Clinical Inquiries

Evidence summary

A prospective cohort study of 96 symptomatic women, average age 55.8 years, who were referred for coronary angiography, examined the accuracy of ETT compared with the gold standard of conventional coronary angiography.¹ Sensitivity, specificity, and diagnostic accuracy were comparatively low for ETT (TABLE). The authors concluded that ETT has limited diagnostic value in women with suspected CAD. Myocardial perfusion imaging (MPI) is more predictive of CAD, as a prospective cohort study of 68 symptomatic women demonstrated.²

TABLE
Suspect CAD in your female patient? Here’s how various tests compare with coronary angiography

A meta-analysis of 14 studies that compared dobutamine stress echocardiography with conventional coronary angiography in 901 women found an overall sensitivity of 72% and specificity of 88% for echocardiography.³

MDCT has high accuracy, but also some limitations
Three prospective cohort studies compared 64-, 40-, and 16-slice MDCT with conventional coronary angiography in 123, 21, and 70 symptomatic women, respectively, and each study demonstrated high sensitivity and specificity for MDCT in diagnosing CAD.^4-6 Diagnostic accuracy was similar among slice techniques. The studies had multiple limitations, including location (potential population bias), patient symptoms, and setting (potential referral bias).

All the studies of MDCT included symptomatic patients from cardiologists or tertiary care centers in Europe and Israel, potentially lessening the technique’s generalizability to many clinical settings. Moreover, the availability of MDCT is limited, especially compared with stress echocardiogram and MPI.

MDCT requires a heart rate <60 to 70 beats per minute, which necessitates giving beta-blockers to patients with higher heart rates; not all patients can tolerate the medication or lower heart rate. MDCT also requires giving intravenous contrast media to visualize the coronary arteries and exposes the patient to a high level of radiation.

Notably, all studies of ETT, MPI, stress echocardiography, and MDCT enrolled symptomatic patients, limiting their evaluation as screening tools.

Recommendations

The American Heart Association recommends testing symptomatic women with a Framing-ham risk score of 10% or greater. A 2005 consensus statement allows providers to rely on local practices and available tests, with the caveat that ETT is the preferred initial test.⁷

The American College of Radiology expert consensus panel recommends the use of stress nuclear imaging and chest radiography to evaluate patients with chronic chest pain and suspected CAD; the recommendation does not specify testing method based on sex.⁸

Evidence summary

A prospective cohort study of 96 symptomatic women, average age 55.8 years, who were referred for coronary angiography, examined the accuracy of ETT compared with the gold standard of conventional coronary angiography.¹ Sensitivity, specificity, and diagnostic accuracy were comparatively low for ETT (TABLE). The authors concluded that ETT has limited diagnostic value in women with suspected CAD. Myocardial perfusion imaging (MPI) is more predictive of CAD, as a prospective cohort study of 68 symptomatic women demonstrated.²

TABLE
Suspect CAD in your female patient? Here’s how various tests compare with coronary angiography

A meta-analysis of 14 studies that compared dobutamine stress echocardiography with conventional coronary angiography in 901 women found an overall sensitivity of 72% and specificity of 88% for echocardiography.³

MDCT has high accuracy, but also some limitations
Three prospective cohort studies compared 64-, 40-, and 16-slice MDCT with conventional coronary angiography in 123, 21, and 70 symptomatic women, respectively, and each study demonstrated high sensitivity and specificity for MDCT in diagnosing CAD.^4-6 Diagnostic accuracy was similar among slice techniques. The studies had multiple limitations, including location (potential population bias), patient symptoms, and setting (potential referral bias).

All the studies of MDCT included symptomatic patients from cardiologists or tertiary care centers in Europe and Israel, potentially lessening the technique’s generalizability to many clinical settings. Moreover, the availability of MDCT is limited, especially compared with stress echocardiogram and MPI.

MDCT requires a heart rate <60 to 70 beats per minute, which necessitates giving beta-blockers to patients with higher heart rates; not all patients can tolerate the medication or lower heart rate. MDCT also requires giving intravenous contrast media to visualize the coronary arteries and exposes the patient to a high level of radiation.

Notably, all studies of ETT, MPI, stress echocardiography, and MDCT enrolled symptomatic patients, limiting their evaluation as screening tools.

Recommendations

The American Heart Association recommends testing symptomatic women with a Framing-ham risk score of 10% or greater. A 2005 consensus statement allows providers to rely on local practices and available tests, with the caveat that ETT is the preferred initial test.⁷

The American College of Radiology expert consensus panel recommends the use of stress nuclear imaging and chest radiography to evaluate patients with chronic chest pain and suspected CAD; the recommendation does not specify testing method based on sex.⁸

Evidence summary

A prospective cohort study of 96 symptomatic women, average age 55.8 years, who were referred for coronary angiography, examined the accuracy of ETT compared with the gold standard of conventional coronary angiography.¹ Sensitivity, specificity, and diagnostic accuracy were comparatively low for ETT (TABLE). The authors concluded that ETT has limited diagnostic value in women with suspected CAD. Myocardial perfusion imaging (MPI) is more predictive of CAD, as a prospective cohort study of 68 symptomatic women demonstrated.²

TABLE
Suspect CAD in your female patient? Here’s how various tests compare with coronary angiography

A meta-analysis of 14 studies that compared dobutamine stress echocardiography with conventional coronary angiography in 901 women found an overall sensitivity of 72% and specificity of 88% for echocardiography.³

MDCT has high accuracy, but also some limitations
Three prospective cohort studies compared 64-, 40-, and 16-slice MDCT with conventional coronary angiography in 123, 21, and 70 symptomatic women, respectively, and each study demonstrated high sensitivity and specificity for MDCT in diagnosing CAD.^4-6 Diagnostic accuracy was similar among slice techniques. The studies had multiple limitations, including location (potential population bias), patient symptoms, and setting (potential referral bias).

All the studies of MDCT included symptomatic patients from cardiologists or tertiary care centers in Europe and Israel, potentially lessening the technique’s generalizability to many clinical settings. Moreover, the availability of MDCT is limited, especially compared with stress echocardiogram and MPI.

MDCT requires a heart rate <60 to 70 beats per minute, which necessitates giving beta-blockers to patients with higher heart rates; not all patients can tolerate the medication or lower heart rate. MDCT also requires giving intravenous contrast media to visualize the coronary arteries and exposes the patient to a high level of radiation.

Notably, all studies of ETT, MPI, stress echocardiography, and MDCT enrolled symptomatic patients, limiting their evaluation as screening tools.

Recommendations

The American Heart Association recommends testing symptomatic women with a Framing-ham risk score of 10% or greater. A 2005 consensus statement allows providers to rely on local practices and available tests, with the caveat that ETT is the preferred initial test.⁷

The American College of Radiology expert consensus panel recommends the use of stress nuclear imaging and chest radiography to evaluate patients with chronic chest pain and suspected CAD; the recommendation does not specify testing method based on sex.⁸

Evidence summary

Patients with either IFG or IGT have a significant risk of progressing to diabetes. A recent Cochrane review evaluated studies that randomized patients to intensive exercise and diet counseling or standard advice with follow-up for 1 to 6 years.¹ Although treatment arms varied from study to study, exercise recommendations averaged at least 150 minutes a week and diet recommendations included counseling by dieticians. These lifestyle interventions reduced progression to diabetes by 37%. Another meta-analysis showed a relative risk reduction of 49% for lifestyle changes.²

Metformin is the most effective drug; acarbose and orlistat also help
This meta-analysis also encompassed 10 RCTs that evaluated the effectiveness of pharmacologic interventions, including oral diabetes drugs (metformin, phenformin, acarbose, glipizide, flumamine) and an antiobesity drug (orlistat).² Metformin was the most effective drug, with a 31% to 35% relative risk reduction (number needed to treat [NNT]=7-14), although acarbose and orlistat also produced significant reductions. In a small study, glipizide didn’t prevent development of diabetes.

A 2006 Cochrane review of acarbose encompassed 5 RCTs, including the Study to Prevent Non-Insulin-Dependent Diabetes (STOP-NIDDM), which showed a relative risk reduction of 22%.³

Rosiglitazone offers benefit, but also hazard
The Diabetes Reduction Assessment with ramipril and rosiglitazone Medication (DREAM) Trial of 5269 participants with IGT or IFG compared treatment with rosiglitazone and placebo.⁴ Rosiglitazone reduced development of diabetes for participants (hazard ratio=0.40; 95% confidence interval [CI], 0.35-0.46; P<.0001; NNT=5).

However, the risk of heart failure was higher in the rosiglitazone arm, with a risk ratio of 7.00 (95% CI, 1.59-30.76) and a number needed to harm of 250. No statistically significant difference was noted in cardiovascular-related deaths. This trial is consistent with recent evidence showing an increased risk of fluid overload and heart failure in patients with diabetes who take thiazolidinediones.⁵

ACE inhibitors aren’t routinely recommended
Early evidence suggested that blockade of the renin-angiotensin system might delay the onset of diabetes.⁶ The DREAM trial included a ramipril arm to evaluate for this effect in IGT and IFG.⁷ After 3 years of follow-up, no significant decrease in the incidence of diabetes was found among participants taking ramipril compared with placebo.

However, a significant regression to normoglycemia was observed in participants taking ramipril, which suggests that ACE inhibitors may have a modest favorable effect on glucose metabolism. Routine use of ACE inhibitors for the express purpose of preventing diabetes isn’t indicated at this time.

Recommendations

The American Diabetes Association’s (ADA) 2009 position statement recommends starting treatment for IGT or IFG with intensive lifestyle modifications, including referral to an effective ongoing support program for loss of 5% to 10% of body weight and increasing exercise to at least 150 minutes a week of moderate aerobic activity (50%-70% of maximum heart rate).⁸ Follow-up counseling is important for success.

Metformin can be considered in addition to lifestyle interventions for patients at high risk for progression to diabetes, defined as:

• both IGT and IFG plus 1 other risk factor, such as hemoglobin A1C >6%, hypertension, low levels of high-density lipoprotein, elevated triglycerides, or diabetes in a first-degree relative
• obesity
• <60 years of age.

The ADA recommends against using other drugs for diabetes prevention because of issues of cost, side effects, and failure to produce a persistent pharmacologic effect. Patients with prediabetes should be monitored annually for progression to diabetes, using either fasting glucose or a 2-hour oral glucose tolerance test.

Evidence summary

Patients with either IFG or IGT have a significant risk of progressing to diabetes. A recent Cochrane review evaluated studies that randomized patients to intensive exercise and diet counseling or standard advice with follow-up for 1 to 6 years.¹ Although treatment arms varied from study to study, exercise recommendations averaged at least 150 minutes a week and diet recommendations included counseling by dieticians. These lifestyle interventions reduced progression to diabetes by 37%. Another meta-analysis showed a relative risk reduction of 49% for lifestyle changes.²

Metformin is the most effective drug; acarbose and orlistat also help
This meta-analysis also encompassed 10 RCTs that evaluated the effectiveness of pharmacologic interventions, including oral diabetes drugs (metformin, phenformin, acarbose, glipizide, flumamine) and an antiobesity drug (orlistat).² Metformin was the most effective drug, with a 31% to 35% relative risk reduction (number needed to treat [NNT]=7-14), although acarbose and orlistat also produced significant reductions. In a small study, glipizide didn’t prevent development of diabetes.

A 2006 Cochrane review of acarbose encompassed 5 RCTs, including the Study to Prevent Non-Insulin-Dependent Diabetes (STOP-NIDDM), which showed a relative risk reduction of 22%.³

Rosiglitazone offers benefit, but also hazard
The Diabetes Reduction Assessment with ramipril and rosiglitazone Medication (DREAM) Trial of 5269 participants with IGT or IFG compared treatment with rosiglitazone and placebo.⁴ Rosiglitazone reduced development of diabetes for participants (hazard ratio=0.40; 95% confidence interval [CI], 0.35-0.46; P<.0001; NNT=5).

However, the risk of heart failure was higher in the rosiglitazone arm, with a risk ratio of 7.00 (95% CI, 1.59-30.76) and a number needed to harm of 250. No statistically significant difference was noted in cardiovascular-related deaths. This trial is consistent with recent evidence showing an increased risk of fluid overload and heart failure in patients with diabetes who take thiazolidinediones.⁵

ACE inhibitors aren’t routinely recommended
Early evidence suggested that blockade of the renin-angiotensin system might delay the onset of diabetes.⁶ The DREAM trial included a ramipril arm to evaluate for this effect in IGT and IFG.⁷ After 3 years of follow-up, no significant decrease in the incidence of diabetes was found among participants taking ramipril compared with placebo.

However, a significant regression to normoglycemia was observed in participants taking ramipril, which suggests that ACE inhibitors may have a modest favorable effect on glucose metabolism. Routine use of ACE inhibitors for the express purpose of preventing diabetes isn’t indicated at this time.

