Validation of two age dependent D-dimer cut-off values for exclusion of deep vein thrombosis in suspected elderly patients in primary care: retrospective, cross sectional, diagnostic analysis

Objective To determine whether the use of age adapted D-dimer cut-off values can be translated to primary care patients who are suspected of deep vein thrombosis

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

Advantages of the nested case-control design in diagnostic research

Abstract 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.</p

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

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

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

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 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

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.)

Diagnostic classification in patients with suspected deep venous thrombosis: physicians' judgement or a decision rule?

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. To compare the performance of a clinical decision rule with the probability of DVT presence as estimated by GPs. Cross-sectional survey. Primary care practices in The Netherlands. 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. 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%). 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 makin