Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction.

Restless legs syndrome (RLS) affects up to 10% of older adults. Their healthcare is impeded by delayed diagnosis and insufficient treatment. To advance disease prediction and find new entry points for therapy, we performed meta-analyses of genome-wide association studies in 116,647 individuals with RLS (cases) and 1,546,466 controls of European ancestry. The pooled analysis increased the number of risk loci eightfold to 164, including three on chromosome X. Sex-specific meta-analyses revealed largely overlapping genetic predispositions of the sexes (rg = 0.96). Locus annotation prioritized druggable genes such as glutamate receptors 1 and 4, and Mendelian randomization indicated RLS as a causal risk factor for diabetes. Machine learning approaches combining genetic and nongenetic information performed best in risk prediction (area under the curve (AUC) = 0.82-0.91). In summary, we identified targets for drug development and repurposing, prioritized potential causal relationships between RLS and relevant comorbidities and risk factors for follow-up and provided evidence that nonlinear interactions are likely relevant to RLS risk prediction.

Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity.

BACKGROUND: Obstructive sleep apnea is characterized by disordered breathing during sleep and is associated with major cardiovascular complications; excess adiposity is an etiologic risk factor. Tirzepatide may be a potential treatment. METHODS: We conducted two phase 3, double-blind, randomized, controlled trials involving adults with moderate-to-severe obstructive sleep apnea and obesity. Participants who were not receiving treatment with positive airway pressure (PAP) at baseline were enrolled in trial 1, and those who were receiving PAP therapy at baseline were enrolled in trial 2. The participants were assigned in a 1:1 ratio to receive either the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or placebo for 52 weeks. The primary end point was the change in the apnea-hypopnea index (AHI, the number of apneas and hypopneas during an hour of sleep) from baseline. Key multiplicity-controlled secondary end points included the percent change in AHI and body weight and changes in hypoxic burden, patient-reported sleep impairment and disturbance, high-sensitivity C-reactive protein (hsCRP) concentration, and systolic blood pressure. RESULTS: At baseline, the mean AHI was 51.5 events per hour in trial 1 and 49.5 events per hour in trial 2, and the mean body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) was 39.1 and 38.7, respectively. In trial 1, the mean change in AHI at week 52 was -25.3 events per hour (95% confidence interval [CI], -29.3 to -21.2) with tirzepatide and -5.3 events per hour (95% CI, -9.4 to -1.1) with placebo, for an estimated treatment difference of -20.0 events per hour (95% CI, -25.8 to -14.2) (P<0.001). In trial 2, the mean change in AHI at week 52 was -29.3 events per hour (95% CI, -33.2 to -25.4) with tirzepatide and -5.5 events per hour (95% CI, -9.9 to -1.2) with placebo, for an estimated treatment difference of -23.8 events per hour (95% CI, -29.6 to -17.9) (P<0.001). Significant improvements in the measurements for all prespecified key secondary end points were observed with tirzepatide as compared with placebo. The most frequently reported adverse events with tirzepatide were gastrointestinal in nature and mostly mild to moderate in severity. CONCLUSIONS: Among persons with moderate-to-severe obstructive sleep apnea and obesity, tirzepatide reduced the AHI, body weight, hypoxic burden, hsCRP concentration, and systolic blood pressure and improved sleep-related patient-reported outcomes. (Funded by Eli Lilly; SURMOUNT-OSA ClinicalTrials.gov number, NCT05412004.).

European expert guidance on management of sleep onset insomnia and melatonin use in typically developing children.

