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Dive into the research topics where José Haba-Rubio is active.

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Featured researches published by José Haba-Rubio.


The Lancet Respiratory Medicine | 2015

Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study

Raphael Heinzer; S. Vat; Pedro Marques-Vidal; Helena Marti-Soler; Dana Andries; Nadia Tobback; V Mooser; Martin Preisig; Atul Malhotra; Waeber G; Peter Vollenweider; Mehdi Tafti; José Haba-Rubio

BACKGROUND Sleep-disordered breathing is associated with major morbidity and mortality. However, its prevalence has mainly been selectively studied in populations at risk for sleep-disordered breathing or cardiovascular diseases. Taking into account improvements in recording techniques and new criteria used to define respiratory events, we aimed to assess the prevalence of sleep-disordered breathing and associated clinical features in a large population-based sample. METHODS Between Sept 1, 2009, and June 30, 2013, we did a population-based study (HypnoLaus) in Lausanne, Switzerland. We invited a cohort of 3043 consecutive participants of the CoLaus/PsyCoLaus study to take part. Polysomnography data from 2121 people were included in the final analysis. 1024 (48%) participants were men, with a median age of 57 years (IQR 49-68, range 40-85) and mean body-mass index (BMI) of 25·6 kg/m(2) (SD 4·1). Participants underwent complete polysomnographic recordings at home and had extensive phenotyping for diabetes, hypertension, metabolic syndrome, and depression. The primary outcome was prevalence of sleep-disordered breathing, assessed by the apnoea-hypopnoea index. FINDINGS The median apnoea-hypopnoea index was 6·9 events per h (IQR 2·7-14·1) in women and 14·9 per h (7·2-27·1) in men. The prevalence of moderate-to-severe sleep-disordered breathing (≥15 events per h) was 23·4% (95% CI 20·9-26·0) in women and 49·7% (46·6-52·8) in men. After multivariable adjustment, the upper quartile for the apnoea-hypopnoea index (>20·6 events per h) was associated independently with the presence of hypertension (odds ratio 1·60, 95% CI 1·14-2·26; p=0·0292 for trend across severity quartiles), diabetes (2·00, 1·05-3·99; p=0·0467), metabolic syndrome (2·80, 1·86-4·29; p<0·0001), and depression (1·92, 1·01-3·64; p=0·0292). INTERPRETATION The high prevalence of sleep-disordered breathing recorded in our population-based sample might be attributable to the increased sensitivity of current recording techniques and scoring criteria. These results suggest that sleep-disordered breathing is highly prevalent, with important public health outcomes, and that the definition of the disorder should be revised. FUNDING Faculty of Biology and Medicine of Lausanne, Lausanne University Hospital, Swiss National Science Foundation, Leenaards Foundation, GlaxoSmithKline, Ligue Pulmonaire Vaudoise.


Clinical Neurophysiology | 2005

Cardiovascular variability during periodic leg movements: a spectral analysis approach

Emilia Sforza; Vincent Pichot; Jean Claude Barthélémy; José Haba-Rubio; Frédéric Roche

