Citations

Abstract Introduction Obstructive sleep apnea (OSA) is characterized by repetitive airway narrowing or collapse during sleep. Hypoglossal nerve stimulation (HNS) is one alternative therapy. After device implantation and activation, it is patient-titrated based on symptoms. A sleep study then confirms effective settings based on an apnea-hypopnea index (AHI) below 5. Symptomatic control alone may not entail low AHI. Objective data with overnight oximetry during titration may help bridge this. We describe a patient in whom Wellue pulse oximeter was used during self-titration of the Inspire HNS. Report of case(s) A 63 year-old male presented in June 2022 for HNS evaluation due to gasping and witnessed apneas. AutoPAP trial had failed. In November 2022 diagnostic polysomnography revealed an AHI of 18 and lowest oxygen saturation (OS) of 80%. Sleep endoscopy in February 2023 confirmed no concentric collapse at the level of the velum. He underwent HNS implantation in May 2023 and activation in June. Initial sensation and functional thresholds were 0.6 volts. Amplitude range was 0.6 to 1.6 volts, pulse width 90 microseconds, rate 33 hertz, pause time 15 minutes, electrode configuration [+,-,+], and duration 8 hours. In July, he felt 0.7 volts controlled symptoms. A Watchpat home sleep study revealed an AHI of 46.2 and lowest OS of 82%. He purchased a pulse oximeter and was shown the oxygen desaturation index (ODI) at >3%. On increasing to 1.0 volts, oximetry revealed ODI 8.65 averaged over 4 nights. At 1.1 volts, ODI improved to 0.9-4.14. Since ODI was below 5, he had subsequent in-laboratory titration, revealing at 1.1 volts the residual AHI was 2.5. The lowest OS was 89% with a mean of 95%. Conclusion The post-activation procedure for HNS utilizes symptom-based self-titration. Sleep studies may reveal continued apnea despite self-reported symptom control. We suspect overnight oximetry during self-titration may improve efficacy. In this case, after self-titration with oximetry to decide an amplitude setting, home and in-laboratory sleep studies confirmed effective control. This preliminarily suggests that overnight oximetry used with HNS during the self-titration phase may improve titration outcomes as confirmed by formal polysomnography. Support (if any)

Abstract Introduction Inflammatory bowel disease (IBD) is a chronic immune-mediated disease that includes Crohn’s disease and ulcerative colitis. People with IBD experience poor sleep health, including short and highly fragmented sleep and extraintestinal manifestations including alterations to cognitive functioning; however, the relationships between sleep health and cognitive symptoms have not been evaluated in this population. The purpose of this study was to identify the associations between sleep health and perceived cognitive impairments in adults with IBD. Methods We conducted a descriptive, correlational study of adults (18 to 59 years old) with IBD. We used the Pittsburgh Sleep Quality Index (PSQI) to obtain self-reported data on sleep health, the FACT-Cog Perceived Cognitive Impairments questionnaire to elicit cognitive symptoms, and the Manitoba IBD Index to describe IBD disease activity. Descriptive statistics, point-biserial correlations, and Pearson’s correlations were used to describe relationships. Results Of the 59 participants [Mean age 40.8 (SD 10.5), 71.2% female, 94.9% white], 67.8% (n=40) had clinically active IBD. 79.7% (n=47) had a PSQI total score >5, indicating poor sleep health. The most common cognitive symptoms, occurring two or more times a week, were trouble concentrating (55.9%), walking into a room and forgetting an intended task (44.1%), and forgetting the names of people soon after being introduced (44.0%). PSQI total score was positively and significantly correlated with 12 of 13 questions on the FACT-Cog. The strongest correlations included trouble concentrating (r = .497, P<.001), slower thinking (r = .450, p<.001), trouble forming thoughts (r=.550, p<.001), and difficulty finding the right words to express oneself (r=.546, p<.001). Longer self-reported sleep latency was associated with higher frequency of 12 out of 13 cognitive symptoms, while sleep efficiency was associated with 4 and sleep duration was associated with 2. Having clinically active IBD was associated with trouble forming thoughts (r=-.261, p=.046), slower thinking (r=-.307, p=.018), and trouble concentrating (r=-.346, p=.007). Conclusion Cognitive symptoms are common among people with IBD, highly correlated with sleep health, and not fully explained by IBD disease activity. Future studies should include objective measures of sleep health and cognition to further elucidate these relationships. Support (if any) Mayo Clinic Bonner Fund

