Noninvasive diagnostic work-up for suspected acute pulmonary embolism during pregnancy: a systematic review and meta-analysis of individual patient data.

BACKGROUND: Few studies evaluated the performance of noninvasive diagnostic strategies for suspected acute pulmonary embolism (PE) in pregnant women. OBJECTIVES: The aim of this study was to establish the safety and efficiency of the Wells rule with fixed and adapted D-dimer threshold, and the YEARS algorithm, combined with compression ultrasonography (CUS), in pregnant women with suspected PE in an individual patient data meta-analysis. METHODS: We performed a systematic review to identify prospective diagnostic management studies in pregnant women with suspected PE. Primary outcomes were safety, defined as the failure rate, ie, the 3-month venous thromboembolism (VTE) incidence after excluding PE without chest imaging, and efficiency, defined as the proportion of patients in whom chest imaging could be avoided. RESULTS: We identified 2 relevant studies, of which individual patient-level data were analyzed in a fixed-effect meta-analysis, totaling 893 pregnant women. The Wells rule with fixed and adapted D-dimer threshold as well as the YEARS algorithm could safely rule out acute PE (failure rate, 0·37%-1·4%), but efficiency improved considerably when applying pretest probability-adapted D-dimer thresholds. The efficiency of bilateral CUS was limited (2·3% overall; number needed to test 43), especially in patients without symptoms of deep-vein thrombosis (efficiency 0·79%; number needed to test 127). CONCLUSION: This study supports the latest guideline recommendations (European Society of Cardiology 2019) to apply pretest probability assessment and D-dimer tests to rule out PE in pregnant women. From an efficiency perspective, the use of a strategy with pretest probability-adapted D-dimer threshold is preferred. The yield of CUS was very limited in patients without concomitant symptoms of deep-vein thrombosis.

Evaluating the Increased Burden of Cardiorespiratory Illness Visits to Adult Emergency Departments During Flu and Bronchiolitis Outbreaks in the Pediatric Population: Retrospective Multicentric Time Series Analysis.

BACKGROUND: Cardiorespiratory decompensation (CRD) visits have a profound effect on adult emergency departments (EDs). Respiratory pathogens like respiratory syncytial virus (RSV) and influenza virus are common reasons for increased activity in pediatric EDs and are associated with CRD in the adult population. Given the seasonal aspects of such challenging pathology, it would be advantageous to predict their variations. OBJECTIVE: The goal of this study was to evaluate the increased burden of CRD in adult EDs during flu and bronchiolitis outbreaks in the pediatric population. METHODS: An ecological study was conducted, based on admissions to the adult ED of the Centre Hospitalier Universitaire (CHU) of Grenoble and Saint Etienne from June 29, 2015 to March 22, 2020. The outbreak periods for bronchiolitis and flu in the pediatric population were defined with a decision-making support tool, PREDAFLU, used in the pediatric ED. A Kruskal-Wallis variance analysis and a Spearman monotone dependency were performed in order to study the relationship between the number of adult ED admissions for the International Classification of Diseases (ICD)-10 codes related to cardiorespiratory diagnoses and the presence of an epidemic outbreak as defined with PREDAFLU. RESULTS: The increase in visits to the adult ED for CRD and the bronchiolitis and flu outbreaks had a similar distribution pattern (CHU Saint Etienne: χ23=102.7, P<.001; CHU Grenoble: χ23=126.67, P<.001) and were quite dependent in both hospital settings (CHU Saint Etienne: Spearman ρ=0.64; CHU Grenoble: Spearman ρ=0.71). The increase in ED occupancy for these pathologies was also significantly related to the pediatric respiratory infection outbreaks. These 2 criteria gave an idea of the increased workload in the ED due to CRD during the bronchiolitis and flu outbreaks in the pediatric population. CONCLUSIONS: This study established that CRD visits and bed occupancy for adult EDs were significantly increased during bronchiolitis and pediatric influenza outbreaks. Therefore, a prediction tool for these outbreaks such as PREDAFLU can be used to provide early warnings of increased activity in adult EDs for CRD visits.

Management of pharmaceutical and recreational drug poisoning.

