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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.

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.

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.)

ObjectiveClinical 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.DesignCross-sectional cohort study.SettingPrimary care in the Netherlands.ParticipantsPatients with suspected deep venous thrombosis (n=993) and suspected pulmonary embolism (n=484).InterventionsGeneral 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 measuresPrimary 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.ResultsIn 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).ConclusionsCorrect 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.

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 practise 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.

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, Geert-Jan Geersing and colleagues investigate the clinical impact of the Vienna Prediction model on reducing recurrence risk in patients with unprovoked venous thromboembolism, compared to usual care., Author summary Why was this study done? Patients with clots in the leg or lung without a clear explanation are treated with anticoagulants. After the initial treatment phase is complete (after 3–6 months), a relatively large group of patients will then experience new clots if treatment is then discontinued. Physicians struggle with identifying the group of patients in need of prolonged anticoagulant treatment, which can be protective for recurrent clots, yet also inherently introduces bleeding risk. What did the researchers do and find? The researchers performed a randomized trial comparing the use of a prediction tool with usual care. This prediction tool can help identify patients at increased risk of recurrent clots. Treatment can then be tailored accordingly. The study found that, overall, the risk of recurrent clots was not reduced by applying this tool. The prediction tool, however, was able to identify a group of patients with a low risk of recurrent clots. What do these findings mean? On a population level, the researchers were unable to find a difference in the risk of recurrent clots by using this prediction tool. The study, however, did suggest that it might be safe to stop anticoagulant treatment after the initial treatment phase in those with a low predicted risk of recurrent clots.

Inleiding Op afdelingen Spoedeisende Hulp wordt de diagnose ‘longembolie’ regelmatig later dan gewenst vastgesteld of zelfs helemaal gemist. Hoe vaak deze diagnostische vertraging zich voordoet in de huisartsenpraktijk is slecht bekend. Wij onderzochten dit en keken ook welke determinanten met deze vertraging samenhangen. Methode In dit retrospectieve observationele onderzoek bekeken we in zes Nederlandse huisartsenpraktijken alle elektronische patiëntendossiers waarin een longembolie werd gerapporteerd (ICPC-code K93). Van elk dossier noteerden wij het aantal dagen tussen het eerste contact vanwege klachten die kunnen passen bij een longembolie en de uiteindelijke diagnose, de aanwezigheid van specifieke symptomen en eventuele comorbiditeit. Met behulp van logistische regressieanalyse gingen we na welke determinanten geassocieerd waren met een eventuele diagnostische vertraging. Resultaten We includeerden 128 patiënten met een bewezen longembolie. Bij 33 van hen (26%) lagen er meer dan zeven dagen tussen het eerste relevante contact en de diagnose. Factoren die samenhingen met deze diagnostische vertraging waren: leeftijd ouder dan 75 jaar (OR 5,1; 95%-BI 1,8 tot 14,1; p = 0,002) en thoracale klachten zoals pijn op de borst of pijn bij de ademhaling (OR 5,4; 95%-BI 1,9 tot 15,2; p = 0,002). Patiënten bij wie diagnostische vertraging optrad, hadden significant vaker een luchtweginfectie doorgemaakt in de voorafgaande drie maanden (13 vs. 33%; p = 0,008). Conclusie Diagnostische vertraging tussen de eerste klachtenpresentatie en de diagnose ‘longembolie’ komt frequent voor in de huisartsenpraktijk, vooral bij ouderen en wanneer thoracale klachten ontbreken.

Background Guidelines on atrial fibrillation (AF) recommend the CHA2DS2-VASc rule for anticoagulant decision-making, but underuse exists. We studied the impact of an automated decision support on stroke prevention in patients with AF in a cluster randomised trial in general practice. Methods Intervention practices were provided with a CHA2DS2-VASc based anticoagulant treatment recommendation. Reference practices provided care as usual. The primary outcome was incidence of ischaemic stroke, transient ischaemic attack (TIA) and/or thromboembolism (TE). Secondary outcomes were bleeding and the proportion of patients on guideline recommended anticoagulant treatment. Results In total, 1129 AF patients were included in the 19 intervention practices and 1226 AF patients in the 19 reference practices. The median age was 77 (interquartile range (IQR) 68–75) years, the median CHA2DS2-VASc score was 3.0 (IQR 2.0–5.0). Underuse of anticoagulants in patients with CHA2DS2-VASc score ≥ 2 was 6.6%. After a median follow-up of 2.7 years (IQR 2.3–3.0), the incidence rate per 100 person-years of ischaemic stroke/TIA/TE was 1.96 in the intervention group and 1.42 in the reference group (hazard ratio (HR) 1.3, 95% C.I. 0.8–2.1). No difference was observed in the rate of bleeding (0.79 versus 0.82), or in the underuse (7.2% versus 8.2%) or overuse (8.0% versus 7.9%) of anticoagulation. Conclusions In this study in patients with AF in general practice, underuse of anticoagulants was relatively low. Providing practitioners with CHA2DS2-VASc based decision support did not result in a reduction in stroke incidence, affect bleeding risk or anticoagulant over- or underuse.

