Sonia Oyola, MD

Illustrative case

A 20-year-old woman with an estimated gestational age of 7 weeks comes to your clinic because of vaginal bleeding, which started 4 hours ago. A transvaginal ultrasound is inconclusive for an intrauterine pregnancy. Should you obtain a serum progesterone measurement?

Between 21% and 27% of pregnant women experience vaginal bleeding in their first trimester.^2,3 This leads to concern, both for patients and physicians, as it can be the first sign of a miscarriage or an ectopic pregnancy. A longitudinal population-based Swedish study of women who had ever been pregnant found that one in 4 had experienced an early pregnancy failure. Overall, about 12% of clinically recognized pregnancies ended in miscarriage.⁴

Our ability to predict early pregnancy loss is limited

Tools used by clinicians to evaluate vaginal bleeding or pain in the first trimester include transvaginal ultrasound (TVUS) and serial serum β-hCG measurements.⁵ Even when combined with risk factors for pregnancy loss (serum levels of estradiol, inhibin A, and inhibin B; maternal age; smoking; past history of spontaneous miscarriage; and vaginal bleeding), TVUS is not accurate at predicting early pregnancy loss.^6,7

A suboptimal rise in β-hCG (<66%) after 48 hours has historically been used to indicate possible miscarriage or ectopic pregnancy,¹but studies have found similarly low rates of increase in some viable pregnancies, as well.^8,9 And β-hCG measurements need to be done on more than one occasion, making this an inconvenient means of predicting miscarriage.

Moreover, β-hCG levels vary based on gestational age, leaving family physicians with no solid diagnostic rule regarding the appropriate level of rise in a viable pregnancy.¹⁰ Thus, there is a need for a test that complements TVUS and β-hCG to increase diagnostic accuracy in predicting nonviable pregnancies.

Can serum progesterone testing fill the gap?
Serum progesterone measurement is a noninvasive predictive tool, with low values associated with miscarriage and ectopic pregnancy and higher levels with a viable pregnancy.¹⁰   Studies have found that serum progesterone combined with β-hCG measurements has the highest reliability in predicting nonviable pregnancy, with a diagnostic accuracy of 85.7% (sensitivity, 88.1%; specificity, 84.3%). This compares with a diagnostic accuracy of 72.5% (sensitivity, 76.1%; specificity, 70.4%) for a single progesterone test alone, and 74.8% (sensitivity, 64.1%; specificity, 81.4%) for β-hCG alone.^10-12 The data are from older studies, including a meta-analysis, that did not include the use of TVUS.^10-12 But TVUS is now in widespread use and included in the systematic review and meta-analysis this PURL addresses.

Study summary:

Progesterone test is predictive—when combined with ultrasound
Verhaegen et al performed a comprehensive literature search to identify studies in which a single serum progesterone measurement was used to predict the viability of pregnancy vs miscarriage or ectopic pregnancy. They included studies of women with spontaneous pregnancy of <14 weeks. Trials of women who had conceived after ovulation induction or in vitro fertilization or received progesterone supplementation were excluded.

Twenty-six cohort studies met the inclusion criteria. These included 7 mostly high-quality studies, with a total of 2379 women with pain or bleeding and inconclusive TVUS, and 19 intermediate-quality studies (n=7057) of women who had pain or bleeding but no ultrasound.

Five of the 7 studies in women with symptoms and inconclusive TVUS had a similar progesterone test cutoff value (3.2-6 ng/mL). In these 5 studies (n=1998), the progesterone test predicted a nonviable pregnancy with a pooled sensitivity of 74.6% (95% CI, 50.6%-89.4%) and specificity of 98.4% (95% CI, 90.9%-99.7%), a positive likelihood ratio of 45 (7.1- 289) and a negative likelihood ratio of 0.26 (0.12-0.57). When progesterone was below the cutoff value, the probability of a nonviable pregnancy increased to 99.2%. In women with pain or bleeding but no ultrasound, a single progesterone test is less accurate in ruling out a viable pregnancy.

What's new

This test can end days of anxious waiting

This meta-analysis provides strong evidence that a single progesterone measurement is useful in predicting nonviable pregnancies in women with pain or bleeding when TVUS is inconclusive. In such patients, a low serum progesterone is highly predictive of a nonviable pregnancy.¹ This finding enables the physician to counsel the woman immediately on the likely pregnancy loss, without waiting days for serial β-hCG results.

Caveats

Progesterone is a poor predictor of ectopic pregnancy

An important caveat to our recommendation is that a single serum progesterone test has a poor predictive value for ectopic pregnancy and should not be used for this purpose. A combination of TVUS and serial β-hCG remains the optimal strategy for diagnosing ectopic pregnancy.¹³

It is important to note that there is no universally accepted definition of a low serum progesterone level: This meta-analysis included studies with a cutoff value of 3.2 to 6 ng/mL in women who had had a previous ultrasound. What’s more, these studies did not evaluate the predictive value of a serum progesterone test combined with β-hCG measurements.

Challenges to implementation

There are none
We do not see any challenges to the implementation of this recommendation.

ACKNOWLEDGEMENT 

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center of Research Resources or the National Institutes of Health.

Illustrative case

A 20-year-old woman with an estimated gestational age of 7 weeks comes to your clinic because of vaginal bleeding, which started 4 hours ago. A transvaginal ultrasound is inconclusive for an intrauterine pregnancy. Should you obtain a serum progesterone measurement?

Between 21% and 27% of pregnant women experience vaginal bleeding in their first trimester.^2,3 This leads to concern, both for patients and physicians, as it can be the first sign of a miscarriage or an ectopic pregnancy. A longitudinal population-based Swedish study of women who had ever been pregnant found that one in 4 had experienced an early pregnancy failure. Overall, about 12% of clinically recognized pregnancies ended in miscarriage.⁴

Our ability to predict early pregnancy loss is limited

Tools used by clinicians to evaluate vaginal bleeding or pain in the first trimester include transvaginal ultrasound (TVUS) and serial serum β-hCG measurements.⁵ Even when combined with risk factors for pregnancy loss (serum levels of estradiol, inhibin A, and inhibin B; maternal age; smoking; past history of spontaneous miscarriage; and vaginal bleeding), TVUS is not accurate at predicting early pregnancy loss.^6,7

A suboptimal rise in β-hCG (<66%) after 48 hours has historically been used to indicate possible miscarriage or ectopic pregnancy,¹but studies have found similarly low rates of increase in some viable pregnancies, as well.^8,9 And β-hCG measurements need to be done on more than one occasion, making this an inconvenient means of predicting miscarriage.

Moreover, β-hCG levels vary based on gestational age, leaving family physicians with no solid diagnostic rule regarding the appropriate level of rise in a viable pregnancy.¹⁰ Thus, there is a need for a test that complements TVUS and β-hCG to increase diagnostic accuracy in predicting nonviable pregnancies.

Can serum progesterone testing fill the gap?
Serum progesterone measurement is a noninvasive predictive tool, with low values associated with miscarriage and ectopic pregnancy and higher levels with a viable pregnancy.¹⁰   Studies have found that serum progesterone combined with β-hCG measurements has the highest reliability in predicting nonviable pregnancy, with a diagnostic accuracy of 85.7% (sensitivity, 88.1%; specificity, 84.3%). This compares with a diagnostic accuracy of 72.5% (sensitivity, 76.1%; specificity, 70.4%) for a single progesterone test alone, and 74.8% (sensitivity, 64.1%; specificity, 81.4%) for β-hCG alone.^10-12 The data are from older studies, including a meta-analysis, that did not include the use of TVUS.^10-12 But TVUS is now in widespread use and included in the systematic review and meta-analysis this PURL addresses.

Study summary:

Progesterone test is predictive—when combined with ultrasound
Verhaegen et al performed a comprehensive literature search to identify studies in which a single serum progesterone measurement was used to predict the viability of pregnancy vs miscarriage or ectopic pregnancy. They included studies of women with spontaneous pregnancy of <14 weeks. Trials of women who had conceived after ovulation induction or in vitro fertilization or received progesterone supplementation were excluded.

Twenty-six cohort studies met the inclusion criteria. These included 7 mostly high-quality studies, with a total of 2379 women with pain or bleeding and inconclusive TVUS, and 19 intermediate-quality studies (n=7057) of women who had pain or bleeding but no ultrasound.

Five of the 7 studies in women with symptoms and inconclusive TVUS had a similar progesterone test cutoff value (3.2-6 ng/mL). In these 5 studies (n=1998), the progesterone test predicted a nonviable pregnancy with a pooled sensitivity of 74.6% (95% CI, 50.6%-89.4%) and specificity of 98.4% (95% CI, 90.9%-99.7%), a positive likelihood ratio of 45 (7.1- 289) and a negative likelihood ratio of 0.26 (0.12-0.57). When progesterone was below the cutoff value, the probability of a nonviable pregnancy increased to 99.2%. In women with pain or bleeding but no ultrasound, a single progesterone test is less accurate in ruling out a viable pregnancy.

What's new

This test can end days of anxious waiting

This meta-analysis provides strong evidence that a single progesterone measurement is useful in predicting nonviable pregnancies in women with pain or bleeding when TVUS is inconclusive. In such patients, a low serum progesterone is highly predictive of a nonviable pregnancy.¹ This finding enables the physician to counsel the woman immediately on the likely pregnancy loss, without waiting days for serial β-hCG results.

Caveats

Progesterone is a poor predictor of ectopic pregnancy

An important caveat to our recommendation is that a single serum progesterone test has a poor predictive value for ectopic pregnancy and should not be used for this purpose. A combination of TVUS and serial β-hCG remains the optimal strategy for diagnosing ectopic pregnancy.¹³

It is important to note that there is no universally accepted definition of a low serum progesterone level: This meta-analysis included studies with a cutoff value of 3.2 to 6 ng/mL in women who had had a previous ultrasound. What’s more, these studies did not evaluate the predictive value of a serum progesterone test combined with β-hCG measurements.

Challenges to implementation

There are none
We do not see any challenges to the implementation of this recommendation.

ACKNOWLEDGEMENT 

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center of Research Resources or the National Institutes of Health.

Illustrative case

A 20-year-old woman with an estimated gestational age of 7 weeks comes to your clinic because of vaginal bleeding, which started 4 hours ago. A transvaginal ultrasound is inconclusive for an intrauterine pregnancy. Should you obtain a serum progesterone measurement?

Between 21% and 27% of pregnant women experience vaginal bleeding in their first trimester.^2,3 This leads to concern, both for patients and physicians, as it can be the first sign of a miscarriage or an ectopic pregnancy. A longitudinal population-based Swedish study of women who had ever been pregnant found that one in 4 had experienced an early pregnancy failure. Overall, about 12% of clinically recognized pregnancies ended in miscarriage.⁴

Our ability to predict early pregnancy loss is limited

Tools used by clinicians to evaluate vaginal bleeding or pain in the first trimester include transvaginal ultrasound (TVUS) and serial serum β-hCG measurements.⁵ Even when combined with risk factors for pregnancy loss (serum levels of estradiol, inhibin A, and inhibin B; maternal age; smoking; past history of spontaneous miscarriage; and vaginal bleeding), TVUS is not accurate at predicting early pregnancy loss.^6,7

A suboptimal rise in β-hCG (<66%) after 48 hours has historically been used to indicate possible miscarriage or ectopic pregnancy,¹but studies have found similarly low rates of increase in some viable pregnancies, as well.^8,9 And β-hCG measurements need to be done on more than one occasion, making this an inconvenient means of predicting miscarriage.

Moreover, β-hCG levels vary based on gestational age, leaving family physicians with no solid diagnostic rule regarding the appropriate level of rise in a viable pregnancy.¹⁰ Thus, there is a need for a test that complements TVUS and β-hCG to increase diagnostic accuracy in predicting nonviable pregnancies.