Recommendations

The American Diabetes Association’s (ADA) 2009 position statement recommends starting treatment for IGT or IFG with intensive lifestyle modifications, including referral to an effective ongoing support program for loss of 5% to 10% of body weight and increasing exercise to at least 150 minutes a week of moderate aerobic activity (50%-70% of maximum heart rate).⁸ Follow-up counseling is important for success.

Metformin can be considered in addition to lifestyle interventions for patients at high risk for progression to diabetes, defined as:

• both IGT and IFG plus 1 other risk factor, such as hemoglobin A1C >6%, hypertension, low levels of high-density lipoprotein, elevated triglycerides, or diabetes in a first-degree relative
• obesity
• <60 years of age.

The ADA recommends against using other drugs for diabetes prevention because of issues of cost, side effects, and failure to produce a persistent pharmacologic effect. Patients with prediabetes should be monitored annually for progression to diabetes, using either fasting glucose or a 2-hour oral glucose tolerance test.

Evidence summary

Patients with either IFG or IGT have a significant risk of progressing to diabetes. A recent Cochrane review evaluated studies that randomized patients to intensive exercise and diet counseling or standard advice with follow-up for 1 to 6 years.¹ Although treatment arms varied from study to study, exercise recommendations averaged at least 150 minutes a week and diet recommendations included counseling by dieticians. These lifestyle interventions reduced progression to diabetes by 37%. Another meta-analysis showed a relative risk reduction of 49% for lifestyle changes.²

Metformin is the most effective drug; acarbose and orlistat also help
This meta-analysis also encompassed 10 RCTs that evaluated the effectiveness of pharmacologic interventions, including oral diabetes drugs (metformin, phenformin, acarbose, glipizide, flumamine) and an antiobesity drug (orlistat).² Metformin was the most effective drug, with a 31% to 35% relative risk reduction (number needed to treat [NNT]=7-14), although acarbose and orlistat also produced significant reductions. In a small study, glipizide didn’t prevent development of diabetes.

A 2006 Cochrane review of acarbose encompassed 5 RCTs, including the Study to Prevent Non-Insulin-Dependent Diabetes (STOP-NIDDM), which showed a relative risk reduction of 22%.³

Rosiglitazone offers benefit, but also hazard
The Diabetes Reduction Assessment with ramipril and rosiglitazone Medication (DREAM) Trial of 5269 participants with IGT or IFG compared treatment with rosiglitazone and placebo.⁴ Rosiglitazone reduced development of diabetes for participants (hazard ratio=0.40; 95% confidence interval [CI], 0.35-0.46; P<.0001; NNT=5).

However, the risk of heart failure was higher in the rosiglitazone arm, with a risk ratio of 7.00 (95% CI, 1.59-30.76) and a number needed to harm of 250. No statistically significant difference was noted in cardiovascular-related deaths. This trial is consistent with recent evidence showing an increased risk of fluid overload and heart failure in patients with diabetes who take thiazolidinediones.⁵

ACE inhibitors aren’t routinely recommended
Early evidence suggested that blockade of the renin-angiotensin system might delay the onset of diabetes.⁶ The DREAM trial included a ramipril arm to evaluate for this effect in IGT and IFG.⁷ After 3 years of follow-up, no significant decrease in the incidence of diabetes was found among participants taking ramipril compared with placebo.

However, a significant regression to normoglycemia was observed in participants taking ramipril, which suggests that ACE inhibitors may have a modest favorable effect on glucose metabolism. Routine use of ACE inhibitors for the express purpose of preventing diabetes isn’t indicated at this time.

Recommendations

The American Diabetes Association’s (ADA) 2009 position statement recommends starting treatment for IGT or IFG with intensive lifestyle modifications, including referral to an effective ongoing support program for loss of 5% to 10% of body weight and increasing exercise to at least 150 minutes a week of moderate aerobic activity (50%-70% of maximum heart rate).⁸ Follow-up counseling is important for success.

Metformin can be considered in addition to lifestyle interventions for patients at high risk for progression to diabetes, defined as:

• both IGT and IFG plus 1 other risk factor, such as hemoglobin A1C >6%, hypertension, low levels of high-density lipoprotein, elevated triglycerides, or diabetes in a first-degree relative
• obesity
• <60 years of age.

The ADA recommends against using other drugs for diabetes prevention because of issues of cost, side effects, and failure to produce a persistent pharmacologic effect. Patients with prediabetes should be monitored annually for progression to diabetes, using either fasting glucose or a 2-hour oral glucose tolerance test.

Evidence summary

A 2009 Cochrane review analyzed the results of 28 RCTs that evaluated the effect of exercise (aerobic, resistance, or mixed aerobic and resistance) compared with no exercise, pharmacotherapy, CBT, and light therapy on symptoms of depression as measured by several validated depression scales.¹ The authors of the review compared pooled data from several different psychometric scales by calculating the standard mean difference (SMD) and used the following “rule of thumb” when interpreting the data: 0.2 represents a small effect, 0.5 a moderate effect, and 0.8 a large effect.

Pooled analysis of 23 RCTs (N=907) comparing exercise with no exercise found that exercise significantly reduced symptoms of depression (SMD=-0.82; 95% confidence interval [CI], -1.12 to -0.51). However, significant heterogeneity between the studies limits these conclusions. Five RCTs (N= 218) showed a moderate effect of exercise on maintaining the antidepressant effect for 4 to 26 months after the intervention (SMD=-0.44; 95% CI, -0.71 to -0.18).

Subgroup analyses in the same review showed no significant difference between exercise and CBT (6 RCTs, N=152; SMD=-0.17; 95% CI, -0.51 to 0.18) or between exercise and antidepressant drugs in reducing depressive symptoms (2 RCTs, N=201; SMD=-0.04; 95% CI, -0.31 to 0.24). The small size of these studies limits the ability to detect a potentially important clinical difference. One small RCT (N=18) in the review showed that exercise reduced symptoms more effectively than light therapy (SMD=-6.4; 95% CI, -10.2 to -2.6).

Mixed exercise and more of it get better results
Subgroup analyses within the same Cochrane review showed that resistance exercise (SMD=-1.34; 95% CI, -2.07 to -0.61) and mixed exercise (SMD=-1.47; 95% CI, -2.56 to -0.37) reduced symptoms of depression more than aerobic exercise alone (SMD=-0.63; 95% CI, -0.95 to -0.30). A very small RCT (N=23) noted larger reductions in Beck Depression Inventory scores among patients who exercised 3 to 5 times a week—30-minute sessions at 60% to 80% maximum heart rate—compared with patients who exercised only once a week (mean difference=-10.46; 95% CI, -16.06 to -4.85).²

Meditative exercise shows positive effect
A systematic review in 2008 assessed 6 RCTs that evaluated meditative exercises such as yoga, tai chi, and qigong for treating depression. All 6 studies showed a “positive response” to treatment, with 5 studies reporting a statistically significant reduction in depression scores. Because a great deal of heterogeneity existed among study parameters, no quantitative analysis was done to estimate the size of the positive effect.³

Recommendations

The National Institute for Health and Clinical Excellence recommends structured, supervised exercise programs, 3 times a week for 45 to 60 minutes each session over 10 to 14 weeks to treat mild depression.⁴

The Institute for Clinical Systems Improvement guideline recommends physical activity for 30 minutes 3 to 5 days a week to decrease symptoms of major depression.⁵

Evidence summary

A 2009 Cochrane review analyzed the results of 28 RCTs that evaluated the effect of exercise (aerobic, resistance, or mixed aerobic and resistance) compared with no exercise, pharmacotherapy, CBT, and light therapy on symptoms of depression as measured by several validated depression scales.¹ The authors of the review compared pooled data from several different psychometric scales by calculating the standard mean difference (SMD) and used the following “rule of thumb” when interpreting the data: 0.2 represents a small effect, 0.5 a moderate effect, and 0.8 a large effect.

Pooled analysis of 23 RCTs (N=907) comparing exercise with no exercise found that exercise significantly reduced symptoms of depression (SMD=-0.82; 95% confidence interval [CI], -1.12 to -0.51). However, significant heterogeneity between the studies limits these conclusions. Five RCTs (N= 218) showed a moderate effect of exercise on maintaining the antidepressant effect for 4 to 26 months after the intervention (SMD=-0.44; 95% CI, -0.71 to -0.18).

Subgroup analyses in the same review showed no significant difference between exercise and CBT (6 RCTs, N=152; SMD=-0.17; 95% CI, -0.51 to 0.18) or between exercise and antidepressant drugs in reducing depressive symptoms (2 RCTs, N=201; SMD=-0.04; 95% CI, -0.31 to 0.24). The small size of these studies limits the ability to detect a potentially important clinical difference. One small RCT (N=18) in the review showed that exercise reduced symptoms more effectively than light therapy (SMD=-6.4; 95% CI, -10.2 to -2.6).

Mixed exercise and more of it get better results
Subgroup analyses within the same Cochrane review showed that resistance exercise (SMD=-1.34; 95% CI, -2.07 to -0.61) and mixed exercise (SMD=-1.47; 95% CI, -2.56 to -0.37) reduced symptoms of depression more than aerobic exercise alone (SMD=-0.63; 95% CI, -0.95 to -0.30). A very small RCT (N=23) noted larger reductions in Beck Depression Inventory scores among patients who exercised 3 to 5 times a week—30-minute sessions at 60% to 80% maximum heart rate—compared with patients who exercised only once a week (mean difference=-10.46; 95% CI, -16.06 to -4.85).²

Meditative exercise shows positive effect
A systematic review in 2008 assessed 6 RCTs that evaluated meditative exercises such as yoga, tai chi, and qigong for treating depression. All 6 studies showed a “positive response” to treatment, with 5 studies reporting a statistically significant reduction in depression scores. Because a great deal of heterogeneity existed among study parameters, no quantitative analysis was done to estimate the size of the positive effect.³

Recommendations

The National Institute for Health and Clinical Excellence recommends structured, supervised exercise programs, 3 times a week for 45 to 60 minutes each session over 10 to 14 weeks to treat mild depression.⁴

The Institute for Clinical Systems Improvement guideline recommends physical activity for 30 minutes 3 to 5 days a week to decrease symptoms of major depression.⁵

Evidence summary

A 2009 Cochrane review analyzed the results of 28 RCTs that evaluated the effect of exercise (aerobic, resistance, or mixed aerobic and resistance) compared with no exercise, pharmacotherapy, CBT, and light therapy on symptoms of depression as measured by several validated depression scales.¹ The authors of the review compared pooled data from several different psychometric scales by calculating the standard mean difference (SMD) and used the following “rule of thumb” when interpreting the data: 0.2 represents a small effect, 0.5 a moderate effect, and 0.8 a large effect.

Pooled analysis of 23 RCTs (N=907) comparing exercise with no exercise found that exercise significantly reduced symptoms of depression (SMD=-0.82; 95% confidence interval [CI], -1.12 to -0.51). However, significant heterogeneity between the studies limits these conclusions. Five RCTs (N= 218) showed a moderate effect of exercise on maintaining the antidepressant effect for 4 to 26 months after the intervention (SMD=-0.44; 95% CI, -0.71 to -0.18).

Subgroup analyses in the same review showed no significant difference between exercise and CBT (6 RCTs, N=152; SMD=-0.17; 95% CI, -0.51 to 0.18) or between exercise and antidepressant drugs in reducing depressive symptoms (2 RCTs, N=201; SMD=-0.04; 95% CI, -0.31 to 0.24). The small size of these studies limits the ability to detect a potentially important clinical difference. One small RCT (N=18) in the review showed that exercise reduced symptoms more effectively than light therapy (SMD=-6.4; 95% CI, -10.2 to -2.6).

