Clinical judgement in primary care is more often decisive than in the hospital. Clinical decision rules (CDRs) can help general practitioners facilitating the work-through of differentials that follows an initial suspicion, resulting in a concrete ‘course of action’: a ‘rule-out’ without further testing, a need for further testing, or a specific treatment. However, in daily primary care, the use of CDRs is limited to only a few isolated rules. In this paper, we aimed to provide insight into the laborious path required to implement a viable CDR. At the same time, we noted that the limited use of CDRs in primary care cannot be explained by implementation barriers alone. Through the case study of the Oudega rule for the exclusion of deep vein thrombosis, we concluded that primary care CDRs come out best if they are tailor-made, taking into consideration the specific context of primary health care. Current CDRs should be evaluated frequently, and future decision rules should anticipate the latest developments such as the use of point-of-care (POC) tests. Hence, such new powerful diagnostic CDRs could improve and expand the possibilities for patient-oriented primary care.

D-dimer level on admission is a promising biomarker to predict mortality in patients with COVID-19. In this study, we reviewed the association between on-admission D-dimer levels and all-cause mortality risk in COVID-19 patients. Peer-reviewed studies and preprints reporting categorised D-dimer levels on admission and all-cause mortality until 24 May 2020 were searched for using the following keywords: ‘COVID-19’, ‘D-dimer’ and ‘Mortality’. A meta-analysis was performed to determine the pooled risk ratio (RR) for all-cause mortality. In total, 2911 COVID-19 patients from nine studies were included in this meta-analysis. Regardless of the different D-dimer cut-off values used, the pooled RR for all-cause mortality in patients with elevated vs. normal on-admission D-dimer level was 4.77 (95% confidence interval (CI) 3.02–7.54). Sensitivity analysis did not significantly affect the overall mortality risk. Analysis restricted to studies with 0.5 μg/ml as the cut-off value resulted in a pooled RR for mortality of 4.60 (95% CI 2.72–7.79). Subgroup analysis showed that the pooled all-cause mortality risk was higher in Chinese vs. non-Chinese studies (RR 5.87; 95% CI 2.67–12.89 and RR 3.35; 95% CI 1.66–6.73; P = 0.29). On-admission D-dimer levels showed a promising prognostic role in predicting all-cause mortality in COVID-19 patients, elevated D-dimer levels were associated with increased risk of mortality.

Over the years, the practice of medicine has evolved from authority-based to experience-based to evidence-based with the introduction of the scientific process, clinical trials, and outcomes-based data analysis (Tebala GD. Int J Med Sci. 2018;15(12):1397-1405). The time required to perform the necessary randomized controlled trials, a systematic literature review, and meta-analysis of these trials to then create, accept, promulgate, and educate the practicing clinicians to use the evidence-based clinical guidelines is typically measured in years. When the severe acute respiratory syndrome novel coronavirus-2 (SARS-nCoV-2) pandemic commenced in Wuhan, China at the end of 2019, there were few available clinical guidelines to deploy, let alone adapt and adopt to treat the surge of coronavirus disease 2019 (COVID-19) patients. The aim of this study is to first explain how clinical guidelines, on which bedside clinicians have grown accustomed, can be created in the midst of a pandemic, with an evolving scientific understanding of the pathophysiology of the hypercoagulable state. The second is to adapt and adopt current venous thromboembolism diagnostic and treatment guidelines, while relying on the limited available observational reporting of COVID-19 patients to create a comprehensive clinical guideline to treat COVID-19 patients.

