Search

AIM There is a crucial need for pharmacokinetic (PK) data of oral vinorelbine (VNR) in pediatric population. The aim of this work was to assess the PK profile of orally administered VNR in children with recurrent/progressive primary low-grade glioma (LGG). METHODS A multicentric, open-label, single-arm intervention phase II study was conducted. Patients, aged between 6 and 18 years, with histologically confirmed recurrent or progressive primary LGG or non-documented typical optic pathway tumors, were included. PK parameters were estimated by non-compartmental analysis using Phoenix WinNonlin® software (version 8.0, Certara, Inc.). The Influence of demographic and biological covariates on VNR PK parameters was investigated using a multivariate linear regression analysis. RESULTS PK analysis included 36 patients with a median age (range) of 11 (6-17) years. Estimates of apparent oral clearance (CL/F), apparent volume of distribution (V/F), half-life (t1/2 ) and their between-subject variability (CV%) at 60 mg.m-2 dose level, were 472 L.h-1 (51.8%), 7002 L (57.9%) and 10 h (21.0%), respectively. Negligible accumulation of VNR between C1 and C2 was observed. CL/F and V/F were found to increase with body surface area (BSA) (p = 0.004). Lower area under the concentration-time curve (AUC) levels were observed among children in comparison to adults. CONCLUSION Higher doses may be necessary for children with LGG. BSA showed a significant impact on VNR systemic exposure. We believe that our findings will serve as a basis for further studies to better characterize the concentration-response relationships of VNR among pediatric patients.

International audience; OBJECTIVES: Geotrichum spp can be responsible for severe infections in immunocompromised patients. We aim to describe Geotrichum-related infections in the ICU and to assess risk factors of mortality. METHODS: Retrospective multicentre study, conducted in 14 French ICUs between 2002 and 2018, including critically ill adult patients with proven or probable infection related to Geotrichum species. Data were obtained from the medical charts. RESULTS: Thirty-six patients, median age 60 years IQR [53; 66] were included. Most of the patients had haematological malignancies (78%). The reason for ICU admission was shock in half of the patients (n = 19, 53%) and respiratory failure in thirteen patients (36%). Median SOFA score was 8.5 IQR [7; 15]. Time between ICU admission and fungal diagnosis was 2.5 days [-1; 4]. Infection was disseminated in 27 (75%) patients with positive blood cultures in 25 patients (69%). Thirty patients (83%) received curative antifungal treatment in the ICU, in a median time of 1 day [0;1] after ICU admission. Twenty-four patients (67%) died in the ICU and hospital mortality rate was 69%. The number and extent of organ failures, as represented by SOFA score, were associated with mortality. CONCLUSIONS: This study demonstrates poor outcome in critically ill patients with Geotrichum-related infections, which encourages a high level of suspicion.

Purpose The purpose of this study was to compare the effect of speech intervention provided with a low intensity with speech intervention provided with a high intensity on the speech and health-related quality of life (HRQoL) in Dutch-speaking children with a cleft palate with or without a cleft lip (CP ± L) between 4 and 12 years. Method A longitudinal, prospective, randomized controlled trial with a multiple baseline design was used. Twelve children with a CP ± L ( M age = 8.0 years, SD = 1.54) were divided into two groups using block randomization stratified by age and gender: One group received low-intensity speech intervention (LISI; n = 6) and one group received high-intensity speech intervention (HISI; n = 6). Children in the LISI group received intervention with a session duration of 1 hr, a dose frequency of 1 session per week, and a total intervention duration of 10 weeks. Children in the HISI group received intervention with a session duration of 1 hr, a dose frequency of 5 sessions per week, and a total intervention duration of 2 weeks. The cumulative intervention intensity was kept constant. Both groups received identical therapy programs provided by the same experienced speech therapist. Perceptual speech assessments were performed on baseline and posttreatment data points. Changes in HRQoL were assessed using the Velopharyngeal Insufficiency Effects on Life Outcomes (VELO) questionnaire. Both groups were compared over time using (generalized) linear mixed models. Results No significant Time × Group interactions were observed for the percentage of correctly produced consonants at the word and sentence levels, indicating no differences in evolution over time among the two groups. The variables speech understandability, speech acceptability, and the total VELO scores significantly improved following HISI, but not following LISI. Conclusions Children in the HISI group made equal and, for some variables, even superior progress in only 2 weeks of therapy compared to children in the LISI group who received 10 weeks of therapy. HISI is a promising strategy to improve speech outcomes and HRQoL in a shorter time period.

Background Working in the ICU during the first COVID-19 wave was associated with high levels of mental health disorders. Research Question What are the mental health symptoms in health care providers (HCPs) facing the second wave? Study Design and Methods A cross-sectional study (October 30-December 1, 2020) was conducted in 16 ICUs during the second wave in France. HCPs completed the Hospital Anxiety and Depression Scale, the Impact of Event Scale-Revised (for post-traumatic stress disorder), and the Maslach Burnout Inventory. Results Of 1,203 HCPs, 845 responded (70%) (66% nursing staff, 32% medical staff, 2% other professionals); 487 (57.6%) had treated more than 10 new patients with COVID-19 in the previous week. Insomnia affected 320 (37.9%), and 7.7% were taking a psychotropic drug daily. Symptoms of anxiety, depression, post-traumatic stress disorder, and burnout were reported in 60.0% (95% CI, 56.6%-63.3%), 36.1% (95% CI, 32.9%-39.5%), 28.4% (95% CI, 25.4%-31.6%), and 45.1% (95% CI, 41.7%-48.5%) of respondents, respectively. Independent predictors of such symptoms included respondent characteristics (sex, profession, experience, personality traits), work organization (ability to rest and to care for family), and self-perceptions (fear of becoming infected or of infecting family and friends, feeling pressure related to the surge, intention to leave the ICU, lassitude, working conditions, feeling they had a high-risk profession, and “missing the clapping”). The number of patients with COVID-19 treated in the first wave or over the last week was not associated with symptoms of mental health disorders. Interpretation The prevalence of symptoms of mental health disorders is high in ICU HCPs managing the second COVID-19 surge. The highest tiers of hospital management urgently need to provide psychological support, peer-support groups, and a communication structure that ensure the well-being of HCPs.

International audience; We identified three cases of congenital disorders of glycosylation (CDG) with Golgi homeostasis disruption, one ATP6V0A2-CDG and two COG4-CDG, with normal transferrin screening analyses. Patient 1 (P1) presented at birth with cutis laxa. Patient 2 (P2) and patient 3 (P3) are adult siblings and presented with severe symptoms evocative of inborn errors of metabolism. Targeted gene sequencing in P1 revealed pathogenic ATP6V0A2 variants, shared by her affected older brother. In P2 and P3, whole exome sequencing revealed a homozygous COG4 variant of unknown significance. In all affected individuals, transferrin analysis was normal. Mass-spectrometry based serum N-glycome analysis and two-dimensional electrophoresis (2-DE) of haptoglobin and of mucin core 1 O-glycosylated apolipoprotein C-III (apoC-III) were performed. All results of second-line N-glycosylation analyses were initially normal. However, apoC-III 2-DE revealed characteristic "apoC-III1" pattern in P1 and specific "apoC-III0" patterns in P2 and P3. In P2 and P3, this allowed reclassifying the variant as likely pathogenic according to ACMG guidelines. These cases highlight the existence of normal transferrin patterns in CDG with Golgi homeostasis disruption, putting the clinicians at risk of misdiagnosing patients. Furthermore, they show the potential of apoC-III 2-DE in diagnosing this type of CDG, with highly specific patterns in COG-CDG.

