Obesity as a Predictor for Pulmonary Embolism and Performance of the Age-Adjusted D-Dimer Strategy in Obese Patients with Suspected Pulmonary Embolism.

INTRODUCTION: Obesity is a risk factor for venous thromboembolism, but studies evaluating its association with pulmonary embolism (PE) in patients with suspected PE are lacking. OBJECTIVES: To evaluate whether body mass index (BMI) and obesity (i.e., BMI ≥30 kg/m2) are associated with confirmed PE in patients with suspected PE and to assess the efficiency and safety of the age-adjusted D-dimer strategy in obese patients. METHODS: We conducted a secondary analysis of a multinational, prospective study, in which patients with suspected PE were managed according to the age-adjusted D-dimer strategy and followed for 3 months. Outcomes were objectively confirmed PE at initial presentation, and efficiency and failure rate of the diagnostic strategy. Associations between BMI and obesity, and PE were examined using a log-binomial model that was adjusted for clinical probability and hypoxia. RESULTS: We included 1,593 patients (median age: 59 years; 56% women; 22% obese). BMI and obesity were not associated with confirmed PE. The use of the age-adjusted instead of the conventional D-dimer cut-off increased the proportion of obese patients in whom PE was considered ruled out without imaging from 28 to 38%. The 3-month failure rate in obese patients who were left untreated based on a negative age-adjusted D-dimer cut-off test was 0.0% (95% confidence interval: 0.0-2.9%). CONCLUSION: BMI on a continuous linear scale and obesity were not predictors of confirmed PE among patients presenting with a clinical suspicion of PE. The age-adjusted D-dimer strategy appeared safe in ruling out PE in obese patients with suspected PE.

Recovery of right ventricular function after intermediate-risk pulmonary embolism: results from the multicentre Pulmonary Embolism International Trial (PEITHO)-2.

BACKGROUND: Right ventricular (RV) function plays a critical role in the pathophysiology and acute prognosis of pulmonary embolism (PE). We analyzed the temporal changes of RV function in the cohort of a prospective multicentre study investigating if an early switch to oral anticoagulation in patients with intermediate-risk PE is effective and safe. METHODS: Echocardiographic and laboratory examinations were performed at baseline (PE diagnosis), 6 days and 6 months. Echocardiographic parameters were classified into categories representing RV size, RV free wall/tricuspid annulus motion, RV pressure overload and right atrial (RA)/central venous pressure. RESULTS: RV dysfunction based on any abnormal echocardiographic parameter was present in 84% of patients at baseline. RV dilatation was the most frequently abnormal finding (40.6%), followed by increased RA/central venous pressure (34.6%), RV pressure overload (32.1%), and reduced RV free wall/tricuspid annulus motion (20.9%). As early as day 6, RV size remained normal or improved in 260 patients (64.7%), RV free wall/tricuspid annulus motion in 301 (74.9%), RV pressure overload in 297 (73.9%), and RA/central venous pressure in 254 (63.2%). At day 180, the frequencies slightly increased. The median NT-proBNP level decreased from 1448 pg/ml at baseline to 256.5 on day 6 and 127 on day 180. CONCLUSION: In the majority of patients with acute intermediate-risk PE switched early to a direct oral anticoagulant, echocardiographic parameters of RV function normalised within 6 days and remained normal throughout the first 6 months. Almost one in four patients, however, continued to have evidence of RV dysfunction over the long term.

Peer overmarking and insufficient diagnosticity: the impact of the rating method for peer assessment.

The present study explores two rating methods for peer assessment (analytical rating using criteria and comparative judgement) in light of concurrent validity, reliability and insufficient diagnosticity (i.e. the degree to which substandard work is recognised by the peer raters). During a second-year undergraduate course, students wrote a one-page essay on an air pollutant. A first cohort (N = 260) relied on analytical rating using criteria to assess their peers' essays. A total of 1297 evaluations were made, and each essay received at least four peer ratings. Results indicate a small correlation between peer and teacher marks, and three essays of substandard quality were not recognised by the group of peer raters. A second cohort (N = 230) used comparative judgement. They completed 1289 comparisons, from which a rank order was calculated. Results suggest a large correlation between the university teacher marks and the peer scores and acceptable reliability of the rank order. In addition, the three essays of substandard quality were discerned as such by the group of peer raters. Although replication research is warranted, the results provide the first evidence that, when peer raters overmark and fail to identify substandard work using analytical rating with criteria, university teachers may consider changing the rating method of the peer assessment to comparative judgement.

