Adrenergic reactions during N3 sleep arousals in sleepwalking and sleep terrors: The chicken or the egg?

To understand the mechanisms of N3 sleep interruptions in patients with sleepwalking episodes and/or sleep terrors (SW/ST), we evaluated whether autonomic reactions preceded or accompanied behavioural arousals from NREM sleep stage N3. In 20 adult patients with SW/ST and 20 matched controls without parasomnia, heart rate and pulse wave amplitude were measured beat-to-beat during the 10 beats preceding and during the 15 beats succeeding a motor arousal from N3 sleep. Respiratory rate and amplitude were measured during the same 25 successive beats. In patients with SW/ST, the N3 arousals were associated with a 33% increase in heart rate, a 57% decrease in pulse wave amplitude (indicating a major vasoconstriction), a 24% increase in respiratory rate and a doubling of respiratory amplitude. Notably, tachycardia and vasoconstriction started 4 s before motor arousals. A similar profile (tachycardia and vasoconstriction gradually increasing from the 4 s preceding arousal and post-arousal increase of respiratory amplitude, but no polypnea) was also observed, with a lower amplitude, during the less frequent 38 quiet N3 arousals in control subjects. Parasomniac arousals were associated with greater tachycardia, vasoconstriction and polypnea than quiet arousals, with the same pre-arousal gradual increases in heart rate and vasoconstriction. Autonomic arousal occurs 4 s before motor arousal from N3 sleep in patients with SW/ST (with a higher adrenergic reaction than in controls), suggesting that an alarming event during sleep (possibly a worrying sleep mentation or a local subcortical arousal) causes the motor arousal.

The supplementary motor area modulates interhemispheric interactions during movement preparation.

The execution of coordinated hand movements requires complex interactions between premotor and primary motor areas in the two hemispheres. The supplementary motor area (SMA) is involved in movement preparation and bimanual coordination. How the SMA controls bimanual coordination remains unclear, although there is evidence suggesting that the SMA could modulate interhemispheric interactions. With a delayed-response task, we investigated interhemispheric interactions underlying normal movement preparation and the role of the SMA in these interactions during the delay period of unimanual or bimanual hand movements. We used functional MRI and transcranial magnetic stimulation in 22 healthy volunteers (HVs), and then in two models of SMA dysfunction: (a) in the same group of HVs after transient disruption of the right SMA proper by continuous transcranial magnetic theta-burst stimulation; (b) in a group of 22 patients with congenital mirror movements (CMM), whose inability to produce asymmetric hand movements is associated with SMA dysfunction. In HVs, interhemispheric connectivity during the delay period was modulated according to whether or not hand coordination was required for the forthcoming movement. In HVs following SMA disruption and in CMM patients, interhemispheric connectivity was modified during the delay period and the interhemispheric inhibition was decreased. Using two models of SMA dysfunction, we showed that the SMA modulates interhemispheric interactions during movement preparation. This unveils a new role for the SMA and highlights its importance in coordinated movement preparation.

Modified ROTEM for the detection of rivaroxaban and apixaban anticoagulant activity in whole blood: A diagnostic test study.

