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==Clinical Prediction Rules==
==Clinical Prediction Rules==
Clinical prediction rule is a type of medical research study in which the researchers try to identify the best combination of [[medical sign]], [[symptoms]], and other findings to predict the probability of a specific disease or outcome.<ref name="pmid10872017">{{cite journal |author=McGinn TG, Guyatt GH, Wyer PC, Naylor CD, Stiell IG, Richardson WS |title=Users' guides to the medical literature: XXII: how to use articles about clinical decision rules. Evidence-Based Medicine Working Group |journal=[[JAMA : the Journal of the American Medical Association]] |volume=284 |issue=1 |pages=79–84 |year=2000 |month=July |pmid=10872017 |doi= |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=10872017 |accessdate=2012-04-26}}</ref>
Clinical prediction rule is a type of medical research study in which the researchers try to identify the best combination of [[medical sign]], [[symptoms]], and other findings to predict the probability of a specific disease or outcome.<ref name="pmid10872017">{{cite journal |author=McGinn TG, Guyatt GH, Wyer PC, Naylor CD, Stiell IG, Richardson WS |title=Users' guides to the medical literature: XXII: how to use articles about clinical decision rules. Evidence-Based Medicine Working Group |journal=[[JAMA : the Journal of the American Medical Association]] |volume=284 |issue=1 |pages=79–84 |year=2000 |month=July |pmid=10872017 |doi= |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=10872017 |accessdate=2012-04-26}}</ref> Clinical prediction rules for PE include: the Wells score, the Geneva score and the PE rule-out criteria. Its noteworthy that the use of '''any clinical prediction rule''' is associated with reduction in recurrent [[thromboembolism]].<ref name="pmid16461959">{{cite journal |author=Roy PM, Meyer G, Vielle B, Le Gall C, Verschuren F, Carpentier F, Leveau P, Furber A |title=Appropriateness of diagnostic management and outcomes of suspected pulmonary embolism |journal=Ann. Intern. Med. |volume=144 |issue=3 |pages=157-64 |year=2006 |pmid=16461959}}</ref>
 
Clinical prediction rules for PE include: the Wells score, the revised Geneva score. Its noteworthy that the use of '''any rule''' is associated with reduction in recurrent thromboembolism.<ref name="pmid16461959">{{cite journal |author=Roy PM, Meyer G, Vielle B, Le Gall C, Verschuren F, Carpentier F, Leveau P, Furber A |title=Appropriateness of diagnostic management and outcomes of suspected pulmonary embolism |journal=Ann. Intern. Med. |volume=144 |issue=3 |pages=157-64 |year=2006 |pmid=16461959}}</ref>


===Wells Score===
===Wells Score===
=====Development of the Wells score=====
=====Development of the Wells score=====
The most commonly used method to predict clinical probability is the Wells score.  
*The most commonly used method to predict clinical probability is the '''''Wells score'''''. It was initially developed in 1995<ref name="pmid7752753">{{cite journal |author=Wells PS, Hirsh J, Anderson DR, Lensing AW, Foster G, Kearon C, Weitz J, D'Ovidio R, Cogo A, Prandoni P |title=Accuracy of clinical assessment of deep-vein thrombosis |journal=[[Lancet]] |volume=345 |issue=8961 |pages=1326–30 |year=1995 |month=May |pmid=7752753 |doi= |url= |accessdate=2012-04-26}}</ref> and has undergo modifications since.<ref name="pmid9867786">{{cite journal |author=Wells PS, Ginsberg JS, Anderson DR, Kearon C, Gent M, Turpie AG, Bormanis J, Weitz J, Chamberlain M, Bowie D, Barnes D, Hirsh J |title=Use of a clinical model for safe management of patients with suspected pulmonary embolism |journal=Ann Intern Med |volume=129 |issue=12 |pages=997-1005 |year=1998 |pmid=9867786}}</ref><ref name="pmid10744147">{{cite journal | author = Wells P, Anderson D, Rodger M, Ginsberg J, Kearon C, Gent M, Turpie A, Bormanis J, Weitz J, Chamberlain M, Bowie D, Barnes D, Hirsh J | title = Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer. | journal = Thromb Haemost | volume = 83 | issue = 3 | pages = 416-20 | year = 2000 | id = PMID 10744147}}</ref><ref name="pmid11453709">{{cite journal |author=Wells PS, Anderson DR, Rodger M, Stiell I, Dreyer JF, Barnes D, Forgie M, Kovacs G, Ward J, Kovacs MJ |title=Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer |journal=Ann Intern Med |volume=135 |issue=2 |pages=98-107 |year=2001 |pmid=11453709 | url=http://www.annals.org/cgi/content/full/135/2/98}}</ref>  
 
