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A Noninvasive Strategy for the Treatment of Patients With Suspected Pulmonary Embolism

A Noninvasive Strategy for the Treatment of Patients With Suspected Pulmonary Embolism Abstract Background: Pulmonary embolism has historically presented a formidable diagnostic problem because of the nonspecificity of the clinical findings associated with this disorder and the diagnostic uncertainties and challenges presented by both ventilation-perfusion lung scanning and pulmonary angiography. We have reported previously that serial noninvasive leg testing provides a practical noninvasive alternative to pulmonary angiography in patients with nonhigh probability (nondiagnostic) lung scans and adequate cardiorespiratory reserve. We have reevaluated this observation prospectively to (1) confirm or refute our original observation in an independent cohort and (2) to increase the numbers sufficiently to provide narrow confidence limits for the observed outcomes. Methods: A prospective comparative study in 1564 consecutive patients with suspected pulmonary embolism who underwent ventilation-perfusion lung scanning and objective testing for proximal-vein thrombosis. Results: On long-term follow-up of 627 patients with the following characteristics: (1) abnormal, nondiagnostic lung scans, (2) not taking anticoagulant therapy, and (3) serial noninvasive test results negative for proximal-vein thrombosis, only 12 patients (1.9%; 95% confidence limits, 0.8% to 3.0%) had venous thromboembolism. By comparison, venous thromboembolism on follow-up occurred in four (0.7%) of 586 patients (95% confidence limits, 0.02% to 1.3%) with normal lung scans in whom anticoagulant therapy was withheld and in eight (5.5%) of 145 patients (95% confidence limits, 1.8% to 9.2%) with high probability lung scans who received anticoagulant therapy. Conclusions: Our findings indicate that the clinician has a practical noninvasive strategy in patients with adequate cardiorespiratory reserve and nondiagnostic lung scans that (1) avoids pulmonary angiography, (2) identifies patients with proximal-vein thrombosis who require treatment, and (3) avoids the need for treatment and further investigation in the majority of patients.(Arch Intern Med. 1994;154:289-297) References 1. Anderson FA, Wheeler HB, Goldberg RJ, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism: the Worcester DVT Study . Arch Intern Med. 1991;151:933-938.Crossref 2. Moser KM. Venous thromboembolism . Am Rev Respir Dis. 1990;141:235-249.Crossref 3. Kelley MA, Carson JL, Palevsky HI, Schwartz JS. Diagnosing pulmonary embolism: new facts and strategies . Ann Intern Med. 1991;114:300-306.Crossref 4. Stein PD, Saltzman HA, Weg JG. Clinical characteristics of patients with acute pulmonary embolism . Am J Cardiol. 1991;68:1723-1724.Crossref 5. Prospective Investigation of Pulmonary Embolism Diagnosis Investigators. Value of the ventilation-perfusion scan in acute pulmonary embolism: results of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) . JAMA . 1990;263:2753-2759.Crossref 6. Hull R, Raskob G. Low probability lung scan findings: a need for change . Ann Intern Med. 1991;114:142-143.Crossref 7. Hull RD, Hirsh J, Carter CJ, et al. Diagnostic value of ventilation-perfusion lung scanning in patients with suspected pulmonary embolism . Chest . 1985;88:819-828.Crossref 8. Hull RD, Hirsh J, Carter CJ, et al. Pulmonary angiography ventilation lung scanning and venography for clinically suspected pulmonary embolism with abnormal perfusion lung scan . Ann Intern Med. 1983;98:891-899.Crossref 9. Gottschalk A. Lung scan interpretation: a physiologic, user friendly approach . J Nucl Med. 1992;33:1422-1424. 