypertension; Obstructive Sleep Apnea; Berlin Questionnaire
5.  The effect of adding gender item to Berlin Questionnaire in determining obstructive sleep apnea in sleep clinics 
Annals of Thoracic Medicine  2015;10(1):25-28.
BACKGROUND AND AIM:
We aimed to validate the Turkish version of Berlin Questionnaire (BQ) and developped a BQ-gender (BQ-G) form by adding gender component. We aimed to compare the two forms in defining patients with moderate to severe obstructive sleep apnea (OSA) in sleep clinics.
METHODS:
Four hundred and eighty five consecutive patients, refered to our sleep clinic for snoring, witnessed apnea and/or excessive daytime sleepiness were enrolled to the study. All patients underwent in-laboratory polysomnography (PSG). Patients with sleep efficiency less than 40% and total sleep time less than 4 hours, chronic anxiolitic/sedative drug usage, respiratory tract infection within past two weeks were excluded from the study. All the patients fulfilled BQ. The test and retest for BQ were applied in 15-day interval in 30 patients.
RESULTS:
Totally 433 patients were enrolled to the study (285 male, 148 female). The mean age of the patients was 47,5 ± 10.5 (21-79). 180 patients (41.6%) had apnea-hypopnea index (AHI) ≤ 15, while 253 patients (58,4%) had AHI > 15. The κ value was 48–94 and the the truth value was 69-94% for the test-retest procedure. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and area under the curve AUC were 84.2%, 31.7%, 48.7%, 63.4%, and 0.579 in order for BQ and 79.9 %, 51.7%, 63.2% , 69.6%, and 0.652 for BQ-G.
CONCLUSION:
The results showed that BQ-G is relatively better than BQ in determining moderate to severe OSA in sleep clinics where most of the patients are sleep apneic but both of the tests were found to have insufficient validities in defining moderate to severe OSA in sleep clinics.
doi:10.4103/1817-1737.146856
PMCID: PMC4286840  PMID: 25593603
Breathing sleep disorder; Berlin questionnaire; gender; sleep apnea
6.  Validation of the Persian Version of Berlin Sleep Questionnaire for Diagnosing Obstructive Sleep Apnea 
Background:
Obstructive sleep apnea (OSA) is a common but usually under-diagnosed sleep disorder. Objective diagnosis is based on polysomnography, which is an expensive test. We assessed the reliability and diagnostic accuracy of the Berlin questionnaire (BQ) in diagnosis of OSA in Iranian sleep clinic patients.
Methods:
A cross-sectional linguistic validation study was conducted on consecutive Iranian patients with Persian language attending one sleep clinic in Isfahan (Iran) were studied. Patients completed the Persian BQ (contains 10 questions in 3 categories), developed by forward-backward translation method. The patients underwent an overnight polysomnographic study at the clinic. Apneas/hypopnea index of >5/Hour was considered for diagnosis of OSA.
Results:
One hundred and fifty seven patients (55.4% male, mean age = 52.3 ± 13.6 years) were evaluated. Sleep study confirmed OSA diagnosis in 91.7% of the studied patients. The reliability analysis of the BQ categories showed alpha Cronbach's as 0.70 and 0.50 for category 1 and category 2, respectively. BQ categories 1-3 were positive respectively in 88.5%, 67.5%, and 66.9% of the patients. The BQ and sleep study were in agreement for 82.1% of the cases. The sensitivity, specificity, positive and negative predictive values, and positive, and negative likelihood ratio of the BQ were calculated as 84.0%, 61.5%, 96.0%, 25.8%, 2.18%, and 0.26% respectively.
Conclusions:
BQ is useful as a screening test for diagnosing OSA in Iranian patients with sleep complaints; however, the test cannot be used for rolling out the OSA. Further studies on editing, modifying, and applying the BQ in a larger sample of patients are warranted in our society.
PMCID: PMC3634173  PMID: 23626891
Apnea hypopnea index; Berlin questionnaire; obstructive sleep apnea; Persian version of Berlin questionnaire; reliability and validity
7.  Preliminary validity and reliability of a Thai Berlin questionnaire in stroke patients 
BMC Research Notes  2014;7:348.
Background
Obstructive sleep apnea (OSA) is a major risk factor for stroke. The Berlin Questionnaire (BQ) has been shown to be a valid tool to screen for OSA. The literature has limited data on using the BQ in stroke patients; particularly in Thailand and other developing countries. Here, we aimed to develop a Thai-language Berlin Questionnaire (Thai BQ) and to preliminarily assess construct validity, test-retest reliability and the agreement of the Thai BQ with the Thai Epworth Sleepiness Scale (Thai ESS), another screening tool for OSA.
Methods
A hospital-based cross-sectional study was performed from January to July, 2011. One hundred first-ever stroke patients, including acute and chronic cases, and their caregivers were enrolled. The Thai BQ was developed using the forward-backward translation method. Evaluation of construct validity was done by factor analysis. Internal consistency of the Thai BQ and the Thai ESS were evaluated using Cronbach’s alpha coefficient. Test-retest reliability and the agreement of the Thai BQ and the Thai ESS were evaluated using Cohen’s kappa coefficient.
