Carin E. Reust, MD

Recommendations from others

According to the Canadian Association of Gastroenterology Practice guidelines, an elevation in AP is associated with cholestatic liver disease, pregnancy, bone disease, and occasionally with inflammatory bowel disease. For an elevation in AP greater than 1.5 times the upper limits of normal (ULN) on 2 occasions at least 6 months apart, a workup for liver and bone disease is recommended followed by a referral to a specialist in hepatobiliary disease.³

Evidence summary

Liver, bone, and placental isoenzymes of AP are the most common sources of elevations reported in standard textbooks. Studies of men, women, and children have identified factors associated with normal elevations in AP. Hospital and laboratory-based studies report a variety of diseases associated with elevated AP. Within-day biologic variation is estimated at 4%, and day-to-day variation is estimated at 8% to 10%.² The Table 1 shows the causes of normal or physiologic elevations and pathologic elevations.

In a case series of hospitalized Department of Veterans Affairs patients (95% men; average age=62), 87 charts were reviewed.⁴ Those patients had elevated AP with normal aspartate aminotransferase (serum glutamate oxaloacetate transaminase) and calcium values. Seventy-eight percent of the diagnoses could be made through a careful history, physical examination, routine laboratory tests (lactate dehydrogenase, bilirubin, phosphorus, creatinine, protein, and albumin), and admitting chest X-ray. In this cohort, 32% of elevated AP values resolved in 3 months, another 20% resolved in 12 months, and 20% persisted. In the remaining 28%, an explanation was not sought because of the presence of an obvious terminal illness or severe dementia. Persistence was associated with an AP value greater than 1.5 times the ULN. In 19 (22%), the AP elevation was unexplained. In a case series of patients referred for bone scan secondary to an elevated AP not due to hepatic causes, 21% had normal findings, and of these, 92% had AP values less than 3 times the ULN.⁵ In this group, patients were subsequently found to have uncontrolled diabetes mellitus, ethanol abuse, drug toxicity, renal abnormalities, and chronic active hepatitis.

Expert opinion as reflected in standard textbooks and opinion pieces suggests values of 1.5 to 3 times the ULN are consistent with hepatocellular (viral infection, drug toxicity, alcohol) etiology, while values greater than 3 times the ULN are usually associated with biliary involvement. Bone involvement can be found at any value. Extremely high values (>7 times the ULN) are associated with the familial and transient isolated hyperphosphatasemia of infancy. Further workup should evaluate the presence of liver or bone disease, familial patterns, and rarely preclinical cancers.

Recommendations from others

According to the Canadian Association of Gastroenterology Practice guidelines, an elevation in AP is associated with cholestatic liver disease, pregnancy, bone disease, and occasionally with inflammatory bowel disease. For an elevation in AP greater than 1.5 times the upper limits of normal (ULN) on 2 occasions at least 6 months apart, a workup for liver and bone disease is recommended followed by a referral to a specialist in hepatobiliary disease.³

Evidence summary

Liver, bone, and placental isoenzymes of AP are the most common sources of elevations reported in standard textbooks. Studies of men, women, and children have identified factors associated with normal elevations in AP. Hospital and laboratory-based studies report a variety of diseases associated with elevated AP. Within-day biologic variation is estimated at 4%, and day-to-day variation is estimated at 8% to 10%.² The Table 1 shows the causes of normal or physiologic elevations and pathologic elevations.

In a case series of hospitalized Department of Veterans Affairs patients (95% men; average age=62), 87 charts were reviewed.⁴ Those patients had elevated AP with normal aspartate aminotransferase (serum glutamate oxaloacetate transaminase) and calcium values. Seventy-eight percent of the diagnoses could be made through a careful history, physical examination, routine laboratory tests (lactate dehydrogenase, bilirubin, phosphorus, creatinine, protein, and albumin), and admitting chest X-ray. In this cohort, 32% of elevated AP values resolved in 3 months, another 20% resolved in 12 months, and 20% persisted. In the remaining 28%, an explanation was not sought because of the presence of an obvious terminal illness or severe dementia. Persistence was associated with an AP value greater than 1.5 times the ULN. In 19 (22%), the AP elevation was unexplained. In a case series of patients referred for bone scan secondary to an elevated AP not due to hepatic causes, 21% had normal findings, and of these, 92% had AP values less than 3 times the ULN.⁵ In this group, patients were subsequently found to have uncontrolled diabetes mellitus, ethanol abuse, drug toxicity, renal abnormalities, and chronic active hepatitis.

