bluuebunny/crossref_metadata_2025_split huggingface dataset:
0761 Adaptability of the Treating Obstructive Sleep Apnea Using Targeted Hypoglossal Nerve Stimulation (OSPREY) Trial
Authors: Jacobowitz Ofer , Schwartz Alan , Lovett Eric , Ranuzzi Giovanni , Malhotra Atul 
Published: May 2022

Abstract

Introduction
With few exceptions, clinical trials of hypoglossal nerve stimulation (HGNS) for obstructive sleep apnea (OSA) are single-arm, open-label studies sometimes followed by short-term, unblinded, randomized withdrawal. By contrast, the THN3 study was a parallel-arm, randomized, controlled trial (RCT) of targeted HGNS (THN) in moderate to severe OSA, and provided higher-level evidence of HGNS safety and efficacy.Despite generating strong evidence, conventional RCTs are risky due to their inherent inflexible designs. We therefore launched a confirmatory THN RCT (OSPREY) with an adaptive, Bayesian “Goldilocks” design that optimize its sample size dynamically, yet achieve high-confidence results.

Methods
Four scenarios were simulated within the OSPREY design framework (randomized 2:1 Treatment:Control) for the primary endpoint of apnea-hypopnea index (AHI) response rate (RR): nominal with results equal to those of THN3 (Treatment AHI RR 52%/Control AHI RR 20%), improved Treatment RR (63%/20%), worsened Treatment RR (41%/20%) and null [Treatment RR=Control RR] (20%/20%). Each scenario was simulated 10 times with 10,000 simulations of each interim analysis. Subject outcomes were determined by randomly drawing from a binomial distribution with the relevant AHI RR.Interim analyses in OSPREY begin at 50 randomized subjects and repeat every 20 additional subjects to the maximum sample size of 150, with opportunities for early success and futility at each milestone to generate high-confidence results from an optimal sample size. OSPREY assesses secondary endpoints including quality of life inventories (Epworth Sleepiness Scale; Functional Outcomes of Sleep Questionnaire; EQ-5D, SF-6D and PROMIS sleep questionnaires) and oximetry metrics (Oxygen Desaturation Index, %sleep time below 90% oxygen saturation). Previous results suggest secondary endpoints will be adequately powered at the final sample size determined by AHI RR.

Results
Simulations produced the following outcomes formatted as [scenario: randomized sample size, overall success rate, probability of early success, mean success probability]: null: 150, 0%, 0%, 2.47%; nominal: 130-150, 100%, 80%, 95.3%; improved: 90-130, 100%, 100%, 98.9%; worsened: 150, 100%, 0%, 68.6%.

Conclusion
OSPREY is uniquely able to adapt to various Treatment/Control response scenarios and should provide high-confidence confirmation of the safety and efficacy of THN therapy in moderate to severe OSA.

Support (If Any)
LivaNova
0783 Compliance with Follow-up Polysomnogram in Patients Prescribed Oral Appliance Therapy for Treatment of Obstructive Sleep Apnea
Authors: Kouassiaman Courtland , Foster Shannon , Powell Tyler , Hansen Shana , Brock Matthew 
Published: May 2022

Abstract

Introduction
Literature supports Oral Appliance Therapy (OAT) for mild-to-moderate obstructive sleep apnea (OSA) with evidence showing clinical benefits. The long-term ease of follow makes these devices attractive options for many though requires upfront provider and patient coordination. After prescription of OAT, a dental professional qualified in fabrication must evaluate the patient, the device must be fabricated and a follow-up polysomnogram (PSG) with the device in place should be obtained to determine treatment efficacy. If this guideline is followed in clinical practice is unknown with limited research. Our study evaluates the frequency of follow-up PSG in patients referred for OAT for treatment of OSA in a combined sleep and dental clinic.

Methods
A retrospective chart review was performed to determine if OSA patients who elected to pursue OAT subsequently underwent a follow up PSG after obtaining their device. Patients who did not have their diagnostic study at our institution were excluded. Patients prescribed OAT for primary snoring were also excluded.

