bluuebunny/crossref_metadata_2025 huggingface dataset:
0647 DSM-V Diagnosed Post-traumatic Stress Disorder (PTSD) is Associated with Reported Dream Enactment Independently from Gender, Race or Education in a Psychiatric Outpatient Population
Authors: Bliwise Donald , Greer Sophia , Black Kathryn , Wise Anna , Rauch Sheila , Rothbaum Barbara
Published: May 2022

Introduction

PTSD has been associated with PSG-derived measurements of REM without atonia suggestive of RBD (Elliott et al, Sleep 2020 Mar 12;43(3):zsz237). Those findings have been reported in men in their mid-50’s. In a relatively younger, diverse, help-seeking, psychiatric outpatient population enriched with PTSD, we examined the impact of demographics (self-reported gender, race, education) on the association between primary diagnosis of PTSD and probable RBD assessed with a validated questionnaire.

Methods

Patients (n = 1,658) were enrolled in a non-VA based treatment program for veterans. Patients underwent detailed diagnostic interviews and psychometrics. About 48% (549 men, 251 women; mean age 40.0 [SD = 9.6] years; 381 non-white) met criteria for PTSD. Typical other diagnoses included Axis I defined major depression and various anxiety disorders (without re-experiencing). Dream enactment was assessed with the previously validated University of Michigan RBD Questionnaire (UMRBDQ), completed either by patient or bedpartner. Mean (SD) and 50th% UMRBDQ scores were 0.52 (SD = 0.26) and 0.50. We defined likelihood of RBD by the 90th% of UMRBDQ score (> .80), based on previously published psychometrics, and used multiple logistic regression to define predictors of high vs low UMRBDQ scores. Predictors were diagnosis, self-reported gender (male), race (non-white [vs white]) and education (at least partial college).

Results

PTSD diagnosis was strongly associated with positive UMRBDQ (31.5% vs 22.0%; OR = 1.77; 95% CI 1.40-2.23). Significant predictors were male gender (OR = 1.93, 95% CI 1.45-2.58) and non-white race (OR = 1.81; 95% CI 1.03-1.65) but not education (OR = 0.86; 95% CI 0.68-1.09). Models of 2-way interactions were all non-significant. Linear models employing UMRBDQ as continuous scores yielded similar results.

Conclusion

These results confirmed that PTSD may be associated with higher likelihood of reported dream enactment and that these results were not dependent on self-reported gender, race or education.

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Wounded Warrior Project
0662 Comparative efficacy of digital CBT-I versus stepped-care CBT-I to prevent depression
Authors: Cheng Philip , Kalmbach David , Sultan Zain , Fellman-Couture Cynthia , Drake Christopher
Published: May 2022

Introduction

Insomnia is a robust risk factor for depression. Treating insomnia with digital CBT-I (dCBT-I) has been shown to prevent future episodes of depression; however, remission rate of insomnia following dCBT-I is lower compared to face-to-face CBT-I (fCBT-I), which may reduce the effect on depression prevention. A stepped-care model can optimize care by starting with a least resource intensive intervention (step 1: dCBT-I) and stepping-up non-remitters to specialized treatment (step 2: face-to-face CBT-I). This study examined the efficacy of a stepped-care approach to prevent depression.

Methods

341 individuals with DSM-5 insomnia and no depression were randomized into two conditions at step 1: dCBT-I (n=161), or an online sleep education control (n=188). Participants in the dCBT-I condition who did not show remission for insomnia (ISI>9) were further randomized to either face-to-face CBT-I (n=40) or sleep education (n=47). Rates of clinically significant depression was assessed post-step 2.

Results

Insomnia remission rates were higher in the dCBT-I group (46%) compared to the control group (22%); however, 54% remained symptomatic after dCBT-I and were rerandomized to step 2 treatments (fCBT-I or sleep education control). Insomnia remission rates following fCBT-I was 70% compared to 23% in the step 2 control.Rate of depression in those who received step 2 control (following non-remission to dCBT-I in step 1; 15%) was not significantly different from the step 1 control group (20%). In contrast, those who received step 2 fCBT-I reported significantly lower rates of depression (5%, OR=.22, p < .05) compared to the step 1 control. Those who remitted to dCBT-I in step 1 also reported comparably low rates of depression (8%, OR=.36, p < .05)

Conclusion

Preliminary evidence from this study provide supported that a stepped-care approach may produce greater protection against incident depression than dCBT-I alone.

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R01MH122636
0663 Association of Insomnia Phenotypes based on Objective Sleep Duration with Suicide Attempts, Ideation and Completion
Authors: Saulnier Kevin , Singh Rupsha , Lenker Kristina , Calhoun Susan , Liao Duanping , Bixler Edward , Vgontzas Alexandros , Fernandez-Mendoza Julio
Published: May 2022

Introduction

Sleep disturbances, including insomnia and short sleep duration, are known risk factors for suicidal ideation, attempts, and death. Insomnia is a heterogeneous disorder, with phenotypes of short and normal sleep duration based on objective sleep measures showing differential pathophysiology, natural course, cardiometabolic and neurocognitive morbidity. However, little is known about the association of these insomnia phenotypes with suicidality in adults.

Methods

We analyzed data from the Penn State Adult Cohort (N = 1741, M age = 52.46, SD = 13.43, 57.4% female), a randomly selected population-based sample who underwent a thorough clinical history and in-lab polysomnography (PSG). Suicidality was ascertained by a lifetime history of suicide attempts, suicidal ideation or suicide as cause of death by December 31 2018 (n = 102). Insomnia symptoms were defined as a complaint of moderate-to-severe difficulties initiating or maintaining sleep, early morning awakening and non-restorative sleep, or chronic insomnia (n = 719). Short sleep duration was defined as < 6-h of in-lab PSG-measured sleep (n = 879). Binary logistic regression was used to examine the association between insomnia phenotypes with suicidality, while controlling for sex, age, race/ethnicity, and medical and psychiatric comorbidities. Given the low suicidality prevalence in this sample, 1000 bootstrapped samples were drawn to provide stable estimates.

