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Should you evaluate for CAD in seniors with premature ventricular contractions?
Yes. Current guidelines suggest evaluating patients with premature ventricular contractions (PVCs) and associated risk factors for underlying coronary artery disease (strength of recommendation [SOR]: C, expert opinion).
Frequent PVCs are associated with acute myocardial infarction and sudden death in patients without known coronary artery disease (CAD). They are linked to increased mortality from all causes in elderly patients with a history of CAD, left ventricular dysfunction, hypertension, or valvular heart disease. Frequent PVCs during recovery from exercise stress testing are also associated with increased mortality.
There is strong evidence against suppressing PVCs with antiarrhythmics (SOR: A, randomized controlled trials [RCTs]).
Stress preventive measures
Jennifer Lochner, MD
Oregon Health and Sciences University, Portland
I find myself discussing PVCs most often with young women who don’t have known heart disease—rather than the elderly. I often discover PVCs on physical examination in the office or see them on a Holter monitor ordered to rule out other more worrisome arrhythmias.
This reminds me that I need to not only consider the issue of treatment aimed at suppressing PVCs (not helpful except when the patient has significant symptoms), but also to consider whether the patient has risk factors for CAD.
In future discussions with patients about PVCs, I plan to shift the focus to measures to prevent CAD—specifically tobacco cessation, weight management, daily physical activity, and a healthy diet.
Evidence summary
A consistent definition of frequent PVCs doesn’t exist in the literature. Some studies have found a significant risk of death or acute myocardial infarction associated with >30 PVCs per hour.1,2 The 2006 American College of Cardiology/American Heart Association/European Society of Cardiology guideline defines frequent PVCs as >10 per hour.3
Despite the association between frequent PVCs and increased risk of death and cardiac events, our review didn’t find studies that indicate the utility of evaluation strategies for higher-risk patients.
Frequent PVCs predict increased mortality
The Framingham study looked at the prognostic implications of frequent PVCs (>30 per hour) in a cohort of symptomatic patients examined over a 6-year period.1 Men, but not women, had a significant increase in all-cause mortality (relative risk [RR]=2.36; 95% confidence interval [CI], 1.65-3.2) and myocardial infarction or sudden death (RR=2.12; 95% CI, 1.33-3.38). The Copenhagen Holter study of a cohort of healthy patients demonstrated an increased risk of myocardial infarction or cardiovascular death in patients with >30 PVCs per hour (hazard ratio [HR]=2.85, 95% CI, 1.16-7.0).2
Frequent PVCs occurring during recovery from stress testing are also associated with increased mortality. A large prospective cohort study followed more than 29,000 patients with varying degrees of risk for 5 years. After adjusting for confounding variables, frequent PVCs (≥7 per minute or more complex ventricular ectopy) during recovery predicted an increased risk of death (HR=1.5; 95% CI, 1.1-1.9). Frequent PVCs arising during exercise stress testing were not associated with increased risk.4
Suppressing PVCs is a bad idea
Studies have evaluated whether suppressing PVCs with antiarrhythmic agents improves prognosis. Both Cardiac Arrhythmia Suppression Trials (CAST I: encainide and flecainide; CAST II: moricizine) showed that suppressing frequent PVCs significantly increased mortality in the treatment groups.5,6
Recommendations
In 2006, the American College of Cardiology, American Heart Association, and European Society of Cardiology published their Guidelines for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death.3
The TABLE summarizes characteristics of patients with PVCs who were at higher risk of underlying cardiac disease and death. All patients with PVCs should have a history and physical examination, electrocardiogram, and electrolyte studies. Higher-risk patients should be considered for further evaluation, including stress testing, echocardiography, and ambulatory electrocardiogram (SOR: C, opinion).
TABLE
Characteristics of patients with PVCs who are at higher risk of cardiac disease/death
| PATIENT CHARACTERISTICS | LOWER RISK | HIGHER RISK |
|---|---|---|
| Morphology | Unifocal PVCs<10 PVCs per hour | Complex multifocal PVCs Ventricular tachycardia Ventricular fibrillation >10 PVCs per hour |
| Symptoms | Asymptomatic | Palpitations Presyncope Syncope |
| Preexisting conditions | None | Known history of CAD Structural heart disease Valvular heart disease Cardiomyopathy |
| CAD, coronary artery disease, PVCs, premature ventricular contractions. | ||
| Source: American College of Cardiology et al.3 | ||
1. Bikkina M, Larson MG, Levy D. Prognostic implications of asymptomatic ventricular arrhythmias: the Framingham heart study. Ann Intern Med. 1992;117:990-996.
2. Sajadieh A, Nielsen OW, Rasmussen V, et al. Ventricular arrhythmias and risk of death and acute myocardial infarction in apparently healthy subjects of age 55 or older. Am J Cardiol. 2006;97:1351-1357.
3. American College of Cardiology, American Heart Association, European Society of Cardiology. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. J Am Coll Cardiol. 2006;48:e247-e346.
4. Frolkis JP, Pothier CE, Blackstone EH, et al. Frequent ventricular ectopy after exercise as a predictor of death. N Engl J Med. 2003;348:781-790.
5. The Cardiac Arrhythmia Suppression Trial (CAST) Investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med. 1989;321:406-412.
6. The Cardiac Arrhythmia Suppression Trial II Investigators. Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. N Engl J Med. 1992;327:227-233.
Yes. Current guidelines suggest evaluating patients with premature ventricular contractions (PVCs) and associated risk factors for underlying coronary artery disease (strength of recommendation [SOR]: C, expert opinion).
Frequent PVCs are associated with acute myocardial infarction and sudden death in patients without known coronary artery disease (CAD). They are linked to increased mortality from all causes in elderly patients with a history of CAD, left ventricular dysfunction, hypertension, or valvular heart disease. Frequent PVCs during recovery from exercise stress testing are also associated with increased mortality.
There is strong evidence against suppressing PVCs with antiarrhythmics (SOR: A, randomized controlled trials [RCTs]).
Stress preventive measures
Jennifer Lochner, MD
Oregon Health and Sciences University, Portland
I find myself discussing PVCs most often with young women who don’t have known heart disease—rather than the elderly. I often discover PVCs on physical examination in the office or see them on a Holter monitor ordered to rule out other more worrisome arrhythmias.
This reminds me that I need to not only consider the issue of treatment aimed at suppressing PVCs (not helpful except when the patient has significant symptoms), but also to consider whether the patient has risk factors for CAD.
In future discussions with patients about PVCs, I plan to shift the focus to measures to prevent CAD—specifically tobacco cessation, weight management, daily physical activity, and a healthy diet.
Evidence summary
A consistent definition of frequent PVCs doesn’t exist in the literature. Some studies have found a significant risk of death or acute myocardial infarction associated with >30 PVCs per hour.1,2 The 2006 American College of Cardiology/American Heart Association/European Society of Cardiology guideline defines frequent PVCs as >10 per hour.3
Despite the association between frequent PVCs and increased risk of death and cardiac events, our review didn’t find studies that indicate the utility of evaluation strategies for higher-risk patients.
Frequent PVCs predict increased mortality
The Framingham study looked at the prognostic implications of frequent PVCs (>30 per hour) in a cohort of symptomatic patients examined over a 6-year period.1 Men, but not women, had a significant increase in all-cause mortality (relative risk [RR]=2.36; 95% confidence interval [CI], 1.65-3.2) and myocardial infarction or sudden death (RR=2.12; 95% CI, 1.33-3.38). The Copenhagen Holter study of a cohort of healthy patients demonstrated an increased risk of myocardial infarction or cardiovascular death in patients with >30 PVCs per hour (hazard ratio [HR]=2.85, 95% CI, 1.16-7.0).2
Frequent PVCs occurring during recovery from stress testing are also associated with increased mortality. A large prospective cohort study followed more than 29,000 patients with varying degrees of risk for 5 years. After adjusting for confounding variables, frequent PVCs (≥7 per minute or more complex ventricular ectopy) during recovery predicted an increased risk of death (HR=1.5; 95% CI, 1.1-1.9). Frequent PVCs arising during exercise stress testing were not associated with increased risk.4
Suppressing PVCs is a bad idea
Studies have evaluated whether suppressing PVCs with antiarrhythmic agents improves prognosis. Both Cardiac Arrhythmia Suppression Trials (CAST I: encainide and flecainide; CAST II: moricizine) showed that suppressing frequent PVCs significantly increased mortality in the treatment groups.5,6
Recommendations
In 2006, the American College of Cardiology, American Heart Association, and European Society of Cardiology published their Guidelines for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death.3
The TABLE summarizes characteristics of patients with PVCs who were at higher risk of underlying cardiac disease and death. All patients with PVCs should have a history and physical examination, electrocardiogram, and electrolyte studies. Higher-risk patients should be considered for further evaluation, including stress testing, echocardiography, and ambulatory electrocardiogram (SOR: C, opinion).
