bluuebunny/crossref_metadata_2025 huggingface dataset:
0624 Voice of the Patient: A Patient-Centered Exploration of Factors Influencing Obstructive Sleep Apnea Care
Authors: Puravath F M , Ash T , Rottapel R , Spadola C , Bandana S , Schonberg M , Redline S , Bertisch S
Published: May 2020

Introduction

Despite widely available efficacious treatments for obstructive sleep apnea (OSA), patients commonly report frustration in accessing and adhering to treatments. Sparse research has explored factors influencing OSA care from the patient perspective, which may limit provision of patient-centered care: care responsive to patient preferences, needs, and values. To this end, we conducted qualitative research to identify factors, voiced by patients, that influence OSA treatment initiation and adherence.

Methods

We performed semi-structured interviews with 15 patients previously diagnosed with OSA from Boston, MA and a national patient portal (MyApnea.Org). Patients were asked about barriers and facilitators to their diagnosis and treatment as well as about their preferences and values that informed their treatment decisions. Interviews were audio-recorded and transcribed. A qualitative content analysis was performed to identify themes. After developing a codebook, interviews were coded. Codes were then audited and finalized by study team consensus.

Results

Our sample was aged 25-74 years; 71% identified as female. Among participants, 57.1% identified as White, 14.3% Black, 14.3% Asian, and 14.3% Other. Major themes were broadly classified as (1) facilitators (provision of useful information on treatment options, participation in shared decision-making, continued clinician support); (2) barriers (inconvenience of treatment, difficulty of habit formation, treatment side effects, competing comorbid conditions); (3) motivators (value of improving chronic health, family support, positive treatment effects); (4) contextual factors (insufficient knowledge/awareness of OSA, navigating healthcare systems, access to informational resources). Awareness of OSA symptoms and treatments, and ongoing support were cited as the most common factors influencing the patient experience.

Conclusion

This formative research highlights that diverse factors impact the OSA evaluation and treatment patient experience. Further research should test interventions that promote effective patient-centered care for OSA, such as shared decision-making tools.

Support

Brigham and Women’s Hospital Research Institute Patient-Centered Comparative Effectiveness Research Center Grant
0628 An Observational Report of Clinical Outcomes Among Veterans with Obstructive Sleep Apnea Treated with Hypoglossal Nerve Stimulation
Authors: Raman S , Fernandez A D , Mathew E V , Hudgins L E , Cornman E
Published: May 2020

Introduction

The efficacy of positive airway pressure (PAP) therapy in the management of obstructive sleep apnea (OSA) is limited by inadequate patient adherence. Hypoglossal nerve stimulation (HNS) is an FDA approved PAP-alternate surgical treatment option that is available for patients with poor PAP tolerance. The purpose of this pilot study was to review outcome measures and adherence data for patients treated with HNS therapy in a military veteran population.

Methods

Methodology involved a retrospective chart review of 30 PAP intolerant cases referred for HNS treatment over the course of 2 years. The inclusion criteria were Body Mass Index (BMI) < 35 kg/m2, Apnea Hypopnea Index (AHI) of 15-65/hour and drug induced sleep endoscopy (DISE) showing antero-posterior pharyngeal collapse. Qualified veterans proceeded to HNS implantation. Variables for analysis included BMI, Epworth sleep scale (ESS), DISE results, pre- and post-treatment AHI and adherence data.

Results

Of the 30 veterans, 17 proceeded to DISE. 15 had partial or complete AP collapse and 2 had concentric collapse. 12 veterans proceeded to HNS implantation. 6 veterans who completed HNS titration studies showed an average improvement of 77% from baseline AHI. There was significant decrease in mean AHI from 43.95/hour to 10.52/hour. The mean ESS decreased from 13 to 11. The mean compliance was 6.66 hours/night.

Conclusion

This limited veteran observational study supports that HNS is an effective treatment option for the management of PAP-intolerant patients with OSA. Our preliminary data suggests improved treatment adherence. Future prospective large-scale cohort studies should be considered.

Support

The authors declare no conflicts of interest nor any financial support
0633 Volume Assured Pressure Support is an Effective Treatment in Patients with Central Sleep Apnea Syndrome
Authors: Levri J M , Watanabe N , Peng V , Scharf S M , Diaz M
Published: May 2020

Introduction

Central sleep apnea syndrome (CSA) is commonly found in patients with congestive heart failure, brainstem disorders, and narcotic use. Various treatment modalities have been used with varied effectiveness in reducing the apnea-hypopnea index (AHI) and improving ventilation in patients with CSA. This study assessed whether Volume Assured Pressure Support (VAPS), a BiLevel mode of ventilation, is effective in treating CSA.

Methods

We performed a retrospective review of polysomnography (PSG) and VAPS titration studies on 11 patients at our institution: 7 patients had CSA with Cheyne-Stokes Respiration, 2 patients had CSA attributed to narcotic use, and 2 patients had primary CSA. CSA was diagnosed if more than 50% of the disordered breathing events were central. Five patients had failed a Continuous Positive Airway Pressure (CPAP) titration and then proceeded to VAPS while in 6 patients, VAPS was the initial treatment modality tried. We examined the effectiveness of VAPS in reducing AHI, improving oxygenation, and improving sleep architecture.

Results

Among the 11 patients, age was 63.0±12.1 yo, BMI was 33.7 ±4.5, 7 were males, Epworth sleepiness score was 9.3±4.9. The following significant changes from baseline PSG to VAPS titration were observed: AHI: 59.1± 8.0 to 27.2 ± 9.9 (p<.01); Time ≤ 88% O2 saturation (min): 48.1±14.5 to 15.4±6.1 (p<.05). Improvement in AHI was not related to gender, body mass index, narcotic use, or age. No significant changes in sleep architecture between the two studies were found. Ten (91%) patients had AHI > 30 on initial PSG. In 6 (55%) patients AHI was reduced to <15 with VAPS use. An additional patient had AHI reduced to 22.2, while 4 (36%) patients did not achieve an AHI < 30 with VAPS.