Results
We identified 104 patients who were referred for OAT for treatment of OSA; 90 (86.5%) of which followed up with the dental clinic, 84 (80.8%) of which obtained devices, and 14 (13.5%) of which completed a PSG after obtaining their device. Additional review of the original 104 patients demonstrated: 88 (84.6%) were male, mean BMI was 27.6, mean AHI 15.1/hr, and mean age 38.9 years. Review of the 14 patients who obtained follow up PSGs with OAT showed: all were male, mean BMI 27.0, mean AHI 13.8/hr and mean age 38.6 years. Total sleep time (TST) in patients who had a follow up PSG with OAT (mean = 344.2 min) was significantly less than on their diagnostic PSG (mean = 367.2 min, p= 0.043).

Conclusion
Although the AASM CPG for treatment of OSA with OAT recommends follow-up sleep testing to confirm efficacy, the follow-up PSG rate of 13.5% in a single-center closed system indicates poor patient adherence. Increased communication between the dental providers and sleep clinic is encouraged for proper follow up. Further research will need to be done to elucidate the individual and systemic barriers to appropriate follow-up.

Support (If Any)
0785 Cardiovascular Outcomes For Obstructive Sleep Apnea With HGNS Therapy
Authors: Tangutur Akshay , Seay Everett , Boon Maurits , Huntley Colin , Thaler Erica , Dedhia Raj 
Published: May 2022

Abstract

Introduction
Obstructive sleep apnea (OSA) is linked to cardiovascular disease, particularly when left untreated. Hypoglossal nerve stimulation (HGNS) is a novel and promising PAP alternative as it is well-tolerated and reduces OSA severity; however, its effect on mitigating cardiovascular risk secondary to OSA is unknown. The aim of this study is to evaluate the effect of HGNS on sympathetic and vascular function. Our hypothesis is mean 24-hour systolic blood pressures (SBP) will be improved at “active” levels of HGNS.

Methods
This study is a double-blinded, sham-controlled, randomized controlled therapy crossover trial. Subjects are randomized for four weeks in each arm to either “active” HGNS or “sham” HGNS, with “sham” HGNS being defined as the lowest voltage at which HGNS was sensed by the patient and/or visualized by the principal investigator. Included patients had already been implanted with the Inspire® device. Patients were excluded for active PAP therapy use, recent automobile accidents, a minimum difference (&lt;30%) between “active” and “sham” voltages, and pregnancy.

Results
53 patients met all inclusion criteria. Overall, the study cohort was older (mean [SD] age 66.8 [10.2]), overweight (BMI 28.8 [4.36]), 60% male, and predominantly of white race. There was no significant difference in mean 24-hour SBP between “active” and “sham” HGNS (122.4 mmHg [12.2] vs. 122.4 mmHg [11.2], respectively). Further, there was no significant difference in mean SBP during sleep between “active” and “sham” HGNS (115.0 mmHg [15.2] vs. 115.2 mmHg [14.4], respectively).

Conclusion
This is a randomized controlled trial evaluating cardiovascular outcomes in patients with OSA using HGNS therapy. The HGNS system permits a unique investigation of the therapy “on/off” effect on measures of the sympathetic nervous system and vascular health. “Active” HGNS levels, compared to “sham” HGNS levels, do not appear to reduce mean systolic blood pressure during wake or sleep periods.

Support (If Any)
Raj C. Dedhia, MD, MSCR is supported by the American Heart Association and the American Sleep Medicine Foundation.
0794 Understanding Barriers and Communication Behaviors Impacting Referral to Sleep Surgery: Qualitative Patient Perspectives
Authors: Ikeda Allison , McShay Crystina , Marsh Robin , Saini Shireen , Weaver Edward 
Published: May 2022

Abstract

Introduction
Shared decision-making is a process when patients, families, and clinicians work together to make optimal, personalized medical choices in the face of more than one reasonable treatment option. These interactions can influence the joint decision and may have lasting impressions for future healthcare encounters. Considering the American Academy of Sleep Medicine’s recent clinical practice guideline on the referral of adults with obstructive sleep apnea (OSA) for surgical consultation, we aimed to understand patient experiences, in terms of barriers and communication behaviors in the referral process to sleep surgery consultation.

Methods
We performed a qualitative study consisting of in-depth semi-structured virtual interviews with adult patients (aged ≥18 years) with OSA (apnea-hypopnea index ≥5 events per hour of sleep, scored by AASM-accredited standards) and who were recommended for sleep surgery at a tertiary Sleep Surgery Clinic. Open ended questions focused on patient experiences during healthcare encounters from diagnosis, trials with noninvasive management options and ultimate referral to sleep surgery. The interviews were audio-recorded, transcribed, and analyzed using content analysis to identify themes.