10. Secker-Walker RH. On purple emperors, pulmonary embolism and venous thrombosis . Ann Intern Med. 1983;98:1006-1008.Crossref 11. Cheely R, McCartney WH, Perry JR, et al. The role of non-invasive tests vs pulmonary in the diagnosis of pulmonary embolism . Am J Med. 1981;70:17-22.Crossref 12. McNeil BJ. Ventilation-perfusion studies and the diagnosis of pulmonary embolism: concise communication J Nucl Med. 1980;21:319-323. 13. Biello DR, Mattar AG, McKnight RC, Siegel BA. Ventilation-perfusion studies in suspected pulmonary embolism . AJR Am J Roentgenol. 1979;133:1033-1037.Crossref 14. Alderson PO, Rujanavech N, Secker-Walker RH, McKnight RC. The role of 133Xe ventilation studies in the scintigraphic detection of pulmonary embolism . Radiology . 1976;120:633-640.Crossref 15. Dalen JE, Brooks HL, Johnson LW, Meister SG, Szucs MM, Dexter L. Pulmonary angiography in acute pulmonary embolism: indications, techniques, and results in 367 patients . Am Heart J. 1971;81:175-185.Crossref 16. Stein PD, Athanasoulis C, Alavi A, et al. Complications and validity of pulmonary angiography in acute pulmonary embolism . Circulation . 1992;85:462-468.Crossref 17. Bone RC. Ventilation-perfusion scan in pulmonary embolism: the emperor is incompletely attired . JAMA . 1990;263:2794-2795.Crossref 18. Kakkar W, Flanc C, Howe CT, Clarke MB. Natural history of post-operative deep-vein thrombosis . Lancet . 1969;2:230-232.Crossref 19. Moser KM, LeMoine JR. Is embolic risk conditioned by location of deep venous thrombosis? Ann Intern Med. 1981;94:439-444.Crossref 20. Hull RD, Delmore T, Genton E, et al. Warfarin sodium vs low-dose heparin in the long-term treatment of venous thrombosis . N Engl J Med. 1979;301:855-858.Crossref 21. Hull RD, Raskob GE, Hirsh J, et al. Continuous intravenous heparin compared with intermittent subcutaneous heparin in the initial treatment of proximal-vein thrombosis . N Engl J Med. 1986;315:1109-1114.Crossref 22. Brandjes DPM, Heijboer H, Buller HR, De Rijk M, Jagt H, Ten Cate JW. Acenocoumarol and heparin compared with acenocoumarol alone in the initial treatment of proximal-vein thrombosis . N Engl J Med. 1992;327:1485-1489.Crossref 23. Wheeler HB, Anderson FA Jr. Can noninvasive tests be used as the basis for treatment of deep-vein thrombosis? In: Bernstein EF, ed. Noninvasive Diagnostic Techniques in Vascular Disease . 3rd ed. St Louis, Mo: Mosby—Year Book; 1985:805-818. 24. Hull RD, Hirsh J, Carter CJ, et al. Diagnostic efficacy of impedance plethysmography for clinically suspected deep-vein thrombosis: a randomized trial . Ann Intern Med. 1985;102:21-28.Crossref 25. Huisman MV, Buller HR, Ten Cate JW, Vreeken J. Serial impedance plethysmography for suspected deep venous thrombosis in outpatients: the Amsterdam General Practitioner Study . N Engl J Med. 1986;814:823-828.Crossref 26. Huisman MV, Buller HR, Ten Cate JW, Heijermans HS, Van der Laan J, Van Maanen DJ. Management of clinically suspected acute venous thrombosis in outpatients with serial impedance plethysmography in a community hospital setting . Arch Intern Med. 1989;149:511-513.Crossref 27. Heijboer H, Brandjes D, Lensing AW, Buller HR, Ten Cate JW. Efficacy of real-time B-mode ultrasonography vs impedance plethysmography in the diagnosis of deepvein thrombosis in symptomatic outpatients . Thromb Haemost. 1991;65:436. 28. White RH, McGahan JP, Daschbach MM, Hartling RP. Diagnosis of deep-vein thrombosis using Duplex ultrasound . Ann Intern Med. 1989;111:297-304.Crossref 29. Lensing AW, Prandoni P, Brandjes DPM, et al. Detection of deep-vein thrombosis by real-time B-mode ultrasonography . N Engl J Med. 1989;320:342-345.Crossref 30. Cronan JJ. Ultrasound evaluation of deep venous thrombosis . Semin Roentgenol. 