Commentary

Rates of preterm birth in the United States have been falling since 2006, but the rates of early preterm birth in singletons (those under 34 weeks’ gestation), specifically, have not trended downward as dramatically as have late preterm birth in singletons (34-36 weeks). According to 2015 data from the National Vital Statistics Reports, the rate of early preterm births is still 3.4% in all pregnancies and 2.7% among singletons.

While the number of neonates born before 37 weeks of gestation remains high – approximately 11% in 2013 – and signifies a continuing public health problem, the rate of early preterm birth is particularly concerning because early preterm birth is more significantly associated with neonatal mortality, long-term morbidity and extended neonatal intensive care unit stays, all leading to increased health care expenditures.

Finding predictors for preterm birth that are stronger than traditional clinical factors has long been a goal of ob.gyns. because the vast majority of all spontaneous preterm births occur to women without known risk factors (i.e., multiple gestations or prior preterm birth).

Cervical length in the midtrimester is now a well-verified predictor of preterm birth, for both low- and high-risk women. Furthermore, vaginal progesterone has been shown to be a safe and beneficial intervention for women with no known risk factors who are diagnosed with a shortened cervical length (< 2 cm), and cervical cerclage has been suggested to reduce the risk of preterm birth for women with a history of prior preterm birth who also have a shortened cervical length.

Some are now advocating universal cervical length screening for women with singleton gestations, but before universal screening is mandated, the downstream effect of such a change in practice must be considered.

Backdrop to screening

Cervical length measurement was first investigated more than 25 years ago as a possible predictor of preterm birth. In 1996, a prospective multicenter study of almost 3,000 women with singleton pregnancies showed that the risk of preterm delivery is inversely and directly related to the length of the cervix, as measured with vaginal ultrasonography (N. Engl. J. Med. 1996;334:567-72).

In fact, at 24 weeks’ gestation, every 1 mm of additional cervical length equates to a significant decrease in preterm birth risk (odds ratio, 0.91). Several other studies, in addition to the landmark 1996 study, have similarly demonstrated this inverse relationship between preterm birth risk and cervical length between 18 and 24 weeks’ gestation.

However, the use of cervical measurement did not achieve widespread use until more than a decade later, when researchers began to identify interventions that could prolong pregnancy if a short cervix was diagnosed in the second trimester.

For example, Dr. E.B. Fonseca’s study of almost 25,000 asymptomatic pregnant women, demonstrated that daily vaginal progesterone reduced the risk of spontaneous delivery before 34 weeks by approximately 44% in women identified with a cervical length of 1.5 cm or less (N. Engl. J. Med. 2007;357:462-9). The vast majority of the women in this study had singleton pregnancies.

Shortly thereafter, Dr. S.S. Hassan and her colleagues completed a similar trial in women with singleton gestations and transvaginal cervical lengths between 1.0 and 2.0 cm at 20-23 weeks’ gestation. In this trial, nightly progesterone gel (with 90 mg progesterone per application) was associated with a 45% reduction in preterm birth before 33 weeks and a 38% reduction in preterm birth before 35 weeks (Ultrasound. Obstet. Gynecol. 2011;38:18-31).

A meta-analysis led by Dr. Roberto Romero, which included the Fonseca and Hassan trials, looked specifically at 775 women with a midtrimester cervical length of 2.5 cm or less. Women with a singleton gestation who had no history of preterm birth had a 40% reduction in the rate of early preterm birth when they were treated with vaginal progesterone (Am. J. Obstet. Gynecol. 2012;206:124-e1-19).

The benefits of identifying a short cervix likely extend to women with a history of prior preterm birth. A patient-level meta-analysis published in 2011 demonstrated that cervical cerclage placement was associated with a significant reduction in preterm birth before 35 weeks’ gestation in women with singleton gestations, previous spontaneous preterm birth, and cervical length less than 2.5 cm before 24 weeks’ gestation (Obstet. Gynecol. 2011;117:663-71).

The possible benefits of diagnosing and intervening for a shortened cervix have tipped many experts and clinicians toward the practice of universal cervical length screening of all singleton pregnancies. Research has shown that we can accurately obtain a cervical-length measurement before 24 weeks, and that we have effective and safe interventions for cases of short cervix: cerclage in women with a history of preterm birth who are already receiving progesterone, and vaginal progesterone in women without such a history.

Screening certainties and doubts

In 2011, my colleagues and I compared the cost effectiveness of two approaches to preterm birth prevention in low-risk pregnancies: no screening versus a single transvaginal ultrasound cervical-length measurement in all asymptomatic, low-risk singleton pregnant individuals between 18 and 24 weeks’ gestation.

In our model, women identified as having a cervical length less than 1.5 cm would be offered vaginal progesterone. Based on published data, we assumed there would be a 92% adherence rate, and a 45% reduction in deliveries before 34 weeks with progesterone treatment.

We found that in low-risk pregnancies, universal transvaginal cervical-length ultrasound screening and progesterone intervention would be cost effective and in many cases cost saving. We estimated that screening would prevent 248 early preterm births – as well as 22 neonatal deaths or neonates with long-term neurologic deficits – per 100,000 deliveries.

Our sensitivity analyses showed that screening remained cost saving under a range of clinical scenarios, including varied preterm birth rates and predictive values of a shortened cervix. Screening was not cost saving, but remained cost effective, when the expense of a transvaginal ultrasound scan exceeds $187 or when vaginal progesterone is assumed to reduce the risk of early preterm delivery by less than 20% (Ultrasound Obstet. Gynecol. 2011;38;32-37).

Neither the American College of Obstetricians and Gynecologists nor the Society for Maternal-Fetal Medicine support mandated universal transvaginal ultrasound cervical length screening. Both organizations state, however, that the approach may be considered in women with singleton gestations without prior spontaneous preterm birth.

Interestingly, Thomas Jefferson University in Philadelphia, which uses a universal screening program for singleton gestations without prior preterm birth, has recently published data that complicate the growing trend toward universal cervical length screening.

The Philadelphia clinicians followed a strategy whereby women with a transvaginal cervical length of 2 cm or less were prescribed vaginal progesterone (90 mg vaginal progesterone gel, or 200 mg micronized progesterone gel capsules). Those with a cervical length between approximately 2 cm and 2.5 cm were asked to return for a follow-up cervical length measurement before 24 weeks’ gestation.

What they found in this cohort was surprising: a rate of short cervix that is significantly lower than what previous research has shown.

Among those screened, 0.8% of women had a cervical length of 2 cm or less on an initial transvaginal ultrasonogram. Previously, a prevalence of 1%-2% for an even shorter cervical length (less than 1.5 cm) was fairly consistent in the literature.

As Dr. Kelly M. Orzechowski and her colleagues point out, the low incidence of short cervix “raises questions regarding whether universal transvaginal ultrasonogram cervical length screening in low-risk asymptomatic women is beneficial” (Obstet. Gynecol. 2014;124:520-5).

In our 2011 cost-effectiveness analysis, we found that screening was no longer a cost-saving practice when the incidence of cervical length less than 1.5 cm falls below 0.8%. Screening remained cost effective, however.

Recently, we found that if the Philadelphia protocol is followed and the U.S. population has an incidence of shortened cervix similar to that described by Dr. Orzechowski and her colleagues, universal cervical length screening in low-risk singleton pregnancies is cost effective but not cost saving. Furthermore, we found several additional plausible situations in this unpublished analysis in which universal screening ceased to be cost effective.

Thus, before we move to a strategy of mandated universal screening, we need better population-based estimates of the incidence of short cervix in a truly low-risk population.

We also must consider the future costs of progesterone. It is possible that costs may increase significantly if vaginal progesterone wins approval from the Food and Drug Administration for this indication.

Finally, if universal cervical length screening is to become the standard of care, we need policies in place to prevent misuse of the screening technology that would inevitably drive up costs without improving outcomes. For example, we must ensure that one cervical length measurement does not transition into serial cervical length measurements over the course of pregnancy, since measurement after 24 weeks has limited clinical utility. Similarly, progesterone use for a cervical length less than or equal to 2.0 cm cannot progress to progesterone for anyone approaching 2.0 cm (i.e. 2.5 cm or even 3 cm) as there is no evidence to suggest a benefit for women with longer cervixes.

Over time, it would be beneficial to have additional data on how best to manage patients who have a cervical length of 2 cm-2.5 cm before 24 weeks’ gestation. Many of us ask these women to return for a follow-up measurement and some may prescribe progesterone. However, we lack evidence for either approach; while a cervical length measurement less than 2.5 cm is clearly associated with an increased risk of preterm birth, the benefit of treatment has been demonstrated only with a cervical length of 2 cm or less.

Today and the future

For women with a history of preterm birth, cervical length screening is now routine. For low-risk pregnant women – those without a history of previous spontaneous preterm delivery – various approaches are currently taken. Most physicians recommend assessing the cervical length transabdominally at the time of the 18-20-week ultrasound, and proceeding to transvaginal ultrasonography if the cervical length is less than 3 cm or 3.5 cm.

To reliably image the cervix with transabdominal ultrasound, it should be performed with a full bladder and with the understanding that the cervix appears longer (6 mm longer, on average) when the bladder is full (Aust. N. Z. J. Obstet. Gynaecol. 2014;54:250-55).

Transvaginal ultrasound has been widely recognized as a sensitive and reproducible method for detecting shortened cervical length. Overall, this tool has several advantages over the transabdominal approach. However, the lack of universal access to transvaginal ultrasound and to consistently reliable cervical length measurements have been valid concerns of those who oppose universal transvaginal ultrasound cervical length screening.

Such concerns likely will lessen over time as transvaginal ultrasound continues to become more pervasive. Several years ago, the Perinatal Quality Foundation set standards for measuring the cervix and launched the Cervical Length Education and Review (CLEAR) program. When sonographers and physicians obtain training and credentialing, there appears to be only a 5%-10% intraobserver variability in cervical length measurement. (The PQF’s initial focus in 2005 was the Nuchal Translucency Quality Review program.)

Increasingly, I believe, transvaginal ultrasound cervical length measurement will be utilized to identify women at high risk for early preterm birth so that low-risk women can receive progesterone and high-risk women (those with a history of preterm birth) can be considered as candidates for cerclage placement. In the process, the quality of clinical care as well as the quality of our research data will improve. Whether and when such screening will become universal, however, is still uncertain.