Conclusion

VAPS is an effective mode of treating CSA in the majority of patients.

Support

NA
0647 The Effect of CPAP on the Blood Flow to the Brain: A Preliminary Report
Authors: Alperin N , Hernandez-Cardenache R , Lee S , Junco B , Ramos A R
Published: May 2020

Introduction

We aim to determine the effect of positive airway pressure (PAP) on total cerebral blood flow in a sample of middle-aged to older male patients with obstructive sleep apnea (OSA).

Methods

We evaluated consecutive treatment-naïve male OSA patients with Apnea hypopnea Index (AHI)≥15, from January to November of 2019. We obtained demographic variables, vascular risk factors, the Epworth sleepiness scale (ESS) and the Pittsburgh sleep quality index (PSQI). Brain magnetic resonance imaging (MRI) consisted of high resolution anatomical imaging and velocity encoded phase contrast MRI to measure volumetric blood flow rate to the brain, or the total cerebral blood flow (tCBF), by summation of the flow rate through the two internal carotid and vertebral arteries. Positive airway pressure at various pressures was provided during the MRI, while subjects were awake, starting at 0 cm H20, then 5 cmH20, 10, 15, and 20 cmH20. Each setting was applied for six minutes. Two subjects did not tolerate pressure setting of 20 cmH2O.

Results

We had a total of 11 participants’ age 40-73 years, 70% Hispanic/Latino background. The average ESS was 8.2±6.0, PSQI=5.7±4.9, and AHI=48.9±25.5. Five of the subjects had hypertension and a quarter had diabetes. In all subjects total CBF monotonically decreased with increasing PAP. The initial decreases in total CBF (PAP from 0 to 5 and 5 to 10) where significantly larger than the decrease in the higher pressure range. In two subjects the total decrease in tCBF was nearly 50%. The average tCBF was 682.3 mL/min at 0 cmH20 and 506.3 ml/min at 20 cmH20.

Conclusion

Incremental increases in PAP lead to substantial decrease in tCBF during wake. Substantial decrease in tCBF is possibly explained by decreasing end tidal CO2 pressure. The specific physiologic cause and the neurologic impact of prolonged decreased tCBF during CPAP therapy needs to be further investigated.

Support

Scientific Advisory Committee, Pilot grant, Miller School of Medicine; R21AG056952; R21HL140437; Jazz-Pharmaceutical.
0648 Impact of Positive Airway Pressure (PAP) Troubleshooting Clinic Visits on Patient Satisfaction, PAP Use, Mask Leak, and Prolonged Use
Authors: Bennett K L
Published: May 2020

Introduction

Patients with sleep apnea are often prescribed positive airway pressure (PAP) treatment. Some patients have difficulty consistently using a PAP machine due to problems such as air leak, mask discomfort, and dry mouth. The purpose of this project is to evaluate the satisfaction and efficacy of a PAP Troubleshooting Clinic lead by a RN and a respiratory technician (RT). This clinic seeks to improve PAP compliance, increase PAP tolerability and increase PAP treatment efficacy

Methods

The PAP Troubleshooting Clinic consists of a RN and RT with specialized knowledge about sleep apnea and PAP treatment. During a 30 or 60-minute clinic visit, these providers review the patient’s experience with PAP, assess mask fit, review PAP data and PAP settings, and recommend treatment adjustments for the primary Sleep Clinic provider’s consideration. Outcomes assessment includes satisfaction (a telephone survey one week after the visit) and efficacy (30-day data on overall use, mask leak, and days with ≥ 4 hours of use downloaded from PAP machines).

Results

To date, 58 patients have received care in the clinic and 56 (96.5%) patients reported they were satisfied/highly satisfied with the PAP Troubleshooting Clinic. From the sample, forty-three (74.1%) patients were compliant with mask use over 30 days. Twenty-four (55.81%) showed a greater than 10% reduction in mask leak after intervention. Ten patients (23.3%) achieved an improvement with a 10% increase in number of days with > than 4 hours of PAP use.

Conclusion

Patients and Sleep Clinic providers are very satisfied with the PAP Troubleshooting Clinic. Patients are referred to this clinic because they have significant issues with PAP usage and are at high risk of discontinuing use. Patients find the clinic helpful and encouraging, while sleep medicine physicians and APPs appreciate the assistance in helping patients succeed with PAP, especially during the 30-day time period where PAP compliance receives scrutiny from clinics and payers.

Support

A PAP Troubleshooting Clinic is an effective way to improve patient PAP Use, Mask Leak, Prolonged Use and Patient Satisfaction. Importantly, this new clinical model offers a valuable alternative to provide patients with the appropriate level of care.
0667 Positive Airway Pressure Non-Adherence Interacts With Post-Traumatic Stress Disorder to Increase Risk of Back Pain
Authors: Taylor K A , Schwartz S W , Sebastião Y V , Anderson W M , Foulis P R
Published: May 2020

Introduction

Altered sleep, as is associated with obstructive sleep apnea (OSA), may increase the risk of back pain (BP). However, little to no evidence regarding the effect of OSA on musculoskeletal pain is currently available, let alone the effect of positive airway pressure (PAP) treatment non-adherence. The purpose of this analysis is to investigate the effect of PAP non-adherence on future BP diagnosis.

