Thromboprophylaxis in lower limb immobilisation after injury (TiLLI).

Venous thromboembolic disease is a major global cause of morbidity and mortality. An estimated 10 million episodes are diagnosed yearly; over half of these episodes are provoked by hospital admission/procedures and result in significant loss of disability adjusted life years. Temporary lower limb immobilisation after injury is a significant contributor to the overall burden of venous thromboembolism (VTE). Existing evidence suggests that pharmacological prophylaxis could reduce overall VTE event rates in these patients, but the proportional reduction of symptomatic events remains unclear. Recent studies have used different pharmacological agents, dosing regimens and outcome measures. Consequently, there is wide variation in thromboprophylaxis strategies, and international guidelines continue to offer conflicting advice for clinicians. In this review, we provide a summary of recent evidence assessing both the clinical and cost effectiveness of thromboprophylaxis in patients with temporary immobilisation after injury. We also examine the evidence supporting stratified thromboprophylaxis and the validity of widely used risk assessment methods.

Obstacle course runs: review of acquired injuries and illnesses at a series of Canadian events (RACE).

BACKGROUND: The growing popularity of obstacle course runs (OCRs) has led to significant concerns regarding their safety. The influx of injuries and illnesses in rural areas where OCRs are often held can impose a large burden on emergency medical services (EMS) and local EDs. Literature concerning the safety of these events is minimal and mostly consists of media reports. We sought to characterise the injury and illness profile of OCRs and the level of medical care required. METHODS: This study analysed OCR events occurring in eight locations across Canada from May to August 2015 (total 45 285 participants). Data were extracted from event medical charts of patients presenting to the onsite medical team, including injury or illness type, onsite treatment and disposition. RESULTS: There were 557 race participants treated at eight OCR events (1.2% of all participants). There were 609 medical complaints in total. Three quarters of injuries were musculoskeletal in nature. Eighty-nine per cent returned to the event with no need for further medical care. The majority of treatments were completed with first aid and basic medical equipment. Eleven patients (2% of patients) required transfer to hospital by EMS for presentations including fracture, dislocation, head injury, chest pain, fall from height, and abdominal pain. CONCLUSIONS: We found that 1.2% of race participants presented to onsite medical services. The majority of complaints were minor and musculoskeletal in nature. Only 2% of those treated were transferred to hospital through EMS. This is consistent with other types of mass gathering events.

Overview of the new oral anticoagulants: opportunities and challenges.

The non-vitamin K antagonist oral anticoagulants (NOACs) are replacing warfarin for many indications. These agents include dabigatran, which inhibits thrombin, and rivaroxaban, apixaban, and edoxaban, which inhibit factor Xa. All 4 agents are licensed in the United States for stroke prevention in atrial fibrillation and for treatment of venous thromboembolism and rivaroxaban and apixaban are approved for thromboprophylaxis after elective hip or knee arthroplasty. The NOACs are at least as effective as warfarin, but are not only more convenient to administer because they can be given in fixed doses without routine coagulation monitoring but also are safer because they are associated with less intracranial bleeding. As part of a theme series on the NOACs, this article (1) compares the pharmacological profiles of the NOACs with that of warfarin, (2) identifies the doses of the NOACs for each approved indication, (3) provides an overview of the completed phase III trials with the NOACs, (4) briefly discusses the ongoing studies with the NOACs for new indications, (5) reviews the emerging real-world data with the NOACs, and (6) highlights the potential opportunities for the NOACs and identifies the remaining challenges.

BET 2: Acupuncture and fibromyalgia.

A shortcut review was carried out to see if acupuncture is an effective pain treatment in fibromyalgia. One Cochrane review and five subsequent papers and conference abstracts were identified. There are no large studies addressing this question and acupuncture has been compared with many different treatment modalities. Acupuncture may be a valid treatment for pain in fibromyalgia, but more research is required to validate this.

Should we be looking for and treating isolated calf vein thrombosis?

