Clete A. Kushida

Comparison of actigraphic, polysomnographic, and subjective assessment of sleep parameters in sleep-disordered patients

OBJECTIVE Comparison of polysomnography (PSG)-derived sleep parameters (total sleep time, sleep efficiency, and number of awakenings) to those derived from actigraphy and subjective questionnaires. BACKGROUND Actigraphy is commonly used to assist sleep specialists in the diagnosis of various sleep and circadian-rhythm disorders. However, few validation studies incorporate large sample sizes, typical sleep clinic patients, or comparisons with subjective reports of sleep parameters. METHODS Clinical series with 100 consecutive sleep-disordered patients (69 men, 31 women, mean age of 49+/-14.7 years) at a tertiary sleep disorders center. Sensitivity, specificity, and accuracy measures were obtained from epoch-by-epoch comparison of PSG and actigraphic data. Subjective sleep parameter data were derived from questionnaires given to subjects in the morning following their recording night. RESULTS We found that total sleep time and sleep efficiency did not significantly differ between PSG data and the combined data obtained from actigraphy and subjective reports. Using a high-threshold (low-wake-sensitivity) actigraphic algorithm, the number of awakenings was not significantly different from those detected by PSG. CONCLUSIONS We recommend the use of subjective data as an adjunct to actigraphic data in estimating total sleep time and sleep efficiency in sleep-disordered patients, especially those with disorders of excessive somnolence.