Methods

A sample of 1,662 veterans who had a sleep study between January 2003 and October 2006 and receiving PAP treatment for OSA were used for analysis. Measures at baseline included demographic and OSA symptom severity data. Up to 3 weeks of PAP adherence data were collected and patient chart data was collected through May 2010 to determine outcomes. Time was calculated from PAP treatment start to BP diagnosis or censoring, which occurred at date of death or last recorded encounter. Survival analysis was conducted to obtain the hazard ratios (HR) for the effect of PAP non-adherence on BP diagnosis and to investigate whether post-traumatic stress disorder (PTSD) is an effect modifier of this relationship.

Results

PAP treatment non-adherence significantly increased the risk of BP diagnosis (HR 1.88 [95% CI: 1.08, 3.27]) among veterans with PTSD, while non-adherence among veterans without PTSD was not a statistically significant risk factor. Relative excess risk due to interaction (RERI) was 0.97 (95% CI: -0.07, 2.02; p-value=0.068). These estimates are independent of age, sex, race, body mass index, apnea severity (based on Apnea-Hypopnea Index), PTSD diagnosis, income level, and marital status.

Conclusion

PAP treatment non-adherence among veterans with PTSD appears to result in a significant increase in risk of future BP diagnosis. The interaction between PAP non-adherence and PTSD appears to be borderline synergistic. Therefore, improving PAP adherence among veterans with PTSD may decrease risk of future BP diagnosis.

Support

This material is the result of work supported with resources and the use of facilities at the James A. Haley Veterans’ Hospital.
0669 The Effects Of Continuous Positive Airway Pressure Therapy In Moderate To Severe Obstructive Sleep Apnea: A High-density EEG Study
Authors: D’Rozario A L , Kao C , Mullins A E , Memarian N , Yee B , Duffy S , Banerjee D , Cho G , Wong K K , Kremerskothen K , Chapman J , Haroutonian C , Bartlett D J , Naismith S L , Grunstein R R
Published: May 2020

Introduction

A previous high-density electroencephalography (EEG) investigation in asymptomatic OSA showed regional deficits in sleep EEG power particularly slow wave activity (SWA) during NREM sleep in the parietal region. It is unclear whether treatment with CPAP can reverse local sleep EEG abnormalities in OSA, and whether any recovery is related to improvement in sleep-dependent memory consolidation.

Methods

Fifteen male participants (age 50.4±6.5yrs, AHI 51.7±23.5/h) with moderate-severe OSA (AHI>15/h) underwent overnight polysomnography with 256-channel high-density EEG at baseline and following 3 months of CPAP therapy. A word paired associates declarative memory task was administered before and after sleep. After artefact removal, spectral analysis was performed for all channels. Topographical power maps were calculated for standard frequency ranges for NREM sleep (164 channels within a 0.57 radius from the vertex). Maps were compared using both absolute and normalized power (z-scores computed for each subject) and differences between baseline and treatment were determined by statistical nonparametric mapping.

Results

In 11 CPAP compliant patients (intolerant of CPAP [n=3]/high-density EEG [n=1]), analysis of polysomnographic variables showed that total sleep time did not differ but N1 (baseline vs. treatment: 66.9 vs. 39.5 mins,p=0.008) and N2 (195.0 vs. 150.6 mins,p=0.002) sleep was lower and N3 (89.8 vs. 128.7 mins,p=0.003) was higher after CPAP. Topographic analysis of high-density EEG data revealed a regional increase in SWA (1-4.5Hz) EEG power during N3 sleep in a cluster of electrodes overlying the centro-parietal cortex (cluster mean t-value=2.87,p=0.02). The change in overnight declarative memory consolidation (% recognition) after CPAP was significantly correlated with the change in slow spindle frequency activity in frontal regions (cluster mean r=0.875,p=0.003).

Conclusion

CPAP treatment may enhance localised deficits in sleep EEG activity in OSA, and specific regional recovery may translate to memory improvements in the short-term. These data also highlight the potential for long-term therapeutic effects on cognitive outcomes in OSA.

Support
0677 Patient Preferences On Initiating Treatment With Continuous Positive Airway Pressure
Authors: Borker P V , Wyland C , Patel S R
Published: May 2020

Introduction

Clinical guidelines recommend continuous positive airway pressure (CPAP) therapy be initiated in patients with obstructive sleep apnea (OSA) either at home using an auto-titrating device or following manual titration in the sleep laboratory. Patient preference between these two options is unknown.

Methods

Patients newly prescribed CPAP therapy for the treatment of OSA at an academic sleep medicine clinic were surveyed by telephone within one month of initiating treatment. Data on demographics, disease severity and CPAP adherence were obtained from the medical record.

Results

A total of 75 participants (56% male, mean age 52±15 yrs, 48% moderate to severe OSA) were surveyed. Physicians prescribed home initiation of CPAP in 51%, lab initiation in 23%, and allowed the patient to choose in 27% of cases. Overall, 67% of participants (95% CI [56%-77%]) reported preference for home initiation. Preference for home initiation did not vary by age, sex, AHI, degree of sleepiness, or type of diagnostic study (home vs. lab sleep study) performed (p>0.10 for all). Convenience (44%) and starting treatment faster (44%) were the most common reasons provided for those favoring home initiation, while sleep technician availability (40%), optimization of pressure settings (32%), and ability to try multiple masks (28%) were cited by those favoring lab initiation. The prevalence of CPAP adherence at 90 days tended to be higher in those whose treatment was initiated aligned to preference (79% in those whose treatment initiation was concordant with preference vs. 64% in those whose treatment initiation was discordant, p=0.16).

Conclusion

Overall, two-thirds of patients with OSA prefer initiation of CPAP be done at home. This preference does not vary by demographics, OSA severity or diagnostic modality. Initiating treatment concordant with patient preference may lead to greater adherence.

