H, Tamao Y. Syntheses and platelet aggregation inhibitory and antithrombotic properties of [2-[(omega-aminoalkoxy)

Summary. Background: Compression ultrasonography (US) confined to the proximal veins is usually performed to detect deep vein thrombosis (DVT) in patients with suspected pulmonary embolism (PE). Recent studies suggested a limited yield of proximal US when multislice computed tomography (MSCT) was used. Objectives: To assess whether performing an additional distal vein US would increase the diagnostic yield of the test. Patients and methods: Data of 855 consecutive outpatients included in a multicenter randomized controlled trial were analyzed. Patients were investigated by a sequential diagnostic strategy including clinical probability assessment, Ddimer measurement, proximal US and MSCT. Proximal US was completed by an examination of the distal veins, the result of which was not disclosed to the physician in charge of the patient. Results: US was positive in 21% of patients, of whom 10% (53/541) had proximal DVT and 11% (59/541) isolated distal DVT. Of the 59 patients with distal DVT, 21 (36%) had no PE on MSCT. Twenty of those 21 patients were not given anticoagulant therapy and had an uneventful follow-up. The diagnostic performance of distal US for the diagnosis of PE was as follows: sensitivity 22% [95% confidence interval (CI) 17-29]; specificity 94% (95% CI 91-96); positive likelihood ratio 3.9 (95% CI 2.4-6.4). Conclusions: In patients with suspected PE, distal US has limited diagnostic performance, and its additional use only modestly increases the yield of US. Moreover, it carries a high false-positive rate, impeding the use of distal US as a confirmatory test for PE.

Summary. Background: The Pulmonary Embolism Rule-out Criteria (PERC) rule is a clinical diagnostic rule designed to exclude pulmonary embolism (PE) without further testing. We sought to externally validate the diagnostic performance of the PERC rule alone and combined with clinical probability assessment based on the revised Geneva score. Methods: The PERC rule was applied retrospectively to consecutive patients who presented with a clinical suspicion of PE to six emergency departments, and who were enrolled in a randomized trial of PE diagnosis. Patients who met all eight PERC criteria [PERC ()) ] were considered to be at a very low risk for PE. We calculated the prevalence of PE among PERC ()) patients according to their clinical pretest probability of PE. We estimated the negative likelihood ratio of the PERC rule to predict PE. Results: Among 1675 patients, the prevalence of PE was 21.3%. Overall, 13.2% of patients were PERC ()) . The prevalence of PE was 5.4% [95% confidence interval (CI): 3.1-9.3%] among PERC ()) patients overall and 6.4% (95% CI: 3.7-10.8%) among those PERC ()) patients with a low clinical pretest probability of PE. The PERC rule had a negative likelihood ratio of 0.70 (95% CI: 0.67-0.73) for predicting PE overall, and 0.63 (95% CI: 0.38-1.06) in low-risk patients. Conclusions: Our results suggest that the PERC rule alone or even when combined with the revised Geneva score cannot safely identify very low risk patients in whom PE can be ruled out without additional testing, at least in populations with a relatively high prevalence of PE.

