Idiopathic Hypersomnia and Kleine-Levin Syndrome: Primary Disorders of Hypersomnolence Beyond Narcolepsy.

Daytime sleepiness is common amongst children and adolescents. Inadequate sleep duration, inappropriate school start times, and the delay in sleep phase of adolescence may all contribute. Nocturnal sleep disruption due to sleep disorders such as obstructive sleep apnea or restless legs syndrome/periodic limb movement disorder may also lead to daytime sleepiness. Profound sleepiness however, when occurring in the setting of adequate sleep duration, is rare amongst children and adolescents and may prompt consideration of a central disorder of hypersomnolence (CDH). Narcolepsy is the archetypal and most studied form of CDH and a detailed review of the presentation, evaluation, treatment of narcolepsy is included separately in this edition of Seminars in Pediatric Neurology. In addition to narcolepsy, 2 other forms of primary CDH exist, idiopathic hypersomnia (IH) and Kleine-Levin syndrome (KLS). Onset of IH and KLS occurs most frequently during the pediatric age range and presentation may include signs of encephalopathy in addition to hypersomnolence. As such, they are of particular relevance to pediatric neurology and associated fields. Unfortunately, when compared to narcolepsy little is known about IH and KLS, at both the physiologic and clinical level. This review will focus on the presentation, evaluation, and management of idiopathic hypersomnia and Kleine-Levin syndrome in the pediatric population.

Clinical Evaluation and Management of Narcolepsy in Children and Adolescents.

While sleepiness is common among children, and particularly adolescents, profound sleepiness in the setting of apparently adequate sleep should prompt consideration of a central disorder of hypersomnolence. These disorders, which include narcolepsy, idiopathic hypersomnia, Kleine-Levin syndrome, and others, are likely underrecognized in the pediatric population. Narcolepsy in particular should be of interest to child neurologists as the unique signs and symptoms of this disease often prompt evaluation in pediatric neurology clinics. While sleepiness may appear to be a straightforward complaint, its evaluation requires a nuanced approach. Cataplexy, a hallmark of narcolepsy, can be confused for other neurologic conditions, though understanding its various manifestations makes it readily identifiable. Clinicians should be aware of these symptoms, as delay in diagnosis and misdiagnosis are common in childhood narcolepsy. While treatment options have been limited in the past, many new therapeutic options have become available and can result in significant improvement in symptoms. Given the age at presentation, paroxysmal and chronic features, diagnostic modalities, and available treatment options, the field of child neurology is well equipped to see patients with narcolepsy. In this review, I will focus on the presentation, evaluation, and management of pediatric patients with narcolepsy.

Recommendations for clinical management of excessive daytime sleepiness in obstructive sleep apnoea - A Delphi consensus study.

STUDY OBJECTIVE: Excessive daytime sleepiness is common with obstructive sleep apnoea and can persist despite efforts to optimise primary airway therapy. The literature lacks recommendations regarding differential diagnosis and management of excessive daytime sleepiness in obstructive sleep apnoea. This study sought to develop expert consensus statements to bridge the gap between existing literature/guidelines and clinical practice. METHODS: A panel of 10 international experts was convened to undertake a modified Delphi process. Statements were developed based on available evidence identified through a scoping literature review, and expert opinion. Consensus was achieved through 3 rounds of iterative, blinded survey voting and revision to statements until a predetermined level of agreement was met (≥80 % voting "strongly agree" or "agree with reservation"). RESULTS: Consensus was achieved for 32 final statements. The panel agreed excessive daytime sleepiness is a patient-reported symptom. The importance of subjective/objective evaluation of excessive daytime sleepiness in the initial evaluation and serial management of obstructive sleep apnoea was recognised. The differential diagnosis of residual excessive daytime sleepiness in obstructive sleep apnoea was discussed. Optimizing airway therapy (eg, troubleshooting issues affecting effectiveness) was addressed. The panel recognised occurrence of residual excessive daytime sleepiness in obstructive sleep apnoea despite optimal airway therapy and the need to evaluate patients for underlying causes. CONCLUSIONS: Excessive daytime sleepiness in patients with obstructive sleep apnoea is a public health issue requiring increased awareness, recognition, and attention. Implementation of these statements may improve patient care, long-term management, and clinical outcomes in patients with obstructive sleep apnoea.