In 1995, based on literature search and clinical criteria, Wells et al developed a [[clinical prediction rule|prediction rule]] to predict the likelihood of pulmonary embolism.<ref name="pmid7752753">{{cite journal |author=Wells PS, Hirsh J, Anderson DR, Lensing AW, Foster G, Kearon C, Weitz J, D'Ovidio R, Cogo A, Prandoni P |title=Accuracy of clinical assessment of deep-vein thrombosis |journal=[[Lancet]] |volume=345 |issue=8961 |pages=1326–30 |year=1995 |month=May |pmid=7752753 |doi= |url= |accessdate=2012-04-26}}</ref> The prediction rule was revised initially 1998<ref name="pmid9867786">{{cite journal |author=Wells PS, Ginsberg JS, Anderson DR, Kearon C, Gent M, Turpie AG, Bormanis J, Weitz J, Chamberlain M, Bowie D, Barnes D, Hirsh J |title=Use of a clinical model for safe management of patients with suspected pulmonary embolism |journal=Ann Intern Med |volume=129 |issue=12 |pages=997-1005 |year=1998 |pmid=9867786}}</ref> and a further revision in 2000.<ref name="pmid10744147">{{cite journal | author = Wells P, Anderson D, Rodger M, Ginsberg J, Kearon C, Gent M, Turpie A, Bormanis J, Weitz J, Chamberlain M, Bowie D, Barnes D, Hirsh J | title = Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer. | journal = Thromb Haemost | volume = 83 | issue = 3 | pages = 416-20 | year = 2000 | id = PMID 10744147}}</ref> This year, Wells proposed two different scoring systems using cutoffs of 2 or 4 with the same prediction rule. In 2001, Wells published the results using a more conservative cutoff of 2, to create three categories.<ref name="pmid11453709">{{cite journal |author=Wells PS, Anderson DR, Rodger M, Stiell I, Dreyer JF, Barnes D, Forgie M, Kovacs G, Ward J, Kovacs MJ |title=Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer |journal=Ann Intern Med |volume=135 |issue=2 |pages=98-107 |year=2001 |pmid=11453709 | url=http://www.annals.org/cgi/content/full/135/2/98}}</ref>  


*An additional version, the '''''modified extended version''''', using the more recent cutoff of 2 but including findings from Wells's initial studies were proposed.<ref name="pmid10739372">{{cite journal |author=Sanson BJ, Lijmer JG, Mac Gillavry MR, Turkstra F, Prins MH, Büller HR |title=Comparison of a clinical probability estimate and two clinical models in patients with suspected pulmonary embolism. ANTELOPE-Study Group |journal=Thromb. Haemost. |volume=83 |issue=2 |pages=199-203 |year=2000 |pmid=10739372}}</ref>  
*An additional '''''modified extended version''''' of the Welle's score was developed using the more recent cutoff score of 2 with findings incorporated from the initial studies that Welle's proposed.<ref name="pmid10739372">{{cite journal |author=Sanson BJ, Lijmer JG, Mac Gillavry MR, Turkstra F, Prins MH, Büller HR |title=Comparison of a clinical probability estimate and two clinical models in patients with suspected pulmonary embolism. ANTELOPE-Study Group |journal=Thromb. Haemost. |volume=83 |issue=2 |pages=199-203 |year=2000 |pmid=10739372}}</ref>  