G Ga as st tr ri ic c i in nt tr ra am mu uc co os sa al l p pH H: : a an n i in nd di ic ca at to or r o of f w we ea an ni in ng g o ou ut tc co om me e f fr ro om m m me ec ch ha an ni ic ca al l v ve en nt ti il la at ti io on n i in n C CO OP PD D p pa at ti ie en nt ts s G. Bouachour, M-P. Guiraud, J-P. Gouello, P-M. Roy, P. Alquier ABSTRACT: The aim of this study was to determine whether gastric intramucosal pH (pHim) and/or gastric intramucosal carbon dioxide tension (PCO 2 ,im) measured by tonometry can be used to predict the success of weaning in chronic obstructive pulmonary disease (COPD) patients. Twenty six consecutive COPD patients, undergoing mechanical ventilation for acute respiratory failure and satisfying the criteria of weaning from mechanical ventilation with nasogastric tonometer in place, were studied. Arterial blood gas values and PCO 2 ,im were measured 24 h before (H-24), just before (H0), and after 20 min of a weaning trial on T-piece (H20min). Weaning failure was defined as the development of respiratory distress and/or arterial blood gas impairments during the first 2 h of spontaneous breathing on T-piece, or reintubation within 24 h after extubation.Between the weaning failure (n=6) and weaning success (n=20) groups, there were no differences in blood gas analysis readings at H-24 and H0 before the weaning period, age, Simplified Acute Physiology Score (SAPS) on admission, SAPS on the day of weaning trial, and duration of ventilation. Clinical status, tonometric and arterial gasometric data were similar at H-24 and H0 in all patients. During mechanical ventilation, pHim was ≤7.30 in patients who failed weaning and >7.30 in patients who were successfully weaned (p<0.001; 100% sensitivity and specificity). The threshold value for PCO 2 ,im of 8.0 kPa (60 mmHg) represents a clear demarcation with respect to outcome before the weaning trial. PCO 2 ,im values during mechanical ventilation are significantly different (p<0.001) between patients who were successfully weaned and those who were not (6.9±0.9 vs 9.9±1.1 kPa (51.9±6.7 vs 74.3±8.0 mmHg, respectively)). At H20min, pHim and PCO 2 ,im were still statistically different between the weaning failure and the weaning success group.We conclude that measurement of gastric intramucosal pH (or gastric intramucosal carbon dioxide tension) represents a simple and accurate index to predict weaning outcome in chronic obstructive pulmonary disease patients before attempting weaning.

Summary. Background: A pulmonary embolism (PE) is thought to be associated with atrial fibrillation (AF). Nevertheless, this association is based on weak data. Objectives: To assess whether the presence of AF influences the clinical probability of PE in a cohort of patients with suspected PE and to confirm the association between PE and AF. Patients/ methods: We retrospectively analyzed the data from two trials that included 2449 consecutive patients admitted for a clinically suspected PE. An electrocardiography (ECG) was systematically performed and a PE was diagnosed by computer tomography (CT). The prevalence of AF among patients with or without a PE was compared in a multivariate logistic regression model. Results: The prevalence of PE was 22.8% (519/2272) in patients without AF and 18.8% (25/133) in patients with AF (P = 0.28). After adjustment for confounding factors, AF did not significantly modify the probability of PE (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.42-1.11). However, when PE suspicion was based on new-onset dyspnea, AF significantly decreased the probability of PE (OR 0.47, 95% CI 0.26-0.84). If isolated chest pain without dyspnea was the presenting complaint, AF tended to increase the probability of PE (OR 2.42, 95% CI 0.97-6.07). Conclusions: Overall, the presence of AF does not increase the probability of PE when this diagnosis is suspected. Nevertheless, when PE suspicion is based on new-onset dyspnea, AF significantly decreases the probability of PE, as AF may mimic its clinical presentation. However, in patients with chest pain alone, AF tends to increase PE probability.

Background When clinical trials use clinical endpoints, establishing independent Clinical Events Committees (CECs) is recommended to homogenize the interpretation of investigators' data. However, the reproducibility of CEC adjudications is almost unexplored. Objectives To assess the reproducibility of CEC adjudications in a trial of venous thromboembolism (VTE) prevention. Methods The PREVENU trial, a multicenter trial of VTE prevention, included 15 351 hospitalized medical patients. The primary endpoint was the composite of symptomatic VTE, major bleeding or unexplained sudden death (interpreted as possible fatal pulmonary embolism [PE]) at 3 months. The CEC comprised a chairman and four pairs of adjudicators. Of 2970 adjudicated clinical events, a random selection of 179 events (121 deaths, 40 bleeding events, and 18 VTE events) was blindly resubmitted to the CEC. Kappa values and their 95% confidence intervals (CIs) were calculated to measure adjudication agreement. Results Overall, 18 of 179 (10.1%, 95% CI 6.5-15.3%) adjudications proved discordant. Agreement for the PREVENU composite primary endpoint was good (kappa = 0.73, 95% CI 0.61-0.85). When analyzed separately, agreements were very good for non-fatal VTE events (1, 95% CI not applicable), moderate for all (fatal and non-fatal) VTE events (0.58, 95% CI 0.34-0.82), good for fatal and non-fatal major bleeding events (0.71, 95% CI 0.55-0.88), and moderate for all fatal events (0.60, 95% CI 0.40-0.81). Unexplained sudden death interpreted as possible fatal PE was responsible for nine of 18 (50%) discordant adjudications. Conclusion The reproducibility of CEC adjudications was good or very good for non-fatal VTE and bleeding events, but insufficient for VTE-related deaths, for which more precise and widely accepted definitions are needed.