Abstract Introduction Sleep disturbance and circadian rhythm disruptions are common among adults with chronic heart failure (HF), and are related to cognitive impairment. Although light levels are known to influence sleep quality, cognition, and the circadian system, little is known about the role of light among adults with HF. The purpose of this study is to investigate the association between light exposure and sleep, diurnal rest-activity rhythms (RAR), and cognitive function among adults with HF. Methods We retrospectively analyzed baseline data from a randomized controlled trial of cognitive behavioral therapy for insomnia for adults with HF and insomnia. We measured light levels and sleep with 24-hour wrist actigraphy and computed the circadian quotient, inter-daily stability, and intra-daily variability (strength of the RAR) using cosinor and non-parametric methods. We computed time above threshold (TAT) (100, 500, and 1000 lux), ratio of light exposure in daytime to evening (AUC ratio), and light regularity index (LRI) (20, 50, and 100 lux) to assess the intensity and consistency of light exposure patterns. Lapses in performance on the Psychomotor Vigilance Task (PVT lapse) measured cognitive function. Multiple linear regressions tested if the light exposure metrics could predict the RAR, sleep efficiency, and PVT lapses after adjusting for age, sex, and comorbidities. Results The sample included 167 participants (M age=63.8 (SD =12.9) years; 45.5%female). The AUC ratio and TAT500 were associated with a stronger circadian quotient in males (0.339 ± 0.095, p=.0005; 0.296 ± 0.085, p=.0006) compared to females (0.058 ± 0.106, p=.5800; -0.061 ± 0.128, p=.6364), after controlling for age and comorbidities. TAT500 was associated with better inter-daily stability (0.221 ± 0.077, p=.0044) than the other thresholds. Higher light exposure intensity (TAT100) (0.129 ± 0.065, p=.0492) and a greater circadian quotient (0.267±0.076, p=.0006) were associated with improved sleep efficiency. TAT100 was associated with fewer PVT lapses (-0.229 ± 0.082, p=.0061), after controlling for total sleep time, circadian quotient, and demographics. Conclusion Light exposure, particularly at certain intensities and regularity, predicted RARs, sleep efficiency, and cognitive function in adults with HF. Future tailored light interventions with varying intensities and regularity may improve HF outcomes. Support (if any)

Abstract Introduction Regular exercise improves sleep quality by reducing sleep onset latency, extending total sleep duration, and enhancing sleep efficiency, which may alleviate daytime sleepiness. However, the specific impact of exercise on daytime sleepiness remains unclear, with conflicting findings in the literature. We analyzed existing interventional studies which used Epworth Sleepiness Scale (ESS) to measure changes in degree of daytime sleepiness before and after an exercise regimen, allowing us to explore the relationship between exercise and daytime sleepiness. Methods Following PRISMA guidelines, a systematic search was conducted in electronic database of PubMed and Google Scholar from 1991 to the present. Thorough screening and inclusion criteria were applied to identify relevant studies which included ESS assessment before and after an exercise intervention. Also assessed sleep quality by Pittsburgh Sleep Quality Index (PSQI). Results Seven studies met all the inclusion criteria and were included in this study. Exercise exhibited a significantly beneficial impact on sleepiness measured by ESS in four out of seven studies we included in review while two studies showed a marginal reduction in ESS without statistical significance, and one study indicated no change. Additionally, exercise showed an improvement in sleep quality in four out of five studies that included PSQI. Variability in results was noted, influenced by factors such as exercise type, intensity, duration, and timing, as well as individual adherence. Additionally, exercise interventions improved sleep quality, as suggested by reduced scores in PSQI which may indirectly improve daytime sleepiness. Conclusion This analysis of existing interventional studies on exercise and daytime sleepiness suggests exercise can be beneficial for reducing daytime sleepiness and improving sleep quality. While the exact mechanism remains elusive, several factors contribute to the impact of both acute and chronic exercise on daytime sleepiness such as improved sleep quality, regulation of circadian rhythm, neurotransmitters release, stress reduction, increased energy levels, and weight reduction ultimately alleviating daytime sleepiness. Future research will be essential for addressing gaps on how exercise regimen and the underlying mechanisms may prove efficacious on improving daytime sleepiness. Support (if any) Mayo Clinic Florica Research Accelerator for Clinicians Engaged in Research Program