Dr. Werner reported that she has no financial disclosures relevant to this Master Class.

Rates of preterm birth in the United States have been falling since 2006, but the rates of early preterm birth in singletons (those under 34 weeks’ gestation), specifically, have not trended downward as dramatically as have late preterm birth in singletons (34-36 weeks). According to 2015 data from the National Vital Statistics Reports, the rate of early preterm births is still 3.4% in all pregnancies and 2.7% among singletons.

While the number of neonates born before 37 weeks of gestation remains high – approximately 11% in 2013 – and signifies a continuing public health problem, the rate of early preterm birth is particularly concerning because early preterm birth is more significantly associated with neonatal mortality, long-term morbidity and extended neonatal intensive care unit stays, all leading to increased health care expenditures.

Finding predictors for preterm birth that are stronger than traditional clinical factors has long been a goal of ob.gyns. because the vast majority of all spontaneous preterm births occur to women without known risk factors (i.e., multiple gestations or prior preterm birth).

Cervical length in the midtrimester is now a well-verified predictor of preterm birth, for both low- and high-risk women. Furthermore, vaginal progesterone has been shown to be a safe and beneficial intervention for women with no known risk factors who are diagnosed with a shortened cervical length (< 2 cm), and cervical cerclage has been suggested to reduce the risk of preterm birth for women with a history of prior preterm birth who also have a shortened cervical length.

Some are now advocating universal cervical length screening for women with singleton gestations, but before universal screening is mandated, the downstream effect of such a change in practice must be considered.

Backdrop to screening

Cervical length measurement was first investigated more than 25 years ago as a possible predictor of preterm birth. In 1996, a prospective multicenter study of almost 3,000 women with singleton pregnancies showed that the risk of preterm delivery is inversely and directly related to the length of the cervix, as measured with vaginal ultrasonography (N. Engl. J. Med. 1996;334:567-72).

In fact, at 24 weeks’ gestation, every 1 mm of additional cervical length equates to a significant decrease in preterm birth risk (odds ratio, 0.91). Several other studies, in addition to the landmark 1996 study, have similarly demonstrated this inverse relationship between preterm birth risk and cervical length between 18 and 24 weeks’ gestation.

However, the use of cervical measurement did not achieve widespread use until more than a decade later, when researchers began to identify interventions that could prolong pregnancy if a short cervix was diagnosed in the second trimester.

For example, Dr. E.B. Fonseca’s study of almost 25,000 asymptomatic pregnant women, demonstrated that daily vaginal progesterone reduced the risk of spontaneous delivery before 34 weeks by approximately 44% in women identified with a cervical length of 1.5 cm or less (N. Engl. J. Med. 2007;357:462-9). The vast majority of the women in this study had singleton pregnancies.

Shortly thereafter, Dr. S.S. Hassan and her colleagues completed a similar trial in women with singleton gestations and transvaginal cervical lengths between 1.0 and 2.0 cm at 20-23 weeks’ gestation. In this trial, nightly progesterone gel (with 90 mg progesterone per application) was associated with a 45% reduction in preterm birth before 33 weeks and a 38% reduction in preterm birth before 35 weeks (Ultrasound. Obstet. Gynecol. 2011;38:18-31).

A meta-analysis led by Dr. Roberto Romero, which included the Fonseca and Hassan trials, looked specifically at 775 women with a midtrimester cervical length of 2.5 cm or less. Women with a singleton gestation who had no history of preterm birth had a 40% reduction in the rate of early preterm birth when they were treated with vaginal progesterone (Am. J. Obstet. Gynecol. 2012;206:124-e1-19).

The benefits of identifying a short cervix likely extend to women with a history of prior preterm birth. A patient-level meta-analysis published in 2011 demonstrated that cervical cerclage placement was associated with a significant reduction in preterm birth before 35 weeks’ gestation in women with singleton gestations, previous spontaneous preterm birth, and cervical length less than 2.5 cm before 24 weeks’ gestation (Obstet. Gynecol. 2011;117:663-71).

The possible benefits of diagnosing and intervening for a shortened cervix have tipped many experts and clinicians toward the practice of universal cervical length screening of all singleton pregnancies. Research has shown that we can accurately obtain a cervical-length measurement before 24 weeks, and that we have effective and safe interventions for cases of short cervix: cerclage in women with a history of preterm birth who are already receiving progesterone, and vaginal progesterone in women without such a history.

Screening certainties and doubts

In 2011, my colleagues and I compared the cost effectiveness of two approaches to preterm birth prevention in low-risk pregnancies: no screening versus a single transvaginal ultrasound cervical-length measurement in all asymptomatic, low-risk singleton pregnant individuals between 18 and 24 weeks’ gestation.

In our model, women identified as having a cervical length less than 1.5 cm would be offered vaginal progesterone. Based on published data, we assumed there would be a 92% adherence rate, and a 45% reduction in deliveries before 34 weeks with progesterone treatment.

We found that in low-risk pregnancies, universal transvaginal cervical-length ultrasound screening and progesterone intervention would be cost effective and in many cases cost saving. We estimated that screening would prevent 248 early preterm births – as well as 22 neonatal deaths or neonates with long-term neurologic deficits – per 100,000 deliveries.

Our sensitivity analyses showed that screening remained cost saving under a range of clinical scenarios, including varied preterm birth rates and predictive values of a shortened cervix. Screening was not cost saving, but remained cost effective, when the expense of a transvaginal ultrasound scan exceeds $187 or when vaginal progesterone is assumed to reduce the risk of early preterm delivery by less than 20% (Ultrasound Obstet. Gynecol. 2011;38;32-37).

Neither the American College of Obstetricians and Gynecologists nor the Society for Maternal-Fetal Medicine support mandated universal transvaginal ultrasound cervical length screening. Both organizations state, however, that the approach may be considered in women with singleton gestations without prior spontaneous preterm birth.

Interestingly, Thomas Jefferson University in Philadelphia, which uses a universal screening program for singleton gestations without prior preterm birth, has recently published data that complicate the growing trend toward universal cervical length screening.

The Philadelphia clinicians followed a strategy whereby women with a transvaginal cervical length of 2 cm or less were prescribed vaginal progesterone (90 mg vaginal progesterone gel, or 200 mg micronized progesterone gel capsules). Those with a cervical length between approximately 2 cm and 2.5 cm were asked to return for a follow-up cervical length measurement before 24 weeks’ gestation.

What they found in this cohort was surprising: a rate of short cervix that is significantly lower than what previous research has shown.

Among those screened, 0.8% of women had a cervical length of 2 cm or less on an initial transvaginal ultrasonogram. Previously, a prevalence of 1%-2% for an even shorter cervical length (less than 1.5 cm) was fairly consistent in the literature.

As Dr. Kelly M. Orzechowski and her colleagues point out, the low incidence of short cervix “raises questions regarding whether universal transvaginal ultrasonogram cervical length screening in low-risk asymptomatic women is beneficial” (Obstet. Gynecol. 2014;124:520-5).

In our 2011 cost-effectiveness analysis, we found that screening was no longer a cost-saving practice when the incidence of cervical length less than 1.5 cm falls below 0.8%. Screening remained cost effective, however.

Recently, we found that if the Philadelphia protocol is followed and the U.S. population has an incidence of shortened cervix similar to that described by Dr. Orzechowski and her colleagues, universal cervical length screening in low-risk singleton pregnancies is cost effective but not cost saving. Furthermore, we found several additional plausible situations in this unpublished analysis in which universal screening ceased to be cost effective.

Thus, before we move to a strategy of mandated universal screening, we need better population-based estimates of the incidence of short cervix in a truly low-risk population.

We also must consider the future costs of progesterone. It is possible that costs may increase significantly if vaginal progesterone wins approval from the Food and Drug Administration for this indication.

Finally, if universal cervical length screening is to become the standard of care, we need policies in place to prevent misuse of the screening technology that would inevitably drive up costs without improving outcomes. For example, we must ensure that one cervical length measurement does not transition into serial cervical length measurements over the course of pregnancy, since measurement after 24 weeks has limited clinical utility. Similarly, progesterone use for a cervical length less than or equal to 2.0 cm cannot progress to progesterone for anyone approaching 2.0 cm (i.e. 2.5 cm or even 3 cm) as there is no evidence to suggest a benefit for women with longer cervixes.

Over time, it would be beneficial to have additional data on how best to manage patients who have a cervical length of 2 cm-2.5 cm before 24 weeks’ gestation. Many of us ask these women to return for a follow-up measurement and some may prescribe progesterone. However, we lack evidence for either approach; while a cervical length measurement less than 2.5 cm is clearly associated with an increased risk of preterm birth, the benefit of treatment has been demonstrated only with a cervical length of 2 cm or less.

Today and the future

For women with a history of preterm birth, cervical length screening is now routine. For low-risk pregnant women – those without a history of previous spontaneous preterm delivery – various approaches are currently taken. Most physicians recommend assessing the cervical length transabdominally at the time of the 18-20-week ultrasound, and proceeding to transvaginal ultrasonography if the cervical length is less than 3 cm or 3.5 cm.

To reliably image the cervix with transabdominal ultrasound, it should be performed with a full bladder and with the understanding that the cervix appears longer (6 mm longer, on average) when the bladder is full (Aust. N. Z. J. Obstet. Gynaecol. 2014;54:250-55).

Transvaginal ultrasound has been widely recognized as a sensitive and reproducible method for detecting shortened cervical length. Overall, this tool has several advantages over the transabdominal approach. However, the lack of universal access to transvaginal ultrasound and to consistently reliable cervical length measurements have been valid concerns of those who oppose universal transvaginal ultrasound cervical length screening.

Such concerns likely will lessen over time as transvaginal ultrasound continues to become more pervasive. Several years ago, the Perinatal Quality Foundation set standards for measuring the cervix and launched the Cervical Length Education and Review (CLEAR) program. When sonographers and physicians obtain training and credentialing, there appears to be only a 5%-10% intraobserver variability in cervical length measurement. (The PQF’s initial focus in 2005 was the Nuchal Translucency Quality Review program.)

