Centre d'Études et de Recherches sur les Qualifications

An accurate genome sequence of a desired species is now a pre-requisite for genome research. An important step in obtaining a high-quality genome sequence is to correctly assemble short reads into longer sequences accurately representing contiguous genomic regions. Current sequencing technologies continue to offer increases in throughput, and corresponding reductions in cost and time. Unfortunately, the benefit of obtaining a large number of reads is complicated by sequencing errors, with different biases being observed with each platform. Although software are available to assemble reads for each individual system, no procedure has been proposed for high-quality simultaneous assembly based on reads from a mix of different technologies. In this paper, we describe a parallel short-read assembler, called Ray, which has been developed to assemble reads obtained from a combination of sequencing platforms. We compared its performance to other assemblers on simulated and real datasets. We used a combination of Roche/454 and Illumina reads to assemble three different genomes. We showed that mixing sequencing technologies systematically reduces the number of contigs and the number of errors. Because of its open nature, this new tool will hopefully serve as a basis to develop an assembler that can be of universal utilization (availability: http://deNovoAssembler.sf.Net/). For online Supplementary Material , see www.liebertonline.com.

The French Society of Intensive Care Medicine (SRLF), jointly with the French-Speaking Group of Paediatric Emergency Rooms and Intensive Care Units (GFRUP) and the French-Speaking Association of Paediatric Surgical Intensivists (ADARPEF), worked out guidelines for the management of central venous catheters (CVC), arterial catheters and dialysis catheters in intensive care unit. For adult patients: Using GRADE methodology, 36 recommendations for an improved catheter management were produced by the 22 experts. Recommendations regarding catheter-related infections' prevention included the preferential use of subclavian central vein (GRADE 1), a one-step skin disinfection(GRADE 1) using 2% chlorhexidine (CHG)-alcohol (GRADE 1), and the implementation of a quality of care improvement program. Antiseptic- or antibiotic-impregnated CVC should likely not be used (GRADE 2, for children and adults). Catheter dressings should likely not be changed before the 7th day, except when the dressing gets detached, soiled or impregnated with blood (GRADE 2- adults). CHG dressings should likely be used (GRADE 2+). For adults and children, ultrasound guidance should be used to reduce mechanical complications in case of internal jugular access (GRADE 1), subclavian access (Grade 2) and femoral venous, arterial radial and femoral access (Expert opinion). For children, an ultrasound-guided supraclavicular approach of the brachiocephalic vein was recommended to reduce the number of attempts for cannulation and mechanical complications. Based on scarce publications on diagnostic and therapeutic strategies and on their experience (expert opinion), the panel proposed definitions, and therapeutic strategies.

In a metal-polluted stream in the Riou Mort watershed in SW France, periphytic biofilm was analyzed for diatom cell densities and taxonomic composition, dry weight and metal bio-accumulation (cadmium and zinc). Periphytic diatom communities were affected by the metal but displayed induced tolerance, seen through structural impact (dominance of small, adnate species) as well as morphological abnormalities particularly in the genera Ulnaria and Fragilaria. Species assemblages were characterized by taxa known to occur in metal-polluted environments, and shifts in the community structure expressed seasonal patterns: high numbers of Eolimna minima, Nitzschia palea and Pinnularia parvulissima were recorded in Summer and Autumn, whereas the species Surirella brebissonii, Achnanthidium minutissimum, Navicula lanceolata and Surirella angusta were dominant in Winter and Spring. Commonly used indices such as the Shannon diversity index and Specific Pollution Sensitivity Index reflected the level of pollution and suggest seasonal periodicity, the lowest diversities being observed in Summer.