Support

American Thoracic Society Academic Sleep Pulmonary Integrated Research/Clinical (ASPIRE) Fellowship, K24 HL127307
0680 The Effect of Continuous Positive Airway Pressure on the Levels of the Proinflammatory Markers in Patients with Obstructive Sleep Apnea
Authors: Wali S O , Al-Mughales J , Alhejaili F , Manzar M , Alsallum F , Almojaddidi H , Gozal D
Published: May 2020

Introduction

Obstructive sleep apnea (OSA) develops systemic inflammation, with increased levels of mediators. In general, significant elevations in serum levels of C-reactive proteins (CRP), and interleukin 6 (IL-6) are seen in patients with OSA. The literature is inconsistent regarding the effect of Continuous Positive Airway Pressure (CPAP) on the level of CRP and IL-6. The aim of this study is to evaluate the effect of CPAP on the levels of IL-6 and CRP in patients with OSA.

Methods

All patients newly diagnosed with moderate-severe OSA at the King Abdulaziz university sleep center were targeted. Patients with conditions that may affect the levels of inflammatory markers were excluded. All included patients had their fasting blood taken post the initial diagnostic polysomnography for pro-inflammatory markers. Patients were then classified into two groups. The first group included those that accepted treatment with CPAP (CPAPG). The second group included patients with OSA but refused treatment (No-CPAPG). Each group had been followed for one month, and then another blood samples were drawn for the levels of the pro-inflammatory biomarkers.

Results

Twenty patients in each group were recruited. At baseline IL-6 was significantly higher in the No-CPAPG compared to CPAPG (median 6.7 pg/ml [interquartile range 1.6-7.6] vs. 1.6 pg/ml [1.3-1.9], respectively; p = 0.006) despite similar OSA severity. At 1-month follow-up, IL-6 remained significantly higher in the No-CPAPG; p = 0.003 and there was no effect of CPAP on IL-6 in the CPAPG. There was no significant difference in CRP level at baseline or at 1-month follow-up among the two groups. However, there was neither an effect of time (F (1, 38) = 0.08, p = 0.78), nor an interaction effect between CPAP and time (F(1, 38) = 0.006, p = 0.94) on IL-6 level. Similarly, there was neither an effect of time (F(1, 38) = 1.68, p = 0.20), nor an interaction effect between CPAP and time (F(1, 38) = 0.17, p = 0.68) on CRP level.

Conclusion

IL-6 and CRP levels did not change significantly with CPAP over a one month period in OSA patients.

Support

By the DSR, KAU, Jeddah, KSA. No: KEP-2-140-39
0683 CPAP Adherence Relative To Sleep Duration And Sleep Period In Different Study Populations
Authors: Deering S , Shumard T , Zamora T , Martinez S , Stepnowsky C J
Published: May 2020

Introduction

CPAP is intended for use during sleep to alleviate disordered breathing. Most patients who use CPAP do so for only a portion of their sleep period, although anecdotally it is known that some also use CPAP while awake. We compared the unusually high levels of CPAP adherence found in a recent study of patients with Overlap Syndrome to a VA clinical population and to participants from the APPLES study.

Methods

CPAP adherence levels were taken from three sources: (1) The O2VERLAP Study, a large comparative effectiveness trial that used two different methods of providing information and support to current CPAP users diagnosed with both OSA and COPD. (2) Combined data from the four most recent clinical CPAP trials conducted at VA San Diego Healthcare System. (3) The APPLES study. Total sample sizes were 332, 957, and 405, respectively. Total sleep time (TST) and total sleep period (TSP) were assessed via the Pittsburgh Sleep Quality Index (PSQI) for (1) and (2) and via polysomnography for (3).

Results

Mean CPAP use, TST, and TSP for each source were: (1) 6.7, 6.8, & 8.1; (2) 4.0, 6.1, & 7.5; (3) 4.5, 6.6, & 8.0. We examined the ratios of adherence over either TST or TSP, and the ratios for each source were: (1) 98% & 83%; (2) 66% & 55%; (3) 68% & 56%.

Conclusion

This comparison demonstrates that unlike many CPAP users who tend to use therapy for only a fraction of time spent asleep, patients with COPD and OSA exhibit higher levels of adherence which often exceed sleep time and may be obtaining additional benefits from CPAP use during non-sleep periods. More research is needed both to improve CPAP delivery and support for patients who are using CPAP sub optimally and to understand the factors that account for the heightened levels of CPAP adherence in COPD.

Support

PPRND #1507-31666; IIR 02-275; IIR 07-163; IIR 12-069; PULM-028-12F.
0685 Safety Evaluation Of An Algorithm Determining Needs For Treatment In Obese Sleep Apnea Patient Awaiting Bariatric Surgery: Results Of A Prospective 1103 Patients Cohort Study
Authors: Sériès F , genest C , Boutin I , Marceau S , Bussieres J , Minville C
Published: May 2020

Introduction

Screening for obstructive sleep apnea (OSA) is recommended before bariatric surgery. We developed an algorithm based on results of nocturnal oximetry and capillary gas. According to this algorithm, CPAP/BiPAP is prescribed only in severe OSA (ODI ≥ 25/h) and/or with features of hypoventilation. The objective of this prospective cohort study was to determine the safety of our algorithm comparing peri and post-operative outcomes in patients not receiving pre-operative treatment (without/mild OSA (ODI < 10 /h: controls or ODI 10-24 /h: OSA untreated) and in those receiving CPAP/BiPAP (severe OSA: OSA treated or hypoventilation).

Methods

We collected data from 1103 subjects undergoing bariatric surgery (447 controls; 358 OSA untreated, 289 OSA treated and 9 hypoventilation). For treated patients, a good CPAP/BiPAP compliance was mandatory for surgery with treatment installed immediately after extubation and continued after. Peri and post-operative outcomes were compared according to apnea status with adjustment for the type of surgery when applicable.

