Establishing the content validity of the Epworth Sleepiness Scale for Children and Adolescents in Prader-Willi syndrome.

An Obese Female with Prader-Willi Syndrome and Daytime Sleepiness

To assess the impact of coronavirus disease 2019 (COVID-19)-related restrictions on narcolepsy type 1 (NT2), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH). Participants with NT1, NT2, and IH followed in a university hospital completed an online 78-question survey assessing demographic, clinical, and occupational features of the population during the first COVID-19-related lockdown. A total of 219 of 851 (25.7%) respondents of the survey reported a mean increase of 1.2 ± 1.9 hours (P < .001) in night sleep time and a mean decrease of 1.0 ± 3.4 points (P < .001) on the Epworth Sleepiness Scale during lockdown. Bedtime was delayed by 46.1% of participants and wakeup time was delayed by 59.6%, driven primarily by participants with IH. Teleworkers (but not in-person workers) reported a mean increase of 0.9 ± 1.2 hours in night sleep (P < .001) and a mean decrease in sleepiness score of 1.6 ± 3.1 (P < .001). Cataplexy improved in 54.1% of participants with NT1. Sleepiness correlated with psychological wellness (r = .3, P < .001). As many as 42.5% enjoyed the lockdown, thanks to reallocation of time usually spent commuting toward longer sleep time, hobbies, and family time, and appreciated a freer napping schedule. Conversely, 13.2% disliked the lockdown, feeling isolation and psychological distress. Extended sleep time, circadian delay (in patients with IH), and teleworking resulted in decreased symptoms of central hypersomnias. These findings suggest that people with IH, NT1, and NT2 may benefit from a decrease in social and professional constraints on sleep-wake habits, and support advocacy efforts aimed at facilitating workplace and schedule accommodations for this population. Nigam M, Hippolyte A, Dodet P, etal. Sleeping through a pandemic: impact of COVID-19-related restrictions on narcolepsy and idiopathic hypersomnia. J Clin Sleep Med. 2022;18(1):255-263.

Subjective-objective sleepiness discrepancy in adult-onset myotonic dystrophy type 1.

Seasonality of excessive daytime sleepiness has been proposed, yet no research has specifically investigated its impact on daytime sleepiness and cataplexy in central disorders of hypersomnolence. This study examined seasonal variations in daytime sleepiness and cataplexy in narcolepsy type 1, narcolepsy type 2 and idiopathic hypersomnia. Patients included in the study were on stable pharmacological treatment, and participated in sleep medicine interviews to assess diurnal sleepiness and daytime napping and completed the Epworth Sleepiness Scale to assess excessive daytime sleepiness (Epworth Sleepiness Scale ≥ 10). Patients with narcolepsy type 1 also maintained a cataplexy diary. Evaluations were conducted in autumn, winter, spring and summer. The study included 29 patients with narcolepsy type 1, 16 patients with narcolepsy type 2 and 10 patients with idiopathic hypersomnia. Patients with narcolepsy type 1 and narcolepsy type 2 showed higher Epworth Sleepiness Scale scores in summer compared with other seasons, while patients with idiopathic hypersomnia showed no changes in excessive daytime sleepiness across the four seasons. Epworth Sleepiness Scale scores were higher in idiopathic hypersomnia patients compared to narcolepsy type 1 and narcolepsy type 2 patients in spring, autumn, and winter; conversely, in summer there were no differences in Epworth Sleepiness Scale scores among the three groups. No significant differences in Epworth Sleepiness Scale scores were noted between patients with narcolepsy type 1 and narcolepsy type 2 throughout the year. Furthermore, no seasonal effect on cataplexy frequency was found in patients with narcolepsy type 1. This study demonstrates that seasonality may influence daytime sleepiness in patients with narcolepsy type 1 and narcolepsy type 2 but not in patients with idiopathic hypersomnia, while cataplexy symptoms remain unaffected by seasonal changes. The underlying mechanisms linking excessive daytime sleepiness to seasonality have yet to be explored, though social factors and vacation time may contribute to increased excessive daytime sleepiness in narcolepsy.

Excessive daytime sleepiness (EDS) is a key symptom of obstructive sleep apnea (OSA). The Psychomotor Vigilance Task (PVT) has been suggested as an objective easy-to-use, inexpensive alternative to the Multiple Sleep Latency Test (MSLT) to measure EDS. In patients with OSA, physiological sleepiness, but not subjective EDS (Epworth Sleepiness Scale [ESS]), has been associated with increased levels of the sleep- inducing proinflammatory cytokine interleukin-6 (IL-6). The goal of this study was to assess the association of PVT with objectively measured sleepiness (MSLT) and subjectively measured sleepiness (ESS) and IL-6 levels in patients with OSA. We studied 58 untreated patients with OSA who underwent an 8-hour in-laboratory polysomnography for 4 consecutive nights. MSLT, PVT, and 24-hour serial profiles of IL-6 were assessed on the fourth day. PVT variables included number of lapses, mean reciprocal of the fastest 10% and slowest 10% reaction times, and median of 1/reaction time. ESS was assessed on day 1 of the study. Higher ESS scores were significantly associated with greater number of lapses (β = .34, P = .02) and lower values of 1/RT (β = -.36, P = .01) and slowest 10% RTs (β = -.30, P = .04). No significant association was observed between PVT and MSLT, nor PVT and IL-6 levels. Our findings suggest that PVT is associated with subjectively assessed daytime sleepiness, but not with physiological sleepiness nor IL-6 levels in patients with OSA. It appears that ESS and PVT may be useful in predicting risks associated with impaired performance, such as traffic accidents, in patients with OSA.