Alzheimer's disease and other related disorders (ADRD) represent a major challenge for health care systems within the aging population. It is therefore important to develop better instruments to assess the disease severity and progression, as well as to improve its treatment, stimulation, and rehabilitation. This is the underlying idea for the development of Serious Games (SG). These are digital applications specially adapted for purposes other than entertaining; such as rehabilitation, training and education. Recently, there has been an increase of interest in the use of SG targeting patients with ADRD. However, this field is completely uncharted, and the clinical, ethical, economic and research impact of the employment of SG in these target populations has never been systematically addressed. The aim of this paper is to systematically analyze the Strengths, Weaknesses, Opportunities, and Threats (SWOT) of employing SG with patients with ADRD in order to provide practical recommendations for the development and use of SG in these populations. These analyses and recommendations were gathered, commented on and validated during a 2-round workshop in the context of the 2013 Clinical Trial of Alzheimer's Disease (CTAD) conference, and endorsed by stakeholders in the field. The results revealed that SG may offer very useful tools for professionals involved in the care of patients suffering from ADRD. However, more interdisciplinary work should be done in order to create SG specifically targeting these populations. Furthermore, in order to acquire more academic and professional credibility and acceptance, it will be necessary to invest more in research targeting efficacy and feasibility. Finally, the emerging ethical challenges should be considered a priority.

The present study was designed to evaluate the performance of alternative bio-based solvents, more especially 2-methyltetrahydrofuran, obtained from crop's byproducts for the substitution of petroleum solvents such as hexane in the extraction of fat and oils for food (edible oil) and non-food (bio fuel) applications. First a solvent selection as well as an evaluation of the performance was made with Hansen Solubility Parameters and the COnductor-like Screening MOdel for Realistic Solvation (COSMO-RS) simulations. Experiments were performed on rapeseed oil extraction at laboratory and pilot plant scale for the determination of lipid yields, extraction kinetics, diffusion modeling, and complete lipid composition in term of fatty acids and micronutrients (sterols, tocopherols and tocotrienols). Finally, economic and energetic evaluations of the process were conducted to estimate the cost of manufacturing using 2-methyltetrahydrofuran (MeTHF) as alternative solvent compared to hexane as petroleum solvent.

Summary The relative importance of different binding mechanisms and associated biological binding agents on aggregate stability is still unclear. The aim of this study was to evaluate the role of various aggregate binding agents during the decomposition of cauliflower residues, wheat straw, cattle manure and poultry woody compost. We measured aggregate stability, hot‐water extractable polysaccharide, C mineralization, fungal and microbial biomass dynamics in an amended silt loam soil, under controlled conditions. Soil aggregate stability was measured using three methods involving fast wetting, slow wetting and mechanical breakdown. Aggregate stability to slow wetting followed the same dynamics as C mineralization and was well correlated with polysaccharide content for cauliflower residues and wheat straw. This relationship is in agreement with the hypothesis that the rapid microbially induced improvement in aggregate stability that follows fresh organic residue additions at least partly involves labile polysaccharides. The transient increase in the two other types of stability was not directly related to C mineralization dynamics and seemed to be influenced by fungal hyphal length. Fungi would provide resistance to mechanical breakdown and slaking. The dynamic behaviour of biological binding agents was only partly explained by the initial quality of the organic materials, as characterized by Van Soest proximal fractionation. Dynamique de la stabilité structurale et des facteurs agrégeants biologiques associée à la décomposition de produits organiques. Résumé L’importance relative des différents mécanismes d’agrégation et des facteurs agrégeants biologiques associés n’est toujours pas clairement établie. L’objectif de cette étude est d’évaluer l’effet de différents facteurs agrégeants sur la stabilité structurale au cours de la décomposition de produits organiques: de résidus de chou‐fleur, de paille de blé, d’un fumier de bovin et d’un compost de fientes de volailles et d’écorce de peuplier. Nous avons mesuré les dynamiques de stabilité des agrégats, de minéralisation du C et des biomasses microbienne et fongique d’un sol limoneux amendé pour des conditions contrôlées. La stabilité structurale est mesurée par trois traitements d’intensités différentes correspondant à une humectation rapide, une humectation lente et une désagrégation mécanique sur des agrégats. La stabilité structurale soumise à l’humectation lente suit les mêmes dynamiques que la minéralisation du C et est bien corrélée avec la concentration en polysaccharides pour les résidus de chou‐fleur et la paille de blé. Cette corrélation confirme l’hypothèse que les polysaccharides labiles participent au moins partiellement à l’amélioration rapide de la stabilité des agrégats induite par l’activité microbienne à la suite d’apports de produits organiques frais. L’augmentation transitoire des deux autres types de stabilité structurale n’est pas directement liée aux dynamiques de minéralisation du C et est plutôt influencée par la longueur des hyphes mycéliens. Le rôle des champignons serait alors d’accroître la résistance des agrégats soumis à des forces de désagrégation plus importantes. Le comportement des différents agents agrégeants biologiques n’est que partiellement expliqué par la composition initiale des produits organiques, caractérisés par la méthode de fractionnement Van Soest.

