A Real-World Cost-Effectiveness Analysis of Rivaroxaban versus Vitamin K Antagonists for the Treatment of Symptomatic Venous Thromboembolism: Lessons from the REMOTEV Registry.

Background and objectives: Venous thromboembolism (VTE) represents a health and economic burden with consequent healthcare resource utilization. Direct oral anticoagulants (DOACs) have emerged as the mainstay option for VTE treatment but few data exist on their cost-effectiveness as compared to the standard therapy (vitamin K antagonists (VKAs)). This study aimed to assess the cost-effectiveness of rivaroxaban compared to VKAs in VTE treatment by calculating the incremental cost effectiveness ratio (ICER). Materials and methods: We conducted a prospective observational study based on the REMOTEV registry, including patients hospitalized for VTE from 23 October 2013 to 31 July 2015, to evaluate the impact of the anticoagulant treatment (DOACs versus VKAs) on 6-month complications: major or clinically relevant non-major bleeding, VTE recurrence and all-cause death. Rivaroxaban was the only DOAC prescribed in this study. The ICER was calculated as the difference in costs divided by the difference in effectiveness. Results: Among the 373 patients included, 279 were treated with rivaroxaban (63.1 ± 17.9 years old; 49% men) and 94 with VKAs (71.3 ± 16.6 years old; 46% men). The mean cost was EUR 5662 [95% CI 6606; 9060] for rivaroxaban and EUR 7721 [95% CI 5130; 6304] for VKAs, while effectiveness was 0.0586 95% CI [0.0114; 0.126] for DOACs and 0.0638 [95% CI 0.0208; 0.109] for VKAs. The rivaroxaban treatment strategy was dominant with costs per patient EUR 2059 lower [95% CI -3582; -817] and a higher effectiveness of 0.00527 [95% CI -0.0606; 0.0761] compared to VKAs. Conclusions: This study provides real-world evidence that rivaroxaban is not only an efficient and safe alternative to VKAs for eligible VTE patients, but also cost-saving.

A Real-World Cost-Effectiveness Study Evaluating Imaging Strategies for the Diagnostic Workup of Renal Colic in the Emergency Department.

Introduction Both non-contrast Computed Tomography (CT) and ultrasound (US) are used for the diagnosis of renal colic in the emergency department (ED). Although US reduces radiation exposure, its diagnostic accuracy is inferior to that of CT. In this context, data regarding the cost and organizational impact of these strategies represent essential elements in the choice of imaging; however, they remain poorly documented. Aim of the study The aim of this study was to compare the costs and effectiveness of diagnostic workup by US and CT for patients consulting with renal colic in the ED. Methods We conducted a monocentric real-life retrospective study of patients consulting for a renal colic in an ED between 1 July 2018 and 31 December 2018. We estimated length of stay (LOS), total hospital costs at 60 days including ED, and initial and repeat admissions. Patients with initial US in the ED were compared to patients with initial CT using inverse probability weighting of the propensity score calculated from demographic variables, vital parameters, and clinical presentation. We calculated the incremental cost effectiveness ratio as the difference in costs by the difference in LOS. The variability of the results was assessed using non-parametric bootstrapping. Results In this study, of the 273 patients included, 67 were patients assessed with US and 206 with CT. The average costs were €1159 (SD 1987) and €956 (SD 1462) for US and CT, respectively, and the ED LOS was 8.9 [CI 95% 8.1; 9.4] and 8.7 [CI 95% 7.9; 9.9] hours for US and CT, respectively. CT was associated with a decreased LOS by 0.139 [CI 95% -1.1; 1.5] hours and was cost-saving, with a €199 [CI 95% -745; 285] reduction per patient. Conclusion When imaging is required in the ED for suspected renal colic as recommended, there is real-life evidence that CT is a cost-effective strategy compared to US, reducing costs and LOS in the ED.

Organizational Benefits of Ultra-Low-Dose Chest CT Compared to Chest Radiography in the Emergency Department for the Diagnostic Workup of Community-Acquired Pneumonia: A Real-Life Retrospective Analysis.