Results

Patients with severe OSA/hypoventilation were significantly older and heavier than other patients. Hypertension and diabetes were less prevalent in controls than in the other groups. No difference was found between the 3 groups regarding occurrence of 10 days reoperation and 30 days rehospitalisation. No difference was found regarding occurrence of cardiopulmonary complications except that admission to ICU was more frequent in patients with hypoventilation and occurrence of cardiac arrhythmia was higher in the OSA/hypoventilation treated patients than in the other groups (2.4%, 11.1 %, 0.4% and 0.6%, p = 0.01). OSA/hypoventilation patients had a longer length of stay in the recovery room (1.7 ± 0.5, 1.9 ± 0.6, 1.5 ± 0.5 and 1.5 ± 0.5 hours p<0.0001) and longer length of hospital stay (2.8 ± 1.8, 3.2 ± 1.1, 2.6 ±2.1 and 2.6 ±1.8 days, p<0.0001) than controls and OSA untreated patients.

Conclusion

Our algorithm safely selects patients who don’t need treatment before surgery, with no increase in risk of complications following bariatric surgery not treating OSA patients with mild/moderate sleep apnea without hypoventilation. Patients with severe OSA/hypoventilation, even when correctly treated remain at higher risk of complications.

Support

Fondation IUCPQ-UL
0707 “What We’Ve Got Here Is Failure To Communicate”: Apnea Patients And Their DME Suppliers
Authors: Thapa S , Agrawal S , Kryger M
Published: May 2020

Introduction

Successful treatment of obstructive sleep apnea requires adherence to positive airway pressure (PAP) therapy. A key factor is the relationship between the DME provider and the patient so that treatment can be initiated and continued in a timely manner. Our quality improvement project aims to empower and enable patients towards active participation in their sleep apnea care. Our goal is to ultimately increase patients’ knowledge of their Durable Medical Equipment (DME) supplies company, and thus improve their treatment. The first step was to determine patients’ familiarity with their DME.

Methods

Forty-one patients with sleep apnea on PAP therapy volunteered to be questioned about their DME company during clinic visits at the Yale North Haven Sleep Center, Connecticut, starting November 2019. Patients were asked if they knew the name or the contact of their DME; whether they received adequate training on PAP therapy initiation; if they were receiving timely and correct PAP therapy supplies. They were asked to rate their satisfaction with the DME on a scale of 1 to 5; one being very dissatisfied and five being very satisfied.

Results

Only 12 out of 41 patients (29.3 percent) knew the names of their DME companies. The average satisfaction rating was 3 (neutral); 44% of patients were dissatisfied, or very dissatisfied with the performance of their DME. Detailed comments were mostly related to poor contact and communication with the DME.

Conclusion

Most apnea patients had difficulty identifying and contacting their DME. As the next step of this quality improvement project we plan to intervene to ensure that the patients have the name and contact information of their DME available and attached to their PAP machine equipment. We plan to repeat this questionnaire after this intervention to study the impact of this quality improvement project.

Support

None
0711 Select Symptoms From The Epworth Sleepiness Scale Questionnaire And Response To Therapy Of Central Sleep Apnea With Phrenic Nerve Stimulation
Authors: Javaheri S , McKane S , Meyer T E , Germany R
Published: May 2020

Introduction

Some subjects with central sleep apnea (CSA) complain of subjective excessive daytime sleepiness (EDS), as assessed by the Epworth Sleepiness Score (ESS). However, there is considerable variability in the level of chances of dozing for each of the 8 ESS questions, as each reflects a different situation. The aim of this analysis was to examine individual situations of the ESS and determine if transvenous phrenic nerve stimulation (TPNS) resulted in improvements of individual ESS situations which were scored moderate to high (2 and 3) at baseline. Patient Global Assessment (PGA) was also assessed.

Methods

All 151 subjects enrolled in the randomized (Treatment vs Control) remedē System pivotal trial were included in the analysis. All subjects were implanted, but activation in Control arm was delayed 6 months.

Results

Greater than or equal to 50% of patients scored moderate-high on several individual ESS situations: chance of dozing while sitting and reading (57%), watching television (62%), while lying down to rest in the afternoon when circumstances permit (76%). In the active arm, 68%, 44% and 29% of patients with moderate-high at baseline, respectively, for sitting and reading, watching television, and lying down to rest in the afternoon shifted to less than moderate at 6 months. Respective shifts for the control arm were 29%, 23% and 13%. Seventy-two percent of treated subjects with baseline ESS>10 shifted to ≤10 at 6 months compared to 26% of control patients. Additionally, 72% of treated compared to 7% of control subjects with baseline ESS>10 reported markedly or moderately improved QoL.

Conclusion

Results of this randomized controlled trial shows that compared to the control arm, TPNS leads to improvements in various situations of the ESS as well as QoL. The most improved situations were less chance of dozing while reading and watching television.

Support

Respicardia
0719 The Association of Sleep Apnea and Cardiorespiratory Fitness with Long-Term Major Cardiovascular Events
Authors: Barillas-Lara M , Medina-Inojosa J , Kolla B , Smith J R , Bonikowske A R , Allison T G , Olson T , Lopez-Jimenez F , Somers V K , Caples S M , Mansukhani M P
Published: May 2020

Introduction

Sleep disordered breathing (SDB) is associated with adverse cardiovascular outcomes and decreased cardiorespiratory fitness (CRF). The risk of long-term major adverse cardiovascular events (MACE) when SDB and decreased CRF co-occur has not been determined.

Methods

We included consecutive patients that underwent a symptom-limited cardiopulmonary exercise test followed by first-time diagnostic polysomnography within 6 months. Patients were stratified based on the presence of moderate-severe SDB (apnea/hypopnea index ≥15/hour) and decreased CRF defined as <70% predicted peak oxygen consumption (VO2). MACE was a composite outcome of myocardial infarction (MI), coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), stroke/transient ischemic attack (TIA) and death. Cox-proportional hazard models adjusting for factors known to influence CRF and MACE were constructed.

