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Factors Influencing the Treatment of COPD
Lindenauer PK, Pekow P, Gao S, et al. Quality of care for patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease. Ann Intern Med. 2006;144:894-903.
Background
Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States, resulting in more than $18 billion in annual health costs. Acute exacerbations of COPD can lead to respiratory compromise and are one of the 10 leading causes of hospitalization in the United States.
Hospitalists currently have evidence-based guidelines available that recommend therapies for patients with acute exacerbations of COPD. This study was designed to evaluate the practice patterns in the United States and to evaluate the quality of care provided to hospitalized patients based on comparisons with these published guidelines. The authors did not report any conflicts of interest, and this work was performed without external grant support.
Methods
Using administrative data from the 360 hospitals that participate in Perspective, a database developed for measuring healthcare quality and utilization, the authors performed a retrospective cohort study. Patients hospitalized for a primary diagnosis of acute exacerbation of COPD were chosen. Patients with pneumonia were specifically excluded. The outcomes of interest included adherence to the diagnostic and therapeutic recommendations of the joint American College of Physicians and American College of Chest Physicians evidence-based COPD guideline, published in 2001.
Results
Of the 69,820 patients included in the analysis, 33% received “ideal care,” defined as all of the recommended care and none of the non-beneficial interventions. Specific results included varied utilization of recommended care: 95% had chest radiography, 91% received supplemental oxygen, 97% had bronchodilators, 85% were given systemic steroids, and 85% received antibiotics.
Overall, 45% of patients received at least one non-beneficial intervention specified in the guidelines: 24% were treated with methylxanthines, 14% underwent sputum testing, 12% had acute spirometry, 6% received chest physiotherapy, and 2% were given mucolytics.
Older patients and women were more likely to receive ideal care as defined, but hospitals with a higher annual volume of COPD cases were not associated with improved performance in this analysis.
Conclusions
Given a widely accepted evidence-based practice guideline as a benchmark, significant variation exists across hospitals in the quality of care for acute exacerbations of COPD. Opportunities exist to improve the quality of care, in particular by increasing the use of systemic corticosteroids and antibiotic therapy and reducing the utilization of many diagnostic and therapeutic interventions that are not only not recommended but are also potentially harmful.
Commentary
COPD management in the acute inpatient setting is on the horizon as a focus of policymakers, and this study suggests that significant opportunities exist for inpatient physicians to reduce variation in practice and utilize an evidence-based approach to the treatment of acute exacerbations of COPD. This study is limited by its use of administrative data, its inability to use clinical data to best determine appropriate care processes for individual patients, and its retrospective design.
As we move toward external quality metrics for the care of patients with acute exacerbations of COPD, further prospective studies evaluating clinical outcomes of interest, including mortality and readmission rates, are needed to determine the effects of adherence to ideal or recommended care for acute exacerbations of COPD.1-3
References
- Snow V, Lascher S, Mottur-Pilson C, et al. Evidence base for management of acute exacerbations of chronic obstructive pulmonary disease. Ann Intern Med. 2001 Apr 3;134(7):595-599.
- American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, November 1986. Am Rev Respir Dis. 1987 Jul;136(1):225-244.
- Agency for Healthcare Research and Quality. Management of Acute Exacerbations of Chronic Obstructive Pulmonary Disease. Rockville, Md.: Agency for Healthcare Research and Quality; 2000.
The Role of Dipyridamole in the Secondary Prevention of Stroke
ESPRIT Study Group. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomized controlled trial. Lancet. 2006 May 20;367(9623):1665-1673.
Background
To date, studies have resulted in inconsistent results in trials of aspirin versus aspirin in combination with dipyridamole for secondary prevention of ischemic stroke. Four early, smaller studies have yielded non-significant results, in contrast to the statistically significant relative risk reduction seen with the addition of dipyridamole to aspirin in the European Stroke Prevention Study 2 (ESPS-2).1-2
Methods
The European/Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) study group conducted a prospective randomized controlled trial of 2,763 patients with transient ischemic attacks or minor ischemic stroke of presumed arterial origin who received aspirin (30-325 mg daily) with or without dipyridamole (200 mg twice daily) as secondary prevention. The primary outcome for this study was a composite of death from vascular causes, nonfatal stroke, nonfatal myocardial infarction, or major bleeding complication. Mean follow-up of patients enrolled was 3.5 years.
Results
In an intention-to-treat analysis, the primary combined endpoint occurred in 16% (216) of the patients on aspirin alone (median aspirin dose was 75 mg in both groups) compared with 13% (173) of the patients on aspirin plus dipyridamole. This result was statistically significant, with an absolute risk reduction of 1% per year. As noted in other trials, patients on dipyridamole discontinued their study medication more frequently than patients on aspirin alone, mostly due to headache.