BACKGROUND: Rapid response teams are intended to improve early diagnosis and intervention in ward patients who develop acute respiratory or circulatory failure. A management protocol including the use of a handheld ultrasound device for immediate point-of-care ultrasound (POCUS) examination at the bedside may improve team performance. The main objective of the study was to assess the impact of implementing such a POCUS-guided management on the proportion of adequate immediate diagnoses in two groups. Secondary endpoints included time to treatment and patient outcomes. METHODS: A prospective, observational, controlled study was conducted in a single university hospital. Two teams alternated every other day for managing in-hospital ward patients developing acute respiratory and/or circulatory failures. Only one of the team used an ultrasound device (POCUS group). RESULTS: We included 165 patients (POCUS group 83, control group 82). Proportion of adequate immediate diagnoses was 94% in the POCUS group and 80% in the control group (p = 0.009). Time to first treatment/intervention was shorter in the POCUS group (15 [10-25] min vs. 34 [15-40] min, p < 0.001). In-hospital mortality rates were 17% in the POCUS group and 35% in the control group (p = 0.007), but this difference was not confirmed in the propensity score sample (29% vs. 34%, p = 0.53). CONCLUSION: Our study suggests that protocolized use of a handheld POCUS device at the bedside in the ward may improve the proportion of adequate diagnosis, the time to initial treatment and perhaps also survival of ward patients developing acute respiratory or circulatory failure. Clinical Trial Registration NCT02967809. Registered 18 November 2016, https://clinicaltrials.gov/ct2/show/NCT02967809 .

Les techniques de modélisation causale, en particulier les équations structurelles (et notamment celles basées sur la covariance), ont connu un succès croissant auprès des chercheurs en management depuis une vingtaine d’années. Parmi elles, l’approche PLS (Partial Least Squares) commence à être diffusée depuis quelques années au sein de la communauté de la recherche en management. Or, les connaissances sur cette méthode sont peu approfondies et peu diffusées. Cet article tente de démontrer en quoi l’approche PLS est une méthode riche et subtile offrant des opportunités pour la recherche en management qui méritent d’être saisies. Pour cela, la méthode et ses principes sont exposés puis illustrés par une recherche menée dans le domaine des relations clients-fournisseurs. Puis, les spécificités de l’approche PLS sont abordées et l’utilisation de l’outil est étudiée à travers l’analyse empirique de 51 articles en management et stratégie. On en conclut que, même si des efforts restent encore à fournir au niveau de la fiabilité statistique de certaines études, l’approche PLS permet indéniablement d’offrir de réelles opportunités aux chercheurs en management, les affranchissant de certaines difficultés techniques et leur permettant de se concentrer alors sur l’essentiel, leur objet de recherche. La diffusion de l’approche PLS au sein de la communauté des chercheurs en management pourrait donc contribuer de façon très significative à l’enrichissement scientifique de la discipline.

BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord. Nusinersen has been covered by public healthcare in France since May 2017. The aim of this article is to report results after 1 year of treatment with intrathecal nusinersen in children with SMA types 1 and 2 in France. Comparisons between treatment onset (T0) and after 1 year of treatment (Y1) were made in terms of motor function and need for nutritional and ventilatory support. Motor development milestone achievements were evaluated using the modified Hammersmith Infant Neurologic Examination-Part 2 (HINE-2) for patients under 2 years of age and Motor Function Measure (MFM) scores for patients over 2 years of age. RESULTS: Data on 204 SMA patients (type 1 or 2) were retrospectively collected from the 23 French centers for neuromuscular diseases. One hundred and twenty three patients had been treated for at least 1 year and were included, 34 of whom were classified as type 1 (10 as type 1a/b and 24 as type 1c) and 89 as type 2. Survival motor Neuron 2 (SMN2) copy numbers were available for all but 6 patients. Patients under 2 years of age (n = 30), had significantly higher HINE-2 scores at year 1 than at treatment onset but used more nutritional and ventilatory support. The 68 patients over 2 years of age evaluated with the Motor Function Measure test had significantly higher overall scores after 1 year, indicating that their motor function had improved. The scores were higher in the axial and proximal motor function (D2) and distal motor function (D3) parts of the MFM scale, but there was no significant difference for standing and transfer scores (D1). No child in either of the two groups achieved walking. CONCLUSION: Nusinersen offers life-changing benefits for children with SMA, particularly those with more severe forms of the disorder. Caregiver assessments are positive. Nevertheless, patients remain severely disabled and still require intensive support care. This new treatment raises new ethical challenges.

The antioxidant properties of nine tannins isolated and characterized from different parts of Guiera senegalensis were evaluated. Interesting results showed that galloylquinic acids (hydrolysable tannins), resulting from a tri- or tetra-substitution of galloyl groups on the quinic acid skeleton, played a crucial role in the inhibitory effect on Fe2+-induced lipid peroxidation in rat liver microsomes and radical scavenger activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) test. The effects of all tannins were markedly higher than that of gallic acid. Condensed tannins such as epicatechin and epigallocatechin gallate also showed fairly significant effects in both tests. © 1998 John Wiley & Sons, Ltd.

Abstract Rationale Dyspnea is a traumatic experience. Only limited information is available on dyspnea in intubated critically ill patients. Objectives Our objectives were 1) to quantify the prevalence and severity of dyspnea; and 2) to evaluate the impact of dyspnea on ICU length of stay and post-traumatic stress disorder (PTSD) 90 days after ICU discharge. Methods This was a prospective cohort study in 10 ICUs in France. In patients intubated for more than 24 hours, dyspnea was quantified with a visual analog scale (from 0 to 10) as soon as they were able to communicate, the following day, and before spontaneous breathing trials. PTSD was defined by an Impact of Event Scale-Revised score of at least 22. Measurements and Main Results Among the 612 patients assessed, 34% reported dyspnea, with a median dyspnea rating of 5 (interquartile range, 4–7). ICU length of stay was not significantly different between patients with versus without dyspnea (6 [3–12] and 6 [3–13] days, respectively; P = 0.781). Mortality was not different between groups. Of the 153 patients interviewed on Day 90, a higher proportion of individuals with probable PTSD was observed among patients who were dyspneic on enrollment (29% vs. 13%; P = 0.017). The density of dyspnea (number of dyspneic episodes divided by time from enrollment to extubation) was independently associated with PTSD (odds ratio, 1.07; 95% confidence interval, 1.01–1.13; P = 0.031). Conclusions Dyspnea was frequent and intense in intubated critically ill patients. ICU length of stay was not significantly different among patients reporting dyspnea, but PTSD was more frequent at Day 90. Clinical trial registered with www.clinicaltrials.gov(NCT 02336464).