Abstract Introduction Patients presenting with daytime somnolence need to be evaluated for common etiologies including sleep-related breathing disorders, shift work disorder, insufficient sleep, insomnia and disorders of hypersomnolence. Sleep disordered breathing (SDB) is one of the most common causes of daytime sleepiness. We postulate that treatment of SDB may actually worsen symptoms, if associated with poor sleep due to positive airway pressure (PAP) therapy. Methods N/A Results A 49-year-old female presented to our clinic with increased daytime somnolence. She was diagnosed with obstructive sleep apnea (OSA) at an outside center 3 years ago and was started on auto PAP therapy with pressure settings at 6-10 cmH2O. She had 100% usage, 95th percentile pressure of 9 cm H2O, and a residual Apnea Hypopnea Index (AHI) of 1.1. The patient reported excessive daytime sleepiness, with an Epworth Sleepiness Scale of 16, requiring a daily 3-hour nap. Further sleep history revealed that she had multiple nocturnal awakenings due to discomfort with PAP therapy, including mask related issues causing sleep disruption. Several mask adjustments did not result in any sleep improvement. We decided to re-evaluate her with an in-lab polysomnography. Diagnostic data revealed an overall AHI of 1.6, supine AHI of 12.0, and lateral AHI of 1.5. Mean oxygen saturation was 94.6% with a nadir of 89.0%. The patient was advised to discontinue PAP therapy, and to sleep on her sides, which led to improvement in her sleep quality and daytime sleepiness. Conclusion Positional OSA, defined by greater than 50% increase in AHI in supine position compared to non-supine position, with or without AHI less than 5 in non-supine position, is seen in up to 50-60% of patients with OSA. In addition, intolerance to CPAP has been noted in 29-83% of patients. We need to be clinically aware of the potential effect of PAP devices, or oral appliances, on sleep disruption among intolerant patients. Among this group, conservative therapies like positional therapy or weight loss may be more effective for symptom management, especially for mild SDB. Support (if any)

Abstract Introduction Polysomnography (PSG) requires on-body sensors for respiratory effort measurement, that can adversely affect sleep quality and accuracy of detection of sleep related breathing disorders (SRBD). We developed a non-contact 60 Hz pulsed wave radar system with integrated advanced signal processing to collect respiratory effort, heart rate and gross body movements data using phase differencing to a sub-mm resolution. In this study we tested the performance of this system in detecting SRBD events against standard PSG in human participants. Methods During participants’ clinically indicated PSG, we collected concurrent data from the radar system placed under the bed on a tripod mount. Algorithms were developed to quantify breath amplitude reductions collected by radar and compared to the time-synced signals derived from respiratory impedance plethysmography belts. A Convolutional Neural Network (CNN) was trained on radar in-phase/quadrature (I/Q) data for each 30 second epoch to output probability of apnea and hypopnea events using standard event definitions. Receiver Operating Characteristics (ROC) plot and confusion matrix for the trained network were generated to provide accuracy of event predictions. Results A total of 60 participants completed the study. The participants had a mean age of 65 years (Inter Quartile Range 13.5 years), and 56% subjects were male. The mean AHI for the entire cohort was 12.9 (IQR 14.75) events/hour. ROC plots showed an Area Under the Curve (AUC) of 0.98 for events detection by radar compared to human scored PSGs. The confusion matrix was generated at an operating point of 95% sensitivity and 80% specificity. Conclusion The non-contact high frequency radar system showed excellent performance in respiratory event detection in patients with sleep-related breathing disorders in comparison to the gold standard PSG system. Use of this technology is expected to reduce the number of body contact sensors used during conventional sleep studies and thus improve patient comfort and accuracy of results. Support (if any) Research reported in this abstract was supported by National Institute of Aging of the NIH under award number: R44AG060779