Conclusions
The results of this trial, taken in the context of previously published data, support the combination of aspirin plus dipyridamole over aspirin alone for the secondary prevention of ischemic stroke of presumed arterial origin. Addition of these data to the previous meta-analysis of trials resulted in a statistically significant risk ratio for the composite endpoint of 0.82 (95% confidence interval, 0.74-0.91).1
Commentary
Ischemic stroke and transient ischemic attacks remain a challenge to effectively manage medically and are appropriately greatly feared health complications for many patients, resulting in significant morbidity and mortality. Prior studies of secondary prevention with aspirin therapy have demonstrated only a modest reduction in vascular complications in these patients.3-4
The results of this trial are consistent with data from the Second European Stroke Prevention Study, and in combination, these data confirm that the addition of dipyridamole for patients who can tolerate it offers significant benefit.2 The magnitude of the effect results in a number needed to treat of 100 patients for one year to prevent one vascular death, stroke, or myocardial infarction. Given the clinical significance of these outcomes, many patients may prefer a trial on combination therapy.
References
- Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002 Jan 12;324(7329):71-86.
- Diener HC, Cunha L, Forbes C, et al. European Stroke Prevention Study. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci. 1996;143:1-13.
- Warlow C. Secondary prevention of stroke. Lancet. 1992;339:724-727.
- Algra A, van Gijn J. Cumulative meta-analysis of aspirin efficacy after cerebral ischaemia of arterial origin. J Neurol Neurosurg Psychiatry. 1999 Feb;66(2):255.
The Effectiveness of CTA in Diagnosing Acute Pulmonary Embolism
Stein PD, Fowler SE, Goodman LR, et al. Multidetector computed tomography for acute pulmonary embolism. N Engl J Med. 2006 Jun 1;354(22):2317-2327.
Background
The Prospective Investigation of Pulmonary Embolism Diagnosis II (PIOPED II) trial was designed to answer questions about the accuracy of contrast-enhanced multidetector computed tomographic angiography (CTA). Recent studies of the use of single-row or multidetector CTA alone have suggested a low incidence of pulmonary embolism in follow-up of untreated patients with normal findings on CTA.
The specific goals of this study were to determine the ability of multidetector CTA to rule out or detect pulmonary embolism, and to evaluate whether the addition of computed tomographic venography (CTV) improves the diagnostic accuracy of CTA.
Methods
Using a technique similar to PIOPED I, the investigators performed a prospective, multi-center trial using a composite reference standard to confirm the diagnosis of pulmonary embolism. Once again, for ethical reasons, the use of pulmonary artery digital-subtraction angiography was limited to patients whose diagnosis could neither be confirmed nor ruled out by less invasive tests. In contrast to PIOPED I, a clinical scoring system was used to assess the clinical probability of pulmonary embolism. Central readings were performed on all imaging studies except for venous ultrasonography.
Results
Of the 7,284 patients screened for the study, 3,262 were eligible, and 1,090 were enrolled. Of those, 824 patients received a completed CTA study and a reference standard for analysis. In 51 patients, the quality of the CTA was not suitable for interpretation, and these patients were excluded from the subsequent analysis. Pulmonary embolism was diagnosed in192 patients.
CTA was found to have a sensitivity of 83% and a specificity of 96%, yielding a likelihood ratio for a positive multidetector CTA test of 19.6 (95% confidence interval, 13.3 to 29.0), while the likelihood ratio for a negative test was 0.18 (95% confidence interval, 0.13 to 0.24). The quality of results on CTA-CTV was not adequate for interpretation in 87 patients; when these patients were excluded from analysis, the sensitivity was 90% with a specificity of 95%, yielding likelihood ratios of 16.5 (95% confidence interval, 11.6 to 23.5) for a positive test and 0.11 (95% confidence interval, 0.07 to 0.16) for a negative test.
Conclusions
Multidetector CTA and CTA-CTV perform well when the results of these tests are concordant with pre-test clinical probabilities of pulmonary embolism. CTA-CTV offers slightly increased sensitivity compared with CTA alone, with no significant difference in specificity. If the results of CTA or CTA-CTV are inconsistent with the clinical probability of pulmonary embolism, additional diagnostic testing is indicated.
Commentary
CTA has been used widely, and in many centers has largely replaced other diagnostic tests for pulmonary embolism. This well-done study incorporated recent advances in technology with multidetector CTA-CTV, along with a clinical prediction rule to better estimate pre-test probabilities of pulmonary embolism.2 It is important to recognize that 266 of the 1,090 patients enrolled were not included in the calculations of sensitivity and specificity for CTA-CTV because they did not have interpretable test results.
Although the specificity of both CTA and the CTA-CTV combination were high, the sensitivity was not sufficient to identify all cases of pulmonary embolism. This result contrasts to the recent outcomes studies of CTA, in which low rates of venous thromboembolism were seen in follow-up of patients with negative multidetector CTA.3,4 Although multidetector CTA has a higher sensitivity than single-slice technology, this test may still miss small subsegmental thrombi that might be detected using other diagnostic tests (ventilation-perfusion scintigraphy and/or pulmonary digital-subtraction angiography).
An important take-home message from this study is to recognize once again the importance of utilizing established clinical prediction rules for venous thrombosis and pulmonary embolism (such as the Wells clinical model).2 As with the majority of diagnostic tests at our disposal, when our clinical judgment is in contrast with test results, as in the case of a high likelihood of a potentially fatal disease like pulmonary embolism with a normal CTA result, additional diagnostic testing is necessary.
