Detection of atrial fibrillation in primary care with radial pulse palpation, electronic blood pressure measurement and handheld single-lead electrocardiography: a diagnostic accuracy study.

OBJECTIVE: To determine the diagnostic accuracy of three tests-radial pulse palpation, an electronic blood pressure monitor and a handheld single-lead ECG device-for opportunistic screening for unknown atrial fibrillation (AF). DESIGN: We performed a diagnostic accuracy study in the intention-to-screen arm of a cluster randomised controlled trial aimed at opportunistic screening for AF in general practice. We performed radial pulse palpation, followed by electronic blood pressure measurement (WatchBP Home A) and handheld ECG (MyDiagnostick) in random order. If one or more index tests were positive, we performed a 12-lead ECG at shortest notice. Similarly, to limit verification bias, a random sample of patients with three negative index tests received this reference test. Additionally, we analysed the dataset using multiple imputation. We present pooled diagnostic parameters. SETTING: 47 general practices participated between September 2015 and August 2018. PARTICIPANTS: In the electronic medical record system of the participating general practices (n=47), we randomly marked 200 patients of ≥65 years without AF. When they visited the practice for any reason, we invited them to participate. Exclusion criteria were terminal illness, inability to give informed consent or visit the practice or having a pacemaker or an implantable cardioverter-defibrillator. OUTCOMES: Diagnostic accuracy of individual tests and test combinations to detect unknown AF. RESULTS: We included 4339 patients; 0.8% showed new AF. Sensitivity and specificity were 62.8% (range 43.1%-69.7%) and 91.8% (91.7%-91.8%) for radial pulse palpation, 70.0% (49.0%-80.6%) and 96.5% (96.3%-96.7%) for electronic blood pressure measurement and 90.1% (60.8%-100%) and 97.9% (97.8%-97.9%) for handheld ECG, respectively. Positive predictive values were 5.8% (5.3%-6.1%), 13.8% (12.2%-14.8%) and 25.2% (24.2%-25.8%), respectively. All negative predictive values were ≥99.7%. CONCLUSION: In detecting AF, electronic blood pressure measurement (WatchBP Home A), but especially handheld ECG (MyDiagnostick) showed better diagnostic accuracy than radial pulse palpation. TRIAL REGISTRATION NUMBER: Netherlands Trial Register No. NL4776 (old NTR4914).

Process evaluation of a programme to empower community nurse leadership.

BACKGROUND: The Nurses in the Lead (NitL) programme consists of a systematic approach and training to 1) empower community nurses in implementing evidence, targeted at encouraging functional activities of older adults, and 2) train community nurses in enabling team members to change their practice. This article aims to describe the process evaluation of NitL. METHODS: A mixed-methods formative process evaluation with a predominantly qualitative approach was conducted. Qualitative data were collected by interviews with community nurses (n = 7), focus groups with team members (n = 31), and reviewing seven implementation plans and 28 patient records. Quantitative data were collected among community nurses and team members (N = 90) using a questionnaire to assess barriers in encouraging functional activities and attendance lists. Data analysis was carried out through descriptive statistics and content analysis. RESULTS: NitL was largely executed according to plan. Points of attention were the use and value of the background theory within the training, completion of implementation plans, and reporting in patient records by community nurses. Inhibiting factors for showing leadership and encouraging functional activities were a lack of time and a high complexity of care; facilitating factors were structure and clear communication within teams. Nurses considered the systematic approach useful and the training educational for their role. Most team members considered NitL practical and were satisfied with the coaching provided by community nurses. To optimise NitL, community nurses recommended providing the training first and extending the training. The team members recommended continuing clinical lessons, which were an implementation strategy from the community nurses. CONCLUSIONS: NitL was largely executed as planned, and appears worthy of further application in community care practice. However, adaptations are recommended to make NitL more promising in practice in empowering community nurse leadership in implementing evidence.

The content of the nurses in the lead programme for empowering community nurse leadership in implementing evidence.

PURPOSE: This study aims to provide a detailed description of the nurses in the lead (NitL) programme for empowering community nurse leadership in implementing evidence. DESIGN/METHODOLOGY/APPROACH: The NitL programme is described using the template for intervention description and replication-checklist. FINDINGS: The NitL programme consists of two components. The first component is a systematic approach with implementation steps and tools to empower community nurses in implementing evidence targeted at encouraging functional activities of older adults offered via a Web-based eLearning programme. The second component is training to empower community nurses in enabling team members to change their practice, which focussed on motivational interviewing, influencing behaviour, dealing with resistance to change and coaching delivered as a combination of group training in practice and background theory via a web-based eLearning programme. RESEARCH LIMITATIONS/IMPLICATIONS: Further research is needed to evaluate the feasibility and effects of the NitL programme. PRACTICAL IMPLICATIONS: The NitL programme has been developed in cooperation with community nurses to meet their needs in practice and has the potential to develop leadership for the core tasks of community nurses. ORIGINALITY/VALUE: The NitL programme has been developed to empower the leadership of community nurses in implementing evidence targeted at encouraging functional activities of older adults. The leadership role of community nurses is key for delivering high-quality care and implementing evidence within the community care setting for encouraging functional activities of older adults to preserve their independence.

