Adolescent- and adult-onset neuroblastic tumor: A retrospective multicenter observational study of patients diagnosed in France between 2000 and 2020.

BACKGROUND: Adult- and adolescent-onset neuroblastomas are rare, with no established therapy. In addition, rare pheochromocytomas may harbor neuroblastic components. This study was designed to collect epidemiological, diagnostic and therapeutic data in order to better define the characteristics of malignant peripheral neuroblastic tumors (MPNT) and composite pheochromocytomas (CP) with MPNT. PROCEDURE: Fifty-nine adults and adolescents (aged over 15 years) diagnosed with a peripheral or composite neuroblastic tumor, who were treated in one of 17 institutions between 2000 and 2020, were retrospectively studied. RESULTS: Eighteen patients with neuroblastoma (NB) or ganglioneuroblastoma (GNB) had locoregional disease, and 28 patients had metastatic stage 4 NB. Among the 13 patients with CP, 12 had locoregional disease. Fifty-eight percent of the population were adolescents and young adults under 24 years of age. The probability of 5-year event-free survival (EFS) was 40% (confidence interval: 27%-53%). CONCLUSIONS: Outcomes were better for patients with localized tumor than for patients with metastases. For patients with localized tumor, in terms of survival, surgical treatment was the best therapeutic option. Multimodal treatment with chemotherapy, surgery, radiotherapy, and immunotherapy-based maintenance allowed long-term survival for some patients. Adolescent- and adult-onset neuroblastoma appeared to have specific characteristics associated with poorer outcomes compared to pediatric neuroblastoma. Nevertheless, complete disease control improved survival. The presence of a neuroblastic component in pheochromocytoma should be considered when making therapeutic management decisions. The development of specific tools/resources (Tumor Referral Board, Registry, biology, and trials with new agents or strategies) may help to improve outcomes for patients.

Oral anticoagulant safety in family practice: prognostic accuracy of Bleeding Risk Scores (from the CACAO study).

BACKGROUND: To assess bleeding risk of patients treated by oral anticoagulants, several scores have been constructed to assist physicians in the evaluation of the benefit risk. Most of these scores lack a strong enough level of evidence for use in family practice. OBJECTIVE: To assess the predictive prognostic accuracy of 13 scores designed to assess the risk of major or clinically relevant non-major (CRNM) bleeding events in a French ambulatory cohort receiving Vitamin-K antagonists (VKA) or direct oral anticoagulants (DOACs) in a family practice setting. METHODS: CACAO (Comparison of Accidents and their Circumstances with Oral Anticoagulants) was a multicentre prospective cohort of ambulatory patients prescribed oral anticoagulants. We selected patients from the cohort who had received an oral anticoagulant because of non-valvular atrial fibrillation (NVAF) and/or venous thromboembolism (VTE) to be followed during one year by their GP. The following scores were calculated: mOBRI, Shireman, Kuijer, HEMORR2HAGES, ATRIA, HAS-BLED, RIETE, VTE-BLEED, ACCP score, Rutherford, ABH-Score, GARFIEL-AF, and Outcomes Registry for Better InformedTreatment of Atrial Fibrillation (ORBIT). Prognostic accuracy was assessed by using receiver operating characteristic curves and c-statistics. RESULTS: During 1 year, 3,082 patients were followed. All of the scores demonstrated only poor to moderate ability to predict major bleeding or CRNM in NVAF patients on DOACs (c-statistic: 0.41-0.66 and 0.45-0.58), respectively. The results were only slightly better for patients prescribed VKA (0.47-0.66 and 0.5-0.55, respectively) in this indication. The results were also unsatisfactory in patients treated for VTE. CONCLUSION: None of the scores demonstrated satisfactory discriminatory ability when used in family practice. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02376777.

Early extubation in extracorporeal life support patients: A propensity score-matched study.

BACKGROUND: Extubation strategy in extracorporeal life support patients remains unclear, and literature only reports studies with significant biases. OBJECTIVES: To explore the prognostic impact of an early ventilator-weaning strategy in assisted patients after controlling for confounding factors. METHODS: A 10-year retrospective study included 241 patients receiving extracorporeal life support for at least 48 h, corresponding to a total of 977 days spent on assistance. The a priori probability of extubation for each day of assistance was calculated according to daily biological examinations, drug doses, clinical observations, and admission data to pair each day containing an extubation with one on which the patient was not extubated. The primary outcome was survival at day 28. The secondary outcomes were survival at day 7, respiratory infections, and safety criteria. RESULTS: Two similar cohorts of 61 patients were generated. Survival at day 28 was better in patients extubated under assistance in univariate and multivariate (HR = 0.37 [0.2-0.68], p-value = 0.002) analyses. Patients who underwent failed early extubation did not have a different prognosis from those without early extubation. Successful early extubation was associated with a better outcome than a failed or no attempt at early extubation. Survival at day 7 and the rate of respiratory infections were better in early-extubated patients. Safety data did not differ between the two groups. CONCLUSIONS: Early extubation during assistance was associated with a superior outcome in our propensity-matched cohort study. The safety data were reassuring. However, due to the lack of prospective randomized studies, the causality remains uncertain.

