bluuebunny/crossref_metadata_2025 huggingface dataset:
0679 CBT-I for Psychosis Leads to Reduced Insomnia Severity and Improved Sleep-Related Functioning in Veterans with Psychosis and Insomnia: Results from a Preliminary RCT
Authors: Klingaman Elizabeth , Fischer Melanie , Howell Mary Katherine , Brown Clayton , Li Lan
Published: May 2022

Introduction

People with psychosis often suffer from insomnia. Even when psychotic symptoms are well-controlled, sleep disturbances persist, which puts these individuals at a higher risk of psychiatric relapse. We have developed guidelines and materials for conducting CBT-I with people living with psychotic disorders so it can be conducted according to their needs and experiences.

Methods

We conducted a preliminary efficacy study comparing CBT-I using novel psychosis-specific guidelines against an active treatment control (Health and Wellness [HW] intervention). Veterans with insomnia and psychosis (N=47) completed the Insomnia Severity Index (ISI), Functional Outcomes of Sleep Questionnaire (FOSQ), and Veterans RAND-36 (VR-36) at baseline, post-treatment, and 3-month follow-up.

Results

Participants (mean age=52 years) were primarily Black (55.3%), male (76.6%), and not married (76.6%). Using a repeated measures model (SAS proc mixed), mean change from baseline was compared between CBT-I for psychosis and HW at post and follow-up. There was a significant group difference on ISI at post (t=-2.07, df=46, p=.044, Cohen’s d=-.70), but not follow-up (t=-0.22, df=46, p=.827, Cohen’s d=-.10). Similarly, there was a significant group difference on the FOSQ at post (t=2.21, df=46, p=.032, Cohen’s d=.46), but not follow-up (t=1.05, df=46, p=.298, Cohen’s d=.33). The VR-36 Physical Component Scale showed no group difference at post (t=-1.43, df=46, p=.159, Cohen’s d=-.35), but a difference at follow-up (t=-3.11, df=46, p=.003, Cohen’s d=-.67) favoring the HW group, although about 50% were lost to follow-up on this item. For the VR-36 Mental Component Scale, there was no significant group difference at either timepoint (t=.20, df=46, p=.841, Cohen’s d=.05; t=.77, df=46, p=.444, Cohen’s d=.26).

Conclusion

At both post and follow-up, the CBT-I group surpassed estimated thresholds for clinically important improvements in both insomnia severity and sleep-related functioning, whereas HW did not. CBT-I for psychosis should be investigated with a larger, fully-powered randomized controlled trial, using sleep-specific functioning outcome measures.

Support (If Any)

This material is the result of work supported by: resources and facilities at the VA Maryland Health Care System, Baltimore, Maryland; the U.S. Department of Veterans Affairs, Rehabilitation Research and Development Service-1IK2RX001836 (NCT02535923), PI: Elizabeth A. Klingaman. Contents do not represent the views of the U.S. Government or Department of Veterans Affairs.
0680 Nocturnal wakefulness and suicide risk in the Australian population
Authors: Wasgewatta Sanjiwika , mansfield darren , Drummond Sean , Tubbs Andrew , Grandner Miachael , Perlis Michael
Published: May 2022

Introduction

Temporal patterns for suicide over a 24-hour period have shown mixed results among prior studies. However, analyses of 24-hour temporal patterns for wakeful actions including suicidal behavior, should adjust for expected sleep requirements that inherently skew such activities to conventional wakeful times. This study analysed the time-of-day for suicide cases from the Australian population for the year 2017, adjusting for expected sleep patterns. Identification of time-of-day trends using this methodology may reveal risk factors for suicide and potentially modifiable contributors.

Methods

The Australian Coronal database was accessed and data for suicide deaths were extracted for the most recent completed year, 2017. Time of suicidal action is frequently unable to be pinpointed and for this analysis an estimation was performed from time last seen alive and time found subsequently using data extracted from police and coronial reports. Time of suicide was allocated to one of four 6-hourly time bins across 24 hours from the mid position of time last seen alive and time found subsequently. Cases were excluded if allocation to a time bin was not able to be confidently determined if time last seen and time found crossed both boundaries for a given time bin. Prevalence of suicide for each time bin was adjusted for the likelihood of being awake for each bin according to sleep-wake norms published in 2020 from a large Australian community survey of 1966 subjects. Observed prevalence of suicide were compared to expected values predicted from likelihood of being awake across each time bin calculated as a standardised incidence ratio (SIR).

Results

For year 2017 there were 2208 suicides for which 1407 were able to be allocated into one of four 6-hourly time bins. Reasons for exclusion were cases for which allocaton into a time bin was not able to be performed. When adjusted for the likelihood of being awake based from population norms, cases were significantly more likely to enact suicide between the hours of 2301-0500 than predicted (SIR 3.93, P< 0.001). Furthermore, there was a lower-than expected rate of suicide for the time bins, 1101-1700 (SIR 0.86, P=0.002). When subcategories of suicide cases were analsysed, suicide death in asssociation with alcohol consumption demonstrated the strongest for relatoinship to the 2301-0500 time bin (SIR 6.03, P< 0.001).

Conclusion

Higher than expected rates of suicide overnight associated proposes that nocturnal wakefulness may represent a modifiable risk factor for triggering suicide events. Nocturnal wakefulness may be linked to increased rates of loneliness and depair as well as greater tendency toward impusive actions and behaviors. Impusivity may be compounded by alcohol consumption Our findings offer a potential mechanism for which individuals with insomnia have increased suicidal thoughts and behaviors.