Results
Ten adult patients with OSA who were evaluated in sleep surgery clinic were approached and enrolled from March through April 2021. Barriers to sleep surgery clinic included delays in OSA diagnosis due to limited OSA awareness and perceived inconvenience of sleep study, providers faulting patient for persistent sleep symptoms, patient-reported lack of urgency by providers in troubleshooting noninvasive management options, scheduling delays and waitlists, and cost. Patients were open to trialing noninvasive treatment options, though opportunities for reevaluation and shared decision-making may address unmet needs, as inadequate improvements led to frustration after multiple encounters. Patients appreciated providers who were empathetic and provided information sharing, in terms of transparent and understandable explanations.

Conclusion
This study focused on experiences of patients with OSA and barriers faced to reach sleep surgery consultation. Improved communication structure to discuss unresolved concerns and remaining management options, as well as vetted resources, would set the foundation for effective shared decision-making and timely referral for sleep surgery consultation.

Support (If Any)
Academy of Otolaryngology Head and Neck Surgery Resident Research Centralized Otolaryngology Research Efforts (CORE). NIH T32 DC000018.
0798 Detriggered - a case of tenosynovitis ameliorated by CPAP
Authors: Yuan Nathaniel , Padilla Alfonso 
Published: May 2022

Abstract

Introduction
The influence of sleep quality and pain is bidirectional (1). Sleep loss can induce hyperalgesia through upregulated inflammatory mediators such as IL-6 and TNF (2, 3). Obstructive sleep apnea (OSA) is characterized by obstructive respiratory events, hypoxemia, sleep fragmentation, and ultimately poor quality sleep. Here we present a case of how the treatment of OSA with continuous positive airway pressure (CPAP) mitigated hand inflammation and trigger finger symptoms.
Report of Cases: A 60 year old male with prediabetes, hypertension, and BMI 30 presented to primary care with bilateral finger pain and stiffness. Hand orthopedics noted a tender left A1-pully 4th finger with 20 degree flexion contracture and a palpable right 3rd finger flexor tendon nodule causing definite triggering. He was diagnosed with trigger finger and initially treated with steroid injections and again 5 months later due to persistent symptoms. 10 months after the initial orthopedic visit, orthopedics planned for surgical intervention, but patient missed his surgery for unknown reasons.
7 months later, sleep medicine evaluated the patient for snoring and daytime fatigue. He
underwent home sleep apnea testing which revealed a respiratory event index (REI) of 36.7
which necessitated CPAP therapy. Unfortunately, the patient was then lost to follow up in sleep medicine clinic. More than a year later, the patient showed to clinic and found to have 100% CPAP compliance with residual REI of 0.7. He enthusiastically noted improvement of daytime fatigue and trigger finger symptoms when using CPAP. When he would forget to use CPAP at night or during naps, he would wake up with returned finger pain and stiffness. Per patient, the symptoms would then resolve after re-initiation of CPAP. This consistent association of CPAP and finger symptom amelioration continued even 8 months later in most recent follow up.

Conclusion
To our knowledge, this is the first report of trigger finger symptoms improving with treatment of OSA. One hypothesis is that through improved sleep quality, there is a dampening of chondrocyte proliferation of the retinacular sheath and allowing unrestricted motion of the flexor tendon (4). More studies are needed to evaluate the musculoskeletal benefits of CPAP for OSA.

Support (If Any)
1. Haack M. Scott Sutherlandj. Et al. Pain sensitivity and modulation in primary insomnia. Eur J Pain. 2012, 16: 522-533.2. Chhangani BS, Roehrs Ta et al. Pain sensitivity in sleepy pain-free normals. Sleep, 209, 32:1011-1017.3. Li, Joule Sarah Appleton. Association of Musculoskeletal Joint Pain with Obstructive Sleep Apena, Daytime Sleepiness, and Poor Sleep Quality in Men. Arthritis Care and Research Vol 69. No 5. May 2017.4. Makkouk Al Hasan et al. Trigger finger: etology, evaluation, and treatment. Curr Rev Musculoskeltal Med 2008. 1:92-96.
0801 Melatonin Induced Autoimmune Hepatitis in the Setting of the Management of REM Sleep Behavior Disorder
Authors: Moshtagh-Sisan Mahtab , Sarrami Kayvon , Patel Jay , Harris Brian , Avidan Alon 
Published: May 2022