Sleeping problems are prevalent among children and adolescents, often leading to frequent consultations with pediatricians. While cognitive-behavioral therapy has shown effectiveness, especially in the short term, there is a lack of globally endorsed guidelines for the use of pharmaceuticals or over-the-counter remedies in managing sleep onset insomnia. An expert panel of pediatric sleep specialists and chronobiologists met in October 2023 to develop practical recommendations for pediatricians on the management of sleep onset insomnia in typically developing children. When sleep onset insomnia is present in otherwise healthy children, the management should follow a stepwise approach. Practical sleep hygiene indications and adaptive bedtime routine, followed by behavioral therapies, must be the first step. When these measures are not effective, low-dose melatonin, administered 30-60 min before bedtime, might be helpful in children over 2 years old. Melatonin use should be monitored by pediatricians to evaluate the efficacy as well as the presence of adverse effects.    Conclusion: Low-dose melatonin is a useful strategy for managing sleep onset insomnia in healthy children who have not improved or have responded insufficiently to sleep hygiene and behavioral interventions.

Tirzepatide for the treatment of obstructive sleep apnea: Rationale, design, and sample baseline characteristics of the SURMOUNT -OSA phase 3 trial.

BACKGROUND: Weight reduction is a standard recommendation for obstructive sleep apnea (OSA) treatment in people with obesity or overweight; however, weight loss can be challenging to achieve and maintain without bariatric surgery. Currently, no approved anti-obesity medication has demonstrated effectiveness in OSA management. This study is evaluating the efficacy and safety of tirzepatide for treatment of moderate to severe OSA in people with obesity. METHODS: SURMOUNT-OSA, a randomized, placebo -controlled, 52-week phase 3 trial, is investigating the efficacy and safety of tirzepatide for treatment of moderate to severe OSA (apnea hypopnea- index ≥15 events/h) in participants with obesity (body mass index ≥30 kg/m2) and an established OSA diagnosis. SURMOUNT-OSA is made of 2 intervention-specific appendices (ISAs): ISA-1 includes participants with no current OSA treatment, and ISA-2 includes participants using positive airway pressure therapy. Overall, 469 participants have been randomized 1:1 to receive tirzepatide or placebo across the master protocol (ISA-1, n = 234; ISA-2, n = 235). All participants are also receiving lifestyle intervention for weight reduction. RESULTS: The primary endpoint for the individual ISAs is the difference in apnea hypopnea- index response, as measured by polysomnography, between tirzepatide and placebo arms at week 52. Secondary endpoints include sleep apnea-specific hypoxic burden, functional outcomes, and cardiometabolic biomarkers. The trial employs digital wearables, including home sleep testing to capture time to improvement and accelerometry for daily physical activity assessment, to evaluate exploratory outcomes. CONCLUSION: SURMOUNT-OSA brings a novel design to investigate if tirzepatide provides clinically meaningful improvement in obesity-related OSA by targeting the underlying etiology. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05412004.

Childhood maltreatment and sleep apnea: Findings from a cross-sectional general population study.

OBJECTIVE: Cumulative evidence indicates that childhood maltreatment (CM) is associated with sleep disturbances possibly suggesting sleep apnea. However, the relation between CM and objective measures of sleep apnea as determined by polysomnography (PSG) has not yet been assessed. METHODS: Using a cross-sectional design and based on PSG measurements from N = 962 subjects from the SHIP-Trend general population study, we used linear regression models to investigate the relationship between apnea-hypopnea (AHI) and oxygen desaturation index (ODI) and Epworth sleepiness scale (ESS) metrics and the Childhood Trauma Questionnaire (CTQ). All significant models were additionally adjusted for obesity, depression, metabolic syndrome, risky health behaviors, and socioeconomic factors. RESULTS: While both AHI and ESS were positively associated with the CTQ sum score, ODI was not. Investigating the CTQ subscales, ESS was associated with emotional abuse and emotional neglect; AHI was associated with physical and sexual abuse as well as physical neglect. For both the sum score and the subscales of the CTQ, ESS effects were partially mediated by depressive symptoms, while AHI effects were mediated by obesity, risky health behaviors, and metabolic syndrome. CONCLUSION: The findings of this general population study suggest an association between CM, particularly physical neglect, and objective as well as subjective indicators of sleep apnea, which were partially mediated by depressive symptoms and obesity.

Enhanced conductive body heat loss during sleep increases slow-wave sleep and calms the heart.

