Sex-dependent evolution of whole-body postural alignment with age.

PURPOSE: The goal of this study was to explore sex-related variations of global alignment parameters and their distinct evolution patterns across age groups. METHODS: This multicentric retrospective study included healthy volunteers with full-body biplanar radiographs in free-standing position. All radiographic data were collected from 3D reconstructions: global and lower limb parameters, pelvic incidence (PI) and sacral slope (SS). Lumbar lordosis (LL), thoracic kyphosis (TK) and cervical lordosis (CL) were also assessed as well as the lumbar and thoracic apex, and thoracolumbar inflexion point. The population was divided into five 5 age groups: Children, Adolescents, Young, Middle-Aged and Seniors. RESULTS: This study included 861 subjects (53% females) with a mean age of 34 ± 17 years. Mean PI was 49.6 ± 11.1 and mean LL was - 57.1 ± 11.6°. Females demonstrated a PI increase between Young and Middle-Aged groups (49 ± 11° vs. 55 ± 12°, p < 0.001) while it remained stable in males. SS and LL increased with age in females while remaining constant in males between Children and Middle-aged and then significantly decreased for both sexes between Middle-Aged and Seniors. On average, lumbar apex, inflexion point, and thoracic apex were located one vertebra higher in females (p < 0.001). After skeletal maturity, males had greater TK than females (64 ± 11° vs. 60 ± 12°, p = 0.04), with significantly larger CL (-13 ± 10° vs. -8 ± 10°, p = 0.03). All global spinal parameters indicated more anterior alignment in males. CONCLUSION: Males present more anteriorly tilted spine with age mainly explained by a PI increase in females between Young and Middle-Aged, which may be attributed to childbirth. Consequently, SS and LL increased before decreasing at senior age.

Auto-adjusted versus fixed positive airway pressure in patients with severe OSA: A large randomized controlled trial.

BACKGROUND AND OBJECTIVE: Continuous positive airway pressure (CPAP) in the treatment of severe obstructive sleep apnoea (OSA) can be used in fixed CPAP or auto-adjusted (APAP) mode. The aim of this prospective randomized controlled clinical study was to evaluate the 3 month-efficacy of CPAP used either in fixed CPAP or APAP mode. METHODS: Eight hundred one patients with severe OSA were included in twenty-two French centres. After 7 days during which all patients were treated with APAP to determine the effective pressure level and its variability, 353 and 351 patients were respectively randomized in the fixed CPAP group and APAP group. After 3 months of treatment, 308 patients in each group were analysed. RESULTS: There was no difference between the two groups in terms of efficacy whatever the level of efficient pressure and pressure variability (p = 0.41). Exactly, 219 of 308 patients (71.1%) in the fixed CPAP group and 212 of 308 (68.8%) in the APAP group (p = 0.49) demonstrated residual apnoea hypopnoea index (AHI) <10/h and Epworth Score <11. Tolerance and adherence were also identical with a similar effect on quality of life and blood pressure evaluation. CONCLUSION: The two CPAP modes, fixed CPAP and APAP, were equally effective and tolerated in severe OSA patients.

Moderate-to-severe obstructive sleep apnea syndrome is associated with altered tongue motion during wakefulness.

PURPOSE: Impairment of genioglossus control is a frequent "non-anatomical" cause of obstructive sleep apnea syndrome (OSAS) in non- or mildly obese patients. Although wake-related compensatory mechanisms prevent the occurrence of obstructive events, the genioglossus control is often impaired during wakefulness. We hypothesized that the lingual motion would be altered during wakefulness in this population in patients with moderate-to-severe OSAS. METHODS: We included non- or mildly obese participants with suspected OSAS. They underwent a Bucco-Linguo-Facial Motor Skills assessment using the MBLF ("Motricité Bucco-Linguo-Faciale"), which includes an evaluation of 13 movements of the tongue. This was followed by a night-attended polysomnography. We compared patients with moderate-to-severe OSAS (apnea-hypopnea index (AHI) ≥ 15/h; n = 15) to patients without or with mild OSAS (AHI < 15/h; n = 24). RESULTS: MBLF total and "tongue" sub-scores were lower in patients with moderate-to-severe OSAS: total z-score - 0.78 [- 1.31; 0.103] versus 0.20 [- 0.26; 0.31], p = 0.0011; "tongue" z-sub-score (- 0.63 [- 1.83; 0.41] versus 0.35 [0.26; 0.48], p = 0.014). There was a significant age-adjusted correlation between the "tongue" sub-score and AHI. The logistic regression model for the prediction of moderate-to-severe OSAS gave area under the curve ratio of 88.2% for MBLF score plus age. CONCLUSIONS: Myofunctional activity of the tongue is impaired during wakefulness in non- or mildly obese patients with moderate-to-severe OSAS. This study supports the lingual myofunctional assessment using the MBLF in screening of moderate-to-severe OSAS. This simple tool could help clinicians to select patients with suspected moderate-to-severe OSAS for polysomnography.

