Marie-Françoise Vecchierini

Sleep debt and obesity

Abstract Short sleep duration has been shown to be associated with elevated body mass index (BMI) in many epidemiological studies. Several pathways could link sleep deprivation to weight gain and obesity, including increased food intake, decreased energy expenditure, and changes in levels of appetite-regulating hormones, such as leptin and ghrelin. A relatively new factor that is contributing to sleep deprivation is the use of multimedia (e.g. television viewing, computer, and internet), which may aggravate sedentary behavior and increase caloric intake. In addition, shift-work, long working hours, and increased time commuting to and from work have also been hypothesized to favor weight gain and obesity-related metabolic disorders, because of their strong link to shorter sleep times. This article reviews the epidemiological, biological, and behavioral evidence linking sleep debt and obesity.

A custom-made mandibular repositioning device for obstructive sleep apnoea–hypopnoea syndrome: the ORCADES study

BACKGROUND Mandibular repositioning devices (MRDs) are usually recommended as the first therapy option in patients with mild-to-moderate obstructive sleep apnoea (OSA). However, data on the long-term efficacy of MRDs are limited, not only in OSA patients who are noncompliant with continuous positive airway pressure (CPAP) but also in those with more severe OSA. The ORCADES study aimed to prospectively determine the long-term efficacy and tolerability of two custom-made Narval(™) MRDs for obstructive sleep apnoea-hypopnoea syndrome (OSAHS) patients. The interim 3- to 6-month data are reported. METHODS Eligible patients had OSAHS and had refused or were noncompliant with prescribed CPAP. Outcome measurements after gradual mandibular advancement titration included: apnoea-hypopnoea index (AHI), oxygen saturation, sleepiness, symptoms, quality of life, side effects and compliance. RESULTS A total of 369 patients were included. Overall, MRD treatment was successful (≥50% decrease in AHI) in 76.2% of the participants; complete response (AHI <10/h) was achieved in 63.5%. Severe OSAHS was effectively treated (AHI <15/h) in about 60% of the participants; 38% had complete symptom resolution. Mandibular repositioning devices significantly decreased subjective sleepiness, eliminated symptoms and improved quality of life. They were well tolerated and compliance was excellent. Only 8% of the participants stopped MRD treatment due to side effects. CONCLUSION Custom-made Narval(™) MRDs are effective for mild to severe OSA in patients who refuse or are noncompliant with CPAP. They are well tolerated and have excellent compliance.

Safety profile of tasimelteon, a melatonin MT1 and MT2 receptor agonist: pooled safety analyses from six clinical studies.

Introduction: Tasimelteon, a novel circadian regulator, is the first product for the treatment of Non-24-hour Sleep-Wake Disorder (Non-24) approved by either the FDA or the European Medicines Agency (EMA). Tasimelteon is a potent and specific melatonin (MT1 and MT2) receptor agonist with 2 – 4 times greater affinity for the MT2 receptor. Methods: Safety was assessed in two controlled and two open-label studies in blind individuals with Non-24 and in two controlled studies of primary insomnia. Periodic assessments included collection of adverse events (AEs), laboratory testing, electrocardiograms (ECGs), vital sign monitoring, physical examinations and assessment for the potential for suicide. One study included additional assessments for endocrine function. Results: A total of 184 blind individuals with Non-24 received tasimelteon nightly with a median exposure > 1 year. In placebo-controlled studies, 387 patients with insomnia and 42 patients with Non-24 received tasimelteon nightly for 4 – 26 weeks. The total patient years exposure for the six studies assessed here is 258.64 patient years. Discontinuations due to AEs were similar across treatment groups. Overall in the clinical studies described here, AEs attributable to tasimelteon treatment were headache, diarrhea, dry mouth, alanine aminotransferase increased, somnolence, dizziness and nightmare/abnormal dreams. There were no clinically significant differences in treatment group with ECGs, vital signs, withdrawal, endocrine function and suicidality assessments. Conclusion: Long-term tasimelteon administration was safe and well-tolerated. This is supported by placebo-controlled data in both Non-24 and insomnia patients.