Results

Compared to normal sleepers who slept > 6-h, subjects with insomnia symptoms who slept < 6-h and those who slept > 6-h were associated with 1.96-fold (95%CI = 1.04-4.00) and 2.46-fold (95%CI = 1.30-5.04) increased odds of suicidality, respectively. After further adjusting for substance use, subjects with insomnia symptoms who slept < 6-h and those who slept > 6-h were associated with 1.72-fold (95%CI = 0.90-3.58) and 2.22-fold (95%CI = 1.15-4.60) increased odds of suicidality, respectively. Normal sleepers who slept < 6-h were not associated with significantly increased odds of suicidality (OR = 1.32; 95%CI = 0.56-2.94).

Conclusion

Adults with insomnia, particularly those with normal sleep duration, were associated with increased suicidality. These data further support that objectively-defined insomnia phenotypes may confer risk for differential adverse health outcomes (e.g., cardiometabolic vs. psychopathologic) via distinct mechanistic pathways.

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American Heart Association (14SDG19830018)
0698 Genetic susceptibility to elevated C-reactive protein and risk of obstructive sleep apnea in US men and women
Authors: Huang Tianyi , Goodman Matthew , Wang Heming , Sofer Tamar , Tworoger Shelley , Stampfer Meir , Saxena Richa , Redline Susan
Published: May 2022

Introduction

Obstructive sleep apnea (OSA) may trigger inflammation. However, growing evidence suggests a role for inflammation in predisposing OSA through increased upper airway size/collapsibility and altered ventilatory control. Inflammation also promotes sleep disturbance and excessive daytime sleepiness (EDS). Genetic analysis may provide further insights into the causal relationship between chronic inflammation and OSA incidence.

Methods

In 33,171 participants of European ancestry from the Nurses’ Health Study (NHS), NHS2 and the Health Professionals Follow-up Study, we quantified genetic predisposition to inflammation using a weighted polygenic risk score (PRS) based on 51 loci identified for C-reactive protein (CRP) in a recent genome-wide association meta-analysis. OSA was determined using self-reported diagnoses, which were demonstrated to reliably indicate moderate-to-severe OSA in these cohorts. EDS was defined based on self-reports of disrupted daily activities due to sleepiness ≥4 days/week. Multivariable logistic regression was used to estimate the odds ratio (OR) for OSA risk according to the number of risk alleles, adjusted for age, sex, BMI, genotyping platforms and 10 genetic principal components. Mendelian randomization using individual-level participant data was performed to evaluate the association between genetically determined CRP levels and OSA risk.

Results

A total of 3,163 participants (9.5%) had clinically diagnosed OSA (575 with EDS). While the CRP PRS (explained 5.0% variance in circulating levels) was not associated with OSA risk overall (OR per increment of 5 risk alleles: 1.00; 95% CI: 0.96, 1.04; p=0.96), a significant positive association was observed for OSA with concurrent EDS (Comparable OR: 1.13; 95% CI: 1.04, 1.23; p=0.003). In contrast, among participants without clinically diagnosed OSA, there was no association between the PRS and EDS (Comparable OR for EDS: 1.02; 95% CI: 0.98, 1.06; p=0.28). In Mendelian randomization, each doubling of genetically elevated CRP was associated with 44% higher odds of OSA with EDS (95% CI: 1.13, 1.82).

Conclusion

Chronic inflammation (characterized by elevated CRP levels) may be casually associated with risk of developing symptomatic OSA with EDS, but not OSA or EDS alone. To confirm our findings, future investigations are needed to evaluate the genetic associations with objective measures of OSA severity across diverse populations and elucidate mechanisms driven by specific inflammatory mediators.

Support (If Any)

NIH grants UM1CA186107, U01CA176726, U01CA167552, K01HL143034, R35HL135818
0704 Association of high-risk obstructive sleep apnea with inflammatory markers in asymptomatic young and middle-aged adults in Miami Heart (MiHeart) Study at Baptist Health South Florida
Authors: Walia Harneet , Saxena Anshul , Ali Shozab , Valero-Elizondo Javier , Cainzos-Achirica Miguel , Feldman Theodore , Nasir Khurram , Fialkow Jonathan
Published: May 2022

Introduction

Obstructive Sleep Apnea (OSA) is associated with elevated inflammatory markers in those with cardiovascular disease (CVD). In contrast, there are limited data to support this association in asymptomatic individuals. The Miami Heart Study measured high sensitivity C-reactive protein (hs-CRP), Interleukin 6 (IL-6) and TNF- Alpha in a cohort of asymptomatic individuals from the general population. We hypothesized that there will be significant association of high OSA risk with inflammatory markers in Miami Heart Study cohort free of CVD.

Methods

We analyzed data for 2359 clinical CVD-free participants from the Miami Heart Study, age 40-65 years (May 2015-Sept 2018). High OSA risk included those with an OSA diagnosis and/or those with high risk using the Berlin questionnaire. Poisson regression analyses were utilized to examine the associations between high OSA risk (reference: low risk) and hs-CRP, IL-6 and TNF alpha levels (continuous), in univariate and multivariate models (adjusting for age, sex, race/ethnicity [model 2], and BMI, diabetes, hypertension, high cholesterol and smoking [model 3]).