Introduction: Diagnosing pulmonary embolism (PE) can be challenging because the signs and symptoms are often non-specific. Studies have shown that evidence-based algorithms are not always adhered to in the Emergency Department (ED) and are often not used correctly, which leads to unnecessary CT scanning. The YEARS diagnostic algorithm, consisting of three items (clinical signs of deep vein thrombosis, hemoptysis, and whether pulmonary embolism is the most likely diagnosis) and D-dimer, is a novel and simplified way to approach suspected acute PE. The purpose of this study was to 1) evaluate the use of the YEARS algorithm in the ED and 2) to compare the rates of testing for PE if the YEARS algorithm was used. Methods: This was a health records review of ED patients investigated for PE at two emergency departments over a two-year period (April 2013-March 2015). Inclusion criteria were ED physician ordered CT pulmonary angiogram, ventilation-perfusion scan, or D-dimer for investigation of PE. Patients under the age of 18 and those without a D-dimer test were excluded. PE was considered to be present during the emergency department visit if PE was diagnosed on CT or VQ (subsegmental level or above), or if the patient was subsequently found to have PE or deep vein thrombosis during the next 30 days. Trained researchers extracted anonymized data. The rate of CT/VQ imaging and the false negative rate was calculated. Results: There were 1,163 patients that were tested for PE and 1,083 patients were eligible for our analysis. Of the total, 317/1,083 (29.3%; 95%CI 26.6-32.1%) had CT/VQ imaging for PE, and 41/1,083 (3.8%; 95%CI 2.8-5.1%) patients were diagnosed with PE at baseline. Three patients had a missed PE, resulting in a false negative rate of 0.4% (95%CI 0.1-1.2%). If the YEARS algorithm was used, 211/1,083 (19.5%; 95%CI 17.2-22.0%) would have required imaging for PE. Of the patients who would not have required imaging according to the YEARS algorithm, 8/872 (0.9%; 95%CI 0.5-1.8%) would have had a missed PE. Conclusion: If the YEARS algorithm was used in all patients with suspected PE, fewer patients would have required imaging with a small increase in the false negative rate.

Introduction: Diagnosing pulmonary embolism (PE) can be challenging because the signs and symptoms are often non-specific. Studies have shown that evidence-based algorithms are not always adhered to in the Emergency Department (ED), which leads to unnecessary CT scanning. The pulmonary embolism rule-out criteria (PERC) can identify patients who can be safely discharged from the ED without further investigation for PE. The purpose of this study is to evaluate the use of the PERC rule in the ED and to compare the rates of testing for PE if the PERC rule was used. Methods: This was a health records review of ED patients investigated for PE at two emergency departments over a two-year period (April 2013-March 2015). Inclusion criteria were ED physician ordered CT pulmonary angiogram, ventilation-perfusion scan, or D-dimer for investigation of PE. Patients under the age of 18 were excluded. PE was considered to be present during the emergency department visit if PE was diagnosed on CT or VQ (subsegmental level or above), or if the patient was subsequently found to have PE or deep vein thrombosis during the next 30 days. Trained researchers extracted anonymized data. The rate of CT/VQ imaging and the negative predictive value was calculated. Results: There were 1,163 patients that were tested for PE and 1,097 patients were eligible for our analysis. Of the total, 330/1,097 (30.1%; 95%CI 27.4-32.3%) had CT/VQ imaging for PE, and 48/1,097 (4.4%; 95%CI 3.3-5.8%) patients were diagnosed with PE. 806/1,097 (73.5%; 95%CI 70.8-76.0%) were PERC positive, and of these, 44 patients had a PE (5.5%; 95%CI 4.1-7.3%). Conversely, 291/1,097 (26.5%; 95%CI 24.0-29.2%) patients were PERC negative, and of these, 4 patients had a PE (1.4%; 95%CI 0.5-3.5%). Of the PERC negative patients, 291/291 (100.0%; 95%CI 98.7-100.0%) had a D-dimer test done, and 33/291 (11.3%; 95%CI 8.2-15.5%) had a CT angiogram. If PERC was used, CT/VQ imaging would have been avoided in 33/1,097 (3%; 95%CI 2.2-4.2%) patients and the D-dimer would have been avoided in 291/1,097 (26.5%; 95%CI 24.0-29.2%) patients. Conclusion: If the PERC rule was used in all patients with suspected PE, fewer patients would have further testing. The false negative rate for the PERC rule was low.