References
- The PIOPED 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.
- Wells PS, Anderson DR, Rodger M, et al. 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. 2001 Jul 17;135(2):98-107.
- Perrier A, Roy PM, Sanchez O, et al. Multidetector-row computed tomography in suspected pulmonary embolism. N Engl J Med. 2005 Apr;352(17):1760-1768.
- van Belle A, Buller HR, Huisman MV, et al. Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. JAMA. 2006 Jan 11;295(2):172-179.
Classic Article:
PIOPED Investigators
The PIOPED Investigators. Value of ventilation/perfusion scan in acute pulmonary embolism: results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA. 1990;263:2753-2759.
Background
The risk of untreated pulmonary embolism requires either the diagnosis or the exclusion of this diagnosis when clinical suspicion exists. The reference test for pulmonary embolism, standard pulmonary angiography, is invasive and expensive, and carries with it a measurable procedural risk.
Non-invasive diagnostic tests, including ventilation/perfusion (V/Q) scintigraphy, have been used to detect perfusion defects consistent with pulmonary embolism, though the performance characteristics of this diagnostic test were not well known prior to 1990. This study was designed to evaluate the sensitivity and specificities of ventilation/perfusion lung scans for pulmonary embolism in the acute setting.
Methods
This prospective, multi-center study evaluated V/Q scintigraphy on a random sample of 931 patients. A composite reference standard was used because only 755 patients underwent scintigraphy and pulmonary angiography. Clinical follow-up and subsequent diagnostic testing were employed in untreated patients with low clinical probabilities of pulmonary embolism who did not undergo angiography. Clinical assessment of the probability of pulmonary embolism was determined on the basis of the clinician’s judgment, without systematic prediction rules.
Results
Almost all patients with pulmonary embolism had abnormal ventilation/perfusion lung scans of high, intermediate, or low probability. Unfortunately, most patients without pulmonary embolism also had abnormal studies, limiting the utility of this test. Clinical follow-up and angiography revealed that pulmonary embolism occurred among 12% of patients with low-probability scans.
Conclusions
V/Q scintigraphy is useful in establishing or excluding the diagnosis of pulmonary embolism in only a minority of patients, where clinical suspicion of pulmonary embolism is concordant with the diagnostic test findings. The likelihood of pulmonary embolism in patients with a high pre-test probability of pulmonary embolism and a high probability scan is 95%, while in low probability patients with a low probability or normal scan the probability is 4% or 2%, respectively.
Commentary
This original PIOPED study established the diagnostic characteristics of V/Q scintigraphy and demonstrated, for the first time, evidence of the role of clinical assessment and prior probability in a diagnostic strategy for pulmonary embolism. Although subsequent studies have significantly advanced our knowledge of clinical prediction and diagnostic strategies in venous thromboembolism, the first PIOPED study continues to serve as an example of a high-quality, multi-center diagnostic test study utilizing a composite reference standard in a difficult-to-study disease. Unfortunately, the results of this study demonstrated that V/Q scintigraphy performs well for only a minority of patients. The majority of patients (72%) had clinical probabilities of pulmonary embolism and ventilation/perfusion scan results, which yielded post-test probabilities of 15-86%, leaving, in many cases, enough remaining diagnostic uncertainty to warrant additional testing.—TO TH
Factors Influencing the Treatment of COPD
Lindenauer PK, Pekow P, Gao S, et al. Quality of care for patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease. Ann Intern Med. 2006;144:894-903.
Background
Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States, resulting in more than $18 billion in annual health costs. Acute exacerbations of COPD can lead to respiratory compromise and are one of the 10 leading causes of hospitalization in the United States.
Hospitalists currently have evidence-based guidelines available that recommend therapies for patients with acute exacerbations of COPD. This study was designed to evaluate the practice patterns in the United States and to evaluate the quality of care provided to hospitalized patients based on comparisons with these published guidelines. The authors did not report any conflicts of interest, and this work was performed without external grant support.
Methods
Using administrative data from the 360 hospitals that participate in Perspective, a database developed for measuring healthcare quality and utilization, the authors performed a retrospective cohort study. Patients hospitalized for a primary diagnosis of acute exacerbation of COPD were chosen. Patients with pneumonia were specifically excluded. The outcomes of interest included adherence to the diagnostic and therapeutic recommendations of the joint American College of Physicians and American College of Chest Physicians evidence-based COPD guideline, published in 2001.
Results
Of the 69,820 patients included in the analysis, 33% received “ideal care,” defined as all of the recommended care and none of the non-beneficial interventions. Specific results included varied utilization of recommended care: 95% had chest radiography, 91% received supplemental oxygen, 97% had bronchodilators, 85% were given systemic steroids, and 85% received antibiotics.
Overall, 45% of patients received at least one non-beneficial intervention specified in the guidelines: 24% were treated with methylxanthines, 14% underwent sputum testing, 12% had acute spirometry, 6% received chest physiotherapy, and 2% were given mucolytics.