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 Euro8354 per patient. All POC D-dimer tests resulted in health outcomes similar to the Laboratory' strategy. The Simplify' strategy maximized cost savings (-Euro155 [95% CI: -Euro246 to -Euro83]). 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.

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.

Platelet-activation and agonist-induced platelet aggregation process to the pathogenesis of Infective Endocarditis (IE), bacteremia symptoms or other thrombotic complications and cardiovascular diseases. Activation of platelets by probiotic lactic acid bacteria strains is considered as thrombotic initiative factor contributing to the development and progression of Lactobacillus endocarditis. The main purpose of the current study was to evaluate the immunologic enhancement effect of probiotic strains L. plantarum, L. acidophilus and L. rhamnosus on the activation of blood platelets. Whole fresh blood flow cytometry was used to measure p-selectin expression and fibrinogen binding at basal levels and following stimulation with platelet agonists and probiotic lactic acid bacteria strains. Platelet activation was determined by labelling with FITC-conjugated anti-human fibrinogen and phycoerythrin (PE)- conjugated anti-human CD62p before analysis by flow cytometry. Thrombin Receptor Activator Peptide-6 (TRAP-6) was used as positive control. The percentage of CD62p-positive platelets, FITC-conjugated and the light scatter profiles of the agonist-activated platelets were used to identify the occurrence and degree of platelet activation. Probiotic lactic acid bacteria strains included in this study did not show any effect on spontaneous activation of human blood platelets. These test strains also failed to exacerbate or diminish the platelet activation property when co-incubated with TRAP-6 platelet agonist. Hence, this is the first in vitro report showing the safety of a group of probiotic lactic acid bacteria in terms of their potential to contribute to the pathogenesis of infective endocarditic (IE), bacteremia symptoms or other thrombotic disorders and correlated cardiovascular complications by initiating the platelet activation.

Geersing G-J, Zuithoff P, Kearon C, Anderson D, Ten Cate-Hoek A, Elf J, et al. Uitsluiten van DVT met een klinische beslisregel. Huisarts Wet 2014;57(12):626-8. Huisartsen zien geregeld patienten die mogelijk een trombosebeen hebben. De symptomen van een trombosebeen zijn vaak weinig specifiek. Een groot deel van de patienten bij wie de huisarts aan trombose denkt heeft geen trombosebeen. Om die reden zijn er beslisregels ontwikkeld, die in combinatie met een D-dimeertest, bij een groot deel van de patienten een trombose kunnen uitsluiten. De veiligheid van deze strategie is bewezen voor de meeste patienten, maar er blijft onduidelijkheid bestaan over de veiligheid ervan in bijzondere patientengroepen. Daarom hebben we individuele patientengegevens uit 13 onderzoeken (n = 10.002) gecombineerd en de veiligheid van een beslisregel (in dit geval de Wells-beslisregel) en een D-dimeertest onderzocht om een trombosebeen uit te sluiten bij bijzondere patientengroepen. Ons onderzoek laat zien dat de huisarts bij de meeste patienten veilig en efficient een trombosebeen kan uitsluiten: in 29% van de gevallen (95%-BI 20 tot 40) scoort de patient laag op de beslisregel en is de D-dimeertest ook negatief; de kans op trombose is dan nog slechts 1,2% (95%-BI 0,7 tot 1,8). Bij patienten bij wie tijdens een oncologische behandeling het vermoeden bestaat dat ze een trombosebeen hebben komt deze combinatie van een lage score op de beslisregel en een negatieve D-dimeertest slechts voor in 9% van de gevallen. Ook is de kans op trombose in die groep bijna twee keer zo groot (2,2%). Voor patienten die eerder een trombose hebben doorgemaakt en bij wie sprake kan zijn van een recidief moet een punt worden opgeteld op de Wells-beslisregel om veilig een trombosebeen te kunnen uitsluiten. De huisarts kan met een beslisregel en een D-dimeertest veilig een trombosebeen uitsluiten. Alleen is extra aandacht nodig bij oncologische patienten met een verdenking op een trombosebeen en bij patienten die eerder een trombosebeen hebben doorgemaakt. De Wells-beslisregel is in die gevallen respectievelijk minder efficient en minder veilig.

