bluuebunny/crossref_metadata_2025_split huggingface dataset:
446 Acute effect of acetazolamide in high loop gain sleep apnea
Authors: Ni Yuenan , Thomas Robert 
Published: May 2021

Abstract

Introduction
Obstructive sleep apnea is a disease with different driver phenotypes, including high loop gain (HLG). Acetazolamide (AZT) reduces HLG through multiple mechanisms. The acute effect of AZT used during titration polysomnography in HLG sleep apnea (HLGSA, predominantly obstructive) is described here. HLGSA is a NREM-dominant disease.

Methods
HLGSA was identified by one or more of the following: 1) baseline or titration CAHI of 5 or more, baseline or titration periodic breathing, or high residual apnea on CPAP in the absence of large leak. Retrospective analysis of polysomnograms from patients with HLGSA who underwent a PAP titration study and took ATZ (125 or 250 mg) after a baseline component of PAP titration. A responder was defined as a minimum reduction of the AHI3% of 50%. Multivariable logistic regression model estimated responder predictors.

Results
Two hundred and thirty-six patients with a median age of 60 (50.25–68) years and 189 (80.1%) males, were included. 69 patients were given 125 mg ATZ and 157 patients took 250 mg after about 3 hours of initial drug-free titration. Compared to PAP alone, PAP plus ATZ reduced the breathing related arousal index (8.45[3.03–15.60] vs. 4.8[2.1–10.15], p&lt;0.001), AHI3% (19.09[7.34–37.28] vs. 10.63[4.46–20.56], p&lt;0.001), AHI4% (1.89[0.23–8.58] vs. 1.19 [0.42–4.70], p=0.001), RDI (24.01[10.55–41.46] vs. 13.55[7.24–25.66], p&lt;0.001). ATZ minimally improved the Min SpO2 (90[87–92] vs. 91[88–92], p=0.014). 101 patients were responders. Multiple logistic regression analysis showed that the NREM AHI3% was the only predictor for responder status with ATZ exposure (OR 1.022, 95%CI [1.004–1.041], p=0.018)

Conclusion
ATZ acutely improves PAP efficacy in HLGSA. The NREM AHI3% is a predictor for the ATZ responders.

Support (if any)
This study was supported by American Academy of Sleep Medicine Foundation, category-I award to RJT
456 Esomeprazole Use in Upper Airway Stimulation Patients Associated with Lower Functional Threshold
Authors: Klug Theodore , Sagalow Emily , Ananth Ashwin , Huntley Colin , Boon Maurits 
Published: May 2021

Abstract

Introduction
Proton pump inhibitors (PPIs) are widely used for gastroesophageal reflux disease (GERD) despite possible side effects including increased susceptibility to infections, secondary hypergastrinemia, and incomplete absorption of micronutrients. Upper airway stimulation (UAS) surgery involves delivering an electrical impulse to the distal hypoglossal nerve for the management of obstructive sleep apnea.. The functional threshold (FT) is the minimum stimulation required to achieve bulk tongue motion. The minimum therapeutic amplitude (MTA) is the lowest voltage required to achieve clinical benefit during titration at postoperative attended overnight polysomnography. We sought to analyze the effect of perioperative PPI use upon patients who had undergone upper airway stimulation (UAS) surgery. We hypothesized that the ion transport-related effects of PPIs would impact the amplitude necessary for tongue protrusion (FT) and clinical benefit (MTA).

Methods
A retrospective chart review was conducted at a single tertiary care facility. Baseline demographic data, medication history, and comorbidities were collected from December 2014 through August 2019 on patients undergoing UAS surgery. Patients that were taking a PPI at the time of surgery and postoperatively were included.