BACKGROUND: Poisoning is one of the leading causes of admission to the emergency department and intensive care unit. A large number of epidemiological changes have occurred over the last years such as the exponential growth of new synthetic psychoactive substances. Major progress has also been made in analytical screening and assays, enabling the clinicians to rapidly obtain a definite diagnosis. METHODS: A committee composed of 30 experts from five scientific societies, the Société de Réanimation de Langue Française (SRLF), the Société Française de Médecine d'Urgence (SFMU), the Société de Toxicologie Clinique (STC), the Société Française de Toxicologie Analytique (SFTA) and the Groupe Francophone de Réanimation et d'Urgences Pédiatriques (GFRUP) evaluated eight fields: (1) severity assessment and initial triage; (2) diagnostic approach and role of toxicological analyses; (3) supportive care; (4) decontamination; (5) elimination enhancement; (6) place of antidotes; (7) specificities related to recreational drug poisoning; and (8) characteristics of cardiotoxicant poisoning. Population, Intervention, Comparison, and Outcome (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Analysis of the literature and formulation of recommendations were then conducted according to the GRADE® methodology. RESULTS: The SRLF-SFMU guideline panel provided 41 statements concerning the management of pharmaceutical and recreational drug poisoning. Ethanol and chemical poisoning were excluded from the scope of these recommendations. After two rounds of discussion and various amendments, a strong consensus was reached for all recommendations. Six of these recommendations had a high level of evidence (GRADE 1±) and six had a low level of evidence (GRADE 2±). Twenty-nine recommendations were in the form of expert opinion recommendations due to the low evidences in the literature. CONCLUSIONS: The experts reached a substantial consensus for several strong recommendations for optimal management of pharmaceutical and recreational drug poisoning, mainly regarding the conditions and effectiveness of naloxone and N-acetylcystein as antidotes to treat opioid and acetaminophen poisoning, respectively.

Major bleeding risk associated with oral anticoagulant in real clinical practice. A multicentre 3-year period population-based prospective cohort study.

AIMS: The objective was to compare major bleeding risk of direct oral anticoagulants (DOACs; per type and dose) with vitamin K antagonists (VKAs), irrespective of indication, using real-world data. METHODS: A population-based prospective cohort study, using the French national health data system (SNIIRAM), identified 47 469 adults living within 5 well-defined geographical areas, who were new users of oral anticoagulants in the period 2013-2015: 20 205 VKA users, 19 579 rivaroxaban users, 4225 dabigatran users and 3460 apixaban users. From all emergency departments within these areas, clinical data for all adults referred for bleeding was collected and medically validated. The databases were linked for common key variables. The main outcome measure was major bleeding: intracranial haemorrhage, major gastrointestinal bleeding and other major bleeding events. Hazard ratios were derived from adjusted Cox proportional hazard models. We used propensity score weighting as a sensitivity analysis, with separate analyses according to indications (atrial fibrillation or venous thromboembolism). RESULTS: Compared to VKAs, high and low-dose DOACs were associated with a reduced risk of intracranial haemorrhage (adjusted hazard ratio 0.55, 95% confidence interval 0.37-0.82 and 0.54, 0.26-1.12 respectively), and a reduced risk of other major bleeding events (0.41, 0.29-0.58 and 0.41, 0.22-0.79 respectively), irrespective of duration and indication. Neither DOAC dose evidenced any significant difference from VKAs in terms of risk of major gastrointestinal bleeding. CONCLUSION: There is a clear benefit of using DOACs with regard to intracranial haemorrhage. The study provides new insight into major gastrointestinal and other major bleeding events.

Multiple criteria decision analysis approach to consider therapeutic innovations in the emergency department: The methoxyflurane organizational impact in acute trauma pain.

