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What is the best approach to a solitary pulmonary nodule identified by chest x-ray?
Your initial risk assessment should include the patient’s smoking history, advancing age, cancer history, and chest radiography features (strength of recommendation [SOR]: A, based on a validated clinical decision rule). You’ll also need to review old chest radiographs (SOR: C, based on expert opinion). A solitary pulmonary nodule unchanged for >2 years on chest radiograph or containing benign central calcifications requires no further work-up (SOR: B, based on historical cohort studies).
While radiologists’ interpretations of a nodule’s calcification on chest radiograph and malignancy on computed tomography (CT) are incorrect in a substantial portion of cases (SOR: B, based on limited-quality diagnostic cohort studies), spiral CT with contrast is still diagnostically useful in making decisions regarding watchful waiting, needle biopsy, or surgery (SOR: B, based on a decision analysis study).
18-fluorodeoxyglucose positron emission tomography (FDG PET) is useful for assessing malignancy risk (SOR: B, based on decision analysis study), but not for solitary pulmonary nodules <1 cm (SOR: C, based on expert opinion).
Direct more costly, invasive tests to those with higher risk of malignancy
Parul Harsora, MD
Rhesa Sanni-Thomas, DO
UT Southwestern Medical Center, Dallas, Tex
Risk stratification of a solitary pulmonary nodule allows the clinician to direct more costly and invasive testing to patients with a higher probability of malignancy. Historical factors such as previous cancer, advanced age, and smoking increase suspicion for malignancy, but CT is generally warranted in all new solitary pulmonary nodules found on chest radiographs. It’s important to obtain a thorough history regarding symptoms (cough, night sweats, weight loss), occupational exposure (asbestos, bird droppings, decaying wood), travel, and comorbid conditions (especially immunocompromised states); this is likely to prove helpful in the workup.
Evidence summary
A solitary pulmonary nodule, or “coin lesion,” is an intraparenchymal finding on chest radiograph or CT that is less than 3 to 4 cm in diameter and not associated with atelectasis or adenopathy. Malignancy rates range from 15% to 75%, depending on the population studied.1 Although early detection of malignancy portends a major improvement in survival (up to 75% at 5 years following surgical resection of stage IA disease), most lung cancers progress asymptomatically until quite advanced.2
The presumed benign nature of lesions that are either unchanged over 2 years or have central calcifications is based on 3 retrospective studies from the 1950s.3-6 However, these should not be considered absolutes. A recent study revisiting the original data calculated the predictive value of benign nature based on no growth to be only 65% (95% confidence interval [CI], 47%–83%).7 Also, a study assessing the accuracy of radiologists’ assessment of calcification in solitary pulmonary nodules compared with thin-section CT found that 7% of “definitely calcified” nodules on chest radiograph lacked calcification on thin-section CT.8
Which clinical variables best predict malignancy?
The best available clinical decision rule was derived and validated from a single split population of patients with solitary pulmonary nodules.9 The outcome variable was defined as malignancy based on histologic tissue analysis or benignity by radiographic stability or resolution over 2 years. The authors did not report whether those determining outcomes and predictors were appropriately blinded.
The authors found that 3 clinical variables (age, smoking history, and cancer history) plus 3 radiographic variables (diameter, spiculation, and nodule location in the upper lobes) were independent predictors of malignancy. An online calculator using this prediction model is available at www.chestx-ray.com/SPN/ SPNProb.html.10
CT or PET?
Three comparative studies observed 8 to 12 radiologists’ readings of high-resolution CT images of 28 to 56 patients with solitary pulmonary nodules (established diagnoses by either histology or stability over time).11-13 Approximately half the nodules represented malignant lesions.
Radiologists assigned a level of confidence to their assessment of each case as benign or malignant. At a minimum, they were informed of each patient’s age and gender, and in 2 studies they also knew other information, such as the patient’s smoking and cancer histories. The study showed that the radiologists would have correctly diagnosed a pair of solitary pulmonary nodule cases, one malignant and one benign, between 75% and 83% of the time. Conversely, 17% to 25% of the time they would have diagnosed the case pair incorrectly.
A meta-analysis of 40 studies of FDG PET scanning for solitary pulmonary nodules yielded a maximum joint sensitivity and specificity of 90% (95% CI, 86.4%– 92.7%).14 The methodological quality of studies included in the meta-analysis was fair, with small sample sizes (inclusion criteria were for a minimum of 10 patients with pulmonary nodules and malignant prevalence of at least 0.5); masking was frequently incomplete.
Sensitivity of histologic/cytologic tests varies
A recent systematic review of studies evaluating patients with suspected lung cancer looked into the diagnostic sensitivity of various methods of histologic and cytologic tests.15 Researchers compared the evaluated test results to a reference standard of pathology/histology, definitive cytology, or at least 1-year radiographic follow-up.
Transbronchial needle aspiration showed a sensitivity of 67% (95% CI, 64%–70%) for peripheral lung malignancy of any size; however, only 5 studies met study criteria and their sample sizes varied greatly (n=20 to n=480). Eight studies looking at bronchoscopy (including brush or biopsy) for peripheral lung lesions <2 cm in diameter yielded a sensitivity of only 33% (95% CI, 28%–38%). In the same systematic review, 61 studies of transthoracic needle aspiration for localized pulmonary lesions of any size had a pooled sensitivity of 90% (95% CI, 88%–92%). The prevalence of malignancy in the studies ranged from 0.58 to 0.93.15 Factors affecting heterogeneity between studies included the wide range in study dates, imaging technology used, and study sizes.
What test is most cost-effective?
CT appears cost-effective when the pretest probability of malignancy is <90%; therefore, consider it on virtually all new cases of solitary pulmonary nodules.1 Also, when CT and pretest risk-assessments are discordant (eg, a patient has a low pretest probability of malignancy but his CT is suggestive of malignancy), the FDG PET scan is the most economically feasible at less than $20,000 per quality-adjusted life year.
Recommendations from others
The American College of Chest Physicians (ACCP)2 suggests pursuing no further evaluation if a nodule is unchanged for >2 years or has benign central calcifications. They recommend that physicians perform CT on every patient with a new nodule to characterize the nodule, its location, and the mediastinum. They do not recommend PET scans for nodules <1 cm. Patients who are marginal surgical candidates and have a negative PET scan should have a repeat CT scan in 3 months; serial CTs at 3, 6, 12, and 24 months are suggested, too, if prior chest radiographs are negative.