Background Clinical decision rules can aid in referral decisions for ultrasonography in patients suspected of having deep venous thrombosis (DVT), but physicians are not always convinced of their usefulness and rely on their own judgement. Aim To compare the performance of a clinical decision rule with the probability of DVT presence as estimated by GPs. Design of study Cross-sectional survey. Setting Primary care practices in The Netherlands. Method GPs ( n = 300) estimated the probability of the presence of DVT (range 0–100%) and calculated the score for the clinical decision rule in 1028 consecutive patients with suspected DVT. The clinical decision rule uses a threshold of three points and so, for the GP estimates, thresholds were introduced at 10% and 20%. If scores were below these estimates, it was not considered necessary to refer patients for further examination. Differences between the clinical decision rule and the GP estimates were calculated; this is discrimination ( c -statistic) and classification of patients. Results Data of 1002 patients were eligible for analysis. DVT was observed in 136 (14%) patients. Both the clinical decision rule and GP estimates had good discriminative power ( c -statistic of 0.80 and 0.82 respectively). Fewer patients were referred when using the clinical decision rule compared with a referral decision based on GP estimates: 51% versus 79% and 65% (thresholds at 10% and 20% respectively). Both strategies missed a similar and low proportion of patients who did have DVT (range 1.4–2.0%). Conclusion In patients suspected of DVT both GP estimates and a clinical decision rule can safely discriminate in patients with and without DVT. However, fewer patients are referred for ultrasonography when GPs rely on a clinical decision rule to guide their decision making.

Summary. Background: Referral for ultrasound testing in all patients suspected of DVT is inefficient, because 80–90% have no DVT. Objective: To assess the incremental cost-effectiveness of a diagnostic strategy to select patients at first presentation in primary care based on a point of care D-dimer test combined with a clinical decision rule (AMUSE strategy), compared with hospital-based strategies. Patients/Methods: A Markov-type cost-effectiveness model with a societal perspective and a 5-year time horizon was used to compare the AMUSE strategy with hospital-based strategies. Data were derived from the AMUSE study (2005–2007), the literature, and a direct survey of costs (2005–2007). Results of base-case analysis: Adherence to the AMUSE strategy on average results in savings of €138 ($185) per patient at the expense of a very small health loss (0.002 QALYs) compared with the best hospital strategy. The iCER is €55 753($74 848). The cost-effectiveness acceptability curves show that the AMUSE strategy has the highest probability of being cost-effective. Results of sensitivity analysis: Results are sensitive to decreases in sensitivity of the diagnostic strategy, but are not sensitive to increase in age (range 30–80), the costs for health states, and events. Conclusion: A diagnostic management strategy based on a clinical decision rule and a point of care D-dimer assay to exclude DVT in primary care is not only safe, but also cost-effective as compared with hospital-based strategies.

