James J. Stevermer, MD, MSPH

ILLUSTRATIVE CASE

You are working in the emergency department (ED) of a rural hospital when a 26-year-old man is brought in with multiple injuries sustained in a high-speed collision and motor vehicle rollover. The nearest trauma center is more than an hour away. Should you administer TXA to the patient before transferring him?

Trauma is a leading cause of death among those younger than 40 years, and in 30% of such fatalities, hemorrhage is the cause.² Tranexamic acid (TXA) minimizes blood loss by inhibiting lysine binding sites on plasminogen, thereby preventing the conversion of plasminogen to plasmin. This inhibits fibrinolysis and reduces clot breakdown, resulting in a reduction in bleeding.³

TXA has a proven track record
TXA is not new. It has been used to minimize blood loss associated with surgery for decades.⁴ A retrospective cohort study involving recent military engagements in Afghanistan showed a reduction in both coagulopathy and mortality in trauma patients who were given TXA.⁵ The CRASH-2 randomized controlled trial (RCT), initially published in 2010⁶ and further analyzed in the study detailed below,¹ was the first extensive multicenter trial to evaluate the use of TXA in civilian trauma care.

STUDY SUMMARY: TXA saves lives— within a 3-hour window

CRASH-2 studied the early administration of TXA in adult trauma patients in 274 hospitals in 40 countries.^1,6 Patients (N = 20,211) were enrolled if the treating physician judged them to have or be at risk for significant hemorrhage and were randomized to either TXA or placebo, administered in identical-looking packs. Within 8 hours of injury, participants received a 1-g intravenous (IV) loading dose of either TXA or placebo over 10 minutes; a 1-g infusion over 8 hours followed. Patients and study staff were blinded to the treatment groups.

The primary outcome was overall mortality in the 4 weeks after injury. Secondary outcomes included vascular occlusive events (myocardial infarction, stroke, pulmonary embolism, and deep venous thrombosis), major surgical intervention, quantity of blood transfusion (if any), and cause of death (bleeding, vascular occlusion, multi-organ failure, head injury, or other cause). In this analysis, the researchers considered the effect of TXA on mortality based on time to administration of treatment after injury, severity of blood loss as assessed by systolic blood pressure, Glasgow coma scale score, and type of injury. All analyses were intention to treat, and follow-up was 99.6%.

TXA reduced all-cause mortality in the first month after trauma (relative risk [RR] = 0.91; 95% confidence interval [CI], 0.85-0.97; P = .0035; number needed to treat [NNT] = 68). There were 3076 deaths from all causes in both groups, 35% of which were the result of bleeding. Among patients who received TXA, the overall risk of death due to bleeding was 4.9%, vs 5.4% in the placebo group (RR = 0.85; 95% CI, 0.76-0.96; P = .0077; NNT = 119).

After 3 hours, TXA may do more harm than good
For those treated with TXA within the first hour of injury, the risk of death due to bleeding was 5.3%, vs 7.7% for the placebo group (RR = 0.68; 95% CI, 0.57-0.82; P<.0001; NNT = 41). Giving TXA between one and 3 hours of injury also reduced the risk of death due to bleeding, to 4.8% vs 6.1% for the placebo group (RR = 0.79; 95% CI, 0.64-0.97; P = .03; NNT = 77).

TXA administered more than 3 hours after injury, however, appeared to increase the risk of death due to bleeding, to 4.4% compared with 3.1% for the placebo group (RR = 1.44; 95% CI, 1.12-1.84; P = .004; number needed to harm = 77). The researchers found no evidence that TXA’s effect on death due to bleeding varied on the basis of systolic pressure, Glasgow coma score, or type of injury.

The rate of occlusive vascular events over the 4-week study period was similar in both groups (RR = 0.84; 95% CI, 0.68-1.02; P = .08). Of note, the rate of myocardial infarction was reduced by TXA (RR = 0.64; 95% CI, 0.42-0.97; P = .035; NNT = 504).

WHAT’S NEW: Greater emphasis on TXA timing

Current practice for the treatment of traumatic hemorrhage includes fluid resuscitation and the administration of blood products. This analysis of the CRASH-2 refines our understanding of TXA, revealing that the earlier it is given after injury, the better the outcome. A 2011 Cochrane review found only one other small RCT (N = 240), which had findings consistent with the CRASH-2 results.⁷

TXA is easy to administer and to store and does not require refrigeration or reconstitution prior to administration. TXA has been included in both the US and British Army trauma protocols.⁸ In addition, TXA is used by National Health Service ambulances in the United Kingdom, and given to all adults and teenagers who incur major traumatic injury.⁸

CAVEATS: Potential for thromboembolic events, need for high time sensitivity

Because the enrollment criteria for the study were based entirely on clinical findings, there may have been some participants who were not actively bleeding. However, this would have been true for both the treatment and placebo groups and, if anything, would have diluted the effects of TXA.

There was no increase in vaso-occlusive events in the CRASH-2 study. However, some studies of TXA have found an increase in instances of pulmonary embolism, deep vein thrombosis, and ureteral obstruction in patients with genitourinary bleeding.³

This analysis showed that early administration of TXA is the key to its success—and highlighted the importance of avoiding giving it more than 3 hours after traumatic injury. Although most of the 40 countries in which the CRASH-2 study was conducted have less well developed trauma systems than those in the United States, a subgroup analysis of patients in Europe, North America, and Australia (n = 1960) still showed a mortality benefit (RR = 0.63; 95% CI, 0.42-0.94).⁸

CHALLENGES TO IMPLEMENTATION: Bringing TXA into the mainstream

The acceptance of TXA in trauma care guidelines may be one of the biggest barriers to its use. Currently, the American College of Surgeons does not include the use of TXA in its Advanced Trauma Life Support manual.⁹

Given the short time window for its benefit, TXA may be most appropriate in the prehospital setting. However, there are no studies of its use in this setting. Lack of knowledge and access are also barriers in the emergency setting, as many ED clinicians, particularly in rural settings, may not yet have access to TXA. Physicians in the United Kingdom have tried a variety of methods, including the unorthodox use of comic books targeted to health care providers,¹⁰ in an effort to get the word out.

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

You are working in the emergency department (ED) of a rural hospital when a 26-year-old man is brought in with multiple injuries sustained in a high-speed collision and motor vehicle rollover. The nearest trauma center is more than an hour away. Should you administer TXA to the patient before transferring him?

Trauma is a leading cause of death among those younger than 40 years, and in 30% of such fatalities, hemorrhage is the cause.² Tranexamic acid (TXA) minimizes blood loss by inhibiting lysine binding sites on plasminogen, thereby preventing the conversion of plasminogen to plasmin. This inhibits fibrinolysis and reduces clot breakdown, resulting in a reduction in bleeding.³

TXA has a proven track record
TXA is not new. It has been used to minimize blood loss associated with surgery for decades.⁴ A retrospective cohort study involving recent military engagements in Afghanistan showed a reduction in both coagulopathy and mortality in trauma patients who were given TXA.⁵ The CRASH-2 randomized controlled trial (RCT), initially published in 2010⁶ and further analyzed in the study detailed below,¹ was the first extensive multicenter trial to evaluate the use of TXA in civilian trauma care.

STUDY SUMMARY: TXA saves lives— within a 3-hour window

CRASH-2 studied the early administration of TXA in adult trauma patients in 274 hospitals in 40 countries.^1,6 Patients (N = 20,211) were enrolled if the treating physician judged them to have or be at risk for significant hemorrhage and were randomized to either TXA or placebo, administered in identical-looking packs. Within 8 hours of injury, participants received a 1-g intravenous (IV) loading dose of either TXA or placebo over 10 minutes; a 1-g infusion over 8 hours followed. Patients and study staff were blinded to the treatment groups.

The primary outcome was overall mortality in the 4 weeks after injury. Secondary outcomes included vascular occlusive events (myocardial infarction, stroke, pulmonary embolism, and deep venous thrombosis), major surgical intervention, quantity of blood transfusion (if any), and cause of death (bleeding, vascular occlusion, multi-organ failure, head injury, or other cause). In this analysis, the researchers considered the effect of TXA on mortality based on time to administration of treatment after injury, severity of blood loss as assessed by systolic blood pressure, Glasgow coma scale score, and type of injury. All analyses were intention to treat, and follow-up was 99.6%.

TXA reduced all-cause mortality in the first month after trauma (relative risk [RR] = 0.91; 95% confidence interval [CI], 0.85-0.97; P = .0035; number needed to treat [NNT] = 68). There were 3076 deaths from all causes in both groups, 35% of which were the result of bleeding. Among patients who received TXA, the overall risk of death due to bleeding was 4.9%, vs 5.4% in the placebo group (RR = 0.85; 95% CI, 0.76-0.96; P = .0077; NNT = 119).

After 3 hours, TXA may do more harm than good
For those treated with TXA within the first hour of injury, the risk of death due to bleeding was 5.3%, vs 7.7% for the placebo group (RR = 0.68; 95% CI, 0.57-0.82; P<.0001; NNT = 41). Giving TXA between one and 3 hours of injury also reduced the risk of death due to bleeding, to 4.8% vs 6.1% for the placebo group (RR = 0.79; 95% CI, 0.64-0.97; P = .03; NNT = 77).

TXA administered more than 3 hours after injury, however, appeared to increase the risk of death due to bleeding, to 4.4% compared with 3.1% for the placebo group (RR = 1.44; 95% CI, 1.12-1.84; P = .004; number needed to harm = 77). The researchers found no evidence that TXA’s effect on death due to bleeding varied on the basis of systolic pressure, Glasgow coma score, or type of injury.

The rate of occlusive vascular events over the 4-week study period was similar in both groups (RR = 0.84; 95% CI, 0.68-1.02; P = .08). Of note, the rate of myocardial infarction was reduced by TXA (RR = 0.64; 95% CI, 0.42-0.97; P = .035; NNT = 504).

WHAT’S NEW: Greater emphasis on TXA timing

Current practice for the treatment of traumatic hemorrhage includes fluid resuscitation and the administration of blood products. This analysis of the CRASH-2 refines our understanding of TXA, revealing that the earlier it is given after injury, the better the outcome. A 2011 Cochrane review found only one other small RCT (N = 240), which had findings consistent with the CRASH-2 results.⁷

TXA is easy to administer and to store and does not require refrigeration or reconstitution prior to administration. TXA has been included in both the US and British Army trauma protocols.⁸ In addition, TXA is used by National Health Service ambulances in the United Kingdom, and given to all adults and teenagers who incur major traumatic injury.⁸

CAVEATS: Potential for thromboembolic events, need for high time sensitivity

Because the enrollment criteria for the study were based entirely on clinical findings, there may have been some participants who were not actively bleeding. However, this would have been true for both the treatment and placebo groups and, if anything, would have diluted the effects of TXA.

There was no increase in vaso-occlusive events in the CRASH-2 study. However, some studies of TXA have found an increase in instances of pulmonary embolism, deep vein thrombosis, and ureteral obstruction in patients with genitourinary bleeding.³

This analysis showed that early administration of TXA is the key to its success—and highlighted the importance of avoiding giving it more than 3 hours after traumatic injury. Although most of the 40 countries in which the CRASH-2 study was conducted have less well developed trauma systems than those in the United States, a subgroup analysis of patients in Europe, North America, and Australia (n = 1960) still showed a mortality benefit (RR = 0.63; 95% CI, 0.42-0.94).⁸

CHALLENGES TO IMPLEMENTATION: Bringing TXA into the mainstream

The acceptance of TXA in trauma care guidelines may be one of the biggest barriers to its use. Currently, the American College of Surgeons does not include the use of TXA in its Advanced Trauma Life Support manual.⁹

Given the short time window for its benefit, TXA may be most appropriate in the prehospital setting. However, there are no studies of its use in this setting. Lack of knowledge and access are also barriers in the emergency setting, as many ED clinicians, particularly in rural settings, may not yet have access to TXA. Physicians in the United Kingdom have tried a variety of methods, including the unorthodox use of comic books targeted to health care providers,¹⁰ in an effort to get the word out.

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

You are working in the emergency department (ED) of a rural hospital when a 26-year-old man is brought in with multiple injuries sustained in a high-speed collision and motor vehicle rollover. The nearest trauma center is more than an hour away. Should you administer TXA to the patient before transferring him?

Trauma is a leading cause of death among those younger than 40 years, and in 30% of such fatalities, hemorrhage is the cause.² Tranexamic acid (TXA) minimizes blood loss by inhibiting lysine binding sites on plasminogen, thereby preventing the conversion of plasminogen to plasmin. This inhibits fibrinolysis and reduces clot breakdown, resulting in a reduction in bleeding.³

TXA has a proven track record
TXA is not new. It has been used to minimize blood loss associated with surgery for decades.⁴ A retrospective cohort study involving recent military engagements in Afghanistan showed a reduction in both coagulopathy and mortality in trauma patients who were given TXA.⁵ The CRASH-2 randomized controlled trial (RCT), initially published in 2010⁶ and further analyzed in the study detailed below,¹ was the first extensive multicenter trial to evaluate the use of TXA in civilian trauma care.

