Chad Ruoff

Myofunctional Therapy to Treat Obstructive Sleep Apnea: A Systematic Review and Meta-analysis

OBJECTIVE To systematically review the literature for articles evaluating myofunctional therapy (MT) as treatment for obstructive sleep apnea (OSA) in children and adults and to perform a meta-analysis on the polysomnographic, snoring, and sleepiness data. DATA SOURCES Web of Science, Scopus, MEDLINE, and The Cochrane Library. REVIEW METHODS The searches were performed through June 18, 2014. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was followed. RESULTS Nine adult studies (120 patients) reported polysomnography, snoring, and/or sleepiness outcomes. The pre- and post-MT apneahypopnea indices (AHI) decreased from a mean ± standard deviation (M ± SD) of 24.5 ± 14.3/h to 12.3 ± 11.8/h, mean difference (MD) -14.26 [95% confidence interval (CI) -20.98, -7.54], P < 0.0001. Lowest oxygen saturations improved from 83.9 ± 6.0% to 86.6 ± 7.3%, MD 4.19 (95% CI 1.85, 6.54), P = 0.0005. Polysomnography snoring decreased from 14.05 ± 4.89% to 3.87 ± 4.12% of total sleep time, P < 0.001, and snoring decreased in all three studies reporting subjective outcomes. Epworth Sleepiness Scale decreased from 14.8 ± 3.5 to 8.2 ± 4.1. Two pediatric studies (25 patients) reported outcomes. In the first study of 14 children, the AHI decreased from 4.87 ± 3.0/h to 1.84 ± 3.2/h, P = 0.004. The second study evaluated children who were cured of OSA after adenotonsillectomy and palatal expansion, and found that 11 patients who continued MT remained cured (AHI 0.5 ± 0.4/h), whereas 13 controls had recurrent OSA (AHI 5.3 ± 1.5/h) after 4 y. CONCLUSION Current literature demonstrates that myofunctional therapy decreases apnea-hypopnea index by approximately 50% in adults and 62% in children. Lowest oxygen saturations, snoring, and sleepiness outcomes improve in adults. Myofunctional therapy could serve as an adjunct to other obstructive sleep apnea treatments.

Narcolepsy and Predictors of Positive MSLTs in the Wisconsin Sleep Cohort

STUDY OBJECTIVES To study whether positive multiple sleep latency tests (MSLTs, mean sleep latency [MSL] ≤ 8 minutes, ≥ 2 sleep onset REM sleep periods [SOREMPs]) and/or nocturnal SOREMP (REM sleep latency ≤ 15 minutes during nocturnal polysomonography [NPSG]) are stable traits and can reflect incipient narcolepsy. DESIGN AND SETTING Cross-sectional and longitudinal investigation of the Wisconsin Sleep Cohort Study. PARTICIPANTS Adults (44% females, 30-81 years) underwent NPSG (n = 4,866 in 1,518 subjects), and clinical MSLT (n = 1,135), with 823 having a repeat NPSG-MSLT at 4-year intervals, totaling 1725 NPSG with MSLT studies. Data were analyzed using linear mixed-effects models, and the stability of positive MSLTs was explored using κ statistics. MEASUREMENTS AND RESULTS Prevalence of a nocturnal SOREMP on a NPSG, of ≥ 2 SOREMPs on the MSLT, of MSL ≤ 8 minutes on the MSLT, and of a positive MSLT (MSL ≤ 8 minutes plus ≥ 2 SOREMPs) were 0.35%, 7.0%, 22%, and 3.4%, respectively. Correlates of a positive MSLT were shift work (OR = 7.8, P = 0.0001) and short sleep (OR = 1.51/h, P = 0.04). Test-retest for these parameters was poor, with κ < 0.2 (n.s.) after excluding shift workers and short sleepers. Excluding shift-work, short sleep, and subjects with negative MSLTs, we found one undiagnosed subject with possible cataplexy (≥ 1/month) and a NPSG SOREMPs; one subject previously diagnosed with narcolepsy without cataplexy with 2 NPSG SOREMPs and a positive MSLT, and two subjects with 2 independently positive MSLTs (66% human leukocyte antigen [HLA] positive). The proportions for narcolepsy with and without cataplexy were 0.07% (95% CI: 0.02-0.37%) and 0.20% (95% CI: 0.07-0.58%), respectively. CONCLUSIONS The diagnostic value of multiple sleep latency tests is strongly altered by shift work and to a lesser extent by chronic sleep deprivation. The prevalence of narcolepsy without cataplexy may be 3-fold higher than that of narcolepsy-cataplexy.