Older patients and women were more likely to receive ideal care as defined, but hospitals with a higher annual volume of COPD cases were not associated with improved performance in this analysis.
Conclusions
Given a widely accepted evidence-based practice guideline as a benchmark, significant variation exists across hospitals in the quality of care for acute exacerbations of COPD. Opportunities exist to improve the quality of care, in particular by increasing the use of systemic corticosteroids and antibiotic therapy and reducing the utilization of many diagnostic and therapeutic interventions that are not only not recommended but are also potentially harmful.
Commentary
COPD management in the acute inpatient setting is on the horizon as a focus of policymakers, and this study suggests that significant opportunities exist for inpatient physicians to reduce variation in practice and utilize an evidence-based approach to the treatment of acute exacerbations of COPD. This study is limited by its use of administrative data, its inability to use clinical data to best determine appropriate care processes for individual patients, and its retrospective design.
As we move toward external quality metrics for the care of patients with acute exacerbations of COPD, further prospective studies evaluating clinical outcomes of interest, including mortality and readmission rates, are needed to determine the effects of adherence to ideal or recommended care for acute exacerbations of COPD.1-3
References
- Snow V, Lascher S, Mottur-Pilson C, et al. Evidence base for management of acute exacerbations of chronic obstructive pulmonary disease. Ann Intern Med. 2001 Apr 3;134(7):595-599.
- American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, November 1986. Am Rev Respir Dis. 1987 Jul;136(1):225-244.
- Agency for Healthcare Research and Quality. Management of Acute Exacerbations of Chronic Obstructive Pulmonary Disease. Rockville, Md.: Agency for Healthcare Research and Quality; 2000.
The Role of Dipyridamole in the Secondary Prevention of Stroke
ESPRIT Study Group. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomized controlled trial. Lancet. 2006 May 20;367(9623):1665-1673.
Background
To date, studies have resulted in inconsistent results in trials of aspirin versus aspirin in combination with dipyridamole for secondary prevention of ischemic stroke. Four early, smaller studies have yielded non-significant results, in contrast to the statistically significant relative risk reduction seen with the addition of dipyridamole to aspirin in the European Stroke Prevention Study 2 (ESPS-2).1-2
Methods
The European/Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) study group conducted a prospective randomized controlled trial of 2,763 patients with transient ischemic attacks or minor ischemic stroke of presumed arterial origin who received aspirin (30-325 mg daily) with or without dipyridamole (200 mg twice daily) as secondary prevention. The primary outcome for this study was a composite of death from vascular causes, nonfatal stroke, nonfatal myocardial infarction, or major bleeding complication. Mean follow-up of patients enrolled was 3.5 years.
Results
In an intention-to-treat analysis, the primary combined endpoint occurred in 16% (216) of the patients on aspirin alone (median aspirin dose was 75 mg in both groups) compared with 13% (173) of the patients on aspirin plus dipyridamole. This result was statistically significant, with an absolute risk reduction of 1% per year. As noted in other trials, patients on dipyridamole discontinued their study medication more frequently than patients on aspirin alone, mostly due to headache.
Conclusions
The results of this trial, taken in the context of previously published data, support the combination of aspirin plus dipyridamole over aspirin alone for the secondary prevention of ischemic stroke of presumed arterial origin. Addition of these data to the previous meta-analysis of trials resulted in a statistically significant risk ratio for the composite endpoint of 0.82 (95% confidence interval, 0.74-0.91).1
Commentary
Ischemic stroke and transient ischemic attacks remain a challenge to effectively manage medically and are appropriately greatly feared health complications for many patients, resulting in significant morbidity and mortality. Prior studies of secondary prevention with aspirin therapy have demonstrated only a modest reduction in vascular complications in these patients.3-4
The results of this trial are consistent with data from the Second European Stroke Prevention Study, and in combination, these data confirm that the addition of dipyridamole for patients who can tolerate it offers significant benefit.2 The magnitude of the effect results in a number needed to treat of 100 patients for one year to prevent one vascular death, stroke, or myocardial infarction. Given the clinical significance of these outcomes, many patients may prefer a trial on combination therapy.
References
- Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002 Jan 12;324(7329):71-86.
- Diener HC, Cunha L, Forbes C, et al. European Stroke Prevention Study. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci. 1996;143:1-13.
- Warlow C. Secondary prevention of stroke. Lancet. 1992;339:724-727.
- Algra A, van Gijn J. Cumulative meta-analysis of aspirin efficacy after cerebral ischaemia of arterial origin. J Neurol Neurosurg Psychiatry. 1999 Feb;66(2):255.
The Effectiveness of CTA in Diagnosing Acute Pulmonary Embolism
Stein PD, Fowler SE, Goodman LR, et al. Multidetector computed tomography for acute pulmonary embolism. N Engl J Med. 2006 Jun 1;354(22):2317-2327.
Background
The Prospective Investigation of Pulmonary Embolism Diagnosis II (PIOPED II) trial was designed to answer questions about the accuracy of contrast-enhanced multidetector computed tomographic angiography (CTA). Recent studies of the use of single-row or multidetector CTA alone have suggested a low incidence of pulmonary embolism in follow-up of untreated patients with normal findings on CTA.