Opportunistic screening versus usual care for detection of atrial fibrillation in primary care: cluster randomised controlled trial.

OBJECTIVE: To investigate whether opportunistic screening in primary care increases the detection of atrial fibrillation compared with usual care. DESIGN: Cluster randomised controlled trial. SETTING: 47 intention-to-screen and 49 usual care primary care practices in the Netherlands, not blinded for allocation; the study was carried out from September 2015 to August 2018. PARTICIPANTS: In each practice, a fixed sample of 200 eligible patients, aged 65 or older, with no known history of atrial fibrillation in the electronic medical record system, were randomly selected. In the intention-to-screen group, 9218 patients eligible for screening were included, 55.0% women, mean age 75.2 years. In the usual care group, 9526 patients were eligible for screening, 54.3% women, mean age 75.0 years. INTERVENTIONS: Opportunistic screening (that is, screening in patients visiting their general practice) consisted of three index tests: pulse palpation, electronic blood pressure measurement with an atrial fibrillation algorithm, and electrocardiography (ECG) with a handheld single lead electrocardiographic device. The reference standard was 12 lead ECG, performed in patients with at least one positive index test and in a sample of patients (10%) with three negative tests. If 12 lead ECG showed no atrial fibrillation, patients were invited for more screening by continuous monitoring with a Holter electrocardiograph for two weeks. MAIN OUTCOME MEASURES: Difference in the detection rate of newly diagnosed atrial fibrillation over one year in intention-to-screen versus usual care practices. RESULTS: Follow-up was complete for 8874 patients in the intention-to-screen practices and for 9102 patients in the usual care practices. 144 (1.62%) new diagnoses of atrial fibrillation in the intention-to-screen group versus 139 (1.53%) in the usual care group were found (adjusted odds ratio 1.06 (95% confidence interval 0.84 to 1.35)). Of 9218 eligible patients in the intention-to-screen group, 4106 (44.5%) participated in the screening protocol. In these patients, 12 lead ECG detected newly diagnosed atrial fibrillation in 26 patients (0.63%). In the 266 patients who continued with Holter monitoring, four more diagnoses of atrial fibrillation were found. CONCLUSIONS: Opportunistic screening for atrial fibrillation in primary care patients, aged 65 and over, did not increase the detection rate of atrial fibrillation, which implies that opportunistic screening for atrial fibrillation is not useful in this setting. TRIAL REGISTRATION: Netherlands Trial Register No NL4776 (old NTR4914).

The perceived behavior and barriers of community care professionals in encouraging functional activities of older adults: the development and validation of the MAINtAIN-C questionnaire.

BACKGROUND: Community care professionals need to encourage older adults in performing functional activities to maintain independence. However, professionals often perform functional activities on behalf of older adults. To change this, insights into the behavior and barriers of professionals in encouraging activities are required. In the current study, the MAINtAIN questionnaire, which was developed for nursing homes, was adopted. The objective was to create a modified version that is suitable for measuring behavior and barriers of community care professionals in encouraging functional activities of clients in the community care setting. The overall aims were to assess the content validity, construct validity, and internal consistency of the modified version. METHODS: Data was collected by qualitative and quantitative methods in two phases. During phase one, the MAINtAIN was assessed on appropriateness and feasibility by community nurses (N = 7), and the adapted questionnaire was assessed on content validity by research experts (N = 9) and community care professionals (N = 18). During phase two, the psychometric properties of the adapted MAINtAIN-C were assessed in community care professionals (N = 80). Construct validity was evaluated by an Exploratory Factor Analysis (EFA), and internal consistency was determined by calculating Cronbach's alpha coefficients. RESULTS: The formulation, verbs, and wording of the MAINtAIN were adapted; some items were excluded and relevant items were added, resulting in the MAINtAIN-C with two scales, showing good content validity. The Behaviors scale (20 items) measures perceived behavior in encouraging functional activities, expressing good internal consistency (Cronbach's alpha: .92). The Barriers scale measures barriers in encouraging functional activities related to two dimensions: 1) the clients' context (7 items), with good internal consistency (.78); and 2) the professional, social, and organizational contexts (21 items), showing good internal consistency (.83). CONCLUSIONS: The MAINtAIN-C seems promising to assess the behavior and barriers of community care professionals in encouraging functional activities. It can be used to display a possible difference between perceived and actual behavior, to develop strategies for removing barriers in encouraging activities to foster behavioral change. The results also provide guidance for further research in a larger sample to obtain more insight into the psychometric properties.