Support (If Any)

Untied grant provided by Rhinomed LTD
0689 Sedative and Stimulant Misuse and Suicide Ideation in a Community Sample
Authors: Bobadilla Vanessa , Fernandez Fabian-Xosé , Tubbs Andrew , Chakravorty Subhajit , Perlis Michael , Hale Lauren , Branas Charles , Killgore William , Wills Chloe , Grandner Michael
Published: May 2022

Introduction

Previous studies have shown that prescription sleep medications are associated with suicide ideation. In this study we seek to identify the risk of off-label or illicit use of sedatives/hypnotics to predict suicidal ideation.

Methods

Data were from the Sleep and Healthy Activity, Diet, Environment, and Socialization (SHADES) Study, including N=1,003 working-age adults. For the present study, the data on off-label or illicit stimulants and sedatives were examined. Suicide ideation was assessed by whether participant reported any ideation in the past 2 weeks (PHQ, Item #9). Covariates included age, sex, education, race/ethnicity, and smoking. Additional models included adjustment for insomnia severity (ISI), daytime sleepiness (ESS), sleep duration (NHANES), psychiatric health (PHQ4), and general stress (PSS).

Results

In adjusted models examining sedatives/hypnotic use, higher likelihood of suicidal ideation was associated with any use (OR=1.77, 95%CI[1.26,2.47]), recent use (OR=2.71, 95%CI[1.77,4.15]), desire to use (OR=2.14, 95%CI[2.74,6.26]),problematic use (OR=7.39, 95%CI[3.32,16.47]), role limitations (OR=7.94, 95%CI[3.39,18.59]), others expressing concern (OR=4.38, 95%CI([2.29,8.41]), and inability to control use (OR=7.15, 95%CI[3.60,14.20]). Similarly, models examining stimulant use showed that higher likelihood of suicide ideation was associated with history of use (OR=1.81, 95%CI[2.01,3.93]), recent use (OR=4.44, 95%CI[2.63,7.49]), desire to use (4.82, 95%CI[2.78,8.34]), problematic use (OR=17.04, 95%CI[5.67,51.24]), role limitations (OR=9.07, 95%CI[3.47,23.68]), others expressing concern (OR=17.26, 95%CI([7.48,39.84]), and inability to control use (OR=6.44, 95%CI[3.26,12.71]). When sleep and mental health variables were added to the model, results were attenuated but remained significant at the p<.05 level.

Conclusion

Illicit use of substances that both promote sleep or arousal are associated with suicidal ideation, over and above contributions of sleep disturbance and mood/stress. It is possible that these behaviors represent self-medication attempts or an adverse effect of these drugs. Further research on these problematic associations is recommended.

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0693 A Characterization of Social Rhythms in Obsessive-Compulsive Disorder
Authors: Pinney Elizabeth , Boland Eliane , Coles Meredith
Published: May 2022

Introduction

Recent evidence has shown that obsessive-compulsive disorder (OCD) is linked to shifts in biologically driven sleep timing, indicating the role of biological rhythms within the disorder. Specifically, initial evidence suggests that biological disruptions in OCD may play a role in symptom severity and OCD treatment efficacy. Germane to the study of biological rhythmicity is the consideration of social rhythms within OCD. Disruptions in social rhythmicity are found in other psychological disorders associated with biological rhythm vulnerabilities (i.e., Bipolar Spectrum Disorder, Depression, and Post-Traumatic Stress Disorder.) Given the shared features and high rates of comorbidity between OCD and these disorders, it is reasonable that social rhythm disruptions would be found in OCD as well. As no research to date has examined this, we sought to examine the regularity and distribution of social rhythm in individuals with clinically significant obsessive-compulsive symptoms. Further, we examined the role of affect and symptom severity across OCD subtypes.

Methods

19 adults meeting criteria for a primary diagnosis of obsessive-compulsive disorder completed the Social Rhythm Metric at home for a period of 7 days. As part of a larger study, participants completed measures of sleep (Pittsburgh Sleep Quality Index), affect (Positive and Negative Affect Schedule), and obsessive-compulsive symptom severity and subtype (Obsessive-Compulsive Inventory) following diagnosis.

Results

We found the mean social rhythmicity in those with an OCD diagnosis to be 3.05 (SD=1.14.), similar to means found previously in other psychiatric disorders such as Bipolar Spectrum Disorder and Post-Traumatic Stress Disorder. Individuals with OCD who also reported delayed bedtimes were shown to have significantly lower social rhythmicity (p=.005) than those without delayed bedtimes. Additionally, we found that social rhythmicity correlated similarly across OCD subtypes and was not strongly correlated with negative affect.

Conclusion

In the current study, we provide a preliminary characterization of social rhythmicity in those with OCD. Results suggest that social rhythm may play a role in OCD similar to bipolar disorder and further study is warranted. Overall, this study contributes to burgeoning research into the association between biological rhythms and OCD.

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0699 Predictors of Mortality in Obesity Hypoventilation Syndrome: A National Inpatient Sample Study
Authors: Shah Syed , Alqalyoobi Shehabaldin , Qureshi Waqas , Obi Ogugua , Ibrahim Mohammed , Teodorescu Mihaela
Published: May 2022

Introduction

Obesity Hypoventilation Syndrome (OHS) has been linked to adverse cardiovascular outcomes and mortality in multiple observational studies. Few single-center observational studies have reported poor outcomes of inpatient admissions in OHS. Data regarding nationwide outcomes of hospital admissions in OHS is scarce. We conducted a retrospective study to identify predictors associated with mortality using the National Inpatient Sample (NIS) database.