Results
Factor analysis identified 4 main factors: Factor 1–Snoring behaviour; Factor 2–Sleepiness during driving; Factor 3–Daytime fatigue; and Factor 4–Hypertension or obesity. Cronbach’s alpha coefficient was 0.77 (95% confidence interval (CI) = 0.69-0.83) and Cohen’s kappa coefficient was 0.86 (95% CI = 0.74-0.98) in the Thai BQ. Cronbach’s alpha coefficient was 0.59 (95% CI = 0.45-0.70) and the Cohen’s kappa coefficient was 0.81 (95% CI = 0.60-1.00) in the Thai ESS. The agreement between the Thai ESS and the Thai BQ was fair.
Conclusions
The Thai BQ is a valid and reliable tool to screen for OSA in stroke patients. As factor analysis revealed 4 factors in contrast to the 3 factors in the original BQ, further modification of the Thai BQ is required.
doi:10.1186/1756-0500-7-348
PMCID: PMC4060851  PMID: 24910253
Stroke; Obstructive sleep apnea; Berlin questionnaire; Epworth sleepiness scale; Validity
8.  Validation of the MediByte® type 3 portable monitor compared with polysomnography for screening of obstructive sleep apnea 
BACKGROUND:
Portable monitors are increasingly being used as a diagnostic screening tool for obstructive sleep apnea (OSA), and in-laboratory validation of these devices with polysomnography (PSG) is required.
OBJECTIVE:
To assess the reliability of the MediByte (Braebon Medical Corporation, Canada) type 3 screening device compared with overnight PSG.
METHODS:
To cover a range of OSA severity, a consecutive series of patients wore the screening device while simultaneously undergoing PSG. Data acquired from the screener and PSG were blinded and scored separately. The number of apneas and hypopneas per hour were calculated using recording time (respiratory disturbance index [RDI]) for the MediByte device, and sleep time (apnea-hypopnea index [AHI]) for PSG.
RESULTS:
Data from 73 patients with a mean age of 53 years and body mass index of 32.2 kg/m2 showed high measurement association between the RDI and AHI, with a Pearson correlation of 0.92, accounting for 85% of the variance. Based on Bland-Altman measurement agreement, the mean difference between the RDI and AHI (−5.9±11.2 events/h) indicated screener under-reporting. For an AHI of greater than 15 events/h, the sensitivity and specificity of the screener was 80% and 97%, respectively; for an AHI of greater than 30 events/h, the positive predictive value was 100%, while the negative predictive value was 88%.
CONCLUSION:
The MediByte device accurately identified patients without OSA and had a high sensitivity for moderate-to-severe OSA.
PMCID: PMC3328875  PMID: 21766076
Diagnostic screening; Home sleep testing; Obstructive sleep apnea; OSA screener; PM studies; Portable monitor
9.  Comparison of polysomnographic and portable home monitoring assessments of obstructive sleep apnea in Saskatchewan women 
OBJECTIVES:
To compare a commercially available, level III in-home diagnostic sleep test (Embletta, Embletta USA) and in-laboratory polysomnography (PSG) in women with suspected obstructive sleep apnea (OSA).
METHODS:
Consecutive women scheduled for routine PSG testing for evaluation of clinically suspected OSA and who met inclusion/exclusion criteria, were invited to participate. An in-home Embletta portable monitor test was performed one week before or after diagnostic PSG.
RESULTS:
Forty-seven of 96 women who met the inclusion/exclusion criteria agreed to participate. The mean (± SD) age of the patients was 52.0±11.0 years, with a mean body mass index of 34.86±9.04 kg/m2, and 66% (31 of 47) of patients were at high risk for OSA according to the Berlin score. Paired analysis of the overall population revealed no significant difference in mean apnea/hypopnea index (AHI) between the two diagnostic methods (P=0.475). At an AHI of ≥5, the Embletta test was highly sensitive (90.6%) in determining abnormal versus normal OSA, with a positive predictive value of 82.7%. However, a higher Embletta AHI threshold of ≥10 may be more useful, with a higher level of agreement (kappa coefficient) with PSG testing and a positive predictive value of 92.3%. The in-home study was less useful at distinguishing severe from nonsevere OSA, yielding a sensitivity of 50%.
CONCLUSIONS:
In women believed to be at high-risk for OSA, Embletta in-home sleep testing is useful for the detection of sleep disordered breathing.
PMCID: PMC3267604  PMID: 21969928
Obstructive sleep apnea; Polysomnography; Women
10.  Sleep estimation using BodyMedia's SenseWear™ armband in patients with obstructive sleep apnea 
Annals of Thoracic Medicine  2013;8(1):53-57.
OBJECTIVES:
We aimed to evaluate the validity of the BodyMedia's SenseWear™ Armband (BSA) device in estimating total sleep time (TST) in patients with obstructive sleep apnea (OSA).
METHODS:
Simultaneous overnight recordings of in-laboratory polysomnography (PSG) and BSA were performed on (1) 107 OSA patients (mean age of 45.2 ± 14.3 years, mean apnea hypopnea index of 43 ± 35.7/hr and (2) 30 controls matched with OSA patients for age and body mass index. An agreement analysis between the PSG and BSA scoring results was performed using the Bland and Altman method.