TABLE
Characteristics of patients with PVCs who are at higher risk of cardiac disease/death
| PATIENT CHARACTERISTICS | LOWER RISK | HIGHER RISK |
|---|---|---|
| Morphology | Unifocal PVCs<10 PVCs per hour | Complex multifocal PVCs Ventricular tachycardia Ventricular fibrillation >10 PVCs per hour |
| Symptoms | Asymptomatic | Palpitations Presyncope Syncope |
| Preexisting conditions | None | Known history of CAD Structural heart disease Valvular heart disease Cardiomyopathy |
| CAD, coronary artery disease, PVCs, premature ventricular contractions. | ||
| Source: American College of Cardiology et al.3 | ||
Yes. Current guidelines suggest evaluating patients with premature ventricular contractions (PVCs) and associated risk factors for underlying coronary artery disease (strength of recommendation [SOR]: C, expert opinion).
Frequent PVCs are associated with acute myocardial infarction and sudden death in patients without known coronary artery disease (CAD). They are linked to increased mortality from all causes in elderly patients with a history of CAD, left ventricular dysfunction, hypertension, or valvular heart disease. Frequent PVCs during recovery from exercise stress testing are also associated with increased mortality.
There is strong evidence against suppressing PVCs with antiarrhythmics (SOR: A, randomized controlled trials [RCTs]).
Stress preventive measures
Jennifer Lochner, MD
Oregon Health and Sciences University, Portland
I find myself discussing PVCs most often with young women who don’t have known heart disease—rather than the elderly. I often discover PVCs on physical examination in the office or see them on a Holter monitor ordered to rule out other more worrisome arrhythmias.
This reminds me that I need to not only consider the issue of treatment aimed at suppressing PVCs (not helpful except when the patient has significant symptoms), but also to consider whether the patient has risk factors for CAD.
In future discussions with patients about PVCs, I plan to shift the focus to measures to prevent CAD—specifically tobacco cessation, weight management, daily physical activity, and a healthy diet.
Evidence summary
A consistent definition of frequent PVCs doesn’t exist in the literature. Some studies have found a significant risk of death or acute myocardial infarction associated with >30 PVCs per hour.1,2 The 2006 American College of Cardiology/American Heart Association/European Society of Cardiology guideline defines frequent PVCs as >10 per hour.3
Despite the association between frequent PVCs and increased risk of death and cardiac events, our review didn’t find studies that indicate the utility of evaluation strategies for higher-risk patients.
Frequent PVCs predict increased mortality
The Framingham study looked at the prognostic implications of frequent PVCs (>30 per hour) in a cohort of symptomatic patients examined over a 6-year period.1 Men, but not women, had a significant increase in all-cause mortality (relative risk [RR]=2.36; 95% confidence interval [CI], 1.65-3.2) and myocardial infarction or sudden death (RR=2.12; 95% CI, 1.33-3.38). The Copenhagen Holter study of a cohort of healthy patients demonstrated an increased risk of myocardial infarction or cardiovascular death in patients with >30 PVCs per hour (hazard ratio [HR]=2.85, 95% CI, 1.16-7.0).2
Frequent PVCs occurring during recovery from stress testing are also associated with increased mortality. A large prospective cohort study followed more than 29,000 patients with varying degrees of risk for 5 years. After adjusting for confounding variables, frequent PVCs (≥7 per minute or more complex ventricular ectopy) during recovery predicted an increased risk of death (HR=1.5; 95% CI, 1.1-1.9). Frequent PVCs arising during exercise stress testing were not associated with increased risk.4
Suppressing PVCs is a bad idea
Studies have evaluated whether suppressing PVCs with antiarrhythmic agents improves prognosis. Both Cardiac Arrhythmia Suppression Trials (CAST I: encainide and flecainide; CAST II: moricizine) showed that suppressing frequent PVCs significantly increased mortality in the treatment groups.5,6
Recommendations
In 2006, the American College of Cardiology, American Heart Association, and European Society of Cardiology published their Guidelines for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death.3
The TABLE summarizes characteristics of patients with PVCs who were at higher risk of underlying cardiac disease and death. All patients with PVCs should have a history and physical examination, electrocardiogram, and electrolyte studies. Higher-risk patients should be considered for further evaluation, including stress testing, echocardiography, and ambulatory electrocardiogram (SOR: C, opinion).
TABLE
Characteristics of patients with PVCs who are at higher risk of cardiac disease/death
| PATIENT CHARACTERISTICS | LOWER RISK | HIGHER RISK |
|---|---|---|
| Morphology | Unifocal PVCs<10 PVCs per hour | Complex multifocal PVCs Ventricular tachycardia Ventricular fibrillation >10 PVCs per hour |
| Symptoms | Asymptomatic | Palpitations Presyncope Syncope |
| Preexisting conditions | None | Known history of CAD Structural heart disease Valvular heart disease Cardiomyopathy |
| CAD, coronary artery disease, PVCs, premature ventricular contractions. | ||
| Source: American College of Cardiology et al.3 | ||
1. Bikkina M, Larson MG, Levy D. Prognostic implications of asymptomatic ventricular arrhythmias: the Framingham heart study. Ann Intern Med. 1992;117:990-996.
2. Sajadieh A, Nielsen OW, Rasmussen V, et al. Ventricular arrhythmias and risk of death and acute myocardial infarction in apparently healthy subjects of age 55 or older. Am J Cardiol. 2006;97:1351-1357.
3. American College of Cardiology, American Heart Association, European Society of Cardiology. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. J Am Coll Cardiol. 2006;48:e247-e346.
4. Frolkis JP, Pothier CE, Blackstone EH, et al. Frequent ventricular ectopy after exercise as a predictor of death. N Engl J Med. 2003;348:781-790.
5. The Cardiac Arrhythmia Suppression Trial (CAST) Investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med. 1989;321:406-412.
6. The Cardiac Arrhythmia Suppression Trial II Investigators. Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. N Engl J Med. 1992;327:227-233.
1. Bikkina M, Larson MG, Levy D. Prognostic implications of asymptomatic ventricular arrhythmias: the Framingham heart study. Ann Intern Med. 1992;117:990-996.
2. Sajadieh A, Nielsen OW, Rasmussen V, et al. Ventricular arrhythmias and risk of death and acute myocardial infarction in apparently healthy subjects of age 55 or older. Am J Cardiol. 2006;97:1351-1357.
3. American College of Cardiology, American Heart Association, European Society of Cardiology. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. J Am Coll Cardiol. 2006;48:e247-e346.
4. Frolkis JP, Pothier CE, Blackstone EH, et al. Frequent ventricular ectopy after exercise as a predictor of death. N Engl J Med. 2003;348:781-790.
5. The Cardiac Arrhythmia Suppression Trial (CAST) Investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med. 1989;321:406-412.
6. The Cardiac Arrhythmia Suppression Trial II Investigators. Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. N Engl J Med. 1992;327:227-233.
Evidence-based answers from the Family Physicians Inquiries Network
How useful is ultrasound to evaluate patients with postmenopausal bleeding?
Using a threshold of ≤5 mm, transvaginal ultrasound (TVUS) can be used to identify those patients with postmenopausal bleeding who are at low risk for endometrial cancer, polyps, or atypical hyperplasia at a sensitivity comparable with that of endometrial biopsy and dilatation and curettage (D&C) (strength of recommendation: B, based on systematic reviews of consistent exploratory cohort studies.)