Results

Of 498 included patients (60±13 years, 28.1% female), 175 (35%) had MACE (MI=17, PCI=14, CABG=13, stroke=20, TIA=12, deaths=99) at a median follow-up of 8.7 years (interquartile range=6.5-10.3 years). After adjusting for age, sex, beta-blockers, systemic hypertension, diabetes mellitus, coronary artery disease, cardiac arrhythmia, chronic obstructive pulmonary disease, smoking and positive airway pressure (PAP) usage, decreased CRF alone (HR=1.91, 95%CI=1.15-3.18, p=0.012), but not SDB alone (HR=1.26, 95%CI=0.75-2.13, p=0.389) was associated with increased risk of MACE. Those with SDB and decreased CRF had increased risk of MACE compared to patients with decreased CRF alone (HR=1.85, 95%CI=1.21-2.84, p<0.005) after accounting for these confounders; the risk was attenuated after additionally adjusting for adequate adherence to PAP (HR=1.85, 95%CI=0.99-3.05, p=0.05).

Conclusion

The incidence of MACE, including mortality, was high in this sample. Moderate-severe SDB with concurrent decreased CRF was associated with higher risk of MACE than decreased CRF alone. These results highlight the importance of including CRF in the risk assessment of patients with SDB, and conversely, that of screening for SDB in patients with low peak VO2.

Support

None.
0745 The Pharmacokinetics of FT218, Once Nightly Sodium Oxybate: Food Effect and Bioavailability Compared to Twice Nightly Sodium Oxybate
Authors: Thorpy M , Seiden D , Grassot J , Monteith D , Dubow J , Corser B
Published: May 2020

Introduction

Sodium oxybate is an effective treatment for excessive daytime sleepiness and cataplexy in patients with narcolepsy. The FDA approved formulation requires twice-nightly dosing; at bedtime and 2.5 - 4 hours later. FT218 is a controlled-release formulation of sodium oxybate intended for once-nightly dosing, using Avadel’s proprietary Micropump™ technology. The objective of this study was to evaluate the relative bioavailability of investigational once-nightly sodium oxybate, FT218, 6 g, compared to commercially available twice-nightly sodium oxybate and the food effect of FT218.

Methods

Two crossover, single-dose pharmacokinetic studies were conducted in healthy volunteers. The first, a relative bioavailability study (n=28) was completed comparing FT218 6 g to twice-nightly sodium oxybate 6 g (in two divided doses of 3 g). The second, evaluated the food effect (n=16) of FT218 6g in the Fed vs. Fasted state.

Results

FT218 had a lower overall Cmax than twice-nightly sodium oxybate, while AUC was equivalent. C8h level and variability was comparable between FT218 and twice-nightly sodium oxybate. In the Fed, compared to the Fasted state, FT218 had a longer Tmax, lower Cmax and decreased AUC (Cmax 67%, AUC 86%, Tmax 1-hour slower than Fasted values). Adverse Events with FT218 were mostly mild or moderate in severity, non-serious and known AEs associated with sodium oxybate. The safety profiles of FT218 and twice-nightly sodium oxybate at 6 g appeared similar.

Conclusion

Once-nightly FT218 at 6 g demonstrated a lower overall Cmax and similar exposure to twice-nightly sodium oxybate, with similar C8h plasma levels and C8h variability. In the Fed state, AUC and Cmax of FT218 was lower than in the Fasted State. FT218 was generally safe and well tolerated and the safety profile appeared comparable to twice-nightly sodium oxybate.

Support

This work was supported by Avadel Pharmaceuticals.
0746 Dynamics of Sleep Stage Transitions in Patients with Narcolepsy and Other Hypersomnias
Authors: Kishi A , Kitajima T , Kawai R , Hirose M , Iwata N , Yamamoto Y
Published: May 2020

Introduction

Narcolepsy is a chronic sleep disorder characterized by excessive daytime sleepiness and abnormal REM sleep phenomena. Narcolepsy can be distinguished into type 1 (NT1; with cataplexy) and type 2 (NT2; without cataplexy). It has been reported that sleep stage sequences at sleep-onset as well as sleep-wake dynamics across the night may be useful in the differential diagnosis of hypersomnia. Here we studied dynamic features of sleep stage transitions during whole night sleep in patients with NT1, NT2, and other types of hypersomnia (o-HS).

Methods

Twenty patients with NT1, 14 patients with NT2, and 35 patients with o-HS underwent overnight PSG. Transition probabilities between sleep stages (wake, N1, N2, N3, and REM) and survival curves of continuous runs of each sleep stage were compared between groups. Transition-specific survival curves of continuous runs of each sleep stage, dependent on the subsequent stage of the transition, were also compared.

Results

The probability of transitions from N1-to-wake was significantly greater in NT1 than in NT2 and o-HS while that from N1-to-N2 was significantly smaller in NT1 than in NT2 and o-HS. The probability of transitions from N2-to-REM was significantly smaller in NT1 than in o-HS. Wake and N1 were significantly more continuous in NT1 than in NT2; specifically, N1 followed by N2 was significantly more continuous in NT1 than in NT2 and o-HS. N2 was significantly less continuous in NT1 and NT2 than in o-HS; this was specifically confirmed for N2 followed by N1/wake. REM sleep was significantly less continuous in NT1 than in NT2 and o-HS; specifically, REM sleep followed by wake was significantly less continuous in NT1 than in o-HS. Continuity of N3 did not differ significantly between groups.