Sleep Disorders in Childhood.

OBJECTIVE: This article provides a comprehensive review of pediatric sleep disorders including the clinical features, diagnosis, and treatment of sleep-disordered breathing, insomnia, parasomnias, restless sleep disorder, restless legs syndrome, narcolepsy in childhood, and Kleine-Levin syndrome. LATEST DEVELOPMENTS: Our understanding of pediatric sleep pathophysiology continues to evolve, and diagnostic and treatment modalities have expanded. A low-sodium oxybate formulation was approved in July 2020 in the United States to treat cataplexy and excessive daytime sleepiness in patients 7 years old and older with narcolepsy. A validated pediatric hypersomnolence survey for pediatric narcolepsy and idiopathic hypersomnia with high sensitivity, specificity, and interrater reliability is now available. ESSENTIAL POINTS: The clinical presentation, diagnostics, and treatment of children with sleep disorders differ from those of adults. Untreated sleep disorders in childhood can lead to adverse physical and psychological consequences in adults. Correctly diagnosing and treating sleep disorders in youth can prevent a significant burden of disease in adulthood.

Impact of chronotype, insomnia symptoms, sleep duration, and electronic devices on nonrestorative sleep and daytime sleepiness among Japanese adolescents.

OBJECTIVES: Nonrestorative sleep (NRS) and excessive daytime sleepiness (EDS) are important indicators of daytime dysfunction. Electronic media use before bedtime greatly affects adolescent sleep quality. However, few studies have examined factors associated with these symptoms. Therefore, we aimed to investigate the impact of chronotype, electronic device use before bedtime, and insomnia symptoms on NRS and EDS in Japanese adolescents. METHODS: A web-based cross-sectional survey of 2067 adolescents was conducted in 2022 to mainly assess sleep-related issues (sleep duration, chronotype, insomnia symptoms, NRS, and EDS), time spent using electronic devices, physical activity, and mental health. RESULTS: We analyzed data of 1880 adolescents (age, 16.4 ± 0.8 years; males, 56.7%). NRS and EDS prevalence rates were 54.9% and 39.4%, respectively. In multivariate analysis, evening chronotype [odds ratio (OR): 2.14, 95% confidence interval (CI): 1.58-2.89], difficulty initiating sleep (OR: 1.94, 95% CI: 1.43-2.64), <5 h sleep (OR: 1.77, 95% CI: 1.24-2.54), 5-6 h sleep (OR: 1.52, 95% CI: 1.20-1.93), and using electronic devices just before bedtime (OR: 1.48, 95% CI: 1.08-2.04) were associated with NRS. Evening chronotype (OR: 1.40, 95% CI: 1.07-1.82), early morning awakening (OR: 1.60, 95% CI: 1.02-2.50), using electronic devices just before bedtime (OR: 2.08, 95% CI: 1.48-2.93), and using electronic devices 30 min before bedtime (OR: 1.57, 95% CI: 1.07-2.29) were associated with EDS. CONCLUSION: Chronotype may be an important factor influencing NRS and EDS. Discontinuing electronic device use at least 30 min before bedtime could benefit affected adolescents.

Influence of excessive daytime sleepiness on the treatment adherence of obstructive sleep apnea.

OBJECTIVES: To compare positive airway pressure (PAP) adherence between patients with or without excessive daytime sleepiness (EDS) in mild, moderate and severe obstructive sleep apnea (OSA). METHODS: Patients ≥18 years diagnosed with OSA in 2018 and 2019, without previous history of PAP usage and with adherence registration in the first medical consultation after treatment initiation, were included. EDS was defined as a score of ≥10 on the Epworth Scale. Patients were divided into two groups according to the adherence to PAP: "Adherent" if using the device for ≥4 h for ≥70% of the nights and "Nonadherent" otherwise. Simple and multiple logistic regression models for adherence were determined. RESULTS: 321 patients were included, most male (64.2%), with mean age 56.56 years. Most patients had severe OSA (n = 159; 49.5%), and median AHI was 29.3/h [16.8; 47.5]. Being older or having a severe OSA resulted in an increased adherence (OR = 1.020, CI95% = [1.002; 1.039] and OR = 2.299, CI95% = [1.273; 4.191], respectively). In patients without EDS a statistically significant difference was found in adherence between those with severe OSA and both mild and moderate OSA categories (OR = 0.285, p = 0.023 and OR = 0.387, p = 0.026, respectively), with patients with severe OSA being adherent. There was no statistical difference in adherence between patients with or without EDS (OR 1.083; p = 0.876), nor in the different degrees of severity in those with EDS. CONCLUSION: In our study there were no differences in PAP therapy adherence between patients with or without excessive daytime sleepiness. Older age and higher OSA severity resulted in higher adherence rates.

