Citations

Abstract Introduction Sleep-related painful erection (SRPE) is a rare parasomnia characterized by painful penile erections during rapid eye movement sleep. Normal, painless erections continue to occur while awake. Approximately thirty cases have been reported in the literature. Multiple theories about potential pathophysiology have been proposed including neurologic dysfunction of the ischiocavernosus and bulbocavernosus, correlation with obstructive sleep apnea, and/or autonomic dysfunction. There is no known single effective treatment to date resulting in durable response despite multiple attempts at therapy. Report of case(s) A 39-year-old male presented with SRPE. This started in 2018 and occurred in the second half of the night every twenty minutes, contributing to discomfort and poor sleep quality. While awake, his erections were painless. He was prescribed baclofen at doses up to 30mg daily decreasing episode frequency to 1-6 times per night, but disabling somnolence precluded continuation. Pelvic physiotherapy was unhelpful while imipramine and clonazepam provided partial relief. Tadalafil was ineffective and cinitapride was not available in the United States. Oxycodone used for pain after a motor vehicle accident did effectively treat him for five hours per night, so morphine was trialed. This was effective for two weeks, but symptoms returned. In April 2022, he was begun on sodium oxybate. With an initial dose of 2.25 g twice nightly, symptoms were treated for four hours a night. After increasing to 2.75 g twice nightly, the SRPE was effectively treated. As of September 2022, he is taking sodium oxybate 3 g at bedtime, 3 g 3.5 hours later and the final 3 g at the 7th hour, promoting 9.5 hours of sleep without SRPE. Conclusion This 39-year-old male who presented with SRPE was trialed on multiple therapies without success, and ultimately successfully treated with an appropriate and titrated dose of sodium oxybate. This may represent a new treatment option, which we hypothesize may act by modulating GABA to result in relaxation of the bulbospongiosus and ischiocavernosus muscles. Further studies should include the study of both the efficacy of this drug for SRPE as well as potential mechanisms of action. Support (if any)

Abstract Introduction Several studies suggest an association between periodic limb movements during sleep (PLMS) and hypertension; however, a systematic evaluation of this relationship is lacking. Methods We conducted a systematic review and meta-analysis of observational studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio, comparing the risk of hypertension in persons with PLMS (defined by the level of periodic limb movements per hour of sleep depended on individual studies) versus those without PLMS. After assessing heterogeneity and bias, the pooled risk ratio and 95% confidence intervals (CIs) were determined using a random-effect, generic inverse variance method of DerSimonian and Laird. Results Out of 572 potentially relevant articles, six eligible cross-sectional studies were included in the data analysis which included 8,949 participants. The statistical heterogeneity of this study was insignificant, with an I2 of 0%. A funnel plot showed no publication bias. The pooled risk ratio of hypertension in patients with PLMS was 1.26 (95% CI, 1.12–1.41). Conclusion Our analysis demonstrates an increased hypertension risk among patients with PLMS. Prospective or interventional studies are needed to confirm this association. Support (if any)

Abstract Introduction Research was undertaken to better understand the path to a narcolepsy diagnosis, common symptoms, and the impact of narcolepsy on work, social interactions, and mental health. Methods In February 2022, an email invitation to an online, 27-question survey was sent to US members of MyNarcolepsyTeam, a social network of >9,800 members. Results In total, 110 members completed the survey. 38% of respondents started to experience symptoms before reaching 16 years of age. Most commonly experienced symptoms included excessive daytime sleepiness (EDS; 93%) and fatigue (84%). In total, 72% were also experiencing some form of sleep disturbance and 67% were already suffering from cognitive/memory challenges. 68% who were eventually diagnosed with narcolepsy type 1 (NT1) had cataplexy attacks. For 31%, getting to a narcolepsy diagnosis took ≥10 years. In fact, 64% were initially under- or misdiagnosed with something other than narcolepsy, including depression (73%), sleep apnea (36%), or attention-deficit/hyperactivity disorder (16%). 74% of patients with NT1 have continued to experience cataplexy, with 46% having some form of a cataplexy episode a few times per week. Cataplexy episodes were triggered by a wide range of emotional situations, including over-tiredness (70%), anger (48%), being startled (46%), laughter (46%), fear (44%), excitement (38%), or crying (33%). 76% of respondents indicated that the impact of narcolepsy on daily life is extremely or very severe. The far-reaching impact on quality of life was evident in that most respondents reported that narcolepsy interfered with work (82%), social life (86%), everyday chores (85%), and exercise (85%) and has limited career options (76%). The emotional toll of narcolepsy manifested in feeling isolated (83%), depressed (81%), anxious (80%), or embarrassed (75%). Conclusion Patients routinely experienced a misdiagnosis or a “missed” diagnosis based on common symptoms experienced. Being able to quickly identify narcolepsy as the root cause for symptoms of EDS, fatigue, and sleep disturbances can lead to getting the patient on the best treatment path as early as possible. Understanding the physical, emotional, and quality-of-life impact of narcolepsy can help clinicians provide a more holistic approach to treating their patients. Support (if any) Avadel Pharmaceuticals