BACKGROUND: Rapid detection of the anticoagulant effect of oral factor Xa (FXa) inhibitors may be essential in several emergency clinical situations. Specific assays quantifying the drugs are performed in plasma and require a turnaround time that is too long to be useful in emergency situations. Rotational thromboelastometry (ROTEM) is a whole blood coagulation assay of blood viscoelasticity and could be of interest for FXa inhibitor detection in emergency. However, conventional ROTEM reagents only detect high amounts of inhibitors. OBJECTIVE: The aim of this study was first to assess the effect of whole blood components on the viscoelastic measurement of the effects of FXa inhibitors, and second to evaluate whether a modified ROTEM, triggered with a low amount of tissue factor and a saturating amount of phospholipid vesicles, can reliably detect low levels of FXa inhibitor activity in whole blood. DESIGN: Diagnostic test study. SETTINGS: A university research laboratory. From November 2014 to April 2016. PATIENTS: Sixty-six patients: 30 treated with rivaroxaban, 17 with apixaban and 19 without treatment. INTERVENTION: ROTEM was triggered with 2.5 pmol l of tissue factor and 10 µmol l of phospholipid vesicles. MAIN OUTCOME MEASURES: Modified ROTEM parameters were measured in different experimental conditions: platelet-poor plasma (PPP), platelet-rich plasma, PPP supplemented with fibrinogen and reconstituted whole blood with various haematocrit levels adjusted between 30 and 60%. Modified ROTEM was further validated using whole blood from patients who were either treated or not treated with FXa inhibitors. RESULTS: Modified ROTEM allowed detection of as little as 25 ng ml FXa inhibitors in PPP, with at least a 1.4-fold increase of the clotting time (P ≤ 0.02). Neither changes of fibrinogen concentration nor variations of platelet count or haematocrit precluded FXa inhibitor detection. A lengthened modified ROTEM clotting time of more than 197 s allowed detection of FXa inhibitor concentrations above 30 ng ml in whole blood with 90% sensitivity and 85% specificity. CONCLUSION: Modified ROTEM may be applicable in emergency situations for the detection of FXa inhibitors in whole blood.

Case-Control Retrospective Study of Child Sexual Abuse History among Psychiatric Consultations in a General Hospital Emergency Room.

BACKGROUND: A history of childhood sexual abuse (CSA) has been linked to a variety of physical and psychiatric illnesses, including ischemic heart disease and post-traumatic stress disorder (PTSD). OBJECTIVES: To determine the prevalence of past CSA and re-traumatization among hospital psychiatric consultations and to determine whether a CSA group in a hospital setting shared characteristics with community samples described in the literature. METHODS: We divided 228 consecutive psychiatric consultations into two groups. One group comprised patients with a past history of CSA while the other group had no such history. Both groups were further divided into a subgroup that presented with features of re-traumatization. RESULTS: In the cohort, 38% described a history of CSA. Twenty patients were identified as presenting with features of re-traumatization. There were significant differences between the two groups. The patients with a history of CSA were more likely to have arrived at the emergency department (ED) during the preceding 12 months with a diagnosis of PTSD, personality disorder, and substance use disorder. There was a greater proportion of patients in the CSA group who had grown up in an ultra-Orthodox Jewish household and who currently identified as being secular. CONCLUSIONS: The characteristics of the patients with past CSA in this study are similar to community-based samples, except for a significant gender difference. To the best of our knowledge, this study is the first to investigate CSA history during hospital ED psychiatric consultations. A history of CSA should be considered during psychiatric consultations in a general hospital ED admission.

Recalibrated MELD and hepatic encephalopathy are prognostic factors in cirrhotic patients with acute variceal bleeding.

BACKGROUND & AIMS: Early TIPS placement must be considered in patients with Child-Pugh B and active bleeding at endoscopy or in patients with Child-Pugh C 10-13 and variceal bleeding. However, active bleeding at endoscopy is a subjective criterion. Moreover, a previous study has shown that a MELD-based score accurately predicted 6-week mortality and helped to stratify patients. Using a prospective series of patients included in a multicentre study before the era of early TIPS, we aimed (i) to identify factors associated with 6-week mortality, focusing on the prognostic value of active bleeding; and (ii) to assess whether a recalibrated MELD-based score accurately predicted 6-week mortality. METHODS: Ancillary study of the prospective multicentre Baveno IV study, including patients with acute variceal bleeding. RESULTS: Two hundred and nineteen patients were analysed (Child-Pugh A/B/C = 18/45/37%). The overall actuarial likelihood of survival on day 42 was 84%. The variability for the diagnosis of active bleeding at endoscopy was high (range, 41.4% to 84.6% among the centres). Active bleeding at endoscopy was not associated with 6-week mortality in the entire population or in Child-Pugh B patients. In a multivariate analysis, independent factors associated with mortality were liver function, infection, HE and HCC. The recalibrated MELD-based score was accurate in predicting 6-week mortality (AUROC = 0.787). The recalibrated MELD-based score demonstrated better performance compared to the MELD score. CONCLUSION: The recalibrated MELD-based score accurately predicted mortality in our prospective cohort. Active bleeding at endoscopy had no prognostic value in cirrhotic patients presenting with acute variceal bleeding. Standardizing active bleeding assessment at endoscopy is warranted.