Results
167 patients that underwent UAS surgery between 2014 – 2019 were studied. 74 patients were found to be taking a PPI perioperatively. Specifically, 38 patients were found to be on omeprazole, compared to 17 on pantoprazole, 13 on esomeprazole, 4 on lansoprazole, and 2 on rabeprazole. Overall, esomeprazole was a statistically significant predictor (p=0.0359) of a lower functional threshold amplitude: 1.58 mV in controls as compared to 2.09 mV for omeprazole, 2.12 mV for pantoprazole, 2.14 mV for lansoprazole, and 2.7 mV for rabeprazole. Use of PPI, while associated with lower FT voltage, was not a predictor of statistically significant changes in initial UAS minimum therapeutic amplitude settings.

Conclusion
The functional threshold amplitude for patients taking esomeprazole was significantly different compared to patients not on a PPI. However, the use of PPI overall was not a statistically significant predictor of initial difference in UAS mean therapeutic amplitude settings. Future studies examining tolerance of therapy and voltage changes over time in patients on proton-pump inhibitors are needed.
Support (if any):
457 The Impact of PAP Therapy on Hematocrit in OSA and Polycythemia: A Pilot Study
Authors: Jafri Mustafa , Rosa-Acosta Gabrielle , Martinez Jose Flores , Schofield Elizabeth , Wilkins Cy , Mulhall John , Tan Miranda 
Published: May 2021

Abstract

Introduction
Untreated polycythemia leads to complications including thrombosis. Obstructive sleep apnea (OSA) is commonly associated with secondary erythrocytosis, which testosterone therapy can perpetuate. Effects of positive airway pressure (PAP) on elevated hematocrit (HCT) is unknown. We hypothesize PAP adherence can reduce HCT in men with OSA and polycythemia.

Methods
Retrospective chart review of male outpatients with newly diagnosed OSA and HCT≥45% at or 3 months before polysomnography (PSG) was conducted. Intervention group consisted of patients initiating PAP for OSA. HCT within 6 months of PAP initiation and PSG were recorded for intervention and control groups, respectively. Primary endpoint was time-to-HCT reduction of HCT&lt;50% plus 3% decrease. Cox proportional-hazards analysis was used to assess time-to-HCT response. Demographics, smoking history, testosterone administration, STOP-Bang score, AHI, and PAP compliance data were obtained. Patients excluded if PAP not indicated, or if PSG, PAP compliance, or repeat HCT were unavailable.

Results
41 men with OSA had HCT≥45%, of which 16 had HCT≥50%. Median age was 60 years and median BMI was 32 kg/m2. 28 started PAP. 21 met definition for PAP compliance within 6 months. Median AHI of intervention and control groups were 23 and 19 events/hr, respectively. Mean baseline HCT of both groups were 49 and 50, respectively. No significant difference in age, BMI, smoking history, testosterone therapy, and baseline HCT between both groups noted. 39% of intervention group exhibited HCT response at 1 or more longitudinal assessments, versus 38% of control. Intervention group had higher mean STOP-Bang than control (mean 5.9 vs. 4.6, p=0.01) and trended towards higher mean baseline AHI (27.4 vs. 19.0, p= 0.06). Time-to-event analysis controlling for STOP-Bang and AHI demonstrated PAP was not associated with time-to-HCT response (HR = 1.3, 95% CI = 0.4–4.4). In moderate-severe OSA patients, 40% of intervention group had HCT response compared to 14% of control, though difference was not significant (HR = 2.5, 95% CI = 0.3–20.0).

Conclusion
Moderate-severe OSA patients trended towards reduction in HCT with PAP, although not statistically significant. Testosterone administration did not affect HCT response to PAP in this cohort. Larger studies are required to determine HCT response to PAP in these patients.
Support (if any):
464 Long term effects of Continuous Positive Airway Pressure on the weight of Obstructive Sleep Apnea patients in the southeast USA
Authors: Joseph Carmel , Puthenveetil Noel , Joe Allen , Therattil Jaya 
Published: May 2021

Abstract

Introduction
Obesity has been linked to exacerbating Obstructive Sleep Apnea in patients. Paradoxically however, effective CPAP therapy has been noted to lead to weight increases even while improving hypersomnia and daytime neurocognitive functioning. Prior studies have demonstrated inconsistent results regarding weight changes while on CPAP therapy. Our study aims to clarify these inconsistencies and provide specific recommendations for CPAP compliant patients to prevent weight gain.