Mixed exercise and more of it get better results
Subgroup analyses within the same Cochrane review showed that resistance exercise (SMD=-1.34; 95% CI, -2.07 to -0.61) and mixed exercise (SMD=-1.47; 95% CI, -2.56 to -0.37) reduced symptoms of depression more than aerobic exercise alone (SMD=-0.63; 95% CI, -0.95 to -0.30). A very small RCT (N=23) noted larger reductions in Beck Depression Inventory scores among patients who exercised 3 to 5 times a week—30-minute sessions at 60% to 80% maximum heart rate—compared with patients who exercised only once a week (mean difference=-10.46; 95% CI, -16.06 to -4.85).²

Meditative exercise shows positive effect
A systematic review in 2008 assessed 6 RCTs that evaluated meditative exercises such as yoga, tai chi, and qigong for treating depression. All 6 studies showed a “positive response” to treatment, with 5 studies reporting a statistically significant reduction in depression scores. Because a great deal of heterogeneity existed among study parameters, no quantitative analysis was done to estimate the size of the positive effect.³

Recommendations

The National Institute for Health and Clinical Excellence recommends structured, supervised exercise programs, 3 times a week for 45 to 60 minutes each session over 10 to 14 weeks to treat mild depression.⁴

The Institute for Clinical Systems Improvement guideline recommends physical activity for 30 minutes 3 to 5 days a week to decrease symptoms of major depression.⁵

Evidence summary

A systematic review of 9 RCTs demonstrated that aspirin (75-325 mg) started soon after the onset of acute MI significantly reduced mortality, reinfarction, and stroke at 1 month compared with placebo (absolute risk reduction [ARR]=3.8%; number needed to treat [NNT]=26; 95% confidence interval [CI], 23-30).¹

One large RCT involving 17,187 patients with suspected acute MI showed that 162 mg aspirin given on the day of the MI resulted in a 2.6% ARR (NNT=38; 95% CI, 29-63) in vascular deaths at 35 days compared with placebo.² The survival benefit persisted for as long as 10 years. The RCT also found no significant difference between aspirin and placebo in rates of cerebral hemorrhage or bleeding requiring transfusions.

Patients who have had an MI without ST segment elevation should take clopidogrel (75 mg/d) and aspirin (81 mg/d) for 12 months. The combination has been shown to result in a 2.1% ARR (NNT=48) in deaths, recurrent MI, and stroke compared with aspirin alone.³ Patients who have had an ST segment elevation MI should take clopidogrel in combination with aspirin for at least 2 weeks.⁴

TABLE
Recommended drugs for post-MI patients

Intensive atorvastatin therapy lowers risk of death

The PROVE IT-TIMI 22 trial showed the benefit of early intensive therapy with the hydroxymethyl glutaryl coenzyme A reductase inhibitor atorvastatin to lower low-density lipoprotein <70 mg/dL post-MI.⁵ At 30 days after the event, atorvastatin 80 mg daily resulted in a 1.2% ARR in death and recurrent acute coronary syndrome (NNT=83; hazard ratio [HR]=0.72; 95% CI, 0.52-0.99). From 6 months to 24 months after the event, the ARR was 2.6% (NNT=38; HR=0.82; 95% CI, 0.69-0.99).

Beta-blockers significantly decrease late mortality
One systematic review of 63 RCTs showed that, in long-term trials, use of a beta-blocker significantly reduced the late mortality rate (NNT=48; odds ratio [OR]=0.77; 95% CI, 0.70-0.85).⁶ In another review of 82 RCTs, the mortality rate between 6 months and 4 years after MI decreased markedly in patients receiving a beta-blocker (OR=0.77; 95% CI, 0.69-0.85).⁷

ACE inhibitors decrease overall mortality, sudden cardiac death
An ACE inhibitor should be started regardless of the ejection fraction or the presence or absence of left ventricular systolic dysfunction. One systematic review that compared long-term mortality rates of patients started on an ACE inhibitor within 14 days of acute MI versus placebo found that ACE inhibitors significantly decreased overall mortality and sudden cardiac deaths between 2 and 42 months after the MI (NNT=42; OR=0.83; 95% CI, 0.71-0.97).⁸

Eplerenone + ACE inhibitor benefit patients with post-MI heart failure
The selective aldosterone blocker eplerenone appears to benefit patients with a decreased ejection fraction post-MI. The EPHESUS study demonstrated that eplerenone, when added to an ACE inhibitor, reduced all-cause mortality (ARR=1.4%; NNT=71; 95% CI, 47-200; RR=0.69; 95% CI, 0.54-0.89) and sudden cardiac death (ARR=0.5%; NNT=200; 95% CI, 125-∞; RR=0.63; 95% CI, 0.40-1.00) up to 30 days in patients with post-MI heart failure. Benefits were also seen after 16 months of treatment.⁹

Recommendations

The American College of Cardiology (ACC) and American Heart Association (AHA) provide the following recommendations in their joint 2006 Guidelines for Secondary Prevention for Patients with Coronary and Other Atherosclerotic Vascular Disease:¹⁰

• Low-dose aspirin should be used, as well as clopidogrel in combination with aspirin for up to 12 months after a non-ST elevation MI
• ACE inhibitors or angiotensin receptor blockers should be considered in all patients, and an aldosterone antagonist should be prescribed for patients with a diminished ejection fraction post-MI
• Beta-blockers should be used in all post-MI patients without contraindications.

The ACC/AHA 2007 Guidelines for the Management of Patients with Unstable Angina/Non–ST-Elevation Myocardial Infarction recommend the same medication combinations.¹¹ So does the 2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction, with the exception that clopidogrel in combination with aspirin is recommended for at least 14 days.¹²

Similarly, the British National Institute for Clinical Excellence Clinical Guideline 48 recommends that all post-MI patients be offered a combination of an ACE inhibitor, aspirin with clopidogrel, a beta-blocker, and a statin.¹³

Acknowledgement
The opinions and assertions contained herein are the private views of the authors and should not be construed as official or as reflecting the views of the US Department of the Navy or the Department of Defense.

Evidence summary

A systematic review of 9 RCTs demonstrated that aspirin (75-325 mg) started soon after the onset of acute MI significantly reduced mortality, reinfarction, and stroke at 1 month compared with placebo (absolute risk reduction [ARR]=3.8%; number needed to treat [NNT]=26; 95% confidence interval [CI], 23-30).¹

One large RCT involving 17,187 patients with suspected acute MI showed that 162 mg aspirin given on the day of the MI resulted in a 2.6% ARR (NNT=38; 95% CI, 29-63) in vascular deaths at 35 days compared with placebo.² The survival benefit persisted for as long as 10 years. The RCT also found no significant difference between aspirin and placebo in rates of cerebral hemorrhage or bleeding requiring transfusions.

Patients who have had an MI without ST segment elevation should take clopidogrel (75 mg/d) and aspirin (81 mg/d) for 12 months. The combination has been shown to result in a 2.1% ARR (NNT=48) in deaths, recurrent MI, and stroke compared with aspirin alone.³ Patients who have had an ST segment elevation MI should take clopidogrel in combination with aspirin for at least 2 weeks.⁴

TABLE
Recommended drugs for post-MI patients

Intensive atorvastatin therapy lowers risk of death

The PROVE IT-TIMI 22 trial showed the benefit of early intensive therapy with the hydroxymethyl glutaryl coenzyme A reductase inhibitor atorvastatin to lower low-density lipoprotein <70 mg/dL post-MI.⁵ At 30 days after the event, atorvastatin 80 mg daily resulted in a 1.2% ARR in death and recurrent acute coronary syndrome (NNT=83; hazard ratio [HR]=0.72; 95% CI, 0.52-0.99). From 6 months to 24 months after the event, the ARR was 2.6% (NNT=38; HR=0.82; 95% CI, 0.69-0.99).

Beta-blockers significantly decrease late mortality
One systematic review of 63 RCTs showed that, in long-term trials, use of a beta-blocker significantly reduced the late mortality rate (NNT=48; odds ratio [OR]=0.77; 95% CI, 0.70-0.85).⁶ In another review of 82 RCTs, the mortality rate between 6 months and 4 years after MI decreased markedly in patients receiving a beta-blocker (OR=0.77; 95% CI, 0.69-0.85).⁷

ACE inhibitors decrease overall mortality, sudden cardiac death
An ACE inhibitor should be started regardless of the ejection fraction or the presence or absence of left ventricular systolic dysfunction. One systematic review that compared long-term mortality rates of patients started on an ACE inhibitor within 14 days of acute MI versus placebo found that ACE inhibitors significantly decreased overall mortality and sudden cardiac deaths between 2 and 42 months after the MI (NNT=42; OR=0.83; 95% CI, 0.71-0.97).⁸

Eplerenone + ACE inhibitor benefit patients with post-MI heart failure
The selective aldosterone blocker eplerenone appears to benefit patients with a decreased ejection fraction post-MI. The EPHESUS study demonstrated that eplerenone, when added to an ACE inhibitor, reduced all-cause mortality (ARR=1.4%; NNT=71; 95% CI, 47-200; RR=0.69; 95% CI, 0.54-0.89) and sudden cardiac death (ARR=0.5%; NNT=200; 95% CI, 125-∞; RR=0.63; 95% CI, 0.40-1.00) up to 30 days in patients with post-MI heart failure. Benefits were also seen after 16 months of treatment.⁹

Recommendations

The American College of Cardiology (ACC) and American Heart Association (AHA) provide the following recommendations in their joint 2006 Guidelines for Secondary Prevention for Patients with Coronary and Other Atherosclerotic Vascular Disease:¹⁰

• Low-dose aspirin should be used, as well as clopidogrel in combination with aspirin for up to 12 months after a non-ST elevation MI
• ACE inhibitors or angiotensin receptor blockers should be considered in all patients, and an aldosterone antagonist should be prescribed for patients with a diminished ejection fraction post-MI
• Beta-blockers should be used in all post-MI patients without contraindications.

The ACC/AHA 2007 Guidelines for the Management of Patients with Unstable Angina/Non–ST-Elevation Myocardial Infarction recommend the same medication combinations.¹¹ So does the 2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction, with the exception that clopidogrel in combination with aspirin is recommended for at least 14 days.¹²

Similarly, the British National Institute for Clinical Excellence Clinical Guideline 48 recommends that all post-MI patients be offered a combination of an ACE inhibitor, aspirin with clopidogrel, a beta-blocker, and a statin.¹³

Acknowledgement
The opinions and assertions contained herein are the private views of the authors and should not be construed as official or as reflecting the views of the US Department of the Navy or the Department of Defense.

Evidence summary

A systematic review of 9 RCTs demonstrated that aspirin (75-325 mg) started soon after the onset of acute MI significantly reduced mortality, reinfarction, and stroke at 1 month compared with placebo (absolute risk reduction [ARR]=3.8%; number needed to treat [NNT]=26; 95% confidence interval [CI], 23-30).¹

One large RCT involving 17,187 patients with suspected acute MI showed that 162 mg aspirin given on the day of the MI resulted in a 2.6% ARR (NNT=38; 95% CI, 29-63) in vascular deaths at 35 days compared with placebo.² The survival benefit persisted for as long as 10 years. The RCT also found no significant difference between aspirin and placebo in rates of cerebral hemorrhage or bleeding requiring transfusions.

Patients who have had an MI without ST segment elevation should take clopidogrel (75 mg/d) and aspirin (81 mg/d) for 12 months. The combination has been shown to result in a 2.1% ARR (NNT=48) in deaths, recurrent MI, and stroke compared with aspirin alone.³ Patients who have had an ST segment elevation MI should take clopidogrel in combination with aspirin for at least 2 weeks.⁴

TABLE
Recommended drugs for post-MI patients

Intensive atorvastatin therapy lowers risk of death

The PROVE IT-TIMI 22 trial showed the benefit of early intensive therapy with the hydroxymethyl glutaryl coenzyme A reductase inhibitor atorvastatin to lower low-density lipoprotein <70 mg/dL post-MI.⁵ At 30 days after the event, atorvastatin 80 mg daily resulted in a 1.2% ARR in death and recurrent acute coronary syndrome (NNT=83; hazard ratio [HR]=0.72; 95% CI, 0.52-0.99). From 6 months to 24 months after the event, the ARR was 2.6% (NNT=38; HR=0.82; 95% CI, 0.69-0.99).

Beta-blockers significantly decrease late mortality
One systematic review of 63 RCTs showed that, in long-term trials, use of a beta-blocker significantly reduced the late mortality rate (NNT=48; odds ratio [OR]=0.77; 95% CI, 0.70-0.85).⁶ In another review of 82 RCTs, the mortality rate between 6 months and 4 years after MI decreased markedly in patients receiving a beta-blocker (OR=0.77; 95% CI, 0.69-0.85).⁷

ACE inhibitors decrease overall mortality, sudden cardiac death
An ACE inhibitor should be started regardless of the ejection fraction or the presence or absence of left ventricular systolic dysfunction. One systematic review that compared long-term mortality rates of patients started on an ACE inhibitor within 14 days of acute MI versus placebo found that ACE inhibitors significantly decreased overall mortality and sudden cardiac deaths between 2 and 42 months after the MI (NNT=42; OR=0.83; 95% CI, 0.71-0.97).⁸

Eplerenone + ACE inhibitor benefit patients with post-MI heart failure
The selective aldosterone blocker eplerenone appears to benefit patients with a decreased ejection fraction post-MI. The EPHESUS study demonstrated that eplerenone, when added to an ACE inhibitor, reduced all-cause mortality (ARR=1.4%; NNT=71; 95% CI, 47-200; RR=0.69; 95% CI, 0.54-0.89) and sudden cardiac death (ARR=0.5%; NNT=200; 95% CI, 125-∞; RR=0.63; 95% CI, 0.40-1.00) up to 30 days in patients with post-MI heart failure. Benefits were also seen after 16 months of treatment.⁹

Recommendations

The American College of Cardiology (ACC) and American Heart Association (AHA) provide the following recommendations in their joint 2006 Guidelines for Secondary Prevention for Patients with Coronary and Other Atherosclerotic Vascular Disease:¹⁰

• Low-dose aspirin should be used, as well as clopidogrel in combination with aspirin for up to 12 months after a non-ST elevation MI
• ACE inhibitors or angiotensin receptor blockers should be considered in all patients, and an aldosterone antagonist should be prescribed for patients with a diminished ejection fraction post-MI
• Beta-blockers should be used in all post-MI patients without contraindications.

