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What is the best way to evaluate acute diarrhea?
Limited evidence delineates the relative probabilities of causes of acute diarrhea, typically defined as a diarrheal disease lasting 14 days or fewer, in the developed world. Viruses (rotavirus, Norwalk, and other enteric viruses) are responsible for most cases. Stool culture helps to identify bacterial causes (Salmonella, Shigella, enterotoxic Escherichia coli), especially in patients with fever and bloody stool. A modified 3-day rule (eg, performing only Clostridium difficile toxin tests on low-risk patients who have been hospitalized for 3 or more days) leads to a more rational use of stool cultures without missing cases of clinically significant disease. (Grade of recommendation: D, based on limited studies, reliance on expert opinion, and consensus.)
Evidence summary
More than 2 million cases of infectious diarrhea are documented in the United States annually. Infectious diarrhea is the second leading cause of morbidity and mortality worldwide. Published data have focused on the etiology of diarrhea in the developing world, and more commonly on the clinical evaluation and treatment of patients with diarrhea and dehydration.
While most research on acute diarrhea focuses on infectious causes, noninfectious causes should also be considered (eg, drug-induced diarrhea, inflammatory bowel disease).1 Viral causes are most common; in children, viruses are responsible for 70% to 80% of cases of diarrhea.2 A prospective study of 147 US children with acute, mild diarrhea demonstrated that rectal swabs yielded a positive test for an infectious agent in 60.5% of cases (Table).3
A case-control study of stool cultures for rotavirus in adult patients found that 14% of 683 with diarrhea and 5% of 1115 without diarrhea shed rotavirus.4 A recent systematic review found no published studies about the likelihood of specific diagnoses in children presenting to the hospital with diarrhea.5
Some evidence supports a structured diagnostic strategy for hospitalized patients with acute diarrhea. Using retrospective reviews, Bauer and colleagues6 developed a prediction rule for cases of infectious diarrhea. The “modified 3-day rule” recommends stool cultures for patients with diarrhea beginning more than 3 days after hospitalization only when they fall into 1 of the following groups: patients older than 65 years with permanently altered organ function, those with HIV or neutropenia, those hospitalized during suspected nosocomial outbreaks, and those suspected of nondiarrheal manifestations of enteric infection.6 When the modified rule was applied prospectively, only 2 cases were missed. Both patients were at risk for immunosuppression, although they did not strictly meet the modified criteria. Neither required treatment.6
TABLE 1
Etiologic agents in US children with acute diarrhea
| Infectious agent | Percent |
|---|---|
| Rotavirus | 29.3% |
| Giardia lamblia | 15% |
| Pathogenic Escherichia coli | 15% |
| Multiple agents | 10% |
| Data from Caeiro JP, Mathewson JJ, Smith MA, Jiang ZD, Kaplan MA, Dupont HL. Etiology of outpatient pediatric nondysenteric diarrhea: a multicenter study in the United States. Pediatr Infect Dis J 1999; 18:94–7. | |
Recommendations from others
The Infectious Diseases Society of America’s practice guidelines for the evaluation and treatment of acute diarrhea recommends that stool culture for bacteria (including enterotoxic E coli) should be considered in patients with community- or travel-acquired diarrhea, especially when fever or bloody stool is present. In hospitalized patients, only toxin tests for C difficile are recommended. Testing for acute parasitic diseases should be reserved only for patients whose symptoms persist after 7 days.1
Clinical Commentary by Les Hall, MD, at http://www.fpin.org.
1. Guerrant RL, Van Gilder T, Steiner TS, et al. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis 2001;32:331-51.
2. Merrick N, Davidson B, Fox S. Treatment of acute gastroenteritis: too much and too little care. Clin Pediatr (Phila) 1996;35:429-35.
3. Caeiro JP, Mathewson JJ, Smith MA, Jiang ZD, Kaplan MA, Dupont HL. Etiology of outpatient pediatric nondysenteric diarrhea: a multicenter study in the United States. Pediatr Infect Dis J 1999;18:94-7.
4. Nakajima H, Nakagomi T, Kamisawa T, et al. Winter seasonality and rotavirus diarrhoea in adults. Lancet 2001;357(9272):1950.-
5. Armon K, Stephenson T, MacFaul R, Eccleston P, Werneke U. An evidence and consensus based guideline for acute diarrhoea management. Arch Dis Child 2001;85:132-42.
6. Bauer TM, Lalvani A, Fehrenbach J, et al. Derivation and validation of guidelines for stool cultures for enteropathogenic bacteria other than Clostridium difficile in hospitalized adults. JAMA 2001;285:313-9.
Limited evidence delineates the relative probabilities of causes of acute diarrhea, typically defined as a diarrheal disease lasting 14 days or fewer, in the developed world. Viruses (rotavirus, Norwalk, and other enteric viruses) are responsible for most cases. Stool culture helps to identify bacterial causes (Salmonella, Shigella, enterotoxic Escherichia coli), especially in patients with fever and bloody stool. A modified 3-day rule (eg, performing only Clostridium difficile toxin tests on low-risk patients who have been hospitalized for 3 or more days) leads to a more rational use of stool cultures without missing cases of clinically significant disease. (Grade of recommendation: D, based on limited studies, reliance on expert opinion, and consensus.)
Evidence summary
More than 2 million cases of infectious diarrhea are documented in the United States annually. Infectious diarrhea is the second leading cause of morbidity and mortality worldwide. Published data have focused on the etiology of diarrhea in the developing world, and more commonly on the clinical evaluation and treatment of patients with diarrhea and dehydration.
While most research on acute diarrhea focuses on infectious causes, noninfectious causes should also be considered (eg, drug-induced diarrhea, inflammatory bowel disease).1 Viral causes are most common; in children, viruses are responsible for 70% to 80% of cases of diarrhea.2 A prospective study of 147 US children with acute, mild diarrhea demonstrated that rectal swabs yielded a positive test for an infectious agent in 60.5% of cases (Table).3
A case-control study of stool cultures for rotavirus in adult patients found that 14% of 683 with diarrhea and 5% of 1115 without diarrhea shed rotavirus.4 A recent systematic review found no published studies about the likelihood of specific diagnoses in children presenting to the hospital with diarrhea.5
Some evidence supports a structured diagnostic strategy for hospitalized patients with acute diarrhea. Using retrospective reviews, Bauer and colleagues6 developed a prediction rule for cases of infectious diarrhea. The “modified 3-day rule” recommends stool cultures for patients with diarrhea beginning more than 3 days after hospitalization only when they fall into 1 of the following groups: patients older than 65 years with permanently altered organ function, those with HIV or neutropenia, those hospitalized during suspected nosocomial outbreaks, and those suspected of nondiarrheal manifestations of enteric infection.6 When the modified rule was applied prospectively, only 2 cases were missed. Both patients were at risk for immunosuppression, although they did not strictly meet the modified criteria. Neither required treatment.6
TABLE 1
Etiologic agents in US children with acute diarrhea
| Infectious agent | Percent |
|---|---|
| Rotavirus | 29.3% |
| Giardia lamblia | 15% |
| Pathogenic Escherichia coli | 15% |
| Multiple agents | 10% |
| Data from Caeiro JP, Mathewson JJ, Smith MA, Jiang ZD, Kaplan MA, Dupont HL. Etiology of outpatient pediatric nondysenteric diarrhea: a multicenter study in the United States. Pediatr Infect Dis J 1999; 18:94–7. | |
Recommendations from others
The Infectious Diseases Society of America’s practice guidelines for the evaluation and treatment of acute diarrhea recommends that stool culture for bacteria (including enterotoxic E coli) should be considered in patients with community- or travel-acquired diarrhea, especially when fever or bloody stool is present. In hospitalized patients, only toxin tests for C difficile are recommended. Testing for acute parasitic diseases should be reserved only for patients whose symptoms persist after 7 days.1
Clinical Commentary by Les Hall, MD, at http://www.fpin.org.
Limited evidence delineates the relative probabilities of causes of acute diarrhea, typically defined as a diarrheal disease lasting 14 days or fewer, in the developed world. Viruses (rotavirus, Norwalk, and other enteric viruses) are responsible for most cases. Stool culture helps to identify bacterial causes (Salmonella, Shigella, enterotoxic Escherichia coli), especially in patients with fever and bloody stool. A modified 3-day rule (eg, performing only Clostridium difficile toxin tests on low-risk patients who have been hospitalized for 3 or more days) leads to a more rational use of stool cultures without missing cases of clinically significant disease. (Grade of recommendation: D, based on limited studies, reliance on expert opinion, and consensus.)
Evidence summary
More than 2 million cases of infectious diarrhea are documented in the United States annually. Infectious diarrhea is the second leading cause of morbidity and mortality worldwide. Published data have focused on the etiology of diarrhea in the developing world, and more commonly on the clinical evaluation and treatment of patients with diarrhea and dehydration.
While most research on acute diarrhea focuses on infectious causes, noninfectious causes should also be considered (eg, drug-induced diarrhea, inflammatory bowel disease).1 Viral causes are most common; in children, viruses are responsible for 70% to 80% of cases of diarrhea.2 A prospective study of 147 US children with acute, mild diarrhea demonstrated that rectal swabs yielded a positive test for an infectious agent in 60.5% of cases (Table).3
A case-control study of stool cultures for rotavirus in adult patients found that 14% of 683 with diarrhea and 5% of 1115 without diarrhea shed rotavirus.4 A recent systematic review found no published studies about the likelihood of specific diagnoses in children presenting to the hospital with diarrhea.5
Some evidence supports a structured diagnostic strategy for hospitalized patients with acute diarrhea. Using retrospective reviews, Bauer and colleagues6 developed a prediction rule for cases of infectious diarrhea. The “modified 3-day rule” recommends stool cultures for patients with diarrhea beginning more than 3 days after hospitalization only when they fall into 1 of the following groups: patients older than 65 years with permanently altered organ function, those with HIV or neutropenia, those hospitalized during suspected nosocomial outbreaks, and those suspected of nondiarrheal manifestations of enteric infection.6 When the modified rule was applied prospectively, only 2 cases were missed. Both patients were at risk for immunosuppression, although they did not strictly meet the modified criteria. Neither required treatment.6
TABLE 1
Etiologic agents in US children with acute diarrhea
| Infectious agent | Percent |
|---|---|
| Rotavirus | 29.3% |
| Giardia lamblia | 15% |
| Pathogenic Escherichia coli | 15% |
| Multiple agents | 10% |
| Data from Caeiro JP, Mathewson JJ, Smith MA, Jiang ZD, Kaplan MA, Dupont HL. Etiology of outpatient pediatric nondysenteric diarrhea: a multicenter study in the United States. Pediatr Infect Dis J 1999; 18:94–7. | |
Recommendations from others
The Infectious Diseases Society of America’s practice guidelines for the evaluation and treatment of acute diarrhea recommends that stool culture for bacteria (including enterotoxic E coli) should be considered in patients with community- or travel-acquired diarrhea, especially when fever or bloody stool is present. In hospitalized patients, only toxin tests for C difficile are recommended. Testing for acute parasitic diseases should be reserved only for patients whose symptoms persist after 7 days.1
Clinical Commentary by Les Hall, MD, at http://www.fpin.org.
1. Guerrant RL, Van Gilder T, Steiner TS, et al. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis 2001;32:331-51.
2. Merrick N, Davidson B, Fox S. Treatment of acute gastroenteritis: too much and too little care. Clin Pediatr (Phila) 1996;35:429-35.
3. Caeiro JP, Mathewson JJ, Smith MA, Jiang ZD, Kaplan MA, Dupont HL. Etiology of outpatient pediatric nondysenteric diarrhea: a multicenter study in the United States. Pediatr Infect Dis J 1999;18:94-7.
4. Nakajima H, Nakagomi T, Kamisawa T, et al. Winter seasonality and rotavirus diarrhoea in adults. Lancet 2001;357(9272):1950.-
5. Armon K, Stephenson T, MacFaul R, Eccleston P, Werneke U. An evidence and consensus based guideline for acute diarrhoea management. Arch Dis Child 2001;85:132-42.
6. Bauer TM, Lalvani A, Fehrenbach J, et al. Derivation and validation of guidelines for stool cultures for enteropathogenic bacteria other than Clostridium difficile in hospitalized adults. JAMA 2001;285:313-9.
1. Guerrant RL, Van Gilder T, Steiner TS, et al. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis 2001;32:331-51.
2. Merrick N, Davidson B, Fox S. Treatment of acute gastroenteritis: too much and too little care. Clin Pediatr (Phila) 1996;35:429-35.
3. Caeiro JP, Mathewson JJ, Smith MA, Jiang ZD, Kaplan MA, Dupont HL. Etiology of outpatient pediatric nondysenteric diarrhea: a multicenter study in the United States. Pediatr Infect Dis J 1999;18:94-7.
4. Nakajima H, Nakagomi T, Kamisawa T, et al. Winter seasonality and rotavirus diarrhoea in adults. Lancet 2001;357(9272):1950.-
5. Armon K, Stephenson T, MacFaul R, Eccleston P, Werneke U. An evidence and consensus based guideline for acute diarrhoea management. Arch Dis Child 2001;85:132-42.
6. Bauer TM, Lalvani A, Fehrenbach J, et al. Derivation and validation of guidelines for stool cultures for enteropathogenic bacteria other than Clostridium difficile in hospitalized adults. JAMA 2001;285:313-9.
Evidence-based answers from the Family Physicians Inquiries Network
How beneficial are thiazolidinediones for diabetes mellitus?
The thiazolidinediones pioglitazone (Actos) and rosiglitazone (Avandia) are effective at lowering fasting plasma glucose (FPG) and glycosylated hemoglobin (Hb A1c) in patients with type 2 diabetes when used either as monotherapy or in combination with sulfonylureas, metformin, or insulin. The glucose-lowering effects appear comparable with those of sulfonylureas and metformin alone. Currently, there are no randomized trials directly comparing patient-oriented outcomes of the thiazolidinediones with those of sulfonylureas and metformin. Grade of recommendation: B (on the basis of extrapolations from randomized trials and low quality randomized trials).
Evidence summary
Proper nutrition and exercise remain the cornerstones of diabetes therapy; medication management, however, is often necessary.1 Both pioglitazone and rosiglitazone have similar glucose-lowering effects. See the tables in the online version of this Clinical Inquiry at www.fpin.org for a summary of monotherapy and combination clinical trials.