The rib cage: a new element in the spinopelvic chain.

INTRODUCTION: This study analyzes anatomical variations of the thoracic cage (TC) according to spinopelvic alignment, age and gender using stereoradiography in erect position. METHODS: This retrospective multicentric study analyzed computed parameters collected from free-standing position bi-planar radiographs, among healthy subjects. Collected data were: age, gender, pelvic parameters (Pelvic Incidence, Pelvic Tilt (PT) and Sacral Slope), T1-T12 Kyphosis (TK), L1-S1 Lordosis (LL), curvilinear spinal length, global TC parameters (maximum thickness and width, rib cage volume, mean Spinal Penetration Index (SPI)), 1st-10th rib parameters (absolute and relative (to the corresponding vertebra) sagittal angles). RESULTS: Totally, 256 subjects were included (140 females). Mean age was 34 (range: 8-83). Significant correlations were found between TK and TC thickness (0.3, p < 0.001) and with TC Volume (0.3, p = 0.04), as well as rib absolute sagittal angle for upper and middle ribs (0.2, p = 0.02). Conversely, a -0.3 correlation has been exhibited between SPI and TK. Similar correlations were found with LL. PT significantly correlated with TC thickness (0.4, p = 0.003), SPI (-0.3, p = 0.03), and all rib relative sagittal angles. Among global TC parameters, only thickness and SPI significantly changed after 20 years (respectively, 0.39 and -0.52, p < 0.001). Ribs relative sagittal angle showed negative correlation with age in skeletally mature subjects (p < 0.001). CONCLUSION: This study demonstrates the correlation between TC anatomy and spinopelvic parameters, confirming its part of the spinopelvic chain of balance. Indeed, higher spinal curvatures were associated with lower SPI and higher TC thickness, TC volume and rib absolute sagittal angles.

Baclofen destabilises breathing during sleep in healthy humans: A randomised, controlled, double-blind crossover trial.

AIMS: Periodic breathing is frequent in patients with severe heart failure. Apart from being an indicator of severity, periodic breathing has its own deleterious consequences (sleep-related oxygen desaturations, sleep fragmentation), which justifies attempts to correct it irrespective of the underlying disease. Animal models and human data suggest that baclofen can reconfigure respiratory central pattern generators. We hypothesised that baclofen, a GABAB agonist, may thus be able to correct periodic breathing in humans. METHODS: Healthy volunteers were exposed to hypoxia during sleep. Participants who developed periodic breathing (n = 14 [53 screened]) were randomly assigned to double-blind oral baclofen (progressively increased to 60 mg/d) or placebo. The primary outcome was the coefficient of variation (CoVar) of respiratory cycle total time considered as an indicator of breathing irregularity. Secondary outcomes included the CoVar of tidal volume, apnoea-hypopnoea index, sleep fragmentation index and ventilatory complexity (noise limit). RESULTS: The analysis was conducted in 9 subjects after exclusion of incomplete datasets. CoVar of respiratory cycle total time significantly increased with baclofen during non-rapid eye movement sleep (median with placebo 56.00% [37.63-78.95]; baclofen 85.42% [68.37-86.40], P = .020; significant difference during the N1-N2 phases of sleep but not during the N3 phase). CoVar of tidal volume significantly increased during N1-N2 sleep. The apnoea-hypopnoea index, sleep fragmentation index and ventilatory complexity were not significantly different between placebo and baclofen. CONCLUSION: Baclofen did not stabilise breathing in our model. On the contrary, it increased respiratory variability. Baclofen should probably not be used in patients with or at risk of periodic breathing.