RESULTS:
There was no significant difference in OSA patients between BSA and PSG with regard to TST, total wake time, and sleep efficiency. There was also no significant difference in the controls between BSA and PSG with regard to TST, total wake time, and sleep efficiency. Bland Altman plots showed strong agreement between TST, wake time, and sleep efficiency for both OSA and the controls. The intraclass correlation coefficients revealed perfect agreement between BSA and PSG in different levels of OSA severity and both genders.
CONCLUSION:
The current data suggest that BSA is a reliable method for determining sleep in patients with OSA when compared against the gold standard test (PSG). BSA can be a useful tool in determining sleep in patients with OSA and can be combined with portable sleep studies to determine TST.
doi:10.4103/1817-1737.105720
PMCID: PMC3573559  PMID: 23440703
Actigraphy; armband; polysomnography; portable monitoring; sleep apnea; sleep duration; sleep-disordered breathing; type 4 sleep study
11.  The impact of obstructive sleep apnea variability measured in-lab versus in-home on sample size calculations 
Background
When conducting a treatment intervention, it is assumed that variability associated with measurement of the disease can be controlled sufficiently to reasonably assess the outcome. In this study we investigate the variability of Apnea-Hypopnea Index obtained by polysomnography and by in-home portable recording in untreated mild to moderate obstructive sleep apnea (OSA) patients at a four- to six-month interval.
Methods
Thirty-seven adult patients serving as placebo controls underwent a baseline polysomnography and in-home sleep study followed by a second set of studies under the same conditions. The polysomnography studies were acquired and scored at three independent American Academy of Sleep Medicine accredited sleep laboratories. The in-home studies were acquired by the patient and scored using validated auto-scoring algorithms. The initial in-home study was conducted on average two months prior to the first polysomnography, the follow-up polysomnography and in-home studies were conducted approximately five to six months after the initial polysomnography.
Results
When comparing the test-retest Apnea-hypopnea Index (AHI) and apnea index (AI), the in-home results were more highly correlated (r = 0.65 and 0.68) than the comparable PSG results (r = 0.56 and 0.58). The in-home results provided approximately 50% less test-retest variability than the comparable polysomnography AHI and AI values. Both the overall polysomnography AHI and AI showed a substantial bias toward increased severity upon retest (8 and 6 events/hr respectively) while the in-home bias was essentially zero. The in-home percentage of time supine showed a better correlation compared to polysomnography (r = 0.72 vs. 0.43). Patients biased toward more time supine during the initial polysomnography; no trends in time supine for in-home studies were noted.
Conclusion
Night-to-night variability in sleep-disordered breathing can be a confounding factor in assessing treatment outcomes. The sample size of this study was small given the night-to-night variability in OSA and limited understanding of polysomnography reliability. We found that in-home studies provided a repeated measure of sleep disordered breathing less variable then polysomnography. Investigators using polysomnography to assess treatment outcomes should factor in the increased variability and bias toward increased AHI values upon retest to ensure the study is adequately powered.
doi:10.1186/1755-7682-2-2
PMCID: PMC2639556  PMID: 19121211
12.  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
13.  Obstructive Airway Disease and Obstructive Sleep Apnea: Effect of Pulmonary Function 
Lung  2010;189(1):37-41.
This study sought to determine whether reduced pulmonary function in obstructive airway disease (OAD) is an independent risk factor for obstructive sleep apnea (OSA). This was a prospective observational study conducted at an outpatient pulmonary clinic. Adults with a known diagnosis of COPD/asthma were enrolled as OAD group. Family members without a history of COPD/asthma who accompanied these patients to the clinic were enrolled as a control group. The Berlin Questionnaire (BQ) was used to assess OSA risk in the OAD group and controls. Forced expiratory volume in 1 second (FEV1 % predicted) was determined from spirometry. The subjects at high risk for OSA were referred for a full overnight polysomnogram (PSG). The prevalence of patients with a high risk of OSA was 55.2% in the OAD group, which was higher than in the controls (7.5%, p < 0.0001). OAD subjects had a higher body mass index (BMI) and larger neck circumference than controls (p < 0.01). There was no difference in FEV1 % predicted between the OAD patients at high risk and low risk of OSA. On receiver operator curve (ROC) analysis, FEV1 % predicted was not a significant predictor of high OSA risk. Using logistic regression, FEV1 % predicted had no association with OSA risk. There was no correlation between FEV1 % predicted and total apnea-hypopnea index (AHI), oxygen desaturation index, % time spent below oxygen saturation 90%, and mean oxygen saturation on multiple regression analysis. OSA appears to be common in patients with COPD or asthma in an urban outpatient pulmonary clinic. However, the high prevalence of OSA in OAD patients appears to be due to obesity, and reduced pulmonary function is not an independent risk factor for OSA.
doi:10.1007/s00408-010-9270-3
PMCID: PMC3417329  PMID: 21132554
Asthma; Chronic obstructive pulmonary disease; COPD; Lung; Obstructive sleep apnea; OSA; Pulmonary function
14.  Treating obstructive sleep apnea in adults with epilepsy 
Neurology  2008;71(8):572-577.
Objective:
Small uncontrolled series suggest that treatment of obstructive sleep apnea (OSA) in patients with epilepsy may improve seizure control. Prior to conducting a definitive randomized controlled trial, we addressed critical design issues in a pilot study.
