bluuebunny/crossref_metadata_2025_split huggingface dataset:
0710 Effects of tonic motor activation (TOMAC) therapy on sleep quality for refractory restless legs syndrome
Authors: Bogan Richard , Roy Asim , Kram Jerrold , Ojile Joseph , Hudson J Douglas , Rosenberg Russell , Scheuller H Samuel , Charlesworth Jonathan 
Published: May 2023

Abstract

Introduction
Tonic motor activation (TOMAC) is a noninvasive medical device therapy that has been shown to reduce symptoms of refractory restless legs syndrome (RLS). Here, we evaluated the effects of TOMAC on subjective sleep quality.

Methods
One hundred and thirty-three adults with primary moderate-severe refractory RLS were 1:1 randomized to TOMAC or sham control for 4 weeks. Participants were instructed to self-administer a 30-minute TOMAC session bilaterally over the head of the fibula to electrically stimulate the peroneal nerve whenever RLS symptoms presented. Sleep quality was assessed through prespecified analysis of changes to Medical Outcomes Study Sleep Scale (MOS-Sleep) Sleep Problems Index I (MOS-I) and II (MOS-II) scores from baseline to Week 4. Post hoc t-tests were conducted on each MOS-Sleep item included in the MOS-I or MOS-II.

Results
MOS-I score changed by -11.8 points (48.5 to 36.7) for TOMAC and -2.8 points for sham (44.5 to 41.7), a difference of -9.0 points (p&lt; 0.001). MOS-II score changed by -13.7 points (52.5 to 38.9) for TOMAC and -4.0 points for sham (48.3 to 44.3), a difference of -9.7 points (p&lt; 0.001), which exceeds the proposed minimal clinically important difference (MCID) of 6 points. Post hoc analysis demonstrated statistically significant reductions in trouble falling asleep (item #7; -34.0% for TOMAC vs. -5.8% for sham; p&lt; 0.01) and trouble staying awake during the day (item #9; -33.6% for TOMAC vs. -2.1% for sham; p&lt; 0.05), which exceeded the standard MCID threshold of 30% relative to baseline.

Conclusion
For adults with refractory RLS, TOMAC improved subjective sleep quality, sleep latency, and daytime somnolence relative to sham control. Each of these improvements represented clinically important improvements. These data demonstrate that TOMAC can provide meaningful improvements to sleep quality and daytime functioning for patients with refractory RLS.

Support (if any)
Funding was provided by Noctrix Health, Inc.
0711 Health-Economic Implications of Tonic Motor Activation (TOMAC) therapy for RLS: An Exploratory Analysis based on the RESTFUL study
Authors: Ryschon Anne , Cao Khoa , Roy Asim , Pietzsch Jan 
Published: May 2023

Abstract

Introduction
Restless legs syndrome (RLS) is a debilitating condition associated with reduced health-related quality of life (HRQoL) and increased resource utilization. Recently, the RESTFUL study demonstrated significant improvement in RLS severity following treatment with a novel non-invasive neuromodulation treatment (Tonic Motor Activation; TOMAC). Our objective was to provide model-based estimates of quality-adjusted life year (QALY) gain and reduction in healthcare utilization that might be expected for the observed changes in symptom severity.

Methods
The RESTFUL study randomized n=133 subjects 1:1 to active TOMAC treatment and sham control, with change in International Restless Legs Scale (IRLS) scores reported at four weeks at the end of the randomization period. Functional relationships between IRLS and HRQoL and resource utilization were derived from two prior health-economic studies (Happe et al. 2009 and Durgin et al. 2015). Model-projected quality-adjusted life year (QALY) gain and events avoided at a five-year analysis horizon were calculated based on assumption of maintained treatment effect.

Results
From baseline of 25.2, change in IRLS at four weeks was -7.2 for the active and -3.8 for the sham group (between group difference -3.4, p&lt; 0.01). Based on this effect size, TOMAC was projected to add 0.16 QALYs over 5 years (0.39 when considering reduction from baseline). Based on lower symptom severity, TOMAC was projected to avoid 3.80 (8.05) health care provider visits, 0.29 (0.62) ER visits, and 0.12 (0.26) hospitalizations over 5 years, resulting in a relative risk (RR) of composite healthcare utilization of 0.94 (0.88).

