Development and Reporting of Prediction Models: Guidance for Authors From Editors of Respiratory, Sleep, and Critical Care Journals.

Prediction models aim to use available data to predict a health state or outcome that has not yet been observed. Prediction is primarily relevant to clinical practice, but is also used in research, and administration. While prediction modeling involves estimating the relationship between patient factors and outcomes, it is distinct from casual inference. Prediction modeling thus requires unique considerations for development, validation, and updating. This document represents an effort from editors at 31 respiratory, sleep, and critical care medicine journals to consolidate contemporary best practices and recommendations related to prediction study design, conduct, and reporting. Herein, we address issues commonly encountered in submissions to our various journals. Key topics include considerations for selecting predictor variables, operationalizing variables, dealing with missing data, the importance of appropriate validation, model performance measures and their interpretation, and good reporting practices. Supplemental discussion covers emerging topics such as model fairness, competing risks, pitfalls of "modifiable risk factors", measurement error, and risk for bias. This guidance is not meant to be overly prescriptive; we acknowledge that every study is different, and no set of rules will fit all cases. Additional best practices can be found in the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines, to which we refer readers for further details.

The utility of patient-completed and partner-completed Epworth Sleepiness Scale scores in the evaluation of obstructive sleep apnea.

PURPOSE: Excessive daytime sleepiness in obstructive sleep apnea (OSA) is often rated differently by patients and their partners. This cross-sectional study compared the utility of patient-completed and partner-completed Epworth Sleepiness Scale (ESS) scores in the evaluation of suspected OSA. METHODS: Eighty-five patient-partner pairs were enrolled, and 75 patients completed diagnostic sleep studies. The individual and combined utilities of patient-completed and partner-completed ESS scores in identifying OSA and predicting various sleep study-derived indicators of disease severity were determined. RESULTS: Mean partner-completed ESS scores were higher than patient-completed ESS scores (12.3 ± 4.2 vs. 9.4 ± 4.8, p < 0.0001); Bland-Altman plot showed significant bias (partner-completed ESS scores 33.5 % higher, SD ±55.2 %). Partner-completed and combined (but not patient-completed) ESS scores correlated weakly with the apnea-hypopnea index (AHI; partner-completed ESS score r s  = 0.25, p = 0.029; combined ESS score r s  = 0.29, p = 0.013) and oxygen desaturation index (partner-completed ESS score r s  = 0.26, p = 0.025; combined ESS score r s  = 0.23, p = 0.047). None of the ESS scores correlated with body mass index, arousal index, or other parameters of nocturnal oxygen desaturation. In OSA (AHI > 15/h) detection, partner-completed ESS scores had greater sensitivity than patient-completed ESS scores (76.9 vs. 46.2 %) but poorer specificity (39.1 vs. 65.2 %); sensitivity was greatest (82.7 %) when either patient-completed or partner-completed ESS score was 10 or higher, and specificity was greatest (80.8 %) when both scores were 10 or higher. CONCLUSIONS: Neither patient-completed nor partner-completed ESS scores by themselves have great utility in identifying OSA or predicting its severity. However, taking both scores into consideration together improves the sensitivity and specificity of the screening process.

The impact of Sleep Time-Related Information and Communication Technology (STRICT) on sleep patterns and daytime functioning in American adolescents.

This cross-sectional study explored the extent and impact of mobile device-based Sleep Time-Related Information and Communication Technology (STRICT) use among American adolescents (N = 3139, 49.3% female, mean age = 13.3 years). Nearly 62% used STRICT after bedtime, 56.7% texted/tweeted/messaged in bed, and 20.8% awoke to texts. STRICT use was associated with insomnia, daytime sleepiness, eveningness, academic underperformance, later bedtimes and shorter sleep duration. Moderation analysis demonstrated that the association between STRICT use and insomnia increased with age, the association between STRICT use and daytime sleepiness decreased with age, and the association between STRICT use and shorter sleep duration decreased with age and was stronger in girls. Insomnia and daytime sleepiness partially mediated the relationship between STRICT use and academic underperformance. Our results illustrate the adverse interactions between adolescent STRICT use and sleep, with deleterious effects on daytime functioning. These worrisome findings suggest that placing reasonable limitations on adolescent STRICT use may be appropriate.