Can serum progesterone testing fill the gap?
Serum progesterone measurement is a noninvasive predictive tool, with low values associated with miscarriage and ectopic pregnancy and higher levels with a viable pregnancy.¹⁰   Studies have found that serum progesterone combined with β-hCG measurements has the highest reliability in predicting nonviable pregnancy, with a diagnostic accuracy of 85.7% (sensitivity, 88.1%; specificity, 84.3%). This compares with a diagnostic accuracy of 72.5% (sensitivity, 76.1%; specificity, 70.4%) for a single progesterone test alone, and 74.8% (sensitivity, 64.1%; specificity, 81.4%) for β-hCG alone.^10-12 The data are from older studies, including a meta-analysis, that did not include the use of TVUS.^10-12 But TVUS is now in widespread use and included in the systematic review and meta-analysis this PURL addresses.

Study summary:

Progesterone test is predictive—when combined with ultrasound
Verhaegen et al performed a comprehensive literature search to identify studies in which a single serum progesterone measurement was used to predict the viability of pregnancy vs miscarriage or ectopic pregnancy. They included studies of women with spontaneous pregnancy of <14 weeks. Trials of women who had conceived after ovulation induction or in vitro fertilization or received progesterone supplementation were excluded.

Twenty-six cohort studies met the inclusion criteria. These included 7 mostly high-quality studies, with a total of 2379 women with pain or bleeding and inconclusive TVUS, and 19 intermediate-quality studies (n=7057) of women who had pain or bleeding but no ultrasound.

Five of the 7 studies in women with symptoms and inconclusive TVUS had a similar progesterone test cutoff value (3.2-6 ng/mL). In these 5 studies (n=1998), the progesterone test predicted a nonviable pregnancy with a pooled sensitivity of 74.6% (95% CI, 50.6%-89.4%) and specificity of 98.4% (95% CI, 90.9%-99.7%), a positive likelihood ratio of 45 (7.1- 289) and a negative likelihood ratio of 0.26 (0.12-0.57). When progesterone was below the cutoff value, the probability of a nonviable pregnancy increased to 99.2%. In women with pain or bleeding but no ultrasound, a single progesterone test is less accurate in ruling out a viable pregnancy.

What's new

This test can end days of anxious waiting

This meta-analysis provides strong evidence that a single progesterone measurement is useful in predicting nonviable pregnancies in women with pain or bleeding when TVUS is inconclusive. In such patients, a low serum progesterone is highly predictive of a nonviable pregnancy.¹ This finding enables the physician to counsel the woman immediately on the likely pregnancy loss, without waiting days for serial β-hCG results.

Caveats

Progesterone is a poor predictor of ectopic pregnancy

An important caveat to our recommendation is that a single serum progesterone test has a poor predictive value for ectopic pregnancy and should not be used for this purpose. A combination of TVUS and serial β-hCG remains the optimal strategy for diagnosing ectopic pregnancy.¹³

It is important to note that there is no universally accepted definition of a low serum progesterone level: This meta-analysis included studies with a cutoff value of 3.2 to 6 ng/mL in women who had had a previous ultrasound. What’s more, these studies did not evaluate the predictive value of a serum progesterone test combined with β-hCG measurements.

Challenges to implementation

There are none
We do not see any challenges to the implementation of this recommendation.

ACKNOWLEDGEMENT 

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center of Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 60-year-old assembly line worker reports bilateral hand numbness and tingling that frequently awaken her at night. What is the best office test to determine if she has CTS?

CTS is one of the most common causes of disability in the United States.² Among patients with hand paresthesias, one in five has CTS.² Factory workers whose jobs involve repetitive hand movements, women, and the elderly are at increased risk.³ If left untreated, the symptoms are likely to become constant, with thenar muscle wasting and weakness.

Traditional diagnostic test 
has only 50% sensitivity
In the traditional Phalen’s test (TPT)—commonly used in an office setting—the patient holds his or her wrists in a position of fixed flexion for one minute. The onset of paresthesias is considered a positive result.

The TPT was found in the study reported here to be 100% specific;¹ however, other studies have found a wider range of specificity (33% to 86%).⁴ The TPT has a sensitivity of only 50%, which increases the risk that cases of CTS will be missed. This is an important consideration, because establishing a diagnosis early in the course of CTS has been shown to minimize disability.⁵

STUDY SUMMARY
Modified Phalen’s has higher sensitivity
Bilkis et al developed a modified Phalen’s test and compared it with the TPT, as well as with electrodiagnostic studies (EDS)—the gold standard for CTS diagnosis. The MPT begins with the TPT position and adds sensory testing with a Semmes-Weinstein 2.83-unit monofilament.

See how the modified Phalen’s test is done

The filament is applied perpendicular to the palmar and lateral surface of each distal finger three times, with enough pressure to bend the monofilament. In this study, the test was considered “positive” if the patient did not feel the monofilament in any finger along the distribution of the median nerve. The MPT was “negative” if the patient correctly reported being touched along this distribution. The fifth, or “pinkie,” finger, which is less likely to be affected by CTS, was used as a control.

Participants in the study were adult patients—mostly women between the ages of 27 and 88—at a neurology clinic. Exclusion criteria included cervical radiculopathy, a history of stroke, diabetes, and concomitant neck injury. A total of 66 hands (and 37 participants) underwent TPT and MPT testing by trained examiners, followed by EDS to confirm the findings.

EDS found evidence of CTS in 46 of the 66 hands studied. The MPT correctly identified 39 of the 46, while the TPT correctly identified 23. Both the traditional and the modified Phalen’s tests were found to be 100% specific, but the sensitivity of the MPT was 85% (95% confidence interval [CI], 71% to 93%), compared with 50% (95% CI, 35% to 65%) for the TPT.

WHAT’S NEW
Better results can be achieved in seconds
The addition of monofilament testing to the TPT increases the sensitivity in identifying CTS. The MPT is simple to learn and, based on our observations, adds only about 10 to 15 seconds to the clinical exam.

CAVEATS
Modification is untested in primary care
A diagnosis of CTS is rarely made on the basis of one test, but rather on a set of signs, symptoms, and physical exam maneuvers. The added value of the MPT needs to be evaluated in the larger context of the comprehensive clinical examination for CTS.⁶

Notably, the study participants were seen in a neurology clinic, which suggests that they may have had more advanced CTS than typical primary care patients. That would help explain the 100% specificity of both the traditional and modified tests reported by the researchers. The sensitivity of the MPT may therefore be lower in a family practice because the spectrum of disease may be wider. Another study is needed to evaluate the performance of the MPT in a primary care setting.

The monofilament used (Semmes-Weinstein 2.83) is not the same as the typical 5.07 (10-g) monofilament used in diabetic foot screenings. Using this heavier monofilament with a stronger pressure point would likely decrease the sensitivity of the MPT.

CHALLENGES TO IMPLEMENTATION
Taking the time, obtaining the monofilament
Additional time to obtain the correct monofilament and administer the MPT are the key challenges to implementation.

REFERENCES
1. Bilkis S, Loveman DM, Eldridge JA, et al. Modified Phalen’s test as an aid in diagnosing carpal tunnel syndrome. Arthritis Care Res. 2012;64:287-289.

2. Atroshi I, Gummesson C, Johnsson R, et al. Prevalence of carpal tunnel syndrome in a general population. JAMA. 1999;282:153-158.

3. National Institute of Neurological Disorders and Stroke. Carpal tunnel syndrome fact sheet. National Institutes of Health. July 2012. www.ninds.nih.gov/disorders/carpal_tunnel/detail_carpal_tunnel.htm. Accessed April 15, 2013.

4. McGee SR. Evidence-Based Physical Diagnosis. 3rd ed. Philadelphia, PA: Saunders; 2012:chap 62.

5. Daniell WE, Fulton-Kehoe D, Franklin GM. Work-related carpal tunnel syndrome in Washington State workers’ compensation: utilization of surgery and the duration of lost work. Am J Ind Med. 2009;52:931-942.

6. D’Arcy CA, McGee S. Does this patient have carpal tunnel syndrome? JAMA. 2000;282:3110-3117.

ACKNOWLEDGEMENT
The PURLs Surveillance System was developed with support from Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2013. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2013;62(5):253-254.

ILLUSTRATIVE CASE

A 60-year-old assembly line worker reports bilateral hand numbness and tingling that frequently awaken her at night. What is the best office test to determine if she has CTS?

CTS is one of the most common causes of disability in the United States.² Among patients with hand paresthesias, one in five has CTS.² Factory workers whose jobs involve repetitive hand movements, women, and the elderly are at increased risk.³ If left untreated, the symptoms are likely to become constant, with thenar muscle wasting and weakness.

Traditional diagnostic test 
has only 50% sensitivity
In the traditional Phalen’s test (TPT)—commonly used in an office setting—the patient holds his or her wrists in a position of fixed flexion for one minute. The onset of paresthesias is considered a positive result.

The TPT was found in the study reported here to be 100% specific;¹ however, other studies have found a wider range of specificity (33% to 86%).⁴ The TPT has a sensitivity of only 50%, which increases the risk that cases of CTS will be missed. This is an important consideration, because establishing a diagnosis early in the course of CTS has been shown to minimize disability.⁵

STUDY SUMMARY
Modified Phalen’s has higher sensitivity
Bilkis et al developed a modified Phalen’s test and compared it with the TPT, as well as with electrodiagnostic studies (EDS)—the gold standard for CTS diagnosis. The MPT begins with the TPT position and adds sensory testing with a Semmes-Weinstein 2.83-unit monofilament.

See how the modified Phalen’s test is done

The filament is applied perpendicular to the palmar and lateral surface of each distal finger three times, with enough pressure to bend the monofilament. In this study, the test was considered “positive” if the patient did not feel the monofilament in any finger along the distribution of the median nerve. The MPT was “negative” if the patient correctly reported being touched along this distribution. The fifth, or “pinkie,” finger, which is less likely to be affected by CTS, was used as a control.

Participants in the study were adult patients—mostly women between the ages of 27 and 88—at a neurology clinic. Exclusion criteria included cervical radiculopathy, a history of stroke, diabetes, and concomitant neck injury. A total of 66 hands (and 37 participants) underwent TPT and MPT testing by trained examiners, followed by EDS to confirm the findings.

EDS found evidence of CTS in 46 of the 66 hands studied. The MPT correctly identified 39 of the 46, while the TPT correctly identified 23. Both the traditional and the modified Phalen’s tests were found to be 100% specific, but the sensitivity of the MPT was 85% (95% confidence interval [CI], 71% to 93%), compared with 50% (95% CI, 35% to 65%) for the TPT.

WHAT’S NEW
Better results can be achieved in seconds
The addition of monofilament testing to the TPT increases the sensitivity in identifying CTS. The MPT is simple to learn and, based on our observations, adds only about 10 to 15 seconds to the clinical exam.

CAVEATS
Modification is untested in primary care
A diagnosis of CTS is rarely made on the basis of one test, but rather on a set of signs, symptoms, and physical exam maneuvers. The added value of the MPT needs to be evaluated in the larger context of the comprehensive clinical examination for CTS.⁶

Notably, the study participants were seen in a neurology clinic, which suggests that they may have had more advanced CTS than typical primary care patients. That would help explain the 100% specificity of both the traditional and modified tests reported by the researchers. The sensitivity of the MPT may therefore be lower in a family practice because the spectrum of disease may be wider. Another study is needed to evaluate the performance of the MPT in a primary care setting.

The monofilament used (Semmes-Weinstein 2.83) is not the same as the typical 5.07 (10-g) monofilament used in diabetic foot screenings. Using this heavier monofilament with a stronger pressure point would likely decrease the sensitivity of the MPT.

CHALLENGES TO IMPLEMENTATION
Taking the time, obtaining the monofilament
Additional time to obtain the correct monofilament and administer the MPT are the key challenges to implementation.