STUDY SUMMARY: TXA saves lives— within a 3-hour window

CRASH-2 studied the early administration of TXA in adult trauma patients in 274 hospitals in 40 countries.^1,6 Patients (N = 20,211) were enrolled if the treating physician judged them to have or be at risk for significant hemorrhage and were randomized to either TXA or placebo, administered in identical-looking packs. Within 8 hours of injury, participants received a 1-g intravenous (IV) loading dose of either TXA or placebo over 10 minutes; a 1-g infusion over 8 hours followed. Patients and study staff were blinded to the treatment groups.

The primary outcome was overall mortality in the 4 weeks after injury. Secondary outcomes included vascular occlusive events (myocardial infarction, stroke, pulmonary embolism, and deep venous thrombosis), major surgical intervention, quantity of blood transfusion (if any), and cause of death (bleeding, vascular occlusion, multi-organ failure, head injury, or other cause). In this analysis, the researchers considered the effect of TXA on mortality based on time to administration of treatment after injury, severity of blood loss as assessed by systolic blood pressure, Glasgow coma scale score, and type of injury. All analyses were intention to treat, and follow-up was 99.6%.

TXA reduced all-cause mortality in the first month after trauma (relative risk [RR] = 0.91; 95% confidence interval [CI], 0.85-0.97; P = .0035; number needed to treat [NNT] = 68). There were 3076 deaths from all causes in both groups, 35% of which were the result of bleeding. Among patients who received TXA, the overall risk of death due to bleeding was 4.9%, vs 5.4% in the placebo group (RR = 0.85; 95% CI, 0.76-0.96; P = .0077; NNT = 119).

After 3 hours, TXA may do more harm than good
For those treated with TXA within the first hour of injury, the risk of death due to bleeding was 5.3%, vs 7.7% for the placebo group (RR = 0.68; 95% CI, 0.57-0.82; P<.0001; NNT = 41). Giving TXA between one and 3 hours of injury also reduced the risk of death due to bleeding, to 4.8% vs 6.1% for the placebo group (RR = 0.79; 95% CI, 0.64-0.97; P = .03; NNT = 77).

TXA administered more than 3 hours after injury, however, appeared to increase the risk of death due to bleeding, to 4.4% compared with 3.1% for the placebo group (RR = 1.44; 95% CI, 1.12-1.84; P = .004; number needed to harm = 77). The researchers found no evidence that TXA’s effect on death due to bleeding varied on the basis of systolic pressure, Glasgow coma score, or type of injury.

The rate of occlusive vascular events over the 4-week study period was similar in both groups (RR = 0.84; 95% CI, 0.68-1.02; P = .08). Of note, the rate of myocardial infarction was reduced by TXA (RR = 0.64; 95% CI, 0.42-0.97; P = .035; NNT = 504).

WHAT’S NEW: Greater emphasis on TXA timing

Current practice for the treatment of traumatic hemorrhage includes fluid resuscitation and the administration of blood products. This analysis of the CRASH-2 refines our understanding of TXA, revealing that the earlier it is given after injury, the better the outcome. A 2011 Cochrane review found only one other small RCT (N = 240), which had findings consistent with the CRASH-2 results.⁷

TXA is easy to administer and to store and does not require refrigeration or reconstitution prior to administration. TXA has been included in both the US and British Army trauma protocols.⁸ In addition, TXA is used by National Health Service ambulances in the United Kingdom, and given to all adults and teenagers who incur major traumatic injury.⁸

CAVEATS: Potential for thromboembolic events, need for high time sensitivity

Because the enrollment criteria for the study were based entirely on clinical findings, there may have been some participants who were not actively bleeding. However, this would have been true for both the treatment and placebo groups and, if anything, would have diluted the effects of TXA.

There was no increase in vaso-occlusive events in the CRASH-2 study. However, some studies of TXA have found an increase in instances of pulmonary embolism, deep vein thrombosis, and ureteral obstruction in patients with genitourinary bleeding.³

This analysis showed that early administration of TXA is the key to its success—and highlighted the importance of avoiding giving it more than 3 hours after traumatic injury. Although most of the 40 countries in which the CRASH-2 study was conducted have less well developed trauma systems than those in the United States, a subgroup analysis of patients in Europe, North America, and Australia (n = 1960) still showed a mortality benefit (RR = 0.63; 95% CI, 0.42-0.94).⁸

CHALLENGES TO IMPLEMENTATION: Bringing TXA into the mainstream

The acceptance of TXA in trauma care guidelines may be one of the biggest barriers to its use. Currently, the American College of Surgeons does not include the use of TXA in its Advanced Trauma Life Support manual.⁹

Given the short time window for its benefit, TXA may be most appropriate in the prehospital setting. However, there are no studies of its use in this setting. Lack of knowledge and access are also barriers in the emergency setting, as many ED clinicians, particularly in rural settings, may not yet have access to TXA. Physicians in the United Kingdom have tried a variety of methods, including the unorthodox use of comic books targeted to health care providers,¹⁰ in an effort to get the word out.

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.

Practice Changer
Reconsider the intervals at which you recommend rescreening for osteoporosis; for postmenopausal women with a baseline of normal bone mineral density (BMD) or mild osteopenia, a 15-year interval is probably sufficient.¹

Strength of recommendation
B: Based on a single cohort study.

Illustrative Case
A 67-year-old woman whose recent dual-energy x-ray absorptiometry (DEXA) scan showed mild osteopenia asks when she should have her next bone scan. What should you tell her?

One in five people who sustain a hip fracture die within a year,² and as many as 36% die prematurely.³ Osteoporosis is the primary predictor of fracture risk and, in older white women in particular, low BMD increases the likelihood of fracture by 70% to 80%.⁴

Optimal Screening Frequency Not Known
The US Preventive Services Task Force (USPSTF) guideline for osteoporosis screening concludes that there is a lack of evidence about optimal rescreening intervals and states that intervals > 2 years may be necessary to better predict fracture risk.⁵ In addition, the USPSTF cites a prospective study showing that repeat measurement of BMD after eight years added little predictive value, compared with baseline DEXA scan results.⁶

The prospective cohort study detailed below was undertaken to help guide decisions about how frequently to screen.

Study Summary
Longer intervals are reasonable for those at low risk
Gourlay et al followed 4,957 women ages 67 or older with normal BMD or osteopenia and no history of hip or clinical vertebral fracture or osteoporosis treatment. The primary outcome was the estimated time it would take for 10% of the women to develop osteoporosis. The time until 2% of the women developed such a fracture was the secondary outcome.

Participants had baseline DEXA scans, which were repeated at years 2, 6, 8, 10, and 16. The researchers followed the women until they were diagnosed with osteoporosis, started on medication for osteoporosis, or developed a hip or clinical vertebral fracture.

After adjusting for multiple covariates (age, body mass index, smoking status, use of glucocorticoids, fracture after age 50, estrogen use, and rheumatoid arthritis), the intervals between baseline testing and the development of osteoporosis were:

• 16.8 years for women with normal BMD

• 17.3 years for women with mild osteopenia

• 4.7 years for women with moderate osteopenia

• 1.1 year for women with advanced osteopenia.

Intervals until 2% of the cohort developed fractures were similar.

Overall, a sensible approach was used to estimate reasonable intervals between DEXA screenings: 15 years for women with normal/mild osteopenia (T-score, > –1.50), five years for those with moderate osteopenia (–1.50 to –1.99), and one year for those with advanced osteopenia (–2.00 to –2.49).

What’s New
Many DEXA scans can be eliminated
Rescreening all postmenopausal women every two years is unlikely to reduce osteoporotic fractures. This cohort study provides evidence that rescreening can often be delayed for many years, depending on the patient’s baseline risk. Changing practice based on these findings can reduce resource utilization without adversely affecting women’s health.

Caveats
Questions about applicability may remain
This analysis was limited to women ≥ 67, so different results might be obtained from analyses that included younger postmenopausal women. In addition, 99% of the participants were white. Because the prevalence of osteoporosis of the hip among white women is equal to or slightly higher than it is among nonwhite women, it is likely that the suggested intervals are reasonable estimates for women of all races.

In women older than 80, the interval between baseline testing and the development of osteoporosis was shorter than that of their younger counterparts. Thus, it might be reasonable to reduce rescreening intervals by one-third for women in their 80s.

Challenges to Implementation
Education needed for patients and clinicians
This study is the best so far to address the frequency of rescreening. In order to implement it, patients as well as clinicians will need to be educated. Effective long-term (> 10 y) reminder systems would improve implementation.

The recommendations of professional associations may also be a factor. The National Osteoporosis Foundation recommends assessing BMD every two years, but notes that more frequent testing may sometimes be warranted.⁷ The American College of Preventive Medicine recommends that screening for osteoporosis not occur more often than every two years.⁸             

REFERENCES
1. Gourlay ML, Fine JP, Preisser JS, et al. Bone-density testing interval and transition to osteoporosis in older women. N Engl J Med. 2012;366:225-233.

2. Leibson CL, Tosteson AN, Gabriel SE, et al. Mortality, disability, and nursing home use for persons with and without hip fracture. J Am Geriatr Soc. 2002;50:1644-1650.

3. Abrahamsen B, van Staa T, Ariely R, et al. Excess mortality following hip fracture: a systematic epidemiological review. Osteoporosis Int. 2009;20: 1633-1650.

4. Smith J, Shoukri K. Diagnosis of osteoporosis. Clin Cornerstone. 2000;2:22-33.

5. US Preventive Services Task Force. Screening for osteoporosis: US Preventive Services Task Force recommendation statement. www.uspreventiveservicestaskforce.org/uspstf10/osteoporosis/osteors.htm. Accessed June 15, 2012.

6. Hillier TA, Stone KL, Bauer DC, et al. Evaluating the value of repeat bone mineral density measurement and prediction of fractures in older women. Arch Intern Med. 2007;167:155-160.

7. National Osteoporosis Foundation. Clinician’s guide to prevention and treatment of osteoporosis. 2010. www.nof.org/sites/default/files/pdfs/NOF_ClinicianGuide2009_v7.pdf. Accessed June 30, 2012.

8. Lim LS, Hoeksema LJ, Sherin K; ACPM Prevention Practice Committee. Screening for osteoporosis in the adult US population: ACPM position statement on preventive practice. Am J Prev Med. 2009;36:366-375.

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(9):555-556.

Practice Changer
Reconsider the intervals at which you recommend rescreening for osteoporosis; for postmenopausal women with a baseline of normal bone mineral density (BMD) or mild osteopenia, a 15-year interval is probably sufficient.¹

Strength of recommendation
B: Based on a single cohort study.

Illustrative Case
A 67-year-old woman whose recent dual-energy x-ray absorptiometry (DEXA) scan showed mild osteopenia asks when she should have her next bone scan. What should you tell her?

One in five people who sustain a hip fracture die within a year,² and as many as 36% die prematurely.³ Osteoporosis is the primary predictor of fracture risk and, in older white women in particular, low BMD increases the likelihood of fracture by 70% to 80%.⁴

Optimal Screening Frequency Not Known
The US Preventive Services Task Force (USPSTF) guideline for osteoporosis screening concludes that there is a lack of evidence about optimal rescreening intervals and states that intervals > 2 years may be necessary to better predict fracture risk.⁵ In addition, the USPSTF cites a prospective study showing that repeat measurement of BMD after eight years added little predictive value, compared with baseline DEXA scan results.⁶

The prospective cohort study detailed below was undertaken to help guide decisions about how frequently to screen.

Study Summary
Longer intervals are reasonable for those at low risk
Gourlay et al followed 4,957 women ages 67 or older with normal BMD or osteopenia and no history of hip or clinical vertebral fracture or osteoporosis treatment. The primary outcome was the estimated time it would take for 10% of the women to develop osteoporosis. The time until 2% of the women developed such a fracture was the secondary outcome.

Participants had baseline DEXA scans, which were repeated at years 2, 6, 8, 10, and 16. The researchers followed the women until they were diagnosed with osteoporosis, started on medication for osteoporosis, or developed a hip or clinical vertebral fracture.

After adjusting for multiple covariates (age, body mass index, smoking status, use of glucocorticoids, fracture after age 50, estrogen use, and rheumatoid arthritis), the intervals between baseline testing and the development of osteoporosis were:

• 16.8 years for women with normal BMD

• 17.3 years for women with mild osteopenia

• 4.7 years for women with moderate osteopenia

• 1.1 year for women with advanced osteopenia.

Intervals until 2% of the cohort developed fractures were similar.

Overall, a sensible approach was used to estimate reasonable intervals between DEXA screenings: 15 years for women with normal/mild osteopenia (T-score, > –1.50), five years for those with moderate osteopenia (–1.50 to –1.99), and one year for those with advanced osteopenia (–2.00 to –2.49).

What’s New
Many DEXA scans can be eliminated
Rescreening all postmenopausal women every two years is unlikely to reduce osteoporotic fractures. This cohort study provides evidence that rescreening can often be delayed for many years, depending on the patient’s baseline risk. Changing practice based on these findings can reduce resource utilization without adversely affecting women’s health.

Caveats
Questions about applicability may remain
This analysis was limited to women ≥ 67, so different results might be obtained from analyses that included younger postmenopausal women. In addition, 99% of the participants were white. Because the prevalence of osteoporosis of the hip among white women is equal to or slightly higher than it is among nonwhite women, it is likely that the suggested intervals are reasonable estimates for women of all races.