The ACC/AHA 2007 Guidelines for the Management of Patients with Unstable Angina/Non–ST-Elevation Myocardial Infarction recommend the same medication combinations.¹¹ So does the 2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction, with the exception that clopidogrel in combination with aspirin is recommended for at least 14 days.¹²

Similarly, the British National Institute for Clinical Excellence Clinical Guideline 48 recommends that all post-MI patients be offered a combination of an ACE inhibitor, aspirin with clopidogrel, a beta-blocker, and a statin.¹³

Acknowledgement
The opinions and assertions contained herein are the private views of the authors and should not be construed as official or as reflecting the views of the US Department of the Navy or the Department of Defense.

Evidence summary

No RCTs have evaluated the risks, benefits, and clinical outcomes of screening for GDM. A review of universal screening compared with risk factor screening included 2 retrospective studies, 1 observational cohort study, and 1 nonconcurrent cohort study.^1-4

Risk factor screening misses women with GDM
All 4 studies clearly show that risk factor screening would miss patients with GDM.^1-4 Two studies found that the detection rate of GDM increases when universal screening is performed.^1,4

One observational study in a multiethnic cohort concluded that risk factor screening missed 30% of patients with GDM and that universal screening increased the detection rate from 8.3% to 12.6% (P=.001) compared with risk factor screening.¹ Similarly, a retrospective study of 147 pregnant women with GDM found that risk factor screening would have missed 23%.²

Universal screening diagnoses GDM earlier than risk factor screening
One prospective randomized study that compared universal screening (using a 50-g 1-hour glucose challenge test) in 1853 women with risk factor screening in 1299 women demonstrated that nearly half of those with GDM had no historical risk factors and would have been missed by risk factor screening in a low-prevalence, mostly Caucasian sample. The prevalence was 2.7% in the universal screening group vs 1.45% in the risk factor screening group (P<.03). Universal screening diagnosed GDM earlier than risk factor screening (mean gestation 30 ± 2.6 weeks vs 33 ± 3.7 weeks; P<.05).³

Need for insulin is similar, with and without GDM risk factors
A retrospective cohort study demonstrated that risk factor screening misses 43% of women with GDM. The study also showed that women with GDM who had identifiable risk factors and women without identifiable risk factors were equally likely to require insulin to control their GDM. Adverse birth outcomes such as macrosomia and shoulder dystocia or cesarean section were similar in patients with and without risk factors for GDM.⁴

Macrosomia and primary C-section increase along with glucose intolerance
The prospective cohort Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study of 23,316 women at 15 centers in 9 countries used the 2-hour 75-g oral glucose tolerance test at 24 to 32 weeks’ gestation to clarify the risks of adverse outcomes associated with varying degrees of maternal glucose intolerance. The study found a linear increase in the risk of macrosomia and primary cesarean section as glucose intolerance levels increased from normal to the gestational diabetes range.⁵

Recommendations

The US Preventive Services Task Force states that evidence is insufficient to advise for or against routine screening for GDM.⁶

The American College of Obstetricians and Gynecologists considers universal glucose challenge screening for GDM to be the most sensitive approach, but notes that some pregnant women at low risk may be less likely to benefit from testing.⁷

The Cochrane review protocol states that universally accepted screening is controversial because of a lack of clearly defined, universally accepted screening criteria and uncertainty about the severity of glucose intolerance at which treatment is beneficial.⁸

Evidence summary

No RCTs have evaluated the risks, benefits, and clinical outcomes of screening for GDM. A review of universal screening compared with risk factor screening included 2 retrospective studies, 1 observational cohort study, and 1 nonconcurrent cohort study.^1-4

Risk factor screening misses women with GDM
All 4 studies clearly show that risk factor screening would miss patients with GDM.^1-4 Two studies found that the detection rate of GDM increases when universal screening is performed.^1,4

One observational study in a multiethnic cohort concluded that risk factor screening missed 30% of patients with GDM and that universal screening increased the detection rate from 8.3% to 12.6% (P=.001) compared with risk factor screening.¹ Similarly, a retrospective study of 147 pregnant women with GDM found that risk factor screening would have missed 23%.²

Universal screening diagnoses GDM earlier than risk factor screening
One prospective randomized study that compared universal screening (using a 50-g 1-hour glucose challenge test) in 1853 women with risk factor screening in 1299 women demonstrated that nearly half of those with GDM had no historical risk factors and would have been missed by risk factor screening in a low-prevalence, mostly Caucasian sample. The prevalence was 2.7% in the universal screening group vs 1.45% in the risk factor screening group (P<.03). Universal screening diagnosed GDM earlier than risk factor screening (mean gestation 30 ± 2.6 weeks vs 33 ± 3.7 weeks; P<.05).³

Need for insulin is similar, with and without GDM risk factors
A retrospective cohort study demonstrated that risk factor screening misses 43% of women with GDM. The study also showed that women with GDM who had identifiable risk factors and women without identifiable risk factors were equally likely to require insulin to control their GDM. Adverse birth outcomes such as macrosomia and shoulder dystocia or cesarean section were similar in patients with and without risk factors for GDM.⁴

Macrosomia and primary C-section increase along with glucose intolerance
The prospective cohort Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study of 23,316 women at 15 centers in 9 countries used the 2-hour 75-g oral glucose tolerance test at 24 to 32 weeks’ gestation to clarify the risks of adverse outcomes associated with varying degrees of maternal glucose intolerance. The study found a linear increase in the risk of macrosomia and primary cesarean section as glucose intolerance levels increased from normal to the gestational diabetes range.⁵

Recommendations

The US Preventive Services Task Force states that evidence is insufficient to advise for or against routine screening for GDM.⁶

The American College of Obstetricians and Gynecologists considers universal glucose challenge screening for GDM to be the most sensitive approach, but notes that some pregnant women at low risk may be less likely to benefit from testing.⁷

The Cochrane review protocol states that universally accepted screening is controversial because of a lack of clearly defined, universally accepted screening criteria and uncertainty about the severity of glucose intolerance at which treatment is beneficial.⁸

Evidence summary

No RCTs have evaluated the risks, benefits, and clinical outcomes of screening for GDM. A review of universal screening compared with risk factor screening included 2 retrospective studies, 1 observational cohort study, and 1 nonconcurrent cohort study.^1-4

Risk factor screening misses women with GDM
All 4 studies clearly show that risk factor screening would miss patients with GDM.^1-4 Two studies found that the detection rate of GDM increases when universal screening is performed.^1,4

One observational study in a multiethnic cohort concluded that risk factor screening missed 30% of patients with GDM and that universal screening increased the detection rate from 8.3% to 12.6% (P=.001) compared with risk factor screening.¹ Similarly, a retrospective study of 147 pregnant women with GDM found that risk factor screening would have missed 23%.²

Universal screening diagnoses GDM earlier than risk factor screening
One prospective randomized study that compared universal screening (using a 50-g 1-hour glucose challenge test) in 1853 women with risk factor screening in 1299 women demonstrated that nearly half of those with GDM had no historical risk factors and would have been missed by risk factor screening in a low-prevalence, mostly Caucasian sample. The prevalence was 2.7% in the universal screening group vs 1.45% in the risk factor screening group (P<.03). Universal screening diagnosed GDM earlier than risk factor screening (mean gestation 30 ± 2.6 weeks vs 33 ± 3.7 weeks; P<.05).³

Need for insulin is similar, with and without GDM risk factors
A retrospective cohort study demonstrated that risk factor screening misses 43% of women with GDM. The study also showed that women with GDM who had identifiable risk factors and women without identifiable risk factors were equally likely to require insulin to control their GDM. Adverse birth outcomes such as macrosomia and shoulder dystocia or cesarean section were similar in patients with and without risk factors for GDM.⁴

Macrosomia and primary C-section increase along with glucose intolerance
The prospective cohort Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study of 23,316 women at 15 centers in 9 countries used the 2-hour 75-g oral glucose tolerance test at 24 to 32 weeks’ gestation to clarify the risks of adverse outcomes associated with varying degrees of maternal glucose intolerance. The study found a linear increase in the risk of macrosomia and primary cesarean section as glucose intolerance levels increased from normal to the gestational diabetes range.⁵

Recommendations

The US Preventive Services Task Force states that evidence is insufficient to advise for or against routine screening for GDM.⁶

The American College of Obstetricians and Gynecologists considers universal glucose challenge screening for GDM to be the most sensitive approach, but notes that some pregnant women at low risk may be less likely to benefit from testing.⁷

The Cochrane review protocol states that universally accepted screening is controversial because of a lack of clearly defined, universally accepted screening criteria and uncertainty about the severity of glucose intolerance at which treatment is beneficial.⁸

Evidence summary

Upper extremity venous thrombosis (UEVT)—which typically refers to thrombosis of the brachial, axillary, or subclavian veins—accounts for approximately 10% of all cases of venous thromboembolism.¹ UEVT can occur spontaneously (Paget-Schroetter syndrome) or develop as a complication of cancer or in-dwelling medical devices (such as long-term central venous catheters).

Although significant evidence-based data exist on treatment of lower extremity venous thrombosis, no good-quality studies specifically address management of UEVT. Review of the current literature revealed several small studies that compared various treatment strategies.

Thrombolytics may work better than anticoagulants in some patients
A small retrospective study randomized 20 patients with UEVT to either treatment with anticoagulant therapy with heparin and warfarin (n=11) or thrombolytic therapy (n=9).² After a mean follow-up period of 81.7 months for the anticoagulation group and 52.1 months for the thrombolytic group, 4 more patients in the thrombolytic group achieved complete clinical recovery and vein patency than in the anticoagulant group (P=.04). When patients who recovered completely were added to those who showed some clinical improvement, 89% of the thrombolytic therapy group had satisfactory outcomes, compared with 36% of the anticoagulant group (P=.028).

Another small retrospective study looked at 10 consecutive patients with UEVT who were treated with either anticoagulant therapy (n=6) or thrombolytics (n=4).³ Fifty percent of patients treated with anticoagulants experienced partial or complete improvement in symptoms, whereas 100% of patients treated with thrombolytics had partial or complete resolution of both symptoms and thrombi.

Overall, both studies raise the possibility that thrombolytic therapy is more effective than anticoagulation therapy in certain patients. The studies evaluated only active patients, 23 to 58 years of age, who had no contraindications to thrombolytic therapy. Neither study reported data on long-term outcomes such as recurrences, bleeding, or post-thrombotic sequelae.

Surgery may avoid long-term anticoagulation
Two case studies evaluated treatment of UEVT with thrombolytic therapy followed by various surgical interventions (angioplasty, thrombectomy, decompression via first rib resection or anterior scalenectomy, and venous bypass).^4,5 The first study reported that 8 of 9 patients who underwent first-rib resection and 1 of 2 who underwent scalenectomy were free of residual symptoms at follow-up (mean 2 years, range 6 months to 5 years).⁴ All patients were treated with thrombolytics before surgery.

The second study demonstrated that 50% of the patients treated with a surgical intervention without thrombolysis had complete symptom relief, while the remaining 50% reported relief from pain but still had occasional swelling.⁵ Although more invasive, surgery may eliminate the need for long-term anticoagulation therapy and enable a more rapid return to normal activities.

Data on vena cava filters are limited
Data supporting superior vena cava Green-field filters to treat UEVT are extremely limited. Of 6 patients with contraindications to anticoagulation therapy who were treated with a Greenfield filter, none had clinical evidence of pulmonary embolism at 14 months.⁶ The study reported no data regarding long-term sequelae or effects of the UEVT on the patients’ upper extremity.⁶

When in doubt, don’t (necessarily) take it out
For patients with central venous catheter-related deep vein thrombosis, taking out the catheter as part of treatment is controversial and should depend on clinical symptoms, the reason for the catheter, and duration of use, as well as physician judgment.⁷ No RCTs have studied the effects of catheter removal as part of initial treatment. Current guidelines recommend removing the catheter from patients with persistent symptoms who have failed anticoagulant or thrombolytic treatment.¹

Recommendations

The American College of Chest Physicians recommends therapeutic doses of intravenous unfractionated heparin, low-molecular-weight heparin, or fondaparinux for initial treatment of UEVT, followed by at least 3 months of treatment with a vitamin K antagonist.¹ The organization also suggests that surgical thrombectomy, superior vena caval filters, thrombolytic therapy, or catheter extraction may benefit selected patients.