Changes in cognitive function and daytime sleepiness in patients with chronic heart failure and Cheyne-Stokes respiration with adaptive servo ventilation treatment.

STUDY OBJECTIVES: Cheyne - Stokes respiration (CSR) is prevalent in patients with chronic heart failure (CHF). Adaptive Servo Ventilation (ASV) alleviates CSR and improves objective sleep quality. We investigated the effects of ASV on neurocognitive function in the symptomatic phenotype of patients with CSR and CHF. METHODS: This case series included patients diagnosed with stable CHF (NYHA ≥ II) and CSR (N = 8). Sleep and neurocognitive function were assessed at baseline and after 1- and 6-months following initiation of ASV treatment. RESULTS: In CHF patients (n = 8, median age 78.0[64.5-80.8] years and BMI 30.0[27.0-31.5] kg/m2, median ejection fraction 30[24-45]%, Epworth Sleepiness Scale (ESS) score 11.5[9.0-15.0]), ASV markedly improved respiration during sleep (Apnea-Hypopnea Index (AHI) 44.1[39.0-51.5]n/h at baseline, 6.3[2.4-9.7]n/h at 6 months treatment, respectively, p < 0.01). The 6-min-walk test distance increased by treatment from (295.0[178.8-385.0] m to 356.0[203.8-495.0] m (p = 0.05)). Sleep structure was modified, and Stage 3 increased markedly from 6.4[1.7-20.1] % to 20.8[14.2-25.3] %, p < 0.02). Sleep latency in the Maintenance of Wakefulness Test increased from 12.0[6.0-30.0] min to 26.3[12.0-30.0] min, (p = 0.04). In the Attention Network Test, evaluating neurocognition, the number of lapses decreased from 6.0[1.0-44.0] to 2.0[0.3-8.0], (p = 0.05) and the overall number of responses to a preset stimulus increased after treatment (p = 0.04). CONCLUSIONS: ASV treatment in CHF patients with CSR may improve sleep quality, neurocognition and daytime performance.

Narcolepsy and Idiopathic Hypersomnia.

Narcolepsy types 1 and 2 and idiopathic hypersomnia are primary Central Nervous System (CNS) disorders of hypersomnolence characterized by profound daytime sleepiness and/or excessive sleep need. Onset of symptoms begins typically in childhood or adolescence, and children can have unique presentations compared with adults. Narcolepsy type 1 is likely caused by immune-mediated loss of orexin (hypocretin) neurons in the hypothalamus; however, the causes of narcolepsy type 2 and idiopathic hypersomnia are unknown. Existing treatments improve daytime sleepiness and cataplexy but there is no cure for these disorders.

Approach to a sleepy child: Diagnosis and treatment of excessive daytime sleepiness in children and adolescents.

PURPOSE: The aim of this review is to give updated information to pediatric neurologists on the correct diagnostic approach and treatment of excessive daytime sleepiness (EDS) in children and adolescents. Due to the change in the society habits, EDS is becoming an emerging problem for the health system. At the present there are few articles specifically devoted to the evaluation of EDS. EDS is often reported in several manuscripts as a side effect of other sleep disorders (obstructive sleep apnea, circadian disorders, etc.) or of the use of drugs or of the substance abuse or as a consequence of bad sleep habits and poor sleep hygiene. EDS, especially in children, may manifest with paradoxical symptoms like hyperactivity, inattention, and impulsiveness. However, common sign of EDS in children are the propensity to sleep longer than usual, the difficulty waking up in the morning, and falling asleep frequently during the day in monotonous situation. The diagnosis should include subjective (sleep diaries, questionnaires) and objective (polysomnography, multiple sleep latency test, etc.) instruments to avoid misdiagnosis. Narcolepsy is the most studied central disorder of hypersomnolence, and it is a predominantly pediatric disease with a peak age of onset in prepuberty but the diagnosis is often delayed especially in mild forms. The early and correct treatment of narcolepsy and of other form of EDS is extremely important since late and inappropriate treatments can affect the psychosocial development of the children and adolescents.