A randomized controlled trial of the intraoperative use of noninvasive ventilation versus supplemental oxygen by face mask for procedural sedation in an electrophysiology laboratory.

PURPOSE: The efficacy of noninvasive ventilation (NIV) during procedures that require sedation and analgesia has not been established. We evaluated whether NIV reduces the incidence of respiratory events. METHODS: In this randomized controlled trial, we included 195 patients with an American Society of Anesthesiologists Physical Status of III or IV during electrophysiology laboratory procedures. We compared NIV with face mask oxygen therapy for patients under sedation. The primary outcome was the incidence of respiratory events determined by a computer-driven blinded analysis and defined by hypoxemia (peripheral oxygen saturation < 90%) or apnea/hypopnea (absence of breathing for 20 sec on capnography). Secondary outcomes included hemodynamic variables, sedation, patient safety (composite scores of major or minor adverse events), and adverse outcomes at day 7. RESULTS: A respiratory event occurred in 89/98 (95%) patients in the NIV group and in 69/97 (73%) patients with face masks (risk ratio [RR], 1.29; 95% confidence interval [CI], 1.13 to 1.47; P < 0.001). Hypoxemia occurred in 40 (42%) patients in the NIV group and in 33 (34%) patients with face masks (RR, 1.21; 95% CI, 0.84 to 1.74; P = 0.30). Apnea/hypopnea occurred in 83 patients (92%) in the NIV group vs 65 patients (70%) with face masks (RR, 1.32; 95% CI, 1.14 to 1.53; P < 0.001). Hemodynamic variables, sedation, major or minor safety events, and patient outcomes were not different between the groups. CONCLUSIONS: Respiratory events were more frequent among patients receiving NIV without any safety or outcome impairment. These results do not support the routine use of NIV intraoperatively. STUDY REGISTRATION: ClinicalTrials.gov (NCT02779998); registered 4 November 2015.

RéSUMé: OBJECTIF: L'efficacité de la ventilation non invasive (VNI) pendant les interventions nécessitant une sédation et une analgésie n'a pas été établie. Nous avons évalué si la VNI réduisait l'incidence des complications respiratoires. MéTHODE: Dans cette étude randomisée contrôlée, nous avons inclus 195 patient·es de statut physique III ou IV selon l'American Society of Anesthesiologists pendant des interventions en laboratoire d'électrophysiologie. Nous avons comparé la VNI à l'oxygénothérapie par masque facial pour les patient·es sous sédation. Le critère d'évaluation principal était l'incidence des complications respiratoires déterminée par une analyse en aveugle assistée par ordinateur et définie par une hypoxémie (saturation périphérique en oxygène < 90 %) ou une apnée/hypopnée (absence de respiration pendant 20 secondes à la capnographie). Les critères d'évaluation secondaires comprenaient les variables hémodynamiques, la sédation, la sécurité des patient·es (scores composites des événements indésirables majeurs ou mineurs) et les issues indésirables au jour 7. RéSULTATS: Un événement respiratoire est survenu chez 89/98 (95 %) patient·es du groupe VNI et chez 69/97 (73 %) patient·es ayant un masque facial (risque relatif [RR], 1,29; intervalle de confiance [IC] à 95 %, 1,13 à 1,47; P < 0,001). Une hypoxémie est survenue chez 40 (42 %) patient·es du groupe VNI et chez 33 (34 %) patient·es ayant un masque facial (RR, 1,21 ; IC à 95 %, 0,84 à 1,74; P = 0,30). Une hypoxémie est survenue chez 40 (42 %) patient·es du groupe VNI et chez 33 (34 %) patient·es ayant un masque facial (RR, 1,21; IC 95 %, 0,84 à 1,74; P = 0,30). Les variables hémodynamiques, la sédation, les événements de sécurité majeurs ou mineurs et les issues pour les patient·es n'étaient pas différents entre les groupes. CONCLUSION: Les complications respiratoires étaient plus fréquentes chez les patient·es recevant une VNI sans aucun impact sur la sécurité ou les issues. Ces résultats n'appuient pas l'utilisation systématique de la VNI en peropératoire. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT02779998); enregistrée le 4 novembre 2015.

Development of Indirect Health Data Linkage on Health Product Use and Care Trajectories in France: Systematic Review.

