Whole blood transcriptome signature predicts severe forms of COVID-19: Results from the COVIDeF cohort study.

COVID-19 is associated with heterogeneous outcome. Early identification of a severe progression of the disease is essential to properly manage the patients and improve their outcome. Biomarkers reflecting an increased inflammatory response, as well as individual features including advanced age, male gender, and pre-existing comorbidities, are risk factors of severe COVID-19. Yet, these features show limited accuracy for outcome prediction. The aim was to evaluate the prognostic value of whole blood transcriptome at an early stage of the disease. Blood transcriptome of patients with mild pneumonia was profiled. Patients with subsequent severe COVID-19 were compared to those with favourable outcome, and a molecular predictor based on gene expression was built. Unsupervised classification discriminated patients who would later develop a COVID-19-related severe pneumonia. The corresponding gene expression signature reflected the immune response to the viral infection dominated by a prominent type I interferon, with IFI27 among the most over-expressed genes. A 48-genes transcriptome signature predicting the risk of severe COVID-19 was built on a training cohort, then validated on an external independent cohort, showing an accuracy of 81% for predicting severe outcome. These results identify an early transcriptome signature of severe COVID-19 pneumonia, with a possible relevance to improve COVID-19 patient management.

Effect of a Diagnostic Strategy Using an Elevated and Age-Adjusted D-Dimer Threshold on Thromboembolic Events in Emergency Department Patients With Suspected Pulmonary Embolism: A Randomized Clinical Trial.

Importance: Uncontrolled studies suggest that pulmonary embolism (PE) can be safely ruled out using the YEARS rule, a diagnostic strategy that uses varying D-dimer thresholds. Objective: To prospectively validate the safety of a strategy that combines the YEARS rule with the pulmonary embolism rule-out criteria (PERC) rule and an age-adjusted D-dimer threshold. Design, Settings, and Participants: A cluster-randomized, crossover, noninferiority trial in 18 emergency departments (EDs) in France and Spain. Patients (N = 1414) who had a low clinical risk of PE not excluded by the PERC rule or a subjective clinical intermediate risk of PE were included from October 2019 to June 2020, and followed up until October 2020. Interventions: Each center was randomized for the sequence of intervention periods. In the intervention period (726 patients), PE was excluded without chest imaging in patients with no YEARS criteria and a D-dimer level less than 1000 ng/mL and in patients with 1 or more YEARS criteria and a D-dimer level less than the age-adjusted threshold (500 ng/mL if age <50 years or age in years × 10 in patients ≥50 years). In the control period (688 patients), PE was excluded without chest imaging if the D-dimer level was less than the age-adjusted threshold. Main Outcomes and Measures: The primary end point was venous thromboembolism (VTE) at 3 months. The noninferiority margin was set at 1.35%. There were 8 secondary end points, including chest imaging, ED length of stay, hospital admission, nonindicated anticoagulation treatment, all-cause death, and all-cause readmission at 3 months. Results: Of the 1414 included patients (mean age, 55 years; 58% female), 1217 (86%) were analyzed in the per-protocol analysis. PE was diagnosed in the ED in 100 patients (7.1%). At 3 months, VTE was diagnosed in 1 patient in the intervention group (0.15% [95% CI, 0.0% to 0.86%]) vs 5 patients in the control group (0.80% [95% CI, 0.26% to 1.86%]) (adjusted difference, -0.64% [1-sided 97.5% CI, -∞ to 0.21%], within the noninferiority margin). Of the 6 analyzed secondary end points, only 2 showed a statistically significant difference in the intervention group compared with the control group: chest imaging (30.4% vs 40.0%; adjusted difference, -8.7% [95% CI, -13.8% to -3.5%]) and ED median length of stay (6 hours [IQR, 4 to 8 hours] vs 6 hours [IQR, 5 to 9 hours]; adjusted difference, -1.6 hours [95% CI, -2.3 to -0.9]). Conclusions and Relevance: Among ED patients with suspected PE, the use of the YEARS rule combined with the age-adjusted D-dimer threshold in PERC-positive patients, compared with a conventional diagnostic strategy, did not result in an inferior rate of thromboembolic events. Trial Registration: ClinicalTrials.gov Identifier: NCT04032769.