Methods:
We identified a cohort of adult patients with medically refractory epilepsy and coexisting OSA, documented by polysomnography (PSG). After an 8-week baseline period, subjects with OSA were randomized to therapeutic or sham continuous positive airway pressure (CPAP) for 10 weeks. Subjects maintained seizure calendars and antiepileptic drug dosages were held constant.
Results:
Sixty-eight subjects with suspected OSA were enrolled and 35 subjects randomized to therapeutic CPAP (22 subjects) or sham (13 subjects) CPAP. Male gender and an elevated sleep apnea questionnaire score were predictive of OSA on PSG. Nineteen subjects in the therapeutic group and all 13 subjects in the sham group completed the trial. Baseline apnea-hypopnea index (AHI) and CPAP adherence were comparable between groups. A significant reduction in AHI was observed in the therapeutic CPAP group as compared to the sham group. Subjects, study coordinators, and principal investigators were unable to predict treatment allocation.
Conclusions:
This pilot study provided critical information related to study design and feasibility for planning a comprehensive trial to test the hypothesis that treating obstructive sleep apnea in patients with epilepsy improves seizure control.
GLOSSARY
= antiepileptic drugs;
= apnea-hypopnea index;
= body mass index;
= continuous positive airway pressure;
= obstructive sleep apnea;
= polysomnography.
doi:10.1212/01.wnl.0000323927.13250.54
PMCID: PMC2676992  PMID: 18711110
15.  Untreated Sleep-Disordered Breathing: Links to Aging-Related Decline in Sleep-Dependent Memory Consolidation 
PLoS ONE  2014;9(1):e85918.
Background
Increasing age is associated with a decline in cognition and motor skills, while at the same time exacerbating one's risk of developing obstructive sleep apnea (OSA). OSA-related cognitive deficits are highly prevalent and can affect various memory systems including overnight memory consolidation on a motor sequence task.
Thus, the aim of our study was to examine the effect of aging on sleep-dependent motor memory consolidation in patients with and without OSA.
Methods
We studied 44 patients (19–68 years) who had been referred by a physician for a baseline polysomnography (PSG) evaluation. Based on their PSG, patients were assigned either to the OSA group (AHI>5/h), or control (Non-OSA) group (AHI<5/h).
All subjects performed the Psychomotor Vigilance Task (PVT) and the Motor Sequence Learning Task (MST) in the evening and again in the morning after their PSG.
Results
Despite similar learning in the evening, OSA subjects showed significantly less overnight improvement on the MST, both for immediate (OSA −2.7%±2.8% vs. controls 12.2%±3.5%; p = 0.002) and plateau improvement (OSA 4.9%±2.3% vs. controls 21.1%±4.0%; p = 0.001). Within the OSA group, there was a significant negative correlation between overnight MST improvement and age (r2 = 0.3; p = 0.01), an effect that was not observed in the Non-OSA group (r2 = 0.08; p = 0.23)
Conclusions
Consistent with previous research, healthy sleepers demonstrated a higher degree of sleep-dependent overnight improvement on the MST, an effect not mitigated by increasing age. However, the presence of untreated obstructive sleep apnea is associated with an aging-related cognitive deficit, otherwise not present in individuals without OSA. As other research has linked the presence of OSA to a higher likelihood of developing dementia, future studies are necessary to examine if the inhibition of memory consolidation is tied to the onset of neurodegenerative disease.
doi:10.1371/journal.pone.0085918
PMCID: PMC3906012  PMID: 24489679
16.  Prevalence and predictors of headache in patients referred to polysomnography 
Background
The objectives of this study were; (1) to assess the prevalence and frequency of headache in patients referred to polysomnography (PSG) due to a clinical suspicion of obstructive sleep apnea (OSA) or another sleep disturbance and compare with a reference population, and (2) to assess the association of OSA severity with headache and headache frequency.
Methods
A total of 784 participants filled in a headache questionnaire between 2003 and 2009 at the Department of Clinical Neurophysiology, Akershus University Hospital. Of these patients 477 were suspected to have OSA, and 307 had other sleep complaints. We assessed the prevalence of headache and monthly headache frequencies, as well as sleep apnea severity using an apnea-hypopnea index (AHI). The association of headache and monthly headache frequencies with PSG subgroups was assessed using multivariate logistic and ordered logistic regression analysis.
Results
The frequency of headache was not associated with the severity of OSA. Patients referred to a sleep study for any reason had higher odds ratio (OR) for having experienced headache during the past year than population controls after adjustment for age, gender and education, i.e. patients with normal AHI had OR of 3.56, patients with OSA had OR of 3.51, and patients with other sleep disturbances had OR of 3.33. Similarly, the adjusted OR of being in a higher category of monthly headache frequency compared to controls was higher in those with normal AHI (OR 3.42), OSA (OR 3.29), and other sleep disturbances (OR 3.00).
Conclusions
The odds of headache and headache frequency were higher in subjects referred to a PSG for any sleep disturbance independently of OSA, compared to general population controls. However, there was no association between experiencing headache during the past year or headache frequency with OSA severity.
doi:10.1186/1129-2377-14-90
PMCID: PMC3835865  PMID: 24246019
Obstructive sleep apnea; Polysomnography; Headache; Headache frequency
17.  Associations of Moderate to Severe Asthma with Obstructive Sleep Apnea 
Yonsei Medical Journal  2013;54(4):942-948.