Abstract Introduction Sleep markers can assess prodromal risk for neurodegenerative disorders (NDD). In a recent study conducted by the Mayo Clinic, most isolated REM sleep behavior disorder patients preferred knowing about their risk for parkinsonism or dementia. In their email survey, patients indicated a strong preference for disclosure of prognostic NDD risk in order to spur family discussions and plan for the future. For this pilot study, the Mayo questions were modified in order to investigate the perspectives and preferences of community-based adults about potentially being at-risk of a NDD and how it might impact their lives. Methods A brief survey was administered to Rotary Club attendees prior to a presentation on sleep and neurodegenerative disease. Each question offered five responses: strongly disagree, disagree, neutral, agree, or strongly agree. Personal identifiers were not obtained. Thirty-four surveys were completed from approximately equal numbers of older men and women with estimated ages above 50 years. Personal information were not obtained (e.g., age and sex). Results When asked whether it was important to know their NDD risk given the fact that there are no known methods to prevent or cure the disease, most (83%) strongly agreed or agreed, while only 18% preferred not to know their NDD risk. The majority felt they would be more pessimistic about their future if identified as being at risk of NDD the (62% strongly agreed/agreed). Most believed their priorities and plans for living life would change (68% strongly agreed/agreed). Further, the vast majority felt that knowing NDD risk would help them plan for the future (89% strongly agreed/agreed), including planning for health resources and support (88% strongly agreed/agreed). Conclusion Eighty-three percent of those surveyed reported they would benefit from knowing if they were at risk of NDD, even though the majority would feel more pessimistic about their future. The vast majority (89%) responded that knowing their NDD risk would help them plan for the future. These results suggest that most community adults might be receptive to future sleep screening for NDD with results. Investigations are underway to confirm these findings in a broader community-based study. Support (if any) NIA-R44AG050326