Ruling Out Pulmonary Embolism in Primary Care: Comparison of the Diagnostic Performance of "Gestalt" and the Wells Rule.

PURPOSE: Diagnostic prediction models such as the Wells rule can be used for safely ruling out pulmonary embolism (PE) when it is suspected. A physician's own probability estimate ("gestalt"), however, is commonly used instead. We evaluated the diagnostic performance of both approaches in primary care. METHODS: Family physicians estimated the probability of PE on a scale of 0% to 100% (gestalt) and calculated the Wells rule score in 598 patients with suspected PE who were thereafter referred to secondary care for definitive testing. We compared the discriminative ability (c statistic) of both approaches. Next, we stratified patients into PE risk categories. For gestalt, a probability of less than 20% plus a negative point-of-care d-dimer test indicated low risk; for the Wells rule, we used a score of 4 or lower plus a negative d-dimer test. We compared sensitivity, specificity, efficiency (percentage of low-risk patients in total cohort), and failure rate (percentage of patients having PE within the low-risk category). RESULTS: With 3 months of follow-up, 73 patients (12%) were confirmed to have venous thromboembolism (a surrogate for PE at baseline). The c statistic was 0.77 (95% CI, 0.70-0.83) for gestalt and 0.80 (95% CI, 0.75-0.86) for the Wells rule. Gestalt missed 2 out of 152 low-risk patients (failure rate = 1.3%; 95% CI, 0.2%-4.7%) with an efficiency of 25% (95% CI, 22%-29%); the Wells rule missed 4 out of 272 low-risk patients (failure rate = 1.5%; 95% CI, 0.4%-3.7%) with an efficiency of 45% (95% CI, 41%-50%). CONCLUSIONS: Combined with d-dimer testing, both gestalt using a cutoff of less than 20% and the Wells rule using a score of 4 or lower are safe for ruling out PE in primary care. The Wells rule is more efficient, however, and PE can be ruled out in a larger proportion of suspected cases.

Detecting and Diagnosing Atrial Fibrillation (D2AF): study protocol for a cluster randomised controlled trial.

BACKGROUND: Atrial fibrillation is a common cause of stroke and other morbidity. Adequate treatment with anticoagulants reduces the risk of stroke by 60 %. Early detection and treatment of atrial fibrillation could prevent strokes. Atrial fibrillation is often asymptomatic and/or paroxysmal. Case-finding with pulse palpation is an effective screening method, but new methods for detecting atrial fibrillation have been developed. To detect paroxysmal atrial fibrillation ambulatory rhythm recording is needed. This study aims to determine the yield of case-finding for atrial fibrillation in primary care patients. In addition, it will determine the diagnostic accuracy of three different case-finding methods. METHODS/DESIGN: In a multicenter cluster randomised controlled trial, we compare an enhanced protocol for case-finding of atrial fibrillation with usual care. We recruit 96 practices. We include primary care patients aged 65 years or older not diagnosed with atrial fibrillation. Within each practice, a cluster of 200 patients is randomly selected and marked. Practices are evenly randomised to intervention or control group. The allocation is not blinded. When a marked patient visits an intervention practice, the case-finding protocol starts, consisting of: pulse palpation, sphygmomanometer with automated atrial fibrillation detection and handheld single-lead electrocardiogram (ECG). All patients with at least 1 positive test and a random sample of patients with negative tests receive a 12-lead ECG. Patients without atrial fibrillation on the 12-lead ECG, undergo additional continuous Holter and use the handheld single-lead ECG at home for 2 weeks. Control practices provide care as usual. The study runs for 1 year in each cluster. The primary outcomes are the difference in detection rate of new AF between intervention and control practices and the accuracy of three index tests to diagnose AF. We are currently recruiting practices. The 'Detecting and Diagnosing Atrial Fibrillation' (D2AF) study will determine the yield of an intensive case-finding strategy and the diagnostic accuracy of three index tests to diagnose atrial fibrillation in a primary care setting. TRIAL REGISTRATION: Netherlands Trial Register: NTR4914 , registered on the 25 of November 2014.

Diagnostic prediction models for suspected pulmonary embolism: systematic review and independent external validation in primary care.