Background: Relationships between malocclusion and orofacial myofunctional disorders (OMD), as well as malocclusions and articulation disorders (AD) have been described, though the exact relationships remain unclear. Given the high prevalence of these disorders in children, more clarity is needed. Summary: The purpose of this study was to determine the association between OMD (specifically, bruxism, deviate swallowing, caudal resting tongue posture, and biting habits), AD, and malocclusions in children and adolescents aged between 3 and 18 years. To conduct a systematic review, 4 databases were searched (MEDLINE, Embase, Web of Science, and Scopus). The identified articles were screened for the eligibility criteria. Data were extracted from the selected articles and quality assessment was performed using the tool of Munn et al. [Int J Health Policy Manag. 2014;3:123–81] in consensus. Using the search strategy, the authors identified 2,652 articles after the removal of duplicates. After reviewing the eligibility criteria, 17 articles were included in this study. One of the included articles was deemed to have an unclear risk of bias, whereas all other articles were considered to have a low risk of bias. The articles showed a relationship between anterior open bite and apico-alveolar articulatory distortions, as well as between anterior open bite and deviate swallowing. For the biting habits, bruxism, and low tongue position no clear conclusions could be drawn. Key Messages: The current review suggests a link between specific types of malocclusion and OMD and AD. However, more high-quality evidence (level 1 and level 2, Oxford Levels of Evidence) is needed to clarify the cooccurrence of other OMD, AD, and malocclusions.

This paper focuses on R&D employment effects due to financial slack generated by an R&D tax exemption scheme in Belgium. The tax exemption is granted without firm level requirements, which facilitates testing firm level contingencies on the influence of the generated financial slack. We find that R&D employment effects increase with the level of the R&D tax exemption related financial slack resources, and that this positive relation is more outspoken for older firms and for firms with an intermediate share of R&D tax exemptions in the overall mix of R&D policy support. No effects are found for firm size and its R&D intensity. These findings suggest targeting the R&D tax exemption support according to firm characteristics to obtain longer term R&D employment effects. The focus on R&D employment adds to the literature on evaluation of R&D policies which is largely oriented towards R&D expenditure and innovation outputs. ispartof: R&D Management vol:52 issue:1 status: published

International audience; OBJECTIVES: To provide an overview of the spectrum, characteristics and outcomes of neurologic manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We conducted a single-centre retrospective study during the French coronavirus disease 2019 (COVID-19) epidemic in March-April 2020. All COVID-19 patients with de novo neurologic manifestations were eligible. RESULTS: We included 222 COVID-19 patients with neurologic manifestations from 46 centres in France. Median (interquartile range, IQR) age was 65 (53-72) years and 136 patients (61.3%) were male. COVID-19 was severe or critical in 102 patients (45.2%). The most common neurologic diseases were COVID-19-associated encephalopathy (67/222, 30.2%), acute ischaemic cerebrovascular syndrome (57/222, 25.7%), encephalitis (21/222, 9.5%) and Guillain-Barré syndrome (15/222, 6.8%). Neurologic manifestations appeared after the first COVID-19 symptoms with a median (IQR) delay of 6 (3-8) days in COVID-19-associated encephalopathy, 7 (5-10) days in encephalitis, 12 (7-18) days in acute ischaemic cerebrovascular syndrome and 18 (15-28) days in Guillain-Barré syndrome. Brain imaging was performed in 192 patients (86.5%), including 157 magnetic resonance imaging (70.7%). Among patients with acute ischaemic cerebrovascular syndrome, 13 (22.8%) of 57 had multiterritory ischaemic strokes, with large vessel thrombosis in 16 (28.1%) of 57. Brain magnetic resonance imaging of encephalitis patients showed heterogeneous acute nonvascular lesions in 14 (66.7%) of 21. Cerebrospinal fluid of 97 patients (43.7%) was analysed, with pleocytosis found in 18 patients (18.6%) and a positive SARS-CoV-2 PCR result in two patients with encephalitis. The median (IQR) follow-up was 24 (17-34) days with a high short-term mortality rate (28/222, 12.6%). CONCLUSIONS: Clinical spectrum and outcomes of neurologic manifestations associated with SARS-CoV-2 infection were broad and heterogeneous, suggesting different underlying pathogenic processes.

We investigate whether the presence of outside members in the board or buying ad hoc professional advisory services fuel short-term start-up growth. Furthermore, how the founding team’s initial knowledge stock as well as environmental uncertainty affect this relationship is examined. Our results only suggest a positive association between professional advisory services and start-up growth, which seem to suggest that the presence of an outside board member does not affect short-term start-up growth. We also find that the relationship between professional advisory services and growth is more pronounced when previous relevant industry expertise of the founding team is lower and technological opportunities in the environment are larger. Our findings advance understanding of the determinants of short-term start-up growth and are of practical relevance to entrepreneurs and policymakers.

International audience; Complementary tools are warranted to increase the sensitivity of the initial testing for COVID-19. We identified a specific ‘sandglass’ aspect on the white blood cell scattergram of COVID-19 patients reflecting the presence of circulating plasmacytoid lymphocytes. Patients were dichotomized as COVID-19-positive or -negative based on reverse transcriptase polymerase chain reaction (RT-PCR) and chest computed tomography (CT) scan results. Sensitivity and specificity of the ‘sandglass’ aspect were 85·9% and 83·5% respectively. The positive predictive value was 94·3%. Our findings provide a non-invasive and simple tool to quickly categorize symptomatic patients as either COVID-19-probable or -improbable especially when RT-PCR and/or chest CT are not rapidly available.

We present here a new method for bioethics: systemic modelling. In this method, the complex phenomenon being studied (e.g. personalized medicine, genetic testing, gene therapy, genetically modified organisms) is modelled as a whole, to shed light on its organization and functioning, and major (bio)ethical issues and solutions for their resolution are then identified. This systemic modelling method is ideal for use in the identification of solutions, rather than their validation, with other methods then used to test the solutions found. We provide a description and reproducible instructions for the application of systemic modelling in bioethics, together with a brief example of the application of this method to the study of the impact of personalized medicine on French society.

