Natural history of excessive daytime sleepiness : a population-based 5-year longitudinal study

Study Objective: To document the rates of persistent, remitted, and intermittent excessive daytime sleepiness (EDS) in a longitudinal 5-year community study of adults and to assess how changes in risk factors over time can predict improvement of daytime sleepiness (DS). Methods: Participants were recruited in 2007–2008 as part of a population-based epidemiological study implemented in Canada. They completed postal assessments at baseline and at each yearly follow-up. An Epworth Sleepiness Scale total score >10 indicated clinically significant EDS; a 4-point reduction between two consecutive evaluations defined DS improvement. Socio-demographic, lifestyle, health characteristics, and sleep-related measures (e.g. insomnia symptoms, sleep duration, sleep medication) were self-reported at each time point. Cox proportional-hazard models were used to predict EDS and DS remissions over 5 years. Results: Among the 2167 participants, 33% (n = 714) met criteria for EDS at baseline, of whom 33% had persistent EDS, 44% intermittent EDS, and 23% remitted EDS over the follow-up. Furthermore, 61.4% of 2167 initial participants had stable DS, 27.1% sustained DS improvement and 8.5% transient improvement over the follow-up. The main predictors of EDS remission or DS improvement were normal weight, taking less hypnotics, having hypertension, increased nighttime sleep duration, and decreased insomnia, and depressive symptoms. Conclusion: EDS waxes and wanes over time with frequent periods of remission and is influenced by behavioral characteristics and changes in psychological, metabolic, and nighttime sleep patterns. Targeting these predictors in future interventions is crucial to reduce DS in the general adult population

Non-Dipping Blood Pressure Profile in Narcolepsy with Cataplexy

BACKGROUND: Patients with narcolepsy-cataplexy (NC) mostly exhibit undetectable hypocretin levels. Hypocretin system is one of the key players in the complex interaction between sleep and the cardiovascular system. We tested the hypothesis that hypocretin deficiency affects cardiovascular risk factors by measuring nighttime and daytime ambulatory blood pressure (BP) and the night-to-day BP ratio as well as endothelial dysfunction by the digital pulse amplitude response in drug-free patients with NC compared to controls. METHODOLOGY: Sleep, clinical and biological cardiovascular risk factors, fingertip peripheral arterial tonometry, and 24-hour ambulatory BP monitoring were recorded in 50 drug-free patients with NC and 42 healthy control subjects, except for BP monitoring available in all controls but in 36 patients with NC. PRINCIPAL FINDINGS: More patients than controls were smokers, obese and with dyslipidemia. One-third of patients with NC were "non-dippers" (defined as <10% drop in BP during sleep) compared to only 3% of controls. The diastolic non-dipper BP profile had up to 12-fold higher odds of being associated with NC. We noted negative correlations between mean diastolic BP fall during night, REM sleep percentage and number of sleep onset REM periods, and a positive correlation with mean sleep latency on the MSLT. The digital pulse amplitude response measured by fingertip was similar between NC and controls. CONCLUSION: We found a high percentage of non-dippers in patients with NC with association with REM sleep dysregulation. The blunted sleep-related BP dip in NC may be of clinical relevance, as it may indicate increased risk for cardiovascular events

An approach for data mining of electronic health record data for suicide risk management: Database analysis for clinical decision support

Background: In an electronic health context, combining traditional structured clinical assessment methods and routine electronic health-based data capture may be a reliable method to build a dynamic clinical decision-support system (CDSS) for suicide prevention. Objective: The aim of this study was to describe the data mining module of a Web-based CDSS and to identify suicide repetition risk in a sample of suicide attempters. Methods: We analyzed a database of 2802 suicide attempters. Clustering methods were used to identify groups of similar patients, and regression trees were applied to estimate the number of suicide attempts among these patients. Results: We identified 3 groups of patients using clustering methods. In addition, relevant risk factors explaining the number of suicide attempts were highlighted by regression trees. Conclusions: Data mining techniques can help to identify different groups of patients at risk of suicide reattempt. The findings of this study can be combined with Web-based and smartphone-based data to improve dynamic decision making for clinicians.This study received a Hospital Clinical Research Grant (PHRC 2009) from the French Health Ministry. None of the funding sources had any involvement in the study design; collection, analysis, or interpretation of data; writing of the report; or the decision to submit the paper for publication. This study was funded partially by Instituto de Salud Carlos III (ISCIII PI13/02200; PI16/01852), Delegación del Gobierno para el Plan Nacional de Drogas (20151073), and the American Foundation for Suicide Prevention (LSRG-1-005-16)