In women older than 80, the interval between baseline testing and the development of osteoporosis was shorter than that of their younger counterparts. Thus, it might be reasonable to reduce rescreening intervals by one-third for women in their 80s.

Challenges to Implementation
Education needed for patients and clinicians
This study is the best so far to address the frequency of rescreening. In order to implement it, patients as well as clinicians will need to be educated. Effective long-term (> 10 y) reminder systems would improve implementation.

The recommendations of professional associations may also be a factor. The National Osteoporosis Foundation recommends assessing BMD every two years, but notes that more frequent testing may sometimes be warranted.⁷ The American College of Preventive Medicine recommends that screening for osteoporosis not occur more often than every two years.⁸             

REFERENCES
1. Gourlay ML, Fine JP, Preisser JS, et al. Bone-density testing interval and transition to osteoporosis in older women. N Engl J Med. 2012;366:225-233.

2. Leibson CL, Tosteson AN, Gabriel SE, et al. Mortality, disability, and nursing home use for persons with and without hip fracture. J Am Geriatr Soc. 2002;50:1644-1650.

3. Abrahamsen B, van Staa T, Ariely R, et al. Excess mortality following hip fracture: a systematic epidemiological review. Osteoporosis Int. 2009;20: 1633-1650.

4. Smith J, Shoukri K. Diagnosis of osteoporosis. Clin Cornerstone. 2000;2:22-33.

5. US Preventive Services Task Force. Screening for osteoporosis: US Preventive Services Task Force recommendation statement. www.uspreventiveservicestaskforce.org/uspstf10/osteoporosis/osteors.htm. Accessed June 15, 2012.

6. Hillier TA, Stone KL, Bauer DC, et al. Evaluating the value of repeat bone mineral density measurement and prediction of fractures in older women. Arch Intern Med. 2007;167:155-160.

7. National Osteoporosis Foundation. Clinician’s guide to prevention and treatment of osteoporosis. 2010. www.nof.org/sites/default/files/pdfs/NOF_ClinicianGuide2009_v7.pdf. Accessed June 30, 2012.

8. Lim LS, Hoeksema LJ, Sherin K; ACPM Prevention Practice Committee. Screening for osteoporosis in the adult US population: ACPM position statement on preventive practice. Am J Prev Med. 2009;36:366-375.

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(9):555-556.

Practice Changer
Reconsider the intervals at which you recommend rescreening for osteoporosis; for postmenopausal women with a baseline of normal bone mineral density (BMD) or mild osteopenia, a 15-year interval is probably sufficient.¹

Strength of recommendation
B: Based on a single cohort study.

Illustrative Case
A 67-year-old woman whose recent dual-energy x-ray absorptiometry (DEXA) scan showed mild osteopenia asks when she should have her next bone scan. What should you tell her?

One in five people who sustain a hip fracture die within a year,² and as many as 36% die prematurely.³ Osteoporosis is the primary predictor of fracture risk and, in older white women in particular, low BMD increases the likelihood of fracture by 70% to 80%.⁴

Optimal Screening Frequency Not Known
The US Preventive Services Task Force (USPSTF) guideline for osteoporosis screening concludes that there is a lack of evidence about optimal rescreening intervals and states that intervals > 2 years may be necessary to better predict fracture risk.⁵ In addition, the USPSTF cites a prospective study showing that repeat measurement of BMD after eight years added little predictive value, compared with baseline DEXA scan results.⁶

The prospective cohort study detailed below was undertaken to help guide decisions about how frequently to screen.

Study Summary
Longer intervals are reasonable for those at low risk
Gourlay et al followed 4,957 women ages 67 or older with normal BMD or osteopenia and no history of hip or clinical vertebral fracture or osteoporosis treatment. The primary outcome was the estimated time it would take for 10% of the women to develop osteoporosis. The time until 2% of the women developed such a fracture was the secondary outcome.

Participants had baseline DEXA scans, which were repeated at years 2, 6, 8, 10, and 16. The researchers followed the women until they were diagnosed with osteoporosis, started on medication for osteoporosis, or developed a hip or clinical vertebral fracture.

After adjusting for multiple covariates (age, body mass index, smoking status, use of glucocorticoids, fracture after age 50, estrogen use, and rheumatoid arthritis), the intervals between baseline testing and the development of osteoporosis were:

• 16.8 years for women with normal BMD

• 17.3 years for women with mild osteopenia

• 4.7 years for women with moderate osteopenia

• 1.1 year for women with advanced osteopenia.

Intervals until 2% of the cohort developed fractures were similar.

Overall, a sensible approach was used to estimate reasonable intervals between DEXA screenings: 15 years for women with normal/mild osteopenia (T-score, > –1.50), five years for those with moderate osteopenia (–1.50 to –1.99), and one year for those with advanced osteopenia (–2.00 to –2.49).

What’s New
Many DEXA scans can be eliminated
Rescreening all postmenopausal women every two years is unlikely to reduce osteoporotic fractures. This cohort study provides evidence that rescreening can often be delayed for many years, depending on the patient’s baseline risk. Changing practice based on these findings can reduce resource utilization without adversely affecting women’s health.

Caveats
Questions about applicability may remain
This analysis was limited to women ≥ 67, so different results might be obtained from analyses that included younger postmenopausal women. In addition, 99% of the participants were white. Because the prevalence of osteoporosis of the hip among white women is equal to or slightly higher than it is among nonwhite women, it is likely that the suggested intervals are reasonable estimates for women of all races.

In women older than 80, the interval between baseline testing and the development of osteoporosis was shorter than that of their younger counterparts. Thus, it might be reasonable to reduce rescreening intervals by one-third for women in their 80s.

Challenges to Implementation
Education needed for patients and clinicians
This study is the best so far to address the frequency of rescreening. In order to implement it, patients as well as clinicians will need to be educated. Effective long-term (> 10 y) reminder systems would improve implementation.

The recommendations of professional associations may also be a factor. The National Osteoporosis Foundation recommends assessing BMD every two years, but notes that more frequent testing may sometimes be warranted.⁷ The American College of Preventive Medicine recommends that screening for osteoporosis not occur more often than every two years.⁸             

REFERENCES
1. Gourlay ML, Fine JP, Preisser JS, et al. Bone-density testing interval and transition to osteoporosis in older women. N Engl J Med. 2012;366:225-233.

2. Leibson CL, Tosteson AN, Gabriel SE, et al. Mortality, disability, and nursing home use for persons with and without hip fracture. J Am Geriatr Soc. 2002;50:1644-1650.

3. Abrahamsen B, van Staa T, Ariely R, et al. Excess mortality following hip fracture: a systematic epidemiological review. Osteoporosis Int. 2009;20: 1633-1650.

4. Smith J, Shoukri K. Diagnosis of osteoporosis. Clin Cornerstone. 2000;2:22-33.

5. US Preventive Services Task Force. Screening for osteoporosis: US Preventive Services Task Force recommendation statement. www.uspreventiveservicestaskforce.org/uspstf10/osteoporosis/osteors.htm. Accessed June 15, 2012.

6. Hillier TA, Stone KL, Bauer DC, et al. Evaluating the value of repeat bone mineral density measurement and prediction of fractures in older women. Arch Intern Med. 2007;167:155-160.

7. National Osteoporosis Foundation. Clinician’s guide to prevention and treatment of osteoporosis. 2010. www.nof.org/sites/default/files/pdfs/NOF_ClinicianGuide2009_v7.pdf. Accessed June 30, 2012.

8. Lim LS, Hoeksema LJ, Sherin K; ACPM Prevention Practice Committee. Screening for osteoporosis in the adult US population: ACPM position statement on preventive practice. Am J Prev Med. 2009;36:366-375.

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(9):555-556.

ILLUSTRATIVE CASE

A 55-year-old man is brought to the emergency department with shortness of breath, pleuritic chest pain, and hypoxia shortly after returning from an overseas business trip. High-resolution spiral computed tomography (CT) reveals a PE.

How should he be treated?

Pulmonary embolism (PE) is fairly common—with an annual incidence estimated at 69 per 100,000²—and the cause of significant morbidity and mortality. Up to 30% of patients with venous thromboembolism (VTE) die within a month of diagnosis, mostly from PE, and in about 25% of cases, PE presents as sudden death.³

Warfarin has a significant downside
Standard therapy consists of either unfractionated heparin or LMWH followed by warfarin, a vitamin K antagonist (VKA), for ≥3 months.⁴ In addition to requiring frequent laboratory monitoring, warfarin has potentially significant interactions with many prescription drugs. Numerous trials have investigated novel anticoagulants for treatment of VTE in recent years. In one randomized controlled trial (RCT), rivaroxaban (Xarelto)was found to be noninferior to a VKA for treating acute deep vein thrombosis (DVT).⁵

STUDY SUMMARY: Major bleeding is less likely with rivaroxaban

The EINSTEIN PE investigators conducted a randomized, unblinded noninferiority trial to determine whether rivaroxaban was at least as effective as the standard therapy—enoxaparin, followed by a dose-adjusted VKA (warfarin [for US patients] or acenocoumarol) for acute symptomatic PE.¹ To be included, participants had to have PE confirmed by CT, ventilation perfusion scan, or pulmonary angiography, with or without accompanying DVT. Exclusion criteria included active bleeding, significant renal impairment (creatinine clearance <30 mL/min), >48 hours of heparin treatment, or more than one dose of a VKA.

Participants (N=4832 in 38 countries) were randomized to receive either rivaroxaban (15 mg twice daily for 3 weeks, then 20 mg once a day thereafter) or standard therapy. The intervention and control groups were similar. Just over half were male, with an average age of 58 years; three-quarters of the patients had an intermediate to extensive PE burden; and 90% were hospitalized for initial treatment. The researchers listed the etiology as unprovoked in 64% of the cases, followed by recent surgery or trauma and immobilization (17% and 16%, respectively).

After VKA initiation, the international normalized ratio (INR) was checked at least monthly. Patients in the control groups were within the target range (INR 1-2) 62% of the time, which is similar to other studies of anticoagulation in patients with VTE. Adherence to rivaroxaban was at least 80% in more than 94% of patients. Treatment lasted 3, 6, or 12 months, with the duration determined before randomization by the treating physician.

There was no difference in dropout rates (10.7% of rivaroxaban patients withdrew for any reason, vs 12.3% of the controls). Fewer than 0.5% of participants were lost to follow-up.

Symptomatic recurrent VTE, the primary outcome, occurred in 50 patients receiving rivaroxaban vs 44 of those on standard therapy (2.1% vs 1.8%; P=.003 for noninferiority using an intention-to-treat analysis). Major bleeding, defined as overt bleeding causing death, a drop in hemoglobin of ≥2 points, needing a transfusion, or bleeding in a critical site, occurred less often in the rivaroxaban group (1.1% vs 2.2%, P=.003, NNT=91). There was no significant difference in overall bleeding rates between the 2 groups.¹

WHAT’S NEW: Rivaroxaban is easier to use—and on label

This trial found rivaroxaban to be at least as effective as enoxaparin followed by a dose-adjusted VKA for acute symptomatic PE, with fewer major bleeding events. What’s more, rivaroxaban—which now has US Food and Drug Administration approval for the prevention and treatment of PE and DVT⁶—does not require laboratory monitoring.

CAVEATS: Questions about study population, duration remain

This was an open-label study—neither patients nor investigators were blinded to the group assignments after randomization. The investigators suspected more recurrent VTE in those receiving rivaroxaban, which could have biased their findings in favor of the standard treatment. However, actual rates of recurrence were similar.

Study participants were <60 years old, on average, which may limit extrapolation to an older population. This trial lasted 12 months; the effects of longer treatment with rivaroxaban are unknown. Bayer HealthCare and Janssen Pharmaceuticals, who jointly manufacture rivaroxaban, funded the study.

CHALLENGES TO IMPLEMENTATION: Cost and lack of antidote may limit use

Rivaroxaban is more expensive than warfarin: A one-month supply costs approximately $260, while a month’s supply of warfarin plus lab monitoring runs less than $100.⁷ What’s more, factor Xa inhibitors, unlike VKAs, do not have a readily available pharmacologic antidote.

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 55-year-old man is brought to the emergency department with shortness of breath, pleuritic chest pain, and hypoxia shortly after returning from an overseas business trip. High-resolution spiral computed tomography (CT) reveals a PE.

How should he be treated?

Pulmonary embolism (PE) is fairly common—with an annual incidence estimated at 69 per 100,000²—and the cause of significant morbidity and mortality. Up to 30% of patients with venous thromboembolism (VTE) die within a month of diagnosis, mostly from PE, and in about 25% of cases, PE presents as sudden death.³

Warfarin has a significant downside
Standard therapy consists of either unfractionated heparin or LMWH followed by warfarin, a vitamin K antagonist (VKA), for ≥3 months.⁴ In addition to requiring frequent laboratory monitoring, warfarin has potentially significant interactions with many prescription drugs. Numerous trials have investigated novel anticoagulants for treatment of VTE in recent years. In one randomized controlled trial (RCT), rivaroxaban (Xarelto)was found to be noninferior to a VKA for treating acute deep vein thrombosis (DVT).⁵

STUDY SUMMARY: Major bleeding is less likely with rivaroxaban

The EINSTEIN PE investigators conducted a randomized, unblinded noninferiority trial to determine whether rivaroxaban was at least as effective as the standard therapy—enoxaparin, followed by a dose-adjusted VKA (warfarin [for US patients] or acenocoumarol) for acute symptomatic PE.¹ To be included, participants had to have PE confirmed by CT, ventilation perfusion scan, or pulmonary angiography, with or without accompanying DVT. Exclusion criteria included active bleeding, significant renal impairment (creatinine clearance <30 mL/min), >48 hours of heparin treatment, or more than one dose of a VKA.

