The latest medical research on Sleep Medicine

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about sleep medicine gathered by our medical AI research bot.

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Combination CPAP and bilateral hypoglossal nerve stimulation for obstructive sleep apnea in Treacher Collins syndrome: first case report.

J Clin Sleep

We report the first case of bilateral hypoglossal nerve stimulator implantation in a patient with Treacher Collins syndrome and very severe obstruc...

Impact of adenotonsillectomy on growth trajectories in preschool children with mild-moderate obstructive sleep apnea.

J Clin Sleep

Adenotonsillectomy (AT) forms part of first-line management for pediatric obstructive sleep apnea (OSA). In non-randomized studies of preschool-aged children, postoperative weight gain has been seen following AT, raising concerns regarding later obesity. Using longitudinal data from a multicenter randomized controlled trial (RCT), we assessed the impact of AT on growth trajectories in preschool-aged children with mild-moderate OSA.

A total of 190 children (aged 3-5 years) with obstructive apnea hypopnea index ≤10 per hour were randomly assigned to early (within 2 months) or routine (12-month wait) AT. Anthropometry and PSG were performed at baseline, 12-month and 24-month timepoints for 126 children. Baseline characteristics were compared using a Mann-Whitney or t-test for continuous variables, and Fisher's exact test for categorical variables. Longitudinal data underwent linear mixed modelling.

For BMI z-score, there was a significant increase in the early surgery group between 0 and 12 months (0.4, 95% CI 0.1-0.8) but not from 12-24 months. For the routine surgery group, there was an identical significant BMI z-score increase in the first 12 months following surgery ie. between 12 and 24 month timepoints (0.45, 95% CI 0.1-0.8), but not from 0-12 months (pre-operative time). Final BMI z-score was similar between groups. Findings for weight-for-age z-score were similar to the findings for BMI z-score. Height-for-age z-score was not significantly different between different timepoints or intervention groups.

This study provides RCT evidence of notable, but time-limited, increase in the BMI and weight of preschool children with mild-moderate OSA in the months immediately following AT.

Registry: Australian and New Zealand Clinical Trials Registry; Trial name: POSTA Child Study (Preschool Obstructive Sleep Apnea Tonsillectomy Adenoidectomy Study); Identifier: ACTRN12611000021976.

The norepinephrine reuptake inhibitor reboxetine alone reduces obstructive sleep apnea severity: a double blind, placebo controlled, randomized, cross-over trial.

J Clin Sleep

Recent findings indicate that noradrenergic and muscarinic processes are crucial for pharyngeal muscle control during sleep. However, to date, reductions in obstructive sleep apnea (OSA) severity have only been detected when noradrenergic agents are combined with an antimuscarinic. Accordingly, this study aimed to determine if reboxetine alone and combined with oxybutynin reduces OSA severity. The pathophysiological mechanisms underpinning the effects of these agents were also investigated via endotyping analysis.

16 people (6 women) with OSA completed three polysomnograms (∼1-week washout) according to a double-blind, placebo-controlled, three-way crossover design across two sites. Single doses of 4 mg reboxetine, placebo, or 4 mg reboxetine+5 mg oxybutynin were administered before sleep (order randomized).

Reboxetine reduced the apnea-hypopnea index (AHI-primary outcome) by 5.4 [95% CI -10.4 to -0.3] events/h, P=0.03 (-24 ± 27% in men; -0.7 ± 32% in women). Oxybutynin did not cause additional reductions in AHI. Reboxetine alone reduced the 4% oxygen desaturation index by (mean ± SD) 5.2 ± 7.2 events/h and reboxetine+oxybutynin by 5.1 ± 10.6 events/h versus placebo, P=0.02. Nadir oxygen saturation also increased by 7 ± 11% with reboxetine and 5 ± 9% with reboxetine+oxybutynin versus placebo, P=0.01. Mechanistically, reboxetine and reboxetine+oxybutynin improved pharyngeal collapsibility and respiratory control (loop gain). Larger reductions in AHI with reboxetine in men were associated with higher baseline loop gain.

These findings show the first evidence that reboxetine alone reduces OSA severity. The data provide novel insight into the role of norepinephrine reuptake inhibitors on upper airway stability during sleep and are important to inform future pharmacotherapy development for OSA.

Registry: Australian New Zealand Clinical Trials Registry; Trial name: Reboxetine and combination therapy with AD128 in sleep apnoea trial: A double-blind, 3-way cross-over study; Identifier: ACTRN12620000662965; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374614&isReview=true.

Validation of STOP, STOP-BANG, STOP-BAG, STOP-B28 and GOAL screening tools for identification of obstructive sleep apnea in patients with Parkinson disease.