Substantial evidence suggests that the circadian decline of core body temperature (CBT) triggers the initiation of human sleep, with CBT continuing to decrease during sleep. Although the connection between habitual sleep and CBT patterns is established, the impact of external body cooling on sleep remains poorly understood. The main aim of the present study is to show whether a decline in body temperatures during sleep can be related to an increase in slow wave sleep (N3). This three-center study on 72 individuals of varying age, sex, and BMI used an identical type of a high-heat capacity mattress as a reproducible, non-disturbing way of body cooling, accompanied by measurements of CBT and proximal back skin temperatures, heart rate and sleep (polysomnography). The main findings were an increase in nocturnal sleep stage N3 (7.5 ± 21.6 min/7.5 h, mean ± SD; p = 0.0038) and a decrease in heart rate (- 2.36 ± 1.08 bpm, mean ± SD; p < 0.0001); sleep stage REM did not change (p = 0.3564). Subjects with a greater degree of body cooling exhibited a significant increase in nocturnal N3 and a decrease in REM sleep, mainly in the second part of the night. In addition, these subjects showed a phase advance in the NREM-REM sleep cycle distribution of N3 and REM. Both effects were significantly associated with increased conductive inner heat transfer, indicated by an increased CBT- proximal back skin temperature -gradient, rather than with changes in CBT itself. Our findings reveal a previously far disregarded mechanism in sleep research that has potential therapeutic implications: Conductive body cooling during sleep is a reliable method for promoting N3 and reducing heart rate.

Positive airway pressure telehealth models and long-term therapy termination: a healthcare database analysis.

Background: Telemonitoring-guided interventions can improve short-term positive airway pressure (PAP) therapy adherence, but long-term effects are unknown. This study investigated long-term PAP therapy termination in patients with sleep apnoea managed with standard care, telemonitoring-guided proactive care or telemonitoring-guided proactive care + patient engagement tool. Methods: German healthcare provider data were analysed retrospectively. Individuals aged 18-100 years who started PAP from 2014 to 2019 and had device type/interface data were included. Time-to-termination periods were analysed using Kaplan-Meier plots and Cox proportional hazards regression, adjusted for age, sex, insurance type, and device and mask type. Results: The per-protocol population (valid telemonitoring data) included 104 612 individuals (71% male; 95% aged >40 years). Mean follow-up was 3.3±2.0 years. The overall therapy termination rate was significantly lower in the telemonitoring-guided proactive care group versus standard care (20% versus 27%; p<0.001), and even lower in the telemonitoring-guided care + patient engagement tool group (11%; p<0.001 versus other treatment groups). Adjusted risk of therapy termination was lower versus standard care (hazard ratio 0.76, 95% confidence interval 0.74-0.78; and 0.41 (0.38-0.44) for telemonitoring-guided proactive care alone + patient engagement). Age <50 or >59 years and use of a nasal pillows or full-face mask were significant predictors of therapy termination; male sex, use of telemonitoring-guided proactive care (± patient engagement) and private insurance were significantly associated with lower therapy termination rates. Conclusions: Use of telemonitoring-guided proactive care and a patient engagement tool was associated with lower rates of PAP therapy termination.

Sleep characteristics and parameters of bone turnover and strength in the adult population: results from the Study of Health in Pomerania-TREND.

