bluuebunny/crossref_metadata_2025 huggingface dataset:
482 Solriamfetol Titration & AdministRaTion (START): dosing and titration strategies in patients with narcolepsy starting solriamfetol
Authors: Thorpy Michael , Hyman Danielle , Parks Gregory , Chen Abby , Foley Catherine , Ito Diane , Singh Haramandeep
Published: May 2021

Introduction

Solriamfetol (Sunosi®), a dopamine/norepinephrine reuptake inhibitor, is approved (US and EU) to treat excessive daytime sleepiness (EDS) in adults with narcolepsy (75–150 mg/day) or obstructive sleep apnea (OSA) (37.5–150 mg/day). Previous research examined the use of solriamfetol in clinical trial settings but research in real-world settings was not previously conducted. This study characterized real-world dosing and titration with solriamfetol.

Methods

This virtual, descriptive study included a quantitative retrospective patient chart review among US-based physicians prescribing solriamfetol. Target enrollment was 25 physicians treating patients with EDS associated with OSA or narcolepsy. Titration strategies were classified as de novo (no prior EDS medication), transition (switched/switching from existing EDS medications onto solriamfetol), or add-on (adding solriamfetol to current EDS medication).

Results

Twenty-six physicians participated. Seventy patients with narcolepsy were analyzed (type 1, n=24; type 2, n=46; mean±SD age, 40±11 years; 57% female; 6 also had OSA); EDS was primarily moderate (59%) or severe (36%). Solriamfetol initiation was de novo for 19 (27%) patients, transition for 31 (44%), and add-on for 20 (29%). Most patients (86%) started solriamfetol at 75 mg; 11% and 3% started at 37.5 mg and 150 mg, respectively. The final/stable dose was 150 mg for 76% (53/70) of patients and 75 mg for 24% (17/70). Most patients (67%) had 1 dose adjustment to reach their final dose; 4% had 2 adjustments, 4% had 3 adjustments, and 24% had none. Mean±SD time to reach a stable dose was 15.1±11.8 days overall, 19.4±9.3 days with de novo treatment, 15.0±13.7 days for transition, and 11.9±8.6 days for add-on. Physicians most frequently considered EDS severity (44% of patients) when titrating. Among patients transitioning, 14/22 (64%) taking a wake-promoting agent (WPA) discontinued it abruptly while 5/9 (56%) taking a stimulant were tapered off. Physicians were overall likely (n=33, 47%) or very likely (n=30, 43%) to recommend their approach for similar patients.

Conclusion

In a real-world study, the majority of physicians prescribing solriamfetol for patients with narcolepsy started at the 75-mg dose, tapered stimulants but abruptly discontinued WPAs, and made 1 adjustment to reach a stable dose across 15 days on average.

Support (if any)

Jazz Pharmaceuticals
485 Efficacy and Safety of Once- and Twice-Nightly Dosing of Lower-Sodium Oxybate in Adults With Idiopathic Hypersomnia
Authors: Arnulf Isabelle , Morse Anne Marie , Chandler Patricia , Parvataneni Rupa , Chen Dan , Dauvilliers Yves
Published: May 2021

Introduction

Idiopathic hypersomnia (IH) is a rare central hypersomnolence disorder. In a randomized, controlled study of lower-sodium oxybate (LXB; Xywav™) in adults with IH (NCT03533114), significant differences for LXB compared with placebo were observed in Epworth Sleepiness Scale (ESS; primary efficacy endpoint), self-reported Patient Global Impression of Change (PGIc), and IH Severity Scale (IHSS; key secondary endpoints). In this clinical study, investigators were permitted to initiate LXB dosing on a once-nightly or twice-nightly regimen.

Methods

Eligible participants aged 18–75 years began LXB treatment, administered once or twice nightly during an open-label treatment/titration and optimization period (OLTTOP; 10–14 weeks); dose amount/regimen could be adjusted during this period. Participants next entered a 2-week, open-label, stable-dose period (SDP), then were randomized to placebo or to continue LXB treatment during a 2-week, double-blind, randomized withdrawal period (DBRWP). P values are nominal for this exploratory analysis.

Results

Of 154 enrolled participants, 40 (26%) initiated LXB treatment on a once-nightly regimen. In the efficacy population (n=115), 27 participants were on a once-nightly regimen during SDP (48.1% of whom initiated treatment once nightly during OLTTOP) and 88 participants were on a twice-nightly regimen during SDP (86.4% of whom initiated treatment twice nightly during OLTTOP). During SDP, median (min, max) LXB total dose was 4.5 (2.5, 6) g/night (once-nightly group) and 7.5 (4.5, 9) g/night (twice-nightly group). ESS scores worsened in participants randomized to placebo vs those continuing LXB in the once-nightly group (n=11 and n=15, respectively; LS mean difference [95% CI]: −4.93 [−7.41, −2.46]; P=0.0004) and twice-nightly group (n=47 and n=41, respectively; LS mean difference [95% CI]: −7.44 [−9.15, −5.72]; P<0.0001). Worsening was also observed in PGIc (once-nightly: 81.8% [placebo] vs 26.7% [LXB]; P=0.0077; twice-nightly: 89.4% [placebo] vs 19.5% [LXB]; P<0.0001) and IHSS score (estimated median difference [95% CI], once-nightly: −9.00 [−16.0, −3.0]; P=0.0028; twice-nightly: −12.00 [−15.0, −8.0]; P<0.0001). Common adverse events included nausea (21.4%), headache (16.2%), anxiety (14.9%), dizziness (11.7%), insomnia (11.7%), and vomiting (10.4%).

Conclusion

The efficacy and safety of LXB in IH were demonstrated for both once-nightly and twice-nightly regimens. The majority of participants initiated and remained on a twice-nightly regimen.