A Predictive Morphometric Model for the Obstructive Sleep Apnea Syndrome

The obstructive sleep apnea syndrome (OSAS) is a sleep disorder associated with excessive day-time sleepiness; sleep fragmentation; intermittent hypoxia; and increased risk for diurnal hypertension, myocardial infarction, ventricular failure, pulmonary hypertension, cardiac dysrhythmias, and stroke [1]. Recent epidemiologic surveys indicate that this syndrome is seen in at least 4% of men and 2% of women 30 to 60 years of age and that the incidence is higher in the elderly [2]. Polysomnography is used to confirm the diagnosis of OSAS; however, the time and labor needed to perform polysomnography are problematic. A quick and reliable screening test would enable clinicians to detect the possibility of OSAS during initial office visits and then decide which patients are at high risk (and urgently need polysomnography) and which are at low risk (and do not need polysomnography). Previous investigators [3-7] have developed mathematical formulas for the clinical prediction of OSAS. These models used various measures, such as body mass index (BMI), neck circumference, oxygen saturation, witnessed apneas, and questionnaire data. Unfortunately, these models were limited because they did not account for craniofacial dysmorphism or disproportionate craniofacial anatomy [8-14], which are risk factors for the development of OSAS independent of obesity. The craniofacial dysmorphism that leads to OSAS may involve a delayed growth of the mandible, producing the mandibular retroposition [9] commonly found in patients with OSAS. Mandibular retroposition is associated with posterior displacement of the tongue base. This narrows the upper airway, predisposing it to collapse and contributing to the development of OSAS. A high arched palate is also common in patients with OSAS because the posterior tongue displacement may force the lateral palatine processes to expand over the abnormally placed tongue before fusing at the midline. Evidence that these events may occur in patients with OSAS is found in the Robin sequence (the Pierre Robin syndrome) [15-17] and the Treacher Collins syndrome [17, 18], in which early mandibular hypoplasia from maldevelopment of the first branchial arch results in the above sequence of events in infants. The mandibular and palatal abnormalities seen in these infants invariably result in OSAS; not only do these cases provide an embryologic substrate for the craniofacial dysmorphism leading to OSAS, but they represent extremes of the craniofacial dysmorphism seen in adults with OSAS. These observations provide a rationale for including mandibular size and palatal height in our model for OSAS prediction. The utility of any model is directly proportional to its accuracy and ease of use. We present a predictive morphometric model for OSAS that has a high sensitivity, high specificity, and good intermeasurer and test-retest reliability. The necessary measurements and calculations can be completed in an ambulatory setting (such as a clinicians office) within 5 minutes. Methods Model Derivation The morphometric model was developed from a test sample of 30 representative patients who were studied with polysomnography: Fifteen had documented OSAS, and 15 had no evidence of OSAS. The criteria used to diagnose OSAS were 1) characteristic presenting symptoms (such as snoring, nocturnal breathing pauses, and excessive daytime sleepiness [19]; an Epworth Sleepiness Scale score > 10 was used to confirm the presence of excessive daytime sleepiness [20] and 2) a respiratory disturbance index (RDI) score (number of apneas and hypopneas per hour of sleep) of 5 or more on polysomnography. Body mass index and neck circumference were incorporated into the model because univariate linear regression analyses in this study and previous studies [21, 22] indicated that these variables correlated significantly with the RDI. We noted correlation coefficients of 0.54 (P = 0.002) for the RDI compared with BMI and 0.53 (P = 0.002) for the RDI compared with neck circumference. These values are similar to those reported by previous investigators (0.51 for RDI compared with BMI and 0.53 for RDI compared with neck circumference [21]). A model that combines both BMI and neck circumference or that includes oral cavity dimensions has not been previously proposed. Various methods for measuring mandibular size and palatal height were tested for comfort, reproducibility, and rapidity and ease of use. These measurements, plus BMI and neck circumference, ultimately made up the model. Separate prototype versions of the model were developed from different arrangements of these variables on the basis of trial-and-error experimentation and clinical experience, and they were combined with integer weights and mathematical operands. The model divided the test sample of 30 patients into OSAS and non-OSAS groups. The model cutoff value of 70 was calculated from the critical region containing the highest 5% of the non-OSAS group. This value was derived by adding the mean of the non-OSAS group to the product of the SE of the mean and the z-score of the highest 5% of the non-OSAS group by a one-tailed test [23]. An RDI of 5 or more was used as a cutoff value for OSAS; thus, the model treats the RDI as a dichotomous variable. Model Measurements The following morphometric data were incorporated in the model, and diagrams and detailed descriptions of the measurements are shown in Figure 1. Oral cavity measurements were made with electrocardiographic calipers after removal of the sharp tips and sterilization. These measurements were obtained by placing the caliper tips between the oral cavity structures to be measured, carefully removing the caliper, and measuring the distance between the caliper tips with a ruler. Figure 1. Oral cavity measurements for the morphometric model. Top. Bottom left. Bottom right. The morphometric model is as follows: (Equation 1) where P is palatal height (in millimeters), or the distance from the dorsum of the tongue at the median lingual sulcus to the highest point of the palate, measured with the tongue in a relaxed position and the maxillary and mandibular incisor tips subtending an angle of 20 degrees from the mandibular condyle; Mx is the maxillary intermolar distance (in millimeters) between the mesial surfaces of the crowns of the maxillary second molars; Mn is the mandibular intermolar distance (in millimeters) between the mesial surfaces of the crowns of the mandibular second molars; OJ is the overjet (in millimeters), or the horizontal overlap of the crowns of the maxillary and mandibular right central incisors; BMI [24] is the body mass index (kg/m2; ideal BMI 25); and NC is neck circumference (in centimeters) measured at the level of the cricothyroid membrane. Precise measurement of these anatomic distances is critical for the accuracy of the model. The bordered area of the formula reflects the contribution of craniofacial dysmorphism, as measured from the oral cavity, to the prediction of OSAS. The nonbordered area reflects the contribution of obesity, as measured by BMI and neck circumference, to the prediction of OSAS. The fraction NC BMI was selected to scale neck circumference relative to body size. The segment of the model enclosed within square brackets is limited to the larger of the two quantities: BMI 25, or zero. For example, if BMI is 25 or less, then [Max (BMI 25, 0)] is zero: That is, if BMI is 23, then (23 25) = 2 and, because 0 is greater than 2,the maximum is zero. Therefore, if a patient is not obese (BMI 25), the contribution of the second part of the model to the final index value is nil; the final index value reflects only the degree of craniofacial dysmorphism. Model Testing After developing the model from the test sample of 30 patients, we prospectively tested it on 423 patients during a 6-month period to investigate its clinical utility and accuracy in predicting OSAS. The patients were self-referred or were referred from outside clinics; they had diverse primary symptoms, including fatigue, sleeplessness or sleepiness, rest-less legs, periodic limb movements, sleepwalking, and witnessed snoring or apneas, or they were recruited for research projects. Only patients who were visiting the clinic for the first time were included. Each patient had a clinical evaluation, which consisted of a discussion of symptoms and medical history as well as a general physical examination. The oral cavity, body weight, height, and neck circumference were measured during the examination. At the completion of the clinical evaluation, a physician who was not involved in the study decided whether the patient should be scheduled for polysomnography; this physician was blinded to the results of the model measurements. Patients with unequivocal insomnia or a previous diagnosis (established on the basis of symptoms and polysomnography) of OSAS or another sleep disorder (for example, the restless legs syndrome, periodic limb movements, or sleepwalking) were not scheduled for polysomnography. The polysomnograms of the 300 patients included in the final study were independently reviewed by experienced physicians and technologists who were blinded to the results of the model measurements. The diagnosis of OSAS was then established in each patient on the basis of the criteria for the syndrome, as described above. Patients without symptomatic and polysomnographic evidence of OSAS made up the non-OSAS comparison group. The morphometric model results were matched to each patient; these data, combined with the polysomnographic data, were analyzed. Statistical analyses were done with Stat-View (Abacus Concepts, Inc., Berkeley, California), BMDP (BMDP Statistical Software, Inc., Los Angeles, California), and Splus [Math Soft, Cambridge, Massachusetts]) computer programs. To treat the model as objectively as possible, we cross-validated it as if it had been developed from the prospective 300 patients instead of from the initial sample

Obstructive sleep apnea syndrome: a comparison between Far-East Asian and white men.