Sleep and Parkinson's disease: a review of case-control polysomnography studies.

The link between Parkinson's disease (PD) and certain primary sleep disorders has yet to be clarified. We performed a systematic review of case-control polysomnography studies to evaluate the relationship between PD and sleep disorders. A PubMed literature search and bibliography review yielded 15 case-control polysomnography studies in patients with PD. Studies differed by recruitment methods, duration of polysomnography monitoring, and sleep parameters measured. Subjective sleepiness was greater in patients than controls (50%-66% vs 2.9%-12%) despite lack of objective increase in daytime sleepiness by mean sleep latency testing. The 4 case-control polysomnography studies investigating rapid eye movement behavior disorder support a higher prevalence in PD (0%-47% vs 0%-1.8% in controls), although differences in diagnostic criteria hamper interpretation. The preponderance of evidence did not support an increased incidence of obstructive sleep apnea (27%-60% vs 13%-65%) or periodic leg movements of sleep in patients compared to controls. Adequately powered, prospective studies with uniform methodology and healthy controls are needed to further address the association and pathophysiological significance between PD and sleep problems.

Increasing off-time improves sleep-disordered breathing induced by vagal nerve stimulation.

Vagal nerve stimulation (VNS) has been reported to adversely impact breathing in sleep. While continuous positive airway pressure is often employed to treat these patients, little data exist on the effects of adjusting various settings on VNS-induced sleep-disordered breathing. We describe a patient in whom increasing off-time caused resolution of VNS-induced arterial oxygen desaturations in sleep, which we believe is a novel observation.

Sleep disorders and COVID-19.

This chapter summarizes the known associations between COVID-19 and sleep dysfunction, including insomnia, excessive daytime sleepiness, restless legs syndrome and nightmares, and touches upon pandemic-related considerations for obstructive sleep apnea and continuous positive airway pressure treatment. Treatment strategies and management approaches are also briefly discussed.

Long-term management issues in restless legs syndrome.

Restless legs syndrome is a neurologic movement and sleep disorder with lifelong symptoms causing considerable morbidity. Several short-term and some long-term open-label and double-blind clinical trials have demonstrated the efficacy and safety of dopaminergic treatment in restless legs syndrome. Long-term treatment, however, is associated with the emergence of vexing long-term side effects that pose a challenge for physicians. These long-term complications can be broadly categorized as disease-related (impact on sleep and acute exacerbation of restless legs syndrome symptoms), and medication issues (augmentation, sleep attacks, impulse control disorders, addiction and dependence, site reaction, occasionally sleep apnea, fibrotic complications, and weight gain).

Sleep and neurodegenerative diseases.

Sleep disturbances are common in neurodegenerative diseases. Disturbed sleep can result in fatigue, irritability, morning headaches, impaired motor and cognitive skills, depression, and daytime somnolence. The major sleep complaints include insomnia, hypersomnia, parasomnia, excessive nocturnal motor activity, circadian sleep-wake rhythm disturbance, and respiratory dysrhythmia. The pathogenetic mechanisms of sleep disturbances may be secondary to direct structural alteration of the sleep-wake generating neurons or from several other indirect mechanisms. At the biochemical level, neurodegenerative diseases may be largely classified as tauopathies, alpha-synucleinopathies, and other diseases. Overnight polysomnography (PSG), Multiple Sleep Latency Test, Maintenance of Wakefulness Test, and actigraphy are some important diagnostic laboratory tests in the evaluation of sleep disturbances. Management of sleep disturbances is complex and is based primarily on the nature of the sleep disturbance. The clinical profiles, pathogenetic mechanisms, PSG findings, and management issues are discussed here with reference to some common neurodegenerative diseases.