Individuals with Prader-Willi syndrome (PWS) often have excessive daytime sleepiness and emotional/behavioral disturbances. The objective of this study was to examine whether daytime sleepiness was associated with these emotional/behavioral problems, independent of nighttime sleep-disordered breathing, or the duration of sleep. Caregivers of individuals with PWS (aged 3 to 25 years) completed the Pediatric Sleep Questionnaire (PSQ), Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD), and the parent version of the Developmental Behavior Checklist (DBC-P). Sleep adequacy was adjusted for age by computing sleep duration against age-specific recommendations. The associations between ESS-CHAD and the total DBC and its subscale scores were evaluated by linear regression, adjusted for sleep-related breathing difficulties, sleep adequacy, and body mass index (BMI). There were 54 responses for individuals with PWS (including 22 males) aged 4.4–24.0 (mean 12.5) years. Daytime sleepiness predicted a substantial proportion of the variance in total DBC-P scores in the unadjusted model (28%; β = 0.028; p < 0.001) and when adjusted for sleep adequacy, BMI, and sleep-related breathing difficulties (29%; β = 0.023; p = 0.007). This relationship was not moderated by BMI Z-scores, but the relationship was more prominent for children younger than 12 years than for children older than 12 years.Conclusions: These findings provide preliminary novel evidence that daytime sleepiness may drive the expression of emotional/behavioral disturbances, and should be explored as a potential modifiable risk factor for these disturbances in PWS, particularly pre-adolescent children.What is Known:• Individuals with Prader-Willi syndrome (PWS) commonly experience excessive daytime sleepiness and exhibit emotional/behavioral disturbances.• In the typically developing population, sleepiness is associated with emotional/behavioral disturbances, independently of sleep-disordered breathing..What is New:• This study found evidence for a direct link between daytime sleepiness and emotional/behavioral disturbances, independent of sleep-related breathing difficulties, sleep adequacy, and body mass index.• Excessive daytime sleepiness may be a modifiable risk factor for emotional/behavioral disturbances in PWS.

Development of a Patient Reported Outcome Daily Diary to Assess Symptom Burden in Sickle Cell Disease

This systematic review provides supporting evidence for the accompanying clinical practice guideline on the treatment of central disorders of hypersomnolence in adults and children. The review focuses on prescription medications with U.S. Food & Drug Administration approval and nonpharmacologic interventions studied for the treatment of symptoms caused by central disorders of hypersomnolence. The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine to perform a systematic review. Randomized controlled trials and observational studies addressing pharmacological and nonpharmacological interventions for central disorders of hypersomnolence were identified. Statistical analyses were performed to determine the clinical significance of all outcomes. Finally, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process was used to assess the evidence for the purpose of making specific treatment recommendations. The literature search identified 678 studies; 144 met the inclusion criteria and 108 provided data suitable for statistical analyses. Evidence for the following interventions is presented: armodafinil, clarithromycin, clomipramine, dextroamphetamine, flumazenil, intravenous immune globulin (IVIG), light therapy, lithium, l-carnitine, liraglutide, methylphenidate, methylprednisolone, modafinil, naps, pitolisant, selegiline, sodium oxybate, solriamfetol, and triazolam. The task force provided a detailed summary of the evidence along with the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations. Maski K, Trotti LM, Kotagal S, etal. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2021;17(9):1895-1945.

Hypocretin (Hcrt) is a neurotransmitter of the dorsal and lateral hypothalamus that regulates sleep, appetite, and energy consumption. Recent evidence indicates that it is also involved in pleasure/reward-seeking. Mutation of the Hcrt-receptor gene causes narcolepsy in canines, and Hcrt knockout mice exhibit narcolepsy-like symptoms. Human narcoleptics do not commonly have mutations in the ligand or receptor but do have degeneration of Hcrt-containing neurons, possibly through an autoimmune mechanism. When Hcrt neurons degenerate in mice, hypophagia and obesity are observed, symptoms that are also present in some human narcoleptics. This article reviews the recent literature with regard to the many functions of this single molecule. The authors suggest that eating habits and impulsivity may be topics worth exploring in the evaluation of narcoleptic patients.