1992;27:39-52.Crossref 31. Hull R, Raskob G, Coates G, Panju A, Gill GJ. A new noninvasive management strategy for patients with suspected pulmonary embolism . Arch Intern Med. 1989;149:2549-2555.Crossref 32. Hull R, Raskob G, Coates G, Panju A. Clinical validity of a normal perfusion lung scan in patients with suspected pulmonary embolism . Chest . 1990;97:23-26.Crossref 33. Kipper MS, Moser KM, Kortman KE, Ashburn WL. Long-term follow-up of patients with suspected pulmonary embolism and a normal lung scan . Chest . 1982;82:411-415.Crossref 34. Hull R, Raskob G, Rosenbloom D, et al. Heparin for 5 days compared with 10 days in the initial treatment of proximal venous thrombosis . N Engl J Med. 1990;322:1260-1264.Crossref 35. Hull R, Hirsh J, Jay R, et al. Different intensities of oral anticoagulant therapy in the treatment of proximal-vein thrombosis . N Engl J Med. 1982;307:1676-1681.Crossref 36. Greenfield LJ. Current indications for and results of Greenfield filter placement . J Vasc Surg. 1984;1:502-504.Crossref 37. Bookstein JJ, Silver TM. The angiographic differential diagnosis of acute pulmonary embolism . Radiology . 1974;110:25-33.Crossref 38. Hull RD, Carter CJ, Jay RM, et al. The diagnosis of acute recurrent deep-vein thrombosis: a diagnostic challenge . Circulation . 1983;67:901-906.Crossref 39. Hull RD, Van Aken WG, Hirsh J, et al. Impedance plethysmography using the occlusive cuff technique in the diagnosis of venous thrombosis . Circulation . 1976;53:696-700.Crossref 40. Hull RD, Taylor DW, Hirsh J, et al. Impedance plethysmography: the relationship between venous filling and sensitivity and specificity for proximal-vein thrombosis . Circulation . 1978;58:898-902.Crossref 41. Rabinov K, Paulin S. Roentgen diagnosis of venous thrombosis in the leg . Arch Surg. 1972;104:134-144.Crossref 42. Coates G, Dolovich M, Koehler D, Newhouse J. Ventilation scanning with technetium labeled aerosols: DTPA or sulfur colloid? Clin Nucl Med. 1985;10:835-838.Crossref 43. Hull RD, Hirsh J, Sackett DL, et al. Clinical validity of a negative venogram in patients with clinically suspected venous thrombosis . Circulation . 1981;64:622-625.Crossref 44. Novelline RA, Baltarowich OH, Athanasoulis CA, Waltman A, Greenfield AJ, McKusick KA. The clinical course of patients with suspected pulmonary embolism and a negative pulmonary arteriogram . Radiology . 1978;126:561-567.Crossref 45. Carter C, Gent M, Leclerc JR. The epidemiology of venous thrombosis . In: Coleman RW, Hirsh J, Marder J, Salzman EW, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice . Philadelphia, Pa: JB Lippincott; 1987:1185-1198. 46. Salzman EW, Hirsh J. Prevention of venous thromboembolism . In: Coleman RW, Hirsh J, Marder V, Salzman EW, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice . 2nd ed. Philadelphia, Pa: JB Lippincott; 1987:1252-1265. 47. Sackett DL, Haynes RB, Tugwell P. Clinical Epidemiology: A Basic Science for Clinical Medicine . Boston, Mass: Little Brown & Co Inc; 1985:159-169. 48. Sackett DL. Bias in analytic research . J Chronic Dis. 1979;32:51-63.Crossref 49. Palevsky HI, Alavi A. A noninvasive strategy for the management of patients suspected of pulmonary embolism . Semin Nucl Med. 1991;21:325-331.Crossref 50. Anderson DR, Lensing AW, Wells PS, Levine MN, Weitz JI, Hirsh J. Limitations of impedance plethysmography in the diagnosis of clinically suspected deepvein thrombosis . Ann Intern Med. 1993;118:25-30.Crossref 51. Heijboer H, Cogo A, Buller HR, Prandoni P, Ten Cate JW. Detection of deep-vein thrombosis with impedance plethysmography and real-time compression ultrasonography in hospitalized patients . Arch Intern Med. 1992;152:1901-1903.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

A Noninvasive Strategy for the Treatment of Patients With Suspected Pulmonary Embolism