Background and Objectives: Chest radiography remains the most frequently used examination in emergency departments (ED) for the diagnosis of community-acquired pneumonia (CAP), despite its poor diagnostic accuracy compared with ultra-low-dose (ULD) chest computed tomography (CT). However, although ULD CT appears to be an attractive alternative to radiography, its organizational impact in ED remains unknown. Our objective was to compare the relevant timepoints in ED management of CT and chest radiography. Materials and Methods: We conducted a retrospective study in two ED of a University Hospital including consecutive patients consulting for a CAP between 1 March 2019 and 29 February 2020 to assess the organizational benefits of ULD chest CT and chest radiography (length of stay (LOS) in the ED, time of clinical decision after imaging). Overlap weights (OW) were used to reduce covariate imbalance between groups. Results: Chest radiography was performed for 1476 patients (mean age: 76 years [63; 86]; 55% men) and ULD chest CT for 133 patients (mean age: 71 [57; 83]; 53% men). In the weighted population with OW, ULD chest CT did not significantly alter the ED LOS compared with chest radiography (11.7 to 12.2; MR 0.96 [0.85; 1.09]), although it did significantly reduce clinical decision time (6.9 and 9.5 h; MR 0.73 [0.59; 0.89]). Conclusion: There is real-life evidence that a strategy with ULD chest CT can be considered to be a relevant approach to replace chest radiography as part of the diagnostic workup for CAP in the ED without increasing ED LOS.

MRI dedicated to the emergency department for diplopia or dizziness: a cost-effectiveness analysis.

OBJECTIVES: The purpose of this study was to compare the costs and organizational benefits of diagnostic workup without and with MRI dedicated to the ED. METHODS: We conducted a prospective observational uncontrolled before-after study in one ED of a university hospital in France from July 1, 2018, and January 3, 2020. We included all consecutive patients presenting with dizziness or diplopia. The main outcomes were the clinical decision time of ED physicians and the total costs for each strategy. Outcomes were compared using propensity score with inverse probability weighting in the 2 arms and an incremental cost-effectiveness ratio (ICER) was calculated. RESULTS: Among the 199 patients during the "before" period (average age: 60.4 years ± 17.6): 112 men (57%), and 181 during the "after" period (average age, 54.8 years ± 18.5): 107 men (59%), the average costs were €2701 (95% CI 1918; 3704) and €2389 (95% CI: €1627; 3280) per patient, respectively. The average time to clinical decision was 9.8 h (95% CI: 8.9 10.7) in the group "before" and 7.7 h (95% CI: 7.1; 8.4) in the group "after" (ICER: €151 saved for a reduction of 1 h in clinical decision time). The probabilistic sensitivity analysis estimated a 71% chance that the MRI dedicated to ED was dominant (less costly and more effective). CONCLUSION: Easy access to MRI in the ED for posterior circulation stroke-like symptoms must be considered a relevant approach to help physicians for an appropriate and rapid diagnostic with reduction of costs. TRIAL REGISTRATION: NCT03660852 KEY POINTS: • A dedicated MRI in the ED for diplopia or dizziness may be considered an efficient strategy improving diagnostic performance, reducing physicians' decision time, and decreasing hospital costs. • This strategy supports clinical decision-making with early treatment and management of patients with posterior circulation-like symptoms in the ED. • There is 71% chance that the MRI dedicated to ED was dominant (less costly and more effective) compared with a strategy without dedicated MRI.

Normal chest CT in 1091 symptomatic patients with confirmed Covid-19: frequency, characteristics and outcome.