*Most recently, a further study reverted to Wells's earlier use of a cutoff of 4 points to create only two categories.<ref name="pmid16403929">{{cite journal |author=van Belle A, Büller H, Huisman M, Huisman P, Kaasjager K, Kamphuisen P, Kramer M, Kruip M, Kwakkel-van Erp J, Leebeek F, Nijkeuter M, Prins M, Sohne M, Tick L |title=Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography |journal=JAMA |volume=295 |issue=2 |pages=172-9 |year=2006 |pmid=16403929 | url=http://jama.ama-assn.org/cgi/content/full/295/2/172 | doi=10.1001/jama.295.2.172}}</ref>
*Most recently in 2006, Van Belle et al, reverted to Welle's earlier use of 4 point cut-ff score to create only two categories to increase the effectiveness of managing patients suspected pulmonary embolism.<ref name="pmid16403929">{{cite journal |author=van Belle A, Büller H, Huisman M, Huisman P, Kaasjager K, Kamphuisen P, Kramer M, Kruip M, Kwakkel-van Erp J, Leebeek F, Nijkeuter M, Prins M, Sohne M, Tick L |title=Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography |journal=JAMA |volume=295 |issue=2 |pages=172-9 |year=2006 |pmid=16403929 | url=http://jama.ama-assn.org/cgi/content/full/295/2/172 | doi=10.1001/jama.295.2.172}}</ref>


====Wells score<ref name="pmid12952389">{{cite journal |author=Neff MJ |title=ACEP releases clinical policy on evaluation and management of pulmonary embolism |journal=American family physician |volume=68 |issue=4 |pages=759-60 |year=2003 |pmid=12952389 |doi=|url=http://www.aafp.org/afp/20030815/practice.html}}</ref> ====
====Wells score<ref name="pmid12952389">{{cite journal |author=Neff MJ |title=ACEP releases clinical policy on evaluation and management of pulmonary embolism |journal=American family physician |volume=68 |issue=4 |pages=759-60 |year=2003 |pmid=12952389 |doi=|url=http://www.aafp.org/afp/20030815/practice.html}}</ref> ====

Revision as of 14:06, 27 April 2012

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Editor(s)-In-Chief: The APEX Trial Investigators, C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]

Overview

The diagnosis of pulmonary embolism is based on clinical evaluation in conjunction with imaging modalities. Despite their individual sensitivities and specificities, studies have demonstrated that a combination of both these variables may help to discriminate suspected patients depending on their risk of developing pulmonary embolism and offer immediate management which is life-saving.

Pretest Probability

The diagnosis of PE is based primarily on the clinical evaluation combined with diagnostic modalities such as spiral CT, V/Q scan, use of the D-dimer and lower extremity ultrasound.

Although, the clinical pretest probability has shown to be fairly accurate,[1] the lack of validation has led to the use of a combination of both: clinical and diagnostic variables to predict the pretest probability that aids in the immediate management of high-risk patients.

Supportive trial data

  • The Prospective Investigation On Pulmonary Embolism Diagnosis (PIOPED) investigators demonstrated that all patients with or without pulmonary embolism had abnormal V/Q scans of high, intermediate, or low probability (sensitivity, 98%; specificity, 10%). Furthermore, of the 116 patients with high-probability scans and definitive angiograms, only 88% had pulmonary embolism. On the contrary, only a minority of patients with pulmonary embolism demonstrated high-probability scans (sensitivity, 41%; specificity, 97%). Similarly, of the 322 patients with intermediate-probability scans and definitive angiograms, only 33% had pulmonary embolism. Despite these contrast findings, classification of patients based on clinical probability was fairly accurate and that with increasing clinical probability, an increase in PE prevalence was also observed. However, majority of these patients demonstrated low to moderate clinical probability which required no further intervention.[1]
  • Another prospective multicentre outcome study by Musset et al, demonstrated that with-holding anticoagulation in patients with low or intermediate clinical probability and negative spiral CT and ultrasonagraphy was safe. Of the 1041 patients enrolled in the study, 525 were assessed as having low or intermediate clinical probability and 507 were not treated with anticoagulation. During a 3-month follow-up, only 9 patients experienced venous thromboembolism (1.8% [0.8-3.3]) and the diagnostic strategy proved inconclusive in 95 (9.1%) patients.[2][3]

Clinical Prediction Rules

Clinical prediction rule is a type of medical research study in which the researchers try to identify the best combination of medical sign, symptoms, and other findings to predict the probability of a specific disease or outcome.[4] Clinical prediction rules for PE include: the Wells score, the Geneva score and the PE rule-out criteria. Its noteworthy that the use of any clinical prediction rule is associated with reduction in recurrent thromboembolism.[5]