Expert opinion as reflected in standard textbooks and opinion pieces suggests values of 1.5 to 3 times the ULN are consistent with hepatocellular (viral infection, drug toxicity, alcohol) etiology, while values greater than 3 times the ULN are usually associated with biliary involvement. Bone involvement can be found at any value. Extremely high values (>7 times the ULN) are associated with the familial and transient isolated hyperphosphatasemia of infancy. Further workup should evaluate the presence of liver or bone disease, familial patterns, and rarely preclinical cancers.

Recommendations from others

According to the Canadian Association of Gastroenterology Practice guidelines, an elevation in AP is associated with cholestatic liver disease, pregnancy, bone disease, and occasionally with inflammatory bowel disease. For an elevation in AP greater than 1.5 times the upper limits of normal (ULN) on 2 occasions at least 6 months apart, a workup for liver and bone disease is recommended followed by a referral to a specialist in hepatobiliary disease.³

Evidence summary

Liver, bone, and placental isoenzymes of AP are the most common sources of elevations reported in standard textbooks. Studies of men, women, and children have identified factors associated with normal elevations in AP. Hospital and laboratory-based studies report a variety of diseases associated with elevated AP. Within-day biologic variation is estimated at 4%, and day-to-day variation is estimated at 8% to 10%.² The Table 1 shows the causes of normal or physiologic elevations and pathologic elevations.

In a case series of hospitalized Department of Veterans Affairs patients (95% men; average age=62), 87 charts were reviewed.⁴ Those patients had elevated AP with normal aspartate aminotransferase (serum glutamate oxaloacetate transaminase) and calcium values. Seventy-eight percent of the diagnoses could be made through a careful history, physical examination, routine laboratory tests (lactate dehydrogenase, bilirubin, phosphorus, creatinine, protein, and albumin), and admitting chest X-ray. In this cohort, 32% of elevated AP values resolved in 3 months, another 20% resolved in 12 months, and 20% persisted. In the remaining 28%, an explanation was not sought because of the presence of an obvious terminal illness or severe dementia. Persistence was associated with an AP value greater than 1.5 times the ULN. In 19 (22%), the AP elevation was unexplained. In a case series of patients referred for bone scan secondary to an elevated AP not due to hepatic causes, 21% had normal findings, and of these, 92% had AP values less than 3 times the ULN.⁵ In this group, patients were subsequently found to have uncontrolled diabetes mellitus, ethanol abuse, drug toxicity, renal abnormalities, and chronic active hepatitis.

Expert opinion as reflected in standard textbooks and opinion pieces suggests values of 1.5 to 3 times the ULN are consistent with hepatocellular (viral infection, drug toxicity, alcohol) etiology, while values greater than 3 times the ULN are usually associated with biliary involvement. Bone involvement can be found at any value. Extremely high values (>7 times the ULN) are associated with the familial and transient isolated hyperphosphatasemia of infancy. Further workup should evaluate the presence of liver or bone disease, familial patterns, and rarely preclinical cancers.

BACKGROUND: Calcium channel blockers (CCBs) are more effective than placebo in lowering blood pressure and in preventing subsequent cardiovascular outcomes. However, observational studies of short-acting CCBs and controlled trials of long-acting CCBs have shown that although blood pressure is controlled, cardiovascular event rates increase. The authors performed a meta-analysis of randomized controlled trials comparing CCBs with first-line antihypertensives regarding their effects on cardiovascular events. population studied The analysis included 9 studies involving 27,743 patients. The mean age range was 53.9 to 76.1 years. Both men and women were represented in the analysis. Follow-up was 2 to 7 years with an estimated total follow-up of 120,000 person-years.

STUDY DESIGN AND VALIDITY: This is a meta-analysis of the existing literature. Studies were identified for inclusion through a systematic search of MEDLINE. To be included the randomized trials had to have more than 100 participants, follow-up longer than 2 years, compare CCBs with other first-line agents, and evaluate the effect on cardiovascular outcomes. The studies compared CCBs with diuretics, b-blockers, angiotensin-converting enzyme inhibitors, and clonidine. Two investigators independently abstracted data. Outcome data were analyzed by intention to treat except in one study that consisted of 429 patients. Tests for heterogeneity were performed. The meta-analysis is well done although limited by the quality of the included studies. Each of the 9 studies in the analysis has a limitation. Five of the studies were open design, and in 4 studies the authors had to contact investigators to obtain information on the primary outcomes. Two studies dealt primarily with patients with diabetes. In one study randomization favored the CCB arm, while in another the non-CCB arm had a more favorable baseline. The dropout rate for the studies ranged from 7% to 60%. A variety of sensitivity analyses were done to determine if one study, one drug type, or one type of patient profile contributed to the results. This did not appear to be the situation, although there was insufficient power in some of the sensitivity analyses to answer this question confidently.