OBJECTIVE: To validate all diagnostic prediction models for ruling out pulmonary embolism that are easily applicable in primary care. DESIGN: Systematic review followed by independent external validation study to assess transportability of retrieved models to primary care medicine. SETTING: 300 general practices in the Netherlands. PARTICIPANTS: Individual patient dataset of 598 patients with suspected acute pulmonary embolism in primary care. MAIN OUTCOME MEASURES: Discriminative ability of all models retrieved by systematic literature search, assessed by calculation and comparison of C statistics. After stratification into groups with high and low probability of pulmonary embolism according to pre-specified model cut-offs combined with qualitative D-dimer test, sensitivity, specificity, efficiency (overall proportion of patients with low probability of pulmonary embolism), and failure rate (proportion of pulmonary embolism cases in group of patients with low probability) were calculated for all models. RESULTS: Ten published prediction models for the diagnosis of pulmonary embolism were found. Five of these models could be validated in the primary care dataset: the original Wells, modified Wells, simplified Wells, revised Geneva, and simplified revised Geneva models. Discriminative ability was comparable for all models (range of C statistic 0.75-0.80). Sensitivity ranged from 88% (simplified revised Geneva) to 96% (simplified Wells) and specificity from 48% (revised Geneva) to 53% (simplified revised Geneva). Efficiency of all models was between 43% and 48%. Differences were observed between failure rates, especially between the simplified Wells and the simplified revised Geneva models (failure rates 1.2% (95% confidence interval 0.2% to 3.3%) and 3.1% (1.4% to 5.9%), respectively; absolute difference -1.98% (-3.33% to -0.74%)). Irrespective of the diagnostic prediction model used, three patients were incorrectly classified as having low probability of pulmonary embolism; pulmonary embolism was diagnosed only after referral to secondary care. CONCLUSIONS: Five diagnostic pulmonary embolism prediction models that are easily applicable in primary care were validated in this setting. Whereas efficiency was comparable for all rules, the Wells rules gave the best performance in terms of lower failure rates.

Self-reported adherence to anticoagulation and its determinants using the Morisky medication adherence scale.

BACKGROUND: Direct oral anticoagulants (DOACs) are used for treatment of venous thromboembolism (VTE) and stroke prevention in atrial fibrillation (AF). Given the shorter half-life and lack of laboratory monitoring compared to vitamin-K antagonists (VKAs), adequate adherence to DOACs is important. Reported anticoagulation adherence is unclear in clinical practice. OBJECTIVES: To assess self-reported anticoagulation adherence in a tertiary center anticoagulation clinic. PATIENTS/METHODS: Cross-sectional study of patients on oral anticoagulants (VKAs, rivaroxaban, dabigatran and apixaban). Anticoagulation adherence was assessed using the 4-item Morisky score. Baseline characteristics were evaluated for association with adherence. RESULTS: Five hundred patients completed the survey; 74% were on VKAs and 26% on DOACs: rivaroxaban 102 (79%); dabigatran 26 (19%); apixaban 2 (2%). Main indications for anticoagulation were VTE (72%) and AF (18%). Self-reported anticoagulation adherence using the 4-item Morisky scale was 56.2% for patients on VKAs and 57.1% for patients on DOACs. Predictors of anticoagulation adherence were age (OR=1.02; 95% CI:1.01-1.03), female gender (OR=1.58; 95% CI:1.10-2.27), use of additional oral medications (OR=2.78; 95% CI:1.67-4.63), and retired employment status (OR=2.31; 95% CI:1.51-3.55). In backward selection multivariate analyses age, female gender and use of other oral medications remained significantly associated with anticoagulation adherence. CONCLUSIONS: Self-reported anticoagulation adherence was similar between VKAs and DOACs. Until laboratory assays are universally available to evaluate DOAC adherence, physicians should emphasize the importance of anticoagulation adherence at each patient encounter. The Morisky scale provides simple assessment of anticoagulation adherence; however it has not yet been validation for this purpose.

Thromboembolic resolution assessed by CT pulmonary angiography after treatment for acute pulmonary embolism.

The systematic assessment of residual thromboembolic obstruction after treatment for acute pulmonary embolism (PE) has been understudied. This assessment is of potential clinical importance, should clinically suspected recurrent PE occur, or as tool for risk stratification of cardiopulmonary complications or recurrent venous thromboembolism (VTE). This study aimed to assess the rate of PE resolution and its implications for clinical outcome. In this prospective, multi-center cohort study, 157 patients with acute PE diagnosed by CT pulmonary angiography (CTPA) underwent follow-up CTPA-imaging after six months of anticoagulant treatment. Two expert thoracic radiologists independently assessed the presence of residual thromboembolic obstruction. The degree of obstruction at baseline and follow-up was calculated using the Qanadli obstruction index. All patients were followed-up for 2.5 years. At baseline, the median obstruction index was 27.5 %. After six months of treatment, complete PE resolution had occurred in 84.1 % of the patients (95 % confidence interval (CI): 77.4-89.4 %). The median obstruction index of the 25 patients with residual thrombotic obstruction was 5.0 %. During follow-up, 16 (10.2 %) patients experienced recurrent VTE. The presence of residual thromboembolic obstruction was not associated with recurrent VTE (adjusted hazard ratio: 0.92; 95 % CI: 0.2-4.1).This study indicates that the incidence of residual thrombotic obstruction following treatment for PE is considerably lower than currently anticipated. These findings, combined with the absence of a correlation between residual thrombotic obstruction and recurrent VTE, do not support the routine use of follow-up CTPA-imaging in patients treated for acute PE.