Poor sleep quality or sleep deprivation may be related to decreased bone mineral density. We aimed to assess whether associations of sleep characteristics and bone turnover or strength are present in adults from the general population and whether these are independent of common risk factors such as sex, age, and obesity. A total of 1037 participants from the Study of Health in Pomerania-TREND underwent laboratory-based polysomnography and quantitative ultrasound measurements at the heel. Of these participants, 804 completed standardised questionnaires to assess daytime sleepiness, insomnia, and sleep quality. Serum concentrations of two bone turnover markers, intact amino-terminal propeptide of type 1 procollagen (P1NP) and carboxy-terminal telopeptide of type 1 collagen (CTX) were measured. Cross-sectional associations of polysomnography variables (total sleep time, sleep efficiency, time spent wake after sleep onset, oxygen desaturation index, apnea-hypopnea index, and obstructive sleep apnea [OSA]), as well as sleep questionnaire scores with the bone turnover markers and the ultrasound-based stiffness index were assessed in linear regression models. In adjusted models, higher insomnia scores and lower sleep quality scores were related to a higher bone turnover in women but not in men. However, associations between polysomnography variables or questionnaire scores and the stiffness index were absent. Our study provides limited evidence for relationships between sleep characteristics and bone turnover and strength independent of common risk factors for OSA and osteoporosis. Nevertheless, women reporting poor sleep or insomnia in combination with risk factors for osteoporosis might benefit from an evaluation of bone health.

Obstructive sleep apnea heterogeneity and autonomic function: a role for heart rate variability in therapy selection and efficacy monitoring.

Obstructive sleep apnea is a highly prevalent sleep-related breathing disorder, resulting in a disturbed breathing pattern, changes in blood gases, abnormal autonomic regulation, metabolic fluctuation, poor neurocognitive performance, and increased cardiovascular risk. With broad inter-individual differences recognised in risk factors, clinical symptoms, gene expression, physiological characteristics, and health outcomes, various obstructive sleep apnea subtypes have been identified. Therapeutic efficacy and its impact on outcomes, particularly for cardiovascular consequences, may also vary depending on these features in obstructive sleep apnea. A number of interventions such as positive airway pressure therapies, oral appliance, surgical treatment, and pharmaceutical options are available in clinical practice. Selecting an effective obstructive sleep apnea treatment and therapy is a challenging medical decision due to obstructive sleep apnea heterogeneity and numerous treatment modalities. Thus, an objective marker for clinical evaluation is warranted to estimate the treatment response in patients with obstructive sleep apnea. Currently, while the Apnea-Hypopnea Index is used for severity assessment of obstructive sleep apnea and still considered a major guide to diagnosis and managements of obstructive sleep apnea, the Apnea-Hypopnea Index is not a robust marker of symptoms, function, or outcome improvement. Abnormal cardiac autonomic modulation can provide additional insight to better understand obstructive sleep apnea phenotyping. Heart rate variability is a reliable neurocardiac tool to assess altered autonomic function and can also provide cardiovascular information in obstructive sleep apnea. Beyond the Apnea-Hypopnea Index, this review aims to discuss the role of heart rate variability as an indicator and predictor of therapeutic efficacy to different modalities in order to optimise tailored treatment for obstructive sleep apnea.

Bed partner perception of CPAP therapy on relationship satisfaction and intimacy-A European perspective from the ESADA network.

Obstructive sleep apnea increases morbidity and mortality risks. The most common treatment is continuous positive airway pressure, with nasal mask usage being important, but not always optimal. While most research on treatment adherence focuses on the patient, the bed partner's involvement may be detrimental. Our study aim is to obtain a European-wide picture of the bed partner's attitude and support towards continuous positive airway pressure therapy, including effects on relationship satisfaction and intimacy. The English translation of a German bed partner questionnaire, assessing relationship satisfaction and three major components (general attitude, perceived mask looks, intimacy effects) was distributed within the European Sleep Apnea Database Network and translated in participating countries' local language. Data were collected for 2 years. In total, 10 European countries (13 sleep centres) participated with 1546 questionnaires. Overall, 91% of bed partners had a positive attitude towards continuous positive airway pressure therapy, 86% perceived mask looks not negative, 64% stated no negative intimacy effects. More specifically, 71% mentioned improved sleep quality, 68% supported nightly device usage. For 41% of bed partners, relationship satisfaction increased (no change for 47%). These results were significantly more pronounced in Eastern/Southern Europe compared with Middle Europe, especially regarding intimacy effects. However, increased continuous positive airway pressure therapy length affected attitude negatively. These results provide necessary information to improve treatment strategies by including educational couple-focused approaches. Among others, we revealed that negative intimacy effects are not considered a barrier to continuous positive airway pressure adherence. These results may inspire more research identifying regional gaps with need for treatment adjustments.