Support (if any)

Jazz Pharmaceuticals
487 Effect of Lower-Sodium Oxybate on Sleep Inertia in Idiopathic Hypersomnia in a Double-Blind, Randomized Withdrawal Study
Authors: Bogan Richard , Dauvilliers Yves , Thorpy Michael , Chandler Patricia , Chen Abby , Chen Dan , Arnulf Isabelle
Published: May 2021

Introduction

Idiopathic hypersomnia (IH) is a rare central hypersomnolence disorder characterized by excessive daytime sleepiness. A common feature is sleep inertia, which is prolonged difficulty waking up accompanied by confusion, disorientation, poor motor coordination, and repeated returns to sleep. Sleep inertia is burdensome to patients, resulting in missed work or school, and patients may be dependent on others to wake them. No treatment is currently approved for IH. The efficacy and safety of lower-sodium oxybate (LXB; Xywav™), a novel oxybate treatment with 92% less sodium than sodium oxybate (Xyrem®), was evaluated in a phase 3 study (NCT03533114) in adults with IH. We focus here on the drug effect on sleep inertia.

Methods

Eligible participants aged 18–75 years with IH began LXB treatment with an open-label treatment titration and optimization period (OLTTOP; 10–14 weeks), followed by a 2-week, open-label, stable-dose period (SDP). Participants were randomized to placebo or to continue LXB treatment during a 2-week, double-blind, randomized withdrawal period (DBRWP). The primary efficacy endpoint was change in Epworth Sleepiness Scale score. The visual analog scale for sleep inertia (VAS-SI) was included as an exploratory endpoint. The VAS-SI, administered daily during the last 2 weeks of screening before baseline, SDP, and DBRWP, is a self-reported retrospective measure of difficulty awakening each morning using a 100-mm line with anchors 0 (very easy) and 100 (very difficult).

Results

The safety population included 154 participants (mean±SD age, 40±14 years; 68% female); modified intent-to-treat population, n=115. VAS-SI scores gradually decreased from week 2 of screening (mean±SD, 56.6±25.1) to week 2 of SDP (29.0±20.8). During week 2 of DBRWP, VAS-SI scores worsened in participants randomized to placebo (n=59) compared with maintenance of improvement in participants continuing LXB treatment (n=56); LS mean difference (95% CI) in change from SDP, −22.2 (−29.7, −14.8); P<0.0001 (nominal). Common adverse events included nausea (21.4%), headache (16.2%), anxiety (14.9%), dizziness (11.7%), insomnia (11.7%), and vomiting (10.4%).

Conclusion

Sleep inertia improved with LXB treatment and significant differences were seen between placebo and LXB after DBRWP. The overall safety profile in participants with IH is consistent with that of LXB in narcolepsy.

Support (if any)

Jazz Pharmaceuticals, Inc
500 Correlation of the Idiopathic Hypersomnia Severity Scale With Other Measures of Sleep Parameters in a Phase 3 Trial
Authors: Dauvilliers Yves , Arnulf Isabelle , Foldvary-Schaefer Nancy , Chen Abby , Chandler Patricia , Chen Dan , Thorpy Michael
Published: May 2021

Introduction

The Idiopathic Hypersomnia Severity Scale (IHSS) is a 14-item, self-reported questionnaire that assesses core Idiopathic Hypersomnia (IH) symptom severity. The relationship between IHSS scores and other IH symptom measures, such as the Epworth Sleepiness Scale (ESS; measures daytime sleepiness), sleep inertia visual analog scale (VAS-SI; measures sleep inertia), and Patient Global Impression of Change (PGIc; measures patients’ self-assessed change in symptoms), has not been established. This post hoc analysis analyzed correlations between the IHSS and ESS, VAS-SI, and PGIc using data from a clinical trial (NCT03533114) evaluating lower-sodium oxybate (LXB; Xywav™) for the treatment of IH.

Methods

During a clinical trial, the IHSS (0–50 score range) and ESS (0–24 score range) were completed at baseline; the IHSS, ESS, and PGIc (ordinal, 7 categories) were completed during an open-label treatment titration and optimization period (OLTTOP), after the OLTTOP, after a stable-dose period (SDP), and after a double-blind, randomized withdrawal period (DBRWP). The VAS-SI (0–100 score range) was completed during screening, SDP, and DBRWP. Correlation coefficients (rs) for IHSS vs ESS and VAS-SI were estimated from the within-subject variance matrix using a repeated-measures linear mixed model (LMM). The correlation between changes in IHSS score and PGIc was assessed using a Kruskal-Wallis test.

Results

IHSS scores correlated positively with ESS scores (rs [95% CI], 0.77 [0.73, 0.81]) and VAS-SI scores (0.69 [0.63, 0.75]). IHSS total score change was correlated with PGIc rank (chi-square with 6 degrees of freedom = 595.8, nominal P<0.001). The LMM showed that a 3-point change in ESS score corresponded to an average 3.99-point change in IHSS score; a 10-point change in VAS-SI score corresponded to an average 3-point change in IHSS score. Participants very much improved in the PGIc had a −12.13 (95% CI: −13.23, −11.04) expected change in IHSS score. Participants much improved in the PGIc had a −8.39 (95% CI: −9.30, −7.48) expected change in IHSS score.

Conclusion

IHSS scores or score changes strongly correlated with individual instruments assessing excessive daytime sleepiness, sleep inertia, and self-reported global symptoms, suggesting that the IHSS is a reliable, comprehensive measure of these symptoms of IH.