Objectives: Cancer affects up to 20% of critically ill patients, and sepsis is one of the leading reasons for ICU admission in this setting. Early signals suggested that survival might be increasing in this population. However, confirmation studies have been lacking. The goal of this study was to assess trends in survival rates over time in cancer patients admitted to the ICU for sepsis or septic shock over the last 2 decades. Data Source: Seven European ICUs. Study Selection: A hierarchical model taking into account the year of admission and the source dataset as random variables was used to identify risk factors for day 30 mortality. Data Extraction: Data from cancer patients admitted to ICUs for sepsis or septic shock were extracted from the Groupe de Recherche Respiratoire en Reanimation Onco-Hematologique database (1994-2015). Data Synthesis: Overall, 2,062 patients (62% men, median [interquartile range] age 59 yr [48-67 yr]) were included in the study. Underlying malignancies were solid tumors (n = 362; 17.6%) or hematologic malignancies (n = 1,700; 82.4%), including acute leukemia (n = 591; 28.7%), non-Hodgkin lymphoma (n = 461; 22.3%), and myeloma (n = 244; 11.8%). Two-hundred fifty patients (12%) underwent allogeneic hematopoietic stem cell transplantation and 640 (31.0%) were neutropenic at ICU admission. Day 30 mortality was 39.9% (823 deaths). The year of ICU admission was associated with significant decrease in day 30 mortality over time (odds ratio, 0.96; 95% CI, 0.93-0.98; p = 0.001). Mechanical ventilation (odds ratio, 3.25; 95% CI, 2.52-4.19; p < 0.01) and vasopressors use (odds ratio, 1.42; 95% CI, 1.10-1.83; p < 0.01) were independently associated with day 30 mortality, whereas underlying malignancy, allogeneic hematopoietic stem cell transplantation, and neutropenia were not. Conclusions: Survival in critically ill oncology and hematology patients with sepsis improved significantly over time. As outcomes improve, clinicians should consider updating admission policies and goals of care in this population.

Background Vitamin C has potential protective effects through antioxidant and anti-inflammatory properties. However, the effect of vitamin C supplementation on microvascular function and peripheral tissue perfusion in human sepsis remains unknown. We aimed to determine vitamin C effect on microvascular endothelial dysfunction and peripheral tissue perfusion in septic shock patients. Methods Patients with septic shock were prospectively included after initial resuscitation. Bedside peripheral tissue perfusion and skin microvascular reactivity in response to acetylcholine iontophoresis in the forearm area were measured before and 1 h after intravenous vitamin C supplementation (40 mg/kg). Norepinephrine dose was not modified during the studied period. Results We included 30 patients with septic shock. SOFA score was 11 [8–14], SAPS II was 66 [54–79], and in-hospital mortality was 33%. Half of these patients had vitamin C deficiency at inclusion. Vitamin C supplementation strongly improved microvascular reactivity (AUC 2263 [430–4246] vs 5362 [1744–10585] UI, p = 0.0004). In addition, vitamin C supplementation improved mottling score (p = 0.06), finger-tip (p = 0.0003) and knee capillary refill time (3.7 [2.6–5.5] vs 2.9 [1.9–4.7] s, p p Conclusion In septic shock patients being resuscitated, vitamin C supplementation improved peripheral tissue perfusion and microvascular reactivity whatever plasma levels of vitamin C. ClinicalTrials.gov Identifier: NCT04778605 registered 26 January 2021.

Background Congenital disorders of glycosylation are rare inherited diseases affecting many different proteins. The lack of glycosylation notably affects the hemostatic system and leads to deficiencies of both procoagulant and anticoagulant factors. Objective To assess the hemostatic balance in patients with multiple coagulation disorders by using a thrombin generation assay. Method We performed conventional coagulation assays and a thrombin generation assay on samples from patients with congenital disorder of glycosylation. The thrombin generation assay was performed before and after activation of the protein C system by the addition of soluble thrombomodulin. Results A total of 35 patients were included: 71% and 57% had low antithrombin and factor XI levels, respectively. Protein C and protein S levels were abnormally low in 29% and 26% of the patients, respectively, whereas only 11% displayed low factor IX levels. Under baseline conditions, the thrombin generation assay revealed a significantly higher endogenous thrombin potential and thrombin peak in patients, relative to controls. After spiking with thrombomodulin, we observed impaired involvement of the protein C system. Hence, 54% of patients displayed a hypercoagulant phenotype in vitro. All the patients with a history of stroke-like episodes or thrombosis displayed this hypercoagulant phenotype. Conclusion A thrombin generation assay revealed a hypercoagulant in vitro phenotype under baseline condition; this was accentuated by impaired involvement of the protein C system. This procoagulant phenotype may thus reflect the risk of severe vascular complications. Further research will have to determine whether the thrombin generation assay is predictive of vascular events.

Background: The aim of this study was to assess the benefit of direct ICU admission from the emergency department (ED) compared to admission from wards, in patients with hematological malignancies requiring critical care. Methods: Post hoc analysis derived from a prospective, multicenter cohort study of 1011 critically ill adult patients with hematologic malignancies admitted to 17 ICU in Belgium and France from January 2010 to May 2011. The variable of interest was a direct ICU admission from the ED and the outcome was in-hospital mortality. The association between the variable of interest and the outcome was assessed by multivariable logistic regression after multiple imputation of missing data. Several sensitivity analyses were performed: complete case analysis, propensity score matching and multivariable Cox proportional-hazards analysis of 90-day survival. Results: Direct ICU admission from the ED occurred in 266 (26.4%) cases, 84 of whom (31.6%) died in the hospital versus 311/742 (41.9%) in those who did not. After adjustment, direct ICU admission from the ED was associated with a decreased in-hospital mortality (adjusted OR: 0.63; 95% CI 0.45–0.88). This was confirmed in the complete cases analysis (adjusted OR: 0.64; 95% CI 0.45–0.92) as well as in terms of hazard of death within the 90 days after admission (adjusted HR: 0.77; 95% CI 0.60–0.99). By contrast, in the propensity score-matched sample of 402 patients, direct admission was not associated with in-hospital mortality (adjusted OR: 0.92; 95% CI 0.84–1.01). Conclusions: In this study, patients with hematological malignancies admitted to the ICU were more likely to be alive at hospital discharge if they were directly admitted from the ED rather than from the wards. Assessment of early predictors of poor outcome in cancer patients admitted to the ED is crucial so as to allow early referral to the ICU and avoid delays in treatment initiation and mis-orientation., SCOPUS: ar.j, info:eu-repo/semantics/published