Objectives To investigate the possible differences between Far‐East Asian men and white men in obstructive sleep apnea syndrome (OSAS).

Efficacy and safety of pramipexole in restless legs syndrome

Objective: To evaluate the efficacy and safety of pramipexole in patients with moderate to severe restless legs syndrome (RLS) Methods: The authors conducted a 12-week, double-blind, randomized, placebo-controlled trial of fixed doses of pramipexole (0.25, 0.50, and 0.75 mg/day). Patients (N = 344) were up-titrated to their randomized dose over 3 weeks. The primary efficacy endpoints were patient ratings of symptom severity on the International RLS Study Group Rating Scale (IRLS) and clinician ratings of improvement on the Clinical Global Impressions-Improvement (CGI-I) scale. Secondary efficacy endpoints included visual analogue ratings of sleep and quality of life (QOL) Results: By both primary measures, pramipexole was superior to placebo. For IRLS, the adjusted mean (SE) change from baseline to week 12 was −9.3 (1.0) for placebo, −12.8 (1.0) for 0.25 mg/day, −13.8 (1.0) for 0.50 mg/day, and −14.0 (1.0) for 0.75 mg/day (all p < 0.01). Similarly, pramipexole increased the percentage of patients with a CGI-I rating of “very much improved” or “much improved” at the end of the trial (51.2% for placebo and 74.7%, 67.9%, and 72.9% for pramipexole; all p < 0.05). Pramipexole significantly improved ratings of symptom severity, day and night, and also ratings of sleep satisfaction and QOL. Pramipexole was well tolerated: The most frequent adverse events with higher occurrence in the pramipexole group were nausea (19.0% vs 4.7%) and somnolence (10.1% vs 4.7%) Conclusion: As rated by patients and by clinicians, pramipexole was efficacious and safe in reducing the symptoms of restless legs syndrome.

Effects of continuous positive airway pressure on neurocognitive function in obstructive sleep apnea patients: The Apnea Positive Pressure Long-term Efficacy Study (APPLES).

STUDY OBJECTIVE To determine the neurocognitive effects of continuous positive airway pressure (CPAP) therapy on patients with obstructive sleep apnea (OSA). DESIGN, SETTING, AND PARTICIPANTS The Apnea Positive Pressure Long-term Efficacy Study (APPLES) was a 6-month, randomized, double-blind, 2-arm, sham-controlled, multicenter trial conducted at 5 U.S. university, hospital, or private practices. Of 1,516 participants enrolled, 1,105 were randomized, and 1,098 participants diagnosed with OSA contributed to the analysis of the primary outcome measures. INTERVENTION Active or sham CPAP MEASUREMENTS: THREE NEUROCOGNITIVE VARIABLES, EACH REPRESENTING A NEUROCOGNITIVE DOMAIN: Pathfinder Number Test-Total Time (attention and psychomotor function [A/P]), Buschke Selective Reminding Test-Sum Recall (learning and memory [L/M]), and Sustained Working Memory Test-Overall Mid-Day Score (executive and frontal-lobe function [E/F]) RESULTS The primary neurocognitive analyses showed a difference between groups for only the E/F variable at the 2 month CPAP visit, but no difference at the 6 month CPAP visit or for the A/P or L/M variables at either the 2 or 6 month visits. When stratified by measures of OSA severity (AHI or oxygen saturation parameters), the primary E/F variable and one secondary E/F neurocognitive variable revealed transient differences between study arms for those with the most severe OSA. Participants in the active CPAP group had a significantly greater ability to remain awake whether measured subjectively by the Epworth Sleepiness Scale or objectively by the maintenance of wakefulness test. CONCLUSIONS CPAP treatment improved both subjectively and objectively measured sleepiness, especially in individuals with severe OSA (AHI > 30). CPAP use resulted in mild, transient improvement in the most sensitive measures of executive and frontal-lobe function for those with severe disease, which suggests the existence of a complex OSA-neurocognitive relationship. CLINICAL TRIAL INFORMATION Registered at clinicaltrials.gov. Identifier: NCT00051363. CITATION Kushida CA; Nichols DA; Holmes TH; Quan SF; Walsh JK; Gottlieb DJ; Simon RD; Guilleminault C; White DP; Goodwin JL; Schweitzer PK; Leary EB; Hyde PR; Hirshkowitz M; Green S; McEvoy LK; Chan C; Gevins A; Kay GG; Bloch DA; Crabtree T; Demen WC. Effects of continuous positive airway pressure on neurocognitive function in obstructive sleep apnea patients: the Apnea Positive Pressure Long-term Efficacy Study (APPLES). SLEEP 2012;35(12):1593-1602.