Unexpected death within 72 hours of emergency department visit: were those deaths preventable?

INTRODUCTION: We aimed to determine the rate of preventable death in patients who died early and unexpectedly following hospital admission from the emergency department (ED). METHODS: We conducted a retrospective multicenter study in four centers from the Paris metropolitan area. Inclusion criteria were medical patients who died in hospital within 72 hours of ED attendance and were not admitted to the intensive care unit (unexpected death). Exclusion criteria were limitations of care determined by treating physicians. The existence of a limitation of care decision was adjudicated by two independent chart abstractors. Preventable death was defined as death occurring as a result of medical error. For each selected patient with unexpected death, charts were examined for medical errors and rated on a 1 to 5 preventability scale (from very unlikely to very likely) for the preventability of the death. The primary endpoint was the likely preventable death, rated as 4 or 5 on the preventability scale. RESULTS: We retrieved 555 charts; 47 unexpected deaths were analysed; 24 (51%) were considered as preventable. There was a median number of medical errors of two. The most common process breakdowns were incorrect choice of treatment (47% of patients) and failure to order appropriate diagnostic tests (38% of patients). The most common medical error was a severe delay or absence of recommended treatment for severe sepsis, which occurred in 10 (42%) patients. CONCLUSIONS: In our sample, more than half of unexpected deaths are related to a medical error, and could have been prevented.

Cross-checking to reduce adverse events resulting from medical errors in the emergency department: study protocol of the CHARMED cluster randomized study.

BACKGROUND: Medical errors and preventable adverse events are a major cause of concern, especially in the emergency department (ED) where its prevalence has been reported to be roughly of 5-10% of visits. Due to a short length of stay, emergency patients are often managed by a sole physician - in contrast with other specialties where they can benefit from multiples handover, ward rounds and staff meetings. As some studies report that the rate and severity of errors may decrease when there is more than one physician involved in the management in different settings, we sought to assess the impact of regular systematic cross-checkings between physicians in the ED. DESIGN: The CHARMED (Cross-checking to reduce adverse events resulting from medical errors in the emergency department) study is a multicenter cluster randomized study that aim to evaluate the reduction of the rate of severe medical errors with implementation of systematic cross checkings between emergency physician, compared to a control period with usual care. This study will evaluate the effect of this intervention on the rate of severe medical errors (i.e. preventable adverse events or near miss) using a previously described two-level chart abstraction. We made the hypothesis that implementing frequent and systematic cross checking will reduce the rate of severe medical errors from 10 to 6% - 1584 patients will be included, 140 for each period in each center. DISCUSSION: The CHARMED study will be the largest study that analyse unselected ED charts for medical errors. This could provide evidence that frequent systematic cross-checking will reduce the incidence of severe medical errors. TRIAL REGISTRATION: Clinical Trials, NCT02356926.

Effect of the 1-h bundle on mortality in patients with suspected sepsis in the emergency department: a stepped wedge cluster randomized clinical trial.