Management of isolated calf deep vein thrombosis is an area of significant international debate and variable clinical practice. Both therapeutic anticoagulation and conservative management carry risk. As clinical care of suspected and confirmed venous thromboembolic disease increasingly becomes the remit of emergency medicine, complex decisions are left to practising clinicians at the front door. We aim to provide a contemporary overview of recent evidence on this topic and associated challenges facing clinicians. Given the lack of high-level evidence, we present this work as a narrative review, based on structured literature review and expert opinion. A decision to manage calf thrombosis is principally dependent on the risk of complications without treatment balanced against the risks of therapeutic anticoagulation. Estimates of the former risks taken from systematic review, meta-analysis, observational cohort and recent pilot trial evidence include proximal propagation 7%-10%, pulmonary embolism 2%-3% and death <1%. Fatal bleeding with therapeutic anticoagulation stands at <0.5%, and major bleeding at approximately 2%. Estimates of haemorrhagic risk are based on robust data from large prospective management studies of venous thromboembolic disease; the risks of untreated calf deep vein thrombosis are based on small cohorts and therefore less exact. Pending further trial evidence, these risks should be discussed with patients openly, in the context of personal preference and shared decision-making. Anticoagulation may maximally benefit those patients with extensive and/or symptomatic disease or those with higher risk for complication (unprovoked, cancer-associated or pregnancy).

Towards evidence-based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 1: Which form of aspirin is the fastest to inhibit platelet aggregation in emergency department patients with non-ST segment elevation myocardial infarction?

A short cut review was carried out to establish whether, in patients with suspected acute coronary syndromes presenting to the emergency department, what form of aspirin has the most rapid onset of action. Papers comparing the speed of onset of chewable aspirin, or soluble aspirin or solid aspirin were included. This summarises all three parts of a combined best evidence topic report (BET). The clinical bottom line is that chewable aspirin may be faster than soluble aspirin at decreasing the amount of time to achieve platelet inhibition in a patient. Soluble aspirin is faster than whole solid aspirin, which is faster than enteric-coated aspirin.

Single whole-leg compression ultrasound for exclusion of deep vein thrombosis in symptomatic ambulatory patients: a prospective observational cohort study.

International guidance has recently recommended serial proximal compression ultrasound (CUS) as first line imaging for suspected deep vein thrombosis (DVT). Single whole-leg CUS is a routine alternative diagnostic strategy that can reduce repeated attendances and identify alternative pathology. We conducted a prospective observational cohort study. Consecutive ambulatory, adult patients with suspected DVT and negative or inconclusive whole-leg CUS had anticoagulation withheld and were followed for 3 months. The primary outcome was a predefined clinically relevant adverse event rate. Secondary outcomes included technical failure, alternative diagnoses and all cause mortality. 212 patients agreed to participate and completed follow up. One patient was subsequently diagnosed with an isolated distal DVT. The adverse event rate was thus 1/212, 0·47% (95% confidence interval [CI] 0·08-2·62). Technical imaging failure occurred in 11·3% of cases (95% CI 7·7-16·3). Several potential predictors of an inconclusive result were identified on multivariate analysis. 150 (70·8%) patients were provided with a documented alternative diagnosis. Patients who have anticoagulation withheld following a negative or inconclusive whole-leg CUS for suspected DVT have a low rate of adverse events. Technical failure remains an issue: several factors were significantly associated with inconclusive results and may warrant an alternative diagnostic approach.

The diagnosis of venous thromboembolism.

Venous thromboembolism (VTE) is a serious and potentially fatal medical condition. Correct diagnosis and early treatment of VTE with anticoagulant drugs are critical steps in preventing further complications and recurrence. Evidence suggests that patients with suspected deep vein thrombosis (DVT) or pulmonary embolism (PE) should be managed with a diagnostic strategy that includes clinical pretest probability assessment, D-dimer test, and imaging. Clinical probability scoring, complemented by selective D-dimer testing, has become the recommended strategy for diagnosis. The reason is that overwhelming evidence suggests that patients with suspected VTE are better managed with a diagnostic strategy. If diagnostic algorithms are followed correctly, the chances of adverse events are extremely low (< 1%) in patients in whom VTE has been ruled out, whereas incomplete strategies leads to an increased risk of recurrent VTE or death. This review focuses on the application of diagnostic strategies with suspected DVT or PE into daily clinical practice while discussing the benefits and disadvantages of different approaches.

Is ischaemia-modified albumin a test for venous thromboembolism?