The Effect of Nasal Surgery on Continuous Positive Airway Pressure Device Use and Therapeutic Treatment Pressures: A Systematic Review and Meta-Analysis

BACKGROUND The relationship between nasal surgery and its effect on continuous positive airway pressure (CPAP) device therapeutic treatment pressures and CPAP device use has not been previously systematically examined. STUDY OBJECTIVES To conduct a systematic review and meta-analysis evaluating the effect of isolated nasal surgery on therapeutic CPAP device pressures and use in adults with obstructive sleep apnea (OSA). METHODS MEDLINE, Scopus, Web of Science, and The Cochrane Library were searched through July 15, 2014. The MOOSE consensus statement and PRISMA statement were followed. RESULTS Eighteen studies (279 patients) reported CPAP data after isolated nasal surgery. Seven studies (82 patients) reported preoperative and postoperative mean therapeutic CPAP device pressures and standard deviations (SD), which reduced from 11.6 ± 2.2 to 9.5 ± 2.0 centimeters of water pressure (cwp) after nasal surgery. Pooled random effects analysis demonstrated a statistically significant pressure reduction, with a mean difference (MD) of -2.66 cwp (95% confidence interval (CI), -3.65 to -1.67); P < 0.00001. Eleven studies (153 patients) reported subjective, self-reported data for CPAP use; and a subgroup analysis demonstrated that 89.1% (57 of 64 patients) who were not using CPAP prior to nasal surgery subsequently accepted, adhered to, or tolerated it after nasal surgery. Objective, device meter-based hours of use increased in 33 patients from 3.0 ± 3.1 to 5.5 ± 2.0 h in the short term (<6 mo of follow-up). CONCLUSION Isolated nasal surgery in patients with OSA and nasal obstruction reduces therapeutic CPAP device pressures and the currently published literatures objective and subjective data consistently suggest that it also increases CPAP use in select patients.

The Burden of Narcolepsy Disease (BOND) study: health-care utilization and cost findings.

OBJECTIVES The aim of this study was to characterize health-care utilization, costs, and productivity in a large population of patients diagnosed with narcolepsy in the United States. METHODS This retrospective, observational study using data from the Truven Health Analytics MarketScan Research Databases assessed 5 years of claims data (2006-2010) to compare health-care utilization patterns, productivity, and associated costs among narcolepsy patients (identified by International Classification of Diseases, Ninth Revision (ICD9) narcolepsy diagnosis codes) versus matched controls. A total of 9312 narcolepsy patients (>18 years of age, continuously insured between 2006 and 2010) and 46,559 matched controls were identified. RESULTS Compared with controls, narcolepsy subjects had approximately twofold higher annual rates of inpatient admissions (0.15 vs. 0.08), emergency department (ED) visits w/o admission (0.34 vs. 0.17), hospital outpatient (OP) visits (2.8 vs. 1.4), other OP services (7.0 vs. 3.2), and physician visits (11.1 vs. 5.6; all p<0.0001). The rate of total annual drug transactions was doubled in narcolepsy versus controls (26.4 vs. 13.3; p<0.0001), including a 337% and 72% higher usage rate of narcolepsy drugs and non-narcolepsy drugs, respectively (both p<0.0001). Mean yearly costs were significantly higher in narcolepsy compared with controls for medical services (

Effect of Oral JZP-110 (ADX-N05) on Wakefulness and Sleepiness in Adults with Narcolepsy: A Phase 2b Study

8346 vs.