Participants (N=4832 in 38 countries) were randomized to receive either rivaroxaban (15 mg twice daily for 3 weeks, then 20 mg once a day thereafter) or standard therapy. The intervention and control groups were similar. Just over half were male, with an average age of 58 years; three-quarters of the patients had an intermediate to extensive PE burden; and 90% were hospitalized for initial treatment. The researchers listed the etiology as unprovoked in 64% of the cases, followed by recent surgery or trauma and immobilization (17% and 16%, respectively).

After VKA initiation, the international normalized ratio (INR) was checked at least monthly. Patients in the control groups were within the target range (INR 1-2) 62% of the time, which is similar to other studies of anticoagulation in patients with VTE. Adherence to rivaroxaban was at least 80% in more than 94% of patients. Treatment lasted 3, 6, or 12 months, with the duration determined before randomization by the treating physician.

There was no difference in dropout rates (10.7% of rivaroxaban patients withdrew for any reason, vs 12.3% of the controls). Fewer than 0.5% of participants were lost to follow-up.

Symptomatic recurrent VTE, the primary outcome, occurred in 50 patients receiving rivaroxaban vs 44 of those on standard therapy (2.1% vs 1.8%; P=.003 for noninferiority using an intention-to-treat analysis). Major bleeding, defined as overt bleeding causing death, a drop in hemoglobin of ≥2 points, needing a transfusion, or bleeding in a critical site, occurred less often in the rivaroxaban group (1.1% vs 2.2%, P=.003, NNT=91). There was no significant difference in overall bleeding rates between the 2 groups.¹

WHAT’S NEW: Rivaroxaban is easier to use—and on label

This trial found rivaroxaban to be at least as effective as enoxaparin followed by a dose-adjusted VKA for acute symptomatic PE, with fewer major bleeding events. What’s more, rivaroxaban—which now has US Food and Drug Administration approval for the prevention and treatment of PE and DVT⁶—does not require laboratory monitoring.

CAVEATS: Questions about study population, duration remain

This was an open-label study—neither patients nor investigators were blinded to the group assignments after randomization. The investigators suspected more recurrent VTE in those receiving rivaroxaban, which could have biased their findings in favor of the standard treatment. However, actual rates of recurrence were similar.

Study participants were <60 years old, on average, which may limit extrapolation to an older population. This trial lasted 12 months; the effects of longer treatment with rivaroxaban are unknown. Bayer HealthCare and Janssen Pharmaceuticals, who jointly manufacture rivaroxaban, funded the study.

CHALLENGES TO IMPLEMENTATION: Cost and lack of antidote may limit use

Rivaroxaban is more expensive than warfarin: A one-month supply costs approximately $260, while a month’s supply of warfarin plus lab monitoring runs less than $100.⁷ What’s more, factor Xa inhibitors, unlike VKAs, do not have a readily available pharmacologic antidote.

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 55-year-old man is brought to the emergency department with shortness of breath, pleuritic chest pain, and hypoxia shortly after returning from an overseas business trip. High-resolution spiral computed tomography (CT) reveals a PE.

How should he be treated?

Pulmonary embolism (PE) is fairly common—with an annual incidence estimated at 69 per 100,000²—and the cause of significant morbidity and mortality. Up to 30% of patients with venous thromboembolism (VTE) die within a month of diagnosis, mostly from PE, and in about 25% of cases, PE presents as sudden death.³

Warfarin has a significant downside
Standard therapy consists of either unfractionated heparin or LMWH followed by warfarin, a vitamin K antagonist (VKA), for ≥3 months.⁴ In addition to requiring frequent laboratory monitoring, warfarin has potentially significant interactions with many prescription drugs. Numerous trials have investigated novel anticoagulants for treatment of VTE in recent years. In one randomized controlled trial (RCT), rivaroxaban (Xarelto)was found to be noninferior to a VKA for treating acute deep vein thrombosis (DVT).⁵

STUDY SUMMARY: Major bleeding is less likely with rivaroxaban

The EINSTEIN PE investigators conducted a randomized, unblinded noninferiority trial to determine whether rivaroxaban was at least as effective as the standard therapy—enoxaparin, followed by a dose-adjusted VKA (warfarin [for US patients] or acenocoumarol) for acute symptomatic PE.¹ To be included, participants had to have PE confirmed by CT, ventilation perfusion scan, or pulmonary angiography, with or without accompanying DVT. Exclusion criteria included active bleeding, significant renal impairment (creatinine clearance <30 mL/min), >48 hours of heparin treatment, or more than one dose of a VKA.

Participants (N=4832 in 38 countries) were randomized to receive either rivaroxaban (15 mg twice daily for 3 weeks, then 20 mg once a day thereafter) or standard therapy. The intervention and control groups were similar. Just over half were male, with an average age of 58 years; three-quarters of the patients had an intermediate to extensive PE burden; and 90% were hospitalized for initial treatment. The researchers listed the etiology as unprovoked in 64% of the cases, followed by recent surgery or trauma and immobilization (17% and 16%, respectively).

After VKA initiation, the international normalized ratio (INR) was checked at least monthly. Patients in the control groups were within the target range (INR 1-2) 62% of the time, which is similar to other studies of anticoagulation in patients with VTE. Adherence to rivaroxaban was at least 80% in more than 94% of patients. Treatment lasted 3, 6, or 12 months, with the duration determined before randomization by the treating physician.

There was no difference in dropout rates (10.7% of rivaroxaban patients withdrew for any reason, vs 12.3% of the controls). Fewer than 0.5% of participants were lost to follow-up.

Symptomatic recurrent VTE, the primary outcome, occurred in 50 patients receiving rivaroxaban vs 44 of those on standard therapy (2.1% vs 1.8%; P=.003 for noninferiority using an intention-to-treat analysis). Major bleeding, defined as overt bleeding causing death, a drop in hemoglobin of ≥2 points, needing a transfusion, or bleeding in a critical site, occurred less often in the rivaroxaban group (1.1% vs 2.2%, P=.003, NNT=91). There was no significant difference in overall bleeding rates between the 2 groups.¹

WHAT’S NEW: Rivaroxaban is easier to use—and on label

This trial found rivaroxaban to be at least as effective as enoxaparin followed by a dose-adjusted VKA for acute symptomatic PE, with fewer major bleeding events. What’s more, rivaroxaban—which now has US Food and Drug Administration approval for the prevention and treatment of PE and DVT⁶—does not require laboratory monitoring.

CAVEATS: Questions about study population, duration remain

This was an open-label study—neither patients nor investigators were blinded to the group assignments after randomization. The investigators suspected more recurrent VTE in those receiving rivaroxaban, which could have biased their findings in favor of the standard treatment. However, actual rates of recurrence were similar.

Study participants were <60 years old, on average, which may limit extrapolation to an older population. This trial lasted 12 months; the effects of longer treatment with rivaroxaban are unknown. Bayer HealthCare and Janssen Pharmaceuticals, who jointly manufacture rivaroxaban, funded the study.

CHALLENGES TO IMPLEMENTATION: Cost and lack of antidote may limit use

Rivaroxaban is more expensive than warfarin: A one-month supply costs approximately $260, while a month’s supply of warfarin plus lab monitoring runs less than $100.⁷ What’s more, factor Xa inhibitors, unlike VKAs, do not have a readily available pharmacologic antidote.

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, full-term baby is admitted to the newborn nursery. Antenatal surveillance, including routine ultrasound, was normal, as are physical examinations, both on admittance to the nursery and on the following day. Should the infant undergo pulse oximetry screening prior to discharge?

Congenital heart defects (CHD) are a leading cause of infant deaths in the developed world, occurring in approximately 9 of every 1000 live births.² Roughly a quarter of those affected will have CHD serious enough to require either surgery or catheterization within the first year of life. These newborns are susceptible to sudden cardiovascular collapse due to changes in pulmonary vascular resistance and closure of the ductus arteriosus²—changes that often occur after the babies have gone home.

Delayed diagnosis is linked to worsening disease
A study evaluating 286 neonates admitted for cardiac surgery found that delayed diagnosis of CHD was associated with a worse preoperative condition. Cardiovascular compromise and end-organ dysfunction were most common in infants who presented with symptoms after they had gone home, the researchers found.³

In the past, screening for CHD hinged on mid-trimester ultrasound and postnatal physical examination. However, these methods do not reliably detect the condition in a timely fashion.^4,5 More recently, pulse oximetry has been used for screening.

International studies prompt US recommendation
In a prospective multicenter trial in Saxony, Germany, more than 41,000 infants born between 2006 and 2008 underwent pulse oximetry screening at 24 to 72 hours of life.⁵ If the oxygen saturation was ≤95% and confirmed an hour later, echocardiography was performed. Pulse oximetry screening yielded true-positive results in 14 cases, false-positive results in 40, and false-negative results in 4. Sensitivity and specificity were 77.8% and 99.9%, respectively.

In another German study, 3364 term neonates underwent pulse oximetry screening between 6 and 36 hours of life.⁶ Eighteen neonates (0.5%) had abnormal results, 9 (50%) of whom were found to have heart defects. In this study, pulse oximetry had a sensitivity of 82% and a specificity of 99.9%.

A cohort study of 39,821 newborns in a single region of Sweden found that combining physical examination with pulse oximetry screening had a sensitivity of 82.8% and a specificity of 98%.⁷ No infants who underwent screening died from undiagnosed ductus arteriosus-dependent lung circulation, compared with 5 such deaths in regions where pulse oximetry screening was not done.

Encouraged by these findings, in late 2011 the US Secretary of Health and Human Services, with strong backing from the American Academy of Pediatrics, recommended universal pulse oximetry screening to detect critical CHD.⁸ The study detailed below took another look at its efficacy.

STUDY SUMMARY: Detection rate is higher for critical heart defects

The cohort study by Ewer et al enrolled 20,055 neonates born at >34 weeks’ gestation.¹ All were screened with pulse oximetry on the right hand and on either foot and had a physical exam within their first 24 hours (The TABLE describes the screening protocol). Infants with a normal pulse oximetry and normal clinical exam were followed for a year to identify late-presenting heart defects.

One hundred ninety-five of the neonates who were screened had abnormal pulse oximetry test results; of these, 26 (13%) were found to have either critical (requiring intervention <28 days) or major (requiring intervention <12 months of age) CHD. Of the 169 infants who had positive pulse oximetry results but did not have critical or major heart defects, 6 were found to have less serious heart defects and 40 had infective or respiratory disorders that also required medical intervention.

Among the 19,860 infants with normal pulse oximetry, 27 (0.1%) were found to have either critical or major heart defects.

Pulse oximetry had a sensitivity of 75% (95% confidence interval [CI], 53.3-90.2) and a specificity of 99.1% (95% CI, 98.98-99.24) for detecting critical CHD. Sensitivity of pulse oximetry for all major CHD was 49% (95% CI, 35.0-63.2) and the specificity was 99.2% (95% CI, 99.02-99.28). The specificity may have been better if screening had been done after 24 hours of life; as seen in other studies,^5,6 screening within the first 24 hours leads to more false-positive results.

The detection rate for critical CHD was higher than for major defects. However, most of the defects missed by screening were noncritical lesions, eg, ventricular septal defects.

The authors estimated that in a population of 100,000 newborns, about 120 would have critical CHD, and 90 of those 120 cases would be detected by pulse oximetry. There would be 843 false positives (although 229 of the infants with false-positive results would have other noncardiac conditions). It would be necessary to perform 10.4 echocardiograms to detect one patient with critical CHD.

WHAT’S NEW: A stronger case for newborn pulse oximetry screening

Pulse oximetry prior to discharge from the newborn nursery is not performed routinely in all institutions. And even when screening is done, there may not be a protocol addressing abnormal results. Pulse oximetry is a safe, noninvasive, inexpensive, and reasonably sensitive test that will detect many cases of critical CHD, some of which will not be diagnosed antenatally. Earlier diagnosis of CHD may lead to earlier interventions and improved patient outcomes.

CAVEATS: Timing of screening may alter results

This trial was a cohort study, not a randomized controlled trial (RCT)—the gold standard method of validating a screening test. It is unlikely, however, that an RCT will ever be done.

Screening occurred within the first 24 hours; other investigators have screened >24 hours (up to 38 hours), which may have better results. The critical lesions most likely to be missed by pulse oximetry screening were those causing obstruction to the aortic arch,¹ a finding that was also seen in other studies.^5,7

TABLE
Screening newborns for congenital heart defects: The protocol¹

CHALLENGES TO IMPLEMENTATION: Early discharge, lack of equipment may interfere

Determining the timing of pulse oximetry screening is important. That’s particularly true because early discharge is a common practice, and early screening may increase the number of false-positive results. As a screening tool, pulse oximetry is inexpensive, and follow-up echocardiography—which is needed to exclude serious cases of CHD in patients with positive pulse oximetry—is noninvasive and relatively inexpensive. Echocardiography is not readily available in all communities, however, and transportation to a facility that offers this test would likely increase the cost of screening.