PURPOSE: The efficacy of the 1-h bundle for emergency department (ED) patients with suspected sepsis, which includes lactate measurement, blood culture, broad-spectrum antibiotics administration, administration of 30 mL/kg crystalloid fluid for hypotension or lactate ≥ 4 mmol/L, remains controversial. METHODS: We carried out a pragmatic stepped-wedge cluster-randomized trial in 23 EDs in France and Spain. Adult patients with Sepsis-3 criteria or a quick sequential organ failure assessment (SOFA) score ≥ 2 or a lactate > 2 mmol/L were eligible. The intervention was the implementation of the 1-h sepsis bundle. The primary outcome was in-hospital mortality truncated at 28 days. Secondary outcomes included volume of fluid resuscitation at 24 h, acute heart failure at 24 h, SOFA score at 72 h, intensive care unit (ICU) length of stay, number of days on mechanical ventilation or renal replacement therapy, vasopressor free days, unnecessary antibiotic administration, and mortality at 28 days. 1148 patients were planned to be analysed; the study period ended after 873 patients were included. RESULTS: 872 patients (mean age 66, 42% female) were analyzed: 387 (44.4%) in the intervention group and 485 (55.6%) in the control group. Median SOFA score was 3 [1-5]. Median time to antibiotic administration was 40 min in the intervention group vs 113 min in the control group (difference - 73 [95% confidence interval (CI) - 93 to - 53]). There was a significantly higher rate, volume, and shorter time to fluid resuscitation within 3 h in the intervention group. There were 47 (12.1%) in-hospital deaths in the intervention group compared to 61 (12.6%) in the control group (difference in percentage - 0.4 [95% CI - 5.1 to 4.2], adjusted relative risk (aRR) 0.81 [95% CI 0.48 to 1.39]). There were no differences between groups for other secondary endpoints. CONCLUSIONS: Among patients with suspected sepsis in the ED, the implementation of the 1-h sepsis bundle was not associated with significant difference in in-hospital mortality. However, this study may be underpowered to report a statistically significant difference between groups.

Factors associated with adverse events resulting from medical errors in the emergency department: two work better than one.

BACKGROUND: The Emergency Department (ED) is an environment at risk for medical errors. OBJECTIVE: Our aim was to determine the factors associated with the adverse events resulting from medical errors in the ED among patients who were admitted. METHODS: This was a prospective observational study. For a 1-month period, we included all ED patients who were subsequently admitted to the medical ward. Detection of medical errors was made by the admitting physician and then validated by two experts who reviewed all available data and medical charts pertaining to the patient's hospital stay, including the first review from the ward physician. Related adverse events resulting from medical errors were then classified by type and severity. Adverse events were defined as medical errors that needed an intervention or caused harm to the patient. Univariate analysis examined relationships between characteristics of both patients and physicians and the risk of adverse events. RESULTS: From 197 analyzed patients, 130 errors were detected, of these, 34 were categorized as adverse events among 19 patients (10%). Seventy-six percent of these were categorized as proficiency errors. The only factors associated with a lower risk of adverse events were the transition of care involving a handoff within the ED (0% vs. 19%; p = 0.03) and the involvement of a resident (junior doctor) in addition to the senior physician (37% vs. 67%; p < 0.01). CONCLUSIONS: In our study, the involvement of more than one physician was associated with a lower risk of adverse events.

Serum lactate and procalcitonin measurements in emergency room for the diagnosis and risk-stratification of patients with suspected infection.

OBJECTIVE: To study the contribution of lactate and procalcitonin (PCT) serum measurements for the diagnosis and the risk-stratification of patients with suspected infection presenting to the ED. METHODS: Single-center one year observational study on 462 consecutive patients. Multivariate analysis to assess variables associated with sepsis, severe sepsis, septic shock and severe outcome. RESULTS: Multivariate analysis (Odds ratio [95% CI]), showed that PCT was the best independent variable to identify sepsis (3.98 [2.60-6.10]), while lactate was the best to diagnose severe sepsis (10.88 [6.51-18.19]). Patients with both lactate above 2 mmol·L(-1) and PCT above 0.8 ng·mL(-1) had an enhanced risk of severe outcome. CONCLUSIONS: the dosages of lactate and PCT are complementary for the diagnosis and risk-stratification of patients evaluated in the ED for suspected infection.

Morphine consumption is not modified in patients with severe pain and classified by the DN4 score as neuropathic.

