Clinical decision rules in primary care: necessary investments for sustainable healthcare.

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.

Performance of C-Reactive Protein, Procalcitonin, TAT Complex, and Factor VIII in Addition to D-Dimer in the Exclusion of Venous Thromboembolism in Primary Care Patients.

BACKGROUND: In primary care, D-dimer-combined with a clinical assessment-is recommended for ruling-out venous thromboembolism (VTE). However, D-dimer testing frequently yields false-positive results, notably in the elderly, and the search for novel biomarkers thus continues. We assessed the added diagnostic value of 4 promising laboratory tests. METHODS: Plasma samples from 256 primary care patients suspected of VTE were collected. We explored added value (beyond D-dimer) of C-reactive protein (CRP), procalcitonin (PCT), thrombin-antithrombin III complex (TAT-c), and factor VIII (FVIII). Diagnostic performance of these biomarkers was assessed univariably and by estimating their area under the receiver operating curve (AUC). Added diagnostic potential beyond D-dimer testing was assessed using multivariable logistic regression. RESULTS: Plasma samples of 237 VTE-suspected patients were available for analysis-36 patients (25%) confirmed deep vein thrombosis, 11 patients (12%) pulmonary embolism. Apart from D-dimer, only CRP, and FVIII levels appeared to be higher in patients with VTE compared to patients without VTE. The AUCs for these 3 markers were 0.76 (95% CI: 0.69-0.84) and 0.75 (95% CI: 0.68-0.83), respectively, whereas the AUC for D-dimer was 0.90 (95% CI: 0.86-0.94). Combining these biomarkers in a multivariable logistic model with D-dimer did not improve these AUCs meaningfully. CONCLUSIONS: In our dataset, we were unable to demonstrate any added diagnostic performance beyond D-dimer testing of novel biomarkers in patients suspected of VTE in primary care. As such, D-dimer testing appears to remain the best choice in the exclusion of clinically suspected VTE in this setting. TRIAL REGISTRATION: Netherlands Trial Register NL5974. (METC protocol number: 16-356/M; NL56475.041.16.).

Real-life impact of clinical prediction rules for venous thromboembolism in primary care: a cross-sectional cohort study.

OBJECTIVE: Clinical prediction rules (CPRs) followed by D-dimer testing were shown to safely rule out venous thromboembolism (VTE) in about half of all suspected patients in controlled and experienced study settings. Yet, its real-life impact in primary care is unknown. The aim of this study was to determine the real-life impact of CPRs for suspected VTE in primary care. DESIGN: Cross-sectional cohort study. SETTING: Primary care in the Netherlands. PARTICIPANTS: Patients with suspected deep venous thrombosis (n=993) and suspected pulmonary embolism (n=484). INTERVENTIONS: General practitioners received an educational instruction on how to use CPRs in suspected VTE. We did not rectify incorrect application of the CPR in order to mimic daily clinical care. MAIN OUTCOME MEASURES: Primary outcomes were the diagnostic failure rate, defined as the 3-month incidence of VTE in the non-referred group, and the efficiency, defined as the proportion of non-referred patients in the total study population. Secondary outcomes were determinants for and consequences of incorrect application of the CPRs. RESULTS: In 267 of the included 1477 patients, VTE was confirmed. When CPRs were correctly applied, the failure rate was 1.51% (95% CI 0.77 to 2.86), and the efficiency was 58.1% (95% CI 55.2 to 61.0). However, the CPRs were incorrectly applied in 339 patients, which resulted in an increased failure rate of 3.31% (95% CI 1.07 to 8.76) and a decreased efficiency of 35.7% (95% CI 30.6 to 41.1). The presence of concurrent heart failure increased the likelihood of incorrect application (adjusted OR 3.26; 95% CI 1.47 to 7.21). CONCLUSIONS: Correct application of CPRs for VTE in primary care is associated with an acceptable low failure rate at a high efficiency. Importantly, in nearly a quarter of patients, the CPRs were incorrectly applied that resulted in a higher failure rate and a considerably lower efficiency.

Effect of tailoring anticoagulant treatment duration by applying a recurrence risk prediction model in patients with venous thromboembolism compared to usual care: A randomized controlled trial.