Predictors of pre-procedural concentrations of direct oral anticoagulants: a prospective multicentre study.

AIMS: Patients receiving direct oral anticoagulants (DOACs) frequently undergo elective invasive procedures. Their management is challenging. We aimed to determine the optimal duration of DOAC discontinuation that ensures a minimal anticoagulant effect during the procedure. METHODS AND RESULTS: This prospective multicentre study included 422 DOAC-treated patients requiring an invasive procedure. Pre-procedural DOAC concentration ([DOAC]) and routine haemostasis assays were performed to determine i/the proportion of patients who achieved a minimal pre-procedural [DOAC] (≤30 ng/mL) according to the duration of DOAC discontinuation, ii/the predictors of minimal [DOAC] and, iii/the ability of routine assays to predict minimal [DOAC]. Lastly, we assessed the predictors of peri-procedural bleeding events. The duration of DOAC discontinuation ranged from 1 to 218 h and pre-procedural [DOAC] from ≤30 to 527 ng/mL. After a 49-72-h discontinuation, 95% of the [DOAC] were ≤30 ng/mL. A 72-h discontinuation predicted concentrations ≤30 ng/mL with 91% specificity. In multivariable analysis, duration of DOAC discontinuation, creatinine clearance <50 mL/min and antiarrhythmics were independent predictors of minimal pre-procedural [DOAC] (concordance statistic 0.869; 95% confidence interval: 0.829-0.912). Conversely, routine haemostasis assays were poor predictors. Last, creatinine clearance <50 mL/min, antiplatelets and high-bleeding risk procedures were predictors of bleeding events. CONCLUSION: A last DOAC intake 3 days before a procedure resulted in minimal pre-procedural anticoagulant effect for almost all patients. Moderate renal impairment, especially in dabigatran-treated patients, and antiarrhythmics in anti-Xa-treated patients should result in a longer DOAC interruption. In situations requiring testing, routine assays should not replace DOAC concentration measurement.

Psychopathology of Israeli Soldiers Presenting to a General Hospital Emergency Department: Lessons for the Attending Physician and Psychiatrist.

BACKGROUND: There is scant research on the psychopathology of Israeli soldiers who present to a general hospital emergency department (ED). OBJECTIVES: To assess the psychopathology among a cohort of Israeli soldiers who presented to a general hospital ED for mental health assessment. METHODS: The demographic and clinical characteristics of 124 consecutive soldiers who presented to the ED for psychiatric assessment between January 2008 and September 2012 were reviewed. Twenty-seven soldiers from the cohort were contacted for follow-up by telephone on average 52 months later. RESULTS: The reasons for presentation to the ED, usually during the early stages of military service, included self-harming behavior, suicidal ideation, somatoform complaints, and dissatisfaction with their military service. Psychiatric diagnoses included adjustment disorder and personality disorder. Self-harming behavior/suicidal ideation was significantly correlated with unspecified adjustment disorder (P = 0.02) and personality disorder (P = 0.001). At follow-up, there was a lack of substantial psychopathology: none of the subjects engaged in self-harming behavior/suicidal ideation and a consistent trend was observed toward clinical improvement. CONCLUSIONS: Psychiatric intervention of soldiers who present to a general hospital ED because of emotional difficulties may provide the opportunity for crisis intervention and validation of the soldier's distress. To the best of our knowledge this is the first Israeli study of psychopathology among soldiers who presented to an ED.