Abstract

Introduction
Melatonin is a neurohormone that serves a key role in human circadian physiology. It is widely used in the United States as an over-the-counter (OTC) sleep aid for managing insomnia, circadian rhythm disorders, and parasomnias. The US Food and Drug do not regulate it as a dietary supplement. However, insufficient data currently exist about formulations and overall safety for long-term usage. While serious adverse events with melatonin are rare, we describe a patient in whom clinical, laboratory, and biopsy features of autoimmune-mediated hepatitis developed in temporal association with time-release melatonin (MLTR) therapy for the treatment of dream enactment behaviors in the setting of REM-sleep behavior disorder (RBD).
Report of Cases: A 78-year-old female was referred to our clinic to manage disruptive dream enactment in the setting of RBD. The patient had been previously treated with Clonazepam, Diazepam, and Temazepam but remained refractory. Management with MLTR at 5 mg achieved clinical improvement and titration over a month up to 10 and 15 mg fully controlled dream enactment. Unfortunately, during this time, the patient developed swollen and erythematous joints and abdominal pain. Liver biopsy demonstrated lymphoplasmacytic infiltrate with rosette formation consistent with autoimmune hepatitis consistent with idiosyncratic drug-induced hepatitis associated with elevated liver function enzymes [AST 184 (H) (NL &lt;39U/L), ALT 395 (H) (NL&lt;56 U/L), Bilirubin, Direct= 0.3 (H) (NL&lt;=0.2 mg/dL)]. Melatonin was discontinued achieving complete resolution of symptoms and normalization of liver function indicating its
causal association with hepatitis.

Conclusion
This unusual report of melatonin-induced autoimmune hepatitis is uncommon but points to intriguing immunostimulatory effects of melatonin. Our case highlights an important and sometimes overlooked attribute of melatonin that prescribers and patients must recognize. While melatonin is often viewed as a safe dietary supplement, its use, particularly among people with autoimmune disorders, should be documented and monitored with care.

Support (If Any)
0810 Management of Narcolepsy In A Patient With Severe Chronic Iron Deficiency: The Importance of Addressing Nutritional Deficiencies In The Treatment of Narcolepsy and Hypersomnias
Authors: Baldridge Scott , Khan Yousaf , Ghildiyal Naomi , Monceaux Brittany , Asghar Sheila , Liendo Cesar , Chernyshev Oleg 
Published: May 2022

Abstract

Introduction
Since iron is a cofactor used in the synthesis of CNS dopamine, some of which is then converted into norepinephrine, CNS iron deficiency will have an impact on the availability of dopamine and norepinephrine. Medications for narcolepsy and hypersomnia, such as stimulants and wakefulness medications, are dependent on the availability of these neurotransmitters to achieve their clinical response. Unrecognized and untreated nutritional deficiencies may contribute to inadequate responses to treatment of these sleep disorders.
Report of Cases: A 26-year-old female with a history of iron deficiency since her pre-kindergarten health evaluation had a history of inadequate responses to stimulants and wakefulness medications. Additional labs were drawn to evaluate for nutritional deficiencies that could be contributing to the combination of fatigue and hypersomnolence. These revealed continued severe iron deficiency along with vitamin B6, B12, and D deficiencies. The treatment plan then expanded to include treatment of the nutritional deficiencies and a trial of pitolisant, which works to increase histamine levels in the brain. Sadly, pitolisant resulted in intolerable headaches, so it was discontinued.

Conclusion
This author feels that patients with hypersomnia warrant a broader approach that includes evaluating for nutritional deficiencies which may contribute to fatigue and hypersomnolence. In this case, the plan was to address the patient’s nutritional deficiencies and switch to pitolisant which mediates increased CNS histamine levels. This was unsuccessful due to the side effect of increased frequency and intensity of headaches related to pitolisant. Treating her iron deficiency with iron infusions should increase CNS synthesis of dopamine and norepinephrine. She may now have a better response to stimulants or wakefulness medications which depend on the availability of these neurotransmitters. She may also benefit from combination therapy by adding sodium oxybate to one of these medications.