We aim to assess physicians’ level of resilience and define factors that improve or decrease the resilience level during the COVID-19 pandemic. Physicians from hospitals located in areas with different COVID-19 caseload levels, were invited to participate in a national e-survey between April and May 2020. Study participants were mainly emergency physicians, and anaesthesiologists, infectious disease consultants, and intensive care. The survey assessed participant’s characteristics, factors potentially associated with resilience, and resilience using the Connor-Davidson Resilience Scale (RISC-25), with higher scores indicative of greater resilience. Factors associated with the resilience score were assessed using a multivariable linear regression. Of 451 responding physicians involved in the care of COVID-19 patients, 442 were included (98%). Age was 36.1 ± 10.3 years and 51.8% were male; 63% worked in the emergency department (n = 282), 10.4% in anesthesiology (n = 46), 9.9% in infectious disease department (n = 44), 4.8% in intensive care unit (n = 21) or other specialties (n = 49). The median RISC-25 score was at 69 (IQR 62–75). Factors associated with higher RISC scores were anesthesia as a specialty, parenthood, no previous history of anxiety or depression and nor increased anxiety. To conclude, this study is the first to characterize levels of resilience among physicians involved in COVID-19 unit. Our data points to certain protective characteristics and some detrimental factors, such as anxiety or depression, that could be amenable to remediating or preventing strategies to promote resilience and support caregivers in a pandemic.

Background The HOME-CoV rule is a checklist of eligibility criteria for home treatment of patients with COVID-19, defined using a Delphi method. Research Question Is the HOME-CoV rule reliable for identifying a subgroup of COVID-19 patients with a low risk of adverse outcomes who can be safely treated at home? Study Design and Methods We aimed to validate the HOME-CoV rule in a prospective multicenter study before and after trial on patients with probable or confirmed COVID-19 who presented at the emergency departments (ED) of 34 hospitals. The main outcome was an adverse evolution, i.e., invasive ventilation or death, occurred within the 7 days following the patients’ admission. The performance of the rule was assessed by the false negative rate. The impact of the rule implementation was assessed by the absolute differences in the rate of patients who required invasive ventilation or who died and in the rate of patients treated at home, between an observational and an interventional period after implementation of the HOME-CoV rule, with propensity score adjustment. Results Among 3000 prospectively enrolled patients, 1239 (41.3%) had a negative HOME-CoV rule. The false negative rate of the HOME-CoV rule and its AUC were 4/1239: 0.32% (95%CI: 0.13 to 0.84%) and 80.9 (95%CI: 76.5 to 85.2), respectively. On the adjusted populations, 25/1274 (1.95%) patients experienced an adverse evolution during the observational period versus 12/1274 (0.95%) during the interventional period: -1.00 (95%CI: -1.86 to -0.15). During the observational period, 858 (67.35%) patients were treated at home versus 871 (68.37%) patients during the interventional period: -1.02 (95%CI -4.46 to 2.26). Interpretation A large proportion of ED patients with probable or confirmed COVID-19 have a negative HOME-CoV rule and can be safely treated at home with a very low risk of complication.