The specific goals of this study were to determine the ability of multidetector CTA to rule out or detect pulmonary embolism, and to evaluate whether the addition of computed tomographic venography (CTV) improves the diagnostic accuracy of CTA.
Methods
Using a technique similar to PIOPED I, the investigators performed a prospective, multi-center trial using a composite reference standard to confirm the diagnosis of pulmonary embolism. Once again, for ethical reasons, the use of pulmonary artery digital-subtraction angiography was limited to patients whose diagnosis could neither be confirmed nor ruled out by less invasive tests. In contrast to PIOPED I, a clinical scoring system was used to assess the clinical probability of pulmonary embolism. Central readings were performed on all imaging studies except for venous ultrasonography.
Results
Of the 7,284 patients screened for the study, 3,262 were eligible, and 1,090 were enrolled. Of those, 824 patients received a completed CTA study and a reference standard for analysis. In 51 patients, the quality of the CTA was not suitable for interpretation, and these patients were excluded from the subsequent analysis. Pulmonary embolism was diagnosed in192 patients.
CTA was found to have a sensitivity of 83% and a specificity of 96%, yielding a likelihood ratio for a positive multidetector CTA test of 19.6 (95% confidence interval, 13.3 to 29.0), while the likelihood ratio for a negative test was 0.18 (95% confidence interval, 0.13 to 0.24). The quality of results on CTA-CTV was not adequate for interpretation in 87 patients; when these patients were excluded from analysis, the sensitivity was 90% with a specificity of 95%, yielding likelihood ratios of 16.5 (95% confidence interval, 11.6 to 23.5) for a positive test and 0.11 (95% confidence interval, 0.07 to 0.16) for a negative test.
Conclusions
Multidetector CTA and CTA-CTV perform well when the results of these tests are concordant with pre-test clinical probabilities of pulmonary embolism. CTA-CTV offers slightly increased sensitivity compared with CTA alone, with no significant difference in specificity. If the results of CTA or CTA-CTV are inconsistent with the clinical probability of pulmonary embolism, additional diagnostic testing is indicated.
Commentary
CTA has been used widely, and in many centers has largely replaced other diagnostic tests for pulmonary embolism. This well-done study incorporated recent advances in technology with multidetector CTA-CTV, along with a clinical prediction rule to better estimate pre-test probabilities of pulmonary embolism.2 It is important to recognize that 266 of the 1,090 patients enrolled were not included in the calculations of sensitivity and specificity for CTA-CTV because they did not have interpretable test results.
Although the specificity of both CTA and the CTA-CTV combination were high, the sensitivity was not sufficient to identify all cases of pulmonary embolism. This result contrasts to the recent outcomes studies of CTA, in which low rates of venous thromboembolism were seen in follow-up of patients with negative multidetector CTA.3,4 Although multidetector CTA has a higher sensitivity than single-slice technology, this test may still miss small subsegmental thrombi that might be detected using other diagnostic tests (ventilation-perfusion scintigraphy and/or pulmonary digital-subtraction angiography).
An important take-home message from this study is to recognize once again the importance of utilizing established clinical prediction rules for venous thrombosis and pulmonary embolism (such as the Wells clinical model).2 As with the majority of diagnostic tests at our disposal, when our clinical judgment is in contrast with test results, as in the case of a high likelihood of a potentially fatal disease like pulmonary embolism with a normal CTA result, additional diagnostic testing is necessary.
References
- The PIOPED 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.
- Wells PS, Anderson DR, Rodger M, et al. 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. 2001 Jul 17;135(2):98-107.
- Perrier A, Roy PM, Sanchez O, et al. Multidetector-row computed tomography in suspected pulmonary embolism. N Engl J Med. 2005 Apr;352(17):1760-1768.
- van Belle A, Buller HR, Huisman MV, et al. Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. JAMA. 2006 Jan 11;295(2):172-179.
Classic Article:
PIOPED Investigators
The PIOPED Investigators. Value of ventilation/perfusion scan in acute pulmonary embolism: results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA. 1990;263:2753-2759.
Background
The risk of untreated pulmonary embolism requires either the diagnosis or the exclusion of this diagnosis when clinical suspicion exists. The reference test for pulmonary embolism, standard pulmonary angiography, is invasive and expensive, and carries with it a measurable procedural risk.
Non-invasive diagnostic tests, including ventilation/perfusion (V/Q) scintigraphy, have been used to detect perfusion defects consistent with pulmonary embolism, though the performance characteristics of this diagnostic test were not well known prior to 1990. This study was designed to evaluate the sensitivity and specificities of ventilation/perfusion lung scans for pulmonary embolism in the acute setting.
Methods
This prospective, multi-center study evaluated V/Q scintigraphy on a random sample of 931 patients. A composite reference standard was used because only 755 patients underwent scintigraphy and pulmonary angiography. Clinical follow-up and subsequent diagnostic testing were employed in untreated patients with low clinical probabilities of pulmonary embolism who did not undergo angiography. Clinical assessment of the probability of pulmonary embolism was determined on the basis of the clinician’s judgment, without systematic prediction rules.