Pioglitazone has consistently been shown to decrease triglycerides and increase high-density lipoprotein and rosiglitazone increases total cholesterol, HDL, and low-density lipoprotein. The clinical significance of these effects has not been established. Both medications are generally well tolerated but have the potential to cause edema and mildly decrease hemoglobin and hematocrit.2-9
To date, there have been reports of pulmonary edema and hepatotoxicity associated with the use of rosiglitazone. In all cases, rosiglitazone was found to be a possible, not a definite, cause.10-12
Recommendations from others
The American Diabetes Association and the American Association of Clinical Endocrinologists do not recommend one class of antidiabetic medication over another.1,13 Both of the thiazolidinediones are indicated for monotherapy and in combination with a sulfonylurea and metformin. However, only pioglitazone is indicated in combination with insulin. They are highly metabolized by the liver and should not be used in patients with liver enzymes greater than 2.5 times the upper limit of normal. Routine liver monitoring is recommended at baseline, every 2 months for the first year, and then periodically thereafter.1 Patients with New York Heart Association class III or IV heart failure should not use thiazolidinediones. In addition, thiazolidinediones cost considerably more than sulfonylureas and metformin.14 Therefore, thiazolidinediones are not generally considered for first-line therapy.15 These agents may be most beneficial in patients with insulin resistance and patients with renal dysfunction.1
TABLE
Effects of rosiglitazone and pioglitazone, by dosage
| Drug and dosage | Control | Adjunct medication | Change in Hb A1c vs comparison (%) | Change in FPG vs comparison (mg/dL) |
|---|---|---|---|---|
| Rosiglitazone | ||||
| 4 mg bid2 | placebo | none | -1.5* | -73* |
| 2 mg bid3 | glyburide | none | +0.4 | +5 |
| 4 mg bid | +0.2† | -11 | ||
| 8 mg bid4 | placebo | metformin | -1.3* | -54.3* |
| 2 mg bid5 | placebo | sulfonylurea | -1.1* | -43.6* |
| 4 mg bid6 | placebo | insulin | -1.3‡ | -55.8‡ |
| Pioglitazone | ||||
| 45 mg qd7 | placebo | none | -1.6* | -65.3* |
| 30 mg qd8 | placebo | sulfonylurea | -1.3* | -57.9* |
| 30 mg qd9 | placebo | metformin | -0.83* | -37.7* |
| Hb A1cdenotes glycosylated hemoglobin; FPG, fasting plasma glucose; bid, twice a day; qd, every day. | ||||
| *P < .05 versus control. | ||||
| †P= not significant. | ||||
| ‡P= < .006 versus placebo plus insulin. | ||||
| Find further details online at www.fpin.org. | ||||
Read a clinical commentary by Steven Zweig, MD, at www.fpin.org
1. The American Association of Clinical Endocrinologists. Endocrin Pract 2000;
2. Lebovitz HE, Dole JF, Patwardhan R, et al. J Clin Endocrinol Metab 2001;86:280-8.
3. Charbonnel B, Lonnqvist F, Jones N, et al. Diabetes 1999;48 (suppl 1):A114.-
4. Fonseca V, Rosenstock J, Patwardhan R, et al. JAMA 2000;283:1695-702.
5. Wolffenbuttel BH, Gomist R, Squatrito S, et al. Diabet Med 2000;17:40-7.
6. Raskin P, Rendell M, Riddle MC, et al. Diabetes Care 2001;24:1226-32.
7. Aronoff S, Rosenblatt S, Braithwaite S, et al. Diabetes Care 2000;23:1605-11.
8. Kipnes MS, Krosnick A, Rendell MS, et al. Am J Med 2001;111:10-7.
9. Einhorn D, Rendell M, Rosenzweig J, et al. Clin Ther 2000;22:1395-409.
10. Thomas ML, Lloyd SJ. Ann Pharmacother 2001;35:123-4.
11. Al-Salman J, Arjomand H, Kemp DG, et al. Ann Intern Med 2000;132:121-4.
12. Forman LM, Simmons DA, Diamond RH. Ann Intern Med 2000;132:118-20.
13. The American Diabetes Association. Diabetes 2001;(suppl 1):S1-S133.
14. Holmboe ES. Clinical applications. JAMA 2002;287:373-6.
15. Inzucchi SE. Scientific review. JAMA 2002;287:360-72.
The thiazolidinediones pioglitazone (Actos) and rosiglitazone (Avandia) are effective at lowering fasting plasma glucose (FPG) and glycosylated hemoglobin (Hb A1c) in patients with type 2 diabetes when used either as monotherapy or in combination with sulfonylureas, metformin, or insulin. The glucose-lowering effects appear comparable with those of sulfonylureas and metformin alone. Currently, there are no randomized trials directly comparing patient-oriented outcomes of the thiazolidinediones with those of sulfonylureas and metformin. Grade of recommendation: B (on the basis of extrapolations from randomized trials and low quality randomized trials).
Evidence summary
Proper nutrition and exercise remain the cornerstones of diabetes therapy; medication management, however, is often necessary.1 Both pioglitazone and rosiglitazone have similar glucose-lowering effects. See the tables in the online version of this Clinical Inquiry at www.fpin.org for a summary of monotherapy and combination clinical trials.
Pioglitazone has consistently been shown to decrease triglycerides and increase high-density lipoprotein and rosiglitazone increases total cholesterol, HDL, and low-density lipoprotein. The clinical significance of these effects has not been established. Both medications are generally well tolerated but have the potential to cause edema and mildly decrease hemoglobin and hematocrit.2-9
To date, there have been reports of pulmonary edema and hepatotoxicity associated with the use of rosiglitazone. In all cases, rosiglitazone was found to be a possible, not a definite, cause.10-12
Recommendations from others
The American Diabetes Association and the American Association of Clinical Endocrinologists do not recommend one class of antidiabetic medication over another.1,13 Both of the thiazolidinediones are indicated for monotherapy and in combination with a sulfonylurea and metformin. However, only pioglitazone is indicated in combination with insulin. They are highly metabolized by the liver and should not be used in patients with liver enzymes greater than 2.5 times the upper limit of normal. Routine liver monitoring is recommended at baseline, every 2 months for the first year, and then periodically thereafter.1 Patients with New York Heart Association class III or IV heart failure should not use thiazolidinediones. In addition, thiazolidinediones cost considerably more than sulfonylureas and metformin.14 Therefore, thiazolidinediones are not generally considered for first-line therapy.15 These agents may be most beneficial in patients with insulin resistance and patients with renal dysfunction.1
TABLE
Effects of rosiglitazone and pioglitazone, by dosage
| Drug and dosage | Control | Adjunct medication | Change in Hb A1c vs comparison (%) | Change in FPG vs comparison (mg/dL) |
|---|---|---|---|---|
| Rosiglitazone | ||||
| 4 mg bid2 | placebo | none | -1.5* | -73* |
| 2 mg bid3 | glyburide | none | +0.4 | +5 |
| 4 mg bid | +0.2† | -11 | ||
| 8 mg bid4 | placebo | metformin | -1.3* | -54.3* |
| 2 mg bid5 | placebo | sulfonylurea | -1.1* | -43.6* |
| 4 mg bid6 | placebo | insulin | -1.3‡ | -55.8‡ |
| Pioglitazone | ||||
| 45 mg qd7 | placebo | none | -1.6* | -65.3* |
| 30 mg qd8 | placebo | sulfonylurea | -1.3* | -57.9* |
| 30 mg qd9 | placebo | metformin | -0.83* | -37.7* |
| Hb A1cdenotes glycosylated hemoglobin; FPG, fasting plasma glucose; bid, twice a day; qd, every day. | ||||
| *P < .05 versus control. | ||||
| †P= not significant. | ||||
| ‡P= < .006 versus placebo plus insulin. | ||||
| Find further details online at www.fpin.org. | ||||
Read a clinical commentary by Steven Zweig, MD, at www.fpin.org
The thiazolidinediones pioglitazone (Actos) and rosiglitazone (Avandia) are effective at lowering fasting plasma glucose (FPG) and glycosylated hemoglobin (Hb A1c) in patients with type 2 diabetes when used either as monotherapy or in combination with sulfonylureas, metformin, or insulin. The glucose-lowering effects appear comparable with those of sulfonylureas and metformin alone. Currently, there are no randomized trials directly comparing patient-oriented outcomes of the thiazolidinediones with those of sulfonylureas and metformin. Grade of recommendation: B (on the basis of extrapolations from randomized trials and low quality randomized trials).
Evidence summary
Proper nutrition and exercise remain the cornerstones of diabetes therapy; medication management, however, is often necessary.1 Both pioglitazone and rosiglitazone have similar glucose-lowering effects. See the tables in the online version of this Clinical Inquiry at www.fpin.org for a summary of monotherapy and combination clinical trials.
Pioglitazone has consistently been shown to decrease triglycerides and increase high-density lipoprotein and rosiglitazone increases total cholesterol, HDL, and low-density lipoprotein. The clinical significance of these effects has not been established. Both medications are generally well tolerated but have the potential to cause edema and mildly decrease hemoglobin and hematocrit.2-9
To date, there have been reports of pulmonary edema and hepatotoxicity associated with the use of rosiglitazone. In all cases, rosiglitazone was found to be a possible, not a definite, cause.10-12
Recommendations from others
The American Diabetes Association and the American Association of Clinical Endocrinologists do not recommend one class of antidiabetic medication over another.1,13 Both of the thiazolidinediones are indicated for monotherapy and in combination with a sulfonylurea and metformin. However, only pioglitazone is indicated in combination with insulin. They are highly metabolized by the liver and should not be used in patients with liver enzymes greater than 2.5 times the upper limit of normal. Routine liver monitoring is recommended at baseline, every 2 months for the first year, and then periodically thereafter.1 Patients with New York Heart Association class III or IV heart failure should not use thiazolidinediones. In addition, thiazolidinediones cost considerably more than sulfonylureas and metformin.14 Therefore, thiazolidinediones are not generally considered for first-line therapy.15 These agents may be most beneficial in patients with insulin resistance and patients with renal dysfunction.1
TABLE
Effects of rosiglitazone and pioglitazone, by dosage
| Drug and dosage | Control | Adjunct medication | Change in Hb A1c vs comparison (%) | Change in FPG vs comparison (mg/dL) |
|---|---|---|---|---|
| Rosiglitazone | ||||
| 4 mg bid2 | placebo | none | -1.5* | -73* |
| 2 mg bid3 | glyburide | none | +0.4 | +5 |
| 4 mg bid | +0.2† | -11 | ||
| 8 mg bid4 | placebo | metformin | -1.3* | -54.3* |
| 2 mg bid5 | placebo | sulfonylurea | -1.1* | -43.6* |
| 4 mg bid6 | placebo | insulin | -1.3‡ | -55.8‡ |
| Pioglitazone | ||||
| 45 mg qd7 | placebo | none | -1.6* | -65.3* |
| 30 mg qd8 | placebo | sulfonylurea | -1.3* | -57.9* |
| 30 mg qd9 | placebo | metformin | -0.83* | -37.7* |
| Hb A1cdenotes glycosylated hemoglobin; FPG, fasting plasma glucose; bid, twice a day; qd, every day. | ||||
| *P < .05 versus control. | ||||
| †P= not significant. | ||||
| ‡P= < .006 versus placebo plus insulin. | ||||
| Find further details online at www.fpin.org. | ||||
Read a clinical commentary by Steven Zweig, MD, at www.fpin.org
1. The American Association of Clinical Endocrinologists. Endocrin Pract 2000;
2. Lebovitz HE, Dole JF, Patwardhan R, et al. J Clin Endocrinol Metab 2001;86:280-8.
3. Charbonnel B, Lonnqvist F, Jones N, et al. Diabetes 1999;48 (suppl 1):A114.-
4. Fonseca V, Rosenstock J, Patwardhan R, et al. JAMA 2000;283:1695-702.
5. Wolffenbuttel BH, Gomist R, Squatrito S, et al. Diabet Med 2000;17:40-7.
6. Raskin P, Rendell M, Riddle MC, et al. Diabetes Care 2001;24:1226-32.
7. Aronoff S, Rosenblatt S, Braithwaite S, et al. Diabetes Care 2000;23:1605-11.
8. Kipnes MS, Krosnick A, Rendell MS, et al. Am J Med 2001;111:10-7.
9. Einhorn D, Rendell M, Rosenzweig J, et al. Clin Ther 2000;22:1395-409.
10. Thomas ML, Lloyd SJ. Ann Pharmacother 2001;35:123-4.
11. Al-Salman J, Arjomand H, Kemp DG, et al. Ann Intern Med 2000;132:121-4.
12. Forman LM, Simmons DA, Diamond RH. Ann Intern Med 2000;132:118-20.
13. The American Diabetes Association. Diabetes 2001;(suppl 1):S1-S133.
14. Holmboe ES. Clinical applications. JAMA 2002;287:373-6.
15. Inzucchi SE. Scientific review. JAMA 2002;287:360-72.
1. The American Association of Clinical Endocrinologists. Endocrin Pract 2000;
2. Lebovitz HE, Dole JF, Patwardhan R, et al. J Clin Endocrinol Metab 2001;86:280-8.
3. Charbonnel B, Lonnqvist F, Jones N, et al. Diabetes 1999;48 (suppl 1):A114.-
4. Fonseca V, Rosenstock J, Patwardhan R, et al. JAMA 2000;283:1695-702.
5. Wolffenbuttel BH, Gomist R, Squatrito S, et al. Diabet Med 2000;17:40-7.
6. Raskin P, Rendell M, Riddle MC, et al. Diabetes Care 2001;24:1226-32.
7. Aronoff S, Rosenblatt S, Braithwaite S, et al. Diabetes Care 2000;23:1605-11.
8. Kipnes MS, Krosnick A, Rendell MS, et al. Am J Med 2001;111:10-7.
9. Einhorn D, Rendell M, Rosenzweig J, et al. Clin Ther 2000;22:1395-409.
10. Thomas ML, Lloyd SJ. Ann Pharmacother 2001;35:123-4.
11. Al-Salman J, Arjomand H, Kemp DG, et al. Ann Intern Med 2000;132:121-4.
12. Forman LM, Simmons DA, Diamond RH. Ann Intern Med 2000;132:118-20.
13. The American Diabetes Association. Diabetes 2001;(suppl 1):S1-S133.
14. Holmboe ES. Clinical applications. JAMA 2002;287:373-6.
15. Inzucchi SE. Scientific review. JAMA 2002;287:360-72.
Evidence-based answers from the Family Physicians Inquiries Network
What levels of cholesterol should be treated for primary prevention?
The levels of cholesterol that should be treated for primary prevention are based on low-density lipoprotein cholesterol (LDL-C) levels of > 100 mg/dL to > 190 mg/dL and vary according to whether the patient’s risk is high, moderate, or low. See the table to estimate risk. Grade of recommendation for medication indications: A (on the basis of high-quality randomized controlled trials). Grade of recommendation for lifestyle indications: B (on the basis of extrapolations from randomized controlled trials).
TABLE
Adult treatment recommendations from NCEP, Adult Treatment Panel III
| Risk category | LDL-C level | LDL-C goal* at which to consider medication |
|---|---|---|
| Coronary heart disease risk equivalents | < 100 mg/dL | ≥ 130 mg/dL; ≥100-129 mg/dL optional |
| 2 or more major risk factors† | < 130 mg/dL | 10-year risk‡ 10-20%: ≥ 130 mg/dL; 10-year risk‡ < 10%: ≥160 mg/dL |
| 0 or 1 major risk factor† | < 160 mg/dL | ≥ 190 mg/dL; 160-190 mg/dL optional |
| NOTE: CHD risk equivalents include symptomatic carotid artery disease, peripheral arterial disease, abdominal aortic aneurysm, diabetes, and a 10-year risk of > 20% (see ‡ below). The cutoff points for therapy for patients with clinical CHD are the same as for CHD risk equivalents. | ||
| * Initiate therapeutic lifestyle changes above these levels. | ||
| †Major risk factors include cigarette smoking, hypertension, HDL < 40 mg/dL, family history of premature CHD (CHD in first-degree male relative < 55 y; CHD in first-degree female relative < 65 y), age (men ≥ 45 y, women ≥ 55 y). | ||
| ‡To calculate 10-year risk, use the Framingham Tables, available at http://www.nhlbi.nih.gov/guidelines/cholesterol/risk_tbl.htm. | ||
Evidence summary
Statins are the most effective at reducing LDL-C and the associated cardiovascular risk. The 5-year West of Scotland study (WOSCOPS) showed that a 26% reduction in LDL-C (from a mean of 192 to 142 mg/dL) using pravastatin 40 mg per day reduced the risk of either nonfatal myocardial infarction (MI) or coronary heart disease (CHD) death (number needed to treat [NNT] = 42; relative risk [RR] = 31; 95% confidence interval [CI],17 - 43).1 This trial enrolled middle-aged men with an LDL-C level > 155 mg/dL without a history of prior MI, although subjects with stable angina (5% of the participants) were still eligible. Similar reductions were seen in cardiovascular death and in all-cause death (RR = 22; 95% CI = 0 - 40). Lovastatin reduced the risk of a first major acute coronary event (NNT = 24) in the 5-year AFCAPS/TexCAPS trial that enrolled 5608 men and 997 women with below-average high-density lipoprotein cholesterol (HDL-C) (men, 36 mg/dL; women, 40 mg/dL) without signs or symptoms of CHD.2 LDL-C was lowered 25% (from a mean of 156 to 115 mg/dL). Unpublished results suggest that simvastatin may have a similar effect. Primary prevention data are still lacking for atorvastatin and fluvastatin.