Buller HR, Ten Cate-Hoek AJ, Hoes AW, Joore MA, Moons KGM, Oudega R, Prins MH, Stoffers HEJH, Toll DB, Van der Velde E-F, Van Weert HCPM. De huisarts kan zelf diepe veneuze trombose veilig uitsluiten. Huisarts Wet 2009;52(10):497-502. Achtergrond Tot 90% van de patienten die de huisarts instuurt voor compressie-echografie onder verdenking van diepe veneuze trombose (DVT) blijkt die aandoening niet te hebben. In het AMUSE-1-onderzoek (Amsterdam-Maastricht-Utrecht Study on thrombo-Embolism) is onderzocht of een eenvoudige klinische beslisregel in combinatie met een D-dimeertest in staat is om een trombosebeen al in de eerste lijn op veilige en efficiente wijze uit te sluiten. Methode Driehonderd huisartsen deden mee aan het onderzoek. Patienten bij wie de beslisregel op een lage klinische verdenking wees, stuurden zij niet in voor echografie en behandelden zij niet met antistolling. Patienten die positief scoorden op de beslisregel verwezen zij voor compressie-echografie. Alle patienten volgden wij drie maanden lang om eventuele trombo-embolische complicaties te kunnen vaststellen. Resultaten Uiteindelijk leverde de beslisregel bij 1002 patienten een geldige score op. Bij 500 patienten wees de beslisregel op een lage klinische verdenking (score ≤ 3). Zeven van hen (1,4%, 95%-BI 0,6-2,9%) kregen een trombo-embolische complicatie tijdens de drie maanden follow-up. De overige 502 patienten hadden een score ≥ 4 en werden verwezen voor echografie. Het echogram wees bij 125 (25%) patienten op een DVT. Van de 374 patienten met een normale echo kregen er 4 (1,1%, 95% BI 0,3-2,7%) een trombo-embolische complicatie tijdens de follow-upperiode. Bij 3 patienten werd geen echo verricht. Discussie Ons onderzoek bevestigt dat de diagnostische strategie die de NHG-Standaard Diepe veneuze trombose aanbeveelt, in de dagelijkse praktijk verantwoord is. Een werkwijze waarbij de huisarts een eenvoudige beslisregel combineert met een D-dimeertest is veilig om DVT uit te sluiten in de eigen praktijk of bij de patient thuis. Met deze strategie kan de helft van de verwijzingen voor compressie-echografie worden voorkomen.

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.

In primary care, the physician has to decide which patients with a suspicion of deep vein thrombosis (DVT) have to be referred for further diagnostic work-up. Accurate referral is of utmost importance because unrecognized and therefore untreated DVT may cause pulmonary embolism. The classic clinical findings are not sufficiently accurate for the diagnosis of DVT. The majority of the referred patients, 70 to 80%, do not have DVT and this puts a burden on both patients and health care budgets. Diagnosis in primary care is different from that in secondary care caused by the referral mechanism or spectrum difference. Diagnostic tests derived in secondary care, therefore, cannot simply be generalized to primary-care patients. The well-known diagnostic rule for DVT, the Wells rule, does not adequately rule out DVT in primary-care patients. A proper diagnostic rule for use in primary care is lacking; therefore, we investigated the data of 1,295 patients in primary care suspected of having DVT. We developed and validated a simple diagnostic decision rule to exclude the presence of DVT safely in primary care. Independent diagnostic indicators of the presence of DVT were male gender, oral contraceptive use, presence of malignancy, recent surgery, absence of leg trauma, vein distension, calf circumference difference, and D-dimer test result. Application of this rule could reduce the number of referrals by at least 23%, whereas only 0.7% of the patients with a DVT would not be referred. A diagnosis strategy is given, together with a practical flow diagram.

1. Vanwege de kans op een longembolie is snelle diagnostiek naar diepe veneuze trombose noodzakelijk.

IntroductionIn 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 analysisThe 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 disseminationThe 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 numberThis trial is registered at the Netherlands Trial Register (NTR5532).

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.

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.

Letters to the Editor: Different cut-off values for two D-dimer assays to exclude deep venous thrombosis in primary care

Introduction. Pulmonary embolism (PE) of ten 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 alternati ve 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 w as 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.

Objective To assess the accuracy of the Wells rule for excluding deep vein thrombosis and whether this accuracy applies to different subgroups of patients. Design Meta-analysis of individual patient data. Data sources Authors of 13 studies (n=10 002) provided their datasets, and these individual patient data were merged into one dataset. Eligibility criteria Studies were eligible if they enrolled consecutive outpatients with suspected deep vein thrombosis, scored all variables of the Wells rule, and performed an appropriate reference standard. Main outcome measures Multilevel logistic regression models, including an interaction term for each subgroup, were used to estimate differences in predicted probabilities of deep vein thrombosis by the Wells rule. In addition, D-dimer testing was added to assess differences in the ability to exclude deep vein thrombosis using an unlikely score on the Wells rule combined with a negative D-dimer test result. Results Overall, increasing scores on the Wells rule were associated with an increasing probability of having deep vein thrombosis. Estimated probabilities were almost twofold higher in patients with cancer, in patients with suspected recurrent events, and (to a lesser extent) in males. An unlikely score on the Wells rule (≤1) combined with a negative D-dimer test result was associated with an extremely low probability of deep vein thrombosis (1.2%, 95% confidence interval 0.7% to 1.8%). This combination occurred in 29% (95% confidence interval 20% to 40%) of patients. These findings were consistent in subgroups defined by type of D-dimer assay (quantitative or qualitative), sex, and care setting (primary or hospital care). For patients with cancer, the combination of an unlikely score on the Wells rule and a negative D-dimer test result occurred in only 9% of patients and was associated with a 2.2% probability of deep vein thrombosis being present. In patients with suspected recurrent events, only the modified Wells rule (adding one point for the previous event) is safe. Conclusion Combined with a negative D-dimer test result (both quantitative and qualitative), deep vein thrombosis can be excluded in patients with an unlikely score on the Wells rule. This finding is true for both sexes, as well as for patients presenting in primary and hospital care. In patients with cancer, the combination is neither safe nor efficient. For patients with suspected recurrent disease, one extra point should be added to the rule to enable a safe exclusion.