J Clin Sleep

Obstructive sleep apnea (OSA) is common in Parkinson disease (PD). Questionnaires can be used as screening tools, and have been used as a surrogate definition of OSA in large-scale research. This study aimed to validate the performance of STOP, STOP-BANG, STOP-BAG, STOP-B28 and GOAL and OSA predictors as tools to identify OSA in PD.

Data were analyzed from a PD cohort study in which OSA was diagnosed using laboratory polysomnography (PSG). We calculated sensitivity and specificity of each questionnaire for OSA using different definitions, and performed ROC curve analysis. Linear regression was used to assess adjusted associations between questionnaires and outcomes: Montreal Cognitive Assessment (MOCA), Epworth Sleepiness Scale (ESS), and PD severity (MDS-UPDRS).

Questionnaire data were available for 68 PD patients (61.8% male, mean age 64.5 (SD 9.9) years, and Hoehn & Yahr score 2.1 (0.8)). OSA (apnea-hypopnea index ≥ 15 events/h) occurred in 69.4% of participants. STOP-B28 ≥ 2 presented a higher sensitivity for OSA than STOP ≥ 2 (0.76 vs. 0.65, respectively) and slightly lower specificity (0.65 vs. 0.70, respectively). GOAL ≥ 2 had the highest sensitivity but poor specificity. Loud snoring had sensitivity 0.63 and specificity 0.65. STOP and snoring were significantly associated with MOCA, ESS, and MDS-UPDRS (total, motor and non-motor); STOP-BANG, STOP-BAG and STOP-B28 showed associations with most outcomes but the GOAL showed none.

The STOP-B28, followed by STOP and presence of loud snoring alone, seem to have the best overall properties to identify PD patients with OSA, whose clinical characteristics differ from the general population with OSA.

Analysis of sleep, daytime sleepiness and autonomic function and multiple system atrophy and Parkinson disease: a prospective study.

J Clin Sleep

Sleep disorders, daytime sleepiness and autonomic dysfunction are commonly reported among patients with multiple system atrophy (MSA) and Parkinson disease (PD). We aimed to assess sleep and autonomic function in these patients to evaluate the relationships between sleep disorders, excessive daytime sleepiness (EDS) and autonomic function in these patients.

Twenty patients with MSA (n=7) and PD (n=13) underwent clinical assessment including questionnaires for autonomic function and sleep. Cardiovascular autonomic function tests and two-nights video-polysomnography followed by multiple sleep latency test were performed. REM sleep without atonia (RWA) was quantified in the chin, flexor digitorum superficialis (FDS), tibial anterior and sternocleidomastoid muscles.

REM sleep behavior disorder was associated with orthostatic hypotension (OH) (p=0.017) and constipation (p=0.019) in PD. Patients with OH had higher RWA indices than those without (p<0.001). The SINBAR (Sleep Innsbruck Barcelona) RWA index ("any" chin and/or FDS) correlated with systolic/diastolic blood pressure fall upon tilt table examination in MSA patients (p<0.05), and with gastrointestinal (p=0.010), urinary (p=0.022), and total SCOPA-AUT scores (p=0.006) in all subjects. Patients with pathological deep breathing ratio showed higher SINBAR indices (p=0.031). Objective daytime sleepiness was exclusively present in PD (p=0.034) and correlated with levodopa equivalent dosage (p=0.031).

The relationship of autonomic dysfunction with RWA in PD and MSA is accounted for by shared brainstem neuropathology, and likely identifies patients in a more advanced stage of disease. EDS is found exclusively in PD and might be secondary to levodopa treatment and not related to α-synuclein disease.

The association between sleep disordered breathing and maternal endothelial and metabolic markers in pregnancies complicated by obesity.

J Clin Sleep

To evaluate the impact of sleep-disordered breathing (SDB) on vascular, angiogenic and metabolic analytes in pregnancy.

Participants with a body mass index ≥30 kg/m2 underwent polysomnography (PSG) at 14-20 weeks gestation (visit 1). Participants with SDB (defined as an apnea-hypopnea index (AHI) ≥5), were then enrolled in a separate trial. SDB-negative participants returned for a PSG at 28-31 weeks (visit 2) and were re-categorized as persistent-negative SDB or new-onset SDB. Mean arterial blood pressure (MAP), mean uterine artery doppler pulsatility index (UAD-PI), endoglin, soluble FMS-like tyrosine kinase 1 (sFLT-1), placental growth factor (PlGF) and the homeostatic model assessment for insulin resistance (HOMA-IR) were measured after each visit. Our primary outcome was a composite of: UAD-PI, sFLT-1/PLGF ratio and HOMA-IR. For secondary analyses each outcome variable was analyzed independently.