Results

800 (34%) participants were categorized as high OSA risk. Those with high OSA risk tended to be Hispanic, male, and with a higher CVD risk factor burden, especially obesity (64% vs 17%, p < 0.005) when compared to those with low OSA risk. Patients with high OSA risk had higher median values of hs-CRP (2.1 vs 1.0), IL-6 (2.0 vs 1.4), and TNF-alpha (1.2 vs 1.1) when compared to those with low OSA risk (all p < 0.001). When adjusting for age, sex, and race/ethnicity, the mean difference between patients with high and low OSA risk in hs-CRP was 1.86 (95% CI 1.69, 2.02), and 0.85 (95% CI 0.71, 0.99) in IL6. When further adjusting for CVD risk factors, these differences were attenuated, but statistically significant (hs-CRP [0.32, 95% CI 0.16, 0.48]; IL6 [0.37, 95% CI 0.21, 0.53]). In adjusted analyses, TNF-alpha was not statistically different between OSA risk populations.

Conclusion

Individuals at high risk for OSA had significant higher levels of hs-CRP and IL6, signaling to potential role of OSA in mediating the increased inflammatory markers in asymptomatic CVD risk free individuals.

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Baptist Health South Florida
0708 Stage-dependent Differences in Central Sleep Apnea (CSA) Predominate in remedē System Pivotal Trial Participants
Authors: Schwartz Alan , Germany Robin , Meyer Timothy , McKane Scott
Published: May 2022

Introduction

Differences in neuroventilatory control can impact the type and severity of sleep disordered breathing between non-REM and REM sleep. We examined the distribution of central apneic episodes in polysomnograms from subjects with predominantly central sleep apnea, who received phrenic nerve stimulation.

Methods

Baseline in-lab polysomnograms from patients enrolled in the remedē System Pivotal Trial were scored by a central core laboratory (n=151). Participants with predominantly CSA were enrolled if the apnea-hypopnea index (AHI)≥20/hr, the central apnea index (CAI) exceeded the obstructive apnea index (OAI), and the OAI did not exceed 20% of the total AHI. This post-hoc analysis compared sleep apnea indices in REM and non-REM sleep in those with ≥5 minutes REM sleep (n=131). Within-patient median non-REM - REM differences were calculated and compared.

Results

REM sleep time was 40 [Q1=28, Q3=64] minutes, and non-REM sleep time was 301 [Q1=269,Q3=344] minutes. AHI in REM sleep was 22/hr [Q1=9,Q3=44] and was 46/hr (Q1=33,Q3=60) in non-REM sleep, yielding a within-patient difference between non-REM and REM sleep of 22/hr ([Q1=6, Q3=34], p<.001). CAI in REM was only 4/hr (Q1=0, Q3=11), but in non-REM was 25/hr [Q1=16,Q3=43] with all patients having a CAI≥5/hr during non-REM. In REM, 70% had a CAI>0/hr and 46% had a CAI ≥5/hr. The CAI difference between non-REM and REM sleep was 18/hr [Q1=10, Q3=30; p<.001]. The OAI and mixed apnea index (MAI) differed by <1/hr (p=0.235 and <.001, respectively). Of note, the hypopnea index [HI] did not differ between REM and non-REM sleep (12/hr [Q1=2,Q3=22] vs. 11/hr [Q1=4, Q3=20], respectively, p=0.273), yet hypopneas constituted a greater proportion of total AHI during REM compared to non-REM sleep.

Conclusion

Among subjects with predominantly CSA, the prevalence and severity of CSA was greater in non-REM than REM sleep, yet low-level CSA persisted in REM sleep. Stage-related differences in CAI but not OAI, MAI or HI can be attributed to alterations in ventilatory rather than upper airway control in this CSA cohort. These differences in the type and severity of sleep disordered breathing episodes comprise a key diagnostic signature, for which specific CSA therapeutic strategies are indicated.

Support (If Any)

ZOLL Respicardia, Inc. and NIH R01 HL144859
0729 Assessing the Diagnostic Benefit of Polysomnography with Routine Carbon Dioxide Measurements in Adolescent and Adult Obese Patients
Authors: Beshay Sarah , Bucovschii Serghei , Mathew Reeba , Majid Ruckshanda
Published: May 2022

Introduction

The diagnosis of obstructive sleep apnea (OSA) and obesity hypoventilation syndrome (OHS) has increased with the increasing prevalence of obesity. Adding routine transcutaneous carbon dioxide (TcCO2) or end-tidal carbon dioxide sensors (EtCO2) to a polysomnogram (PSG) may expand the analytic capabilities of the study. Our study looks at the utility of using CO2 monitoring in obese adolescent (age 13-18 years) and obese adults in increasing the diagnostic yield of the polysomnogram.

Methods

A retrospective chart review was conducted on obese adolescents (13-18 years) and obese adults (body mass index [BMI] > 95 percentile and >30 kg/m2 respectively) undergoing a PSG with EtCO2 monitoring. The CO2 values were documented while supine (awake) and while sleeping. The EtCO2 value was correlated with the BMI but the adults were also compared between Group 1 (BMI 30-40 kg/m2) and Group 2 (BMI >40 kg/m2). Patients with known hypoventilation syndromes or studies that had poor EtCO2 waveforms were excluded.

Results

72 patients were identified between December 2019 and November 2020 at the Memorial Hermann Sleep Disorders Center. Amongst the adults, 52% were men, with an average age of 55 years (range 26-77) and an average BMI 40.5 kg/m2 (SD +/- 8.8). The average AHI on the diagnostic study (CMS criteria) was 31 events/hour (SD +/- 34.1) and the average oxygen saturation nadir was 80%. Twenty patients (28%) met the diagnostic criteria for OHS based on the baseline awake EtCO2. The mean EtCO2 was 40.1 mmHg in patients with a BMI between 30 and 40 kg/m2 (Group 1) versus 45.1 mmHg in patients with BMI >40 kg/m2 (Group 2) with a statistically significant p-value of 0.0002. Additionally, we identified 18 patients between the ages of 13-18 years with obesity amongst which, 4 patients also had a baseline EtCO2 of >45 torr (22%) with a potential diagnosis of OHS.