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 3month 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.

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.

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.

The growth in the number of possible medical interventions in the past decennia necessitates physicians to consider whether to use them. Contrary to decisions to withhold treatment, little is known about “non-diagnosis decisions” (NDD) although their consequences seem to be more uncertain. Hence, we hypothesized that “determinants” and “reasons” for NDD are different from those that are associated with non-treatment decisions (NTD). We performed a systematic review on research on physicians' decisions to withhold or withdraw diagnostic or therapeutic interventions. A total of 11,773 unique citations published either in Medline, Embase, or the Cochrane databases were screened, of which 45 articles, –including 4 articles describing NDD in elderly patients suspected of cardiovascular diseases, were considered relevant and analysed in detail. “Determinants” and “reasons” for NDD and NTD were extracted, categorized into predefined categories, and compared with each other. Besides several similarities, we found various differences between NDD and NTD. The proportionality of an intervention (ie, the risk or burden of an intervention opposed to that of no intervention) was associated with NTD but not with NDD. Physician and care institution related characteristics, such as age of the physician or the employment of physician extenders, were more frequently associated with NDD than with NTD. Furthermore, the presence of non-resuscitate directives was correlated with NDD but not with NTD. This systematic review shows that there is little information on NDD in the current literature. Yet, there is not enough evidence to conclude whether NDD can be seen as a separate entity distinct from NTD. More research focusing on NDD seems needed.

With the availability of new treatment for thromboembolism that can be administered at home, the management of pulmonary embolism is changing. This has implications for both the location and provision of care. Pulmonary embolism occurs in 1–2 per 1000 people each year and in up to 10 per 1000

We thank Dr Reynolds1 for carefully reading and commenting on our article,2 and indeed must agree that the maximum score on the Oudega rule is …

SummaryRecently, a diagnostic score was developed to safely exclude deep-vein thrombosis (DVT) in primary care. A large prospective study, in which general practitioners used this diagnostic score to decide which patients needed referral, revealed that the number of referrals for ultra-sound measurements was reduced by almost 50%, at the cost of an acceptably low risk (1.4%, 95% confidence interval [CI] 0.6% to 2.9%) of venous thromboembolic events in non-referred patients. However, simple adjustments to the diagnostic score (so-called updating) might further improve the accuracy; i.e. reduce the proportion of missed diagnoses (safety) or increase the proportion of patients who do not need to be referred (efficiency). We applied two updating methods to determine whether adjusting the weights of the predictors or adding new predictors could further improve the accuracy of the diagnostic score. The weights of the predictors did not need to be adjusted, but inclusion of ‘history of DVT’ and ‘prolonged travelling’ significantly added predictive value (p-values 0.014 and 0.023, respectively). However, adding these predictors to the diagnostic score did not improve the safety and efficiency: at equal safety (1.4% missed diagnoses among the non-referred patients), the efficiency was lower (43.5%, 95% CI 40.4% to 46.6% compared to 49.4%, 95% CI 46.3% to 52.5%). The diagnostic score for excluding DVT in primary care has good accuracy in its original form and could not be improved by including additional predictors. This suggests that the original diagnostic score can be used to safely exclude clinically suspected DVT in primary care.