BACKGROUND: Patients with unprovoked (i.e., without the presence of apparent transient risk factors such as recent surgery) venous thromboembolism (VTE) are at risk of recurrence if anticoagulants are stopped after 3-6 months, yet their risk remains heterogeneous. Thus, prolonging anticoagulant treatment should be considered in high-risk patients, whereas stopping is likely preferred in those with a low predicted risk. The Vienna Prediction Model (VPM) could aid clinicians in estimating this risk, yet its clinical effects and external validity are currently unknown. The aim of this study was to investigate the clinical impact of this model on reducing recurrence risk in patients with unprovoked VTE, compared to usual care. METHODS AND FINDINGS: In a randomized controlled trial, the decision to prolong or stop anticoagulant treatment was guided by predicted recurrence risk using the VPM (n = 441), which was compared with usual care (n = 442). Patients with unprovoked VTE were recruited from local thrombosis services in the Netherlands (in Utrecht, Harderwijk, Ede, Amersfoort, Zwolle, Hilversum, Rotterdam, Deventer, and Enschede) between 22 July 2011 and 30 November 2015, with 24-month follow-up complete for all patients by early 2018. The primary outcome was recurrent VTE during 24 months of follow-up. Secondary outcomes included major bleeding and clinically relevant non-major (CRNM) bleeding. In the total study population of 883 patients, mean age was 55 years, and 507 (57.4%) were men. A total of 96 recurrent VTE events (10.9%) were observed, 46 in the intervention arm and 50 in the control arm (risk ratio 0.92, 95% CI 0.63-1.35, p = 0.67). Major bleeding occurred in 4 patients, 2 in each treatment arm, whereas CRNM bleeding occurred in 20 patients (12 in intervention arm versus 8 in control arm). The VPM showed good discriminative power (c-statistic 0.76, 95% CI 0.69-0.83) and moderate to good calibration, notably at the lower spectrum of predicted risk. For instance, in 284 patients with a predicted risk of >2% to 4%, the observed rate of recurrence was 2.5% (95% CI 0.7% to 4.3%). The main limitation of this study is that it did not enroll the preplanned number of 750 patients in each study arm due to declining recruitment rate. CONCLUSIONS: Our results show that application of the VPM in all patients with unprovoked VTE is unlikely to reduce overall recurrence risk. Yet, in those with a low predicted risk of recurrence, the observed rate was also low, suggesting that it might be safe to stop anticoagulant treatment in these patients. TRIAL REGISTRATION: Netherlands Trial Register NTR2680.

Analytical performance and user-friendliness of five novel point-of-care D-dimer assays.

D-dimer testing combined with a clinical assessment has become a standard pathway for ruling-out venous thromboembolism (VTE). Recently, novel Point-of-Care (POC) D-dimer assays have been introduced, enabling low-volume blood sampling for rapid exclusion of VTE in a one-step procedure. We assessed the analytical validity and user-friendliness of a set of these novel POC D-dimer assays, and compared the results with a standard laboratory assay. Plasma samples were run on our reference assay (STA-Liatest D-di PLUS®) and five POC assays: Nano-Checker 710®, AFIAS-1®; iChroma-II®; Standard F200® and Hipro AFS/1®). After evaluating imprecision, Pearson Product-Moment correlation coefficients were calculated, Passing Bablok regression was performed and Bland-Altman plots were generated. User-friendliness was evaluated using the System Usability Scale (SUS). A set of 238 plasma samples of patients clinically suspected of VTE in general practice was available for analysis. Only one POC D-dimer assay (Nano-Checker 710) demonstrated an insufficient degree of imprecision. Pearson correlation coefficients and mean biases ranged from 0.68 to 0.93 and -165 to -53 µg/L respectively, and concordance with our reference assay varied from 71.8% to 89.5% using a 500 µg/L cut-off point. While we found considerable variation in overall user-friendliness, most devices were judged easy to use. In view of our findings regarding analytical performance and user-friendliness, we consider most of the novel POC D-dimer assays can be used in settings outside of the laboratory such as general practice, combining the possibility of multi-testing with low-volume capillary blood sampling and processing times of less than 15 min.

Integrated management of atrial fibrillation in primary care: results of the ALL-IN cluster randomized trial.

