bluuebunny/crossref_metadata_2025_split huggingface dataset:
0622 Remote Patient Monitoring to Manage OSA Using a Variety of Therapeutic Approaches in an Active Sleep Practice
Authors: Simmons Jerald , Sadeghian Sam , Lavender Maggie , Hua Olivia , Jarreau Jordan , Mira Catherine , Lopez Stormy 
Published: April 2024

Abstract

Introduction
Remote Patient Monitoring (RPM) using the REST-Tracker system incorporates FDA cleared SleepImage OSA analysis from a ring oximeter worn nightly providing output metrics corresponding to the AASMs 1A/1B Hypopnea rules (sAHI3%/sAHI4% respectively). The REST-Tracker system assists in improving clinical decisions, reducing treatment failures and lowering the burden of repeated (in-lab/home) OSA sleep testing. Other systems currently in use for OSA management rely on PAP derived indexes, loosely labeled as an AHI equivalent, and are falsely considered by many as equivalent to FDA cleared HSAT derived metrics. Such systems only provide data while using PAP devices and have no utility with other treatment approaches such as Inspire or OAT. Our OSA patients are treated via a variety of therapeutic approaches and we provide here a summarization of our current experience using this new REST-Tracker approach and an additional PAP-subanalysis to assess the sensitivity of the PAP derived AHI metric (pAHI) metric which is used by other RPM systems.

Methods
OSA patients undergoing treatments ranging from PAP, OAT, Inspire, surgery, or in-combination were monitored nightly with the REST-Tracker ring RPM platform. The sAHI3%/sAHI4% output metrics were managed by staff using REST-Tracker and therapy adjusted in accordance with patients' circumstances, optimizing treatment. PAP-subanalysis: A subset of 10 PAP patients data was extracted to compare the pAHI metric to the corresponding sAHIs(3%&4%).

Results
95 patients monitored, ranging 6-28 months, across all treatment groups (39-PAP, 14-Inspire, 7-OAT, 9-combo-PAP-OAT, 16-combo-Inspire-PAP and 10-Combo-MMA-Inspire/other), with an average Diagnostic 1A AHI=30.4(+/-21.0)/1B AHI=15.65(+/-17.8) improved with most recent 30-day data demonstrating average sAHI3%=11.5(+/- 8.0) sAHI4%=6.3(+/-5.6). For the PAP-subanalysis, duration ranged/per patient from 120-284 nights, Median values of pAHI=2.6, sAHI3%=10.4 & sAHI4%=3.4

Conclusion
The REST-Tracker provides longitudinal nightly assessment giving clinicians objective measures to assist treatment decisions and is superior to single-night testing and agnostic to treatment approaches, unlike other PAP-dependant RPM systems. A more elaborate detailed presentation with clinical examples will be presented at the conference, demonstrating this futuristic approach in sleep health disease management.

Support (if any)
0624 A Mass Spectrometry Method Evaluating Orexin Metabolites Suggest Abnormalities in Hypersomnias of Central Origin
Authors: Horie Kanta , Steger Christopher , Koppisetti Rama Krishna , Mignot Emmanuel , Lucey Brendan 
Published: April 2024

Abstract

Introduction
Narcolepsy type 1 (NT1) is caused by orexin (hypocretin) deficiency with 85-95% loss of orexinergic neurons reported in the hypothalamus. Patients with NT1 have cerebrospinal fluid (CSF) orexin-A immunoreactivity deficiency ≤110 pg/ml, as detected using a polyclonal anti-orexin-A radioimmunoassay (RIA). Although some narcolepsy type 2 patients (NT2) have been reported to have a partial loss of orexinergic neurons, the large majority of patients with NT2 have normal levels of CSF orexin-A. Previous work has shown that the RIA measures &lt; 10% of the intact orexin-A peptide, suggesting that the RIA for CSF orexin-A primarily measures unauthentic orexin-A-related metabolites. In this study, we developed a novel mass spectrometry assay to measure intact prepro-orexin, orexin-A, and orexin-B, and their metabolites, in CSF collected from patients with NT1, NT2, idiopathic hypersomnia (IH), and controls.

Methods
Using a novel sequential immunoprecipitation/mass spectrometry method, all orexin species (intact-long and short-metabolite forms) were comprehensively measured in CSF collected from patients diagnosed with NT1 (N=15), NT2 (N=15), IH (N=15), and controls (N=15). Orexin peptides were analyzed by a nanoAcquity ultra-performance liquid chromatography system coupled to an Orbitrap Tribid Eclipse mass spectrometer.