The ACCP states that transthoracic needle aspiration is not indicated in surgical candidates unless they decline surgery; then transthoracic needle aspiration or a transbronchial approach are the preferred procedure. Transthoracic needle aspiration may also be useful in establishing a diagnosis for patients who are not surgical candidates or who have a high surgical risk.
ACCP expert consensus favors the reference standard of video-assisted thoracoscopic surgery with wedge resection as the ideal method for obtaining tissue diagnosis in consenting, operable patients with solitary pulmonary nodules. Objective evidence is lacking on follow-up monitoring methods for patients with a nodule who do not have a tissue diagnosis and observation alone is chosen. ACCP expert consensus favors a 2-year follow-up with CT scanning at 3, 6, 12, and 24 months to monitor for nodule growth.2
1. Gould MK, Sanders GD, Barnett PG, et al. Cost-effectiveness of alternative management strategies for patients with solitary pulmonary nodules. Ann Intern Med 2003;138:724-735.
2. Tan BB, Flaherty KR, Kazerooni EA, Iannettoni MD. The solitary pulmonary nodule. Chest 2003;123(1 suppl):89S-96S.
3. Hood RT, Good CA, Clagett OT, McDonald JR. Solitary circumscribed lesions of lung: study of 156 cases in which resection was performed. JAMA 1953;152:1175-1181.
4. Good CA, Hood RT, McDonald JR. Significance of solitary mass in lung. AJR Am J Roentgenol 1953;70:543-554.
5. Good CA. Management of patient with solitary mass in lung. Chic Med Soc Bull 1953;55:893-896.
6. Good CA, Wilson TW. The solitary circumscribed pulmonary nodule: study of 705 cases encountered roentgenologically in a period of three and one-half years. JAMA 1958;166:210-215.
7. Yankelevitz DF, Henschke CI. Does 2-year stability imply that pulmonary nodules are benign? AJR Am J Roentgenol 1997;168:325-328.
8. Berger WG, Erly WK, Krupinski EA, Standen JR, Stern RG. The solitary pulmonary nodule on chest radiography: can we really tell if the nodule is calcified? AJR Am J Roentgenol 2001;176:201-204.
9. Swensen SG, Silverstein MD, Ilstrup DM, Schleck CD, Edell ES. The probability of malignancy in solitary pulmonary nodules: application to small radiographically intermediate nodules. Arch Intern Med 1997;157:849-855.
10. Gurney JW. Probability of malignancy in SPN [Web page]. Available at: www.chestx-ray.com/SPN/ SPNProb.html. Accessed on September 7, 2007.
11. Li F, Aoyama M, Shiraishi J, et al. Radiologists’ performance for differentiating benign from malignant lung nodules on high-resolution CT using computer-estimated likelihood of malignancy. AJR Am J Roentgenol 2004;183:1209-1215.
12. Shah SK, McNitt-Gray MF, De Zoysa KR, et al. Solitary pulmonary nodule diagnosis on CT: results of an observer study. Acad Radiol 2005;12:496-501.
13. Matsuki Y, Nakamura K, Watanabe H, Aoki T, et al. Usefulness of an artificial neural network for differentiating benign from malignant pulmonary nodules on high-resolution CT: evaluation with receiver operating characteristic analysis. AJR Am J Roentgenol 2002;178:657-663.
14. Gould MK, Maclean CC, Kuschner WG, Rydzak CE, Owens DK. Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA 2001;285:914-924.
15. Schreiber G, McCrory DC. Performance characteristics of different modalities for diagnosis of suspected lung cancer. Chest 2003;123:115S-128S.
Your initial risk assessment should include the patient’s smoking history, advancing age, cancer history, and chest radiography features (strength of recommendation [SOR]: A, based on a validated clinical decision rule). You’ll also need to review old chest radiographs (SOR: C, based on expert opinion). A solitary pulmonary nodule unchanged for >2 years on chest radiograph or containing benign central calcifications requires no further work-up (SOR: B, based on historical cohort studies).
While radiologists’ interpretations of a nodule’s calcification on chest radiograph and malignancy on computed tomography (CT) are incorrect in a substantial portion of cases (SOR: B, based on limited-quality diagnostic cohort studies), spiral CT with contrast is still diagnostically useful in making decisions regarding watchful waiting, needle biopsy, or surgery (SOR: B, based on a decision analysis study).
18-fluorodeoxyglucose positron emission tomography (FDG PET) is useful for assessing malignancy risk (SOR: B, based on decision analysis study), but not for solitary pulmonary nodules <1 cm (SOR: C, based on expert opinion).
Direct more costly, invasive tests to those with higher risk of malignancy
Parul Harsora, MD
Rhesa Sanni-Thomas, DO
UT Southwestern Medical Center, Dallas, Tex
Risk stratification of a solitary pulmonary nodule allows the clinician to direct more costly and invasive testing to patients with a higher probability of malignancy. Historical factors such as previous cancer, advanced age, and smoking increase suspicion for malignancy, but CT is generally warranted in all new solitary pulmonary nodules found on chest radiographs. It’s important to obtain a thorough history regarding symptoms (cough, night sweats, weight loss), occupational exposure (asbestos, bird droppings, decaying wood), travel, and comorbid conditions (especially immunocompromised states); this is likely to prove helpful in the workup.
Evidence summary
A solitary pulmonary nodule, or “coin lesion,” is an intraparenchymal finding on chest radiograph or CT that is less than 3 to 4 cm in diameter and not associated with atelectasis or adenopathy. Malignancy rates range from 15% to 75%, depending on the population studied.1 Although early detection of malignancy portends a major improvement in survival (up to 75% at 5 years following surgical resection of stage IA disease), most lung cancers progress asymptomatically until quite advanced.2
The presumed benign nature of lesions that are either unchanged over 2 years or have central calcifications is based on 3 retrospective studies from the 1950s.3-6 However, these should not be considered absolutes. A recent study revisiting the original data calculated the predictive value of benign nature based on no growth to be only 65% (95% confidence interval [CI], 47%–83%).7 Also, a study assessing the accuracy of radiologists’ assessment of calcification in solitary pulmonary nodules compared with thin-section CT found that 7% of “definitely calcified” nodules on chest radiograph lacked calcification on thin-section CT.8
Which clinical variables best predict malignancy?
The best available clinical decision rule was derived and validated from a single split population of patients with solitary pulmonary nodules.9 The outcome variable was defined as malignancy based on histologic tissue analysis or benignity by radiographic stability or resolution over 2 years. The authors did not report whether those determining outcomes and predictors were appropriately blinded.