Introduction:Over the past decade, health technology assessment (HTA) agencies have become interested in improving the patient-centeredness of their assessments. A common approach has been to prioritize patient-reported outcomes (PROs), often describing PROs as patient-relevant or patient-oriented. However, it is often unclear whether and to what degree PRO measures (PROMs) truly reflect what is important to patients. This review examined the pedigree of a sample of measures used as primary or secondary endpoints in trials and discussed in Food and Drug Administration (FDA) approved product labels between 2003 and 2014.Methods:We examined all 26 PROs included in chapters 1 (Office of Microbial Products) and 2 (Office of Drug Evaluation I) of the FDA's Pilot Clinical Outcome Assessment (COA) Compendium. Three reviewers independently searched PubMed and Google to identify publications or other relevant materials related to method and stage of measure development where patient engagement took place.Results:Among 26 evaluated PROMs, we were unable to locate any information on development or validation for 12 (patient diary=9; rating scale=3). Among the remaining 14 PROMs, 5 did not include any evidence of patient engagement (questionnaire=1; patient diary=2; rating scale=2); 3 engaged patients during concept elicitation or psychometric validation only (disease-specific questionnaires=3); and 6 engaged patients during both concept elicitation and cognitive interviewing (disease-specific questionnaires=6). PROMs either previously qualified or submitted for qualification by FDA were more likely to include patient engagement.Conclusions:PROs can provide patient-centered data useful for HTA; however, patient-reported information is not inherently patient-centered. This study found that only a minority of sampled PROMs engaged patients during both concept elicitation and cognitive interviewing. To facilitate patient-centered HTA, manufacturers should ensure that PROMs incorporated into clinical trials measure concepts important to patients. Similarly, HTAs should request data on development and validation of all outcome measures incorporated into trials.

Common causes for chronic cough include gastroesophageal reflux disease , cough-variant asthma, and upper airway cough syndrome . Despite following the recommendations of current guideline for diagnosis and treatment, a significant proportion of chronic cough patients fail to resolve their cough. Recent studies indicate that the treatment of concomitant obstructive sleep apnea syndrome (OSAS) may help with cough resolution. We investigated the prevalence of OSAS, cough severities, and the effect of continuous positive airway pressure (CPAP) therapy in patients with difficult chronic cough without daytime sleepiness. We investigated 4 difficult chronic cough patients who were intractable for treatment according to current guidelines. Clinical data, treatments provided, cough duration, cough severity (visual analogue scale: VAS), Epworth sleepiness scale (ESS), and apnea hypopnea index (AHI) were evaluated. All patients did not exhibit daytime sleepiness, according to ESS score (ESS: 2-3), but eventually they were diagnosed with severe OSAS (AHI: 42-90). Cough duration was 5 months to 10 years. Cough severities were moderate to severe . The cough of all patients improved after CPAP therapy. There was no relationship between severity of cough and cough duration, BMI, or AHI (cough duration r=0.5, p=0.5; BMI r=-0.21, p=0.79; AHI r=-0.21, p=0.78). These results suggest that examination for OSAS in the case of difficult chronic cough should be considered even without daytime sleepiness. The symptom of daytime sleepiness may be masked by the severity of the cough. Further studies are required to examine the mechanisms underlying OSAS that induce chronic cough and the effect of CPAP in such cases.

Real-time assessment of daytime sleepiness in drivers with multiple sclerosis

Given that intelligence quotient (IQ) has not previously been assessed in idiopathic hypersomnia (IH) and only rarely in adults with narcolepsy type 1 (NT1), this study examined IQ in adults with IH and NT1. The Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV), comprising the Full Scale IQ, four indices and 10 subtests, was administered to 29 participants with IH (22 women; age: 34.1±11.3y [mean±SD]; Epworth Sleepiness Scale [ESS] score: 12.4±4.7), 30 with NT1 (19 women; age: 30.1±10.6y; ESS: 15.5±5), and 30 healthy controls (21 women, age: 30.7±8.7y; ESS: 5.0±3.6). Full-Scale IQ scores differed across groups (IH: 114.6±13.4; NT1: 104.1±14.3; and controls: 108.4±17.0; p=0.03, medium effect size). Both IH and NT1 groups showed IQ comparable to controls, although IH participants tended to outperform those with NT1. Group differences emerged in the perceptual reasoning and working memory domains, although none of pairwise comparisons reached significance. The only cognitive area showing group differences was visuospatial reasoning. Global cognitive abilities, including Full-scale IQ, General Ability Index, Verbal Comprehension Index and Working Memory Index showed moderate correlation with years of education, though not with disease duration, daytime sleepiness or treatment status. Pre-test fatigue, though not daytime sleepiness, was associated with poorer working memory performances. Adults with IH and NT1 exhibit normal-range IQs despite chronic hypersomnolence and cognitive complaints. Emphasizing preserved intellectual functioning may contribute to enhanced self-esteem and support professional development in these populations.

PHP154 - Patient-Reported Outcome Measures in the FDA Pilot Compendium: Meeting Today’s Standards for Patient Engagement in Development?

The Role of Patient-reported Outcomes and Medication Adherence Assessment in Patient-focused Drug Development for Solid Organ Transplantation.