Bilateral hypoglossal nerve stimulation for treatment of adult obstructive sleep apnoea.

BACKGROUND AND AIM: Hypoglossal nerve stimulation (HNS) decreases obstructive sleep apnoea (OSA) severity via genioglossus muscle activation and decreased upper airway collapsibility. This study assessed the safety and effectiveness at 6 months post-implantation of a novel device delivering bilateral HNS via a small implanted electrode activated by a unit worn externally, to treat OSA: the Genio™ system. METHODS: This prospective, open-label, non-randomised, single-arm treatment study was conducted at eight centres in three countries (Australia, France and the UK). Primary outcomes were incidence of device-related serious adverse events and change in the apnoea-hypopnoea index (AHI). The secondary outcome was the change in the 4% oxygen desaturation index (ODI). Additional outcomes included measures of sleepiness, quality of life, snoring and device use. This trial was registered with ClinicalTrials.gov, number NCT03048604. RESULTS: 22 out of 27 implanted participants (63% male, aged 55.9±12.0 years, body mass index (BMI) 27.4±3.0 kg·m-2) completed the protocol. At 6 months BMI was unchanged (p=0.85); AHI decreased from 23.7±12.2 to 12.9±10.1 events·h-1, a mean change of 10.8 events·h-1 (p<0.001); and ODI decreased from 19.1±11.2 to 9.8±6.9 events·h-1, a mean change of 9.3 events·h-1 (p<0.001). Daytime sleepiness (Epworth Sleepiness Scale; p=0.01) and sleep-related quality of life (Functional Outcomes of Sleep Questionnaire-10; p=0.02) both improved significantly. The number of bed partners reporting loud, very intense snoring, or leaving the bedroom due to participant snoring decreased from 96% to 35%. 91% of participants reported device use >5 days per week, and 77% reported use for >5 h per night. No device-related serious adverse events occurred during the 6-month post-implantation period. CONCLUSIONS: Bilateral HNS using the Genio™ system reduces OSA severity and improves quality of life without device-related complications. The results are comparable with previously published HNS systems despite minimal implanted components and a simple stimulation algorithm.

Postural preinspiratory cortical activity, genioglossus activity and fluid shift in awake obstructive sleep apnoea patients.

NEW FINDING: What is the central question of this study? Transition to supine posture induces an inspiratory load associated with cortical activation in awake healthy subjects. Some obstructive sleep apnoea patients exhibit this cortical activity in the sitting position contributing to the arousal-dependent compensation of their upper airway abnormalities. Does a transition to the supine posture in awake obstructive sleep apnoea patients increase this cortical activity? What is the main finding and its importance? The transition to supine posture induces a reduction in the cortical activity despite evidence of an increase in genioglossus activity, suggesting that genioglossus activation is not driven by cortical activity. ABSTRACT: The anatomy and mechanical properties of the upper airway (UA) depend on posture. Lying in a supine position causes cephalad fluid shift to the neck, thus narrowing the UA and predisposing the individual to obstructive sleep apnoea (OSA). Increased UA dilator muscle activity during wakefulness prevents the UA collapse but the underlying mechanism has not yet been elucidated. In the sitting position during wakefulness, some OSA patients exhibit preinspiratory cortical activity (preinspiratory potential, PIP) probably related to UA abnormalities. The aim of this study was to investigate changes in the preinspiratory cortical activity and UA dilator muscle in OSA patients during postural challenge. An electroencephalogram was used to detect PIP, and the genioglossus electromyographic activity and ventilation were analysed in 17 awake, male OSA patients while they were sitting, just after lying down, and then in response to leg positive pressure to enhance cephalad fluid shift. The prevalence of PIP decreased from 53% (sitting) to 12% (supine) (P = 0.002) in association with increased genioglossus activity (tonic from median (25th, 75th centiles) 2.3 (1.8, 2.8)% to 3.6 (1.7, 5.0)% of voluntary deglutition, P = 0.019; phasic from 2.3 (1.9, 2.8)% to 3.7 (2.0, 6.1)%, P = 0.024), and with increased transcutaneous carbon dioxide pressure (from 43.0 (42.4, 44.2) to 44.6 (43.5, 45.2) mmHg). No change was observed during leg-positive-pressure application. Moving from the sitting position to the supine position reduces respiratory-related premotor cortical activity in awake OSA patients. The concomitant increase in genioglossus activity, therefore, is not driven by cortical respiratory activity.