Conclusion

Patients diagnosed with OHS are reported to have a higher overall greater mortality. Our study suggests a higher diagnostic yield of OHS in adults and adolescents with the use of CO2 monitoring especially in the morbidly obese. This evidence would advocate for the routine use of CO2 monitoring in the obese patient population.

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0730 Validation studies for scoring polysomnograms and home sleep apnea tests with artificial intelligence: Sleep stage probabilities (hypnodensity) derived from neurological or cardiorespiratory signals
Authors: Anderer Peter , Ross Marco , Cerny Andreas , Fonseca Pedro , Shaw Edmund , Bakker Jessie
Published: May 2022

Introduction

There have been significant advances in machine learning in recent years. This means that powerful methods are now available for classification problems, such as scoring sleep stages from neurological or cardiorespiratory signals. In the present work, validation studies for both applications are presented.

Methods

To determine the 5 sleep stages from the neurological signals, 54 sleep-wake-related features were calculated and classified by a bidirectional long short-term memory (LSTM) network which had been trained on 1956 manual scorings of 588 PSGs from 294 subjects (supervised deep learning). To determine the 4 stages (wake, light sleep, deep sleep, REM) from cardiorespiratory signals, a convolutional neural network combined with LSTM layers was used for feature extraction and classification. This network had been trained on 685 PSGs from 391 subjects (Bakker et al. JCSM 2021). The networks obtained were validated in 428 PSGs with one and 10 PSGs with 12 manual scorings (neurological staging) as well as in 2 two datasets, each containing 296 ambulatory recordings (cardiorespiratory staging).

Results

Cohen’s kappa between autoscoring based on neurological signals and manual scoring was 0.74 (95%-confidence interval: 0.74-0.74) for the 428 PSGs. The intraclass correlation coefficient (ICC) for absolute agreement between autoscoring and manual scoring was for the AHI 0.97 (0.96-0.98), for the arousal index 0.79 (0.67-0.86) and for the PLMSI 0.91 (0.88-0.93). The ICC between the sleep stage probabilities derived from the 12 manual scorings and the artificial intelligence (AI) derived hypnodensity was 0.91 (0.91-0.91). Cohen’s kappa values for the cardiorespiratory sleep staging were 0.68 (0.68-0.68) and 0.64 (0.63-0.64) for the 2 datasets with 296 ambulatory recordings each.

Conclusion

All metrics from the PSG validation studies show substantial (Cohen’s kappa > 0.6) as well as good to excellent agreement (ICC > 0.75 or > 0.90) compared to manual scorings. As an added value of the AI-supported PSG evaluation, the probabilities of the sleep stages per epoch are determined (hypnodensity graph). The valid estimation of the sleep stages from cardiorespiratory signals by means of AI may result in improved clinical interpretation of home sleep apnea tests, which are increasingly used in the sleep-disordered breathing diagnostic pathway.

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0732 Sonographic Phenotyping of the Upper Airway in OSA Using Backscattered Imaging Analyzed by Machine-Learning
Authors: Liu Stanley Yung Chuan , Abdelwahab Mohamed , Chao Peiyu , Lee Yili , Chen Argon , Kushida Clete
Published: May 2022

Introduction

Anatomic characterization of the upper airway remains important in directing and monitoring care of patients with obstructive sleep apnea (OSA). Nasopharyngoscopy is routine in clinical practice, but it is invasive, non-reproducible, and only allows subjective assessment. We used machine-learning enabled ultrasonography to correlate upper airway tissue characteristics with OSA severity.

Methods

Sixty-three subjects (14 female) with a mean age of 39.4±12.6 years, BMI of 26.4±4.6 kg/m2, and AHI of 19.0±16.1 were consented from Stanford Sleep Surgery (July 2020 to May 2021). Standardized ultrasound protocol was used to image the soft palate, oropharynx, and tongue-base. Via machine learning, an FDA-cleared backscattered ultrasound imaging (BUI) of the upper airway was performed. Combined with B-mode measurements of airway muscular cross-sections, a logistic regression model was built to correlate with OSA severity.

Results

BUI of subjects with mild OSA was different from moderate-severe (AHI≥15) OSA at the soft palate (p=0.0007). The axial-to-lateral ratio of upper airway length was reduced in the lower soft palate of the moderate-severe group (p =0.0207). The logistic regression model with BUI, axial-to-lateral ratio at the soft palate, and BMI showed an Area Under the Receiver Operating Characteristic (AUROC) curve of 0.84 (95% CI 0.726 to 0.920) in moderate-severe OSA.

Conclusion

A non-invasive yet replicable technique to visualize and phenotype the upper airway is critical in the management of patients with sleep-disordered breathing. Sonographic BUI combined with B-mode airway measurements analyzed by machine learning show promise in characterizing the upper airway in patients with moderate-severe OSA.

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0735 Sleep Disturbances in Post-Acute Sequelae of COVID-19 (PASC)
Authors: Orbea Cinthya Pena , Lapin Brittany , Katzan Irene , Englund Kristin , Foldvary-Schaefer Nancy , Mehra Reena
Published: May 2022

Introduction

Sleep difficulties and fatigue are highly prevalent, pervasive symptoms reported in patients with Post-Acute Sequelae of COVID-19 (PASC). As little is known of the predictors and severity of PASC-related sleep disturbance and intersection with fatigue, we leverage systematic data collected from the Cleveland Clinic ReCOVer Clinic for further elucidation

Methods

Analysis of data collected from Cleveland Clinic ReCOVer Clinic patients (February-November 2021) who completed the Patient-Reported Outcomes Measurement (PROMIS) Sleep Disturbance and PROMIS Fatigue questionnaires was performed. Data were extracted from the Cleveland Clinic COVID-19 registry and the electronic health record.PROMIS scores are standardized to the general U.S. adult population on a T-scale with mean 50±10. PROMIS sleep disturbance and fatigue T-scores ≥60 indicates at least moderate disturbance and ≥70 indicate severe disturbance. T-test and Chi-square tests were used to examine cross-group differences. Multivariable logistic regression adjusted for age, race, sex, and body mass index(kg/m2) was performed to investigate factors associated with sleep disturbance severity.