The 7-year Lipid Research Clinics Coronary Prevention Trial (LRC-CPPT) documented a reduction in CHD death and/or nonfatal MI (NNT = 59) with a 12.6% reduction in LDL-C with the use of cholestyramine, a bile acid resin, 24 g per day.3
Results of studies of the fibric acid derivatives are mixed. Subjects taking gemfibrozil 1200 mg per day in the 5-year Helsinki Heart Study had fewer coronary events compared with those taking a placebo (NNT = 71).4 Subsequent analysis suggests that patients with a high LDL-C/HDL-C ratio (> 5) plus hypertriglyceridemia ( 205 mg/dL) benefited the most.5 Clofibrate is no longer used because of an unexplained increase in deaths in the WHO Cooperative Trial.6 To date, outcomes in fenofibrate trials have only focused on surrogate markers and not long-term clinical outcomes.
Recommendations from others
The recommendations of the Third Report of the National Cholesterol Education Program7 (NCEP, Adult Treatment Panel III) are in the table. This report is an excellent source of additional information (http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3xsum.pdf).
Read a clinical commentary by David Switzer, MD, at www.fpin.org.
1. Shepard J, Cobbe SM, Ford I, et al. West of Scotland Coronary Prevention Study Group. N Engl J Med 1995;333:1301-7.
2. Downs JR, Clearfield M, Weis S, et al. JAMA 1998;279:1615-22.
3. The Lipid Research Clinics Coronary Primary Prevention Trial results. JAMA 1984;251:351-64,365-74.
4. Frick MH, Elo O, Happa K, et al. N Engl J Med 1987;317:1237-45.
5. Manninen V, Tenkanen L, Koskinen P, et al. Circulation 1992;85:37-45.
6. WHO cooperative trial. Lancet 1984;2:600-4.
7. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-97.
The levels of cholesterol that should be treated for primary prevention are based on low-density lipoprotein cholesterol (LDL-C) levels of > 100 mg/dL to > 190 mg/dL and vary according to whether the patient’s risk is high, moderate, or low. See the table to estimate risk. Grade of recommendation for medication indications: A (on the basis of high-quality randomized controlled trials). Grade of recommendation for lifestyle indications: B (on the basis of extrapolations from randomized controlled trials).
TABLE
Adult treatment recommendations from NCEP, Adult Treatment Panel III
| Risk category | LDL-C level | LDL-C goal* at which to consider medication |
|---|---|---|
| Coronary heart disease risk equivalents | < 100 mg/dL | ≥ 130 mg/dL; ≥100-129 mg/dL optional |
| 2 or more major risk factors† | < 130 mg/dL | 10-year risk‡ 10-20%: ≥ 130 mg/dL; 10-year risk‡ < 10%: ≥160 mg/dL |
| 0 or 1 major risk factor† | < 160 mg/dL | ≥ 190 mg/dL; 160-190 mg/dL optional |
| NOTE: CHD risk equivalents include symptomatic carotid artery disease, peripheral arterial disease, abdominal aortic aneurysm, diabetes, and a 10-year risk of > 20% (see ‡ below). The cutoff points for therapy for patients with clinical CHD are the same as for CHD risk equivalents. | ||
| * Initiate therapeutic lifestyle changes above these levels. | ||
| †Major risk factors include cigarette smoking, hypertension, HDL < 40 mg/dL, family history of premature CHD (CHD in first-degree male relative < 55 y; CHD in first-degree female relative < 65 y), age (men ≥ 45 y, women ≥ 55 y). | ||
| ‡To calculate 10-year risk, use the Framingham Tables, available at http://www.nhlbi.nih.gov/guidelines/cholesterol/risk_tbl.htm. | ||
Evidence summary
Statins are the most effective at reducing LDL-C and the associated cardiovascular risk. The 5-year West of Scotland study (WOSCOPS) showed that a 26% reduction in LDL-C (from a mean of 192 to 142 mg/dL) using pravastatin 40 mg per day reduced the risk of either nonfatal myocardial infarction (MI) or coronary heart disease (CHD) death (number needed to treat [NNT] = 42; relative risk [RR] = 31; 95% confidence interval [CI],17 - 43).1 This trial enrolled middle-aged men with an LDL-C level > 155 mg/dL without a history of prior MI, although subjects with stable angina (5% of the participants) were still eligible. Similar reductions were seen in cardiovascular death and in all-cause death (RR = 22; 95% CI = 0 - 40). Lovastatin reduced the risk of a first major acute coronary event (NNT = 24) in the 5-year AFCAPS/TexCAPS trial that enrolled 5608 men and 997 women with below-average high-density lipoprotein cholesterol (HDL-C) (men, 36 mg/dL; women, 40 mg/dL) without signs or symptoms of CHD.2 LDL-C was lowered 25% (from a mean of 156 to 115 mg/dL). Unpublished results suggest that simvastatin may have a similar effect. Primary prevention data are still lacking for atorvastatin and fluvastatin.
The 7-year Lipid Research Clinics Coronary Prevention Trial (LRC-CPPT) documented a reduction in CHD death and/or nonfatal MI (NNT = 59) with a 12.6% reduction in LDL-C with the use of cholestyramine, a bile acid resin, 24 g per day.3
Results of studies of the fibric acid derivatives are mixed. Subjects taking gemfibrozil 1200 mg per day in the 5-year Helsinki Heart Study had fewer coronary events compared with those taking a placebo (NNT = 71).4 Subsequent analysis suggests that patients with a high LDL-C/HDL-C ratio (> 5) plus hypertriglyceridemia ( 205 mg/dL) benefited the most.5 Clofibrate is no longer used because of an unexplained increase in deaths in the WHO Cooperative Trial.6 To date, outcomes in fenofibrate trials have only focused on surrogate markers and not long-term clinical outcomes.
Recommendations from others
The recommendations of the Third Report of the National Cholesterol Education Program7 (NCEP, Adult Treatment Panel III) are in the table. This report is an excellent source of additional information (http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3xsum.pdf).
Read a clinical commentary by David Switzer, MD, at www.fpin.org.
The levels of cholesterol that should be treated for primary prevention are based on low-density lipoprotein cholesterol (LDL-C) levels of > 100 mg/dL to > 190 mg/dL and vary according to whether the patient’s risk is high, moderate, or low. See the table to estimate risk. Grade of recommendation for medication indications: A (on the basis of high-quality randomized controlled trials). Grade of recommendation for lifestyle indications: B (on the basis of extrapolations from randomized controlled trials).
TABLE
Adult treatment recommendations from NCEP, Adult Treatment Panel III
| Risk category | LDL-C level | LDL-C goal* at which to consider medication |
|---|---|---|
| Coronary heart disease risk equivalents | < 100 mg/dL | ≥ 130 mg/dL; ≥100-129 mg/dL optional |
| 2 or more major risk factors† | < 130 mg/dL | 10-year risk‡ 10-20%: ≥ 130 mg/dL; 10-year risk‡ < 10%: ≥160 mg/dL |
| 0 or 1 major risk factor† | < 160 mg/dL | ≥ 190 mg/dL; 160-190 mg/dL optional |
| NOTE: CHD risk equivalents include symptomatic carotid artery disease, peripheral arterial disease, abdominal aortic aneurysm, diabetes, and a 10-year risk of > 20% (see ‡ below). The cutoff points for therapy for patients with clinical CHD are the same as for CHD risk equivalents. | ||
| * Initiate therapeutic lifestyle changes above these levels. | ||
| †Major risk factors include cigarette smoking, hypertension, HDL < 40 mg/dL, family history of premature CHD (CHD in first-degree male relative < 55 y; CHD in first-degree female relative < 65 y), age (men ≥ 45 y, women ≥ 55 y). | ||
| ‡To calculate 10-year risk, use the Framingham Tables, available at http://www.nhlbi.nih.gov/guidelines/cholesterol/risk_tbl.htm. | ||
Evidence summary
Statins are the most effective at reducing LDL-C and the associated cardiovascular risk. The 5-year West of Scotland study (WOSCOPS) showed that a 26% reduction in LDL-C (from a mean of 192 to 142 mg/dL) using pravastatin 40 mg per day reduced the risk of either nonfatal myocardial infarction (MI) or coronary heart disease (CHD) death (number needed to treat [NNT] = 42; relative risk [RR] = 31; 95% confidence interval [CI],17 - 43).1 This trial enrolled middle-aged men with an LDL-C level > 155 mg/dL without a history of prior MI, although subjects with stable angina (5% of the participants) were still eligible. Similar reductions were seen in cardiovascular death and in all-cause death (RR = 22; 95% CI = 0 - 40). Lovastatin reduced the risk of a first major acute coronary event (NNT = 24) in the 5-year AFCAPS/TexCAPS trial that enrolled 5608 men and 997 women with below-average high-density lipoprotein cholesterol (HDL-C) (men, 36 mg/dL; women, 40 mg/dL) without signs or symptoms of CHD.2 LDL-C was lowered 25% (from a mean of 156 to 115 mg/dL). Unpublished results suggest that simvastatin may have a similar effect. Primary prevention data are still lacking for atorvastatin and fluvastatin.
The 7-year Lipid Research Clinics Coronary Prevention Trial (LRC-CPPT) documented a reduction in CHD death and/or nonfatal MI (NNT = 59) with a 12.6% reduction in LDL-C with the use of cholestyramine, a bile acid resin, 24 g per day.3
Results of studies of the fibric acid derivatives are mixed. Subjects taking gemfibrozil 1200 mg per day in the 5-year Helsinki Heart Study had fewer coronary events compared with those taking a placebo (NNT = 71).4 Subsequent analysis suggests that patients with a high LDL-C/HDL-C ratio (> 5) plus hypertriglyceridemia ( 205 mg/dL) benefited the most.5 Clofibrate is no longer used because of an unexplained increase in deaths in the WHO Cooperative Trial.6 To date, outcomes in fenofibrate trials have only focused on surrogate markers and not long-term clinical outcomes.
Recommendations from others
The recommendations of the Third Report of the National Cholesterol Education Program7 (NCEP, Adult Treatment Panel III) are in the table. This report is an excellent source of additional information (http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3xsum.pdf).
Read a clinical commentary by David Switzer, MD, at www.fpin.org.
1. Shepard J, Cobbe SM, Ford I, et al. West of Scotland Coronary Prevention Study Group. N Engl J Med 1995;333:1301-7.
2. Downs JR, Clearfield M, Weis S, et al. JAMA 1998;279:1615-22.
3. The Lipid Research Clinics Coronary Primary Prevention Trial results. JAMA 1984;251:351-64,365-74.
4. Frick MH, Elo O, Happa K, et al. N Engl J Med 1987;317:1237-45.
5. Manninen V, Tenkanen L, Koskinen P, et al. Circulation 1992;85:37-45.
6. WHO cooperative trial. Lancet 1984;2:600-4.
7. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-97.
1. Shepard J, Cobbe SM, Ford I, et al. West of Scotland Coronary Prevention Study Group. N Engl J Med 1995;333:1301-7.
2. Downs JR, Clearfield M, Weis S, et al. JAMA 1998;279:1615-22.
3. The Lipid Research Clinics Coronary Primary Prevention Trial results. JAMA 1984;251:351-64,365-74.
4. Frick MH, Elo O, Happa K, et al. N Engl J Med 1987;317:1237-45.
5. Manninen V, Tenkanen L, Koskinen P, et al. Circulation 1992;85:37-45.
6. WHO cooperative trial. Lancet 1984;2:600-4.
7. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-97.
Evidence-based answers from the Family Physicians Inquiries Network
What is the prognosis for acute low back pain?
The proportion of patients who are pain free or completely recovered after an acute episode of low back pain within 2 weeks to 6 months ranges from 21% to 90%, depending on the population studied and the method of measuring outcomes. The reported recurrence rates are also variable, from a low of 35% to a high of 75%, again depending on the length of follow-up and the study design. Grade of recommendation: C (on the basis of case-series, poor quality cohort studies, and case-control studies).
Evidence summary
It has been widely stated that 80% to 90% of attacks of acute low back pain resolve within approximately 6 weeks,1 though there is little evidence to support this claim. Although there are many studies and guidelines regarding treatment methods for low back pain, few studies evaluate the natural history of low back pain. One prospective series in a primary care setting found that 90% of patients were without pain 2 weeks after initial evaluation by their physician.2 This study had a 3-month follow-up period for 103 patients presenting with pain of less than 72 hours’ duration.
Another prospective study found that 94% of patients evaluated for a new episode of low back pain were no longer visiting their physician for treatment after 3 months. However, this was not an adequate measure of resolution of pain. Only 21% (39/188) were pain free at 3 months and only 25% (42/170) were pain free at 12 months.3 A larger study involved 1555 patients during a 6-month follow up after an episode of acute low back pain. The article reports a mean of 16 days to functional recovery, although only 69% of the patients considered themselves “completely recovered” at 6 months.4
Recurrences of low back pain are common. In one prospective cohort study of 443 patients with low back pain, 75% had a recurrence with a mean of 2 relapses in 1 year of follow-up, but only 228 patients completed the study.5 Another prospective study of 208 patients found that 35% to 44% of patients had recurrence of pain within 6 months of their first episode, and 50% to 59% had a recurrence in 22 months of follow-up.6 No studies identified findings or risk factors associated with higher recurrence rates.
Recommendations from others
The Agency for Healthcare Research and Quality (www.ahcpr.gov) section on health outcomes (see http://www.ahcpr.gov/research/jan99/ra6.htm) states, “recent studies suggest that once experienced, low back pain becomes a part of life for almost half of those affected, and for many, it is intermittently disabling. Repeated visits and procedures do not appear to improve patients’ long-term well-being, but they clearly account for substantial health care costs. Finally, back pain prognosis does not differ based on the type of provider initially seen or the level of practitioner confidence.” This site offers several nice summaries of studies on low back pain.
Read the clinical commentary by Anne Fitzsimmons, MD, at www.fpin.org.
1. Dixon AJ. Rheumatol Rehabil 1973;12:165-75.
2. Coste J, Delecoeuillerie G, Cohen de Lara A, Le Parc JM, Paolaggi JB. BMJ 1994;308:577-80.
3. Croft PR, Macfarlane GJ, Papageorgiou AC, Thomas E, Silman AJ. BMJ 1998;316:1356-9.
4. Carey TS, Garrett JM, Jackman A, et al. N Engl J Med 1995;333:913.-
5. van den Hoogen HJ, Koes BW, van Eijk JT, Bouter LM, Deville W. Ann Rheum Dis 1998;57:13-9.
6. Carey TS, Garrett JM, Jackman A, Hadler N. Med Care 1999;37:157-64.
The proportion of patients who are pain free or completely recovered after an acute episode of low back pain within 2 weeks to 6 months ranges from 21% to 90%, depending on the population studied and the method of measuring outcomes. The reported recurrence rates are also variable, from a low of 35% to a high of 75%, again depending on the length of follow-up and the study design. Grade of recommendation: C (on the basis of case-series, poor quality cohort studies, and case-control studies).
Evidence summary
It has been widely stated that 80% to 90% of attacks of acute low back pain resolve within approximately 6 weeks,1 though there is little evidence to support this claim. Although there are many studies and guidelines regarding treatment methods for low back pain, few studies evaluate the natural history of low back pain. One prospective series in a primary care setting found that 90% of patients were without pain 2 weeks after initial evaluation by their physician.2 This study had a 3-month follow-up period for 103 patients presenting with pain of less than 72 hours’ duration.