Procedural Sedation With Dexmedetomidine in Combination With Ketamine in the Emergency Department.

BACKGROUND: Dexmedetomidine is an alternative agent for procedural sedation in the emergency department thanks to its ability to maintain hemodynamic and respiratory stability. Dexmedetomidine must, however, be combined with a powerful analgesic. OBJECTIVE: Our aim was to evaluate the quality and safety of procedural sedation using the combination of dexmedetomidine and ketamine for patients undergoing painful procedures in the emergency department. METHODS: This prospective interventional single-center study was conducted in an academic emergency department of an urban hospital in Brussels, Belgium. Patients received a bolus injection of 1 µg/kg dexmedetomidine over 10 min and then a continuous infusion of 0.6 µg/kg/h followed by a bolus of 1 mg/kg ketamine. The painful procedure was carried out 1 min later. The level of pain was evaluated with a numerical rating scale from 0 (no pain) to 10 (maximal pain). The level of patient comfort for the procedure was measured using a comfort scale. RESULTS: Thirty patients were included. Overall, 90% of patients felt little or no pain (n = 29 of 30) or discomfort (n = 28 of 30) during the procedure. One patient experienced apnea with desaturation, which was resolved by a jaw-thrust maneuver. Although 23% of patients had significant arterial hypertension, none required drug treatment. CONCLUSIONS: The combination of dexmedetomidine and ketamine provides conscious sedation, bringing comfort and pain relief to patients in optimal conditions for respiratory and hemodynamic safety. However, sedation and recovery times are longer than with conventional drug combinations. The dexmedetomidine-ketamine combination should therefore be recommended for nonurgent procedures and fragile patients.

The emergency department arrival mode and its relations to ED management and 30-day mortality in acute heart failure: an ancillary analysis from the EURODEM study.

BACKGROUND: Acute heart failure patients are often encountered in emergency departments (ED) from 11% to 57% using emergency medical services (EMS). Our aim was to evaluate the association of EMS use with acute heart failure patients' ED management and short-term outcomes. METHODS: This was a sub-analysis of a European EURODEM study. Data on patients presenting with dyspnoea were collected prospectively from European EDs. Patients with ED diagnosis of acute heart failure were categorized into two groups: those using EMS and those self-presenting (non- EMS). The independent association between EMS use and 30-day mortality was evaluated with logistic regression. RESULTS: Of the 500 acute heart failure patients, with information about the arrival mode to the ED, 309 (61.8%) arrived by EMS. These patients were older (median age 80 vs. 75 years, p < 0.001), more often female (56.4% vs. 42.1%, p = 0.002) and had more dementia (18.7% vs. 7.2%, p < 0.001). On admission, EMS patients had more often confusion (14.2% vs. 2.1%, p < 0.001) and higher respiratory rate (24/min vs. 21/min, p = 0.014; respiratory rate > 30/min in 17.1% patients vs. 7.5%, p = 0.005). The only difference in ED management appeared in the use of ventilatory support: 78.3% of EMS patients vs. 67.5% of non- EMS patients received supplementary oxygen (p = 0.007), and non-invasive ventilation was administered to 12.5% of EMS patients vs. 4.2% non- EMS patients (p = 0.002). EMS patients were more often hospitalized (82.4% vs. 65.9%, p < 0.001), had higher in-hospital mortality (8.7% vs. 3.1%, p = 0.014) and 30-day mortality (14.3% vs. 4.9%, p < 0.001). The use of EMS was an independent predictor of 30-day mortality (OR = 2.54, 95% CI 1.11-5.81, p = 0.027). CONCLUSION: Most acute heart failure patients arrive at ED by EMS. These patients suffer from more severe respiratory distress and receive more often ventilatory support. EMS use is an independent predictor of 30-day mortality.