Increasingly, I believe, transvaginal ultrasound cervical length measurement will be utilized to identify women at high risk for early preterm birth so that low-risk women can receive progesterone and high-risk women (those with a history of preterm birth) can be considered as candidates for cerclage placement. In the process, the quality of clinical care as well as the quality of our research data will improve. Whether and when such screening will become universal, however, is still uncertain.

Dr. Werner reported that she has no financial disclosures relevant to this Master Class.

Rates of preterm birth in the United States have been falling since 2006, but the rates of early preterm birth in singletons (those under 34 weeks’ gestation), specifically, have not trended downward as dramatically as have late preterm birth in singletons (34-36 weeks). According to 2015 data from the National Vital Statistics Reports, the rate of early preterm births is still 3.4% in all pregnancies and 2.7% among singletons.

While the number of neonates born before 37 weeks of gestation remains high – approximately 11% in 2013 – and signifies a continuing public health problem, the rate of early preterm birth is particularly concerning because early preterm birth is more significantly associated with neonatal mortality, long-term morbidity and extended neonatal intensive care unit stays, all leading to increased health care expenditures.

Finding predictors for preterm birth that are stronger than traditional clinical factors has long been a goal of ob.gyns. because the vast majority of all spontaneous preterm births occur to women without known risk factors (i.e., multiple gestations or prior preterm birth).

Cervical length in the midtrimester is now a well-verified predictor of preterm birth, for both low- and high-risk women. Furthermore, vaginal progesterone has been shown to be a safe and beneficial intervention for women with no known risk factors who are diagnosed with a shortened cervical length (< 2 cm), and cervical cerclage has been suggested to reduce the risk of preterm birth for women with a history of prior preterm birth who also have a shortened cervical length.

Some are now advocating universal cervical length screening for women with singleton gestations, but before universal screening is mandated, the downstream effect of such a change in practice must be considered.

Backdrop to screening

Cervical length measurement was first investigated more than 25 years ago as a possible predictor of preterm birth. In 1996, a prospective multicenter study of almost 3,000 women with singleton pregnancies showed that the risk of preterm delivery is inversely and directly related to the length of the cervix, as measured with vaginal ultrasonography (N. Engl. J. Med. 1996;334:567-72).

In fact, at 24 weeks’ gestation, every 1 mm of additional cervical length equates to a significant decrease in preterm birth risk (odds ratio, 0.91). Several other studies, in addition to the landmark 1996 study, have similarly demonstrated this inverse relationship between preterm birth risk and cervical length between 18 and 24 weeks’ gestation.

However, the use of cervical measurement did not achieve widespread use until more than a decade later, when researchers began to identify interventions that could prolong pregnancy if a short cervix was diagnosed in the second trimester.

For example, Dr. E.B. Fonseca’s study of almost 25,000 asymptomatic pregnant women, demonstrated that daily vaginal progesterone reduced the risk of spontaneous delivery before 34 weeks by approximately 44% in women identified with a cervical length of 1.5 cm or less (N. Engl. J. Med. 2007;357:462-9). The vast majority of the women in this study had singleton pregnancies.

Shortly thereafter, Dr. S.S. Hassan and her colleagues completed a similar trial in women with singleton gestations and transvaginal cervical lengths between 1.0 and 2.0 cm at 20-23 weeks’ gestation. In this trial, nightly progesterone gel (with 90 mg progesterone per application) was associated with a 45% reduction in preterm birth before 33 weeks and a 38% reduction in preterm birth before 35 weeks (Ultrasound. Obstet. Gynecol. 2011;38:18-31).

A meta-analysis led by Dr. Roberto Romero, which included the Fonseca and Hassan trials, looked specifically at 775 women with a midtrimester cervical length of 2.5 cm or less. Women with a singleton gestation who had no history of preterm birth had a 40% reduction in the rate of early preterm birth when they were treated with vaginal progesterone (Am. J. Obstet. Gynecol. 2012;206:124-e1-19).

The benefits of identifying a short cervix likely extend to women with a history of prior preterm birth. A patient-level meta-analysis published in 2011 demonstrated that cervical cerclage placement was associated with a significant reduction in preterm birth before 35 weeks’ gestation in women with singleton gestations, previous spontaneous preterm birth, and cervical length less than 2.5 cm before 24 weeks’ gestation (Obstet. Gynecol. 2011;117:663-71).

The possible benefits of diagnosing and intervening for a shortened cervix have tipped many experts and clinicians toward the practice of universal cervical length screening of all singleton pregnancies. Research has shown that we can accurately obtain a cervical-length measurement before 24 weeks, and that we have effective and safe interventions for cases of short cervix: cerclage in women with a history of preterm birth who are already receiving progesterone, and vaginal progesterone in women without such a history.

Screening certainties and doubts

In 2011, my colleagues and I compared the cost effectiveness of two approaches to preterm birth prevention in low-risk pregnancies: no screening versus a single transvaginal ultrasound cervical-length measurement in all asymptomatic, low-risk singleton pregnant individuals between 18 and 24 weeks’ gestation.

In our model, women identified as having a cervical length less than 1.5 cm would be offered vaginal progesterone. Based on published data, we assumed there would be a 92% adherence rate, and a 45% reduction in deliveries before 34 weeks with progesterone treatment.

We found that in low-risk pregnancies, universal transvaginal cervical-length ultrasound screening and progesterone intervention would be cost effective and in many cases cost saving. We estimated that screening would prevent 248 early preterm births – as well as 22 neonatal deaths or neonates with long-term neurologic deficits – per 100,000 deliveries.

Our sensitivity analyses showed that screening remained cost saving under a range of clinical scenarios, including varied preterm birth rates and predictive values of a shortened cervix. Screening was not cost saving, but remained cost effective, when the expense of a transvaginal ultrasound scan exceeds $187 or when vaginal progesterone is assumed to reduce the risk of early preterm delivery by less than 20% (Ultrasound Obstet. Gynecol. 2011;38;32-37).

Neither the American College of Obstetricians and Gynecologists nor the Society for Maternal-Fetal Medicine support mandated universal transvaginal ultrasound cervical length screening. Both organizations state, however, that the approach may be considered in women with singleton gestations without prior spontaneous preterm birth.

Interestingly, Thomas Jefferson University in Philadelphia, which uses a universal screening program for singleton gestations without prior preterm birth, has recently published data that complicate the growing trend toward universal cervical length screening.

The Philadelphia clinicians followed a strategy whereby women with a transvaginal cervical length of 2 cm or less were prescribed vaginal progesterone (90 mg vaginal progesterone gel, or 200 mg micronized progesterone gel capsules). Those with a cervical length between approximately 2 cm and 2.5 cm were asked to return for a follow-up cervical length measurement before 24 weeks’ gestation.

What they found in this cohort was surprising: a rate of short cervix that is significantly lower than what previous research has shown.

Among those screened, 0.8% of women had a cervical length of 2 cm or less on an initial transvaginal ultrasonogram. Previously, a prevalence of 1%-2% for an even shorter cervical length (less than 1.5 cm) was fairly consistent in the literature.

As Dr. Kelly M. Orzechowski and her colleagues point out, the low incidence of short cervix “raises questions regarding whether universal transvaginal ultrasonogram cervical length screening in low-risk asymptomatic women is beneficial” (Obstet. Gynecol. 2014;124:520-5).

In our 2011 cost-effectiveness analysis, we found that screening was no longer a cost-saving practice when the incidence of cervical length less than 1.5 cm falls below 0.8%. Screening remained cost effective, however.

Recently, we found that if the Philadelphia protocol is followed and the U.S. population has an incidence of shortened cervix similar to that described by Dr. Orzechowski and her colleagues, universal cervical length screening in low-risk singleton pregnancies is cost effective but not cost saving. Furthermore, we found several additional plausible situations in this unpublished analysis in which universal screening ceased to be cost effective.

Thus, before we move to a strategy of mandated universal screening, we need better population-based estimates of the incidence of short cervix in a truly low-risk population.

We also must consider the future costs of progesterone. It is possible that costs may increase significantly if vaginal progesterone wins approval from the Food and Drug Administration for this indication.

Finally, if universal cervical length screening is to become the standard of care, we need policies in place to prevent misuse of the screening technology that would inevitably drive up costs without improving outcomes. For example, we must ensure that one cervical length measurement does not transition into serial cervical length measurements over the course of pregnancy, since measurement after 24 weeks has limited clinical utility. Similarly, progesterone use for a cervical length less than or equal to 2.0 cm cannot progress to progesterone for anyone approaching 2.0 cm (i.e. 2.5 cm or even 3 cm) as there is no evidence to suggest a benefit for women with longer cervixes.

Over time, it would be beneficial to have additional data on how best to manage patients who have a cervical length of 2 cm-2.5 cm before 24 weeks’ gestation. Many of us ask these women to return for a follow-up measurement and some may prescribe progesterone. However, we lack evidence for either approach; while a cervical length measurement less than 2.5 cm is clearly associated with an increased risk of preterm birth, the benefit of treatment has been demonstrated only with a cervical length of 2 cm or less.

Today and the future

For women with a history of preterm birth, cervical length screening is now routine. For low-risk pregnant women – those without a history of previous spontaneous preterm delivery – various approaches are currently taken. Most physicians recommend assessing the cervical length transabdominally at the time of the 18-20-week ultrasound, and proceeding to transvaginal ultrasonography if the cervical length is less than 3 cm or 3.5 cm.

To reliably image the cervix with transabdominal ultrasound, it should be performed with a full bladder and with the understanding that the cervix appears longer (6 mm longer, on average) when the bladder is full (Aust. N. Z. J. Obstet. Gynaecol. 2014;54:250-55).

Transvaginal ultrasound has been widely recognized as a sensitive and reproducible method for detecting shortened cervical length. Overall, this tool has several advantages over the transabdominal approach. However, the lack of universal access to transvaginal ultrasound and to consistently reliable cervical length measurements have been valid concerns of those who oppose universal transvaginal ultrasound cervical length screening.

Such concerns likely will lessen over time as transvaginal ultrasound continues to become more pervasive. Several years ago, the Perinatal Quality Foundation set standards for measuring the cervix and launched the Cervical Length Education and Review (CLEAR) program. When sonographers and physicians obtain training and credentialing, there appears to be only a 5%-10% intraobserver variability in cervical length measurement. (The PQF’s initial focus in 2005 was the Nuchal Translucency Quality Review program.)