PURPOSE The Wells rule is widely used for clinical assessment of patients with suspected deep vein thrombosis (DVT), especially in the secondary care setting. Recently a new clinical decision rule for primary care patients (the primary care rule) has been proposed, because the Wells rule is not sufficient to rule out DVT in this setting. The objective was to compare the ability of both rules to safely rule out DVT and to efficiently reduce the number of referrals for leg ultrasound investigation that would result in a negative finding. METHODS Family physicians collected data on 1,086 patients to calculate the scores for both decision rules before leg ultrasonography was performed. In all patients D-dimer (dimerized plasmin fragment D) testing was performed using a rapid point-of-care assay. Patients were stratified into risk categories defined by each rule and the D-dimer result. Outcomes were DVT (diagnosed by ultrasonography) and venous thromboembolic complications or death caused by a possible thromboembolic event during a 90-day follow-up period. We calculated the differences between the 2 rules in the number of missed diagnoses and the proportions of patients that needed ultrasound testing. RESULTS Data from 1,002 eligible patients were used for this analysis. A venous thromboembolic event occurred during follow-up in 7 patients with a low score and negative D-dimer finding, both with the Wells rule (7 of 447; 1.6%; 95% confidence interval [CI], 0.7%-3.3%) and the primary care rule (7 of 495; 1.4%; 95% CI, 0.6%-3.0%). Using the Wells rule, 447 patients (45%) would not need referral for further testing compared with 495 patients (49%) when using the primary care rule (McNemar P

BACKGROUND Point-of-care D-dimer tests have recently been introduced to enable rapid exclusion of deep venous thrombosis (DVT) without the need to refer a patient for conventional laboratory-based D-dimer testing. Before implementation in practice, however, the diagnostic accuracy of each test should be validated. METHODS We analyzed data of 577 prospectively identified consecutive primary care patients suspected to have DVT, who underwent 5 point-of-care D-dimer tests—4 quantitative (Vidas®, Pathfast™, Cardiac®, and Triage®) and 1 qualitative (Clearview Simplify®)—and ultrasonography as the reference method. We evaluated the tests for the accuracy of their measurements and submitted a questionnaire to 20 users to assess the user-friendliness of each test. RESULTS All D-dimer tests showed negative predictive values higher than 98%. Sensitivity was high for all point-of-care tests, with a range of 0.91 (Clearview Simplify) to 0.99 (Vidas). Specificity varied between 0.39 (Pathfast) and 0.64 (Clearview Simplify). The quantitative point-of-care tests showed similar and high discriminative power for DVT, according to calculated areas under the ROC curves (range 0.88–0.89). The quantitative Vidas and Pathfast devices showed limited user-friendliness for primary care, owing to a laborious calibration process and long analyzer warm-up time compared to the Cardiac and Triage. For the qualitative Clearview Simplify assay, no analyzer or calibration was needed, but interpretation of a test result was sometimes difficult because of poor color contrast. CONCLUSIONS Point-of-care D-dimer assays show good and similar diagnostic accuracy. The quantitative Cardiac and Triage and the qualitative Clearview Simplify D-dimer seem most user-friendly for excluding DVT in the doctor's office.

Background Physicians committed to the care of elderly patients, are challenged with the diagnosis of venous thromboembolism (VTE: deep venous thrombosis and pulmonary embolism) due to a higher incidence, co-morbidities masking signs and symptoms and burdening referrals. Clinical decision rules (CDRs) have been developed and implemented for VTE. Yet, until now, no study has evaluated the existing evidence of the diagnostic accuracy of CDRs for VTE in elderly. Purpose To assess the effect of increasing age on diagnostic accuracy of CDRs for VTE in elderly. Data sources A computerized systematic search was performed in Medline and Embase from 1950 to 2010. After checking reference lists and field experts, all key journals were hand searched. Study selection After review of 1538 eligible citations, nine articles were included and critically appraised on methodological quality by two reviewers using the QUADAS criteria. Data extraction Data on age subgroups, type of CDRs, sensitivity, specificity, safety, efficiency and the prevalence of deep venous thrombosis (DVT) and pulmonary embolism (PE) were extracted. Data synthesis Although sensitivity and safety of the CDRs for VTE in elderly remained high, the specificity and efficiency decreased substantially in older age groups. Limitations A limited number of studies met our inclusion criteria. Possible referral bias due to inclusion of relatively high risk elderly patients. Conclusions This diagnostic review demonstrates an increase of prevalence of PE with age and a strong decrease of specificity and efficiency for CDRs of VTE in older patients. Moreover, due to referral bias the decrease in specificity in the elderly may even be underestimated. Although the safety of CDRs for VTE is high, adapting these rules for elderly is much needed to make them more efficient for aged patients.