242 and 130 participants completed visit 1 and visit 2, respectively. Newly-diagnosed SDB was present in 37% of individuals at visit 1 and 31% of individuals at visit 2. No significant differences in our composite outcome vector were observed in individuals with and without SDB at either visit. In our secondary analysis, MAP (88.7 ± 7.3 mmHg vs 85.4 ± 7.1 mmHg, p-value=0.04) and fasting glucose (92.4 ± 15.2 mg/dL vs 86.6 ± 11.5 mg/dL, p-value=0.05) were higher in participants with early pregnancy SDB. These associations were not observed for new-onset SDB. No associations were observed between UAD-PI and angiogenic markers and SDB in pregnancy.

SDB in early pregnancy was not associated with our composite primary outcome, but was associated with higher MAP and fasting glucose. The pathophysiologic changes that occur in pregnant individuals with SDB and how they lead to an increased risk of preeclampsia and GDM remain poorly understood.

Registry: ClinicalTrials.gov; Trial name: Sleep Disordered Breathing, Obesity and Pregnancy Study (SOAP); Identifier: NCT02086448; URL: https://clinicaltrials.gov/ct2/show/NCT02086448.

Regional differences in the contribution of smoking, dietary and cooking behaviours to airflow obstruction in China: A population-based case-control study.

Respirology

The major contributing risk factors to airflow obstruction (AO) in China remain largely unknown. We examined the environmental and lifestyle risk factors of unrecognized AO in the baseline of a population-based cohort drawn from 115 urban and rural communities across 12 provinces in China.

Amongst 46,285 adults recruited from 2005 to 2009, 3686 were identified with AO on spirometry (defined by the ratio of forced expiratory volume in the first second to forced vital capacity <0.7) and without known chronic lung disease. These cases were age- and sex-matched to 11,129 controls with normal spirometry and no chronic lung disease from the same community. Conditional multivariable adjusted OR and population attributable fraction (PAF) were calculated for each identified risk factor and their combined effect.

Compared to controls, smoking initiation age <20 years (OR 1.22 [95% CI 1.01-1.48]), smoking duration ≥40 years (OR 1.82 [1.50-2.22]), low vegetables (OR 1.86 [1.67-2.07]) and fruits (OR 1.14 [1.02-1.29]) intake, cooking with biomass fuels (OR 2.54 [2.32-2.78]) and poor kitchen ventilation (OR 1.37 [1.19-1.58]) were significantly associated with elevated risks of unrecognized AO. The combined effect of these lifestyle factors significantly elevated the odds by 25 fold (18.6-34.3). The addition of prior tuberculosis and low socioeconomic status further increased the odds to 40.1 (28.2-57.0) and the PAF to 66.7% (51.1-78.1).

Smoking, unhealthy diet, biomass cooking fuels and low socioeconomic status are strongly associated with AO. Addressing these risk factors could substantially reduce the burden of AO in China.

Determination of optimal 25-hydroxyvitamin D cut-off values for the evaluation of restless legs syndrome among pregnant women.

J Clin Sleep

Vitamin D deficiency is associated with restless legs syndrome (RLS). However, a cut-off value for serum 25-hydroxyvitamin D (25[OH]D) level associated with RLS has yet to be clearly determined. We evaluated the association between 25(OH)D and RLS in pregnant women.

Data from 203 pregnant women were evaluated using blood samples taken in the third trimester. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and ligand binding assays were used to measure 25(OH)D. RLS was diagnosed based on International Classification of Sleep Disorders-Third Edition criteria. The cut-off value for serum 25(OH)D associated with RLS was explored using receiver operating characteristic (ROC) curve and classification and regression tree (CART) analyses.

The results of LC-MS/MS (x) and ligand binding assays (y) for serum 25(OH)D in the RLS (N = 35, 17.2%) and non-RLS (N = 168) groups showed a relationship of y = -2.65 + 0.08x. The RLS group showed lower serum 25(OH)D and folate levels. ROC curve and CART analyses revealed cut-off values of 10-12.7 ng/mL and 6.6-7.2 ng/mL for 25(OH)D and folate, respectively. Of the five women with RLS symptoms persisting at a moderate-to-severe level after delivery, four had 25(OH)D levels of < 10 ng/mL and all had folate levels of < 6 ng/mL.

Vitamin D and folate deficiency were associated with RLS in pregnant women and may be associated with persistent moderate-to-severe postpartum RLS symptomatology; it is essential to examine associations with RLS while accounting for measurement methods and assay systems.

Pulmonary function testing during SARS-CoV-2: An ANZSRS/TSANZ position statement.

Respirology

The Thoracic Society of Australia and New Zealand (TSANZ) and the Australian and New Zealand Society of Respiratory Science (ANZSRS) commissioned a...

Device-based and subjective measurements of sleep in children with cerebral palsy: a comparison of sleep diary, actigraphy, and bed sensor data.

J Clin Sleep

To investigate how subjective assessments and device-based measurements of sleep relate to each other in children with cerebral palsy (CP).