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References (57)

Publisher
American Medical Association
Copyright
Copyright © 1994 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.1994.00420030093009
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Abstract

Abstract Background: Pulmonary embolism has historically presented a formidable diagnostic problem because of the nonspecificity of the clinical findings associated with this disorder and the diagnostic uncertainties and challenges presented by both ventilation-perfusion lung scanning and pulmonary angiography. We have reported previously that serial noninvasive leg testing provides a practical noninvasive alternative to pulmonary angiography in patients with nonhigh probability (nondiagnostic) lung scans and adequate cardiorespiratory reserve. We have reevaluated this observation prospectively to (1) confirm or refute our original observation in an independent cohort and (2) to increase the numbers sufficiently to provide narrow confidence limits for the observed outcomes. Methods: A prospective comparative study in 1564 consecutive patients with suspected pulmonary embolism who underwent ventilation-perfusion lung scanning and objective testing for proximal-vein thrombosis. Results: On long-term follow-up of 627 patients with the following characteristics: (1) abnormal, nondiagnostic lung scans, (2) not taking anticoagulant therapy, and (3) serial noninvasive test results negative for proximal-vein thrombosis, only 12 patients (1.9%; 95% confidence limits, 0.8% to 3.0%) had venous thromboembolism. By comparison, venous thromboembolism on follow-up occurred in four (0.7%) of 586 patients (95% confidence limits, 0.02% to 1.3%) with normal lung scans in whom anticoagulant therapy was withheld and in eight (5.5%) of 145 patients (95% confidence limits, 1.8% to 9.2%) with high probability lung scans who received anticoagulant therapy. Conclusions: Our findings indicate that the clinician has a practical noninvasive strategy in patients with adequate cardiorespiratory reserve and nondiagnostic lung scans that (1) avoids pulmonary angiography, (2) identifies patients with proximal-vein thrombosis who require treatment, and (3) avoids the need for treatment and further investigation in the majority of patients.(Arch Intern Med. 1994;154:289-297) References 1. Anderson FA, Wheeler HB, Goldberg RJ, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism: the Worcester DVT Study . Arch Intern Med. 1991;151:933-938.Crossref 2. Moser KM. Venous thromboembolism . Am Rev Respir Dis. 1990;141:235-249.Crossref 3. Kelley MA, Carson JL, Palevsky HI, Schwartz JS. Diagnosing pulmonary embolism: new facts and strategies . Ann Intern Med. 1991;114:300-306.Crossref 4. Stein PD, Saltzman HA, Weg JG. Clinical characteristics of patients with acute pulmonary embolism . Am J Cardiol. 1991;68:1723-1724.Crossref 5. Prospective Investigation of Pulmonary Embolism Diagnosis Investigators. Value of the ventilation-perfusion scan in acute pulmonary embolism: results of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) . JAMA . 1990;263:2753-2759.Crossref 6. Hull R, Raskob G. Low probability lung scan findings: a need for change . Ann Intern Med. 1991;114:142-143.Crossref 7. Hull RD, Hirsh J, Carter CJ, et al. Diagnostic value of ventilation-perfusion lung scanning in patients with suspected pulmonary embolism . Chest . 1985;88:819-828.Crossref 8. Hull RD, Hirsh J, Carter CJ, et al. Pulmonary angiography ventilation lung scanning and venography for clinically suspected pulmonary embolism with abnormal perfusion lung scan . Ann Intern Med. 1983;98:891-899.Crossref 9. Gottschalk A. Lung scan interpretation: a physiologic, user friendly approach . J Nucl Med. 1992;33:1422-1424. 