Abstract Introduction Oral Appliance Therapy (OAT) is a management option for patients with Obstructive Sleep Apnea (OSA). A reported drawback to OAT is symptoms relating to Temporomandibular Joint Disorder (TMD), including post-procedure jaw pain. Some studies reported TMD in over 50% of patients prior to OAT. The aim of this study was to evaluate the prevalence of TMD and oral Parafunction Habits (PFH) in patients with OSA referred for OAT, and determine any relationship between patient characteristics, demographics, medical history, and degree of OAT advancement with post-procedure jaw pain. Methods A retrospective analysis was conducted, reviewing the electronic health records of 125 patients with OSA referred to the division of dental sleep medicine in Mayo Clinic Rochester, for OAT. Records reviewed included patient demographics, TMD-PFH symptoms and signs before and after initiation of OAT, self-reported history of, and signs of PFH, AHI pre-initiation of OAT, presence of fibromyalgia, SSRI use, and percent advancement of appliance at time of re-evaluation. Results The median age of patients reviewed was 58 (Interquartile Range (IQR) 20), median BMI 30.5 (IQR 7), median AHI 11.3 (IQR 9.5). 57% were male, 43% female. 20.8% patients had TMD history, 37.6% had TMD signs, 47.2% had PFH history (jaw clenching, lip biting, and/or thumb sucking). 96% had signs of PFH. 15.2% reported post-procedure jaw pain. There was a statistically significant relationship between both TMD history and TMD signs, with post-procedure jaw pain (p value 0.002 and 0.013 respectively), although after multi-variate analysis, only TMD history remained associated with post-procedure jaw pain (Odd’s Ratio 3.385, 95% Confidence Interval 1.081 – 10.601, p value = 0.036). Age, BMI, gender, PFH signs and history, SSRI use, fibromyalgia history, % advancement of OA had no statistical association with post-procedure jaw pain. Conclusion Having a history of TMD symptoms prior to OAT is a risk factor for post-OAT jaw pain. A thorough oral and maxillofacial history in patients being considered for OAT is important to identify patients with TMD history, to establish a clear path to initiate OAT and to closely monitor, reduce or potentially eliminate the reported side effect. Support (if any)

Abstract Introduction Restless legs syndrome (RLS) is a common disorder of unpleasant sensations during inactivity, an urge to move the legs, and hyperarousal. The pathophysiology is incompletely understood. Treatments are not always successful or carry side effects. Methods (Case Report) Results A 45-year-old woman presented with over a decade of RLS and sleep-onset insomnia. The diagnosis was based on the International RLS Study Group criteria. The severity was assessed by the nightly occurrence and Insomnia Severity Index (ISI) of 25. Interfering neurologic or sleep disorders, medications, and abnormal blood work were ruled out. Different dopamine agonists resulted in augmentation. Caffeine was stopped. Polysomnography revealed periodic limb movement with sleep fragmentation. Gabapentin was partially effective and poorly tolerated at high doses, but continued at 600 mg. While using Dextromethorphan (DXM) for an upper respiratory infection, the patient found dramatic improvement of her RLS symptoms. Independently, she discontinued Gabapentin, and continued DXM 30 mg for 6 months, with consistent improvement. ISI decreased to 10. Ultimately, considering its expense, DXM was tapered, and Tramadol initiated. The pathophysiology of RLS is partially understood. Studies showed abnormalities in iron regulation, low adenosine tone, enhanced glutamatergic activity, inflammation, and a genetic predisposition, as contributing factors. Alpha-2-delta calcium channel ligands inhibit the presynaptic glutamate release. Central nervous system iron deficiency may increase glutamatergic tone. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, inhibits the activation of NMDA receptor by glutamate and decreases glutamate presynaptic release. Ketamine was reported to effectively treat RLS. DXM, another NMDA receptor antagonist, has not been reported to treat RLS in the literature. Additionally, an association between inflammation and RLS was described, and limited data showed anti-inflammatory effect of DXM. Conclusion Patients with RLS suffer from their symptoms’ burden. Approved medications could carry side effects, or augmentation. We report a case of severe RLS with dramatic and sustained improvement with DXM. Support (if any)