Increasingly, I believe, transvaginal ultrasound cervical length measurement will be utilized to identify women at high risk for early preterm birth so that low-risk women can receive progesterone and high-risk women (those with a history of preterm birth) can be considered as candidates for cerclage placement. In the process, the quality of clinical care as well as the quality of our research data will improve. Whether and when such screening will become universal, however, is still uncertain.

Dr. Werner reported that she has no financial disclosures relevant to this Master Class.

If you ask a primary care pediatrician who has been practicing for more than 2 decades, she will tell you that her practice has tilted steeply toward complaints with a more developmental and behavioral flavor. In the lead article of the April 2015 Pediatrics (“Are We on the Right Track? Examining the Role of Developmental Behavioral Pediatrics”) Dr. Ruth E.K. Stein, a recent recipient of the C. Anderson Aldrich Award given by the American Academy of Pediatrics section on children with developmental and behavioral pediatrics, questions whether we, both general pediatricians and specialists in developmental and behavioral pediatrics, are on the right path in addressing this shifting mix in our patient populations.

Dr. Stein observes that while she and other pioneers in the creation of her specialty began as general pediatricians, today physicians typically enter developmental and behavioral fellowship programs without the benefit of practicing the runny nose–earache–diaper rash kind of pediatrics that many of us enjoy. She worries that from this early branching point in training, developmental and behavioral specialists have become “sequestered and siloed – increasingly seen only as people who take care of children who have special needs.” The problem is that, as Dr. Stein wisely observes, developmental and behavioral issues “are the core constructs of pediatrics and its backbone and that they must be incorporated into every primary care and specialty encounter and included in every educational experience.”

Dr. Stein continues her essay by proposing a handful of strategies for bridging the gap between developmental and behavioral specialists and general pediatricians, and strengthening the training of house officers, which currently requires only a pitifully inadequate month devoted to developmental and behavioral issues. While it is hard to argue with Dr. Stein’s suggestions, they only nibble around the edges of the real problem.

If one really believes as she and I do, that behavior and development must be considered in every patient encounter and educational experience, then the solution lies in changing how we teach medicine from the very beginning instead of waiting until postgraduate education. Everyone mouths the importance of the mind-body connection, but it is often just so much hot air. The relationship between behavior and development, and what Dr. Stein refers to as “biomedical” conditions, exists in every patient. It is often said it is the fact that our patients are growing and developing that keeps pediatrics apart from the rest of medicine. But the same process of change over time occurs in adults as well; we call it aging instead of development. Understanding where our patients are positioned on this trajectory from birth to death is critical in helping us understand what is troubling them, and how best to help them manage their concerns.

For pediatricians, our preverbal patients’ behavior is often the only way we have of knowing there is a problem. Behavior can be their unspoken chief complaint. The failure by a physician to interpret her patient’s behavior as either a result or the cause of the problem can lead to an unfortunate outcome.

This means, as we teach aspiring doctors the art of medicine, we must make it clear that the patient’s behavior and stage of development must be considered equally with the more traditional biomedical etiologies, not as an afterthought. For example, any discussion of nonacute recurrent abdominal pain in children that fails to acknowledge from the outset that most of these patients will not have an abnormality detectable by lab work and imaging studies is doing the young physician and his patients a disservice. I am suggesting that we adopt a more patient-centered rather than a disease-centered approach to training all physicians.

While every patient must be viewed in the proper behavioral and developmental context, there are those in whom a behavior problem dominates. Given the patient mix that the new millennium pediatrician is going to face, 1 month in postgraduate training is clearly insufficient. One cannot begin to learn even the rudiments of managing common problems such as attention-deficit/hyperactivity disorder, disordered sleep, temper tantrums, and school refusal in 30 days. Finding room in a training program to give behavioral and developmental problems more than a quick nod is going to require some rethinking of how we train pediatricians. It may be that training programs will need to selectively trim back some programs that may be of only limited long-term use to most general office-based pediatricians and offer them as electives. For example, how many of us still practice the kind of neonatology we were exposed to in the special care nursery? These are not easy decisions, but as Dr. Reid has suggested, we need to reconsider whether we are on the right track.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “Coping with a Picky Eater.” E-mail him at [email protected].

If you ask a primary care pediatrician who has been practicing for more than 2 decades, she will tell you that her practice has tilted steeply toward complaints with a more developmental and behavioral flavor. In the lead article of the April 2015 Pediatrics (“Are We on the Right Track? Examining the Role of Developmental Behavioral Pediatrics”) Dr. Ruth E.K. Stein, a recent recipient of the C. Anderson Aldrich Award given by the American Academy of Pediatrics section on children with developmental and behavioral pediatrics, questions whether we, both general pediatricians and specialists in developmental and behavioral pediatrics, are on the right path in addressing this shifting mix in our patient populations.

Dr. Stein observes that while she and other pioneers in the creation of her specialty began as general pediatricians, today physicians typically enter developmental and behavioral fellowship programs without the benefit of practicing the runny nose–earache–diaper rash kind of pediatrics that many of us enjoy. She worries that from this early branching point in training, developmental and behavioral specialists have become “sequestered and siloed – increasingly seen only as people who take care of children who have special needs.” The problem is that, as Dr. Stein wisely observes, developmental and behavioral issues “are the core constructs of pediatrics and its backbone and that they must be incorporated into every primary care and specialty encounter and included in every educational experience.”

Dr. Stein continues her essay by proposing a handful of strategies for bridging the gap between developmental and behavioral specialists and general pediatricians, and strengthening the training of house officers, which currently requires only a pitifully inadequate month devoted to developmental and behavioral issues. While it is hard to argue with Dr. Stein’s suggestions, they only nibble around the edges of the real problem.

If one really believes as she and I do, that behavior and development must be considered in every patient encounter and educational experience, then the solution lies in changing how we teach medicine from the very beginning instead of waiting until postgraduate education. Everyone mouths the importance of the mind-body connection, but it is often just so much hot air. The relationship between behavior and development, and what Dr. Stein refers to as “biomedical” conditions, exists in every patient. It is often said it is the fact that our patients are growing and developing that keeps pediatrics apart from the rest of medicine. But the same process of change over time occurs in adults as well; we call it aging instead of development. Understanding where our patients are positioned on this trajectory from birth to death is critical in helping us understand what is troubling them, and how best to help them manage their concerns.

For pediatricians, our preverbal patients’ behavior is often the only way we have of knowing there is a problem. Behavior can be their unspoken chief complaint. The failure by a physician to interpret her patient’s behavior as either a result or the cause of the problem can lead to an unfortunate outcome.

This means, as we teach aspiring doctors the art of medicine, we must make it clear that the patient’s behavior and stage of development must be considered equally with the more traditional biomedical etiologies, not as an afterthought. For example, any discussion of nonacute recurrent abdominal pain in children that fails to acknowledge from the outset that most of these patients will not have an abnormality detectable by lab work and imaging studies is doing the young physician and his patients a disservice. I am suggesting that we adopt a more patient-centered rather than a disease-centered approach to training all physicians.

While every patient must be viewed in the proper behavioral and developmental context, there are those in whom a behavior problem dominates. Given the patient mix that the new millennium pediatrician is going to face, 1 month in postgraduate training is clearly insufficient. One cannot begin to learn even the rudiments of managing common problems such as attention-deficit/hyperactivity disorder, disordered sleep, temper tantrums, and school refusal in 30 days. Finding room in a training program to give behavioral and developmental problems more than a quick nod is going to require some rethinking of how we train pediatricians. It may be that training programs will need to selectively trim back some programs that may be of only limited long-term use to most general office-based pediatricians and offer them as electives. For example, how many of us still practice the kind of neonatology we were exposed to in the special care nursery? These are not easy decisions, but as Dr. Reid has suggested, we need to reconsider whether we are on the right track.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “Coping with a Picky Eater.” E-mail him at [email protected].

If you ask a primary care pediatrician who has been practicing for more than 2 decades, she will tell you that her practice has tilted steeply toward complaints with a more developmental and behavioral flavor. In the lead article of the April 2015 Pediatrics (“Are We on the Right Track? Examining the Role of Developmental Behavioral Pediatrics”) Dr. Ruth E.K. Stein, a recent recipient of the C. Anderson Aldrich Award given by the American Academy of Pediatrics section on children with developmental and behavioral pediatrics, questions whether we, both general pediatricians and specialists in developmental and behavioral pediatrics, are on the right path in addressing this shifting mix in our patient populations.

Dr. Stein observes that while she and other pioneers in the creation of her specialty began as general pediatricians, today physicians typically enter developmental and behavioral fellowship programs without the benefit of practicing the runny nose–earache–diaper rash kind of pediatrics that many of us enjoy. She worries that from this early branching point in training, developmental and behavioral specialists have become “sequestered and siloed – increasingly seen only as people who take care of children who have special needs.” The problem is that, as Dr. Stein wisely observes, developmental and behavioral issues “are the core constructs of pediatrics and its backbone and that they must be incorporated into every primary care and specialty encounter and included in every educational experience.”

Dr. Stein continues her essay by proposing a handful of strategies for bridging the gap between developmental and behavioral specialists and general pediatricians, and strengthening the training of house officers, which currently requires only a pitifully inadequate month devoted to developmental and behavioral issues. While it is hard to argue with Dr. Stein’s suggestions, they only nibble around the edges of the real problem.

If one really believes as she and I do, that behavior and development must be considered in every patient encounter and educational experience, then the solution lies in changing how we teach medicine from the very beginning instead of waiting until postgraduate education. Everyone mouths the importance of the mind-body connection, but it is often just so much hot air. The relationship between behavior and development, and what Dr. Stein refers to as “biomedical” conditions, exists in every patient. It is often said it is the fact that our patients are growing and developing that keeps pediatrics apart from the rest of medicine. But the same process of change over time occurs in adults as well; we call it aging instead of development. Understanding where our patients are positioned on this trajectory from birth to death is critical in helping us understand what is troubling them, and how best to help them manage their concerns.

For pediatricians, our preverbal patients’ behavior is often the only way we have of knowing there is a problem. Behavior can be their unspoken chief complaint. The failure by a physician to interpret her patient’s behavior as either a result or the cause of the problem can lead to an unfortunate outcome.