Results

Out of 1321, 682 patients completed the PROMIS Sleep Disturbance questionnaire with age 49.8±13.6, 75.2% female and 12.3% black race. Average T-scores were 57.7±8.3, 281 (41.2%) patients reported at least moderate sleep disturbance and 50 (7.3%) reported severe sleep disturbances. Average PROMIS Fatigue T-score was 63.0±9.2; 68.6% patients reported at least moderate fatigue, 22.6% reported severe fatigue. Patients with moderate-severe compared to normal-to-mild sleep disturbances respectively had higher BMI (32.3±8.7 vs 30.9±7.5, p=0.049), were more likely of black race (40.0±10.0 vs 41.0±15.7,p=0.010), had worse eneral Anxiety Disorder (GAD)-2 questionnaires scores (2.8±2.1 vs 1.6±1.7,p<0.001), Patient Health Questionnaire (PHQ)-2 scores (2.8±2.0 vs 1.6±1.7,p<0.001) and PROMIS fatigue scores (66.7±7.8 vs 60.4±9.1,p<0.001) with no difference in age, sex, or hospitalization due to COVID-19. In the adjusted model, black race was associated with moderate-severe sleep disturbance (OR=3.42, 95%CI:1.64-7.13).

Conclusion

The prevalence of moderate to severe sleep disturbances reported by patients presenting for PASC was very high i.e.>40% and associated with obesity, black race and mood symptoms. Notably, after adjustment for demographics, black race conferred a 3-fold higher odds of moderate-severe sleep disturbance emphasizing the need to characterize race-specific determinants and disparities in COVID-19 survivors.

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0743 Should We Use AHI or RDI to Diagnose Obstructive Sleep Apnea?
Authors: Palombini Luciana , Godoy Luciana , Poyares Dalva , Andersen Monica , Pires Gabriel , Tufik Sergio
Published: May 2022

Introduction

Sleep disordered breathing (SDB) is defined based on clinical complaints and polysomnography events. Obstructive sleep apnea (OSA) was initially diagnosed based on the apnea hypopnea index (AHI), but the ICSD-3 has defined the respiratory disturbance index (RDI) as the actual diagnostic criteria. This study aimed to evaluate and compare clinical outcomes related to daytime function in OSA patients defined by AHI and RDI.

Methods

This study was derived from the São Paulo Epidemiological Sleep Study (EPISONO), in its 3rd edition (2007) and follow up edition (2015). A total of 557 individuals had polysomnographies evaluated according to the 2012 American Academy of Sleep Medicine Scoring Manual in both editions. The scores of the Epworth Sleepiness Scale (ESS), Chalder Fatigue Scale (CFS), Pittsburgh Sleep Quality Index (PSQI), Beck Anxiety and Depression Inventories (BAI and BDI) and Insomnia Severity Index (ISI) were compared between individuals who sustained the same AHI level in both editions (either AHI<15 or AHI≥15). We did the same comparison between individuals who had either RDI<15 or RDI≥15.

Results

The grouping by AHI included 348 participants with AHI<15 and 107 with AHI≥15; while the grouping by RDI was composed by 335 with RDI<15 and 118 with RDI≥15. Considering the AHI grouping, there was no statistically significant differences in ESS, PSQI, BDI and ISI scores after 8 years of follow up (p=0.2, p=0.3, p=0.09 and p=0.7 respectively), but a significant increase in the CFS and BAI scores (p=0.05 and p=0.01, respectively) was observed. Considering the RDI grouping, there was no statistically significant difference on ESS, PSQI and ISI scores after 8 years of follow up (p=0.3, p=0.1 and p=0.4 respectively), but there was a significant increased on CFS, BAI and BDI.

Conclusion

OSA diagnosed by either AHI or RDI is associated with increase in fatigue levels. However, when OSA is diagnosed according to RDI, a worse depression score is observed. Depression complaints can significantly impair quality of life and should be consider an important SDB outcome.

Support (If Any)

AFIP, CNPq, CAPES.
0745 Sleep-Related Hypoxemia Association with Incident Atrial Fibrillation in a Clinic-Based Cohort
Authors: Heinzinger Catherine , Thompson Nicolas , Milinovich Alex , Foldvary-Schaefer Nancy , Van Wagoner David , Chung Mina , Mehra Reena
Published: May 2022

Introduction

Sleep disordered breathing (SDB) has been implicated in atrial fibrillation (AF) in population-based studies, however, its role remains unclear and inconsistent. We hypothesize greater risk of 5-year incident AF with SDB and sleep-related hypoxia in a clinic-based cohort.

Methods

Cleveland Clinic patients (age>18) who underwent polysomnogram (PSG) or split studies 11/27/2004-12/30/2015 with >3 hours diagnostic time were examined. Predictors include AHI, % sleep time oxygen saturation<90% (T90), and minimum and mean oxygen saturation(minSaO2 and meanSaO2, respectively). Cox proportional hazard models were fit with time from sleep study to AF diagnosis as the dependent variable. Covariates included age, sex, race, body mass index(BMI), cardiovascular risk factors (hypertension, diabetes mellitus, hyperlipidemia), heart failure, coronary artery disease, myocardial infarction, history of coronary artery bypass grafting, chronic obstructive pulmonary disease, tobacco use, and use of anti-arrhythmic drugs. Data were censored at date of last follow up or at 5-years.