AVAPS-AE versus ST mode: A randomized controlled trial in patients with obesity hypoventilation syndrome.

BACKGROUND AND OBJECTIVE: Average volume-assured pressure support-automated expiratory positive airway pressure (AVAPS-AE) combines an automated positive expiratory pressure to maintain upper airway patency to an automated pressure support with a targeted tidal volume. The aim of this study was to compare the effects of 2-month AVAPS-AE ventilation versus pressure support (ST) ventilation on objective sleep quality in stable patients with OHS. Secondary outcomes included arterial blood gases, health-related quality of life, daytime sleepiness, subjective sleep quality and compliance to NIV. METHODS: This is a prospective multicentric randomized controlled trial. Consecutive OHS patients included had daytime Pa CO2 > 6 kPa, BMI ≥ 30 kg/m2 , clinical stability for more than 2 weeks and were naive from home NIV. PSG were analysed centrally by two independent experts. Primary endpoint was sleep quality improvement at 2 months. RESULTS: Among 69 trial patients, 60 patients had successful NIV setup. Baseline and follow-up PSG were available for 26 patients randomized in the ST group and 30 in the AVAPS-AE group. At baseline, Pa CO2 was 6.94 ± 0.71 kPa in the ST group and 6.61 ± 0.71 in the AVAPS-AE group (P = 0.032). No significant between-group difference was observed for objective sleep quality indices. Improvement in Pa CO2 was similar between groups with a mean reduction of -0.87 kPa (95% CI: -1.12 to -0.46) in the ST group versus -0.87 kPa (95% CI: -1.14 to -0.50) in the AVAPS-AE group (P = 0.984). Mean NIV use was 6.2 h per night in both groups (P = 0.93). NIV setup duration was shorter in the AVAPS-AE group (P = 0.012). CONCLUSION: AVAPS-AE and ST ventilation for 2 months had similar impact on sleep quality and gas exchange.

Decreased respiratory-related postural perturbations at the cervical level under cognitive load.

PURPOSE: In healthy humans, postural and respiratory dynamics are intimately linked and a breathing-related postural perturbation is evident in joint kinematics. A cognitive dual-task paradigm that is known to induce both postural and ventilatory disturbances can be used to modulate this multijoint posturo-ventilatory (PV) interaction, particularly in the cervical spine, which supports the head. The objective of this study was to assess this modulation. METHODS: With the use of optoelectronic sensors, the breathing profile, articular joint motions of the cervical spine, hip, knees and ankles, and centre of pressure (CoP) displacement were measured in 20 healthy subjects (37 years old [29; 49], 10 females) during natural breathing (NB), a cognitive dual task (COG), and eyes-closed and increased-tidal-volume conditions. The PV interaction in the CoP and joint motions were evaluated by calculating the respiratory emergence (REm). RESULTS: Only the COG condition induced a decrease in the cervical REm (NB: 17.2% [7.8; 37.2]; COG: 4.2% [1.8; 10.0] p = 0.0020) concurrent with no changes in the cervical motion. The CoP REm (NB: 6.2% [3.8; 10.3]; COG: 12.9% [5.8; 20.7] p = 0.0696) and breathing frequency (NB: 16.6 min-1 [13.3; 18.7]; COG: 18.6 min-1 [16.3; 19.4] p = 0.0731) tended to increase, while the CoP (p = 0.0072) and lower joint motion displacements (p < 0.05) increased. CONCLUSION: This study shows stable cervical spine motion during a cognitive dual task, as well as increased postural perturbations globally and in other joints. The concurrent reduction in the PV interaction at the cervical spine suggests that this "stabilization strategy" is centrally controlled and is achieved by a reduction in the breathing-related postural perturbations at this level. Whether this strategy is a goal for maintaining balance remains to be studied.