Residual sleepiness in veterans with post-traumatic stress disorder and obstructive sleep apnea.

PURPOSE: The causes of residual excessive sleepiness (RES) in patients with post-traumatic stress disorder (PTSD) and obstructive sleep apnea (OSA) are multifactorial and modulated by comorbid conditions. The aim of the present study was to elucidate clinical and polysomnographic determinants of RES in continuous positive airway pressure (CPAP)-adherent OSA veterans with PTSD. METHODS: The study protocol consisted of a retrospective analysis of consecutive cases of patients with PTSD who presented to the Veterans Affairs sleep clinics with adequately treated OSA between June 1, 2017 and October 15, 2021. Based on the Epworth Sleepiness Scale (ESS), patients were categorized into RES (ESS ≥ 11) and no RES (ESS < 11) groups. Demographic and PSG data were subjected to univariate and multivariate analyses to ascertain predictive factors of RES. RESULTS: Out of 171 veterans with PTSD who were adherent to CPAP, 59 (35%) continued to experience RES. The RES group had a decrease in mean ESS score of 1.2 ± 4.5 after CPAP treatment compared with 4.6 ± 4.9 for the no RES group (< 0.001). A dose-response was observed between CPAP use and RES (p = 0.003). Multivariate regression analysis identified higher baseline ESS (OR 1.30; 95% CI 1.16-1.44), greater percentage of time spent in REM sleep (OR 0.91; 95% CI 0.85-0.96), CPAP use less than 6 h (OR 2.82; 95% CI 1.13-7.01), and a positive screen for depression (OR 1.69; 95% CI 1.03-4.72) as independent predictors of RES in patients with PTSD and OSA. CONCLUSION: RES is highly prevalent in patients with PTSD and OSA despite adherence to CPAP and is independently associated with percentage time spent in REM, duration of CPAP utilization, and symptoms of depression.

Effect of CPAP vs. mandibular advancement device for excessive daytime sleepiness, fatigue, mood, sustained attention, and quality of life in patients with mild OSA.

OBJECTIVE: This study's objective was to compare the best long-term treatment, mandibular advancement device (MAD) or continuous positive airway pressure (CPAP), for patients with mild obstructive sleep apnea (OSA) in improving excessive daytime sleepiness, fatigue, mood, sustained attention, and quality of life. METHODS: This study was a single-blind, parallel, randomized clinical trial with controls. The sample was composed of individuals between 18 and 65 years of age with a body mass index of < 35 kg/m2 and apnea/hypopnea index above five and less than 15. Participants were submitted to physical examination, polysomnography, and the following questionnaires: Pittsburgh Sleep Quality Index, Berlin Questionnaire, Epworth Sleepiness Scale, Stanford Sleepiness Scale, Karolinska Sleepiness Scale, Modified Fatigue Impact Scale, Functional Outcomes of Sleep Questionnaire, Beck Anxiety Inventory, and Beck Depression Inventory. They were also presented with the following tests: maintenance of wakefulness test and psychomotor vigilance task. RESULTS: Of 79 patients, 25 were in the MAD group, 31 in the CPAP group, and 23 in the control group. Polysomnographic parameters were best normalized with CPAP compared with MAD. Fatigue was improved in the MAD and CPAP groups, with no difference between these treatments. Quality of life was also improved with both treatments, but CPAP was superior to MAD. Daytime sleepiness, mood, and sustained attention showed no difference with the interventions. Greater adherence was obtained with MAD patients than with CPAP measured by hours of use. CONCLUSIONS: Treatment with CPAP was better at normalizing polysomnographic parameters and improving quality of life in patients with mild OSA. Both treatments improved fatigue with no difference between the two treatments. Neither treatment improved daytime sleepiness, mood or sustained attention. CLINICAL TRIALS DATABASE: NTC01461486.

Parameters affecting improvement of excessive daytime sleepiness in obstructive sleep apnea patients.