Another prospective study found that 94% of patients evaluated for a new episode of low back pain were no longer visiting their physician for treatment after 3 months. However, this was not an adequate measure of resolution of pain. Only 21% (39/188) were pain free at 3 months and only 25% (42/170) were pain free at 12 months.3 A larger study involved 1555 patients during a 6-month follow up after an episode of acute low back pain. The article reports a mean of 16 days to functional recovery, although only 69% of the patients considered themselves “completely recovered” at 6 months.4
Recurrences of low back pain are common. In one prospective cohort study of 443 patients with low back pain, 75% had a recurrence with a mean of 2 relapses in 1 year of follow-up, but only 228 patients completed the study.5 Another prospective study of 208 patients found that 35% to 44% of patients had recurrence of pain within 6 months of their first episode, and 50% to 59% had a recurrence in 22 months of follow-up.6 No studies identified findings or risk factors associated with higher recurrence rates.
Recommendations from others
The Agency for Healthcare Research and Quality (www.ahcpr.gov) section on health outcomes (see http://www.ahcpr.gov/research/jan99/ra6.htm) states, “recent studies suggest that once experienced, low back pain becomes a part of life for almost half of those affected, and for many, it is intermittently disabling. Repeated visits and procedures do not appear to improve patients’ long-term well-being, but they clearly account for substantial health care costs. Finally, back pain prognosis does not differ based on the type of provider initially seen or the level of practitioner confidence.” This site offers several nice summaries of studies on low back pain.
Read the clinical commentary by Anne Fitzsimmons, MD, at www.fpin.org.
The proportion of patients who are pain free or completely recovered after an acute episode of low back pain within 2 weeks to 6 months ranges from 21% to 90%, depending on the population studied and the method of measuring outcomes. The reported recurrence rates are also variable, from a low of 35% to a high of 75%, again depending on the length of follow-up and the study design. Grade of recommendation: C (on the basis of case-series, poor quality cohort studies, and case-control studies).
Evidence summary
It has been widely stated that 80% to 90% of attacks of acute low back pain resolve within approximately 6 weeks,1 though there is little evidence to support this claim. Although there are many studies and guidelines regarding treatment methods for low back pain, few studies evaluate the natural history of low back pain. One prospective series in a primary care setting found that 90% of patients were without pain 2 weeks after initial evaluation by their physician.2 This study had a 3-month follow-up period for 103 patients presenting with pain of less than 72 hours’ duration.
Another prospective study found that 94% of patients evaluated for a new episode of low back pain were no longer visiting their physician for treatment after 3 months. However, this was not an adequate measure of resolution of pain. Only 21% (39/188) were pain free at 3 months and only 25% (42/170) were pain free at 12 months.3 A larger study involved 1555 patients during a 6-month follow up after an episode of acute low back pain. The article reports a mean of 16 days to functional recovery, although only 69% of the patients considered themselves “completely recovered” at 6 months.4
Recurrences of low back pain are common. In one prospective cohort study of 443 patients with low back pain, 75% had a recurrence with a mean of 2 relapses in 1 year of follow-up, but only 228 patients completed the study.5 Another prospective study of 208 patients found that 35% to 44% of patients had recurrence of pain within 6 months of their first episode, and 50% to 59% had a recurrence in 22 months of follow-up.6 No studies identified findings or risk factors associated with higher recurrence rates.
Recommendations from others
The Agency for Healthcare Research and Quality (www.ahcpr.gov) section on health outcomes (see http://www.ahcpr.gov/research/jan99/ra6.htm) states, “recent studies suggest that once experienced, low back pain becomes a part of life for almost half of those affected, and for many, it is intermittently disabling. Repeated visits and procedures do not appear to improve patients’ long-term well-being, but they clearly account for substantial health care costs. Finally, back pain prognosis does not differ based on the type of provider initially seen or the level of practitioner confidence.” This site offers several nice summaries of studies on low back pain.
Read the clinical commentary by Anne Fitzsimmons, MD, at www.fpin.org.
1. Dixon AJ. Rheumatol Rehabil 1973;12:165-75.
2. Coste J, Delecoeuillerie G, Cohen de Lara A, Le Parc JM, Paolaggi JB. BMJ 1994;308:577-80.
3. Croft PR, Macfarlane GJ, Papageorgiou AC, Thomas E, Silman AJ. BMJ 1998;316:1356-9.
4. Carey TS, Garrett JM, Jackman A, et al. N Engl J Med 1995;333:913.-
5. van den Hoogen HJ, Koes BW, van Eijk JT, Bouter LM, Deville W. Ann Rheum Dis 1998;57:13-9.
6. Carey TS, Garrett JM, Jackman A, Hadler N. Med Care 1999;37:157-64.
1. Dixon AJ. Rheumatol Rehabil 1973;12:165-75.
2. Coste J, Delecoeuillerie G, Cohen de Lara A, Le Parc JM, Paolaggi JB. BMJ 1994;308:577-80.
3. Croft PR, Macfarlane GJ, Papageorgiou AC, Thomas E, Silman AJ. BMJ 1998;316:1356-9.
4. Carey TS, Garrett JM, Jackman A, et al. N Engl J Med 1995;333:913.-
5. van den Hoogen HJ, Koes BW, van Eijk JT, Bouter LM, Deville W. Ann Rheum Dis 1998;57:13-9.
6. Carey TS, Garrett JM, Jackman A, Hadler N. Med Care 1999;37:157-64.
Evidence-based answers from the Family Physicians Inquiries Network
What are the indications for tonsillectomy in children?
Tonsillectomy with or without adenoidectomy is minimally effective when combined with tympanostomy tube placement in preventing recurrent otitis media in the 3 years following surgery. The risks of surgery must be weighed against potential benefit. (Grade of recommendation: B, based on low-quality randomized controlled trials [RCTs]). The evidence supporting tonsillectomy for recurrence of sore throat is controversial.1 There is insufficient evidence to recommend other potential indications (Table). (Grade of recommendation: C, based on case series.)
TABLE
INDICATIONS FOR TONSILLECTOMY
| Potential Indication | Evidence of Effectiveness? | Grade of Recommendation | |
|---|---|---|---|
| Preventing recurrent otitis media in the 3 years following surgery | Yes, small effect size | B (RCTs, case series) | |
| Preventing recurrent sore throat caused by tonsillitis | No | B (systematic review of flawed RCTs) | |
| Preventing recurrent peritonsillar abscess | No | C (case series, consensus statements) | |
| Treating sleep apnea in children | No | C (case series2) | |
| Treating IgA nephropathy | No | C (case series) | |
| Treating guttate psoriasis | No | C (case series3) | |
| Treating nocturnal enuresis | No | C (case series) | |
| IgA denotes immunoglobulin A; RCTs, randomized controlled trials. | |||
Evidence summary
Cochrane: “There is no evidence from randomized controlled trials to guide the clinician in formulating the indications for surgery in adults or children.”1 The few existing trials are complicated by differences in treatment and control groups at baseline and by differential complication rates in groups receiving tonsillectomy or adenotonsillectomy. For example, 2 RCTs showed minimal effect at 1 year and no effect at 3 years of follow-up in preventing recurrent sore throat.2,3 However, 1 of these could not be critically appraised because it was published in abstract format only.
Two other trials of tonsillectomy and adenotonsillectomy in children, both with and without tympanostomy tube placement, have shown a small, brief reduction in episodes of recurrent otitis.4-6 In the largest study,6 controls had a mean of 2.1 episodes of recurrent otitis media in the first postoperative year while those undergoing adenotonsillectomy had had 1.8 episodes (P= .25) and those undergoing adenoidectomy had 1.4 episodes (P< .001). However, these benefits did not persist beyond the first year. Several case series report no evidence of effectiveness of tonsillectomy for immunoglobulin A (IgA) nephropathy, psoriasis, or nocturnal enuresis.
Recommendations from others
The Infectious Diseases Society of America states: “Surgical removal of the tonsils may be considered for the rare patient whose symptomatic episodes [of strep pharyngitis] do not diminish in frequency over time and for whom no alternative explanation for the recurrent pharyngitis is evident. Tonsillectomy may decrease recurrences of symptomatic pharyngitis in selected patients, but only for a limited period of time.”4
The American Academy of Pediatrics position is as follows: “Tonsillectomy, either alone or with adenoidectomy, has not been found effective for treatment of otitis media with effusion.”5 The Scottish Intercollegiate Guidelines Network (SIGN): “The following are recommended as reasonable indications for consideration of tonsillectomy in both children and adults, based on the current level of knowledge, clinical observation in the field and the results of clinical audit.” According to SIGN, patients should meet all these criteria: sore throats are caused by tonsillitis; 5 or more episodes of sore throat per year; symptoms have lasted for at least 1 year; and the episodes of sore throat “are disabling and prevent normal functioning.”7
Clinical Commentary by Jeff Belden, MD, at http://www.fpin.org.
1. Burton MJ, Towler B, Glasziou P. Cochrane Database of Systematic Reviews, Issue 2, 2001. Oxford, England: Update Software.
2. Paradise JL, Bluestone CD, Bachman RZ, et al. N Engl J Med 1984;310:674-83.
3. Paradise JL, Bluestone CD, Rogers KD, et al. Pediatr Res 1992;31:126A.-
4. Bisno AL, Gerber MA, Gwaltney JM, Jr, et al [abstract]. Clin Infect Dis 1997;25:574-83.
5. American Academy of Pediatrics. Pediatrics 1994;94:766-73.
6. Paradise JL, Bluestone CD, Colborn DK, et al. JAMA 1999;282:945-53.
7. Scottish Intercollegiate Guidelines Network, Scottish Cancer Therapy Network. SIGN publication no. 34; January 1999.
Tonsillectomy with or without adenoidectomy is minimally effective when combined with tympanostomy tube placement in preventing recurrent otitis media in the 3 years following surgery. The risks of surgery must be weighed against potential benefit. (Grade of recommendation: B, based on low-quality randomized controlled trials [RCTs]). The evidence supporting tonsillectomy for recurrence of sore throat is controversial.1 There is insufficient evidence to recommend other potential indications (Table). (Grade of recommendation: C, based on case series.)
TABLE
INDICATIONS FOR TONSILLECTOMY
| Potential Indication | Evidence of Effectiveness? | Grade of Recommendation | |
|---|---|---|---|
| Preventing recurrent otitis media in the 3 years following surgery | Yes, small effect size | B (RCTs, case series) | |
| Preventing recurrent sore throat caused by tonsillitis | No | B (systematic review of flawed RCTs) | |
| Preventing recurrent peritonsillar abscess | No | C (case series, consensus statements) | |
| Treating sleep apnea in children | No | C (case series2) | |
| Treating IgA nephropathy | No | C (case series) | |
| Treating guttate psoriasis | No | C (case series3) | |
| Treating nocturnal enuresis | No | C (case series) | |
| IgA denotes immunoglobulin A; RCTs, randomized controlled trials. | |||
Evidence summary
Cochrane: “There is no evidence from randomized controlled trials to guide the clinician in formulating the indications for surgery in adults or children.”1 The few existing trials are complicated by differences in treatment and control groups at baseline and by differential complication rates in groups receiving tonsillectomy or adenotonsillectomy. For example, 2 RCTs showed minimal effect at 1 year and no effect at 3 years of follow-up in preventing recurrent sore throat.2,3 However, 1 of these could not be critically appraised because it was published in abstract format only.
Two other trials of tonsillectomy and adenotonsillectomy in children, both with and without tympanostomy tube placement, have shown a small, brief reduction in episodes of recurrent otitis.4-6 In the largest study,6 controls had a mean of 2.1 episodes of recurrent otitis media in the first postoperative year while those undergoing adenotonsillectomy had had 1.8 episodes (P= .25) and those undergoing adenoidectomy had 1.4 episodes (P< .001). However, these benefits did not persist beyond the first year. Several case series report no evidence of effectiveness of tonsillectomy for immunoglobulin A (IgA) nephropathy, psoriasis, or nocturnal enuresis.
Recommendations from others
The Infectious Diseases Society of America states: “Surgical removal of the tonsils may be considered for the rare patient whose symptomatic episodes [of strep pharyngitis] do not diminish in frequency over time and for whom no alternative explanation for the recurrent pharyngitis is evident. Tonsillectomy may decrease recurrences of symptomatic pharyngitis in selected patients, but only for a limited period of time.”4
The American Academy of Pediatrics position is as follows: “Tonsillectomy, either alone or with adenoidectomy, has not been found effective for treatment of otitis media with effusion.”5 The Scottish Intercollegiate Guidelines Network (SIGN): “The following are recommended as reasonable indications for consideration of tonsillectomy in both children and adults, based on the current level of knowledge, clinical observation in the field and the results of clinical audit.” According to SIGN, patients should meet all these criteria: sore throats are caused by tonsillitis; 5 or more episodes of sore throat per year; symptoms have lasted for at least 1 year; and the episodes of sore throat “are disabling and prevent normal functioning.”7
Clinical Commentary by Jeff Belden, MD, at http://www.fpin.org.
Tonsillectomy with or without adenoidectomy is minimally effective when combined with tympanostomy tube placement in preventing recurrent otitis media in the 3 years following surgery. The risks of surgery must be weighed against potential benefit. (Grade of recommendation: B, based on low-quality randomized controlled trials [RCTs]). The evidence supporting tonsillectomy for recurrence of sore throat is controversial.1 There is insufficient evidence to recommend other potential indications (Table). (Grade of recommendation: C, based on case series.)
TABLE
INDICATIONS FOR TONSILLECTOMY
| Potential Indication | Evidence of Effectiveness? | Grade of Recommendation | |
|---|---|---|---|
| Preventing recurrent otitis media in the 3 years following surgery | Yes, small effect size | B (RCTs, case series) | |
| Preventing recurrent sore throat caused by tonsillitis | No | B (systematic review of flawed RCTs) | |
| Preventing recurrent peritonsillar abscess | No | C (case series, consensus statements) | |
| Treating sleep apnea in children | No | C (case series2) | |
| Treating IgA nephropathy | No | C (case series) | |
| Treating guttate psoriasis | No | C (case series3) | |
| Treating nocturnal enuresis | No | C (case series) | |
| IgA denotes immunoglobulin A; RCTs, randomized controlled trials. | |||
Evidence summary
Cochrane: “There is no evidence from randomized controlled trials to guide the clinician in formulating the indications for surgery in adults or children.”1 The few existing trials are complicated by differences in treatment and control groups at baseline and by differential complication rates in groups receiving tonsillectomy or adenotonsillectomy. For example, 2 RCTs showed minimal effect at 1 year and no effect at 3 years of follow-up in preventing recurrent sore throat.2,3 However, 1 of these could not be critically appraised because it was published in abstract format only.
Two other trials of tonsillectomy and adenotonsillectomy in children, both with and without tympanostomy tube placement, have shown a small, brief reduction in episodes of recurrent otitis.4-6 In the largest study,6 controls had a mean of 2.1 episodes of recurrent otitis media in the first postoperative year while those undergoing adenotonsillectomy had had 1.8 episodes (P= .25) and those undergoing adenoidectomy had 1.4 episodes (P< .001). However, these benefits did not persist beyond the first year. Several case series report no evidence of effectiveness of tonsillectomy for immunoglobulin A (IgA) nephropathy, psoriasis, or nocturnal enuresis.
Recommendations from others
The Infectious Diseases Society of America states: “Surgical removal of the tonsils may be considered for the rare patient whose symptomatic episodes [of strep pharyngitis] do not diminish in frequency over time and for whom no alternative explanation for the recurrent pharyngitis is evident. Tonsillectomy may decrease recurrences of symptomatic pharyngitis in selected patients, but only for a limited period of time.”4
The American Academy of Pediatrics position is as follows: “Tonsillectomy, either alone or with adenoidectomy, has not been found effective for treatment of otitis media with effusion.”5 The Scottish Intercollegiate Guidelines Network (SIGN): “The following are recommended as reasonable indications for consideration of tonsillectomy in both children and adults, based on the current level of knowledge, clinical observation in the field and the results of clinical audit.” According to SIGN, patients should meet all these criteria: sore throats are caused by tonsillitis; 5 or more episodes of sore throat per year; symptoms have lasted for at least 1 year; and the episodes of sore throat “are disabling and prevent normal functioning.”7
Clinical Commentary by Jeff Belden, MD, at http://www.fpin.org.