Conclusion
The findings of this exploratory analysis suggest TOMAC-associated improvements in RLS severity as observed in the RESTFUL study may lead to meaningful improvements in patient quality-of-life and concurrent reductions in healthcare utilization. Further investigation is warranted.

Support (if any)
Wing Tech Inc. (AMR, KNC, JBP) received consulting fees from Noctrix Health. AR is an investigator in the RESTFUL study.
0713 Long-term response to tonic motor activation (TOMAC) therapy for refractory restless legs syndrome
Authors: Roy Asim , Ojile Joseph , Kram Jerrold , Rosenberg Russell , Olin Jonathan , Hudson J Douglas , Bogan Richard , Charlesworth Jonathan 
Published: May 2023

Abstract

Introduction
There is a large population of patients who have become refractory to first-line treatments for Restless Legs Syndrome, partially due to augmentation to dopamine agonist medications. For patients with refractory RLS, tonic motor activation (TOMAC) is a noninvasive medical device therapy with promising short-term safety and efficacy. Here, we evaluated the response to TOMAC over a longer duration of &gt;24 weeks.

Methods
In the RESTFUL study, 133 patients with primary moderate-severe refractory RLS were 1:1 randomized to TOMAC or sham control for weeks 1 to 4 followed by open-label TOMAC for weeks 5 to 8. The final 50 participants to complete the RESTFUL study were invited to continue TOMAC treatment for an additional 24 weeks (weeks 9 to 32) in an extension study. Participants were instructed to self-administer one 30-minute TOMAC session bilaterally over the peroneal nerve whenever RLS symptoms presented. Efficacy was assessed by comparing responses from baseline (RESTFUL study entry, week 0) to week 32 on Clinician Global Impressions-Improvement (CGI-I) responder rate, Patient Global Impressions-Improvement (PGI-I) responder rate, and International RLS Study Group Rating Scale (IRLS) total score. Additional analyses compared responses from week 8 (RESTFUL study completion) to week 32.

Results
Of the 50 eligible participants, 44 consented to the extension study and 42 completed. CGI-I responder rate relative to baseline increased from 64% at week 8 to 76% at week 32. PGI-I responder rate relative to baseline increased from 68% at week 8 to 77% at week 32. IRLS total score reduced from 24.5 at baseline to 17.1 at week 8 to 12.9 at week 32, a reduction of 11.6 points from baseline to week 32. There were no moderate or severe device-related AEs.

Conclusion
TOMAC resulted in substantial and clinically significant reduction in RLS symptom severity that was maintained through &gt;24 weeks of treatment. Furthermore, there was a trend towards increased efficacy with continued use of TOMAC. These data suggest that TOMAC could represent a potential long-term treatment for the chronic condition of refractory RLS.

Support (if any)
Funding was provided by Noctrix Health, Inc.
0714 Machine learning model for Predicting phenoconversion in patients with Rem behavior disorder using clinical markers
Authors: Shin Yong Woo , Lee Seolah , Kim Han-Joon , Sunwoo Jun-Sang , Jung Ki-Young 
Published: May 2023

Abstract

Introduction
Idiopathic Rapid eye movement (REM) sleep behavior disorder is a condition that can be an early sign of alpha-synuclein-mediated neurodegenerative diseases, and the course of the disease can vary greatly from patient to patient. It is important to identify patients who are at risk of developing neurodegenerative diseases in the future for the purpose of future clinical trials and for patients to plan their lives accordingly. Previous research has identified various risk factors for phenoconversion in RBD patients, but these studies are not practical for use in clinical settings due to resource availability or the rarity of certain features. Additionally, most of these studies have been conducted on non-Asian populations, which may have different genetic backgrounds than Asian populations. This study aimed to develop a machine learning model to predict survival in RBD patients using clinical features commonly available in routine clinical settings.

Methods
This study recruited patients diagnosed with RBD based on polysomnography results and collected 34 features for each patient. Missing data were imputed and various models were applied to the data to improve performance. The model's predictive performance was evaluated using an integrated Brier score and the concordance index. Mean performance indicators were calculated from 5-fold cross-validation results. A web application hosting the final prediction model was developed and deployed on a server for use by physicians or patients.