Results

The sample was comprised of 43,634 patients: age 51.7±14.5, 51.9% male, 74.5% White, and 7.1%(n=3,090) with AF. Of those without AF, 1,176(2.9%) developed 5-year incident AF. For each 10% increase in T90, incident AF increased by 7% (HR=1.07, 95%CI=1.05-1.10). Compared to reference, patients with 25.01-50%, 50.01-75%, and 75.01-100% time T90 had 22% (HR=1.22, 95%CI=1.01-1.46), 49% (HR=1.49, 95%CI=1.20-1.85), and 65% (HR=1.65, 95%CI=1.26-2.15) higher incident AF, respectively. For every 10-unit increase in minSaO2 and meanSaO2, incident AF decreased by 11%(HR=0.89, 95%CI=0.83-0.95) and 23% (HR=0.77, 95%CI=0.68-0.86), respectively. AHI did not demonstrate a statistically significant relationship with incident AF at a significance level of 0.05.

Conclusion

Sleep-related hypoxemia, defined by cumulative burden below 90% SaO2, demonstrated an association with incident AF in this large clinic-based cohort, even considering confounding factors. On the other hand, SDB severity as defined by AHI did not demonstrate this relationship. These findings are consistent with experimental models that identify intermittent hypoxia and oxidative stress leading to alterations of the cardiac substrate, thus implicating sleep-related hypoxemic mechanisms as a salient driver in the evolution of atrial arrhythmogenesis.

Support (If Any)

Cleveland Clinic Neurological Institute Center for Outcomes Research & Education Pilot Grant, Neuroscience Transformative Research Resource Development Award
0781 Neck circumference: A surrogate predictive variable of hypoglossal nerve stimulator therapy outcome
Authors: Plata Diana , McTabi Omar , Herdegen James , LoSavio Phillip , Hutz Michael
Published: May 2022

Introduction

Hypoglossal nerve stimulation therapy has strict eligibility requirements including a body mass index < 32kg/m2 for non-Medicare patients and body mass index < 35kg/m2 for Medicare patients. However, there is a wide variability in body fat distribution including variability between the sexes. We theorize that neck circumference may be a better surrogate predictive variable for hypoglossal nerve stimulation outcomes than body mass index.

Methods

A retrospective chart review was conducted at a single tertiary care center on adults who underwent hypoglossal nerve stimulator implantation by a single surgeon from March 2017 to October 2021. Baseline demographic data including neck circumference, diagnostic polysomnography and post-implantation polysomnography titration studies were collected. Patients without neck circumference measurements were excluded. Surgical success was defined by Sher criteria of apnea hypopnea index < 20 and reduction of the apnea hypopnea index by 50%.

Results

75 patient charts were reviewed. 44 of these patients had neck circumference, body mass index, and AHI at effective voltage (AHI-v) data recorded. These were included in the analysis. Overall, AHI-v positively correlated with neck circumference (r2=0.20, p= 0.0025). Conversely, no significant association was apparent between AHI-v and BMI (r2=0.04, p=0.18). AHI-v appeared to worsen at a specific neck circumference of > 15 inches. T-test analysis showed significant difference in AHI-v comparing the groups of neck circumference ≤15in. vs > 15in. (x̄=27.58 vs 7.68, respectively, p=<0.001). However, no significant difference was found in mean BMI, age or baseline AHI between the neck circumference groups (p=0.15, 0.26, 0.10, respectively).

Conclusion

Findings suggest that neck circumference correlates to AHI at effective voltage during the post-implantation titration study. Our data indicates that neck circumference may be a better outcome predictor than BMI, baseline AHI or age for hypoglossal nerve stimulator effectiveness.

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0796 The sleep instability in chronic rhinosinusitis patients with nasal polyps using CAP analyses during NREM sleep
Authors: Lopes Maria-Cecilia , Lacerda Glenda , Migueis Debora
Published: May 2022

Introduction

The sleep instability can increase the impact of several sleep disorders. The chronic rhinosinusitis leads to sleep fragmentation, and changes in systemic inflammatory biomarkers followed by upper airway flow limitation or nasal mucosa inflammation near the skull base. To evaluate the effect of sleep dysruption in chronic rhinosinusitis patients with nasal polyps using CAP analyses, this study aimed to analyse these patients before and after the anti-inflammatory effect of intranasal corticosteroids on nasal obstruction.

Methods

After two months of washout, thirty individuals with nasal polyps and sleep-disordered breathing used intranasal budesonide 400 mcg every day for one month. Before and after the treatment, they underwent the same exams: nasal endoscopy, subjective nasal resistance scores, fatigue severity scale, and Epworth sleepiness scale. Besides, T helper-two inflammation was measured by serum levels of eosinophils, interleukin-four and five. Intermittent hypoxia impact was documented using serum levels of IL-6 and tumor necrosis factor-alpha. Type 1 polysomnography was performed. It was scored according to the last manual of AASM and Terzano’s rules. The nonparametric Wilcoxon test was used to assess within-group differences before and after exposure to corticosteroids. Correlation between quantitative variables was analyzed by using the Spearman correlation coeficient, and p< 0.05 was statistically significant.

Results

All the participants had sleep' fragmentation in non-REM sleep. The treatment decreased the subjective nasal obstruction (p<0.005) and IL-5 levels (p<0.05), without significant impact on other biomarkers, nasal endoscopy results, fatigue or somnolence scales, and sleep architecture. Interestingly, the subtypes of phase A of CAP weren′t statistically significant (p>0.05) decreased compared two groups (before and after treatment).

Conclusion

The anti-inflammatory effects of intranasal corticosteroid decreased the nasal resistance and Th2 systemic inflammation without any changes in sleep fragmentation, highlighting. Terzano’s manual quantifies the sleep fragmentation using the cyclic alternating pattern, and it can be a sensitive electroencephalogram analysis of the non-NREM sleep described as a marker of sleep instability, however the analyse of phase A subtypes CAP did not show changes sleep disruption in patients with nasal polyps after their treatment of nasal mucosa inflammation. More studies are need to clarify the sleep complaints in these patients.