BACKGROUND: European national disparities in the integration of data linkage (ie, being able to match patient data between databases) into routine public health activities were recently highlighted. In France, the claims database covers almost the whole population from birth to death, offering a great research potential for data linkage. As the use of a common unique identifier to directly link personal data is often limited, linkage with a set of indirect key identifiers has been developed, which is associated with the linkage quality challenge to minimize errors in linked data. OBJECTIVE: The aim of this systematic review is to analyze the type and quality of research publications on indirect data linkage on health product use and care trajectories in France. METHODS: A comprehensive search for all papers published in PubMed/Medline and Embase databases up to December 31, 2022, involving linked French database focusing on health products use or care trajectories was realized. Only studies based on the use of indirect identifiers were included (ie, without a unique personal identifier available to easily link the databases). A descriptive analysis of data linkage with quality indicators and adherence to the Bohensky framework for evaluating data linkage studies was also realized. RESULTS: In total, 16 papers were selected. Data linkage was performed at the national level in 7 (43.8%) cases or at the local level in 9 (56.2%) studies. The number of patients included in the different databases and resulting from data linkage varied greatly, respectively, from 713 to 75,000 patients and from 210 to 31,000 linked patients. The diseases studied were mainly chronic diseases and infections. The objectives of the data linkage were multiple: to estimate the risk of adverse drug reactions (ADRs; n=6, 37.5%), to reconstruct the patient's care trajectory (n=5, 31.3%), to describe therapeutic uses (n=2, 12.5%), to evaluate the benefits of treatments (n=2, 12.5%), and to evaluate treatment adherence (n=1, 6.3%). Registries are the most frequently linked databases with French claims data. No studies have looked at linking with a hospital data warehouse, a clinical trial database, or patient self-reported databases. The linkage approach was deterministic in 7 (43.8%) studies, probabilistic in 4 (25.0%) studies, and not specified in 5 (31.3%) studies. The linkage rate was mainly from 80% to 90% (reported in 11/15, 73.3%, studies). Adherence to the Bohensky framework for evaluating data linkage studies showed that the description of the source databases for the linkage was always performed but that the completion rate and accuracy of the variables to be linked were not systematically described. CONCLUSIONS: This review highlights the growing interest in health data linkage in France. Nevertheless, regulatory, technical, and human constraints remain major obstacles to their deployment. The volume, variety, and validity of the data represent a real challenge, and advanced expertise and skills in statistical analysis and artificial intelligence are required to treat these big data.

Early prediction of in-hospital mortality utilizing multivariate predictive modelling of electronic medical records and socio-determinants of health of the first day of hospitalization.

BACKGROUND: In France an average of 4% of hospitalized patients die during their hospital stay. To aid medical decision making and the attribution of resources, within a few days of admission the identification of patients at high risk of dying in hospital is essential. METHODS: We used de-identified routine patient data available in the first 2 days of hospitalization in a French University Hospital (between 2016 and 2018) to build models predicting in-hospital mortality (at ≥ 2 and ≤ 30 days after admission). We tested nine different machine learning algorithms with repeated 10-fold cross-validation. Models were trained with 283 variables including age, sex, socio-determinants of health, laboratory test results, procedures (Classification of Medical Acts), medications (Anatomical Therapeutic Chemical code), hospital department/unit and home address (urban, rural etc.). The models were evaluated using various performance metrics. The dataset contained 123,729 admissions, of which the outcome for 3542 was all-cause in-hospital mortality and 120,187 admissions (no death reported within 30 days) were controls. RESULTS: The support vector machine, logistic regression and Xgboost algorithms demonstrated high discrimination with a balanced accuracy of 0.81 (95%CI 0.80-0.82), 0.82 (95%CI 0.80-0.83) and 0.83 (95%CI 0.80-0.83) and AUC of 0.90 (95%CI 0.88-0.91), 0.90 (95%CI 0.89-0.91) and 0.90 (95%CI 0.89-0.91) respectively. The most predictive variables for in-hospital mortality in all three models were older age (greater risk), and admission with a confirmed appointment (reduced risk). CONCLUSION: We propose three highly discriminating machine-learning models that could improve clinical and organizational decision making for adult patients at hospital admission.

Efficacy and Safety of Early Administration of 4-Factor Prothrombin Complex Concentrate in Patients With Trauma at Risk of Massive Transfusion: The PROCOAG Randomized Clinical Trial.

