Wim Lucassen

Clinical decision rules for excluding pulmonary embolism: a meta-analysis.

BACKGROUND Clinical probability assessment is combined with d-dimer testing to exclude pulmonary embolism (PE). PURPOSE To compare the test characteristics of gestalt (a physicians unstructured estimate) and clinical decision rules for evaluating adults with suspected PE and assess the failure rate of gestalt and rules when used in combination with d-dimer testing. DATA SOURCES Articles in MEDLINE and EMBASE in English, French, German, Italian, Spanish, or Dutch that were published between 1966 and June 2011. STUDY SELECTION 3 reviewers, working in pairs, selected prospective studies in consecutive patients suspected of having PE. Studies had to estimate the probability of PE by using gestalt or a decision rule and verify the diagnosis by using an appropriate reference standard. DATA EXTRACTION Data on study characteristics, test performance, and prevalence were extracted. Reviewers constructed 2 × 2 tables and assessed the methodological quality of the studies. DATA SYNTHESIS 52 studies, comprising 55 268 patients, were selected. Meta-analysis was performed on studies that used gestalt (15 studies; sensitivity, 0.85; specificity, 0.51), the Wells rule with a cutoff value less than 2 (19 studies; sensitivity, 0.84; specificity, 0.58) or 4 or less (11 studies; sensitivity, 0.60; specificity, 0.80), the Geneva rule (5 studies; sensitivity, 0.84; specificity, 0.50), and the revised Geneva rule (4 studies; sensitivity, 0.91; specificity, 0.37). An increased prevalence of PE was associated with higher sensitivity and lower specificity. Combining a decision rule or gestalt with d-dimer testing seemed safe for all strategies, except when the less-sensitive Wells rule (cutoff value ≤4) was combined with less-sensitive qualitative d-dimer testing. LIMITATIONS Studies had substantial heterogeneity due to prevalence of PE and differences in threshold. Many studies (63%) had potential bias due to differential disease verification. CONCLUSION Clinical decision rules and gestalt can safely exclude PE when combined with sensitive d-dimer testing. The authors recommend standardized rules because gestalt has lower specificity, but the choice of a particular rule and d-dimer test depend on both prevalence and setting.

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.

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

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

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

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

Excluding pulmonary embolism in primary care using the Wells-rule in combination with a point-of care D-dimer test: a scenario analysis

BackgroundIn secondary care the Wells clinical decision rule (CDR) combined with a quantitative D-dimer test can exclude pulmonary embolism (PE) safely. The introduction of point-of-care (POC) D-dimer tests facilitates a similar diagnostic strategy in primary care.We estimated failure-rate and efficiency of a diagnostic strategy using the Wells-CDR combined with a POC-D-dimer test for excluding PE in primary care.We considered ruling out PE safe if the failure rate was <2% with a maximum upper confidence limit of 2.7%.MethodsWe performed a scenario-analysis on data of 2701 outpatients suspected of PE. We used test characteristics of two qualitative POC-D-dimer tests, as derived from a meta-analysis and combined these with the Wells-CDR-score.ResultsIn scenario 1 (SimpliRed-D-dimer sensitivity 85%, specificity 74%) PE was excluded safely in 23.8% of patients but only by lowering the cut-off value of the Wells rule to <2. (failure rate: 1.4%, 95% CI 0.6-2.6%)In scenario 2 (Simplify-D-dimer sensitivity 87%, specificity 62%) PE was excluded safely in 12.4% of patients provided that the Wells-cut-off value was set at 0. (failure rate: 0.9%, 95% CI 0.2-2.6%)ConclusionTheoretically a diagnostic strategy using the Wells-CDR combined with a qualitative POC-D-dimer test can be used safely to exclude PE in primary care albeit with only moderate efficiency.

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

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

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

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

Klinische blik versus beslisregel bij longembolie

SamenvattingHendriksen JM, Lucassen WA, Erkens PM, Stoffers HE, Van Weert HC, Büller HR, Hoes AW, Moons KG, Geersing GJ. Klinische blik versus beslisregel bij longembolie. Huisarts Wet 2017;60(4):152-4.Achtergrond Om de diagnose ‘longembolie’ uit te sluiten adviseert de NHG-Standaard een diagnostisch predictiemodel te gebruiken, zoals de Wells-beslisregel, in combinatie met een D-dimeerbepaling. Veel huisartsen gebruiken echter geregeld hun eigen impliciete kansschatting. Wij onderzochten of longembolie bij eerstelijnspatiënten met de klinische blik even veilig en efficiënt kan worden uitgesloten als met de Wells-beslisregel.Methode In een cohort van 598 patiënten met mogelijk een longembolie gaf de huisarts de eigen klinische inschatting aan op een schaal van 0-100%, met daarnaast de kans volgens de Wells-beslisregel. Alle patiënten werden vervolgens verwezen naar het ziekenhuis voor een referentietest. Wij deelden de patiënten in in laag- en hoogrisicogroepen op basis van beide strategieën. Als afkapwaarden kozen we een score < 20% voor de klinische blik respectievelijk een score ≤ 4 voor de Wells-beslisregel, beide in combinatie met een negatieve D-dimeerbepaling. Wij vergeleken de efficiëntie en de veiligheid van beide strategieën.Resultaten Van de 598 deelnemers hadden er 73 (12%) een veneuze trombo-embolie. Op basis van klinische blik werden 152 patiënten als laag risico geclassificeerd (efficiëntie 25%; 95%-BI 22-29). Van deze 152 bleken er twee alsnog een longembolie te hebben (veiligheid 1,3%; 95%-BI 0,2-4,7). Met de Wells-beslisregel werden 272 patiënten als laag risico geclassificeerd (efficiëntie 45%; 95%-BI 41-50), van wie er vier alsnog een longembolie hadden (veiligheid 1,5%; 95%-BI 0,4-3,7).Conclusie Om een longembolie veilig uit te sluiten, is de Wells-beslisregel even veilig als de klinische blik van de huisarts, en aanzienlijk efficiënter.