This means, as we teach aspiring doctors the art of medicine, we must make it clear that the patient’s behavior and stage of development must be considered equally with the more traditional biomedical etiologies, not as an afterthought. For example, any discussion of nonacute recurrent abdominal pain in children that fails to acknowledge from the outset that most of these patients will not have an abnormality detectable by lab work and imaging studies is doing the young physician and his patients a disservice. I am suggesting that we adopt a more patient-centered rather than a disease-centered approach to training all physicians.

While every patient must be viewed in the proper behavioral and developmental context, there are those in whom a behavior problem dominates. Given the patient mix that the new millennium pediatrician is going to face, 1 month in postgraduate training is clearly insufficient. One cannot begin to learn even the rudiments of managing common problems such as attention-deficit/hyperactivity disorder, disordered sleep, temper tantrums, and school refusal in 30 days. Finding room in a training program to give behavioral and developmental problems more than a quick nod is going to require some rethinking of how we train pediatricians. It may be that training programs will need to selectively trim back some programs that may be of only limited long-term use to most general office-based pediatricians and offer them as electives. For example, how many of us still practice the kind of neonatology we were exposed to in the special care nursery? These are not easy decisions, but as Dr. Reid has suggested, we need to reconsider whether we are on the right track.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “Coping with a Picky Eater.” E-mail him at [email protected].

Well, in a remarkable moment in what is likely the most dysfunctional American government on record, all sides agreed to repeal the sustainable growth rate formula and change the way Medicare payments are done.

For the foreseeable future, this eliminates the annual game of chicken that political parties play at our expense.

For more than 10 years now, the cuts have come up, the medical journals decry them, doctors threaten to stop seeing Medicare patients, and eventually the politicians reach an agreement to stop the cuts that had grown to a high of 27.4% in 2012 ... until the next year. The classic game of political kick the can.

The dysfunctional waltz had been going on for so long that only the medical press and doctors seemed to care.

So, after years of wrapping duct tape around a leaking pipe, they called a plumber and replaced the pipe. The cost is far higher than it would have been if they’d actually addressed the problem when it started in 2003.

I’m sure the new law will have its own issues, but it stops – for now – the nightmare scenario where the cuts are allowed to go through. That would have left many of us in the difficult situation of turning away new Medicare patients. None of us wants to do that.

It’s nice to have seen the government function in the way it’s supposed to – with negotiations and compromise – rather than more threats, vitriolic posturing, and finger-pointing that have been the recent norm. Members of Congress, regrettably, don’t have their health care affected by their decisions. Regardless of age, the majority aren’t on Medicare. They’re all covered through the Federal Employees Health Benefits Program, which uses private plans. So it doesn’t directly affect them if a doctor’s office is shuttered or sick constituents can’t find someone to help them. They figure by the next election cycle they’ll be able to distract voters with some other topic.

I’m glad that reason and concern for the health care of ordinary citizens prevailed. It’s easy to play chicken when someone else’s life and livelihood are involved, and not yours. I hope this leads to greater cooperation and willingness to work together between the two sides in the future.

But I’m not optimistic.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Well, in a remarkable moment in what is likely the most dysfunctional American government on record, all sides agreed to repeal the sustainable growth rate formula and change the way Medicare payments are done.

For the foreseeable future, this eliminates the annual game of chicken that political parties play at our expense.

For more than 10 years now, the cuts have come up, the medical journals decry them, doctors threaten to stop seeing Medicare patients, and eventually the politicians reach an agreement to stop the cuts that had grown to a high of 27.4% in 2012 ... until the next year. The classic game of political kick the can.

The dysfunctional waltz had been going on for so long that only the medical press and doctors seemed to care.

So, after years of wrapping duct tape around a leaking pipe, they called a plumber and replaced the pipe. The cost is far higher than it would have been if they’d actually addressed the problem when it started in 2003.

I’m sure the new law will have its own issues, but it stops – for now – the nightmare scenario where the cuts are allowed to go through. That would have left many of us in the difficult situation of turning away new Medicare patients. None of us wants to do that.

It’s nice to have seen the government function in the way it’s supposed to – with negotiations and compromise – rather than more threats, vitriolic posturing, and finger-pointing that have been the recent norm. Members of Congress, regrettably, don’t have their health care affected by their decisions. Regardless of age, the majority aren’t on Medicare. They’re all covered through the Federal Employees Health Benefits Program, which uses private plans. So it doesn’t directly affect them if a doctor’s office is shuttered or sick constituents can’t find someone to help them. They figure by the next election cycle they’ll be able to distract voters with some other topic.

I’m glad that reason and concern for the health care of ordinary citizens prevailed. It’s easy to play chicken when someone else’s life and livelihood are involved, and not yours. I hope this leads to greater cooperation and willingness to work together between the two sides in the future.

But I’m not optimistic.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Well, in a remarkable moment in what is likely the most dysfunctional American government on record, all sides agreed to repeal the sustainable growth rate formula and change the way Medicare payments are done.

For the foreseeable future, this eliminates the annual game of chicken that political parties play at our expense.

For more than 10 years now, the cuts have come up, the medical journals decry them, doctors threaten to stop seeing Medicare patients, and eventually the politicians reach an agreement to stop the cuts that had grown to a high of 27.4% in 2012 ... until the next year. The classic game of political kick the can.

The dysfunctional waltz had been going on for so long that only the medical press and doctors seemed to care.

So, after years of wrapping duct tape around a leaking pipe, they called a plumber and replaced the pipe. The cost is far higher than it would have been if they’d actually addressed the problem when it started in 2003.

I’m sure the new law will have its own issues, but it stops – for now – the nightmare scenario where the cuts are allowed to go through. That would have left many of us in the difficult situation of turning away new Medicare patients. None of us wants to do that.

It’s nice to have seen the government function in the way it’s supposed to – with negotiations and compromise – rather than more threats, vitriolic posturing, and finger-pointing that have been the recent norm. Members of Congress, regrettably, don’t have their health care affected by their decisions. Regardless of age, the majority aren’t on Medicare. They’re all covered through the Federal Employees Health Benefits Program, which uses private plans. So it doesn’t directly affect them if a doctor’s office is shuttered or sick constituents can’t find someone to help them. They figure by the next election cycle they’ll be able to distract voters with some other topic.

I’m glad that reason and concern for the health care of ordinary citizens prevailed. It’s easy to play chicken when someone else’s life and livelihood are involved, and not yours. I hope this leads to greater cooperation and willingness to work together between the two sides in the future.

But I’m not optimistic.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

“Bath salts” is a dangerous illicit drug that teens may be using. It hit the U.S. scene in 2010 after being a big hit in Europe. It’s called “bath salts” because it resembled Epsom salt, but shares no chemical properties with it.

Because it was called bath salts, it initially evaded the Food and Drug Administration, and was sold at gas stations and clubs marked “not for human consumption,” which earned it its name as the “legal high.” Bath salts are creatively packaged in containers that are colorful and attractive, and have aliases such as “plant food,” “Ivory Wave,” “Purple Wave,” “Bloom,” “Cloud Nine,” or “Vanilla Sky,” according to the National Institute on Drug Abuse.

Shortly after the drug’s debut, emergency departments were seeing several hundreds of people with amphetamine-like intoxication and “naked rages.” In 2012, when it became known that these substances were being use as illicit drugs, they were made illegal, but the problem now is there are many derivatives of this drug and their use is becoming more widespread.

Mephedrone is one of the possible active ingredients, and it is derived from the synthetic cathinone, similar to cathinone found naturally in the khat plant (Catha edulis). It stimulates the adrenergic receptors to release dopamine and norepinephrine, and block their reuptake, which makes them act like a stimulant on the nervous system. The result is agitation, hyperalertness, hypertension, tachycardia, diaphoresis, and elevated temperatures to 106<scaps>˚ </scaps>F. The term “naked rage” came into use because users would become overheated and angry, and would rip off their clothes as they raged.

Other synthetic canthinones being used as drugs of abuse include butylone, dimethylcathinone, ethcathinone, ethylone, 3- and 4-fluoromethcathinone, mephedrone, methedrone, methylenedioxypyrovalerone (MDPV), methylone, and pyrovalerone (J. Med. Toxicol. 2012;8:33-42).

MDPV raises dopamine levels in the brain as does cocaine, but is at least 10 times as potent, according to the National Institute on Drug Abuse.

Bath salts can be administered by snorting, ingesting, smoking, or injecting. Necrotizing fasciitis has been associated with its use. Most patients present with elevated temperatures, hypertension, palpitations, and delirium. Hydration and sedation are usually required, and patients usually need to be restrained to prevent them from hurting themselves further. Psychiatric symptoms may include paranoia, hallucinations, and panic attacks. Several deaths have been reported in association with its use.

In the time since this drug was made illegal, several other designer drugs have presented, which are just modifications of the mephedrone. “Flakka” and “jewelry cleaner” are examples of the modified synthetic cathinone. They all cause amphetamine-like reactions and the risk of overdose is great.

The cost to manufacture the drug is about $8 per unit, but its retail price is $20-$40. Though it takes only 3-5 mg to be effective, packages are sold with 500 mg, making the risk for overdose even greater. It usually takes about 1.5 hours to reach peak rush and the entire experience can last 6-8 hours. There is little difference between the euphoric level and intoxication level, which is what makes the drug so dangerous.

Synthetic drugs are a great danger to all age groups, including toddlers, because of the misleading packaging. But they are especially dangerous because the ingredients vary, and overdose occurs quickly.

It is imperative that parents and teens are made aware of the dangers associated with these drugs and their street names; www.streetdrugs.org is a website designed to educate teachers, parents and students about these drugs and their dangers.

Dr. Pearce is a pediatrician in Frankfort, Ill. E-mail her at [email protected].

“Bath salts” is a dangerous illicit drug that teens may be using. It hit the U.S. scene in 2010 after being a big hit in Europe. It’s called “bath salts” because it resembled Epsom salt, but shares no chemical properties with it.

Because it was called bath salts, it initially evaded the Food and Drug Administration, and was sold at gas stations and clubs marked “not for human consumption,” which earned it its name as the “legal high.” Bath salts are creatively packaged in containers that are colorful and attractive, and have aliases such as “plant food,” “Ivory Wave,” “Purple Wave,” “Bloom,” “Cloud Nine,” or “Vanilla Sky,” according to the National Institute on Drug Abuse.