OBJECTIVE Changes in cardiovascular measures have been advocated as sensitive markers of phasic events arising from sleep. The current study was aimed to analyse the effects of periodic leg movements (PLMS) on heart rate variability (HRV) during NREM sleep in patients having restless legs syndrome and periodic leg movements during sleep. METHODS The absolute and normalized high- and low-frequency peaks from spectral analysis (FFT) of R-R intervals, the HRV changes using wavelet transform, the geometric and time domain HRV were measured in 14 patients with restless legs syndrome and PLMS. The analysis was done comparing one hundred, 10 min periods with PLMS (PLMS+) and 60 periods without PLMS (PLMS-) in stage 2 of NREM sleep. In 8 patients analysis was also done in slow wave sleep (SWS). RESULTS Occurrence of PLMS induced changes in geometrical indices of HRV, with a rise of the triangular index and the triangular interpolation of R-R intervals in PLMS+ periods (P < 0.0001). Small changes in time domain indices were found during PLMS+ periods, while the SD of the R-R intervals (SDNN), reflecting global HRV, was significantly higher (P = 0.001). While the low frequency (LF) power significantly increased in PLMS+ periods (P < 0.0001), high frequency (HF) power showed a weak and not significant reduction. The rise in sympathetic activity as detected by frequency domain HRV analysis was related to density and interval of PLMS. Comparison between sleep stages of NREM sleep demonstrated lower values of HRV measures when PLMS+ periods occur in SWS. CONCLUSIONS Overall, PLMS occurrence was associated with a shift to increased sympathetic activity without significant changes in cardiac parasympathetic activity. The frequency domain analysis of HRV appears to be an easy tool to estimate the autonomic changes related to PLMS and PLMS- arousals and to differentiate their occurrence during stage 2 and deep sleep. SIGNIFICANCE Spectral HRV measures may offer a simple approach to estimate the degree of autonomic changes occurring in relation to periodic leg movements in restless legs patients.


Journal of Sleep Research | 2013

Clinical, polysomnographic and genome-wide association analyses of narcolepsy with cataplexy: a European Narcolepsy Network study

Gianina Luca; José Haba-Rubio; Yves Dauvilliers; G. J. Lammers; Sebastiaan Overeem; Claire E. H. M. Donjacour; Geert Mayer; Sirous Javidi; Alex Iranzo; Joan Santamaria; Rosa Peraita-Adrados; Hyun Hor; Zoltán Kutalik; Giuseppe Plazzi; Francesca Poli; Fabio Pizza; Isabelle Arnulf; Michel Lecendreux; Claudio L. Bassetti; Johannes Mathis; Raphael Heinzer; Poul Jennum; Stine Knudsen; Peter Geisler; Aleksandra Wierzbicka; Eva Feketeova; Corinne Pfister; Ramin Khatami; Christian R. Baumann; Mehdi Tafti

The aim of this study was to describe the clinical and PSG characteristics of narcolepsy with cataplexy and their genetic predisposition by using the retrospective patient database of the European Narcolepsy Network (EU‐NN). We have analysed retrospective data of 1099 patients with narcolepsy diagnosed according to International Classification of Sleep Disorders‐2. Demographic and clinical characteristics, polysomnography and multiple sleep latency test data, hypocretin‐1 levels, and genome‐wide genotypes were available. We found a significantly lower age at sleepiness onset (men versus women: 23.74 ± 12.43 versus 21.49 ± 11.83, P = 0.003) and longer diagnostic delay in women (men versus women: 13.82 ± 13.79 versus 15.62 ± 14.94, P = 0.044). The mean diagnostic delay was 14.63 ± 14.31 years, and longer delay was associated with higher body mass index. The best predictors of short diagnostic delay were young age at diagnosis, cataplexy as the first symptom and higher frequency of cataplexy attacks. The mean multiple sleep latency negatively correlated with Epworth Sleepiness Scale (ESS) and with the number of sleep‐onset rapid eye movement periods (SOREMPs), but none of the polysomnographic variables was associated with subjective or objective measures of sleepiness. Variant rs2859998 in UBXN2B gene showed a strong association (P = 1.28E‐07) with the age at onset of excessive daytime sleepiness, and rs12425451 near the transcription factor TEAD4 (P = 1.97E‐07) with the age at onset of cataplexy. Altogether, our results indicate that the diagnostic delay remains extremely long, age and gender substantially affect symptoms, and that a genetic predisposition affects the age at onset of symptoms.