Evidence summary
A 1998 meta-analysis of 35 exploratory cohort studies published between 1966 and 1996 included a total of 5892 women with postmenopausal bleeding.1 TVUS evaluations were followed by endometrial tissue sampling and results were compared. Using endometrial thickness of ≤5 mm as the threshold, ultrasound was very accurate at ruling out patients with endometrial cancer but only fair at diagnosing cancer (likelihood ratio for a positive test [LR+]=2.5; LR for a negative test [LR–]=0.06). In addition, the 5-mm threshold was accurate at ruling out any endometrial abnormality (cancer, polyp, atypical hyperplasia: LR– = 0.01). The authors suggested that TVUS can reliably rule out significant endometrial disease among postmenopausal women with vaginal bleeding.
A 2002 meta-analysis of 57 cohort studies, without consistently applied reference standards, published between 1966 and 2000 included a total of 9031 women with postmenopausal bleeding.2 Because many of the studies were felt to use inadequately stringent criteria for diagnosis, the authors limited their final analysis to only 4 studies. They concluded that a negative result using a 5-mm threshold rules out endometrial pathology with fair certainty (LR– = 0.21).
Recommendations from others
A Consensus Conference Statement from the Society of Radiologists in Ultrasound recommended that either TVUS or endometrial biopsy could be used in the initial evaluation of patients with postmenopausal bleeding.3 Using a threshold of >5 mm as abnormal, they concluded that the sensitivities of TVUS and endometrial biopsy are comparable when “sufficient tissue” is obtained with endometrial biopsy. They felt that data was currently insufficient to clearly state which technique is more effective.
TVUS is an effective, relatively noninvasive way to rule out significant pathology
Postmenopausal women need accurate diagnostic evaluation when they have abnormal bleeding. While the majority have a benign cause of bleeding, such as atrophic endometrium, many have significant pathology, including cancer (Table). Many older patients are reluctant to undergo invasive sampling studies. Cervical stenosis, a common occurrence in this age group, further complicates matters. Evidence suggests that TVUS with a full endometrial thickness of 5 mm or less, full visualization of the cavity, and no other abnormal findings, can identify patients at low risk for significant abnormalities. The false negative rate for TVUS (8%) compares quite favorably with endometrial biopsy (5%–15%) and even D&C (2%–6%).1 TVUS is an effective and relatively noninvasive strategy for ruling out significant pathology. Given the false negative rates of these techniques, all patients with postmenopausal bleeding require close follow-up.
TABLE
Differential diagnosis of postmenopausal bleeding
| Histologic diagnosis | Incidence (n=1138) |
|---|---|
| Atrophy | 59% |
| Endometrial polyp | 12% |
| Hyperplasia | 10% |
| Endometrial cancer | 10% |
| Hormonal effect | 7% |
| Cervical cancer | 2% |
| Other | <1% |
| Source: Karlsson et al 1995.4 | |
1. Smith-Bindman R, Kerlikowske K, Feldstein VA, et al. Endovaginal ultrasound to exclude endometrial cancer and other endometrial abnormalities. JAMA 1998;280:1510-1517.
2. Gupta JK, Chien PF, Voit D, Clark TJ, Khan KS. Ultrasonographic endometrial thickness for diagnosing endometrial pathology in women with postmenopausal bleeding: a meta-analysis. Acta Obstet Gynecol Scand 2002;81:799-816.
3. Evaluation of the woman with postmenopausal bleeding. Society of Radiologists in Ultrasound-Sponsored Consensus Conference statement. J Ultrasound Med 2001;20:1025-1036.
4. Karlsson B, Granberg S, Wikland M, et al. Transvaginal ultrasonography of the endometrium in women with postmenopausal bleeding—a Nordic multicenter study. Am J Obstet Gynecol 1995;172:1488-1494.
Using a threshold of ≤5 mm, transvaginal ultrasound (TVUS) can be used to identify those patients with postmenopausal bleeding who are at low risk for endometrial cancer, polyps, or atypical hyperplasia at a sensitivity comparable with that of endometrial biopsy and dilatation and curettage (D&C) (strength of recommendation: B, based on systematic reviews of consistent exploratory cohort studies.)
Evidence summary
A 1998 meta-analysis of 35 exploratory cohort studies published between 1966 and 1996 included a total of 5892 women with postmenopausal bleeding.1 TVUS evaluations were followed by endometrial tissue sampling and results were compared. Using endometrial thickness of ≤5 mm as the threshold, ultrasound was very accurate at ruling out patients with endometrial cancer but only fair at diagnosing cancer (likelihood ratio for a positive test [LR+]=2.5; LR for a negative test [LR–]=0.06). In addition, the 5-mm threshold was accurate at ruling out any endometrial abnormality (cancer, polyp, atypical hyperplasia: LR– = 0.01). The authors suggested that TVUS can reliably rule out significant endometrial disease among postmenopausal women with vaginal bleeding.
A 2002 meta-analysis of 57 cohort studies, without consistently applied reference standards, published between 1966 and 2000 included a total of 9031 women with postmenopausal bleeding.2 Because many of the studies were felt to use inadequately stringent criteria for diagnosis, the authors limited their final analysis to only 4 studies. They concluded that a negative result using a 5-mm threshold rules out endometrial pathology with fair certainty (LR– = 0.21).
Recommendations from others
A Consensus Conference Statement from the Society of Radiologists in Ultrasound recommended that either TVUS or endometrial biopsy could be used in the initial evaluation of patients with postmenopausal bleeding.3 Using a threshold of >5 mm as abnormal, they concluded that the sensitivities of TVUS and endometrial biopsy are comparable when “sufficient tissue” is obtained with endometrial biopsy. They felt that data was currently insufficient to clearly state which technique is more effective.
TVUS is an effective, relatively noninvasive way to rule out significant pathology
Postmenopausal women need accurate diagnostic evaluation when they have abnormal bleeding. While the majority have a benign cause of bleeding, such as atrophic endometrium, many have significant pathology, including cancer (Table). Many older patients are reluctant to undergo invasive sampling studies. Cervical stenosis, a common occurrence in this age group, further complicates matters. Evidence suggests that TVUS with a full endometrial thickness of 5 mm or less, full visualization of the cavity, and no other abnormal findings, can identify patients at low risk for significant abnormalities. The false negative rate for TVUS (8%) compares quite favorably with endometrial biopsy (5%–15%) and even D&C (2%–6%).1 TVUS is an effective and relatively noninvasive strategy for ruling out significant pathology. Given the false negative rates of these techniques, all patients with postmenopausal bleeding require close follow-up.
TABLE
Differential diagnosis of postmenopausal bleeding
| Histologic diagnosis | Incidence (n=1138) |
|---|---|
| Atrophy | 59% |
| Endometrial polyp | 12% |
| Hyperplasia | 10% |
| Endometrial cancer | 10% |
| Hormonal effect | 7% |
| Cervical cancer | 2% |
| Other | <1% |
| Source: Karlsson et al 1995.4 | |
Using a threshold of ≤5 mm, transvaginal ultrasound (TVUS) can be used to identify those patients with postmenopausal bleeding who are at low risk for endometrial cancer, polyps, or atypical hyperplasia at a sensitivity comparable with that of endometrial biopsy and dilatation and curettage (D&C) (strength of recommendation: B, based on systematic reviews of consistent exploratory cohort studies.)
Evidence summary
A 1998 meta-analysis of 35 exploratory cohort studies published between 1966 and 1996 included a total of 5892 women with postmenopausal bleeding.1 TVUS evaluations were followed by endometrial tissue sampling and results were compared. Using endometrial thickness of ≤5 mm as the threshold, ultrasound was very accurate at ruling out patients with endometrial cancer but only fair at diagnosing cancer (likelihood ratio for a positive test [LR+]=2.5; LR for a negative test [LR–]=0.06). In addition, the 5-mm threshold was accurate at ruling out any endometrial abnormality (cancer, polyp, atypical hyperplasia: LR– = 0.01). The authors suggested that TVUS can reliably rule out significant endometrial disease among postmenopausal women with vaginal bleeding.
A 2002 meta-analysis of 57 cohort studies, without consistently applied reference standards, published between 1966 and 2000 included a total of 9031 women with postmenopausal bleeding.2 Because many of the studies were felt to use inadequately stringent criteria for diagnosis, the authors limited their final analysis to only 4 studies. They concluded that a negative result using a 5-mm threshold rules out endometrial pathology with fair certainty (LR– = 0.21).