Objective To review the evidence on the diagnostic accuracy of the currently available point of care D-dimer tests for excluding venous thromboembolism. Design Systematic review of research on the accuracy of point of care D-dimer tests, using bivariate regression to examine sources of variation and to estimate sensitivity and specificity. Data sources Studies on the diagnostic accuracy of point of care D-dimer tests published between January 1995 and September 2008 and available in either Medline or Embase. Review methods The analysis included studies that compared point of care D-dimer tests with predefined reference criteria for venous thromboembolism, enrolled consecutive outpatients, and allowed for construction of a 2×2 table. Results 23 studies (total number of patients 13 959, range in mean age 38-65 years, range of venous thromboembolism prevalence 4-51%) were included in the meta-analysis. The studies reported two qualitative point of care D-dimer tests (SimpliRED D-dimer (n=12) and Clearview Simplify D-dimer (n=7)) and two quantitative point of care D-dimer tests (Cardiac D-dimer (n=4) and Triage D-dimer (n=2)). Overall sensitivity ranged from 0.85 (95% confidence interval 0.78 to 0.90) to 0.96 (0.91 to 0.98) and overall specificity from 0.48 (0.33 to 0.62) to 0.74 (0.69 to 0.78). The two quantitative tests Cardiac D-dimer and Triage D-dimer scored most favourably. Conclusions In outpatients suspected of venous thromboembolism, point of care D-dimer tests can contribute important information and guide patient management, notably in low risk patients (that is, those patients with a low score on a clinical decision rule).

Up to 90% of patients referred for ultrasonography with suspected deep venous thrombosis (DVT) of the leg do not have the disease.To evaluate the safety and efficiency of using a clinical decision rule that includes a point-of-care d-dimer assay at initial presentation in primary care to exclude DVT.A prospective management study.Approximately 300 primary care practices in 3 regions of the Netherlands (Amsterdam, Maastricht, and Utrecht).1028 consecutive patients with clinically suspected DVT.Patients were managed on the basis of the result of the clinical decision rule, which included a d-dimer result. Patients with a score of 3 or less were not referred for ultrasonography and received no anticoagulant treatment; patients with a score of 4 or more were referred for ultrasonography.The primary outcome was symptomatic, objectively confirmed, venous thromboembolism during 3-month follow-up.The mean age of the 1028 study patients was 58 years, and 37% of patients were men. A valid score was obtained in 1002 patients (98%). In 500 patients (49%), with a score of 3 or less, 7 developed venous thromboembolism within 3 months (incidence, 1.4% [95% CI, 0.6% to 2.9%]). A total of 502 patients (49%) had a score of 4 or more; 3 did not have ultrasonography. Ultrasonography showed DVT in 125 patients (25%), for an overall prevalence in evaluable patients of 13% (125 of 1002). Of the 374 patients who had normal ultrasonography results, 4 developed venous thromboembolism within 3 months (1.1% [CI, 0.3% to 2.7%]).The study lacked a randomized design and relied on clinical follow-up to detect missed thrombotic disease.A diagnostic management strategy in primary care by using a simple clinical decision rule and a point-of-care d-dimer assay reduces the need for referral to secondary care of patients with clinically suspected DVT by almost 50% and is associated with a low risk for subsequent venous thromboembolic events.The Netherlands Organization for Scientific Research.

BACKGROUND: Up to 90% of patients referred for ultrasonography with suspected deep venous thrombosis (DVT) of the leg do not have the disease. OBJECTIVE: To evaluate the safety and efficiency of using a clinical decision rule that includes a point-of-care d-dimer assay at initial presentation in primary care to exclude DVT. DESIGN: A prospective management study. SETTING: Approximately 300 primary care practices in 3 regions of the Netherlands (Amsterdam, Maastricht, and Utrecht). PATIENTS: 1028 consecutive patients with clinically suspected DVT. INTERVENTION: Patients were managed on the basis of the result of the clinical decision rule, which included a d-dimer result. Patients with a score of 3 or less were not referred for ultrasonography and received no anticoagulant treatment; patients with a score of 4 or more were referred for ultrasonography. MEASUREMENTS: The primary outcome was symptomatic, objectively confirmed, venous thromboembolism during 3-month follow-up. RESULTS: The mean age of the 1028 study patients was 58 years, and 37% of patients were men. A valid score was obtained in 1002 patients (98%). In 500 patients (49%), with a score of 3 or less, 7 developed venous thromboembolism within 3 months (incidence, 1.4% [95% CI, 0.6% to 2.9%]). A total of 502 patients (49%) had a score of 4 or more; 3 did not have ultrasonography. Ultrasonography showed DVT in 125 patients (25%), for an overall prevalence in evaluable patients of 13% (125 of 1002). Of the 374 patients who had normal ultrasonography results, 4 developed venous thromboembolism within 3 months (1.1% [CI, 0.3% to 2.7%]). Limitation: The study lacked a randomized design and relied on clinical follow-up to detect missed thrombotic disease. CONCLUSION: A diagnostic management strategy in primary care by using a simple clinical decision rule and a point-of-care d-dimer assay reduces the need for referral to secondary care of patients with clinically suspected DVT by almost 50% and is associated with a low risk for subsequent venous thromboembolic events. Funding: The Netherlands Organization for Scientific Research