Wells Score

Development of the Wells score
  • The most commonly used method to predict clinical probability is the Wells score. It was initially developed in 1995[6] and has undergo modifications since.[7][8][9]
  • An additional modified extended version of the Welle's score was developed using the more recent cutoff score of 2 with findings incorporated from the initial studies that Welle's proposed.[10]
  • Most recently in 2006, Van Belle et al, reverted to Welle's earlier use of 4 point cut-ff score to create only two categories to increase the effectiveness of managing patients suspected pulmonary embolism.[11]

Wells score[12]

Variables:
  • Immobilization/surgery in previous four weeks - 1.5 points
  • History of DVT or PE - 1.5 points
  • Malignancy (treatment for within 6 months, palliative) - 1.0 points
  • Tachycardia - 1.5 points
  • Clinically suspected DVT (leg swelling, pain with palpation) - 3.0 points
  • Alternative diagnosis is less likely than PE - 3.0 points
Traditional interpretation (Wells criteria) [8][9]
  • Score >6.0 - High (probability 59% based on pooled data[13])
  • Score 2.0 to 6.0 - Moderate (probability 29% based on pooled data[13])
  • Score <2.0 - Low (probability 15% based on pooled data[13])
Alternate interpretation (Modified Wells criteria) [8][11]
  • Score > 4 - PE likely. Consider diagnostic imaging.
  • Score 4 or less - PE unlikely. Consider D-dimer to rule out PE.

Geneva Score[14]

The Geneva score is a clinical prediction rule used in determining the pre-test probability of pulmonary embolism (PE) based on a patient's risk factors and clinical findings. It has been shown to be as accurate as the Wells Score, and is less reliant on the physicians judgement applying the rule.[15]The Geneva score has been revised and simplified from its original version. The simplified Geneva score is the newest version and predicted to have the same diagnostic utility as the original Geneva score.[16]

Original Geneva Score

The original Geneva score is calculated using 7 risk factors and clinical variables:

Variable Score
Age
60–79 years 1
80+ years 2
Previous venous thromboembolism
Previous DVT or PE 2
Previous surgery
Recent surgery within 4 weeks 3
Heart rate
Heart rate >100 beats per minute 1
PaCO2 (partial pressure of CO2 in arterial blood)
<35mmHg 2
35-39mmHg 1
PaO2 (partial pressure of O2 in arterial blood)
<49mmHg 4
49-59mmHg 3
60-71mmHg 2
72-82mmHg 1
Chest X-ray findings
Band atelectasis 1
Elevation of hemidiaphragm 1

The score obtained relates to the probability of the patient having had a pulmonary embolism (the lower the score, the lower the probability):

  • <5 points indicates a low probability of PE
  • 5 - 8 points indicates a moderate probability of PE
  • >8 points indicates a high probability of PE

Revised Geneva Score

More recently, the revised Geneva score has been introduced.[17] This simplifies the scoring process, and has also been shown to be as effective as the Wells score.[18] The revised score uses 8 parameters, but does not include arterial blood gas sample to be performed:

Variable Score
Age 65 years or over 1
Previous DVT or PE 3
Surgery or fracture within 1 month 2
Active malignant condition 2
Unilateral lower limb pain 3
Haemoptysis 2
Heart rate 75 to 94 beats per minute 3
Heart rate 95 or more beats per minute 5
Pain on deep palpation of lower limb and unilateral oedema 4

The score obtained relates to probability of PE:

  • 0 - 3 points indicates low probability (8%)
  • 4 - 10 points indicates intermediate probability (28%)
  • 11 points or more indicates high probability (74%)

The probabilities derived from the scoring systems can be used to determine the need for, and nature of, further investigations such as D-dimer, ventilation/perfusion scanning and CT pulmonary angiography to confirm or refute the diagnosis of PE.

Simplified Geneva Score

The simplified scoring system replaced the weighted scores for each parameter with a 1 point score for each parameter present to reduce the likelihood of error when the score is used in a clinical setting. The report noted that the simplified Geneva score does not lead to a decrease in diagnostic utility in evaluating patients for a PE when compared to previous Geneva scores.