Recommendations from others
A Consensus Conference Statement from the Society of Radiologists in Ultrasound recommended that either TVUS or endometrial biopsy could be used in the initial evaluation of patients with postmenopausal bleeding.3 Using a threshold of >5 mm as abnormal, they concluded that the sensitivities of TVUS and endometrial biopsy are comparable when “sufficient tissue” is obtained with endometrial biopsy. They felt that data was currently insufficient to clearly state which technique is more effective.
TVUS is an effective, relatively noninvasive way to rule out significant pathology
Postmenopausal women need accurate diagnostic evaluation when they have abnormal bleeding. While the majority have a benign cause of bleeding, such as atrophic endometrium, many have significant pathology, including cancer (Table). Many older patients are reluctant to undergo invasive sampling studies. Cervical stenosis, a common occurrence in this age group, further complicates matters. Evidence suggests that TVUS with a full endometrial thickness of 5 mm or less, full visualization of the cavity, and no other abnormal findings, can identify patients at low risk for significant abnormalities. The false negative rate for TVUS (8%) compares quite favorably with endometrial biopsy (5%–15%) and even D&C (2%–6%).1 TVUS is an effective and relatively noninvasive strategy for ruling out significant pathology. Given the false negative rates of these techniques, all patients with postmenopausal bleeding require close follow-up.
TABLE
Differential diagnosis of postmenopausal bleeding
| Histologic diagnosis | Incidence (n=1138) |
|---|---|
| Atrophy | 59% |
| Endometrial polyp | 12% |
| Hyperplasia | 10% |
| Endometrial cancer | 10% |
| Hormonal effect | 7% |
| Cervical cancer | 2% |
| Other | <1% |
| Source: Karlsson et al 1995.4 | |
1. Smith-Bindman R, Kerlikowske K, Feldstein VA, et al. Endovaginal ultrasound to exclude endometrial cancer and other endometrial abnormalities. JAMA 1998;280:1510-1517.
2. Gupta JK, Chien PF, Voit D, Clark TJ, Khan KS. Ultrasonographic endometrial thickness for diagnosing endometrial pathology in women with postmenopausal bleeding: a meta-analysis. Acta Obstet Gynecol Scand 2002;81:799-816.
3. Evaluation of the woman with postmenopausal bleeding. Society of Radiologists in Ultrasound-Sponsored Consensus Conference statement. J Ultrasound Med 2001;20:1025-1036.
4. Karlsson B, Granberg S, Wikland M, et al. Transvaginal ultrasonography of the endometrium in women with postmenopausal bleeding—a Nordic multicenter study. Am J Obstet Gynecol 1995;172:1488-1494.
1. Smith-Bindman R, Kerlikowske K, Feldstein VA, et al. Endovaginal ultrasound to exclude endometrial cancer and other endometrial abnormalities. JAMA 1998;280:1510-1517.
2. Gupta JK, Chien PF, Voit D, Clark TJ, Khan KS. Ultrasonographic endometrial thickness for diagnosing endometrial pathology in women with postmenopausal bleeding: a meta-analysis. Acta Obstet Gynecol Scand 2002;81:799-816.
3. Evaluation of the woman with postmenopausal bleeding. Society of Radiologists in Ultrasound-Sponsored Consensus Conference statement. J Ultrasound Med 2001;20:1025-1036.
4. Karlsson B, Granberg S, Wikland M, et al. Transvaginal ultrasonography of the endometrium in women with postmenopausal bleeding—a Nordic multicenter study. Am J Obstet Gynecol 1995;172:1488-1494.
Evidence-based answers from the Family Physicians Inquiries Network
Can transvaginal ultrasound detect endometrial disease among asymptomatic postmenopausal patients?
Transvaginal ultrasound should not replace endometrial biopsy for detection of endometrial disease among asymptomatic postmenopausal patients. Endometrial biopsy has been considered a standard for the clinical diagnosis of endometrial disease among asymptomatic patients, but it is invasive, may be uncomfortable, and may not be able to be performed for some patients with cervical stenosis. Ultrasound evaluation is less invasive and more comfortable and can be performed for patients with cervical stenosis. The positive predictive value of ultrasound is not adequate to allow it to replace endometrial biopsy for screening of asymptomatic women (strength of recommendation: B, based on cohort studies).
Evidence summary
In a trial of postmenopausal estrogen use, 448 asymptomatic postmenopausal women were monitored with both endometrial biopsy and transvaginal ultrasound.1 Biopsy detected 11 cases of serious disease. At a threshold of 5 mm for endometrial thickness, ultrasound had a positive predictive value of 9% for detecting any abnormality with 90% sensitivity and 48% specificity. At this threshold, more than half of women evaluated with ultrasound would require endometrial biopsy as well, and only 4% of these patients would have serious disease. This study concludes that transvaginal ultrasound has a poor positive predictive value but a high negative predictive value for detecting serious endometrial disease for this asymptomatic population.
An additional study evaluated 1926 asymptomatic postmenopausal women with transvaginal ultrasound.2 Of these, 1833 had endometrial thickness <6 mm and 1750 of this cohort underwent biopsy. Five cases of serious endometrial abnormality were identified in this group (1 adenocarcinoma and 4 atypical hyperplasia). Specificity in this group was 98%, but sensitivity for accurately detecting an abnormality was low at 17%.
The negative predictive value was greater than 99%. An inadequate number of patients with endometrial thickness >6 mm were biopsied (45%) to allow for accurate calculation of positive predictive value in those with a >6 mm stripe. The study concludes that transvaginal ultrasonography may not be an effective screening procedure for this population.
The relevance of several other studies is affected by small sample size (range, 36–85).3-6 Other studies did not attempt to biopsy all patients screened with ultrasound.7,8
Recommendations from others
The National Cancer Institute states finds the evidence insufficient to recommend any routine screening for endometrial cancer with either endometrial biopsy or transvaginal ultrasound. The American Cancer Society does not recommend routine screening of asymptomatic patients for endometrial cancer. They recommend prompt recognition and evaluation of abnormal uterine bleeding. The US Preventive Services Task Force and American Academy of Family Physicians have not issued recommendations related to endometrial cancer screening.
No need to screen postmenopausal women for endometrial disease
Paul V. Aitken, Jr., MD, MPH
New Hanover Regional Medical Center, Wilmington, NC/University of North Carolina at Chapel Hill
This Clinical Inquiry appears to draw appropriate conclusions to the question as presented. However, the question implies tacit approval of the notion of screening asymptomatic postmenopausal women. As pointed out above, no major organization recommends screening of these women. When reviewing a study we must also ask if the original study question is similar to our own clinical question. A critical piece of information regarding this answer is that references 1 and 2 are “nested” studies done within the context of large drug trials originally designed to answer very different questions. These asymptomatic women were being screened as part of the study protocol to ensure drug safety. Any effort on our part to apply this data to our asymptomatic patients should be considered with this significant limitation in mind.
1. Langer RD, Pierce JJ, O’Hanlan KA, et al. Transvaginal ultrasonography compared with endometrial biopsy for the detection of endometrial disease. Postmenopausal Estrogen/Progestin Intervention Trial. N Engl J Med 1997;337:1792-1798.
2. Fleischer AC, Wheeler JE, Lindsay I, et al. An assessment of the value of ultrasonographic screening for endometrial disease in postmenopausal women without symptoms. Am J Obstet Gynecol 2001;184:70-75.
3. Hanggi W, Bersinger N, Altermatt HJ, Birkhauser MH. Comparison of transvaginal ultrasonography and endometrial biopsy in surveillance in postmenopausal HRT users. Maturitas 1997;27:133-143.
4. Shipley CF, 3rd, Simmons CL, Nelson GH. Comparison of transvaginal sonography with endometrial biopsy in asymptomatic postmenopausal women. J Ultrasound Med 1994;13:99-104.
5. Paraskevaidis E, Papadimitriou D, Kalantaridou SN, et al. Screening transvaginal uterine ultrasonography for identifying endometrial pathology in postmenopausal women. Anticancer Res 2002;22:1127-1130.
6. Castelo-Branco C, Puerto B, Duran M, et al. Transvaginal sonography of the endometrium in postmenopausal women: monitoring the effect of hormone replacement therapy. Maturitas 1994;19:59-65.