OBJECTIVE: Frequency of normal chest CT in symptomatic COVID-19 patients as well as the outcome of these patients remains unknown. The objectives of this work were to assess the incidence of initially normal chest CT in a cohort of consecutive confirmed COVID-19 patients with respiratory symptoms and to compare their clinical characteristics and their outcome to matched patients with typical COVID-19 lesions at initial CT. METHODS: From March 6th to April 22nd, all consecutive adult patients referred to the COVID-19 clinic of our Emergency Department were retrospectively analyzed. Each patient with a positive SARS-CoV-2 RT-PCR and a normal initial chest CT after second reading was 1:1 matched based on sex, age and date of CT acquisition to a patient with positive RT-PCR and initial chest CT with typical COVID-19 lesions. Clinical data, laboratory results and outcomes (major being mechanical ventilation and/or death) were compared between both groups, using Wilcoxon signed-rank test, McNemar's chi-squared test and/or exact McNemar's test where appropriate. RESULTS: Fifty-seven chest CT out of 1091 (5.2%, 95% CI 4.0-6.7) in symptomatic patients with positive RT-PCR were normal, with a median onset of symptoms of 4.5 days (IQR [1.25-10.25]). After a median follow-up of 43 days, death and/or mechanical ventilation occurred in 3 patients (5.3%) in the study group, versus 11 (19.3%) in the control group (p = 0.011). CONCLUSIONS: Normal initial chest CT occurred in 5.2% of symptomatic confirmed COVID-19 cases in our cohort. While better than those with abnormal chest CT, outcome was not entirely benign with 5.3% death and/or mechanical ventilation. KEY POINTS: • In a cohort of 1091 symptomatic COVID-19 patients, initial chest CT was normal in 5.2% of cases. • Normal chest CT in confirmed COVID-19 is frequent even when onset of symptoms is greater than 3 days. • The outcome of COVID-19 patients with initial normal chest CT, while better than those with abnormal CT, was not entirely benign with 5.3% death and/or mechanical ventilation.

A case of an injured calcaneus secundarius in a professional soccer player.

BACKGROUND: The calcaneus secundarius (CS) is an accessory ossicle of the anterior facet of the calcaneus and is usually asymptomatic. This accessory bone can be frequently mistaken for a fracture of the anterior process of the calcaneus. Few reports of symptomatic CS have been published, and physicians need to be familiar with imaging strategies when encountering chronic ankle pain or in case of suspicion of fracture of the anterior process of the calcaneus. CASE PRESENTATION: We describe the case of symptomatic CS in a professional soccer player injured during a match. First, computed tomography showed a large CS. Second, magnetic resonance imaging (MRI) demonstrated synchondrosis between the CS and the calcaneus, as well as edema (high MR T2 signal) within it, corresponding to posttraumatic edema. The patient was successfully treated with nonsteroidal anti-inflammatory drugs and physiotherapy; no surgical management was necessary. At the 4-week follow-up, he was pain-free and returned to activity. CONCLUSION: This case illustrates the role of imaging for the diagnosis of CS in cases of acute pain of the foot. CT, as well as MRI, helped to confirm the diagnosis of CS traumatized synchondrosis, which can be mistaken for a fracture.

Acute Pulmonary Embolism in Patients with COVID-19 at CT Angiography and Relationship to d-Dimer Levels.

Online supplemental material is available for this article.

White blood cell count and eosinopenia as valuable tools for the diagnosis of bacterial infections in the ED.

Identifying an infection may be difficult in the ED. Neutrophilic leukocytosis is often used in the diagnosis of infection despite its lack of specificity in situations of stress. Our objective was to study the value of each parameter of the WBC count, in particular eosinopenia, to diagnose bacterial infections in the ED. We conducted a retrospective and observational study over a period of 6 months. All patients with one of the following diagnoses were eligible: pneumonia (9.9%), pyelonephritis (26.2%), prostatitis (8.4%), appendicitis (26.2%), cholecystitis (8.4%), and diverticular sigmoiditis (5%). A total of 466 infected patients were included for statistical analysis, and a control group of 466 uninfected patients was randomly selected in the same period of time. All leukocyte count parameters were significantly modified (p < 0.001) in the infected group compared with the control group. Neutrophils and total leukocytes remain the two most suitable parameters for the diagnosis of infections in the ED. Eosinopenia represented the most efficient parameter of the WBC count for the diagnosis of urinary and biliary tract infections. Deep eosinopenia presented a specificity of 94% for the diagnosis of infection. Any modification of the WBC count associated with an elevation of CRP (> 40 mg/L) or fever (> 38.5 °C) showed a high specificity for the diagnosis of infection. A careful analysis of the WBC count remains a valuable tool for the diagnosis of infection in the ED.

[An underestimated cause of seizure in Europe]. / Une cause sous-estimée de convulsion en Europe.