Results
173 patients were included in the study. We used the likelihood ratio test to calculate the p-values of all variables and selected the following 8 variables with p-values less than 0.1: UPDRS part III, age, history of antidepressant use, history of alcohol use, MoCA (Montreal Cognitive Assessment), PSQI-TST (Pittsburgh Sleep Quality Index - total sleep time), AHI-REM (apnea-hypopnea index - REM sleep), and education level. The random survival forest model had the best mean IBS of 0.07 and the best C-index of 0.93

Conclusion
We showed that it is possible for a machine learning model to predict phenoconversion in patients with RBD using features that are commonly available in routine clinical settings

Support (if any)
0717 Restless sleep associated with low ferritin levels: A Retrospective Study in a Pediatric Sleep Center
Authors: Smith Sherrie , White Jay , Jambhekar Supriya 
Published: May 2023

Abstract

Introduction
A significant challenge in diagnosing Restless Leg Syndrome in children is the child’s inability to verbally describe their symptoms. In our pediatric sleep clinic, it has been recognized that restless sleep is a routine element of the clinical history for children presenting with a wide range of sleep disturbances. A literature review showed substantial literature about the prevalence and characteristics of restless sleep in children, but there is little showing the effect of ferrous sulfate on symptoms in children. A deficiency of brain iron stores results in a reduction of dopamine production and the clinical expression of RLS. Brain iron stores cannot be directly quantified for clinical purposes but can be evaluated indirectly by measuring serum ferritin. In the clinical framework of RLS, it is generally accepted that a serum ferritin &lt; 50 ng/ml is too low, despite still being considered within normal range for most reference labs and replacing this with oral elemental iron should be considered the first line treatment.

Methods
A retrospective chart review was performed of patients seen in the Sleep Clinic at Arkansas Children's Hospital from 2018-2021 who had a report of restless sleep and a serum ferritin drawn. If the ferritin was lower than 50 ng/ml, they were treated with ferrous sulfate for a minimum of three months. After three months, patient’s symptoms were reevaluated, and ferritin levels drawn to determine if improvement had occurred.

Results
In total, 1,000 charts were reviewed. Ferritin levels &lt; 50 ng/ml were found in 75.2% of the patients. Of the patients with a serum ferritin &gt;50 ng/ml after treatment with ferrous sulfate, 62.8% reported an improvement in restless sleep and 37.2% reported no change in symptoms.

Conclusion
Low ferritin levels were found in a large number of our pediatric patients with restless sleep. The administration of ferrous sulfate in the patient population showed an improvement in symptoms of restless sleep in a majority of patients.

Support (if any)
0722 Sleep disturbances and subsequent mobility disability in chronic disease: Findings from the Nurses’ Health Study
Authors: Whibley Daniel , Shieu Monica , Dunietz Galit , Braley Tiffany 
Published: May 2023

Abstract

Introduction
Impaired mobility is the leading cause of disability in the U.S. Across chronic neurological, metabolic, and musculoskeletal conditions, mobility reductions are observed beyond expected effects of aging. Poor sleep health may be one common factor that drives accelerated reduction in mobility among people with chronic conditions. This study compared longitudinal associations between self-reported sleep disturbances and mobility disability progression among women with and without multiple sclerosis (MS), diabetes, and osteoarthritis (OA).

Methods
This prospective cohort study used data from four waves of the Nurses’ Health Study (2008, 2012, 2014, 2016). Logistic regression and the Kaplan-Meier method were used to quantify associations between baseline sleep-related variables and subsequent increase in mobility disability.

Results
Of 70,303 women (mean age 73), 392 had MS, 7,302 had diabetes, and 24,099 had OA. Between 2008-2016, mobility disability increased in 16.9% of the sample overall, 27.8% in the MS subgroup, 27.0% in the diabetes subgroup, and 23.7% in the OA subgroup. Between 2008-2016, known/suspected OSA was significantly associated with increased mobility disability in the overall sample (OR:1.4, 95%CI:1.2,1.5), and within the diabetes (OR:1.5, 95%CI:1.2,1.9) and OA subgroups (OR:1.2, 95%CI:1.0,1.4), but not the MS subgroup (OR:2.3, 95%CI:0.6,8.9); however, across 2012-2016, this association was significant for MS (OR:4.0, 95%CI:1.0,16.1). Suboptimal sleep duration was significantly associated with increased odds of mobility disability progression in the overall sample, but not within disease subgroups. Conversely, perception of adequate sleep was significantly associated with lower odds of mobility disability progression overall (OR:0.82, 95%CI:0.78,0.87) and for the OA subgroup (OR:0.83, 95%CI:0.76,0.91). Excessive daytime sleepiness was significantly associated with mobility disability progression overall (OR:1.2, 95%CI:1.1,1.4) and for the OA subgroup (OR:1.2, 95%CI:1.0,1.4).