Clinical Applicability of Ultrasound Shear Wave Elastography in Patients under Hypoglossal Nerve Stimulation Therapy.

Relationship between stiffness of genioglossi (GG) and geniohyoidei (GH) muscles under electric hypoglossal nerve stimulation therapy (HNS) in relation to success of therapy was investigated with additional special focus on tongue movement. PATIENTS AND METHODS: Clinical and sleep laboratory parameters of a cohort of 18 patients with known shear wave velocity (SWV) data of the ipsilateral and contralateral musculi GG and GH (sGG, sGH and nGG, nGH) before and under HNS therapy were analyzed. The SWV was already determined using the ultrasonic shear wave elastography (US-SWE) technique. RESULTS: Median Epworth Sleepiness Scale (ESS) was 8 (IQR 12), median baseline Apnoe-Hypopnoe Index (AHI) 31.65 (IQR 25.1), median AHI under HNS therapy 16.3 (IQR 20.03). Therapy success: 9/18 patients (AHI during therapy < 15/h). There was no significant difference in SWV (sGG, sGH, nGG and nGH) between therapy responders and non-responders during therapy. Also, no difference could be seen with respect to the difference and increase in SWV values without and with stimulation. Examination of SWV values (sGG, sGH, nGG, nGH during stimulation, difference of SWV values stimulation - no stimulation, increase factor of SWV) revealed a significant negative correlation between the AHI under therapy and the measured SWV of the musculus GH of the contralateral side during stimulation (-0.622, p = 0.006). Patients with bilateral protrusion of the tongue differed regarding to therapy success in increase in SWV in sGG (p = 0.032). Tongue protrusion to contralateral: A significant difference between patients with AHI during therapy < 15/h in SWV values at sGG without stimulation (p = 0.021) was seen, with also a correlation to the current AHI under therapy (p = 0.047) and the change factor of the AHI (p = 0.015). CONCLUSION: Stiffness of the target muscle does not appear to be an isolated measure of the success of HNS therapy. This observation may have implications for future decision-making processes in the process of titrating electrical therapy parameters. But the technique of US-SWE may be useful for future research of the neurophysiology of the tongue and OSA phenotyping.

Polysomnographic characteristics of sleep in adults with and without physician-diagnosed atopic dermatitis: results from the Study of Health in Pomerania.

PURPOSE: To analyze sleep characteristics as measured with polysomnography (PSG) in adults from the general population with and without physician-diagnosed atopic dermatitis (AD). METHODS: We analyzed data from participants from the German population-based Study of Health in Pomerania (SHIP) TREND-0. AD was diagnosed in a standardized skin examination. The following polysomnographic parameters were measured: total sleep duration (min), sleep latency (min), wake after sleep onset (WASO; min), rapid eye movement (REM) latency (min), sleep efficiency (%), total number of wakefulness and movement episodes, stages of sleep (%), and apnea-hypopnea index (AHI). Additionally, the subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). We compared sleep characteristics of participants with and without AD. RESULTS: Among 1187 participants, 47 (4.0%) had AD. We found no differences between participants with and without AD in any of the analyzed PSG parameters except for the total number of wakefulness and movement episodes and the percentage of REM sleep. Participants with AD had a higher number of wakefulness and movement episodes, and a lower proportion of REM sleep compared to those without AD. Regarding subjective sleep parameters, no significant differences were found between participants with and without AD. CONCLUSION: Our data do not provide evidence for poor sleep quality in individuals with AD. Major limitations of the study include the unavailability of data on AD severity and the small number of participants with AD. Larger-scaled longitudinal studies considering disease severity and specific AD symptoms with an effect on sleep are required.

Nocturnal positive pressure ventilation improves relationship satisfaction of patients with OSA and their partners.