AIMS: To evaluate whether integrated care for atrial fibrillation (AF) can be safely orchestrated in primary care. METHODS AND RESULTS: The ALL-IN trial was a cluster randomized, open-label, pragmatic non-inferiority trial performed in primary care practices in the Netherlands. We randomized 26 practices: 15 to the integrated care intervention and 11 to usual care. The integrated care intervention consisted of (i) quarterly AF check-ups by trained nurses in primary care, also focusing on possibly interfering comorbidities, (ii) monitoring of anticoagulation therapy in primary care, and finally (iii) easy-access availability of consultations from cardiologists and anticoagulation clinics. The primary endpoint was all-cause mortality during 2 years of follow-up. In the intervention arm, 527 out of 941 eligible AF patients aged ≥65 years provided informed consent to undergo the intervention. These 527 patients were compared with 713 AF patients in the control arm receiving usual care. Median age was 77 (interquartile range 72-83) years. The all-cause mortality rate was 3.5 per 100 patient-years in the intervention arm vs. 6.7 per 100 patient-years in the control arm [adjusted hazard ratio (HR) 0.55; 95% confidence interval (CI) 0.37-0.82]. For non-cardiovascular mortality, the adjusted HR was 0.47 (95% CI 0.27-0.82). For other adverse events, no statistically significant differences were observed. CONCLUSION: In this cluster randomized trial, integrated care for elderly AF patients in primary care showed a 45% reduction in all-cause mortality when compared with usual care.

Integrated management of atrial fibrillation including tailoring of anticoagulation in primary care: study design of the ALL-IN cluster randomised trial.

INTRODUCTION: In our ageing society, we are at the merge of an expected epidemic of atrial fibrillation (AF). AF management requires an integrated approach, including rate or rhythm control, stroke prevention with anticoagulation and treatment of comorbidities such as heart failure or type 2 diabetes. As such, primary care seems to be the logical healthcare setting for the chronic management of patients with AF. However, primary care has not yet played a dominant role in AF management, which has been in fact more fragmented between different healthcare providers. This fragmentation might have contributed to high healthcare costs. To demonstrate the feasibility of managing AF in primary care, studies are needed that evaluate the safety and (cost-)effectiveness of integrated AF management in primary care. METHODS AND ANALYSIS: The ALL-IN trial is a multicentre, pragmatic, cluster randomised, non-inferiority trial performed in primary care practices in a suburban region in the Netherlands. We aim to include a minimum of 1000 patients with AF aged 65 years or more from around 18 to 30 practices. Duration of the study is 2 years. Practices will be randomised to either the intervention arm (providing integrated AF management, involving a trained practice nurse and collaboration with secondary care) or the control arm (care as usual). The primary endpoint is all-cause mortality. Secondary endpoints are cardiovascular mortality, (non)-cardiovascular hospitalisation, major adverse cardiac events, stroke, major bleeding, clinically relevant non-major bleeding, quality of life and cost-effectiveness. ETHICS AND DISSEMINATION: The protocol was approved by the Medical Ethical Committee of the Isala Hospital Zwolle, the Netherlands. Patients in the intervention arm will be asked informed consent for participating in the intervention. Results are expected in 2019 and will be disseminated through both national and international journals and conferences. TRIAL REGISTRATION NUMBER: This trial is registered at the Netherlands Trial Register (NTR5532).

Clinical characteristics associated with diagnostic delay of pulmonary embolism in primary care: a retrospective observational study.

OBJECTIVES: To evaluate the extent of delay in the diagnosis of pulmonary embolism (PE) in primary care, and to identify determinants that are associated with such diagnostic delay. DESIGN: Retrospective observational study. SETTING: 6 primary care practices across the Netherlands. PARTICIPANTS: Data from patients with an objectively confirmed diagnosis of PE (International Classification of Primary Care (ICPC) code K93) up to June 2015 were extracted from the electronic medical records. For all these PE events, we reviewed all consultations with their general practitioner (GP) and scored any signs and symptoms that could be attributed to PE in the 3 months prior to the event. Also, we documented actual comorbidity and the diagnosis considered initially. PRIMARY AND SECONDARY OUTCOME MEASURES: Delay was defined as a time gap of >7 days between the first potentially PE-related contact with the GP and the final PE diagnosis. Multivariable logistic regression analysis was performed to identify independent determinants for delay. RESULTS: In total, 180 incident PE cases were identified, of whom 128 patients had 1 or more potential PE-related contact with their GP within the 3 months prior to the diagnosis. Based on our definition, in 33 of these patients (26%), diagnostic delay was observed. Older age (age >75 years; OR 5.1 (95% CI 1.8 to 14.1)) and the absence of chest symptoms (ie, chest pain or pain on inspiration; OR 5.4 (95% CI 1.9 to 15.2)) were independent determinants for diagnostic delay. A respiratory tract infection prior to the PE diagnosis was reported in 13% of cases without delay, and in 33% of patients with delay (p=0.008). CONCLUSIONS: Diagnostic delay of more than 7 days in the diagnosis of PE is common in primary care, especially in the elderly, and if chest symptoms, like pain on inspiration, are absent.