Results
NT1 showed pan-orexin deficiency with lower predicted levels of prepro-orexin, orexin-A, and orexin-B species compared to NT2, IH, and controls (all p&lt; 0.05 after Tukey correction for multiple comparisons). Short-form metabolites of orexin-B differentiated both NT2 and IH from NT1 and from controls (all p&lt; 0.05 after Tukey correction for multiple comparisons). Further, the ratio of the shortest form of orexin-B/longer orexin-B species was decreased in NT2 compared to IH and controls (all p&lt; 0.05 after Tukey correction for multiple comparisons).

Conclusion
A novel mass spectrometry assay comprehensively measuring different forms of CSF orexin differentiated among the hypersomnias of central origin and may have diagnostic utility. As expected, all forms of orexin were lower in CSF collected from NT1 patients compared to other groups. We also found that short metabolites of orexin-B are reduced in participants with NT2 and IH. Abnormal orexin transmission may also be involved in the pathophysiology of NT2 and IH, with differential impact on orexin peptide species.

Support (if any)
R21 AG074151 and Eisai
0626 Impact of Washout Timing of Psychotropic Medications on the MSLT
Authors: Farris Alex , Araujo Matheus Lima Diniz , Saribalas Michael , Foldvary-Schaefer Nancy 
Published: April 2024

Abstract

Introduction
While highly reproducible in narcolepsy type 1, MSLT results are more variable in other CNS hypersomnolence disorders. Use of psychotropic medications is a known contributor to MSLT validity given the high comorbidity of psychiatric illness in patients with hypersomnolence disorders. We leveraged a large MSLT database to study the impact of timing of washout of psychotropic medications with known REM-suppressing effects on MSLT results.

Methods
This was a retrospective analysis of MSLTs performed 2012-2023 at Cleveland Clinic. Medication groups studied included selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs). Date of last dose prior to MSLT was collected and categorized as ≤14 days or &gt;14 days prior to MSLT. Multivariable adjusted regression analyses (linear and logistic) adjusting for age, sex, and BMI were conducted to evaluate the influence of a late washout (ie ≤14 days prior to MSLT) on recording ≥2 sleep onset REM periods (SOREMPs) and on recording a mean sleep latency (MSL) &lt; 8 minutes.

Results
180 unique MSLTs were analyzed. Of these, 80 patients had recorded use of SSRIs, SNRIs, and/or TCAs leading up to the MSLT, and 63 of these 80 patients used such a medication ≤14 days before the MSLT. Seven of 80 patients (8.8%) had ≥2 SOREMPs, and 27 (33.8%) had MSL &lt; 8 minutes. Logistic regression analysis showed a negative correlation between a late washout and obtaining ≥2 SOREMPs (OR 0.05, p&lt; 0.01), but no significant correlation with obtaining MSL &lt; 8 minutes (p=0.07). Linear regression analysis similarly showed a negative correlation between a late washout and obtaining ≥2 SOREMPs (coefficient -0.77, p&gt;0.001) but no significant correlation with obtaining MSL &lt; 8 minutes.

Conclusion
These findings underscore the importance of appropriately timed REM suppressant washout prior to MSLT to optimize test validity. Further analyses will examine the effects of other CNS-active medication classes in a larger cohort of patients.

Support (if any)
NIH grant R21HL170206
0627 Influenza HA Antibody Titers in Recent Onset Type-1 Narcolepsy
Authors: Yan Han , Lin Ling , Zhang Jing , Mignot Emmanuel 
Published: April 2024

Abstract

Introduction
Epidemiological studies have shown associations between pandemic H1N1 2009 Influenza-A infection and vaccination (only using Pandemrix®) and the onset of narcolepsy, an autoimmune disease associated with HLA-DQB1*0602. We tested whether recent onset type 1 narcolepsy patients have increased influenza antibody titers comparing with matched HLA-DQB1*0602 positive controls.

Methods
Sera of 82 recent onset type-1 narcolepsy patients (12 [1-25] months) and 84 healthy controls matched by sex, age, and year and season of sample collection were used. Sera were tested for Influenza-A and B HA antibodies using hemagglutinin inhibition (HAI) assays against the dominant strains known to circulate at time of collection. HAI assays against H1N1pdm09 were also tested independently in samples collected after 2009. Antibody titers were log2 transformed into geometric mean, with zero being &lt; 1/10 dilution, 1 as 1/10, 2 as 1/20 etc., so that every dilution represents an increment of 1 unit. Further analysis using multiple variable linear regression and logistic regression were done to analyze association between confounding factors and disease status and HA antibody titers.