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, full-term baby is admitted to the newborn nursery. Antenatal surveillance, including routine ultrasound, was normal, as are physical examinations, both on admittance to the nursery and on the following day. Should the infant undergo pulse oximetry screening prior to discharge?

Congenital heart defects (CHD) are a leading cause of infant deaths in the developed world, occurring in approximately 9 of every 1000 live births.² Roughly a quarter of those affected will have CHD serious enough to require either surgery or catheterization within the first year of life. These newborns are susceptible to sudden cardiovascular collapse due to changes in pulmonary vascular resistance and closure of the ductus arteriosus²—changes that often occur after the babies have gone home.

Delayed diagnosis is linked to worsening disease
A study evaluating 286 neonates admitted for cardiac surgery found that delayed diagnosis of CHD was associated with a worse preoperative condition. Cardiovascular compromise and end-organ dysfunction were most common in infants who presented with symptoms after they had gone home, the researchers found.³

In the past, screening for CHD hinged on mid-trimester ultrasound and postnatal physical examination. However, these methods do not reliably detect the condition in a timely fashion.^4,5 More recently, pulse oximetry has been used for screening.

International studies prompt US recommendation
In a prospective multicenter trial in Saxony, Germany, more than 41,000 infants born between 2006 and 2008 underwent pulse oximetry screening at 24 to 72 hours of life.⁵ If the oxygen saturation was ≤95% and confirmed an hour later, echocardiography was performed. Pulse oximetry screening yielded true-positive results in 14 cases, false-positive results in 40, and false-negative results in 4. Sensitivity and specificity were 77.8% and 99.9%, respectively.

In another German study, 3364 term neonates underwent pulse oximetry screening between 6 and 36 hours of life.⁶ Eighteen neonates (0.5%) had abnormal results, 9 (50%) of whom were found to have heart defects. In this study, pulse oximetry had a sensitivity of 82% and a specificity of 99.9%.

A cohort study of 39,821 newborns in a single region of Sweden found that combining physical examination with pulse oximetry screening had a sensitivity of 82.8% and a specificity of 98%.⁷ No infants who underwent screening died from undiagnosed ductus arteriosus-dependent lung circulation, compared with 5 such deaths in regions where pulse oximetry screening was not done.

Encouraged by these findings, in late 2011 the US Secretary of Health and Human Services, with strong backing from the American Academy of Pediatrics, recommended universal pulse oximetry screening to detect critical CHD.⁸ The study detailed below took another look at its efficacy.

STUDY SUMMARY: Detection rate is higher for critical heart defects

The cohort study by Ewer et al enrolled 20,055 neonates born at >34 weeks’ gestation.¹ All were screened with pulse oximetry on the right hand and on either foot and had a physical exam within their first 24 hours (The TABLE describes the screening protocol). Infants with a normal pulse oximetry and normal clinical exam were followed for a year to identify late-presenting heart defects.

One hundred ninety-five of the neonates who were screened had abnormal pulse oximetry test results; of these, 26 (13%) were found to have either critical (requiring intervention <28 days) or major (requiring intervention <12 months of age) CHD. Of the 169 infants who had positive pulse oximetry results but did not have critical or major heart defects, 6 were found to have less serious heart defects and 40 had infective or respiratory disorders that also required medical intervention.

Among the 19,860 infants with normal pulse oximetry, 27 (0.1%) were found to have either critical or major heart defects.

Pulse oximetry had a sensitivity of 75% (95% confidence interval [CI], 53.3-90.2) and a specificity of 99.1% (95% CI, 98.98-99.24) for detecting critical CHD. Sensitivity of pulse oximetry for all major CHD was 49% (95% CI, 35.0-63.2) and the specificity was 99.2% (95% CI, 99.02-99.28). The specificity may have been better if screening had been done after 24 hours of life; as seen in other studies,^5,6 screening within the first 24 hours leads to more false-positive results.

The detection rate for critical CHD was higher than for major defects. However, most of the defects missed by screening were noncritical lesions, eg, ventricular septal defects.

The authors estimated that in a population of 100,000 newborns, about 120 would have critical CHD, and 90 of those 120 cases would be detected by pulse oximetry. There would be 843 false positives (although 229 of the infants with false-positive results would have other noncardiac conditions). It would be necessary to perform 10.4 echocardiograms to detect one patient with critical CHD.

WHAT’S NEW: A stronger case for newborn pulse oximetry screening

Pulse oximetry prior to discharge from the newborn nursery is not performed routinely in all institutions. And even when screening is done, there may not be a protocol addressing abnormal results. Pulse oximetry is a safe, noninvasive, inexpensive, and reasonably sensitive test that will detect many cases of critical CHD, some of which will not be diagnosed antenatally. Earlier diagnosis of CHD may lead to earlier interventions and improved patient outcomes.

CAVEATS: Timing of screening may alter results

This trial was a cohort study, not a randomized controlled trial (RCT)—the gold standard method of validating a screening test. It is unlikely, however, that an RCT will ever be done.

Screening occurred within the first 24 hours; other investigators have screened >24 hours (up to 38 hours), which may have better results. The critical lesions most likely to be missed by pulse oximetry screening were those causing obstruction to the aortic arch,¹ a finding that was also seen in other studies.^5,7

TABLE
Screening newborns for congenital heart defects: The protocol¹

CHALLENGES TO IMPLEMENTATION: Early discharge, lack of equipment may interfere

Determining the timing of pulse oximetry screening is important. That’s particularly true because early discharge is a common practice, and early screening may increase the number of false-positive results. As a screening tool, pulse oximetry is inexpensive, and follow-up echocardiography—which is needed to exclude serious cases of CHD in patients with positive pulse oximetry—is noninvasive and relatively inexpensive. Echocardiography is not readily available in all communities, however, and transportation to a facility that offers this test would likely increase the cost of screening.

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, full-term baby is admitted to the newborn nursery. Antenatal surveillance, including routine ultrasound, was normal, as are physical examinations, both on admittance to the nursery and on the following day. Should the infant undergo pulse oximetry screening prior to discharge?

Congenital heart defects (CHD) are a leading cause of infant deaths in the developed world, occurring in approximately 9 of every 1000 live births.² Roughly a quarter of those affected will have CHD serious enough to require either surgery or catheterization within the first year of life. These newborns are susceptible to sudden cardiovascular collapse due to changes in pulmonary vascular resistance and closure of the ductus arteriosus²—changes that often occur after the babies have gone home.

Delayed diagnosis is linked to worsening disease
A study evaluating 286 neonates admitted for cardiac surgery found that delayed diagnosis of CHD was associated with a worse preoperative condition. Cardiovascular compromise and end-organ dysfunction were most common in infants who presented with symptoms after they had gone home, the researchers found.³

In the past, screening for CHD hinged on mid-trimester ultrasound and postnatal physical examination. However, these methods do not reliably detect the condition in a timely fashion.^4,5 More recently, pulse oximetry has been used for screening.

International studies prompt US recommendation
In a prospective multicenter trial in Saxony, Germany, more than 41,000 infants born between 2006 and 2008 underwent pulse oximetry screening at 24 to 72 hours of life.⁵ If the oxygen saturation was ≤95% and confirmed an hour later, echocardiography was performed. Pulse oximetry screening yielded true-positive results in 14 cases, false-positive results in 40, and false-negative results in 4. Sensitivity and specificity were 77.8% and 99.9%, respectively.

In another German study, 3364 term neonates underwent pulse oximetry screening between 6 and 36 hours of life.⁶ Eighteen neonates (0.5%) had abnormal results, 9 (50%) of whom were found to have heart defects. In this study, pulse oximetry had a sensitivity of 82% and a specificity of 99.9%.

A cohort study of 39,821 newborns in a single region of Sweden found that combining physical examination with pulse oximetry screening had a sensitivity of 82.8% and a specificity of 98%.⁷ No infants who underwent screening died from undiagnosed ductus arteriosus-dependent lung circulation, compared with 5 such deaths in regions where pulse oximetry screening was not done.

Encouraged by these findings, in late 2011 the US Secretary of Health and Human Services, with strong backing from the American Academy of Pediatrics, recommended universal pulse oximetry screening to detect critical CHD.⁸ The study detailed below took another look at its efficacy.

STUDY SUMMARY: Detection rate is higher for critical heart defects

The cohort study by Ewer et al enrolled 20,055 neonates born at >34 weeks’ gestation.¹ All were screened with pulse oximetry on the right hand and on either foot and had a physical exam within their first 24 hours (The TABLE describes the screening protocol). Infants with a normal pulse oximetry and normal clinical exam were followed for a year to identify late-presenting heart defects.

One hundred ninety-five of the neonates who were screened had abnormal pulse oximetry test results; of these, 26 (13%) were found to have either critical (requiring intervention <28 days) or major (requiring intervention <12 months of age) CHD. Of the 169 infants who had positive pulse oximetry results but did not have critical or major heart defects, 6 were found to have less serious heart defects and 40 had infective or respiratory disorders that also required medical intervention.

Among the 19,860 infants with normal pulse oximetry, 27 (0.1%) were found to have either critical or major heart defects.

Pulse oximetry had a sensitivity of 75% (95% confidence interval [CI], 53.3-90.2) and a specificity of 99.1% (95% CI, 98.98-99.24) for detecting critical CHD. Sensitivity of pulse oximetry for all major CHD was 49% (95% CI, 35.0-63.2) and the specificity was 99.2% (95% CI, 99.02-99.28). The specificity may have been better if screening had been done after 24 hours of life; as seen in other studies,^5,6 screening within the first 24 hours leads to more false-positive results.

The detection rate for critical CHD was higher than for major defects. However, most of the defects missed by screening were noncritical lesions, eg, ventricular septal defects.

The authors estimated that in a population of 100,000 newborns, about 120 would have critical CHD, and 90 of those 120 cases would be detected by pulse oximetry. There would be 843 false positives (although 229 of the infants with false-positive results would have other noncardiac conditions). It would be necessary to perform 10.4 echocardiograms to detect one patient with critical CHD.

WHAT’S NEW: A stronger case for newborn pulse oximetry screening

Pulse oximetry prior to discharge from the newborn nursery is not performed routinely in all institutions. And even when screening is done, there may not be a protocol addressing abnormal results. Pulse oximetry is a safe, noninvasive, inexpensive, and reasonably sensitive test that will detect many cases of critical CHD, some of which will not be diagnosed antenatally. Earlier diagnosis of CHD may lead to earlier interventions and improved patient outcomes.

CAVEATS: Timing of screening may alter results

This trial was a cohort study, not a randomized controlled trial (RCT)—the gold standard method of validating a screening test. It is unlikely, however, that an RCT will ever be done.

Screening occurred within the first 24 hours; other investigators have screened >24 hours (up to 38 hours), which may have better results. The critical lesions most likely to be missed by pulse oximetry screening were those causing obstruction to the aortic arch,¹ a finding that was also seen in other studies.^5,7

TABLE
Screening newborns for congenital heart defects: The protocol¹

CHALLENGES TO IMPLEMENTATION: Early discharge, lack of equipment may interfere

Determining the timing of pulse oximetry screening is important. That’s particularly true because early discharge is a common practice, and early screening may increase the number of false-positive results. As a screening tool, pulse oximetry is inexpensive, and follow-up echocardiography—which is needed to exclude serious cases of CHD in patients with positive pulse oximetry—is noninvasive and relatively inexpensive. Echocardiography is not readily available in all communities, however, and transportation to a facility that offers this test would likely increase the cost of screening.

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

In the last trimester of pregnancy, a patient asks about her options for postpartum contraception. She plans to breastfeed and does not want to have another child for several years, she says. Her family is scheduled to move 2 weeks after her due date, and she wants to begin using contraception before then. She’s interested in the etonogestrel implant (Implanon) and wonders whether she can have it inserted before she leaves the hospital. What can you tell her?

Approximately 4 million women give birth each year in the United States,² 77% of whom choose to breastfeed their babies.³ Postpartum contraception is recommended, to ensure adequate spacing between (or prevention of) pregnancies.

Hormonal options are limited for nursing moms
Due to the negative effect of estrogens on lactation,⁴ women who wish to use birth control while breastfeeding have limited choices. Their options include progestin-only oral contraceptives; intrauterine devices, including the levonorgestrel intrauterine contraceptive; barrier methods; and the etonogestrel implant. Yet concerns remain that using a progestin contraceptive in the early postpartum period could negatively affect lactogenesis, as well as the quantity and quality of the breast milk.⁵

Starting contraception after 6 weeks? The opportunity is often missed
A 2010 systematic review found that progestin-only contraception can be safely used in breastfeeding women. However, the studies included in the review did not consider timing. Thus, the researchers concluded only that initiation of a progestin contraception >6 weeks postpartum is safe.⁶ The World Health Organization recommends waiting >6 weeks, as well.⁷ But studies have found that between 10% and 40% of women miss their 6-week postpartum visit,⁸ thereby missing the opportunity to start contraception.