Shortly after the drug’s debut, emergency departments were seeing several hundreds of people with amphetamine-like intoxication and “naked rages.” In 2012, when it became known that these substances were being use as illicit drugs, they were made illegal, but the problem now is there are many derivatives of this drug and their use is becoming more widespread.

Mephedrone is one of the possible active ingredients, and it is derived from the synthetic cathinone, similar to cathinone found naturally in the khat plant (Catha edulis). It stimulates the adrenergic receptors to release dopamine and norepinephrine, and block their reuptake, which makes them act like a stimulant on the nervous system. The result is agitation, hyperalertness, hypertension, tachycardia, diaphoresis, and elevated temperatures to 106<scaps>˚ </scaps>F. The term “naked rage” came into use because users would become overheated and angry, and would rip off their clothes as they raged.

Other synthetic canthinones being used as drugs of abuse include butylone, dimethylcathinone, ethcathinone, ethylone, 3- and 4-fluoromethcathinone, mephedrone, methedrone, methylenedioxypyrovalerone (MDPV), methylone, and pyrovalerone (J. Med. Toxicol. 2012;8:33-42).

MDPV raises dopamine levels in the brain as does cocaine, but is at least 10 times as potent, according to the National Institute on Drug Abuse.

Bath salts can be administered by snorting, ingesting, smoking, or injecting. Necrotizing fasciitis has been associated with its use. Most patients present with elevated temperatures, hypertension, palpitations, and delirium. Hydration and sedation are usually required, and patients usually need to be restrained to prevent them from hurting themselves further. Psychiatric symptoms may include paranoia, hallucinations, and panic attacks. Several deaths have been reported in association with its use.

In the time since this drug was made illegal, several other designer drugs have presented, which are just modifications of the mephedrone. “Flakka” and “jewelry cleaner” are examples of the modified synthetic cathinone. They all cause amphetamine-like reactions and the risk of overdose is great.

The cost to manufacture the drug is about $8 per unit, but its retail price is $20-$40. Though it takes only 3-5 mg to be effective, packages are sold with 500 mg, making the risk for overdose even greater. It usually takes about 1.5 hours to reach peak rush and the entire experience can last 6-8 hours. There is little difference between the euphoric level and intoxication level, which is what makes the drug so dangerous.

Synthetic drugs are a great danger to all age groups, including toddlers, because of the misleading packaging. But they are especially dangerous because the ingredients vary, and overdose occurs quickly.

It is imperative that parents and teens are made aware of the dangers associated with these drugs and their street names; www.streetdrugs.org is a website designed to educate teachers, parents and students about these drugs and their dangers.

Dr. Pearce is a pediatrician in Frankfort, Ill. E-mail her at [email protected].

“Bath salts” is a dangerous illicit drug that teens may be using. It hit the U.S. scene in 2010 after being a big hit in Europe. It’s called “bath salts” because it resembled Epsom salt, but shares no chemical properties with it.

Because it was called bath salts, it initially evaded the Food and Drug Administration, and was sold at gas stations and clubs marked “not for human consumption,” which earned it its name as the “legal high.” Bath salts are creatively packaged in containers that are colorful and attractive, and have aliases such as “plant food,” “Ivory Wave,” “Purple Wave,” “Bloom,” “Cloud Nine,” or “Vanilla Sky,” according to the National Institute on Drug Abuse.

Shortly after the drug’s debut, emergency departments were seeing several hundreds of people with amphetamine-like intoxication and “naked rages.” In 2012, when it became known that these substances were being use as illicit drugs, they were made illegal, but the problem now is there are many derivatives of this drug and their use is becoming more widespread.

Mephedrone is one of the possible active ingredients, and it is derived from the synthetic cathinone, similar to cathinone found naturally in the khat plant (Catha edulis). It stimulates the adrenergic receptors to release dopamine and norepinephrine, and block their reuptake, which makes them act like a stimulant on the nervous system. The result is agitation, hyperalertness, hypertension, tachycardia, diaphoresis, and elevated temperatures to 106<scaps>˚ </scaps>F. The term “naked rage” came into use because users would become overheated and angry, and would rip off their clothes as they raged.

Other synthetic canthinones being used as drugs of abuse include butylone, dimethylcathinone, ethcathinone, ethylone, 3- and 4-fluoromethcathinone, mephedrone, methedrone, methylenedioxypyrovalerone (MDPV), methylone, and pyrovalerone (J. Med. Toxicol. 2012;8:33-42).

MDPV raises dopamine levels in the brain as does cocaine, but is at least 10 times as potent, according to the National Institute on Drug Abuse.

Bath salts can be administered by snorting, ingesting, smoking, or injecting. Necrotizing fasciitis has been associated with its use. Most patients present with elevated temperatures, hypertension, palpitations, and delirium. Hydration and sedation are usually required, and patients usually need to be restrained to prevent them from hurting themselves further. Psychiatric symptoms may include paranoia, hallucinations, and panic attacks. Several deaths have been reported in association with its use.

In the time since this drug was made illegal, several other designer drugs have presented, which are just modifications of the mephedrone. “Flakka” and “jewelry cleaner” are examples of the modified synthetic cathinone. They all cause amphetamine-like reactions and the risk of overdose is great.

The cost to manufacture the drug is about $8 per unit, but its retail price is $20-$40. Though it takes only 3-5 mg to be effective, packages are sold with 500 mg, making the risk for overdose even greater. It usually takes about 1.5 hours to reach peak rush and the entire experience can last 6-8 hours. There is little difference between the euphoric level and intoxication level, which is what makes the drug so dangerous.

Synthetic drugs are a great danger to all age groups, including toddlers, because of the misleading packaging. But they are especially dangerous because the ingredients vary, and overdose occurs quickly.

It is imperative that parents and teens are made aware of the dangers associated with these drugs and their street names; www.streetdrugs.org is a website designed to educate teachers, parents and students about these drugs and their dangers.

Dr. Pearce is a pediatrician in Frankfort, Ill. E-mail her at [email protected].

The 8-year-old child presented to the emergency department with bilateral ankle pain that had progressively worsened over the past 24 hours. This morning he would not walk. He also had a rash on his legs. The astute ED doctor recognized the diagnosis as Henoch-Schönlein purpura (HSP) and arranged admission to the ward. Things were flowing smoothly that day, and the child was soon on the ward and being examined by me and the resident team during morning rounds. In that 45-minute gap, the father had been on his smartphone. At that point he knew more about HSP than my senior resident. Truth be told, I was glad I had treated two cases in the previous 3 months (after going more than 2 years without any cases) so I didn’t feel foolish myself.

Technology is making progressively larger amounts of medical information available to the lay public. That information is being organized in ways that can actually impart knowledge. The Wikipedia entry on HSP has far more information, and has it arranged in a much more useful fashion, than my textbook on pediatrics. Making that comparison was the first time in 5 years that the textbook has even been taken off the shelf. If you have Googled tonsillitis, sprained ankle, or measles in the past 2 months, instead of just a list of websites, you also would have seen half the page filled with images and vetted information about those illnesses. There are apps that help you create a differential diagnosis and even estimate the probabilities of each one.

The victory of Watson, IBM's supercomputer, on Jeopardy showed how information can be organized and retrieved by a computer. It is a good facsimile for knowledge. But what about the wisdom of clinical judgment? Can a computer replace that? Keith Rabois, a member of the PayPal mafia, recently predicted that it will.

Further progress toward replacing doctors has come through changes in legislation to permit all lab tests to be offered directly to consumers. Arizona’s governor signed a law in April 2015 that will change that policy for his state. This isn’t major news, because already more than half the states allow this direct to consumer approach. But what was special about this particular signing ceremony was the involvement of billionaire Elizabeth Holmes, CEO of Theranos, a start-up company prepared to provide the lab testing service.

If done without a doctor’s order, which documents medical necessity, under current practice rules an insurance company won’t pay for these direct to consumer tests. The consumer must pay out of pocket. Of course, those rules may change. If patients want a throat swab to test for strep, maybe it is cheaper to have them go directly to the neighborhood lab than to see a doctor, especially if, when the test is positive, they then expect to phone their doctor for free and get a prescription.

Most medical tests have significant false-positive and false-negative results. Simple rapid strep throat tests and rapid influenza nasal swabs have a sensitivity of only 90%-95%. Many doctors, even those who use the results on a daily basis, cannot convert that information into a positive and negative predictive value. So if a company offers the test directly to the consumer, and reports it out with a “Just the facts, Ma’am” positive or negative result, is the consumer responsible for any misinterpretation, or has the laboratory company deceptively marketed a defective, imperfect product?

The bigger financial impact will be all the follow-up labs and imaging tests generated by the initial false-positive screening labs. Insurance probably will pay for those. Using a similar business model, a few hospitals nationwide now offer free (or close to it) low-dose chest CT scans to smokers and ex-smokers. This is done as a loss leader that generates profits for the hospital from all the follow-up tests, imaging, and biopsies. Compare this model with the old-time practice in which pediatricians in the 1950s to 1980s (and in many places, against guidelines, in the 1990s) had parents bring in a sample of the child’s urine for each well-child visit. That practice was abandoned on cost-benefit-harm arguments because of all the unnecessary subsequent testing, especially kidney ultrasounds, generated by the false positives. Now parents will be able to order the test themselves.

I’m skeptical about how soon a computer will completely replace a physician. Peter Thiel said, “We were promised flying cars and instead what we got was 140 characters.” But Google has finally created the self-driving car. And Elizabeth Holmes has averaged making more money in a week than I will in a career. So who are you going to believe?

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. E-mail him at [email protected].

The 8-year-old child presented to the emergency department with bilateral ankle pain that had progressively worsened over the past 24 hours. This morning he would not walk. He also had a rash on his legs. The astute ED doctor recognized the diagnosis as Henoch-Schönlein purpura (HSP) and arranged admission to the ward. Things were flowing smoothly that day, and the child was soon on the ward and being examined by me and the resident team during morning rounds. In that 45-minute gap, the father had been on his smartphone. At that point he knew more about HSP than my senior resident. Truth be told, I was glad I had treated two cases in the previous 3 months (after going more than 2 years without any cases) so I didn’t feel foolish myself.