7. Vuento MH, Pirhonen JP, Makinen JI, et al. Screening for endometrial cancer in asymptomatic postmenopausal women with conventional and colour Doppler sonography. Br J Obstet Gynaecol 1999;106:14-20.
8. Ciatto S, Cecchini S, Bonardi R, Grazzini G, Mazotta A, Zappa M. A feasibility study of screening for endometrial carcinoma in postmenopausal women by ultrasonography. Tumori 1995;81:334-337.
Transvaginal ultrasound should not replace endometrial biopsy for detection of endometrial disease among asymptomatic postmenopausal patients. Endometrial biopsy has been considered a standard for the clinical diagnosis of endometrial disease among asymptomatic patients, but it is invasive, may be uncomfortable, and may not be able to be performed for some patients with cervical stenosis. Ultrasound evaluation is less invasive and more comfortable and can be performed for patients with cervical stenosis. The positive predictive value of ultrasound is not adequate to allow it to replace endometrial biopsy for screening of asymptomatic women (strength of recommendation: B, based on cohort studies).
Evidence summary
In a trial of postmenopausal estrogen use, 448 asymptomatic postmenopausal women were monitored with both endometrial biopsy and transvaginal ultrasound.1 Biopsy detected 11 cases of serious disease. At a threshold of 5 mm for endometrial thickness, ultrasound had a positive predictive value of 9% for detecting any abnormality with 90% sensitivity and 48% specificity. At this threshold, more than half of women evaluated with ultrasound would require endometrial biopsy as well, and only 4% of these patients would have serious disease. This study concludes that transvaginal ultrasound has a poor positive predictive value but a high negative predictive value for detecting serious endometrial disease for this asymptomatic population.
An additional study evaluated 1926 asymptomatic postmenopausal women with transvaginal ultrasound.2 Of these, 1833 had endometrial thickness <6 mm and 1750 of this cohort underwent biopsy. Five cases of serious endometrial abnormality were identified in this group (1 adenocarcinoma and 4 atypical hyperplasia). Specificity in this group was 98%, but sensitivity for accurately detecting an abnormality was low at 17%.
The negative predictive value was greater than 99%. An inadequate number of patients with endometrial thickness >6 mm were biopsied (45%) to allow for accurate calculation of positive predictive value in those with a >6 mm stripe. The study concludes that transvaginal ultrasonography may not be an effective screening procedure for this population.
The relevance of several other studies is affected by small sample size (range, 36–85).3-6 Other studies did not attempt to biopsy all patients screened with ultrasound.7,8
Recommendations from others
The National Cancer Institute states finds the evidence insufficient to recommend any routine screening for endometrial cancer with either endometrial biopsy or transvaginal ultrasound. The American Cancer Society does not recommend routine screening of asymptomatic patients for endometrial cancer. They recommend prompt recognition and evaluation of abnormal uterine bleeding. The US Preventive Services Task Force and American Academy of Family Physicians have not issued recommendations related to endometrial cancer screening.
No need to screen postmenopausal women for endometrial disease
Paul V. Aitken, Jr., MD, MPH
New Hanover Regional Medical Center, Wilmington, NC/University of North Carolina at Chapel Hill
This Clinical Inquiry appears to draw appropriate conclusions to the question as presented. However, the question implies tacit approval of the notion of screening asymptomatic postmenopausal women. As pointed out above, no major organization recommends screening of these women. When reviewing a study we must also ask if the original study question is similar to our own clinical question. A critical piece of information regarding this answer is that references 1 and 2 are “nested” studies done within the context of large drug trials originally designed to answer very different questions. These asymptomatic women were being screened as part of the study protocol to ensure drug safety. Any effort on our part to apply this data to our asymptomatic patients should be considered with this significant limitation in mind.
Transvaginal ultrasound should not replace endometrial biopsy for detection of endometrial disease among asymptomatic postmenopausal patients. Endometrial biopsy has been considered a standard for the clinical diagnosis of endometrial disease among asymptomatic patients, but it is invasive, may be uncomfortable, and may not be able to be performed for some patients with cervical stenosis. Ultrasound evaluation is less invasive and more comfortable and can be performed for patients with cervical stenosis. The positive predictive value of ultrasound is not adequate to allow it to replace endometrial biopsy for screening of asymptomatic women (strength of recommendation: B, based on cohort studies).
Evidence summary
In a trial of postmenopausal estrogen use, 448 asymptomatic postmenopausal women were monitored with both endometrial biopsy and transvaginal ultrasound.1 Biopsy detected 11 cases of serious disease. At a threshold of 5 mm for endometrial thickness, ultrasound had a positive predictive value of 9% for detecting any abnormality with 90% sensitivity and 48% specificity. At this threshold, more than half of women evaluated with ultrasound would require endometrial biopsy as well, and only 4% of these patients would have serious disease. This study concludes that transvaginal ultrasound has a poor positive predictive value but a high negative predictive value for detecting serious endometrial disease for this asymptomatic population.
An additional study evaluated 1926 asymptomatic postmenopausal women with transvaginal ultrasound.2 Of these, 1833 had endometrial thickness <6 mm and 1750 of this cohort underwent biopsy. Five cases of serious endometrial abnormality were identified in this group (1 adenocarcinoma and 4 atypical hyperplasia). Specificity in this group was 98%, but sensitivity for accurately detecting an abnormality was low at 17%.
The negative predictive value was greater than 99%. An inadequate number of patients with endometrial thickness >6 mm were biopsied (45%) to allow for accurate calculation of positive predictive value in those with a >6 mm stripe. The study concludes that transvaginal ultrasonography may not be an effective screening procedure for this population.
The relevance of several other studies is affected by small sample size (range, 36–85).3-6 Other studies did not attempt to biopsy all patients screened with ultrasound.7,8
Recommendations from others
The National Cancer Institute states finds the evidence insufficient to recommend any routine screening for endometrial cancer with either endometrial biopsy or transvaginal ultrasound. The American Cancer Society does not recommend routine screening of asymptomatic patients for endometrial cancer. They recommend prompt recognition and evaluation of abnormal uterine bleeding. The US Preventive Services Task Force and American Academy of Family Physicians have not issued recommendations related to endometrial cancer screening.
No need to screen postmenopausal women for endometrial disease
Paul V. Aitken, Jr., MD, MPH
New Hanover Regional Medical Center, Wilmington, NC/University of North Carolina at Chapel Hill
This Clinical Inquiry appears to draw appropriate conclusions to the question as presented. However, the question implies tacit approval of the notion of screening asymptomatic postmenopausal women. As pointed out above, no major organization recommends screening of these women. When reviewing a study we must also ask if the original study question is similar to our own clinical question. A critical piece of information regarding this answer is that references 1 and 2 are “nested” studies done within the context of large drug trials originally designed to answer very different questions. These asymptomatic women were being screened as part of the study protocol to ensure drug safety. Any effort on our part to apply this data to our asymptomatic patients should be considered with this significant limitation in mind.
1. Langer RD, Pierce JJ, O’Hanlan KA, et al. Transvaginal ultrasonography compared with endometrial biopsy for the detection of endometrial disease. Postmenopausal Estrogen/Progestin Intervention Trial. N Engl J Med 1997;337:1792-1798.
2. Fleischer AC, Wheeler JE, Lindsay I, et al. An assessment of the value of ultrasonographic screening for endometrial disease in postmenopausal women without symptoms. Am J Obstet Gynecol 2001;184:70-75.
3. Hanggi W, Bersinger N, Altermatt HJ, Birkhauser MH. Comparison of transvaginal ultrasonography and endometrial biopsy in surveillance in postmenopausal HRT users. Maturitas 1997;27:133-143.
4. Shipley CF, 3rd, Simmons CL, Nelson GH. Comparison of transvaginal sonography with endometrial biopsy in asymptomatic postmenopausal women. J Ultrasound Med 1994;13:99-104.
5. Paraskevaidis E, Papadimitriou D, Kalantaridou SN, et al. Screening transvaginal uterine ultrasonography for identifying endometrial pathology in postmenopausal women. Anticancer Res 2002;22:1127-1130.