Treatment of pulmonary embolism with rivaroxaban: outcomes by simplified Pulmonary Embolism Severity Index score from a post hoc analysis of the EINSTEIN PE study.

OBJECTIVES: The objective was to assess adverse outcomes in relation to the simplified Pulmonary Embolism Severity Index (PESI) score in patients treated with rivaroxaban or standard therapy in the phase III EINSTEIN PE study and to evaluate the utility of the simplified PESI score to identify low-risk pulmonary embolism (PE) patients. METHODS: A post hoc analysis of EINSTEIN PE data was performed to assess the efficacy and safety of rivaroxaban in patients with a range of simplified PESI scores. Recurrent venous thromboembolism, fatal PE, all-cause mortality, and major bleeding were stratified by simplified PESI scores of 0, 1, or ≥2 and according to treatment period at 7, 14, 30, and 90 days and at the end of the full intended treatment period. RESULTS: Simplified PESI scores could be calculated in 4,831 of the 4,832 randomized patients; of those, 53.6, 36.7, and 9.7% had PESI scores of 0, 1, and ≥2, respectively. Among patients with simplified PESI scores of 0 or 1, fatal PE, all-cause mortality, and other adverse outcomes were uncommon within the first 7, 14, and 30 days. Patients with simplified PESI scores of ≥2 had more frequent adverse outcomes. Major bleeding was lower in the rivaroxaban group, particularly in those with simplified PESI scores of 1 or ≥2. CONCLUSIONS: The findings support using risk stratification with the simplified PESI score to identify low-risk patients with PE.

Patient-reported treatment satisfaction with oral rivaroxaban versus standard therapy in the treatment of pulmonary embolism; results from the EINSTEIN PE trial.

INTRODUCTION: Rivaroxaban is an oral, direct Factor Xa inhibitor, approved for the treatment of pulmonary embolism (PE) and deep vein thrombosis (DVT) and the secondary prevention of recurrent PE and DVT as a fixed-dose, monotherapy regimen that does not require initial heparinisation, routine coagulation monitoring or dose adjustment. Approval in this indication was supported by results from EINSTEIN PE, a large, randomised, open-label study that compared rivaroxaban with enoxaparin/vitamin K antagonist (VKA) therapy in patients with acute symptomatic PE with or without DVT. MATERIALS AND METHODS: Patient-reported treatment satisfaction was evaluated in a predefined subanalysis of EINSTEIN PE to enable monitoring and optimisation of patient-reported outcomes and, therefore, patient compliance. As part of EINSTEIN PE, 2,397 patients in seven countries were asked to complete a validated measure of treatment satisfaction, the Anti-Clot Treatment Scale (ACTS) throughout the duration of treatment (up to 12 months). RESULTS: Patients reported greater satisfaction in the rivaroxaban treatment arm as compared with the enoxaparin/VKA treatment arm. Treatment with rivaroxaban was reported as being significantly less burdensome than enoxaparin/VKA therapy, and the benefits of treatment were significantly greater. CONCLUSION: Rivaroxaban treatment resulted in improved treatment satisfaction compared with enoxaparin/VKA in PE patients, particularly in reducing patient-reported anticoagulation burden.

Alternative diagnoses in patients in whom the GP considered the diagnosis of pulmonary embolism.