Support (If Any)
0821 Narcolepsy after West Nile Virus Meningoencephalitis infection
Authors: Tarpara Kishan , Khan Safia 
Published: May 2022

Abstract

Introduction
Narcolepsy is a sleep disorder characterized by hypersomnia and inappropriate intrusion of REM sleep into wakefulness. Etiology is heterogeneous, and is broadly classified into Narcolepsy Type 1 and Type 2. There is growing evidence that the pathogenesis in many cases have a post-infectious autoimmune basis. We present the case of a patient seen in our sleep clinic who was eventually diagnosed with Narcolepsy type 2 following West Nile Virus (WNV) Meningoencephalitis.
Report of Cases: · The patient is a 44 year old Hispanic woman who had no prior sleep difficulties before 2013, when she was diagnosed with WNV meningitis. Lumbar puncture results from the time of infection are not available, as this evaluation occurred in the Dominican Republic. Subsequent lumbar punctures have shown the presence of anti-WNV IgG antibodies in her CSF. MRI and MRA brain were unremarkable.
· She also has a history of migraine, fibromyalgia, depression, and adrenal insufficiency.
· She presented with sleep complaints, including sleep onset insomnia, symptoms of sleep
disordered breathing, and excessive daytime sleepiness.
· She underwent home sleep apnea test in 12/2020 which revealed mild obstructive sleep
apnea. Overall AHI was 7.9/hour without significant hypoxemia. She was subsequently started on CPAP therapy with good adherence, but she continued to have significant daytime sleepiness, notably with an Epworth Sleepiness Scale score of 21/24.
· She subsequently underwent overnight polysomnogram and multiple sleep latency test in our sleep laboratory.
· Overnight PSG confirmed mild obstructive sleep apnea (AHI 12.0) along with short REM
latency (10.5 minutes). Next day MSLT showed mean sleep latency of 2.3 minutes, for 5
attended naps, with 2 SOREMPs, which was diagnostic of Narcolepsy type 2.

Conclusion
This case demonstrates the onset of narcolepsy after WNV meningoencephalitis.

Support (If Any)
0829 Workup of Nocturnal Hypoxemia Leads to Diagnosis of Patent Foramen Ovale
Authors: Stanton Crystal , Francis Natalie , Bashir Ahsan , Freire Amado 
Published: May 2022

Abstract

Introduction
Patent foramen ovale (PFO) in adults often remains asymptomatic until clinical manifestations such as cryptogenic stroke, migraine headache, air embolism, hypoxemia, or platypnea-orthodeoxia syndrome occur. In this case, prior workup of cryptogenic stroke failed to identify a PFO that was diagnosed after further investigation of polycythemia which revealed nocturnal hypoxemia on polysomnogram.
Report of Cases: A 60-year-old male with history of recurrent venous thromboembolic events (VTE), secondary polycythemia, and cryptogenic strokes was referred for a polysomnogram during the evaluation of polycythemia. Over the span of six years, he had multiple cryptogenic strokes and VTEs in the setting of polycythemia and normal hypercoagulability labs. Further evaluation suggested secondary polycythemia after serum erythropoietin and JAK2 mutation testing were negative. The patient was a never smoker without evidence of malignancy or renal disease leading to suspicion that his polycythemia was due to hypoxemia despite normal oxygen saturations during point of care evaluations. He frequently reported shortness of breath during
appointments.
During a polysomnogram, the patient was found to have a total apnea-hypopnea index of fewer
than 5 events per hour but demonstrated hypoxemia with 49.7% of total sleep time spent
below an oxygen saturation of 90%. He was referred to pulmonology for further evaluation that
showed normal resting oxygen saturation, no desaturation on a six-minute walk test, mild
restrictive defect on pulmonary function testing, and a normal chest computed tomography
with angiography. Prior transthoracic echocardiogram had demonstrated an atrial septal
aneurysm without communication between the atrial chambers. No evidence suggestive of a
right-to-left shunt was found on lateral imaging of the brain during a ventilation-perfusion scan.
Further evaluation of the aneurysmal atrial septum on transesophageal echocardiogram with an
agitated saline bubby study demonstrated a patent foramen ovale with a right-to-left shunt. In
the setting of hypoxia leading to secondary polycythemia, the patient was scheduled for PFO
closure.

Conclusion
Hypoxemia out of proportion to sleep-disordered breathing on polysomnogram should prompt further evaluation. Despite multiple prior strokes, our patient’s PFO had gone undiagnosed until polycythemia prompted a polysomnogram that demonstrated isolated nocturnal hypoxemia and prompted a further workup. Clinically significant hypoxemia is an indication for PFO closure.

Support (If Any)