10. Secker-Walker RH. On purple emperors, pulmonary embolism and venous thrombosis . Ann Intern Med. 1983;98:1006-1008.Crossref 11. Cheely R, McCartney WH, Perry JR, et al. The role of non-invasive tests vs pulmonary in the diagnosis of pulmonary embolism . Am J Med. 1981;70:17-22.Crossref 12. McNeil BJ. Ventilation-perfusion studies and the diagnosis of pulmonary embolism: concise communication J Nucl Med. 1980;21:319-323. 13. Biello DR, Mattar AG, McKnight RC, Siegel BA. Ventilation-perfusion studies in suspected pulmonary embolism . AJR Am J Roentgenol. 1979;133:1033-1037.Crossref 14. Alderson PO, Rujanavech N, Secker-Walker RH, McKnight RC. The role of 133Xe ventilation studies in the scintigraphic detection of pulmonary embolism . Radiology . 1976;120:633-640.Crossref 15. Dalen JE, Brooks HL, Johnson LW, Meister SG, Szucs MM, Dexter L. Pulmonary angiography in acute pulmonary embolism: indications, techniques, and results in 367 patients . Am Heart J. 1971;81:175-185.Crossref 16. Stein PD, Athanasoulis C, Alavi A, et al. Complications and validity of pulmonary angiography in acute pulmonary embolism . Circulation . 1992;85:462-468.Crossref 17. Bone RC. Ventilation-perfusion scan in pulmonary embolism: the emperor is incompletely attired . JAMA . 1990;263:2794-2795.Crossref 18. Kakkar W, Flanc C, Howe CT, Clarke MB. Natural history of post-operative deep-vein thrombosis . Lancet . 1969;2:230-232.Crossref 19. Moser KM, LeMoine JR. Is embolic risk conditioned by location of deep venous thrombosis? Ann Intern Med. 1981;94:439-444.Crossref 20. Hull RD, Delmore T, Genton E, et al. Warfarin sodium vs low-dose heparin in the long-term treatment of venous thrombosis . N Engl J Med. 1979;301:855-858.Crossref 21. Hull RD, Raskob GE, Hirsh J, et al. Continuous intravenous heparin compared with intermittent subcutaneous heparin in the initial treatment of proximal-vein thrombosis . N Engl J Med. 1986;315:1109-1114.Crossref 22. Brandjes DPM, Heijboer H, Buller HR, De Rijk M, Jagt H, Ten Cate JW. Acenocoumarol and heparin compared with acenocoumarol alone in the initial treatment of proximal-vein thrombosis . N Engl J Med. 1992;327:1485-1489.Crossref 23. Wheeler HB, Anderson FA Jr. Can noninvasive tests be used as the basis for treatment of deep-vein thrombosis? In: Bernstein EF, ed. Noninvasive Diagnostic Techniques in Vascular Disease . 3rd ed. St Louis, Mo: Mosby—Year Book; 1985:805-818. 24. Hull RD, Hirsh J, Carter CJ, et al. Diagnostic efficacy of impedance plethysmography for clinically suspected deep-vein thrombosis: a randomized trial . Ann Intern Med. 1985;102:21-28.Crossref 25. Huisman MV, Buller HR, Ten Cate JW, Vreeken J. Serial impedance plethysmography for suspected deep venous thrombosis in outpatients: the Amsterdam General Practitioner Study . N Engl J Med. 1986;814:823-828.Crossref 26. Huisman MV, Buller HR, Ten Cate JW, Heijermans HS, Van der Laan J, Van Maanen DJ. Management of clinically suspected acute venous thrombosis in outpatients with serial impedance plethysmography in a community hospital setting . Arch Intern Med. 1989;149:511-513.Crossref 27. Heijboer H, Brandjes D, Lensing AW, Buller HR, Ten Cate JW. Efficacy of real-time B-mode ultrasonography vs impedance plethysmography in the diagnosis of deepvein thrombosis in symptomatic outpatients . Thromb Haemost. 1991;65:436. 28. White RH, McGahan JP, Daschbach MM, Hartling RP. Diagnosis of deep-vein thrombosis using Duplex ultrasound . Ann Intern Med. 1989;111:297-304.Crossref 29. Lensing AW, Prandoni P, Brandjes DPM, et al. Detection of deep-vein thrombosis by real-time B-mode ultrasonography . N Engl J Med. 1989;320:342-345.Crossref 30. Cronan JJ. Ultrasound evaluation of deep venous thrombosis . Semin Roentgenol. 