OUTCOMES MEASURED: The outcomes measured were changes in systolic and diastolic blood pressure, acute myocardial infarctions, congestive heart failure, stroke, and all-cause mortality. The authors also evaluated the effect of treatment on the combined outcome of major cardiovascular events including acute myocardial infarction, congestive heart failure, stroke, and cardiovascular mortality.

RESULTS: CCBs lowered both systolic and diastolic blood pressure comparably with first-line agents. CCBs had a higher risk of acute myocardial infarction (odds ratio [OR]=1.26; 95% confidence interval [CI], 1.11-1.43), congestive heart failure (OR=1.25; 95% CI, 1.07-1.46), and major cardiovascular events (OR=1.10; 95% CI, 1.02-1.18). CCBs were comparable with other agents for reducing the risk of stroke (OR=0.90; 95% CI, 0.80-1.02) and all-cause mortality (OR=1.03; 95% CI, 0.94-1.13).

BACKGROUND: Calcium channel blockers (CCBs) are more effective than placebo in lowering blood pressure and in preventing subsequent cardiovascular outcomes. However, observational studies of short-acting CCBs and controlled trials of long-acting CCBs have shown that although blood pressure is controlled, cardiovascular event rates increase. The authors performed a meta-analysis of randomized controlled trials comparing CCBs with first-line antihypertensives regarding their effects on cardiovascular events. population studied The analysis included 9 studies involving 27,743 patients. The mean age range was 53.9 to 76.1 years. Both men and women were represented in the analysis. Follow-up was 2 to 7 years with an estimated total follow-up of 120,000 person-years.

STUDY DESIGN AND VALIDITY: This is a meta-analysis of the existing literature. Studies were identified for inclusion through a systematic search of MEDLINE. To be included the randomized trials had to have more than 100 participants, follow-up longer than 2 years, compare CCBs with other first-line agents, and evaluate the effect on cardiovascular outcomes. The studies compared CCBs with diuretics, b-blockers, angiotensin-converting enzyme inhibitors, and clonidine. Two investigators independently abstracted data. Outcome data were analyzed by intention to treat except in one study that consisted of 429 patients. Tests for heterogeneity were performed. The meta-analysis is well done although limited by the quality of the included studies. Each of the 9 studies in the analysis has a limitation. Five of the studies were open design, and in 4 studies the authors had to contact investigators to obtain information on the primary outcomes. Two studies dealt primarily with patients with diabetes. In one study randomization favored the CCB arm, while in another the non-CCB arm had a more favorable baseline. The dropout rate for the studies ranged from 7% to 60%. A variety of sensitivity analyses were done to determine if one study, one drug type, or one type of patient profile contributed to the results. This did not appear to be the situation, although there was insufficient power in some of the sensitivity analyses to answer this question confidently.

OUTCOMES MEASURED: The outcomes measured were changes in systolic and diastolic blood pressure, acute myocardial infarctions, congestive heart failure, stroke, and all-cause mortality. The authors also evaluated the effect of treatment on the combined outcome of major cardiovascular events including acute myocardial infarction, congestive heart failure, stroke, and cardiovascular mortality.

RESULTS: CCBs lowered both systolic and diastolic blood pressure comparably with first-line agents. CCBs had a higher risk of acute myocardial infarction (odds ratio [OR]=1.26; 95% confidence interval [CI], 1.11-1.43), congestive heart failure (OR=1.25; 95% CI, 1.07-1.46), and major cardiovascular events (OR=1.10; 95% CI, 1.02-1.18). CCBs were comparable with other agents for reducing the risk of stroke (OR=0.90; 95% CI, 0.80-1.02) and all-cause mortality (OR=1.03; 95% CI, 0.94-1.13).