INTRODUCTION: Pulmonary embolism (PE) often presents with nonspecific symptoms and may be an easily missed diagnosis. When the differential diagnosis includes PE, an empirical list of frequently occurring alternative diagnoses could support the GP in diagnostic decision making. OBJECTIVES: To identify common alternative diagnoses in patients in whom the GP suspected PE but in whom PE could be ruled out. To investigate how the Wells clinical decision rule for PE combined with a point-of-care d-dimer test is associated with these alternative diagnoses. METHODS: Secondary analysis of the Amsterdam Maastricht Utrecht Study on thrombo-Embolism (Amuse-2) study, which validated the Wells PE rule combined with point-of-care d-dimer testing in primary care. All 598 patients had been referred to and diagnosed in secondary care. All diagnostic information was retrieved from the GPs' medical records. RESULTS: In 516 patients without PE, the most frequent alternative diagnoses were nonspecific thoracic pain/dyspnoea (42.6%), pneumonia (13.0%), myalgia (11.8%), asthma/chronic obstructive pulmonary disease (4.8%), panic disorder/hyperventilation (4.1%) and respiratory tract infection (2.3%). Pneumonia occurred almost as frequent as PE. Patients without PE with either a positive Wells rule (>4) or a positive d-dimer test, were more often (odds ratio = 2.1) diagnosed with a clinically relevant disease than patients with a negative Wells rule and negative d-dimer test. CONCLUSION: In primary care patients suspected of PE, the most common clinically relevant diagnosis other than PE was pneumonia. A positive Wells rule or a positive d-dimer test are not only positively associated with PE, but also with a high probability of other clinically relevant disease.

Diagnostic outcome management study in patients with clinically suspected recurrent acute pulmonary embolism with a structured algorithm.

INTRODUCTION: The value of diagnostic strategies in patients with clinically suspected recurrent pulmonary embolism (PE) has not been established. The aim was to determine the safety of a simple diagnostic strategy using the Wells clinical decision rule (CDR), quantitative D-dimer testing and computed tomography pulmonary angiography (CTPA) in patients with clinically suspected acute recurrent PE. MATERIALS AND METHODS: Multicenter clinical outcome study in 516 consecutive patients with clinically suspected acute recurrent PE without using anticoagulants. RESULTS: An unlikely clinical probability (Wells rule 4 points or less) was found in 182 of 516 patients (35%), and the combination of an unlikely CDR-score and normal D-dimer result excluded PE in 88 of 516 patients (17%), without recurrent venous thromboembolism (VTE) during 3month follow-up (0%; 95% CI 0.0-3.4%). CTPA was performed in all other patients and confirmed recurrent PE in 172 patients (overall prevalence of PE 33%) and excluded PE in the remaining 253 patients (49%). During follow-up, seven of these 253 patients returned with recurrent VTE (2.8%; 95% CI 1.2-5.5%), of which in one was fatal (0.4 %; 95 % CI 0.02-1.9%). The diagnostic algorithm was feasible in 98% of patients. CONCLUSIONS: A diagnostic algorithm consisting of a clinical decision rule, D-dimer test and CTPA is effective in the management of patients with clinically suspected acute recurrent PE. CTPA provides reasonable safety in excluding acute recurrent PE in patients with a likely clinical probability or an elevated D-dimer test for recurrent PE, with a low risk for fatal PE at follow-up.

Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study.

IMPORTANCE: D-dimer measurement is an important step in the diagnostic strategy of clinically suspected acute pulmonary embolism (PE), but its clinical usefulness is limited in elderly patients. OBJECTIVE: To prospectively validate whether an age-adjusted D-dimer cutoff, defined as age × 10 in patients 50 years or older, is associated with an increased diagnostic yield of D-dimer in elderly patients with suspected PE. DESIGN, SETTINGS, AND PATIENTS: A multicenter, multinational, prospective management outcome study in 19 centers in Belgium, France, the Netherlands, and Switzerland between January 1, 2010, and February 28, 2013. INTERVENTIONS: All consecutive outpatients who presented to the emergency department with clinically suspected PE were assessed by a sequential diagnostic strategy based on the clinical probability assessed using either the simplified, revised Geneva score or the 2-level Wells score for PE; highly sensitive D-dimer measurement; and computed tomography pulmonary angiography (CTPA). Patients with a D-dimer value between the conventional cutoff of 500 µg/L and their age-adjusted cutoff did not undergo CTPA and were left untreated and formally followed-up for a 3-month period. MAIN OUTCOMES AND MEASURES: The primary outcome was the failure rate of the diagnostic strategy, defined as adjudicated thromboembolic events during the 3-month follow-up period among patients not treated with anticoagulants on the basis of a negative age-adjusted D-dimer cutoff result. RESULTS: Of the 3346 patients with suspected PE included, the prevalence of PE was 19%. Among the 2898 patients with a nonhigh or an unlikely clinical probability, 817 patients (28.2%) had a D-dimer level lower than 500 µg/L (95% CI, 26.6%-29.9%) and 337 patients (11.6%) had a D-dimer between 500 µg/L and their age-adjusted cutoff (95% CI, 10.5%-12.9%). The 3-month failure rate in patients with a D-dimer level higher than 500 µg/L but below the age-adjusted cutoff was 1 of 331 patients (0.3% [95% CI, 0.1%-1.7%]). Among the 766 patients 75 years or older, of whom 673 had a nonhigh clinical probability, using the age-adjusted cutoff instead of the 500 µg/L cutoff increased the proportion of patients in whom PE could be excluded on the basis of D-dimer from 43 of 673 patients (6.4% [95% CI, 4.8%-8.5%) to 200 of 673 patients (29.7% [95% CI, 26.4%-33.3%), without any additional false-negative findings. CONCLUSIONS AND RELEVANCE: Compared with a fixed D-dimer cutoff of 500 µg/L, the combination of pretest clinical probability assessment with age-adjusted D-dimer cutoff was associated with a larger number of patients in whom PE could be considered ruled out with a low likelihood of subsequent clinical venous thromboembolism. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01134068.