Support (if any)

Jazz Pharmaceuticals
507 Clinical Impression of Excessive Daytime Sleepiness (EDS) at initial Sleep Medicine (SM) consultation and its clinical correlates
Authors: Rosenthal Leon , Roblero Raúl Aguilar
Published: May 2021

Introduction

EDS represents a cardinal symptom in SM. Use of subjective scales are prevalent, which have a modest correlation with the MSLT. While the Clinical Global Impression has been used in research, reports of clinical impression (CI) in medical practice are lacking. We report on the CI of EDS in a convenience sample of patients undergoing initial consultation.

Methods

Patients reported primary, secondary symptoms and completed the Sleep Wake Activity Inventory (SWAI) prior to Tele-Medicine consultation. A SM physician completed the assessment which included ascertainment of CI of EDS (presence S+ / absence S-).

Results

There were 39 ♂and 13 ♀. The CI identified 26 patients in each group (S+/S-). Age (52 [14]), BMI (33 [7]), reported time in bed, sleep time, sleep onset latency and # of awakenings did not differ. All identified a primary symptom (S-: 21, S+: 19 reported snoring or a previous Dx of OSA). Sleepiness as a 1ry or 2ry symptom was identified by 0 in the S- and by 13 in the S+ groups. Refreshing quality of sleep differed (χ2 <0.05): un-refreshing sleep was reported by 7 (S-) and by 13 (S+). Naps/week: 0.7 [1.5] and 1.57 [1.5] for the S-, S+ groups respectively (p<0.05). A main effect (p<0.01) was documented on the SWAI. We report on the Sleepiness [SS] and Energy Level [EL] scales (lower scores on the SS reflect higher sleepiness while lower scores on EL denote higher energy). Higher sleepiness (p<0.01) 43 [12] and lower energy levels 24 [6] (p<0.05) were documented on the S+ group (S- 61 [17], and 18 [6] respectively). Available spouse’s Epworth score on 29 patients: S- patients 5.8 [4] and S+ 10.2 [6] (p<0.05). Dx of OSA was identified among all but 1 in the S+ group. Also, Insomnia was diagnosed among 11 (S-) and 19 (S+) patients (p<0.05) despite only 3 and 7 (respectively) identifying it as a presenting symptom.

Conclusion

While snoring or previous Dx of OSA were prevalent motivations for consultation, sleepiness and insomnia were clinically relevant among a substantial number of patients. Unrefreshing sleep, daytime naps, lower energy, and higher sleepiness were ubiquitous among S+ patients.

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514 Narcocataplectic patients, psychiatric symptoms and executive functions: is there a link?
Authors: Mombelli Samantha , Castelnuovo Alessandra , Marelli Sara , Gialdi Giulia , Somma Antonella , Zucconi Marco , Fossati Andrea , Ferini-Strambi Luigi
Published: May 2021

Introduction

Narcolepsy with cataplexy (NC) is a neurological disorder characterized by orexin deficiency in the hypothalamus with associations to areas implied in emotion. Several studies highlighted a deficit in executive functions in narcoleptic patients. Moreover literature reports a wide comorbidity between NC and psychiatric disorders, but the relationships in NC patients are still unclear. The aim of our study is to evaluate possible mood and anxiety disorders in NC patients and understand their relationship with cognitive performances.

Methods

We assessed 15 NC patients with questionnaires concerning degree of somnolence [ESS], depression [BDI-II], perceived stress [PSS], state and trait anxiety [STAY-Y I and II]. Furthermore, patients performed a battery test (PEBL - psychology experiment building language) to investigate executive functions through 7 tests (Berg’s Card Sorting Test [BCST]; Tower of London [TOL]; Continuous Performance Task [CPT]; Go / No-go Task; Victoria Stroop Test [VST]; Balloon Analogue Risk Task [BART]; Digit Span Forward).

Results

Descriptive analyses show that NC subjects have pathological daytime sleepiness (16,07±2,94), moderate perceived stress (19,73±3,95), mild state anxiety (48,67±15,77). However, subjects do not show pathological indexes in depression and in trait anxiety. We also found a positive correlation in both state and trait anxiety with failure to maintain set in the BCST test (r=0,644; p=0,010 and r=0,573; p=0,025, respectively). However, no significant correlations were found between PEBL scores and excessive daytime sleepiness, depression, and perceived stress.

Conclusion

Our data confirm that NC subjects show symptoms related to stress and anxiety, that can facilitate the change of the set during cognitive performances. Since the neurotransmission of hypocretin is involved in the regulation of stress and anxiety, it is important to understand whether these symptoms are primary pathological phenomena in NC patients. Our data suggest that sleep medicine experts should also consider psychiatric aspects during the cognitive assessment of NC patients.

Support (if any)

None
519 Restless Legs and Periodic Limb Movements in 86 patients with Multiple Sclerosis
Authors: Sparasci Davide , Ferri Raffaele , Castelnovo Anna , Gobbi Claudio , Zecca Chiara , Riccitelli Gianna , Disanto Giulio , Carelli Chiara , Miano Silvia , Tanioka Kosuke , Tachibana Naoko , Manconi Mauro
Published: May 2021

Introduction

The aim of this study was to assess the prevalence of restless legs syndrome (RLS), periodic limb movements during sleep (PLMS) and their overlap in a large population of patients with multiple sclerosis (MS), and to compare clinical and paraclinical findings between patients with and without RLS/PLMS.

Methods

In this cross–sectional, observational, instrumental study, eighty-six patients (M/F: 27/59; mean age 48.0 ± 10.8 years) with a diagnosis of MS underwent a structured telephone interview assessing the five standard diagnostic criteria for RLS. Seventy-six participants underwent Video-polysomnography and Maintenance of Wakefulness Test (MWT). Instrumental and clinical findings were subsequently statistically compared to investigate their association with RLS and PLMS index (PLMSI).