Adolescent obesity is a serious health problem associated with many comorbidities. Obesity-related alterations in circadian rhythm have been described for nocturnal blood pressure and for metabolic functions. We believe renal circadian rhythm is also disrupted in obesity, though this has not yet been investigated. This study aimed to examine renal circadian rhythm in obese adolescents before and after weight loss.In 34 obese adolescents (median age 15.7 years) participating in a residential weight loss program, renal function profiles and blood samples were collected at baseline, after 7 months, and again after 12 months of therapy. The program consisted of dietary restriction, increased physical activity, and psychological support. The program led to a median weight loss of 24 kg and a reduction in blood pressure. Initially, lower diurnal free water clearance (- 1.08 (- 1.40-- 0.79) mL/min) was noticed compared with nocturnal values (0.75 (- 0.89-- 0.64) mL/min). After weight loss, normalization of this inverse rhythm was observed (day - 1.24 (- 1.44-1.05) mL/min and night - 0.98 (- 1.09-- 0.83) mL/min). A clear circadian rhythm in diuresis rate and in renal clearance of creatinine, solutes, sodium, and potassium was seen at all time points. Furthermore, we observed a significant increase in sodium clearance. Before weight loss, daytime sodium clearance was 0.72 mL/min (0.59-0.77) and nighttime clearance was 0.46 mL/min (0.41-0.51). After weight loss, daytime clearance increased to 0.99 mL/min (0.85-1.17) and nighttime clearance increased to 0.78 mL/min (0.64-0.93).Conclusion: In obese adolescents, lower diurnal free water clearance was observed compared with nocturnal values. Weight loss led to a normalization of this inverse rhythm, suggesting a recovery of the anti-diuretic hormone activity. Both before and after weight loss, clear circadian rhythm of diuresis rate and renal clearance of creatinine, solutes, sodium, and potassium was observed.What is Known:• Obesity-related alterations in circadian rhythm have been described for nocturnal blood pressure and for metabolic functions. We believe renal circadian rhythm is disrupted in obesity, though this has not been investigated yet.What is New:• In obese adolescents, an inverse circadian rhythm of free water clearance was observed, with higher nighttime free water clearance compared with daytime values. Weight loss led to a normalization of this inverse rhythm, suggesting a recovery of the anti-diuretic hormone activity.• Circadian rhythm in diuresis rate and in the renal clearance of creatinine, solutes, sodium, and potassium was preserved in obese adolescents and did not change after weight loss.

Cloud infrastructures are becoming a common platform for storage and workload operations for industries. With increasing rate of data generation, the cloud storage industry has already grown into a multi-billion dollar industry. This industry offers services with very strict service level agreements (SLAs) to insure a high Quality of Service (QoS) for its clients. A breach of these SLAs results in a heavy economic loss for the service provider. We study a queueing model of data backup systems with a focus on the age of data. The age of data is roughly defined as the time for which data has not been backed up and is therefore a measure of uncertainty for the user. We precisely define the performance measure and compute the generating function of its distribution. It is critical to ensure that the tail probabilities are small so that the system stays within SLAs with a high probability. Therefore, we also analyze the tail distribution of the age of data by performing dominant singularity analysis of its generating function. Our formulas can help the service providers to set the system parameters adequately. (C) 2019 Elsevier B.V. All rights reserved.

This paper investigates the problem of surgery sequencing under uncertain surgery durations, with the objective of minimizing the expected maximum waiting time that emergent patients may endure before an operating room becomes available. Given the sets of surgeries assigned to each operating room as well as the distribution of each surgery’s duration, we aim to find the room sequences that minimize the expected largest interval between consecutive completion times. To solve the resulting stochastic optimization problem called the Stochastic Break-In Moment problem (SBIM), we implement a new MILP based on Sample Average Approximation. An algorithm that more intelligently segments the search further improves performance. We also create a variance-based heuristic and adapt a variety of local search methods to the SBIM case. Numerical experiments based on a surgery scheduling benchmark set show that stochastic solution methods outperform their deterministic counterparts, and highlight the value of the stochastic solution.

PMM2-CDG is the most common congenital disorder of glycosylation (CDG), which presents with either a neurologic or multisystem phenotype. Little is known about the longitudinal evolution. We performed data analysis on PMM2-CDG patients’ clinical features according to the Nijmegen CDG severity score and laboratory data. Seventy-five patients (28 males) were followed up from 11.0 ± 6.91 years for an average of 7.4 ± 4.5 years. On a group level, there was no significant evolution in overall clinical severity. There was some improvement in mobility and communication, liver and endocrine function, and strabismus and eye movements. Educational achievement and thyroid function worsened in some patients. Overall, the current clinical function, the system-specific involvement, and the current clinical assessment remained unchanged. On follow-up there was improvement of biochemical variables with (near) normalization of activated partial thromboplastin time (aPTT), factor XI, protein C, antithrombin, thyroid stimulating hormone, and liver transaminases. PMM2-CDG patients show a spontaneous biochemical improvement and stable clinical course based on the Nijmegen CDG severity score. This information is crucial for the definition of endpoints in clinical trials.

Objectives Recently, the Velopharyngeal Insufficiency (VPI) Effects on Life Outcomes (VELO) questionnaire, which evaluates the impact of speech and swallowing difficulties on health-related quality of life (HRQoL) in patients with VPI (Skirko et al., 2012), was translated to Dutch (Bruneel et al., 2017). The purpose of this study was to evaluate the reproducibility, responsiveness and construct validity of this Dutch version of the questionnaire. Methods To evaluate the reproducibility, 50 parents and 14 children with cleft palate re-completed the questionnaire after two weeks. Thirty-five parents and 8 children with cleft palate completed the VELO questionnaire after one year for the evaluation of the responsiveness. The correlation between age and the VELO questionnaire (construct validity), and the internal consistency (Cronbach's α) were re-determined based on the responses of 73 parents and 24 children. Results Based on descriptive statistics, results of the Wilcoxon signed rank-test, and the absolute (SEM) and relative (ICC) consistency, the questionnaire showed good reproducibility. VELO scores did not significantly differ after one year, neither when performing separate analyses for the intervention (speech therapy) and the non-intervention group. Correlations indicated higher HRQoL, as perceived by the parents, with increasing age. The reverse was the case for the youth report. Cronbach's α showed excellent internal consistency for both reports. Conclusions The VELO questionnaire showed good reproducibility and internal consistency. Moreover, results reconfirmed the age effect on VELO scores. To understand the implications of the results regarding the questionnaire's responsiveness, future research should focus on the identification of factors influencing the patient's evolution in HRQoL.

Purpose The aim of this study was to compare the effect of a short-term intensive voice therapy (IVT) with a long-term traditional voice therapy (TVT) on the vocal quality, vocal capacities, psychosocial impact, vocal tract discomfort, laryngological anatomy/physiology, and session attendance of patients with dysphonia. An additional comparison was made between an individual IVT (IVT-I) and a group IVT (IVT-G). Method A longitudinal, prospective controlled trial was used. Forty-six adults diagnosed with dysphonia were assigned to 1 of the 3 treatment groups. The IVT groups practiced with a frequency of 1 hr 20 min a day and a duration of 2 weeks. The TVT group practiced with a frequency of two 30-min sessions a week and a duration of 6 months. Both therapy programs were content-identical and guided by the same voice therapist. A multidimensional voice assessment consisting of both objective (maximum performance task, aerodynamic measurements, voice range profile, acoustic analysis, multiparametric voice quality indices) and subjective (subject's self-report, auditory-perceptual evaluation, flexible videolaryngostroboscopy) outcomes was used to evaluate the participants' voice. Results IVT made an equal progress in only 2 weeks and 12 hr of therapy compared with TVT that needed 6 months and 24 hr of therapy. IVT-I and IVT-G showed comparable results. Session attendance was clearly higher in IVT compared with TVT. Long-term follow-up results (1 year) were positive for the 3 groups, except for the self-reported psychosocial impact that increased in the IVT-I group. Conclusions Short-term IVT is at least equally effective in treating patients with dysphonia as long-term TVT. Group treatment seemed as effective as individual treatment. Attendance and cost-effectiveness are important advantages of IVT. A potential drawback might be an insufficient psychosocial progress. The golden mean between intensive and traditional treatment might therefore be an achievable, effective, and efficient solution for everyday clinical practice. Supplemental Material https://doi.org/10.23641/asha.7761872