BACKGROUND: Acute trauma pain is poorly managed in the emergency department (ED). The reasons are partly organizational: ED crowding and rare trauma care pathways contribute to oligoanalgesia. Anticipating the organizational impact of an innovative care procedure might facilitate the decision-making process and help to optimize pain management. METHODS: We used a multiple criteria decision analysis (MCDA) approach to consider the organizational impact of methoxyflurane (self-administered) in the ED, introduced alone or supported by a trauma care pathway. A MCDA experiment was designed for this specific context, 8 experts in emergency trauma care pathways (leading physicians and pharmacists working in French urban tertiary hospitals) were recruited. The study involved four steps: (i) Selection of organizational criteria for evaluating the innovation's impact; (ii) assessment of the relative weight of each criterion; (iii) choice of appropriate scenarios for exploring the organizational impact of MEOX under various contexts; and (iv) software-assisted simulation based on pairwise comparisons of the scenarios. The final outcome measure was the expected overall organizational impact of methoxyflurane on a 0-to-100 scale (score >50: positive impact). RESULTS: Nine organizational criteria were selected. "Mean length of stay in the ED" was the most weighted. Methoxyflurane alone obtained 59 as a total score, with a putative positive impact for eight criteria, and a neutral effect on one. When a trauma care pathway was introduced concomitantly, the impact of methoxyflurane was greater overall (score: 75) and for each individual criterion. CONCLUSIONS: Our model highlighted the putative positive organizational impact of methoxyflurane in the ED-particularly when supported by a trauma care pathway-and the relevance of expert consensus in this particular pharmacoeconomic context. The MCDA approach could be extended to other research fields and healthcare challenges in emergency medicine.

Screening of hepatitis E in patients presenting for acute neurological disorders.

INTRODUCTION: Hepatitis E virus (HEV) infection has been reported to be associated with neurological disorders. However, the real prevalence of acute hepatitis E in those diseases is still unknown. We determined the prevalence of anti-HEV IgM antibody in a population with acute non-traumatic, non-metabolic, non-vascular neurological injury. METHOD: A registry was created in Grenoble Hospital University from 2014 to 2018 to collect data on patients with acute (<3 months) non-traumatic, non-metabolic, non-vascular neurological injuries. Acute hepatitis E was defined as anti-HEV IgM-positive serum in immunocompetent patient, and as anti-HEV IgM-positive serum or HEV RNA-positive serum in immunocompromised patients. RESULTS: One hundred fifty-nine patients were included. Anti-HEV IgM seroprevalence in our cohort of non-traumatic, non-metabolic, non-vascular neurological injuries was 6.9% (eleven patients, including 4 Parsonage-Turner syndrome (PTS) and 2 Guillain-Barré syndrome (GBS)). Elevated transaminases were observed in only 64% of hepatitis E patients and cholestasis in 64%. CONCLUSION: In this study, 6·9% of patients with acute non-traumatic, non-metabolic, non-vascular neurological injuries had a probable recent HEV infection. HEV serology should be systematically performed in this population, even in patients with normal transaminase level.

Opioid drug use in emergency and adverse outcomes among patients with chronic obstructive pulmonary disease: a multicenter observational study.

There is still debate as to the safety of non-palliative opioid administration to chronic obstructive pulmonary disease (COPD) patients punctually treated for an acute complaint. All patients over 40 presenting at two university hospital emergency departments (Montréal Qc, Grenoble Fr) from March 2008 to September 2014 with dyspnea, abdominal pain or trauma were retrieved, and COPD patients were selected. Our primary endpoint was a composite criterion including invasive ventilation and death. Comparisons between visits in which opioid drugs were prescribed and those without opioids were performed using an inverse probability of treatment and censoring weight (IPTCW) estimator to adjust for baseline confounders. A survival weighted Cox model was used. 7799 visits by COPD patients were identified, corresponding to 4173 unique patients. Opioid drug prescription was reported in 1317 (16.9%) visits. After applying IPCTW weighting, opioid prescription was found to be associated with the composite criterion of poor clinical outcomes (HR = 4.73 (2.94; 7.61), p < 0.01). When taken separately, this association remained significant for invasive ventilation and death, but not for NIV. All sensitivity analyses confirmed the association, except for patients with trauma or abdominal pain as the main complaint. This excess risk is observed whatever the route of administration.

Evaluation of a new respiratory monitoring tool "Early Warning ScoreO2" for patients admitted at the emergency department with dyspnea.