Neuropathic pain has been poorly investigated in the emergency department, although it is known to be less sensitive to opioids than other forms of pain. We tested the hypothesis that morphine requirements are increased in patients having severe pain classified as neuropathic using the DN4 score. We included adult patients with acute severe pain (visual analog scale ≥ 70), assessed using the DN4 score, and treated with intravenous morphine titration (bolus of 2 or 3 mg [body weight >60 kg] with 5-minute intervals between each bolus). Pain relief was defined as a visual analog scale 30 or less. Patients were divided into 2 groups: control group (DN4 score <4) and neuropathic pain group (DN4 score ≥ 4). The main outcome was the total dose of morphine administered. Data are mean ± SD or median (interquartile range). Among the 239 patients included (mean age, 43+14 years), 35 patients (15%) had a DN4 score 4 or more. The main characteristics of the 2 groups were comparable. There were no significant differences between the 2 groups in morphine dose (0.16+0.09 vs 0.17+0.11 mg/kg, P=.32), number of boluses administered (3.5 [3-5] vs 3 [3-6], P=.97), proportion of patients with pain relief (75 vs 83%, P=.39), or morphine-related adverse effects (11% vs 3%, P=.14). In conclusion, morphine consumption was not significantly modified in patients having severe pain classified as neuropathic using the DN4 score as compared with a control group, suggesting that specific detection of neuropathic pain may not be useful in the emergency department.

Concordance between transcutaneous and arterial measurements of carbon dioxide in an ED.

BACKGROUND: Transcutaneous carbon dioxide pressure (PtcCO(2)) has been suggested as a noninvasive surrogate of arterial carbon dioxide pressure (PaCO(2)). Our study evaluates the reliability of this method in spontaneously breathing patients in an emergency department. PATIENTS AND METHODS: A prospective, observational study was performed in nonintubated dyspneic patients who required measurement of arterial blood gases. Simultaneously and blindly to the physicians in charge, PtcCO(2) was measured using a TOSCA 500 monitor (Radiometer, Villeurbanne, France). Agreement between PaCO(2) and PtcCO(2) was assessed using the Bland-Altman method. RESULTS: Forty-eight patients (mean age, 65 years) were included, and 50 measurements were done. Eleven (23%) had acute heart failure; 10 (21%), pneumonia; 7 (15%), acute asthma; and 7 (15%), exacerbation of chronic obstructive pulmonary disease. Median PaCO(2) was 42 mm Hg (range, 17-109). Mean difference between PaCO(2) and PtcCO(2) was 1 mm Hg with 95% limits of agreement of -3.4 to +5.6 mm Hg. All measurement differences were within 5 mm Hg, and 32 (64%) were within 2 mm Hg. CONCLUSION: Transcutaneous carbon dioxide pressure accurately predicts PaCO(2) in spontaneously breathing patients.

Red Blood Cell Transfusion in the Emergency Department: An Observational Cross-Sectional Multicenter Study.

BACKGROUND: We aimed to describe red blood cell (RBC) transfusions in the emergency department (ED) with a particular focus on the hemoglobin (Hb) level thresholds that are used in this setting. METHODS: This was a cross-sectional study of 12 EDs including all adult patients that received RBC transfusion in January and February 2018. Descriptive statistics were reported. Logistic regression was performed to assess variables that were independently associated with a pre-transfusion Hb level ≥ 8 g/dL. RESULTS: During the study period, 529 patients received RBC transfusion. The median age was 74 (59-85) years. The patients had a history of cancer or hematological disease in 185 (35.2%) cases. Acute bleeding was observed in the ED for 242 (44.7%) patients, among which 145 (59.9%) were gastrointestinal. Anemia was chronic in 191 (40.2%) cases, mostly due to vitamin or iron deficiency or to malignancy with transfusion support. Pre-transfusion Hb level was 6.9 (6.0-7.8) g/dL. The transfusion motive was not notified in the medical chart in 206 (38.9%) cases. In the multivariable logistic regression, variables that were associated with a higher pre-transfusion Hb level (≥8 g/dL) were a history of coronary artery disease (OR: 2.09; 95% CI: 1.29-3.41), the presence of acute bleeding (OR: 2.44; 95% CI: 1.53-3.94), and older age (OR: 1.02/year; 95% CI: 1.01-1.04). CONCLUSION: RBC transfusion in the ED was an everyday concern and involved patients with heterogeneous medical situations and severity. Pre-transfusion Hb level was rather restrictive. Almost half of transfusions were provided because of acute bleeding which was associated with a higher Hb threshold.