Methods

We reviewed the NIS database to assess the outcomes of all weighted hospitalizations with an ICD 9 or ICD 10 code for OHS from 2007 to 2018. Patients with age <18, BMI <35, and ICD 9 and ICD 10 codes for neuromuscular disorders, chest wall disorders, or miscellaneous disorders of hypoventilation during the index hospitalization were excluded. The primary outcome was in-hospital mortality. We applied multivariable Cox regression modeling for the association of inpatient mortality with the diagnosis of OHS adjusted for age, sex, race, smoking history, BMI, GERD, OSA, renal failure, use of non-invasive and invasive MV, bronchoscopy, urban vs. rural hospital location, academic hospital status, COPD, asthma, acute PE, pulmonary hypertension, pneumonia and dependence on long-term oxygen or invasive or non-invasive mechanical ventilation. Hazard ratios (HR) with 95% confidence intervals (CI) were reported.

Results

A total of 1,115,927 hospitalizations were included in the final analysis. Increasing age, Native American race (compared to White), higher BMI, renal failure, a requirement of invasive and non-invasive mechanical ventilation, acute pulmonary embolism, ILD, and pulmonary hypertension were independently associated with increased risk of mortality during the hospitalization (p-value <0.05). Female sex, academic and urban hospital status, smoking, COPD, asthma, GERD, and OSA were independently associated with reduced risk for inpatient mortality (p-value <0.05). Black, Hispanic, Asian or Pacific Islander races (compared to White) were also associated with decreased risk of mortality (p-value <0.05). Home ventilator dependence, pneumonia, or oxygen dependence were not significantly associated with the risk of death.

Conclusion

Invasive mechanical ventilation (aHR 3.71, 95%CI 3.62-3.81) acute renal failure (aHR 1.93, 95%CI 1.87-2.00), and BMI > 70 (aHR 1.54, 95%CI 1.46-1.63) were the strongest predictors of inpatient mortality in our review of nationwide hospitalizations in OHS.

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0711 Do postmenopausal women with insomnia and obstructive sleep apnea have deterioration in sexual function?
Authors: Ishikura Isabela , Lucena Leandro , Andersen Monica , Tufik Sergio , Girão Manoel , Hachul Helena
Published: May 2022

Introduction

Sleep problems and sexual dissatisfaction are among the most common complaints during and after the menopause transition. The prevalence of insomnia and obstructive sleep apnea (OSA) reach 31% and 44% of postmenopausal women, respectively. The sexual dissatisfaction is frequently caused by a decline in hormonal levels and urogenital atrophy, resulting in inadequate lubrication and pain during intercourse, with orgasm difficulties and low sexual. Both behaviors – sleep and sexual function - play an important part in women’s wellness. The objective of this study was to investigate whether insomnia in association with OSA would increase climacteric and sexual symptoms compared with women with only insomnia or OSA.

Methods

Our sample comprised 47 postmenopausal women distributed into 3 groups: 1) insomnia, 2) OSA, and 3) OSA+insomnia. All participants completed the questionnaires: Insomnia Severity Index, Female Sexual Function Index, and Blatt-Kupperman menopausal index. Of the 47 participants, 34 women undergone polysomnography. The 3 groups were compared in respect of climacteric symptoms, sexual function score, and sleep.

Results

Our results showed that 85.1% of the postmenopausal women were classified with insomnia, 46.8% were diagnosed with OSA, and 82.9% had low sexual function. All groups had sleep efficiency of <80%, wake after sleep onset of >65 min, and a total sleep time of <6h, indicating poor sleep quality. There were no statistically significant differences among the groups in all sexual domains. The group of OSA+insomnia reported more climacteric symptoms (27.1±9.7) when compared to OSA group (15.7±9.6, P=0.03).

Conclusion

In our sample, the presence of insomnia and OSA associated with postmenopause revealed a low score for sexual function. Climacteric symptoms were higher in the groups with insomnia, and the association with low sexual function can lead to worsening of clinical condition.

Support (If Any)

Support: AFIP and CNPq. ACKNOWLEDGEMENTSOur studies are supported by the following funding agencies: AFIP (Associação Fundo de Incentivo à Pesquisa), CNPq (fellowships to LL, MLA, HH and ST). This study received indirect funding from AFIP and CNPq.
0714 Population-Level Snoring and Probable Sleep-Disordered Breathing Associated with Greater Sedentary Activity
Authors: Abdi Harun , Mason Brooke , Wills Chloe , Tubbs Andrew , Killgore William , Grandner Michael
Published: May 2022

Introduction

Increased frequency of snoring can be an indicator of sleep-disordered breathing, which is associated with a myriad of comorbidities, including increased cardiovascular disease risk. Previous studies have shown that sleep-disordered breathing is associated with less physical activity, but few studies examined this at the population lavel, or relative to primary snoring.