BACKGROUND: Patients with schizophrenia represent a vulnerable, underserved, and undertreated population who have been neglected in health disparities work. Understanding of end-of-life care in patients with schizophrenia and cancer is poor. We aimed to establish whether end-of-life care delivered to patients with schizophrenia and cancer differed from that delivered to patients with cancer who do not have diagnosed mental illness. METHODS: We did a population-based cohort study of all patients older than 15 years who had a diagnosis of advanced cancer and who died in hospital in France between Jan 1, 2013, and Dec 31, 2016. We divided this population into cases (ie, patients with schizophrenia) and controls (ie, patients without a diagnosis of mental illness) and compared access to palliative care and indicators of high-intensity end-of-life care between groups. In addition to unmatched analyses, we also did matched analyses (matched in terms of age at death, sex, and site of primary cancer) between patients with schizophrenia and matched controls (1:4). Multivariable generalised linear models were done with adjustment for social deprivation, year of death, time from cancer diagnosis to death, metastases, comorbidity, and hospital type (ie, specialist cancer centre vs non-specialist centre). FINDINGS: The main analysis included 2481 patients with schizophrenia and 222 477 controls. The matched analyses included 2477 patients with schizophrenia and 9896 controls. Patients with schizophrenia were more likely to receive palliative care in the last 31 days of life (adjusted odds ratio 1·61 [95% CI 1·45-1·80]; p<0·0001) and less likely to receive high-intensity end-of-life care-such as chemotherapy and surgery-than were matched controls without a diagnosis of mental illness. Patients with schizophrenia were also more likely to die younger, had a shorter duration between cancer diagnosis and death, and were more likely to have thoracic cancers and comorbidities than were controls. INTERPRETATION: Our findings suggest the existence of disparities in health and health care between patients with schizophrenia and patients without a diagnosis of mental illness. These findings underscore the need for better understanding of health inequalities so that effective interventions can be developed for this vulnerable population. FUNDING: Assistance Publique des Hôpitaux de Marseille and Aix-Marseille University.

Purpose The purpose of this paper is to question the appropriateness of a proposal for a new European Qualifications Framework. The framework has three perspectives: historical; analytical; and national. Design/methodology/approach The approaches are diverse since the first insists on the institutional and decision‐making processes at European level questioning the impact that could have on the recently formalised Open Method of Coordination. The second goes into more detailed analyses of the instrument itself and of its shortcomings both in conceptual terms and on its pragmatic ones. The last approach is a comparative one by which the French system is “benchmarked” against EQF guidelines. Findings The main conclusion is that there is obviously a political will to question the role and the structure of qualifications in view of an economy and a society of knowledge and that research has much to contribute – on very different levels – like the three chosen for this article. Research limitations/implications Choosing to mix three quite different approaches in one short text is an attempt to be valued since it shows the different aspects under which a so‐called “neutral” instrument needs to be regarded. Practical implications Practically, this speaks for the further involvement of research in the present, very institutional and organisational discussions on European qualifications. Originality/value In terms of research, it is seldom that these various levels are considered together. The article proves that there is a case to do so.

techniques, and is a useful model to assess and longitudinally monitor early neurotransmission dysfunction and neuroinflammation in AD.

Nous poursuivons dans cet article le travail théorique déjà largement entamé en didactique, autour du concept de « milieu ». Nous prenons d’abord appui sur une étude empirique concernant la comparaison de séances ordinaires d’enseignement de l’éducation physique et sportive (EPS) et de physique menées par deux professeurs d’un même collège « ambition réussite ». Les phénomènes didactiques étant exacerbés dans le contexte d’enseignement difficile, celui-ci permet de mieux saisir certains aspects critiques (décrits dans l’article) des processus mésogénétiques à l’œuvre dans l’action conjointe professeur élèves. Nous revenons ensuite sur les principales conceptualisations de la notion de milieu. Nous avançons l’idée que les points de vue différents qu’elles présentent peuvent être dépassés en considérant la complémentarité des dimensions institutionnelles et situationnelles à l’œuvre. Cette analyse et les résultats de l’étude empirique nous conduisent à envisager au sein de la théorie de l’action didactique conjointe, le milieu comme résultant d’un processus dynamique, généralement différentiel, inscrit dans des échelles temporelles multiples articulant les registres de l’activité et de l’action didactiques.