Purpose
This study aimed to evaluate the correlation between associating factors of moderate to severe asthma with obstructive sleep apnea (OSA).
Materials and Methods
One hundred and sixty-seven patients who visited the pulmonary and sleep clinic in Severance Hospital presenting with symptoms of sleep-disordered breathing were evaluated. All subjects were screened with ApneaLink. Thirty-two subjects with a high likelihood of having OSA were assessed with full polysomnography (PSG).
Results
The mean age was 58.8±12.0 years and 58.7% of subjects were male. The mean ApneaLink apnea-hypopnea index (AHI) was 12.7±13.0/hr. The mean ApneaLink AHI for the 32 selected high risk patients of OSA was 22.3±13.2/hr, which was lower than the sleep laboratory-based PSG AHI of 39.1±20.5/hr. When OSA was defined at an ApneaLink AHI ≥5/hr, the positive correlating factors for OSA were age, male gender, and moderate to severe asthma.
Conclusion
Moderate to severe asthma showed strong correlation with OSA when defined at an ApneaLink AHI ≥5/hr.
doi:10.3349/ymj.2013.54.4.942
PMCID: PMC3663231  PMID: 23709430
Apnea-hypopnea index; ApneaLink; asthma; obstructive sleep apnea; sleep-disordered breathing
18.  Uvulopalatopharyngoplasty in the Management of Obstructive Sleep Apnea: The Mayo Clinic Experience 
Mayo Clinic Proceedings  2009;84(9):795-800.
OBJECTIVE: To assess the role of uvulopalatopharyngoplasty (UPPP) in the treatment of obstructive sleep apnea (OSA) using polysomnography (PSG) data within 6 months before and after surgery.
PATIENTS AND METHODS: We analyzed PSG and body mass index (BMI) data from patients with OSA who were 18 years or older and who underwent UPPP between January 1, 1988, and August 31, 2006.
RESULTS: Sixty-three patients (51 men [81.0%]; mean ± SD age, 42.1±13.9 years; mean ± SD BMI, 34.9±7.2) underwent PSG a mean ± SD of 50±47 days before and 88.5±34.0 days after UPPP. Surgical cure was defined as a postoperative apnea-hypopnea index (AHI) of 5 or less. Fifteen patients (24%) achieved a surgical cure. Twenty-one patients (33%) had a postoperative AHI of 10 or less, whereas 32 (51%) achieved a 50% or greater reduction in AHI and/or an AHI of 20 or less. No significant changes were noted in BMI before and 6 months after UPPP. Patients who attained an AHI of 5 or less were younger (mean ± SD age, 35.9±13.1 vs 44±13.7 years; P=.05), had lower BMIs (mean ± SD, 30.8±6.5 vs 34.6±6.6; P=.05), and had less severe OSA (mean ± SD AHI, 38.1±33.6 vs 69.6±32.8; P=.004). Of the 48 patients (76%) with a post-UPPP AHI greater than 5, 35 (56%) received continuous positive airway pressure, with a mean reduction in pressure of 1.4 cm H2O (95% confidence interval, -0.4 to -2.4 cm H2O).
CONCLUSION: Independent of changes in BMI, in our retrospective analysis, UPPP achieved an AHI of 5 or less in 24% and an AHI of 10 or less in 33% of patients with OSA who underwent PSG 6 months before and after surgery. In those with residual OSA who received continuous positive airway pressure, the required pressure setting decreased by 1.4 cm H2O.
Independent of changes in body mass index, uvulopalatopharyngoplasty achieved an apnea-hypopnea index of 5 or less in 15 patients and of 10 or less in 21 patients with obstructive sleep apnea (OSA) who underwent polysomnography 6 months before and after surgery. In those with residual OSA who received continuous positive airway pressure, the required pressure setting decreased by 1.4 cm H2O.
PMCID: PMC2735429  PMID: 19720777
19.  Translation and validation of Berlin questionnaire in primary health care in Greece 
Background
The aim of our study was to validate a Greek translation of the Berlin Questionnaire (BQ) for obstructive sleep apnoea syndrome (OSAS) and to explore whether this screening questionnaire could be used to help identify primary care patients at greater risk of having OSAS.
Methods
We recruited 189 patients visiting a primary health care setting on the island of Crete, Greece. They all completed the Greek Version of the BQ. Patients were then referred to a Sleep Disorders Unit for evaluation of suspected sleep-disordered breathing.
Results
A PSG study was performed in 129 of the 189 subjects (68.3%). BQ identified 74.4% (n = 96) of the patients as high-risk for OSAS and the remaining 25.6% (n = 33) as low-risk. The sensitivity and specificity of BQ for OSAS diagnosis were 76% and 40%, respectively, for an apnoea–hypopnoea index (AHI) ≥5 per hour but <15 per hour, 84% and 61% for an AHI ≥15 per hour but ≤30 per hour, and 79% and 39% for an AHI >30 per hour.