Awakening efficacy of a vibrotactile device in patients on home nocturnal ventilatory assistance and healthy subjects as family caregiver proxies.

The objective of this study was to test the capacity of vibrotactile stimulation transmitted to the wrist bones by a vibrating wristband to awaken healthy individuals and patients requiring home mechanical ventilation during sleep. Healthy subjects (n = 20) and patients with central hypoventilation (CH) (Congenital Central Hypoventilation syndrome n = 7; non-genetic form of CH n = 1) or chronic obstructive pulmonary disease (COPD) (n = 9), underwent a full-night polysomnography while wearing the wristband. Vibrotactile alarms were triggered five times during the night at random intervals. Electroencephalographic (EEG), clinical (trunk lift) and cognitive (record the time on a sheet of paper) arousals were recorded. Cognitive arousals were observed for 94% of the alarms in the healthy group and for 66% and 63% of subjects in the CH and COPD groups, respectively (p < 0.01). The percentage of participants experiencing cognitive arousals for all alarms, was 72% for healthy subjects, 37.5% for CH patients and 33% for COPD patients (ns) (94%, 50% and 44% for clinical arousals (p < 0.01) and 100%, 63% and 44% for EEG arousals (p < 0.01)). Device acceptance was good in the majority of cases, with the exception of one CH patient and eight healthy participants. In summary this study shows that a vibrotactile stimulus is effective to induce awakenings in healthy subjects, but is less effective in patients, supporting the notion that a vibrotactile stimulus could be an effective backup to a home mechanical ventilator audio alarm for healthy family caregivers.

Postural respiratory-related cortical activation and rostral fluid shift in awake healthy humans.

NEW FINDINGS: What is the central question of this study? Moving to supine induces upper airway modifications and a fluid shift to the neck, which represent inspiratory load that predisposes to upper airway collapse. Is there cortical participation in the response to the load induced by transition to a supine posture in awake healthy subjects? What is the main finding and its importance? Moving to supine induces transient cortical activation in awake healthy subjects, with greater fluid shift, supporting possible cortical participation in the response to upper airway load induced by transition to a supine posture. Our findings open new perspectives in the understanding of the pathogenesis of obstructive sleep apnoea. ABSTRACT: Moving from sitting upright to lying supine causes anatomical modifications and a fluid shift to the neck, which represent inspiratory loads that predispose to upper airway collapse. The pre-inspiratory potential (PIP) corresponds to the cortical activity observed during inspiratory load. In the sitting position during wakefulness, some obstructive sleep apnoea patients exhibit PIP, probably in relationship to upper airway abnormalities. The aim of this study was to investigate whether moving to the supine position induces respiratory-related cortical activation (PIP) in awake healthy subjects. The ECG was analysed to detect PIP, and EMG activity of the genioglossus muscle and ventilation were measured in the sitting position, immediately after moving to the supine position, and during application of leg positive pressure in the supine position to promote fluid shift, which was measured by bioelectrical impedance. Twenty-four subjects were included. From sitting to lying, PIP prevalence increased from 1/24 to 11/24 (P = 0.002), and ventilation decreased with no change in genioglossus activity. The fluid shift from sitting to supine was higher in the subjects exhibiting PIP while supine compared with the subjects without PIP [median (25th; 75th centiles) 440 (430; 520) versus 320 (275; 385) ml, P = 0.018], without any other differences. From before to during leg positive pressure, PIP disappeared (P = 0.006). These results indicate that moving from sitting to lying induces transient respiratory-related cortical activity in awake healthy subjects with greater fluid shift, supporting possible cortical participation in the response to upper airway loading induced by moving from sitting upright to lying supine. This study offers new perspectives in the understanding of obstructive sleep apnoea pathogenesis.

Sex differences in mandibular repositioning device therapy effectiveness in patients with obstructive sleep apnea syndrome.