Modification of Tracheal Cuff Shape and Continuous Cuff Pressure Control to Prevent Microaspiration in an Ex Vivo Pig Tracheal Two-Lung Model.

OBJECTIVES: Microaspiration of subglottic secretions plays a pivotal role in ventilator-associated pneumonia. Impact of endotracheal tube cuff material and shape on tracheal sealing performance remains debated. The primary objective was to compare the tracheal sealing performance of polyvinyl chloride tapered, cylindrical and spherical cuffs. Secondary objectives were to determine the impact of continuous cuff pressure control on sealing performance and pressure variability. DESIGN: Prospective randomized ex vivo animal study. SETTING: French research laboratory. SUBJECTS: Seventy-two ex vivo pig tracheal two-lung blocks. INTERVENTIONS: Blocks were randomly intubated with cylindrical (n = 26), tapered (n = 24), or spherical (n = 22) polyvinyl chloride endotracheal tube cuffs. Two milliliter of methylene blue were instilled above the cuff to quantify microaspirations, and lungs were ventilated for 2 hours. Continuous cuff pressure control was implemented in 33 blocks. MEASUREMENTS AND MAIN RESULTS: Cuff pressures were continuously recorded, and after 2 hours, a microaspiration score was calculated. Tapered cuffs improved cuff sealing performance compared with spherical cuffs with or without continuous cuff pressure control. Compared with spherical cuffs, tapered cuffs reduced the microaspiration score without and with continuous pressure control by 65% and 72%, respectively. Continuous cuff pressure control did not impact sealing performance. Tapered cuffs generated higher cuff pressures and increased the time spent with overinflation compared with spherical cuffs (median [interquartile range], 77.9% [0-99.8] vs. 0% [0-0.5]; p = 0.03). Continuous cuff pressure control reduced the variability of tapered and spherical cuffs likewise the time spent with overinflation of tapered and cylindrical cuffs. CONCLUSIONS: Polyvinyl chloride tapered cuffs sealing enhanced performance at the cost of an increase in cuff pressure and in time spent with overinflation. Continuous cuff pressure control reduced the variability and normalized cuff pressures without impacting sealing performance.

Long-term outcome of ovarian function in women with intermittent premature ovarian insufficiency.

CONTEXT: Spontaneous resumption of ovarian function is not a rare phenomenon in patients with premature ovarian insufficiency (POI). The outcome of this resumption is not known. OBJECTIVE: To describe the outcome following the resumption of ovarian function in POI patients. DESIGN: Cross-sectional study. SETTING: University medical centre. PATIENTS AND MAIN OUTCOME MEASURES: Cumulative incidence of ovarian function resumption and risk factors arresting this resumption during follow-up were determined in a large cohort of POI women. RESULTS: Five hundred and seven patients were included in the study, with a follow-up of 3·44 ± 4·05 years (0-29). Of these, 117 (23%) had features of ovarian function resumption. The cumulative incidence of pregnancy was 3·5% among the whole cohort and 15·3% among patients with resumption of ovarian function. Fifty-five patients (47%) experienced an arrest of their resumption during the follow-up period. In univariate analysis, high FSH and DHEA levels at initial evaluation were risk factors for the arrest of the resumption of ovarian function. In multivariate analysis, high FSH levels at the initial evaluation [1·89 (1·10-3·23), P = 0·03] and older age at diagnosis [1·53 (1·01-2·33), P = 0·04] were risk factors for the arrest of this resumption. CONCLUSION: Resumption of ovarian function is not a rare or brief phenomenon in POI women. The identification of predictive factors of this resumption, as well as its duration, increases our knowledge of the natural history of POI, and will improve the medical management, especially infertility counselling of these patients.

Flow cytometry minimal residual disease after allogeneic transplant for chronic lymphocytic leukemia.