Importance: Optimal transfusion strategies in traumatic hemorrhage are unknown. Reports suggest a beneficial effect of 4-factor prothrombin complex concentrate (4F-PCC) on blood product consumption. Objective: To investigate the efficacy and safety of 4F-PCC administration in patients at risk of massive transfusion. Design, Setting, and Participants: Double-blind, randomized, placebo-controlled superiority trial in 12 French designated level I trauma centers from December 29, 2017, to August 31, 2021, involving consecutive patients with trauma at risk of massive transfusion. Follow-up was completed on August 31, 2021. Interventions: Intravenous administration of 1 mL/kg of 4F-PCC (25 IU of factor IX/kg) vs 1 mL/kg of saline solution (placebo). Patients, investigators, and data analysts were blinded to treatment assignment. All patients received early ratio-based transfusion (packed red blood cells:fresh frozen plasma ratio of 1:1 to 2:1) and were treated according to European traumatic hemorrhage guidelines. Main Outcomes and Measures: The primary outcome was 24-hour all blood product consumption (efficacy); arterial or venous thromboembolic events were a secondary outcome (safety). Results: Of 4313 patients with the highest trauma level activation, 350 were eligible for emergency inclusion, 327 were randomized, and 324 were analyzed (164 in the 4F-PCC group and 160 in the placebo group). The median (IQR) age of participants was 39 (27-56) years, Injury Severity Score was 36 (26-50 [major trauma]), and admission blood lactate level was 4.6 (2.8-7.4) mmol/L; prehospital arterial systolic blood pressure was less than 90 mm Hg in 179 of 324 patients (59%), 233 patients (73%) were men, and 226 (69%) required expedient hemorrhage control. There was no statistically or clinically significant between-group difference in median (IQR) total 24-hour blood product consumption (12 [5-19] U in the 4F-PCC group vs 11 [6-19] U in the placebo group; absolute difference, 0.2 U [95% CI, -2.99 to 3.33]; P = .72). In the 4F-PCC group, 56 patients (35%) presented with at least 1 thromboembolic event vs 37 patients (24%) in the placebo group (absolute difference, 11% [95% CI, 1%-21%]; relative risk, 1.48 [95% CI, 1.04-2.10]; P = .03). Conclusions and Relevance: Among patients with trauma at risk of massive transfusion, there was no significant reduction of 24-hour blood product consumption after administration of 4F-PCC, but thromboembolic events were more common. These findings do not support systematic use of 4F-PCC in patients at risk of massive transfusion. Trial Registration: ClinicalTrials.gov Identifier: NCT03218722.

The impact of pathogen-reduced platelets in acute leukaemia treatment on the total blood product requirement: a subgroup analysis of an EFFIPAP randomised trial.

OBJECTIVE: To evaluate the impact of pathogen-reduced (PR) platelet transfusions on blood products requirement for clinical practice. BACKGROUND: PR platelets are increasing in use as standard blood products. However, few randomised trials have evaluated their impact on bleeding control or prevention. Furthermore, PR platelets recirculate less than untreated platelets. METHODS: A subgroup study of the randomised clinical trial EFFIPAP compared three arms of platelet preparations (PR: P-PRP/PAS, additive solution: P-PAS and plasma P-P arms respectively). The subgroup of acute leukaemia patients, in their chemotherapy induction phase, included 392 patients (133 P-PRP/PAS arm, 132 P-PAS arm and 130 P-P arm). Blood requirements were analysed across over periods of 7 days. RESULTS: The number of platelet transfusions per week was significantly higher in the P-PRP/PAS group 2.3 [1.6-3.3] compared to the control groups 1.9 [1.3-2.8] and 2.0 [1.3-3.0] for P-P and P-PAS groups respectively (p < 0.0001). However, the total number of platelets transfused per week was not different. The number of red blood cell concentrates (RBC) transfusion per week did not differ either. CONCLUSION: In a homogeneous group of patients, platelet pathogen reduction resulted in an increased number of platelet units transfused per week while having no impact on the total number of platelets transfused or the number of RBC transfusion; resulting to an average requirement of 2 RBC and 2-3 platelets transfusions per week of marrow aplasia.

Procalcitonin to reduce exposure to antibiotics and individualise treatment in hospitalised old patients with pneumonia: a randomised study.

BACKGROUND: Treating pneumonia in old patients remains challenging for clinicians. Moreover, bacterial antimicrobial resistance is a major public health threat. OBJECTIVE: The PROPAGE study evaluated the interest of a strategy using serial measurements of procalcitonin (PCT) to reduce the duration of antibiotic therapy in old patients with pneumonia. METHODS: PROPAGE took place from Dec.-2013 to Jun.-2016 in eight French geriatric units. It was a prospective, comparative, randomised, open-label study involving old patients (≥ 80 years) who had initiated antibiotic treatment for pneumonia in the previous 48 h. PCT was monitored in all patients and two decision-making PCT-based algorithms guided antibiotic therapy in patients from the PCT group. RESULTS: 107 patients were randomised (PCT, n = 50; Control, n = 57). Antibiotic therapy exposure was reduced in the PCT group as compared to the Control group (median duration of antibiotic therapy, 8 vs. 10 days [rank-test, p = 0.001]; antibiotic persistence rates on Days 6 and 8, 54% and 44% vs. 91% and 72%) and no significant difference was found in recovery rate (84% vs. 89.5%; Pearson Chi² test, p = 0.402). CONCLUSION: Although, the superiority of the strategy was not tested using a composite criterion combining antibiotic therapy duration and recovery rate was not tested due to the small sample size, the present study showed that monitoring associated with PCT-guided algorithm could help shorten antibiotic treatment duration in the very old patients without detrimental effects. Measuring PCT levels between Day 4 and Day 6 could be helpful when making the decision regarding antibiotic discontinuation. TRIAL REGISTRATION: NCT02173613. This study was first registered on 25/06/2014.