Methods

This analysis used a linear regression analysis on the 2017- March 2020 data collected from the National Health and Nutrition Examination Survey (NHANES) to explore the relationship between the minutes of sedentary activity and the frequency of snoring. Participants were asked how often they snored in the last 12 months. Responses were categorized as “Never”, “Rarely-- 1-2 nights/week”, “Occasionally-- 3-4 nights/week”, or “Frequently-- >=5 nights/week.” Self-reported sedentary activity was measured in minutes during a typical day. A modified STOP-BANG score was created based on NHANES measures of snoring, daytime tiredness, snorting/gasping during sleep, hypertension, body mass index, age, and gender (no measure of neck circumference). Reported results were unweighted; weighted results forthcoming.

Results

Significant unadjusted results indicate that those who reported snoring frequently had 19.2 minutes more sedentary time ([7.98,30.4], p<0.0001); and those with estimated sleep apnea had 16.2 more minutes of sedentary time than those without sleep apnea ([7.19,25.2], p<0.001). When adjusted for sex, age, race, education level, and marital status, the estimated difference between frequent snorers and those that reported never snoring increased to 35.9 minutes of more sedentary activity ([24.4,47.3], p<0.0001) a day. After adjusting for covariates, those with probable sleep apnea showed 43.9 more minutes of sedentary activity compared to those without sleep apnea ([34.1,53.6], p<0.001).

Conclusion

Overall, those who snore frequently (5 or more nights a week) or have a high risk of sleep apnea show a larger number of sedentary minutes per day then those that don’t snore or have probable sleep apnea. These relationships may be bidirectional, and directionality should be addressed in future studies.

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0718 Is There a way to Predict abnormal Polysomnography Following a Negative Home Sleep Apnea Test?
Authors: Aydinoz Secil , Thakkar Mahesh , Sahota Pradeep
Published: May 2022

Introduction

Obstructive sleep apnea (OSA) is characterized by recurrent episodes of obstruction of the upper airway that cause decreased or absent breathing during sleep. An OSA diagnosis is made when the patient experiences recurrent episodes of partial or complete collapse of the upper airway during sleep, which results in apneas or hypopneas, respectively. Polysomnography (PSG) is the gold standard test for diagnosis. HSATs (Home Sleep Apnea Tests) are types of sleep tests that can be conducted in a patient's home to detect obstructive sleep apnea. These tests are becoming increasingly common due to their affordability and convenience. Currently, an in-lab PSG is recommended if the initial HSAT is negative and there is a high clinical suspicion of OSA. Aim of this study is to identify a predictive component of negative HSAT which in turn shows positive PSG.

Methods

We reviewed 50 electronic medical records of patients who underwent an HSAT followed by an in-lab PSG at our Sleep Disorders Center. Patient demographics, comorbidities, HSAT data and PSG data were analyzed. Chi-square test and independent sample t-test were used to compare groups. Predictors of the negative PGA was assessed with Logistic regression. Statistical analysis was performed using Statistical Package of Social Science (SPSS) for Windows, version 15.0 (SPSS Inc, Chicago, IL). A p value <0.05 was considered as statistically significant.

Results

There was no correlation between age, gender, body mass index, comorbidities, and lowest oxygen level in HSAT to predict the result of following PSG.

Conclusion

The results of this study showed no statistically significant predictor in patients who underwent an HSAT followed by an in-lab PSG, although there seems to be a weak correlation between the lowest oxygen levels in HSAT and positive PSG. The gold standard for diagnosing OSA remains in-laboratory PSG; HSAT is an alternative in a select group of patients. For most patients with suspected mild OSA, in-laboratory PSG is preferred since HSAT may under-detect sleep-related events.

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0719 The Risk Of Progression Of Chronic Kidney Failure In Patients With Obstructive Sleep Apnea
Authors: Salman Salam , Chovatiya Jasmine , Justice Brittney , Holley Dallin , Verplancke Kiana , Kerr Christian , Walters Ryan , Ng Ian , Nazmul mohammed
Published: May 2022

Introduction

To describe the risks of chronic kidney disease (CKD) progression in patients with obstructive sleep apnea (OSA)

Methods

In this retrospective case control study; patients with CKD and OSA compared to patients with CKD without OSA who followed up at Creighton University Hospital Clinic. Data retrieved from Electronic Medical Records: demographics, time of diagnosis severity of OSA , apnea hypopnea index, severity of chronic kidney disease using serum creatinine and CKD -EPI equation for glomerular filtration rate cut offs. Patient’s kidney function was followed up for 10 years from their diagnosis of OSA. Worsening kidney function is defined on the basis of laboratory values including estimaed GFR( eGFR) and serum creatinine as well as Kidney Diseases Outcome Quality Initiative (KDOQI) 2002 definition and staging. We calculated the mean and SD when appropriate. P values less than 0.05 were considered statistically significant.

Results

269 patients without OSA included in the study. 416 patients with mild OSA, 343 with moderate OSA and 225 with severe OSA mean (SD) age 46.6 (16.3), 52.9(13.5), 56.9(14.1) and 55.3(15.1) years respectively; 59.1, 56.5, 39.1 and 35.6% were females respectively. CKD stage 1 42.8, 26.9, 26.5 and 28.9% respectively. Stage 246.5, 56.3, 54.2 and 46.7% respectively. Stage 3 10.7, 16.9, 19.2 and 24.3% respectivelyPatient’s renal functions who had CKD stage 2 or 3 with mild., moderate and severe OSA got worse in 21.2,31.5 and 26.7% respectively. compared to 13.1% with no sleep apnea.(p <.001)) ,There was no significant difference on progression of CKD in late stages( CKD IV/V)

Conclusion

Patients with OSA and CKD are more likely to have worsening renal function compared to patients without OSA and this association may depend on severity of both CKD and OSA.