Factors to improve quality for older patients in the emergency department: a qualitative study of patient trajectory.

BACKGROUND: Managing older people in the emergency department remains a challenge. We aimed to identify the factors influencing the care quality of older patients in the emergency department, to fine-tune future interventions for older people, considering the naturalistic context of the ED. METHODS: This is a qualitative study of some 450 h of observations performed in three emergency departments selected for their diverse contexts. We performed seventy observations of older patient trajectories admitted to the emergency department. Themes were extracted from the material using an inductive reasoning approach, to highlight factors positively or negatively influencing management of patient's trajectories, in particular those presenting with typically geriatric syndromes. RESULTS: Four themes were developed: no geriatric flow routine; risk of discontinuity of care; unmet basic needs and patient-centered care; complex older patients are unwelcome in EDs. CONCLUSIONS: The overall process of care was based on an organ- and flow-centered paradigm, which ignored older people's specific needs and exposed them to discontinuity of care. Their basic needs were neglected and, when their management slowed the emergency department flow, older people were perceived as unwelcome. Findings of our study can inform the development of interventions about the influence of context and organizational factors.

Early switch to oral anticoagulation in patients with acute intermediate-risk pulmonary embolism (PEITHO-2): a multinational, multicentre, single-arm, phase 4 trial.

BACKGROUND: Current guidelines recommend a risk-adjusted treatment strategy for the management of acute pulmonary embolism. This is a particular patient category for whom optimal treatment (anticoagulant treatment, reperfusion strategies, and duration of hospitalisation) is currently unknown. We investigated whether treatment of acute intermediate-risk pulmonary embolism with parenteral anticoagulation for a short period of 72 h, followed by a switch to a direct oral anticoagulant (dabigatran), is effective and safe. METHODS: We did a multinational, multicentre, single-arm, phase 4 trial at 42 hospitals in Austria, Belgium, France, Germany, Italy, Netherlands, Romania, Slovenia, and Spain. Adult patients (aged ≥18 years) with symptomatic intermediate-risk pulmonary embolism, with or without deep-vein thrombosis, were enrolled. Patients received parenteral low-molecular-weight or unfractionated heparin for 72 h after diagnosis of pulmonary embolism before switching to oral dabigatran 150 mg twice per day following a standard clinical assessment. The primary outcome was recurrent symptomatic venous thromboembolism or pulmonary embolism-related death within 6 months. The primary and safety outcomes were assessed in the intention-to-treat population. The study was terminated early, as advised by the data safety and monitoring board, following sample size adaptation after the predefined interim analysis on Dec 18, 2018. This trial is registered with the EU Clinical Trials Register (EudraCT 2015-001830-12) and ClinicalTrials.gov (NCT02596555). FINDINGS: Between Jan 1, 2016, and July 31, 2019, 1418 patients with pulmonary embolism were screened, of whom 402 were enrolled and were included in the intention-to-treat analysis (median age was 69·5 years [IQR 60·0-78·0); 192 [48%] were women and 210 [52%] were men). Median follow-up was 217 days (IQR 210-224) and 370 (92%) patients adhered to the protocol. The primary outcome occurred in seven (2% [upper bound of right-sided 95% CI 3]; p<0·0001 for rejecting the null hypothesis) patients, with all events occurring in those with intermediate-high-risk pulmonary embolism (seven [3%; upper bound of right-sided 95% CI 5] of 283). At 6 months, 11 (3% [95% CI 1-5]) of 402 patients had at least one major bleeding event and 16 (4% [2-6]) had at least one clinically relevant non-major bleeding event; the only fatal haemorrhage occurred in one (<1%) patient before the switch to dabigatran. INTERPRETATION: A strategy of early switch from heparin to dabigatran following standard clinical assessment was effective and safe in patients with intermediate-risk pulmonary embolism. Our results can help to refine guideline recommendations for the initial treatment of acute intermediate-risk pulmonary embolism, optimising the use of resources and avoiding extended hospitalisation. FUNDING: German Federal Ministry of Education and Research, University Medical Center Mainz, and Boehringer Ingelheim.