Background New diagnostic tools have been developed to improve the diagnosis of infectious encephalitis. Using a prospective cohort of encephalitis patients, our objective was to identify possible clusters of patients with similar patterns among encephalitis of unknown cause (EUC) and to describe to what extent a patient’s initial presentation may be predictive of encephalitis etiology, particularly herpes simplex virus (HSV) and varicella-zoster virus (VZV). Methods The National Cohort of Infectious Encephalitis in France is an ongoing prospective cohort study implemented in France in 2016. Patients who present with documented or suspected acute infectious encephalitis were included. Focusing on the variables that describe the initial presentation, we performed a factor analysis of mixed data (FAMD) to investigate a pattern of association between the initial presentation of a patient and the etiologic pathogen. Results As of 1 August 2018, data from 349 patients were analyzed. The most frequent pathogens were HSV (25%), VZV (11%), tick-borne encephalitis virus (6%), Listeria (5%), influenza virus (3%), and EUC (34%). Using the FAMD, it was not possible to identify a specific pattern related to the group of EUC. Age, temporal or hemorrhagic lesions, and cerebral spinal fluid lymphocytosis were significantly associated with HSV/VZV encephalitis. Conclusions No initial clinical/imaging/biology pattern was identified at admission among EUC, despite the improvement in diagnostic tools. In this context, the recommendation for a universal, early, probabilistic, initial treatment against HSV and VZV is still relevant, regardless of the initial clinical presentation of the encephalitis.

We describe a case report of hypermucoviscous Klebsiella pneumoniae (KP) promptly diagnosed by blood and cerebrospinal fluid (CSF) culture with positive string test. The patient, without medical history, developed in a few hours multiple localizations, typical of hypervirulent KP. Combination of multiple typical localizations (eye, CSF, pulmonary, hepatic) and string test enabled rapid diagnosis of hypermcoviscous and hypervirulent KP.

International audience; BACKGROUND: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. METHODS: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. FINDINGS: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I(2)=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [\textless1%], adjusted OR 5·58 [1·22-25·50]; p=0·024). INTERPRETATION: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. FUNDING: None.

Background Intravenous artesunate is the World Health Organization–recommended first-line treatment for severe malaria worldwide, but it is still not fully licensed in Europe. Observational studies documenting its safety and efficacy in imported malaria are thus essential. Methods We prospectively collected clinical and epidemiological features of 1391 artesunate-treated patients among 110 participant centers during the first 7 years (2011–2017) of a national program implemented by the French Drug Agency. Results Artesunate became the most frequent treatment for severe malaria in France, rising from 9.9% in 2011 to 71.4% in 2017. Mortality was estimated at 4.1%. Treatment failure was recorded in 27 patients, but mutations in the Kelch-13 gene were not observed. Main reported adverse events (AEs) were anemia (136 cases), cardiac events (24, including 20 episodes of conduction disorders and/or arrhythmia), and liver enzyme elevation (23). Mortality and AEs were similar in the general population and in people with human immunodeficiency virus, who were overweight, or were pregnant, but the only pregnant woman treated in the first trimester experimented a hemorrhagic miscarriage. The incidence of post-artesunate–delayed hemolysis (PADH) was 42.8% when specifically assessed in a 98-patient subgroup, but was not associated with fatal outcomes or sequelae. PADH was twice as frequent in patients of European compared with African origin. Conclusions Artesunate was rapidly deployed and displayed a robust clinical benefit in patients with severe imported malaria, despite a high frequency of mild to moderate PADH. Further explorations in the context of importation should assess outcomes during the first trimester of pregnancy and collect rare but potentially severe cardiac AEs.

Background Mucormycosis is an emerging fungal infection that may lead to multi-organ failure, especially in patients with hematological malignancies (HM). We performed a retrospective, cohort study, in five intensive care units (ICU) to assess the outcome of critically ill patients with HM and mucormycosis between 2002 and 2018. The secondary objective was to identify prognostic factors in this setting. Results Twenty-six patients were included with a median age of 38 years [IQR, 26–57]). Acute leukemia was the most frequent underlying disease (50%). Nine patients (35%) underwent allogeneic stem cell transplantation (SCT). Nineteen patients (73%) had neutropenia and 16 (62%) had received steroids. The main reason for admission was acute respiratory failure (n = 14, 54%) followed by shock (n = 5 19%). The median SOFA score at admission was 7 [5–8]. According to EORTC/MSG criteria, mucormycosis was "proven" in 14 patients (54%), "probable" in 5 (19%) and “possible” in 7 (27%) in whom diagnosis was made by qPCR. Rhizopus and Mucor were the most frequent documented species. Seven patients (27%) had concurrent Aspergillus infection. Mucormycosis was diagnosed 1 day [−4 to + 6] after ICU admission. Sixteen patients (62%) had pulmonary involvement and ten (38%) rhino-cerebral involvement. Infection was disseminated in eight patients (31%). Twenty-two patients (85%) were treated with liposomal amphotericin B; 12 (46%) received antifungal combination including posaconazole in 7. Eight patients (31%) underwent curative surgery. Twenty-one patients (81%) required invasive mechanical ventilation (IMV), 18 (69%) vasopressors, and 9 (35%) renal replacement therapy. ICU and hospital mortality rates were 77% and 88%, respectively. The median overall survival was 9 days [3–22]. IMV was strongly associated with ICU mortality (p Conclusions Mucormycosis is associated with a high mortality rate in patients with HM, especially in allogeneic SCT recipients. Benefit of ICU management in these patients should be assessed before admission and strategies aiming to improve these patients’ outcome are urgently needed.

Fisheries play a significant role in the livelihoods of the world population, while the dependence on fisheries is acute in developing countries. Fisheries are consequently a critical element for meeting the sustainable development (SDG) and FAO goals to reduce poverty, hunger and improve health and well-being. However, 90% of global marine fish stocks are fully or over-exploited. The amount of biologically unsustainable stocks increased from 10% in 1975 to 33% in 2015. Freshwater ecosystems are the most endangered ecosystems and freshwater fish stocks are worldwide in a state of crisis. The continuous fish stock decline indicates that the world is still far from achieving SDG 14 (Life Below Water), FAO’s Blue Growth Initiative goal and SDG 15 (Life on Land, including freshwater systems). Failure to effectively manage world fish stocks can have disastrous effects on biodiversity and the livelihoods and socio-economic conditions of millions of people. Therefore, management strategies that successfully conserve the stocks and provide optimal sustainable yields are urgently needed. However, successful management is only possible when the necessary data are obtained and decision-makers are well informed. The main problem for the management of fisheries, particularly in developing countries, is the lack of information on the past and current status of the fish stocks. Sound data collection and validation methods are, therefore, important. Stock assessment models, which support sustainable fisheries, require life history traits as input parameters. In order to provide accurate estimates of these life history traits, standardized methods for otolith preparation and validation of the rate of growth zone deposition are essential. This review aims to assist researchers and fisheries managers, working on marine and freshwater fish species, in understanding concepts and processes related to stock assessment and population dynamics. Although most examples and case studies originate from developing countries in the African continent, the review remains of great value to many other countries.