OBJECTIVE: Patients with symptoms of deep vein thrombosis (DVT) and pulmonary embolism (PE) commonly present to the emergency department (ED). The aim of this study was to assess the role of ischaemia-modified albumin (IMA) testing in the diagnosis of venous thromboembolism (VTE). METHODS: This was a prospective diagnostic cohort study. Inpatients and ED patients >16 years of age investigated for PE or DVT at a single hospital were eligible for study consent. Blinded IMA analysis was performed on the first blood sample taken from each patient. Patients underwent reference standard investigation for PE or DVT, including 3-month follow-up. Receiver operating characteristic (ROC) curves were constructed for IMA and the IMA:albumin ratio in the diagnosis of all VTE, PE and DVT. A sensitivity analysis was performed. RESULTS: 452 patients were consented and investigated for DVT, and 354 patients were consented and investigated for PE (806 in total). 348 patients investigated for PE had IMA testing as did 195 of the first 199 DVT patients. VTE prevalence was 19.7%. The IMA:albumin ratio performed better than IMA alone. The area under the ROC curve (AUC) for IMA:albumin in all VTE was 0.60 (95% CI 0.54 to 0.66), in DVT 0.56 (95% CI 0.46 to 0.65) and in PE 0.63 (95% CI 0.56 to 0.71). In ED patients with symptoms of PE, the AUC for IMA:albumin was 0.69 (95% CI 0.60 to 0.78). CONCLUSIONS: IMA testing cannot be used alone to diagnose DVT or PE, although there is a moderate association with PE in ED patients.

Diagnosing pulmonary embolism: a comparison of clinical probability scores.

Pulmonary embolism (PE) is a major cause of community and in-hospital mortality. This study aimed to compare the performance of the British Thoracic Society (BTS) score to the Wells' score in diagnosing PE. Data from two separate prospective diagnostic PE studies were analysed. All patients underwent gold standard investigation to determine the presence or absence of PE, together with a 3-month follow-up. The posttest prevalence of PE was compared using both scores and the receiver operating characteristic (ROC) curves. Seven hundred and seventy-nine patients were consented and investigated for PE. In patients with pleuritic chest pain, respiratory rate <20 breaths/min and absence of dyspnoea, 4·0% [95% confidence interval (CI) 1·9-7·9%] had PE. The BTS score allocated 463/779 patients as low probability, compared to 565/779 according to the Wells' score. Both scores identified a low risk group in the Manchester Investigation of Pulmonary Embolism Diagnosis cohort, however the BTS low probability group in the Thromboembolism Assessment and Diagnosis study had a prevalence of 9·7% (95% CI 5·8-15·9%). For the BTS score, the areas under the ROC curves were 0·67 (95% CI 0·61-0·72) and 0·71 (95% CI 0·61-0·75). For the Wells' score these were 0·76 (95%CI 0·71-0·81) and 0·68 (95%CI 0·64-0·73). Given the lack of BTS validation studies to date, the Wells' score appears to be the safer assessment option.

Estimating the pretest probability threshold to justify empiric administration of heparin prior to pulmonary vascular imaging for pulmonary embolism.

Expertly interpreted pulmonary vascular imaging (either ventilation-perfusion scan or computed tomography chest angiography) is not uniformly available at most hospitals, including those in the US. When evaluating a patient with suspected pulmonary embolism during times when pulmonary vascular imaging is not available, clinicians frequently face the decision of whether to administer heparin while awaiting availability of imaging. In this report, we analyze published data to quantitate the probability of death or disability from untreated pulmonary embolism versus the probability of serious bleeding for one, two and seven days of heparin therapy. For these three time points, we estimate the pretest probability of pulmonary embolism to justify the empiric administration of heparin.

Direct oral anticoagulants: a practical guide for the emergency physician.

The direct oral anticoagulants (DOACs) are the mainstay for stroke prophylaxis in nonvalvular atrial fibrillation and treatment of acute venous thrombosis. They are attractive alternatives to warfarin because of their efficacy, ease of prescription and safety profile. The emergency department has gained expertise in the management of DOAC bleeding complications, but has been slower to adopt prescription decisions. Emergency clinicians are in a unique position to identify patients who are prescribed DOACs and are at high risk of impending bleeding. This is a practical guide for the emergency clinician on how to prescribe DOACs, the red flags for DOAC patients in the emergency department and advances in the treatment of bleeding.

Respiratory dead space measurement in the investigation of pulmonary embolism in outpatients with pleuritic chest pain.