A 2009 pilot study found that the implant can be safely used <4 weeks postpartum, and did not affect breastfeeding.⁹ The study we review here is the first RCT to evaluate the impact of early insertion (1-3 days postpartum) of the etonogestrel implant on lactogenesis.

STUDY SUMMARY: Timing of implant did not affect outcomes

The study by Gurtcheff et al was a randomized controlled noninferiority trial of 69 women who wanted to use Implanon for postpartum birth control. Inclusion criteria included good health (of the babies as well as the mothers), the intention to breastfeed, and the willingness to be randomly assigned to either early (1-3 days) or standard (4-8 weeks) insertion. The study was not blinded. No other source of bias was identified.

The primary outcomes studied were time to stage II of lactogenesis (based on maternal perception of when her milk “had come in”) and rates of lactation failure.

Early insertion, the researchers found, was noninferior to standard insertion, both in the time to stage II of lactogenesis and the risk of lactation failure. The time to lactogenesis was 64.3 hours (mean standard deviation [SD], 19.6 hours) for early insertion vs 65.2 hours (mean SD, 18.5 hours) for standard insertion. The mean difference was -1.4 hours (95% confidence interval [CI], -10.6 to 7.7 hours). For lactation failure, the absolute risk difference was 0.03 (95% CI, -0.02 to 0.08).

Secondary outcomes included breastfeeding status, side effects, and bleeding patterns, as well as the contraceptive method actually being used at the time. This information was gathered at 2 weeks, 6 weeks, 3 months, and 6 months postpartum.

There were no statistically significant differences in breastfeeding, formula supplementation, or patient-reported bleeding patterns. However, a third of the women (11 of 34) in the standard group did not have the implant inserted, and opted for an alternate form of birth control.

At 6 weeks, women in both groups had a milk sample analyzed for fat and energy content. There was no significant difference in mean creamatocrit values between the groups.

WHAT’S NEW: Early insertion is safe and fosters compliance

Lactogenesis and lactation failure rates were comparable, whether the etonogestrel implant was inserted between 1 and 3 days postpartum or 4 to 8 weeks postpartum. An advantage of early insertion was increased contraceptive compliance. At 3 months postpartum, 13% of the women in the standard group were not using any birth control. Among those in the early insertion group, compliance was 100%.

CAVEATS: Study sample may not be representative

This was a small study, but it was powered to detect ≥8 hour difference in onset of stage II lactogenesis. Participants were not representative of all populations (91% were white, 73% of whom were Hispanic). Both the mothers and babies were healthy, so we can’t extrapolate to situations where either mom or baby is sick.

CHALLENGES TO IMPLEMENTATION: Finding clinicians trained in insertion technique

Health care providers trained in insertion of the etonogestrel implant would need to be available to promote insertion in the early postpartum period. Ensuring availability of the device in hospitals may require extra logistical planning; incorporating etonogestrel implant insertion into already-hectic morning rounds may be challenging, as well.

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.

Click here to view PURL METHODOLOGY

ILLUSTRATIVE CASE

In the last trimester of pregnancy, a patient asks about her options for postpartum contraception. She plans to breastfeed and does not want to have another child for several years, she says. Her family is scheduled to move 2 weeks after her due date, and she wants to begin using contraception before then. She’s interested in the etonogestrel implant (Implanon) and wonders whether she can have it inserted before she leaves the hospital. What can you tell her?

Approximately 4 million women give birth each year in the United States,² 77% of whom choose to breastfeed their babies.³ Postpartum contraception is recommended, to ensure adequate spacing between (or prevention of) pregnancies.

Hormonal options are limited for nursing moms
Due to the negative effect of estrogens on lactation,⁴ women who wish to use birth control while breastfeeding have limited choices. Their options include progestin-only oral contraceptives; intrauterine devices, including the levonorgestrel intrauterine contraceptive; barrier methods; and the etonogestrel implant. Yet concerns remain that using a progestin contraceptive in the early postpartum period could negatively affect lactogenesis, as well as the quantity and quality of the breast milk.⁵

Starting contraception after 6 weeks? The opportunity is often missed
A 2010 systematic review found that progestin-only contraception can be safely used in breastfeeding women. However, the studies included in the review did not consider timing. Thus, the researchers concluded only that initiation of a progestin contraception >6 weeks postpartum is safe.⁶ The World Health Organization recommends waiting >6 weeks, as well.⁷ But studies have found that between 10% and 40% of women miss their 6-week postpartum visit,⁸ thereby missing the opportunity to start contraception.

A 2009 pilot study found that the implant can be safely used <4 weeks postpartum, and did not affect breastfeeding.⁹ The study we review here is the first RCT to evaluate the impact of early insertion (1-3 days postpartum) of the etonogestrel implant on lactogenesis.

STUDY SUMMARY: Timing of implant did not affect outcomes

The study by Gurtcheff et al was a randomized controlled noninferiority trial of 69 women who wanted to use Implanon for postpartum birth control. Inclusion criteria included good health (of the babies as well as the mothers), the intention to breastfeed, and the willingness to be randomly assigned to either early (1-3 days) or standard (4-8 weeks) insertion. The study was not blinded. No other source of bias was identified.

The primary outcomes studied were time to stage II of lactogenesis (based on maternal perception of when her milk “had come in”) and rates of lactation failure.

Early insertion, the researchers found, was noninferior to standard insertion, both in the time to stage II of lactogenesis and the risk of lactation failure. The time to lactogenesis was 64.3 hours (mean standard deviation [SD], 19.6 hours) for early insertion vs 65.2 hours (mean SD, 18.5 hours) for standard insertion. The mean difference was -1.4 hours (95% confidence interval [CI], -10.6 to 7.7 hours). For lactation failure, the absolute risk difference was 0.03 (95% CI, -0.02 to 0.08).

Secondary outcomes included breastfeeding status, side effects, and bleeding patterns, as well as the contraceptive method actually being used at the time. This information was gathered at 2 weeks, 6 weeks, 3 months, and 6 months postpartum.

There were no statistically significant differences in breastfeeding, formula supplementation, or patient-reported bleeding patterns. However, a third of the women (11 of 34) in the standard group did not have the implant inserted, and opted for an alternate form of birth control.

At 6 weeks, women in both groups had a milk sample analyzed for fat and energy content. There was no significant difference in mean creamatocrit values between the groups.

WHAT’S NEW: Early insertion is safe and fosters compliance

Lactogenesis and lactation failure rates were comparable, whether the etonogestrel implant was inserted between 1 and 3 days postpartum or 4 to 8 weeks postpartum. An advantage of early insertion was increased contraceptive compliance. At 3 months postpartum, 13% of the women in the standard group were not using any birth control. Among those in the early insertion group, compliance was 100%.

CAVEATS: Study sample may not be representative

This was a small study, but it was powered to detect ≥8 hour difference in onset of stage II lactogenesis. Participants were not representative of all populations (91% were white, 73% of whom were Hispanic). Both the mothers and babies were healthy, so we can’t extrapolate to situations where either mom or baby is sick.

CHALLENGES TO IMPLEMENTATION: Finding clinicians trained in insertion technique

Health care providers trained in insertion of the etonogestrel implant would need to be available to promote insertion in the early postpartum period. Ensuring availability of the device in hospitals may require extra logistical planning; incorporating etonogestrel implant insertion into already-hectic morning rounds may be challenging, as well.

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.

Click here to view PURL METHODOLOGY

ILLUSTRATIVE CASE

In the last trimester of pregnancy, a patient asks about her options for postpartum contraception. She plans to breastfeed and does not want to have another child for several years, she says. Her family is scheduled to move 2 weeks after her due date, and she wants to begin using contraception before then. She’s interested in the etonogestrel implant (Implanon) and wonders whether she can have it inserted before she leaves the hospital. What can you tell her?

Approximately 4 million women give birth each year in the United States,² 77% of whom choose to breastfeed their babies.³ Postpartum contraception is recommended, to ensure adequate spacing between (or prevention of) pregnancies.

Hormonal options are limited for nursing moms
Due to the negative effect of estrogens on lactation,⁴ women who wish to use birth control while breastfeeding have limited choices. Their options include progestin-only oral contraceptives; intrauterine devices, including the levonorgestrel intrauterine contraceptive; barrier methods; and the etonogestrel implant. Yet concerns remain that using a progestin contraceptive in the early postpartum period could negatively affect lactogenesis, as well as the quantity and quality of the breast milk.⁵

Starting contraception after 6 weeks? The opportunity is often missed
A 2010 systematic review found that progestin-only contraception can be safely used in breastfeeding women. However, the studies included in the review did not consider timing. Thus, the researchers concluded only that initiation of a progestin contraception >6 weeks postpartum is safe.⁶ The World Health Organization recommends waiting >6 weeks, as well.⁷ But studies have found that between 10% and 40% of women miss their 6-week postpartum visit,⁸ thereby missing the opportunity to start contraception.

A 2009 pilot study found that the implant can be safely used <4 weeks postpartum, and did not affect breastfeeding.⁹ The study we review here is the first RCT to evaluate the impact of early insertion (1-3 days postpartum) of the etonogestrel implant on lactogenesis.

STUDY SUMMARY: Timing of implant did not affect outcomes

The study by Gurtcheff et al was a randomized controlled noninferiority trial of 69 women who wanted to use Implanon for postpartum birth control. Inclusion criteria included good health (of the babies as well as the mothers), the intention to breastfeed, and the willingness to be randomly assigned to either early (1-3 days) or standard (4-8 weeks) insertion. The study was not blinded. No other source of bias was identified.

The primary outcomes studied were time to stage II of lactogenesis (based on maternal perception of when her milk “had come in”) and rates of lactation failure.

Early insertion, the researchers found, was noninferior to standard insertion, both in the time to stage II of lactogenesis and the risk of lactation failure. The time to lactogenesis was 64.3 hours (mean standard deviation [SD], 19.6 hours) for early insertion vs 65.2 hours (mean SD, 18.5 hours) for standard insertion. The mean difference was -1.4 hours (95% confidence interval [CI], -10.6 to 7.7 hours). For lactation failure, the absolute risk difference was 0.03 (95% CI, -0.02 to 0.08).

Secondary outcomes included breastfeeding status, side effects, and bleeding patterns, as well as the contraceptive method actually being used at the time. This information was gathered at 2 weeks, 6 weeks, 3 months, and 6 months postpartum.

There were no statistically significant differences in breastfeeding, formula supplementation, or patient-reported bleeding patterns. However, a third of the women (11 of 34) in the standard group did not have the implant inserted, and opted for an alternate form of birth control.

At 6 weeks, women in both groups had a milk sample analyzed for fat and energy content. There was no significant difference in mean creamatocrit values between the groups.

WHAT’S NEW: Early insertion is safe and fosters compliance

Lactogenesis and lactation failure rates were comparable, whether the etonogestrel implant was inserted between 1 and 3 days postpartum or 4 to 8 weeks postpartum. An advantage of early insertion was increased contraceptive compliance. At 3 months postpartum, 13% of the women in the standard group were not using any birth control. Among those in the early insertion group, compliance was 100%.

CAVEATS: Study sample may not be representative

This was a small study, but it was powered to detect ≥8 hour difference in onset of stage II lactogenesis. Participants were not representative of all populations (91% were white, 73% of whom were Hispanic). Both the mothers and babies were healthy, so we can’t extrapolate to situations where either mom or baby is sick.

CHALLENGES TO IMPLEMENTATION: Finding clinicians trained in insertion technique

Health care providers trained in insertion of the etonogestrel implant would need to be available to promote insertion in the early postpartum period. Ensuring availability of the device in hospitals may require extra logistical planning; incorporating etonogestrel implant insertion into already-hectic morning rounds may be challenging, as well.

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.

Click here to view PURL METHODOLOGY

ILLUSTRATIVE CASE

Alarmed because she recently noticed a decrease in her hearing, a 61-year-old woman requests an urgent visit. When you examine her ears, you find bilateral occlusion with cerumen. The patient says that she’s needed office irrigation multiple times in the past and wants to know how to clean her ears at home to prevent wax build-up. What can you recommend?

Cerumen impaction is associated with a variety of symptoms, including hearing loss, pain, itching, and a feeling of fullness, as well as dizziness, tinnitus, and a reflex cough.² Eight million ear irrigations are carried out in US medical offices each year.³ Yet there is no reason to believe (and little evidence to suggest) that home irrigation would not be an effective approach.

Drops and wax removal kits are widely available
Patients can purchase wax-softening drops. Carbamide peroxide substances, for instance, are sold under a variety of trade names, such as Auraphene-B, Debrox, Mollifene, and Murine Ear Drops. Mineral oil is a common home remedy, as well, although it has no official indication for ear wax removal.

Home irrigation kits, which typically include a bulb syringe, are sold over the counter and cost anywhere from $3 to $400.⁴ These prices represent the varying degrees of automation available for cerumen removal, from wax-softening drops and a bulb syringe packed together in a “kit” to systems that connect to the faucet for continuous water pressure and include a temperature sensor. Most kits cost less than $20.

Bulb syringe irrigation is generally considered safe and effective. But it has never been compared with other methods⁵ and clinicians rarely recommend it, we suspect because of a lack of knowledge of its safety and efficacy.