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0756 Preclinical Pharmacology of Solriamfetol: Potential Mechanisms for Wake Promotion
Authors: Gursahani Hema , Jolas Thierry , Martin Maryse , Cotier Sandrine , Hughes Sandrine , Macfadden Wayne
Published: May 2022

Introduction

Solriamfetol is a wake-promoting agent (WPA) approved for the treatment of excessive daytime sleepiness associated with narcolepsy and obstructive sleep apnea. The wake-promoting mechanism of solriamfetol may result from dopamine and norepinephrine reuptake inhibition. Preclinical pharmacology studies were conducted to further elucidate the molecular targets activated by solriamfetol and compare them to that of known WPAs and traditional stimulants.

Methods

In vitro binding and functional studies were conducted in a panel of cell lines or membrane preparations expressing transmembrane receptors and monoamine transporters to measure the activity of solriamfetol, comparator WPAs, and traditional stimulants. Electrophysiology studies were conducted in slice preparations from mouse ventral tegmental area (VTA). Studies to measure locomotor activity and wake-promoting effects were conducted in mice.

Results

In vitro functional studies showed agonist activity of solriamfetol at human, mouse, and rat TAAR1 receptors. hTAAR1 EC50 values (10–16 µM) were within the clinically observed therapeutic solriamfetol plasma concentration range and overlapped with the observed DAT/NET inhibitory potencies of solriamfetol in vitro. TAAR1 agonist activity was unique to solriamfetol; neither the WPA modafinil nor the DAT/NET inhibitor bupropion had TAAR1 agonist activity. Solriamfetol (1–10 µM) dose-dependently inhibited the firing frequency of dopaminergic VTA neurons in mouse brain slices, similar to known TAAR1 agonists; however, these effects were inhibited by a D2 antagonist, suggesting a DAT-mediated effect. Unlike traditional stimulants, solriamfetol did not increase locomotor activity in naive mice, but inhibited the increase in locomotor activity in DAT knockout mice.

Conclusion

Preclinical studies have identified agonist activity at the TAAR1 receptor and, possibly, lower potency agonist activity at 5-HT1A receptors as potential pharmacological targets for solriamfetol, in addition to its activity as a DAT/NET inhibitor. Given the current understanding of TAAR1 agonists as modulators of monoamine transmission with potential wake-promoting effects in multiple preclinical species, agonist activity at the hTAAR1 receptor may represent an additional pharmacological target underlying the wake-promoting effects for solriamfetol, in addition to its DNRI activity.

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Jazz Pharmaceuticals
0792 Exploring Symptomatic Relief of Patients with Central Sleep Apnea when using CPAP or BiPAP Therapy
Authors: Kachechian Talar , Jamil Saad Bin , Armache Maria , Fast Zhanna
Published: May 2022

Introduction

About 0.9% of peoples over the age of 40 in the United States have Central Sleep Apnea (CSA). The key to treating CSA is to address any underlying health issues causing the condition as there are no clear, established treatment guidelines. For example, approaches will be made to mitigrate congestive heart failure. Often, patients may require the use of CPAP or BiPAP device to decrease cessations in respiration during sleep.

Methods

We investigated those patients diagnosed with CSA who use CPAP or BiPAP therapy and it's potential therapeutic effects through a retrospective chart review over a three-year period. We excluded those who were diagnosed with treatment emergent CSA and those using ASV. Data was collected from each patient's chart about patient demographics, modality of PAP therapy, and information pertaining to symptomatic relief.

Results

42 patients were identified who had a diagnosis of CSA. 25 of 42 (59.5%) were excluded as they were using alternative therapies. Of the 17 patients, 14 (82.4%) were male with an average age of 70.7 and 3 (17.6%) were females with an average age of 50. 15 of the 17 (88.2%) used CPAP therapy and the 2 (11.8%) patients used BiPAP.Prior to PAP therapy, the average Epworth Sleepiness Scale was 8.08 which improved to 3.79 post therapy. 9 out of the 17 (52.9%) patients reported improvement in nocturnal gasping while 2 (11.8%) did not report relief and 6 (35.3%) patients we were unable to determine through chart review. 9 out of 17 (52.9%) patients reported unrefreshed sleep and later 6 of the 9 (66.7%) patients reported refreshed sleep with initiation of PAP therapy while 1 patient reported no improvement and 2 (22%) we were unable to determine. 15 of the 17 (88.2%) patients complained of waking up multiple times throughout the night before PAP therapy. 5 (33.3%) patients had improvement of the frequency of nighttime awakenings while we were unable to determine the remaining 10 patients.

Conclusion

When central sleep apnea persists despite adequate treatment of the primary cause, CPAP or BiPAP may be used for symptomatic relief.

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0799 Precipitation of Dream Enactment Behavior in the setting of β -Blocker therapy
Authors: Patel Jay , Moshtagh-Sisan Mahtab , Sarrami Kayvon , Avidan Alon
Published: May 2022

Introduction

REM sleep behavior disorder (RBD) is defined by dream enactment behavior (DEB) and REM sleep without muscle atonia (RWA). It is proposed that in both isolated and secondary RBD, the loss of REM sleep atonia is related to a failure of spinal motoneuron inhibition in the rostral pons. RBD is most commonly isolated, although it has been attributed to serotonergic antidepressant medication. This is the first report of metoprolol succinate (MS) provoking DEB in patients with RWA which helps shed more light on the mechanism of DEB in RBD.