Seizures are very common in the Emergency Department (ED). We present here a case of a young woman with neurocysticercosis ; a worldwide and nearly endemic cause of seizure in the southern hemisphere. Clinical manifestations are very different between patients from asymptomatic to life-threatening hydrocephalus. Diagnosis is based on a combination of clinical presentation, neuroimaging (CT and MRI) findings, history of exposure, and serologic testing.

Les convulsions sont un motif fréquent de consultation aux urgences. Nous présentons ici le cas d'une jeune patiente qui illustre une cause rare de convulsions en Europe : la neurocysticercose. La présentation initiale de cette maladie souvent hétérogène rend son diagnostic difficile pour le clinicien. Celui-ci repose sur un ensemble d'arguments clinico-immunologiques associé à un séjour en zone d'endémie de cysticercose. La neuro-imagerie (scanner et IRM) joue un rôle prépondérant dans le diagnostic et le suivi des différentes phases de la maladie.

Progression-free survival, overall survival and quality of life: What is their medicoeconomic importance in oncology?

Medico-economic evaluations estimate, for a given health technology, the added cost and the clinical benefit compared to a reference strategy. The objective here is to analyze the criteria used to measure clinical benefit as the basis for market access and reimbursement decisions for drugs in oncology both in France and in Europe. Prolonged overall survival is the criterion of choice to demonstrate the benefit of an anticancer drug; a survival gain of 2 to 3 months or more would be considered as relevant for a new product versus the comparator. In the absence of survival benefit or mature data on survival, progression-free survival or symptom-free survival and the availability of alternative curative treatments, decrease in drug toxicity and quality of life improvement may be considered. Differences in clinical benefit assessment between regulatory agencies and payers are not specific to France. Case studies show that it is difficult to find a consistency in reimbursement and pricing decisions and to identify factors that may fully explain reimbursement decisions when survival benefit is not demonstrated.

[Not Available]. / Recommandations en matière de communication et de sollicitation de patients pouvant participer ou participant déjà à des études cliniques.

The active patient participation in clinical trials is key for a competitive clinical research. Given this, the Health Industry Physicians and Actors Association (AMIPS) has set up a working group to make communication recommendations towards patients. The group was made of patients, investigators and industry sponsors representatives. Efficacious communication is rarely obtained because it is not clear what is possible to do ethically and regulatory and because of technical and financial constraints. After having identified the expectations and limitations for every actor category, the group has summarized all types of communication, in a sort of tool box, before and during the whole of a study. The benefits and regulatory prerequisites such as the submission to the Ethical Committee and to the National Data Information and Freedom Commission (CNIL) as well as the practical feasibility are described for each tool.

[Recommendations for Communication and Solicitation of Patients Potentially or Already Involved in Clinical Studies]. / Recommandations en matière de communication et de sollicitation de patients pouvant participer ou participant déjà à des études cliniques.

The active patient participation in clinical trials is key for a competitive clinical research. Given this, the Health Industry Physicians and Actors Association (AMIPS) has set up a working group to make communication recommendations towards patients. The group was made of patients, investigators and industry sponsors representatives. Efficacious communication is rarely obtained because it is not clear what is possible to do ethically and regulatory and because of technical and financial constraints. After having identified the expectations and limitations for every actor category, the group has summarized all types of communication, in a sort of tool box, before and during the whole of a study. The benefits and regulatory prerequisites such as the submission to the Ethical Committee and to the National Data Information and Freedom Commission (CNIL) as well as the practical feasibility are described for each tool.

Creating conditions for the success of the French industrial advanced therapy sector.