Sleep and its relation to cognition and behaviour in preschool‐aged children of the general population: a systematic review

This is the first systematic review of the literature on sleep and its relation to cognition and behaviour in preschool‐aged children. In comparison with the literature focused on school‐aged children, knowledge involving preschoolers is rather sparse. A total of 26 studies was included in this review, which revealed a high degree of heterogeneity regarding the type and means of measuring sleep variables and behavioural and cognitive variables, as well as the statistical methods employed. Amongst the 13 articles with the largest sample sizes (top 50% of the included studies, 12 different populations), 12 found that a higher quantity or quality of sleep was associated with better behavioural and/or cognitive outcomes. Results point to an association between sleep, behaviour and cognition as early as preschool years, but the strengths of associations reported in the articles were relatively small. Studies with a smaller sample size were less concordant. It is consistent with our findings that the strengths of association are small, and thus require large sample sizes to ensure statistical detection power. Different aspects of sleep were not associated with all cognitive or behavioural features in the same way, which underscores the need for specific measures rather than general ones such as ‘sleep problems’ or ‘behaviour problems’ to be able to decipher the relationships. There is also a need for large longitudinal studies using objective measures and accounting for confounding factors. The childs genotype has recently been shown to have a moderating role in the association between sleep and behaviour, and should be further explored.

French Consensus: How to diagnose restless legs syndrome

Correct diagnosis of restless legs syndrome (RLS) is essential to patient care and treatment. Diagnosis is most often clinical and based on diagnostic criteria: the need to move the legs accompanied to varying degrees by unpleasant sensations, predominantly during the evening and improved by movement. In rare cases, clinical examination is insufficient and a polysomnography is necessary. Once a positive diagnosis has been made, a neurological examination and an assessment of iron status are required. The severity of the RLS must be evaluated to determine whether a specific treatment is necessary. Before treatment, it is essential to ensure that a definite diagnosis of RLS has been made and the phenotype characterised. This enables a personal treatment plan and limits the risk of augmentation syndrome.

LATE-BREAKING ABSTRACT: 2-years follow-up (FU) results of ORCADES study: Long-term mandibular repositioning device (MRD) therapy in patients treated for obstructive sleep apnea (OSA)

INTRODUCTION: ORCADES, a national prospective multicentre cohort study is evaluating the long-term benefits of a custom-made MRD in OSA patients noncompliant with Continuous Positive Airway Pressure (CPAP). AIMS AND METHODS: 379 OSA pts fitted with a custom-made titratable MRD (ResMed, Narval™) are evaluated over 5 years for evolution of respiratory and sleep data, symptoms, quality of life, compliance and side effects. Interim data of systematic polygraphy/polysomnography and dental sleep assessment at 2 years minimum FU are presented here. RESULTS: 73% of patients treated with MRD were kept in the study at 2 years FU. 16% stopped prematurely MRD for either side effect (8%) or lack of efficacy (8%), and 11% withdrew the study or returned to CPAP therapy. AHI decreased globally under MRD therapy from 28±14/h (median [Q1; Q3]: 26 [18; 37]) at baseline to 12±12/h (median [Q1; Q3]: 8 [4; 16]) at 2-year FU. An AHI In severe OSA patients (AHI>30), AHI was reduced from 41±11 (median [Q1; Q3]: 37 [32; 47]) at baseline to 18±15 (median [Q1; Q3]: 14 [8; 23]) at 2-year FU. Moreover, a decrease in baseline AHI by ≥50% + post-treatment AHI Compared to previous 3 month-FU evaluation, MRD efficacy and compliance (6.7h/night, 6.6 days/week) were kept at similar level in the 3 OSA severity groups. CONCLUSION: Effectiveness of custom-made Narval MRD in noncompliant CPAP patients is satisfactorily maintained at long-term FU irrespective of initial OSA severity.