OBJECTIVES: Obstructive sleep apnea (OSA) is a sleep-related breathing disorder caused by repetitive obstruction of the upper airway; this impairs gaseous exchange, resulting in hypoxia, hypercapnia, and frequent arousals. Excessive daytime sleepiness (EDS) is a common daytime symptom of OSA. EDS manifests as fatigue and impaired attention, leading to poor performance at work and falling asleep while driving, which is a major socioeconomic problem. Therefore, it is important to properly treat EDS and accurately predict the response to treatment. However, few studies have compared OSA patients showing and not showing improvement in EDS. Therefore, this study aimed to objectively analyze and compare EDS improvement and non-improvement groups. SUBJECTS AND METHODS: We retrospectively reviewed the medical records of 57 OSA patients with EDS. Patients were divided into two groups according to the improvement in EDS after positive airway pressure (PAP) device treatment. We analyzed differences in clinical records including patients' age, sex, history of smoking, hypertension, diabetes, myocardial infarction, and cerebrovascular disease between the two groups. Systolic, diastolic blood pressure, blood test including blood glucose, total cholesterol, high- and low-density lipoprotein cholesterol, and triglyceride levels were also analyzed. Polysomnography (PSG) data, PAP device treatment compliance and scores of questionnaires related to various psychiatric symptoms, subjective sleep quality between the two groups were also analyzed. RESULTS: There was no statistically significant difference in age, gender, or past medical history between the two groups. Systolic and diastolic blood pressure, and blood test results, were also not significantly different. Among the questionnaires related to various psychiatric symptoms, the groups showed statistically significant differences in Social Avoidance and Distress Scale (SADS) and Fear of Negative Evaluation (FNE) scores (P = 0.001 and 0.020, respectively). The group differences in the scores on the other questionnaires were not significantly different. Among the PSG items, significant group differences were observed in the percentage of stage 2 non-REM sleep (N2%, P = 0.023), apnea index (AI, P = 0.005), apnea-hypopnea index (AHI, P = 0.023), and frequency of 3 % oxygen desaturation (ODI3, P = 0.001). No obesity-related parameters showed significant group differences. The percentage of days on which a PAP device was used (out of 90 days; PAP%) and percentage of days on which a PAP device was used for >4 h (Time4%) did not differ significantly. CONCLUSIONS: The SADS, FNE, AI, AHI, N2%, and ODI3 parameters differed significantly between the EDS improvement and non-improvement groups. These parameters may help clinicians treat and predict the prognosis of patients suffering with EDS.

The effect of tongue elevation muscle training in patients with obstructive sleep apnea: A randomised controlled trial.

BACKGROUND: Oropharyngeal myofunctional therapy is a multi-component therapy effective to reduce the severity of obstructive sleep apnoea (OSA). However, existing protocols are difficult to replicate in the clinical setting. There is a need to isolate the specific effectiveness of each component of the therapy. OBJECTIVE: To assess the effects of a 6 weeks tongue elevation training programme in patients with OSA. METHODS: We conducted a multicentre randomised controlled trial. Eligible participants were adults diagnosed with moderate OSA who presented low adherence to continuous positive airway pressure therapy (mean use <4 h per night). The intervention group completed a 6 weeks tongue elevation training protocol that consisted in anterior tongue elevation strength and endurance tasks with the Iowa Oral Performance Instrument. The control group completed a 6 weeks sham training protocol that involved expiratory muscle training at very low intensity. Polygraphy data, tongue force and endurance, and OSA symptoms were evaluated pre- and post-intervention. The primary outcome was apneoa-hypopnea index (AHI). RESULTS: Twenty-seven patients (55 ± 11 years) were recruited. According to modified intention-to-treat analysis (n = 25), changes in AHI and c did not significantly differ between groups. Daytime sleepiness (Epworth Sleepiness Scale) and tongue endurance significantly improved in the intervention group compared to the control group (p = .015 and .022, respectively). In the intervention group, 75% of participants had a decrease in daytime sleepiness that exceeded the minimal clinically important difference. CONCLUSION: Six weeks of tongue elevation muscle training had no effect on OSA severity.

Effects of repetitive transcranial magnetic stimulation over right dorsolateral prefrontal cortex on excessive daytime sleepiness in patients with Parkinson's disease.