Conclusions
In conclusion, the Greek Version of the BQ is a useful instrument for identifying patients at risk for OSAS in primary health care in Greece. The findings of our study confirm that such screening tools should be used by primary care clinicians for OSAS prediction.
doi:10.1186/1471-2466-13-6
PMCID: PMC3561101  PMID: 23347772
Berlin questionnaire; Obstructive sleep apnoea syndrome; Primary care patients; Screening tool; Greece; validation
20.  Non drowsy obstructive sleep apnea as a potential cause of resistant hypertension: a case report 
Background
Obstructive sleep apnea (OSA) and arterial hypertension (AH) are common and underrecognized medical disorders. OSA is a potential risk factor for the development of AH and/or may act as a factor complicating AH management. The symptoms of excessive daytime sleepiness (EDS) are considered essential for the initiation of continuous positive airway pressure (CPAP) therapy, which is a first line treatment of OSA. The medical literature and practice is controversial about the treatment of people with asymptomatic OSA. Thus, OSA patients without EDS may be left at increased cardiovascular risk.
Case presentation
The report presents a case of 42year old Asian woman with symptoms of heart failure and angina like chest pain upon admission. She didnt experience symptoms of EDS, and the Epworth Sleepiness Scale was seven points. Snoring was reported on direct questioning. The patient had prior medical history of three unsuccessful pregnancies complicated by gestational AH and preeclampsia with C-section during the last pregnancy. The admission blood pressure (BP) was 200/120mm Hg. The patients treatment regimen consisted of five hypotensive medications including diuretic. However, a target BP wasnt achieved in about one and half month. The patient was offered to undergo a polysomnography (PSG) study, which she rejected. One month after discharge the PSG study was done, and this showed an apnea-hypopnea index (AHI) of 46 events per hour. CPAP therapy was initiated with a pressure of 11H20cm. After 2months of compliant CPAP use, adherence to pharmacologic regimen and lifestyle modifications the patients BP decreased to 134/82mm Hg.
Conclusions
OSA and AH are common and often underdiagnosed medical disorders independently imposing excessive cardiovascular risk on a diseased subject. When two conditions coexist the cardiovascular risk is likely much greater. This case highlights a possible clinical phenotype of OSA without EDS and its association with resistant AH. Most importantly a good hypotensive response to medical treatment in tandem with CPAP therapy was achieved in this patient. Thus, it is reasonable to include OSA in the differential list of resistant AH, even if EDS is not clinically obvious.
doi:10.1186/1471-2466-12-16
PMCID: PMC3355001  PMID: 22533344
Sleep Apnea; Arterial Hypertension; Resistant Hypertension; Obesity
21.  Childhood Obstructive Sleep Apnea Associates with Neuropsychological Deficits and Neuronal Brain Injury 
PLoS Medicine  2006;3(8):e301.
Background
Childhood obstructive sleep apnea (OSA) is associated with neuropsychological deficits of memory, learning, and executive function. There is no evidence of neuronal brain injury in children with OSA. We hypothesized that childhood OSA is associated with neuropsychological performance dysfunction, and with neuronal metabolite alterations in the brain, indicative of neuronal injury in areas corresponding to neuropsychological function.
Methods and Findings
We conducted a cross-sectional study of 31 children (19 with OSA and 12 healthy controls, aged 6–16 y) group-matched by age, ethnicity, gender, and socioeconomic status. Participants underwent polysomnography and neuropsychological assessments. Proton magnetic resonance spectroscopic imaging was performed on a subset of children with OSA and on matched controls. Neuropsychological test scores and mean neuronal metabolite ratios of target brain areas were compared.
Relative to controls, children with severe OSA had significant deficits in IQ and executive functions (verbal working memory and verbal fluency). Children with OSA demonstrated decreases of the mean neuronal metabolite ratio N-acetyl aspartate/choline in the left hippocampus (controls: 1.29, standard deviation [SD] 0.21; OSA: 0.91, SD 0.05; p = 0.001) and right frontal cortex (controls: 2.2, SD 0.4; OSA: 1.6, SD 0.4; p = 0.03).
Conclusions
Childhood OSA is associated with deficits of IQ and executive function and also with possible neuronal injury in the hippocampus and frontal cortex. We speculate that untreated childhood OSA could permanently alter a developing child's cognitive potential.
Childhood obstructive sleep apnea is associated with deficits of IQ and executive function and also with possible neuronal injury in the hippocampus and frontal cortex.
Editors' Summary
Background.
Sleep is essential for health, and in children it is crucial to normal development. Symptomatic childhood sleep-disordered breathing (SDB) is the name for a range of conditions in which children have difficulties with breathing when they are asleep. The conditions range from simple snoring to the most severe condition, known as obstructive sleep apnea (OSA). Apnea means a temporary absence of breathing, and in OSA this is caused by a temporary but repeated blockage of the flow of air to the lungs. In children, OSA occurs for a number of reasons including enlarged tonsils, long-term allergy, and obesity. About two in every hundred children have OSA. The symptoms of OSA are loud snoring at night, disrupted, restless sleep, undue tiredness, and difficulties in concentration. The main test for it is a sleep study (polysomnography). If untreated, researchers believe that it may lead to a number of long-term problems with health and learning; children with disorders of sleep have been shown to have memory problems, lower general intelligence, and worse executive function (the ability to adapt to new situations), and may have behavioral problems similar to those of attention deficit hyperactivity disorder (ADHD).