Evaluation of the benefit of thermal spa therapy in plaque psoriasis: the PSOTHERMES randomized clinical trial.

Spa therapy is considered an add-on treatment for psoriasis, but without any objective evaluation in the absence of randomized trials. This multicenter, open-label, randomized trial compared immediate spa therapy versus a control group having usual treatments until study assessments at 4.5 months. Spa therapy was proposed in five French spa resorts with standardized programs. Inclusion criteria were adults with plaque psoriasis, Dermatology Life Quality Index (DLQI) > 10, and stable medical treatment in the last 6 months. The main objective was DLQI ≤ 10 at 4.5 months after inclusion. VQ-Dermato and EQ5D-3L also assessed quality of life (QoL), Perceived Stress Scale (PSS) stress, and visual analogue scales (VAS) pain and pruritus. Between January 2015 and November 2018, 128 patients were randomized to either immediate spa therapy (64) (within 34 days, median) or usual treatments (61) until assessment at 4.5 months. Most were first-time spa users (71.2%). Mean DLQI and Psoriasis Area and Severity Index at inclusion were 16.7 and 10.5, respectively. Immediate spa therapy patients achieved the primary objective for 66.1% [95% CI 52.6% > 77.9%] vs 41.4% [95% CI 28.6% > 55.1%] control group patients (p = 0.007). VQ-Dermato scores and pruritus VAS significantly improved. Outcomes at 12-month follow-up of the immediate spa therapy group showed persistent improvement of DLQI, VQ-Dermato, and pruritus. This randomized controlled trial demonstrated that a cure of spa therapy improves QoL and alleviates certain symptoms of psoriasis, in short and long terms. This justifies its integration in the therapeutic strategies for psoriasis. Trial registration number: ClinicalTrials.gov Identifier: NCT02098213.

Ten-year outcomes of islet transplantation in patients with type 1 diabetes: Data from the Swiss-French GRAGIL network.

To describe the 10-year outcomes of islet transplantation within the Swiss-French GRAGIL Network, in patients with type 1 diabetes experiencing high glucose variability associated with severe hypoglycemia and/or with functional kidney graft. We conducted a retrospective analysis of all subjects transplanted in the GRAGIL-1c and GARGIL-2 islet transplantation trials and analyzed components of metabolic control, graft function and safety outcomes over the 10-year period of follow-up. Forty-four patients were included between September 2003 and April 2010. Thirty-one patients completed a 10-year follow-up. Ten years after islet transplantation, median HbA1c was 7.2% (6.2-8.0) (55 mmol/mol [44-64]) versus 8.0% (7.1-9.1) (64 mmol/mol [54-76]) before transplantation (p < .001). Seventeen of 23 (73.9%) recipients were free of severe hypoglycemia, 1/21 patients (4.8%) was insulin-independent and median C-peptide was 0.6 ng/ml (0.2-1.2). Insulin requirements (UI/kg/day) were 0.3 (0.1-0.5) versus 0.5 (0.4-0.6) before transplantation (p < .001). Median (IQR) ß-score was 1 (0-4) (p < .05 when comparing with pre-transplantation values) and 51.9% recipients had a functional islet graft at 10 years. With a 10-year follow-up in a multicentric network, islet transplantation provided sustained improvement of glycemic control and was efficient to prevent severe hypoglycemia in almost 75% of the recipients.

EASL-ALEH 2015 algorithm for the use of transient elastography in treatment-naive patients with hepatitis B: An independent validation.