Report of Cases: A 51-year-old male with a new diagnosis of atrial fibrillation (AF) was referred for evaluation of snoring and hypersomnolence. Polysomnography (PSG) revealed obstructive sleep apnea and RWA. DEB was not observed. Compliance with PAP therapy improved his symptoms. Persistent AF required the use of Metoprolol Succinate (MS), which precipitated aggressive DEB.

Discontinuation of MS resulted in clinical resolution of DEB.

Conclusion

The data sheds more light on the potential role of β- blockers, in general, and MS, in particular, in precipitating DEB in susceptible individuals with RWA. While MS is an uncommon cause of visual hallucinations, the data here indicates that it might increase susceptibility to DEB in those who are at risk (RWA). Potential mechanisms include the following: β-blockers bind to serotonin receptors and precipitate DEB in the setting of RWA. β-blockers may also precipitate DEB by suppressing melatonin release via specific inhibition of central beta-adrenoreceptors culminating in sleep instability and DEB as a consequence. This case illustrates a clinically important role of the β-blocker MS, in precipitating DEB, and the need to avoid these agents in the setting of injurious parasomnias. We recommend that clinicians keep a vigilant eye for the exacerbation of DEB in people with RBD who are prescribed β-blockers.

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0817 Conquering Two Sleep Birds with One Iron stone: The Case of Resolved Restless Sleep Disorder and Parasomnia with Iron Therapy
Authors: Richens Zachary , Ibrahim Sally
Published: May 2022

Introduction

Restless Sleep Disorder (RSD) is characterized by frequent nocturnal movements of large muscle groups or a complaint of restless sleep by observers with associated daytime dysfunction.1 RSD, like other movement disorders of sleep, is associated with low iron stores.2 Children with RSD have increased NREM sleep instability and a propensity for parasomnia.2 No reports to date have demonstrated the use of iron therapy for parasomnia in patients with RSD. Furthermore, studies are limited in very young children with this disorder as they currently fall outside proposed diagnostic criteria.1

Report of Cases: A 2 year-old male presented to the sleep clinic with parental complaints of nightly sleep initiation and maintenance difficulty, mild snoring, restless sleep, episodes of sleepwalking and night terrors multiple times per week. Symptoms worsened over 6 months and were associated with daytime irritability and behavioral problems. Sleep quality measures assessed progress between visits: the PROMIS Sleep Disturbance (PROMIS SD) and Sleep Related Impairment (PROMIS SRI). Serum ferritin was initially 20ug/L. Polysmnogram demonstrated no significant sleep related breathing disorder, a large muscle group movement index of 14, periodic limb movement index of 3. Initial treatment included oral iron therapy, scheduled awakenings, and hypnotic dose melatonin. The sleep psychologist addressed limit setting and negative sleep associations with improved insomnia symptoms but parasomnia and restless sleep continued. The parent noted reduction in both movements and parasomnia frequency after one month of iron therapy. After a 3 month period on treatment, the parent reported complete cessation of the parasomnia, drastic reduction in restlessness, and near resolution of insomnia. Sleep quality measure PROMIS SD improved by 11, demonstrating reduced sleep disturbance. PROMIS SRI did not change. Ferritin level increased to 47ug/L.

Conclusion

RSD in a very young child with NREM parasomnia responded to oral iron therapy improving overall sleep quality. This case demonstrates the relationship between relative iron deficiency, RSD and associated parasomnia.

Support (If Any)

1. DelRosso LM, Ferri R, Allen RP, et al. Consensus diagnostic criteria for a newly defined pediatric sleep disorder: restless sleep disorder(RSD).SleepMed.2020;75:335-340. 2. Leung W, Singh I, McWilliams S, Stockler S, Ipsiroglu OS. Iron deficiency and sleep - A scoping review. SleepMedRev.2020;51:101274
The association between race- and ethnicity-related stressors and sleep: the role of rumination and anxiety sensitivity
Authors: Otto Michael W , Lubin Rebecca E , Rosenfield David , Taylor Daniel J , Birk Jeffrey L , Espie Colin A , Shechter Ari , Edmondson Donald , Shepherd Justin M , Zvolensky Michael J
Published: May 2022

Study Objectives

This study was designed to investigate the association between psychosocial factors and self-reported sleep duration and two indices of sleep quality in a racially and ethnically diverse sample of adults. We investigated the relations between both rumination and anxiety sensitivity with these self-reported sleep outcomes. We also examined rumination and anxiety sensitivity as moderators of three race- and ethnicity-related stressors: discrimination, acculturative stress, and socioeconomic status.

Methods

In a cross-sectional design, we assessed 1326 adults (ages 18–48 years) selected for self-reported racial and ethnic minority status. Regression analyses were used to examine the associations between demographic, social/environmental stressors, depression severity, rumination, and anxiety sensitivity and three sleep outcomes: sleep duration, sleep quality subscale, and global sleep quality.

Results

Our findings supported the hypothesized role of rumination as an amplification factor for the influence of race- and ethnicity-related stressors on sleep duration and quality. Rumination was associated with all three sleep outcomes (sleep duration, sleep quality subscale, and global sleep quality) and was a moderator of the associations between discrimination and all 3 sleep outcomes. Anxiety sensitivity was not consistently associated with these sleep outcomes. Depression symptoms did not account for these findings.