Prevalence of pulmonary embolism in emergency department patients with isolated syncope: a prospective cohort study.

BACKGROUNDS: Paramount to guide the diagnostic strategy, the prevalence of pulmonary embolism in patients with syncope and no other symptoms is uncertain. We aimed to assess the pulmonary embolism prevalence in patients that present to the emergency department (ED) with syncope and no chest pain nor dyspnea. METHODS: Multicenter prospective cohort study in seven EDs in France. Adult patients who presented to the ED with syncope (transient loss of consciousness) were included. Patients with chest pain or dyspnea were excluded. Included patients underwent formal work-up for pulmonary embolism, including D-dimer testing and further imaging if positive. Cases of pulmonary embolism were adjudicated by two independent expert radiologists with the review of imaging studies. Secondary objectives included the pulmonary embolism prevalence in the subgroup of patients with cancer, in patients with negative Pulmonary Embolism Rule Out criteria (PERC) score, and according to the clinical probability assessed either by Wells or revised Geneva score. RESULTS: We analyzed 411 patients, in whom 128 (31%) underwent a computed tomographic pulmonary angiogram and 9 (2%) a ventilation-perfusion scan. A pulmonary embolism was confirmed in nine patients (prevalence of 2.2%, 95% confidence interval, 1.1-4.3%), including one subsegmental pulmonary embolism. This prevalence was of 18% (3-52%) in patients with cancer and 0.7% (0.1-4%) in PERC negative patients. CONCLUSION: In our sample of patients with isolated syncope, the prevalence of pulmonary embolism was 2.2%. This value is not sufficiently low to negate the requirement for a formal work up in the ED, even in the absence of chest pain or dyspnea. However, the large confidence interval precludes any strong conclusion.

Glucocorticoids for acute urticaria: study protocol for a double-blind non-inferiority randomised controlled trial.

INTRODUCTION: This study protocol describes a trial designed to investigate whether antihistamine alone in patients with acute urticaria does not increase the 7-day Urticaria Activity Score (UAS7) in comparison with an association of antihistamine and glucocorticoids and reduces short-term relapses and chronic-induced urticaria. METHODS AND ANALYSIS: This is a prospective, double-blind, parallel-group, multicentre non-inferiority randomised controlled trial. Two-hundred and forty patients with acute urticaria admitted to emergency department will be randomised in a 1:1 ratio to receive levocetirizine or an association of levocetirizine and prednisone. Randomisation will be stratified by centre. The primary outcome will be the UAS7 at day 7. The secondary outcomes will encompass recurrence of hives and/or itch at day 7; occurrence of spontaneous hives or itch for >6 weeks; patients with angioedema at day 7, and 2, 6, 12 and 24 weeks; new emergency visits for acute urticaria recurrences at days 7 and 14, and 3 months; Dermatology Life Quality Index at days 7 and 14, and 3 and 6 months; and Chronic Urticaria Quality of Life Questionnaire at 6 weeks. ETHICS AND DISSEMINATION: The protocol has been approved by the Comité de Protection des PersonnesSud-Méditerranée II and will be carried out in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. A steering committee will oversee the progress of the study. Findings will be disseminated through national and international scientific conferences and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03545464.

Effect of Systematic Physician Cross-checking on Reducing Adverse Events in the Emergency Department: The CHARMED Cluster Randomized Trial.