BACKGROUND: Many scores derived from Early Warning Scores have been developed to detect patients at risk of poor outcome. Few of these scores incorporate the oxygen flow rate while this is a major marker in patients with respiratory complaint. We developed and evaluated a new automatable monitoring tool (Early Warning Score O2: EWS.O2) that incorporates cardio-respiratory parameters (Respiratory rate, Heart rate, SpO2, and FiO2 derived from oxygen flow rate), aiming to achieve early detection of poor outcome among patients with dyspnea. METHODS: All patients presenting at an emergency department for dyspnea from June 2011 to June 2018 with available initial value (nurse triage) of respiratory parameters were included. Our primary endpoint was a composite criterion including the use of non-invasive ventilation, ICU admission and death. The Area under the Receiver Operating Characteristic curve (AUROC) of the SpO2/FiO2 index, NEWS, NEWS2, and the EWS.O2 were compared, including in subgroup analysis by final diagnosis or oxygen supplementation. RESULTS: Among the 1729 patients retrieved, the composite outcome was observed in 288 (16.7%). The EWS.O2 displayed better or comparable predictive accuracy at triage (AUROC: 0.704, 95% CI 0.672-0.736) compared to NEWS (0.662, p < 0.01), NEWS2 (0.672, p = 0.02) and SpO2/FiO2 (0.695, p = 0.46). CONCLUSIONS: This new ScoreO2 is equivalent or superior to common early warning scores and index to predict poor outcome at first medical contact. This score may be automatically and continuously recorded with new closed-loop devices to titrate oxygen flow. Further prospective studies will allow to verify its accuracy at multiple time points of the patient's journey.

Contribution of Capillary Refilling Time and Skin Mottling Score to Predict ICU Admission of Patients with Septic or haemorrhagic Shock Admitted to the Emergency Department: A TRCMARBSAU Study.

OBJECTIVE: In the emergency department (ED), the severity assessment of shock is a fundamental step prior to the admission in the intensive care unit (ICU). As biomarkers are time consuming to evaluate the severity of micro- and macro-circulation alteration, capillary refill time and skin mottling score are two simple, available clinical criteria validated to predict mortality in the ICU. The aim of the present study is to provide clinical evidence that capillary refill time and skin mottling score assessed in the ED also predict ICU admission of patients with septic or haemorrhagic shock. METHODS: This trial is an observational, non-randomised controlled study. A total of 1500 patients admitted to the ED for septic or haemorrhagic shock will be enrolled into the study. The primary outcome is the admission to the ICU. RESULTS: The study will not impact the treatments provided to each patient. Capillary refill time and skin mottling score will not be taken into account to decide patient's treatments and/or ICU admission. Patients will be followed up during their hospital stay to determine their precise destination after the ED (home, ICU or ward) and the 28- and 90-day mortality after hospital admission. CONCLUSION: The results from the present study will provide clinical evidence on the correlation between the ICU admission and the capillary refill time and the skin mottling score in septic or haemorrhagic shock admitted to the ED. The aim of the present study is to provide two simple, reliable and non-invasive tools for the triage and early orientation of these patients.

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.

Multimodal oral analgesia for non-severe trauma patients: evaluation of a triage-nurse directed protocol combining methoxyflurane, paracetamol and oxycodone.

Insufficient analgesia affects around 50% of emergency department patients. The use of a protocol helps to reduce the risk of oligoanalgesia in this context. Our objective was to describe the feasibility and efficacy of a multimodal analgesia protocol (combining paracetamol, oxycodone, and inhaled methoxyflurane) initiated by triage nurse. We performed a prospective, observational study in an emergency department (Grenoble Alpes University Hospital, France) between December 2017 and April 2018. Adult non-severe trauma patients with a numerical pain rating scale (NRS) score ≥ 4 were included. The primary efficacy criterion was the proportion of patients with an NRS score ≤ 3 at 15 min. Pain intensity was measured for 60 min and during radiography. Data on adverse events and satisfaction were recorded. A total of 200 adult patients were included (median [interquartile range (IQR)] age: 32 [23-49] years; 126 men (63%)). Sixty-six patients (33%) reported an NRS score ≤ 3 at 15 min. The time required to achieve a decrease of at least 2 points in the NRS score was 10 (5-20) min. The median [IQR] pain intensity was 4 [2-5] before radiography and 4 [2-6] during radiography. Adverse events were frequent (n = 128, 64%). No serious adverse events were reported. The patients and caregivers reported good levels of satisfaction. The administration of a nurse-driven multimodal analgesia protocol (combining paracetamol, oxycodone, and methoxyflurane) was feasible on admission to the emergency department. It rapidly produced long-lasting analgesia in adult trauma patients.Trial registration: NCT03380247.