PURPOSE: Mandibular repositioning devices (MRDs) are an effective treatment option for obstructive sleep apnea syndrome (OSAS), particularly in patients who refuse or cannot tolerate continuous positive airway pressure (CPAP). However, sex differences in the response to therapy and predictors of response are not clearly defined. This analysis of data from the long-term prospective ORCADES trial compared MRD efficacy in men and women with OSAS. METHODS: The ORCADES study included patients with newly diagnosed mild-to-moderate or severe OSAS who refused or were non-compliant with CPAP. MRD therapy was titrated over 3-6 months. The primary endpoint was treatment success (≥ 50% decrease in apnea-hypopnea index (AHI)). Complete response was defined using a range of AHI cut-off values (< 5/h, < 10/h, < 15/h). RESULTS: Overall treatment success rates were 89% in women and 76% in men (p = 0.019); corresponding rates in those with severe OSAS (AHI > 30/h) were 100% and 68% (p = 0.0015). In women vs. men, overall complete response rates at AHI cut-off values of < 5/h, <10/h, and < 15/h were 49 vs. 34% (p = 0.0052), 78 vs. 62% (p = 0.016), and 92 vs. 76% (p = 0.0032). On multivariate analysis, significant predictors of MRD treatment success were overbite and baseline apnea index in men, and neck circumference and no previous CPAP therapy in women. There were sex differences in the occurrence of side effects. Temporomandibular joint pain was the most common reason for stopping MRD therapy. CONCLUSIONS: MRD therapy was effective in women with OSA of any severity, with significantly higher response rates compared with men especially in severe OSAS. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT01326143).

Upper airway stabilization by osteopathic manipulation of the sphenopalatine ganglion versus sham manipulation in OSAS patients: a proof-of-concept, randomized, crossover, double-blind, controlled study.

BACKGROUND: Osteopathic manipulative treatment (OMT) of the sphenopalatine ganglion (SPG) is used empirically for the treatment of rhinitis and snoring and is thought to increase pharyngeal stability. This trial was designed to study the effects of this treatment on pharyngeal stability evaluated by critical closing pressure in obstructive sleep apnoea syndrome. METHODS: This single-centre, randomized, crossover, double-blind study compared active manipulation and sham manipulation of the SPG. Randomization was computer-generated. Patients each received one active manipulation and one sham manipulation at an interval of 21 days and were evaluated 30 min and 48 h after each session administered by a qualified osteopath. Neither the patients, nor the investigator performing the evaluations were informed about the order of the two techniques (double-blind). The primary endpoint was the percentage of responding patients presenting increased pharyngeal stability defined by a variation of critical closing pressure (Pcrit) of at least -4 cmH2O at 30 min. Secondary endpoints were the variation of Pcrit in absolute values, sleepiness and snoring. Others endpoints were lacrimation (Schirmer's test), induced pain, sensations experienced during OMT. RESULTS: Ten patients were included and nine (57 [50; 58] years, comprising 7 men, with an apnoea-hypopnoea index of 31.0 [25.5; 33.2]/h; (values are median [quartiles])) were analysed. Seven patients were analysed for the primary endpoint and nine patients were analysed for secondary endpoints. Five patients responded after active manipulation versus no patients after sham manipulation (p = 0.0209). Active manipulation induced more intense pain (p = 0.0089), increased lacrimation (ns) and more tactile, nociceptive and gustatory sensations (13 versus 1) compared to sham manipulation. No significant difference was observed for the other endpoints. CONCLUSIONS: Osteopathic manipulative treatment of the SPG may improve pharyngeal stability in obstructive sleep apnoea syndrome. This trial validates the feasibility of the randomized, controlled, double-blind methodology for evaluation of this osteopathic treatment. Studies on a larger sample size must specify the efficacy on the apnoea-hypopnoea index. TRIAL REGISTRATION: The study was retrospectively registered in the clinicaltrial.gov registry under reference NCT01193738 on 1st September 2010 (first inclusion May 19, 2010).

Reduced survival in patients with ALS with upper airway obstructive events on non-invasive ventilation.