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0797 Reclaiming Her Life: Successful Treatment of Kleine-Levin Syndrome with Transdermal Flumazenil
Authors: Sajid Mehwish , Rupani Nawaz
Published: May 2022

Introduction

Kleine-Levin Syndrome (KLS) is a rare disorder of hypersomnolence with cognitive and behavioral disturbances. Currently, there are no definitive treatment recommendations although stimulants, mood stabilizers, and even electroconvulsive therapy have been utilized with inconsistent results.

Report of Cases: A 23-year-old female with a history of depression, anxiety, obsessive-compulsive disorder, Hashimoto's thyroiditis, lupus, and morbid obesity presented to our facility for management of debilitating episodes of sleepiness due to KLS, diagnosed at the age of 22.

She reported good health until a series of viral illnesses at the age of 20. She then began experiencing sleep episodes requiring 20-22 hours of sleep per day, only awakening to eat and use the bathroom.

These episodes typically lasted for two weeks and were preceded by periods of hyperphagia

and hypersexuality. When she presented to our facility, she was using lithium and modafinil daily along with amantadine and clarithromycin twice daily as needed for episodes of sleepiness.

At her initial visit, she was prescribed transdermal flumazenil, a GABA-A receptor/benzodiazepine antagonist, to be used as needed to supplement amantadine and clarithromycin. She was initially requiring flumazenil every other month. After seven months of flumazenil use, the frequency of episodes decreased to every 3-4 months. She would administer two clicks of flumazenil cream on each forearm with the prodrome symptom of fogginess, which would abort the episode. Rarely, she required a second dose 12 hours later.

With flumazenil and avoidance of triggers, such as alcohol and sleep deprivation, she reported completing her master’s degree and finally maintaining a job. Ultimately, she discontinued lithium, modafinil, amantadine, and clarithromycin use without reoccurrence of her symptoms.

Conclusion

This case demonstrates successful treatment of KLS with the use of a GABA-A receptor/benzodiazepine antagonist, flumazenil. Reduction in episodes of sleepiness with flumazenil ultimately led to discontinuing stimulant, mood stabilizer, and clarithromycin use. Early trials of transdermal flumazenil and continued research regarding the use of this medication for patients with KLS may prove to be a promising intervention.

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None.
0808 Worsening central sleep apnea: A sole diagnostic marker of a brain tumor in a child
Authors: Mechineni Ashesha , Pattisapu Anil , Mann Harkirat , Adavadkar Pranshu
Published: May 2022

Introduction

Central sleep apnea (CSA) in children is a relatively uncommon and under-studied sleep disorder. A small subset of patients may have intracranial anomalies, but clinical presentation varies. We present a case of malignant intracranial tumor diagnosed primarily due to the unusual presentation and progression of CSA.

Report of Cases: The presented patient is a 12-year-old developmentally appropriate female with a history of obstructive sleep apnea (OSA) status post adenotonsillectomy at two years of age who presented with snoring without witnessed apnea, sleep interruptions, and unrefreshing sleep. Other sleep-related history was unremarkable. No daytime sleepiness or behavioral or learning concerns were noted. Physical examination was unremarkable with normal growth parameters. Initial diagnostic PSG demonstrated severe OSA with an obstructive apnea-hypopnea index (OAHI) of 16/h and mild CSA (CAI:6.7/h); therefore, PAP therapy was pursued after ruling out adenoid regrowth. However, during the first PAP titration study(incomplete study due to mask intolerance), treatment-emergent central apneas were noted (OAHI: 9.8/h; CAI:25.8/h), which were noted even during the second titration study (OAHI:2.7/h; CAI:59.2/h). Even though ordered earlier, the brain MRI was not performed until after the repeat PSG one year later showed persistence of severe CSA (OAHI of 4.5/h and CAHI of 39.5/h) after much persuasion. Interestingly, snoring had reportedly improved with no daytime symptoms or neurologic complaints. The brain MRI demonstrated compressing brainstem lesion highly suspicious for glioma. The patient was emergently sent to neurosurgical care and had chosen hospice care after a few weeks.

Conclusion

CSA can be an early or the only finding in patients with brainstem tumors, even before neurologic signs and symptoms. The PSG findings changed from mild CSA to treatment-emergent CSA to severe CSA, possibly with the progression of underlying disease. Close follow-up and ensuring patient compliance are essential in CSA patients. CSA severity should prompt MRI brain even with an intact neurological examination. More research is needed to fully understand the link between cerebral disease and polysomnographic data. This could aid in early diagnosis and treatment.

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no conflicting or financial interests to disclose
0814 Three Sleepy Siblings
Authors: Guzman Maria Paula , Trotti Lynn Marie
Published: May 2022

Introduction

Narcolepsy type 1 is caused by destruction of hypocretin-producing neurons, likely via a T-cell mediated autoimmune process, and clinically identified either by CSF hypocretin deficiency or the presence of cataplexy. Individuals with narcolepsy type 1 have an underlying genetic predisposition attributed to the HLA DQB1*0602 gene. This genetic variant has been linked to increased propensity for sleepiness even in healthy adults. Relatives of patients with narcolepsy type 1 appear to be at increased risk for other disorders of hypersomnolence such as idiopathic hypersomnia. Here we describe three siblings, all positive for HLA DQB1*0602, who presented with distinct clinical features diagnostic for narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia.