Various non-invasive methods have been evaluated in chronic hepatitis B, but none of them have been fully validated for the assessment of liver fibrosis. The issued EASL-ALEH 2015 guidelines provide detailed algorithms based on LSM and ALT serum levels. The aim of our study was to validate the diagnostic accuracy of this algorithm and to better understand discrepancies. Four hundred and thirteen patients from 3 centres were retrospectively included. All included patients were classified for fibrosis stage according to results of a liver biopsy. The overall diagnostic value was expressed with AUROCs given with 95% confidence intervals for the diagnostic targets. For each diagnostic target, optimal cut-offs were determined according to the Youden method. For the population of patients with ALT9 kPa, respectively. For patients with ALT>N but ≤5N (n = 306), AUROCs of transient elastography were 0.79 (0.73-0.84) and 0.84 (0.75-0.92) for F ≥ 2 and F ≥ 3 diagnostic targets. The prevalence of significant fibrosis was, respectively, 15%, 52% and 85% when LSM was <6kPa, between 6 and 12 kPa or >12 kPa. Our study independently validates the EASL-ALEH algorithm based on ALT levels and LSM assessed by transient elastography.

Description of an influenza outbreak in a French university hospital and risk factors of nosocomial influenza.

Our objective was to evaluate risk factors of nosocomial influenza (NI) in an university hospital during the 2015/2016 influenza season. All hospitalized patients with influenza-like illness associated with laboratory confirmation by polymerase chain reaction were included in a prospective observational study. We identified 44 cases (19%) of NI among the 233 cases of influenza: 38/178 (21%) in adults and 6/55 (11%) in children. Among adults, hospitalization in a double or multi-occupancy room was independently associated with NI (adjusted Odds Ratio, 3.42; 95% CI, 1.29-9.08; p = 0.013). The results of the study underline the importance of single room to prevent NI.

Positive communication behaviour during handover and team-based clinical performance in critical situations: a simulation randomised controlled trial.

BACKGROUND: Positive communication behaviour within anaesthesia teams may decrease stress response and improve clinical performance. We aimed to evaluate the effect of positive communication during medical handover on the subsequent team-based clinical performance in a simulated critical situation. We also assessed the effect of positive communication behaviour on stress response. METHODS: This single-centre RCT involved anaesthesia teams composed of a resident and a nurse in a high-fidelity scenario of anaesthesia-related paediatric laryngospasm after a standardised handover. During the handover, similar information was provided to all teams, but positive communication behaviour was adopted only for teams in the intervention group. Primary outcome was team-based clinical performance, assessed by an independent blinded observer, using video recordings and a 0-to 100-point scenario-specific scoring tool. Three categories of tasks were considered: safety checks before the incision, diagnosis/treatment of laryngospasm, and crisis resource management/non-technical skills. Individual stress response was monitored by perceived level of stress and HR variability. RESULTS: The clinical performance of 64 anaesthesia professionals (grouped into 32 teams) was analysed. The mean (standard deviation) team-based performance score in the intervention group was 44 (10) points vs 35 (12) in the control group (difference: +8.4; CI95% [0.4-16.4]; P=0.04). The effects were homogeneous over the three categories of tasks. Perceived level of stress and HR variability were not significantly different between groups. CONCLUSIONS: Positive communication behaviour between healthcare professionals during medical handover improved team-based performance in a simulation-based critical situation. CLINICAL TRIAL REGISTRATION: NCT03375073.

Impact of Head-of-Bed Posture on Brain Oxygenation in Patients with Acute Brain Injury: A Prospective Cohort Study.

BACKGROUND: Therapeutic head positioning plays a role in the management of patients with acute brain injury. Although intracranial pressure (ICP) is typically lower in an upright posture than in a flat position, limited data exist concerning the effect of upright positioning on brain oxygenation and circulation. We sought to determine the impact of supine (0°) and semirecumbent (15° and 30°) postures on ICP, brain oxygenation, and brain circulation. METHODS: An observational cohort study was conducted between February 2012 and September 2015. Twenty-three patients with severe acute brain injury were successively observed at head elevations of 30°, 15°, and 0°. Postural-induced changes in ICP, cerebral perfusion pressure, brain tissue oxygenation pressure, and transcranial Doppler findings were simultaneously measured during three repeated experiments: 24 h after admission to the intensive care unit (exp1), 24 h later (exp2), and 96 h later (exp3). Cerebral perfusion pressure, arterial blood gases, hemoglobin content, and body temperature remained unchanged during the three experiments. RESULTS: Using linear random-slope mixed models, we found that during the early phase of acute brain injury (exp1), lowering the head posture from 30° to 15°, and then to 0°, was associated with a gradual mean ICP increase of 2.6 mm Hg (1.4-3.7 mm Hg; P < 0.001); and from 30° to 0°, an increase of 7.4 mm Hg (6.3-8.6 mm Hg; P < 0.001). Furthermore, brain tissue oxygenation pressure and mean blood flow velocity improved when the head posture was lowered from 30° to 0° by 1.2 mm Hg (0.2-2.3 mm Hg) and 4.1 cm/s (0.0-8.2 cm/s), respectively (both P < 0.05). CONCLUSIONS: Changing the positioning of stable patients with acute brain injury resulted in opposite changes of ICP versus brain oxygenation and circulation. This information supports the concept of an individualized approach to head positioning that is based on the multimodal monitoring of brain parameters.