REFERENCES
1. Bilkis S, Loveman DM, Eldridge JA, et al. Modified Phalen’s test as an aid in diagnosing carpal tunnel syndrome. Arthritis Care Res. 2012;64:287-289.

2. Atroshi I, Gummesson C, Johnsson R, et al. Prevalence of carpal tunnel syndrome in a general population. JAMA. 1999;282:153-158.

3. National Institute of Neurological Disorders and Stroke. Carpal tunnel syndrome fact sheet. National Institutes of Health. July 2012. www.ninds.nih.gov/disorders/carpal_tunnel/detail_carpal_tunnel.htm. Accessed April 15, 2013.

4. McGee SR. Evidence-Based Physical Diagnosis. 3rd ed. Philadelphia, PA: Saunders; 2012:chap 62.

5. Daniell WE, Fulton-Kehoe D, Franklin GM. Work-related carpal tunnel syndrome in Washington State workers’ compensation: utilization of surgery and the duration of lost work. Am J Ind Med. 2009;52:931-942.

6. D’Arcy CA, McGee S. Does this patient have carpal tunnel syndrome? JAMA. 2000;282:3110-3117.

ACKNOWLEDGEMENT
The PURLs Surveillance System was developed with support from Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2013. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2013;62(5):253-254.

ILLUSTRATIVE CASE

A 60-year-old assembly line worker reports bilateral hand numbness and tingling that frequently awaken her at night. What is the best office test to determine if she has CTS?

CTS is one of the most common causes of disability in the United States.² Among patients with hand paresthesias, one in five has CTS.² Factory workers whose jobs involve repetitive hand movements, women, and the elderly are at increased risk.³ If left untreated, the symptoms are likely to become constant, with thenar muscle wasting and weakness.

Traditional diagnostic test 
has only 50% sensitivity
In the traditional Phalen’s test (TPT)—commonly used in an office setting—the patient holds his or her wrists in a position of fixed flexion for one minute. The onset of paresthesias is considered a positive result.

The TPT was found in the study reported here to be 100% specific;¹ however, other studies have found a wider range of specificity (33% to 86%).⁴ The TPT has a sensitivity of only 50%, which increases the risk that cases of CTS will be missed. This is an important consideration, because establishing a diagnosis early in the course of CTS has been shown to minimize disability.⁵

STUDY SUMMARY
Modified Phalen’s has higher sensitivity
Bilkis et al developed a modified Phalen’s test and compared it with the TPT, as well as with electrodiagnostic studies (EDS)—the gold standard for CTS diagnosis. The MPT begins with the TPT position and adds sensory testing with a Semmes-Weinstein 2.83-unit monofilament.

See how the modified Phalen’s test is done

The filament is applied perpendicular to the palmar and lateral surface of each distal finger three times, with enough pressure to bend the monofilament. In this study, the test was considered “positive” if the patient did not feel the monofilament in any finger along the distribution of the median nerve. The MPT was “negative” if the patient correctly reported being touched along this distribution. The fifth, or “pinkie,” finger, which is less likely to be affected by CTS, was used as a control.

Participants in the study were adult patients—mostly women between the ages of 27 and 88—at a neurology clinic. Exclusion criteria included cervical radiculopathy, a history of stroke, diabetes, and concomitant neck injury. A total of 66 hands (and 37 participants) underwent TPT and MPT testing by trained examiners, followed by EDS to confirm the findings.

EDS found evidence of CTS in 46 of the 66 hands studied. The MPT correctly identified 39 of the 46, while the TPT correctly identified 23. Both the traditional and the modified Phalen’s tests were found to be 100% specific, but the sensitivity of the MPT was 85% (95% confidence interval [CI], 71% to 93%), compared with 50% (95% CI, 35% to 65%) for the TPT.

WHAT’S NEW
Better results can be achieved in seconds
The addition of monofilament testing to the TPT increases the sensitivity in identifying CTS. The MPT is simple to learn and, based on our observations, adds only about 10 to 15 seconds to the clinical exam.

CAVEATS
Modification is untested in primary care
A diagnosis of CTS is rarely made on the basis of one test, but rather on a set of signs, symptoms, and physical exam maneuvers. The added value of the MPT needs to be evaluated in the larger context of the comprehensive clinical examination for CTS.⁶

Notably, the study participants were seen in a neurology clinic, which suggests that they may have had more advanced CTS than typical primary care patients. That would help explain the 100% specificity of both the traditional and modified tests reported by the researchers. The sensitivity of the MPT may therefore be lower in a family practice because the spectrum of disease may be wider. Another study is needed to evaluate the performance of the MPT in a primary care setting.

The monofilament used (Semmes-Weinstein 2.83) is not the same as the typical 5.07 (10-g) monofilament used in diabetic foot screenings. Using this heavier monofilament with a stronger pressure point would likely decrease the sensitivity of the MPT.

CHALLENGES TO IMPLEMENTATION
Taking the time, obtaining the monofilament
Additional time to obtain the correct monofilament and administer the MPT are the key challenges to implementation.

REFERENCES
1. Bilkis S, Loveman DM, Eldridge JA, et al. Modified Phalen’s test as an aid in diagnosing carpal tunnel syndrome. Arthritis Care Res. 2012;64:287-289.

2. Atroshi I, Gummesson C, Johnsson R, et al. Prevalence of carpal tunnel syndrome in a general population. JAMA. 1999;282:153-158.

3. National Institute of Neurological Disorders and Stroke. Carpal tunnel syndrome fact sheet. National Institutes of Health. July 2012. www.ninds.nih.gov/disorders/carpal_tunnel/detail_carpal_tunnel.htm. Accessed April 15, 2013.

4. McGee SR. Evidence-Based Physical Diagnosis. 3rd ed. Philadelphia, PA: Saunders; 2012:chap 62.

5. Daniell WE, Fulton-Kehoe D, Franklin GM. Work-related carpal tunnel syndrome in Washington State workers’ compensation: utilization of surgery and the duration of lost work. Am J Ind Med. 2009;52:931-942.

6. D’Arcy CA, McGee S. Does this patient have carpal tunnel syndrome? JAMA. 2000;282:3110-3117.

ACKNOWLEDGEMENT
The PURLs Surveillance System was developed with support from Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2013. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2013;62(5):253-254.

PRACTICE CHANGER
After patients with unprovoked venous thromboembolism (VTE) complete a 6- to 18-month course of oral anticoagulation therapy, consider a switch to aspirin.¹

STRENGTH OF

RECOMMENDATION
A: Based on one well-designed, randomized controlled trial (RCT).

ILLUSTRATIVE CASE
A 62-year-old patient comes to your office for follow-up of a primary unprovoked VTE. He has been on an oral anticoagulant for 12 months. Should he continue anticoagulation therapy despite the increased risk for major bleeding?

Patients who survive VTE—defined as either deep venous thrombosis (DVT) or pulmonary embolism (PE)—are put on anticoagulant therapy to prevent a recurrence, typically for six to 18 months. But about 20% of patients with unprovoked VTE have a recurrence within two years of anticoagulation withdrawal.² Extending anticoagulation prevents recurrences but increases the risk for bleeding.³

Is aspirin a viable alternative?

Until recently, the efficacy of aspirin for the prevention of recurrent VTE was unknown. Becattini et al¹ investigated it in the multicenter RCT detailed in this PURL.

STUDY SUMMARY
Aspirin can prevent recurrence with minimal risk
To determine whether aspirin was a viable alternative to oral anticoagulation, the researchers compared aspirin with placebo in patients with primary unprovoked VTE who had completed a course of oral anticoagulation treatment.

To be considered for the study, patients had to be older than 18 and have had their first-ever objectively confirmed, symptomatic unprovoked proximal DVT PE, or both. They also had to have completed six to 18 months of anticoagulant therapy, with a target international normalized ratio (INR) of 2.0 to 3.0. Exclusion criteria included a history of cancer, clinically significant thrombophilia, atrial fibrillation, and a bleeding event that occurred during the course of anticoagulation therapy.

Becattini et al identified 403 eligible patients. Two weeks after stopping anticoagulation, patients were randomly assigned to receive either aspirin 100 mg/d (n = 205) or placebo (n = 198) for two years. (One patient in the placebo group never received treatment.)

At baseline, there were no significant differences in patient characteristics. All were evaluated every three months in the first year and every six months in the second year.

The primary efficacy outcome was objectively confirmed recurrent VTE. The primary safety outcome was major bleeding, defined as bleeding that occurred in a critical location (eg, intracranial bleeding), was associated with a decrease of hemoglobin of at least 2 g/dL, required a transfusion of two units of whole blood or red blood cells, or was fatal. Overt bleeding, which required medical intervention but did not meet the criteria for major bleeding, was a secondary safety outcome.

Twenty-eight of the 205 patients in the aspirin group experienced a recurrence, compared with 43 of the 197 patients on placebo (6.6% vs 11.2% per year; hazard ratio [HR] = 0.58).

Adverse events were reported by seven patients in the aspirin therapy group and six in the placebo group. One patient in each group experienced major bleeding, and three in each group experienced clinically relevant but nonmajor bleeding.

Withdrawal rates were similar (10 in the group receiving aspirin vs 9 in the group receiving placebo), as were the number of patients who developed new indications for aspirin or anticoagulation therapy or were lost to follow-up.

An analysis adjusted for age, sex, index event (DVT or PE) and duration of initial anticoagulation treatment confirmed that aspirin reduced the risk for recurrence (adjusted HR = 0.53). No association was found between recurrent VTE and duration of anticoagulation therapy (six months vs longer). Nor was there a difference in recurrence rates based on the index event.

WHAT'S NEW
Aspirin has a key role

in preventing recurrence
This study found that for patients with unprovoked VTE who completed a course of oral anticoagulation, aspirin was effective in preventing a recurrence, with no apparent increase in the risk for major bleeding. Protection in year 2 was nearly as great as in year 1.¹

CAVEAT
Patients were followed

for just two years
It is unclear whether continuing aspirin therapy beyond two years would continue to confer protection against a VTE recurrence without an increase in adverse effects.

CHALLENGE TO IMPLEMENTATION
Some patients can't tolerate chronic aspirin therapy
Although this study investigated aspirin in a dosage of 100 mg/d, this strength is not readily available in the United States.⁴ There is no evidence to suggest that the 81-mg strength that is available in this country would provide a diminished antiplatelet effect.

And, as is already customary, patients undergoing chronic aspirin therapy must be monitored for major bleeding, GI irritation, and renal compromise. A few patients will be ineligible for prophylaxis due to a history of intolerance to aspirin or NSAIDs.

REFERENCES
1. Becattini C, Agnelli G, Schenone A, et al. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med. 2012;366:1959-1967.

2. Prandoni P, Lensing AW, Cogo A, et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med. 1996;125:1-7.

3. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis. American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141 (2 suppl):e419S-e494S.

4. Daily Med. Aspirin. dailymed.nlm.nih.gov/dailymed/search.cfm?startswith=aspirin. Accessed September 6, 2012.

Acknowledgement
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2012. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2012;61:673-674.

PRACTICE CHANGER
After patients with unprovoked venous thromboembolism (VTE) complete a 6- to 18-month course of oral anticoagulation therapy, consider a switch to aspirin.¹

STRENGTH OF

RECOMMENDATION
A: Based on one well-designed, randomized controlled trial (RCT).

ILLUSTRATIVE CASE
A 62-year-old patient comes to your office for follow-up of a primary unprovoked VTE. He has been on an oral anticoagulant for 12 months. Should he continue anticoagulation therapy despite the increased risk for major bleeding?

Patients who survive VTE—defined as either deep venous thrombosis (DVT) or pulmonary embolism (PE)—are put on anticoagulant therapy to prevent a recurrence, typically for six to 18 months. But about 20% of patients with unprovoked VTE have a recurrence within two years of anticoagulation withdrawal.² Extending anticoagulation prevents recurrences but increases the risk for bleeding.³

Is aspirin a viable alternative?