J Sleep Res

Many studies suggest a relationship between excessive daytime sleepiness (EDS) and dementia incidence, but the underlying mechanisms remain uncertain. The study aimed to investigate the role of cardiovascular burden in the relationship between EDS and dementia incidence over a 12-year follow-up in community-dwelling older adults. We performed analyses on 6171 subjects (aged ≥65 years) free of dementia and vascular disease at baseline. Participants self-reported EDS at baseline and an expert committee validated both prevalent and incident dementia. We defined cardiovascular burden by a low Cardiovascular Health score, constructed using the American Heart Association metrics, and incident vascular events. To explore the potential role of the cardiovascular burden in the relationship between EDS and dementia, we conducted mediation analyses with inverse odds ratio-weighted estimation, using multivariable-adjusted proportional hazard Cox and logistic regression models. Subjects with EDS had a higher risk of all-cause dementia (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.13-1.69) and dementia with vascular component (DVC) (HR 2.14, 95% CI 1.30-3.51), but not Alzheimer's disease (HR 1.18, 95% CI 0.93-1.51). Cardiovascular burden explained 5% (95% CI 4.1-5.2) and 11% (95% CI 9.7-11.3) of the relationship between EDS and all-cause dementia and DVC, respectively. These findings confirm that EDS may be implicated in the development of dementia and indicate a weaker than expected role of cardiovascular burden in the relationship between EDS and DVC.COGINUT : Cognition, anti-oxydants, acides gras: approche interdisciplinaire du rôle de la nutrition dans le vieillissement du cerveauInteraction entre la vulnérabilité génétique, la dysrégulation biologique et le stress dans la dépression du sujet âg

Low Vitamin D in Narcolepsy with Cataplexy

Narcolepsy with cataplexy (NC) is currently thought to be an autoimmune-mediated disorder in which environmental risk factors make a significant contribution to its development. It was proposed that vitamin D deficiency plays a role in autoimmune diseases. Here we investigated whether NC can be associated with 25-hydroxyvitamin D (25(OH)D) level deficiency in patients with NC compared with gender- and age-matched normal controls.Serum level of 25 (OH)D was determined in 51 European patients with typical NC compared to 55 age-, gender-, and ethnicity-matched healthy controls. Demographic and clinical data (age at onset, duration and severity of disease at baseline, and treatment intake at time of study) and season of blood sampling were collected to control for confounding variables.Serum 25(OH)D concentration was lower in NC compared to controls (median, 59.45 nmol/l [extreme values 24.05-124.03] vs. 74.73 nmol/l [26.88-167.48] p = 0.0039). Patients with NC had significantly greater vitamin D deficiency (<75 nmol/l) than controls (72.5% vs 50.9%, p = 0.0238). Division into quartiles of the whole sample revealed that the risk of being affected with NC increased with lower 25(OH)D level, with a 5.34 OR [1.65-17.27] for the lowest quartile (p = 0.0051). Further adjustment for BMI did not modify the strength of the association (OR: 3.63, 95% CI = 1.06-12.46, p = 0.0191). No between BMI and 25(OH)D interaction, and no correlation between 25(OH)D level and disease duration or severity or treatment intake were found in NC.We found a higher frequency of vitamin D deficiency in NC. Further studies are needed to assess the contribution of hypovitaminosis D to the risk of developing narcolepsy, and to focus on the utility of assessing vitamin D status to correct potential deficiency

Characteristics of Suicide Attempts in Anorexia and Bulimia Nervosa: A Case–Control Study

Objective: Compared to other eating disorders, anorexia nervosa (AN) has the highest rates of completed suicide whereas suicide attempt rates are similar or lower than in bulimia nervosa (BN). Attempted suicide is a key predictor of suicide, thus this mismatch is intriguing. We sought to explore whether the clinical characteristics of suicidal acts differ between suicide attempters with AN, BN or without an eating disorders (ED). Method: Case-control study in a cohort of suicide attempters (n = 1563). Forty-four patients with AN and 71 with BN were compared with 235 non-ED attempters matched for sex, age and education, using interview measures of suicidal intent and severity. Results: AN patients were more likely to have made a serious attempt (OR = 3.4, 95 % CI 1.4–7.9), with a higher expectation of dying (OR = 3.7,95 % CI 1.1–13.5), and an increased risk of severity (OR = 3.4,95 % CI 1.2–9.6). BN patients did not differ from the control group. Clinical markers of the severity of ED were associated with the seriousness of the attempt. Conclusion: There are distinct features of suicide attempts in AN. This may explain the higher suicide rates in AN. Higher completed suicide rates in AN may be partially explained by AN patients ’ higher desire to die and their more severe and lethal attempts

Bone Biomarkers Help Grading Severity of Coronary Calcifications in Non Dialysis Chronic Kidney Disease Patients