The relationships between improvements in daytime sleepiness, fatigue and depression and psychomotor vigilance task testing with CPAP use in patients with obstructive sleep apnea.

OBJECTIVE: The purpose of this study was to determine if the subjective improvements in daytime sleepiness, fatigue and depression experienced by patients with obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) therapy predict an objective improvement in vigilance, and whether patients with mild-to-moderate OSA differ from patients with severe OSA in this regard. METHODS: A total of 182 patients underwent psychomotor vigilance task (PVT) testing and measurements of subjective daytime sleepiness, fatigue and depression at baseline and after a minimum of one month of adherent CPAP use at an adequate pressure. RESULTS: Patients with both mild-to-moderate (n = 92) and severe (n = 90) OSA experienced improvements in subjective daytime sleepiness, fatigue and depression, but objective improvement in vigilance was only seen in patients with severe OSA. In patients with severe OSA, while a correlation was found between improvements in daytime sleepiness and some PVT parameters, changes in subjective daytime sleepiness, fatigue and depression scores were not predictive of objective improvement in vigilance while controlling for all these subjective symptoms and for age, gender, body mass index, apnea-hypopnea index/respiratory event index and total sleep time/total recording time with pulse oximetry below 90%. CONCLUSIONS: We found no predictive relationship between subjective improvements in daytime sleepiness, fatigue and depression and objective vigilance with CPAP use in patients with OSA. These results suggest that subjective complaints of daytime impairment and objective measures of vigilance in patients with OSA should be assessed separately while evaluating the efficacy of CPAP therapy on daytime functioning.

Rise of blood pressure with periodic limb movements in sleep and wakefulness.

OBJECTIVE: To measure changes in blood pressure and pulse rate associated with periodic limb movements in sleep (PLMS) in patients with restless legs syndrome (RLS). METHODS: We measured autonomic activation as indicated by a rise in blood pressure and pulse rate during periodic limb movements in sleep (PLMS) in 8 patients (6 women average age 57.6+/-16.5 yr and 2 men average age 34+/-28 yr) with RLS. The patients had overnight polysomnographic (PSG) recordings with continuous monitoring of blood pressure (BP) and heart rate (HR). The patients were asked to perform voluntary movements mimicking PLMS (Fake PLMS) which served as controls for PLMS during PSG. We analyzed 601 movements: 145 periodic limb movements in wakefulness (PLMW), 173 periodic limb movements in sleep with cortical arousal (PLMSA), 168 periodic limb movements in sleep without cortical arousal (PLMSNA) and 115 respiratory related limb movements (RRLM). RESULTS: There was a statistically significant rise in systolic blood pressure (SBP), diastolic blood pressure (DBP) after PLMW (SBP 11.7+/-7.6 mm Hg), PLMSA (SBP 16.7+/-9.4 mm Hg), PLMSNA (SBP 11.2+/-8.7 mm Hg) and RRLM (SBP 18.9+/-14.9 mm Hg) which exceeded that seen with Fake PLMS (SBP 3.2+/-3.1 mm Hg) in wakefulness. There were comparable increases in heart rate that did not quite reach statistical significance. CONCLUSIONS: There is a rise in SBP, DBP and HR with PLMW, PLMSNA, PLMSA and RRLM as compared to Fake PLMS. SIGNIFICANCE: One possibility is that the concomitant rise in the blood pressure and heart rate after periodic limb movements indicating autonomic activation may have long-term adverse cardiovascular consequences. This remains to be determined in future experiments.

Hypersomnia in Neurodegenerative Diseases.