Results

RLS and PLMS (PLMSI ≥15/h) prevalence in patients with MS was of 31.4% and 31.6% respectively. Among patients with RLS, 37.5% had a PLMSI ≥15/h. In the group with PLMS, 37.5% met all diagnostic criteria for RLS. No differences were found between patients with and without RLS (F = 0.99, p = 0.45), and between patients with and without a PLMSI ≥15/hour (F = 0.32 p = 0.94) on the pool of clinical and instrumental variables.

Conclusion

RLS is highly prevalent and severe in patients with MS. The prevalence of PLMS is comparable to the general population. The low percentage of patients with RLS having a high PLMSI, together with the absence of correlation between RLS and female gender and older age, support the existence of a distinct symptomatic form of RLS in MS.

Support (if any):
523 Characteristics of Patients with REM Sleep without Atonia/Periodic Limb Movements of Sleep without Dream Enactment Behaviors
Authors: Barker Lina , Tippmann-Peikert Maja
Published: May 2021

Introduction

While REM sleep without atonia (RSWA) in REM sleep behavior disorder (RBD) is associated with male sex, age greater than or equal to 50 years, alpha-synucleinopathies, and narcolepsy, the characteristics of patients with RSWA/persistent periodic limb movements of sleep in REM sleep (RSWA/PLMS-REM) without dream enactment behaviors are unexplored. The aim of this study was to compare the demographics, comorbidities, and concomitant medication use between RSWA/PLMS-REM patients and non-RSWA/non-PLMS-REM controls. Based on anecdotal clinical observations, we hypothesized that these patients are more commonly young, women, have psychiatric or neurological diseases, and use antidepressants.

Methods

We conducted a retrospective review of the Mayo Clinic electronic medical record to identify all patients with RSWA/PLMS-REM between November 2018 and November 2020. After excluding all patients with RBD, restless legs syndrome, narcolepsy, and RSWA/non-PLMS-REM, we identified 27 patients. All in-lab polysomnograms (PSGs) were reviewed to calculate the periodic limb movement index per hour of REM sleep (REM-PLMI). We also identified a control group of 15 individuals without RSWA, reviewed their PSGs, and calculated the REM-PLMI.

Results

The mean REM-PLMI of patients with RSWA was 64 +/- 8.3 (standard error of mean (SEM)) per hour versus 1 +/- 0.6 (SEM) per hour in non-RSWA controls (p < 0.001). Patients with RSWA/PLMS-REM and non-RSWA controls had similar age and gender, 62 +/- 3 (SEM) versus 58 +/- 3 (SEM) years and 81% versus 87% men, respectively. However, psychiatric diagnosis, neurological disorders, and antidepressants use were more common among RSWA/PLMS-REM patients compared to non-RSWA controls with p = 0.0002, p = 0.0035 and p = 0.0074 respectively (Fisher’s Exact Test).

Conclusion

Psychiatric diagnosis, neurological disorders, and antidepressant use are more common among RSWA/PLMS-REM patients compared to non-RSWA/non-PLMS-REM controls. Further research to determine the implications of a diagnosis of RSWA/PLMS-REM for the future development of alpha-synucleinopathies are needed and currently ongoing.

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530 Restless Legs Syndrome Prevalence and Severity Among Patients Treated with Buprenorphine and Naloxone for Opioid Use Disorder
Authors: Wipper Benjamin , Cooke Michelle , Winkelman John
Published: May 2021

Introduction

Restless Legs Syndrome (RLS) is a sensory-motor neurological disorder which is associated with sleep disturbance and emotional distress. Opioid medications are effective treatments for RLS, and a high percentage of patients undergoing opioid withdrawal exhibit symptoms of RLS. Despite the known connection between RLS and opioids, there has been no assessment of RLS in patients actively treated with buprenorphine and naloxone for opioid use disorder (OUD).

Methods

We conducted a study to determine the prevalence of RLS among patients with OUD at an outpatient buprenorphine and naloxone clinic at Lemuel Shattuck Hospital in Jamaica Plain, Massachusetts. With the help of nurses, participants completed questionnaires which inquired about demographic information, previous opioid use, current medications, and RLS. Patients were categorized as having RLS if, according to the Cambridge-Hopkins Questionnaire, they answered positively to the four essential RLS criteria and if common mimics were not endorsed. A final determination of RLS status in those with ambiguous answers to RLS mimics was made by a trained sleep medicine physician (JWW).

Results

Participants (n=129) were primarily male (n=86; 66.7%), white (n=101; 78.3%), and the median age was 37.5 years. Approximately half of the sample (n=59; 45.7%) used medications for depression and/or anxiety. The median duration of buprenorphine and naloxone use was 3 years. 13.2% were judged to have RLS. RLS symptoms tended to be of moderate severity, disturb sleep to a moderate degree, and occur 5–15 days per month. There were no significant demographic or clinical differences in those with and without RLS. Of the 103 participants without suspected RLS, 15.5% (n=16) were taking a non-opioid medication known to treat RLS symptoms (e.g. gabapentin). Only 1/17 people (5.9%) with RLS were taking a treatment that would control such symptoms.

Conclusion

Approximately 13% of this sample currently taking buprenorphine and naloxone for OUD had RLS. RLS can greatly interfere with sleep and quality of life, and those with untreated or partially treated symptoms may be motivated to use unprescribed opioids to control them. With this in mind, clinicians treating OUD should be aware that there are effective non-opioid medications that can treat RLS.

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532 Two-Year Longitudinal Data From the National Restless Legs Syndrome Opioid Registry
Authors: Winkelman John , Wipper Benjamin , Purks Julia
Published: May 2021

Introduction

Restless Legs Syndrome (RLS) is a sensory-motor neurological disorder which is associated with sleep disturbance and emotional distress. Low dose opioid medications are prescribed for treatment-refractory RLS. We now report two-year longitudinal data from the National RLS Opioid Registry, a national sample of patients using opioids for RLS.