Although the European Union merely followed the initiatives of the United States and Japan by introducing special regimes for orphan medicinal products, it has introduced a special status for a new category of biological medicinal products, advanced therapy medicinal products (ATMPs), adopting specific associated regulations. European Regulation (which constitutes the highest legal instrument in the hierarchy of European law texts) [EC] No. 1394/2007, published in 2007, uses this term to define somatic cell therapy medicinal products, tissue-engineered products, and gene therapy medicinal products, possibly combined with medical devices. The stated objective was two-fold: both to promote their industrialization and market access, while guaranteeing a high level of health protection for patients. Since publication of the regulation, few marketing authorizations have been granted in Europe, and these have not been accompanied by commercial success. However, certain recent studies show that this is a growing sector and that France remains the leading European nation in terms of clinical trials. This round table brought together a panel of representatives of French public and private protagonists from the advanced therapy sector. The discussions focused on the conditions to ensure the success of translational research and, more generally, the French advanced therapy sector. These enabled a number of obstacles to be identified, which once lifted, by means of recommendations, would facilitate the development and success of this sector.

Promoting the place of the allied health professions in clinical research.

Clinical research is of major importance to today's society, as scientific evidence is increasingly demanded as a basis for progress, whether this involves developing new healthcare products, improving clinical practice and care protocols or progress in prevention. Clinical research therefore requires professionals who are both experienced and increasingly well trained. Against this background, allied health professionals are becoming involved more and more, both as team members supporting clinical research projects and as managers or coordinators of projects in their own field. Clinical research activities provide an ideal opportunity for continuing professional development. All of this means that the professional skills of the allied health professions and clinical research support professions must be enhanced, their role promoted in the context of lecturer status and in the longer term, their status recognised by the supervisory authorities.

Training approaches and devices utilization during endotracheal intubation in French Emergency Departments: a nationwide survey.

BACKGROUND AND IMPORTANCE: Endotracheal intubation is a lifesaving procedure that is reportedly associated to a significant risk of adverse events. Recent trials have reported that the use of videolaryngoscope and of a stylet might limit this risk during emergency intubation. OBJECTIVES: The objective of this study was to provide a national description of intubation practices in French Emergency Departments (EDs). SETTINGS AND PARTICIPANTS: We conducted an online nationwide survey by sending an anonymous 37-item questionnaire via e-mail to 629 physicians in French EDs between 2020 and 2022. INTERVENTION: A single questionnaire was sent to a sole referent physician in each ED. OUTCOME MEASURES AND ANALYSIS: The primary endpoint was to assess the proportion of French EDs in which videolaryngoscopy was available for emergency intubation and its use in routine practice. Secondary endpoints included the presence of local protocol or standard of procedure for intubation, availability of capnography, and routine use of a stylet. MAIN RESULTS: Of the surveyed EDs, 342 (54.4%) returned the completed questionnaire. A videolaryngoscope was available in 193 (56%) EDs, and direct laryngoscopy without a stylet was majorly used as the primary approach in 280 (82%) EDs. Among the participating EDs, 74% had an established protocol for intubation and 92% provided a capnography device for routine verification of tube position. In cases of difficult intubation, the use of a bougie was recommended in 227 (81%) EDs, and a switch to a videolaryngoscope in 16 (6%) EDs. The most frequently used videolaryngoscope models were McGrath Mac Airtraq (51%), followed by Airtraq (41%), and Glidescope (14%). CONCLUSION: In this large French survey, the majority of EDs recommended direct laryngoscopy without stylet, with seldom use of videolaryngoscopy.

Pharmacoepidemiology studies: what levels of evidence and how can they be reached?

In pharmacoepidemiology studies, the nature of the research question will dictate the choice of methodological approach and the conditions for optimizing the level of evidence. Thus, to document the treated population and the modes of use of a new drug in real-life prescribing conditions, a descriptive approach through cross-sectional or longitudinal studies conducted on databases, or else ad-hoc studies, will be preferred. On the other hand, evaluation of the real-life "effectiveness" of a new drug will be based on cohort, case-control or scientific modeling, depending on the drug and the disease of interest. For questions involving drug risks and safety, it is the adverse effects profile that will guide the choice of study design, both for identification of the effect (signal) and assessment of causation. In all cases, in the post-marketing authorization (MA) setting, the evidence acquired in pre-MA studies serves as the basis for generating hypotheses. Whatever the research question and the method chosen to address it, the potential biases and their impact on the results need to be identified. In certain cases, a combination of several complementary approaches may prove preferable to a single study.

Symptomatic Postoperative Compressive Pneumocephalus After Cholecystectomy.