Epidemiology, treatment and outcome of patients with lower respiratory tract infection presenting to emergency departments with dyspnoea (AANZDEM and EuroDEM studies).

OBJECTIVE: Lower respiratory tract infection (LRTI) is a frequent cause of dyspnoea in EDs, and is associated with considerable morbidity and mortality. We described and compared the management of this disease in Europe and Oceania/South-East Asia (SEA) cohorts. METHODS: We conducted a prospective cohort study with three time points in Europe and Oceania/SEA. We included in this manuscript patients presenting to EDs with dyspnoea and a diagnosis of LRTI in ED. We collected comorbidities, chronic medication, clinical signs at arrival, laboratory parameters, ED management and patient outcomes. RESULTS: A total of 1389 patients were included, 773 in Europe and 616 in SEA. The European cohort had more comorbidities including chronic heart failure, obesity, chronic obstructive pulmonary disease and smoking. Levels of inflammatory markers were higher in Europe. There were more patients with inflammatory markers in Europe and more hypercapnia in Oceania/SEA. The use of antibiotics was higher in SEA (72.2% vs 61.8%, P < 0.001) whereas intravenous diuretics, non-invasive and invasive ventilation were higher in Europe. Intensive care unit admission rate was 9.9% in Europe cohort and 3.4% in Oceania/SEA cohort. ED mortality was 1% and overall in-hospital mortality was 8.7% with no differences between regions. CONCLUSIONS: More patients with LRTI in Europe presented with cardio-respiratory comorbidities, they received more adjunct therapies and had a higher intensive care unit admission rate than patients from Oceania/SEA, although mortality was similar between the two cohorts.

Seasonal variations of patients presenting dyspnea to emergency departments in Europe: Results from the EURODEM Study

Background/aim: To describe seasonal variations in epidemiology, management, and short-term outcomes of patients in Europe presenting to an emergency department (ED) with a main complaint of dyspnea. Materials and methods: Anobservational prospective cohort study was performed in 66 European EDs which included consecutive patients presenting to EDs with dyspnea as the main complaint during 3 72-h study periods. Data were collected on demographics, comorbidities, chronic treatment, prehospital treatment, mode of arrival of patient to ED, clinical signs at admission, treatment in the ED, ED diagnosis, discharge from ED, and in-hospital outcome. Results: The study included 2524 patients with a median age of 69 (53­80) years old. Of the patients presented, 991 (39.3%) were in autumn, 849 (33.6%) were in spring, and 48 (27.1%) were in winter. The winter population was significantly older (P < 0.001) and had a lower rate of ambulance arrival to ED (P < 0.001). In the winter period, there was a higher rate for lower respiratory tract infection (35.1%), and patients were more hypertensive, more hypoxic, and more hyper/hypothermic compared to other seasons. The ED mortality was about 1% and, in hospital, mortality for admitted patients was 7.4%. Conclusion: The analytic method and the outcome of this study may help to guide the allocation of ED resources more efficiently and to recommend seasonal ED management protocols based on the seasonal trend of dyspneic patients.

Get with the guidelines: management of chronic obstructive pulmonary disease in emergency departments in Europe and Australasia is sub-optimal.

BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD) are common in emergency departments (ED). Guidelines recommend administration of inhaled bronchodilators, systemic corticosteroids and antibiotics along with non-invasive ventilation (NIV) for patients with respiratory acidosis. AIM: To determine compliance with guideline recommendations for patients treated for COPD in ED in Europe (EUR) and South East Asia/Australasia (SEA) and to compare management and outcomes. METHODS: In each region, an observational prospective cohort study was performed that included patients presenting to ED with the main complaint of dyspnoea during three 72-h periods. This planned sub-study included those with an ED primary discharge diagnosis of COPD. Data were collected on demographics, clinical features, treatment, disposition and in-hospital mortality. We determined overall compliance with guideline recommendations and compared treatments and outcome between regions. RESULTS: A total of 801 patients was included from 122 ED (66 EUR and 46 SEA). Inhaled bronchodilators were administered to 80.3% of patients, systemic corticosteroids to 59.5%, antibiotics to 44 and 60.6% of patients with pH <7.3 received NIV. The proportion administered systemic corticosteroids was higher in SEA (EUR vs SEA for all comparisons; 52 vs 66%, P < 0.001) as was administration of antibiotics (40 vs 49%, P = 0.02). Rates of NIV and mechanical ventilation were similar. Overall in-hospital mortality was 4.2% (SEA 3.9% vs EUR 4.5%, P = 0.77). CONCLUSION: Compliance with guideline recommended treatments, in particular administration of corticosteroids and NIV, was sub-optimal in both regions. Improved compliance has the potential to improve patient outcome.

Treatment and outcome of adult patients with acute asthma in emergency departments in Australasia, South East Asia and Europe: Are guidelines followed? AANZDEM/EuroDEM study.

OBJECTIVE: Asthma exacerbations are common presentations to ED. Key guideline recommendations for management include administration of inhaled bronchodilators, systemic corticosteroids and titrated oxygen therapy. Our aim was to compare management and outcomes between patients treated for asthma in Europe (EUR) and South East Asia/Australasia (SEA) and compliance with international guidelines. METHODS: In each region, prospective, interrupted time series studies were performed including adult (age >18 years) patients presenting to ED with the main complaint of dyspnoea during three 72 h periods. This was a planned sub-study that included those with an ED primary diagnosis of asthma. Data was collected on demographics, clinical features, treatment in ED, diagnosis, disposition and in-hospital outcome. The results of interest were differences in treatment and outcome between EUR and SEA cohorts. RESULTS: Five hundred and eighty-four patients were identified from 112 EDs (66 EUR and 46 SEA). The cohorts had similar demographics and co-morbidity patterns, with 89% of the cohort having a previous diagnosis of asthma. There were no significant differences in treatment between EUR and SEA patients - inhaled beta-agonists were administered in 86% of cases, systemic corticosteroids in 66%, oxygen therapy in 44% and antibiotics in 20%. Two thirds of patients were discharged home from the ED. CONCLUSION: The data suggests that compliance with guideline-recommended therapy in both regions, particularly corticosteroid administration, is sub-optimal. It also suggests over-use of antibiotics.

Symptoms Predictive of Acute Myocardial Infarction in the Troponin Era: Analysis From the TRAPID-AMI Study.

The TRAPID-AMI (High Sensitivity Cardiac Troponin T assay for rapid Rule-out of Acute Myocardial Infarction) study evaluated a rapid "rule-out" acute myocardial infarction (AMI). We evaluated what symptoms were associated with AMI as part of a substudy of TRAPID-AMI. There were 1282 patients evaluated from 12 centers in Europe, the United States of America, and Australia from 2011 to 2013. Multiple symptom variables were prospectively obtained and evaluated for association with the final diagnosis of AMI. Multivariate logistic regression analysis was done, and odds ratios (OR) were calculated. There were 213/1282 (17%) AMIs. Four independent predictors for the diagnosis of AMI were identified: radiation to right arm or shoulder [OR = 3.0; confidence interval (CI): 1.8-5.0], chest pressure (OR = 2.5; CI: 1.3-4.6), worsened by physical activity (OR = 1.7; CI: 1.2-2.5), and radiation to left arm or shoulder (OR = 1.7; CI: 1.1-2.4). In the entire group, 131 (10%) had radiation to right arm or shoulder, 897 (70%) had chest pressure, 385 (30%) worsened with physical activity, and 448 (35%) had radiation to left arm or shoulder. Duration of symptoms was not predictive of AMI. There were no symptoms predictive of non-AMI. Relationship between AMI size and symptoms was also studied. For 213 AMI patients, cardiac troponins I values were divided into 4 quartiles. Symptoms including pulling chest pain, supramammillary right location, and right arm/shoulder radiation were significantly more likely to occur in patients with larger AMIs. In a large multicenter trial, only 4 symptoms were associated with the diagnosis of AMI, and no symptoms that were associated with a non-AMI diagnosis.