6. Castelo-Branco C, Puerto B, Duran M, et al. Transvaginal sonography of the endometrium in postmenopausal women: monitoring the effect of hormone replacement therapy. Maturitas 1994;19:59-65.
7. Vuento MH, Pirhonen JP, Makinen JI, et al. Screening for endometrial cancer in asymptomatic postmenopausal women with conventional and colour Doppler sonography. Br J Obstet Gynaecol 1999;106:14-20.
8. Ciatto S, Cecchini S, Bonardi R, Grazzini G, Mazotta A, Zappa M. A feasibility study of screening for endometrial carcinoma in postmenopausal women by ultrasonography. Tumori 1995;81:334-337.
1. Langer RD, Pierce JJ, O’Hanlan KA, et al. Transvaginal ultrasonography compared with endometrial biopsy for the detection of endometrial disease. Postmenopausal Estrogen/Progestin Intervention Trial. N Engl J Med 1997;337:1792-1798.
2. Fleischer AC, Wheeler JE, Lindsay I, et al. An assessment of the value of ultrasonographic screening for endometrial disease in postmenopausal women without symptoms. Am J Obstet Gynecol 2001;184:70-75.
3. Hanggi W, Bersinger N, Altermatt HJ, Birkhauser MH. Comparison of transvaginal ultrasonography and endometrial biopsy in surveillance in postmenopausal HRT users. Maturitas 1997;27:133-143.
4. Shipley CF, 3rd, Simmons CL, Nelson GH. Comparison of transvaginal sonography with endometrial biopsy in asymptomatic postmenopausal women. J Ultrasound Med 1994;13:99-104.
5. Paraskevaidis E, Papadimitriou D, Kalantaridou SN, et al. Screening transvaginal uterine ultrasonography for identifying endometrial pathology in postmenopausal women. Anticancer Res 2002;22:1127-1130.
6. Castelo-Branco C, Puerto B, Duran M, et al. Transvaginal sonography of the endometrium in postmenopausal women: monitoring the effect of hormone replacement therapy. Maturitas 1994;19:59-65.
7. Vuento MH, Pirhonen JP, Makinen JI, et al. Screening for endometrial cancer in asymptomatic postmenopausal women with conventional and colour Doppler sonography. Br J Obstet Gynaecol 1999;106:14-20.
8. Ciatto S, Cecchini S, Bonardi R, Grazzini G, Mazotta A, Zappa M. A feasibility study of screening for endometrial carcinoma in postmenopausal women by ultrasonography. Tumori 1995;81:334-337.
Evidence-based answers from the Family Physicians Inquiries Network
Are antibiotics effective in preventing pneumonia for nursing home patients?
Antibiotics should not be used for prophylaxis of pneumonia in nursing homes. We found no studies testing the effectiveness of antibiotics in preventing pneumonia in any population, including persons with predisposing conditions such as influenza. Three measures effectively prevent pneumonia in nursing home patients: influenza vaccination of residents (strength of recommendation [SOR]: B, based on systematic review of homogenous cohort observational studies); influenza vaccination of caregivers (SOR: B, based on individual randomized controlled trial); pneumococcal vaccination of residents (SOR: B, based on randomized, nonblinded clinical trials and consistent case-control studies).
Two other suggested interventions have not been extensively tested: antiviral chemoprophylaxis during an influenza outbreak in the nursing home, and oral hygiene programs for nursing home residents.
Evidence summary
Overuse of antibiotics is already a problem in nursing homes. A large portion of bacterial pneumonia in the nursing home population results from aspiration of oropharyngeal bacteria, which is more likely to be drug-resistant if the resident has been on antibiotics.1 We found no studies that testing antibacterial agents for prevention of pneumonia in nursing home patients. However, 3 measures are clearly helpful in preventing pneumonia in nursing home patients:
- Influenza vaccination of residents: A meta-analysis of 20 cohort studies showed a 53% efficacy (95% confidence interval [CI], 35–66)—defined as 1 minus the odds ratio—for influenza immunization in preventing pneumonia.2
- Influenza vaccination of caregivers: A cluster randomized trial in British long-term care facilities demonstrated that influenza vaccination of health care workers (61% of 1078 workers) reduced the total nursing home mortality rate (odds ratio [OR]=0.56 [95% CI, 0.4–0.8]) for a drop in mortality rate from 17% to 10% (number needed to treat [NNT]=14.3).3
- Pneumococcal vaccination of residents: This evidence was reviewed in a prior Clinical Inquiry.4 The evidence comes primarily from 2 clinical trials in which the NNT to prevent 1 episode of pneumonia was about 35.
Two other proposed interventions require further study to evaluate their role in prophylaxis. Antiviral prophylaxis to prevent pneumonia during nursing home outbreaks of influenza has not been evaluated in controlled trials. Observational studies strongly suggest that amantadine, rimantadine, and oseltamivir are all effective in reducing spread of influenza during outbreaks in nursing homes (Table). Oseltamivir acts against influenza B as well as A and has fewer side effects, but it is more expensive.5,6 Presumably, decreasing the rate of influenza also reduces the rate of subsequent pneumonia.
Oral hygiene programs for nursing home residents may also reduce pneumonia. In a single study, 366 patients in 11 Japanese nursing homes were divided into controls (self-care) and those treated with rigorous oral care (by staff). The intervention group had a relative risk of 0.6 (95% CI, 0.36–0.99; NNT=12.5) for pneumonia over a 2-year period.7 The NNT for preventing a death by pneumonia was 11 (P<.01). This intriguing result merits follow up in larger groups in US nursing homes to see if this approach is feasible.
TABLE
Available treatment and prophylactic regimens for influenza
| Drug name | Regimen for treatment* | Regimen for prophylaxis† | Comments | Cost‡ |
|---|---|---|---|---|
| Oseltamivir (Tamiflu) | 75 mg orally twice daily for 5 days | 75 mg orally once daily for >7 days | Influenza A and B | 10 tabs $59.99 (no generic) |
| Rimantidine (Flumadine) | 100 mg orally twice daily (100 mg orally once daily in elderly) | 100 mg orally twice daily (100 mg orally once daily in elderly) | Influenza A only | 14 tabs $33.45 (no generic) |
| Amantadine (Symmetrel) | 100 mg orally twice daily (100 mg orally once daily in elderly) | 100 mg orally twice daily (100 mg orally once daily in elderly) | Influenza A only (consider lower doses in debilitated patients) | 60 tabs $75.58 (brand), $18.99 (generic) |
| Zanamivir (Relenza) | 2 inhalations (10 mg) every 12 hours for 5 days | Not indicated | Influenza A and B (inhalations may be difficult to administer to debilitated patients) | 20 inhalation doses $54.41 (no generic) |
| Source: Epocrates RX: Online and PDA-Based Reference, June 12, 2004. | ||||
| * Start treatment within 48 hours of onset of symptoms. | ||||
| † Start prophylaxis immediately or within 48 hours of exposure. | ||||
| ‡ Approximate retail price from www.drugstore.com, June 2004. | ||||
Recommendations from others
There are no recommendations about the use of antibiotic prophylaxis for pneumonia in either the nursing home or in the outpatient settings; however, there are clear recommendations against the overuse of antibiotics.8
The CDC Advisory Committee on Immunization Practices (ACIP) recommends:
- annual influenza vaccine for persons residing in nursing homes9
- annual influenza vaccine for health care workers in long-term care facilities9
- pneumococcal vaccine for persons residing in a nursing home (the schedule for an immunocompetent adult is a single dose, followed by a booster after age 65 if the first dose was before age 65, or after 5 years for persons <65 years with compromised immune status)10
- chemoprophylaxis for influenza outbreaks in nursing homes.11
Prevention is key for reducing pneumonia mortality
Jon O. Neher, MD
Valley Medical Center, Renton, Wash
Pneumonia is one of the most common causes of death for nursing home patients. While pneumonia can present with the classic fever, productive cough, and air hunger, it often presents with such nonspecific findings as altered mental status or mild tachypnea, which can significantly delay diagnosis. Additionally, many older adults poorly tolerate the metabolic demands of the disease and become critically ill very rapidly. Thus, prevention remains a key strategy for reducing mortality. Nursing home policies that facilitate vaccination and reduce disease transmission are critically important in this regard.