BACKGROUND: Excessive daytime sleepiness (EDS) is a common sleep disorder in Parkinson's disease (PD), which seriously affects patients' quality of life. Repetitive transcranial magnetic stimulation (rTMS) can be used as an add-on therapy to a variety of non-motor symptoms of PD. However, little is known on the treatment of EDS in PD patients. OBJECTIVE: To explore the effects of low frequency rTMS over right dorsolateral prefrontal cortex (DLPFC) in the treatment of EDS in PD. METHODS: We conducted a sham-controlled, parallel study including 25 individuals of PD with possible EDS based on Epworth Sleepiness Scale (ESS ≥8 points) and randomly divided them into active group (n = 15) and sham group (n = 10). 1 Hz rTMS was administrated over right DLPFC for 10 consecutive days. In the active group, we further classified them into responsive group and non-responsive group according to change of ESS score in comparison with baseline. Clinical assessments on motor and non-motor symptoms were completed at baseline, at the end of treatment and 1 month after treatment. RESULTS: Compared to baseline, active group showed significant improvement on ESS score 10 days and 1 month after treatment (P < 0.05 for both). The percentage change of ESS score was positively related to disease duration during follow-up. No significant changes were observed on ESS score change in the sham group. Further analysis of individuals in the active group showed that, relative to those with non-response to rTMS, individuals with therapeutic response exhibited longer disease duration and lower baseline levodopa equivalent dose. CONCLUSION: Low frequency rTMS over right DLPFC may improve symptoms of EDS in PD.

Investigation of the Effectiveness of Traditional Breathing Therapy on Pulmonary Function in College Students with Obstructive Sleep Apnea.

Background: Obstructive sleep apnea (OSA) is a problem that involves many body systems, but its impact on the respiratory system deserves special attention. While there are many studies investigating the use of continuous positive airway pressure (CPAP) to treat lung function in patients with sleep apnea, the lack of studies in the literature on the effects of traditional breathing therapy on lung function in patients with OSA prompted us to conduct such a study. Objective: The present randomized trial aims to assess the effect of traditional breathing therapy on daytime sleepiness and pulmonary function in college students with OSA. Methods: Forty college students (male) with OSA were randomly divided into two groups: the control group (CG) and the traditional breathing therapy group (TG). Daytime sleepiness symptoms in OSA are measured primarily by the Epworth Sleepiness Scale (ESS). Pulmonary function measurements included FVC, FEV1, PEE, and MEF50%. The changes in morning blood pressure (BP), including diastolic BP and systolic BP, were also recorded. Data were recorded before and after the experiment. Results: A decrease in ESS at 12 weeks after intervention had statistical significance compared with values recorded before intervention (P < 0.05). A decrease in systolic and diastolic BP at 12 weeks after intervention had statistical significance compared with values recorded before intervention (P < 0.05). Comparisons made in terms of pulmonary functions demonstrated a statistically significant increase in 12-week postintervention values of FVC, FEV1, PEF, and MEF50% (P < 0.05). Conclusion: Our study shows the positive effects of traditional breathing therapy on pulmonary function parameters. This suggests that traditional breathing therapy treatment in OSA patients is as effective as CPAP on pulmonary function, while there is an improvement in daytime sleepiness and a modest decline in the mean daytime systolic and diastolic BP.

Stellate ganglion block rectifies excessive daytime sleepiness: a case report.

Excessive daytime sleepiness (EDS) is classified as a neurofunctional disorder that manifests as uncontrolled sleeping propensity in the daytime. Currently, consistent and effective therapeutic approaches for EDS are lacking. Stellate ganglion block (SGB) has a clear effect in various complicated pain syndromes, vascular insufficiency, hyperhidrosis, and posttraumatic stress syndrome. We report an EDS case that involved a patient who recovered after several sessions of SGB.

The effect of breathing exercise on daytime sleepiness and fatigue among patients with obstructive sleep apnea syndrome.