COVID-19 Repeated Convalescent Plasma Collection: Analysis of 149 Donations from 88 French Military Health Workers.

BACKGROUND: Passive therapy with convalescent plasma (CP) could be an effective and safe treatment option in COVID-19 patients. Neutralizing antibodies present in CP generated in response to SARS-CoV-2 infection and directed against the receptor-binding domain of the spike protein are considered to play a major role in the viral clearance. CP infusion may also contribute to the modulation of the immune response through its immunomodulatory effect. We describe for the first time the effectiveness of a CP collection protocol from repeated donations in young patients. MATERIALS AND METHODS: We enrolled health service workers who experienced mild to moderate COVID-19 and from whom several donations have been collected. No minimal severity threshold and no biological cure criteria were required. Donors could return to a second plasma donation 14 days after the first donation. A minimal neutralizing antibody titer of 1:40 was considered for clinical use. RESULTS: Eighty-eight donors were included (median age 35 [28-48] years, 41 women), and 149 plasma products were collected. COVID-19 were mainly WHO stage 2 infections (96%). Among the 88 first donations, 76% had neutralizing antibody titers higher than or equal to 1:40. Eighty-eight percent of donors who came for a second donation had a neutralizing antibody titer of 1:40. Median durations were 15 (15-19) and 38 (33-46) days from the first to the second donation and from recovery to the second donation, respectively. Sixty-nine percent of donors who came for a third donation had a neutralizing antibody titer of 1:40. Median durations were 16 (13-37) and 54 (49-61) days from the second to the third donation and from recovery to the third donation, respectively. No significant difference was observed between the IgG ratio and the age of the donors or the time between recovery and donation. The average IgG ratio did not significantly vary between donations. When focused on repeated blood donors, no significant differences were observed either. CONCLUSION: The recruitment of young patients with a mild to moderate CO-VID-19 course is an efficient possibility to collect CP with a satisfactory level of neutralizing antibodies. Repeated donations are a well-tolerated and effective way of CP collection.

Anticoagulants' Safety and Effectiveness in General Practice: A Nationwide Prospective Cohort Study.

PURPOSE: Most real-world studies on anticoagulants have been based on health insurance databases or performed in secondary care. The aim of this study was to compare safety and effectiveness between patients treated with vitamin K antagonists (VKAs) and patients treated with direct oral anticoagulants (DOACs) in a general practice setting. METHODS: The CACAO study (Comparison of Accidents and their Circumstances with Oral Anticoagulants) is a multicenter prospective cohort study conducted among ambulatory patients taking an oral anticoagulant. Participants were patients from the study's cross-sectional phase receiving oral anticoagulants because of nonvalvular atrial fibrillation, for secondary prevention of venous thromboembolism, or both. They were followed as usual for 1 year by their general practitioners, who collected data on changes in therapy, thromboembolic events, bleeding, and deaths. All events were adjudicated by an independent committee. We used a propensity score and a Cox regression model to derive hazard ratios. RESULTS: Between April and December 2014, a total of 3,082 patients were included. At 1 year, 42 patients (1.7%) had experienced an arterial or venous event; 151 (6.1%) had experienced bleeding, including 47 (1.9%) who experienced major bleeding; and 105 (4.1%) had died. There was no significant difference between the VKA and DOAC groups regarding arterial or venous events, or major bleeding. The VKA group had a lower risk of overall bleeding (hazard ratio = 0.65; 95% CI, 0.43-0.98) but twice the risk of death (hazard ratio = 1.98; 95% CI, 1.15-3.42). CONCLUSIONS: VKAs and DOACs had fairly similar safety and effectiveness in general practice. The substantially higher incidence of deaths with VKAs is consistent with known data from health insurance databases and calls for further research to understand its cause.

Six months versus two years of oral anticoagulation after a first episode of unprovoked deep-vein thrombosis. The PADIS-DVT randomized clinical trial.