Intranasal sufentanil versus intravenous morphine for acute severe trauma pain: A double-blind randomized non-inferiority study.

BACKGROUND: Intravenous morphine (IVM) is the most common strong analgesic used in trauma, but is associated with a clear time limitation related to the need to obtain an access route. The intranasal (IN) route provides easy administration with a fast peak action time due to high vascularization and the absence of first-pass metabolism. We aimed to determine whether IN sufentanil (INS) for patients presenting to an emergency department with acute severe traumatic pain results in a reduction in pain intensity non-inferior to IVM. METHODS AND FINDINGS: In a prospective, randomized, multicenter non-inferiority trial conducted in the emergency departments of 6 hospitals across France, patients were randomized 1:1 to INS titration (0.3 µg/kg and additional doses of 0.15 µg/kg at 10 minutes and 20 minutes if numerical pain rating scale [NRS] > 3) and intravenous placebo, or to IVM (0.1 mg/kg and additional doses of 0.05 mg/kg at 10 minutes and 20 minutes if NRS > 3) and IN placebo. Patients, clinical staff, and research staff were blinded to the treatment allocation. The primary endpoint was the total decrease on NRS at 30 minutes after first administration. The prespecified non-inferiority margin was -1.3 on the NRS. The primary outcome was analyzed per protocol. Adverse events were prospectively recorded during 4 hours. Among the 194 patients enrolled in the emergency department cohort between November 4, 2013, and April 10, 2016, 157 were randomized, and the protocol was correctly administered in 136 (69 IVM group, 67 INS group, per protocol population, 76% men, median age 40 [IQR 29 to 54] years). The mean difference between NRS at first administration and NRS at 30 minutes was -4.1 (97.5% CI -4.6 to -3.6) in the IVM group and -5.2 (97.5% CI -5.7 to -4.6) in the INS group. Non-inferiority was demonstrated (p < 0.001 with 1-sided mean-equivalence t test), as the lower 97.5% confidence interval of 0.29 (97.5% CI 0.29 to 1.93) was above the prespecified margin of -1.3. INS was superior to IVM (intention to treat analysis: p = 0.034), but without a clinically significant difference in mean NRS between groups. Six severe adverse events were observed in the INS group and 2 in the IVM group (number needed to harm: 17), including an apparent imbalance for hypoxemia (3 in the INS group versus 1 in the IVM group) and for bradypnea (2 in the INS group versus 0 in the IVM group). The main limitation of the study was that the choice of concomitant analgesics, when they were used, was left to the discretion of the physician in charge, and co-analgesia was more often used in the IVM group. Moreover, the size of the study did not allow us to conclude with certainty about the safety of INS in emergency settings. CONCLUSIONS: We confirm the non-inferiority of INS compared to IVM for pain reduction at 30 minutes after administration in patients with severe traumatic pain presenting to an emergency department. The IN route, with no need to obtain a venous route, may allow early and effective analgesia in emergency settings and in difficult situations. Confirmation of the safety profile of INS will require further larger studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT02095366. EudraCT 2013-001665-16.

Accuracy of low-weight versus standard syringe infusion pump devices depending on altitude.