The simplified Geneva score:

Variable Score
Age >65 1
Previous DVT or PE 1
Surgery or fracture within 1 month 1
Active malignancy 1
Unilateral lower limb pain 1
Hemoptysis 1
Pain on deep vein palpation of lower limb and unilateral edema 1
Heart rate 75 to 94 bpm 1
Heart rate greater than 94 bpm* +1
* Heart rates of 75 to 94 bpm receive 1 point, while heart rates higher than 94bpm receive a further point (i.e. 2 points in total)

Patients with a score of 2 or less are considered unlikely to have a current PE.

PE Rule-out Criteria(PERC)

The Pulmonary Embolism Rule-out Criteria, or PERC rule, helps assess people in whom pulmonary embolism is suspected, but unlikely. Unlike the Wells Score and Geneva score, which are clinical prediction rules intended to risk stratify patients with suspected PE, the PERC rule is designed to rule out risk of PE in patients when the physician has already stratified them into a low-risk category.

  • Age less than 50 years
  • Heart rate less than 100 bpm
  • Oxyhemoglobin saturation ≥95 percent
  • No hemoptysis
  • No estrogen use
  • No prior DVT or PE
  • No unilateral leg swelling
  • No surgery or trauma requiring hospitalization within the past four weeks.

The PERC rule has a sensitivity of 97.4% and specificity of 21.9% with a false negative rate of 1.0% [19]