STUDY SUMMARY: Every 2 patients given wax removal kits = 1 less office visit

Coppin et al conducted a blinded study of adults with cerumen impaction to assess the efficacy of bulb syringe irrigation compared with standard care.¹ The authors recruited patients from 7 practices in England. To be eligible for the study, patients had to have symptoms of blockage and visible occluding ear wax. The researchers assessed 434 patients and randomized 237; of these, only 3 were lost to follow-up.

Using concealed allocation, a nurse randomly gave all the patients identical-looking envelopes. Half of the envelopes contained ear drops and instructions in usual care (ear irrigation by a clinician after the use of ear drops). The other half contained ear drops and a 25-mL ear bulb syringe (not available over the counter in the United Kingdom). Instructions provided with the syringes indicated that they could be cleaned and reused, but did not specifically instruct patients as to when to use them. Baseline characteristics were balanced between the 2 groups.

After 2 weeks, the nurse reassessed the patients and irrigated the ears of any patient with evidence of occlusion. The authors used National Health Service computerized records to track ear wax–related visits over the next 2 years for participants in both groups.

During the 2-year follow-up, more of the patients in the control group returned to the clinic with episodes of ear wax compared with those in the intervention group (73% vs 60%; risk ratio=1.21; 95% confidence interval [CI], 1.01-1.37; P=.038).

The researchers also found that, among the returnees, patients in the control group had, on average, 50% more visits. That is, for every 2 patients who were given a bulb syringe, there was one less visit (incidence rate ratio=1.79; 95% CI, 1.05-3.04; P=.032). A secondary analysis found no significant difference in adverse events between the intervention and the control groups.

WHAT’S NEW: Do-it-yourself wax removal is now evidence-based

The American Academy of Otolaryngology-Head and Neck Surgery Foundation’s 2008 clinical practice guideline—based primarily on expert opinion—recommends clinician irrigation only, due to a lack of quality evidence.³

This RCT is the first to provide evidence that some patients do not need to spend time (or money) on a medical visit for ear wax irrigation. The fact that patients who were given bulb syringes had fewer visits, not only for the initial wax removal but also for subsequent episodes of cerumen impaction, suggests that they were self-treating at home without an increase in adverse effects.

CAVEATS: Home irrigation is not for every patient

This intervention cannot be extrapolated to young children or to others who are unable to perform self-irrigation. It is possible that if a patient self-irrigates without prior visualization by a clinician, a contraindication such as ruptured tympanic membrane or active infection could be present.

This study was performed in England, where bulb syringes are not readily available. It is possible that this intervention may be less effective at avoiding cerumen-related office visits in the United States, especially if patients are already using bulb syringes for this purpose. Finally, we note that 60% of the patients in the home irrigation group did return for a visit for cerumen removal during the 2-year follow-up, so home irrigation did not entirely replace office irrigation.

CHALLENGES TO IMPLEMENTATION: Getting buy-in from patients

The greatest challenge to implementation might be convincing patients that they can safely perform self-irrigation at home. This may require written patient instructions, preferably with illustrations. The steps will need to be written clearly and include details such as recommended ear wax softeners, water temperature, use of peroxide (or not), warning symptoms, and when to contact a physician.

A healthy physician-patient relationship, and perhaps, giving patients the bulb syringe and instructions in using it before they leave the clinic, will help to overcome patient hesitancy. Physician inertia may also be a problem, but it should be easy to put this new information into practice once provider resistance is overcome.

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.

Click here to view PURL METHODOLOGY

ILLUSTRATIVE CASE

Alarmed because she recently noticed a decrease in her hearing, a 61-year-old woman requests an urgent visit. When you examine her ears, you find bilateral occlusion with cerumen. The patient says that she’s needed office irrigation multiple times in the past and wants to know how to clean her ears at home to prevent wax build-up. What can you recommend?

Cerumen impaction is associated with a variety of symptoms, including hearing loss, pain, itching, and a feeling of fullness, as well as dizziness, tinnitus, and a reflex cough.² Eight million ear irrigations are carried out in US medical offices each year.³ Yet there is no reason to believe (and little evidence to suggest) that home irrigation would not be an effective approach.

Drops and wax removal kits are widely available
Patients can purchase wax-softening drops. Carbamide peroxide substances, for instance, are sold under a variety of trade names, such as Auraphene-B, Debrox, Mollifene, and Murine Ear Drops. Mineral oil is a common home remedy, as well, although it has no official indication for ear wax removal.

Home irrigation kits, which typically include a bulb syringe, are sold over the counter and cost anywhere from $3 to $400.⁴ These prices represent the varying degrees of automation available for cerumen removal, from wax-softening drops and a bulb syringe packed together in a “kit” to systems that connect to the faucet for continuous water pressure and include a temperature sensor. Most kits cost less than $20.

Bulb syringe irrigation is generally considered safe and effective. But it has never been compared with other methods⁵ and clinicians rarely recommend it, we suspect because of a lack of knowledge of its safety and efficacy.

STUDY SUMMARY: Every 2 patients given wax removal kits = 1 less office visit

Coppin et al conducted a blinded study of adults with cerumen impaction to assess the efficacy of bulb syringe irrigation compared with standard care.¹ The authors recruited patients from 7 practices in England. To be eligible for the study, patients had to have symptoms of blockage and visible occluding ear wax. The researchers assessed 434 patients and randomized 237; of these, only 3 were lost to follow-up.

Using concealed allocation, a nurse randomly gave all the patients identical-looking envelopes. Half of the envelopes contained ear drops and instructions in usual care (ear irrigation by a clinician after the use of ear drops). The other half contained ear drops and a 25-mL ear bulb syringe (not available over the counter in the United Kingdom). Instructions provided with the syringes indicated that they could be cleaned and reused, but did not specifically instruct patients as to when to use them. Baseline characteristics were balanced between the 2 groups.

After 2 weeks, the nurse reassessed the patients and irrigated the ears of any patient with evidence of occlusion. The authors used National Health Service computerized records to track ear wax–related visits over the next 2 years for participants in both groups.

During the 2-year follow-up, more of the patients in the control group returned to the clinic with episodes of ear wax compared with those in the intervention group (73% vs 60%; risk ratio=1.21; 95% confidence interval [CI], 1.01-1.37; P=.038).

The researchers also found that, among the returnees, patients in the control group had, on average, 50% more visits. That is, for every 2 patients who were given a bulb syringe, there was one less visit (incidence rate ratio=1.79; 95% CI, 1.05-3.04; P=.032). A secondary analysis found no significant difference in adverse events between the intervention and the control groups.

WHAT’S NEW: Do-it-yourself wax removal is now evidence-based

The American Academy of Otolaryngology-Head and Neck Surgery Foundation’s 2008 clinical practice guideline—based primarily on expert opinion—recommends clinician irrigation only, due to a lack of quality evidence.³

This RCT is the first to provide evidence that some patients do not need to spend time (or money) on a medical visit for ear wax irrigation. The fact that patients who were given bulb syringes had fewer visits, not only for the initial wax removal but also for subsequent episodes of cerumen impaction, suggests that they were self-treating at home without an increase in adverse effects.

CAVEATS: Home irrigation is not for every patient

This intervention cannot be extrapolated to young children or to others who are unable to perform self-irrigation. It is possible that if a patient self-irrigates without prior visualization by a clinician, a contraindication such as ruptured tympanic membrane or active infection could be present.

This study was performed in England, where bulb syringes are not readily available. It is possible that this intervention may be less effective at avoiding cerumen-related office visits in the United States, especially if patients are already using bulb syringes for this purpose. Finally, we note that 60% of the patients in the home irrigation group did return for a visit for cerumen removal during the 2-year follow-up, so home irrigation did not entirely replace office irrigation.

CHALLENGES TO IMPLEMENTATION: Getting buy-in from patients

The greatest challenge to implementation might be convincing patients that they can safely perform self-irrigation at home. This may require written patient instructions, preferably with illustrations. The steps will need to be written clearly and include details such as recommended ear wax softeners, water temperature, use of peroxide (or not), warning symptoms, and when to contact a physician.

A healthy physician-patient relationship, and perhaps, giving patients the bulb syringe and instructions in using it before they leave the clinic, will help to overcome patient hesitancy. Physician inertia may also be a problem, but it should be easy to put this new information into practice once provider resistance is overcome.

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.

Click here to view PURL METHODOLOGY

ILLUSTRATIVE CASE

Alarmed because she recently noticed a decrease in her hearing, a 61-year-old woman requests an urgent visit. When you examine her ears, you find bilateral occlusion with cerumen. The patient says that she’s needed office irrigation multiple times in the past and wants to know how to clean her ears at home to prevent wax build-up. What can you recommend?

Cerumen impaction is associated with a variety of symptoms, including hearing loss, pain, itching, and a feeling of fullness, as well as dizziness, tinnitus, and a reflex cough.² Eight million ear irrigations are carried out in US medical offices each year.³ Yet there is no reason to believe (and little evidence to suggest) that home irrigation would not be an effective approach.

Drops and wax removal kits are widely available
Patients can purchase wax-softening drops. Carbamide peroxide substances, for instance, are sold under a variety of trade names, such as Auraphene-B, Debrox, Mollifene, and Murine Ear Drops. Mineral oil is a common home remedy, as well, although it has no official indication for ear wax removal.

Home irrigation kits, which typically include a bulb syringe, are sold over the counter and cost anywhere from $3 to $400.⁴ These prices represent the varying degrees of automation available for cerumen removal, from wax-softening drops and a bulb syringe packed together in a “kit” to systems that connect to the faucet for continuous water pressure and include a temperature sensor. Most kits cost less than $20.

Bulb syringe irrigation is generally considered safe and effective. But it has never been compared with other methods⁵ and clinicians rarely recommend it, we suspect because of a lack of knowledge of its safety and efficacy.

STUDY SUMMARY: Every 2 patients given wax removal kits = 1 less office visit

Coppin et al conducted a blinded study of adults with cerumen impaction to assess the efficacy of bulb syringe irrigation compared with standard care.¹ The authors recruited patients from 7 practices in England. To be eligible for the study, patients had to have symptoms of blockage and visible occluding ear wax. The researchers assessed 434 patients and randomized 237; of these, only 3 were lost to follow-up.

Using concealed allocation, a nurse randomly gave all the patients identical-looking envelopes. Half of the envelopes contained ear drops and instructions in usual care (ear irrigation by a clinician after the use of ear drops). The other half contained ear drops and a 25-mL ear bulb syringe (not available over the counter in the United Kingdom). Instructions provided with the syringes indicated that they could be cleaned and reused, but did not specifically instruct patients as to when to use them. Baseline characteristics were balanced between the 2 groups.

After 2 weeks, the nurse reassessed the patients and irrigated the ears of any patient with evidence of occlusion. The authors used National Health Service computerized records to track ear wax–related visits over the next 2 years for participants in both groups.

During the 2-year follow-up, more of the patients in the control group returned to the clinic with episodes of ear wax compared with those in the intervention group (73% vs 60%; risk ratio=1.21; 95% confidence interval [CI], 1.01-1.37; P=.038).

The researchers also found that, among the returnees, patients in the control group had, on average, 50% more visits. That is, for every 2 patients who were given a bulb syringe, there was one less visit (incidence rate ratio=1.79; 95% CI, 1.05-3.04; P=.032). A secondary analysis found no significant difference in adverse events between the intervention and the control groups.

WHAT’S NEW: Do-it-yourself wax removal is now evidence-based

The American Academy of Otolaryngology-Head and Neck Surgery Foundation’s 2008 clinical practice guideline—based primarily on expert opinion—recommends clinician irrigation only, due to a lack of quality evidence.³

This RCT is the first to provide evidence that some patients do not need to spend time (or money) on a medical visit for ear wax irrigation. The fact that patients who were given bulb syringes had fewer visits, not only for the initial wax removal but also for subsequent episodes of cerumen impaction, suggests that they were self-treating at home without an increase in adverse effects.

CAVEATS: Home irrigation is not for every patient

This intervention cannot be extrapolated to young children or to others who are unable to perform self-irrigation. It is possible that if a patient self-irrigates without prior visualization by a clinician, a contraindication such as ruptured tympanic membrane or active infection could be present.

This study was performed in England, where bulb syringes are not readily available. It is possible that this intervention may be less effective at avoiding cerumen-related office visits in the United States, especially if patients are already using bulb syringes for this purpose. Finally, we note that 60% of the patients in the home irrigation group did return for a visit for cerumen removal during the 2-year follow-up, so home irrigation did not entirely replace office irrigation.

CHALLENGES TO IMPLEMENTATION: Getting buy-in from patients

The greatest challenge to implementation might be convincing patients that they can safely perform self-irrigation at home. This may require written patient instructions, preferably with illustrations. The steps will need to be written clearly and include details such as recommended ear wax softeners, water temperature, use of peroxide (or not), warning symptoms, and when to contact a physician.

A healthy physician-patient relationship, and perhaps, giving patients the bulb syringe and instructions in using it before they leave the clinic, will help to overcome patient hesitancy. Physician inertia may also be a problem, but it should be easy to put this new information into practice once provider resistance is overcome.

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.