Methods

Individuals (n=500) taking a prescribed opioid for diagnosed RLS were enrolled in the registry from 12/2017–9/2019. Information on initial and current opioid dosages, side effects, past and current RLS treatments, and RLS severity was collected by interview at baseline. Follow-up online surveys were performed at six-month intervals for two years.

Results

At the time of analysis, 325 participants had reached two years since enrollment and completed the two-year survey (retention rate=95.3%). There were no mean changes from baseline in RLS symptom severity, sleep, or mood measures. Opioid dose changes from baseline to one- and two-year follow-up were: unchanged (51.2%, 43.1%), increased dose (29.7%, 36.7%), decreased dose (19.1%, 20.2%). Only 7.9% of participants increased dose from baseline at both one and two years. The median dose increase from baseline to two-years was just 10 morphine milligram equivalents (MME). Dose increases of >25 MME occurred in 7.3% of participants (vs 5.2% at one-year) and were independently associated with use of an opioid for a comorbid pain condition in addition to RLS (OR 5.91, p=0.02), discontinuing a non-opioid RLS medication (OR 4.26, p=0.01), and age of 55 or younger at baseline (OR 3.60, p=0.01). Being on an opioid medication for <1 year at baseline was a predictor at one-year follow-up but not during year two of participation.

Conclusion

Prescribed opioid doses remained relatively stable over the two years following enrollment into the registry. Of the 37% of participants that increased dose, over half increased by 10 MME or less. Individuals at the start of opioid treatment for RLS do not see elevated rates of dose increase past the first year of use. Future longitudinal data will improve our understanding of the efficacy and tolerability of opioids for RLS.

Support (if any)

The RLS Foundation, Baszucki Brain Research Fund, Florence Petrlik Family Foundation, Diane and Richard Brainerd, and Steven Silin
542 Objective Sleep Duration, Sleep Timing and Completion of In Vitro Fertilization Cycles; a Prospective Cohort Study
Authors: Pimolsri Chawanont , Lyu Xiru , Goldstein Cathy , Fortin Chelsea , Mumford Sunni , Smith Yolanda , Lanham Michael , O’Brien Louise , Dunietz Galit Levi
Published: May 2021

Introduction

Sleep duration and circadian misalignment have been linked to fertility and fecundability. However, sleep in women undergoing IVF has rarely been examined. This study investigated the role of sleep duration and timing with completion of an IVF cycle.

Methods

Prospective study of women undergoing IVF at a tertiary medical center between 2015 and 2017. Sleep was assessed by wrist-worn actigraphy 1–2 weeks prior to the initiation of their IVF cycle. Reproductive profile, IVF cycle details, demographic and health information were obtained from medical charts. Sleep duration, midpoint and bedtime were examined in relation to IVF cycle completion using logistic regression models, adjusted for age and anti-Müllerian hormone levels. A sub-analysis excluded women who worked non-day shifts to control for circadian misalignment.

Results

A total of 48 women were studied. Median age was 33y (range 25–42), with 29% of women older than 35 years. Ten women had an IVF cycle cancellation prior to embryo transfer. These women had shorter sleep duration, more nocturnal awakenings, lower sleep efficiency, and later sleep timing in comparison to those who completed their cycle. Twenty-minute increases in sleep duration were associated with lower odds of an uncompleted IVF cycle (OR = 0.88; 95% CI 0.78, 1.00). Women with later sleep midpoints and later bedtime had higher odds of an uncompleted cycle relative to those with earlier midpoints and earlier bedtime; OR=1.24; 95% CI 1.09, 1.40 and OR=1.33; 95% CI 1.17, 1.53 respectively, per 20-minute increments. These results were independent of age, levels of anti-Müllerian hormone, or sleep duration, and remained unchanged after exclusion of shift-working women.

Conclusion

This study demonstrated the influence of sleep duration and sleep timing on the odds of an uncompleted IVF cycle prior to embryo transfer. Sleep is a modifiable behavior that may contribute to IVF cycle success.

Support (if any):
545 Actigraphic sleep parameters and anxiety symptoms among community-dwelling older adults
Authors: Ding Alice , Smail Emily , Alfini Alfonso , Spira Adam
Published: May 2021

Introduction

A number of cross-sectional studies have found that elevated levels of anxiety are associated with poor sleep among healthy older adults, but most have used self-reported sleep measures. We investigated the longitudinal association between objectively measured sleep (by wrist actigraphy) and subsequent change in anxiety symptoms in this population.

Methods

We studied 555 community-dwelling older adults (mean age 72.52±7.35, 77.48% white, 53.15% women) in the National Social Health and Aging Project (NSHAP) study who completed 3 nights of wrist actigraphy at wave 2 (2010–2011) and the Hospital Anxiety and Depression Scale at waves 2 and 3 (2015–2016). Actigraphic sleep parameters were averaged across nights and included: total sleep time (TST; minutes), percent sleep (%), wake after sleep onset (WASO; minutes), and sleep fragmentation. Change in anxiety was calculated as the difference between anxiety scores at wave 3 and wave 2.

Results

After adjusting for age, race, sex, education, body mass index, number of medical conditions, depression symptoms, and anxiety scores at wave 2, we found no significant associations between any actigraphic sleep parameter and subsequent change in anxiety symptoms (all p ≥ 0.390). Additional analyses revealed no significant cross-sectional associations at wave 2 (p ≥ 0.390).

Conclusion

We found no evidence for an association between actigraphic sleep and anxiety symptoms, or change in anxiety symptoms, in community-dwelling older adults. Additional studies using clinical anxiety disorder diagnoses are needed to evaluate the extent to which objectively measured sleep disturbance predicts clinically significant anxiety in older adults.