The authors found that 3 clinical variables (age, smoking history, and cancer history) plus 3 radiographic variables (diameter, spiculation, and nodule location in the upper lobes) were independent predictors of malignancy. An online calculator using this prediction model is available at www.chestx-ray.com/SPN/ SPNProb.html.10
CT or PET?
Three comparative studies observed 8 to 12 radiologists’ readings of high-resolution CT images of 28 to 56 patients with solitary pulmonary nodules (established diagnoses by either histology or stability over time).11-13 Approximately half the nodules represented malignant lesions.
Radiologists assigned a level of confidence to their assessment of each case as benign or malignant. At a minimum, they were informed of each patient’s age and gender, and in 2 studies they also knew other information, such as the patient’s smoking and cancer histories. The study showed that the radiologists would have correctly diagnosed a pair of solitary pulmonary nodule cases, one malignant and one benign, between 75% and 83% of the time. Conversely, 17% to 25% of the time they would have diagnosed the case pair incorrectly.
A meta-analysis of 40 studies of FDG PET scanning for solitary pulmonary nodules yielded a maximum joint sensitivity and specificity of 90% (95% CI, 86.4%– 92.7%).14 The methodological quality of studies included in the meta-analysis was fair, with small sample sizes (inclusion criteria were for a minimum of 10 patients with pulmonary nodules and malignant prevalence of at least 0.5); masking was frequently incomplete.
Sensitivity of histologic/cytologic tests varies
A recent systematic review of studies evaluating patients with suspected lung cancer looked into the diagnostic sensitivity of various methods of histologic and cytologic tests.15 Researchers compared the evaluated test results to a reference standard of pathology/histology, definitive cytology, or at least 1-year radiographic follow-up.
Transbronchial needle aspiration showed a sensitivity of 67% (95% CI, 64%–70%) for peripheral lung malignancy of any size; however, only 5 studies met study criteria and their sample sizes varied greatly (n=20 to n=480). Eight studies looking at bronchoscopy (including brush or biopsy) for peripheral lung lesions <2 cm in diameter yielded a sensitivity of only 33% (95% CI, 28%–38%). In the same systematic review, 61 studies of transthoracic needle aspiration for localized pulmonary lesions of any size had a pooled sensitivity of 90% (95% CI, 88%–92%). The prevalence of malignancy in the studies ranged from 0.58 to 0.93.15 Factors affecting heterogeneity between studies included the wide range in study dates, imaging technology used, and study sizes.
What test is most cost-effective?
CT appears cost-effective when the pretest probability of malignancy is <90%; therefore, consider it on virtually all new cases of solitary pulmonary nodules.1 Also, when CT and pretest risk-assessments are discordant (eg, a patient has a low pretest probability of malignancy but his CT is suggestive of malignancy), the FDG PET scan is the most economically feasible at less than $20,000 per quality-adjusted life year.
Recommendations from others
The American College of Chest Physicians (ACCP)2 suggests pursuing no further evaluation if a nodule is unchanged for >2 years or has benign central calcifications. They recommend that physicians perform CT on every patient with a new nodule to characterize the nodule, its location, and the mediastinum. They do not recommend PET scans for nodules <1 cm. Patients who are marginal surgical candidates and have a negative PET scan should have a repeat CT scan in 3 months; serial CTs at 3, 6, 12, and 24 months are suggested, too, if prior chest radiographs are negative.
The ACCP states that transthoracic needle aspiration is not indicated in surgical candidates unless they decline surgery; then transthoracic needle aspiration or a transbronchial approach are the preferred procedure. Transthoracic needle aspiration may also be useful in establishing a diagnosis for patients who are not surgical candidates or who have a high surgical risk.
ACCP expert consensus favors the reference standard of video-assisted thoracoscopic surgery with wedge resection as the ideal method for obtaining tissue diagnosis in consenting, operable patients with solitary pulmonary nodules. Objective evidence is lacking on follow-up monitoring methods for patients with a nodule who do not have a tissue diagnosis and observation alone is chosen. ACCP expert consensus favors a 2-year follow-up with CT scanning at 3, 6, 12, and 24 months to monitor for nodule growth.2
Your initial risk assessment should include the patient’s smoking history, advancing age, cancer history, and chest radiography features (strength of recommendation [SOR]: A, based on a validated clinical decision rule). You’ll also need to review old chest radiographs (SOR: C, based on expert opinion). A solitary pulmonary nodule unchanged for >2 years on chest radiograph or containing benign central calcifications requires no further work-up (SOR: B, based on historical cohort studies).
While radiologists’ interpretations of a nodule’s calcification on chest radiograph and malignancy on computed tomography (CT) are incorrect in a substantial portion of cases (SOR: B, based on limited-quality diagnostic cohort studies), spiral CT with contrast is still diagnostically useful in making decisions regarding watchful waiting, needle biopsy, or surgery (SOR: B, based on a decision analysis study).
18-fluorodeoxyglucose positron emission tomography (FDG PET) is useful for assessing malignancy risk (SOR: B, based on decision analysis study), but not for solitary pulmonary nodules <1 cm (SOR: C, based on expert opinion).
Direct more costly, invasive tests to those with higher risk of malignancy
Parul Harsora, MD
Rhesa Sanni-Thomas, DO
UT Southwestern Medical Center, Dallas, Tex
Risk stratification of a solitary pulmonary nodule allows the clinician to direct more costly and invasive testing to patients with a higher probability of malignancy. Historical factors such as previous cancer, advanced age, and smoking increase suspicion for malignancy, but CT is generally warranted in all new solitary pulmonary nodules found on chest radiographs. It’s important to obtain a thorough history regarding symptoms (cough, night sweats, weight loss), occupational exposure (asbestos, bird droppings, decaying wood), travel, and comorbid conditions (especially immunocompromised states); this is likely to prove helpful in the workup.
Evidence summary
A solitary pulmonary nodule, or “coin lesion,” is an intraparenchymal finding on chest radiograph or CT that is less than 3 to 4 cm in diameter and not associated with atelectasis or adenopathy. Malignancy rates range from 15% to 75%, depending on the population studied.1 Although early detection of malignancy portends a major improvement in survival (up to 75% at 5 years following surgical resection of stage IA disease), most lung cancers progress asymptomatically until quite advanced.2
The presumed benign nature of lesions that are either unchanged over 2 years or have central calcifications is based on 3 retrospective studies from the 1950s.3-6 However, these should not be considered absolutes. A recent study revisiting the original data calculated the predictive value of benign nature based on no growth to be only 65% (95% confidence interval [CI], 47%–83%).7 Also, a study assessing the accuracy of radiologists’ assessment of calcification in solitary pulmonary nodules compared with thin-section CT found that 7% of “definitely calcified” nodules on chest radiograph lacked calcification on thin-section CT.8
Which clinical variables best predict malignancy?