Hypersomnia is a common complaint in many patients with neurodegenerative diseases and a major cause of decreased quality of life. This article discusses the prevalence and factors associated with hypersomnia in patients with a variety of neurodegenerative diseases affecting the central nervous system, including tauopathies, synucleinopathies, and other conditions. Common nocturnal sleep problems that may result in daytime hypersomnia are delineated. A clinical approach to hypersomnia in patients with neurodegenerative diseases, recommended diagnostic testing, and available treatment options are also discussed.

The National Sleep Foundation's Sleep Health Index.

OBJECTIVES: A validated survey instrument to assess general sleep health would be a useful research tool, particularly when objective measures of sleep are not feasible. Thus, the National Sleep Foundation spearheaded the development of the Sleep Health Index (SHI). DESIGN: The development of the SHI began with a task force of experts who identified key sleep domains and questions. An initial draft of the survey was created and questions were refined using cognitive testing and pretesting. The resulting 28-question survey was administered via random-sample telephone interviews to nationally representative samples of adults in 2014 (n=1253) and 2015 (n=1250). These data were combined to create the index. A factor analysis linked 14 questions to 3 discrete domains: sleep quality, sleep duration, and disordered sleep. These were assembled as sub-indices, then combined to form the overall SHI, with scores ranging from 0 to 100 (higher score reflects better sleep health). RESULTS: Americans earned an overall SHI score of 76/100, with sub-index scores of 81/100 in disordered sleep, 79/100 in sleep duration, and 68/100 in sleep quality. In regression analyses, the strongest independent predictors of sleep health were self-reported stress (ß=-0.26) and overall health (ß=0.26), which were also the strongest predictors of sleep quality (ß=-0.32 and ß=0.27 respectively). CONCLUSIONS: The current 12-item SHI is a valid, reliable research tool that robustly measures 3 separate but related elements of sleep health-duration, quality, and disorders-and assesses the sleep health status of adults in the United States.

Respiratory and autonomic dysfunction in children with autism spectrum disorders.

INTRODUCTION: Cardiac parasympathetic hypofunction has been reported in autism spectrum disorders (ASD). This usually is linked to respiratory dysrhythmia which has been documented in some children with ASD. OBJECTIVES: This study evaluated the cardiorespiratory functions in ASD to elucidate the physiologic basis of behaviors. METHODS: Nineteen children with ASD and 18 age matched controls underwent autonomic function monitoring at a defined resting state using the NeuroScope. The non-invasive real time beat-to-beat blood pressure was measured by Portapres and fed into the NeuroScope where heart rate, cardiac vagal tone and cardiac sensitivity to baroreceptor were derived from the EKG and blood pressure waveforms using the Vagosoft software; and respiratory rate and rhythm were measured simultaneously by plethysmograph. Respiration was analyzed breath by breath using our prior published methods. RESULTS: Various respiratory dysrhythmias, particularly Biot's and Cheyne-Stokes respiration, were detected in children with ASD, who also exhibited greater variability in respiratory rhythm and amplitudes than controls. The respiratory dysrhythmia in children with ASD was associated with a lower cardiac vagal activity. CONCLUSION: The Biot's breathing and Cheyne-Stokes respiration coupled with cardiac vagal hypofunction in ASD suggest a brainstem dysfunction consistent with our previous findings. The low parasympathetic activity could explain in part the chronic sensory hyperarousal state in children with ASD.

Brainstem hyperexcitability during cataplexy.

The exact cause of narcolepsy-cataplexy syndrome remains unclear; however, the recent discovery of hypocretin deficiency in the lateral hypothalamus of narcoleptic patients has increased our understanding of its etiology. The authors performed masseter reflex, tibial F response, and blink reflex excitability studies during and between attacks in a 66-year-old man with status cataplecticus. Masseter reflex and F responses were inhibited while the blink reflex R2 component was enhanced during attacks, suggesting either hyperexcitability or disinhibition of pontine and/or medullary interneurons but hypoexcitability of pontine and spinal motor neurons during cataplexy.