1. Burton MJ, Towler B, Glasziou P. Cochrane Database of Systematic Reviews, Issue 2, 2001. Oxford, England: Update Software.
2. Paradise JL, Bluestone CD, Bachman RZ, et al. N Engl J Med 1984;310:674-83.
3. Paradise JL, Bluestone CD, Rogers KD, et al. Pediatr Res 1992;31:126A.-
4. Bisno AL, Gerber MA, Gwaltney JM, Jr, et al [abstract]. Clin Infect Dis 1997;25:574-83.
5. American Academy of Pediatrics. Pediatrics 1994;94:766-73.
6. Paradise JL, Bluestone CD, Colborn DK, et al. JAMA 1999;282:945-53.
7. Scottish Intercollegiate Guidelines Network, Scottish Cancer Therapy Network. SIGN publication no. 34; January 1999.
1. Burton MJ, Towler B, Glasziou P. Cochrane Database of Systematic Reviews, Issue 2, 2001. Oxford, England: Update Software.
2. Paradise JL, Bluestone CD, Bachman RZ, et al. N Engl J Med 1984;310:674-83.
3. Paradise JL, Bluestone CD, Rogers KD, et al. Pediatr Res 1992;31:126A.-
4. Bisno AL, Gerber MA, Gwaltney JM, Jr, et al [abstract]. Clin Infect Dis 1997;25:574-83.
5. American Academy of Pediatrics. Pediatrics 1994;94:766-73.
6. Paradise JL, Bluestone CD, Colborn DK, et al. JAMA 1999;282:945-53.
7. Scottish Intercollegiate Guidelines Network, Scottish Cancer Therapy Network. SIGN publication no. 34; January 1999.
Evidence-based answers from the Family Physicians Inquiries Network
What is the most effective treatment for external genital warts?
Podofilox (Condylox), imiquimod (Aldara), cryotherapy, and surgical options all seem reasonable alternatives that are superior to podophyllin. (Grade of recommendation: B, based on systematic review.) No studies of surgical options versus home use preparations have been reported. Trichloroacetic acid and 5-fluorouracil (5-FU) have not been sufficiently studied.
Evidence summary
Nonsurgical treatments that are beneficial in eradicating genital warts are podofilox (Condylox) (8 randomized controlled trials [RCTs] with 1035 participants), imiquimod (Aldara) (2 RCTs with 968 participants), and intralesional interferon (8 RCTs). Cryotherapy is equivalent to trichloroacetic acid1,2 and electrosurgery.3 Although surgical treatments have not been compared with placebo or no treatment, both electrosurgery and surgical excision are superior to podophyllin in clinical trials.4,5 Laser surgery is as effective as surgical excision.6 Studies of topical interferon show conflicting results.7 Systemic interferon is not beneficial.7 Topical 5-FU has not been studied with RCTs. Wart clearance rates are summarized in the Table. Treatment duration for nonsurgical options is 4 to 8 weeks. Treatment of genital warts has not been shown to reduce transmission to sex partners.7
Two RCTs4,5 showed more frequent recurrence with podophyllin (60% to 65%) than with surgical excision (19% to 20%). Another trial1 showed recurrence in 22% of participants receiving electrosurgery, in 21% of those receiving cryotherapy, and in 44% of those receiving podophyllin treatment. Data are lacking on recurrence rates with imiquimod, podofilox, and intralesional interferon.
Pain occurs in less than 20% of people with imiquimod, cryotherapy, podophyllin, and electrosurgery; 39% with topical interferon; 44% with electrosurgery; 75% with podofilox; and 100% with surgical excision or laser surgery.7 However, pain has been measured using methods that are unlikely to be comparable across studies. Flulike symptoms, leukopenia, thrombocytopenia, and elevated aspartate transaminase levels are associated with intralesional interferon.7 Topical medications have not been studied in pregnant patients. Cryotherapy is safe in pregnancy based on case series, if only 3 or 4 treatments are given.7
Direct comparisons between home therapies (imiquimod, podofilox) and other treatments are needed. Products for home use are relatively expensive: a 1-month supply of imiquimod costs approximately $150; a 1-month supply of podofilox, $110 to $130. These are average wholesale prices, rounded to the nearest $10, as of Feb. 15, 2002.
TABLE
CLEARANCE RATES REPORTED IN CLINICAL TRIALS
| Therapy | Clearance Rate (%) |
|---|---|
| Cryotherapy | 63–88 |
| Electrosurgery | 61–94 |
| Imiquimod | 37–56 |
| Interferon (topical) | 6–90 |
| Interferon (intralesional) | 17–63 |
| Laser surgery | 23–52 |
| Podofilox | 45–77 |
| Podophyllin | 32–79 |
| Surgical excision | 35–72 |
| Trichloroacetic acid | 50–81 |
| Placebo or no treatment | 0–56 |
Recommendations from others
The CDC endorses podophyllin, bi- and trichloroacetic acid, podofilox, imiquimod, cryotherapy, intralesional interferon, electrosurgery, laser surgery, and surgical excision.8 A United Kingdom guideline on anogenital warts recommends physical ablative methods such as cryotherapy and surgical options for keratinized lesions and topical medications for soft lesions. The guideline also recommends ablative therapy for persons with a small number of warts regardless of type. Interferon and 5-FU are not recommended.9
Clinical Commentary by David White, MD, at http://www.fpin.org.
1. Abdullah AN, Walzman M, Wade A. Sex Transm Dis 1993;20:344-5.
2. Godley MJ, Bradbeer CS, Gellan M, Thin RN. Genitourin Med 1987;63:390-2.
3. Stone KM, Becker TM, Hadgu A, Kraus SJ. Genitourin Med 1990;66:16-9.
4. Khawaja HT. J Reprod Med 1990;35:1019-22.
5. Jensen SL. Lancet 1985;2:1146-8.
6. Duus BR, Philipsen T, Christensen JD, et al. Genitourin Med 1985;61:59-61.
7. Wiley DJ. Genital warts. Clin Evidence Issue 4, December 2000;910-8.
8. Centers for Disease Control and Prevention. Morbid Mortal Weekly Rep MMWR 1998;47(RR-1):91-4.
9. Clinical Effectiveness Group (Association of Genitourinary Medicine and the Medical Society for the Study of Venereal Diseases). Sex Transm Infect 1999;75(suppl 1):71-5S.
Podofilox (Condylox), imiquimod (Aldara), cryotherapy, and surgical options all seem reasonable alternatives that are superior to podophyllin. (Grade of recommendation: B, based on systematic review.) No studies of surgical options versus home use preparations have been reported. Trichloroacetic acid and 5-fluorouracil (5-FU) have not been sufficiently studied.
Evidence summary
Nonsurgical treatments that are beneficial in eradicating genital warts are podofilox (Condylox) (8 randomized controlled trials [RCTs] with 1035 participants), imiquimod (Aldara) (2 RCTs with 968 participants), and intralesional interferon (8 RCTs). Cryotherapy is equivalent to trichloroacetic acid1,2 and electrosurgery.3 Although surgical treatments have not been compared with placebo or no treatment, both electrosurgery and surgical excision are superior to podophyllin in clinical trials.4,5 Laser surgery is as effective as surgical excision.6 Studies of topical interferon show conflicting results.7 Systemic interferon is not beneficial.7 Topical 5-FU has not been studied with RCTs. Wart clearance rates are summarized in the Table. Treatment duration for nonsurgical options is 4 to 8 weeks. Treatment of genital warts has not been shown to reduce transmission to sex partners.7
Two RCTs4,5 showed more frequent recurrence with podophyllin (60% to 65%) than with surgical excision (19% to 20%). Another trial1 showed recurrence in 22% of participants receiving electrosurgery, in 21% of those receiving cryotherapy, and in 44% of those receiving podophyllin treatment. Data are lacking on recurrence rates with imiquimod, podofilox, and intralesional interferon.
Pain occurs in less than 20% of people with imiquimod, cryotherapy, podophyllin, and electrosurgery; 39% with topical interferon; 44% with electrosurgery; 75% with podofilox; and 100% with surgical excision or laser surgery.7 However, pain has been measured using methods that are unlikely to be comparable across studies. Flulike symptoms, leukopenia, thrombocytopenia, and elevated aspartate transaminase levels are associated with intralesional interferon.7 Topical medications have not been studied in pregnant patients. Cryotherapy is safe in pregnancy based on case series, if only 3 or 4 treatments are given.7
Direct comparisons between home therapies (imiquimod, podofilox) and other treatments are needed. Products for home use are relatively expensive: a 1-month supply of imiquimod costs approximately $150; a 1-month supply of podofilox, $110 to $130. These are average wholesale prices, rounded to the nearest $10, as of Feb. 15, 2002.
TABLE
CLEARANCE RATES REPORTED IN CLINICAL TRIALS
| Therapy | Clearance Rate (%) |
|---|---|
| Cryotherapy | 63–88 |
| Electrosurgery | 61–94 |
| Imiquimod | 37–56 |
| Interferon (topical) | 6–90 |
| Interferon (intralesional) | 17–63 |
| Laser surgery | 23–52 |
| Podofilox | 45–77 |
| Podophyllin | 32–79 |
| Surgical excision | 35–72 |
| Trichloroacetic acid | 50–81 |
| Placebo or no treatment | 0–56 |
Recommendations from others
The CDC endorses podophyllin, bi- and trichloroacetic acid, podofilox, imiquimod, cryotherapy, intralesional interferon, electrosurgery, laser surgery, and surgical excision.8 A United Kingdom guideline on anogenital warts recommends physical ablative methods such as cryotherapy and surgical options for keratinized lesions and topical medications for soft lesions. The guideline also recommends ablative therapy for persons with a small number of warts regardless of type. Interferon and 5-FU are not recommended.9
Clinical Commentary by David White, MD, at http://www.fpin.org.
Podofilox (Condylox), imiquimod (Aldara), cryotherapy, and surgical options all seem reasonable alternatives that are superior to podophyllin. (Grade of recommendation: B, based on systematic review.) No studies of surgical options versus home use preparations have been reported. Trichloroacetic acid and 5-fluorouracil (5-FU) have not been sufficiently studied.
Evidence summary
Nonsurgical treatments that are beneficial in eradicating genital warts are podofilox (Condylox) (8 randomized controlled trials [RCTs] with 1035 participants), imiquimod (Aldara) (2 RCTs with 968 participants), and intralesional interferon (8 RCTs). Cryotherapy is equivalent to trichloroacetic acid1,2 and electrosurgery.3 Although surgical treatments have not been compared with placebo or no treatment, both electrosurgery and surgical excision are superior to podophyllin in clinical trials.4,5 Laser surgery is as effective as surgical excision.6 Studies of topical interferon show conflicting results.7 Systemic interferon is not beneficial.7 Topical 5-FU has not been studied with RCTs. Wart clearance rates are summarized in the Table. Treatment duration for nonsurgical options is 4 to 8 weeks. Treatment of genital warts has not been shown to reduce transmission to sex partners.7
Two RCTs4,5 showed more frequent recurrence with podophyllin (60% to 65%) than with surgical excision (19% to 20%). Another trial1 showed recurrence in 22% of participants receiving electrosurgery, in 21% of those receiving cryotherapy, and in 44% of those receiving podophyllin treatment. Data are lacking on recurrence rates with imiquimod, podofilox, and intralesional interferon.
Pain occurs in less than 20% of people with imiquimod, cryotherapy, podophyllin, and electrosurgery; 39% with topical interferon; 44% with electrosurgery; 75% with podofilox; and 100% with surgical excision or laser surgery.7 However, pain has been measured using methods that are unlikely to be comparable across studies. Flulike symptoms, leukopenia, thrombocytopenia, and elevated aspartate transaminase levels are associated with intralesional interferon.7 Topical medications have not been studied in pregnant patients. Cryotherapy is safe in pregnancy based on case series, if only 3 or 4 treatments are given.7
Direct comparisons between home therapies (imiquimod, podofilox) and other treatments are needed. Products for home use are relatively expensive: a 1-month supply of imiquimod costs approximately $150; a 1-month supply of podofilox, $110 to $130. These are average wholesale prices, rounded to the nearest $10, as of Feb. 15, 2002.
TABLE
CLEARANCE RATES REPORTED IN CLINICAL TRIALS
| Therapy | Clearance Rate (%) |
|---|---|
| Cryotherapy | 63–88 |
| Electrosurgery | 61–94 |
| Imiquimod | 37–56 |
| Interferon (topical) | 6–90 |
| Interferon (intralesional) | 17–63 |
| Laser surgery | 23–52 |
| Podofilox | 45–77 |
| Podophyllin | 32–79 |
| Surgical excision | 35–72 |
| Trichloroacetic acid | 50–81 |
| Placebo or no treatment | 0–56 |
Recommendations from others
The CDC endorses podophyllin, bi- and trichloroacetic acid, podofilox, imiquimod, cryotherapy, intralesional interferon, electrosurgery, laser surgery, and surgical excision.8 A United Kingdom guideline on anogenital warts recommends physical ablative methods such as cryotherapy and surgical options for keratinized lesions and topical medications for soft lesions. The guideline also recommends ablative therapy for persons with a small number of warts regardless of type. Interferon and 5-FU are not recommended.9
Clinical Commentary by David White, MD, at http://www.fpin.org.
1. Abdullah AN, Walzman M, Wade A. Sex Transm Dis 1993;20:344-5.
2. Godley MJ, Bradbeer CS, Gellan M, Thin RN. Genitourin Med 1987;63:390-2.
3. Stone KM, Becker TM, Hadgu A, Kraus SJ. Genitourin Med 1990;66:16-9.
4. Khawaja HT. J Reprod Med 1990;35:1019-22.
5. Jensen SL. Lancet 1985;2:1146-8.
6. Duus BR, Philipsen T, Christensen JD, et al. Genitourin Med 1985;61:59-61.
7. Wiley DJ. Genital warts. Clin Evidence Issue 4, December 2000;910-8.
8. Centers for Disease Control and Prevention. Morbid Mortal Weekly Rep MMWR 1998;47(RR-1):91-4.
9. Clinical Effectiveness Group (Association of Genitourinary Medicine and the Medical Society for the Study of Venereal Diseases). Sex Transm Infect 1999;75(suppl 1):71-5S.
1. Abdullah AN, Walzman M, Wade A. Sex Transm Dis 1993;20:344-5.
2. Godley MJ, Bradbeer CS, Gellan M, Thin RN. Genitourin Med 1987;63:390-2.
3. Stone KM, Becker TM, Hadgu A, Kraus SJ. Genitourin Med 1990;66:16-9.
4. Khawaja HT. J Reprod Med 1990;35:1019-22.
5. Jensen SL. Lancet 1985;2:1146-8.
6. Duus BR, Philipsen T, Christensen JD, et al. Genitourin Med 1985;61:59-61.
7. Wiley DJ. Genital warts. Clin Evidence Issue 4, December 2000;910-8.
8. Centers for Disease Control and Prevention. Morbid Mortal Weekly Rep MMWR 1998;47(RR-1):91-4.
9. Clinical Effectiveness Group (Association of Genitourinary Medicine and the Medical Society for the Study of Venereal Diseases). Sex Transm Infect 1999;75(suppl 1):71-5S.
Evidence-based answers from the Family Physicians Inquiries Network
When should acute nonvenereal conjunctivitis be treated with topical antibiotics?
Children with suspected or culture-proven acute nonvenereal bacterial conjunctivitis should be treated with topical antibiotics, which hastens clinical and microbiological remission and may prevent potentially serious morbidity. In light of recent evidence regarding the self-limiting nature of conjunctivitis in adults and the development of antibiotic resistance, a “wait-and-see” approach with careful follow-up may be reasonable for adults, but this approach has not been evaluated. (Grade of recommendation: C, based on extrapolation from systematic reviews of specialty clinic trials and cohort studies.)