The best available clinical decision rule was derived and validated from a single split population of patients with solitary pulmonary nodules.9 The outcome variable was defined as malignancy based on histologic tissue analysis or benignity by radiographic stability or resolution over 2 years. The authors did not report whether those determining outcomes and predictors were appropriately blinded.
The authors found that 3 clinical variables (age, smoking history, and cancer history) plus 3 radiographic variables (diameter, spiculation, and nodule location in the upper lobes) were independent predictors of malignancy. An online calculator using this prediction model is available at www.chestx-ray.com/SPN/ SPNProb.html.10
CT or PET?
Three comparative studies observed 8 to 12 radiologists’ readings of high-resolution CT images of 28 to 56 patients with solitary pulmonary nodules (established diagnoses by either histology or stability over time).11-13 Approximately half the nodules represented malignant lesions.
Radiologists assigned a level of confidence to their assessment of each case as benign or malignant. At a minimum, they were informed of each patient’s age and gender, and in 2 studies they also knew other information, such as the patient’s smoking and cancer histories. The study showed that the radiologists would have correctly diagnosed a pair of solitary pulmonary nodule cases, one malignant and one benign, between 75% and 83% of the time. Conversely, 17% to 25% of the time they would have diagnosed the case pair incorrectly.
A meta-analysis of 40 studies of FDG PET scanning for solitary pulmonary nodules yielded a maximum joint sensitivity and specificity of 90% (95% CI, 86.4%– 92.7%).14 The methodological quality of studies included in the meta-analysis was fair, with small sample sizes (inclusion criteria were for a minimum of 10 patients with pulmonary nodules and malignant prevalence of at least 0.5); masking was frequently incomplete.
Sensitivity of histologic/cytologic tests varies
A recent systematic review of studies evaluating patients with suspected lung cancer looked into the diagnostic sensitivity of various methods of histologic and cytologic tests.15 Researchers compared the evaluated test results to a reference standard of pathology/histology, definitive cytology, or at least 1-year radiographic follow-up.
Transbronchial needle aspiration showed a sensitivity of 67% (95% CI, 64%–70%) for peripheral lung malignancy of any size; however, only 5 studies met study criteria and their sample sizes varied greatly (n=20 to n=480). Eight studies looking at bronchoscopy (including brush or biopsy) for peripheral lung lesions <2 cm in diameter yielded a sensitivity of only 33% (95% CI, 28%–38%). In the same systematic review, 61 studies of transthoracic needle aspiration for localized pulmonary lesions of any size had a pooled sensitivity of 90% (95% CI, 88%–92%). The prevalence of malignancy in the studies ranged from 0.58 to 0.93.15 Factors affecting heterogeneity between studies included the wide range in study dates, imaging technology used, and study sizes.
What test is most cost-effective?
CT appears cost-effective when the pretest probability of malignancy is <90%; therefore, consider it on virtually all new cases of solitary pulmonary nodules.1 Also, when CT and pretest risk-assessments are discordant (eg, a patient has a low pretest probability of malignancy but his CT is suggestive of malignancy), the FDG PET scan is the most economically feasible at less than $20,000 per quality-adjusted life year.
Recommendations from others
The American College of Chest Physicians (ACCP)2 suggests pursuing no further evaluation if a nodule is unchanged for >2 years or has benign central calcifications. They recommend that physicians perform CT on every patient with a new nodule to characterize the nodule, its location, and the mediastinum. They do not recommend PET scans for nodules <1 cm. Patients who are marginal surgical candidates and have a negative PET scan should have a repeat CT scan in 3 months; serial CTs at 3, 6, 12, and 24 months are suggested, too, if prior chest radiographs are negative.
The ACCP states that transthoracic needle aspiration is not indicated in surgical candidates unless they decline surgery; then transthoracic needle aspiration or a transbronchial approach are the preferred procedure. Transthoracic needle aspiration may also be useful in establishing a diagnosis for patients who are not surgical candidates or who have a high surgical risk.
ACCP expert consensus favors the reference standard of video-assisted thoracoscopic surgery with wedge resection as the ideal method for obtaining tissue diagnosis in consenting, operable patients with solitary pulmonary nodules. Objective evidence is lacking on follow-up monitoring methods for patients with a nodule who do not have a tissue diagnosis and observation alone is chosen. ACCP expert consensus favors a 2-year follow-up with CT scanning at 3, 6, 12, and 24 months to monitor for nodule growth.2
1. Gould MK, Sanders GD, Barnett PG, et al. Cost-effectiveness of alternative management strategies for patients with solitary pulmonary nodules. Ann Intern Med 2003;138:724-735.
2. Tan BB, Flaherty KR, Kazerooni EA, Iannettoni MD. The solitary pulmonary nodule. Chest 2003;123(1 suppl):89S-96S.
3. Hood RT, Good CA, Clagett OT, McDonald JR. Solitary circumscribed lesions of lung: study of 156 cases in which resection was performed. JAMA 1953;152:1175-1181.
4. Good CA, Hood RT, McDonald JR. Significance of solitary mass in lung. AJR Am J Roentgenol 1953;70:543-554.
5. Good CA. Management of patient with solitary mass in lung. Chic Med Soc Bull 1953;55:893-896.
6. Good CA, Wilson TW. The solitary circumscribed pulmonary nodule: study of 705 cases encountered roentgenologically in a period of three and one-half years. JAMA 1958;166:210-215.
7. Yankelevitz DF, Henschke CI. Does 2-year stability imply that pulmonary nodules are benign? AJR Am J Roentgenol 1997;168:325-328.
8. Berger WG, Erly WK, Krupinski EA, Standen JR, Stern RG. The solitary pulmonary nodule on chest radiography: can we really tell if the nodule is calcified? AJR Am J Roentgenol 2001;176:201-204.
9. Swensen SG, Silverstein MD, Ilstrup DM, Schleck CD, Edell ES. The probability of malignancy in solitary pulmonary nodules: application to small radiographically intermediate nodules. Arch Intern Med 1997;157:849-855.