Importance: Emergency departments (ED) are environments that are at high risk for medical errors. Previous studies suggested that the proportion of medical errors may decrease when more than 1 physician is involved. Objective: To reduce the proportion of medical errors by implementing systematic cross-checking between emergency physicians. Design, Setting, and Participants: This cluster randomized crossover trial includes a random sample of 14 adult patients (age ≥18 years) per day during two 10-day period in 6 EDs (n = 1680 patients) in France. Interventions: Systematic cross-checking between emergency physicians, 3 times a day, which included a brief presentation of one physician's case to another, followed by the second physician's feedback to the first. Main Outcomes and Measures: Medical error in the ED, defined as an adverse event (either a near miss or a serious adverse event). The primary end point was identified using a 2-level error detection surveillance system, blinded to the strategy allocation. Results: Among the 1680 included patients (mean [SD] age, 57.5 [21.7] years), 144 (8.6%) had an adverse event. There were 54 adverse events among 840 patients (6.4%) in the cross-check group compared with 90 adverse events among 840 patients (10.7%) in the standard care group (relative risk reduction [RRR], 40% [95% CI, 12% to 59%]; absolute risk reduction [ARR], 4.3%; number needed to treat [NNT], 24). There was also a significant reduction rate of near misses (RRR, 47% [95% CI, 15% to 67%]; ARR, 2.7%; NNT, 37) but not of the rate of preventable serious adverse events (RRR, 29% [95% CI, -18% to 57%]; ARR, 1.2%; NNT, 83). Conclusions and Relevance: The implementation of systematic cross-checking between emergency physicians was associated with a significant reduction in adverse events, mainly driven by a reduction in near misses. Trial Registration: ClinicalTrials.gov Identifier: NCT02356926.

Accuracy of oxygen tissue saturation values in assessing severity in patients with sepsis admitted to emergency departments.

INTRODUCTION: Near-infrared spectrometry assesses hemoglobin saturation of oxygen in tissues (StO2). Although it may provide additional information on local microcirculation function, the usefulness of near-infrared spectrometry in septic patients is debated. This study evaluated whether baseline StO2 value is useful in septic patients admitted to the emergency department with a diagnosis of severe sepsis. MATERIALS AND METHODS: We carried out a prospective multicenter study in three emergency departments in Paris, France. Triage nurses were to record StO2, the results were blinding to the emergency physicians. Patients were eligible when presenting with at least two of the following parameters: temperature higher than 38°C or less than 36°C, respiratory rate greater than 30/min, heart rate greater than 120/min, and systolic arterial blood pressure less than 110 mmHg. Patients with a final diagnosis of sepsis and severe sepsis were analyzed. RESULTS: We analyzed 98 patients (70 with sepsis and 28 with severe sepsis). Thirty-day mortality was 2.9 versus 14.3% (P=0.048) in the sepsis and the severe sepsis group, respectively. No significant difference in the median StO2 was observed in patients with sepsis and severe sepsis [79% (74-85%) vs. 77% (72-83%), respectively; P=0.66]. The area under the curve of the receiver operating characteristic curve for StO2 to predict severe sepsis was 0.53 (0.39-0.66; P=0.5) and the cutoff value was 77%. Median StO2 did not differ in patients admitted to the ICU [80% (60-88%) vs. 79% (74-84%); P=0.78] and in nonsurvivors compared with that of survivors [79% (74-85%) vs. 76% (73-83%); P=0.64]. CONCLUSION: This study fails to show any value of StO2 baseline at triage for early detection of severe sepsis in emergency patients.

Self-perception of knowledge and confidence in performing basic life support among medical students.

AIM: Before implementing new workshops and teaching in our faculty for performing basic life support (BLS), we aimed to determine the level of self-confidence of medical students with regard to the management of cardiac arrest (CA). METHODS: We conducted a preinterventional study. A questionnaire was sent to third-year to sixth-year medical students. We recorded sex, year of training, and personal witnessing of CA. We asked them about their theoretical knowledge on 10 main items of BLS and their self-perception of qualification to conduct a CA situation. We tested the respective influence of sex, year of training, and personal witnessing of CA. RESULTS: In total, 592 (37%) students completed the questionnaire, 42% of them were men. Less than a third of the students (30%) thought of themselves as being sufficiently qualified to conduct BLS. After the third year, the level of study did not influence their theoretical knowledge or their self-perception of qualification. Male sex and the number of CAs witnessed were the only factors positively associated with better self-confidence regarding qualification. CONCLUSION: Self-perception of qualification in BLS is poor in our faculty. In our study, personal witnessing of CA greatly influenced confidence, whereas level of study did not.