OBJECTIVE: Continuous positive airway pressure (CPAP) ventilation is considered the therapeutic standard for obstructed sleep apnea (OSA). Therapy success may also be affected by the patient's bed partner. A questionnaire was developed and tested that measures the attitude of the bed partner towards CPAP therapy and relationship effects. METHODS: A new questionnaire to capture bed partners' attitude towards CPAP mask therapy was used with an anonymous sample of 508 bed partners. Possible constructs underlying the attitude of the bed partner towards mask appearance have been investigated by means of a Principal Components Analysis. RESULTS: The survey revealed bed partners' positive attitude towards their partner's CPAP therapy (over 90% of bed partners were happy with the therapy, over 75% would recommend the therapy). Importantly, the bed partners' satisfaction with the relationship increased significantly during CPAP therapy (before therapy: 49% were satisfied, after therapy initiation: 70%; p<.001). There was a strong correlation between support for CPAP therapy and improved sleep quality of bed partners (r = 0.352, p>.001). Furthermore, the validation of the questionnaire through principal components analysis revealed three major factors: Attitude (of the bed partner towards CPAP therapy), Looks (of the mask perceived by the bed partner), Intimacy (effect of CPAP therapy on relationship and intimacy). CONCLUSION: Both, the OSA patient and the bed partner benefit from CPAP therapy. This is the first bed partner questionnaire - interviewing the bed partner alone and anonymously - that showed that CPAP therapy also positively influences the relationship. We recommend that the bed partner be involved in the CPAP treatment from the start of therapy.

Effect of phrenic nerve stimulation on patients with central sleep apnea: A meta-analysis.

Patients with central sleep apnea (CSA) have a lower quality of life and higher morbidity and mortality. Phrenic nerve stimulation (PNS) is a novel treatment for CSA that has been shown to be safe. However, the effects of PNS on sleep changes are still under debate. This meta-analysis was performed to evaluate the efficacy of PNS in patients with CSA. PubMed, Scopus, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and Web of Science databases were searched for relevant studies published. We performed random-effects meta-analyses of the changes in apnea-hypopnea index (AHI), central apnea index (CAI), Arousal Index, percent of sleep with O2 saturation <90% (T90), Epworth Sleepiness Scale (ESS) and sleep efficiency. Ten studies with a total of 580 subjects were analyzed. Overall meta-analysis showed AHI [SMD: -2.24, 95% confidence interval (CI): was -3.11 to -1.36(p＜0.00001)], CAI [SMD: -2.32, 95% CI: -3.17 to -1.47 (p＜0.00001)] and Arousal Index (p = 0.0002, SMD (95% CI) -1.79 (-2.74 to -0.85)) significantly reduced after PNS. No significant changes were observed in T90, ESS and sleep efficiency (p > 0.05). Meta-analysis of observational studies demonstrated AHI, CAI and Arousal Index had a decreasing trend between before and after PNS (all, p＜0.05). However, ESS and T90 did not change significantly after PNS (p > 0.05). Meta-analysis of RCTs showed that CSA patients had trends of a lower AHI (I2 = 0%), CAI (I2 = 74%), Arousal Index (I2 = 0%), T90 (I2 = 0%) and ESS (I2 = 0%) after PNS (all, p＜0.05). The use of PNS appears to be safe and feasible in patients with CSA. However, larger, independent RCTs are required to investigate the efficacy and long-term effect of PNS and more attention should be paid to T90 and ESS.

Comparative study of the SleepImage ring device and polysomnography for diagnosing obstructive sleep apnea.