Why Was This Study Done?
Adults with sleep apnea have been shown to have abnormalities of parts of their brain, specifically the frontal cortex, cerebellum, and hippocampus, but so far there are no data on whether there are similar changes in children. Children with sleep apnea may have cognitive deficits, but the research on this topic is limited.
What Did the Researchers Do and Find?
The researchers wanted to investigate the brains of children with OSA to see if there was any evidence of changes in the brain and if these changes were associated with any learning problems. They studied 31 children (19 with OSA and 12 healthy controls, aged 6–16 y). Participants underwent polysomnography and neuropsychological assessments, such as IQ tests and tests of their ability to perform tasks involving decision making. Some of the children also had specialized scans of their brains (known as proton magnetic resonance spectroscopic imaging) that can measure the levels of certain metabolites—substances that are produced as a result of brain activity. The researchers then compared the neuropsychological test scores with the levels of the metabolites. They found that relative to controls, children with severe OSA had lower IQ and ability to perform tasks involving decision making. Children with OSA also had changes in metabolites in the brain similar to those seen in diseases in which there is damage to brain cells.
What Do These Findings Mean?
It seems clear that OSA in children is associated with learning problems, and that these learning problems may in turn be associated with changes in brain metabolites. The changes in metabolites are not necessarily permanent—in other diseases where changes have been found they can be reversed with treatment. If these results are confirmed in other children with OSA, it will highlight the importance of treating children for OSA as soon as possible. In addition, the measurement of metabolites may be a way of measuring how well children are responding to treatment.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030301.
MedlinePlus's encyclopedia has an entry on sleep apnea
The American Sleep Apnea Association has information about having a child investigated for sleep apnea
The National Sleep Foundation also provides information about sleep disorders
doi:10.1371/journal.pmed.0030301
PMCID: PMC1551912  PMID: 16933960
22.  Correlation between Obstructive Sleep Apnea Syndrome and Cardiac Disease Severity 
Background. Obstructive sleep apnea (OSA) syndrome is one of the most common respiratory disorders in humans. There is emerging evidence linking OSA to vascular disease, particularly hypertension. The underlying pathophysiological mechanisms that link OSA to cardiovascular diseases such as hypertension, congestive heart failure, and atrial fibrillation are not entirely understood. The aim of this study was to investigate the association of obstructive sleep apnea hypopnea syndrome (OSAHS) with coronary atherosclerotic disease (CAD). Methods. A questionnaire survey based on Berlin questionnaire and Epworth Sleepiness Scale (ESS) was conducted among 406 patients to assess demographic data and the symptoms, such as excessive daytime sleepiness and snoring. Epworth Sleepiness Scale and Berlin questionnaire were completed by all of the patients. Venous blood samples were obtained for biochemical tests. Characteristics of coronary arteries were collected from angiographies' reports. All patients were divided into two groups based on results from Berlin questionnaire: low risk patients for OSA and high risk patients for OSA. Data were analyzed by SPSS software version 13. Results. Mean age of patients was 61.8 ± 10.5. 212 (52.2%) patients were categorized as high risk group for apnea. Also, excessive daytime sleepiness was reported in 186 patients (45.8%). The severity of coronary artery involvement, daytime sleepiness, and electrocardiogram abnormalities was significantly higher in high risk patients for OSA compared with low risk patients. High risk patients had higher level of FBS and LDL and lower level of HDL cholesterol (P < 0.05). Conclusion. Our study found a strong correlation between the number of stenotic vessels and OSA. Based on our findings, OSA can be a predisposing factor for cardiac diseases.
doi:10.1155/2014/631380
PMCID: PMC3950406  PMID: 24701348
23.  Validity and reliability of the Malay version of sleep apnea quality of life index – preliminary results 
Background
The objective of this study was to determine the validity and reliability of the Malay translated Sleep Apnea Quality of Life Index (SAQLI) in patients with obstructive sleep apnea (OSA).
Methods
In this cross sectional study, the Malay version of SAQLI was administered to 82 OSA patients seen at the OSA Clinic, Hospital Universiti Sains Malaysia prior to their treatment. Additionally, the patients were asked to complete the Malay version of Medical Outcomes Study Short Form (SF-36). Twenty-three patients completed the Malay version of SAQLI again after 1–2 weeks to assess its reliability.
Results
Initial factor analysis of the 40-item Malay version of SAQLI resulted in four factors with eigenvalues >1. All items had factor loadings >0.5 but one of the factors was unstable with only two items. However, both items were maintained due to their high communalities and the analysis was repeated with a forced three factor solution. Variance accounted by the three factors was 78.17% with 9–18 items per factor. All items had primary loadings over 0.5 although the loadings were inconsistent with the proposed construct. The Cronbach’s alpha values were very high for all domains, >0.90. The instrument was able to discriminate between patients with mild or moderate and severe OSA. The Malay version of SAQLI correlated positively with the SF-36. The intraclass correlation coefficients for all domains were >0.90.