Technology is making progressively larger amounts of medical information available to the lay public. That information is being organized in ways that can actually impart knowledge. The Wikipedia entry on HSP has far more information, and has it arranged in a much more useful fashion, than my textbook on pediatrics. Making that comparison was the first time in 5 years that the textbook has even been taken off the shelf. If you have Googled tonsillitis, sprained ankle, or measles in the past 2 months, instead of just a list of websites, you also would have seen half the page filled with images and vetted information about those illnesses. There are apps that help you create a differential diagnosis and even estimate the probabilities of each one.

The victory of Watson, IBM's supercomputer, on Jeopardy showed how information can be organized and retrieved by a computer. It is a good facsimile for knowledge. But what about the wisdom of clinical judgment? Can a computer replace that? Keith Rabois, a member of the PayPal mafia, recently predicted that it will.

Further progress toward replacing doctors has come through changes in legislation to permit all lab tests to be offered directly to consumers. Arizona’s governor signed a law in April 2015 that will change that policy for his state. This isn’t major news, because already more than half the states allow this direct to consumer approach. But what was special about this particular signing ceremony was the involvement of billionaire Elizabeth Holmes, CEO of Theranos, a start-up company prepared to provide the lab testing service.

If done without a doctor’s order, which documents medical necessity, under current practice rules an insurance company won’t pay for these direct to consumer tests. The consumer must pay out of pocket. Of course, those rules may change. If patients want a throat swab to test for strep, maybe it is cheaper to have them go directly to the neighborhood lab than to see a doctor, especially if, when the test is positive, they then expect to phone their doctor for free and get a prescription.

Most medical tests have significant false-positive and false-negative results. Simple rapid strep throat tests and rapid influenza nasal swabs have a sensitivity of only 90%-95%. Many doctors, even those who use the results on a daily basis, cannot convert that information into a positive and negative predictive value. So if a company offers the test directly to the consumer, and reports it out with a “Just the facts, Ma’am” positive or negative result, is the consumer responsible for any misinterpretation, or has the laboratory company deceptively marketed a defective, imperfect product?

The bigger financial impact will be all the follow-up labs and imaging tests generated by the initial false-positive screening labs. Insurance probably will pay for those. Using a similar business model, a few hospitals nationwide now offer free (or close to it) low-dose chest CT scans to smokers and ex-smokers. This is done as a loss leader that generates profits for the hospital from all the follow-up tests, imaging, and biopsies. Compare this model with the old-time practice in which pediatricians in the 1950s to 1980s (and in many places, against guidelines, in the 1990s) had parents bring in a sample of the child’s urine for each well-child visit. That practice was abandoned on cost-benefit-harm arguments because of all the unnecessary subsequent testing, especially kidney ultrasounds, generated by the false positives. Now parents will be able to order the test themselves.

I’m skeptical about how soon a computer will completely replace a physician. Peter Thiel said, “We were promised flying cars and instead what we got was 140 characters.” But Google has finally created the self-driving car. And Elizabeth Holmes has averaged making more money in a week than I will in a career. So who are you going to believe?

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. E-mail him at [email protected].

The 8-year-old child presented to the emergency department with bilateral ankle pain that had progressively worsened over the past 24 hours. This morning he would not walk. He also had a rash on his legs. The astute ED doctor recognized the diagnosis as Henoch-Schönlein purpura (HSP) and arranged admission to the ward. Things were flowing smoothly that day, and the child was soon on the ward and being examined by me and the resident team during morning rounds. In that 45-minute gap, the father had been on his smartphone. At that point he knew more about HSP than my senior resident. Truth be told, I was glad I had treated two cases in the previous 3 months (after going more than 2 years without any cases) so I didn’t feel foolish myself.

Technology is making progressively larger amounts of medical information available to the lay public. That information is being organized in ways that can actually impart knowledge. The Wikipedia entry on HSP has far more information, and has it arranged in a much more useful fashion, than my textbook on pediatrics. Making that comparison was the first time in 5 years that the textbook has even been taken off the shelf. If you have Googled tonsillitis, sprained ankle, or measles in the past 2 months, instead of just a list of websites, you also would have seen half the page filled with images and vetted information about those illnesses. There are apps that help you create a differential diagnosis and even estimate the probabilities of each one.

The victory of Watson, IBM's supercomputer, on Jeopardy showed how information can be organized and retrieved by a computer. It is a good facsimile for knowledge. But what about the wisdom of clinical judgment? Can a computer replace that? Keith Rabois, a member of the PayPal mafia, recently predicted that it will.

Further progress toward replacing doctors has come through changes in legislation to permit all lab tests to be offered directly to consumers. Arizona’s governor signed a law in April 2015 that will change that policy for his state. This isn’t major news, because already more than half the states allow this direct to consumer approach. But what was special about this particular signing ceremony was the involvement of billionaire Elizabeth Holmes, CEO of Theranos, a start-up company prepared to provide the lab testing service.

If done without a doctor’s order, which documents medical necessity, under current practice rules an insurance company won’t pay for these direct to consumer tests. The consumer must pay out of pocket. Of course, those rules may change. If patients want a throat swab to test for strep, maybe it is cheaper to have them go directly to the neighborhood lab than to see a doctor, especially if, when the test is positive, they then expect to phone their doctor for free and get a prescription.

Most medical tests have significant false-positive and false-negative results. Simple rapid strep throat tests and rapid influenza nasal swabs have a sensitivity of only 90%-95%. Many doctors, even those who use the results on a daily basis, cannot convert that information into a positive and negative predictive value. So if a company offers the test directly to the consumer, and reports it out with a “Just the facts, Ma’am” positive or negative result, is the consumer responsible for any misinterpretation, or has the laboratory company deceptively marketed a defective, imperfect product?

The bigger financial impact will be all the follow-up labs and imaging tests generated by the initial false-positive screening labs. Insurance probably will pay for those. Using a similar business model, a few hospitals nationwide now offer free (or close to it) low-dose chest CT scans to smokers and ex-smokers. This is done as a loss leader that generates profits for the hospital from all the follow-up tests, imaging, and biopsies. Compare this model with the old-time practice in which pediatricians in the 1950s to 1980s (and in many places, against guidelines, in the 1990s) had parents bring in a sample of the child’s urine for each well-child visit. That practice was abandoned on cost-benefit-harm arguments because of all the unnecessary subsequent testing, especially kidney ultrasounds, generated by the false positives. Now parents will be able to order the test themselves.

I’m skeptical about how soon a computer will completely replace a physician. Peter Thiel said, “We were promised flying cars and instead what we got was 140 characters.” But Google has finally created the self-driving car. And Elizabeth Holmes has averaged making more money in a week than I will in a career. So who are you going to believe?

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. E-mail him at [email protected].

The discipline of orthopedic medicine and surgery has dramatically advanced over the last several decades. Improved understanding of biomechanics, tissue healing, and the pathogenesis of musculoskeletal diseases has allowed us to make significant progress in the diagnosis, treatment, and rehabilitation of our patients. Despite these advancements, there is still much to be learned, especially in the field of orthobiologics and regenerative medicine. As our understanding of existing technologies, such as bone marrow aspirate, platelet-rich plasma, and adult stem cells, continues to evolve, even newer biologic treatment options are being developed. This issue of The American Journal of Orthopedics focuses on emerging biologics across the spectrum of orthopedic care.

In this issue, on pages 202-205, Mansour and Conway describe a new prone retrograde technique for obtaining bone graft using the Reamer/Irrigator/Aspirator (RIA) system (Synthes, West Chester, Pennsylvania). While iliac crest bone graft has been the gold standard for many years, use of the RIA system to obtain bone graft has been studied and has been shown to have decreased morbidity when compared with iliac crest harvest.¹ Additionally, intramedullary bone graft from the femur appears to be just as concentrated with biologically active bone marrow as iliac crest harvest.² This new technique allows increased efficiency, especially for surgeries that are done in the prone position.

Melamed and colleagues examine a new biologic to augment repair of rotator cuff tears (see pages 212-216). Chitosan, a linear polysaccharide, has been shown to help with soft-tissue healing. Although in the past its use has been limited secondary to problems with the compound precipitating at physiologic pH, new formulations mitigate that problem. In the authors’ animal model of acute supraspinatus repair, the use of chitosan gel increased the number of fibroblasts and the amount of repair tissue when compared with untreated controls. Additionally, the experimental group showed a decreased inflammatory response when compared with the control group. This is very exciting research as the biologic enhancement of rotator cuff tendon healing could potentially help decrease the rate of rotator cuff repair failure.

Lenehan and colleagues analyze the long-term outcomes of anterior cruciate ligament reconstruction in a cohort of patients studied over an 8-year period (see pages 217-222). During this period, 99 patients were reconstructed with allograft tissue and 24 with autograft. Their analysis, like other recently published work, shows that the rates of revision were much higher for patients under 25 years of age who were reconstructed using allograft tissue. The rate of revision for NCAA (National Collegiate Athletic Association) Division I athletes reconstructed with allograft tissue was found to be 62%, while the revision rate for all patients under the age of 25 years who received an allograft was found to be 20.5%. Clearly, there is still a great deal to learn about the biology of graft incorporation and healing, especially as it relates to allograft tissue.

These 3 articles exemplify the breadth of orthopedic biologics and their potential role in orthopedic surgery. Through efforts of investigators highlighted in this journal and in others, biologics will become better understood and more widely used when appropriate, leading to improved patient outcomes.

The discipline of orthopedic medicine and surgery has dramatically advanced over the last several decades. Improved understanding of biomechanics, tissue healing, and the pathogenesis of musculoskeletal diseases has allowed us to make significant progress in the diagnosis, treatment, and rehabilitation of our patients. Despite these advancements, there is still much to be learned, especially in the field of orthobiologics and regenerative medicine. As our understanding of existing technologies, such as bone marrow aspirate, platelet-rich plasma, and adult stem cells, continues to evolve, even newer biologic treatment options are being developed. This issue of The American Journal of Orthopedics focuses on emerging biologics across the spectrum of orthopedic care.

In this issue, on pages 202-205, Mansour and Conway describe a new prone retrograde technique for obtaining bone graft using the Reamer/Irrigator/Aspirator (RIA) system (Synthes, West Chester, Pennsylvania). While iliac crest bone graft has been the gold standard for many years, use of the RIA system to obtain bone graft has been studied and has been shown to have decreased morbidity when compared with iliac crest harvest.¹ Additionally, intramedullary bone graft from the femur appears to be just as concentrated with biologically active bone marrow as iliac crest harvest.² This new technique allows increased efficiency, especially for surgeries that are done in the prone position.