Conclusions

If confirmed in longitudinal study, our findings introduce a potentially important treatment target—rumination—for addressing sleep disparities in prevention or intervention models. Rumination appears to amplify the negative sleep consequences of race- and ethnicity-related stressors and is a modifiable treatment target.
Sleep from acute to chronic traumatic brain injury and cognitive outcomes
Authors: Sanchez Erlan , Blais Hélène , Duclos Catherine , Arbour Caroline , Van Der Maren Solenne , El-Khatib Héjar , Baril Andrée-Ann , Bernard Francis , Carrier Julie , Gosselin Nadia
Published: May 2022

Study Objectives

Traumatic brain injuries (TBIs) cause persistent cerebral damage and cognitive deficits. Because sleep may be a critical factor for brain recovery, we characterized the sleep of patients with TBI from early hospitalization to years post-injury and explored the hypothesis that better sleep during hospitalization predicts more favorable long-term cognitive outcomes.

Methods

We tested patients with moderate-to-severe TBI in the hospitalized (n = 11) and chronic (n = 43) stages using full-night polysomnography, with 82% of the hospitalized group being retested years post-injury. Hospitalized patients with severe orthopedic and/or spinal cord injury (n = 14) and healthy participants (n = 36) were tested as controls for the hospitalized and chronic TBI groups, respectively. Groups had similar age and sex and were compared for sleep characteristics, including slow waves and spindles. For patients with TBI, associations between sleep during hospitalization and long-term memory and executive function were assessed.

Results

Hospitalized patients with TBI or orthopedic injuries had lower sleep efficiency, higher wake after sleep onset, and lower spindle density than the chronic TBI and healthy control groups, but only hospitalized patients with brain injury had an increased proportion of slow-wave sleep. During hospitalization for TBI, less fragmented sleep, more slow-wave sleep, and higher spindle density were associated to more favorable cognitive outcomes years post-injury, while injury severity markers were not associated with these outcomes.

Conclusion

These findings highlight the importance of sleep following TBI, as it could be a strong predictor of neurological recovery, either as a promoter or an early marker of cognitive outcomes.
Gender differences in narcolepsy: What are recent findings telling us?
Authors: Schmidt Markus H , Bassetti Claudio L A
Published: May 2022

Three papers currently published in SLEEP using two different mouse models of narcolepsy, including either Hcrt-tTa;TetO diptheria toxin-A (DTA) or Hypocretin knock-out (Hcrt-KO) mice, suggest important gender differences in narcolepsy expression. Specifically, these recent data corroborate previous findings in mice demonstrating that females show more cataplexy events and more total cataplexy expression than males. Moreover, in the neurotoxic DTA mouse model, females show earlier onset of cataplexy expression than males during active Hcrt cell loss. Finally, females show a doubling of cataplexy during estrous compared to other phases of the estrous cycle. These findings are reviewed in the broader context of prior published literature, including reported gender differences in Hcrt expression and hormonal influences on sleep and wakefulness. Although similar findings have not been reported in humans, a systematic evaluation of gender differences in human narcolepsy has yet to be performed. Taken together, these animal data suggest that more research exploring gender differences in human narcolepsy is warranted.
Efforts to advance NIH-funded behavioral and social sciences research on structural racism and health
Authors: Blachman-Demner Dara R , Tyus Nadra C
Published: May 2022

This commentary provides background and context for the increasing attention to research designed to better understand and address the impact of structural racism on health, with particular attention to the role of the behavioral and social sciences. The manuscript describes the impetus provided to this work by recent public health crises of COVID-19 and the racial justice movement that emerged following the murder of George Floyd in the summer of 2020. A range of initiatives from the National Institutes of Health (NIH) focused on structural racism and health equity are discussed in this context and opportunities and gaps for future research are identified.
Early Drug-Induced Liver Injury Risk Screening: “Free,” as Good as It Gets
Authors: Martin Matthew T , Koza-Taylor Petra , Di Li , Watt Eric D , Keefer Christopher , Smaltz Daniel , Cook Jon , Jackson Jonathan P
Published: May 2022

For all the promise of and need for clinical drug-induced liver injury (DILI) risk screening systems, demonstrating the predictive value of these systems versus readily available physicochemical properties and inherent dosing information has not been thoroughly evaluated. Therefore, we utilized a systematic approach to evaluate the predictive value of in vitro safety assays including bile salt export pump transporter inhibition and cytotoxicity in HepG2 and transformed human liver epithelial along with physicochemical properties. We also evaluated the predictive value of in vitro ADME assays including hepatic partition coefficient (Kp) and its unbound counterpart because they provide insight on hepatic accumulation potential. The datasets comprised of 569 marketed drugs with FDA DILIrank annotation (most vs less/none), dose and physicochemical information, 384 drugs with Kp and plasma protein binding data, and 279 drugs with safety assay data. For each dataset and combination of input parameters, we developed random forest machine learning models and measured model performance using the receiver operator characteristic area under the curve (ROC AUC). The median ROC AUC across the various data and parameters sets ranged from 0.67 to 0.77 with little evidence of additive predictivity when including safety or ADME assay data. Subsequent machine learning models consistently demonstrated daily dose, fraction sp3 or ionization, and cLogP/D inputs produced the best, simplest model for predicting clinical DILI risk with an ROC AUC of 0.75. This systematic framework should be used for future assay predictive value assessments and highlights the need for continued improvements to clinical DILI risk annotation.
Gestational cholestasis induced intrauterine growth restriction through triggering IRE1α‐mediated apoptosis of placental trophoblast cells
Authors: Gao Xing‐Xing , Lin Shuai , Jiang Pei‐Ying , Ye Meng‐Ying , Chen Wei , Hu Chuan‐Xiang , Chen Yuan‐Hua
Published: May 2022