BACKGROUND: Intravenous drug infusions in critically ill patients require accurate syringe infusion pumps (SIPs). This is particularly important during transportation of critically ill patients by helicopter emergency medical services (HEMS), where altitude may influence device performance. Because weight is a real concern in HEMS, new low-weight devices are very appealing. The aim of this study was to compare infusion flow rates delivered by low-weight versus standard SIP devices, in the prehospital emergency medicine setting, at different altitudes. METHODS: We conducted a comparative bench study involving five SIP devices (two standard and three low-weight models) at 300, 1700 and 3000 m altitude. The primary endpoint was the flow rate delivered by SIPs for prespecified values. We used two methods to measure flow. The normative method consisted in measuring weight (method A) and the alternate method consisted in measuring instantaneous flow (method B). RESULTS: Using method A, no significant differences were found in median flow rates and interquartile range depending on device and altitude for a prespecified 10-mL/h flow. However, method B showed that low-weight SIPs delivered multiple sequential boluses with substantial variations (1.2-15.8 mL/h) rather than a prespecified continuous 5-mL/h flow. At 1700 m altitude, the interquartile range of delivered flows increased only for low-weight devices (p for interaction< 0.001). CONCLUSIONS: Despite satisfactory normative tests, low-weight SIPs deliver discontinuous flow with potential clinical implications for critically ill patients receiving vasoactive drugs. This study also highlights a thus far unknown negative impact of altitude on SIP function. We believe that normative requirements for SIP approval should be revised accordingly.

Intensity of care delivered by prehospital emergency medical service physicians to patients with deliberate self-poisoning: results from a 2-day cross-sectional study in France.

Emergency management of deliberate self-poisoning (DSP) by drug overdose is common in emergency medicine. There is a paucity of data about the prehospital care of these patients. The principal aim was to describe the intensity of care received by patients with DSP who were managed by prehospital emergency medical service (EMS) physicians. A 48-h cross-sectional study was conducted in 319 EMS and emergency units in France. Patient and poisoning characteristics and treatments administered were recorded. Complications of poisoning, hospitalization, intensive care unit admission and death were recorded until day 30. The primary endpoint was the probability of receiving prehospital intensive care, including fluid resuscitation, vasopressor therapy, invasive ventilation, or antidotal treatments, depending whether prehospital treatment was carried out by an EMS physician or not. Data from 703 patients (median age was 43 [30-52] years, 288 (40%) men) were analyzed. One hundred and fifteen (16%) patients were attended by an EMS physician. Patients attended by EMS physicians were more likely to receive intensive treatment in the prehospital setting [odds ratio (OR) 7.4, 95% confidence interval 4.3-12.9]. These patients had more severe poisoning as suggested mainly by a lower Glasgow Coma Score (13 [8-15] vs. 15 [15-15]; p < 0.001) and a higher rate of admission to an intensive care unit [29 (25%) vs. 15 (2%), p < 0.001]. Patients with DSP attended by prehospital EMS physicians frequently received intensive care. The level of care seemed appropriate for the severity of the poisoning.

Pain during exacerbation of chronic obstructive pulmonary disease: A prospective cohort study.

BACKGROUND AND OBJECTIVE: Pain, a symptom often present in patients with Chronic Obstructive Pulmonary Disease (COPD), alters quality of life. COPD exacerbation augments several mechanisms that may cause pain (dyspnea, hyperinflation and inflammation) and therefore we hypothesized that pain might be increased during exacerbation. METHODS: A prospective cohort study was conducted in patients admitted for acute exacerbations of COPD (AECOPD) in two emergency departments in France and Canada. Patients with cancer-related pain or recent trauma were not included. The Short Form McGill Pain Questionnaire (SF-MPQ) and the Brief Pain Inventory (BPI) scale were used to evaluate pain intensity and location. Patients also completed the Borg Dyspnea Scale and Hospital Anxiety and Depression Scale. The questionnaires were completed again during an outpatient assessment in the stable phase. The primary outcome was difference in pain intensity (SF-MPQ) between the exacerbation and stable phases. RESULTS: Fifty patients were included. During exacerbation, 46 patients (92%) reported pain compared to 29 (58%) in the stable phase (p<0.001). Pain intensity was higher during exacerbation (SF-MPQ 29.7 [13.6-38.2] vs. 1.4 [0.0-11.2]; p<0.001). Pain was predominantly located in the chest during exacerbation and in the limbs during the stable phase. Pain intensity during exacerbation correlated with anxiety score. CONCLUSION: The frequency and intensity of pain were higher during AECOPD, with a specific distribution. Pain should therefore be routinely assessed and treated in patients with AECOPD.