The optimal duration of anticoagulation after a first episode of unprovoked deep-vein thrombosis is uncertain. We aimed to assess the benefits and risks of an additional 18 months of treatment with warfarin versus placebo, after an initial 6 months of anticoagulation for a first unprovoked proximal deep-vein thrombosis. We conducted a multicenter, randomized, double-blind, controlled trial comparing an additional 18 months of warfarin with placebo in patients with a unprovoked proximal deep-vein thrombosis initially treated for 6 months (treatment period: 18 months; follow up after treatment period: 24 months). The primary outcome was the composite of recurrent venous thromboembolism or major bleeding at 18 months. Secondary outcomes were the composite at 42 months, as well as each component of the composite, and death unrelated to pulmonary embolism or major bleeding, at 18 and 42 months. All outcomes were centrally adjudicated. A total of 104 patients, enrolled between July 2007 and October 2013 were analyzed on an intention-to-treat basis; no patient was lost to follow-up. During the 18-month treatment period, the primary outcome occurred in none of the 50 patients in the warfarin group and in 16 out of 54 patients (cumulative risk, 29.6%) in the placebo group (hazard ratio, 0.03; 95% confidence interval: 0.01 to 0.09; P<0.001). During the entire 42-month study period, the composite outcome occurred in 14 patients (cumulative risk, 36.8%) in the warfarin group and 17 patients (cumulative risk, 31.5%) in the placebo group (hazard ratio, 0.72; 95% confidence interval: 0.35-1.46). In conclusion, after a first unprovoked proximal deep-vein thrombosis initially treated for 6 months, an additional 18 months of warfarin therapy reduced the composite of recurrent venous thrombosis and major bleeding compared to placebo. However, this benefit was not maintained after stopping anticoagulation. Clinical registration: this trial was registered at www.clinicaltrials.gov as #NCT00740493.

Apixaban for the prevention of thromboembolism in immunomodulatory-treated myeloma patients: Myelaxat, a phase 2 pilot study.

The risk of venous thromboembolism (VTE) is higher in myeloma patients receiving immunomodulatory compounds. A VTE prophylaxis using low-molecular-weight heparin or aspirin is therefore proposed. Apixaban is an oral direct anti-Xa. Several studies have shown the efficacy and safety of apixaban in VTE prophylaxis compared to enoxaparin. The objective of this prospective phase 2 pilot study was to assess the risk of VTE and bleeding in patients with myeloma treated with immunomodulatory compounds lenalidomide (len) or thalidomide (thal), using apixaban in a preventive scheme. Myeloma patients requiring Melphalan-Prednisone-Thalidomide in the first line, or Lenalidomide-Dexamethasone in the relapse setting received apixaban, 2.5 mg x 2/day for 6 months. Venous (pulmonary embolism-PE, or symptomatic proximal or distal deep vein thrombosis-DVT, or all proximal asymptomatic events detected by systematic proximal bilateral compression ultrasound) or arterial thrombotic events, and bleeding events (ISTH 2005) were registered. One hundred and four patients were enrolled (mean age 69.8 ± 7.8 years), 11 in first line and 93 in relapse. Two venous thrombotic events were observed, for example, an asymptomatic proximal DVT and a symptomatic distal DVT, in the context of apixaban stopped 14 days before, due to lenalidomide-induced thrombocytopenia. No PE or arterial cardiovascular events were reported. Only one major and 11 CRNM hemorrhages were reported. These data must now be confirmed on a randomized large study.

Using Pupillary Pain Index to Assess Nociception in Sedated Critically Ill Patients.

BACKGROUND: Pupillary reflex dilation is a reliable indicator of response to noxious stimulation. In a proof of concept study, we investigated the performance of pupillary pain index, a new score derived from pupillary reflex dilation measurements, to predict nociceptive response to endotracheal suctioning in sedated critically ill patients. METHODS: Twenty brain-injured and 20 non-brain-injured patients were studied within 48 hours of admission (T1) in the intensive care unit and at 48-72 hours later (T2). Video-based pupillometer was used to determine pupillary reflex dilation during tetanic stimulation. The tetanic stimulation (100 Hz) was applied to the skin area innervated by the ulnar nerve and was stepwise increased from 10 to 60 mA until pupil size had increased by 13% compared to baseline. The maximum intensity value allowed the determination of a pupillary pain index score ranging from 1 (no nociception) to 9 (high nociception). The Behavioral Pain Scale response to endotracheal suctioning was measured thereafter. RESULTS: Behavioral Pain Scale responses to endotracheal suctioning and pupillary pain index scores were positively correlated at T1 and T2 (both P < .01). After adjustments for repeated measurements and group of patients, the area under the receiver operating characteristic curve of pupillary pain index to predict Behavioral Pain Scale response to endotracheal suctioning was of 0.862 (95% CI, 0.714-0.954). In the combined set of patients, a pupillary pain index score of ≤4 could predict no nociceptive response to endotracheal suctioning with a sensitivity of 88% (95% CI, 68%-97%) and a specificity of 79% (95% CI, 66%-88%). By contrast with endotracheal suctioning, tetanic stimulation had no effect on intracranial pressure in the brain-injured group. CONCLUSIONS: These results are a proof of concept. The nociceptive response to endotracheal suctioning could be accurately predicted using the determination of pupillary pain index score in sedated critically ill patients whether they have brain injury or not.