Acknowledgement
The opinions and assertions contained herein are the private views of the author and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.

Evidence summary

Upper extremity venous thrombosis (UEVT)—which typically refers to thrombosis of the brachial, axillary, or subclavian veins—accounts for approximately 10% of all cases of venous thromboembolism.¹ UEVT can occur spontaneously (Paget-Schroetter syndrome) or develop as a complication of cancer or in-dwelling medical devices (such as long-term central venous catheters).

Although significant evidence-based data exist on treatment of lower extremity venous thrombosis, no good-quality studies specifically address management of UEVT. Review of the current literature revealed several small studies that compared various treatment strategies.

Thrombolytics may work better than anticoagulants in some patients
A small retrospective study randomized 20 patients with UEVT to either treatment with anticoagulant therapy with heparin and warfarin (n=11) or thrombolytic therapy (n=9).² After a mean follow-up period of 81.7 months for the anticoagulation group and 52.1 months for the thrombolytic group, 4 more patients in the thrombolytic group achieved complete clinical recovery and vein patency than in the anticoagulant group (P=.04). When patients who recovered completely were added to those who showed some clinical improvement, 89% of the thrombolytic therapy group had satisfactory outcomes, compared with 36% of the anticoagulant group (P=.028).

Another small retrospective study looked at 10 consecutive patients with UEVT who were treated with either anticoagulant therapy (n=6) or thrombolytics (n=4).³ Fifty percent of patients treated with anticoagulants experienced partial or complete improvement in symptoms, whereas 100% of patients treated with thrombolytics had partial or complete resolution of both symptoms and thrombi.

Overall, both studies raise the possibility that thrombolytic therapy is more effective than anticoagulation therapy in certain patients. The studies evaluated only active patients, 23 to 58 years of age, who had no contraindications to thrombolytic therapy. Neither study reported data on long-term outcomes such as recurrences, bleeding, or post-thrombotic sequelae.

Surgery may avoid long-term anticoagulation
Two case studies evaluated treatment of UEVT with thrombolytic therapy followed by various surgical interventions (angioplasty, thrombectomy, decompression via first rib resection or anterior scalenectomy, and venous bypass).^4,5 The first study reported that 8 of 9 patients who underwent first-rib resection and 1 of 2 who underwent scalenectomy were free of residual symptoms at follow-up (mean 2 years, range 6 months to 5 years).⁴ All patients were treated with thrombolytics before surgery.

The second study demonstrated that 50% of the patients treated with a surgical intervention without thrombolysis had complete symptom relief, while the remaining 50% reported relief from pain but still had occasional swelling.⁵ Although more invasive, surgery may eliminate the need for long-term anticoagulation therapy and enable a more rapid return to normal activities.

Data on vena cava filters are limited
Data supporting superior vena cava Green-field filters to treat UEVT are extremely limited. Of 6 patients with contraindications to anticoagulation therapy who were treated with a Greenfield filter, none had clinical evidence of pulmonary embolism at 14 months.⁶ The study reported no data regarding long-term sequelae or effects of the UEVT on the patients’ upper extremity.⁶

When in doubt, don’t (necessarily) take it out
For patients with central venous catheter-related deep vein thrombosis, taking out the catheter as part of treatment is controversial and should depend on clinical symptoms, the reason for the catheter, and duration of use, as well as physician judgment.⁷ No RCTs have studied the effects of catheter removal as part of initial treatment. Current guidelines recommend removing the catheter from patients with persistent symptoms who have failed anticoagulant or thrombolytic treatment.¹

Recommendations

The American College of Chest Physicians recommends therapeutic doses of intravenous unfractionated heparin, low-molecular-weight heparin, or fondaparinux for initial treatment of UEVT, followed by at least 3 months of treatment with a vitamin K antagonist.¹ The organization also suggests that surgical thrombectomy, superior vena caval filters, thrombolytic therapy, or catheter extraction may benefit selected patients.

Acknowledgement
The opinions and assertions contained herein are the private views of the author and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.

Evidence summary

Upper extremity venous thrombosis (UEVT)—which typically refers to thrombosis of the brachial, axillary, or subclavian veins—accounts for approximately 10% of all cases of venous thromboembolism.¹ UEVT can occur spontaneously (Paget-Schroetter syndrome) or develop as a complication of cancer or in-dwelling medical devices (such as long-term central venous catheters).

Although significant evidence-based data exist on treatment of lower extremity venous thrombosis, no good-quality studies specifically address management of UEVT. Review of the current literature revealed several small studies that compared various treatment strategies.

Thrombolytics may work better than anticoagulants in some patients
A small retrospective study randomized 20 patients with UEVT to either treatment with anticoagulant therapy with heparin and warfarin (n=11) or thrombolytic therapy (n=9).² After a mean follow-up period of 81.7 months for the anticoagulation group and 52.1 months for the thrombolytic group, 4 more patients in the thrombolytic group achieved complete clinical recovery and vein patency than in the anticoagulant group (P=.04). When patients who recovered completely were added to those who showed some clinical improvement, 89% of the thrombolytic therapy group had satisfactory outcomes, compared with 36% of the anticoagulant group (P=.028).

Another small retrospective study looked at 10 consecutive patients with UEVT who were treated with either anticoagulant therapy (n=6) or thrombolytics (n=4).³ Fifty percent of patients treated with anticoagulants experienced partial or complete improvement in symptoms, whereas 100% of patients treated with thrombolytics had partial or complete resolution of both symptoms and thrombi.

Overall, both studies raise the possibility that thrombolytic therapy is more effective than anticoagulation therapy in certain patients. The studies evaluated only active patients, 23 to 58 years of age, who had no contraindications to thrombolytic therapy. Neither study reported data on long-term outcomes such as recurrences, bleeding, or post-thrombotic sequelae.

Surgery may avoid long-term anticoagulation
Two case studies evaluated treatment of UEVT with thrombolytic therapy followed by various surgical interventions (angioplasty, thrombectomy, decompression via first rib resection or anterior scalenectomy, and venous bypass).^4,5 The first study reported that 8 of 9 patients who underwent first-rib resection and 1 of 2 who underwent scalenectomy were free of residual symptoms at follow-up (mean 2 years, range 6 months to 5 years).⁴ All patients were treated with thrombolytics before surgery.

The second study demonstrated that 50% of the patients treated with a surgical intervention without thrombolysis had complete symptom relief, while the remaining 50% reported relief from pain but still had occasional swelling.⁵ Although more invasive, surgery may eliminate the need for long-term anticoagulation therapy and enable a more rapid return to normal activities.

Data on vena cava filters are limited
Data supporting superior vena cava Green-field filters to treat UEVT are extremely limited. Of 6 patients with contraindications to anticoagulation therapy who were treated with a Greenfield filter, none had clinical evidence of pulmonary embolism at 14 months.⁶ The study reported no data regarding long-term sequelae or effects of the UEVT on the patients’ upper extremity.⁶

When in doubt, don’t (necessarily) take it out
For patients with central venous catheter-related deep vein thrombosis, taking out the catheter as part of treatment is controversial and should depend on clinical symptoms, the reason for the catheter, and duration of use, as well as physician judgment.⁷ No RCTs have studied the effects of catheter removal as part of initial treatment. Current guidelines recommend removing the catheter from patients with persistent symptoms who have failed anticoagulant or thrombolytic treatment.¹

Recommendations

The American College of Chest Physicians recommends therapeutic doses of intravenous unfractionated heparin, low-molecular-weight heparin, or fondaparinux for initial treatment of UEVT, followed by at least 3 months of treatment with a vitamin K antagonist.¹ The organization also suggests that surgical thrombectomy, superior vena caval filters, thrombolytic therapy, or catheter extraction may benefit selected patients.

Acknowledgement
The opinions and assertions contained herein are the private views of the author and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.

Evidence summary

ASD refers to a constellation of psychological symptoms that can occur within 4 weeks after a traumatic event.¹ (For more on ASD, see http://psychcentral.com/disorders/acute-stress-disorder-symptoms/.) Patients with symptoms that persist beyond 4 weeks or develop after 4 weeks are diagnosed with post-traumatic stress disorder (PTSD). Approximately 12.5% of people who experience a traumatic event develop ASD, and 10% develop PTSD, although not all patients who develop PTSD have preceding ASD.² Early identification and treatment of ASD can decrease the percentage of patients who go on to develop PTSD.²

Exposure-based therapy works better than cognitive restructuring
A 2009 meta-analysis of small, limited-quality RCTs noted that CBT based on re-exposure to memories of the traumatic event, when started within 3 months of the event, is more effective than supportive counseling for adults with ASD; supportive counseling is more effective than no treatment at all.³

Exposure-based therapy reduces subsequent PTSD symptoms in adults with ASD more than cognitive restructuring.² Exposure-based CBT attempts to decrease unrealistic anxiety by challenging anxiety-provoking thoughts, situations, activities, and people that are not fundamentally dangerous.⁴ Both exposure-based therapy and cognitive restructuring are better than no treatment at all.³

A small 2008 RCT evaluated the effect of weekly 90-minute CBT sessions with daily homework activities that were started within 1 month after a motor vehicle accident or nonsexual assault for patients with ASD.² Only 33% of patients who received exposure-based therapy had PTSD symptoms 6 weeks after starting treatment, whereas 63% of the cognitive restructuring group and 77% of untreated patients had PTSD at the 6-week follow-up.²

Medication shows no clear benefit over CBT

A 2007 meta-analysis of mixed-method trials concluded that medication should not be substituted for CBT, which is more effective.⁵ The evidence showed no clear benefit for pharmacologic treatment; medication was as effective as placebo, but with higher drop-out rates.⁵

Recommendations

The US Veterans Affairs/Department of Defense Clinical Practice Guideline for the Management of PTSD and the 2007 Australian Guidelines for the Treatment of Adults with ASD and PTSD recommend 3 early interventions for patients exposed to traumatic events:^5,6

• early assessment
• watchful waiting if ASD is not present
• psychological first aid (includes things like reducing physiologic arousal, ensuring patient’s safety and security, and encouraging active use of social support and self-care strategies).

The US and Australian guidelines also recommend educating patients about typical responses to traumatic events (normalizing early responses), referring patients with ASD/ PTSD symptoms to mental health providers for exposure-based psychotherapy, and adding selective serotonin reuptake inhibitors to CBT for patients severely impaired by ASD and patients diagnosed with PTSD.^5,6

A recent comparative analysis⁷ recommends using the Primary Care Post-Traumatic Stress Disorder (PC-PTSD) Screen⁸ as a simple, effective way to identify patients with PTSD (TABLE). This tool hasn’t yet been validated in patients with only ASD, however.

TABLE
The Primary Care Post-Traumatic Stress Disorder Screen (PC-PTSD)

Acknowledgement
The opinions and assertions contained herein are the private views of the authors and are not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.

Evidence summary

ASD refers to a constellation of psychological symptoms that can occur within 4 weeks after a traumatic event.¹ (For more on ASD, see http://psychcentral.com/disorders/acute-stress-disorder-symptoms/.) Patients with symptoms that persist beyond 4 weeks or develop after 4 weeks are diagnosed with post-traumatic stress disorder (PTSD). Approximately 12.5% of people who experience a traumatic event develop ASD, and 10% develop PTSD, although not all patients who develop PTSD have preceding ASD.² Early identification and treatment of ASD can decrease the percentage of patients who go on to develop PTSD.²

Exposure-based therapy works better than cognitive restructuring
A 2009 meta-analysis of small, limited-quality RCTs noted that CBT based on re-exposure to memories of the traumatic event, when started within 3 months of the event, is more effective than supportive counseling for adults with ASD; supportive counseling is more effective than no treatment at all.³

Exposure-based therapy reduces subsequent PTSD symptoms in adults with ASD more than cognitive restructuring.² Exposure-based CBT attempts to decrease unrealistic anxiety by challenging anxiety-provoking thoughts, situations, activities, and people that are not fundamentally dangerous.⁴ Both exposure-based therapy and cognitive restructuring are better than no treatment at all.³

A small 2008 RCT evaluated the effect of weekly 90-minute CBT sessions with daily homework activities that were started within 1 month after a motor vehicle accident or nonsexual assault for patients with ASD.² Only 33% of patients who received exposure-based therapy had PTSD symptoms 6 weeks after starting treatment, whereas 63% of the cognitive restructuring group and 77% of untreated patients had PTSD at the 6-week follow-up.²

Medication shows no clear benefit over CBT

A 2007 meta-analysis of mixed-method trials concluded that medication should not be substituted for CBT, which is more effective.⁵ The evidence showed no clear benefit for pharmacologic treatment; medication was as effective as placebo, but with higher drop-out rates.⁵

Recommendations

The US Veterans Affairs/Department of Defense Clinical Practice Guideline for the Management of PTSD and the 2007 Australian Guidelines for the Treatment of Adults with ASD and PTSD recommend 3 early interventions for patients exposed to traumatic events:^5,6

• early assessment
• watchful waiting if ASD is not present
• psychological first aid (includes things like reducing physiologic arousal, ensuring patient’s safety and security, and encouraging active use of social support and self-care strategies).