Introduction: Diagnosing pulmonary embolism (PE) in the emergency department can be challenging due to non-specific signs and symptoms; this often results in the over-utilization of CT pulmonary angiography (CT-PA). In 2013, the American College of Chest Physicians identified CT-PA as one of the top five avoidable tests. Age-adjusted D-dimer has been shown to decrease CT utilization rates. Recently, clinical-probability adjusted D-dimer has been promoted as an alternative strategy to reduce CT scanning. The aim of this study is to compare the safety and efficacy of the age-adjusted D-dimer rule and the clinical probability-adjusted D-dimer rule in Canadian ED patients tested for PE. Methods: This was a retrospective chart review of ED patients investigated for PE at two hospitals from April 2013 to March 2015 (24 months). Inclusion criteria were the ED physician ordered CT-PA, Ventilation-Perfusion (VQ) scan or D-dimer for investigation of PE. Patients under the age of 18 were excluded. PE was defined as CT/VQ diagnosis of acute PE or acute PE/DVT in 30-day follow-up. Trained researchers extracted anonymized data. The age-adjusted D-dimer and the clinical probability-adjusted D-dimer rules were applied retrospectively. The rate of CT/VQ imaging and the false negative rates were calculated. Results: In total, 1,189 patients were tested for PE. 1,129 patients had a D-dimer test and a Wells score less than 4.0. 364/1,129 (32.3%, 95%CI 29.6-35.0%) would have undergone imaging for PE if the age-adjusted D-dimer rule was used. 1,120 patients had a D-dimer test and a Wells score less than 6.0. 217/1,120 patients (19.4%, 95%CI 17.2-21.2%) would have undergone imaging for PE if the clinical probability-adjusted D-dimer rule was used. The false-negative rate for the age-adjusted D-dimer rule was 0.3% (95%CI 0.1-0.9%). The false-negative rate of the clinical probability-adjusted D-dimer was 1.0% (95%CI 0.5-1.9%). Conclusion: The false-negative rates for both the age-adjusted D-dimer and clinical probability-adjusted D-dimer are low. The clinical probability-adjusted D-dimer results in a 13% absolute reduction in CT scanning compared to age-adjusted D-dimer.

Introduction: It is well established that a negative D-dimer will reliably rule out thromboembolism in selected low risk patients. Multiple modified D-dimer cutoffs have been suggested for older patients to improve diagnostic specificity. However, these approaches are better established for pulmonary embolism than for deep venous thrombosis (DVT). This study will evaluate the diagnostic performance of previously suggested D-dimer cutoffs for low risk DVT patients in the ED, and assess for a novel cutoff with improved performance. Methods: This health records review included patients >50 years with suspected DVT who were low-risk and had a D-dimer performed. Our analysis evaluated the diagnostic accuracy of D-dimer cutoffs of 500 and the age adjusted (age x 10) rule for patients >50 years; and 750, and 1,000 cutoffs for patients >60 years. 30-day outcome was a diagnosis of DVT. We also assessed the diagnostic accuracy for a novel cutoff (age x 12.5). Results: 1,000 patients (mean age 68 years; 59% female) were included. Of these, 110 patients (11%) were diagnosed with DVT. The conventional cutoff of <500 µg/L demonstrated a sensitivity of 99.1% (95% CI 95.0-99.9) and a specificity of 36.4% (95% CI 33.2-39.7). For patients >60 years, the absolute cutoffs of 750 and 1,000 showed sensitivity of 98.7% (95% CI, 92.9, 99.9), and the specificity increased to 48.6% (95% CI, 44.5-52.8%) and 62.1% (95% CI, 58.1-66.1%) respectively. For all study patients, age adjusted D-dimer demonstrated a sensitivity of 99.1% (95% CI 95.0-99.9) and a specificity of 51.2% (95% CI, 47.9-54.6). A novel age adjusted cutoff (age x 12.5) for patients >50, demonstrated a sensitivity of 97.3% (95% CI 92.2-99.4) and a specificity of 61.2% (95% CI 58.0-64.5). When compared to conventional cutoff, the age adjusted cutoffs (age x 10 and age x 12.5) would have resulted in an absolute decrease in further investigations of 13.1% and 22.2%, respectively, with false negative rates of 0.1% and 0.3%. Conclusion: Among older patients with suspected DVT and low clinical probability, the age adjusted D-dimer increases the proportion of patients among whom DVT can be ruled out. A novel cutoff (age x 12.5) demonstrated improved specificity. Future large scale prospective studies are needed to confirm this finding and to explore the cost savings of these approaches.