Quality of life after pulmonary embolism as assessed with SF-36 and PEmb-QoL.

INTRODUCTION: Although quality of life (QoL) is recognized as an important indicator of the course of a disease, it has rarely been addressed in studies evaluating the outcome of care for patients with pulmonary embolism (PE). This study primarily aimed to evaluate the QoL of patients with acute PE in comparison to population norms and to patients with other cardiopulmonary diseases, using a generic QoL questionnaire. Secondary, the impact of time period from diagnosis and clinical patient characteristics on QoL was assessed, using a disease-specific questionnaire. METHODS: QoL was assessed in 109 consecutive out-patients with a history of objectively confirmed acute PE (mean age 60.4 ± 15.0 years, 56 females), using the generic Short Form-36 (SF-36) and the disease specific Pulmonary Embolism Quality of Life questionnaire (PEmb-QoL). The score of the SF-36 were compared with scores of the general Dutch population and reference populations with chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), a history of acute myocardial infarction (AMI), derived from the literature. Scores on the SF-35 and PEmb-QoL were used to evaluate QoL in the short-term and long-term clinical course of patients with acute PE. In addition, we examined correlations between PEmb-QoL scores and clinical patient characteristics. RESULTS: Compared to scores of the general Dutch population, scores of PE patients were worse on several subscales of the SF-36 (social functioning, role emotional, general health (P<0.001), role physical and vitality (P<0.05)). Compared to patients with COPD and CHF, patients with PE scored higher (=better) on all subscales of the SF-36 (P ≤ 0.004) and had scores comparable with patients with AMI the previous year. Comparing intermediately assessed QoL with QoL assessed in long-term follow-up, PE patients scored worse on SF-36 subscales: physical functioning, social functioning, vitality (P<0.05), and on the PEmb-QoL subscales: emotional complaints and limitations in ADL (P ≤ 0.03). Clinical characteristics did not correlate with QoL as measured by PEmb-QoL. CONCLUSION: Our study demonstrated an impaired QoL in patients after treatment of PE. The results of this study provided more knowledge about QoL in patients treated for PE.

Impact of delay in clinical presentation on the diagnostic management and prognosis of patients with suspected pulmonary embolism.

RATIONALE: The nonspecific clinical presentation of pulmonary embolism (PE) frequently leads to delay in its diagnosis. OBJECTIVES: This study aimed to assess the impact of delay in presentation on the diagnostic management and clinical outcome of patients with suspected PE. METHODS: In 4,044 consecutive patients with suspected PE, patients presenting more than 7 days from the onset of symptoms were contrasted with those presenting within 7 days as regards the safety of excluding PE on the basis of a clinical decision rule combined with D-dimer testing. Patients were followed for 3 months to assess the rates of recurrent venous thromboembolism and mortality. MEASUREMENTS AND MAIN RESULTS: A delayed presentation (presentation >7 d) was present in 754 (18.6%) of the patients. The failure rate of an unlikely clinical probability and normal D-dimer test was 0.5% (95% confidence interval [CI], 0.01-2.7) for patients with and 0.5% (95% CI, 0.2-1.2) for those without diagnostic delay. D-dimer testing yielded a sensitivity of 99% (95% CI, 96-99%) and 98% (95% CI, 97-99%) in these groups, respectively. Patients with PE with diagnostic delay more frequently had centrally located PE (41% vs. 26%; P < 0.001). The cumulative rates of recurrent venous thromboembolism (4.6% vs. 2.7%; P = 0.14) and mortality (7.6% vs. 6.6%; P = 0.31) were not different for patients with and without delayed presentation. CONCLUSIONS: PE can be safely excluded based on a clinical decision rule and D-dimer testing in patients with a delayed clinical presentation. A delayed presentation for patients who survived acute PE was associated with a more central PE location, although this did not affect the clinical outcome at 3 months.

The additional value of the CRP test in patients in whom the primary care physician excluded pulmonary embolism.