OBJECTIVES: This study investigates whether achieving complete remission (CR) with undetectable minimal residual disease (MRD) after allogeneic stem cell transplantation (allo-SCT) for chronic lymphocytic leukemia (CLL) affects outcome. METHODS: We retrospectively studied 46 patients transplanted for CLL and evaluated for post-transplant MRD by flow cytometry. RESULTS: At transplant time, 43% of the patients were in CR, including one with undetectable MRD, 46% were in partial response, and 11% had refractory disease. After transplant, 61% of the patients achieved CR with undetectable MRD status. By multivariate analysis, reaching CR with undetectable MRD 12 months after transplant was the only factor associated with better progression-free survival (P = 0.02) and attaining undetectable MRD, independently of the time of negativity, was the only factor that correlated with better overall survival (P = 0.04). CONCLUSION: Thus, achieving undetectable MRD status after allo-SCT for CLL is a major goal to improve post-transplant outcome.

Cigarette Smoking During Pregnancy: Do Complete Abstinence and Low Level Cigarette Smoking Have Similar Impact on Birth Weight?

OBJECTIVES: Despite awareness of negative health outcomes associated with smoking, pregnant smokers might reduce their tobacco consumption thinking that a low smoking rate reduces smoking-related negative birth outcomes. We aimed to assess in a clinical sample whether there is a smoking rate that would not impact on birth weight (BW). METHODS: Pregnant smokers ≥18 years, gestational age of 9-20 weeks of amenorrhea, motivated to quit smoking, smoking ≥5 cigarettes/day (cpd) and their newborns (381 singleton, live births) were included in this secondary analysis of a French smoking cessation trial. RESULTS: The mean BW when the mother quit smoking was 3417 g (95 % CI: 3098-3738 g); when smoking >0<5 cpd, 3081g (3003-3159 g); when smoking 5-9 cpd, 3043 g (2930-3157 g); and when smoking ≥10 cpd, 2831 g (2596-3157 g) (p = .006). The corresponding effect sizes ranged from medium to large (Cohen's d for BW: 0.54, 0.57 and 0.85) compared to BW when the mother quit. In the multivariable analysis, adjusted for all significant confounders, when the mother smoked on average >0<5 cpd, the loss in BW was 228 g; when smoking 5-9 cpd, 251 g; and when smoking ≥10 cpd, 262 g (all p ≤ .02) compared to newborns' BW of mothers who stopped smoking since quit date. CONCLUSIONS: Even low cigarette consumption during pregnancy is associated with BW loss. All efforts should be made to help pregnant smokers quit completely during their pregnancy. IMPLICATIONS: As an alternative to quitting smoking, pregnant smokers reduce their smoking rate thinking that this diminishes smoking-related negative health outcomes. No study has established whether low smoking rate (more than 0 but less than 5 cpd) during pregnancy impacts BW compared to abstinence from smoking. Among treatment-seeking pregnant smokers BW of newborns of mothers who smoked even less than 5 cpd was significantly lower than of those whose mothers quit; effect sizes of different consumption levels on BW ranged from moderate (>0<5 cpd) to large (≥10 cpd). Even low smoking rate is associated with reduced BW compared to complete maternal smoking abstinence.

Evaluation of a Radiological Score in the Management of Pure Fractures of the Orbital Floor.

PURPOSE: The authors had for aim to further assess the predictive power and the relevance of a previously published radiological decision taking score for pure fractures with recording of clinical data. METHODS: The authors retrospectively included all patients managed in the authors' department for a pure orbital floor fracture, from June 2012 to November 2013. The authors collected clinical data including diplopia and enophtalmos, at initial status and after 3-months of follow-up. The radiological data was also recorded: rate of the fractured orbital floor, maximal height of periorbital tissue herniation, and a 4-grade muscular sub score. The treatment determinants were assessed by univariate analysis, with χ tests or Fisher exact tests for qualitative variables, and Student t tests for quantitative ones. A multivariate analysis was then performed with a stepwise logistic regression. RESULTS: The authors included 90 patients. The authors proposed a simple score (with a specificity of 79% and a sensitivity of 56%) for the indication to operate, using the rate, which was a significant predictor of treatment in the multivariate analysis. CONCLUSIONS: The authors' study is another step in the standardization of treatment decision for pure orbital floor fractures. The proposed score requires further clinical research to be validated but already helps to compare series of patients.