STUDY OBJECTIVES: Pleuritic chest pain is a common presenting condition in the emergency department. A noninvasive bedside rule out test for pulmonary embolism would aid investigating this patient group. Our study aimed to compare the clinical utility of three methods for calculating respiratory dead space in the diagnosis of pulmonary embolism in outpatients with pleuritic chest pain. DESIGN: Prospective diagnostic study. SETTING: Large city-center emergency department. PATIENTS: Between February 2002 and June 2003, 425 patients presenting to the emergency department with pleuritic chest pain were prospectively recruited. INTERVENTION: Data collection for respiratory dead space was performed in the emergency department by two researchers. The respiratory dead space fraction was calculated independently using three different methods. All patients underwent an independent reference standard diagnostic algorithm to establish the presence or absence of pulmonary embolism. Those with a low modified Wells clinical probability and a normal quantitative d-dimer finding were discharged home. All others followed a reference standard protocol using Prospective Investigation of Pulmonary Embolism Diagnosis-interpreted ventilation/perfusion scanning, CT pulmonary angiography, and digital subtraction pulmonary angiography. All patients were followed up clinically for 3 months. MEASUREMENTS AND RESULTS: For the Bohr calculation, the area under the receiver operating characteristic curve was 0.62 (95% confidence interval [CI], 0.51 to 0.73), the Enghoff calculation was 0.66 (95% CI, 0.55 to 0.77), and the capillary sample Enghoff was 0.62 (95% CI, 0.49 to 0.65). The optimum Bohr cutoff value gave 100.0% sensitivity (95% CI, 84.5 to 100%) but a low specificity of 22.7% (95% CI, 18.8 to 27.2%). The optimum cutoff points for Enghoff and capillary Enghoff calculations gave sensitivities of 95.3% (95% CI, 77.3 to 99.2%) and 94.4% (95% CI, 74.2 to 99.0%), respectively, with poor specificity. CONCLUSIONS: Respiratory dead space analysis does not perform well as a stand-alone diagnostic test for pulmonary embolism in outpatients presenting with pleuritic chest pain.

The emergency department utility of Simplify D-dimer to exclude pulmonary embolism in patients with pleuritic chest pain.

STUDY OBJECTIVE: Pleuritic chest pain is a common presenting complaint in the emergency department (ED) and a symptom of pulmonary embolism. Patients with pleuritic chest pain would benefit from a simple and rapid way of screening for pulmonary embolism. The aim of this study is to assess the utility of Simplify D-dimer as a rule-out tool for pulmonary embolism in ED patients with pleuritic chest pain. METHODS: This was a prospective diagnostic study in a large city-center ED. Four hundred twenty-five patients with pleuritic chest pain were prospectively recruited between February 2002 and June 2003. Simplify D-dimer testing was performed on each patient in the ED. All patients followed an independent reference standard diagnostic algorithm for pulmonary embolism. Each patient was followed up clinically for 3 months. RESULTS: The calculated sensitivity of Simplify D-dimer for pulmonary embolism was 81.8% (95% confidence interval [CI] 61.4% to 92.7%), and specificity was 74.2% (95% CI 69.6% to 78.4%). The negative predictive value was 98.6% (95% CI 96.6% to 99.6%), positive predictive value 15.0% (95% CI 9.1% to 22.7%), negative likelihood ratio 0.25 (95% CI 0.10 to 0.52) and positive likelihood ratio 3.17 (95% CI 2.30 to 3.97). The study cohort pretest probability was 5.3%. A negative Simplify result reduced the posttest probability to 1.3% (95% CI 0.5% to 3.4%). CONCLUSION: The Simplify D-dimer is not sufficiently sensitive to exclude the diagnosis of pulmonary embolism in all patients presenting to the ED with pleuritic chest pain.

Best evidence topic report. Diagnostic utility of electrocardiogram for diagnosing pulmonary embolism.

A shortcut review was carried out to establish the diagnostic utility of electrocardiography in patients with suspected pulmonary embolus (PE). Altogether 952 papers were found using the reported search, of which five presented the best evidence to answer the clinical question. The author, date, and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these best papers are tabulated (table 1). It is concluded that although there are electrocardiogram (ECG) changes that are more common in PE, the ECG alone is not sufficiently sensitive or specific to rule out or rule in the diagnosis.