Results
H1N1pdm09 HA titers were increased in 25/63 (39.7%) subjects collected after 2009. Increasing HA titers (doubling rate) of H1N1pdm09 [OR=1.2962(1.0513, 1.5984), p=0.015], all H1N1 [OR=1.13(1.03-1.24), p=0.023] and B/Victoria [1.37 (1.16-1.61), p=0.001] were associated with narcolepsy, whereas no association was found with H3N2 and B/Yamagata. Logistic regression shows after controlling sex, age and season of sample collection, narcolepsy is associated with H1N1pdm09 [4.68(1.5281, 14.3392), p=0.007] and B/Victoria strains [5.5306 (2.6039, 11.8224), p=0.001].

Conclusion
Both H1N1 and B/Victoria, but not other strains, may trigger narcolepsy onset. This result is in line with a recent epidemiological study in Europe that reported a strong increase in narcolepsy onset in 2010 (following 2009 H1N1 pandemic) and a secondary peak in 2013 following a season with a dominant B/Victoria infection.

Support (if any)
This work was supported by 5R01AI144798-03/HHS|NIH|National Institute of Allergy and Infectious Diseases (NIAID).
0632 Design Elements for a Switch Study from High- to Low-Sodium Oxybate Evaluating Blood Pressure in Narcolepsy (XYLO)
Authors: White William , Macfadden Wayne , Baranak Christine , Nichols Deborah , Akerman Sarah , Somers Virend 
Published: April 2024

Abstract

Introduction
High sodium intake can increase blood pressure (BP) and future cardiovascular risk. Individuals with narcolepsy have an elevated cardiovascular comorbidity burden before considering medication-specific risks. Low-sodium oxybate (LXB; Xywav®) is approved by the US Food and Drug Administration (FDA) to treat excessive daytime sleepiness or cataplexy in patients ≥7 years of age with narcolepsy and idiopathic hypersomnia in adults. LXB has the same active moiety as high-sodium oxybates (sodium oxybate [SXB, Xyrem®] and fixed-dose SXB [Lumryz™]) but contains 92% less sodium. The objective of XYLO is to measure ambulatory and in-clinic systolic BP (SBP) changes after switching to LXB from a high-sodium oxybate in participants with narcolepsy (NCT05869773).

Methods
This 6-week, open-label, multicenter, switch study is enrolling participants 18–70 years of age with narcolepsy (type 1 or 2) taking 6–9 g/night of high-sodium oxybate for ≥6 weeks. Hybrid enrollment supports both on-site and decentralized (monitored at the participant’s home by mobile health professionals) participation, and may broaden the pool of eligible participants. After ≥2 weeks on stable high-sodium oxybate dose/regimens (screening period), participants switch to the same dose/regimen of LXB for 6 weeks (intervention period). The primary endpoint is the change in 24-hour SBP from baseline (the most recent screening measurement prior to switching) to the end-of-treatment visit (approximately 6 weeks after switching) measured via 24-hour ambulatory BP monitoring (ABPM). Secondary endpoints evaluate change from baseline to end-of-treatment visit in-clinic SBP, as well as daytime average SBP and nighttime average SBP measured via 24-hour ABPM.

Results
Recruitment began in June 2023. This study uses a group sequential design with an adaptive sample size target of 57–77 participants completing the 6-week intervention period. This design provides 90% power to detect a mean difference of 3.5 mmHg (a clinically relevant change) in 24-hour SBP (assuming a standard deviation of the differences in 24-hour SBP of 8 mmHg).

Conclusion
XYLO will enable the assessment of 24-hour BP changes following transition from a high-sodium oxybate to LXB. Planned hybrid enrollment with a decentralized option may increase study access leading to a more diverse clinical trial population.

Support (if any)
Jazz Pharmaceuticals
0638 Stability of Once-Nightly Sodium Oxybate in Alternative Liquid Reconstitution Vehicles
Authors: Lavender Maggie , Wermter Ellen , Morse Anne , Horsnell Matthew , Vaughn Jason , Ascencion Frederik , Gudeman Jennifer 
Published: April 2024

Abstract

Introduction
LUMRYZ™ is a once-nightly formulation of sodium oxybate (ON-SXB) containing both immediate and pH-dependent controlled-release granules designed to be reconstituted in water and administered orally. This study was conducted to determine the dissolution profile of ON-SXB at prescribed doses after reconstitution in alternative liquids.

Methods
Dissolution and pH testing was conducted with ON-SXB 4.5-g and 9-g single-dose packs reconstituted in Milli-Q® water (control), Crystal Light© Raspberry Lemonade (CL), MiO© Fruit Punch Concentrate (Mio), and alkaline water (AW). CL and Mio were prepared with tap water. Dissolution (percent of label claim) was measured at 15 minutes and 1, 2, 2.5, 3, 3.5, 4, 5, 6, and 8 hours after 5-minute (AW only) and 30-minute (CL, Mio, and AW) rest periods. The pH of each reconstitution solution was measured prior to and then 5 and 30 minutes after addition of ON-SXB.