A 75-year-old woman with a history of chronic hydrocephalus due to stenosis of the aqueduct of Sylvius was examined at the emergency department for altered mental status. There was placement of a ventriculoperitoneal shunt in 1970 complicated by meningitis, leading to removal of the material and ventriculociternostomy as definitive treatment in 2004. About one month previously, she had undergone a laparoscopic cholecystectomy complicated by an intra-abdominal collection. Clinical examination at the emergency department revealed a Glasgow score of 8 (E3 V1 M4). In the emergency department the patient presented a tonic-clonic seizure before a cerebral CT scan was performed showing a massive compressive pneumocephalus, then a second seizure. The patient was finally admitted to the neurosurgery department and underwent surgery. LEARNING POINTS: Changes in mental status in a patient with a history of chronic hydrocephalus should alert clinicians to a possible complication.This case reflects the delayed diagnosis of a critically ill patient in the emergency department.

Micro-costing analysis of suspected lower respiratory tract infection care in a French emergency department.

Introduction: In the context of budgetary constraints faced by healthcare systems, the medical-economic evaluation of care strategies becomes essential. In particular, valuing consumed resources in the overcrowded emergency departments (EDs) has become a priority to adopt more efficient approaches in treating the growing number of patients. However, precisely measuring the cost of care is challenging. While bottom-up micro-costing is considered the gold standard, its practical application remains limited. Objective: The objective was to accurately estimate the ED care cost for patients consulting in a French ED for suspected lower respiratory tract infection. Methods: The authors conducted a cost analysis using a bottom-up micro-costing method. Patients were prospectively included between January 1, and March 31, 2023. The primary endpoint was the mean cost of ED care. Resources consumed were collected using direct observation method and cost data were obtained from information available at Strasbourg University Hospital. Results: The mean cost of ED care was €411.68 (SD = 174.49). The cost elements that made the greatest contribution to the total cost were laboratory tests, labor, latency time, imaging and consumables. Considering this cost and the current epidemiological data on respiratory infections in France, the absence of valuation for outpatient care represents an annual loss of over 17 million euros for healthcare facilities. Conclusion: Micro-costing is a key element in valuing healthcare costs. The importance of accurately measuring costs, along with measuring the health outcomes of a defined care pathway, is to enhance the relevance of health economic evaluations and thus ensure efficient care.

Occurrence of Severe Arrhythmias in Patients with Non-ST Elevation Acute Coronary Syndrome (NSTE-ACS): A Retrospective Study.

BACKGROUND: Non-ST elevation acute coronary syndrome (NSTE-ACS) is one of the most frequent manifestations of coronary artery disease. The occurrence of serious heart rhythm disorders (SHRDs) in NSTE-ACS is not well documented. However, continuous heart rhythm monitoring is recommended during the initial management of NSTE-ACS. The targeted monitoring of patients at greater risk for SHRDs could facilitate patients' care in emergency departments (EDs) where the flow of patients is continuously increasing. METHODS: This retrospective single-center study included 480 patients from emergency and cardiology departments within the Strasbourg University Hospital between 1 January 2019 and 31 December 2020. The objective was to estimate the frequency of the occurrence of SHRDs among patients with NSTE-ACS. The secondary objective was to highlight the factors associated with a higher risk of SHRDs. RESULTS: The proportion of SHRDs during the first 48 h of hospital care was 2.3% (CI95%: 1.2-4.1%, n = 11). Two time periods were considered: before coronary angiography (1.0%), and during, or after coronary angiography (1.3%). In the first group, two patients required immediate treatment (0.4% of the patients) and no death occurred. In the univariate analysis, the variables significantly associated with SHRDs were age, anticoagulant medication, a decrease in glomerular filtration rate, plasmatic hemoglobin, and left ventricle ejection fraction (LVEF), and an increase in plasmatic troponin, BNP, and CRP levels. In the multivariable analysis, plasmatic hemoglobin > 12 g/dL seemed to be a protective factor for SHRDs. CONCLUSIONS: In this study, SHRDs were rare and, most often, spontaneously resolved. These data challenge the relevance of systematic rhythm monitoring during the initial management of patients with NSTE-ACS.