References

  1. 1.0 1.1 "Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). The PIOPED Investigators". JAMA : the Journal of the American Medical Association. 263 (20): 2753–9. 1990. PMID 2332918. |access-date= requires |url= (help)
  2. Musset D, Parent F, Meyer G, Maître S, Girard P, Leroyer C, Revel MP, Carette MF, Laurent M, Charbonnier B, Laurent F, Mal H, Nonent M, Lancar R, Grenier P, Simonneau G (2002). "Diagnostic strategy for patients with suspected pulmonary embolism: a prospective multicentre outcome study". Lancet. 360 (9349): 1914–20. doi:10.1016/S0140-6736(02)11914-3. PMID 12493257. Retrieved 2012-04-26. Unknown parameter |month= ignored (help)
  3. Perrier A, Miron MJ, Desmarais S, de Moerloose P, Slosman D, Didier D, Unger PF, Junod A, Patenaude JV, Bounameaux H (2000). "Using clinical evaluation and lung scan to rule out suspected pulmonary embolism: Is it a valid option in patients with normal results of lower-limb venous compression ultrasonography?". Archives of Internal Medicine. 160 (4): 512–6. PMID 10695691. Retrieved 2012-04-26. Unknown parameter |month= ignored (help)
  4. McGinn TG, Guyatt GH, Wyer PC, Naylor CD, Stiell IG, Richardson WS (2000). "Users' guides to the medical literature: XXII: how to use articles about clinical decision rules. Evidence-Based Medicine Working Group". JAMA : the Journal of the American Medical Association. 284 (1): 79–84. PMID 10872017. Retrieved 2012-04-26. Unknown parameter |month= ignored (help)
  5. Roy PM, Meyer G, Vielle B, Le Gall C, Verschuren F, Carpentier F, Leveau P, Furber A (2006). "Appropriateness of diagnostic management and outcomes of suspected pulmonary embolism". Ann. Intern. Med. 144 (3): 157–64. PMID 16461959.
  6. Wells PS, Hirsh J, Anderson DR, Lensing AW, Foster G, Kearon C, Weitz J, D'Ovidio R, Cogo A, Prandoni P (1995). "Accuracy of clinical assessment of deep-vein thrombosis". Lancet. 345 (8961): 1326–30. PMID 7752753. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  7. Wells PS, Ginsberg JS, Anderson DR, Kearon C, Gent M, Turpie AG, Bormanis J, Weitz J, Chamberlain M, Bowie D, Barnes D, Hirsh J (1998). "Use of a clinical model for safe management of patients with suspected pulmonary embolism". Ann Intern Med. 129 (12): 997–1005. PMID 9867786.
  8. 8.0 8.1 8.2 Wells P, Anderson D, Rodger M, Ginsberg J, Kearon C, Gent M, Turpie A, Bormanis J, Weitz J, Chamberlain M, Bowie D, Barnes D, Hirsh J (2000). "Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer". Thromb Haemost. 83 (3): 416–20. PMID 10744147.
  9. 9.0 9.1 Wells PS, Anderson DR, Rodger M, Stiell I, Dreyer JF, Barnes D, Forgie M, Kovacs G, Ward J, Kovacs MJ (2001). "Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer". Ann Intern Med. 135 (2): 98–107. PMID 11453709.
  10. Sanson BJ, Lijmer JG, Mac Gillavry MR, Turkstra F, Prins MH, Büller HR (2000). "Comparison of a clinical probability estimate and two clinical models in patients with suspected pulmonary embolism. ANTELOPE-Study Group". Thromb. Haemost. 83 (2): 199–203. PMID 10739372.
  11. 11.0 11.1 van Belle A, Büller H, Huisman M, Huisman P, Kaasjager K, Kamphuisen P, Kramer M, Kruip M, Kwakkel-van Erp J, Leebeek F, Nijkeuter M, Prins M, Sohne M, Tick L (2006). "Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography". JAMA. 295 (2): 172–9. doi:10.1001/jama.295.2.172. PMID 16403929.
  12. Neff MJ (2003). "ACEP releases clinical policy on evaluation and management of pulmonary embolism". American family physician. 68 (4): 759–60. PMID 12952389.
  13. 13.0 13.1 13.2 Stein PD, Woodard PK, Weg JG, Wakefield TW, Tapson VF, Sostman HD, Sos TA, Quinn DA, Leeper KV, Hull RD, Hales CA, Gottschalk A, Goodman LR, Fowler SE, Buckley JD (2007). "Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II Investigators". Radiology. 242 (1): 15–21. doi:10.1148/radiol.2421060971. PMID 17185658.
  14. Wicki J, Perneger TV, Junod AF, Bounameaux H, Perrier A (2001). "Assessing clinical probability of pulmonary embolism in the emergency ward: a simple score". Arch. Intern. Med. 161 (1): 92–7. PMID 11146703. Retrieved 2012-04-26. Unknown parameter |month= ignored (help)
  15. Iles S, Hodges AM, Darley JR, Frampton C, Epton M, Beckert LE, Town GI (2003). "Clinical experience and pre-test probability scores in the diagnosis of pulmonary embolism". QJM. 96 (3): 211–5. PMID 12615985. Retrieved 2012-04-26. Unknown parameter |month= ignored (help)
  16. Klok FA, Mos IC, Nijkeuter M, Righini M, Perrier A, Le Gal G, Huisman MV (2008). "Simplification of the revised Geneva score for assessing clinical probability of pulmonary embolism". Arch. Intern. Med. 168 (19): 2131–6. doi:10.1001/archinte.168.19.2131. PMID 18955643. Retrieved 2012-04-26. Unknown parameter |month= ignored (help)
  17. Le Gal G, Righini M, Roy PM, Sanchez O, Aujesky D, Bounameaux H, Perrier A (2006). "Prediction of pulmonary embolism in the emergency department: the revised Geneva score". Ann. Intern. Med. 144 (3): 165–71. PMID 16461960. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  18. Righini M, Le Gal G, Aujesky D, Roy PM, Sanchez O, Verschuren F, Rutschmann O, Nonent M, Cornuz J, Thys F, Le Manach CP, Revel MP, Poletti PA, Meyer G, Mottier D, Perneger T, Bounameaux H, Perrier A (2008). "Diagnosis of pulmonary embolism by multidetector CT alone or combined with venous ultrasonography of the leg: a randomised non-inferiority trial". Lancet. 371 (9621): 1343–52. doi:10.1016/S0140-6736(08)60594-2. PMID 18424324. Retrieved 2012-04-26. Unknown parameter |month= ignored (help)
  19. Kline JA, Courtney DM, Kabrhel C, Moore CL, Smithline HA, Plewa MC, Richman PB, O'Neil BJ, Nordenholz K (2008). "Prospective multicenter evaluation of the pulmonary embolism rule-out criteria". J. Thromb. Haemost. 6 (5): 772–80. doi:10.1111/j.1538-7836.2008.02944.x. PMID 18318689. Retrieved 2012-04-26. Unknown parameter |month= ignored (help)

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