Until recently, the efficacy of aspirin for the prevention of recurrent VTE was unknown. Becattini et al¹ investigated it in the multicenter RCT detailed in this PURL.

STUDY SUMMARY
Aspirin can prevent recurrence with minimal risk
To determine whether aspirin was a viable alternative to oral anticoagulation, the researchers compared aspirin with placebo in patients with primary unprovoked VTE who had completed a course of oral anticoagulation treatment.

To be considered for the study, patients had to be older than 18 and have had their first-ever objectively confirmed, symptomatic unprovoked proximal DVT PE, or both. They also had to have completed six to 18 months of anticoagulant therapy, with a target international normalized ratio (INR) of 2.0 to 3.0. Exclusion criteria included a history of cancer, clinically significant thrombophilia, atrial fibrillation, and a bleeding event that occurred during the course of anticoagulation therapy.

Becattini et al identified 403 eligible patients. Two weeks after stopping anticoagulation, patients were randomly assigned to receive either aspirin 100 mg/d (n = 205) or placebo (n = 198) for two years. (One patient in the placebo group never received treatment.)

At baseline, there were no significant differences in patient characteristics. All were evaluated every three months in the first year and every six months in the second year.

The primary efficacy outcome was objectively confirmed recurrent VTE. The primary safety outcome was major bleeding, defined as bleeding that occurred in a critical location (eg, intracranial bleeding), was associated with a decrease of hemoglobin of at least 2 g/dL, required a transfusion of two units of whole blood or red blood cells, or was fatal. Overt bleeding, which required medical intervention but did not meet the criteria for major bleeding, was a secondary safety outcome.

Twenty-eight of the 205 patients in the aspirin group experienced a recurrence, compared with 43 of the 197 patients on placebo (6.6% vs 11.2% per year; hazard ratio [HR] = 0.58).

Adverse events were reported by seven patients in the aspirin therapy group and six in the placebo group. One patient in each group experienced major bleeding, and three in each group experienced clinically relevant but nonmajor bleeding.

Withdrawal rates were similar (10 in the group receiving aspirin vs 9 in the group receiving placebo), as were the number of patients who developed new indications for aspirin or anticoagulation therapy or were lost to follow-up.

An analysis adjusted for age, sex, index event (DVT or PE) and duration of initial anticoagulation treatment confirmed that aspirin reduced the risk for recurrence (adjusted HR = 0.53). No association was found between recurrent VTE and duration of anticoagulation therapy (six months vs longer). Nor was there a difference in recurrence rates based on the index event.

WHAT'S NEW
Aspirin has a key role

in preventing recurrence
This study found that for patients with unprovoked VTE who completed a course of oral anticoagulation, aspirin was effective in preventing a recurrence, with no apparent increase in the risk for major bleeding. Protection in year 2 was nearly as great as in year 1.¹

CAVEAT
Patients were followed

for just two years
It is unclear whether continuing aspirin therapy beyond two years would continue to confer protection against a VTE recurrence without an increase in adverse effects.

CHALLENGE TO IMPLEMENTATION
Some patients can't tolerate chronic aspirin therapy
Although this study investigated aspirin in a dosage of 100 mg/d, this strength is not readily available in the United States.⁴ There is no evidence to suggest that the 81-mg strength that is available in this country would provide a diminished antiplatelet effect.

And, as is already customary, patients undergoing chronic aspirin therapy must be monitored for major bleeding, GI irritation, and renal compromise. A few patients will be ineligible for prophylaxis due to a history of intolerance to aspirin or NSAIDs.

REFERENCES
1. Becattini C, Agnelli G, Schenone A, et al. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med. 2012;366:1959-1967.

2. Prandoni P, Lensing AW, Cogo A, et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med. 1996;125:1-7.

3. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis. American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141 (2 suppl):e419S-e494S.

4. Daily Med. Aspirin. dailymed.nlm.nih.gov/dailymed/search.cfm?startswith=aspirin. Accessed September 6, 2012.

Acknowledgement
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2012. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2012;61:673-674.

PRACTICE CHANGER
After patients with unprovoked venous thromboembolism (VTE) complete a 6- to 18-month course of oral anticoagulation therapy, consider a switch to aspirin.¹

STRENGTH OF

RECOMMENDATION
A: Based on one well-designed, randomized controlled trial (RCT).

ILLUSTRATIVE CASE
A 62-year-old patient comes to your office for follow-up of a primary unprovoked VTE. He has been on an oral anticoagulant for 12 months. Should he continue anticoagulation therapy despite the increased risk for major bleeding?

Patients who survive VTE—defined as either deep venous thrombosis (DVT) or pulmonary embolism (PE)—are put on anticoagulant therapy to prevent a recurrence, typically for six to 18 months. But about 20% of patients with unprovoked VTE have a recurrence within two years of anticoagulation withdrawal.² Extending anticoagulation prevents recurrences but increases the risk for bleeding.³

Is aspirin a viable alternative?

Until recently, the efficacy of aspirin for the prevention of recurrent VTE was unknown. Becattini et al¹ investigated it in the multicenter RCT detailed in this PURL.

STUDY SUMMARY
Aspirin can prevent recurrence with minimal risk
To determine whether aspirin was a viable alternative to oral anticoagulation, the researchers compared aspirin with placebo in patients with primary unprovoked VTE who had completed a course of oral anticoagulation treatment.

To be considered for the study, patients had to be older than 18 and have had their first-ever objectively confirmed, symptomatic unprovoked proximal DVT PE, or both. They also had to have completed six to 18 months of anticoagulant therapy, with a target international normalized ratio (INR) of 2.0 to 3.0. Exclusion criteria included a history of cancer, clinically significant thrombophilia, atrial fibrillation, and a bleeding event that occurred during the course of anticoagulation therapy.

Becattini et al identified 403 eligible patients. Two weeks after stopping anticoagulation, patients were randomly assigned to receive either aspirin 100 mg/d (n = 205) or placebo (n = 198) for two years. (One patient in the placebo group never received treatment.)

At baseline, there were no significant differences in patient characteristics. All were evaluated every three months in the first year and every six months in the second year.

The primary efficacy outcome was objectively confirmed recurrent VTE. The primary safety outcome was major bleeding, defined as bleeding that occurred in a critical location (eg, intracranial bleeding), was associated with a decrease of hemoglobin of at least 2 g/dL, required a transfusion of two units of whole blood or red blood cells, or was fatal. Overt bleeding, which required medical intervention but did not meet the criteria for major bleeding, was a secondary safety outcome.

Twenty-eight of the 205 patients in the aspirin group experienced a recurrence, compared with 43 of the 197 patients on placebo (6.6% vs 11.2% per year; hazard ratio [HR] = 0.58).

Adverse events were reported by seven patients in the aspirin therapy group and six in the placebo group. One patient in each group experienced major bleeding, and three in each group experienced clinically relevant but nonmajor bleeding.

Withdrawal rates were similar (10 in the group receiving aspirin vs 9 in the group receiving placebo), as were the number of patients who developed new indications for aspirin or anticoagulation therapy or were lost to follow-up.

An analysis adjusted for age, sex, index event (DVT or PE) and duration of initial anticoagulation treatment confirmed that aspirin reduced the risk for recurrence (adjusted HR = 0.53). No association was found between recurrent VTE and duration of anticoagulation therapy (six months vs longer). Nor was there a difference in recurrence rates based on the index event.

WHAT'S NEW
Aspirin has a key role

in preventing recurrence
This study found that for patients with unprovoked VTE who completed a course of oral anticoagulation, aspirin was effective in preventing a recurrence, with no apparent increase in the risk for major bleeding. Protection in year 2 was nearly as great as in year 1.¹

CAVEAT
Patients were followed

for just two years
It is unclear whether continuing aspirin therapy beyond two years would continue to confer protection against a VTE recurrence without an increase in adverse effects.

CHALLENGE TO IMPLEMENTATION
Some patients can't tolerate chronic aspirin therapy
Although this study investigated aspirin in a dosage of 100 mg/d, this strength is not readily available in the United States.⁴ There is no evidence to suggest that the 81-mg strength that is available in this country would provide a diminished antiplatelet effect.

And, as is already customary, patients undergoing chronic aspirin therapy must be monitored for major bleeding, GI irritation, and renal compromise. A few patients will be ineligible for prophylaxis due to a history of intolerance to aspirin or NSAIDs.

REFERENCES
1. Becattini C, Agnelli G, Schenone A, et al. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med. 2012;366:1959-1967.

2. Prandoni P, Lensing AW, Cogo A, et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med. 1996;125:1-7.

3. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis. American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141 (2 suppl):e419S-e494S.

4. Daily Med. Aspirin. dailymed.nlm.nih.gov/dailymed/search.cfm?startswith=aspirin. Accessed September 6, 2012.

Acknowledgement
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2012. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2012;61:673-674.

ILLUSTRATIVE CASE

A healthy 27-year-old woman schedules a visit to discuss birth control options. Should you screen her for IPV and if so, what instrument should you use?

Each year in the United States, an estimated 5.3 million women ages 18 and older are affected by IPV, resulting in nearly 2 million injuries and more than $4 billion in direct medical and mental health costs.² In addition to the immediate effects, which include death as well as injuries from physical and sexual assault,² IPV has long-term consequences, such as chronic physical and mental illness and substance abuse.³

Too little evidence of benefit?
In 2011, the Institute of Medicine (IOM) recommended for the first time that all women of childbearing age be screened for IPV-and identified IPV screening as one of a number of preventive services that are important to women’s health.⁴ The IOM’s recommendation is in line with positions held by the American Medical Association’s National Advisory Council on Violence and Abuse⁵ and the American College of Obstetrics and Gynecology.⁶ These recommendations differ from that of the US Preventive Services Task Force (USPSTF), which determined in 2004 that there was insufficient evidence for or against screening women for IPV.⁷ In issuing its “I” rating, the USPSTF cited a lack of studies evaluating the accuracy of screening tools for identifying IPV and a lack of evidence as to whether interventions lead to a reduction in harm.

The 2012 systemic review detailed below was undertaken on behalf of the USPSTF to assess the latest evidence and update its recommendation. The USPSTF and Agency for Healthcare Research and Quality (AHRQ) determined the focus and scope of the review.

STUDY SUMMARY: USPSTF issues a B recommendation for IPV screening

Thirty-four studies of women who sought care in either primary care settings or emergency departments (EDs) but had no complaints related to IPV were included in the review, which addressed 4 key questions.

Question 1: Does screening women for current, past, or increased risk of IPV reduce exposure to IPV, morbidity, or mortality?

No, according to one large RCT whose validity was compromised by high dropout rates. The researchers reviewed a multicenter RCT with 6743 participants ages 18 to 64 years to answer that question. (The study was deemed to be of fair quality because of the high percentage of dropouts from both the screened and unscreened groups.)

The women, recruited from primary care, acute care, and obstetrics and gynecology clinics in Canada, were randomly assigned to either screening with the Woman Abuse Screening Tool (WAST)—an 8-question, self-administered and validated tool—or no screening. Primary outcomes were exposure to abuse and quality of life in the 18 months after screening; secondary outcomes included both mental and physical ailments.

Those in the intervention group underwent screening before seeing their clinicians, who received the positive results before the patient encounter but were not told how, or whether, to respond. Women in both the screened and unscreened groups had access to IPV resources, including psychologists, social workers, crisis hotlines, sexual assault crisis centers, counseling services, and women’s shelters, as well as physician visits. In addition, all participants completed a validated Composite Abuse Scale, a broader (30-question) self-administered measure of IPV, at the end of the visit. Those with positive scores were followed for 18 months.

At follow-up, women in both the screened and unscreened groups had accessed additional health care services. Both groups also had reduced IPV, posttraumatic stress disorder, depression, and alcohol problems, and improved quality of life and mental health. There was no statistical difference in outcomes between the groups.