Sleep | 2014

DQB1 locus alone explains most of the risk and protection in narcolepsy with cataplexy in Europe

Mehdi Tafti; Hyun Hor; Yves Dauvilliers; Gert Jan Lammers; Sebastiaan Overeem; Geert Mayer; Sirous Javidi; Alex Iranzo; Joan Santamaria; Rosa Peraita-Adrados; José L. Vicario; Isabelle Arnulf; Giuseppe Plazzi; Sophie Bayard; Francesca Poli; Fabio Pizza; Peter Geisler; Aleksandra Wierzbicka; Claudio L. Bassetti; Johannes Mathis; Michel Lecendreux; Claire E. H. M. Donjacour; A. van der Heide; Raphael Heinzer; José Haba-Rubio; Eva Feketeova; Birgit Högl; Birgit Frauscher; Antonio Benetó; Ramin Khatami

STUDY OBJECTIVE Prior research has identified five common genetic variants associated with narcolepsy with cataplexy in Caucasian patients. To replicate and/or extend these findings, we have tested HLA-DQB1, the previously identified 5 variants, and 10 other potential variants in a large European sample of narcolepsy with cataplexy subjects. DESIGN Retrospective case-control study. SETTING A recent study showed that over 76% of significant genome-wide association variants lie within DNase I hypersensitive sites (DHSs). From our previous GWAS, we identified 30 single nucleotide polymorphisms (SNPs) with P < 10(-4) mapping to DHSs. Ten SNPs tagging these sites, HLADQB1, and all previously reported SNPs significantly associated with narcolepsy were tested for replication. PATIENTS AND PARTICIPANTS For GWAS, 1,261 narcolepsy patients and 1,422 HLA-DQB1*06:02-matched controls were included. For HLA study, 1,218 patients and 3,541 controls were included. MEASUREMENTS AND RESULTS None of the top variants within DHSs were replicated. Out of the five previously reported SNPs, only rs2858884 within the HLA region (P < 2x10(-9)) and rs1154155 within the TRA locus (P < 2x10(-8)) replicated. DQB1 typing confirmed that DQB1*06:02 confers an extraordinary risk (odds ratio 251). Four protective alleles (DQB1*06:03, odds ratio 0.17, DQB1*05:01, odds ratio 0.56, DQB1*06:09 odds ratio 0.21, DQB1*02 odds ratio 0.76) were also identified. CONCLUSION An overwhelming portion of genetic risk for narcolepsy with cataplexy is found at DQB1 locus. Since DQB1*06:02 positive subjects are at 251-fold increase in risk for narcolepsy, and all recent cases of narcolepsy after H1N1 vaccination are positive for this allele, DQB1 genotyping may be relevant to public health policy.


The Lancet Respiratory Medicine | 2016

The NoSAS score for screening of sleep-disordered breathing: a derivation and validation study

Helena Marti-Soler; Camila Hirotsu; Pedro Marques-Vidal; Peter Vollenweider; Waeber G; Martin Preisig; Mehdi Tafti; Sergio Tufik; Lia Rita Azeredo Bittencourt; José Haba-Rubio; Raphael Heinzer

BACKGROUND Diagnosis of sleep-disordered breathing requires overnight recordings, such as polygraphy or polysomnography. Considering the cost and low availability of these procedures, preselection of patients at high risk is recommended. We aimed to develop a screening tool allowing identification of individuals at risk of sleep-disordered breathing. METHODS We used the participants from the population-based HypnoLaus cohort in Lausanne, Switzerland, who had a clinical assessment and polysomnography at home, to build a clinical score (the NoSAS score) using multiple factor analysis and logistic regression to identify people likely to have clinically significant sleep-disordered breathing. The NoSAS score was externally validated in an independent sleep cohort (EPISONO). We compared its performance to existing screening scores (STOP-Bang and Berlin scores). FINDINGS We used the 2121 participants from the HypnoLaus cohort who were assessed between Sept 1, 2009, and June 30, 2013. The NoSAS score, which ranges from 0 to 17, allocates 4 points for having a neck circumference of more than 40 cm, 3 points for having a body-mass index of 25 kg/m(2) to less than 30 kg/m(2) or 5 points for having a body-mass index of 30 kg/m(2) or more, 2 points for snoring, 4 points for being older than 55 years of age, and 2 points for being male. Using a threshold of 8 points or more, the NoSAS score identified individuals at risk of clinically significant sleep-disordered breathing, with an area under the curve (AUC) of 0·74 (95% CI 0·72-0·76). It showed an even higher performance in the EPISONO cohort, with an AUC of 0·81 (0·77-0·85). The NoSAS score performed significantly better than did the STOP-Bang (AUC 0·67 [95% CI 0·65-0·69]; p<0·0001) and Berlin (0·63 [0·61-0·66]; p<0·0001) scores. INTERPRETATION The NoSAS score is a simple, efficient, and easy to implement score enabling identification of individuals at risk of sleep-disordered breathing. Because of its high discrimination power, the NoSAS score can help clinicians to decide which patients to further investigate with a nocturnal recording. FUNDING Faculty of Biology and Medicine of the University of Lausanne, Lausanne University Hospital, Swiss National Science Foundation, Leenaards Foundation, GlaxoSmithKline, and Vaud Pulmonary League.