The US and Australian guidelines also recommend educating patients about typical responses to traumatic events (normalizing early responses), referring patients with ASD/ PTSD symptoms to mental health providers for exposure-based psychotherapy, and adding selective serotonin reuptake inhibitors to CBT for patients severely impaired by ASD and patients diagnosed with PTSD.^5,6

A recent comparative analysis⁷ recommends using the Primary Care Post-Traumatic Stress Disorder (PC-PTSD) Screen⁸ as a simple, effective way to identify patients with PTSD (TABLE). This tool hasn’t yet been validated in patients with only ASD, however.

TABLE
The Primary Care Post-Traumatic Stress Disorder Screen (PC-PTSD)

Acknowledgement
The opinions and assertions contained herein are the private views of the authors and are not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.

Evidence summary

ASD refers to a constellation of psychological symptoms that can occur within 4 weeks after a traumatic event.¹ (For more on ASD, see http://psychcentral.com/disorders/acute-stress-disorder-symptoms/.) Patients with symptoms that persist beyond 4 weeks or develop after 4 weeks are diagnosed with post-traumatic stress disorder (PTSD). Approximately 12.5% of people who experience a traumatic event develop ASD, and 10% develop PTSD, although not all patients who develop PTSD have preceding ASD.² Early identification and treatment of ASD can decrease the percentage of patients who go on to develop PTSD.²

Exposure-based therapy works better than cognitive restructuring
A 2009 meta-analysis of small, limited-quality RCTs noted that CBT based on re-exposure to memories of the traumatic event, when started within 3 months of the event, is more effective than supportive counseling for adults with ASD; supportive counseling is more effective than no treatment at all.³

Exposure-based therapy reduces subsequent PTSD symptoms in adults with ASD more than cognitive restructuring.² Exposure-based CBT attempts to decrease unrealistic anxiety by challenging anxiety-provoking thoughts, situations, activities, and people that are not fundamentally dangerous.⁴ Both exposure-based therapy and cognitive restructuring are better than no treatment at all.³

A small 2008 RCT evaluated the effect of weekly 90-minute CBT sessions with daily homework activities that were started within 1 month after a motor vehicle accident or nonsexual assault for patients with ASD.² Only 33% of patients who received exposure-based therapy had PTSD symptoms 6 weeks after starting treatment, whereas 63% of the cognitive restructuring group and 77% of untreated patients had PTSD at the 6-week follow-up.²

Medication shows no clear benefit over CBT

A 2007 meta-analysis of mixed-method trials concluded that medication should not be substituted for CBT, which is more effective.⁵ The evidence showed no clear benefit for pharmacologic treatment; medication was as effective as placebo, but with higher drop-out rates.⁵

Recommendations

The US Veterans Affairs/Department of Defense Clinical Practice Guideline for the Management of PTSD and the 2007 Australian Guidelines for the Treatment of Adults with ASD and PTSD recommend 3 early interventions for patients exposed to traumatic events:^5,6

• early assessment
• watchful waiting if ASD is not present
• psychological first aid (includes things like reducing physiologic arousal, ensuring patient’s safety and security, and encouraging active use of social support and self-care strategies).

The US and Australian guidelines also recommend educating patients about typical responses to traumatic events (normalizing early responses), referring patients with ASD/ PTSD symptoms to mental health providers for exposure-based psychotherapy, and adding selective serotonin reuptake inhibitors to CBT for patients severely impaired by ASD and patients diagnosed with PTSD.^5,6

A recent comparative analysis⁷ recommends using the Primary Care Post-Traumatic Stress Disorder (PC-PTSD) Screen⁸ as a simple, effective way to identify patients with PTSD (TABLE). This tool hasn’t yet been validated in patients with only ASD, however.

TABLE
The Primary Care Post-Traumatic Stress Disorder Screen (PC-PTSD)

Acknowledgement
The opinions and assertions contained herein are the private views of the authors and are not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.

Evidence summary

A systematic review conducted for the US Preventive Services Task Force (USPSTF) addressed the use of aspirin for primary prevention of colorectal carcinomas (CRC) and colorectal adenomas (CRA).

Pooled data from 2 randomized-controlled trials (RCTs) with a total of 61,947 patients showed no decrease in CRC incidence (relative risk [RR]=1.02; 95% confidence interval [CI], 0.84-1.25) with regular aspirin use (325 mg every other day for 5 years or 100 mg every other day for 10 years). Six cohort studies that followed a total of 231,252 patients did report a decrease in CRC incidence over 4 to 10 years (RR=0.78; 95% CI, 0.63-0.97).¹

In a pooled analysis evaluating 2 primary prevention RCTs (the British Doctors Aspirin Trial and UK-TIA Aspirin Trial, total N=7588), aspirin was found to reduce the incidence of colorectal cancer (hazard ratio [HR]=0.74; 95% CI, 0.56-0.97; P=.02 overall; for aspirin given for 5 years or longer, HR=0.63; 95% CI, 0.47-0.85; P=.002). The effect was significant only at 10 to 14 years of follow-up (0 to 9 years: HR=0.92, 95% CI, 0.56-1.49, P=.73; 5 to 9 years: HR=1.08, 95% CI, 0.55-2.14, P=.83; 10 to 14 years: HR=0.51, 95% CI, 0.29-0.90, P=.02; 15 to 19 years: HR=0.70, 95% CI, 0.43-1.14, P=.15; ≥20 years: HR=0.90, 95% CI, 0.42-1.95, P=.79).²

Adverse effects, including stroke, are dose-dependent
The USPSTF review also summarized the harms associated with aspirin use. When aspirin was given for secondary prevention of stroke, the risk of hemorrhagic stroke was dose-dependent, varying from 0.3% to 1.1% (100 mg/d: 0.3%, 95% CI, 0.2%-0.4%; 100-325 mg/d: 0.3%, 95% CI, 0.2%-0.3%; 325 mg/d: 1.1%, 95% CI, 0.7%-1.5%).

Aspirin also was associated with an increased risk of gastrointestinal (GI) symptoms (odds ratio [OR]=1.7; 95% CI, 1.5-1.8), GI bleeding (RR=1.6-2.5), and hospitalization for GI bleeding (OR=1.9; 95% CI, 1.1-3.1). The risks of GI bleeding or perforation were dose-dependent.¹

Low-dose aspirin promotes secondary prevention of adenomas
In a Cochrane review evaluating the effects of aspirin on CRA, pooled data from 3 RCTs with a total of 1839 subjects (1322 with a history of CRA and 517 with a history of CRC) showed that aspirin in a daily dose of 81 mg is effective for secondary prevention of sporadic CRA over a 1- to 3-year follow-up period (RR=0.77; 95% CI, 0.61-0.96; number needed to treat=12.5). The outcome measured in these 3 trials was an intermediate clinical finding, CRA, and not the more relevant end point of CRC.³

Recommendations

The USPSTF recommends against routine use of aspirin and nonsteroidal anti-inflammatory drugs to prevent colorectal cancer in people at average risk (grade D recommendation: ineffective or harm outweighs benefits).⁴

The American Gastroenterological Association (AGA) doesn’t recommend aspirin for primary CRC prevention, but acknowledges a possible role in secondary prevention. Aspirin should be considered for patients with a personal history of CRC, advanced CRA, or a strong family history but no history of peptic ulcer disease or hemorrhagic stroke. The AGA notes that 1 in 100 people taking aspirin for 2 years will develop significant GI bleeding.⁵

Evidence summary

A systematic review conducted for the US Preventive Services Task Force (USPSTF) addressed the use of aspirin for primary prevention of colorectal carcinomas (CRC) and colorectal adenomas (CRA).

Pooled data from 2 randomized-controlled trials (RCTs) with a total of 61,947 patients showed no decrease in CRC incidence (relative risk [RR]=1.02; 95% confidence interval [CI], 0.84-1.25) with regular aspirin use (325 mg every other day for 5 years or 100 mg every other day for 10 years). Six cohort studies that followed a total of 231,252 patients did report a decrease in CRC incidence over 4 to 10 years (RR=0.78; 95% CI, 0.63-0.97).¹

In a pooled analysis evaluating 2 primary prevention RCTs (the British Doctors Aspirin Trial and UK-TIA Aspirin Trial, total N=7588), aspirin was found to reduce the incidence of colorectal cancer (hazard ratio [HR]=0.74; 95% CI, 0.56-0.97; P=.02 overall; for aspirin given for 5 years or longer, HR=0.63; 95% CI, 0.47-0.85; P=.002). The effect was significant only at 10 to 14 years of follow-up (0 to 9 years: HR=0.92, 95% CI, 0.56-1.49, P=.73; 5 to 9 years: HR=1.08, 95% CI, 0.55-2.14, P=.83; 10 to 14 years: HR=0.51, 95% CI, 0.29-0.90, P=.02; 15 to 19 years: HR=0.70, 95% CI, 0.43-1.14, P=.15; ≥20 years: HR=0.90, 95% CI, 0.42-1.95, P=.79).²

Adverse effects, including stroke, are dose-dependent
The USPSTF review also summarized the harms associated with aspirin use. When aspirin was given for secondary prevention of stroke, the risk of hemorrhagic stroke was dose-dependent, varying from 0.3% to 1.1% (100 mg/d: 0.3%, 95% CI, 0.2%-0.4%; 100-325 mg/d: 0.3%, 95% CI, 0.2%-0.3%; 325 mg/d: 1.1%, 95% CI, 0.7%-1.5%).

Aspirin also was associated with an increased risk of gastrointestinal (GI) symptoms (odds ratio [OR]=1.7; 95% CI, 1.5-1.8), GI bleeding (RR=1.6-2.5), and hospitalization for GI bleeding (OR=1.9; 95% CI, 1.1-3.1). The risks of GI bleeding or perforation were dose-dependent.¹

Low-dose aspirin promotes secondary prevention of adenomas
In a Cochrane review evaluating the effects of aspirin on CRA, pooled data from 3 RCTs with a total of 1839 subjects (1322 with a history of CRA and 517 with a history of CRC) showed that aspirin in a daily dose of 81 mg is effective for secondary prevention of sporadic CRA over a 1- to 3-year follow-up period (RR=0.77; 95% CI, 0.61-0.96; number needed to treat=12.5). The outcome measured in these 3 trials was an intermediate clinical finding, CRA, and not the more relevant end point of CRC.³

Recommendations

The USPSTF recommends against routine use of aspirin and nonsteroidal anti-inflammatory drugs to prevent colorectal cancer in people at average risk (grade D recommendation: ineffective or harm outweighs benefits).⁴

The American Gastroenterological Association (AGA) doesn’t recommend aspirin for primary CRC prevention, but acknowledges a possible role in secondary prevention. Aspirin should be considered for patients with a personal history of CRC, advanced CRA, or a strong family history but no history of peptic ulcer disease or hemorrhagic stroke. The AGA notes that 1 in 100 people taking aspirin for 2 years will develop significant GI bleeding.⁵

Evidence summary

A systematic review conducted for the US Preventive Services Task Force (USPSTF) addressed the use of aspirin for primary prevention of colorectal carcinomas (CRC) and colorectal adenomas (CRA).

Pooled data from 2 randomized-controlled trials (RCTs) with a total of 61,947 patients showed no decrease in CRC incidence (relative risk [RR]=1.02; 95% confidence interval [CI], 0.84-1.25) with regular aspirin use (325 mg every other day for 5 years or 100 mg every other day for 10 years). Six cohort studies that followed a total of 231,252 patients did report a decrease in CRC incidence over 4 to 10 years (RR=0.78; 95% CI, 0.63-0.97).¹

In a pooled analysis evaluating 2 primary prevention RCTs (the British Doctors Aspirin Trial and UK-TIA Aspirin Trial, total N=7588), aspirin was found to reduce the incidence of colorectal cancer (hazard ratio [HR]=0.74; 95% CI, 0.56-0.97; P=.02 overall; for aspirin given for 5 years or longer, HR=0.63; 95% CI, 0.47-0.85; P=.002). The effect was significant only at 10 to 14 years of follow-up (0 to 9 years: HR=0.92, 95% CI, 0.56-1.49, P=.73; 5 to 9 years: HR=1.08, 95% CI, 0.55-2.14, P=.83; 10 to 14 years: HR=0.51, 95% CI, 0.29-0.90, P=.02; 15 to 19 years: HR=0.70, 95% CI, 0.43-1.14, P=.15; ≥20 years: HR=0.90, 95% CI, 0.42-1.95, P=.79).²

Adverse effects, including stroke, are dose-dependent
The USPSTF review also summarized the harms associated with aspirin use. When aspirin was given for secondary prevention of stroke, the risk of hemorrhagic stroke was dose-dependent, varying from 0.3% to 1.1% (100 mg/d: 0.3%, 95% CI, 0.2%-0.4%; 100-325 mg/d: 0.3%, 95% CI, 0.2%-0.3%; 325 mg/d: 1.1%, 95% CI, 0.7%-1.5%).