INTRODUCTION: Non-invasive ventilation (NIV) is part of standard care in amyotrophic lateral sclerosis (ALS). Intolerance or unavailability of NIV, as well as the quality of correction of nocturnal hypoventilation, has a direct impact on prognosis. OBJECTIVES: We describe the importance of NIV failure due to upper airway obstructive events, the clinical characteristics, as well as their impact on the prognosis of ALS. METHODS: Retrospective analysis of the data of 190 patients with ALS and NIV in a single centre for the period 2011-2014. 179 patients tolerating NIV for more than 4 h per night without leaks were analysed. RESULTS: Among the 179 patients, after correction of leaks, 73 remained inadequately ventilated at night (defined as more than 5% of the night spent at <90% of SpO2), as a result of obstructive events in 67% of cases (n=48). Patients who remained inadequately ventilated after optimal adjustment of ventilator settings presented with shorter survival than adequately ventilated patients. Unexpectedly, patients with upper airway obstructive events without nocturnal desaturation and in whom no adjustment of treatment was therefore performed also presented with shorter survival. On initiation of NIV, no difference was demonstrated between patients with and without upper airway obstructive events. In all patients, upper airway obstruction was concomitant with reduction of ventilatory drive. CONCLUSIONS: This study shows that upper airway obstruction during NIV occurs in patients with ALS and is associated with poorer prognosis. Such events should be identified as they can be corrected by adjusting ventilator settings.

Health-related quality of life in young adults with congenital central hypoventilation syndrome due to PHOX2B mutations: a cross-sectional study.

BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare genetic disease due to PHOX2B mutations. CCHS patients suffer from many autonomic disorders, dominated clinically by defective ventilatory automatisms. From birth, the life of CCHS patients depends on ventilatory support during sleep, involving a high burden of care. Whether or not this impairs the quality of life of these patients during adulthood remains unknown. METHODS: We applied the medical outcome study short form-36 (SF-36) to 12 CCHS patients aged 15-33 (9 women) at the time of their passage from pediatric to adult care. Scores for the SF-36 dimensions were compared to the age- and gender-matched French reference population after transformation into standardized Z-scores. The SF-36 physical component summary score (PCS) and mental component summary score (MCS) were compared to American reference values. RESULTS: Median Z-scores were significantly different from zero for PF (physical functioning, p = 0.020) and GH (general health perception, p = 0.0342) and for PCS (p = 0.020). The other physical dimensions (RP, role limitation due to physical function; BP, bodily pain) and the mental dimensions (VT, vitality; SF, social functioning; RE, role limitation due to emotional function; MH, mental health) and MCS were not altered. CONCLUSIONS: We conclude that, despite the physical constraints imposed by CCHS and its anxiogenic nature, this disease is associated with an impairment of health-related quality of life in young adults that remains moderate. Whatever the underlying explanations, these results convey hope to parents with a child diagnosed with CCHS and for patients themselves.

Neurophysiological basis of respiratory discomfort improvement by mandibular advancement in awake OSA patients.

Patients with obstructive sleep apneas (OSA) do not complain from dyspnea during resting breathing. Placement of a mandibular advancement device (MAD) can lead to a sense of improved respiratory comfort ("pseudo-relief") ascribed to a habituation phenomenon. To substantiate this conjecture, we hypothesized that, in non-dyspneic awake OSA patients, respiratory-related electroencephalographic figures, abnormally present during awake resting breathing, would disappear or change in parallel with MAD-associated pseudo-relief. In 20 patients, we compared natural breathing and breathing with MAD on: breathing discomfort (transitional visual analog scale, VAS-2); upper airway mechanics, assessed in terms of pressure peak/time to peak (TTP) ratio respiratory-related electroencephalography (EEG) signatures, including slow event-related preinspiratory potentials; and a between-state discrimination based on continuous connectivity evaluation. MAD improved breathing and upper airway mechanics. The 8 patients in whom the EEG between-state discrimination was considered effective exhibited higher Peak/TTP improvement and transitional VAS ratings while wearing MAD than the 12 patients where it was not. These results support the notion of habituation to abnormal respiratory-related afferents in OSA patients and fuel the causative nature of the relationship between dyspnea, respiratory-related motor cortical activity and impaired upper airway mechanics in this setting.