Background Despite its benefits, it is uncommon to apply the nested case-control design in diagnostic research. We aim to show advantages of this design for diagnostic accuracy studies. Methods We used data from a full cross-sectional diagnostic study comprising a cohort of 1295 consecutive patients who were selected on their suspicion of having deep vein thrombosis (DVT). We draw nested case-control samples from the full study population with case:control ratios of 1:1, 1:2, 1:3 and 1:4 (per ratio 100 samples were taken). We calculated diagnostic accuracy estimates for two tests that are used to detect DVT in clinical practice. Results Estimates of diagnostic accuracy in the nested case-control samples were very similar to those in the full study population. For example, for each case:control ratio, the positive predictive value of the D-dimer test was 0.30 in the full study population and 0.30 in the nested case-control samples (median of the 100 samples). As expected, variability of the estimates decreased with increasing sample size. Conclusion Our findings support the view that the nested case-control study is a valid and efficient design for diagnostic studies and should also be (re)appraised in current guidelines on diagnostic accuracy research.

SummaryIn primary care, the physician has to decide which patients have to be referred for further diagnostic work-up. At present, only in 20% to 30% of the referred patients the diagnosis DVT is confirmed. This puts a burden on both patients and health care budgets. The question arises whether the diagnostic work-up and referral of patients suspected of DVT in primary care could be more efficient. A simple diagnostic decision rule developed in primary care is required to safely exclude the presence of DVT in patients suspected of DVT, without the need for referral. In a cross-sectional study, we investigated the data of 1295 consecutive patients consulting their primary care physician with symptoms suggestive of DVT, to develop and validate a simple diagnostic decision rule to safely exclude the presence of DVT. Independent diagnostic indicators of the presence of DVT were male gender, oral contraceptive use, presence of malignancy, recent surgery, absence of leg trauma, vein distension, calf difference and D-dimer test result. Application of this rule could reduce the number of referrals by at least 23% while only 0·7% of the patients with a DVT would not be referred. We conclude that by using eight simple diagnostic indicators from patient history, physical examination and the result of D-dimer testing, it is possible to safely rule out DVT in a large number of patients in primary care, reducing unnecessary patient burden and health care costs.

Properly ruling in or out deep vein thrombosis (DVT) is important because of the risk of developing pulmonary embolism if untreated and the risk of bleeding when treated with anticoagulants. In primary care, the diagnosis in suspected DVT is non-specific and the physician has to decide which patients to refer for further diagnostic work-up on the basis of patient history and physical examination alone.To quantify which (combination of) items from patient history and physical examination contribute to the diagnosis of DVT in primary care.A cross-sectional study design was chosen and the setting was all primary care physicians adherent to three local hospitals. 1325 consecutive patients consulting their primary care physician with symptoms suggestive of DVT were included.We studied 1325 patients with suspected DVT. The prevalence of thrombosis (assessed by means of compression ultrasonography) in these patients was 29%. Multivariate regression analysis of 17 candidate predictors resulted in nine independent predictors of DVT: male gender, duration of symptoms, malignancy, immobilization, leg trauma, pain when walking, oedema, calf circumference and dilated veins. The predictive value of the combination of the nine independent variables was low, reflected in the ROC area (as a combination of the sensitivity and specificity) of this model of 0.68. The low discriminative value was also exhibited in the numbers of DVT in the different risk categories. For example, in the low-risk group, the probability of DVT was still 15%. The diagnostic performance of patient history and physical examination was similar (and thus poor) in all clinically relevant subgroups.Patient history and physical examination in patients suspected of DVT are of limited value for the primary care setting to identify patients with a low or high probability of DVT and thus in the decision to refer for further diagnostic work-up.

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 {Eth}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.