Results
Almost all patients with pulmonary embolism had abnormal ventilation/perfusion lung scans of high, intermediate, or low probability. Unfortunately, most patients without pulmonary embolism also had abnormal studies, limiting the utility of this test. Clinical follow-up and angiography revealed that pulmonary embolism occurred among 12% of patients with low-probability scans.
Conclusions
V/Q scintigraphy is useful in establishing or excluding the diagnosis of pulmonary embolism in only a minority of patients, where clinical suspicion of pulmonary embolism is concordant with the diagnostic test findings. The likelihood of pulmonary embolism in patients with a high pre-test probability of pulmonary embolism and a high probability scan is 95%, while in low probability patients with a low probability or normal scan the probability is 4% or 2%, respectively.
Commentary
This original PIOPED study established the diagnostic characteristics of V/Q scintigraphy and demonstrated, for the first time, evidence of the role of clinical assessment and prior probability in a diagnostic strategy for pulmonary embolism. Although subsequent studies have significantly advanced our knowledge of clinical prediction and diagnostic strategies in venous thromboembolism, the first PIOPED study continues to serve as an example of a high-quality, multi-center diagnostic test study utilizing a composite reference standard in a difficult-to-study disease. Unfortunately, the results of this study demonstrated that V/Q scintigraphy performs well for only a minority of patients. The majority of patients (72%) had clinical probabilities of pulmonary embolism and ventilation/perfusion scan results, which yielded post-test probabilities of 15-86%, leaving, in many cases, enough remaining diagnostic uncertainty to warrant additional testing.—TO TH
Factors Influencing the Treatment of COPD
Lindenauer PK, Pekow P, Gao S, et al. Quality of care for patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease. Ann Intern Med. 2006;144:894-903.
Background
Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States, resulting in more than $18 billion in annual health costs. Acute exacerbations of COPD can lead to respiratory compromise and are one of the 10 leading causes of hospitalization in the United States.
Hospitalists currently have evidence-based guidelines available that recommend therapies for patients with acute exacerbations of COPD. This study was designed to evaluate the practice patterns in the United States and to evaluate the quality of care provided to hospitalized patients based on comparisons with these published guidelines. The authors did not report any conflicts of interest, and this work was performed without external grant support.
Methods
Using administrative data from the 360 hospitals that participate in Perspective, a database developed for measuring healthcare quality and utilization, the authors performed a retrospective cohort study. Patients hospitalized for a primary diagnosis of acute exacerbation of COPD were chosen. Patients with pneumonia were specifically excluded. The outcomes of interest included adherence to the diagnostic and therapeutic recommendations of the joint American College of Physicians and American College of Chest Physicians evidence-based COPD guideline, published in 2001.
Results
Of the 69,820 patients included in the analysis, 33% received “ideal care,” defined as all of the recommended care and none of the non-beneficial interventions. Specific results included varied utilization of recommended care: 95% had chest radiography, 91% received supplemental oxygen, 97% had bronchodilators, 85% were given systemic steroids, and 85% received antibiotics.
Overall, 45% of patients received at least one non-beneficial intervention specified in the guidelines: 24% were treated with methylxanthines, 14% underwent sputum testing, 12% had acute spirometry, 6% received chest physiotherapy, and 2% were given mucolytics.
Older patients and women were more likely to receive ideal care as defined, but hospitals with a higher annual volume of COPD cases were not associated with improved performance in this analysis.
Conclusions
Given a widely accepted evidence-based practice guideline as a benchmark, significant variation exists across hospitals in the quality of care for acute exacerbations of COPD. Opportunities exist to improve the quality of care, in particular by increasing the use of systemic corticosteroids and antibiotic therapy and reducing the utilization of many diagnostic and therapeutic interventions that are not only not recommended but are also potentially harmful.
Commentary
COPD management in the acute inpatient setting is on the horizon as a focus of policymakers, and this study suggests that significant opportunities exist for inpatient physicians to reduce variation in practice and utilize an evidence-based approach to the treatment of acute exacerbations of COPD. This study is limited by its use of administrative data, its inability to use clinical data to best determine appropriate care processes for individual patients, and its retrospective design.
As we move toward external quality metrics for the care of patients with acute exacerbations of COPD, further prospective studies evaluating clinical outcomes of interest, including mortality and readmission rates, are needed to determine the effects of adherence to ideal or recommended care for acute exacerbations of COPD.1-3
References
- Snow V, Lascher S, Mottur-Pilson C, et al. Evidence base for management of acute exacerbations of chronic obstructive pulmonary disease. Ann Intern Med. 2001 Apr 3;134(7):595-599.
- American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, November 1986. Am Rev Respir Dis. 1987 Jul;136(1):225-244.
- Agency for Healthcare Research and Quality. Management of Acute Exacerbations of Chronic Obstructive Pulmonary Disease. Rockville, Md.: Agency for Healthcare Research and Quality; 2000.