Long-Term Efficacy and Safety of Pitolisant for Residual Sleepiness Due to OSA.

BACKGROUND: In people with OSA, excessive daytime sleepiness is a prominent symptom and can persist despite adherence to CPAP, the first-line therapy for OSA. Pitolisant was effective in reducing daytime sleepiness in two 12-week randomized controlled trials (RCTs), one in patients adherent to CPAP (BF2.649 in Patients With OSA and Treated by CPAP But Still Complaining of EDS [HAROSA 1]) and the other in patients refusing or not tolerating CPAP (BF2.649 in Patients With OSA, Still Complaining of EDS and Refusing to be Treated by CPAP [HAROSA 2]). RESEARCH QUESTION: Does the efficacy and safety of pitolisant persist when these patients take it long-term? STUDY DESIGN AND METHODS: All adults included in the HAROSA 1 and HAROSA 2 RCTs (both pitolisant and placebo arms) were offered pitolisant (up to 20 mg/d) after completion of the short-term double-anonymized phase (ie, from week 13) in an open-label cohort study. The primary efficacy outcome was the change in Epworth Sleepiness Scale score between baseline and week 52. Safety outcomes were treatment-emergent adverse event(s) (TEAE[s]), serious TEAEs, and special interest TEAEs. RESULTS: Out of 512 adults included in the two RCTs, 376 completed the 1-year follow-up. The pooled mean difference in Epworth Sleepiness Scale score from baseline to 1 year for the intention-to-treat sample was -8.0 (95% CI, -8.3 to -7.5). The overall proportions of TEAEs, serious TEAEs, and TEAEs of special interest were 35.1%, 2.0%, and 11.1%, respectively, without any significant difference between patients in the initial pitolisant and placebo arms. No cardiovascular safety issues were reported. INTERPRETATION: Pitolisant is effective in reducing daytime sleepiness over 1 year in adults with OSA, with or without CPAP treatment. Taken for 1 year, it has a good safety profile (including cardiovascular). TRIAL REGISTRATION: ClinicalTrials.gov; Nos.: NCT01071876 and NCT01072968; URL: www. CLINICALTRIALS: gov.

Full-body Postural Alignment Analysis Through Barycentremetry.

STUDY DESIGN: Multicentric retrospective. OBJECTIVE: The study of center of mass (COM) locations (i.e. barycentremetry) can help us understand postural alignment. This study goal was to determine relationships between COM locations and global postural alignment X-ray parameters in healthy subjects. The second objective was to determine the impact on spinopelvic alignment of increased distance between anterior body envelope and spine at lumbar apex level. SUMMARY OF BACKGROUND DATA: Unexplored relationship between COM location and spinopelvic parameters. METHODS: This study included healthy volunteers with full-body biplanar radiograph including body envelope reconstruction, allowing the estimation of COM location. The following parameters were analyzed: lumbar lordosis (LL), thoracic kyphosis (TK), cervical lordosis (CL), pelvic tilt (PT), Sacro-femoral angle (SFA), Knee flexion angle (KFA), sagittal odontoid-hip axis angle (ODHA). The following COM in the sagittal plane were located: whole body, at thoracolumbar inflexion point, and body segment above TK apex. The body envelope reconstruction also provided the distance between anterior skin and the LL apex vertebral body center ("SV-L distance"). RESULTS: This study included 124 volunteers, with a mean age of 44±19.3. Multivariate analysis confirmed posterior translation of COM above TK apex with increasing LL (P=0.002) through its proximal component, and posterior shift of COM at inflexion point with increasing TK (P=0.008). Increased SV-L distance was associated with greater ODHA (r=0.4) and more anterior body COM (r=0.8), caused by increased TK (r=0.2) and decreased proximal and distal LL (both r=0.3), resulting in an augmentation in SFA (r=0.3) (all P<0.01). CONCLUSIONS: Barycentremetry showed that greater LL was associated with posterior shift of COM above thoracic apex while greater TK was correlated with more posterior COM at inflexion point. Whole-body COM was strongly correlated with ODHA. This study also exhibited significant alignment disruption associated with increased abdominal volume, with compensatory hip extension. LEVEL OF EVIDENCE: II.