Multi-faceted implementation strategy to increase use of a clinical guideline for the diagnosis of deep venous thrombosis in primary care.

Background: A clinical decision rule (CDR), combined with a negative D-dimer test, can safely rule out deep venous thrombosis (DVT) in primary care. This strategy is recommended by guidelines, yet uptake by GPs is low. Objective: To evaluate a multi-faceted implementation strategy aimed at increased use of the guideline recommended CDR plus D-dimer test in primary care patients with suspected DVT. Methods: This multi-faceted implementation strategy consisted of educational outreach visits, financial reimbursements and periodical newsletters. 217 Dutch GPs (implementation group) received this strategy and included patients. Effectiveness was measured through the following patient-level outcomes: (i) proportion of non-referred patients, (ii) proportion of missed DVT cases within this group and (iii) the proportion of patients in whom the guideline was applied incorrectly. Implementation outcomes ('acceptability', 'feasibility', 'fidelity' and 'sustainability') were assessed with an online questionnaire. Patient-level outcomes were compared with those of patients included by 450 GPs, uninformed about the study's purposes providing information about usual care. Results: 336 (54%) of 619 analyzable implementation group patients were not referred, missing 6 [1.8% (95% confidence interval 0.7% to 3.9%)] DVT cases. Incorrect guideline use was observed in 199 patients (32%). Self-reported acceptability, feasibility and expected sustainability were high. Guideline use increased from 42% to an expected continuation of use of 91%. Only 32 usual care GPs included 62 patients, making formal comparison unreliable. Conclusions: This multi-faceted implementation strategy safely reduced patient referral to secondary care, despite frequently incorrect application of the guideline and resulted in high acceptability, feasibility and expected sustainability.

Clinical evaluation of eight different D-dimer tests for the exclusion of deep venous thrombosis in primary care patients.

D-dimer tests are an essential element in the diagnostic work-up of deep venous thrombosis (DVT). However, the poor standardization amongst assays necessitates clinical validation before implementation in daily practice. We therefore evaluated the analytical and diagnostic performance of eight D-dimer tests in a representative group of 290 prospectively identified consecutive primary care patients with suspected DVT. Seven quantitative D-dimer assays, and a qualitative test, Simplify, were evaluated. Correlation between assays was generally poor and several assays showed a significant bias in the method comparison. Nevertheless, the Vidas D-dimer, Innovance D-dimer (CA1500 and BCS), Pathfast D-dimer, and HemosIL HS500 (ACL TOP), all displayed 100% (95% CI: 85-100%) sensitivity. Tina-quant (Modular), AQT90 D-dimer, and Liatest (STA(®)) D-dimer tests showed a slightly lower sensitivity of 95% (78-100%). and the Simplify test reached a sensitivity of 91% (72-99%) that was further improved in combination with a clinical decision rule to 95% (76-100%). In concert with the low (8.2%) prevalence of proximal DVT, diagnosed by compression ultrasonography, in our study, all test reached a negative predictive value (NPV) of at least 99%. The user friendliness of the assays differed mainly by stability of reagents, calibration frequency, time required to obtain a test result and costs of a test. In conclusion, despite considerable analytical differences, in our low-risk population all tests evaluated displayed an excellent NPV. In combination with a validated clinical decision rule to identify low-risk patients, even a straightforward POC solution could safely and cost-efficiently rule out DVT.

The cost-effectiveness of point-of-care D-dimer tests compared with a laboratory test to rule out deep venous thrombosis in primary care.