Epidemiology of patients presenting with dyspnea to emergency departments in Europe and the Asia-Pacific region.

OBJECTIVE: The primary objective of this study was to describe the epidemiology and management of dyspneic patients presenting to emergency departments (EDs) in an international patient population. Our secondary objective was to compare the EURODEM and AANZDEM patient populations. PATIENTS AND METHODS: An observational prospective cohort study was carried out in Europe and the Asia-Pacific region. The study included consecutive patients presenting to EDs with dyspnea as the main complaint. Data were collected on demographics, comorbidities, chronic treatment, clinical signs and investigations, treatment in the ED, diagnosis, and disposition from ED. RESULTS: A total of 5569 patients were included in the study. The most common ED diagnoses were lower respiratory tract infection (LRTI) (24.9%), heart failure (HF) (17.3%), chronic obstructive pulmonary disease (COPD) exacerbation (15.8%), and asthma (10.5%) in the overall population. There were more LRTI, HF, and COPD exacerbations in the EURODEM population, whereas asthma was more frequent in the AANZDEM population. ICU admission rates were 5.5%. ED mortality was 0.6%. The overall in-hospital mortality was 5.0%. In-hospital mortality rates were 8.7% for LRTI, 7.6% for HF, and 5.6% for COPD patients. CONCLUSION: Dyspnea as a symptom in the ED has high ward and ICU admission rates. A variety of causes of dyspnea were observed in this study, with chronic diseases accounting for a major proportion.

Combined testing of copeptin and high-sensitivity cardiac troponin T at presentation in comparison to other algorithms for rapid rule-out of acute myocardial infarction.

BACKGROUND: We aimed to directly compare the diagnostic and prognostic performance of a dual maker strategy (DMS) with combined testing of copeptin and high-sensitivity (hs) cardiac troponin T (cTnT) at time of presentation with other algorithms for rapid rule-out of acute myocardial infarction (AMI). METHODS: 922 patients presenting to the emergency department with suspected AMI and available baseline copeptin measurements qualified for the present TRAPID-AMI substudy. Diagnostic measures using the DMS (copeptin <10, <14 or < 20 pmol/L and hs-cTnT≤14 ng/L), the 1 h-algorithm (hs-cTnT<12 ng/L and change <3 ng/L at 1 h), as well as the hs-cTnT limit-of-blank (LoB, <3 ng/L) and -detection (LoD, <5 ng/L) were compared. Outcomes were assessed as combined end-points of death and myocardial re-infarction. RESULTS: True-negative rule-out using the DMS could be achieved in 50.9%-62.3% of all patients compared to 35.0%, 45.3% and 64.5% using LoB, LoD or the 1 h-algorithm, respectively. The DMS showed NPVs of 98.1%-98.3% compared to 99.2% for the 1 h-algorithm, 99.4% for the LoB and 99.3% for the LoD. Sensitivities were 93.5%-94.8%, as well as 96.8%, 98.7% and 98.1%, respectively. Addition of clinical low-risk criteria such as a HEART-score ≤ 3 to the DMS resulted in NPVs and sensitivities of 100% with a true-negative rule-out to 33.8%-41.6%. Rates of the combined end-point of death/MI within 30 days ranged between 0.2% and 0.3% for all fast-rule-out protocols. CONCLUSION: Depending on the applied copeptin cut-off and addition of clinical low-risk criteria, the DMS might be an alternative to the hs-cTn-only-based algorithms for rapid AMI rule-out with comparable diagnostic measures and outcomes.

Retrospective validation of a new volumetric capnography parameter for the exclusion of pulmonary embolism at the emergency department.