Report of Cases: A 15-year-old female was diagnosed with narcolepsy type 1 based on typical cataplexy, excessive daytime sleepiness, and mean sleep latency of 2 min with 2 SOREMPs on MSLT. Lumbar puncture (LP) performed 5 years after symptom onset showed low CSF hypocretin (9.3 pg/mL). Her older brother presented at age 21 with excessive sleepiness, somewhat atypical cataplexy, hypnagogic hallucinations, and sleep paralysis. MSLT showed mean sleep latency of 6 min with 5 SOREMPs. Despite the presence of cataplexy, LP performed 2 years after symptom onset showed normal CSF hypocretin (296.5 pg/mL) and he was diagnosed with narcolepsy type 2. Their younger sister presented at age 19 with progressive daytime sleepiness. PSG/MSLT showed mild OSA (RDI 9.2) and mean sleep latency of 6.5 min without SOREMPs. She does not have cataplexy, hypnagogic hallucinations, or sleep paralysis. The current findings are most consistent with idiopathic hypersomnia, although an LP to evaluate for hypocretin deficiency is an important next step. Similarly, a repeat LP in the brother might demonstrate change in hypocretin over time.

Conclusion

These cases may support a familial link between narcolepsy type 1, type 2, and idiopathic hypersomnia. The discordant hypocretin and cataplexy statuses of these siblings implies a mechanism for excessive sleepiness beyond hypocretin deficiency, possibly mediated by HLA DQB1*0602. Identifying the mechanisms of familial aggregation of sleepiness in the central disorders of hypersomnolence may shed light on the pathophysiology of these distinct disorders.

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0825 A Case of Familial Restless Legs Syndrome and Raynaud's Phenomenon
Authors: Maniar Ninad , Walters Arthur S , Karroum Elias G
Published: May 2022

Introduction

Restless legs syndrome (RLS) is a common sensory-motor disorder that frequently leads to sleep disturbances and reduced quality of life. Raynaud's phenomenon (RP) is characterized by episodes of reduced blood flow mainly to the fingers due to vasospasms, with subsequent pain and discoloration, usually triggered by cold exposure or by stress. We present an interesting case report of co-occurrence and familial transmission of RLS and RP which has not been reported previously.

Report of Cases: A 64-year-old woman presented for evaluation of long-standing RLS. She had a history of RP, osteoarthritis (OA), and recurrent late pregnancy losses. The patient, and one brother and a sister had RLS and RP. She had another sister and two maternal first cousins with RLS. Her mother suffered from neither and her father and his brother both had RP. She has a daughter who also has RLS. The patient's mother was treated with Diethylstilbestrol (DES) and had five pregnancy losses. The patient also had 3 miscarriages and the patient's daughter miscarried her first pregnancy as well. The patient first experienced RLS symptoms at the age of 12 and has been treated with several medications since then, most recently clonazepam. Since she was taken off clonazepam, she experienced a worsening of RLS and was subsequently started on Pregabalin up to 300 mg at bedtime but without significant relief. She was then started on pramipexole, titrated up to 0.375 mg which resulted in significant improvement of RLS symptoms. Her RP symptoms were infrequent, occurring every few months and not bothersome. She did not report rheumatological complaints other than chronic OA from lifelong sports.

Conclusion

This case report suggests a possible shared genetic abnormality in the transmission of both RLS and RP in this family. This genetic association may be related to a vascular dysfunction common to both disorders. The co-occurrence of frequent miscarriages (although could be related to DES), in association with the presence of RLS and RP, may also suggest an underlying auto-immune disorder. Further genetic research is needed to confirm above findings with the potential uncovering of new therapeutic targets for RLS.

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None.
0853 The role of sleep-disordered breathing in the optimization of pediatric epilepsy management
Authors: Youssef Nada , Gupta Gita , Romanowski Erin Fedak , Lewis Toby , Hassan Fauziya
Published: May 2022

Introduction

There is a known bidirectional relationship between epilepsy severity and disordered sleep; however, both the potential scoring limitations of polysomnograms (PSGs) of children with epilepsy and the effect of treatment of sleep disordered breathing (SDB) on epilepsy severity in these children remain poorly understood.

Report of Cases: We describe a 7-year-old male with a history of prematurity (ex-34 weeks), bronchopulmonary dysplasia, recurrent aspiration pneumonia, and refractory nocturnal epilepsy who experienced acute hypoxemic respiratory failure in the setting of co-infection with rhinoenterovirus and parainfluenza 4 virus. The patient’s epilepsy history is notable for multiple nocturnal seizures most days of the week for a period of several years. His mother endorsed that the nocturnal seizures began shortly after his SDB symptoms, and that the severity of his nocturnal seizures seemed to be associated with the quality of his sleep. Two years prior to admission, he underwent adenotonsillectomy for mild obstructive sleep apnea (AHI 2.5, REM AHI 8.9, minimum SpO2 86%). He continued to have persistent SDB symptoms (e.g. witnessed apneas, nocturnal arousals 5-10 times/night, daytime sleepiness) despite adenotonsillectomy. Notably, the background EEG (in the context of epilepsy) demonstrated obscured sleep architecture and led to unreliable staging of sleep states and cortical arousals. Given the disorganized background EEG, arousal-based hypopneas could have been underestimated.

In the setting of acute respiratory failure, our patient was hospitalized and treated with noninvasive ventilation for 6 days. Collateral benefits included improvements in SDB (evidenced by decreased nocturnal awakenings, lack of obstructive features) and reduction in seizure frequency. His mother noted that this hospitalization was the first time in years that her son did not experience nocturnal seizures.

Conclusion

Sleep apnea can be an important modifiable factor in the treatment of pediatric epilepsy. Some PSGs of children with epilepsy may be falsely reassuring given the potential difficulty with scoring cortical arousal-based hypopneas. Therefore, careful clinical correlation should be made between nocturnal seizures and sleep symptoms, even in the context of reassuring PSG parameters.

Support (If Any)

Cystic Fibrosis Foundation Training Grant, AIRE grant, NIH 2T32HL110952-06