Question 2: How effective are the screening techniques?

The efficacy of at least 5 tools has been demonstrated. Fifteen diagnostic accuracy studies, using cross-sectional and prospective data, evaluated a total of 13 screening instruments.

Five of the 13 screening tools—the face-to-face Hurt, Insult, Threaten, and Scream (HITS) tool, the self-administered Ongoing Violence Assessment Tool (OVAT), the face-to-face Slapped, Threatened and Throw (STaT) instrument, the self-administered Humiliation, Afraid, Rape, Kick (HARK) tool, and the WAST—were at least 80% sensitive and 50% specific in identifying IPV in asymptomatic women.

Question 3: How well do the interventions reduce exposure to IPV, morbidity, or mortality in women with positive screens?

Interventions improve outcomes, according to several studies. One good-quality RCT comparing prenatal behavioral counseling by psychologists or social workers with usual care found that the intervention led to decreased IPV up to 10 weeks’ postpartum and improved birth outcomes. These included a reduction in preterm births, increased mean gestational age, and decreased rates of very low birth weight, although the difference for very low birth weight was not statistically significant.

One fair-quality trial comparing home visitation by paraprofessionals with usual care for postpartum women led to lower rates of IPV for those in the home visitation group 3 years after the intervention.

Another study compared a counseling intervention with usual care for women who had reported recent IPV. The intervention led to a decrease in pregnancy coercion—being physically or verbally threatened with pregnancy or prevented from using contraception—and an increase in the likelihood of ending an unsafe relationship.

Two trials evaluating counseling vs wallet-sized referral cards and nurse management vs usual care during pregnancy showed improved outcomes in both the intervention and control groups, with no statistically significant difference between them.

Question 4: What are the adverse effects of screening for IPV and interventions to reduce harm?

There are few—if any—adverse effects, according to 3 RCTs and several descriptive studies. The RCTs found no adverse effects of screening or IPV interventions. Descriptive studies showed low levels of harm among a wide range of study populations and a variety of methods. However, some women experienced loss of privacy, emotional distress, and concerns about further abuse.

WHAT’S NEW: B recommendation is finalized

Given the relative safety of screening, the potential benefits of interventions for women who have positive screens, and the availability of accurate screening instruments, the USPSTF disseminated a draft recommendation that health care providers screen all women between 14 and 46 years old for IPV.At presstime in late January, the recommendation was finalized.⁸

CAVEATS: Universal screening questions remain

While the findings from this systematic review led the USPSTF to upgrade its recommendation for IPV screening from an I (insufficient evidence) to a B (moderate to substantial benefit of screening), additional high-quality studies are needed to definitively reveal the benefit of screening.

The validity of the large multicenter RCT that found no benefit from IPV screening was compromised by high dropout rates and, potentially, by the fact that women in the control group had access to materials that increased IPV awareness. Overall, the trials included in this systematic review ranged from fair to good quality and had relatively high and differential rates of loss to follow-up, enrollment of dissimilar groups, and concern for the Hawthorne effect (in which participants change their behavior simply as a result of being involved in a study).

What’s more, some trials used narrowly defined populations, which could limit applicability. And, while some earlier studies had found higher rates of IPV disclosure using self-administered instruments compared with face-to-face questioning, more research is needed to identify the optimal screening method.⁹

CHALLENGES TO IMPLEMENTATION: The right screen—and reliable follow-up

Five of the screening instruments used in studies included in this systematic review accurately identified women with past or present IPV. Three of these are suitable for use in primary care:

• HARK, a self-administered screen available at www.ncbi.nlm.nih.gov/pmc/articles/PMC2034562/table/T1
• HITS, a face-to-face screen
• WAST, a self-administered screen (more information about these screens is available at http://www.cdc.gov/ncipc/pub-res/images/ipvandsvscreening.pdf).

After deciding which instrument to use, family physicians still must determine how to incorporate screening into a busy practice.

Finally, physicians should not screen for IPV until reliable procedures and resources for follow-up of patients who screen positive have been identified. Resources are readily available through local and national hotline numbers. The number of the National Domestic Violence Hotline is 800-799-SAFE.

Acknowledgement

The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A healthy 27-year-old woman schedules a visit to discuss birth control options. Should you screen her for IPV and if so, what instrument should you use?

Each year in the United States, an estimated 5.3 million women ages 18 and older are affected by IPV, resulting in nearly 2 million injuries and more than $4 billion in direct medical and mental health costs.² In addition to the immediate effects, which include death as well as injuries from physical and sexual assault,² IPV has long-term consequences, such as chronic physical and mental illness and substance abuse.³

Too little evidence of benefit?
In 2011, the Institute of Medicine (IOM) recommended for the first time that all women of childbearing age be screened for IPV-and identified IPV screening as one of a number of preventive services that are important to women’s health.⁴ The IOM’s recommendation is in line with positions held by the American Medical Association’s National Advisory Council on Violence and Abuse⁵ and the American College of Obstetrics and Gynecology.⁶ These recommendations differ from that of the US Preventive Services Task Force (USPSTF), which determined in 2004 that there was insufficient evidence for or against screening women for IPV.⁷ In issuing its “I” rating, the USPSTF cited a lack of studies evaluating the accuracy of screening tools for identifying IPV and a lack of evidence as to whether interventions lead to a reduction in harm.

The 2012 systemic review detailed below was undertaken on behalf of the USPSTF to assess the latest evidence and update its recommendation. The USPSTF and Agency for Healthcare Research and Quality (AHRQ) determined the focus and scope of the review.

STUDY SUMMARY: USPSTF issues a B recommendation for IPV screening

Thirty-four studies of women who sought care in either primary care settings or emergency departments (EDs) but had no complaints related to IPV were included in the review, which addressed 4 key questions.

Question 1: Does screening women for current, past, or increased risk of IPV reduce exposure to IPV, morbidity, or mortality?

No, according to one large RCT whose validity was compromised by high dropout rates. The researchers reviewed a multicenter RCT with 6743 participants ages 18 to 64 years to answer that question. (The study was deemed to be of fair quality because of the high percentage of dropouts from both the screened and unscreened groups.)

The women, recruited from primary care, acute care, and obstetrics and gynecology clinics in Canada, were randomly assigned to either screening with the Woman Abuse Screening Tool (WAST)—an 8-question, self-administered and validated tool—or no screening. Primary outcomes were exposure to abuse and quality of life in the 18 months after screening; secondary outcomes included both mental and physical ailments.

Those in the intervention group underwent screening before seeing their clinicians, who received the positive results before the patient encounter but were not told how, or whether, to respond. Women in both the screened and unscreened groups had access to IPV resources, including psychologists, social workers, crisis hotlines, sexual assault crisis centers, counseling services, and women’s shelters, as well as physician visits. In addition, all participants completed a validated Composite Abuse Scale, a broader (30-question) self-administered measure of IPV, at the end of the visit. Those with positive scores were followed for 18 months.

At follow-up, women in both the screened and unscreened groups had accessed additional health care services. Both groups also had reduced IPV, posttraumatic stress disorder, depression, and alcohol problems, and improved quality of life and mental health. There was no statistical difference in outcomes between the groups.

Question 2: How effective are the screening techniques?

The efficacy of at least 5 tools has been demonstrated. Fifteen diagnostic accuracy studies, using cross-sectional and prospective data, evaluated a total of 13 screening instruments.

Five of the 13 screening tools—the face-to-face Hurt, Insult, Threaten, and Scream (HITS) tool, the self-administered Ongoing Violence Assessment Tool (OVAT), the face-to-face Slapped, Threatened and Throw (STaT) instrument, the self-administered Humiliation, Afraid, Rape, Kick (HARK) tool, and the WAST—were at least 80% sensitive and 50% specific in identifying IPV in asymptomatic women.

Question 3: How well do the interventions reduce exposure to IPV, morbidity, or mortality in women with positive screens?

Interventions improve outcomes, according to several studies. One good-quality RCT comparing prenatal behavioral counseling by psychologists or social workers with usual care found that the intervention led to decreased IPV up to 10 weeks’ postpartum and improved birth outcomes. These included a reduction in preterm births, increased mean gestational age, and decreased rates of very low birth weight, although the difference for very low birth weight was not statistically significant.

One fair-quality trial comparing home visitation by paraprofessionals with usual care for postpartum women led to lower rates of IPV for those in the home visitation group 3 years after the intervention.

Another study compared a counseling intervention with usual care for women who had reported recent IPV. The intervention led to a decrease in pregnancy coercion—being physically or verbally threatened with pregnancy or prevented from using contraception—and an increase in the likelihood of ending an unsafe relationship.

Two trials evaluating counseling vs wallet-sized referral cards and nurse management vs usual care during pregnancy showed improved outcomes in both the intervention and control groups, with no statistically significant difference between them.

Question 4: What are the adverse effects of screening for IPV and interventions to reduce harm?

There are few—if any—adverse effects, according to 3 RCTs and several descriptive studies. The RCTs found no adverse effects of screening or IPV interventions. Descriptive studies showed low levels of harm among a wide range of study populations and a variety of methods. However, some women experienced loss of privacy, emotional distress, and concerns about further abuse.

WHAT’S NEW: B recommendation is finalized

Given the relative safety of screening, the potential benefits of interventions for women who have positive screens, and the availability of accurate screening instruments, the USPSTF disseminated a draft recommendation that health care providers screen all women between 14 and 46 years old for IPV.At presstime in late January, the recommendation was finalized.⁸

CAVEATS: Universal screening questions remain

While the findings from this systematic review led the USPSTF to upgrade its recommendation for IPV screening from an I (insufficient evidence) to a B (moderate to substantial benefit of screening), additional high-quality studies are needed to definitively reveal the benefit of screening.

The validity of the large multicenter RCT that found no benefit from IPV screening was compromised by high dropout rates and, potentially, by the fact that women in the control group had access to materials that increased IPV awareness. Overall, the trials included in this systematic review ranged from fair to good quality and had relatively high and differential rates of loss to follow-up, enrollment of dissimilar groups, and concern for the Hawthorne effect (in which participants change their behavior simply as a result of being involved in a study).

What’s more, some trials used narrowly defined populations, which could limit applicability. And, while some earlier studies had found higher rates of IPV disclosure using self-administered instruments compared with face-to-face questioning, more research is needed to identify the optimal screening method.⁹

CHALLENGES TO IMPLEMENTATION: The right screen—and reliable follow-up

Five of the screening instruments used in studies included in this systematic review accurately identified women with past or present IPV. Three of these are suitable for use in primary care:

• HARK, a self-administered screen available at www.ncbi.nlm.nih.gov/pmc/articles/PMC2034562/table/T1
• HITS, a face-to-face screen
• WAST, a self-administered screen (more information about these screens is available at http://www.cdc.gov/ncipc/pub-res/images/ipvandsvscreening.pdf).

After deciding which instrument to use, family physicians still must determine how to incorporate screening into a busy practice.

Finally, physicians should not screen for IPV until reliable procedures and resources for follow-up of patients who screen positive have been identified. Resources are readily available through local and national hotline numbers. The number of the National Domestic Violence Hotline is 800-799-SAFE.

Acknowledgement

The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A healthy 27-year-old woman schedules a visit to discuss birth control options. Should you screen her for IPV and if so, what instrument should you use?

Each year in the United States, an estimated 5.3 million women ages 18 and older are affected by IPV, resulting in nearly 2 million injuries and more than $4 billion in direct medical and mental health costs.² In addition to the immediate effects, which include death as well as injuries from physical and sexual assault,² IPV has long-term consequences, such as chronic physical and mental illness and substance abuse.³

Too little evidence of benefit?
In 2011, the Institute of Medicine (IOM) recommended for the first time that all women of childbearing age be screened for IPV-and identified IPV screening as one of a number of preventive services that are important to women’s health.⁴ The IOM’s recommendation is in line with positions held by the American Medical Association’s National Advisory Council on Violence and Abuse⁵ and the American College of Obstetrics and Gynecology.⁶ These recommendations differ from that of the US Preventive Services Task Force (USPSTF), which determined in 2004 that there was insufficient evidence for or against screening women for IPV.⁷ In issuing its “I” rating, the USPSTF cited a lack of studies evaluating the accuracy of screening tools for identifying IPV and a lack of evidence as to whether interventions lead to a reduction in harm.