Impact of a custom-made mandibular repositioning device (MRD) on blood pressure (BP) in obstructive sleep apnea (OSA) patients noncompliant with continuous positive airway pressure (CPAP)

Background: MRD therapy may improve BP in OSA pts with arterial hypertension (HTN). Aims: ORCADES, a French prospective multicenter cohort study is evaluating the long-term effects of a custom-made MRD in OSA pts who refused or did not tolerate CPAP. Interim data are presented at 3-month follow-up. Methods: Clinical benefits and side effects are evaluated in OSA pts fitted with a CAD/CAM MRD (Narval CC™). Patient was hypertensive (HTN) if office systolic and/or diastolic BP were respectively ≥140 and ≥90 mmHg. Results: 77 HTN and 222 non-HTN pts treated with MRD were analysed. Sex ratio (75% male), age (53±11y) and AHI (29±15/h) were similar in both groups. In HTN group, body mass index was higher and nadir SpO2 was lower. Therapy success (AHI reduction ≥50%) was higher in non-HTN group (84% vs. 66%, p=0.0012). Improvement in oxygen saturation, sleepiness or quality of life was equivalent in both groups with no weight change. In HTN group, SBP and DBP were reduced significantly and BP was normalized in 59% of pts. SBP decrease was correlated with mean SpO2 improvement (ρ=-0.30, p=0.022). Only 8% of pts stopped MRD due to side effects and mean usage was similar in both groups (6.7 hours/night). View this table: Evolution of BP under MRD therapy Conclusion: Custom-made CAD/CAM MRD is effective in OSA pts noncompliant with CPAP with additional benefits on blood pressure.

La somnolence au quotidien. Enquête Institut national du sommeil et de la vigilance. Journée du Sommeil® 2011

Adresse e-mail : contact@insv.org (A. Lopez) Objectif.— Évaluer la somnolence pour mieux identifier ses causes et ses conséquences et renforcer la sensibilisation des Français sur ce problème de santé publique largement sous-estimé. Méthode.— Enquête par téléphone du 03 au 13/01/11 auprès d’un échantillon représentatif de 1012 personnes âgées de 18 à 60 ans. Questionnaire élaboré par le conseil scientifique de l’INSV avec profil sociodémographique, structure familiale, horaires de travail, de sommeil, de sieste et niveau de somnolence (Échelle d’Epworth). Résultats.— Au total, 19 % des Français ont un score d’Epworth supérieur à 11 et 3 % sont très sévèrement somnolents avec un score supérieur à 16 ; 7 % des personnes somnolentes s’endorment dans la journée sans pouvoir résister. Pourtant, seuls 20 % des personnes somnolentes abordent ce problème avec leur médecin. Les Français ont un temps de transport moyen d’1h20 par jour. Au total, 18 % passe plus de 2 h dans les transports. Ceux qui sont très somnolents (score > 15) y passent près de 3 h et ont parfois des distances très importantes à parcourir (> 300 km/j). Au cours des 12 derniers mois, 12 % des conducteurs déclarent s’être arrêtés pour dormir au moins une fois et 3 % s’être endormis en conduisant ; 31 % des Français affirment dormir 6 h ou moins par nuit ; 43 % des personnes se disant somnolentes au moins 3 fois par semaine et 56 % des personnes déclarant s’être endormies au volant dorment moins de 6 h par nuit ; 35 % des personnes travaillant en horaires irréguliers ou décalés ont un score supérieur à 15. En semaine, les Français regardent le soir la télé ou des vidéos pendant 2 h 37. Ils passent également beaucoup de temps sur Internet : 1 h 39 en semaine et 1 h 10 le week-end. Conclusion.— La somnolence diurne accompagne une durée de sommeil souvent brève, liée à des temps de transport élevés et à de longs moments passés devant la télé ou avec les nouvelles technologies.