Sleep of children with CP, classified at Gross Motor Function Classification System (GMFCS) levels I-III, was measured during 7 consecutive nights using one subjective (i.e. sleep diary), and two device-based (i.e. actigraphy and bed sensor) instruments. The agreement between the instruments was assessed for all nights, and separately for school- and weekend nights, using intraclass correlation coefficients (ICC) and Bland-Altman plots.

A total of 227 nights from 38 children with CP (53% male; median age (range), 6 (2-12)), were included in the analyses. Sleep parameters showed poor agreement between the three instruments, except for total time in bed, which showed satisfactory agreement between i) actigraphy and sleep diary (ICC > 0.86), ii) actigraphy and bed sensor (ICC > 0.84) and iii) sleep diary and bed sensor (ICC > 0.83). Furthermore, agreement between sleep diary and bed sensor was also satisfactory for total sleep time (ICC > 0.70) and wakefulness after sleep onset (ICC = 0.55; only during weekend nights).

Researchers and clinicians need to be aware of the discrepancies between instruments for sleep monitoring in children with CP. We recommend combining both subjective and device-based measures to provide information on the perception as well as an unbiased estimate of sleep. Further research needs to be conducted on the use of a bed sensor for sleep monitoring in children with CP.

Combination of atomoxetine with the novel antimuscarinic aroxybutynin improves mild to moderate OSA.

J Clin Sleep

Obstructive sleep apnea (OSA) is a common and serious sleep disorder whose treatment remains challenging due to lack of adherence to approved therapies. Previous pharmacological studies addressing sleep-related upper airway muscle hypotonia suggested that the combination of atomoxetine and oxybutynin is effective in treating OSA. The current study is with aroxybutynin (AD109), a new enantiomerically pure form of oxybutynin with better safety profile compared to racemic oxybutynin.

This was a randomized, double-blind, placebo-controlled, crossover study in patients with mild to moderate OSA. Each received low-dose AD109 (37.5/2.5mg), high-dose (75/2.5mg), and placebo at bedtime across three overnight periods in a randomized order. Adverse events were collected by telephone contact with participants during each washout period. The primary endpoint was change in Hypoxic Burden (HB) and secondary endpoint was apnea-hypopnea index (AHI).

Patients treated with both the high and low doses of AD109 had a statistically significant and clinically meaningful difference from placebo in HB. Median[IQR] HB for participants on placebo was 13.9[4.5-21.9]%min/h vs 2.3[0.1-10.5]%min/h for patients on the high dose (p<0.001) and to 7.3[2-12.5]%min/h on the low dose (p<0.01). AHI went from a median of 13.2[8.0-19.1] events/h on placebo reduced to 5.5[2.2 to 9.6] events/h on the high dose (p<0.001) and to 7.8[4-13.7] on the low dose (p<0.05). AD109 demonstrated a favorable safety profile.

This study provides further support that a pharmacological intervention for OSA, namely the combination of atomoxetine and aroxybutynin, offers promising results. Additional development of this compound and others is warranted.

Registry: ClinicalTrials.gov; Identifier: NCT04631107; Title: AD109 Dose Finding in Mild to Moderate OSA; URL: https://clinicaltrials.gov/ct2/show/NCT04631107.

Sleep profiles in children with 22q deletion syndrome: a study of 100 consecutive children seen in a multidisciplinary clinic.

J Clin Sleep

While previous studies have suggested a high prevalence of sleep disorders in children with 22q deletion syndrome (22qDS), they were limited by potential selection bias. In the current investigation, we assessed sleep characteristics in 100 consecutive children presenting to a 22qDS multidisciplinary clinic.

Observational retrospective case series of consecutive children presenting to 22qDS multidisciplinary clinic was performed. Children aged 2 to 17 years of age were included, and data were abstracted including sleep characteristics (sleep history, Childhood Sleep Habits Questionnaire [CSHQ], and free response questions), comorbid medical conditions, and demographics.

Overall, 100 children were included in analysis, 85% of whom had scores on the CSHQ consistent with clinically meaningful sleep disorder. Sleep problems were common in all domains of the CSHQ, including daytime sleepiness (66%), sleep onset delay (54%), parasomnias (52%), night wakings (52%), sleep disordered breathing (49%), sleep duration (45%), bedtime resistance (38%), and sleep anxiety (33%). Overall CSHQ score was significantly associated with daytime behavioral problems and speech delay (F(2,97) = 10.4, p <0.001, adjusted R2 = 0.16). The most common interventions reported to be helpful for sleep by parents were behavioral (routine, bedtime story), environmental (light avoidance at night, calming music), and pharmacologic (melatonin, clonidine).

These data confirm a high prevalence of sleep disorders in a large, unselected sample of children with 22qDS, and suggest an important relationship between sleep dysfunction and daytime behavioral challenges. Our findings highlight the potential role for multimodal treatment approaches including behavioral, environmental, and pharmacologic interventions.