BACKGROUND: Calcium channel blockers (CCBs) are more effective than placebo in lowering blood pressure and in preventing subsequent cardiovascular outcomes. However, observational studies of short-acting CCBs and controlled trials of long-acting CCBs have shown that although blood pressure is controlled, cardiovascular event rates increase. The authors performed a meta-analysis of randomized controlled trials comparing CCBs with first-line antihypertensives regarding their effects on cardiovascular events. population studied The analysis included 9 studies involving 27,743 patients. The mean age range was 53.9 to 76.1 years. Both men and women were represented in the analysis. Follow-up was 2 to 7 years with an estimated total follow-up of 120,000 person-years.

STUDY DESIGN AND VALIDITY: This is a meta-analysis of the existing literature. Studies were identified for inclusion through a systematic search of MEDLINE. To be included the randomized trials had to have more than 100 participants, follow-up longer than 2 years, compare CCBs with other first-line agents, and evaluate the effect on cardiovascular outcomes. The studies compared CCBs with diuretics, b-blockers, angiotensin-converting enzyme inhibitors, and clonidine. Two investigators independently abstracted data. Outcome data were analyzed by intention to treat except in one study that consisted of 429 patients. Tests for heterogeneity were performed. The meta-analysis is well done although limited by the quality of the included studies. Each of the 9 studies in the analysis has a limitation. Five of the studies were open design, and in 4 studies the authors had to contact investigators to obtain information on the primary outcomes. Two studies dealt primarily with patients with diabetes. In one study randomization favored the CCB arm, while in another the non-CCB arm had a more favorable baseline. The dropout rate for the studies ranged from 7% to 60%. A variety of sensitivity analyses were done to determine if one study, one drug type, or one type of patient profile contributed to the results. This did not appear to be the situation, although there was insufficient power in some of the sensitivity analyses to answer this question confidently.

OUTCOMES MEASURED: The outcomes measured were changes in systolic and diastolic blood pressure, acute myocardial infarctions, congestive heart failure, stroke, and all-cause mortality. The authors also evaluated the effect of treatment on the combined outcome of major cardiovascular events including acute myocardial infarction, congestive heart failure, stroke, and cardiovascular mortality.

RESULTS: CCBs lowered both systolic and diastolic blood pressure comparably with first-line agents. CCBs had a higher risk of acute myocardial infarction (odds ratio [OR]=1.26; 95% confidence interval [CI], 1.11-1.43), congestive heart failure (OR=1.25; 95% CI, 1.07-1.46), and major cardiovascular events (OR=1.10; 95% CI, 1.02-1.18). CCBs were comparable with other agents for reducing the risk of stroke (OR=0.90; 95% CI, 0.80-1.02) and all-cause mortality (OR=1.03; 95% CI, 0.94-1.13).

BACKGROUND: The sensitivity of the conventional Pap test is estimated at 51% with a specificity of 98%. Newer technologies including thin-layer cytology (Thin-Prep), computerized re-screening (Papnet), and algorithmic classification (AutoPap) of slides can increase the sensitivity of cervical cancer screening by up to 30% at an increased cost of $5 to $10 per slide. The specificity of the new technologies is not reported. The impact of these tests on cost-effectiveness has not been clearly described. In general, a screening test is cost-effective (less cost and more benefit) when the incidence of the disease is common enough to warrant screening, the disease has a long asymptomatic period during which the disease can be identified, or the specificity of the test is high, resulting in less false-positive tests. An additional way to improve cost-effectiveness is if the cost of the screening test and subsequent treatments can be decreased through better identification or definitive treatment of clinically progressive disease.

POPULATION STUDIED: This theoretical model used data based on American women aged 15 to 85 years who were at average risk for cervical cancer.

STUDY DESIGN AND VALIDITY: This study is a cost-effectiveness analysis designed to estimate the cost of screening assuming several different scenarios. Cost is defined as direct medical costs, including inpatient and outpatient costs associated with the diagnosis and treatment of cervical dysplasia and cancer. Cost-benefit was estimated using several scenarios including varying the screening interval (1-, 2-, 3-, and 5-year intervals), altering the specificity of the test from 80% to 99% with sensitivity constant at 51%, and altering the sensitivity of the initial screening test from 51% to 99% using a constant specificity of 97%. Costs and years of life were discounted at 3% annually and varied 0% to 5% in sensitivity analysis. Overall this was a well-done analysis. The authors focused only on direct costs and did not estimate the effect of screening on other costs such as time lost from work and child care expense. Also, the impact of screening on quality of life was not factored into the analysis. Treatment options for atypical squamous cells of uncertain significance, low- through high-grade squamous intraepithelial lesions, and carcinoma are clearly described for determination of costs. Sensitivity analysis included the pertinent variables of sensitivity and specificity of the screening test, and screening intervals. Discount for costs and benefit was included in this analysis

OUTCOMES MEASURED: Effectiveness as measured is the incremental cost per life-year saved.