Results
After 15 minutes, ON-SXB 4.5 g was 50% dissolved in control, 51% in CL and Mio, and 49% in AW after both rest periods; at 8 hours, 98% was dissolved in control, 101% in CL and Mio, and 99% in AW after both rest periods. At 15 minutes, ON-SXB 9 g was 50% dissolved in control and CL, and 51% in Mio and AW after both rest periods; at 8 hours, 98% was dissolved in control, 101% in CL and Mio, 97% in AW after the 5-minute rest period, and 98% in AW after the 30-minute rest period. Before addition of ON-SXB, the pH of control, CL, Mio, and AW was 7.03, 3.02, 2.95, and 9.53, respectively. For ON-SXB 4.5 g in control, CL, Mio, and AW, the pH was 5.6, 5.3, 5.4, and 5.6 at 5 minutes and 5.6, 5.2, 5.3, and 5.5 at 30 minutes, respectively. For ON-SXB 9 g in control, CL, Mio, and AW, the pH was 5.7, 5.5, 5.6, and 5.7 at 5 minutes and 5.7, 5.6, 5.6, and 5.7 at 30 minutes, respectively.

Conclusion
These results show consistent and acceptable dissolution of ON-SXB in various liquids, which may be preferred by some patients as alternatives to water.

Support (if any)
Avadel Pharmaceuticals
0643 Patient Preferences of Sodium Oxybate Treatment for Narcolepsy: RESTORE End-of-Study Survey Data
Authors: Ajayi Akinyemi , Mignot Emmanuel , Roy Asim , Corser Bruce , Stern Thomas , Hudson J Douglas , Santamaria Adrian , Abaluck Brian , Gudeman Jennifer 
Published: April 2024

Abstract

Introduction
Until recently, the only available oxybate therapy options were immediate-release (IR) formulations requiring patients to awaken 2.5 to 4 hours after their first dose to take a second dose. Once-nightly sodium oxybate (ON-SXB; LUMRYZ™) is an extended-release formulation of sodium oxybate that eliminates the need for a middle-of-the-night dose. RESTORE (NCT04451668) was an open-label/switch study that evaluated the safety and tolerability of ON-SXB and surveyed patient preferences for ON-SXB or IR oxybate therapies.

Methods
Participants were ≥16 years of age with narcolepsy type 1 or 2 who either completed the phase 3 REST-ON trial and were on stable doses of IR oxybate for ≥1 month or oxybate naive. Participants completed end-of-study (EOS) questionnaires to capture their experience with ON-SXB.

Results
As of November 2023, EOS questionnaire data were available for 89 participants, including 21 participants who completed REST-ON or were oxybate naive and 68 participants who switched from IR oxybate to ON-SXB. In total, 71% (63/89) of responders rated their narcolepsy “much better” or “somewhat better” after initiating ON-SXB. After starting ON-SXB, 75% (67/89) were very satisfied with ON-SXB compared to other treatments they had taken, and 89% (79/89) would recommend ON-SXB to a family member or friend with narcolepsy. Approximately 69% (61/89) of participants found it easier to go through the day without falling asleep, 91% (81/89) were better able to sleep through the night, 64% (57/89) were able to get more done at work or school, and 64% (57/89) were better able to socialize with friends or family. Additionally, 43% (38/89) of responders were able to perform or better perform certain daily activities. Of the participants who switched from IR oxybate to ON-SXB, 91% (62/68) were better able to follow the recommended dosing schedule of ON-SXB.

Conclusion
These EOS RESTORE data show a high level of satisfaction with ON-SXB, improved symptom control, and a preference for ON-SXB over other treatment options. A majority switching from IR oxybate treatment reported improvement in dosing as directed.

Support (if any)
Avadel Pharmaceuticals
0646 Efficacy Outcomes Among Male and Female Participant Subgroups: A Post Hoc Analysis from REST-ON
Authors: Thorpy Michael , Ajayi Akinyemi , Corser Bruce , Kushida Clete , Ohayon Maurice , Bogan Richard , Gudeman Jennifer 
Published: April 2024

Abstract

Introduction
Once-nightly sodium oxybate (ON-SXB; LUMRYZ™) is an effective and safe treatment for excessive daytime sleepiness (EDS) and cataplexy in adults with narcolepsy. This post hoc analysis assessed efficacy in female and male participant subgroups from the phase 3 REST-ON trial.