1. Yamaya M, Yanai M, Ohrui T, Arai H, Sasaki H. Interventions to prevent pneumonia among older adults. J Am Geriatr Soc 2001;49:85-90.
2. Gross PA, Hermogenes AW, Sacks HS, Lau J, Levandowski RA. The efficacy of influenza vaccine in elderly persons. A meta-analysis and review of the literature. Ann Intern Med 1995;123:518-527.
3. Potter J, Stott DJ, Roberts MA, et al. Influenza vaccination of health care workers in long-term-care hospitals reduces the mortality of elderly patients. J Infect Dis 1997;175:1-6.
4. McCormack O, Meza J, Martin S, Tatum P. Is pneumococcal vaccine effective in nursing home patients? J Fam Pract 2003;52:150-154.
5. Arden NH, Patriarca PA, Fasano MB, et al. The roles of vaccination and amantadine prophylaxis in controlling an outbreak of influenza A (H3N2) in a nursing home. Arch Intern Med 1988;148:865-868.
6. Parker R, Loewen N, Skowronski D. Experience with oseltamivir in the control of a nursing home influenza B outbreak. Can Commun Dis Rep 2001;27:37-40.
7. Yoneyama T, Yoshida M, Ohrui T, et al. Oral care reduces pneumonia in older patients in nursing homes. J Am Geriatr Soc 2002;50:430-433.
8. Strassbaugh LJ, Crossley KB, Nurse BA, Thrupp LD. Antimicrobial resistance in long-term care facilities. Infection Control and Hospital Epidemiology 1996;17:129-140.
9. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 1999;48(RR-4):1-28.
10. Prevention of Pneumococcal Disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 1997;46(RR-8):1-24.
11. Bridges CB, Fukuda K, Uyeki TM, Cox NJ, Singleton JA. Centers for Disease Control and Prevention, Advisory Committee on Immunization Practices. Prevention and Control of Influenza. Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep 2002;51(RR-3):1-31.
Antibiotics should not be used for prophylaxis of pneumonia in nursing homes. We found no studies testing the effectiveness of antibiotics in preventing pneumonia in any population, including persons with predisposing conditions such as influenza. Three measures effectively prevent pneumonia in nursing home patients: influenza vaccination of residents (strength of recommendation [SOR]: B, based on systematic review of homogenous cohort observational studies); influenza vaccination of caregivers (SOR: B, based on individual randomized controlled trial); pneumococcal vaccination of residents (SOR: B, based on randomized, nonblinded clinical trials and consistent case-control studies).
Two other suggested interventions have not been extensively tested: antiviral chemoprophylaxis during an influenza outbreak in the nursing home, and oral hygiene programs for nursing home residents.
Evidence summary
Overuse of antibiotics is already a problem in nursing homes. A large portion of bacterial pneumonia in the nursing home population results from aspiration of oropharyngeal bacteria, which is more likely to be drug-resistant if the resident has been on antibiotics.1 We found no studies that testing antibacterial agents for prevention of pneumonia in nursing home patients. However, 3 measures are clearly helpful in preventing pneumonia in nursing home patients:
- Influenza vaccination of residents: A meta-analysis of 20 cohort studies showed a 53% efficacy (95% confidence interval [CI], 35–66)—defined as 1 minus the odds ratio—for influenza immunization in preventing pneumonia.2
- Influenza vaccination of caregivers: A cluster randomized trial in British long-term care facilities demonstrated that influenza vaccination of health care workers (61% of 1078 workers) reduced the total nursing home mortality rate (odds ratio [OR]=0.56 [95% CI, 0.4–0.8]) for a drop in mortality rate from 17% to 10% (number needed to treat [NNT]=14.3).3
- Pneumococcal vaccination of residents: This evidence was reviewed in a prior Clinical Inquiry.4 The evidence comes primarily from 2 clinical trials in which the NNT to prevent 1 episode of pneumonia was about 35.
Two other proposed interventions require further study to evaluate their role in prophylaxis. Antiviral prophylaxis to prevent pneumonia during nursing home outbreaks of influenza has not been evaluated in controlled trials. Observational studies strongly suggest that amantadine, rimantadine, and oseltamivir are all effective in reducing spread of influenza during outbreaks in nursing homes (Table). Oseltamivir acts against influenza B as well as A and has fewer side effects, but it is more expensive.5,6 Presumably, decreasing the rate of influenza also reduces the rate of subsequent pneumonia.
Oral hygiene programs for nursing home residents may also reduce pneumonia. In a single study, 366 patients in 11 Japanese nursing homes were divided into controls (self-care) and those treated with rigorous oral care (by staff). The intervention group had a relative risk of 0.6 (95% CI, 0.36–0.99; NNT=12.5) for pneumonia over a 2-year period.7 The NNT for preventing a death by pneumonia was 11 (P<.01). This intriguing result merits follow up in larger groups in US nursing homes to see if this approach is feasible.
TABLE
Available treatment and prophylactic regimens for influenza
| Drug name | Regimen for treatment* | Regimen for prophylaxis† | Comments | Cost‡ |
|---|---|---|---|---|
| Oseltamivir (Tamiflu) | 75 mg orally twice daily for 5 days | 75 mg orally once daily for >7 days | Influenza A and B | 10 tabs $59.99 (no generic) |
| Rimantidine (Flumadine) | 100 mg orally twice daily (100 mg orally once daily in elderly) | 100 mg orally twice daily (100 mg orally once daily in elderly) | Influenza A only | 14 tabs $33.45 (no generic) |
| Amantadine (Symmetrel) | 100 mg orally twice daily (100 mg orally once daily in elderly) | 100 mg orally twice daily (100 mg orally once daily in elderly) | Influenza A only (consider lower doses in debilitated patients) | 60 tabs $75.58 (brand), $18.99 (generic) |
| Zanamivir (Relenza) | 2 inhalations (10 mg) every 12 hours for 5 days | Not indicated | Influenza A and B (inhalations may be difficult to administer to debilitated patients) | 20 inhalation doses $54.41 (no generic) |
| Source: Epocrates RX: Online and PDA-Based Reference, June 12, 2004. | ||||
| * Start treatment within 48 hours of onset of symptoms. | ||||
| † Start prophylaxis immediately or within 48 hours of exposure. | ||||
| ‡ Approximate retail price from www.drugstore.com, June 2004. | ||||
Recommendations from others
There are no recommendations about the use of antibiotic prophylaxis for pneumonia in either the nursing home or in the outpatient settings; however, there are clear recommendations against the overuse of antibiotics.8
The CDC Advisory Committee on Immunization Practices (ACIP) recommends:
- annual influenza vaccine for persons residing in nursing homes9
- annual influenza vaccine for health care workers in long-term care facilities9
- pneumococcal vaccine for persons residing in a nursing home (the schedule for an immunocompetent adult is a single dose, followed by a booster after age 65 if the first dose was before age 65, or after 5 years for persons <65 years with compromised immune status)10
- chemoprophylaxis for influenza outbreaks in nursing homes.11
Prevention is key for reducing pneumonia mortality
Jon O. Neher, MD
Valley Medical Center, Renton, Wash
Pneumonia is one of the most common causes of death for nursing home patients. While pneumonia can present with the classic fever, productive cough, and air hunger, it often presents with such nonspecific findings as altered mental status or mild tachypnea, which can significantly delay diagnosis. Additionally, many older adults poorly tolerate the metabolic demands of the disease and become critically ill very rapidly. Thus, prevention remains a key strategy for reducing mortality. Nursing home policies that facilitate vaccination and reduce disease transmission are critically important in this regard.
Antibiotics should not be used for prophylaxis of pneumonia in nursing homes. We found no studies testing the effectiveness of antibiotics in preventing pneumonia in any population, including persons with predisposing conditions such as influenza. Three measures effectively prevent pneumonia in nursing home patients: influenza vaccination of residents (strength of recommendation [SOR]: B, based on systematic review of homogenous cohort observational studies); influenza vaccination of caregivers (SOR: B, based on individual randomized controlled trial); pneumococcal vaccination of residents (SOR: B, based on randomized, nonblinded clinical trials and consistent case-control studies).
Two other suggested interventions have not been extensively tested: antiviral chemoprophylaxis during an influenza outbreak in the nursing home, and oral hygiene programs for nursing home residents.