Conclusion

Dynamics of sleep stage transitions differed between NT1, NT2, and o-HS. Dynamic features of sleep such as sleep instability, persistency of wake/N1, and REM fragmentation may differentiate NT1 from NT2, while N2 continuity may differentiate narcolepsy from o-HS. The results suggest that sleep transition analysis may be of clinical utility and provide insights into the underlying pathophysiology of hypersomnia and narcolepsy.

Support

JSPS KAKENHI (18K17891 to AK).
0747 Study Design of an Open-Label Extension and Switch Study for Once Nightly Sodium Oxybate, FT218, in NT1 and NT2 Patients
Authors: Wells C , Dubow J , Fenton M , Patel D , Tyler C , Seiden D
Published: May 2020

Introduction

Avadel Pharmaceuticals has developed FT218, a once nightly sodium oxybate (SO) formulation for the treatment of excessive daytime sleepiness (EDS) and cataplexy in narcoleptic patients. REST-ON, a pivotal efficacy/safety study is expected to be completed in the first half of 2020. Previous Phase 1 studies have demonstrated FT218 delivers a pharmacokinetic profile needed for once-nightly dosing. The purpose of this study is to evaluate long-term safety of FT218 in REST-ON completers and dosing strategy when switching from twice-nightly SO to FT218.

Methods

The study will enroll NT1/NT2 patients who completed REST-ON or patients switching from stable dose of twice-nightly SO to FT218. REST-ON completers will initiate FT218 at 4.5 g and increase by 1.5 g to the highest tolerated dose or the dose deemed effective (up to 9 g). Switch patients will initiate FT218 at the equivalent/closest dose to their current twice-nightly SO and titrate in accord with safety/efficacy. The study will enroll approximately 250 patients for a duration of two years.

Results

The primary endpoint for REST-ON completers will be safety and tolerability. Secondary endpoints for REST-ON completers will include changes in ESS, reported cataplexy and other REM associated phenomena as well as changes in clinician and patient global impression. For switch patients, endpoints will include percentage of subjects that stay on the same, higher or lower dose of FT218 compared to twice-nightly SO, as well as the percentage of subjects who report a preference for the once-nightly dosing regimen.

Conclusion

The results of this open label extension/switch study will further elucidate the potential benefits of once-nightly FT218 regarding long term safety/tolerability, nocturnal safety/tolerability and efficacy, and importantly provide dosing and preference data for patients switching from twice-nightly SO to once-nightly FT218.

Support

This work was supported by Avadel Pharmaceuticals.
0748 A Novel, Non-Pharmacological Treatment Option for Patients With Idiopathic Hypersomnia
Authors: Paech G M , Pradeepan S , Suthers B
Published: May 2020

Introduction

There is some evidence suggesting that patients with hypersomnia have delayed circadian timing, which could explain, at least in part, the excessive sleepiness and impaired daytime performance experienced by these individuals. This study investigated the effects of bright light treatment on improving daytime alertness in patients with idiopathic hypersomnia.

Methods

Participants were scheduled to two in-laboratory sessions (baseline and treatment) consisting of overnight sleep monitoring (polysomnography) followed by maintenance of wakefulness tests (MWT) and performance testing (10-min psychomotor vigilance task (PVT)). MWTs were performed at 10:00, 12:00, 14:00 and 16:00 and PVTs were performed at 11:00, 13:00, 15:00 and 15:00. In-laboratory sessions were separated by a two-week at-home treatment period during which participants were instructed to use commercially available light devices for 30-60 min each morning. Participants also completed the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) at baseline and after treatment. Paired t-tests were performed to assess differences in sleep architecture, sleep quality, performance (lapses; reaction time >500ms) and alertness (MWT mean sleep latency) between baseline and treatment.

Results

To date, three participants (2 male) aged 62.7±13.2 (mean±SD) years have completed the study. Lapses (baseline: 17.9±11.9; treatment: 6.3±5.4), ESS (baseline: 17.3±3.1; treatment 12.3±6.8) and PSQI (baseline: 7.7±3.8; treatment: 4.0±1.0) all improved with light treatment, although this did not reach statistical significance. There were no statistical differences between baseline and treatment with regards to sleep architecture or mean sleep latency.

Conclusion

Although preliminary, results suggest that bright light treatment may improve subjective sleepiness, subjective sleep quality and performance. There was some variability between individuals, indicating that this treatment may not offer the same benefits to all patients. Although ongoing, this study suggests that light therapy could be used as an alternative, non-pharmacological treatment option to improve waking functions and sleepiness in hypersomnia patients.

Support

This project is supported by a Hunter Medical Research Institute Research Project Grant
0753 Cataplexy-Free Days in a Phase 3, Placebo-Controlled, Double-Blind, Randomized Withdrawal Study of JZP-258 in Adults With Narcolepsy With Cataplexy
Authors: Dauvilliers Y , Foldvary-Schaefer N , Bogan R K , Šonka K , Profant J , Huang L , Thorpy M J
Published: May 2020

Introduction

Sodium oxybate (SXB) is a standard of care for the treatment of cataplexy and excessive daytime sleepiness in narcolepsy. JZP-258 is an oxybate product candidate with 92% less sodium. This analysis evaluated cataplexy-free days/week, as a measure of treatment impact, in a placebo-controlled randomized withdrawal study of JZP-258 treatment in patients with narcolepsy.

Methods

Treatment for cataplexy at study entry included 1) SXB (SXB-only); 2) SXB plus other anticataplectics (SXB+other); 3) anticataplectics other than SXB (other anticataplectics); or 4) cataplexy treatment-naive (anticataplectic-naive). Participants (aged 18-70 years with narcolepsy with cataplexy) began JZP-258 treatment during a 12-week, open-label, optimized treatment and titration period (OLOTTP), followed by a 2-week stable-dose period (SDP). Participants were randomized to receive placebo or continue JZP-258 treatment during a 2-week, double-blind, randomized withdrawal period (DBRWP).