Recommended Amount of Sleep for a Healthy Adult: A Joint Consensus Statement of the American Academy of Sleep Medicine and Sleep Research Society.

ABSTRACT Sleep is essential for optimal health. The American Academy of Sleep Medicine (AASM) and Sleep Research Society (SRS) developed a consensus recommendation for the amount of sleep needed to promote optimal health in adults, using a modified RAND Appropriateness Method process. The recommendation is summarized here. A manuscript detailing the conference proceedings and evidence supporting the final recommendation statement will be published in SLEEP and the Journal of Clinical Sleep Medicine.

Sleep Deprivation in the Rat: IV. Paradoxical Sleep Deprivation

Twelve rats were subjected to paradoxical sleep deprivation (PSD) by the disk apparatus. All PSD rats died or were sacrificed when death seemed imminent within 16-54 days. No anatomical cause of death was identified. All PSD rats showed a debilitated appearance, lesions on their tails and paws, and weight loss in spite of increased food intake. Their yoked control (PSC) rats remained healthy. Since dehydration was ruled out and several measures indicated normal or accelerated use of nutrients, the food-weight changes in PSD rats were attributed to increased energy expenditure (EE). The measurement of EE, based upon caloric value of food, weight, and wastes, indicated that all PSD rats increased EE, with mean levels reaching more than twice baseline values. All of these changes had been observed in rats deprived totally of sleep; the major difference was that they developed more slowly in PSD rats.

A Comparison of Asian and White Patients With Obstructive Sleep Apnea Syndrome

Objective: To evaluate the possible differences between Asian and white patients with obstructive sleep apnea syndrome.

Oral Appliance Treatment for Obstructive Sleep Apnea: An Update

Oral appliances (OA) have emerged as an alternative to continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA) treatment. The most commonly used OA reduces upper airway collapse by advancing the mandible (OAm). There is a strong evidence base demonstrating OAm improve OSA in the majority of patients, including some with more severe disease. However OAm are not efficacious for all, with approximately one-third of patients experiencing no therapeutic benefit. OAm are generally well tolerated, although short-term adverse effects during acclimatization are common. Long-term dental changes do occur, but these are for the most part subclinical and do not preclude continued use. Patients often prefer OAm to gold-standard CPAP treatment. Head-to-head trials confirm CPAP is superior in reducing OSA parameters on polysomnography; however, this greater efficacy does not necessarily translate into better health outcomes in clinical practice. Comparable effectiveness of OAm and CPAP has been attributed to higher reported nightly use of OAm, suggesting that inferiority in reducing apneic events may be counteracted by greater treatment adherence. Recently, significant advances in commercially available OAm technologies have been made. Remotely controlled mandibular positioners have the potential to identify treatment responders and the level of therapeutic advancement required in single night titration polysomnography. Objective monitoring of OAm adherence using small embedded temperature sensing data loggers is now available and will enhance clinical practice and research. These technologies will further enhance efficacy and effectiveness of OAm treatment for OSA.

Burden of restless legs syndrome on health-related quality of life

ObjectiveTo quantify the total and unique burden of Restless Legs Syndrome (RLS) on patient-reported health-related quality of life (HRQoL).MethodsThe disease burden that RLS places on HRQoL was estimated by comparing Short-Form (SF-36) scores between individuals with RLS and several patient and general populations in the US. Regression methods were applied to estimate SF-36 normative values from the general population sample and statistically adjust them to match age, gender and disease comorbidity characteristics of the RLS sample. Significance tests were then used to compare the means across samples.ResultsAll SF-36 measures were significantly below adjusted US general population norms. Five of the eight scales (physical functioning, role physical, bodily pain, general health, vitality) were below US norms by 0.8 or more standard deviations (SD), while the remaining three (social functioning, role emotional, mental health) were 0.5 SD below norm. The burden of RLS was greater on physical than on mental/emotional HRQoL (physical and mental summary scores were 1.08 and 0.40 SD below norm, respectively), and greater than that observed for type-2 diabetes.ConclusionAfter controlling for the impact of age, gender, and disease comorbidity, RLS was associated with unique burden on both physical and mental aspects of HRQoL.