Introduction: Diagnosing pulmonary embolism (PE) can be challenging because the signs and symptoms are often non-specific. Studies have shown that evidence-based diagnostic algorithms are not always adhered to in the Emergency Department (ED), which leads to unnecessary CT scanning. In 2013, the American College of Chest Physicians identified CT pulmonary angiography as one of the top five avoidable tests. One solution is to use a clinical prediction rule combined with the D-dimer, which safely reduces the use of CT scanning. The objective of this study was to compare the proportion of patients tested for PE in two emergency departments, who 1) had a CT-PE and 2) whose diagnosis of PE was missed. We compared these rates to those if the Wells rule and D-dimer had been applied as standard. Methods: This was a retrospective chart review of ED patients investigated for PE at two hospitals from April 2013 to March 2015 (24 months). Inclusion criteria were the ED physician ordered CT-PE, Ventilation-Perfusion (VQ) scan or D-dimer for investigation of PE. Patients under the age of 18 were excluded. PE was defined as CT/VQ diagnosis of acute PE or acute PE/DVT in 30-day follow-up. Trained researchers extracted anonymized data. The rate of CT/VQ imaging and the false-negative rates were calculated. The false-negative rate was calculated as the number of patients diagnosed with PE within 30 days as a proportion of those patients who did not have a CT/VQ scan at initial presentation. Results: There were 1,189 patients included in this study. 55/1,189 patients (4.6%; 95%CI 3.6-6.0%) were ultimately diagnosed with PE within 30 days. 397/1,189 patients (33.4%; 95%CI 30.8-36.1%) had CT/VQ scans for PE. 3 out of 792 who were not scanned had a missed PE resulting in a false-negative rate of 0.4% (95% CI 0.1-1.1%). 80 patients had an elevated D-dimer or high Wells score but were not imaged. Furthermore, 75 patients who did not have an elevated D-dimer nor a high Wells score were imaged. Had Wells rule/D-dimer been adhered to, 402/1,189 patients (33.8%; 95%CI 31.9-36.6%) would have undergone imaging and the false negative rate would be 0/727, 0% (95%CI 0.0-0.5%). Conclusion: If the Wells rule and D-dimer was used in all patients tested for PE, a similar proportion would have a CT scan but fewer PEs would be missed.

Background: Although D-dimer levels are significantly associated with cardioembolic infarction, the significance of D-dimer levels in relation to the severity and functional outcomes of other stroke subtypes, such as lacunar and large artery atherosclerosis infarction, remains unclear. The purpose of this study was to evaluate whether elevated initial D-dimer levels are significantly and cross-sectionally associated with poor functional outcomes at each time point during a 9-month follow-up period. We also investigated the significance of D-dimer levels in longitudinal temporal changes of functional outcomes in these patients. Methods: We recruited 146 patients with lacunar infarction and 161 patients with large artery atherosclerosis infarction who were consecutively admitted to our hospital after acute stroke. Serum D-dimer levels were evaluated initially and the modified Rankin scale were measured initially and at 1-, 3-, 6-, and 9-month follow-up visits. Results: Patients with higher D-dimer levels had significantly worse initial functional outcomes, and these worse outcomes were maintained throughout the 9-month follow-up period compared with the low D-dimer group. However, regardless of stroke subtype, D-dimer levels did not influence long-term changes in functional outcomes over the 9-month follow-up period. Conclusion: This study suggests that elevated D-dimer levels can be used as a surrogate marker for poor functional outcomes only during the acute stage. Further evaluation of serum D-dimer levels could provide a helpful predictive marker for stroke prognosis.

Introduction: The D-dimer assay is a high sensitivity, low specificity test used to rule out pulmonary embolism (PE) in low risk ED patients. Patients with a positive D-dimer result will likely undergo CT imaging to confirm the diagnosis. Given the time, cost, and radiation exposure associated with CT, and the higher false-positive rate in older patients, an age-adjusted D-dimer threshold may be preferred. Our objective was to evaluate the sensitivity and specificity of an age-adjusted D-dimer and approximate the downstream effect on CT imaging utilization. Methods: This was a retrospective cohort study conducted using administrative data from Calgary emergency departments between July 2013 and January 2015. Eligible patients were individuals aged 50 and older who were undergoing PE workup including D-dimer testing. Outcomes were ascertained using CT imaging reports and by searching the regional administrative database for subsequent diagnosis of PE within 30 days of the index visit. These data were used to calculate the sensitivity, specificity, positive predictive value, and negative predictive value of the D-dimer test using the standard threshold (500 ng/mL) and an age-adjusted threshold (10 ng/mL x patient age as an integer). From this, the potential reduction in CT imaging use and missed PE diagnoses were modeled. Results: Of 6669 patients aged 50 or older who had D-dimer testing for possible PE, 1504 (22.6%) underwent a CT scan, and 217 (14.4% of CT) received a discharge diagnosis of pulmonary embolism, which was confirmed on chart review. When test results were re-interpreted using an age-adjusted threshold, D-dimer specificity increased from 63.9% to 75.4%, while sensitivity decreased from 96.5% to 89.9%. This translates to 888 new true negatives, representing CT scans potentially avoided (a 59% reduction in CT utilization), but with 18 new missed PE diagnoses. Conclusion: The age-adjusted threshold may reduce use of CT imaging among older patients suspected of PE, but at the cost of more missed PE diagnoses.