1992;27:39-52.Crossref 31. Hull R, Raskob G, Coates G, Panju A, Gill GJ. A new noninvasive management strategy for patients with suspected pulmonary embolism . Arch Intern Med. 1989;149:2549-2555.Crossref 32. Hull R, Raskob G, Coates G, Panju A. Clinical validity of a normal perfusion lung scan in patients with suspected pulmonary embolism . Chest . 1990;97:23-26.Crossref 33. Kipper MS, Moser KM, Kortman KE, Ashburn WL. Long-term follow-up of patients with suspected pulmonary embolism and a normal lung scan . Chest . 1982;82:411-415.Crossref 34. Hull R, Raskob G, Rosenbloom D, et al. Heparin for 5 days compared with 10 days in the initial treatment of proximal venous thrombosis . N Engl J Med. 1990;322:1260-1264.Crossref 35. Hull R, Hirsh J, Jay R, et al. Different intensities of oral anticoagulant therapy in the treatment of proximal-vein thrombosis . N Engl J Med. 1982;307:1676-1681.Crossref 36. Greenfield LJ. Current indications for and results of Greenfield filter placement . J Vasc Surg. 1984;1:502-504.Crossref 37. Bookstein JJ, Silver TM. The angiographic differential diagnosis of acute pulmonary embolism . Radiology . 1974;110:25-33.Crossref 38. Hull RD, Carter CJ, Jay RM, et al. The diagnosis of acute recurrent deep-vein thrombosis: a diagnostic challenge . Circulation . 1983;67:901-906.Crossref 39. Hull RD, Van Aken WG, Hirsh J, et al. Impedance plethysmography using the occlusive cuff technique in the diagnosis of venous thrombosis . Circulation . 1976;53:696-700.Crossref 40. Hull RD, Taylor DW, Hirsh J, et al. Impedance plethysmography: the relationship between venous filling and sensitivity and specificity for proximal-vein thrombosis . Circulation . 1978;58:898-902.Crossref 41. Rabinov K, Paulin S. Roentgen diagnosis of venous thrombosis in the leg . Arch Surg. 1972;104:134-144.Crossref 42. Coates G, Dolovich M, Koehler D, Newhouse J. Ventilation scanning with technetium labeled aerosols: DTPA or sulfur colloid? Clin Nucl Med. 1985;10:835-838.Crossref 43. Hull RD, Hirsh J, Sackett DL, et al. Clinical validity of a negative venogram in patients with clinically suspected venous thrombosis . Circulation . 1981;64:622-625.Crossref 44. Novelline RA, Baltarowich OH, Athanasoulis CA, Waltman A, Greenfield AJ, McKusick KA. The clinical course of patients with suspected pulmonary embolism and a negative pulmonary arteriogram . Radiology . 1978;126:561-567.Crossref 45. Carter C, Gent M, Leclerc JR. The epidemiology of venous thrombosis . In: Coleman RW, Hirsh J, Marder J, Salzman EW, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice . Philadelphia, Pa: JB Lippincott; 1987:1185-1198. 46. Salzman EW, Hirsh J. Prevention of venous thromboembolism . In: Coleman RW, Hirsh J, Marder V, Salzman EW, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice . 2nd ed. Philadelphia, Pa: JB Lippincott; 1987:1252-1265. 47. Sackett DL, Haynes RB, Tugwell P. Clinical Epidemiology: A Basic Science for Clinical Medicine . Boston, Mass: Little Brown & Co Inc; 1985:159-169. 48. Sackett DL. Bias in analytic research . J Chronic Dis. 1979;32:51-63.Crossref 49. Palevsky HI, Alavi A. A noninvasive strategy for the management of patients suspected of pulmonary embolism . Semin Nucl Med. 1991;21:325-331.Crossref 50. Anderson DR, Lensing AW, Wells PS, Levine MN, Weitz JI, Hirsh J. Limitations of impedance plethysmography in the diagnosis of clinically suspected deepvein thrombosis . Ann Intern Med. 1993;118:25-30.Crossref 51. Heijboer H, Cogo A, Buller HR, Prandoni P, Ten Cate JW. Detection of deep-vein thrombosis with impedance plethysmography and real-time compression ultrasonography in hospitalized patients . Arch Intern Med. 1992;152:1901-1903.Crossref

Journal

Archives of Internal Medicine – American Medical Association

Published: Feb 14, 1994

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