10. Gurney JW. Probability of malignancy in SPN [Web page]. Available at: www.chestx-ray.com/SPN/ SPNProb.html. Accessed on September 7, 2007.
11. Li F, Aoyama M, Shiraishi J, et al. Radiologists’ performance for differentiating benign from malignant lung nodules on high-resolution CT using computer-estimated likelihood of malignancy. AJR Am J Roentgenol 2004;183:1209-1215.
12. Shah SK, McNitt-Gray MF, De Zoysa KR, et al. Solitary pulmonary nodule diagnosis on CT: results of an observer study. Acad Radiol 2005;12:496-501.
13. Matsuki Y, Nakamura K, Watanabe H, Aoki T, et al. Usefulness of an artificial neural network for differentiating benign from malignant pulmonary nodules on high-resolution CT: evaluation with receiver operating characteristic analysis. AJR Am J Roentgenol 2002;178:657-663.
14. Gould MK, Maclean CC, Kuschner WG, Rydzak CE, Owens DK. Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA 2001;285:914-924.
15. Schreiber G, McCrory DC. Performance characteristics of different modalities for diagnosis of suspected lung cancer. Chest 2003;123:115S-128S.
1. Gould MK, Sanders GD, Barnett PG, et al. Cost-effectiveness of alternative management strategies for patients with solitary pulmonary nodules. Ann Intern Med 2003;138:724-735.
2. Tan BB, Flaherty KR, Kazerooni EA, Iannettoni MD. The solitary pulmonary nodule. Chest 2003;123(1 suppl):89S-96S.
3. Hood RT, Good CA, Clagett OT, McDonald JR. Solitary circumscribed lesions of lung: study of 156 cases in which resection was performed. JAMA 1953;152:1175-1181.
4. Good CA, Hood RT, McDonald JR. Significance of solitary mass in lung. AJR Am J Roentgenol 1953;70:543-554.
5. Good CA. Management of patient with solitary mass in lung. Chic Med Soc Bull 1953;55:893-896.
6. Good CA, Wilson TW. The solitary circumscribed pulmonary nodule: study of 705 cases encountered roentgenologically in a period of three and one-half years. JAMA 1958;166:210-215.
7. Yankelevitz DF, Henschke CI. Does 2-year stability imply that pulmonary nodules are benign? AJR Am J Roentgenol 1997;168:325-328.
8. Berger WG, Erly WK, Krupinski EA, Standen JR, Stern RG. The solitary pulmonary nodule on chest radiography: can we really tell if the nodule is calcified? AJR Am J Roentgenol 2001;176:201-204.
9. Swensen SG, Silverstein MD, Ilstrup DM, Schleck CD, Edell ES. The probability of malignancy in solitary pulmonary nodules: application to small radiographically intermediate nodules. Arch Intern Med 1997;157:849-855.
10. Gurney JW. Probability of malignancy in SPN [Web page]. Available at: www.chestx-ray.com/SPN/ SPNProb.html. Accessed on September 7, 2007.
11. Li F, Aoyama M, Shiraishi J, et al. Radiologists’ performance for differentiating benign from malignant lung nodules on high-resolution CT using computer-estimated likelihood of malignancy. AJR Am J Roentgenol 2004;183:1209-1215.
12. Shah SK, McNitt-Gray MF, De Zoysa KR, et al. Solitary pulmonary nodule diagnosis on CT: results of an observer study. Acad Radiol 2005;12:496-501.
13. Matsuki Y, Nakamura K, Watanabe H, Aoki T, et al. Usefulness of an artificial neural network for differentiating benign from malignant pulmonary nodules on high-resolution CT: evaluation with receiver operating characteristic analysis. AJR Am J Roentgenol 2002;178:657-663.
14. Gould MK, Maclean CC, Kuschner WG, Rydzak CE, Owens DK. Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA 2001;285:914-924.
15. Schreiber G, McCrory DC. Performance characteristics of different modalities for diagnosis of suspected lung cancer. Chest 2003;123:115S-128S.
Evidence-based answers from the Family Physicians Inquiries Network
What common substances can cause false positives on urine screens for drugs of abuse?
False-positive reports on urine drug screens by immunoassay are rare (strength of recommendation [SOR]: C, small controlled-exposure studies, small case series). Nonsteroidal anti-inflammatory drugs, fluoroquinolones, and Vicks Inhaler are most frequently implicated (TABLE).
Ruling out a false-positive result requires confirmation with a more specific test, usually gas chromatography/mass spectrometry (GC-MS). A true-positive drug screen may occur in a urine specimen from a patient who legally or unknowingly ingests a product that is metabolized to a drug of abuse. Passive exposure to a substance is unlikely to cause a positive drug screen (SOR: B, small controlled-exposure studies).
Having a plan makes communication less emotional when the results come back
Mary M. Stephens, MD, MPH
East Tennessee State University, Kingsport
Before I order a urine drug screen I ask myself, “What will I do with the results?” If other substances are present, will I discontinue controlled substances or refer to psychiatry or pain management? I also ask patients what they think I will find. On several occasions, patients have admitted to taking recreational drugs that the drug screen misses. Having a plan makes communication less emotional for both the provider and patient when the results come back.
You should be able to follow-up results promptly and order a GC-MS if indicated. In addition, if working in a group, indicate a plan for follow-up in your progress notes so that the patient gets a consistent message.
Evidence summary
Two different assays are commonly available for urine drug testing. The immunoassay is quick, highly sensitive, and relatively inexpensive but may lack specificity. It tests for classes of drugs (such as opiates) without distinguishing among individual drugs within that class. Gas chromatography in combination with mass spectrometry (GC-MS) is a more expensive and time-consuming test, but is the gold standard for confirming a positive result on immunoassay. By definition, all positive results on GC-MS are true positives.
Reports of false-positive urine drug screening for substances of abuse are infrequent and limited to case reports and a few controlled-exposure studies. The TABLE lists some of the substances reported to cause false-positive results.