The Role of Dipyridamole in the Secondary Prevention of Stroke
ESPRIT Study Group. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomized controlled trial. Lancet. 2006 May 20;367(9623):1665-1673.
Background
To date, studies have resulted in inconsistent results in trials of aspirin versus aspirin in combination with dipyridamole for secondary prevention of ischemic stroke. Four early, smaller studies have yielded non-significant results, in contrast to the statistically significant relative risk reduction seen with the addition of dipyridamole to aspirin in the European Stroke Prevention Study 2 (ESPS-2).1-2
Methods
The European/Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) study group conducted a prospective randomized controlled trial of 2,763 patients with transient ischemic attacks or minor ischemic stroke of presumed arterial origin who received aspirin (30-325 mg daily) with or without dipyridamole (200 mg twice daily) as secondary prevention. The primary outcome for this study was a composite of death from vascular causes, nonfatal stroke, nonfatal myocardial infarction, or major bleeding complication. Mean follow-up of patients enrolled was 3.5 years.
Results
In an intention-to-treat analysis, the primary combined endpoint occurred in 16% (216) of the patients on aspirin alone (median aspirin dose was 75 mg in both groups) compared with 13% (173) of the patients on aspirin plus dipyridamole. This result was statistically significant, with an absolute risk reduction of 1% per year. As noted in other trials, patients on dipyridamole discontinued their study medication more frequently than patients on aspirin alone, mostly due to headache.
Conclusions
The results of this trial, taken in the context of previously published data, support the combination of aspirin plus dipyridamole over aspirin alone for the secondary prevention of ischemic stroke of presumed arterial origin. Addition of these data to the previous meta-analysis of trials resulted in a statistically significant risk ratio for the composite endpoint of 0.82 (95% confidence interval, 0.74-0.91).1
Commentary
Ischemic stroke and transient ischemic attacks remain a challenge to effectively manage medically and are appropriately greatly feared health complications for many patients, resulting in significant morbidity and mortality. Prior studies of secondary prevention with aspirin therapy have demonstrated only a modest reduction in vascular complications in these patients.3-4
The results of this trial are consistent with data from the Second European Stroke Prevention Study, and in combination, these data confirm that the addition of dipyridamole for patients who can tolerate it offers significant benefit.2 The magnitude of the effect results in a number needed to treat of 100 patients for one year to prevent one vascular death, stroke, or myocardial infarction. Given the clinical significance of these outcomes, many patients may prefer a trial on combination therapy.
References
- Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002 Jan 12;324(7329):71-86.
- Diener HC, Cunha L, Forbes C, et al. European Stroke Prevention Study. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci. 1996;143:1-13.
- Warlow C. Secondary prevention of stroke. Lancet. 1992;339:724-727.
- Algra A, van Gijn J. Cumulative meta-analysis of aspirin efficacy after cerebral ischaemia of arterial origin. J Neurol Neurosurg Psychiatry. 1999 Feb;66(2):255.
The Effectiveness of CTA in Diagnosing Acute Pulmonary Embolism
Stein PD, Fowler SE, Goodman LR, et al. Multidetector computed tomography for acute pulmonary embolism. N Engl J Med. 2006 Jun 1;354(22):2317-2327.
Background
The Prospective Investigation of Pulmonary Embolism Diagnosis II (PIOPED II) trial was designed to answer questions about the accuracy of contrast-enhanced multidetector computed tomographic angiography (CTA). Recent studies of the use of single-row or multidetector CTA alone have suggested a low incidence of pulmonary embolism in follow-up of untreated patients with normal findings on CTA.
The specific goals of this study were to determine the ability of multidetector CTA to rule out or detect pulmonary embolism, and to evaluate whether the addition of computed tomographic venography (CTV) improves the diagnostic accuracy of CTA.
Methods
Using a technique similar to PIOPED I, the investigators performed a prospective, multi-center trial using a composite reference standard to confirm the diagnosis of pulmonary embolism. Once again, for ethical reasons, the use of pulmonary artery digital-subtraction angiography was limited to patients whose diagnosis could neither be confirmed nor ruled out by less invasive tests. In contrast to PIOPED I, a clinical scoring system was used to assess the clinical probability of pulmonary embolism. Central readings were performed on all imaging studies except for venous ultrasonography.
Results
Of the 7,284 patients screened for the study, 3,262 were eligible, and 1,090 were enrolled. Of those, 824 patients received a completed CTA study and a reference standard for analysis. In 51 patients, the quality of the CTA was not suitable for interpretation, and these patients were excluded from the subsequent analysis. Pulmonary embolism was diagnosed in192 patients.
CTA was found to have a sensitivity of 83% and a specificity of 96%, yielding a likelihood ratio for a positive multidetector CTA test of 19.6 (95% confidence interval, 13.3 to 29.0), while the likelihood ratio for a negative test was 0.18 (95% confidence interval, 0.13 to 0.24). The quality of results on CTA-CTV was not adequate for interpretation in 87 patients; when these patients were excluded from analysis, the sensitivity was 90% with a specificity of 95%, yielding likelihood ratios of 16.5 (95% confidence interval, 11.6 to 23.5) for a positive test and 0.11 (95% confidence interval, 0.07 to 0.16) for a negative test.