Contains fulltext : 238870.pdf (Publisher’s version ) (Closed access) BACKGROUND: Modifications of facial and oral structures affect aesthetic appearance, orofacial functions, and have impact on quality of life. PURPOSE: This study determined alterations of articulation, oromyofunctional behavior, and Oral Health Related Quality of Life (OHRQoL) in patients replacing complete removable dentures by implant retained overdentures in the mandible. MATERIALS AND METHODS: Twenty-one fully edentulous patients received mandibular overdenture retained on a bar connecting two titanium dental implants. Patients were evaluated after receiving a new set of fully removable dentures (stage 1), after surgery during provisionalization on healing abutments (stage 2), and after final connection to the bar (stage 3). Assessments were taken by speech therapists and included evaluation of: articulation (picture naming and reading); oromyofunctional behavior; OHRQoL (OHIP-14 questionnaire), and overall satisfaction and speech (VAS). To measure changes over time, Wilcoxon matched-pairs signed-rank-test and McNemar test was used. RESULTS: There was no significant impact of the treatment on speech nor on the results of oromyofunction. In stage 1, patients had different kinds of articulation errors (mean:1.21) which evolved to 0.71 and 0.67. In stage 3, especially problems with the /s/ sound are seen in 37% (7/19) of the participants. Results of OHRQoL and satisfaction reveal that the average of satisfaction with oral health evolved from 67% to 63% and finally 78%. OHIP-14 total score was 17.4/56 in stage 1, remained unchanged in stage 2 and evolved in stage 3 to 9.8/56 (P: .010). This indicates improvement. Satisfaction with speech evolved significantly from 68% pretreatment to 82% in stage 3 (P: .013). CONCLUSION: Despite existing articulation and oromyofunctional disorders after treatment, people are very satisfied with their OHRQoL and their speech. Impact of mandibular denture wearing on OHRQoL declines once connected. It's important to inform patients that speech and oromyofunctional disorders may occur during treatment where especially the /s/ sound is vulnerable.

Background: Delayed intubation is associated with high mortality. There is a lack of objective criteria to decide the time of intubation. We assessed a recently described combined oxygenation index (ROX index) to predict intubation in immunocompromised patients. The study is a secondary analysis of randomized trials in immunocompromised patients, including all patients who received high-flow nasal cannula (HFNC). The first objective was to evaluate the accuracy of the ROX index to predict intubation for patients with acute respiratory failure. Results: In the study, 302 patients received HFNC. Acute respiratory failure was mostly related to pneumonia (n = 150, 49.7%). Within 2 (1–3) days, 115 (38.1%) patients were intubated. The ICU mortality rate was 27.4% (n = 83). At 6 h, the ROX index was lower for patients who needed intubation compared with those who did not [4.79 (3.69–7.01) vs. 6.10 (4.48–8.68), p < 0.001]. The accuracy of the ROX index to predict intubation was poor [AUC = 0.623 (0.557–0.689)], with low performance using the threshold previously found (4.88). In multivariate analysis, a higher ROX index was still independently associated with a lower intubation rate (OR = 0.89 [0.82–0.96], p = 0.04). Conclusion: A ROX index greater than 4.88 appears to have a poor ability to predict intubation in immunocompromised patients with acute respiratory failure, although it remains highly associated with the risk of intubation and may be useful to stratify such risk in future studies., SCOPUS: ar.j, info:eu-repo/semantics/published

Purpose: Hyperbilirubinemia is frequent in patients with hematological malignancies admitted to the intensive care unit (ICU). Literature about hepatic dysfunction (HD) in this context is scarce. Methods: We investigated the prognostic impact of HD analyzing a prospective multicenter cohort of 893 critically ill hematology patients. Two groups were defined: patients with HD (total bilirubin ≥33 μmol/L at ICU admission) and patients without HD. Results: Twenty one percent of patients were found to have HD at ICU admission. Cyclosporine, antimicrobials before ICU admission, abdominal symptoms, ascites, history of liver disease, neutropenia, increased serum creatinine and myeloma were independently associated with HD. Etiology remained undetermined in 73% of patients. Hospital mortality was 56.3% and 36.3% respectively in patients with and without HD (p < 0.0001). Prognostic factors independently associated with hospital mortality in HD group were, performance status >1 (OR = 2.07, 95% CI = 1.49–2.87, p < 0.0001), invasive mechanical ventilation (OR = 3.92, 95% CI = 2.69–5.71, p < 0.0001), renal replacement therapy (OR = 1.74, 95% CI = 1.22–2.47, p = 0.002), vasoactive drug (OR = 1.81, 95% CI = 1.21–2.71, p = 0.004) and SOFA score without bilirubin level at ICU admission (OR = 1.09, 95% CI = 1.04–1.14, p < 0.0001). Conclusions: HD is common, underestimated, infrequently investigated, and is associated with impaired outcome in critically ill hematology patients. HD should be considered upon ICU admission and managed as other organ dysfunctions., SCOPUS: ar.j, info:eu-repo/semantics/published

Objective: To provide speech outcomes of English-speaking Ugandan patients with a cleft palate with or without cleft lip (CP±L). Design: Prospective case–control study. Setting: Referral hospital for patients with cleft lip and palate in Uganda. Participants: Twenty-four English-speaking Ugandan children with a CP±L (15 boys, 9 girls, mean 8.4 years) who received palatal closure prior to 6 months of age and an age- and gender-matched control group of Ugandan children without cleft palate. Interventions: Comparison of speech outcomes of the patient and control group. Main Outcome Measures: Perceptual speech outcomes including articulation, resonance, speech understandability and acceptability, and velopharyngeal composite score (VPC-sum). Information regarding speech therapy, fistula rate, and secondary surgery. Results: Normal speech understandability was observed in 42% of the patients, and 38% were judged with normal speech acceptability. Only 16% showed compensatory articulation. Acceptable resonance was found in 71%, and 75% of the patients were judged perceptually to present with competent velopharyngeal function based on the VPC-sum. Additional speech intervention was recommended in 25% of the patients. Statistically significant differences for all these variables were still observed with the control children ( P < .05). Conclusions: Overall, acceptable speech outcomes were found after early primary palatal closure. Comparable or even better results were found in comparison with international benchmarks, especially regarding the presence of compensatory articulation. Whether this approach is transferable to Western countries is the subject for further research.