Support (if any)

American Academy of Sleep Medicine Foundation (#223-BS-19).
562 Adenoid Regrowth after Rapid Maxillary Expansion in Residual Pediatric OSA: Interim analysis of ERMES Randomized Clinical Trial
Authors: Fernández-Barriales Marcos , de Luzuriaga Montserrat López , Álvarez Ainoa , Guerra Lourdes , Aguirre-Urizar Jose Manuel , Santaolalla Carlos Egea
Published: May 2021

Introduction

Residual pediatric Obstructive Sleep Apnea (OSA) after gold-standard treatment with adenotonsillectomy occurs in nearly 20% of the patients. Treatment alternatives are scarce and based upon low-level evidence. Rapid maxillary expansion is an orthodontic-orthopaedic treatment of maxillary transverse hypoplasia that has shown promising results in pediatric OSA based upon nasal and oral cavity enlargement. Revision adenoidectomy of all-purpose adenotonsillectomies in population-based studies is 4,9%, and a three-fold risk in OSA patients has been reported. We present data from an ongoing randomized clinical trial (ERMES) highlighting the importance of nasofibroscopic control of the adenoid tissue in residual pediatric OSA patients.

Methods

According to the study protocol of our ongoing randomized clinical trial (Rapid maxillary expansion for treatment of residual pediatric obstructive sleep apnea; Acronym: ERMES; NCT02947464) patients aged 4 to 9 years old with polysomnographic evidence of OSA persistence after adenotonsillectomy were randomized to either rapid maxillary expansion or wahtchful waiting. They underwent fiberoptic nasopharingoscopy in order to stablish the amount of adenoidal tissue present at the time of inclusion and at polysomnographic control twelve months later. The nasopharyngeal occupation was measured in a 1 to 4 scale. Patients that graded 3 or 4 at the initial nasofibroscopy were excluded from the study due to their surgical revision indication; if they developed grade 3 or 4 adenoid hypertrophy and persistence of symptoms at the final assesment they were offered re-adenoidectomy.

Results

A total of 5 patients developed an adenoid regrowth amenable for revision surgery: 4 of them within the rapid maxillary expansion group and one in the watchful waiting group. All of them had experienced either worsening or very mild improvement in their apnea hypopnea index (AHI).

Conclusion

Adenoid regrowth is a known risk factor for pediatric OSA persistence. The anatomical enlargement of the nasal and oral cavity provided by means of rapid maxillary expansion may trigger such overgrowth in otherwise predisposed residual OSA patients. Fiberoptic nasopharyngoscopy is therefore mandatory in the follow-up of such complex cases, since adenoid regrowth may hinder resolution of OSA and its associated symptoms.

Support (if any)

ERMES Randomized Clincal Trial (NCT02947464) is funded by Departamento de Salud del Gobierno Vasco.
563 Effect of PHOX2B Genotype and Age on Heart Rate Variability in Pediatric Patients with Congenital Central Hypoventilation Syndrome
Authors: Khaytin Ilya , Winston Molly , Rand Casey , Strewart Tracey , Kitsis Leah , Reed Katherine , Menta Nikita , Brogadir Cindy , Slattery Susan , Weese-Mayer Debra
Published: May 2021

Introduction

Congenital Central Hypoventilation Syndrome (CCHS) is a rare neurocristopathy causing a wide array of cardiac autonomic nervous system (ANS) abnormalities (abnormal heart rate (HR) regulation, decreased HR variability (HRV), prolonged sinus pauses). CCHS is caused by mutations throughout the PHOX2B gene. Different types and locations of PHOX2B mutations have been associated with different levels of CCHS cardiac phenotype severity. We hypothesized that HRV in CCHS will be influenced by age and PHOX2B genotype.

Methods

PHOX2B mutation-confirmed CCHS patients in our cohort followed longitudinally with serial Holter monitoring were included. HRV measures were extracted from Holter monitoring reports and analyzed using linear mixed-effect models. Additional analyses explored which variables predicted sinus pauses and cardiac pacemaker implantation using linear and logistic regression. Only data preceding implantation of a cardiac pacemaker were included in analysis.

Results

97 patients (0–18 years old) were enrolled in the study: 21 with the 20/25 genotype, 21 with the 20/26 genotype, 26 with the 20/27 genotype, 7 with genotypes ranging from 20/28-20/33, and 22 with non-polyalanine repeat expansion mutations (NPARMs). There were 965 total observations (Holters). The following HRV metrics were analyzed: min- and max-HR, longest-RR, SDNN, ASDNN5, SDANN5, and RMSDD. Statistically significant differences were observed between PHOX2B genotypes for min-HR and longest-RR (ps<0.05). Age by genotype interactions emerged such that certain metrics in HRV had different developmental trajectories by genotype (ps<0.05). Min-HR and longest-RR predicted eventual cardiac pacemaker implantation (AUCs>0.78). As for predictors of sinus pauses, different HRV metrics emerged as predictors across PHOX2B genotypes suggesting their utility in predicting cardiac pacemaker implantation dependent on genotype.

Conclusion

HRV in patients with CCHS is dependent on age and PHOX2B genotype, with significant differences in HRV metrics between patients with PHOX2B genotypes 20/25, 20/26, and 20/27 and the patients with 20/28-20/33 genotypes as well as those with NPARMs. Consistent with treatment guidelines, min-HR and longest-RR were predictive of eventual cardiac pacemaker implantation. Differences in the HRV metrics which predict sinus pauses as well as the overall group differences observed and trajectory-based differences may improve anticipatory management by earlier risk identification for prolonged sinus pauses in CCHS.