Methods
393 OSA patients were seen for multiple follow ups since initiation of CPAP therapy at a single center sleep clinic. Every visit their weight would be updated along with CPAP compliance. Data was assessed on 1 month, 6 month, and 12 month intervals. Exclusion criteria include diuretic use, diet/exercise additions, and discontinuation of CPAP therapy before the full observation window.

Results
Patients with long term use of their CPAP devices had an average increase of 2.68±11.29 lbs after a year. 233 participants gained weight (an average of 9.8±7.3 lbs) while 141 participants lost weight (an average of -8.5±7.2 lbs) with 19 participants showing no weight change. This weight change could be observed starting as early as one month after CPAP initiation.

Conclusion
CPAP therapy is most likely linked to a lasting increase in weight. Recommendations and patient education for OSA patients should be modified to include an exercise component (10,000 steps/day) and/or caloric restriction (2200 low carb diet) to offset this weight increase. Further study is needed to assess the impact such recommendations could have in long term OSA care beyond the southeast USA.

Support (if any)
Pulmonary Allergy & Sleep Center of Augusta
470 Maternal Habitual Snoring and Blood Pressure Trajectories in Pregnancy
Authors: Dunietz Galit Levi , Hao Wei , Shedden Kerby , Holzman Claudia , Chervin Ronald , Lisabeth Lynda , Treadwell Marjorie , O’Brien Louise 
Published: May 2021

Abstract

Introduction
Habitual snoring has been associated with hypertensive disorders of pregnancy. However, exactly when blood pressure (BP) trajectories diverge between pregnant women with and without habitual snoring is unknown. Moreover, the potentially differential impact of chronic versus pregnancy-onset habitual snoring on maternal BP trajectories during pregnancy has not been examined.

Methods
In a cohort study of 1,305 pregnant women from a large Midwestern medical center, participants were asked about habitual snoring (≥3 nights/week) and whether their symptoms began prior to or during pregnancy. Demographic and BP data throughout pregnancy, systolic (SBP) and diastolic (DBP) were abstracted from medical charts. Linear mixed models were used to examine associations between habitual snoring-onset and pregnancy BP trajectories.

Results
Thirty percent of women reported snoring before pregnancy (chronic snoring) and an additional 23% reported pregnancy-onset snoring. Overall, women with pregnancy-onset snoring had higher mean SBP and DBP compared to those with chronic habitual snoring or controls (non-habitual snoring). In gestational week-specific comparisons with controls, SBP became significantly higher around 20 weeks’ gestation among women with pregnancy-onset snoring and in the third trimester among women with chronic snoring. Pairwise mean differences in DBP were significant only among women with pregnancy-onset snoring relative to controls, after 15 weeks’ gestation.

Conclusion
In a large cohort of pregnant women, those with pregnancy-onset or chronic habitual snoring had significantly elevated systolic BP in comparison to non-habitual snoring controls, in the second and third trimester, respectively. The findings of divergent BP trajectories suggest the two groups of women with habitual snoring in pregnancy should be considered separately when evaluating gestational ‘windows’ for increased BP monitoring and provide insight into pathophysiologic changes.

Support (if any)
Dr. Dunietz was supported by an F32 National Research Service Award from the National Institute of Child Health and Development (NIH/NICHD F32 HD091938); Dr. O’Brien was supported by the following during the course of this study: the Gene and Tubie Gilmore Fund for Sleep Research, the University of Michigan Institute for Clinical and Health Research (MICHR) grants UL1RR024986 and UL1TR000433, MICHR seed pilot grant F021024, the National Heart, Lung, and Blood Institute (R21 HL089918 and K23 HL095739) and in part by R21 HL087819.
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

Abstract

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

Abstract

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&lt;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&lt;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&lt;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

Abstract

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&lt;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

Abstract

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&lt;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