The 2012 systemic review detailed below was undertaken on behalf of the USPSTF to assess the latest evidence and update its recommendation. The USPSTF and Agency for Healthcare Research and Quality (AHRQ) determined the focus and scope of the review.

STUDY SUMMARY: USPSTF issues a B recommendation for IPV screening

Thirty-four studies of women who sought care in either primary care settings or emergency departments (EDs) but had no complaints related to IPV were included in the review, which addressed 4 key questions.

Question 1: Does screening women for current, past, or increased risk of IPV reduce exposure to IPV, morbidity, or mortality?

No, according to one large RCT whose validity was compromised by high dropout rates. The researchers reviewed a multicenter RCT with 6743 participants ages 18 to 64 years to answer that question. (The study was deemed to be of fair quality because of the high percentage of dropouts from both the screened and unscreened groups.)

The women, recruited from primary care, acute care, and obstetrics and gynecology clinics in Canada, were randomly assigned to either screening with the Woman Abuse Screening Tool (WAST)—an 8-question, self-administered and validated tool—or no screening. Primary outcomes were exposure to abuse and quality of life in the 18 months after screening; secondary outcomes included both mental and physical ailments.

Those in the intervention group underwent screening before seeing their clinicians, who received the positive results before the patient encounter but were not told how, or whether, to respond. Women in both the screened and unscreened groups had access to IPV resources, including psychologists, social workers, crisis hotlines, sexual assault crisis centers, counseling services, and women’s shelters, as well as physician visits. In addition, all participants completed a validated Composite Abuse Scale, a broader (30-question) self-administered measure of IPV, at the end of the visit. Those with positive scores were followed for 18 months.

At follow-up, women in both the screened and unscreened groups had accessed additional health care services. Both groups also had reduced IPV, posttraumatic stress disorder, depression, and alcohol problems, and improved quality of life and mental health. There was no statistical difference in outcomes between the groups.

Question 2: How effective are the screening techniques?

The efficacy of at least 5 tools has been demonstrated. Fifteen diagnostic accuracy studies, using cross-sectional and prospective data, evaluated a total of 13 screening instruments.

Five of the 13 screening tools—the face-to-face Hurt, Insult, Threaten, and Scream (HITS) tool, the self-administered Ongoing Violence Assessment Tool (OVAT), the face-to-face Slapped, Threatened and Throw (STaT) instrument, the self-administered Humiliation, Afraid, Rape, Kick (HARK) tool, and the WAST—were at least 80% sensitive and 50% specific in identifying IPV in asymptomatic women.

Question 3: How well do the interventions reduce exposure to IPV, morbidity, or mortality in women with positive screens?

Interventions improve outcomes, according to several studies. One good-quality RCT comparing prenatal behavioral counseling by psychologists or social workers with usual care found that the intervention led to decreased IPV up to 10 weeks’ postpartum and improved birth outcomes. These included a reduction in preterm births, increased mean gestational age, and decreased rates of very low birth weight, although the difference for very low birth weight was not statistically significant.

One fair-quality trial comparing home visitation by paraprofessionals with usual care for postpartum women led to lower rates of IPV for those in the home visitation group 3 years after the intervention.

Another study compared a counseling intervention with usual care for women who had reported recent IPV. The intervention led to a decrease in pregnancy coercion—being physically or verbally threatened with pregnancy or prevented from using contraception—and an increase in the likelihood of ending an unsafe relationship.

Two trials evaluating counseling vs wallet-sized referral cards and nurse management vs usual care during pregnancy showed improved outcomes in both the intervention and control groups, with no statistically significant difference between them.

Question 4: What are the adverse effects of screening for IPV and interventions to reduce harm?

There are few—if any—adverse effects, according to 3 RCTs and several descriptive studies. The RCTs found no adverse effects of screening or IPV interventions. Descriptive studies showed low levels of harm among a wide range of study populations and a variety of methods. However, some women experienced loss of privacy, emotional distress, and concerns about further abuse.

WHAT’S NEW: B recommendation is finalized

Given the relative safety of screening, the potential benefits of interventions for women who have positive screens, and the availability of accurate screening instruments, the USPSTF disseminated a draft recommendation that health care providers screen all women between 14 and 46 years old for IPV.At presstime in late January, the recommendation was finalized.⁸

CAVEATS: Universal screening questions remain

While the findings from this systematic review led the USPSTF to upgrade its recommendation for IPV screening from an I (insufficient evidence) to a B (moderate to substantial benefit of screening), additional high-quality studies are needed to definitively reveal the benefit of screening.

The validity of the large multicenter RCT that found no benefit from IPV screening was compromised by high dropout rates and, potentially, by the fact that women in the control group had access to materials that increased IPV awareness. Overall, the trials included in this systematic review ranged from fair to good quality and had relatively high and differential rates of loss to follow-up, enrollment of dissimilar groups, and concern for the Hawthorne effect (in which participants change their behavior simply as a result of being involved in a study).

What’s more, some trials used narrowly defined populations, which could limit applicability. And, while some earlier studies had found higher rates of IPV disclosure using self-administered instruments compared with face-to-face questioning, more research is needed to identify the optimal screening method.⁹

CHALLENGES TO IMPLEMENTATION: The right screen—and reliable follow-up

Five of the screening instruments used in studies included in this systematic review accurately identified women with past or present IPV. Three of these are suitable for use in primary care:

• HARK, a self-administered screen available at www.ncbi.nlm.nih.gov/pmc/articles/PMC2034562/table/T1
• HITS, a face-to-face screen
• WAST, a self-administered screen (more information about these screens is available at http://www.cdc.gov/ncipc/pub-res/images/ipvandsvscreening.pdf).

After deciding which instrument to use, family physicians still must determine how to incorporate screening into a busy practice.

Finally, physicians should not screen for IPV until reliable procedures and resources for follow-up of patients who screen positive have been identified. Resources are readily available through local and national hotline numbers. The number of the National Domestic Violence Hotline is 800-799-SAFE.

Acknowledgement

The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Practice Changer
Recommend antispasmodics or antidepressants for patients with irritable bowel syndrome (IBS) and explain that, while fiber may have other benefits, it is unlikely to relieve IBS symptoms.¹

Strength of recommendation
A: Based on a meta-analysis.

Illustrative Case
A 25-year-old woman has intermittent bouts of abdominal pain, constipation, gas, and bloating. You believe she can benefit from treatment for IBS. What should you recommend?

IBS is the most common functional disorder of the gastrointestinal (GI) tract, affecting approximately 15% of the US population² and accounting for annual health care costs of roughly $30 billion.³ The primary symptoms are bloating, gas, and abdominal pain that often improves immediately after a bowel movement. Patients may have intermittent diarrhea and constipation, as well.

IBS may be related to “brain-gut dysfunction”
The etiology of IBS is unclear, but many agree that a combination of abnormal GI motility, visceral hypersensitivity, and “brain-gut dysfunction”—the inability of the brain to send signals that turn down pain produced in the GI tract—are contributing factors. Although IBS is not life threatening, it has a significant personal, social, and psychological impact. Despite its high prevalence and impact, only a limited number of large studies have assessed the effectiveness of various treatments.

Study Summary
Antispasmodics, antidepressants offer relief—fiber does not
This Cochrane review included 56 randomized controlled trials (RCTs) comparing the efficacy of bulking agents (fiber supplements), antispasmodics, or antidepressants with placebo for the treatment of IBS. Twelve RCTs (n = 621) focused on bulking agents, 29 (n = 2,333) on antispasmodics, and 15 (n = 922) on antidepressants. Inclusion criteria included age > 12 years and an IBS diagnosis. The outcomes analyzed were improvement in abdominal pain, global health assessments, and IBS symptom scores. Adverse effects were not evaluated.

• Bulking agents. In studies ranging from four to 16 weeks, bulking agents were found to have no significant effect on abdominal pain (4 studies; standardized mean difference [SMD], 0.03) or global functioning (11 studies; risk ratio [RR], 1.11). Nor was there an improvement in IBS symptom score (3 studies; SMD, 0.00).

• Antispasmodics. Assessed in RCTs ranging from one week to six months, antispasmodics significantly improved abdominal pain (RR, 1.3; number needed to treat [NNT], 7); global functioning (RR, 1.5; NNT, 5), and IBS symptom score (RR, 1.9; NNT, 3). Ten different antispasmodic agents were studied; in subgroup analyses, five of them—cimetropium/dicyclomine, peppermint oil, pinaverium, and trimebutine—were found to have statistically significant benefits.

• Antidepressants. In studies of both tricyclics and SSRIs, antidepressants were found to have a significant effect on improving abdominal pain (RR, 1.5; NNT, 5), global functioning (RR, 1.6; NNT, 4), and IBS symptom score (RR, 2.0; NNT, 4). Subgroup analyses found statistically significant benefits in global functioning for SSRIs, and in abdominal pain and symptom scores for tricyclics.

What’s New
More evidence against fiber
This review confirms earlier findings—that both antispasmodics and antidepressants are effective treatments for IBS, but bulking agents are not. This is an important finding because dietary fiber adjustment is still among the first recommendations made by leading organizations.^4,5

Caveats
Limitations of included studies
Adverse effects of antispasmodics and antidepressants, which may limit compliance and treatment efficacy, were not addressed. The total number of participants in trials of bulking agents was much smaller than that of the other treatments, so it is possible that clinically meaningful improvements were missed. In addition, the duration of interventions was highly variable, ranging from one to four months for bulking agents and antidepressants and from one week to six months for antispasmodics.

It is also important to note that eight of the 12 studies of bulking agents were conducted in GI clinics. Given the possibility that patients referred to GI clinics have already tried and failed to respond to fiber (and thus, that those who do respond to fiber are not given referrals), it may be reasonable for clinicians to recommend a trial of bulking agents for patients with IBS and to monitor them for symptom improvement.

Challenges to Implementation
Patients may favor fiber
Patients with IBS may be reluctant to take antidepressants or antispasmodics, due to concern about adverse effects or because of a preference for what they see as a more “natural” remedy. It may be helpful to explain that while fiber may have some health benefits, such as lowering cholesterol,⁶ antispasmodics and antidepressants have been found to improve IBS symptoms but thus far, fiber has not.

REFERENCES
1. Ruepert L, Quartero AO, deWit NJ, et al. Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome. Cochrane Database Syst Rev. 2011;(8):CD003460.

2. Saito YA, Schoenfeld P, Locke GR 3rd. The epidemiology of irritable bowel syndrome in North America: a systematic review. Am J Gastroenterol. 2002;97:1910-1915.

3. Hulisz D. The burden of illness of irritable bowel syndrome: current challenges and hope for the future. J Manag Care Pharm. 2004;10:299-309.

4. American Gastroenterological Association. IBS: A patient’s guide to living with irritable bowel syndrome. www.gastro.org/patient-center/digestive-conditions/irritable-bowel-syndrome. Accessed March 21, 2012.

5. World Gastroenterology Organisation. WGO practice guideline—irritable bowel syndrome: a global perspective (2009). www.worldgastroenterology.org/irritable-bowel-syndrome.html. Accessed March 16, 2012.

6. Gunness P, Gidley MJ. Mechanisms underlying the cholesterol-lowering properties of soluble dietary fibre polysaccharides. Food Funct. 2010; 1:149-155.

Acknowledgement
The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2012. The Family Physicians Inquiries Network. All rights reserved. Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2012;61(4):213-214.