Abstract Introduction Sleep-related symptoms have been associated with adverse health outcomes, including increased mortality risk. Studies that analyzed the correlation between sleep and mortality focused on the single effect of self-reported sleep duration or relied on nonstructured questionnaires about sleep. In order to evaluate the detrimental effects of sleep disorders, studies should be based on well-structured and validated questionnaires that inquire about different components of sleep, including sleep quality. In addition, taking into consideration the fluctuations in sleep duration over the study period is essential. We aimed to assess the association between sleep quality and all-cause mortality in community-dwelling adults living in rural Ecuador. Methods Individuals aged ≥40 years enrolled in the prospective population-based Three Villages Study cohort were included. Sleep quality was assessed by means of the Pittsburgh Sleep Quality Index (PSQI). Study participants were evaluated at baseline and at every annual door-to-door survey until they remained enrolled in the study. Mixed models Poisson regression for repeated PSQI determinations and multivariate Cox-proportional hazards models were fitted to estimate mortality risk according to sleep quality. Results Analysis included 1494 individuals (mean age: 56.6 ± 12.5 years; 56% women) followed for a median of 6.3 ± 3.3 years. At baseline, 978 (65%) individuals had good sleep quality and 516 (35%) had poor sleep quality. The effects of PSQI scores changing over time on mortality was confounded by the impact of the SARS-CoV-2 pandemic on both. One hundred ninety-five individuals (13%) died during the follow-up, resulting in a crude mortality rate of 1.58 per 100 person years (95% C.I.: 1.27-1.88) for individuals with good sleep quality, and 3.18 (95% C.I.: 2.53-3.82) for those with poor sleep quality at baseline. A multivariate Cox-proportional hazards model showed that individuals with poor sleep quality at baseline were 1.38 times (95% C.I.: 1.02-1.85) more likely to die compared to those with good sleep quality; in this model, increased age, poor physical activity, and high fasting glucose remained significant. Conclusion Poor sleep quality is associated with increase mortality risk among middle-aged and older adults. Support (if any)

Abstract Introduction Several studies have shown a positive association between Obstructive Sleep Apnea (OSA) and malignancies such as lung cancer. However, the effects of intermittent hypoxemia in cancer-free survival following curative therapy are not known. We propose that OSA-related episodic hypoxemia and hypoxic burden are independent risk factors for accelerated lung cancer reoccurrence (< 2 years). Methods We performed a retrospective record review of patients 18 years and older from January 2016 to September 2023 with history of non-small cell lung cancer who received an overnight oximetry study (OXY) within three years prior to undergoing curative malignancy treatment. Subjects with history of central sleep apnea, baseline oxygen saturation (SpO2) below 90%, receiving supplemental oxygen or treatment for OSA were excluded. Results 403 patients met inclusion criteria (52% female vs 48% males; median age 74 y). The most common histologic subtypes were adenocarcinoma (68%) followed by squamous cell carcinoma (22%). Most patients fell into Stage IA1 (35%) followed by IA2 (24.1%) and IB (19%) as per TNM 8th edition classification. Over this period, 68 patients (22%) had lung cancer recurrence (median 19 months). A 4% oxygen desaturation index (ODI) of >15 and time spent in desaturation events were found to be a risk factor for cancer reappearance in less than 2 years (p< 0.001). Measures of hypoxic burden such as time spent below 89% SpO2, average SpO2 value below 89%, and single nadir oxygen levels, showed a similar association (p< 0.001). This was irrespective of histologic subtype, stage at diagnosis, and all studied demographic variables. Basal SpO2 demonstrated no correlation. A multivariate proportional hazard survival model showed that ODI>15 was no longer significant, however average SpO2 below 89% and single minimum oxygen level remained strongly correlated with accelerated recurrence. Conclusion This study showed a strong, positive association between accelerated lung cancer recurrence and OSA-related episodic hypoxemia and hypoxic burden on our univariate analysis. The multivariate model demonstrated correlation with hypoxic load measures only, suggesting the need for a larger sample to elucidate the involvement of this highly treatable risk factor. To our knowledge, this is the first study revealing this potential link. Support (if any)