Conclusions
In light of these preliminary observations, we concluded that the Malay version of SAQLI has a high degree of internal consistency and concurrent validity albeit demonstrating a slightly different construct than the original version. The responsiveness of the questionnaire to changes in health-related quality of life following OSA treatment is yet to be determined.
doi:10.1186/1477-7525-11-100
PMCID: PMC3710083  PMID: 23786866
24.  Barriers to Pain Management among Adolescents with Cancer 
Patient-related barriers to reporting pain and using analgesics (e.g., fear of addiction) can detrimentally affect pain management for adolescents with cancer. However, adolescent barriers have not been systematically investigated; furthermore, no instrument exists to measure these barriers. The purposes of this study were to examine the psychometric properties of the newly developed Adolescent Barriers Questionnaire (ABQ) and to describe adolescent barriers to pain management. The study was guided by a barriers model which suggests that barriers (beliefs) influence coping (hesitation to report pain and use analgesics, and adequacy of analgesics), which in turn affects outcomes (pain severity and quality of life). Sixty adolescent patients with cancer aged 12 to 17 years completed the ABQ; twenty-two of which reported pain and also completed measures of hesitation, analgesic use, pain severity, and physical and psychosocial function. Initial testing provided evidence that the ABQ is reliable and valid. Internal consistency estimates for the total scale ranged from 0.91 to 0.94, and for the subscales ranged from 0.54 to 0.96. Test-retest reliability over a 2-week period was r = 0.82. Construct validity was supported by a significant positive relationship between barriers scores and coping (hesitation to report pain and use analgesics). However, coping did not mediate the relationship between barriers and outcomes. All the adolescents reported some barriers. Barriers scores did not vary by age or gender. The leading barrier was concern that social activities would be restricted if pain was reported. Clearly, adolescents have barriers that can interfere with pain management. Interventions are needed to identify and help adolescents overcome these barriers.
doi:10.1016/j.pmn.2009.05.006
PMCID: PMC3011937  PMID: 21095597
Adolescents; Barriers; Pain management; Pain; Cancer
25.  Oral Appliances for Obstructive Sleep Apnea 
Executive Summary
Objective
The objective of this review was to determine the clinical effectiveness of oral appliances compared to ‘no treatment’, continuous positive airway pressure (CPAP), or surgery for the management of obstructive sleep apnea (OSA).
Clinical Need: Condition and Target Population
OSA is characterized by repeated occurrences of upper airway collapse and obstruction during sleep. The condition leads to excessive daytime sleepiness, diminished quality of life, and increased risks of accidents, cardiovascular disease and death. In the general population, the prevalence of OSA is estimated to be 4% in men and 2% in women. Risk factors for OSA include obesity, male gender, increasing age, alcohol use, sedative use, and a family history of OSA.
Description of Oral Appliances
Oral appliances for OSA fall into two broad categories: mandibular advancement splints (MAS), also known as mandibular repositioning devices, and tongue repositioning or retaining devices. The aim of MAS devices is to advance the mandible forward slightly to enlarge the upper airway and prevent it from collapsing. Similarly, tongue repositioning devices suction the tongue forward to prevent it from falling back and obstructing the airway during sleep.
The alternatives to oral appliances include continuous positive airway pressure (CPAP) devices, surgery, drug therapy, positional devices, and lifestyle modification. CPAP is the gold standard of treatment, but despite its effectiveness, compliance rates for CPAP have declined because required systems are noisy and because wearing the mask can be uncomfortable, causing claustrophobia in some users.
Evidence-Based Analysis Methods
Research Questions
Are oral appliances effective in improving sleep-disordered breathing in patients with OSA compared to alternative treatments?
Are there safety concerns with oral appliances?
What is the evidence regarding patient preference, quality of life, and compliance for oral appliances?
If effective, are oral appliances cost effective?
Literature Search
A literature search was conducted up to February 2009. Systematic reviews, meta-analyses and randomized controlled trials (RCTs) with more than 20 adults with OSA were eligible for inclusion. The primary outcomes of interest were the Apnea Hypopnea Index (AHI), measures of daytime sleepiness, patient preference, compliance, and adverse events.
Summary of Findings
Five systematic reviews and 16 RCTs that met the inclusion criteria were identified. The systematic reviews consistently concluded that CPAP was more effective than oral appliances at improving sleep disordered breathing, although there may be a niche area for the latter, especially among those with mild OSA as CPAP is difficult to tolerate by some users.
Based on the results of the RCTs analyzed for this review, MAS devices are less effective than CPAP when AHI is used as the outcome of interest. MAS devices were shown to decrease AHI levels, but whether this reduction is clinically meaningful is uncertain.
The Epworth Sleepiness Scale (ESS) was not able to achieve statistical significance in comparisons of MAS versus CPAP and MAS versus placebo. Nonetheless, after treatment with either MAS or CPAP, patients seem to be able to achieve normal ESS levels. The ESS has substantial limitations including its subjective nature and low construct validity (i.e. it is unclear if the scale is an accurate measure of sleepiness).
Adverse events among patients with MAS devices in the RCTs were common, but mostly mild and transient. Jaw discomfort was the most commonly reported adverse event.
Based on the results of the RCTs, compliance does not seem to be better or worse with MAS or CPAP. Similarly, there is no clear patient preference for MAS or CPAP among the studies reporting preference and satisfaction.
Keywords
Obstructive sleep apnea, oral appliances, mandibular advancement splints, tongue repositioning devices
PMCID: PMC3377505  PMID: 23074535

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