Volumetric capnography might be used to exclude pulmonary embolism (PE) without the need for computed tomography pulmonary angiography. In a pilot study, a new parameter (CapNoPE) combining the amount of carbon dioxide exhaled per breath (carbon dioxide production (V CO2 )), the slope of phase 3 of the volumetric capnogram (slope 3) and respiratory rate (RR) showed promising diagnostic accuracy (where CapNoPE=(V CO2 ×slope 3)/RR). To retrospectively validate CapNoPE for the exclusion of PE, the volumetric capnograms of 205 subjects (68 with PE) were analysed, based on a large multicentre dataset of volumetric capnograms from subjects with suspected PE at the emergency department. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve and diagnostic accuracy of the in-pilot established threshold (1.90 Pa·min) were calculated. CapNoPE was 1.56±0.97 Pa·min in subjects with PE versus 2.51±1.67 Pa·min in those without PE (p<0.001). The AUC of the ROC curve was 0.714 (95% CI 0.64-0.79). For the cut-off of ≥1.90 Pa·min, sensitivity was 64.7%, specificity was 59.9%, the negative predictive value was 77.4% and the positive predictive value was 44.4%. The CapNoPE parameter is decreased in patients with PE but its diagnostic accuracy seems too low to use in clinical practice.

Preventability of serious thromboembolic and bleeding events related to the use of oral anticoagulants: a prospective study.

AIMS: To determine the preventability of serious adverse drug reactions (ADRs) related to the use of direct oral anticoagulants (DOACs), and to explore contributing factors to preventable ADRs. Results were compared with vitamin K antagonists (VKAs). METHODS: We conducted a prospective observational study in the emergency departments of two teaching hospitals from July 2015 to January 2016. Patients admitted with a thrombotic or bleeding event while under DOAC or VKA were included. Four independent reviewers assessed causality, seriousness and preventability of ADRs using pilot-tested scales. For cases of serious and potentially preventable ADRs, we performed semi-structured interviews with general practitioners to identify contributing factors to ADRs. The primary outcome was the proportion of serious ADRs that were potentially preventable. RESULTS: The analysis included 46 DOAC and 43 VKA patients (median age 79 years). Gastrointestinal (n = 34) and intracranial (n = 16) bleedings were the most frequent ADRs. Results were that 53% of DOAC- and 61% of VKA-related serious ADRs were deemed potentially preventable. Prescribing issues and inadequate monitoring were frequent for DOAC and VKA respectively. We identified many causes of preventable ADRs that applied to all oral anticoagulants, such as pharmacodynamic drug interactions and lack of communication. CONCLUSIONS: More than half of serious ADRs were potentially preventable for both DOACs and VKAs. Interventions focusing on prescribing, patient education and continuity of care should help improve the use of DOACs in practice.

Dabigatran after Short Heparin Anticoagulation for Acute Intermediate-Risk Pulmonary Embolism: Rationale and Design of the Single-Arm PEITHO-2 Study.

Patients with intermediate-risk pulmonary embolism (PE) may, depending on the method and cut-off values used for definition, account for up to 60% of all patients with PE and have an 8% or higher risk of short-term adverse outcome. Although four non-vitamin K-dependent direct oral anticoagulants (NOACs) have been approved for the treatment of venous thromboembolism, their safety and efficacy as well as the optimal anticoagulation regimen using these drugs have not been systematically investigated in intermediate-risk PE. Moreover, it remains unknown how many patients with intermediate-high-risk and intermediate-low-risk PE were included in most of the phase III NOAC trials. The ongoing Pulmonary Embolism International Thrombolysis 2 (PEITHO-2) study is a prospective, multicentre, multinational, single-arm trial investigating whether treatment of acute intermediate-risk PE with parenteral heparin anticoagulation over the first 72 hours, followed by the direct oral thrombin inhibitor dabigatran over 6 months, is effective and safe. The primary efficacy outcome is recurrent symptomatic venous thromboembolism or death related to PE within the first 6 months. The primary safety outcome is major bleeding as defined by the International Society on Thrombosis and Haemostasis. Secondary outcomes include all-cause mortality, the overall duration of hospital stay (index event and repeated hospitalizations) and the temporal pattern of recovery of right ventricular function over the 6-month follow-up period. By applying and evaluating a contemporary risk-tailored treatment strategy for acute PE, PEITHO-2 will implement the recommendations of current guidelines and contribute to their further evolution.