Click here to view PURL METHODOLOGY

ILLUSTRATIVE CASE

A mother brings in her 14-year-old daughter for a routine check-up. The girl has no chronic medical problems and an unremarkable physical exam. When you’re alone with your patient, you inquire about substance abuse and sexual activity. She denies both. What questions would you ask to screen for depression?

Estimates of the prevalence of adolescent depression range from 3% to 9%,^2-4 and nearly 20% of teens will experience a depressive disorder before the age of 20.² But less than half of depressed adolescents are diagnosed or treated.²

Depressed teens face multiple risks
Teens with depressive disorders are at elevated risk, not only for poor family and social relationships and difficulties at school, but also for early pregnancy, substance abuse, hospitalization, recurrent episodes of depression, and suicide.^2,4 Thirteen percent of adolescents have seriously contemplated suicide, and 6.3% have made a suicide attempt in the previous 12 months.⁵

The US Preventive Services Task Force (USPSTF) recommends screening all adolescents for depression—provided that effective treatments and counseling are available for those who need it.⁶ Nearly all primary care clinicians agree that it is important to screen for adolescent depression, yet many feel hindered by both a lack of training and time constraints.² The study by Richardson et al¹ shows that targeted screening can be effective, even when time is tight.

STUDY SUMMARY: 2-question screen is fairly accurate

The Patient Health Questionnaire (PHQ)-9 is a simple and reasonably accurate test for depression in adults.⁷ A much shorter version, using only the first 2 of the PHQ-9’s questions, is an effective screening tool for adults.⁸ Richardson et al evaluated this brief screen—the PHQ-2—for adolescent depression.¹

The researchers invited 4000 teens (ages 13-17) who had seen a clinician within the previous 12 months to participate in a mailed survey, with parental or guardian approval. The survey included questions about age, gender, height, weight, sedentary and functional behaviors, and overall health, as well as depressive symptoms identified with the PHQ-2. This simple screen asks patients to rate how often in the past 2 weeks they have had:

1) a depressed mood, and/or

2) a lack of pleasure in usual activities.

Each question is scored from 0 to 3, with 0=not at all, and 3=nearly every day.

Next, the authors randomly selected 271 respondents with scores of ≥3 and 228 respondents with scores <3, matched for age and gender. Of those, 89% (n=444) participated in a longer telephone interview, which included the PHQ-9 and the Diagnostic Interview Schedule for Children (DISC-IV). Participants were predominantly female (60%), Caucasian (71%), and from urban areas (83%), with a mean household income of $57,442.

Compared with the DISC-IV—which the researchers considered the gold standard—the PHQ-2 had a sensitivity of 74% and a specificity of 75% at a cut point score ≥3; the sensitivity and specificity were 96% and 82%, respectively, for detecting young people who met the criteria for major depression on the PHQ-9. The area under the receiver operating curve was 0.84 (95% confidence interval, 0.75-0.92), meaning that the PHQ-2 correctly classified 84% of the participants as depressed or not depressed.

PHQ-2 helps identify related symptoms
Most of those with false-positive screens had other mental health problems. These included depressive symptoms that did not meet the criteria for major depression, an episode of major depression within the past year (but not in the last month), significant psychosocial impairment, and clinically significant anxiety symptoms.

WHAT’S NEW: Screening can be quick

Prior to this study, most validated tools for depression screening of adolescents were relatively time-consuming, and not likely to be performed during routine visits. The PHQ-2 is a reasonably accurate screen that requires minimal time (and minimal training).

CAVEATS: Study assessed a homogenous group

This study included mostly white girls from urban areas, relatively few of whom had public insurance. Whether the results are applicable to teens from different backgrounds is unclear. While the accuracy of the PHQ-2 was not perfect, almost 95% of those with a positive screen had some psychological problems.

CHALLENGES TO IMPLEMENTATION: Physicians may lack psych resources

Routinely using a 2-question screen for adolescent depression is unlikely to interfere with workflow in most practices. However, the USPSTF recommends screening teens only when there are systems in place to ensure accurate diagnosis, psychotherapy, and follow-up. Unfortunately, not all clinicians are adequately trained to diagnose or treat depressed teens, and some may lack access to appropriate psychotherapy referrals or consultation.

Despite the benefit of medications such as selective serotonin reuptake inhibitors (SSRIs) for teens with major depression, the antidepressants carry some risk. The black box warning for suicidality among adolescents treated with SSRIs⁹ necessitates accurate diagnosis, informed consent, and appropriate follow-up with clinicians who are comfortable treating adolescents.

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.

Click here to view PURL METHODOLOGY

ILLUSTRATIVE CASE

A mother brings in her 14-year-old daughter for a routine check-up. The girl has no chronic medical problems and an unremarkable physical exam. When you’re alone with your patient, you inquire about substance abuse and sexual activity. She denies both. What questions would you ask to screen for depression?

Estimates of the prevalence of adolescent depression range from 3% to 9%,^2-4 and nearly 20% of teens will experience a depressive disorder before the age of 20.² But less than half of depressed adolescents are diagnosed or treated.²

Depressed teens face multiple risks
Teens with depressive disorders are at elevated risk, not only for poor family and social relationships and difficulties at school, but also for early pregnancy, substance abuse, hospitalization, recurrent episodes of depression, and suicide.^2,4 Thirteen percent of adolescents have seriously contemplated suicide, and 6.3% have made a suicide attempt in the previous 12 months.⁵

The US Preventive Services Task Force (USPSTF) recommends screening all adolescents for depression—provided that effective treatments and counseling are available for those who need it.⁶ Nearly all primary care clinicians agree that it is important to screen for adolescent depression, yet many feel hindered by both a lack of training and time constraints.² The study by Richardson et al¹ shows that targeted screening can be effective, even when time is tight.

STUDY SUMMARY: 2-question screen is fairly accurate

The Patient Health Questionnaire (PHQ)-9 is a simple and reasonably accurate test for depression in adults.⁷ A much shorter version, using only the first 2 of the PHQ-9’s questions, is an effective screening tool for adults.⁸ Richardson et al evaluated this brief screen—the PHQ-2—for adolescent depression.¹

The researchers invited 4000 teens (ages 13-17) who had seen a clinician within the previous 12 months to participate in a mailed survey, with parental or guardian approval. The survey included questions about age, gender, height, weight, sedentary and functional behaviors, and overall health, as well as depressive symptoms identified with the PHQ-2. This simple screen asks patients to rate how often in the past 2 weeks they have had:

1) a depressed mood, and/or

2) a lack of pleasure in usual activities.

Each question is scored from 0 to 3, with 0=not at all, and 3=nearly every day.

Next, the authors randomly selected 271 respondents with scores of ≥3 and 228 respondents with scores <3, matched for age and gender. Of those, 89% (n=444) participated in a longer telephone interview, which included the PHQ-9 and the Diagnostic Interview Schedule for Children (DISC-IV). Participants were predominantly female (60%), Caucasian (71%), and from urban areas (83%), with a mean household income of $57,442.

Compared with the DISC-IV—which the researchers considered the gold standard—the PHQ-2 had a sensitivity of 74% and a specificity of 75% at a cut point score ≥3; the sensitivity and specificity were 96% and 82%, respectively, for detecting young people who met the criteria for major depression on the PHQ-9. The area under the receiver operating curve was 0.84 (95% confidence interval, 0.75-0.92), meaning that the PHQ-2 correctly classified 84% of the participants as depressed or not depressed.

PHQ-2 helps identify related symptoms
Most of those with false-positive screens had other mental health problems. These included depressive symptoms that did not meet the criteria for major depression, an episode of major depression within the past year (but not in the last month), significant psychosocial impairment, and clinically significant anxiety symptoms.

WHAT’S NEW: Screening can be quick

Prior to this study, most validated tools for depression screening of adolescents were relatively time-consuming, and not likely to be performed during routine visits. The PHQ-2 is a reasonably accurate screen that requires minimal time (and minimal training).

CAVEATS: Study assessed a homogenous group

This study included mostly white girls from urban areas, relatively few of whom had public insurance. Whether the results are applicable to teens from different backgrounds is unclear. While the accuracy of the PHQ-2 was not perfect, almost 95% of those with a positive screen had some psychological problems.

CHALLENGES TO IMPLEMENTATION: Physicians may lack psych resources

Routinely using a 2-question screen for adolescent depression is unlikely to interfere with workflow in most practices. However, the USPSTF recommends screening teens only when there are systems in place to ensure accurate diagnosis, psychotherapy, and follow-up. Unfortunately, not all clinicians are adequately trained to diagnose or treat depressed teens, and some may lack access to appropriate psychotherapy referrals or consultation.

Despite the benefit of medications such as selective serotonin reuptake inhibitors (SSRIs) for teens with major depression, the antidepressants carry some risk. The black box warning for suicidality among adolescents treated with SSRIs⁹ necessitates accurate diagnosis, informed consent, and appropriate follow-up with clinicians who are comfortable treating adolescents.

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.

Click here to view PURL METHODOLOGY

ILLUSTRATIVE CASE

A mother brings in her 14-year-old daughter for a routine check-up. The girl has no chronic medical problems and an unremarkable physical exam. When you’re alone with your patient, you inquire about substance abuse and sexual activity. She denies both. What questions would you ask to screen for depression?

Estimates of the prevalence of adolescent depression range from 3% to 9%,^2-4 and nearly 20% of teens will experience a depressive disorder before the age of 20.² But less than half of depressed adolescents are diagnosed or treated.²

Depressed teens face multiple risks
Teens with depressive disorders are at elevated risk, not only for poor family and social relationships and difficulties at school, but also for early pregnancy, substance abuse, hospitalization, recurrent episodes of depression, and suicide.^2,4 Thirteen percent of adolescents have seriously contemplated suicide, and 6.3% have made a suicide attempt in the previous 12 months.⁵

The US Preventive Services Task Force (USPSTF) recommends screening all adolescents for depression—provided that effective treatments and counseling are available for those who need it.⁶ Nearly all primary care clinicians agree that it is important to screen for adolescent depression, yet many feel hindered by both a lack of training and time constraints.² The study by Richardson et al¹ shows that targeted screening can be effective, even when time is tight.

STUDY SUMMARY: 2-question screen is fairly accurate

The Patient Health Questionnaire (PHQ)-9 is a simple and reasonably accurate test for depression in adults.⁷ A much shorter version, using only the first 2 of the PHQ-9’s questions, is an effective screening tool for adults.⁸ Richardson et al evaluated this brief screen—the PHQ-2—for adolescent depression.¹

The researchers invited 4000 teens (ages 13-17) who had seen a clinician within the previous 12 months to participate in a mailed survey, with parental or guardian approval. The survey included questions about age, gender, height, weight, sedentary and functional behaviors, and overall health, as well as depressive symptoms identified with the PHQ-2. This simple screen asks patients to rate how often in the past 2 weeks they have had:

1) a depressed mood, and/or

2) a lack of pleasure in usual activities.

Each question is scored from 0 to 3, with 0=not at all, and 3=nearly every day.

Next, the authors randomly selected 271 respondents with scores of ≥3 and 228 respondents with scores <3, matched for age and gender. Of those, 89% (n=444) participated in a longer telephone interview, which included the PHQ-9 and the Diagnostic Interview Schedule for Children (DISC-IV). Participants were predominantly female (60%), Caucasian (71%), and from urban areas (83%), with a mean household income of $57,442.

Compared with the DISC-IV—which the researchers considered the gold standard—the PHQ-2 had a sensitivity of 74% and a specificity of 75% at a cut point score ≥3; the sensitivity and specificity were 96% and 82%, respectively, for detecting young people who met the criteria for major depression on the PHQ-9. The area under the receiver operating curve was 0.84 (95% confidence interval, 0.75-0.92), meaning that the PHQ-2 correctly classified 84% of the participants as depressed or not depressed.

PHQ-2 helps identify related symptoms
Most of those with false-positive screens had other mental health problems. These included depressive symptoms that did not meet the criteria for major depression, an episode of major depression within the past year (but not in the last month), significant psychosocial impairment, and clinically significant anxiety symptoms.

WHAT’S NEW: Screening can be quick

Prior to this study, most validated tools for depression screening of adolescents were relatively time-consuming, and not likely to be performed during routine visits. The PHQ-2 is a reasonably accurate screen that requires minimal time (and minimal training).

CAVEATS: Study assessed a homogenous group

This study included mostly white girls from urban areas, relatively few of whom had public insurance. Whether the results are applicable to teens from different backgrounds is unclear. While the accuracy of the PHQ-2 was not perfect, almost 95% of those with a positive screen had some psychological problems.

CHALLENGES TO IMPLEMENTATION: Physicians may lack psych resources

Routinely using a 2-question screen for adolescent depression is unlikely to interfere with workflow in most practices. However, the USPSTF recommends screening teens only when there are systems in place to ensure accurate diagnosis, psychotherapy, and follow-up. Unfortunately, not all clinicians are adequately trained to diagnose or treat depressed teens, and some may lack access to appropriate psychotherapy referrals or consultation.

Despite the benefit of medications such as selective serotonin reuptake inhibitors (SSRIs) for teens with major depression, the antidepressants carry some risk. The black box warning for suicidality among adolescents treated with SSRIs⁹ necessitates accurate diagnosis, informed consent, and appropriate follow-up with clinicians who are comfortable treating adolescents.

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.

Click here to view PURL METHODOLOGY