OBJECTIVE: Point-of-care (POC) D-dimer tests have been developed to exclude deep venous thrombosis quickly and on the spot, but are known to have lower sensitivity compared with laboratory-based tests. Their cost-effectiveness is still unknown. METHODS: We updated and extended a previously published Markov model to assess the cost-effectiveness of POC D-dimer tests ('Simplify', 'Cardiac', 'Triage' and 'Nycocard') compared with a laboratory-based latex assay to diagnose deep venous thrombosis in primary care. RESULTS: The 'Laboratory' strategy resulted in 6.986 quality-adjusted life years at the cost of €8354 per patient. All POC D-dimer tests resulted in health outcomes similar to the 'Laboratory' strategy. The 'Simplify' strategy maximized cost savings (-€155 [95% CI: -€246 to -€83]). CONCLUSIONS: POC D-dimer tests yield similar health outcomes as laboratory-based testing procedures but can be performed more easily and at lower costs. Therefore, these tests are an alternative to laboratory-based testing and might be considered for exclusion of deep venous thrombosis in primary care.

Validation of the Oudega diagnostic decision rule for diagnosing deep vein thrombosis in frail older out-of-hospital patients.

OBJECTIVE: We aimed to validate the Oudega diagnostic decision rule-which was developed and validated among younger aged primary care patients-to rule-out deep vein thrombosis (DVT) in frail older outpatients. METHODS: In older patients (>60 years, either community dwelling or residing in nursing homes) with clinically suspected DVT, physicians recorded the score on the Oudega rule and d-dimer test. DVT was confirmed with a composite reference standard including ultrasonography examination and 3-month follow-up. The proportion of patients with a very low probability of DVT according to the Oudega rule (efficiency), and the proportion of patients with symptomatic venous thromboembolism during 3 months follow-up within this 'very low risk' group (failure rate) was calculated. RESULTS: DVT occurred in 164 (47%) of the 348 study participants (mean age 81 years, 85% residing in nursing homes). The probability of DVT was very low in 69 patients (Oudega score ≤3 points plus a normal d-dimer test; efficiency 20%) of whom four had non-fatal DVT (failure rate 5.8%; 2.3-14%). With a simple revised version of the Oudega rule for older suspected patients, 43 patients had a low risk of DVT (12% of the total population) of whom only one had DVT (failure rate 2.3%; 0.4-12%). CONCLUSIONS: In older suspected patients, application of the original Oudega rule to exclude DVT resulted in a higher failure rate as compared to previous studies. A revised and simplified Oudega strategy specifically developed for elderly suspected patients resulted in a lower failure rate though at the expense of a lower efficiency.

Accuracy of the Wells clinical prediction rule for pulmonary embolism in older ambulatory adults.

OBJECTIVES: To determine whether the Wells clinical prediction rule for pulmonary embolism (PE), which produces a point score based on clinical features and the likelihood of diagnoses other than PE, combined with normal D-dimer testing can be used to exclude PE in older unhospitalized adults. DESIGN: Prospective cohort study. SETTING: Primary care and nursing homes. PARTICIPANTS: Older adults (≥60) clinically suspected of having a PE (N = 294, mean age 76, 44% residing in a nursing home). MEASUREMENTS: The presence of PE was confirmed using a composite reference standard including computed tomography and 3-month follow-up. The proportion of individuals with an unlikely risk of PE was calculated according to the Wells rule (≤4 points) plus a normal qualitative point-of-care D-dimer test (efficiency) and the presence of symptomatic PE during 3 months of follow-up within these patients (failure rate). RESULTS: Pulmonary embolism occurred in 83 participants (28%). Eighty-five participants had an unlikely risk according to the Wells rule and a normal D-dimer test (efficiency 29%), five of whom experienced a nonfatal PE during 3 months of follow-up (failure rate = 5.9%, 95% confidence interval (CI) = 2.5-13%). According to a refitted diagnostic strategy for older adults, 69 had a low risk of PE (24%), two of whom had PE (failure rate = 2.9%, 95% CI = 0.8-10%). CONCLUSION: The use of the well-known and widely used Wells rule (original or refitted) does not guarantee safe exclusion of PE in older unhospitalized adults with suspected PE. This may lead to discussion among professionals as to whether the original or revised Wells rule is useful for elderly outpatients.

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.

Decisions to withhold diagnostic investigations in nursing home patients with a clinical suspicion of venous thromboembolism.