Results

Of 201 enrolled participants, 134 comprised the efficacy population (placebo, n=65; JZP-258, n=69). Median (Q1, Q3) cataplexy-free days/week at first week of OLOTTP (while initiating JZP-258) by prior treatment were SXB-only, 5.8 (2.0, 7.0); SXB+other, 6.4 (5.0, 7.0); other anticataplectics, 4.0 (1.8, 6.0); anticataplectic-naive, 3.5 (0, 5.8). At end of SDP (on stable dose of JZP-258), median (Q1, Q3) cataplexy-free days/week were 6.0 (3.5, 7.0), 6.1 (1.4, 7.0), 6.0 (2.6, 7.0), and 6.2 (4.0, 7.0), respectively. Prior to randomization, there was no difference in median cataplexy-free days/week between participants to be randomized to placebo (6.0 [3.5, 7.0]) or JZP-258 treatment (6.0 [3.0, 7.0]); during DBRWP, median cataplexy-free days/week decreased in participants randomized to placebo (3.5 [0, 5.83]) but remained similar in participants randomized to continue JZP-258 treatment (5.6 [2.8, 7.0]). The overall safety profile of JZP-258 was similar to SXB.

Conclusion

Number of cataplexy-free days/week increased with JZP-258 treatment in participants previously naive to oxybate. Number of cataplexy-free days/week decreased during placebo exposure in participants randomized to placebo.

Support

Jazz Pharmaceuticals
0760 SUVN-G3031, A Potent And Selective Histamine H3 Receptor Inverse Agonist: Safety, Tolerability And Pharmacokinetics Following Single And Multiple Ascending Doses In Healthy Adult Subjects
Authors: Bhyrapuneni G , Goyal V , Pandey S , Muddana N , Palacharla R , Ajjala D , Ravula J , Jetta S , Badange R , Benade V , Nirogi R
Published: May 2020

Introduction

SUVN-G3031 is a potent and selective histamine H3 receptor inverse agonist currently being developed for the treatment of narcolepsy. SUVN-G3031 produced robust wake promoting and anticataplectic effects in animal model relevant to the disease. This supports its therapeutic utility in the treatment of sleep related disorders like narcolepsy with and without cataplexy.

Methods

Two Phase 1 studies were conducted to assess safety, tolerability and pharmacokinetics (PK) of SUVN-G3031. In the first study, single ascending doses of 0.1 mg to 20 mg SUVN-G3031 were administered to healthy subjects. For multiple ascending dose cohorts, doses of 1 mg to 6 mg were administered for 14 days. In the second Phase 1 study, effects of food, gender and age on the PK of SUVN-G3031 were assessed.

Results

SUVN-G3031 absorbed rapidly following single oral administration and the exposures (Cmax and AUC) were dose proportional at the tested doses between 0.1 mg to 20 mg. SUVN-G3031 attained steady state on day six and achieved projected efficacy concentrations following repeated administrations. Food, gender and age had no effect on pharmacokinetics of SUVN-G3031. SUVN-G3031 was well tolerated up to 20 mg/ day single dose and 6 mg repeated dose in healthy adult subjects. There were no serious adverse events reported by any subject during Phase 1 studies.

Conclusion

SUVN-G3031 was well tolerated in humans with adequate plasma exposures for efficacy and has favorable pharmacokinetics suitable for once a day oral administration. SUVN-G3031 is currently being evaluated in a Phase 2 study as monotherapy for the treatment of narcolepsy with and without cataplexy (ClinicalTrials.gov Identifier: NCT04072380).

Support

None
0774 Factors Associated With The Continuous Use Of Psychotropic Treatments For Narcolepsy
Authors: Ohayon M M , Krystal A D , Black J , Shapiro C M , Sullivan S , Swick T J , Wells C C
Published: May 2020

Introduction

Narcolepsy is a debilitating disorder characterized by excessive sleepiness and cataplexy episodes. There is no cure for this disease. Current treatments focus on controlling the symptoms with CNS stimulants for sleepiness and antidepressants and/or CNS depressants for cataplexy. This study examines the factors that can contribute to the cessation of narcolepsy treatment.

Methods

The study includes 291 narcoleptic individuals who were interviewed twice, approximately five to seven years apart, in Wave 1 (W1) and Wave 2 (W2). Telephone interviews were conducted with the help of the Sleep-EVAL system; narcolepsy individuals were initially evaluated and diagnosed by a Sleep Specialist.

Results

At W1, 49.2% of narcoleptic individuals were taking a CNS stimulant; at W2, 37% of narcoleptic individuals were taking a CNS stimulant. The use was chronic (i.e., present at W2 and W1) for 52.7% of the W2 subjects. CNS depressants were used by 19.1% at W1 and 17% at W2. Of the W1 subjects, 67.6% still reported using CNS depressants at W2. In terms of antidepressants, 38.6% and 29.6% of subjects reported using these medications at W1 and W2 respectively. Of those taking antidepressants at W2, 58.9% reported chronic use (ie, were also on antidepressants at W1). At least one of the aforementioned medication classes was used by 72% of participants at W1 and 56.1% at W2. Chronicity of nocturnal awakenings (RR: 2.7), the frequency of cataplexy episodes (RR: 2.3) and the chronicity of hypnopompic hallucinations (RR: 2.8) were associated with long-term use of narcolepsy treatment.

Conclusion

Narcolepsy treatments are mostly taken to long term. Some narcoleptics individuals were able to reduce or stop treatment either because the intensity of symptoms decreased or because they developed coping mechanisms to deal with the symptoms.

Support

NIH (R01NS044199), the Arrillaga Foundation and Jazz Pharmaceuticals Inc.