Abstract Introduction Narcolepsy is a chronic sleep disorder with multiple comorbid conditions. Sodium oxybate (SXB) is strongly recommended for treatment of narcolepsy. This study used aggregate electronic health record (EHR) data to characterize demographic characteristics and comorbidities of patients with narcolepsy treated with or without SXB. Methods An EHR-based search identified first-time Mayo Clinic patients between 1975–2020. Patients had ≥1 narcolepsy-specific ICD-9/-10 code and ≥1 diagnostic mention of narcolepsy in clinical notes (natural-language-processing algorithm). Patients with narcolepsy treated with SXB were age/sex matched with a cohort without SXB treatment. Common comorbidities were identified using ICD-9/-10 codes and compared between cohorts (odds ratio [OR]). Results Of 4387 patients identified, 8% received SXB treatment (n=351; mean [IQR] age at first diagnosis code observed at Mayo Clinic, 32 [23.2-46.1] y; 65.5% female; 92.3% white); 4036 patients had no SXB treatment (mean [IQR] age at first diagnosis code observed at Mayo Clinic, 44.8 [29.8-59.0] y; 58.0% female; 88.9% white). The 10 most commonly reported comorbidities (overall population) were insomnia (46.6%), fatigue (46.3%), depression (42.2%), hypertension (36.2%), hyperlipidemia (34.2%), obstructive sleep apnea (32.3%), diabetes mellitus (31.3%), arrhythmia (27.3%), idiopathic hypersomnia (IH; 26.8%), and coronary artery disease (17.6%). A cohort of 351 patients without SXB were age/sex matched to patients with SXB for comparison of comorbidities. In the unadjusted analysis, P values were significant for differences between cohorts (OR [95% CI] SXB vs no SXB) for fatigue (0.72 [0.54-0.97]; P< 0.05; adjusted P>0.9) and IH (0.60 [0.43-0.84]; P< 0.01; adjusted P=0.29). After P value adjustment (Bonferroni correction), there were no significant differences between these cohorts in ORs for any comorbidity. The matched cohorts, which were younger than the overall population, had numerically lower rates of these diagnoses vs the overall population, except fatigue and IH in patients without SXB and depression in patients with SXB. Conclusion Among age-/gender-matched cohorts of patients with/ without SXB, there were no significant differences in comorbidities. Prevalence of comorbid IH/narcolepsy diagnoses highlight the diagnostic challenge in differentiating IH from narcolepsy type 2. SXB is highly effective but used by < 1:10 patients with narcolepsy in the Mayo Clinic health system. Support (if any) Avadel Pharmaceuticals

Abstract Introduction Managing atrial fibrillation (AF) in patients with obstructive sleep apnea (OSA) is challenging and often associated with worse outcomes. Non-alcoholic fatty liver disease (NAFLD) is shown to be associated with increased cardiovascular morbidity and mortality. The effect of NAFLD on AF in patients with OSA is not well studied. This study aims to investigate this association in hospitalized patients. Methods We queried the National Inpatient Sample (NIS) between 2017-2020 for adult patients hospitalized for AF with history of OSA & had NAFLD. The primary outcome was in-hospital mortality. The secondary outcomes were cardiogenic shock, gastrointestinal bleeding (GIB), cardiac arrest, invasive mechanical ventilation (IMV) and length of stay (LOS). Multivariable logistic and Poisson regression analyses were used to estimate clinical outcomes. Outcomes were adjusted for age, gender, race, heart failure, diabetes, CKD, chronic respiratory failure, stroke and history of MI. P-value < 0.05 was statistically significant. Results We identified 1,843,865 hospitalizations for AF with history of OSA: NAFLD in 61,235 (3.4%). AF with OSA and NAFLD vs. no NAFLD had mean age 68.4 vs. 70.6, males 65.2% vs. 64.1%, white 78.2% vs. 80.2%, black 9.3% vs. 10.2%, obesity 45.7% vs. 46.5%, heart failure 69.2% vs. 59.6%, diabetes 59.2% vs. 51.1%, anemia 23.5% vs. 17.2%, CKD 52.4% vs. 40% and COPD 38.2% vs. 39.1%. In-hospital mortality was 11.4% in the NAFLD group vs. 2.5% in the non-NAFLD group (aOR 5.2, P< 0.001). NAFLD vs. non-NAFLD groups had GIB 9.4% vs. 4.5% (aOR 2.1, P< 0.001), cardiac arrest 3.4% vs. 0.9% (aOR 3.4, P< 0.001), cardiogenic shock 7% vs. 1.2% (aOR 4.9, P< 0.001), IMV 10.9% vs. 3.4% (aOR 3.3, P< 0.001) and LOS 7.7 vs. 5.6 (aIRR 1.27, P< 0.001). Conclusion Our study shows that NAFLD has worsened the outcomes of patients admitted with AF and has history of OSA. The fivefold increase in in-hospital mortality is likely related to the increase in in-hospital hemorrhagic events and cardiac arrest. Clinicians should be aware of this association. Further research is needed to mitigate the detrimental effect of liver disease on OSA and AF patients. Support (if any)