Despite the emergent importance of liquidity events (IPOs and trade sales) as performance indicators for VC-backed academic spin-offs, empirical research on the drivers of liquidity events relating to such spin-offs has been limited. In adopting a search perspective, we analyze how different alliance types impact on VC-backed academic spin-offs’ chances of realizing a liquidity event. We find that market search alliances increase a spin-off’s likelihood of a liquidity event, whereas technology search alliances reduce this likelihood. However, the latter effect is mitigated when the spin-off has a founding team with prior market experience. We explore the implications for practice and policy of the development and success of VC-backed academic spin-offs. ispartof: Research Policy vol:49 issue:10 status: published

International audience; Rationale: Frontline healthcare providers (HCPs) during the coronavirus disease (COVID-19) pandemic are at high risk of mental morbidity.Objectives: To assess the prevalence of symptoms of anxiety, depression, and peritraumatic dissociation in HCPs.Methods: This was a cross-sectional study in 21 ICUs in France between April 20, 2020, and May 21, 2020. The Hospital Anxiety and Depression Scale and the Peritraumatic Dissociative Experience Questionnaire were used. Factors independently associated with reported symptoms of mental health disorders were identified.Measurements and Main Results: The response rate was 67%, with 1,058 respondents (median age 33 yr; 71% women; 68% nursing staff). The prevalence of symptoms of anxiety, depression, and peritraumatic dissociation was 50.4%, 30.4%, and 32%, respectively, with the highest rates in nurses. By multivariable analysis, male sex was independently associated with lower prevalence of symptoms of anxiety, depression, and peritraumatic dissociation (odds ratio of 0.58 [95% confidence interval, 0.42–0.79], 0.57 [95% confidence interval, 0.39–0.82], and 0.49 [95% confidence interval, 0.34–0.72], respectively). HCPs working in non–university-affiliated hospitals and nursing assistants were at high risk of symptoms of anxiety and peritraumatic dissociation. Importantly, we identified the following six modifiable determinants of symptoms of mental health disorders: fear of being infected, inability to rest, inability to care for family, struggling with difficult emotions, regret about the restrictions in visitation policies, and witnessing hasty end-of-life decisions.Conclusions: HCPs experience high levels of psychological burden during the COVID-19 pandemic. Hospitals, ICU directors, and ICU staff must devise strategies to overcome the modifiable determinants of adverse mental illness symptoms.

International audience; Background: In view of the high mortality rate of immunocompromised patients with ARDS, it is important to identify targets for improvement.Research question: This study investigated factors associated with mortality in this specific ARDS population, including factors related to respiratory mechanics (plateau pressure [Pplat,rs], compliance [Crs], and driving pressure [ΔPrs]).Study design and methods: This study consisted of a predefined secondary analysis of the EFRAIM data. Overall, 789 of 1,611 patients met the Berlin criteria for ARDS, and Pplat,rs, ΔPrs, and Crs were available for 494 patients. A hierarchical model was used to assess factors at ARDS onset independently associated with hospital mortality.Results: Hospital mortality was 56.3%. After adjustment, variables independently associated with hospital mortality included ARDS of undetermined etiology (OR, 1.66; 95% CI, 1.01-2.72), need for vasopressors (OR, 1.91; 95% CI, 1.27-2.88), and need for renal replacement therapy (OR, 2.02; 95% CI, 1.37-2.97). ARDS severity according to the Berlin definition, neutropenia on admission, and the type of underlying disease were not significantly associated with mortality. Before adjustment, higher Pplat,rs, higher ΔPrs, and lower Crs were associated with higher mortality. Addition of each of these individual variables to the final hierarchical model revealed a significant association with mortality: ΔPrs (OR, 1.08; 95% CI, 1.05-1.12), Pplat,rs (OR, 1.07; 95% CI, 1.04-1.11), and Crs (OR, 0.97; 95% CI, 0.95-0.98). Tidal volume was not associated with mortality.Interpretation: In immunocompromised patients with ARDS, respiratory mechanics provide additional prognostic information to predictors of hospital mortality. Studies designed to define lung-protective ventilation guided by these physiological variables may be warranted in this specific population.

International audience; Mannose phosphate isomerase MPI-CDG (formerly CDG-1b) is a potentially fatal inherited metabolic disease which is readily treatable with oral D-mannose. We retrospectively reviewed long-term outcomes of patients with MPI-CDG, all but one of whom were treated with D-mannose. Clinical, biological, and histological data were reviewed at diagnosis and on D-mannose treatment. Nine patients were diagnosed with MPI-CDG at a median age of 3 months. The presenting symptoms were diarrhea (n = 9), hepatomegaly (n = 9), hypoglycemia (n = 8), and protein loosing enteropathy (n = 7). All patients survived except the untreated one who died at 2 years of age. Oral D-mannose was started in eight patients at a median age of 7 months (mean 38 months), with a median follow-up on treatment of 14 years 9 months (1.5-20 years). On treatment, two patients developed severe portal hypertension, two developed venous thrombosis, and 1 displayed altered kidney function. Poor compliance with D-mannose was correlated with recurrence of diarrhea, thrombosis, and abnormal biological parameters including coagulation factors and transferrin profiles. Liver fibrosis persisted despite treatment, but two patients showed improved liver architecture during follow-up. This study highlights (i) the efficacy and safety of D-mannose treatment with a median follow-up on treatment of almost 15 years (ii) the need for life-long treatment (iii) the risk of relapse with poor compliance, (iii) the importance of portal hypertension screening (iv) the need to be aware of venous and renal complications in adulthood.

International audience; Introduction: Invasive pulmonary aspergillosis is a well-known complication of acute respiratory distress syndrome, the most serious manifestation of COVID-19. Four recent studies have reported its incidence among ICU COVID-19 patients. However, they do not share the same case definition, and have provided conflicting results. In this paper we have aimed at reported the incidence of invasive pulmonary aspergillosis for COVID-19 patients in our ICU, and at comparing the different definitions in order to assess their respective relevance. Methods: Retrospective cohort study of critically ill patients with severe COVID-19 requiring ICU management between 1st March and 30th April 2020. Results: Our results showed significantly lower incidence of invasive pulmonary aspergillosis (1.8%;1/53), compared to three out of four previous studies, and wide variation in the numbers of cases with regard to the different definitions. Conclusion: Large-scale studies are needed for a better definition and a more accurate estimation of invasive pulmonary aspergillosis coinfection during COVID-19.

Background: Lumbar puncture is among the investigations used to determine the aetiology and prognosis of cardiac arrest, despite a dearth of data on its performance. We aimed to assess the diagnostic and prognostic performance of lumbar puncture after cardiac arrest. Methods: We retrospectively studied data from prospectively established databases of consecutive patients who were admitted to two French ICUs in 2007-2016 with sustained return of spontaneous circulation (ROSC) after cardiac arrest and who underwent lumbar puncture as an aetiological investigation. Results: Of 1984 patients with sustained ROSC, 65 (3.3%) underwent lumbar puncture and were included. Lumbar puncture identified a neurological cause of cardiac arrest in 6/65 (9%) patients, including 5 with neurologic prodromal symptoms before cardiac arrest and 4 with the lumbar puncture done post-mortem. Lumbar puncture performed before death showed nonspecific cerebrospinal fluid abnormalities in 37/53 (69.8%) patients. By univariate analysis, factors significantly associated with cerebrospinal fluid abnormalities were shorter no-flow time (0 min [0-3] versus 4 min [2-10], p=0.004) and post-resuscitation shock (26 [70%] versus 5 [31%], pp=0.06). Conclusions: Lumbar puncture, although rarely performed, can contribute to the aetiological diagnosis of cardiac arrest. As a second-line investigation, it identified the cause in 9% of our patients. Nonspecific cerebrospinal fluid abnormalities are common after cardiac arrest, perhaps due to blood-brain barrier disruption, and may carry prognostic significance.