Practice Changer
Recommend antispasmodics or antidepressants for patients with irritable bowel syndrome (IBS) and explain that, while fiber may have other benefits, it is unlikely to relieve IBS symptoms.¹

Strength of recommendation
A: Based on a meta-analysis.

Illustrative Case
A 25-year-old woman has intermittent bouts of abdominal pain, constipation, gas, and bloating. You believe she can benefit from treatment for IBS. What should you recommend?

IBS is the most common functional disorder of the gastrointestinal (GI) tract, affecting approximately 15% of the US population² and accounting for annual health care costs of roughly $30 billion.³ The primary symptoms are bloating, gas, and abdominal pain that often improves immediately after a bowel movement. Patients may have intermittent diarrhea and constipation, as well.

IBS may be related to “brain-gut dysfunction”
The etiology of IBS is unclear, but many agree that a combination of abnormal GI motility, visceral hypersensitivity, and “brain-gut dysfunction”—the inability of the brain to send signals that turn down pain produced in the GI tract—are contributing factors. Although IBS is not life threatening, it has a significant personal, social, and psychological impact. Despite its high prevalence and impact, only a limited number of large studies have assessed the effectiveness of various treatments.

Study Summary
Antispasmodics, antidepressants offer relief—fiber does not
This Cochrane review included 56 randomized controlled trials (RCTs) comparing the efficacy of bulking agents (fiber supplements), antispasmodics, or antidepressants with placebo for the treatment of IBS. Twelve RCTs (n = 621) focused on bulking agents, 29 (n = 2,333) on antispasmodics, and 15 (n = 922) on antidepressants. Inclusion criteria included age > 12 years and an IBS diagnosis. The outcomes analyzed were improvement in abdominal pain, global health assessments, and IBS symptom scores. Adverse effects were not evaluated.

• Bulking agents. In studies ranging from four to 16 weeks, bulking agents were found to have no significant effect on abdominal pain (4 studies; standardized mean difference [SMD], 0.03) or global functioning (11 studies; risk ratio [RR], 1.11). Nor was there an improvement in IBS symptom score (3 studies; SMD, 0.00).

• Antispasmodics. Assessed in RCTs ranging from one week to six months, antispasmodics significantly improved abdominal pain (RR, 1.3; number needed to treat [NNT], 7); global functioning (RR, 1.5; NNT, 5), and IBS symptom score (RR, 1.9; NNT, 3). Ten different antispasmodic agents were studied; in subgroup analyses, five of them—cimetropium/dicyclomine, peppermint oil, pinaverium, and trimebutine—were found to have statistically significant benefits.

• Antidepressants. In studies of both tricyclics and SSRIs, antidepressants were found to have a significant effect on improving abdominal pain (RR, 1.5; NNT, 5), global functioning (RR, 1.6; NNT, 4), and IBS symptom score (RR, 2.0; NNT, 4). Subgroup analyses found statistically significant benefits in global functioning for SSRIs, and in abdominal pain and symptom scores for tricyclics.

What’s New
More evidence against fiber
This review confirms earlier findings—that both antispasmodics and antidepressants are effective treatments for IBS, but bulking agents are not. This is an important finding because dietary fiber adjustment is still among the first recommendations made by leading organizations.^4,5

Caveats
Limitations of included studies
Adverse effects of antispasmodics and antidepressants, which may limit compliance and treatment efficacy, were not addressed. The total number of participants in trials of bulking agents was much smaller than that of the other treatments, so it is possible that clinically meaningful improvements were missed. In addition, the duration of interventions was highly variable, ranging from one to four months for bulking agents and antidepressants and from one week to six months for antispasmodics.

It is also important to note that eight of the 12 studies of bulking agents were conducted in GI clinics. Given the possibility that patients referred to GI clinics have already tried and failed to respond to fiber (and thus, that those who do respond to fiber are not given referrals), it may be reasonable for clinicians to recommend a trial of bulking agents for patients with IBS and to monitor them for symptom improvement.

Challenges to Implementation
Patients may favor fiber
Patients with IBS may be reluctant to take antidepressants or antispasmodics, due to concern about adverse effects or because of a preference for what they see as a more “natural” remedy. It may be helpful to explain that while fiber may have some health benefits, such as lowering cholesterol,⁶ antispasmodics and antidepressants have been found to improve IBS symptoms but thus far, fiber has not.

REFERENCES
1. Ruepert L, Quartero AO, deWit NJ, et al. Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome. Cochrane Database Syst Rev. 2011;(8):CD003460.

2. Saito YA, Schoenfeld P, Locke GR 3rd. The epidemiology of irritable bowel syndrome in North America: a systematic review. Am J Gastroenterol. 2002;97:1910-1915.

3. Hulisz D. The burden of illness of irritable bowel syndrome: current challenges and hope for the future. J Manag Care Pharm. 2004;10:299-309.

4. American Gastroenterological Association. IBS: A patient’s guide to living with irritable bowel syndrome. www.gastro.org/patient-center/digestive-conditions/irritable-bowel-syndrome. Accessed March 21, 2012.

5. World Gastroenterology Organisation. WGO practice guideline—irritable bowel syndrome: a global perspective (2009). www.worldgastroenterology.org/irritable-bowel-syndrome.html. Accessed March 16, 2012.

6. Gunness P, Gidley MJ. Mechanisms underlying the cholesterol-lowering properties of soluble dietary fibre polysaccharides. Food Funct. 2010; 1:149-155.

Acknowledgement
The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2012. The Family Physicians Inquiries Network. All rights reserved. Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2012;61(4):213-214.

Practice Changer
Recommend antispasmodics or antidepressants for patients with irritable bowel syndrome (IBS) and explain that, while fiber may have other benefits, it is unlikely to relieve IBS symptoms.¹

Strength of recommendation
A: Based on a meta-analysis.

Illustrative Case
A 25-year-old woman has intermittent bouts of abdominal pain, constipation, gas, and bloating. You believe she can benefit from treatment for IBS. What should you recommend?

IBS is the most common functional disorder of the gastrointestinal (GI) tract, affecting approximately 15% of the US population² and accounting for annual health care costs of roughly $30 billion.³ The primary symptoms are bloating, gas, and abdominal pain that often improves immediately after a bowel movement. Patients may have intermittent diarrhea and constipation, as well.

IBS may be related to “brain-gut dysfunction”
The etiology of IBS is unclear, but many agree that a combination of abnormal GI motility, visceral hypersensitivity, and “brain-gut dysfunction”—the inability of the brain to send signals that turn down pain produced in the GI tract—are contributing factors. Although IBS is not life threatening, it has a significant personal, social, and psychological impact. Despite its high prevalence and impact, only a limited number of large studies have assessed the effectiveness of various treatments.

Study Summary
Antispasmodics, antidepressants offer relief—fiber does not
This Cochrane review included 56 randomized controlled trials (RCTs) comparing the efficacy of bulking agents (fiber supplements), antispasmodics, or antidepressants with placebo for the treatment of IBS. Twelve RCTs (n = 621) focused on bulking agents, 29 (n = 2,333) on antispasmodics, and 15 (n = 922) on antidepressants. Inclusion criteria included age > 12 years and an IBS diagnosis. The outcomes analyzed were improvement in abdominal pain, global health assessments, and IBS symptom scores. Adverse effects were not evaluated.

• Bulking agents. In studies ranging from four to 16 weeks, bulking agents were found to have no significant effect on abdominal pain (4 studies; standardized mean difference [SMD], 0.03) or global functioning (11 studies; risk ratio [RR], 1.11). Nor was there an improvement in IBS symptom score (3 studies; SMD, 0.00).

• Antispasmodics. Assessed in RCTs ranging from one week to six months, antispasmodics significantly improved abdominal pain (RR, 1.3; number needed to treat [NNT], 7); global functioning (RR, 1.5; NNT, 5), and IBS symptom score (RR, 1.9; NNT, 3). Ten different antispasmodic agents were studied; in subgroup analyses, five of them—cimetropium/dicyclomine, peppermint oil, pinaverium, and trimebutine—were found to have statistically significant benefits.

• Antidepressants. In studies of both tricyclics and SSRIs, antidepressants were found to have a significant effect on improving abdominal pain (RR, 1.5; NNT, 5), global functioning (RR, 1.6; NNT, 4), and IBS symptom score (RR, 2.0; NNT, 4). Subgroup analyses found statistically significant benefits in global functioning for SSRIs, and in abdominal pain and symptom scores for tricyclics.

What’s New
More evidence against fiber
This review confirms earlier findings—that both antispasmodics and antidepressants are effective treatments for IBS, but bulking agents are not. This is an important finding because dietary fiber adjustment is still among the first recommendations made by leading organizations.^4,5

Caveats
Limitations of included studies
Adverse effects of antispasmodics and antidepressants, which may limit compliance and treatment efficacy, were not addressed. The total number of participants in trials of bulking agents was much smaller than that of the other treatments, so it is possible that clinically meaningful improvements were missed. In addition, the duration of interventions was highly variable, ranging from one to four months for bulking agents and antidepressants and from one week to six months for antispasmodics.

It is also important to note that eight of the 12 studies of bulking agents were conducted in GI clinics. Given the possibility that patients referred to GI clinics have already tried and failed to respond to fiber (and thus, that those who do respond to fiber are not given referrals), it may be reasonable for clinicians to recommend a trial of bulking agents for patients with IBS and to monitor them for symptom improvement.

Challenges to Implementation
Patients may favor fiber
Patients with IBS may be reluctant to take antidepressants or antispasmodics, due to concern about adverse effects or because of a preference for what they see as a more “natural” remedy. It may be helpful to explain that while fiber may have some health benefits, such as lowering cholesterol,⁶ antispasmodics and antidepressants have been found to improve IBS symptoms but thus far, fiber has not.

REFERENCES
1. Ruepert L, Quartero AO, deWit NJ, et al. Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome. Cochrane Database Syst Rev. 2011;(8):CD003460.

2. Saito YA, Schoenfeld P, Locke GR 3rd. The epidemiology of irritable bowel syndrome in North America: a systematic review. Am J Gastroenterol. 2002;97:1910-1915.

3. Hulisz D. The burden of illness of irritable bowel syndrome: current challenges and hope for the future. J Manag Care Pharm. 2004;10:299-309.

4. American Gastroenterological Association. IBS: A patient’s guide to living with irritable bowel syndrome. www.gastro.org/patient-center/digestive-conditions/irritable-bowel-syndrome. Accessed March 21, 2012.

5. World Gastroenterology Organisation. WGO practice guideline—irritable bowel syndrome: a global perspective (2009). www.worldgastroenterology.org/irritable-bowel-syndrome.html. Accessed March 16, 2012.

6. Gunness P, Gidley MJ. Mechanisms underlying the cholesterol-lowering properties of soluble dietary fibre polysaccharides. Food Funct. 2010; 1:149-155.

Acknowledgement
The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2012. The Family Physicians Inquiries Network. All rights reserved. Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2012;61(4):213-214.

ILLUSTRATIVE CASE

A 62-year-old patient comes to your office for follow-up of a primary unprovoked venous thromboembolus. He has been on an oral anticoagulant for 12 months. Should he continue anticoagulation therapy despite the increased risk for major bleeding?

Patients who survive VTE—defined as either deep venous thrombosis or pulmonary embolism—are put on anticoagulant therapy to prevent a recurrence, typically for 6 to 18 months. But about 20% of patients with unprovoked VTE have a recurrence within 2 years of anticoagulation withdrawal.² Extending anticoagulation prevents recurrences but increases the risk of bleeding.³

Is aspirin a viable alternative?
Until recently, the efficacy of aspirin for the prevention of recurrent VTE was unknown. Becattini et al investigated it in the multicenter RCT detailed in this PURL.