This study was conducted with randomized controlled and experimental design to examine the effect of breathing exercise on daytime sleepiness and fatigue on patients with obstructive sleep apnea syndrome. The first application was performed by teaching patients in the intervention group breathing exercises including diaphragmatic and pursed lip breathing via the face-to-face interview technique. Then, the researcher applied breathing exercises in the same patient group every morning/evening for 10-15 min and a total of 20-30 min for eight weeks via the online interview method. The data were collected via a questionnaire, Epworth sleepiness scale (ESS), and Piper Fatigue Scale (PFS). Chi-square, Student's t, Mann Whitney U, paired sample t-test, analysis of variance (ANOVA) and generalized estimating equations were used to assess the data. It was determined that PFS total mean score of the intervention group which was 6.15 ± 1.65 before the application decreased to 5.34 ± 1.94 in the eighth week (p> 0.05) and PFS total mean score of the control group which was 5.59 ± 1.76 before the application increased to 5.77 ± 1.81 in the eighth week (p> 0.05). ESS total mean score of the intervention group which was 12.13 ± 4.34 at the baseline decreased to 9.13 ± 4.71 in the eighth week (p> 0.05) and ESS total mean score of the control group which was 10.37 ± 2.77 at the baseline increased to 10.5 ± 2.85 in the eighth week (p> 0.05). It was concluded that breathing exercise performed in the intervention group decreased the fatigue and daytime sleepiness mean scores of the patients at the end of the fourth and eighth week. In addition, the group-time interaction was significant, which was associated with the intervention group.

Application of Inverse-Probability-of-Treatment Weighting to Estimate the Effect of Daytime Sleepiness in Patients with Obstructive Sleep Apnea.

Rationale: Continuous positive airway pressure (CPAP), the first line therapy for obstructive sleep apnea (OSA), is considered effective in reducing daytime sleepiness. Its efficacy relies on adequate adherence, often defined as >4 hours per night. However, this binary threshold may limit our understanding of the causal effect of CPAP adherence and daytime sleepiness, and a multilevel approach for CPAP adherence can be more appropriate. Objectives: In this study, we show how two causal inference methods can be applied on observational data for the estimation of the effect of different ranges of CPAP adherence on daytime sleepiness as measured by the Epworth Sleepiness Scale (ESS). Methods: Data were collected from a large prospective observational French cohort for patients with OSA. Four groups of CPAP adherence were considered (0-4, 4-6, 6-7, and 7-10 h per night). Multivariable regression, inverse-probability-of-treatment weighting (IPTW), and inverse propensity weighting with regression adjustment (IPW-RA) were used to assess the impact of CPAP adherence level on daytime sleepiness. Results: In this study, 9,244 patients with OSA treated by CPAP were included. The mean initial ESS score was 11 (±5.2), with a mean reduction of 4 points (±5.1). Overall, there was evidence of the causal effect of CPAP adherence on daytime sleepiness which was mainly observed between the lower CPAP adherence group (0-4 h) compared with the higher CPAP adherence group (7-10 h). There are no differences by considering higher level of CPAP adherence (>4 h). Conclusions: We showed that IPTW and IPW-RA can be easily implemented to answer questions regarding causal effects using observational data when randomized trials cannot be conducted. Both methods give a direct causal interpretation at the population level and allow the assessment of the appropriate consideration of measured confounders.

Patient preferences in obstructive sleep apnea-a discrete choice experiment.

BACKGROUND: Obstructive sleep apnea (OSA) is one of the most common chronic sleep disorders, which can be treated by different interventions. It is known that acceptance and adherence to these therapies is influenced by a variety of factors. However, there is a limited understanding of patient preferences and decision-making in the context of OSA treatment. METHODS: A discrete choice experiment was conducted on patients with OSA recruited from a tertiary sleep center to evaluate preferences for different treatment attributes. Participants received four different choice tasks with three hypothetical treatments, each defined by seven attributes. A random-effects logit model was used to estimate the influence of the different attributes on the choice decisions. Multivariate logistic regression analysis was carried out to evaluate interactions with medical variables. RESULTS: In a cohort of 241 subjects with OSA, preferences for treatment attributes and utilities derived from them differed. Most relevant attributes were Reduction in risk of comorbidities, Improvements of daytime sleepiness, Requirement for surgery, and Occurrence of treatment-related side effects. Demographic or medical variables, such as age, gender, or apnea-hypopnea index, did not influence the choice decision. Multivariate logistic regression revealed significant differences in preferences depending on OSA disease history (p = .025) and presence of OSA symptoms (p = .033). CONCLUSIONS: The study identified preferences for attributes of OSA and their utilities from a patient perspective. Relevant differences of preferences in subgroups of patients with OSA were identified, which may be important to consider in selecting appropriate treatments that lead to high rates of acceptance and adherence.