Risk factors for angiographic recurrence after treatment of unruptured intracranial aneurysms: Outcomes from a series of 178 unruptured aneurysms treated by regular coiling or surgery.

BACKGROUND: Long-term stability after intracranial aneurysm exclusion by coiling is still a matter of debate; after surgical clipping little is known. OBJECTIVE: To study outcome after endovascular and surgical treatments for unruptured intracranial aneurysms in terms of short- and long-term angiographic exclusion and risk factors for recanalization. METHODS: From 2004 and 2009, patients treated for unruptured berry intracranial aneurysms by coiling or clipping were reviewed. Aneurysmal exclusion was evaluated using the Roy-Raymond grading scale; immediate clinical outcome was also assessed. Clinical outcome, recanalization, risk factors for recurrence and bleeding during the follow-up period were analyzed by groups; "surgery" and "embolization". RESULTS: From 2004 to 2009, 178 consecutive unruptured aneurysms were treated. The post-procedure angiographic results for "surgery" were: total exclusion 75.6%; residual neck 13.5%; residual aneurysm 10.8%. For "embolization", the results were, respectively: 72%; 20.7%; and 7.2%. Morbidity was 3% for "surgery" and 1.6% for "embolization" (P=0.74); mortality was nil. Mean clinical and angiographic follow-up was 5years. Recurrence rate was of 11.5% for "surgery" vs. 44% for "embolization" with a mean follow-up of 4 and 5.75years, respectively (P=1.10-5). The retreatment rate was 8.4%. Two significant risk factors for recanalization were identified: maximum diameter of the aneurysm sac (P=0.0038) and pericallosal location (P=0.0388). No bleeding event occurred. CONCLUSION: Both techniques are safe. The rate of aneurismal recurrence was significantly higher for embolization, especially for large diameter aneurysms and pericallosal locations. No bleeding event occurred after recanalization.

Multicenter prospective validation of the Baveno IV and Baveno II/III criteria in cirrhosis patients with variceal bleeding.

UNLABELLED: The criteria for defining failure to control bleeding in cirrhosis patients were introduced at the Baveno II/III meetings and were widely used as endpoints in clinical trials. Because they lacked specificity, the Baveno IV criteria were proposed in 2005 and slightly modified in 2010 (Baveno V). These criteria included a new index for patients undergoing transfusion, called adjusted-blood-requirement-index (ABRI=number of blood units/(final-initial hematocrit+0.01)), with a cutoff value of 0.75. In this multicenter prospective study, we sought to 1) validate the Baveno IV/V criteria; 2) compare them to the Baveno II/III criteria; 3) assess ABRI performance using a standardized calculation. The key inclusion criteria were: 1) variceal bleeding; 2) cirrhosis; 3) no need to modify the transfusion policy. The patients were classified according to the Baveno IV, V, and II/III criteria. The gold standard for failure during a 5-day period was the clinical judgment of three independent experts, blinded to the Baveno assessments. A total of 249 patients were included. The experts' agreement in clinical judgment of the failure was 80%. Failure occurred in 20.5% of patients; the c-statistics were 0.72 versus 0.64 and 0.65 for Baveno IV versus Baveno II/III and Baveno V criteria (P=0.001 for both). ABRI did not improve the diagnostic performance of the Baveno IV criteria. The Baveno IV, but not Baveno II/III, criteria independently predicted survival. CONCLUSION: The Baveno IV criteria demonstrated a higher accuracy than the Baveno II/III and Baveno V criteria for assessing failure to control bleeding and predicted survival independently. Together, our results show that ABRI is not a useful metric, and the Baveno IV criteria should replace the Baveno II/III criteria.