Diagnostic accuracy of a rapid RT-PCR assay for point-of-care detection of influenza A/B virus at emergency department admission: A prospective evaluation during the 2017/2018 influenza season.

STUDY OBJECTIVE: To investigate the performance of a rapid RT-PCR assay to detect influenza A/B at emergency department admission. METHODS: This single-center prospective study recruited adult patients attending the emergency department for influenza-like illness. Triage nurses performed nasopharyngeal swab samples and ran rapid RT-PCR assays using a dedicated device (cobas Liat, Roche Diagnostics, Meylan, France) located at triage. The same swab sample was also analyzed in the department of virology using conventional RT-PCR techniques. Patients were included 24 hours-a-day, 7 days-a-week. The primary outcome was the diagnostic accuracy of the rapid RT-PCR assay performed at triage. RESULTS: A total of 187 patients were included over 11 days in January 2018. Median age was 70 years (interquartile range 44 to 84) and 95 (51%) were male. Nine (5%) assays had to be repeated due to failure of the first assay. The sensitivity of the rapid RT-PCR assay performed at triage was 0.98 (95% confidence interval (CI): 0.91-1.00) and the specificity was 0.99 (95% CI: 0.94-1.00). A total of 92 (49%) assays were performed at night-time or during the weekend. The median time from patient entry to rapid RT-PCR assay results was 46 [interquartile range 36-55] minutes. CONCLUSION: Rapid RT-PCR assay performed by nurses at triage to detect influenza A/B is feasible and highly accurate.

Nebulized versus intravenous morphine titration for the initial treatment of severe acute pain in the emergency department: study protocol for a multicenter, prospective randomized and controlled trial, CLIN-AEROMORPH.

BACKGROUND: Intravenous morphine titration (IVMT) is the French gold standard for opioid treatment in the emergency department (ED). Nebulized morphine titration (NMT) may represent an alternative without venous access, but it has not been adequately studied in adults. We test the hypothesis that NMT is at least as effective as IVMT to initially manage severe acute pain in the ED. METHODS/DESIGN: We designed a multicenter (10 French EDs), single-blind, randomized and controlled trial. Adults between 18 and 75 years with visual analog scale (VAS) ≥ 70/100 or numeric rating scale (NRS) ≥ 7/10 will be enrolled. We will randomize 850 patients into two groups to compare two routes of MT as long as VAS >  30 or NRS >  3. In group A (425), patients will receive an initial NMT for 5-25 min associated with titration of an intravenously (IV) administered placebo of physiologic serum (PS). In group B (425), patients will receive IVMT plus nebulized PS placebo. NMT is defined as a minimum of 1 and a maximum of 3 5-min nebulized boluses of 10 mg or 15 mg (weight ≥ 60 kg), at 10-min fixed intervals. IVMT is defined as a minimum of 1 and a maximum of 6 boluses of 2 mg or 3 mg (weight ≥ 60 kg), at 5-min fixed intervals. Nebulized placebo titration will be performed every 10 min. IV titration of PS will be performed every 5 min. In both groups, after 25 min, if VAS > 30/100 or NRS > 3/10, routine IVMT will be continued until pain relief. Pain severity, vital signs, bronchospasm, and Ramsay score will be recorded every 5 min. The primary outcome is the rate of relief obtained 1 h from the start of drug administration. Complete pain relief in both groups will be compared with a non-inferiority design. Secondary outcomes are pain relief at 30 min (the end of NMT) and at 2 h and median pain relief. We will compare final doses, and study the feasibility and tolerance of NMT (protocol deviations, respiratory or hemodynamic depression, sedation, and minor vegetative side effects). Co-analgesia will be recorded. Discharge criteria from the ED and hospital are defined. DISCUSSION: This trial is the first multicenter randomized and controlled NMT protocol for severe pain in the ED using the titration concept. We propose an original approach of combined titration with an endpoint at 1 h and a non-inferiority design. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03257319 . Registered on 22 August 2017.

Guideline-Based Clinical Assessment Versus Procalcitonin-Guided Antibiotic Use in Pneumonia: A Pragmatic Randomized Trial.