Aspirin also was associated with an increased risk of gastrointestinal (GI) symptoms (odds ratio [OR]=1.7; 95% CI, 1.5-1.8), GI bleeding (RR=1.6-2.5), and hospitalization for GI bleeding (OR=1.9; 95% CI, 1.1-3.1). The risks of GI bleeding or perforation were dose-dependent.¹

Low-dose aspirin promotes secondary prevention of adenomas
In a Cochrane review evaluating the effects of aspirin on CRA, pooled data from 3 RCTs with a total of 1839 subjects (1322 with a history of CRA and 517 with a history of CRC) showed that aspirin in a daily dose of 81 mg is effective for secondary prevention of sporadic CRA over a 1- to 3-year follow-up period (RR=0.77; 95% CI, 0.61-0.96; number needed to treat=12.5). The outcome measured in these 3 trials was an intermediate clinical finding, CRA, and not the more relevant end point of CRC.³

Recommendations

The USPSTF recommends against routine use of aspirin and nonsteroidal anti-inflammatory drugs to prevent colorectal cancer in people at average risk (grade D recommendation: ineffective or harm outweighs benefits).⁴

The American Gastroenterological Association (AGA) doesn’t recommend aspirin for primary CRC prevention, but acknowledges a possible role in secondary prevention. Aspirin should be considered for patients with a personal history of CRC, advanced CRA, or a strong family history but no history of peptic ulcer disease or hemorrhagic stroke. The AGA notes that 1 in 100 people taking aspirin for 2 years will develop significant GI bleeding.⁵

Evidence summary

No patient-centered studies have evaluated the effectiveness of male genital examinations during a PPE. Examination is performed mainly to identify an inguinal hernia. The incidence of infantile inguinal hernia is 0.8% to 4.4%, with a male-to-female ratio of 6 to 1.¹ About 4% of the population will develop an inguinal hernia, but its incidence among adolescents and young adults isn’t known.¹ The natural history of inguinal hernias is poorly understood.

Screening turns up hernia more often than other genital problems
In a study involving juniors and seniors attending a Richmond County, Georgia high school, 48 of 562 students (9.1%) and 34 of 706 students (4.8%) were found to have genital problems or a hernia during examinations conducted in 2 consecutive years of preparticipation physicals.² No data were available to differentiate the type or severity of the genitourinary problems identified.

A study of 3205 elementary school boys 6 to 12 years of age in western Iran found that 213 (6.64%) had inguinal hernia and penoscrotal abnormalities. The most common abnormality was indirect inguinal hernia (2.4%).³ The rates of other external genital abnormalities, such as retractile testes (1.22%), undescended testes (1.12%), hydrocele (0.87%), and hypospadias (0.78%), were lower.

Students’ attitudes toward screening aren’t known
Students’ knowledge of, and attitude toward, genital screening during PPE are unknown. In 1 study, 50% of junior high school, high school, and college athletes in northeastern Ohio didn’t know why a genital examination is performed during the PPE.⁴

Sensitivity and specificity of physical examination for hernia
The sensitivity and specificity of physical examination hasn’t been well studied. One study, assessing the accuracy of methods of diagnosing inguinal hernia in 55 laparoscopically documented cases, found that the sensitivity and specificity were 74.5% and 96.3%, respectively, for physical examination; 92.7% and 81.5% for ultrasound; and 94.5% and 96.3% for MRI.⁵ The patients were symptomatic, however, which makes it likely that the accuracy of these diagnostic methods in screening asymptomatic patients would be overestimated.

Managing hernia. Surgery isn’t the only option for managing inguinal hernia.⁶ Watchful waiting is safe and acceptable for asymptomatic or minimally symptomatic individuals. Acute complications are rare, and patients who delay surgery don’t have a higher risk of operative or postoperative complications.

What about routine testicular cancer screening?
The US Preventive Services Task Force (USPSTF) hasn’t made a recommendation on hernia screening, but recommends against routine screening for testicular cancer in asymptomatic adolescents and adults.⁷ The recommendation is based on the low prevalence of testicular cancer and the unknown accuracy of testicular examination in detecting it. Even without screening, current treatments produce very favorable health outcomes.

Although the USPSTF didn’t identify any potential harm from screening for testicular cancer, no evidence suggests that screening provides any benefit over current case-finding practices. Moreover, because some evidence suggests that testicular cancer is often misdiagnosed initially, resources might be better dedicated to proper evaluation of patients with symptoms.

Recommendations

Routine male genitourinary examination during the PPE, including testicular and hernia evaluation, is recommended by the American Academy of Family Physicians (AAFP), American Academy of Pediatrics, American College of Sports Medicine, American Medical Society for Sports Medicine, American Orthopedic Society for Sports Medicine, and American Osteopathic Academy of Sports Medicine.⁸

The latest AAFP position statement reflects the USPSTF recommendation against routine screening for testicular cancer in asymptomatic adolescents and adults.⁹

Evidence summary

No patient-centered studies have evaluated the effectiveness of male genital examinations during a PPE. Examination is performed mainly to identify an inguinal hernia. The incidence of infantile inguinal hernia is 0.8% to 4.4%, with a male-to-female ratio of 6 to 1.¹ About 4% of the population will develop an inguinal hernia, but its incidence among adolescents and young adults isn’t known.¹ The natural history of inguinal hernias is poorly understood.

Screening turns up hernia more often than other genital problems
In a study involving juniors and seniors attending a Richmond County, Georgia high school, 48 of 562 students (9.1%) and 34 of 706 students (4.8%) were found to have genital problems or a hernia during examinations conducted in 2 consecutive years of preparticipation physicals.² No data were available to differentiate the type or severity of the genitourinary problems identified.

A study of 3205 elementary school boys 6 to 12 years of age in western Iran found that 213 (6.64%) had inguinal hernia and penoscrotal abnormalities. The most common abnormality was indirect inguinal hernia (2.4%).³ The rates of other external genital abnormalities, such as retractile testes (1.22%), undescended testes (1.12%), hydrocele (0.87%), and hypospadias (0.78%), were lower.

Students’ attitudes toward screening aren’t known
Students’ knowledge of, and attitude toward, genital screening during PPE are unknown. In 1 study, 50% of junior high school, high school, and college athletes in northeastern Ohio didn’t know why a genital examination is performed during the PPE.⁴

Sensitivity and specificity of physical examination for hernia
The sensitivity and specificity of physical examination hasn’t been well studied. One study, assessing the accuracy of methods of diagnosing inguinal hernia in 55 laparoscopically documented cases, found that the sensitivity and specificity were 74.5% and 96.3%, respectively, for physical examination; 92.7% and 81.5% for ultrasound; and 94.5% and 96.3% for MRI.⁵ The patients were symptomatic, however, which makes it likely that the accuracy of these diagnostic methods in screening asymptomatic patients would be overestimated.

Managing hernia. Surgery isn’t the only option for managing inguinal hernia.⁶ Watchful waiting is safe and acceptable for asymptomatic or minimally symptomatic individuals. Acute complications are rare, and patients who delay surgery don’t have a higher risk of operative or postoperative complications.

What about routine testicular cancer screening?
The US Preventive Services Task Force (USPSTF) hasn’t made a recommendation on hernia screening, but recommends against routine screening for testicular cancer in asymptomatic adolescents and adults.⁷ The recommendation is based on the low prevalence of testicular cancer and the unknown accuracy of testicular examination in detecting it. Even without screening, current treatments produce very favorable health outcomes.

Although the USPSTF didn’t identify any potential harm from screening for testicular cancer, no evidence suggests that screening provides any benefit over current case-finding practices. Moreover, because some evidence suggests that testicular cancer is often misdiagnosed initially, resources might be better dedicated to proper evaluation of patients with symptoms.

Recommendations

Routine male genitourinary examination during the PPE, including testicular and hernia evaluation, is recommended by the American Academy of Family Physicians (AAFP), American Academy of Pediatrics, American College of Sports Medicine, American Medical Society for Sports Medicine, American Orthopedic Society for Sports Medicine, and American Osteopathic Academy of Sports Medicine.⁸

The latest AAFP position statement reflects the USPSTF recommendation against routine screening for testicular cancer in asymptomatic adolescents and adults.⁹

Evidence summary

No patient-centered studies have evaluated the effectiveness of male genital examinations during a PPE. Examination is performed mainly to identify an inguinal hernia. The incidence of infantile inguinal hernia is 0.8% to 4.4%, with a male-to-female ratio of 6 to 1.¹ About 4% of the population will develop an inguinal hernia, but its incidence among adolescents and young adults isn’t known.¹ The natural history of inguinal hernias is poorly understood.

Screening turns up hernia more often than other genital problems
In a study involving juniors and seniors attending a Richmond County, Georgia high school, 48 of 562 students (9.1%) and 34 of 706 students (4.8%) were found to have genital problems or a hernia during examinations conducted in 2 consecutive years of preparticipation physicals.² No data were available to differentiate the type or severity of the genitourinary problems identified.

A study of 3205 elementary school boys 6 to 12 years of age in western Iran found that 213 (6.64%) had inguinal hernia and penoscrotal abnormalities. The most common abnormality was indirect inguinal hernia (2.4%).³ The rates of other external genital abnormalities, such as retractile testes (1.22%), undescended testes (1.12%), hydrocele (0.87%), and hypospadias (0.78%), were lower.

Students’ attitudes toward screening aren’t known
Students’ knowledge of, and attitude toward, genital screening during PPE are unknown. In 1 study, 50% of junior high school, high school, and college athletes in northeastern Ohio didn’t know why a genital examination is performed during the PPE.⁴

Sensitivity and specificity of physical examination for hernia
The sensitivity and specificity of physical examination hasn’t been well studied. One study, assessing the accuracy of methods of diagnosing inguinal hernia in 55 laparoscopically documented cases, found that the sensitivity and specificity were 74.5% and 96.3%, respectively, for physical examination; 92.7% and 81.5% for ultrasound; and 94.5% and 96.3% for MRI.⁵ The patients were symptomatic, however, which makes it likely that the accuracy of these diagnostic methods in screening asymptomatic patients would be overestimated.

Managing hernia. Surgery isn’t the only option for managing inguinal hernia.⁶ Watchful waiting is safe and acceptable for asymptomatic or minimally symptomatic individuals. Acute complications are rare, and patients who delay surgery don’t have a higher risk of operative or postoperative complications.

What about routine testicular cancer screening?
The US Preventive Services Task Force (USPSTF) hasn’t made a recommendation on hernia screening, but recommends against routine screening for testicular cancer in asymptomatic adolescents and adults.⁷ The recommendation is based on the low prevalence of testicular cancer and the unknown accuracy of testicular examination in detecting it. Even without screening, current treatments produce very favorable health outcomes.

Although the USPSTF didn’t identify any potential harm from screening for testicular cancer, no evidence suggests that screening provides any benefit over current case-finding practices. Moreover, because some evidence suggests that testicular cancer is often misdiagnosed initially, resources might be better dedicated to proper evaluation of patients with symptoms.

Recommendations

Routine male genitourinary examination during the PPE, including testicular and hernia evaluation, is recommended by the American Academy of Family Physicians (AAFP), American Academy of Pediatrics, American College of Sports Medicine, American Medical Society for Sports Medicine, American Orthopedic Society for Sports Medicine, and American Osteopathic Academy of Sports Medicine.⁸

The latest AAFP position statement reflects the USPSTF recommendation against routine screening for testicular cancer in asymptomatic adolescents and adults.⁹

Evidence summary

The American Academy of Allergy, Asthma and Immunology (AAAAI) states that a double-blind, placebo-controlled OFC is the best test for diagnosing infants clinically suspected of having food allergies (that is, who develop gastrointestinal symptoms after eating a specific food). However, performing an OFC in an infant is often difficult and potentially dangerous, especially if a severe allergy is suspected; testing also may eliminate nutritious foods, such as milk and eggs, from the infant’s diet.¹ For these reasons, physicians have sought simpler alternatives to the OFC.

Comparisons of serum and skin testing with OFCs produce variable, weak results
Two large cohort studies compared OFCs with serum and skin testing in infants, children, and teenagers. Overall, serum and skin testing didn’t produce robust results and the results varied with the antigen (TABLE).