Conclusion
Prevalent sleep disturbances could increase risk of disability progression among women, particularly in common chronic disease populations. Informed by these data, future research could offer new insight into sleep-based strategies to ameliorate mobility decline.

Support (if any)
This work was supported in part by a Michigan Institute for Clinical and Health Research Pilot Grant (UL1TR002240). Dr. Shieu was supported by a T32 grant from National Heart, Lung, and Blood Institute (T32HL110952).
0724 Objectively Regular Sleep of Optimal Duration and Mortality: The Multi-Ethnic Study of Atherosclerosis
Authors: Chung Joon , Goodman Matthew , Huang Tianyi , Sofer Tamar , Bertisch Suzanne , Purcell Shaun , Castro_Diehl Cecilia , Chen Jarvis , Redline Susan 
Published: May 2023

Abstract

Introduction
Irregularly timed sleep, inconsistent duration, and non-optimal sleep duration have been implicated in the etiology of cardiovascular disease and premature mortality. These dimensions of sleep map behaviorally to regular bed and wake times. Our aim was to estimate the association of regular sleep of optimal sleep duration with all-cause mortality in a diverse US sample.

Methods
We used data from the Multi-Ethnic Study of Atherosclerosis Sleep Study (2010-2013) at Exam 5. Sleep was measured by 7-day wrist actigraphy, concurrent with at-home polysomnography and validated sleep questionnaires. We used K-means clustering on wrist-actigraphy regularity and duration data to assign individuals to categories of ‘regular-optimal’ or ‘irregular-insufficient’ sleep, labels describing sleep tendencies in each group. Using proportional hazard models with multi-variate adjustment for socio-demographics (age, female sex, race/ethnicity, marital status, and day vs non-day work schedules), lifestyle (moderate-vigorous physical activity, smoke status), health status (depressive symptoms, body mass index, total medications, prevalent cardiovascular disease), and measures of major sleep disorders (the Apnea-Hypopnea Index, insomnia severity, restless legs), we estimated all-cause mortality associations with sleep patterns. Sensitivity analyses additionally adjusted or, via propensity scores, matched on income, education, prevalent chronic lung disease, prevalent cancer, hypertension, diabetes, and diet.

Results
Among 1,726 participants who were followed for a median of 7.0 years (Q1-Q3, 6.4-7.4 years,) there were 171 deaths. The ‘regular-optimal’ group had 42% lower mortality risk compared to the ‘irregular-insufficient’ sleep group (Hazard Ratio [95% Confidence Interval]: 0.58 [0.43, 0.80]), in the fully adjusted model and was robust to sensitivity analyses.

Conclusion
Individuals characterized by a sleep pattern of ‘regular and optimal’ duration sleep had significantly lower mortality compared to those with an ‘irregular and less sufficient’ sleep pattern. The regular and optimal duration phenotype maps behaviorally to regular bed and wake times, suggesting potential health benefits of adherence to recommended sleep practices.

Support (if any)
JC was supported by the American Academy of Sleep Medicine’s Foundation Grant: 269-FP-22 This work was also supported by the following National Institute of Health (NIH) grants: 5T32HL007901-19, 5K01HL138211-05, K01HL143034, R01HL098433. SR was partly funded by the NIH National Heart, Lung, and Blood Institute (NHLBI) R35HL135818.
0725 Self-reported sleep quality and sleep architecture are associated with plasma neurofilament light in older adults without dementia
Authors: Li Junxin , Huang Jing , Li Mengchi , Gooneratne Nalaka , Gill Jessica , Spira Adam 
Published: May 2023

Abstract

Introduction
Sleep disruption is common in older adults with multiple chronic conditions and can occur before the clinical onset of Alzheimer’s disease (AD). Sleep disruption plays an important role in AD pathology and has been associated with neuro-imaging evidence of AD, and cerebrospinal fluid elevations of amyloid, tau, and neurodegeneration (ATN) biomarkers. Plasma ATN biomarkers are increasingly used in AD research. We examined the associations of self-reported sleep quality and electroencephalogram (EEG) sleep architecture with plasma ATN biomarkers in sedentary older adults without dementia.