International audience; Objectives: To assess the response to initial oxygenation strategy according to clinical variables available at admission.Design: Multicenter cohort study.Setting: Thirty French and Belgium medical ICU.Subjects: Immunocompromised patients with hypoxemic acute respiratory failure.Interventions: None.Measurements and Main Results: Data were extracted from the Groupe de Recherche en Reanimation Respiratoire du patient d'Onco-Hématologie database. Need for invasive mechanical ventilation was the primary endpoint. Secondary endpoint was day-28 mortality. Six-hundred forty-nine patients were included. First oxygenation strategies included standard oxygen (n = 245, 38%), noninvasive ventilation (n = 285; 44%), high-flow nasal cannula oxygen (n = 55; 8%), and noninvasive ventilation + high-flow nasal cannula oxygen (n = 64; 10%). Bilateral alveolar pattern (odds ratio = 1.67 [1.03–2.69]; p = 0.04), bacterial (odds ratio = 1.98 [1.07–3.65]; p = 0.03) or opportunistic infection (odds ratio = 4.75 [2.23–10.1]; p < 0.001), noninvasive ventilation use (odds ratio = 2.85 [1.73–4.70]; p < 0.001), Sequential Organ Failure Assessment score (odds ratio = 1.19 [1.10–1.28]; p < 0.001), and ratio of PaO2 and FIO2 less than 100 at ICU admission (odds ratio = 1.96 [1.27–3.02]; p = 0.0002) were independently associated with intubation rate. Day-28 mortality was independently associated with bacterial (odds ratio = 2.34 [1.10–4.97]; p = 0.03) or opportunistic infection (odds ratio = 4.96 [2.11–11.6]; p < 0.001), noninvasive ventilation use (odds ratio = 2.35 [1.35–4.09]; p = 0.003), Sequential Organ Failure Assessment score (odds ratio = 1.19 [1.10–1.28]; p < 0.001), and ratio of PaO2 and FIO2 less than 100 at ICU admission (odds ratio = 1.97 [1.26–3.09]; p = 0.003). High-flow nasal cannula oxygen use was neither associated with intubation nor mortality rates.Conclusions: Some clinical characteristics at ICU admission including etiology and severity of acute respiratory failure enable to identify patients at high risk for intubation.

Objectives: Early intensive care unit (ICU) admission, in Critically Ill Cancer Patients (CICP), is believed to have contributed to the prognostic improvement of critically ill cancer patients. The primary objective of this study was to assess the association between early ICU admission and hospital mortality in CICP. Design: Retrospective analysis of a prospective multicenter dataset. Early admission was defined as admission in the ICU < 24 h of hospital admission. We assessed the association between early ICU admission and hospital mortality in CICP via survival analysis and propensity score matching. Results: Of the 1011patients in our cohort, 1005 had data available regarding ICU admission timing and were included. Overall, early ICU admission occurred in 455 patients (45.3%). Crude hospital mortality in patients with early and delayed ICU admission was 33.6% (n = 153) vs. 43.1% (n = 237), respectively (P = 0.02). After adjustment for confounders, early compared to late ICU admission was not associated with hospital mortality (HR 0.92; 95%CI 0.76–1.11). After propensity score matching, hospital mortality did not differ between patients with early (35.2%) and late (40.6%) ICU admission (P = 0.13). In the matched cohort, early ICU admission was not associated with mortality after adjustment on SOFA score (HR 0.89; 95%CI 0.71–1.12). Similar results were obtained after adjustment for center effect. Conclusion: In this cohort, early ICU admission was not associated with a better outcome after adjustment for confounder and center effect. The uncertainty with regard to the beneficial effect of early ICU on hospital mortality suggests the need for an interventional study., SCOPUS: ar.j, info:eu-repo/semantics/published

BackgroundFrench legislation about sedation in palliative medicine evolved in 2016 with the introduction of a right to deep and continuous sedation, maintained until death. The objective was to describe midazolam sedation at the COL (Centre Oscar Lambret[Oscar Lambret Center], French regional center for cancer control), in order to establish a current overview before the final legislative changes.MethodsDescriptive, retrospective and single-center study, concerning major patients in palliative care hospitalized from 01/01/2014 to 12/31/2015, who had been sedated by midazolam. The proven sedations (explicitly named) and the probable sedations were distinguished.ResultsA total of 54 sedations were identified (48 proven, 6 probable). Refractory symptoms accounted for 48.1% of indications, complications with immediate risk of death 46.3%, existential suffering 5.6%. Titration was performed in 44.4% of cases. Sedation was continuous until death for 98.1% of the cases. Probable sedation had a higher failure rate than proven sedation. Significant differences existed for the palliative care unit compared to other units regarding information to the patient, their consent, anticipation, mention by correspondence and carrying out titrations. When patients had already been treated with midazolam, the induction doses, initial maintenance doses, and doses at the time of death were significantly higher. For those receiving opioids, the maintenance dose at the time of death was higher. No comparison found a difference in overall survival.ConclusionsAfter a sufficient follow-up has enabled teams to familiarize with this new legislation, reflection on sedation should be conducted to adapt to final recommendations.

Introduction To meet the scarcity of training and/or educational initiatives in Uganda regarding state-of-the-art speech diagnosis and treatment in patients with cleft palate, a workshop was organized for all interested speech-language pathologists and health care workers. Objective To evaluate and compare the inter- and intra-rater reliability of the perceptual evaluation of hypernasality, hyponasality, nasal emission, nasal turbulence and speech acceptability before and after a two-day workshop in Ugandan speech-language pathologists. Methods On the first day, perceptual speech evaluation was discussed and practiced. Perceptual exercises included individual ratings of a specific speech variable followed by a group discussion and consensus listening exercises in listener pairs. The second day focused on speech treatment. Ten Ugandan speech-language pathologists rated speech samples of Ugandan patients with a CP ± L before and immediately following the two-day workshop. Inter- and intra-rater reliability of the perceptual ratings of hypernasality, hyponasality, nasal emission, nasal turbulence and speech acceptability were determined by means of the absolute percentage of agreement. The Wilcoxon signed-rank test was used to compare results at both time points. Results Overall inter- and intra-rater reliability improved when observing the absolute percentage agreement. However, median agreement results only showed enhanced reliability for hypernasality, hyponasality and nasal turbulence whereas (limited) deteriorated reliability was observed for nasal emission and speech acceptability. Regarding inter-rater reliability only the median percentage agreement for hyponasality exceeded 50% (median: 56.3%). Overall, better results were found for intra-rater reliability, with only weak results for speech acceptability. Discussion and conclusion Training positively affected reliability results. Nonetheless, this improvement was not achieved for each speech variable and reliability improvements were modest. Findings indicate the need for continued training and the search for the most effective training paradigm and feedback techniques, whilst taking into account clinical relevance and practical considerations.