High sensitivity cardiac troponin T in patients not having an acute coronary syndrome: results from the TRAPID-AMI study.

PURPOSE: To describe the baseline, 1 hr and delta high sensitivity cardiac troponin (hs-cTnT) values in patients with suspected acute myocardial infarction (AMI) but without a final acute coronary syndrome (ACS) diagnosis. MATERIALS AND METHODS: hs-cTnT assay for RAPID rule out of acute myocardial infarction (TRAPID-AMI) was a prospective diagnostic trial that enrolled emergency department (ED) patients with suspected AMI. Final patient diagnoses were adjudicated by a clinical events committee and subjects placed in different clinical groups: AMI, unstable angina, non-ACS cardiac, non-cardiac and unknown origin. The baseline, 1 hr and delta hs-cTnT values were analysed in the 902 non-ACS patients. RESULTS: Amongst the 1282 studied the patient groups were 213 (17%) AMI, 167 (13%) unstable angina, 113 (9%) non-ACS cardiac, 288 (22%) non-cardiac and 501 (39%) unknown origin. The hs-cTnT values in the non-cardiac and unknown origin groups were combined. The median hs-cTnT values (ng/L) were higher (p < 0.001) in the non-ACS cardiac compared to the non-cardiac/unknown origin group at baseline (11.8, <5) and 1 hr (12.3, <5). Their negative predictive values were 0.955 (baseline) and 0.954 (1 hr) for predicting non-ACS cardiac versus non-cardiac/unknown origin diagnoses. CONCLUSIONS: Hs-cTnT may help predict whether non-ACS ED patients have a final non-ACS cardiac or non-cardiac/unknown origin diagnoses.

Can we predict functional decline in hospitalized older people admitted through the emergency department? Reanalysis of a predictive tool ten years after its conception.

BACKGROUND: In the Emergency Department (ED), early and rapid identification of older people at risk of adverse outcomes, who could best benefit from complex geriatric intervention, would avoid wasting time, especially in terms of prevention of adverse outcomes, and ensure optimal orientation of vulnerable patients. We wanted to test the predictive ability of a screening tool assessing risk of functional decline (FD), named SHERPA, 10 years after its conception, and to assess the added value of other clinical or biological factors associated with FD. METHODS: A prospective cohort study of older patients (n = 305, ≥ 75 years) admitted through the emergency department, for at least 48 h in non-geriatric wards (mean age 82.5 ± 4.9, 55% women). SHERPA variables (i.e. age, pre-admission instrumental Activity of Daily Living (ADL) status, falls within a year, self-rated health and 21-point MMSE) were collected within 48 h of admission, along with socio-demographic, medical and biological data. Functional status was followed at 3 months by phone. FD was defined as a decrease at 3 months of at least one point in the pre-admission basic ADL score. Predictive ability of SHERPA was assessed using c-statistic, predictive values and likelihood ratios. Measures of discrimination improvement were Net Reclassification Improvement and Integrated Discrimination Improvement. RESULTS: One hundred and five patients (34%) developed 3-month FD. Predictive ability of SHERPA decreased dramatically over 10 years (c = 0.73 vs. 0.64). Only two of its constitutive variables, i.e. falls and instrumental ADL, were significant in logistic regression analysis for functional decline, while 21-point MMSE was kept in the model for clinical relevance. Demographic, comorbidity or laboratory data available upon admission did not improve the SHERPA predictive yield. CONCLUSIONS: Prediction of FD with SHERPA is difficult, but predictive factors, i.e. falls, pre-existing functional limitation and cognitive impairment, stay consistent across time and with literature. As accuracy of SHERPA and others existing screening tools for FD is moderate, using these predictors as flags instead of using composite scales can be a way to screen for high-risk patients.