BACKGROUND: Ultra-lung-protective ventilation may be useful during veno-venous extracorporeal membrane oxygenation (vv-ECMO) for severe acute respiratory distress syndrome (ARDS) to minimize ventilator-induced lung injury and to facilitate lung recovery. The objective was to compare pulmonary and systemic biotrauma evaluated by numerous biomarkers of inflammation, epithelial, endothelial injuries, and lung repair according to two ventilator strategies on vv-ECMO. METHODS: This is a prospective randomized controlled study. Patients were randomized to receive during 48 h either ultra-lung-protective ventilation combining very low tidal volume (1-2 mL/kg of predicted body weight), low respiratory rate (5-10 cycles per minute), positive expiratory transpulmonary pressure, and 16 h of prone position or lung-protective-ventilation which followed the ECMO arm of the EOLIA trial (control group). RESULTS: The primary outcome was the alveolar concentrations of interleukin-1-beta, interleukin-6, interleukin-8, surfactant protein D, and blood concentrations of serum advanced glycation end products and angiopoietin-2 48 h after randomization. Enrollment was stopped for futility after the inclusion of 39 patients. Tidal volume, respiratory rate, minute ventilation, plateau pressure, and mechanical power were significantly lower in the ultra-lung-protective group. None of the concentrations of the pre-specified biomarkers differed between the two groups 48 h after randomization. However, a trend to higher 60-day mortality was observed in the ultra-lung-protective group compared to the control group (45 vs 17%, p = 0.06). CONCLUSIONS: Despite a significant reduction in the mechanical power, ultra-lung-protective ventilation during 48 h did not reduce biotrauma in patients with vv-ECMO-supported ARDS. The impact of this ventilation strategy on clinical outcomes warrants further investigation. Trial registration Clinical trial registered with www. CLINICALTRIALS: gov ( NCT03918603 ). Registered 17 April 2019.

Holoprosencephaly (HPE) is a brain malformation which results from a primary defect in induction and patterning of the rostral neural tube during early embryogenesis and usually considered as an impaired cleavage of the prosencephalon. The review of neuropathologic findings highlights a complex malformation involving not only the prosencephalon but also the whole brain, the eyes, and the cerebral vascularization. The classical form of HPE is divided in three sub-types according to DeMyer classification, although the spectrum is far wider, ranging from the most severe, aprosencephaly/atelencephaly, to milder forms such as syntelencephaly and to the less severe ends of the spectrum. Macroscopy and microscopy abnormality patterns are described extensively, allowing a comparison of the anatomic features between each form. Disturbances observed in the main cerebral structures including the basal ganglia, the commissures, the hippocampus, the brainstem, the cerebellum, and spinal cord are reviewed. Macroscopic and microscopic features of the ophthalmic anomalies are described, as well as brain vascular and associated central nervous system malformations.

Abstract Rationale Whether patients with coronavirus disease (COVID-19) may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. Objectives To estimate the effect of ECMO on 90-day mortality versus IMV only. Methods Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO versus no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/Fi O2 < 80 or PaCO2 ⩾ 60 mm Hg). We controlled for confounding using a multivariable Cox model on the basis of predefined variables. Measurements and Main Results A total of 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability on Day 7 from the onset of eligibility criteria (87% vs. 83%; risk difference, 4%; 95% confidence interval, 0–9%), which decreased during follow-up (survival on Day 90: 63% vs. 65%; risk difference, −2%; 95% confidence interval, −10 to 5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand and when initiated within the first 4 days of IMV and in patients who are profoundly hypoxemic. Conclusions In an emulated trial on the basis of a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and regions with ECMO capacities specifically organized to handle high demand.