STUDY OBJECTIVE: Efforts to reduce unnecessary and unnecessarily long antibiotic treatment for community-acquired pneumonia have been attempted through use of procalcitonin and through guidelines based on serial clinical assessment. Our aim is to compare guideline-based clinical assessment- and procalcitonin algorithm-guided antibiotic use among patients with community-acquired pneumonia. METHODS: We performed a pragmatic, randomized, multicenter trial from November 2012 to April 2015 at 12 French hospitals. We included emergency department (ED) patients older than 18 years with community-acquired pneumonia. Patients were randomly assigned to either the procalcitonin-guided or clinical assessment group. In accordance with past studies, we hypothesized that serial clinical assessment would be superior to procalcitonin-guided care. The primary outcome was antibiotic duration, and secondary outcomes included rates of antibiotic duration less than or equal to 5 days, and clinical success and combined serious adverse outcomes at 30 days in the intention-to-treat population. RESULTS: Of 370 eligible patients, 285 (77%) were randomly assigned to either clinical assessment- (n=143) or procalcitonin-guided care (n=142). Median age was 67 years (range 18 to 93 years) and 40% of patients were deemed to have Pneumonia Severity Index class IV or V. Procalcitonin algorithm adherence was 76%. Antibiotic duration was not significantly different between clinical assessment- and procalcitonin-guided groups (median 9 versus 10 days, respectively). Clinical success rate was 92% in each group and serious adverse outcome rates were similar (15% versus 20%, respectively). CONCLUSION: Guideline-based serial clinical assessment did not reduce antibiotic exposure compared with procalcitonin-guided care among ED patients with community-acquired pneumonia. The strategies were similar in terms of duration of antibiotic use and clinical outcomes.

Pregnancy-Adapted YEARS Algorithm for Diagnosis of Suspected Pulmonary Embolism.

BACKGROUND: Pulmonary embolism is one of the leading causes of maternal death in the Western world. Because of the low specificity and sensitivity of the d-dimer test, all pregnant women with suspected pulmonary embolism undergo computed tomographic (CT) pulmonary angiography or ventilation-perfusion scanning, both of which involve radiation exposure to the mother and fetus. Whether a pregnancy-adapted algorithm could be used to safely avoid diagnostic imaging in pregnant women with suspected pulmonary embolism is unknown. METHODS: In a prospective study involving pregnant women with suspected pulmonary embolism, we assessed three criteria from the YEARS algorithm (clinical signs of deep-vein thrombosis, hemoptysis, and pulmonary embolism as the most likely diagnosis) and measured the d-dimer level. Pulmonary embolism was ruled out if none of the three criteria were met and the d-dimer level was less than 1000 ng per milliliter or if one or more of the three criteria were met and the d-dimer level was less than 500 ng per milliliter. Adaptation of the YEARS algorithm for pregnant women involved compression ultrasonography for women with symptoms of deep-vein thrombosis; if the results were positive (i.e., a clot was present), CT pulmonary angiography was not performed. All patients in whom pulmonary embolism had not been ruled out underwent CT pulmonary angiography. The primary outcome was the incidence of venous thromboembolism at 3 months. The secondary outcome was the proportion of patients in whom CT pulmonary angiography was not indicated to safely rule out pulmonary embolism. RESULTS: A total of 510 women were screened, of whom 12 (2.4%) were excluded. Pulmonary embolism was diagnosed in 20 patients (4.0%) at baseline. During follow-up, popliteal deep-vein thrombosis was diagnosed in 1 patient (0.21%; 95% confidence interval [CI], 0.04 to 1.2); no patient had pulmonary embolism. CT pulmonary angiography was not indicated, and thus was avoided, in 195 patients (39%; 95% CI, 35 to 44). The efficiency of the algorithm was highest during the first trimester of pregnancy and lowest during the third trimester; CT pulmonary angiography was avoided in 65% of patients who began the study in the first trimester and in 32% who began the study in the third trimester. CONCLUSIONS: Pulmonary embolism was safely ruled out by the pregnancy-adapted YEARS diagnostic algorithm across all trimesters of pregnancy. CT pulmonary angiography was avoided in 32 to 65% of patients. (Funded by Leiden University Medical Center and 17 other participating hospitals; Artemis Netherlands Trial Register number, NL5726.).