Melamed and colleagues examine a new biologic to augment repair of rotator cuff tears (see pages 212-216). Chitosan, a linear polysaccharide, has been shown to help with soft-tissue healing. Although in the past its use has been limited secondary to problems with the compound precipitating at physiologic pH, new formulations mitigate that problem. In the authors’ animal model of acute supraspinatus repair, the use of chitosan gel increased the number of fibroblasts and the amount of repair tissue when compared with untreated controls. Additionally, the experimental group showed a decreased inflammatory response when compared with the control group. This is very exciting research as the biologic enhancement of rotator cuff tendon healing could potentially help decrease the rate of rotator cuff repair failure.

Lenehan and colleagues analyze the long-term outcomes of anterior cruciate ligament reconstruction in a cohort of patients studied over an 8-year period (see pages 217-222). During this period, 99 patients were reconstructed with allograft tissue and 24 with autograft. Their analysis, like other recently published work, shows that the rates of revision were much higher for patients under 25 years of age who were reconstructed using allograft tissue. The rate of revision for NCAA (National Collegiate Athletic Association) Division I athletes reconstructed with allograft tissue was found to be 62%, while the revision rate for all patients under the age of 25 years who received an allograft was found to be 20.5%. Clearly, there is still a great deal to learn about the biology of graft incorporation and healing, especially as it relates to allograft tissue.

These 3 articles exemplify the breadth of orthopedic biologics and their potential role in orthopedic surgery. Through efforts of investigators highlighted in this journal and in others, biologics will become better understood and more widely used when appropriate, leading to improved patient outcomes.

The discipline of orthopedic medicine and surgery has dramatically advanced over the last several decades. Improved understanding of biomechanics, tissue healing, and the pathogenesis of musculoskeletal diseases has allowed us to make significant progress in the diagnosis, treatment, and rehabilitation of our patients. Despite these advancements, there is still much to be learned, especially in the field of orthobiologics and regenerative medicine. As our understanding of existing technologies, such as bone marrow aspirate, platelet-rich plasma, and adult stem cells, continues to evolve, even newer biologic treatment options are being developed. This issue of The American Journal of Orthopedics focuses on emerging biologics across the spectrum of orthopedic care.

In this issue, on pages 202-205, Mansour and Conway describe a new prone retrograde technique for obtaining bone graft using the Reamer/Irrigator/Aspirator (RIA) system (Synthes, West Chester, Pennsylvania). While iliac crest bone graft has been the gold standard for many years, use of the RIA system to obtain bone graft has been studied and has been shown to have decreased morbidity when compared with iliac crest harvest.¹ Additionally, intramedullary bone graft from the femur appears to be just as concentrated with biologically active bone marrow as iliac crest harvest.² This new technique allows increased efficiency, especially for surgeries that are done in the prone position.

Melamed and colleagues examine a new biologic to augment repair of rotator cuff tears (see pages 212-216). Chitosan, a linear polysaccharide, has been shown to help with soft-tissue healing. Although in the past its use has been limited secondary to problems with the compound precipitating at physiologic pH, new formulations mitigate that problem. In the authors’ animal model of acute supraspinatus repair, the use of chitosan gel increased the number of fibroblasts and the amount of repair tissue when compared with untreated controls. Additionally, the experimental group showed a decreased inflammatory response when compared with the control group. This is very exciting research as the biologic enhancement of rotator cuff tendon healing could potentially help decrease the rate of rotator cuff repair failure.

Lenehan and colleagues analyze the long-term outcomes of anterior cruciate ligament reconstruction in a cohort of patients studied over an 8-year period (see pages 217-222). During this period, 99 patients were reconstructed with allograft tissue and 24 with autograft. Their analysis, like other recently published work, shows that the rates of revision were much higher for patients under 25 years of age who were reconstructed using allograft tissue. The rate of revision for NCAA (National Collegiate Athletic Association) Division I athletes reconstructed with allograft tissue was found to be 62%, while the revision rate for all patients under the age of 25 years who received an allograft was found to be 20.5%. Clearly, there is still a great deal to learn about the biology of graft incorporation and healing, especially as it relates to allograft tissue.

These 3 articles exemplify the breadth of orthopedic biologics and their potential role in orthopedic surgery. Through efforts of investigators highlighted in this journal and in others, biologics will become better understood and more widely used when appropriate, leading to improved patient outcomes.

At the risk of stating the obvious, our patients are becoming increasingly complex. Life is prolonged and comorbidities accumulate, creating dizzying laundry lists of medical problems.

Within the context of clinical or, increasingly, nonreimbursed telephonic or electronic visits, we attack the medical problem with the worst severity in an attempt to tamp it down to the level of its comorbid brethren.

Almost without exception, depression rears its ugly head in our sickest patients. Antidepressants will be started and added to the three pages (double-spaced, with 1-inch margins) of medications.

But in all of these patients, are we treating the disease or just the symptom? What if inflammation is causing the depression? Will reduction of inflammation treat the depression?

Dr. Ole Köhler of Aarhus University Hospital, Denmark, and his colleagues conducted a systematic review on the antidepressant effects of anti-inflammatory medications (JAMA Psychiatry 2014;71:1381-91). Fourteen trials informed the meta-analysis, 10 that evaluated NSAID drugs (for example, celecoxib, naproxen, ibuprofen), and 4 that investigated cytokine inhibitors (for example, etanercept, infliximab). Six of the 10 NSAID studies evaluated NSAIDs as monotherapy. All four of the cytokine-inhibitor trials evaluated them as monotherapy. Length of treatment was between 6 and 12 weeks.

The pooled effect suggests that anti-inflammatory treatment reduced depressive symptoms. Celecoxib seemed to have the strongest effect on remission and clinical response. No increase in adverse events was reported.

We know that proinflammatory drugs can induce depression. So the opposite is quite possibly true, and these data suggest it to be so. Findings suggest that reducing the inflammatory state among our patients with depression may be a useful adjunct to antidepressant therapy, at least in the initial period.

Whatever we can do to facilitate depressive symptom relief seems a worthy goal. So, here again, we could tell our patients presenting with depression to take two (with an SSRI, perhaps) and call us in the morning. But how best to do this and in what patients remains uncertain.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition, nor should they be used as a substitute for medical advice from a qualified, board-certified, practicing clinician.

At the risk of stating the obvious, our patients are becoming increasingly complex. Life is prolonged and comorbidities accumulate, creating dizzying laundry lists of medical problems.

Within the context of clinical or, increasingly, nonreimbursed telephonic or electronic visits, we attack the medical problem with the worst severity in an attempt to tamp it down to the level of its comorbid brethren.

Almost without exception, depression rears its ugly head in our sickest patients. Antidepressants will be started and added to the three pages (double-spaced, with 1-inch margins) of medications.

But in all of these patients, are we treating the disease or just the symptom? What if inflammation is causing the depression? Will reduction of inflammation treat the depression?

Dr. Ole Köhler of Aarhus University Hospital, Denmark, and his colleagues conducted a systematic review on the antidepressant effects of anti-inflammatory medications (JAMA Psychiatry 2014;71:1381-91). Fourteen trials informed the meta-analysis, 10 that evaluated NSAID drugs (for example, celecoxib, naproxen, ibuprofen), and 4 that investigated cytokine inhibitors (for example, etanercept, infliximab). Six of the 10 NSAID studies evaluated NSAIDs as monotherapy. All four of the cytokine-inhibitor trials evaluated them as monotherapy. Length of treatment was between 6 and 12 weeks.

The pooled effect suggests that anti-inflammatory treatment reduced depressive symptoms. Celecoxib seemed to have the strongest effect on remission and clinical response. No increase in adverse events was reported.

We know that proinflammatory drugs can induce depression. So the opposite is quite possibly true, and these data suggest it to be so. Findings suggest that reducing the inflammatory state among our patients with depression may be a useful adjunct to antidepressant therapy, at least in the initial period.

Whatever we can do to facilitate depressive symptom relief seems a worthy goal. So, here again, we could tell our patients presenting with depression to take two (with an SSRI, perhaps) and call us in the morning. But how best to do this and in what patients remains uncertain.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition, nor should they be used as a substitute for medical advice from a qualified, board-certified, practicing clinician.

At the risk of stating the obvious, our patients are becoming increasingly complex. Life is prolonged and comorbidities accumulate, creating dizzying laundry lists of medical problems.

Within the context of clinical or, increasingly, nonreimbursed telephonic or electronic visits, we attack the medical problem with the worst severity in an attempt to tamp it down to the level of its comorbid brethren.

Almost without exception, depression rears its ugly head in our sickest patients. Antidepressants will be started and added to the three pages (double-spaced, with 1-inch margins) of medications.

But in all of these patients, are we treating the disease or just the symptom? What if inflammation is causing the depression? Will reduction of inflammation treat the depression?

Dr. Ole Köhler of Aarhus University Hospital, Denmark, and his colleagues conducted a systematic review on the antidepressant effects of anti-inflammatory medications (JAMA Psychiatry 2014;71:1381-91). Fourteen trials informed the meta-analysis, 10 that evaluated NSAID drugs (for example, celecoxib, naproxen, ibuprofen), and 4 that investigated cytokine inhibitors (for example, etanercept, infliximab). Six of the 10 NSAID studies evaluated NSAIDs as monotherapy. All four of the cytokine-inhibitor trials evaluated them as monotherapy. Length of treatment was between 6 and 12 weeks.

The pooled effect suggests that anti-inflammatory treatment reduced depressive symptoms. Celecoxib seemed to have the strongest effect on remission and clinical response. No increase in adverse events was reported.

We know that proinflammatory drugs can induce depression. So the opposite is quite possibly true, and these data suggest it to be so. Findings suggest that reducing the inflammatory state among our patients with depression may be a useful adjunct to antidepressant therapy, at least in the initial period.

Whatever we can do to facilitate depressive symptom relief seems a worthy goal. So, here again, we could tell our patients presenting with depression to take two (with an SSRI, perhaps) and call us in the morning. But how best to do this and in what patients remains uncertain.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition, nor should they be used as a substitute for medical advice from a qualified, board-certified, practicing clinician.