Abstract Introduction Individuals with narcolepsy were surveyed to better understand desired treatment outcomes and how those outcomes map to commonly experienced symptoms, treatment awareness, and medication usage. Methods In February 2022, an email invitation to a 27-question online survey was sent to US members of MyNarcolepsyTeam, a social network of >9,800 members. Results In total, 110 members completed the survey. The most frequently mentioned desired treatment goals aligned with the most commonly reported symptoms: being able to stop sleeping during the day (77%); increased energy (62%); improved memory (36%); improved productivity (29%); improved sleep continuity (22%); and for patients with narcolepsy type 1, reducing cataplexy (28%). A common theme was desire for a medication that would treat the underlying cause and not just improve specific symptoms. In one patient’s own words: “I want to see treatments that target the root problem of poor nighttime sleep rather than just being a band-aid for [excessive daytime sleepiness] EDS, like stimulants are.” Only a small percentage of respondents (13%) were not currently taking any type of medication to address narcolepsy symptoms. 64% were currently taking ≥2 medications to address both the daytime and nighttime symptoms. Most commonly mentioned current treatments were dextroamphetamine-amphetamine (30%), modafinil (22%), melatonin (16%), armodafinil (15%), venlafaxine (14%), and oxybate (14%). Notably, 33% of patients taking sodium oxybate chose sleeping through the night as a desired outcome. Most common sources for learning about treatments were narcolepsy-specific websites (53%), MyNarcolepsyTeam specifically (45%), the patient’s doctor (42%), scientific articles (42%), and advocacy groups (37%). Conclusion Patients experience a wide range of both daytime and nighttime symptoms and seek relief from both sets of symptoms including EDS (93%), fatigue (79%), cognitive challenges (74%), as well as sleep disruptions (63%). As a result, the majority need multiple medications. Understanding the experiences and needs of people with narcolepsy provides significant opportunities for clinicians to support, educate, and treat their patients holistically. Additionally, content readily available on the internet, whether it is narcolepsy-specific content or social networks, helps patients proactively discuss options with their clinician. Support (if any) Avadel Pharmaceuticals

Abstract Introduction Epilepsy is frequently encountered in the pediatric population and some patients are treated by stimulation of the vagus nerve to reduce their seizure frequency. Vagus nerve stimulation (VNS) may induce central sleep apnea. Adaptive servo ventilation is a known treatment option for central sleep apnea in certain adult patients with heart failure and Cheyne-Stokes respiration but is infrequently utilized in the pediatric population. Report of case(s) A 17-year-old male with a history of intractable generalized epilepsy, VNS placement, obstructive sleep apnea (OSA) and central sleep apnea (CSA) presented to our tertiary care center for management of his sleep disordered breathing. Initial management of sleep disordered breathing included CPAP for OSA. After VNS placement, the patient began to have a high residual apnea-hypopnea index on data card download of his CPAP. Polysomnography (PSG) was performed on CPAP and CSA events were noted that correlated with VNS firing. BiPAP was titrated and was unsuccessful in treating the CSA. VNS adjustment did not impact the sleep disordered breathing. Repeat titration with adaptive servo ventilation successfully treated the OSA and CSA. In follow up, the patient is tolerating ASV with improvement in his nocturnal sleep disordered breathing events and his daytime functioning. Conclusion Central sleep apnea can be induced by vagus nerve stimulation. This unique case documents successful treatment of vagus nerve stimulation induced central sleep apnea by adaptive servo ventilation in an adolescent patient. Support (if any)