TABLE
How allergy tests in infants and children compare with an oral food challenge

In 1 study, researchers compared specific serum IgE levels with OFC results for 4 foods—milk, eggs, wheat, and soy—in 501 consecutive pediatric patients referred to an allergy ward based on clinical or parental suspicion of food allergy. Children ranged in age from 1 month to 16 years (median age 13 months); results for infants were not provided separately. Eighty-eight percent of the children were atopic. Investigators measured serum IgE (using the Pharmacia CAP-system fluorescence enzyme immunoassay) before administering the OFCs.

Of 992 OFCs performed, 445 (45%) were positive (defined as producing urticaria, angioedema, wheezing, vomiting, diarrhea, abdominal pain, shock, or exacerbation of eczema). Most OFCs (73%) were double-blind placebo-controlled, but investigators performed open OFCs in infants and in children with a history of immediate allergic reactions. Investigators retrospectively analyzed serum-specific IgE levels for the 4 food antigens and compared them with the results of the OFCs. Positive likelihood ratios (LR+) for IgE testing ranged from 1.3 to 2.0 for the 4 antigens; negative likelihood ratios (LR–) ranged from 0.31 to 0.59.²

The second cohort study compared APT and SPT with OFCs for the same 4 food antigens (milk, eggs, wheat, soy) in 437 children. The study population comprised consecutive referrals to a pediatric immunology department based on either parental suspicion of a food allergy or a positive IgE test. The children ranged in age from 3 months to 14 years (median age 13 months); results for infants weren’t provided separately. Ninety percent of the children were atopic. Investigators performed APTs and SPTs for the 4 food antigens on all children and OFCs only for foods that were clinically suspect (total OFCs=873).

As in the previous study, investigators performed open OFCs (23%) in infants and children with a history of immediate reaction. A positive APT was defined by erythema with infiltration or papules, and a positive SPT by a wheal ≥3 mm. For the SPT, the LR+ ranged from 1.9 to 2.8 for the 4 antigens, and the LR–ranged from 0.13 (for egg) to 0.84. For the APT, the LR+ ranged from 1.6 to 6.2 (for milk), whereas the LR– was of little value, ranging from 0.68 to 0.90.³

For milk and eggs, the larger the wheal, the more sensitive the skin test
The size of the wheal may increase the sensitivity of the SPT in some situations. A cohort study similar to the ones described previously compared SPT with OFCs in children with possible food allergies and found that a large SPT wheal was highly correlated with OFC-confirmed allergy to milk and eggs.⁴

Investigators recruited 385 children—3 months to 14 years of age (median age 22 months), results for infants not provided separately—from consecutive referrals to a pediatric immunology department. Most children (87%) were atopic. Investigators performed SPTs, followed by OFCs for milk, egg, wheat, and soy allergens. Overall, 312 (43%) of the OFCs were positive. Wheals measuring ≥13 mm for eggs and ≥12.5 mm for milk correlated well with OFC results (95% positive predictive value). Wheal sizes for wheat and soy were poorly predictive, however.⁴

No validation yet for new techniques to improve accuracy and safety
New techniques to improve the accuracy and safety of allergy testing have yet to be validated clinically. One cohort study of 58 children that used fresh fruit or vegetable preparations for SPT instead of commonly used commercial extracts found added sensitivity.⁵ Another cohort study of 142 children allowed suspect foods to contact only the labial mucosa in order to reduce the risk of systemic reactions (1 case of anaphylaxis occurred nevertheless).⁶

Recommendations

The AAAAI guidelines state that history and physical examination help determine that food is causing symptoms and that an OFC is diagnostic of food allergy (but risks and benefits must be considered, including the possibility of severe adverse reaction).¹ The guidelines note that other available tests, including food-specific IgE and skin tests, are not specific enough for screening but may be used when a particular food allergy is clinically suspected.

Evidence summary

The American Academy of Allergy, Asthma and Immunology (AAAAI) states that a double-blind, placebo-controlled OFC is the best test for diagnosing infants clinically suspected of having food allergies (that is, who develop gastrointestinal symptoms after eating a specific food). However, performing an OFC in an infant is often difficult and potentially dangerous, especially if a severe allergy is suspected; testing also may eliminate nutritious foods, such as milk and eggs, from the infant’s diet.¹ For these reasons, physicians have sought simpler alternatives to the OFC.

Comparisons of serum and skin testing with OFCs produce variable, weak results
Two large cohort studies compared OFCs with serum and skin testing in infants, children, and teenagers. Overall, serum and skin testing didn’t produce robust results and the results varied with the antigen (TABLE).

TABLE
How allergy tests in infants and children compare with an oral food challenge

In 1 study, researchers compared specific serum IgE levels with OFC results for 4 foods—milk, eggs, wheat, and soy—in 501 consecutive pediatric patients referred to an allergy ward based on clinical or parental suspicion of food allergy. Children ranged in age from 1 month to 16 years (median age 13 months); results for infants were not provided separately. Eighty-eight percent of the children were atopic. Investigators measured serum IgE (using the Pharmacia CAP-system fluorescence enzyme immunoassay) before administering the OFCs.

Of 992 OFCs performed, 445 (45%) were positive (defined as producing urticaria, angioedema, wheezing, vomiting, diarrhea, abdominal pain, shock, or exacerbation of eczema). Most OFCs (73%) were double-blind placebo-controlled, but investigators performed open OFCs in infants and in children with a history of immediate allergic reactions. Investigators retrospectively analyzed serum-specific IgE levels for the 4 food antigens and compared them with the results of the OFCs. Positive likelihood ratios (LR+) for IgE testing ranged from 1.3 to 2.0 for the 4 antigens; negative likelihood ratios (LR–) ranged from 0.31 to 0.59.²

The second cohort study compared APT and SPT with OFCs for the same 4 food antigens (milk, eggs, wheat, soy) in 437 children. The study population comprised consecutive referrals to a pediatric immunology department based on either parental suspicion of a food allergy or a positive IgE test. The children ranged in age from 3 months to 14 years (median age 13 months); results for infants weren’t provided separately. Ninety percent of the children were atopic. Investigators performed APTs and SPTs for the 4 food antigens on all children and OFCs only for foods that were clinically suspect (total OFCs=873).

As in the previous study, investigators performed open OFCs (23%) in infants and children with a history of immediate reaction. A positive APT was defined by erythema with infiltration or papules, and a positive SPT by a wheal ≥3 mm. For the SPT, the LR+ ranged from 1.9 to 2.8 for the 4 antigens, and the LR–ranged from 0.13 (for egg) to 0.84. For the APT, the LR+ ranged from 1.6 to 6.2 (for milk), whereas the LR– was of little value, ranging from 0.68 to 0.90.³

For milk and eggs, the larger the wheal, the more sensitive the skin test
The size of the wheal may increase the sensitivity of the SPT in some situations. A cohort study similar to the ones described previously compared SPT with OFCs in children with possible food allergies and found that a large SPT wheal was highly correlated with OFC-confirmed allergy to milk and eggs.⁴

Investigators recruited 385 children—3 months to 14 years of age (median age 22 months), results for infants not provided separately—from consecutive referrals to a pediatric immunology department. Most children (87%) were atopic. Investigators performed SPTs, followed by OFCs for milk, egg, wheat, and soy allergens. Overall, 312 (43%) of the OFCs were positive. Wheals measuring ≥13 mm for eggs and ≥12.5 mm for milk correlated well with OFC results (95% positive predictive value). Wheal sizes for wheat and soy were poorly predictive, however.⁴

No validation yet for new techniques to improve accuracy and safety
New techniques to improve the accuracy and safety of allergy testing have yet to be validated clinically. One cohort study of 58 children that used fresh fruit or vegetable preparations for SPT instead of commonly used commercial extracts found added sensitivity.⁵ Another cohort study of 142 children allowed suspect foods to contact only the labial mucosa in order to reduce the risk of systemic reactions (1 case of anaphylaxis occurred nevertheless).⁶

Recommendations

The AAAAI guidelines state that history and physical examination help determine that food is causing symptoms and that an OFC is diagnostic of food allergy (but risks and benefits must be considered, including the possibility of severe adverse reaction).¹ The guidelines note that other available tests, including food-specific IgE and skin tests, are not specific enough for screening but may be used when a particular food allergy is clinically suspected.

Evidence summary

The American Academy of Allergy, Asthma and Immunology (AAAAI) states that a double-blind, placebo-controlled OFC is the best test for diagnosing infants clinically suspected of having food allergies (that is, who develop gastrointestinal symptoms after eating a specific food). However, performing an OFC in an infant is often difficult and potentially dangerous, especially if a severe allergy is suspected; testing also may eliminate nutritious foods, such as milk and eggs, from the infant’s diet.¹ For these reasons, physicians have sought simpler alternatives to the OFC.

Comparisons of serum and skin testing with OFCs produce variable, weak results
Two large cohort studies compared OFCs with serum and skin testing in infants, children, and teenagers. Overall, serum and skin testing didn’t produce robust results and the results varied with the antigen (TABLE).

TABLE
How allergy tests in infants and children compare with an oral food challenge

In 1 study, researchers compared specific serum IgE levels with OFC results for 4 foods—milk, eggs, wheat, and soy—in 501 consecutive pediatric patients referred to an allergy ward based on clinical or parental suspicion of food allergy. Children ranged in age from 1 month to 16 years (median age 13 months); results for infants were not provided separately. Eighty-eight percent of the children were atopic. Investigators measured serum IgE (using the Pharmacia CAP-system fluorescence enzyme immunoassay) before administering the OFCs.

Of 992 OFCs performed, 445 (45%) were positive (defined as producing urticaria, angioedema, wheezing, vomiting, diarrhea, abdominal pain, shock, or exacerbation of eczema). Most OFCs (73%) were double-blind placebo-controlled, but investigators performed open OFCs in infants and in children with a history of immediate allergic reactions. Investigators retrospectively analyzed serum-specific IgE levels for the 4 food antigens and compared them with the results of the OFCs. Positive likelihood ratios (LR+) for IgE testing ranged from 1.3 to 2.0 for the 4 antigens; negative likelihood ratios (LR–) ranged from 0.31 to 0.59.²

The second cohort study compared APT and SPT with OFCs for the same 4 food antigens (milk, eggs, wheat, soy) in 437 children. The study population comprised consecutive referrals to a pediatric immunology department based on either parental suspicion of a food allergy or a positive IgE test. The children ranged in age from 3 months to 14 years (median age 13 months); results for infants weren’t provided separately. Ninety percent of the children were atopic. Investigators performed APTs and SPTs for the 4 food antigens on all children and OFCs only for foods that were clinically suspect (total OFCs=873).

As in the previous study, investigators performed open OFCs (23%) in infants and children with a history of immediate reaction. A positive APT was defined by erythema with infiltration or papules, and a positive SPT by a wheal ≥3 mm. For the SPT, the LR+ ranged from 1.9 to 2.8 for the 4 antigens, and the LR–ranged from 0.13 (for egg) to 0.84. For the APT, the LR+ ranged from 1.6 to 6.2 (for milk), whereas the LR– was of little value, ranging from 0.68 to 0.90.³

For milk and eggs, the larger the wheal, the more sensitive the skin test
The size of the wheal may increase the sensitivity of the SPT in some situations. A cohort study similar to the ones described previously compared SPT with OFCs in children with possible food allergies and found that a large SPT wheal was highly correlated with OFC-confirmed allergy to milk and eggs.⁴

Investigators recruited 385 children—3 months to 14 years of age (median age 22 months), results for infants not provided separately—from consecutive referrals to a pediatric immunology department. Most children (87%) were atopic. Investigators performed SPTs, followed by OFCs for milk, egg, wheat, and soy allergens. Overall, 312 (43%) of the OFCs were positive. Wheals measuring ≥13 mm for eggs and ≥12.5 mm for milk correlated well with OFC results (95% positive predictive value). Wheal sizes for wheat and soy were poorly predictive, however.⁴

No validation yet for new techniques to improve accuracy and safety
New techniques to improve the accuracy and safety of allergy testing have yet to be validated clinically. One cohort study of 58 children that used fresh fruit or vegetable preparations for SPT instead of commonly used commercial extracts found added sensitivity.⁵ Another cohort study of 142 children allowed suspect foods to contact only the labial mucosa in order to reduce the risk of systemic reactions (1 case of anaphylaxis occurred nevertheless).⁶

Recommendations

The AAAAI guidelines state that history and physical examination help determine that food is causing symptoms and that an OFC is diagnostic of food allergy (but risks and benefits must be considered, including the possibility of severe adverse reaction).¹ The guidelines note that other available tests, including food-specific IgE and skin tests, are not specific enough for screening but may be used when a particular food allergy is clinically suspected.