Conclusions
Multidetector CTA and CTA-CTV perform well when the results of these tests are concordant with pre-test clinical probabilities of pulmonary embolism. CTA-CTV offers slightly increased sensitivity compared with CTA alone, with no significant difference in specificity. If the results of CTA or CTA-CTV are inconsistent with the clinical probability of pulmonary embolism, additional diagnostic testing is indicated.
Commentary
CTA has been used widely, and in many centers has largely replaced other diagnostic tests for pulmonary embolism. This well-done study incorporated recent advances in technology with multidetector CTA-CTV, along with a clinical prediction rule to better estimate pre-test probabilities of pulmonary embolism.2 It is important to recognize that 266 of the 1,090 patients enrolled were not included in the calculations of sensitivity and specificity for CTA-CTV because they did not have interpretable test results.
Although the specificity of both CTA and the CTA-CTV combination were high, the sensitivity was not sufficient to identify all cases of pulmonary embolism. This result contrasts to the recent outcomes studies of CTA, in which low rates of venous thromboembolism were seen in follow-up of patients with negative multidetector CTA.3,4 Although multidetector CTA has a higher sensitivity than single-slice technology, this test may still miss small subsegmental thrombi that might be detected using other diagnostic tests (ventilation-perfusion scintigraphy and/or pulmonary digital-subtraction angiography).
An important take-home message from this study is to recognize once again the importance of utilizing established clinical prediction rules for venous thrombosis and pulmonary embolism (such as the Wells clinical model).2 As with the majority of diagnostic tests at our disposal, when our clinical judgment is in contrast with test results, as in the case of a high likelihood of a potentially fatal disease like pulmonary embolism with a normal CTA result, additional diagnostic testing is necessary.
References
- The PIOPED 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.
- Wells PS, Anderson DR, Rodger M, et al. 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. 2001 Jul 17;135(2):98-107.
- Perrier A, Roy PM, Sanchez O, et al. Multidetector-row computed tomography in suspected pulmonary embolism. N Engl J Med. 2005 Apr;352(17):1760-1768.
- van Belle A, Buller HR, Huisman MV, et al. Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. JAMA. 2006 Jan 11;295(2):172-179.
Classic Article:
PIOPED Investigators
The PIOPED Investigators. Value of ventilation/perfusion scan in acute pulmonary embolism: results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA. 1990;263:2753-2759.
Background
The risk of untreated pulmonary embolism requires either the diagnosis or the exclusion of this diagnosis when clinical suspicion exists. The reference test for pulmonary embolism, standard pulmonary angiography, is invasive and expensive, and carries with it a measurable procedural risk.
Non-invasive diagnostic tests, including ventilation/perfusion (V/Q) scintigraphy, have been used to detect perfusion defects consistent with pulmonary embolism, though the performance characteristics of this diagnostic test were not well known prior to 1990. This study was designed to evaluate the sensitivity and specificities of ventilation/perfusion lung scans for pulmonary embolism in the acute setting.
Methods
This prospective, multi-center study evaluated V/Q scintigraphy on a random sample of 931 patients. A composite reference standard was used because only 755 patients underwent scintigraphy and pulmonary angiography. Clinical follow-up and subsequent diagnostic testing were employed in untreated patients with low clinical probabilities of pulmonary embolism who did not undergo angiography. Clinical assessment of the probability of pulmonary embolism was determined on the basis of the clinician’s judgment, without systematic prediction rules.
Results
Almost all patients with pulmonary embolism had abnormal ventilation/perfusion lung scans of high, intermediate, or low probability. Unfortunately, most patients without pulmonary embolism also had abnormal studies, limiting the utility of this test. Clinical follow-up and angiography revealed that pulmonary embolism occurred among 12% of patients with low-probability scans.
Conclusions
V/Q scintigraphy is useful in establishing or excluding the diagnosis of pulmonary embolism in only a minority of patients, where clinical suspicion of pulmonary embolism is concordant with the diagnostic test findings. The likelihood of pulmonary embolism in patients with a high pre-test probability of pulmonary embolism and a high probability scan is 95%, while in low probability patients with a low probability or normal scan the probability is 4% or 2%, respectively.
Commentary
This original PIOPED study established the diagnostic characteristics of V/Q scintigraphy and demonstrated, for the first time, evidence of the role of clinical assessment and prior probability in a diagnostic strategy for pulmonary embolism. Although subsequent studies have significantly advanced our knowledge of clinical prediction and diagnostic strategies in venous thromboembolism, the first PIOPED study continues to serve as an example of a high-quality, multi-center diagnostic test study utilizing a composite reference standard in a difficult-to-study disease. Unfortunately, the results of this study demonstrated that V/Q scintigraphy performs well for only a minority of patients. The majority of patients (72%) had clinical probabilities of pulmonary embolism and ventilation/perfusion scan results, which yielded post-test probabilities of 15-86%, leaving, in many cases, enough remaining diagnostic uncertainty to warrant additional testing.—TO TH