Annals of Neurology | 2016

Prevalence and Determinants of Periodic Limb Movements in the General Population

José Haba-Rubio; Helena Marti-Soler; Pedro Marques-Vidal; Nadia Tobback; Daniela Andries; Martin Preisig; Gérard Waeber; Peter Vollenweider; Zoltán Kutalik; Mehdi Tafti; Raphael Heinzer

Periodic limb movements during sleep (PLMS) are sleep phenomena characterized by periodic episodes of repetitive stereotyped limb movements. The aim of this study was to describe the prevalence and determinants of PLMS in a middle to older aged general population.


Neurology | 2012

Kleine-Levin syndrome: functional imaging correlates of hypersomnia and behavioral symptoms.

José Haba-Rubio; John O. Prior; Eric Guedj; Mehdi Tafti; Raphael Heinzer; Andrea O. Rossetti

Kleine-Levin syndrome (KLS) is a disorder characterized by recurrent episodes of hypersomnia associated with perception, cognitive, and behavioral disturbances, such as hyperphagia and hypersexuality.1 Episodes are separated by intervals of normal alertness, cognition, and behavior. Primary KLS predominantly affects adolescent males, with a prevalence of 2–10 …


The Lancet Respiratory Medicine | 2016

Prevalence of sleep apnoea syndrome in the middle to old age general population

Raphael Heinzer; Helena Marti-Soler; José Haba-Rubio

On the basis of a large populationbased sample who underwent full polysomnography at home (HypnoLaus cohort), we recently reported that 49·7% of men and 23·4% of women aged 40 years or older had an apnoea-hypopnoea index of 15 events per h or more1 according to the American Academy of Sleep Medicine (AASM) 2013 scoring criteria. When excessive daytime sleepiness (ie, Epworth score >10 [maximum score 24]) was included in the definition with an apnoea-hypopnoea index of 5 events per h or more, the prevalence was 12·5% in men and 5·9% in women. This high prevalence of sleep disordered breathing reinforced the idea that the treatment decision should not only be based the apnoeahypopnoea index, but should also take into account associated symptoms and cardiovascular and metabolic comorbidities. After this Article was published, several readers contacted us to ask for the prevalence of sleep apnoea syndrome in our sample according to the International Classification of Sleep Disorders (ICSD-3) criteria. These criteria include either the presence of an apnoea-hypopnoea index of 5 events per h or more associated with obstructive sleep apnoearelated symptoms or cardiovascular and metabolic comorbidities, or an apnoea-hypopnoea index of 15 events per h or more (figure).


Sleep | 2016

Narcolepsy-Associated HLA Class I Alleles Implicate Cell-Mediated Cytotoxicity.