RESULTS: When a screening Pap test is used at a constant screening interval, increased sensitivity or decreased specificity of the test increases the incremental cost per life-year saved. In this analysis, the diagnosis and treatment of low-grade lesions had the greatest effect on cost-effectiveness estimates. If a new test with increased sensitivity does not cost more than the conventional test, it is only cost-effective if the screening interval is 3 years and the cost of diagnosing and treating low-grade lesions is $550 (which is lower than 75% of the cases in this data). The diagnosis, workup, and treatment of low-grade lesions that may regress contributes to increased cost without benefit. For any screening interval a new screening test with increased sensitivity that costs more than $3 per slide over the conventional test will not be cost-effective.

BACKGROUND: The sensitivity of the conventional Pap test is estimated at 51% with a specificity of 98%. Newer technologies including thin-layer cytology (Thin-Prep), computerized re-screening (Papnet), and algorithmic classification (AutoPap) of slides can increase the sensitivity of cervical cancer screening by up to 30% at an increased cost of $5 to $10 per slide. The specificity of the new technologies is not reported. The impact of these tests on cost-effectiveness has not been clearly described. In general, a screening test is cost-effective (less cost and more benefit) when the incidence of the disease is common enough to warrant screening, the disease has a long asymptomatic period during which the disease can be identified, or the specificity of the test is high, resulting in less false-positive tests. An additional way to improve cost-effectiveness is if the cost of the screening test and subsequent treatments can be decreased through better identification or definitive treatment of clinically progressive disease.

POPULATION STUDIED: This theoretical model used data based on American women aged 15 to 85 years who were at average risk for cervical cancer.

STUDY DESIGN AND VALIDITY: This study is a cost-effectiveness analysis designed to estimate the cost of screening assuming several different scenarios. Cost is defined as direct medical costs, including inpatient and outpatient costs associated with the diagnosis and treatment of cervical dysplasia and cancer. Cost-benefit was estimated using several scenarios including varying the screening interval (1-, 2-, 3-, and 5-year intervals), altering the specificity of the test from 80% to 99% with sensitivity constant at 51%, and altering the sensitivity of the initial screening test from 51% to 99% using a constant specificity of 97%. Costs and years of life were discounted at 3% annually and varied 0% to 5% in sensitivity analysis. Overall this was a well-done analysis. The authors focused only on direct costs and did not estimate the effect of screening on other costs such as time lost from work and child care expense. Also, the impact of screening on quality of life was not factored into the analysis. Treatment options for atypical squamous cells of uncertain significance, low- through high-grade squamous intraepithelial lesions, and carcinoma are clearly described for determination of costs. Sensitivity analysis included the pertinent variables of sensitivity and specificity of the screening test, and screening intervals. Discount for costs and benefit was included in this analysis

OUTCOMES MEASURED: Effectiveness as measured is the incremental cost per life-year saved.

RESULTS: When a screening Pap test is used at a constant screening interval, increased sensitivity or decreased specificity of the test increases the incremental cost per life-year saved. In this analysis, the diagnosis and treatment of low-grade lesions had the greatest effect on cost-effectiveness estimates. If a new test with increased sensitivity does not cost more than the conventional test, it is only cost-effective if the screening interval is 3 years and the cost of diagnosing and treating low-grade lesions is $550 (which is lower than 75% of the cases in this data). The diagnosis, workup, and treatment of low-grade lesions that may regress contributes to increased cost without benefit. For any screening interval a new screening test with increased sensitivity that costs more than $3 per slide over the conventional test will not be cost-effective.

BACKGROUND: The sensitivity of the conventional Pap test is estimated at 51% with a specificity of 98%. Newer technologies including thin-layer cytology (Thin-Prep), computerized re-screening (Papnet), and algorithmic classification (AutoPap) of slides can increase the sensitivity of cervical cancer screening by up to 30% at an increased cost of $5 to $10 per slide. The specificity of the new technologies is not reported. The impact of these tests on cost-effectiveness has not been clearly described. In general, a screening test is cost-effective (less cost and more benefit) when the incidence of the disease is common enough to warrant screening, the disease has a long asymptomatic period during which the disease can be identified, or the specificity of the test is high, resulting in less false-positive tests. An additional way to improve cost-effectiveness is if the cost of the screening test and subsequent treatments can be decreased through better identification or definitive treatment of clinically progressive disease.