BACKGROUND: Osteoprotegerin (OPG) and fibroblast growth factor-23 (FGF23) are recognized as strong risk factors of vascular calcifications in non dialysis chronic kidney disease (ND-CKD) patients. The aim of this study was to investigate the relationships between FGF23, OPG, and coronary artery calcifications (CAC) in this population and to attempt identification of the most powerful biomarker of CAC: FGF23? OPG? METHODOLOGY/PRINCIPAL FINDINGS: 195 ND-CKD patients (112 males/83 females, 70.8 [27.4-94.6] years) were enrolled in this cross-sectional study. All underwent chest multidetector computed tomography for CAC scoring. Vascular risk markers including FGF23 and OPG were measured. Logistic regression analyses were used to study the potential relationships between CAC and these markers. The fully adjusted-univariate analysis clearly showed high OPG (≥10.71 pmol/L) as the only variable significantly associated with moderate CAC ([100-400[) (OR = 2.73 [1.03;7.26]; p = 0.04). Such association failed to persist for CAC scoring higher than 400. Indeed, severe CAC was only associated with high phosphate fractional excretion (FEPO(4)) (≥38.71%) (OR = 5.47 [1.76;17.0]; p = 0.003) and high FGF23 (≥173.30 RU/mL) (OR = 5.40 [1.91;15.3]; p = 0.002). In addition, the risk to present severe CAC when FGF23 level was high was not significantly different when OPG was normal or high. Conversely, the risk to present moderate CAC when OPG level was high was not significantly different when FGF23 was normal or high. CONCLUSIONS: Our results strongly suggest that OPG is associated to moderate CAC while FGF23 rather represents a biomarker of severe CAC in ND-CKD patients

Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression

The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research, and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 datasets containing 38 802 European-ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analyzed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis1) with qualifying unpublished data were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction, and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalizable, but must be of modest effect size and only observable in limited situations

Determinants and consequences of insomnia and sleepiness in the elderly : a study in the general population

Les troubles du sommeil restent peu étudiés chez la personne âgée (PA). Ils sont pourtant fréquents, associés à certaines maladies et peuvent être des marqueurs de pathologies latentes. L'objectif de cette thèse est d'étudier, chez la PA, les liens entre les troubles du sommeil (insomnie et somnolence diurne excessive (SDE)) et la survenue de maladies neuropsychiatriques ou cardiovasculaires à partir d'une cohorte prospective l'étude des 3 cités (3C) (9094 personnes âgées de 65 ans et plus recrutées sur 3 centres en France et suivies tous les 2 ans pendant 12 ans). Quatre études ont été réalisées dans le cadre de cette thèse. La 1ère suggère que les facteurs associés à la nature et au nombre de plaintes d'insomnie chez la PA ne seraient pas significativement différents selon le sexe. Cependant chez les femmes, les facteurs portant sur le style de vie tels que le traitement hormonal substitutif et un indice de masse corporelle élevé pourraient avoir un «effet protecteur». La 2ème montre que l'insomnie et la SDE seraient des facteurs de risque indépendants de dépression chez la PA même après l'exclusion des participants ayant eu une histoire passée de dépression. La 3ème met en évidence que le nombre de plaintes d'insomnie et les difficultés à maintenir le sommeil seraient négativement associés au déclin cognitif et la SDE apparaîtrait comme un facteur de risque de déclin cognitif chez la PA. Enfin, la 4ème indique que les plaintes d'insomnie seraient une conséquence des maladies cardiovasculaires, alors que la SDE serait un déterminant de maladie cardiovasculaire indépendant d'une histoire passée de maladie cardiovasculaire.Cette thèse apporte donc de nouvelles connaissances sur les déterminants de l'insomnie ainsi que sur les conséquences des troubles du sommeil sur la survenue de maladies neuropsychiatriques et cardiovasculaires. Elle suggère de nouvelles approches dans la prise en charge des troubles du sommeil et de leurs conséquences chez la PA.Sleep complaints remain poorly studied in the elderly. However, they are common and associated with a number of specific diseases. They may also be markers of latent disease. The objective of this thesis is to study the relationship between sleep disorders (insomnia and excessive daytime sleepiness (EDS)) and the occurrence of neuropsychiatric and cardiovascular disorders in the elderly from a prospective cohort study: The Three Cities (3C) (9094 subjects aged 65 years and over recruited from three centers in France and followed every 2 years, during 12 years). Four studies were performed drawing from the 3C cohort. The first study suggests that factors associated with the type and the number of insomnia complaints in the elderly do not differ significantly according to gender. However, among women, factors related to lifestyle such as hormone replacement therapy and a higher body mass index may have a "protective effect". The second study shows that insomnia and EDS are independent risk factors for depression even after excluding participants who had a past history of depression. The third study reports that the number of insomnia complaints and difficulty in maintaining sleep appear to be negatively associated with cognitive decline whereas EDS may be a risk factor for cognitive decline in the elderly. Finally, the fourth study indicates that insomnia complaints are more likely a consequence of cardiovascular disease, while EDS seems to be a determinant of future cardiovascular disease independently of a past-history of cardiovascular disease. This thesis provides new knowledge on the determinants of insomnia and on the consequences of sleep complaints for the onset of neuropsychiatric disorders and cardiovascular disease. It suggests also new approaches for the prevention of these sleep complaints and their consequences in the elderly