BACKGROUND: After excluding pulmonary embolism (PE) with an unlikely Wells-decision rule and a negative D-dimer test, the general practitioner still has to differentiate between clinically relevant and clinically non-relevant diseases accounting for the presented symptoms. A negative D-dimer test makes clinically relevant disease less likely. The C-reactive protein (CRP) test could be of additional value to make this differentiation. OBJECTIVES: To assess whether an unlikely Wells-decision rule in combination with a negative point of care D-dimer test not only can safely exclude PE but also, in combination with a negative CRP-test, any other clinically relevant disease. METHODS: We used data of a prospective study including 598 primary care patients suspected of pulmonary embolism. We included all patients, referred to secondary care for reference testing, with an unlikely Wells-decision rule and a negative point of care D-dimer test. We included 191 patients and imputed the CRP-test results in 60 patients. Alternative diagnoses were divided in clinically relevant diseases and clinically non-relevant diseases. A ROC-curve was constructed to determine the optimal CRP-cut-off. RESULTS: The optimal CRP cut-off value appeared to be 10 mg/l. A total of 116 patients had a CRP < 10 mg/l of whom 12 patients (10%) had a clinically relevant disease. Two patients (2%) needed hospital admission. A total of 75 patients had a CRP ≥ 10 mg/l of whom 32 patients (43%) had a clinically relevant disease. Fifteen patients (20%) were admitted to hospital. CONCLUSION: The CRP-test is enhancing diagnostic decision making in patients in whom the general practitioner excluded PE.

Concerns in using multi-detector computed tomography for diagnosing pulmonary embolism in daily practice. A cross-sectional analysis using expert opinion as reference standard.

INTRODUCTION: Multi-detector computed tomography (MDCT) is considered to be the reference standard in diagnosing pulmonary embolism (PE). However, two concerns remain. Firstly, with the introduction of MDCT the prevalence of (sub)segmental emboli increased but the clinical implications of these small clots are uncertain. Secondly, we are not well informed about the number of false-positive CT-scans due to the lack of a gold standard. PATIENTS AND METHODS: We used data from a prospective primary care study including patients suspected of pulmonary embolism. CT-scan-reading by the local radiologist in daily care was retrospectively compared with expert reading as reference standard. Final diagnosis was categorized as central/lobar, segmental or subsegmental PE. RESULTS: A total of 79 patients were included. In 3 of 30 patients (10%) diagnosed with PE by the local radiologist the experts refuted the diagnosis. In 7 of 49 patients (14%) not diagnosed with PE by the local radiologist the experts confirmed the presence of PE. The experts diagnosed 17 of 32 PE-patients (53%) with a central or lobar PE. All these 17 patients were also diagnosed with PE by the local radiologist. The experts diagnosed 15 patients with (sub)segmental PE. In 7 of these 15 patients (47%) the local radiologist refuted PE. CONCLUSIONS: Accuracy of MDCT using the expert radiologist as reference standard is not optimal. On the one hand it shows 10% false-positives exposing patients to anticoagulant treatment unnecessarily. On the other hand small emboli seem to be missed although the clinical implications of this finding are not fully clear.

Benchmark for time in therapeutic range in venous thromboembolism: a systematic review and meta-analysis.

INTRODUCTION: The percentage of time within the target INR range 2.0 to 3.0 (TTR) in patients treated with vitamin K antagonists varies considerably among efficacy-studies of novel anticoagulants. In order to properly asses the quality of anticoagulant control in upcoming cost-effectiveness studies and real life registries this systematic review reports a benchmark of TTR for different treatment durations in patients with venous thromboembolism and discusses ways to calculate TTR. METHODS: Medline and Embase were searched for studies published between January 1990 and May 2012. Randomized controlled trials and cohort studies reporting the TTR in patients with objectively confirmed venous thromboembolism treated with vitamin K antagonists (VKA) were eligible. Duplicate reports, studies only reporting INR during initial treatment or with VKA treatment less than 3 months were excluded. Three authors assessed trials for inclusion and extracted data independently. Discrepancies were resolved by discussion between the reviewers. A meta-analysis was performed by calculating a weighted mean, based on the number of participants in each included study, for each time-period in which the TTR was measured since the confirmation of the diagnosis of VTE. RESULTS: Forty studies were included (26064 patients). The weighted means of TTR were 54.0% in the first month since the start of treatment, 55.6% in months 1 to 3, 60.0% in months 2 to 3, 60.0% in the months 1 to 6+ and 75.2% in months 4 to 12+. Five studies reported TTR in classes. The INR in these studies was ≥ 67% of time in therapeutic range in 72.0% of the patients. CONCLUSION: Reported quality of VKA treatment is highly dependent on the time-period since the start of treatment, with TTR ranging from approximately 56% in studies including the 1(st) month to 75% in studies excluding the first 3 months.