POPULATION STUDIED: This theoretical model used data based on American women aged 15 to 85 years who were at average risk for cervical cancer.

STUDY DESIGN AND VALIDITY: This study is a cost-effectiveness analysis designed to estimate the cost of screening assuming several different scenarios. Cost is defined as direct medical costs, including inpatient and outpatient costs associated with the diagnosis and treatment of cervical dysplasia and cancer. Cost-benefit was estimated using several scenarios including varying the screening interval (1-, 2-, 3-, and 5-year intervals), altering the specificity of the test from 80% to 99% with sensitivity constant at 51%, and altering the sensitivity of the initial screening test from 51% to 99% using a constant specificity of 97%. Costs and years of life were discounted at 3% annually and varied 0% to 5% in sensitivity analysis. Overall this was a well-done analysis. The authors focused only on direct costs and did not estimate the effect of screening on other costs such as time lost from work and child care expense. Also, the impact of screening on quality of life was not factored into the analysis. Treatment options for atypical squamous cells of uncertain significance, low- through high-grade squamous intraepithelial lesions, and carcinoma are clearly described for determination of costs. Sensitivity analysis included the pertinent variables of sensitivity and specificity of the screening test, and screening intervals. Discount for costs and benefit was included in this analysis

OUTCOMES MEASURED: Effectiveness as measured is the incremental cost per life-year saved.

RESULTS: When a screening Pap test is used at a constant screening interval, increased sensitivity or decreased specificity of the test increases the incremental cost per life-year saved. In this analysis, the diagnosis and treatment of low-grade lesions had the greatest effect on cost-effectiveness estimates. If a new test with increased sensitivity does not cost more than the conventional test, it is only cost-effective if the screening interval is 3 years and the cost of diagnosing and treating low-grade lesions is $550 (which is lower than 75% of the cases in this data). The diagnosis, workup, and treatment of low-grade lesions that may regress contributes to increased cost without benefit. For any screening interval a new screening test with increased sensitivity that costs more than $3 per slide over the conventional test will not be cost-effective.

BACKGROUND: Intermittent claudication is a painful symptom of peripheral arterial disease. Nonsurgical treatment consists of modification of lifestyle risk factors (quit smoking, lower cholesterol levels), regular physical exercise, and a variety of medications. The clinical effectiveness of these interventions has usually been modest. Gingko biloba, a commonly used medicinal herb, has active ingredients that inhibit platelets and potentially decrease red blood cell aggregation. Because of these actions, it has been tested for intermittent claudication. Although some controlled studies have suggested benefit, the results have been inconclusive. The authors performed a meta-analysis to better summarize the current evidence.

POPULATION STUDIED: A total of 415 patients were included in this analysis. Their demographic information was not provided.

STUDY DESIGN AND VALIDITY: This was a meta-analysis of the existing literature. Manuscripts were identified for inclusion through a systematic search of 6 appropriate databases, contacting manufacturers of the product for published and unpublished literature, and contacting authors for additional data. Eight randomized controlled trials (RCTs) were identified that compared gingko with placebo and included an assessment of walking distance. Two researchers independently reviewed each study, grading them on quality (randomization strategy, description of withdrawals and dropouts, blinding protocol) and extracting information on pain-free walking distance. Appropriate statistical tools were used to find the pooled difference in pain-free walking distance between gingko and placebo.

OUTCOMES MEASURED: The primary outcome studied was pain-free walking distance. Seven of the 8 studies also reported maximal walking distance at baseline and after randomization to gingko or placebo. Three of the 8 studies used the same standardized assessment of treadmill walking that included ergometer speed of 3 km per hour on a grade of 12%.

RESULTS: Six of the 8 RCTs had a quality score of at least 4 on a scale of 1 to 5. Seven of the studies showed that gingko was more effective than placebo; however, only 4 of those studies were statistically significant. When all 8 studies were pooled, gingko increased pain-free walking distance by 34 meters (95% confidence interval, 26-43 m) more than placebo. When the authors pooled different subsets of articles, similar results were found. Side effects of gingko were not reported in 3 of the studies. In the remaining 5 studies, the primary side effects were abdominal complaints, nausea, and dyspepsia, although the rates were not given.