As the coronavirus disease 2019 (COVID-19) pandemic has spread throughout the world, important efforts have been made to describe its physiopathology and complications.In critically ill patients with COVID-19, a systemic inflammatory response associated with endothelial activation is observed. 1A high rate of thrombotic complications has been described, including deep vein thrombosis. 2 Although the mechanisms of thrombosis are unclear, anticoagulation with high doses of heparin has been proposed for these patients.Heparin-induced thrombocytopenia (HIT) is a severe, life-threatening drug reaction associated with a decrease in platelet count and a high risk of thrombosis caused by platelet-activating antibodies against PF4/heparin complexes. 3he atypical clinical and therapeutic context of the COVID-19 pandemic, with a broader indication of curative anticoagulation, could lead to a higher prevalence of HIT.In this context, we retrospectively reviewed all cases of HIT among patients presenting with COVID-19 acute respiratory distress syndrome (ARDS) in 2 intensive care units in southern France.We described 7 consecutive cases of HIT associated with COVID-19 ARDS between March 30 and April 18, 2020 (Table ).Patients or their relatives received information and signed a nonopposition form, according to French law, to be enrolled in COAG-COVID (Coagulopathy of COVID-19: A Pragmatic Randomized Controlled Trial of Therapeutic Anticoagulation Versus Standard Care).The study was approved by an ethics committee.All patients presented antibodies to PF4/heparin, as detected by a quantitative chemiluminescent immunoassay (HemosIL AcuStar HIT immunoglobulin G, PF4-H, normal value <1 U/ml).Diagnosis was confirmed for the 7 patients using the heparin-induced platelet aggregation test.Six patients were male, with a median age of 57 years (interquartile range, 46-63 years).The median body mass index was 26 (interquartile range, 25-30).Most patients had severe ARDS, with a median Pao 2 /Fio 2 ratio of 80 (interquartile range, 75-113).All but one were intubated and mechanically ventilated.Three were supported by venovenous extracorporeal membrane oxygenation for refractory hypoxemia.All patients were exposed to unfractionated heparin, including 5 after the administration of low-molecular-weight heparin for a median of 14 days (interquartile range, 11-16 days).All patients had curative anticoagulation objectives.The duration of heparin exposure before HIT diagnosis was >10 days for 6 patients.All patients presented a severe drop in platelet count.Five patients experienced at least 1 severe clinical thromboembolic event.Alternative anticoagulation was pursued with either danaparoid or argatroban.All platelet counts returned to normal values after the anticoagulation therapy was switched.At the observation period end point, 5 patients were discharged from the intensive care unit, including 3 from the hospital, and the remaining 2 were still in the intensive care unit.

Mechanical ventilation (MV) is the cornerstone of acute respiratory distress syndrome (ARDS) management. The use of protective ventilation is a priority in this acute phase of lung inflammation. Neuromuscular blocking agents (NMBAs) induce reversible muscle paralysis. Their use in patients with ARDS remains controversial but occurs frequently. NMBAs are used in 25-45% of ARDS patients for a mean period of 1±2 days. The main indications of NMBAs are hypoxemia and facilitation of MV. For ethical reasons, NMBA use is inseparable from sedation in the management of early ARDS. During paralysis, sedation monitoring seems to be necessary to avoid awareness with recall. Three randomized controlled trials (RCTs) have demonstrated that the systematic use of NMBAs in the early management of ARDS patients improves oxygenation. Furthermore, the most recent trial reported a reduction of mortality at 90 days when NMBAs were infused over 48 hours. Spontaneous ventilation (SV) during MV at the acute phase of ARDS could improve oxygenation and alveolar recruitment, but it may not allow protective ventilation. The major risk is an increase in ventilator-induced lung injury. However, the adverse effects of NMBAs are widely discussed, particularly the occurrence of intensive care unit (ICU)-acquired weakness. This review analyses the recent findings in the literature concerning sedation and paralysis in managing ARDS.