Abstract Introduction There is evidence of increased risk of admission with influenza in patients with untreated obstructive sleep apnea (OSA). There is however limited evidence of the impact of OSA on patients admitted with influenza pneumonia. We aim to study this association on a nationwide scale. Methods Using the National Inpatient Sample (NIS) Database from 2017 to 2020, a retrospective study of adult patients with principal diagnosis of influenza viral pneumonia with secondary diagnosis with or without obstructive sleep apnea (OSA) according to ICD-10 codes. Several demographics, including age, race, and gender, were analyzed. The primary endpoint was mortality, while the secondary endpoints included mechanical intubation, length of stay in days, and patient charge in dollars. Multivariate logistic regression model analysis was used to adjust for confounders, with a p value less than 0.05 considered statically significant. Results The study included 174,339 patients admitted with an influenza pneumonia, 13,094 of which had OSA. The Mean age for patients with and without OSA was 67 and 70 years, respectively. In the OSA group, 48% were females compared to 55% in the non-OSA group. Around 73% in both groups were Caucasian white. Statistically significant comorbidities noticed in the OSA group included chronic kidney disease (29% vs. 22%), Diabetes Mellitus (48% vs. 31%), COPD (47% vs. 31%) . In-hospital mortality rate was not higher in the OSA group with statistical significance (2.1% vs. 2.3%, p =0.48). The adjusted Odds ratio was 0.51 without statistical significance. In-hospital mechanical ventilation and tracheotomy rates were higher in the OSA group with statistical significance (5.3 % vs. 3.7%, p < 0.01) (0.31 % vs. 0.12%, p 0.013 ) however the adjusted odds ratio was not statistically significant in either (aOR 1.27, p value 0.14). (aOR 0.9, p value 0.98). The length of stay was higher in the OSA group (5.5 vs. 4.9 days, adjusted means +0.4 days, p value 0.04) Patients in the OSA group had a higher total charge (59,949$ vs. 44,091$, adjusted means +1,997$ p value 0.45) Conclusion Patients admitted with influenza viral pneumonia with associated OSA were not found to have worse clinical outcomes and a higher economic burden. Support (if any)

Abstract Introduction Obstructive Sleep Apnea (OSA) is prevalent in heart failure and is associated with cardiovascular and all-cause mortality. The evidence is growing that Non-Alcoholic Fatty Liver Disease (NAFLD) is associated with increased cardiovascular morbidity and mortality. There is limited scientific evidence of clinical outcomes in patients with Acute Heart Failure (AHF), OSA and NAFLD. Therefore, we sought to investigate this population. Methods We queried the National Inpatient Sample (NIS) between 2017-2020 for adult patients hospitalized for AHF with history of OSA & had NAFLD. The primary outcome was in-hospital mortality. The secondary outcomes were in-hospital cardiogenic shock, gastrointestinal bleeding (GIB), cardiac arrest, invasive mechanical ventilation (IMV) and length of stay (LOS). Multivariable logistic and Poisson regression analyses were used to estimate clinical outcomes. P-value < 0.05 was statistically significant. Results We identified 1,029,785 hospitalizations for AHF with history of OSA: NAFLD in 138,415 (3.7%). AHF with OSA and NAFLD vs. no NAFLD had mean age 65.8 vs. 67.9, males 62.2% vs. 59.2%, Caucasian race 71.6% vs. 68.7%, obesity 50.8%, 55.6%, atrial fibrillation 53.6% vs. 50.5%, diabetes 61.3% vs. 60.4%, anemia 24.8% vs. 20.3%, CKD 56.9% vs. 51.7 and COPD 42.7% vs. 48%. In-hospital mortality was 11.9% in the NAFLD group vs. 2.6% in the non-NAFLD group (aOR 5.2, P< 0.001). AHF and OSA with NAFLD vs. non-NAFLD groups had GIB 6.4% vs. 2.8% (aOR 2.4, P< 0.001), cardiac arrest 4% vs. 1.1% (aOR 3.7, P< 0.001), cardiogenic shock 13.1% vs. 2.6% (aOR 5.2, P< 0.001), IMV 13.2% vs. 5% (aOR 2.9, P< 0.001) and LOS 9.1 vs. 6.6 days (aIRR 1.3, P< 0.001). Conclusion In patients with OSA admitted for AHF, NAFLD is independently associated with five times higher odds of in-hospital mortality. It's also associated with a significantly higher incidence of cardiac arrest, cardiogenic shock, IMV and increased hospital LOS. The NAFLD group patients were younger, less obese, with more anemia and CKD. The chronic inflammatory process and humoral dysregulation associated with OSA and NAFLD would induce worsening outcomes of AHF hospitalization. Further research is needed on the impact of OSA optimization in patients with heart failure and NAFLD. Support (if any)