Evidence summary
Conjunctivitis accounts for 1% to 2% of office visits to primary care practitioners.1 Conjunctivitis is more commonly caused by bacteria in children (50% in 1 study2) than in adults, in whom viral conjunctivitis predominates.3 Treating suspected or culture-proven acute bacterial conjunctivitis with topical antibiotics significantly shortens the clinical course of the disease and results in higher microbiological cure rates than placebo.1,4,5 A meta-analysis of 3 trials based in specialty clinics or hospitals reported significant clinical cure or improvement of bacterial conjunctivitis with 2 to 5 days of topical antibiotics compared with placebo (RR = 1.31, 95% CI, 1.11-1.55, number needed to treat = 5).1 Other articles have reported corneal or systemic complications of bacterial conjunctivitis. For example, 1 review reports that 25% of children with Haemophilus influenzae conjunctivitis develop otitis media.2
Although there is a small risk of complications and longer time course when bacterial conjunctivitis is left untreated, the disease is often self-limited, with a 64% clinical remission rate in patients treated for 2 to 5 days with placebo.1 The rate of spontaneous remission is much higher for adults than for children (71.6% vs 28%, respectively). The Cochrane meta-analysis reported a similar clinical cure rate in children for 6 to 10 days of treatment with topical antibiotics versus placebo. A systematic review of 5 placebo-controlled RCTs reported no serious adverse outcomes in conjunctivitis patients regardless of treatment group.4
Antibiotic resistance is a growing problem. Studies of fluoroquinolone resistance rates report a range of 4% to 50% for ocular bacteria.6 The 50% resistance rate occurred after 4 weeks of topical treatment in postcataract surgery patients.
Overall, this evidence suggests that for adults, watchful waiting rather than initially treating with antibiotics is reasonable, given the self-limited nature and lack of serious outcomes in untreated patients as well as growing concern about antibiotic resistance. Note that this recommendation applies only to acute nonvenereal conjunctivitis. It is generally accepted that conjunctivitis caused by gonococcus or chlamydia should be suspected in all newborns and in severe cases in sexually active young adults. These cases warrant culturing and antibiotic treatment to prevent serious complications.7
Recommendations from others
The American Optometric Association consensus guideline states that ideal treatment should be based on the specific causative organism. The guideline concludes that treatment of bacterial conjunctivitis with antibiotics can reduce symptoms, duration of illness, and chances of recurrence.8
Clinical Commentary by Carin Reust, MD, MSPH, at http://www.fpin.org.
1. Sheikh A, Hurwitz B, Cave J. Antibiotics versus placebo for acute bacterial conjunctivitis (Cochrane Review). In: The Cochrane Library, Issue 3, 2001. Oxford, England: Update Software.
2. Gigliotti F, Hendley JO, Morgan J, Michaels R, Dickens M, Lohr J. J Pediatr 1984;104:623-6.
3. Chung CW, Cohen EJ. West J Med 2000;173:202-5.
4. Sheikh A, Hurwitz B. Br J Gen Pract 2001;51:473-7.
5. Chung C, Cohen E. Bacterial conjunctivitis. Clinical evidence. London: BMJ Publishing Group, 2001: 436-41.
6. Baum J, Barza M. The evolution of antibiotic therapy for bacterial conjunctivitis and keratitis: 1970-2000. Cornea 2000;19:659-72.
7. Morrow GL, Abbott RL. Conjunctivitis. Am Fam Physician 1998;57:735-46.
8. American Optometric Association consensus panel on the care of the patient with conjunctivitis. Optometric clinical practice guideline no. 11, 1996.
Children with suspected or culture-proven acute nonvenereal bacterial conjunctivitis should be treated with topical antibiotics, which hastens clinical and microbiological remission and may prevent potentially serious morbidity. In light of recent evidence regarding the self-limiting nature of conjunctivitis in adults and the development of antibiotic resistance, a “wait-and-see” approach with careful follow-up may be reasonable for adults, but this approach has not been evaluated. (Grade of recommendation: C, based on extrapolation from systematic reviews of specialty clinic trials and cohort studies.)
Evidence summary
Conjunctivitis accounts for 1% to 2% of office visits to primary care practitioners.1 Conjunctivitis is more commonly caused by bacteria in children (50% in 1 study2) than in adults, in whom viral conjunctivitis predominates.3 Treating suspected or culture-proven acute bacterial conjunctivitis with topical antibiotics significantly shortens the clinical course of the disease and results in higher microbiological cure rates than placebo.1,4,5 A meta-analysis of 3 trials based in specialty clinics or hospitals reported significant clinical cure or improvement of bacterial conjunctivitis with 2 to 5 days of topical antibiotics compared with placebo (RR = 1.31, 95% CI, 1.11-1.55, number needed to treat = 5).1 Other articles have reported corneal or systemic complications of bacterial conjunctivitis. For example, 1 review reports that 25% of children with Haemophilus influenzae conjunctivitis develop otitis media.2
Although there is a small risk of complications and longer time course when bacterial conjunctivitis is left untreated, the disease is often self-limited, with a 64% clinical remission rate in patients treated for 2 to 5 days with placebo.1 The rate of spontaneous remission is much higher for adults than for children (71.6% vs 28%, respectively). The Cochrane meta-analysis reported a similar clinical cure rate in children for 6 to 10 days of treatment with topical antibiotics versus placebo. A systematic review of 5 placebo-controlled RCTs reported no serious adverse outcomes in conjunctivitis patients regardless of treatment group.4
Antibiotic resistance is a growing problem. Studies of fluoroquinolone resistance rates report a range of 4% to 50% for ocular bacteria.6 The 50% resistance rate occurred after 4 weeks of topical treatment in postcataract surgery patients.
Overall, this evidence suggests that for adults, watchful waiting rather than initially treating with antibiotics is reasonable, given the self-limited nature and lack of serious outcomes in untreated patients as well as growing concern about antibiotic resistance. Note that this recommendation applies only to acute nonvenereal conjunctivitis. It is generally accepted that conjunctivitis caused by gonococcus or chlamydia should be suspected in all newborns and in severe cases in sexually active young adults. These cases warrant culturing and antibiotic treatment to prevent serious complications.7
Recommendations from others
The American Optometric Association consensus guideline states that ideal treatment should be based on the specific causative organism. The guideline concludes that treatment of bacterial conjunctivitis with antibiotics can reduce symptoms, duration of illness, and chances of recurrence.8
Clinical Commentary by Carin Reust, MD, MSPH, at http://www.fpin.org.
Children with suspected or culture-proven acute nonvenereal bacterial conjunctivitis should be treated with topical antibiotics, which hastens clinical and microbiological remission and may prevent potentially serious morbidity. In light of recent evidence regarding the self-limiting nature of conjunctivitis in adults and the development of antibiotic resistance, a “wait-and-see” approach with careful follow-up may be reasonable for adults, but this approach has not been evaluated. (Grade of recommendation: C, based on extrapolation from systematic reviews of specialty clinic trials and cohort studies.)
Evidence summary
Conjunctivitis accounts for 1% to 2% of office visits to primary care practitioners.1 Conjunctivitis is more commonly caused by bacteria in children (50% in 1 study2) than in adults, in whom viral conjunctivitis predominates.3 Treating suspected or culture-proven acute bacterial conjunctivitis with topical antibiotics significantly shortens the clinical course of the disease and results in higher microbiological cure rates than placebo.1,4,5 A meta-analysis of 3 trials based in specialty clinics or hospitals reported significant clinical cure or improvement of bacterial conjunctivitis with 2 to 5 days of topical antibiotics compared with placebo (RR = 1.31, 95% CI, 1.11-1.55, number needed to treat = 5).1 Other articles have reported corneal or systemic complications of bacterial conjunctivitis. For example, 1 review reports that 25% of children with Haemophilus influenzae conjunctivitis develop otitis media.2
Although there is a small risk of complications and longer time course when bacterial conjunctivitis is left untreated, the disease is often self-limited, with a 64% clinical remission rate in patients treated for 2 to 5 days with placebo.1 The rate of spontaneous remission is much higher for adults than for children (71.6% vs 28%, respectively). The Cochrane meta-analysis reported a similar clinical cure rate in children for 6 to 10 days of treatment with topical antibiotics versus placebo. A systematic review of 5 placebo-controlled RCTs reported no serious adverse outcomes in conjunctivitis patients regardless of treatment group.4
Antibiotic resistance is a growing problem. Studies of fluoroquinolone resistance rates report a range of 4% to 50% for ocular bacteria.6 The 50% resistance rate occurred after 4 weeks of topical treatment in postcataract surgery patients.
Overall, this evidence suggests that for adults, watchful waiting rather than initially treating with antibiotics is reasonable, given the self-limited nature and lack of serious outcomes in untreated patients as well as growing concern about antibiotic resistance. Note that this recommendation applies only to acute nonvenereal conjunctivitis. It is generally accepted that conjunctivitis caused by gonococcus or chlamydia should be suspected in all newborns and in severe cases in sexually active young adults. These cases warrant culturing and antibiotic treatment to prevent serious complications.7
Recommendations from others
The American Optometric Association consensus guideline states that ideal treatment should be based on the specific causative organism. The guideline concludes that treatment of bacterial conjunctivitis with antibiotics can reduce symptoms, duration of illness, and chances of recurrence.8
Clinical Commentary by Carin Reust, MD, MSPH, at http://www.fpin.org.
1. Sheikh A, Hurwitz B, Cave J. Antibiotics versus placebo for acute bacterial conjunctivitis (Cochrane Review). In: The Cochrane Library, Issue 3, 2001. Oxford, England: Update Software.
2. Gigliotti F, Hendley JO, Morgan J, Michaels R, Dickens M, Lohr J. J Pediatr 1984;104:623-6.
3. Chung CW, Cohen EJ. West J Med 2000;173:202-5.
4. Sheikh A, Hurwitz B. Br J Gen Pract 2001;51:473-7.
5. Chung C, Cohen E. Bacterial conjunctivitis. Clinical evidence. London: BMJ Publishing Group, 2001: 436-41.
6. Baum J, Barza M. The evolution of antibiotic therapy for bacterial conjunctivitis and keratitis: 1970-2000. Cornea 2000;19:659-72.
7. Morrow GL, Abbott RL. Conjunctivitis. Am Fam Physician 1998;57:735-46.
8. American Optometric Association consensus panel on the care of the patient with conjunctivitis. Optometric clinical practice guideline no. 11, 1996.
1. Sheikh A, Hurwitz B, Cave J. Antibiotics versus placebo for acute bacterial conjunctivitis (Cochrane Review). In: The Cochrane Library, Issue 3, 2001. Oxford, England: Update Software.
2. Gigliotti F, Hendley JO, Morgan J, Michaels R, Dickens M, Lohr J. J Pediatr 1984;104:623-6.
3. Chung CW, Cohen EJ. West J Med 2000;173:202-5.
4. Sheikh A, Hurwitz B. Br J Gen Pract 2001;51:473-7.
5. Chung C, Cohen E. Bacterial conjunctivitis. Clinical evidence. London: BMJ Publishing Group, 2001: 436-41.
6. Baum J, Barza M. The evolution of antibiotic therapy for bacterial conjunctivitis and keratitis: 1970-2000. Cornea 2000;19:659-72.
7. Morrow GL, Abbott RL. Conjunctivitis. Am Fam Physician 1998;57:735-46.
8. American Optometric Association consensus panel on the care of the patient with conjunctivitis. Optometric clinical practice guideline no. 11, 1996.
Evidence-based answers from the Family Physicians Inquiries Network
What is the differential diagnosis of chronic diarrhea in immunocompetent patients?
Case series from tertiary-care centers report toddler’s diarrhea, cow’s milk sensitivity enteropathy, infection, celiac disease, and idiopathic chronic diarrhea as the most common etiologies in the pediatric population. In adults, the most common etiologies were secretory diarrhea (idiopathic, laxative abuse, irritable bowel syndrome, diabetes mellitus, and fecal incontinence), malabsorption (pancreatic disease, noninflammatory short bowel syndrome, postgastrectomy, hyperthyroidism, and cholestasis), microscopic colitis, inflammatory bowel disease, celiac sprue, and radiation colitis. (Grade of recommendation: C, based on case series.)
Evidence summary
Five case series of chronic diarrhea patients were identified. The largest adult study evaluated 193 patients referred to a tertiary-care center for diarrhea.1 Another adult study evaluated 103 patients referred to the same tertiary-care center. It is unclear whether these patients had a prior workup for chronic diarrhea.2 Secretory diarrhea was the most common etiology overall in the 2 series (21% and 45%, respectively). Other etiologies included malabsorption (35% and 28%), microscopic colitis (15%and9%), inflammatory bowel disease (16% and 10%), and celiac sprue (0% and 3%).1,2
The largest pediatric study included 381 children from a tertiary-care center with chronic diarrhea defined as lasting longer than 14 days.3 In this case series, 31% of children had toddler’s diarrhea, defined as chronic diarrhea with no definitive cause in an otherwise healthy baby who is growing normally. Cow’s milk sensitivity enteropathy comprised an additional 30% of cases. Etiologies for diarrhea in the remaining cases were infectious (11.8%), idiopathic (8.9%), celiac (7.3%), and other (10.2%).
A small tertiary-care pediatric study defining chronic diarrhea as occurring for more than 3 weeks and dependent on parenteral nutrition for more than 50% of daily caloric intake included only 20 patients.4 The diagnoses included autoimmune enteropathy, congenital microvillous atrophy, chronic intestinal pseudo-obstruction, and multiple food intolerance.
A case series study from India evaluated 47 children over 6 months of age who had diarrhea for more than 15 days and were unresponsive to medications (mostly antibiotics) or relapsing after treatment.5 The diagnoses included tropical enteropathy (46.8%), nonspecific diarrhea (21.8%), giardiasis (14.8%), irritable bowel syndrome (10.6%), and celiac disease (6.8%), although these findings probably do not apply to patients in more developed countries.
Recommendations from others
The American Gastroenterological Association divides the differential diagnoses of chronic diarrhea into 4 categories based on stool characteristics (Table).6 A recent review article states that the most common cause among infants taking formula is protein intolerance; for toddlers, irritable colon of infancy, protracted viral enteritis, and giardiasis; and for children and adolescents, ulcerative colitis, Crohn’s disease, and primary acquired lactose intolerance.7
TABLE
MAJOR CAUSES OF CHRONIC DIARRHEA CLASSIFIED BY TYPICAL STOOL CHARACTERISTICS6
| Osmotic diarrhea |
| Mg2+, PO4-3, SO4-2 ingestion |
| Carbohydrate malabsorption |
| Fatty diarrhea |
| Pancreatic disease |
| Short-bowel syndrome |
| Postgastrectomy syndrome |
| Hyperthyroidism |
| Cholestasis |
| Other malabsorption syndromes |
| Inflammatory diarrhea |
| Inflammatory bowel disease |
| Infectious diseases |
| Ischemic colitis |
| Radiation colitis |
| Neoplasia |
| Secretory diarrhea |
| Irritable bowel syndrome |
| Laxative abuse |
| Fecal incontinence |
| Congenital syndromes (chloridorrhea) |
| Idiopathic secretory diarrhea |
| Bacterial toxins |
| Drugs and poisons |
| Disordered motility |
| Neuroendocrine tumors |
| Neoplasia |
| Addison’s disease |
| Epidemic secretory (Brainerd) diarrhea |
Les W. Hall, MD
Department of Internal Medicine University of Missouri Columbia
The patient’s history often provides vital clues to etiology. A number of medications, both prescription and nonprescription, may cause diarrhea. If blood or mucus in stool, abdominal pain, and fever are present, inflammatory diseases of the bowel come to mind. Diarrhea that never awakens the patient from sleep is often caused by bowel hypermotility. Malabsorptive diarrhea should abate with fasting. Copious diarrhea that persists with fasting is usually secretory in mechanism.