Best evidence topic report. Topical analgesia for pain reduction in arterial puncture.

A short cut review was carried out to establish whether topical local anaesthetic reduces the pain of arterial puncture. 431 papers were found using the reported search, of which two presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these best papers are tabulated. A clinical bottom line is stated.

Best evidence topic report. Diagnostic utility of arterial blood gases for investigation of pulmonary embolus.

A short cut review was carried out to establish the diagnostic utility of arterial blood gas analysis in patients with suspected pulmonary embolus. Altogether 459 papers were found using the reported search, of which six presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these best papers are tabulated. A clinical bottom line is stated.

Time trends in intracranial bleeding associated with direct oral anticoagulants: a 5-year cohort study.

BACKGROUND: Over the past 5 years, dabigatran, rivaroxaban and apixaban were approved for stroke prevention. Phase III studies have shown a lower risk of intracranial bleeding with these direct oral anticoagulants than with warfarin; however, there is a lack of real-life data to validate this. We analyzed time trends in atraumatic intracranial bleeding from 2009 to 2013 among patients prescribed oral anticoagulants and those not prescribed oral anticoagulants. METHODS: We used ICD-10-CA (enhanced Canadian version of the 10th revision of the International Statistical Classification of Diseases and Related Health Problems) codes to identify all patients with atraumatic intracranial bleeding who presented to our neurosurgical centre (serving a population of more than 1.2 million). Trained researchers extracted data on anticoagulant medications used in the week before diagnosis of the intracranial bleed. Provincial prescription data for oral anticoagulants were obtained from IMS Brogan CompuScript Market Dynamics. The primary outcome was the time trend in incident intracranial bleeds associated with oral anticoagulation during the period 2009-2013. The secondary outcomes were the time trend in intracranial bleeds not associated with oral anticoagulation and the provincial prescribing patterns for oral anticoagulants during the same period. RESULTS: A total of 2050 patients presented with atraumatic intracranial bleeds during the study period. Of the 371 (18%) prescribed an anticoagulant in the week before presentation, 335 were prescribed an oral anticoagulant. There was an increasing time trend in intracranial bleeding associated with oral anticoagulants (p = 0.009; 6 additional events per year) and in intracranial bleeding not associated with oral anticoagulation (p = 0.06). During 2013, prescriptions for warfarin decreased to 70% of all oral anticoagulant prescriptions in the province, whereas those for dabigatran and rivaroxaban increased to 17% and 12%, respectively. INTERPRETATION: We observed increasing time trends in intracranial bleeding, both associated with and not associated with oral anticoagulants, over the study period. Although aggregate provincial data showed increased prescribing of oral anticoagulants, other more likely explanations for our findings include an aging population or increasing frailty.

A meta-analysis of clinical correlates that predict significant intracranial injury in adults with minor head trauma.

Previous studies have resulted in conflicting results regarding the predictive effect of various clinical symptoms, signs, and plain imaging for intracranial pathology in adults with minor head injury. We sought to perform a meta-analysis of the literature to assess the significance of these factors for the prediction of intracranial hemorrhage (ICH). The literature was searched using Medline, Embase, Experts, and the Grey literature. Reference lists of major guidelines were crosschecked. Included were control or nested case control studies of patients attending hospital with head injury that recorded clinical correlates relating to the outcome variable of presence or absence of ICH. The common relative risk ratio was calculated using the Mantel-Haenszel test with a pooled estimate. Thirty-five papers containing 83,636 patients were included in the meta-analysis after systematic review of the literature. Relative risk ratios were calculated for 23 clinical correlates from the history, the mechanism of injury, and the examination. In addition, adjusted relative risks were presented for those variables that showed significant heterogeneity across studies. Reasons for the heterogeneity are discussed. This study has determined the relative risks of 23 clinical variables that may predict the presence of an ICH in patients after minor head injury. These risks should prove invaluable to clinicians for the assessment of individual patients as well as the assessment of guidelines presented for the management of minor head injuries.

Best evidence topic report. Which facial views for facial trauma?

A short cut review was carried out to establish whether a reduced number of facial radiographs had acceptable clinical utility at detecting facial fractures after trauma. Altogether 614 papers were found using the reported search, of which five presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. A clinical bottom line is stated.