Methods
We used baseline data from an ongoing randomized controlled trial that examines the effect of physical activity on sleep and cognition in community-dwelling sedentary older adults without dementia (Montreal Cognitive Assessment [MoCA]&gt;17, n=102). Participants reported demographics, completed the Pittsburgh Sleep Quality Index (PSQI) questionnaire, and provided blood samples to measure plasma ATN biomarkers [amyloid-beta (Aβ)42/42, total-tau (T-tau), and neurofilament light (NFL)]. Two-night home-based sleep EEG measures (Sleep Profiler) were collected from 56 of the 102 participants. Multiple regression models were conducted to test the associations between sleep measures and plasma ATN biomarkers.

Results
Participants were aged 69.9 ± 6.0 years, 80% were women, and they had 3.1±1.7 chronic conditions. Most had intact cognitive function (68.6% MoCA≥ 26) and 28.6% of the sample had mild cognitive impairment (17&lt; MoCA&lt; 25). In models adjusted for age, sex, race, education, and number of comorbidities, higher PSQI scores (β=0.84, 95% confident interval (CI)= [0.12,1.62]), longer non-rapid eye movement (NREM) N3 duration (β=4.43, 95% CI= [0.48,8.18]), and higher REM latency (β=0.04, 95% CI= [0.02, 0.05]) were associated with higher NFL. Longer REM sleep duration (β=-11.13, 95% CI= [-20.55, -1.71]) was associated with lower NFL. There were no other significant associations of sleep measures with other ATN biomarkers.

Conclusion
Self-reported sleep quality and sleep architecture were associated with plasma NFL among older adults with intact cognition and mild cognitive impairment. Plasma NFL may be a sensitive and promising biomarker that links sleep disruption and AD-related outcomes in older adults without dementia. Future research with a larger sample is needed to further test this association.

Support (if any)
National Institute of Nursing Research R00NR016484
0728 Does Short Sleep Duration Increase Risk for Postpartum Weight Retention?
Authors: Ryan Jeanna , Day Heather , Egger Marlene , Depner Christopher , Shaw Janet 
Published: May 2023

Abstract

Introduction
About 75% of mothers in the United States have postpartum weight retention (PWR), which increases risk for adverse health outcomes in mother and child. Short sleep duration is an important health behavior linked to risk of weight gain in the general population. Although short sleep duration is common in postpartum, findings from the few studies examining sleep duration and PWR are mixed. Thus, we aimed to examine whether sleep duration at 6 months postpartum is associated with PWR at 12 months. We also explored agreement between self-reported and actigraphy-derived sleep duration.

Methods
This is a secondary analysis from a prospective cohort study investigating postpartum pelvic floor outcomes. Participants were healthy, age ≥18 years, and primiparous with a singleton birth. We measured sleep duration by triaxial, wrist accelerometer (Actigraph GT3X+) and by self-report using the Pittsburgh Sleep Quality Index (PSQI). Excessive PWR was defined as ≥7% of pre-pregnancy weight. Log-binomial regression assessed the relationship between sleep duration and PWR, adjusted for pre-pregnancy body mass index, gestational weight gain, and breastfeeding. We analyzed agreement between self-reported and actigraphy-derived sleep duration using Bland-Altman analysis and paired t-test.

Results
Participants (N=467; mean age=29.5±4.78 years; pre-pregnancy BMI= 24.4±5.03 kg/m2) were mostly White (91%) and educated (93%). After adjustment, sleep duration by actigraphy (Risk Ratio (RR)=0.96, 95% confidence interval (CI)=(0.87,1.06), p=0.44,) and by PSQI (RR=0.95, 95%CI=(0.84,1.07), p=0.38) was not associated with PWR. There was a statistically significant correlation between sleep duration by actigraphy and by PSQI (r=0.19, 95% CI=(0.10,0.28), p&lt; 0.001). The limits of agreement were wide (-3.41 to 3.57 hours), and self-reported versus actigraphy-derived sleep duration was not statistically different (bias=0.08 hours, p=0.3313) indicating no pattern of underestimating or overestimating.

Conclusion
In contrast to some previous findings, sleep duration at 6 months postpartum was not associated with PWR at 12 months. The assessment of additional sleep dimensions, such as timing or efficiency, may further refine our understanding of how sleep affects PWR. Self-reported and actigraphy-derived measures of sleep duration evidenced wide discrepancies in postpartum women, suggesting that the method of sleep measurement may contribute to mixed findings related to sleep in this population.

Support (if any)