1. Schiller LR, et al. Dig Dis Sci 1994;39:2216-22.
2. Fine KD, et al. Am J Gastroenterol 1998;93:1300-5.
3. Thomas AG, Phillips AD, Walker-Smith JA. Arch Dis Child 1992;67:741-4.
4. Ventura A, Dragovich D. Eur J Pediatr 1995;154:522-5.
5. Rastogi A, et al. Trop Gastroenterol 1998;19:45-9.
6. American Gastroenterological Association technical review on the evaluation and management of chronic diarrhea. Gastroenterology 1999;116:1464-86.
7. Vanderhoof JA. Pediatr Rev 1998;19:418-22.
Case series from tertiary-care centers report toddler’s diarrhea, cow’s milk sensitivity enteropathy, infection, celiac disease, and idiopathic chronic diarrhea as the most common etiologies in the pediatric population. In adults, the most common etiologies were secretory diarrhea (idiopathic, laxative abuse, irritable bowel syndrome, diabetes mellitus, and fecal incontinence), malabsorption (pancreatic disease, noninflammatory short bowel syndrome, postgastrectomy, hyperthyroidism, and cholestasis), microscopic colitis, inflammatory bowel disease, celiac sprue, and radiation colitis. (Grade of recommendation: C, based on case series.)
Evidence summary
Five case series of chronic diarrhea patients were identified. The largest adult study evaluated 193 patients referred to a tertiary-care center for diarrhea.1 Another adult study evaluated 103 patients referred to the same tertiary-care center. It is unclear whether these patients had a prior workup for chronic diarrhea.2 Secretory diarrhea was the most common etiology overall in the 2 series (21% and 45%, respectively). Other etiologies included malabsorption (35% and 28%), microscopic colitis (15%and9%), inflammatory bowel disease (16% and 10%), and celiac sprue (0% and 3%).1,2
The largest pediatric study included 381 children from a tertiary-care center with chronic diarrhea defined as lasting longer than 14 days.3 In this case series, 31% of children had toddler’s diarrhea, defined as chronic diarrhea with no definitive cause in an otherwise healthy baby who is growing normally. Cow’s milk sensitivity enteropathy comprised an additional 30% of cases. Etiologies for diarrhea in the remaining cases were infectious (11.8%), idiopathic (8.9%), celiac (7.3%), and other (10.2%).
A small tertiary-care pediatric study defining chronic diarrhea as occurring for more than 3 weeks and dependent on parenteral nutrition for more than 50% of daily caloric intake included only 20 patients.4 The diagnoses included autoimmune enteropathy, congenital microvillous atrophy, chronic intestinal pseudo-obstruction, and multiple food intolerance.
A case series study from India evaluated 47 children over 6 months of age who had diarrhea for more than 15 days and were unresponsive to medications (mostly antibiotics) or relapsing after treatment.5 The diagnoses included tropical enteropathy (46.8%), nonspecific diarrhea (21.8%), giardiasis (14.8%), irritable bowel syndrome (10.6%), and celiac disease (6.8%), although these findings probably do not apply to patients in more developed countries.
Recommendations from others
The American Gastroenterological Association divides the differential diagnoses of chronic diarrhea into 4 categories based on stool characteristics (Table).6 A recent review article states that the most common cause among infants taking formula is protein intolerance; for toddlers, irritable colon of infancy, protracted viral enteritis, and giardiasis; and for children and adolescents, ulcerative colitis, Crohn’s disease, and primary acquired lactose intolerance.7
TABLE
MAJOR CAUSES OF CHRONIC DIARRHEA CLASSIFIED BY TYPICAL STOOL CHARACTERISTICS6
| Osmotic diarrhea |
| Mg2+, PO4-3, SO4-2 ingestion |
| Carbohydrate malabsorption |
| Fatty diarrhea |
| Pancreatic disease |
| Short-bowel syndrome |
| Postgastrectomy syndrome |
| Hyperthyroidism |
| Cholestasis |
| Other malabsorption syndromes |
| Inflammatory diarrhea |
| Inflammatory bowel disease |
| Infectious diseases |
| Ischemic colitis |
| Radiation colitis |
| Neoplasia |
| Secretory diarrhea |
| Irritable bowel syndrome |
| Laxative abuse |
| Fecal incontinence |
| Congenital syndromes (chloridorrhea) |
| Idiopathic secretory diarrhea |
| Bacterial toxins |
| Drugs and poisons |
| Disordered motility |
| Neuroendocrine tumors |
| Neoplasia |
| Addison’s disease |
| Epidemic secretory (Brainerd) diarrhea |
Les W. Hall, MD
Department of Internal Medicine University of Missouri Columbia
The patient’s history often provides vital clues to etiology. A number of medications, both prescription and nonprescription, may cause diarrhea. If blood or mucus in stool, abdominal pain, and fever are present, inflammatory diseases of the bowel come to mind. Diarrhea that never awakens the patient from sleep is often caused by bowel hypermotility. Malabsorptive diarrhea should abate with fasting. Copious diarrhea that persists with fasting is usually secretory in mechanism.
Case series from tertiary-care centers report toddler’s diarrhea, cow’s milk sensitivity enteropathy, infection, celiac disease, and idiopathic chronic diarrhea as the most common etiologies in the pediatric population. In adults, the most common etiologies were secretory diarrhea (idiopathic, laxative abuse, irritable bowel syndrome, diabetes mellitus, and fecal incontinence), malabsorption (pancreatic disease, noninflammatory short bowel syndrome, postgastrectomy, hyperthyroidism, and cholestasis), microscopic colitis, inflammatory bowel disease, celiac sprue, and radiation colitis. (Grade of recommendation: C, based on case series.)
Evidence summary
Five case series of chronic diarrhea patients were identified. The largest adult study evaluated 193 patients referred to a tertiary-care center for diarrhea.1 Another adult study evaluated 103 patients referred to the same tertiary-care center. It is unclear whether these patients had a prior workup for chronic diarrhea.2 Secretory diarrhea was the most common etiology overall in the 2 series (21% and 45%, respectively). Other etiologies included malabsorption (35% and 28%), microscopic colitis (15%and9%), inflammatory bowel disease (16% and 10%), and celiac sprue (0% and 3%).1,2
The largest pediatric study included 381 children from a tertiary-care center with chronic diarrhea defined as lasting longer than 14 days.3 In this case series, 31% of children had toddler’s diarrhea, defined as chronic diarrhea with no definitive cause in an otherwise healthy baby who is growing normally. Cow’s milk sensitivity enteropathy comprised an additional 30% of cases. Etiologies for diarrhea in the remaining cases were infectious (11.8%), idiopathic (8.9%), celiac (7.3%), and other (10.2%).
A small tertiary-care pediatric study defining chronic diarrhea as occurring for more than 3 weeks and dependent on parenteral nutrition for more than 50% of daily caloric intake included only 20 patients.4 The diagnoses included autoimmune enteropathy, congenital microvillous atrophy, chronic intestinal pseudo-obstruction, and multiple food intolerance.
A case series study from India evaluated 47 children over 6 months of age who had diarrhea for more than 15 days and were unresponsive to medications (mostly antibiotics) or relapsing after treatment.5 The diagnoses included tropical enteropathy (46.8%), nonspecific diarrhea (21.8%), giardiasis (14.8%), irritable bowel syndrome (10.6%), and celiac disease (6.8%), although these findings probably do not apply to patients in more developed countries.
Recommendations from others
The American Gastroenterological Association divides the differential diagnoses of chronic diarrhea into 4 categories based on stool characteristics (Table).6 A recent review article states that the most common cause among infants taking formula is protein intolerance; for toddlers, irritable colon of infancy, protracted viral enteritis, and giardiasis; and for children and adolescents, ulcerative colitis, Crohn’s disease, and primary acquired lactose intolerance.7
TABLE
MAJOR CAUSES OF CHRONIC DIARRHEA CLASSIFIED BY TYPICAL STOOL CHARACTERISTICS6
| Osmotic diarrhea |
| Mg2+, PO4-3, SO4-2 ingestion |
| Carbohydrate malabsorption |
| Fatty diarrhea |
| Pancreatic disease |
| Short-bowel syndrome |
| Postgastrectomy syndrome |
| Hyperthyroidism |
| Cholestasis |
| Other malabsorption syndromes |
| Inflammatory diarrhea |
| Inflammatory bowel disease |
| Infectious diseases |
| Ischemic colitis |
| Radiation colitis |
| Neoplasia |
| Secretory diarrhea |
| Irritable bowel syndrome |
| Laxative abuse |
| Fecal incontinence |
| Congenital syndromes (chloridorrhea) |
| Idiopathic secretory diarrhea |
| Bacterial toxins |
| Drugs and poisons |
| Disordered motility |
| Neuroendocrine tumors |
| Neoplasia |
| Addison’s disease |
| Epidemic secretory (Brainerd) diarrhea |
Les W. Hall, MD
Department of Internal Medicine University of Missouri Columbia
The patient’s history often provides vital clues to etiology. A number of medications, both prescription and nonprescription, may cause diarrhea. If blood or mucus in stool, abdominal pain, and fever are present, inflammatory diseases of the bowel come to mind. Diarrhea that never awakens the patient from sleep is often caused by bowel hypermotility. Malabsorptive diarrhea should abate with fasting. Copious diarrhea that persists with fasting is usually secretory in mechanism.
1. Schiller LR, et al. Dig Dis Sci 1994;39:2216-22.
2. Fine KD, et al. Am J Gastroenterol 1998;93:1300-5.
3. Thomas AG, Phillips AD, Walker-Smith JA. Arch Dis Child 1992;67:741-4.
4. Ventura A, Dragovich D. Eur J Pediatr 1995;154:522-5.
5. Rastogi A, et al. Trop Gastroenterol 1998;19:45-9.
6. American Gastroenterological Association technical review on the evaluation and management of chronic diarrhea. Gastroenterology 1999;116:1464-86.
7. Vanderhoof JA. Pediatr Rev 1998;19:418-22.
1. Schiller LR, et al. Dig Dis Sci 1994;39:2216-22.
2. Fine KD, et al. Am J Gastroenterol 1998;93:1300-5.
3. Thomas AG, Phillips AD, Walker-Smith JA. Arch Dis Child 1992;67:741-4.
4. Ventura A, Dragovich D. Eur J Pediatr 1995;154:522-5.
5. Rastogi A, et al. Trop Gastroenterol 1998;19:45-9.
6. American Gastroenterological Association technical review on the evaluation and management of chronic diarrhea. Gastroenterology 1999;116:1464-86.
7. Vanderhoof JA. Pediatr Rev 1998;19:418-22.
Evidence-based answers from the Family Physicians Inquiries Network
How often is coughing the presenting complaint in patients with gastroesophageal reflux disease?
Frequent coughing is a concern for approximately 35% of those with typical gastroesophageal reflux disease (GERD) symptoms of heartburn and acid regurgitation as compared with 11% in those who do not have these symptoms. Among pulmonary clinic patients with complaints of chronic cough, GERD may be the underlying cause in 40%. (Grade of recommendation: C, based on extrapolation from cohort studies.) However, no studies directly address prevalence of coughing as a presenting complaint in patients with GERD.
Evidence summary
While many sources state that extraesophageal symptoms (eg, cough, chest pain, asthma) are reported by patients with GERD, only one study reported the frequency of associated symptoms.1 This population-based survey showed that symptoms of reflux and acid regurgitation are experienced by almost 60% of the population each year. The prevalence of frequent heartburn and acid reflux was approximately 20%. Bronchitis, defined as cough that occurs as often as 4 to 6 times per day on 4 or more days per week, was reported by more than 20% of those with frequent typical GERD symptoms (occurring at least weekly) and by 15% of those with infrequent GERD symptoms. Interestingly, bronchitis was reported by almost 11% of those without GERD. This study showed the association of cough with GERD but did not address whether the cough was the initial presenting complaint.
In as many as 40% of patients with cough, GERD is the underlying cause.2-7 Chronic cough may be triggered by more than one condition (eg, GERD, postnasal drip, or asthma) in 18% to 93% of patients.8 Among patients with cough caused by GERD, 50% to 75% do not have classic symptoms of reflux or regurgitation.9 Finally, cough may initiate GERD and start a cough–reflux cycle.9 These studies were conducted in pulmonary clinics. Patients with cough whose underlying GERD was easily diagnosed and treated by their primary physician were probably not referred for evaluation in a pulmonary clinic.
Recommendations from others
The American College of Chest Physicians issued a consensus statement in 1999 regarding the management of cough.10 According to the statement, GERD should be strongly suspected in coughing patients with upper GI symptoms or in those without GI symptoms who have normal chest radiographs, do not smoke, and do not take angiotensin-converting enzyme inhibitors. The statement reports that asthma, postnasal drip syndrome (PNDS), and GERD are the causes of cough in nearly 100% of these patients. The recommendation for evaluation of GERD is a 24-hour pH monitor or an empiric trial of antireflux medication after ruling out asthma and PNDS.
Les W. Hall, MD
Department of Internal Medicine University of Missouri Columbia
Most studies of patients with chronic cough find GERD to be among the top 3 causes of this condition. Although many of these patients report other symptoms of reflux, cough is the sole symptom in some. Monitoring of esophageal pH for 24 hours is considered the gold standard for diagnosis of GERD, but limited availability and variable patient acceptance diminish the universal application of this method. A trial of intensive antireflux therapy may represent a cost-effective and practical approach to such patients, since cough from GERD may take up to 3 months to improve under such a regimen.
1. Locke GR, III, Talley NJ, Fett SL, Zinsmeister AR, Melton LJ. Gastroenterology 1997;112:1448-56.
2. Irwin RS, Curley FJ, French CL. Am Rev Respir Dis 1990;141:640-7.
3. Irwin RS, Corrao WM, Pratter MR. Am Rev Respir Dis 1981;123:413-7.
4. Mello CJ, Irwin RS, Curley FJ. Arch Intern Med 1996;156:997-1003.
5. Poe RH, Israel RH, Utell MJ, Hall WJ. Am Rev Respir Dis 1982;126:160-2.
6. Poe RH, Harder RV, Israel RH, Kallay MC. Chest 1989;95:723-8.
7. Pratter MR, Bartter T, Akers S, Dubois J. Ann Intern Med 1993;119:977-83.
8. Irwin RS, Richter JE. Am J Gastroenterol 2000;95:S9-S14.
9. Ing AJ. Am J Med 1997;103:91S-96S.
10. Irwin RS, Boulet LP, Cloutier MM, et al. Chest 1998;114:133S-181S.
Frequent coughing is a concern for approximately 35% of those with typical gastroesophageal reflux disease (GERD) symptoms of heartburn and acid regurgitation as compared with 11% in those who do not have these symptoms. Among pulmonary clinic patients with complaints of chronic cough, GERD may be the underlying cause in 40%. (Grade of recommendation: C, based on extrapolation from cohort studies.) However, no studies directly address prevalence of coughing as a presenting complaint in patients with GERD.
Evidence summary
While many sources state that extraesophageal symptoms (eg, cough, chest pain, asthma) are reported by patients with GERD, only one study reported the frequency of associated symptoms.1 This population-based survey showed that symptoms of reflux and acid regurgitation are experienced by almost 60% of the population each year. The prevalence of frequent heartburn and acid reflux was approximately 20%. Bronchitis, defined as cough that occurs as often as 4 to 6 times per day on 4 or more days per week, was reported by more than 20% of those with frequent typical GERD symptoms (occurring at least weekly) and by 15% of those with infrequent GERD symptoms. Interestingly, bronchitis was reported by almost 11% of those without GERD. This study showed the association of cough with GERD but did not address whether the cough was the initial presenting complaint.
In as many as 40% of patients with cough, GERD is the underlying cause.2-7 Chronic cough may be triggered by more than one condition (eg, GERD, postnasal drip, or asthma) in 18% to 93% of patients.8 Among patients with cough caused by GERD, 50% to 75% do not have classic symptoms of reflux or regurgitation.9 Finally, cough may initiate GERD and start a cough–reflux cycle.9 These studies were conducted in pulmonary clinics. Patients with cough whose underlying GERD was easily diagnosed and treated by their primary physician were probably not referred for evaluation in a pulmonary clinic.