Kleine-Levin syndrome in 120 patients: differential diagnosis and long episodes.

OBJECTIVE: Kleine-Levin syndrome is a rare disease characterized by recurrent episodes of hypersomnia with behavioral and cognitive disturbances. We aimed at describing the diagnosis procedure, risk factors, and severe forms. METHODS: In consecutive patients referred for suspected Kleine-Levin syndrome, we detailed differential diagnoses, and atypical and secondary cases, compared typical patients with healthy subjects, and examined the characteristics of patients with prolonged (>30 days) episodes. RESULTS: Among 166 referred patients, 120 had typical primary Kleine-Levin syndrome (syndrome secondary to brain diseases; n = 4, atypical syndrome, n = 7; differential diagnoses that were mostly psychiatric, n = 29; incomplete information, n = 6). The prevalence in France was 1.8 per million. The patients were often male (64%) and had more frequent birth and developmental abnormalities (45%) than controls (despite normal karyotypes), and most (80%) had teenage onset, with no difference between patients with prolonged (n = 34) and short (n = 85) episodes. In patients with prolonged episodes, the durations of the first episode (32 ± 33 vs 11 ± 6 days) and subsequent episodes were longer (mean episode duration = 23 ± 19 vs 10 ± 3 days) and the disease course tended to be longer (9 ± 6 vs 6 ± 4 years). During episodes, patients with prolonged episodes had shorter sleep time, higher levels of anxiety, increased agitation, and more feelings of disembodiment and amnesia. Between episodes, they were more tired, needed more naps, fell asleep more rapidly, and had higher anxiety/depression scores. INTERPRETATION: Mental disorders are frequent differential diagnoses of Kleine-Levin syndrome. One-third of patients have prolonged (>1 month) episodes with more frequent immediate and long-term consequences of the disease, prompting therapeutic trials.

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.

Is sleep-related verbal memory consolidation impaired in sleepwalkers?

In order to evaluate verbal memory consolidation during sleep in subjects experiencing sleepwalking or sleep terror, 19 patients experiencing sleepwalking/sleep terror and 19 controls performed two verbal memory tasks (16-word list from the Free and Cued Selective Reminding Test, and a 220- and 263-word modified story recall test) in the evening, followed by nocturnal video polysomnography (n = 29) and morning recall (night-time consolidation after 14 h, n = 38). The following morning, they were given a daytime learning task using the modified story recall test in reverse order, followed by an evening recall test after 9 h of wakefulness (daytime consolidation, n = 38). The patients experiencing sleepwalking/sleep terror exhibited more frequent awakenings during slow-wave sleep and longer wakefulness after sleep onset than the controls. Despite this reduction in sleep quality among sleepwalking/sleep terror patients, they improved their scores on the verbal tests the morning after sleep compared with the previous evening (+16 ± 33%) equally well as the controls (+2 ± 13%). The performance of both groups worsened during the daytime in the absence of sleep (-16 ± 15% for the sleepwalking/sleep terror group and -14 ± 11% for the control group). There was no significant correlation between the rate of memory consolidation and any of the sleep measures. Seven patients experiencing sleepwalking also sleep-talked during slow-wave sleep, but their sentences were unrelated to the tests or the list of words learned during the evening. In conclusion, the alteration of slow-wave sleep during sleepwalking/sleep terror does not noticeably impact on sleep-related verbal memory consolidation.

Prediction of the age at onset in spinocerebellar ataxia type 1, 2, 3 and 6.