Een bruikbare klinische beslisregel voor longembolie

SamenvattingHendriksen JM, Geersing GJ, Lucassen WA, Erkens PM, Stoffers HE, vanWeert HC, Büller HR, Hoes AW, Moons KG. Een bruikbare klinische beslisregelvoor longembolie. Huisarts Wet 2016;59(5):200-3.DoelOm overdiagnostiek te voorkomen, is in de huisartsenpraktijk behoefte aan een bruikbare, efficiënte en veilige beslisregel om longembolie bij een patiënt met klachten uit te sluiten. Wij valideerden in de eerste lijn een aantal klinische beslisregels die gebruikt worden in de tweede en derde lijn.MethodeIn een systematisch literatuuronderzoek zochten wij naar klinische beslisregels voor longembolie. De beslisregels die bruikbaar leken voor de huisarts, valideerden we in een cohort van 598 deelnemers aan het AMUSE-2-onderzoek, allen met vermoede longembolie, uit 300 Nederlandse huisartsenpraktijken in 2007-2010. Van iedere beslisregel bepaalden we de efficiëntie, dat wil zeggen het percentage laagrisicopatiënten dat de beslisregel identificeerde, en de veiligheid, dat wil zeggen het percentage patiënten met een longembolie dat de beslisregel ten onrechte als laagrisicopatiënt categoriseerde.ResultatenIn de literatuur vonden wij tien klinische beslisregels voor longembolie, waarvan er vijf gevalideerd konden worden in onze dataset: de originele, gemodificeerde en gesimplificeerde Wells-beslisregel, de gereviseerde Geneva-score en de gesimplificeerde gereviseerde Geneva-score. Alle beslisregels sloten, in combinatie met een D-dimeersneltest, longembolie uit bij 43-48% van de patiënten, het percentage foutnegatieven lag tussen 1,2% (95%-BI 0,2-3,3) voor de gesimplificeerde Wells-beslisregel en 3,1% (95%-BI 1,4-5,9) voor de gesimplificeerde gereviseerde Geneva-score.ConclusieDe vijf klinische beslisregels die wij valideerden voor de huisartsenpraktijk waren alle ongeveer even efficiënt. Het veiligst zijn de drie Wells-beslisregels. Met deze beslisregels, in combinatie met een D-dimeersneltest, kan de huisarts bij ongeveer 4 op de 10 patiënten longembolie uitsluiten met een percentage foutnegatieven van nog geen 2%, hetgeen naar omstandigheden acceptabel is.

De ziekte van Kawasaki: tijdige diagnose essentieel

SamenvattingDu Perron LJ, Op de Coul ME, Lucassen WAM. De ziekte van Kawasaki: tijdige diagnose essentieel. Huisarts Wet 2014;57(7):370-2. Koorts bij kinderen is meestal zelflimiterend en kan in verreweg de meeste gevallen in de eerste lijn afgewacht of behandeld worden. Soms maakt het kind een ernstig zieke indruk of zijn er andere (alarm)symptomen die verwijzing naar de tweede lijn noodzakelijk maken. Wij beschrijven twee zieke kinderen bij wie de koorts langer dan vijf dagen aanhield, gepaard ging met conjunctivitis en huidafwijkingen, en die ongewoon huilerig waren. Bij beide kinderen bleek sprake te zijn van de ziekte van Kawasaki: een vasculitis die optreedt op de kinderleeftijd, vooral bij kinderen van Aziatische komaf. De ziekte is vrij zeldzaam: een huisarts zal het in een normpraktijk gemiddeld één keer in zijn carrière tegenkomen. De diagnose is op klinische gronden te stellen, maar de differentiële diagnostiek is uitgebreid en maakt verwijzing naar de kinderarts noodzakelijk. Onbehandeld leidt de ziekte van Kawasaki bij 15 tot 25 procent van de kinderen tot coronaire aneurysmata, die fatale complicaties kunnen geven. De behandeling bestaat uit immuunglobulinen die, mits binnen tien dagen toegediend, de kans op mogelijke complicaties aanzienlijk verkleinen.AbstractDu Perron LJ, Op de Coul ME, Lucassen WAM. Kawasaki disease: timely diagnosis is essential. Huisarts Wet 2014;57(7):370-2. Fever is usually self-limiting in children and in most primary-care cases a wait-andwatch policy can be adopted. However, sometimes the child appears to be severely ill or has other symptoms that make referral to secondary care essential. We describe two children who had fever for more than 5 days, accompanied by conjunctivitis, skin disorders, and unusual irritability. Both children were diagnosed with Kawasaki disease – a vasculitis that occurs in children, and especially children of Asian descent. The disease is rare, and general practitioners may encounter only one case in their entire career. The diagnosis can be established on the basis of clinical signs and symptoms, but the differential diagnosis is extensive, making referral to a paediatrician necessary. Untreated, about 15–25% of affected children develop coronary artery aneurysms, which can give rise to fatal complications. Treatment is with immunoglobulins, which, if administered within 10 days, can considerably reduce the risk of possible complications.