Positive confirmation tests may occur in urine specimens from patients who legally or unknowingly ingest products that contain drugs of abuse. In these instances, the finding is a true positive but may not reflect drug abuse by the client. Many products available without prescription outside of the US contain opiates (eg, Donnagel PG from Canada).1 Several controlled-exposure studies have shown that as little as 1 poppy seed muffin (about 15 g of seed) can produce detectable amounts of morphine and codeine by immunoassay as well as GC-MS.1,2 In 1998, the federal government increased the threshold defining a positive screen for urine morphine and codeine from 300 to 2000 ng/mL to reduce spurious reports of opiate-positive tests from poppy seed consumption.1,2
Substances that do not produce positive urine drug screens include passively inhaled crack cocaine or marijuana (unless “extreme”), and ingested products containing hemp or other common herbal preparations.1,2,10 In one study, 6 volunteers in an 8×8×7-ft enclosed room were exposed to 200 mg freebase cocaine vapor; none of their urine samples exceeded the federal GC-MS threshold. In a similar study of 3 non-smokers exposed to 8 marijuana smokers (smoking 32 joints) in a 10×10×8-ft enclosed room, no samples from the nonsmokers exceeded the federal GC-MS threshold.2 In an exposure study of 90 volunteers who ingested 8 different herbal preparations, there were no positive urine drug screens.1
TABLE
Substances reported to cause false-positive urine drug screen results
| SUBSTANCE FALSELY IDENTIFIED ON TEST | ACTUALSUBSTANCE | TYPE OF STUDY | NOTES |
|---|---|---|---|
| Amphetamine and methamphetamine | Selegiline | Single case report1,2 | L-stereoisomer only detected (D-stereoisomer present in illicit drugs) |
| Amphetamine and methamphetamine | Vicks Inhaler | Several case reports, controlled-exposure studies1-3 | L-stereoisomer only detected; most positives noted with twice recommended dosage |
| Barbiturate | NSAIDs (ibuprofen, naproxen) | Controlled-exposure study of 60 subjects (510 specimens)4 | 0.4% false-positive rate |
| Benzodiazepine | Oxaprozin | Controlled-exposure study of 12 patients (36 specimens)5 | 100% false-positive rate, some cases lack controls |
| Cannabinoid | NSAIDs (ibuprofen, naproxen) | Controlled-exposure study of 60 subjects (510 specimens)4 | 0.4% false-positive rate |
| Opiate | Fluoroquinolone* | Controlled-exposure studies (8 subjects) and case series (9 subjects)6 | Most levels detected were below new 1998 threshold (2000 ng/mL) |
| Opiate | Rifampin | 3 case reports7 | |
| Phencyclidine | Venlafaxine | 1case report8 | Confirmed by GC-MS (7200 mg intentionally ingested) |
| Phencyclidine | Dextromethorphan | 1case report9 | (500 mg ingested) |
| *Ofloxacin and levofloxacin most likely to cause false positive. | |||
Recommendations from others
The US Department of Health and Human Services requires confirmation of positive immunoassay results by GC-MS for drug testing in the workplace.1 The College of American Pathologists, the principal organization of board-certified pathologists, states: “Confirmation testing, a standard of practice in forensic toxicology, should be performed in clinical toxicology whenever possible.”11
1. Medical Review Officer Manual for Federal Agency Workplace Drug Testing Programs. US Department of Health and Human Services, Substance Abuse and Mental Health Services Administration, Division of Workplace Programs. Available at: dwp.samhsa.gov/DrugTesting/DTesting.aspx. Accessed on September 6, 2006.
2. elSohly MA, Jones AB. Drug testing in the workplace: could a positive test for one of the mandated drugs be for reasons other than illicit use of the drug? J Anal Toxicol 1995;19:450-458.
3. Poklis A, Moore KA. Response of EMIT amphetamine immunoassays to urinary desoxyephedrine following Vicks inhaler use. Ther Drug Monit 1995;17:89-94.
4. Rollins DE, Jennison TA, Jones G. Investigation of interference by nonsteroidal anti-inflammatory drugs in urine tests for abused drugs. Clin Chem 1990;36:602-606.
5. Fraser AD, Howell P. Oxaprozin cross-reactivity in three commercial immunoassays for benzodiazepines in urine. J Anal Toxicol 1998;22:50-54.
6. Zacher JL, Givone DM. False-positive urine opiate screening associated with fluoroquinolone use. Ann Pharmacother 2004;38:1525-1528.
7. Daher R, Haidar JH, Al-Amin H. Rifampin interference with opiate immunoassays. Clin Chem 2002;48:203-204.
8. Bond GR, Steele PE, Uges DR. Massive venlafaxine overdose resulted in a false positive Abbott AxSYM urine immunoassay for phencyclidine. J Toxicol Clin Toxicol 2003;41:999-1002.
9. Budai B, Iskandar H. Dextromethorphan can produce false positive phencyclidine testing with HPLC. Am J Emerg Med 2002;20:61-62.
10. Markowitz JS, Donovan JL, DeVane CL, Chavin KD. Common herbal supplements did not produce false-positive results on urine drug screens analyzed by enzyme immunoassay. J Anal Toxicol 2004;28:272-273.
11. Caplan YH, Kwong TC. Evaluation of Toxicology Test Results. Available at: www.cap.org/apps/docs/disciplines/toxicology/toxeval.pdf. Accessed on September 6, 2006.
False-positive reports on urine drug screens by immunoassay are rare (strength of recommendation [SOR]: C, small controlled-exposure studies, small case series). Nonsteroidal anti-inflammatory drugs, fluoroquinolones, and Vicks Inhaler are most frequently implicated (TABLE).
Ruling out a false-positive result requires confirmation with a more specific test, usually gas chromatography/mass spectrometry (GC-MS). A true-positive drug screen may occur in a urine specimen from a patient who legally or unknowingly ingests a product that is metabolized to a drug of abuse. Passive exposure to a substance is unlikely to cause a positive drug screen (SOR: B, small controlled-exposure studies).
Having a plan makes communication less emotional when the results come back
Mary M. Stephens, MD, MPH
East Tennessee State University, Kingsport
Before I order a urine drug screen I ask myself, “What will I do with the results?” If other substances are present, will I discontinue controlled substances or refer to psychiatry or pain management? I also ask patients what they think I will find. On several occasions, patients have admitted to taking recreational drugs that the drug screen misses. Having a plan makes communication less emotional for both the provider and patient when the results come back.
You should be able to follow-up results promptly and order a GC-MS if indicated. In addition, if working in a group, indicate a plan for follow-up in your progress notes so that the patient gets a consistent message.
Evidence summary
Two different assays are commonly available for urine drug testing. The immunoassay is quick, highly sensitive, and relatively inexpensive but may lack specificity. It tests for classes of drugs (such as opiates) without distinguishing among individual drugs within that class. Gas chromatography in combination with mass spectrometry (GC-MS) is a more expensive and time-consuming test, but is the gold standard for confirming a positive result on immunoassay. By definition, all positive results on GC-MS are true positives.