Support (if any)

None
573 Obstructive Sleep Apnea and Total Sleep Duration is Associated With Problems with Physical Function Mobility in Children
Authors: Turakhia Sujay , Xu Sarah , Miller Michael , Maddalozzo John , Issa Yazan , Bhushan Bharat
Published: May 2021

Introduction

To identify the effect of Obstructive Sleep Apnea (OSA) and sleep duration on problems with health-related quality of life (HR-QoL) in children.

Methods

Children ages 8–18 years visiting sleep laboratory from 07/2019 to 01/2020 for overnight PSG participated in the study. Controls seen during 01/2020-02/2020 for issues other than sleep disturbance were recruited from the primary care pediatric clinics. HR-QoL was assessed by PROMIS V1.0 questionnaires. Statistical analysis was conducted using R 3.6.0.

Results

122 children were studied: 64 males (52.4%).Twenty-nine(29.2%) had mild OSA, 8 (8.1%) moderate OSA, 17 (17.1%) severe OSA,46 (46.4%) were diagnosed with No-OSA and 22 (18.0%) were controls. Patients visiting the sleep laboratory had lower physical function mobility compared to controls (p=0.004). With increasing severity of OSA, there was a step wise decrease in physical function mobility (p=0.01). Correlation analysis suggested that physical function mobility was positively associated with total sleep duration (p=0.02) and negatively associated with apnea hypopnea index (p=0.01). Symptoms of anxiety in children was positively associated with number of arousals (p=0.04). Age was positively associated with fatigue (p=0.02) and negatively associated with deep sleep (p<0.001). Regression analysis confirmed that physical function mobility was associated with total sleep duration (p=0.04) and AHI (p=0.02) after controlling for age, gender and number of arousals.

Conclusion

We found interrupted sleep associated with symptoms of anxiety. OSA and reduced sleep duration are associated with problems with physical function mobility after adjusting for age, gender and number of arousals.

Support (if any)

None
577 Daily facilitators and barriers to adolescent sleep: Contribution to actual sleep over 28-days of school and vacation
Authors: Maskevich Svetlana , Shen Lin , Wiley Joshua , Drummond Sean , Bei Bei
Published: May 2021

Introduction

Little is known about what adolescents perceive as helping (facilitators) or preventing (barriers) them from getting sufficient and good quality sleep, and how these factors contribute to their actual sleep.

Methods

205 (54.2% female, 64.4% non-white) Year 10–12 adolescents (Mage = 16.9 ± 0.9) completed daily morning surveys, and their sleep was measured via actigraphy over 2 school-weeks and 2 subsequent vacation-weeks. Morning surveys assessed self-reported sleep and the usage of 8 facilitators and 6 barriers of sleep from the previous night. Linear mixed-effects models were used to examine contributions of facilitators/barriers to actigraphy and self-reported total sleep time (TST) and sleep onset latency (SOL), controlling for age, sex, race, place of birth, and study day, separately for school and non-school days.

Results

On average, adolescents reported using 3.7 facilitators and encountering 1.5 barriers daily. Compared to school, non-school days were characterised by more frequent use of facilitators and more barriers encountered. Overall, facilitators or barriers explained an additional 1–7% (p-values < .01) of variance beyond the covariates. Similar facilitators and barriers contributed to actigraphy and self-reported TST and SOL, however, self-reported sleep variables were more affected. Notable facilitators that predicted longer TST and shorter SOL were: “follow body cues”, “avoid activities interfering with sleep”, “create good sleep environment”, “plan bedtime and go to bed as planned” (only TST on school days), and “manage thoughts and emotions” (only SOL). Notable barriers that predicted shorter TST and longer SOL were: “pre-bedtime thoughts and emotions”, “inconsistent routines”, “unconducive sleep environment”, “activities interfering with sleep” (only non-school) and “other household members’ activities” (only SOL).

Conclusion

This intense longitudinal study showed that on a daily basis, adolescents perceive a range of factors as facilitating and preventing sufficient and good quality sleep. These factors are predictive of their actual sleep duration and onset latency and need further research to understand their functions and clinical implications.

Support (if any):
600 Differential Impact of Overnight Delta Power Dynamics on Neurocognition among Adolescents with ADHD versus Healthy Controls
Authors: Lunsford-Avery Jessica , Krystal Andrew , Jackson Leah , Kollins Scott
Published: May 2021

Introduction

Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with neurocognitive impairment; however, mechanisms contributing to neurocognitive deficits in ADHD are poorly understood. Sleep disturbance is common in ADHD, and our previous work has shown associations between overnight delta power dynamics (lower initial delta peak, slower delta decline) and poorer neurocognition among individuals with insomnia, suggesting these processes may underlie sleep restoration. This study investigates relationships between delta power dynamics and neurocognition among adolescents with ADHD versus healthy controls (HC).

Methods

In this ongoing study, 47 adolescents aged 13–17 (19 ADHD, 23 females, mean age=15.26) participated in a psychiatric evaluation and three nights of ambulatory polysomnography (PSG). Following the third night, participants completed the Cambridge Neuropsychological Test Automated Battery (CANTAB). Spectral analysis was conducted on a single O1-C3 channel and epochs were movement/artifact-free. Sleep variables were averaged over 3 nights. General linear models controlling for age, sex, total sleep time (TST), and wake after sleep onset (WASO) examined the effects of delta dynamics on neurocognition (summary score derived from principal components analysis of CANTAB subtests) and whether these associations differed across groups.