Purpose We aim to evaluate the diagnostic performance of the SleepImage Ring device in identifying obstructive sleep apnea (OSA) across different severity in comparison to standard polysomnography (PSG). Methods Thirty-nine patients (mean age, 56.8 ± 15.0 years; 29 [74.3%] males) were measured with the SleepImage Ring and PSG study simultaneously in order to evaluate the diagnostic performance of the SleepImage device for diagnosing OSA. Variables such as sensitivity, specificity, positive and negative likelihood ratio, positive and negative predictive value, and accuracy were calculated with PSG-AHI thresholds of 5, 15, and 30 events/h. Receiver operating characteristic curves were also built according to the above PSG-AHI thresholds. In addition, we analyzed the correlation and agreement between the apnea-hypopnea index (AHI) obtained from the two measurement devices. Results There was a strong correlation (r = 0.89, P < 0.001 and high agreement in AHI between the SleepImage Ring and standard PSG. Also, the SleepImage Ring showed reliable diagnostic capability, with areas under the receiver operating characteristic curve of 1.00 (95% CI, 0.91, 1.00), 0.90 (95% CI, 0.77, 0.97), and 0.98 (95% CI, 0.88, 1.000) for corresponding PSG-AHI of 5, 15 and 30 events/h, respectively. Conclusion The SleepImage Ring could be a clinically reliable and cheaper alternative to the gold standard PSG when aiming to diagnose OSA in adults. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-023-00304-9.

The Beginning of the AI-Enabled Preventative PAP Therapy Era: A First-in-Human Proof of Concept Interventional Study.

Positive Airway Pressure (PAP) therapy is the most common and efficacious treatment for Obstructive Sleep Apnea (OSA). However, it suffers from poor patient adherence due to discomfort and may not fully alleviate all adverse consequences of OSA. Identifying abnormal respiratory events before they have occurred may allow for improved management of PAP levels, leading to improved adherence and better patient outcomes. Our previous work has resulted in the successful development of a Machine-Learning (ML) algorithm for the prediction of future apneic events using existing airflow and air pressure sensors available internally to PAP devices. Although researchers have studied the use of ML for the prediction of apneas, research to date has focused primarily on using external polysomnography sensors that add to patient discomfort and has not investigated the use of internal-to-PAP sensors such as air pressure and airflow to predict and prevent respiratory events. We hypothesized that by using our predictive software, OSA events could be proactively prevented while maintaining patients' sleep quality. An intervention protocol was developed and applied to all patients to prevent OSA events. Although the protocol's cool-down period limited the number of prevention attempts, analysis of 11 participants revealed that our system improved many sleep parameters, which included a statistically significant 31.6% reduction in Apnea-Hypopnea Index, while maintaining sleep quality. Most importantly, our findings indicate the feasibility of unobtrusive identification and unique prevention of each respiratory event as well as paving the path to future truly personalized PAP therapy by further training of ML models on individual patients.

Effects of sleep fragmentation and partial sleep restriction on heart rate variability during night.

We developed a cross-over study design with two interventions in randomized order to compare the effects of sleep fragmentation and partial sleep restriction on cardiac autonomic tone. Twenty male subjects (40.6 ± 7.5 years old) underwent overnight polysomnography during 2 weeks, each week containing one undisturbed baseline night, one intervention night (either sleep restriction with 5 h of sleep or sleep fragmentation with awakening every hour) and two undisturbed recovery nights. Parameters of heart rate variability (HRV) were used to assess cardiac autonomic modulation during the nights. Sleep restriction showed significant higher heart rate (p = 0.018) and lower HRV-pNN50 (p = 0.012) during sleep stage N1 and lower HRV-SDNN (p = 0.009) during wakefulness compared to the respective baseline. For HR and SDNN there were recovery effects. There was no significant difference comparing fragmentation night and its baseline. Comparing both intervention nights, sleep restriction had lower HRV high frequency (HF) components in stage N1 (p = 0.018) and stage N2 (p = 0.012), lower HRV low frequency (LF) (p = 0.007) regarding the entire night and lower SDNN (p = 0.033) during WASO during sleep. Sleep restriction increases sympathetic tone and decreases vagal tone during night causing increased autonomic stress, while fragmented sleep does not affect cardiac autonomic parameters in our sample.

Effects of mindfulness meditation and Acceptance and commitment therapy in patients with obstructive sleep apnea with residual excessive sleepiness: A randomized controlled pilot study.