Reports of false-positive urine drug screening for substances of abuse are infrequent and limited to case reports and a few controlled-exposure studies. The TABLE lists some of the substances reported to cause false-positive results.
Positive confirmation tests may occur in urine specimens from patients who legally or unknowingly ingest products that contain drugs of abuse. In these instances, the finding is a true positive but may not reflect drug abuse by the client. Many products available without prescription outside of the US contain opiates (eg, Donnagel PG from Canada).1 Several controlled-exposure studies have shown that as little as 1 poppy seed muffin (about 15 g of seed) can produce detectable amounts of morphine and codeine by immunoassay as well as GC-MS.1,2 In 1998, the federal government increased the threshold defining a positive screen for urine morphine and codeine from 300 to 2000 ng/mL to reduce spurious reports of opiate-positive tests from poppy seed consumption.1,2
Substances that do not produce positive urine drug screens include passively inhaled crack cocaine or marijuana (unless “extreme”), and ingested products containing hemp or other common herbal preparations.1,2,10 In one study, 6 volunteers in an 8×8×7-ft enclosed room were exposed to 200 mg freebase cocaine vapor; none of their urine samples exceeded the federal GC-MS threshold. In a similar study of 3 non-smokers exposed to 8 marijuana smokers (smoking 32 joints) in a 10×10×8-ft enclosed room, no samples from the nonsmokers exceeded the federal GC-MS threshold.2 In an exposure study of 90 volunteers who ingested 8 different herbal preparations, there were no positive urine drug screens.1
TABLE
Substances reported to cause false-positive urine drug screen results
| SUBSTANCE FALSELY IDENTIFIED ON TEST | ACTUALSUBSTANCE | TYPE OF STUDY | NOTES |
|---|---|---|---|
| Amphetamine and methamphetamine | Selegiline | Single case report1,2 | L-stereoisomer only detected (D-stereoisomer present in illicit drugs) |
| Amphetamine and methamphetamine | Vicks Inhaler | Several case reports, controlled-exposure studies1-3 | L-stereoisomer only detected; most positives noted with twice recommended dosage |
| Barbiturate | NSAIDs (ibuprofen, naproxen) | Controlled-exposure study of 60 subjects (510 specimens)4 | 0.4% false-positive rate |
| Benzodiazepine | Oxaprozin | Controlled-exposure study of 12 patients (36 specimens)5 | 100% false-positive rate, some cases lack controls |
| Cannabinoid | NSAIDs (ibuprofen, naproxen) | Controlled-exposure study of 60 subjects (510 specimens)4 | 0.4% false-positive rate |
| Opiate | Fluoroquinolone* | Controlled-exposure studies (8 subjects) and case series (9 subjects)6 | Most levels detected were below new 1998 threshold (2000 ng/mL) |
| Opiate | Rifampin | 3 case reports7 | |
| Phencyclidine | Venlafaxine | 1case report8 | Confirmed by GC-MS (7200 mg intentionally ingested) |
| Phencyclidine | Dextromethorphan | 1case report9 | (500 mg ingested) |
| *Ofloxacin and levofloxacin most likely to cause false positive. | |||
Recommendations from others
The US Department of Health and Human Services requires confirmation of positive immunoassay results by GC-MS for drug testing in the workplace.1 The College of American Pathologists, the principal organization of board-certified pathologists, states: “Confirmation testing, a standard of practice in forensic toxicology, should be performed in clinical toxicology whenever possible.”11
False-positive reports on urine drug screens by immunoassay are rare (strength of recommendation [SOR]: C, small controlled-exposure studies, small case series). Nonsteroidal anti-inflammatory drugs, fluoroquinolones, and Vicks Inhaler are most frequently implicated (TABLE).
Ruling out a false-positive result requires confirmation with a more specific test, usually gas chromatography/mass spectrometry (GC-MS). A true-positive drug screen may occur in a urine specimen from a patient who legally or unknowingly ingests a product that is metabolized to a drug of abuse. Passive exposure to a substance is unlikely to cause a positive drug screen (SOR: B, small controlled-exposure studies).
Having a plan makes communication less emotional when the results come back
Mary M. Stephens, MD, MPH
East Tennessee State University, Kingsport
Before I order a urine drug screen I ask myself, “What will I do with the results?” If other substances are present, will I discontinue controlled substances or refer to psychiatry or pain management? I also ask patients what they think I will find. On several occasions, patients have admitted to taking recreational drugs that the drug screen misses. Having a plan makes communication less emotional for both the provider and patient when the results come back.
You should be able to follow-up results promptly and order a GC-MS if indicated. In addition, if working in a group, indicate a plan for follow-up in your progress notes so that the patient gets a consistent message.
Evidence summary
Two different assays are commonly available for urine drug testing. The immunoassay is quick, highly sensitive, and relatively inexpensive but may lack specificity. It tests for classes of drugs (such as opiates) without distinguishing among individual drugs within that class. Gas chromatography in combination with mass spectrometry (GC-MS) is a more expensive and time-consuming test, but is the gold standard for confirming a positive result on immunoassay. By definition, all positive results on GC-MS are true positives.
Reports of false-positive urine drug screening for substances of abuse are infrequent and limited to case reports and a few controlled-exposure studies. The TABLE lists some of the substances reported to cause false-positive results.