Epidemiological and animal experimental studies suggest an association between gestational cholestasis and intrauterine growth restriction (IUGR). Here, we explored the mechanism through which gestational cholestasis induced IUGR. To establish gestational cholestasis model, pregnant mice were subcutaneously injected with 17α‐Ethynylestradiol (E2) on gestational day 13 (GD13)–GD17. Some pregnant mice were intraperitoneally injected with 4μ8C on GD13–GD17. The results found that the apoptosis of trophoblast cells was elevated in placentas of mice with gestational cholestasis and in deoxycholic acid (DCA)‐treated human trophoblast cell lines and primary mouse trophoblast cells. Correspondingly, the levels of placental cleaved caspase‐3 and Bax were increased, while placental Bcl2 level was decreased in mice with gestational cholestasis and in DCA‐treated trophoblast cells. Further analysis found that placental IRE1α pathway was activated in mice with gestational cholestasis and in DCA‐treated trophoblast cells. Interestingly, 4μ8C, an IRE1α RNase inhibitor, significantly inhibited caspase‐3 activity and apoptosis of trophoblast cells in vivo and in vitro. Importantly, 4μ8C rescued gestational cholestasis‐induced placental insufficiency and IUGR. Furthermore, a case–control study demonstrated that placental IRE1α and caspase‐3 pathways were activated in cholestasis cases. Our results provide evidence that gestational cholestasis induces placental insufficiency and IUGR may be via triggering IRE1α‐mediated apoptosis of placental trophoblast cells.
Interactions among key residues regulate mammalian odorant receptor trafficking
Authors: Xu Rui , Cong Xiaojing , Zheng Qian , Xu Lun , Ni Mengjue J. , de March Claire A. , Matsunami Hiroaki , Golebiowski Jérôme , Ma Minghong , Yu Yiqun
Published: May 2022

Odorant receptors (ORs) expressed in mammalian olfactory sensory neurons are essential for the sense of smell. However, structure–function studies of many ORs are hampered by unsuccessful heterologous expression. To understand and eventually overcome this bottleneck, we performed heterologous expression and functional assays of over 80 OR variants and chimeras. Combined with literature data and machine learning, we found that the transmembrane domain 4 (TM4) and its interactions with neighbor residues are important for OR functional expression. The data highlight critical roles of T4.62 therein. ORs that fail to reach the cell membrane can be rescued by modifications in TM4. Consequently, such modifications in MOR256‐3 (Olfr124) also alter OR responses to odorants. T1614.62P causes the retention of MOR256‐3 in the endoplasmic reticulum (ER), while T1614.62P/T1484.49A reverses the retention and makes receptor trafficking to cell membrane. This study offers new clues toward wide‐range functional studies of mammalian ORs.
Innovating Health Research Methods, Part II
Authors: Golden Tasha L.
Published: May 2022

Accumulating US studies indicate gender inequities in youth violence research and responses. Improving youth health thus requires greater understanding of how girls and young women perceive and experience violence, and gathering such data demands research methods that are trauma-informed and assets-based. This mixed-methods study addresses these dual needs. To support gender equity in youth violence research, it incorporated 4 violence surveys and 3 arts-based methods to examine girls' and young women's experiences and perceptions of violence. Then, to advance trauma-informed, assets-based research, it used study findings to generate an assessment of all methods employed. Results are presented in a 2-part article, with Part I (published separately) conveying findings about the population's experiences, needs, and assets related to violence and safety. Part II (here) details the development of the arts-based methods, assesses them alongside the surveys, and compares the effectiveness of all methods. Despite overlap across methods, the arts-based strategies offered critical knowledge that was missed by surveys, including actionable data about the population's priorities, experiences, and recommendations. The arts-based methods were also trauma-informed and offered reciprocity via assets-based, community-centered programs and platforms. This study provides justification and a template for further integration of creative practices into research, and for continued innovation to advance access, data quality, and health equity.
Is Methadone Safe for Patients With Opioid Use Disorder and Coronavirus Disease 2019 Infection?
Authors: Owiti John Arianda , Benson Molli , Maplanka Mandisa , Oluseye Lasekan , Carvalho Debora
Published: May 2022

The coronavirus disease 2019 (COVID-19) pandemic has led to not only increase in substance misuse, substance use disorder, and risk of overdose but also lack of access to treatment services. Due to lack of knowledge of the course and impact of COVID-19 and outcomes of it’s interactions with existing treatments, the Substance Misuse Service Team initiated a safety improvement project to review the safety of opioid substitution treatment, particularly the safety of methadone. This preliminary retrospective cross-sectional audit of safety improvement intiative underscores the importance of providing treatment services to those with opioid use disorders and that methadone is safe among this population with a high burden of comorbidity, most of which leads to negative outcomes from COVID-19. The outcomes show that patients who have COVID-19 should continue with opioid substitution treatment with methadone. Although treatment with methadone is safe, symptomatic patients should be monitored. In addition, patients who take methadone at home should be educated on the risk of overdose due to, and adverse outcomes from, COVID-19 infection. Patients should monitor themselves using pulse oximeter for any signs of hypoxia.