Mehdi Tafti; Gert Jan Lammers; Yves Dauvilliers; Sebastiaan Overeem; Geert Mayer; J Jacek Nowak; Corinne Pfister; V Valérie Dubois; J-F Jean-François Eliaou; H-P Hans-Peter Eberhard; R Roland Liblau; Aleksandra Wierzbicka; Peter Geisler; Claudio L. Bassetti; Johannes Mathis; Michel Lecendreux; Ramin Khatami; R Raphaël Heinzer; José Haba-Rubio; Eva Feketeova; Christian R. Baumann; Zoltán Kutalik; J-M Jean-Marie Tiercy

STUDY OBJECTIVES Narcolepsy with cataplexy is tightly associated with the HLA class II allele DQB1*06:02. Evidence indicates a complex contribution of HLA class II genes to narcolepsy susceptibility with a recent independent association with HLA-DPB1. The cause of narcolepsy is supposed be an autoimmune attack against hypocretin-producing neurons. Despite the strong association with HLA class II, there is no evidence for CD4+ T-cell-mediated mechanism in narcolepsy. Since neurons express class I and not class II molecules, the final effector immune cells involved might include class I-restricted CD8+ T-cells. METHODS HLA class I (A, B, and C) and II (DQB1) genotypes were analyzed in 944 European narcolepsy with cataplexy patients and in 4,043 control subjects matched by country of origin. All patients and controls were DQB1*06:02 positive and class I associations were conditioned on DQB1 alleles. RESULTS HLA-A*11:01 (OR = 1.49 [1.18-1.87] P = 7.0*10(-4)), C*04:01 (OR = 1.34 [1.10-1.63] P = 3.23*10(-3)), and B*35:01 (OR = 1.46 [1.13-1.89] P = 3.64*10(-3)) were associated with susceptibility to narcolepsy. Analysis of polymorphic class I amino-acids revealed even stronger associations with key antigen-binding residues HLA-A-Tyr(9) (OR = 1.32 [1.15-1.52] P = 6.95*10(-5)) and HLA-C-Ser(11) (OR = 1.34 [1.15-1.57] P = 2.43*10(-4)). CONCLUSIONS Our findings provide a genetic basis for increased susceptibility to infectious factors or an immune cytotoxic mechanism in narcolepsy, potentially targeting hypocretin neurons.


Sleep and Breathing | 2005

Effect of CPAP treatment on inspiratory arousal threshold during NREM sleep in OSAS

José Haba-Rubio; Emilia Sforza; Thomas Weiss; Carmen Schröder; Jean Krieger

The maximal inspiratory effort recorded at the end of apnea has been considered as an index of arousal threshold in obstructive sleep apnea syndrome (OSAS). Previous investigations have shown that the arousal threshold is higher in patients with OSAS than in normal subjects. The aim of the present study was to investigate the effect of continuous positive airway pressure (CPAP) treatment on the inspiratory-effort-related arousal threshold in patients with OSAS. In ten male patients, 40 episodes of apnea during stage 2 non-REM (NREM) sleep were analyzed. Apnea duration (t), esophageal pressure (Pes) at the first occluded breath (Pes1), the minimum of the three initial Pes swings (Pes min), the maximum of the three final Pes swings (Pes Max), ΔPes (Pes Max−Pes min), RPes (rate of increase of intrathoracic pressure, ΔPes/t), n (number of occluded breaths during apnea), ΔPes/n, n/t, and SaO2 were determined before and after occlusion. These apneic episodes were compared to ten episodes of apnea provoked by a mask occlusion device after 1, 7, 30, and 90 days of CPAP treatment. The therapy resulted in a decrease in the inspiratory-effort-related arousal threshold, as measured by a reduction of Pes Max, without significant changes in apnea duration and apnea-related hypoxemia. Pes1 and ΔPes/n, which are markers of respiratory drive, significantly decreased between observations. CPAP treatment decreases the inspiratory-effort-related arousal threshold and induces a decrease in ventilatory drive in response to upper airway occlusion.

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Raphael Heinzer

University Hospital of Lausanne

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Mehdi Tafti

University of Lausanne

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