Evidence summary
Overuse of antibiotics is already a problem in nursing homes. A large portion of bacterial pneumonia in the nursing home population results from aspiration of oropharyngeal bacteria, which is more likely to be drug-resistant if the resident has been on antibiotics.1 We found no studies that testing antibacterial agents for prevention of pneumonia in nursing home patients. However, 3 measures are clearly helpful in preventing pneumonia in nursing home patients:
- Influenza vaccination of residents: A meta-analysis of 20 cohort studies showed a 53% efficacy (95% confidence interval [CI], 35–66)—defined as 1 minus the odds ratio—for influenza immunization in preventing pneumonia.2
- Influenza vaccination of caregivers: A cluster randomized trial in British long-term care facilities demonstrated that influenza vaccination of health care workers (61% of 1078 workers) reduced the total nursing home mortality rate (odds ratio [OR]=0.56 [95% CI, 0.4–0.8]) for a drop in mortality rate from 17% to 10% (number needed to treat [NNT]=14.3).3
- Pneumococcal vaccination of residents: This evidence was reviewed in a prior Clinical Inquiry.4 The evidence comes primarily from 2 clinical trials in which the NNT to prevent 1 episode of pneumonia was about 35.
Two other proposed interventions require further study to evaluate their role in prophylaxis. Antiviral prophylaxis to prevent pneumonia during nursing home outbreaks of influenza has not been evaluated in controlled trials. Observational studies strongly suggest that amantadine, rimantadine, and oseltamivir are all effective in reducing spread of influenza during outbreaks in nursing homes (Table). Oseltamivir acts against influenza B as well as A and has fewer side effects, but it is more expensive.5,6 Presumably, decreasing the rate of influenza also reduces the rate of subsequent pneumonia.
Oral hygiene programs for nursing home residents may also reduce pneumonia. In a single study, 366 patients in 11 Japanese nursing homes were divided into controls (self-care) and those treated with rigorous oral care (by staff). The intervention group had a relative risk of 0.6 (95% CI, 0.36–0.99; NNT=12.5) for pneumonia over a 2-year period.7 The NNT for preventing a death by pneumonia was 11 (P<.01). This intriguing result merits follow up in larger groups in US nursing homes to see if this approach is feasible.
TABLE
Available treatment and prophylactic regimens for influenza
| Drug name | Regimen for treatment* | Regimen for prophylaxis† | Comments | Cost‡ |
|---|---|---|---|---|
| Oseltamivir (Tamiflu) | 75 mg orally twice daily for 5 days | 75 mg orally once daily for >7 days | Influenza A and B | 10 tabs $59.99 (no generic) |
| Rimantidine (Flumadine) | 100 mg orally twice daily (100 mg orally once daily in elderly) | 100 mg orally twice daily (100 mg orally once daily in elderly) | Influenza A only | 14 tabs $33.45 (no generic) |
| Amantadine (Symmetrel) | 100 mg orally twice daily (100 mg orally once daily in elderly) | 100 mg orally twice daily (100 mg orally once daily in elderly) | Influenza A only (consider lower doses in debilitated patients) | 60 tabs $75.58 (brand), $18.99 (generic) |
| Zanamivir (Relenza) | 2 inhalations (10 mg) every 12 hours for 5 days | Not indicated | Influenza A and B (inhalations may be difficult to administer to debilitated patients) | 20 inhalation doses $54.41 (no generic) |
| Source: Epocrates RX: Online and PDA-Based Reference, June 12, 2004. | ||||
| * Start treatment within 48 hours of onset of symptoms. | ||||
| † Start prophylaxis immediately or within 48 hours of exposure. | ||||
| ‡ Approximate retail price from www.drugstore.com, June 2004. | ||||
Recommendations from others
There are no recommendations about the use of antibiotic prophylaxis for pneumonia in either the nursing home or in the outpatient settings; however, there are clear recommendations against the overuse of antibiotics.8
The CDC Advisory Committee on Immunization Practices (ACIP) recommends:
- annual influenza vaccine for persons residing in nursing homes9
- annual influenza vaccine for health care workers in long-term care facilities9
- pneumococcal vaccine for persons residing in a nursing home (the schedule for an immunocompetent adult is a single dose, followed by a booster after age 65 if the first dose was before age 65, or after 5 years for persons <65 years with compromised immune status)10
- chemoprophylaxis for influenza outbreaks in nursing homes.11
Prevention is key for reducing pneumonia mortality
Jon O. Neher, MD
Valley Medical Center, Renton, Wash
Pneumonia is one of the most common causes of death for nursing home patients. While pneumonia can present with the classic fever, productive cough, and air hunger, it often presents with such nonspecific findings as altered mental status or mild tachypnea, which can significantly delay diagnosis. Additionally, many older adults poorly tolerate the metabolic demands of the disease and become critically ill very rapidly. Thus, prevention remains a key strategy for reducing mortality. Nursing home policies that facilitate vaccination and reduce disease transmission are critically important in this regard.
1. Yamaya M, Yanai M, Ohrui T, Arai H, Sasaki H. Interventions to prevent pneumonia among older adults. J Am Geriatr Soc 2001;49:85-90.
2. Gross PA, Hermogenes AW, Sacks HS, Lau J, Levandowski RA. The efficacy of influenza vaccine in elderly persons. A meta-analysis and review of the literature. Ann Intern Med 1995;123:518-527.
3. Potter J, Stott DJ, Roberts MA, et al. Influenza vaccination of health care workers in long-term-care hospitals reduces the mortality of elderly patients. J Infect Dis 1997;175:1-6.
4. McCormack O, Meza J, Martin S, Tatum P. Is pneumococcal vaccine effective in nursing home patients? J Fam Pract 2003;52:150-154.
5. Arden NH, Patriarca PA, Fasano MB, et al. The roles of vaccination and amantadine prophylaxis in controlling an outbreak of influenza A (H3N2) in a nursing home. Arch Intern Med 1988;148:865-868.
6. Parker R, Loewen N, Skowronski D. Experience with oseltamivir in the control of a nursing home influenza B outbreak. Can Commun Dis Rep 2001;27:37-40.
7. Yoneyama T, Yoshida M, Ohrui T, et al. Oral care reduces pneumonia in older patients in nursing homes. J Am Geriatr Soc 2002;50:430-433.
8. Strassbaugh LJ, Crossley KB, Nurse BA, Thrupp LD. Antimicrobial resistance in long-term care facilities. Infection Control and Hospital Epidemiology 1996;17:129-140.
9. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 1999;48(RR-4):1-28.
10. Prevention of Pneumococcal Disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 1997;46(RR-8):1-24.
11. Bridges CB, Fukuda K, Uyeki TM, Cox NJ, Singleton JA. Centers for Disease Control and Prevention, Advisory Committee on Immunization Practices. Prevention and Control of Influenza. Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep 2002;51(RR-3):1-31.
1. Yamaya M, Yanai M, Ohrui T, Arai H, Sasaki H. Interventions to prevent pneumonia among older adults. J Am Geriatr Soc 2001;49:85-90.
2. Gross PA, Hermogenes AW, Sacks HS, Lau J, Levandowski RA. The efficacy of influenza vaccine in elderly persons. A meta-analysis and review of the literature. Ann Intern Med 1995;123:518-527.
3. Potter J, Stott DJ, Roberts MA, et al. Influenza vaccination of health care workers in long-term-care hospitals reduces the mortality of elderly patients. J Infect Dis 1997;175:1-6.
4. McCormack O, Meza J, Martin S, Tatum P. Is pneumococcal vaccine effective in nursing home patients? J Fam Pract 2003;52:150-154.
5. Arden NH, Patriarca PA, Fasano MB, et al. The roles of vaccination and amantadine prophylaxis in controlling an outbreak of influenza A (H3N2) in a nursing home. Arch Intern Med 1988;148:865-868.
6. Parker R, Loewen N, Skowronski D. Experience with oseltamivir in the control of a nursing home influenza B outbreak. Can Commun Dis Rep 2001;27:37-40.
7. Yoneyama T, Yoshida M, Ohrui T, et al. Oral care reduces pneumonia in older patients in nursing homes. J Am Geriatr Soc 2002;50:430-433.
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Evidence-based answers from the Family Physicians Inquiries Network