BACKGROUND: The most common spinocerebellar ataxias (SCA)--SCA1, SCA2, SCA3, and SCA6--are caused by (CAG)n repeat expansion. While the number of repeats of the coding (CAG)n expansions is correlated with the age at onset, there are no appropriate models that include both affected and preclinical carriers allowing for the prediction of age at onset. METHODS: We combined data from two major European cohorts of SCA1, SCA2, SCA3, and SCA6 mutation carriers: 1187 affected individuals from the EUROSCA registry and 123 preclinical individuals from the RISCA cohort. For each SCA genotype, a regression model was fitted using a log-normal distribution for age at onset with the repeat length of the alleles as covariates. From these models, we calculated expected age at onset from birth and conditionally that this age is greater than the current age. RESULTS: For SCA2 and SCA3 genotypes, the expanded allele was a significant predictor of age at onset (-0.105±0.005 and -0.056±0.003) while for SCA1 and SCA6 genotypes both the size of the expanded and normal alleles were significant (expanded: -0.049±0.002 and -0.090±0.009, respectively; normal: +0.013±0.005 and -0.029±0.010, respectively). According to the model, we indicated the median values (90% critical region) and the expectancy (SD) of the predicted age at onset for each SCA genotype according to the CAG repeat size and current age. CONCLUSIONS: These estimations can be valuable in clinical and research. However, results need to be confirmed in other independent cohorts and in future longitudinal studies. CLINICALTRIALSGOV, NUMBER: NCT01037777 and NCT00136630 for the French patients.

Relationships between nicotine and cotinine concentrations in maternal milk and saliva.

AIM: Breastfeeding may be impaired due to nicotine excreted into the milk of smoking mothers. We investigated the relationships between nicotine and cotinine concentrations in maternal milk and saliva among breastfeeding smokers. METHODS: The 41 mothers reported their cigarette consumption between waking up and milk and saliva sampling. The median sampling time took place four days after delivery. Nicotine and cotinine concentrations were determined by liquid chromatography and UV detection, after a single-step saliva or three-step milk liquid-to-liquid extraction. RESULTS: The median (interquartile range) concentrations in milk and saliva were 7 (6-22) and 27 (4-207) µg/L for nicotine and 24 (5-111) and 22 (4-120) µg/L for cotinine, respectively. Milk cotinine was positively associated with saliva cotinine (p < 0.0001) and cigarette consumption (p = 0.039) and inversely associated with the time since the last cigarette (p = 0.0004, model R(2) = 0.90). Milk nicotine was associated with saliva nicotine concentration (p = 0.0017) and cigarette consumption (p = 0.0023, model R(2) = 0.63). CONCLUSION: Saliva nicotine concentration was not a very good estimate of milk nicotine concentration in breastfeeding mothers. Saliva cotinine concentration may be used instead of milk cotinine concentration to estimate tobacco or nicotine exposure among breastfed neonates or infants.

Prevalence and characteristics of cluster B personality disorder in a consultation-liaison psychiatry practice.

OBJECTIVE: Quantitative studies on cluster B-personality disorder (PD) in the general hospital are scarce. The aim of this study is to examine the prevalence and characteristics of cluster B-PD patients in a consultation-liaison practice. METHODS: Files of 258 consecutive patients referred for psychiatric consultation were examined. Cluster B patients were compared with the remaining patients. RESULTS: Eleven point six percent of these patients were diagnosed with a cluster B-PD. On univariate analysis, cluster B patients were more likely to be younger (P < 0.001), unmarried (P = 0.005), and without organic medical illness (P < 0.001).These patients had a shorter admission (P < 0.0001), and were more frequently treated in the emergency room (66.6% versus 37.5%, P = 0.02).There was a trend toward comorbid substance use disorder (P = 0.09). On multivariate analysis, cluster B patients presented significantly with self-harming behavior/ideation (80% versus 18%, OR = 12.07; 95% CI = 4.37-33.31; P < 0.0001). CONCLUSIONS: In view of the high prevalence of cluster B-PD in our preliminary study, general hospital staff requires practical skills for managing these high-maintenance patients. We believe that this study and further research will promote evidence-based recommendations for consultation-liaison psychiatrists.