Results

PSG sleep variables did not differ by group (p’s>.05). Significant effects of group (F(7,36)=23.10, p<.0001), delta decline (F(7,36)=10.89, p=.002), and the group by delta decline interaction (F(7,36)=14.23, p=.0006) were observed. Results regarding initial delta peak showed a similar pattern, with a trend toward a main effect of initial delta peak (F(7,36)=3.53, p=.07) and a significant group by initial delta peak interaction effect (F(7,36)=9.91, p=.003) on neurocognition. Lower initial delta peak and slower delta decline were associated with poorer cognition among ADHD, but not HC, youth after covarying for age, sex, TST, and WASO.

Conclusion

Overnight delta power dynamics may contribute to neurocognitive performance among adolescents with ADHD after accounting for sleep restriction and nighttime awakenings, highlighting the potential importance of sleep physiology in understanding neurocognitive deficits in this population. Future studies should identify whether there are phenotypic subgroups within ADHD characterized by disrupted overnight delta dynamics and examine whether insomnia treatments that impact delta decline (e.g., Cognitive-Behavioral Treatment—Insomnia) improve neurocognitive performance among adolescents with ADHD.

Support (if any)

This work was supported by K23MH108704 to Dr. Lunsford-Avery.
610 Self-Reported Sleep and Circadian Characteristics Predict Future Substance Use: A Longitudinal Analysis from the NCANDA Study
Authors: Hasler Brant , Graves Jessica , Wallace Meredith , Claudatos Stephanie , Baker Fiona , Clark Duncan
Published: May 2021

Introduction

Growing evidence indicates that sleep characteristics predict later substance use and related problems during adolescence and young adulthood. However, most prior studies have assessed a limited range of sleep characteristics, studied only a narrow age span, and included relatively few follow-up assessments. Here, we used multiple years of data from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study, which spans the adolescent period with an accelerated longitudinal design, to examine whether multiple sleep characteristics in any year predict substance use the following year.

Methods

The sample included 831 participants (423 females; age 12–21 years at baseline) from NCANDA. Sleep variables included the previous year’s circadian preference, sleep quality, daytime sleepiness, timing of midsleep (weekday and weekend), and sleep duration (weekday and weekend). Each sleep variable’s association with the subsequent year’s substance use (cannabis use or alcohol binge severity) across years 1–5 was tested separately using generalized linear mixed models (zero-inflated Negative Binomial for cannabis; ordinal for binge severity) with age, sex, race, visit, parental education, previous year’s substance use (yes/no) as covariates and subject as a random effect.

Results

With regard to cannabis use, greater eveningness and shorter weekday sleep duration predicted an increased risk for additional days of cannabis use the following year, while greater eveningness and later weekend midsleep predicted a greater likelihood of any cannabis use the following year. With regard to alcohol binge severity, greater eveningness, greater daytime sleepiness, and shorter sleep duration (weekday and weekend) all predicted an increased risk for more severe alcohol bingeing the following year. Post-hoc stratified analyses indicated that some of these associations may differ between high school-age and college-age participants.

Conclusion

Our findings extend prior work, indicating that eveningness and later sleep timing, as well as shorter sleep duration, especially on weekdays, are risk factors for future cannabis use and alcohol misuse. These results underscore a need for greater attention to sleep characteristics as potential risk factors for substance use in adolescents and young adults and may inform future areas of intervention.

Support (if any)

Grants from NIH: R01AA025626 (Hasler) and U01AA021690 (Clark) and UO1 AA021696 (Baker & Colrain)
613 Variation in Sleep Beliefs and Behaviors Among Caregiver-Child Dyads Participating in a Sleep Extension Intervention
Authors: Williamson Ariel , Wu Katherine , Jawahar Abigail , Juste Lionola , Zemel Babette , Dinges David , Fiks Alexander , Mitchell Jonathan
Published: May 2021

Introduction

Given the high prevalence and poor outcomes of insufficient child sleep, effective interventions for the pediatric primary care setting are needed. Collecting family perspectives on intervention strategies is critical to understand and enhance outcomes, particularly among children who do not experience improvements. This study examined variation in qualitative family sleep beliefs and behaviors by quantitative child sleep outcomes of a sleep extension intervention.

Methods

A total of 24 caregiver-child dyads (child age 9–12 years, M age 11.3 (SD:1.0) years; 46% male; 50% non-Latinx White; 29% Black) participated in a mobile health sleep extension intervention, between March-December 2019, and completed post-intervention semi-structured telephone interviews to solicit intervention perceptions. The intervention used a 25 factorial design consisting of sleep duration goals and weekly performance feedback, with random assignment to sleep health promotion messaging and financial incentive conditions. Sleep duration was assessed via Fitbit Flex 2 devices during 2-week baseline and 7-week intervention periods. We developed a codebook using a grounded theory approach and conducted coding in NVivo. We compared preliminary qualitative themes among children who showed a >=30-minute improvement in sleep duration (‘responders’) versus those who did not (‘non-responders’).

Results

Of the 24 dyads, 38% (N=9 dyads) were classified as non-responders. Preliminary qualitative themes included: family beliefs about sleep and electronics usage; the study impact on sleep behaviors; and an enhanced awareness of child sleep. Intervention responder and non-responder dyads similarly described family restrictions on evening electronics usage (e.g., electronic parental controls; physical removal of devices) to benefit child sleep. However, more children classified as intervention responders described the benefits of these restrictions and expressed beliefs about the negative impacts of electronics on sleep. Whereas caregivers of both responders and non-responders described efforts to remind their child to go to bed earlier during the intervention, caregivers in the responder group described being more focused on and active in child sleep extension strategies. These included setting bedtime reminders and adjusting family activities to ensure an extended sleep schedule.

Conclusion

Addressing caregiver-child beliefs about sleep behaviors and engagement in sleep extension strategies could augment sleep extension intervention outcomes in future research.

Support (if any)

K01HL123612 (JAM), CHOP (JAM), K23HD094905 (AAW)