Recommendations from others
The American College of Chest Physicians issued a consensus statement in 1999 regarding the management of cough.10 According to the statement, GERD should be strongly suspected in coughing patients with upper GI symptoms or in those without GI symptoms who have normal chest radiographs, do not smoke, and do not take angiotensin-converting enzyme inhibitors. The statement reports that asthma, postnasal drip syndrome (PNDS), and GERD are the causes of cough in nearly 100% of these patients. The recommendation for evaluation of GERD is a 24-hour pH monitor or an empiric trial of antireflux medication after ruling out asthma and PNDS.
Les W. Hall, MD
Department of Internal Medicine University of Missouri Columbia
Most studies of patients with chronic cough find GERD to be among the top 3 causes of this condition. Although many of these patients report other symptoms of reflux, cough is the sole symptom in some. Monitoring of esophageal pH for 24 hours is considered the gold standard for diagnosis of GERD, but limited availability and variable patient acceptance diminish the universal application of this method. A trial of intensive antireflux therapy may represent a cost-effective and practical approach to such patients, since cough from GERD may take up to 3 months to improve under such a regimen.
Frequent coughing is a concern for approximately 35% of those with typical gastroesophageal reflux disease (GERD) symptoms of heartburn and acid regurgitation as compared with 11% in those who do not have these symptoms. Among pulmonary clinic patients with complaints of chronic cough, GERD may be the underlying cause in 40%. (Grade of recommendation: C, based on extrapolation from cohort studies.) However, no studies directly address prevalence of coughing as a presenting complaint in patients with GERD.
Evidence summary
While many sources state that extraesophageal symptoms (eg, cough, chest pain, asthma) are reported by patients with GERD, only one study reported the frequency of associated symptoms.1 This population-based survey showed that symptoms of reflux and acid regurgitation are experienced by almost 60% of the population each year. The prevalence of frequent heartburn and acid reflux was approximately 20%. Bronchitis, defined as cough that occurs as often as 4 to 6 times per day on 4 or more days per week, was reported by more than 20% of those with frequent typical GERD symptoms (occurring at least weekly) and by 15% of those with infrequent GERD symptoms. Interestingly, bronchitis was reported by almost 11% of those without GERD. This study showed the association of cough with GERD but did not address whether the cough was the initial presenting complaint.
In as many as 40% of patients with cough, GERD is the underlying cause.2-7 Chronic cough may be triggered by more than one condition (eg, GERD, postnasal drip, or asthma) in 18% to 93% of patients.8 Among patients with cough caused by GERD, 50% to 75% do not have classic symptoms of reflux or regurgitation.9 Finally, cough may initiate GERD and start a cough–reflux cycle.9 These studies were conducted in pulmonary clinics. Patients with cough whose underlying GERD was easily diagnosed and treated by their primary physician were probably not referred for evaluation in a pulmonary clinic.
Recommendations from others
The American College of Chest Physicians issued a consensus statement in 1999 regarding the management of cough.10 According to the statement, GERD should be strongly suspected in coughing patients with upper GI symptoms or in those without GI symptoms who have normal chest radiographs, do not smoke, and do not take angiotensin-converting enzyme inhibitors. The statement reports that asthma, postnasal drip syndrome (PNDS), and GERD are the causes of cough in nearly 100% of these patients. The recommendation for evaluation of GERD is a 24-hour pH monitor or an empiric trial of antireflux medication after ruling out asthma and PNDS.
Les W. Hall, MD
Department of Internal Medicine University of Missouri Columbia
Most studies of patients with chronic cough find GERD to be among the top 3 causes of this condition. Although many of these patients report other symptoms of reflux, cough is the sole symptom in some. Monitoring of esophageal pH for 24 hours is considered the gold standard for diagnosis of GERD, but limited availability and variable patient acceptance diminish the universal application of this method. A trial of intensive antireflux therapy may represent a cost-effective and practical approach to such patients, since cough from GERD may take up to 3 months to improve under such a regimen.
1. Locke GR, III, Talley NJ, Fett SL, Zinsmeister AR, Melton LJ. Gastroenterology 1997;112:1448-56.
2. Irwin RS, Curley FJ, French CL. Am Rev Respir Dis 1990;141:640-7.
3. Irwin RS, Corrao WM, Pratter MR. Am Rev Respir Dis 1981;123:413-7.
4. Mello CJ, Irwin RS, Curley FJ. Arch Intern Med 1996;156:997-1003.
5. Poe RH, Israel RH, Utell MJ, Hall WJ. Am Rev Respir Dis 1982;126:160-2.
6. Poe RH, Harder RV, Israel RH, Kallay MC. Chest 1989;95:723-8.
7. Pratter MR, Bartter T, Akers S, Dubois J. Ann Intern Med 1993;119:977-83.
8. Irwin RS, Richter JE. Am J Gastroenterol 2000;95:S9-S14.
9. Ing AJ. Am J Med 1997;103:91S-96S.
10. Irwin RS, Boulet LP, Cloutier MM, et al. Chest 1998;114:133S-181S.
1. Locke GR, III, Talley NJ, Fett SL, Zinsmeister AR, Melton LJ. Gastroenterology 1997;112:1448-56.
2. Irwin RS, Curley FJ, French CL. Am Rev Respir Dis 1990;141:640-7.
3. Irwin RS, Corrao WM, Pratter MR. Am Rev Respir Dis 1981;123:413-7.
4. Mello CJ, Irwin RS, Curley FJ. Arch Intern Med 1996;156:997-1003.
5. Poe RH, Israel RH, Utell MJ, Hall WJ. Am Rev Respir Dis 1982;126:160-2.
6. Poe RH, Harder RV, Israel RH, Kallay MC. Chest 1989;95:723-8.
7. Pratter MR, Bartter T, Akers S, Dubois J. Ann Intern Med 1993;119:977-83.
8. Irwin RS, Richter JE. Am J Gastroenterol 2000;95:S9-S14.
9. Ing AJ. Am J Med 1997;103:91S-96S.
10. Irwin RS, Boulet LP, Cloutier MM, et al. Chest 1998;114:133S-181S.
Evidence-based answers from the Family Physicians Inquiries Network
How effective are exercise and physical therapy for chronic low back pain?
Exercise is more effective for chronic low back pain than treatment with medication plus return to usual activity and as effective as conventional physiotherapy. The evidence is less consistent in showing that any particular exercise format provides greater benefit or that exercise provides a long-term increase in function or a decrease in pain or disability. (Grade of recommendation: A, based on systematic reviews of randomized controlled trials [RCTs].)
Evidence summary
The first meta-analysis of 16 chronic low back pain RCTs in 1991 had inconsistent results on the efficacy of exercise and showed little evidence in favor of any specific exercise format.1 The authors conducted another meta-analysis in 2000, since the quality of original studies had improved a great deal during the intervening decade.2 This analysis showed strong evidence favoring exercise over “usual care” by primary care physicians (medications and resumption of usual activities). Exercise was found equally efficacious as conventional physiotherapy. Evidence was conflicting in a comparison of exercise with inactive treatment (ice or heat packs, rest). None of the studies showed a particular exercise format as superior. The included studies included a wide variety of structured exercise programs. Exercise demonstrated no benefit in situations of acute back pain.
Several other systematic reviews have supported the role of exercise in patients with chronic low back pain.3-5 A 1996 review of 13 RCTs examining specific types of exercises found that both intensive dynamic extension exercises and mild isometric flexion and extension exercises were more effective than placebo.3 Although the intensive exercises were more efficacious than normal exercises at the 3-month follow-up, they were equally efficacious at 12 months. Evidence was conflicting in a comparison of flexion and extension exercises. Another review reported that exercise, back manipulation, and intense back schools were equally efficacious.4
Two recent studies were not included in the above reviews. One was an RCT that showed that a progressive intervention program that included cognitive behavioral management was more effective than exercise alone to decrease pain and self-reported disability.6 The other study was a retrospective chart review that reported improved pain and decreased disability in patients with chronic low back pain after 6 weeks of exercise.7
Recommendations from others
The clinical practice guideline for low back pain from the Agency for Health Care Policy and Research deals mainly with acute pain and does not recommend exercise in acute conditions.8
James L. Lord, MD
Department of Family Medicine St. John’s Mercy Medical Center St. Louis, Missouri
In my experience, most patients with low back pain share one characteristic: a sedentary lifestyle. My patients who exercise regularly seem to have fewer problems with back pain or to recover faster from acute episodes of back pain. I generally recommend a combination of aerobic exercise, stretching, and strengthening. Patients who subscribe to any of these activities generally get better over time, but those who adhere to the full prescription get better sooner. “Motion is lotion” is my message to patients.
1. Koes BW, et al. BMJ 1991;302:1572-6.
2. van Tulder MW, et al. In: The Cochrane Library, Issue 4, 2001. Oxford, England: Update Software.
3. Faas A. Spine 1996;21:2874-9.
4. van Tulder MW, et al. Spine 1997;22:2128-56.
5. Hilde G. Physical Ther Rev 1998;3:107-17.
6. Alaranta H, et al. Spine 2001;19:1339-49.
7. van der Velde G, et al. Arch Phys Med Rehab 2000;81:1457-63.
8. Bigos S, et al. Clinical Practice Guideline No 14. AHCPR Publication No 95-0642. Rockville, Md: Public Health Service, US Department of Health and Human Services; 1994.
Exercise is more effective for chronic low back pain than treatment with medication plus return to usual activity and as effective as conventional physiotherapy. The evidence is less consistent in showing that any particular exercise format provides greater benefit or that exercise provides a long-term increase in function or a decrease in pain or disability. (Grade of recommendation: A, based on systematic reviews of randomized controlled trials [RCTs].)
Evidence summary
The first meta-analysis of 16 chronic low back pain RCTs in 1991 had inconsistent results on the efficacy of exercise and showed little evidence in favor of any specific exercise format.1 The authors conducted another meta-analysis in 2000, since the quality of original studies had improved a great deal during the intervening decade.2 This analysis showed strong evidence favoring exercise over “usual care” by primary care physicians (medications and resumption of usual activities). Exercise was found equally efficacious as conventional physiotherapy. Evidence was conflicting in a comparison of exercise with inactive treatment (ice or heat packs, rest). None of the studies showed a particular exercise format as superior. The included studies included a wide variety of structured exercise programs. Exercise demonstrated no benefit in situations of acute back pain.
Several other systematic reviews have supported the role of exercise in patients with chronic low back pain.3-5 A 1996 review of 13 RCTs examining specific types of exercises found that both intensive dynamic extension exercises and mild isometric flexion and extension exercises were more effective than placebo.3 Although the intensive exercises were more efficacious than normal exercises at the 3-month follow-up, they were equally efficacious at 12 months. Evidence was conflicting in a comparison of flexion and extension exercises. Another review reported that exercise, back manipulation, and intense back schools were equally efficacious.4
Two recent studies were not included in the above reviews. One was an RCT that showed that a progressive intervention program that included cognitive behavioral management was more effective than exercise alone to decrease pain and self-reported disability.6 The other study was a retrospective chart review that reported improved pain and decreased disability in patients with chronic low back pain after 6 weeks of exercise.7
Recommendations from others
The clinical practice guideline for low back pain from the Agency for Health Care Policy and Research deals mainly with acute pain and does not recommend exercise in acute conditions.8
James L. Lord, MD
Department of Family Medicine St. John’s Mercy Medical Center St. Louis, Missouri
In my experience, most patients with low back pain share one characteristic: a sedentary lifestyle. My patients who exercise regularly seem to have fewer problems with back pain or to recover faster from acute episodes of back pain. I generally recommend a combination of aerobic exercise, stretching, and strengthening. Patients who subscribe to any of these activities generally get better over time, but those who adhere to the full prescription get better sooner. “Motion is lotion” is my message to patients.
Exercise is more effective for chronic low back pain than treatment with medication plus return to usual activity and as effective as conventional physiotherapy. The evidence is less consistent in showing that any particular exercise format provides greater benefit or that exercise provides a long-term increase in function or a decrease in pain or disability. (Grade of recommendation: A, based on systematic reviews of randomized controlled trials [RCTs].)
Evidence summary
The first meta-analysis of 16 chronic low back pain RCTs in 1991 had inconsistent results on the efficacy of exercise and showed little evidence in favor of any specific exercise format.1 The authors conducted another meta-analysis in 2000, since the quality of original studies had improved a great deal during the intervening decade.2 This analysis showed strong evidence favoring exercise over “usual care” by primary care physicians (medications and resumption of usual activities). Exercise was found equally efficacious as conventional physiotherapy. Evidence was conflicting in a comparison of exercise with inactive treatment (ice or heat packs, rest). None of the studies showed a particular exercise format as superior. The included studies included a wide variety of structured exercise programs. Exercise demonstrated no benefit in situations of acute back pain.
Several other systematic reviews have supported the role of exercise in patients with chronic low back pain.3-5 A 1996 review of 13 RCTs examining specific types of exercises found that both intensive dynamic extension exercises and mild isometric flexion and extension exercises were more effective than placebo.3 Although the intensive exercises were more efficacious than normal exercises at the 3-month follow-up, they were equally efficacious at 12 months. Evidence was conflicting in a comparison of flexion and extension exercises. Another review reported that exercise, back manipulation, and intense back schools were equally efficacious.4
Two recent studies were not included in the above reviews. One was an RCT that showed that a progressive intervention program that included cognitive behavioral management was more effective than exercise alone to decrease pain and self-reported disability.6 The other study was a retrospective chart review that reported improved pain and decreased disability in patients with chronic low back pain after 6 weeks of exercise.7
Recommendations from others
The clinical practice guideline for low back pain from the Agency for Health Care Policy and Research deals mainly with acute pain and does not recommend exercise in acute conditions.8
James L. Lord, MD
Department of Family Medicine St. John’s Mercy Medical Center St. Louis, Missouri
In my experience, most patients with low back pain share one characteristic: a sedentary lifestyle. My patients who exercise regularly seem to have fewer problems with back pain or to recover faster from acute episodes of back pain. I generally recommend a combination of aerobic exercise, stretching, and strengthening. Patients who subscribe to any of these activities generally get better over time, but those who adhere to the full prescription get better sooner. “Motion is lotion” is my message to patients.
1. Koes BW, et al. BMJ 1991;302:1572-6.
2. van Tulder MW, et al. In: The Cochrane Library, Issue 4, 2001. Oxford, England: Update Software.
3. Faas A. Spine 1996;21:2874-9.
4. van Tulder MW, et al. Spine 1997;22:2128-56.
5. Hilde G. Physical Ther Rev 1998;3:107-17.
6. Alaranta H, et al. Spine 2001;19:1339-49.
7. van der Velde G, et al. Arch Phys Med Rehab 2000;81:1457-63.
8. Bigos S, et al. Clinical Practice Guideline No 14. AHCPR Publication No 95-0642. Rockville, Md: Public Health Service, US Department of Health and Human Services; 1994.
1. Koes BW, et al. BMJ 1991;302:1572-6.
2. van Tulder MW, et al. In: The Cochrane Library, Issue 4, 2001. Oxford, England: Update Software.
3. Faas A. Spine 1996;21:2874-9.
4. van Tulder MW, et al. Spine 1997;22:2128-56.
5. Hilde G. Physical Ther Rev 1998;3:107-17.
6. Alaranta H, et al. Spine 2001;19:1339-49.
7. van der Velde G, et al. Arch Phys Med Rehab 2000;81:1457-63.
8. Bigos S, et al. Clinical Practice Guideline No 14. AHCPR Publication No 95-0642. Rockville, Md: Public Health Service, US Department of Health and Human Services; 1994.
Evidence-based answers from the Family Physicians Inquiries Network