STUDY SUMMARY: Aspirin can prevent recurrence with minimal risk

To determine whether aspirin was a viable alternative to oral anticoagulation, the researchers compared aspirin with placebo in patients with primary unprovoked VTE who had completed a course of oral anticoagulation treatment. To be considered for the study, patients had to be >18 years and have had their first-ever objectively confirmed, symptomatic unprovoked proximal deep vein thrombosis, pulmonary embolism, or both. They also had to have completed 6 to 18 months of anticoagulant therapy, with a target international normalized ratio (INR) of 2.0 to 3.0. Exclusion criteria included a history of cancer, clinically significant thrombophilia, atrial fibrillation, and a bleeding event that occurred during the course of anticoagulation therapy.

Becattini et al identified 403 eligible patients. Two weeks after stopping anticoagulation, patients were randomly assigned to receive either aspirin 100 mg once daily (n=205) or placebo (n=198) for 2 years. (One patient in the placebo group never received treatment.) At baseline, there were no significant differences in patient characteristics. All were evaluated every 3 months in the first year and every 6 months in the second year.

The primary efficacy outcome was objectively confirmed recurrent VTE. The primary safety outcome was major bleeding, defined as bleeding that occurred in a critical location (eg, intracranial bleeding), was associated with a decrease of hemoglobin of at least 2 g/dL, required a transfusion of 2 units of whole blood or red blood cells, or was fatal. Overt bleeding, which required medical intervention but did not meet the criteria for major bleeding, was a secondary safety outcome.

Twenty-eight of the 205 patients in the aspirin group experienced a recurrence, compared with 43 of the 197 patients on placebo (6.6% vs. 11.2% per year; hazard ratio [HR]=0.58; 95% confidence interval [CI], 0.36-0.93; P=.02). Adverse events were reported by 7 patients in the aspirin therapy group and 6 in the placebo group. One patient in each group experienced major bleeding, and 3 in each group experienced clinically relevant but nonmajor bleeding. Withdrawal rates were similar (10 in the treatment group vs 9 controls), as were the number of patients who developed new indications for aspirin or anticoagulation therapy or were lost to follow-up.

An analysis adjusted for age, sex, index event (deep vein thrombosis or pulmonary embolism), and duration of initial anticoagulation treatment confirmed that aspirin reduced the risk of recurrence (adjusted HR=0.53; 95% CI, 0.32-0.85; P=.009). No association was found between recurrent VTE and duration of anticoagulation therapy (6 months vs longer). Nor was there a difference in recurrence rates based on the index event.

WHAT’S NEW: Aspirin has a key role in preventing recurrence

This study found that for patients with unprovoked VTE who completed a course of oral anticoagulation, aspirin was effective in preventing a recurrence, with no apparent increase in the risk of major bleeding. Protection in Year 2 was nearly as great as in Year one.¹

CAVEAT: Patients were followed for just 2 years

It is unclear whether continuing aspirin therapy beyond 2 years would continue to confer protection against a VTE recurrence without an increase in adverse effects.

CHALLENGE TO IMPLEMENTATION: Some patients can’t tolerate chronic aspirin therapy

Although this study investigated aspirin in a dosage of 100 mg/d, this strength is not readily available in the United States.⁴ There is no evidence to suggest that the 81-mg strength that is available in this country would provide a diminished antiplatelet effect. And, as is already customary, patients undergoing chronic aspirin therapy must be monitored for major bleeding, GI irritation, and renal compromise. A few patients will be ineligible for prophylaxis due to a history of intolerance to aspirin or nonsteroidal anti-inflammatory drugs.

Acknowledgement

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 62-year-old patient comes to your office for follow-up of a primary unprovoked venous thromboembolus. He has been on an oral anticoagulant for 12 months. Should he continue anticoagulation therapy despite the increased risk for major bleeding?

Patients who survive VTE—defined as either deep venous thrombosis or pulmonary embolism—are put on anticoagulant therapy to prevent a recurrence, typically for 6 to 18 months. But about 20% of patients with unprovoked VTE have a recurrence within 2 years of anticoagulation withdrawal.² Extending anticoagulation prevents recurrences but increases the risk of bleeding.³

Is aspirin a viable alternative?
Until recently, the efficacy of aspirin for the prevention of recurrent VTE was unknown. Becattini et al investigated it in the multicenter RCT detailed in this PURL.

STUDY SUMMARY: Aspirin can prevent recurrence with minimal risk

To determine whether aspirin was a viable alternative to oral anticoagulation, the researchers compared aspirin with placebo in patients with primary unprovoked VTE who had completed a course of oral anticoagulation treatment. To be considered for the study, patients had to be >18 years and have had their first-ever objectively confirmed, symptomatic unprovoked proximal deep vein thrombosis, pulmonary embolism, or both. They also had to have completed 6 to 18 months of anticoagulant therapy, with a target international normalized ratio (INR) of 2.0 to 3.0. Exclusion criteria included a history of cancer, clinically significant thrombophilia, atrial fibrillation, and a bleeding event that occurred during the course of anticoagulation therapy.

Becattini et al identified 403 eligible patients. Two weeks after stopping anticoagulation, patients were randomly assigned to receive either aspirin 100 mg once daily (n=205) or placebo (n=198) for 2 years. (One patient in the placebo group never received treatment.) At baseline, there were no significant differences in patient characteristics. All were evaluated every 3 months in the first year and every 6 months in the second year.

The primary efficacy outcome was objectively confirmed recurrent VTE. The primary safety outcome was major bleeding, defined as bleeding that occurred in a critical location (eg, intracranial bleeding), was associated with a decrease of hemoglobin of at least 2 g/dL, required a transfusion of 2 units of whole blood or red blood cells, or was fatal. Overt bleeding, which required medical intervention but did not meet the criteria for major bleeding, was a secondary safety outcome.

Twenty-eight of the 205 patients in the aspirin group experienced a recurrence, compared with 43 of the 197 patients on placebo (6.6% vs. 11.2% per year; hazard ratio [HR]=0.58; 95% confidence interval [CI], 0.36-0.93; P=.02). Adverse events were reported by 7 patients in the aspirin therapy group and 6 in the placebo group. One patient in each group experienced major bleeding, and 3 in each group experienced clinically relevant but nonmajor bleeding. Withdrawal rates were similar (10 in the treatment group vs 9 controls), as were the number of patients who developed new indications for aspirin or anticoagulation therapy or were lost to follow-up.

An analysis adjusted for age, sex, index event (deep vein thrombosis or pulmonary embolism), and duration of initial anticoagulation treatment confirmed that aspirin reduced the risk of recurrence (adjusted HR=0.53; 95% CI, 0.32-0.85; P=.009). No association was found between recurrent VTE and duration of anticoagulation therapy (6 months vs longer). Nor was there a difference in recurrence rates based on the index event.

WHAT’S NEW: Aspirin has a key role in preventing recurrence

This study found that for patients with unprovoked VTE who completed a course of oral anticoagulation, aspirin was effective in preventing a recurrence, with no apparent increase in the risk of major bleeding. Protection in Year 2 was nearly as great as in Year one.¹

CAVEAT: Patients were followed for just 2 years

It is unclear whether continuing aspirin therapy beyond 2 years would continue to confer protection against a VTE recurrence without an increase in adverse effects.

CHALLENGE TO IMPLEMENTATION: Some patients can’t tolerate chronic aspirin therapy

Although this study investigated aspirin in a dosage of 100 mg/d, this strength is not readily available in the United States.⁴ There is no evidence to suggest that the 81-mg strength that is available in this country would provide a diminished antiplatelet effect. And, as is already customary, patients undergoing chronic aspirin therapy must be monitored for major bleeding, GI irritation, and renal compromise. A few patients will be ineligible for prophylaxis due to a history of intolerance to aspirin or nonsteroidal anti-inflammatory drugs.

Acknowledgement

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 62-year-old patient comes to your office for follow-up of a primary unprovoked venous thromboembolus. He has been on an oral anticoagulant for 12 months. Should he continue anticoagulation therapy despite the increased risk for major bleeding?

Patients who survive VTE—defined as either deep venous thrombosis or pulmonary embolism—are put on anticoagulant therapy to prevent a recurrence, typically for 6 to 18 months. But about 20% of patients with unprovoked VTE have a recurrence within 2 years of anticoagulation withdrawal.² Extending anticoagulation prevents recurrences but increases the risk of bleeding.³

Is aspirin a viable alternative?
Until recently, the efficacy of aspirin for the prevention of recurrent VTE was unknown. Becattini et al investigated it in the multicenter RCT detailed in this PURL.

STUDY SUMMARY: Aspirin can prevent recurrence with minimal risk

To determine whether aspirin was a viable alternative to oral anticoagulation, the researchers compared aspirin with placebo in patients with primary unprovoked VTE who had completed a course of oral anticoagulation treatment. To be considered for the study, patients had to be >18 years and have had their first-ever objectively confirmed, symptomatic unprovoked proximal deep vein thrombosis, pulmonary embolism, or both. They also had to have completed 6 to 18 months of anticoagulant therapy, with a target international normalized ratio (INR) of 2.0 to 3.0. Exclusion criteria included a history of cancer, clinically significant thrombophilia, atrial fibrillation, and a bleeding event that occurred during the course of anticoagulation therapy.

Becattini et al identified 403 eligible patients. Two weeks after stopping anticoagulation, patients were randomly assigned to receive either aspirin 100 mg once daily (n=205) or placebo (n=198) for 2 years. (One patient in the placebo group never received treatment.) At baseline, there were no significant differences in patient characteristics. All were evaluated every 3 months in the first year and every 6 months in the second year.

The primary efficacy outcome was objectively confirmed recurrent VTE. The primary safety outcome was major bleeding, defined as bleeding that occurred in a critical location (eg, intracranial bleeding), was associated with a decrease of hemoglobin of at least 2 g/dL, required a transfusion of 2 units of whole blood or red blood cells, or was fatal. Overt bleeding, which required medical intervention but did not meet the criteria for major bleeding, was a secondary safety outcome.

Twenty-eight of the 205 patients in the aspirin group experienced a recurrence, compared with 43 of the 197 patients on placebo (6.6% vs. 11.2% per year; hazard ratio [HR]=0.58; 95% confidence interval [CI], 0.36-0.93; P=.02). Adverse events were reported by 7 patients in the aspirin therapy group and 6 in the placebo group. One patient in each group experienced major bleeding, and 3 in each group experienced clinically relevant but nonmajor bleeding. Withdrawal rates were similar (10 in the treatment group vs 9 controls), as were the number of patients who developed new indications for aspirin or anticoagulation therapy or were lost to follow-up.

An analysis adjusted for age, sex, index event (deep vein thrombosis or pulmonary embolism), and duration of initial anticoagulation treatment confirmed that aspirin reduced the risk of recurrence (adjusted HR=0.53; 95% CI, 0.32-0.85; P=.009). No association was found between recurrent VTE and duration of anticoagulation therapy (6 months vs longer). Nor was there a difference in recurrence rates based on the index event.

WHAT’S NEW: Aspirin has a key role in preventing recurrence

This study found that for patients with unprovoked VTE who completed a course of oral anticoagulation, aspirin was effective in preventing a recurrence, with no apparent increase in the risk of major bleeding. Protection in Year 2 was nearly as great as in Year one.¹

CAVEAT: Patients were followed for just 2 years

It is unclear whether continuing aspirin therapy beyond 2 years would continue to confer protection against a VTE recurrence without an increase in adverse effects.

CHALLENGE TO IMPLEMENTATION: Some patients can’t tolerate chronic aspirin therapy

Although this study investigated aspirin in a dosage of 100 mg/d, this strength is not readily available in the United States.⁴ There is no evidence to suggest that the 81-mg strength that is available in this country would provide a diminished antiplatelet effect. And, as is already customary, patients undergoing chronic aspirin therapy must be monitored for major bleeding, GI irritation, and renal compromise. A few patients will be ineligible for prophylaxis due to a history of intolerance to aspirin or nonsteroidal anti-inflammatory drugs.

Acknowledgement

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.