BACKGROUND: Intermittent claudication is a painful symptom of peripheral arterial disease. Nonsurgical treatment consists of modification of lifestyle risk factors (quit smoking, lower cholesterol levels), regular physical exercise, and a variety of medications. The clinical effectiveness of these interventions has usually been modest. Gingko biloba, a commonly used medicinal herb, has active ingredients that inhibit platelets and potentially decrease red blood cell aggregation. Because of these actions, it has been tested for intermittent claudication. Although some controlled studies have suggested benefit, the results have been inconclusive. The authors performed a meta-analysis to better summarize the current evidence.

POPULATION STUDIED: A total of 415 patients were included in this analysis. Their demographic information was not provided.

STUDY DESIGN AND VALIDITY: This was a meta-analysis of the existing literature. Manuscripts were identified for inclusion through a systematic search of 6 appropriate databases, contacting manufacturers of the product for published and unpublished literature, and contacting authors for additional data. Eight randomized controlled trials (RCTs) were identified that compared gingko with placebo and included an assessment of walking distance. Two researchers independently reviewed each study, grading them on quality (randomization strategy, description of withdrawals and dropouts, blinding protocol) and extracting information on pain-free walking distance. Appropriate statistical tools were used to find the pooled difference in pain-free walking distance between gingko and placebo.

OUTCOMES MEASURED: The primary outcome studied was pain-free walking distance. Seven of the 8 studies also reported maximal walking distance at baseline and after randomization to gingko or placebo. Three of the 8 studies used the same standardized assessment of treadmill walking that included ergometer speed of 3 km per hour on a grade of 12%.

RESULTS: Six of the 8 RCTs had a quality score of at least 4 on a scale of 1 to 5. Seven of the studies showed that gingko was more effective than placebo; however, only 4 of those studies were statistically significant. When all 8 studies were pooled, gingko increased pain-free walking distance by 34 meters (95% confidence interval, 26-43 m) more than placebo. When the authors pooled different subsets of articles, similar results were found. Side effects of gingko were not reported in 3 of the studies. In the remaining 5 studies, the primary side effects were abdominal complaints, nausea, and dyspepsia, although the rates were not given.

BACKGROUND: Intermittent claudication is a painful symptom of peripheral arterial disease. Nonsurgical treatment consists of modification of lifestyle risk factors (quit smoking, lower cholesterol levels), regular physical exercise, and a variety of medications. The clinical effectiveness of these interventions has usually been modest. Gingko biloba, a commonly used medicinal herb, has active ingredients that inhibit platelets and potentially decrease red blood cell aggregation. Because of these actions, it has been tested for intermittent claudication. Although some controlled studies have suggested benefit, the results have been inconclusive. The authors performed a meta-analysis to better summarize the current evidence.

POPULATION STUDIED: A total of 415 patients were included in this analysis. Their demographic information was not provided.

STUDY DESIGN AND VALIDITY: This was a meta-analysis of the existing literature. Manuscripts were identified for inclusion through a systematic search of 6 appropriate databases, contacting manufacturers of the product for published and unpublished literature, and contacting authors for additional data. Eight randomized controlled trials (RCTs) were identified that compared gingko with placebo and included an assessment of walking distance. Two researchers independently reviewed each study, grading them on quality (randomization strategy, description of withdrawals and dropouts, blinding protocol) and extracting information on pain-free walking distance. Appropriate statistical tools were used to find the pooled difference in pain-free walking distance between gingko and placebo.

OUTCOMES MEASURED: The primary outcome studied was pain-free walking distance. Seven of the 8 studies also reported maximal walking distance at baseline and after randomization to gingko or placebo. Three of the 8 studies used the same standardized assessment of treadmill walking that included ergometer speed of 3 km per hour on a grade of 12%.

RESULTS: Six of the 8 RCTs had a quality score of at least 4 on a scale of 1 to 5. Seven of the studies showed that gingko was more effective than placebo; however, only 4 of those studies were statistically significant. When all 8 studies were pooled, gingko increased pain-free walking distance by 34 meters (95% confidence interval, 26-43 m) more than placebo. When the authors pooled different subsets of articles, similar results were found. Side effects of gingko were not reported in 3 of the studies. In the remaining 5 studies, the primary side effects were abdominal complaints, nausea, and dyspepsia, although the rates were not given.