Hypocretin antagonists in insomnia treatment and beyond.

4147; p<0.0001) and drugs (

The ICSD-3 and DSM-5 guidelines for diagnosing narcolepsy: clinical relevance and practicality

3356 vs.

Smartphone apps for snoring

1114; p<0.0001). CONCLUSIONS Narcolepsy was found to be associated with substantial personal and economic burdens, as indicated by significantly higher rates of health-care utilization and medical costs in this large US group of narcolepsy patients.

A Case of Rapid Eye Movement Sleep Behavior Disorder in Parkinson Disease Treated With Sodium Oxybate.

STUDY OBJECTIVES To evaluate the efficacy and safety of oral JZP-110, a second-generation wake-promoting agent with dopaminergic and noradrenergic activity, for treatment of impaired wakefulness and excessive sleepiness in adults with narcolepsy. METHODS This was a phase 2b, randomized, double-blind, placebo-controlled, parallel-group trial conducted at 28 centers in the United States. Patients were adults with narcolepsy who had baseline scores ≥ 10 on the Epworth Sleepiness Scale (ESS) and baseline sleep latency ≤ 10 min on the Maintenance of Wakefulness Test (MWT). Patients received a daily placebo (n = 49) or JZP-110 (n = 44) 150 mg/day weeks 1-4 and 300 mg/day weeks 5-12. Primary efficacy endpoints were change from baseline in average MWT sleep latency, and the Clinical Global Impression-Change (CGI-C); secondary endpoints were change from baseline in ESS score and Patient Global Impression-Change. RESULTS Improvements were significantly greater with JZP-110 versus placebo on mean MWT sleep latency (4 w, 9.5 versus 1.4 min, P < 0.0001; 12 w, 12.8 versus 2.1 min, P < 0.0001), percentage of patients with CGI-C improvement (4 w, 80% versus 51%, P = 0.0066; 12 w, 86% versus 38%, P < 0.0001), and mean change in ESS (4 w, -5.6 versus -2.4, P = 0.0038; 12 w, -8.5 versus -2.5, P < 0.0001). Three JZP-110-treated patients (6.8%) discontinued due to adverse events (AEs). The most common AEs with JZP-110 versus placebo were insomnia (23% versus 8%), headache (16% versus 10%), nausea (14% versus 6%), diarrhea (11% versus 6%), decreased appetite (14% versus 0%), and anxiety (11% versus 0%). CONCLUSIONS At doses of 150-300 mg/day, JZP-110 was well tolerated and significantly improved the ability to stay awake and subjective symptoms of excessive sleepiness in adults with narcolepsy. CLINICAL TRIALS REGISTRATION Clinicaltrials.gov identifier NCT01681121.

Medical comorbidity in narcolepsy: findings from the Burden of Narcolepsy Disease (BOND) study

Hypocretin neuropeptides have been shown to regulate transitions between wakefulness and sleep through stabilization of sleep promoting GABAergic and wake promoting cholinergic/monoaminergic neural pathways. Hypocretin also influences other physiologic processes such as metabolism, appetite, learning and memory, reward and addiction, and ventilatory drive. The discovery of hypocretin and its effect upon the sleep-wake cycle has led to the development of a new class of pharmacologic agents that antagonize the physiologic effects of hypocretin (i.e. hypocretin antagonists). Further investigation of these agents may lead to novel therapies for insomnia without the side-effect profile of currently available hypnotics (e.g. impaired cognition, confusional arousals, and motor balance difficulties). However, antagonizing a system that regulates the sleep-wake cycle while also influencing non-sleep physiologic processes may create an entirely different but equally concerning side-effect profile such as transient loss of muscle tone (i.e. cataplexy) and a dampened respiratory drive. In this review, we will discuss the discovery of hypocretin and its receptors, hypocretin and the sleep-wake cycle, hypocretin antagonists in the treatment of insomnia, and other implicated functions of the hypocretin system.