OBJECTIVE: Assessing the effects of Mindfulness-Based Stress Reduction (MBSR) on symptoms of OSA, especially on the primary outcome, excessive daytime sleepiness (EDS). METHODS: Parallel randomized controlled trial. 16 OSA patients with residual EDS (rEDS) were randomized and assigned to either a standardized 8-week MBSR program or a time-matched program on Acceptance and Commitment Therapy (ACT). Both programs were conducted online. Participants answered questionnaires online at baseline (pre), post-intervention (post), three months after the intervention (follow-up) and were blinded to whether their group was the treatment or active control group but not to group allocation (partial blinding). Three participants dropped out early. Most analyses are based on the remaining 13 patients. RESULTS: There was a significant difference between the MBSR (n = 7) and ACT group (n = 6) in changes of EDS between pre and post (Cohen's d = 1.24, CI [0.01, 2.42]) and a significant reduction of EDS for patients in the ACT group at post (Cohen's d = 1.18 and [0.08, 2.22]). This EDS reduction averaging 2.17 points on the Epworth Sleepiness Scale reached the prespecified bar for clinical significance of two points on that scale. Insomnia symptoms, a secondary outcome, reduced significantly following ACT (Cohen's d = 1.43 [0.23, 2.58]). In MBSR, both participants and the MBSR-trainer judged movement-based exercises to be most efficacious. CONCLUSION: ACT shows potential as adjunctive therapy for OSA with rEDS, although further studies are needed. It seems promising to develop therapeutic approaches for OSA with rEDS using ACT, especially if they are tailored to the needs specific to this patient group. TRIAL REGISTRATION: https://www.drks.de; Identifier: DRKS00026812.

Menopause Is Associated with Obstructive Sleep Apnea in a Population-Based Sample from Mecklenburg-Western Pomerania, Germany.

Objective: Menopause is associated with multiple health risks. In several studies, a higher incidence or a higher risk for obstructive sleep apnea (OSA) in post-menopausal than pre-menopausal women is reported. This study was designed to verify such a connection between menopause and OSA in a population-based sample. Methods: For a subsample (N = 1209) of the Study of Health in Pomerania (N = 4420), complete polysomnography data was available. Of these, 559 females completed a structured interview about their menstrual cycle. Splines and ordinal regression analysis were used to analyze the resulting data. Results: In the ordinal regression analysis, a significant association between the apnea-hypopnea index (AHI) and menopause indicated that post-menopausal women had a substantially higher risk of OSA. In accordance with previous studies, risk indicators such as body mass index (BMI), age, and the influence of hysterectomies or total oophorectomies were included in the model. Conclusions: Our results clearly confirmed the assumed connection between menopause and OSA. This is important because OSA is most often associated with male patients, and it warrants further research into the underlying mechanisms.

Impact of Gender on Insomnia.

There is a distinct preponderance of female insomniacs when compared to male insomniacs. The aim of this study was to examine possible gender differences in the causes for insomnia, and the phenotypes of insomnia, and to investigate whether gender-specific insomnia diagnosis and treatment could be relevant in clinical practice. Data were collected from 121 insomniac patients by a medical specialist in the framework of normal clinical practice in Germany. The data consist of the patient's medical history and various sleep-related patient questionnaires. Data from both genders were tested for independence using chi-square tests and Mann-Whitney U tests. We found a correlation between the gender of the patient and insomnia phenotypes in several aspects: concomitant lipometabolic disorders, diabetes mellitus, and high BMIs are more common in male insomniacs (p < 0.05). Frequency of insomnia occurrence in certain age groups, insomnia severity, distribution of SOI (sleep onset insomnia), SMI (sleep maintenance insomnia) and combined SOI + SMI, sleep duration, the time needed to seek medical consultation, trying out sleep-inducing drugs/techniques and the trigger, etiology and familial predisposition of the insomniac disorder were independent of the patient's gender. We would like to re-evaluate the results with a larger number of patients in a further study.