BACKGROUND: This study aimed to gather insights in physicians' considerations for decisions to either refer for- or to withhold additional diagnostic investigations in nursing home patients with a suspicion of venous thromboembolism. METHODS: Our study was nested in an observational study on diagnostic strategies for suspected venous thromboembolism in nursing home patients. Patient characteristics, bleeding-complications and mortality were related to the decision to withhold investigations. For a better understanding of the physicians' decisions, 21 individual face-to-face in-depth interviews were performed and analysed using the grounded theory approach. RESULTS: Referal for additional diagnostic investigations was forgone in 126/322 (39.1%) patients with an indication for diagnostic work-up. 'Blind' anticoagulant treatment was initiated in 95 (75.4%) of these patients. The 3 month mortality rates were higher for patients in whom investigations were withheld than in the referred patients, irrespective of anticoagulant treatment (odds ratio 2.45; 95% confidence interval 1.40 to 4.29) but when adjusted for the probability of being referred (i.e. the propensity score), there was no relation of non-diagnosis decisions to mortality (odds ratio 1.75; 0.98 to 3.11). In their decisions to forgo diagnostic investigations, physicians incorporated the estimated relative impact of the potential disease; the potential net-benefits of diagnostic investigations and whether performing investigations agreed with established management goals in advance care planning. CONCLUSION: Referral for additional diagnostic investigations is withheld in almost 40% of Dutch nursing home patients with suspected venous thromboembolism and an indication for diagnostic work-up. We propose that, given the complexity of these decisions and the uncertainty regarding their indirect effects on patient outcome, more attention should be focused on the decision to either use or withhold additional diagnostic tests.

Need for tailored strategies to diagnose venous thrombo-embolism in older primary care patients. Extension of a keynote presentation at the 2012 Wonca Europe conference.

Venous thrombo-embolism (VTE, pulmonary embolism and deep vein thrombosis) is common in the elderly and short-term mortality risk increases with age. Hence, notably in older patients, accurately diagnosing VTE can be lifesaving. However, most clinically suspected individuals turn out to have no VTE after imaging examination. Therefore, many physicians would feel reluctant to refer older patients as this can be very burdensome for these patients. Consequently, it is possible that elderly patients are often not referred for diagnostic work-up (risk of under diagnosis), or that treatment for VTE is initiated without confirmation by further testing (risk of overtreatment). Moreover, anticoagulation treatment of VTE is associated with a higher bleeding risk in the elderly. This bleeding risk might even outweigh the potential benefits in some of these patients. Therefore, availability of an accurate diagnostic strategy to safely exclude, and timely diagnose VTE without the need of burdening referrals in many patients might better serve the needs of older patients. Such strategies have been derived and validated in both primary and secondary care patients suspected of VTE. However, the generalizability of these strategies to older patients may be hampered, and their accuracy has never been tested in elderly populations; this in spite of the high prevalence of VTE and the potential for misdiagnosis and thus mistreatment in these patients. Therefore, we advocate validation and adaptation of current diagnostic strategies for VTE for application in elderly patients.

Safe exclusion of pulmonary embolism using the Wells rule and qualitative D-dimer testing in primary care: prospective cohort study.

OBJECTIVE: To validate the use of the Wells clinical decision rule combined with a point of care D-dimer test to safely exclude pulmonary embolism in primary care. DESIGN: Prospective cohort study. SETTING: Primary care across three different regions of the Netherlands (Amsterdam, Maastricht, and Utrecht). PARTICIPANTS: 598 adults with suspected pulmonary embolism in primary care. INTERVENTIONS: Doctors scored patients according to the seven variables of the Wells rule and carried out a qualitative point of care D-dimer test. All patients were referred to secondary care and diagnosed according to local protocols. Pulmonary embolism was confirmed or refuted on the basis of a composite reference standard, including spiral computed tomography and three months' follow-up. MAIN OUTCOME MEASURES: Diagnostic accuracy (sensitivity and specificity), proportion of patients at low risk (efficiency), number of missed patients with pulmonary embolism in low risk category (false negative rate), and the presence of symptomatic venous thromboembolism, based on the composite reference standard, including events during the follow-up period of three months. RESULTS: Pulmonary embolism was present in 73 patients (prevalence 12.2%). On the basis of a threshold Wells score of ≤ 4 and a negative qualitative D-dimer test result, 272 of 598 patients were classified as low risk (efficiency 45.5%). Four cases of pulmonary embolism were observed in these 272 patients (false negative rate 1.5%, 95% confidence interval 0.4% to 3.7%). The sensitivity and specificity of this combined diagnostic approach was 94.5% (86.6% to 98.5%) and 51.0% (46.7% to 55.4%), respectively. CONCLUSION: A Wells score of ≤ 4 combined with a negative qualitative D-dimer test result can safely and efficiently exclude pulmonary embolism in primary care.