Positive confirmation tests may occur in urine specimens from patients who legally or unknowingly ingest products that contain drugs of abuse. In these instances, the finding is a true positive but may not reflect drug abuse by the client. Many products available without prescription outside of the US contain opiates (eg, Donnagel PG from Canada).1 Several controlled-exposure studies have shown that as little as 1 poppy seed muffin (about 15 g of seed) can produce detectable amounts of morphine and codeine by immunoassay as well as GC-MS.1,2 In 1998, the federal government increased the threshold defining a positive screen for urine morphine and codeine from 300 to 2000 ng/mL to reduce spurious reports of opiate-positive tests from poppy seed consumption.1,2
Substances that do not produce positive urine drug screens include passively inhaled crack cocaine or marijuana (unless “extreme”), and ingested products containing hemp or other common herbal preparations.1,2,10 In one study, 6 volunteers in an 8×8×7-ft enclosed room were exposed to 200 mg freebase cocaine vapor; none of their urine samples exceeded the federal GC-MS threshold. In a similar study of 3 non-smokers exposed to 8 marijuana smokers (smoking 32 joints) in a 10×10×8-ft enclosed room, no samples from the nonsmokers exceeded the federal GC-MS threshold.2 In an exposure study of 90 volunteers who ingested 8 different herbal preparations, there were no positive urine drug screens.1
TABLE
Substances reported to cause false-positive urine drug screen results
| SUBSTANCE FALSELY IDENTIFIED ON TEST | ACTUALSUBSTANCE | TYPE OF STUDY | NOTES |
|---|---|---|---|
| Amphetamine and methamphetamine | Selegiline | Single case report1,2 | L-stereoisomer only detected (D-stereoisomer present in illicit drugs) |
| Amphetamine and methamphetamine | Vicks Inhaler | Several case reports, controlled-exposure studies1-3 | L-stereoisomer only detected; most positives noted with twice recommended dosage |
| Barbiturate | NSAIDs (ibuprofen, naproxen) | Controlled-exposure study of 60 subjects (510 specimens)4 | 0.4% false-positive rate |
| Benzodiazepine | Oxaprozin | Controlled-exposure study of 12 patients (36 specimens)5 | 100% false-positive rate, some cases lack controls |
| Cannabinoid | NSAIDs (ibuprofen, naproxen) | Controlled-exposure study of 60 subjects (510 specimens)4 | 0.4% false-positive rate |
| Opiate | Fluoroquinolone* | Controlled-exposure studies (8 subjects) and case series (9 subjects)6 | Most levels detected were below new 1998 threshold (2000 ng/mL) |
| Opiate | Rifampin | 3 case reports7 | |
| Phencyclidine | Venlafaxine | 1case report8 | Confirmed by GC-MS (7200 mg intentionally ingested) |
| Phencyclidine | Dextromethorphan | 1case report9 | (500 mg ingested) |
| *Ofloxacin and levofloxacin most likely to cause false positive. | |||
Recommendations from others
The US Department of Health and Human Services requires confirmation of positive immunoassay results by GC-MS for drug testing in the workplace.1 The College of American Pathologists, the principal organization of board-certified pathologists, states: “Confirmation testing, a standard of practice in forensic toxicology, should be performed in clinical toxicology whenever possible.”11
1. Medical Review Officer Manual for Federal Agency Workplace Drug Testing Programs. US Department of Health and Human Services, Substance Abuse and Mental Health Services Administration, Division of Workplace Programs. Available at: dwp.samhsa.gov/DrugTesting/DTesting.aspx. Accessed on September 6, 2006.
2. elSohly MA, Jones AB. Drug testing in the workplace: could a positive test for one of the mandated drugs be for reasons other than illicit use of the drug? J Anal Toxicol 1995;19:450-458.
3. Poklis A, Moore KA. Response of EMIT amphetamine immunoassays to urinary desoxyephedrine following Vicks inhaler use. Ther Drug Monit 1995;17:89-94.
4. Rollins DE, Jennison TA, Jones G. Investigation of interference by nonsteroidal anti-inflammatory drugs in urine tests for abused drugs. Clin Chem 1990;36:602-606.
5. Fraser AD, Howell P. Oxaprozin cross-reactivity in three commercial immunoassays for benzodiazepines in urine. J Anal Toxicol 1998;22:50-54.
6. Zacher JL, Givone DM. False-positive urine opiate screening associated with fluoroquinolone use. Ann Pharmacother 2004;38:1525-1528.
7. Daher R, Haidar JH, Al-Amin H. Rifampin interference with opiate immunoassays. Clin Chem 2002;48:203-204.
8. Bond GR, Steele PE, Uges DR. Massive venlafaxine overdose resulted in a false positive Abbott AxSYM urine immunoassay for phencyclidine. J Toxicol Clin Toxicol 2003;41:999-1002.
9. Budai B, Iskandar H. Dextromethorphan can produce false positive phencyclidine testing with HPLC. Am J Emerg Med 2002;20:61-62.
10. Markowitz JS, Donovan JL, DeVane CL, Chavin KD. Common herbal supplements did not produce false-positive results on urine drug screens analyzed by enzyme immunoassay. J Anal Toxicol 2004;28:272-273.
11. Caplan YH, Kwong TC. Evaluation of Toxicology Test Results. Available at: www.cap.org/apps/docs/disciplines/toxicology/toxeval.pdf. Accessed on September 6, 2006.
1. Medical Review Officer Manual for Federal Agency Workplace Drug Testing Programs. US Department of Health and Human Services, Substance Abuse and Mental Health Services Administration, Division of Workplace Programs. Available at: dwp.samhsa.gov/DrugTesting/DTesting.aspx. Accessed on September 6, 2006.
2. elSohly MA, Jones AB. Drug testing in the workplace: could a positive test for one of the mandated drugs be for reasons other than illicit use of the drug? J Anal Toxicol 1995;19:450-458.
3. Poklis A, Moore KA. Response of EMIT amphetamine immunoassays to urinary desoxyephedrine following Vicks inhaler use. Ther Drug Monit 1995;17:89-94.
4. Rollins DE, Jennison TA, Jones G. Investigation of interference by nonsteroidal anti-inflammatory drugs in urine tests for abused drugs. Clin Chem 1990;36:602-606.
5. Fraser AD, Howell P. Oxaprozin cross-reactivity in three commercial immunoassays for benzodiazepines in urine. J Anal Toxicol 1998;22:50-54.
6. Zacher JL, Givone DM. False-positive urine opiate screening associated with fluoroquinolone use. Ann Pharmacother 2004;38:1525-1528.
7. Daher R, Haidar JH, Al-Amin H. Rifampin interference with opiate immunoassays. Clin Chem 2002;48:203-204.
8. Bond GR, Steele PE, Uges DR. Massive venlafaxine overdose resulted in a false positive Abbott AxSYM urine immunoassay for phencyclidine. J Toxicol Clin Toxicol 2003;41:999-1002.
9. Budai B, Iskandar H. Dextromethorphan can produce false positive phencyclidine testing with HPLC. Am J Emerg Med 2002;20:61-62.
10. Markowitz JS, Donovan JL, DeVane CL, Chavin KD. Common herbal supplements did not produce false-positive results on urine drug screens analyzed by enzyme immunoassay. J Anal Toxicol 2004;28:272-273.
11. Caplan YH, Kwong TC. Evaluation of Toxicology Test Results. Available at: www.cap.org/apps/docs/disciplines/toxicology/toxeval.pdf. Accessed on September 6, 2006.
Evidence-based answers from the Family Physicians Inquiries Network