Methods
REST-ON (NCT02720744) participants (≥16 years) with narcolepsy type 1 (NT1) or NT2 were randomized (1:1) to receive ON-SXB at 4.5 g (week 1), 6 g (weeks 2–3), 7.5 g (weeks 4–8), and 9 g (weeks 9–13) or placebo. Data shown are least squares mean changes from baseline (SE) in mean sleep latency on the Maintenance of Wakefulness Test (MWT) and weekly number of cataplexy episodes (NCA; NT1 only) calculated at week 13 (9 g) in the modified intent-to-treat (mITT) population (ie, randomized participants with ≥1 efficacy measurement post 6-g dose).

Results
The mITT population included more female (ON-SXB, n=60; placebo, n=65) than male (ON-SXB, n=37; placebo, n=28) participants. Baseline mean sleep latency (SD) on the MWT (min) was 5.24 (3.41) and 4.59 (2.65) for female and male participants in the ON-SXB arm, respectively. At week 13, improvements on the MWT with ON-SXB were greater for female than for male participants (11.62 [1.39], 9.52 [1.26]). Baseline mean weekly NCA (SD) was 19.63 (9.0) and 17.48 (8.03) for female and male participants, respectively, in the ON-SXB arm. Improvements in weekly NCA with ON-SXB were similar for female and male participants at week 13 (–11.80 [1.23], –11.31 [1.62]).

Conclusion
These post-hoc subgroup data demonstrate improvement with ON-SXB in EDS and in cataplexy for people with narcolepsy regardless of gender.

Support (if any)
Avadel Pharmaceuticals
0647 Efficacy of Low-Sodium Oxybate in Narcolepsy Patients with and Without Cardiovascular or Cardiometabolic Disorders
Authors: Corser Bruce , Candler Shawn , Macfadden Wayne , Fuller Douglas , Measey Thomas , Bogan Richard 
Published: April 2024

Abstract

Introduction
Low-sodium oxybate (LXB; Xywav®) is approved by the US Food and Drug Administration to treat excessive daytime sleepiness or cataplexy in patients ≥7 years of age with narcolepsy, and idiopathic hypersomnia in adults. LXB contains the same active moiety as high-sodium oxybates (sodium oxybate [SXB, Xyrem®] and fixed-dose SXB [Lumryz™]) but with 92% less sodium. Previous studies have reported increased cardiovascular (CV) and cardiometabolic (CM) comorbidities in people with narcolepsy. This post-hoc analysis of a phase 3 trial assessed LXB efficacy and safety in participants with narcolepsy with and without CV/CM comorbidities.

Methods
Participants 18–70 years of age with narcolepsy with cataplexy optimized/titrated their LXB dose (up to 12 weeks) before entering a 2-week stable-dose period (SDP) (NCT03030599). Following SDP, participants withdrew to placebo or continued LXB during a 2-week double-blind randomized-withdrawal period (DBRWP). Epworth Sleepiness Scale (ESS) scores, cataplexy (average N/week), Patient Global Impression of Change (PGIc) scores, and treatment-emergent adverse events (TEAEs) were assessed in participants with and without CV/CM comorbidities, per medical history.

Results
Of 201 participants, 69 reported CV/CM comorbidities at baseline (most commonly hypertension and obesity). Participants with and without CV/CM comorbidities, respectively, had mean (SD) BMI of 31.6 (6.4) and 27.2 (5.3); mean age was 43.4 (12.0) and 33.9 (11.0) years; 66.7% and 57.6% were female. Participants randomized to placebo in the DBRWP in both subgroups showed worsening (increases) in ESS scores compared with those randomized to LXB (least squares mean differences, LXB vs placebo [95% CI], with CV/CM comorbidities: −2.6 [−4.5, −0.70], P=0.0077; without CV/CM comorbidities: −2.7 [−4.2, −1.2], P=0.0004; subgroup interaction, P=0.95). Participants without CV/CM comorbidities randomized to placebo had increased cataplexy attacks compared with those taking LXB (median, placebo, 3.0; LXB, 0.0; P&lt; 0.0001); those with CV/CM comorbidities had similar efficacy (placebo, 1.9; LXB, 0.0; P=0.0745). PGIc scores showed worsening in participants randomized to placebo vs LXB in both subgroups (P&lt; 0.0001 for both). Serious TEAEs were reported by 3% of participants with CV/CM comorbidities and 2% of those without.

Conclusion
In this post-hoc analysis, the efficacy and safety of LXB were similar in participants with narcolepsy with and without CV/CM comorbidities.

Support (if any)
Jazz Pharmaceuticals