In 2013, enough controlled substances were prescribed in Louisiana – 2006.2 prescriptions per 1,000 population – that each and every person in the state could have received two, according to a report from the Centers for Disease Control and Prevention.

The combined prescribing rate for opioids, benzodiazepines, and stimulants in Louisiana topped the eight states included in the CDC report, with West Virginia in second at 1,695.7 prescriptions per 1,000. At the low end, California was the only one of the eight states where the average controlled substance prescription rate was less than one per person, but just barely at 994.8 per 1,000 people, followed by Idaho at 1,292.3 per 1,000, according to the CDC investigators in a Morbidity and Mortality Weekly Report Surveillance Summary (2015 Oct;64[SS09]:1-14).

Of the three categories of controlled substances, opioids were by far the most commonly prescribed. At 1,021.7 prescriptions per 1,000 people, the opioid prescription rate in Louisiana was greater than the total controlled substance prescription rate in California. West Virginia had the second highest rate at 929.3, and California had the lowest at 596.3.

Prescription rates for stimulants and benzodiazepines were highest in Louisiana at 403.9 and 580.6 per 1,000 people, respectively. Maine had the next-highest stimulant prescription rate at 293.9, and West Virginia had the second-highest benzodiazepine prescription rate at 572.1. California had the lowest rate in both categories at 87.7 and 310.8, respectively.

Women received opioids and benzodiazepines at much higher rates than did men in every state, but stimulant-prescribing rates were higher for men in five states.

Opioid use was highest in people aged 55-64 years, though use spiked dramatically past the age of 25. People in Louisiana aged 55-64 receiving opioids had the highest controlled substance prescription rate of any measured age group, at 1,715.7 per 1,000 people. Benzodiazepine use was most common in people over 65 years, and stimulant prescriptions were highest in people younger than 18, likely because of the prevalence of childhood attention-deficit/hyperactivity disorder, the CDC investigators said.

The MMWR report used data collected by the Prescription Behavior Surveillance System. The eight states were included because they submitted data to the Prescription Behavior Surveillance System in time for the report, and they represent about one-quarter of the U.S. population.

[email protected]

In 2013, enough controlled substances were prescribed in Louisiana – 2006.2 prescriptions per 1,000 population – that each and every person in the state could have received two, according to a report from the Centers for Disease Control and Prevention.

The combined prescribing rate for opioids, benzodiazepines, and stimulants in Louisiana topped the eight states included in the CDC report, with West Virginia in second at 1,695.7 prescriptions per 1,000. At the low end, California was the only one of the eight states where the average controlled substance prescription rate was less than one per person, but just barely at 994.8 per 1,000 people, followed by Idaho at 1,292.3 per 1,000, according to the CDC investigators in a Morbidity and Mortality Weekly Report Surveillance Summary (2015 Oct;64[SS09]:1-14).

Of the three categories of controlled substances, opioids were by far the most commonly prescribed. At 1,021.7 prescriptions per 1,000 people, the opioid prescription rate in Louisiana was greater than the total controlled substance prescription rate in California. West Virginia had the second highest rate at 929.3, and California had the lowest at 596.3.

Prescription rates for stimulants and benzodiazepines were highest in Louisiana at 403.9 and 580.6 per 1,000 people, respectively. Maine had the next-highest stimulant prescription rate at 293.9, and West Virginia had the second-highest benzodiazepine prescription rate at 572.1. California had the lowest rate in both categories at 87.7 and 310.8, respectively.

Women received opioids and benzodiazepines at much higher rates than did men in every state, but stimulant-prescribing rates were higher for men in five states.

Opioid use was highest in people aged 55-64 years, though use spiked dramatically past the age of 25. People in Louisiana aged 55-64 receiving opioids had the highest controlled substance prescription rate of any measured age group, at 1,715.7 per 1,000 people. Benzodiazepine use was most common in people over 65 years, and stimulant prescriptions were highest in people younger than 18, likely because of the prevalence of childhood attention-deficit/hyperactivity disorder, the CDC investigators said.

The MMWR report used data collected by the Prescription Behavior Surveillance System. The eight states were included because they submitted data to the Prescription Behavior Surveillance System in time for the report, and they represent about one-quarter of the U.S. population.

[email protected]

In 2013, enough controlled substances were prescribed in Louisiana – 2006.2 prescriptions per 1,000 population – that each and every person in the state could have received two, according to a report from the Centers for Disease Control and Prevention.

The combined prescribing rate for opioids, benzodiazepines, and stimulants in Louisiana topped the eight states included in the CDC report, with West Virginia in second at 1,695.7 prescriptions per 1,000. At the low end, California was the only one of the eight states where the average controlled substance prescription rate was less than one per person, but just barely at 994.8 per 1,000 people, followed by Idaho at 1,292.3 per 1,000, according to the CDC investigators in a Morbidity and Mortality Weekly Report Surveillance Summary (2015 Oct;64[SS09]:1-14).

Of the three categories of controlled substances, opioids were by far the most commonly prescribed. At 1,021.7 prescriptions per 1,000 people, the opioid prescription rate in Louisiana was greater than the total controlled substance prescription rate in California. West Virginia had the second highest rate at 929.3, and California had the lowest at 596.3.

Prescription rates for stimulants and benzodiazepines were highest in Louisiana at 403.9 and 580.6 per 1,000 people, respectively. Maine had the next-highest stimulant prescription rate at 293.9, and West Virginia had the second-highest benzodiazepine prescription rate at 572.1. California had the lowest rate in both categories at 87.7 and 310.8, respectively.

Women received opioids and benzodiazepines at much higher rates than did men in every state, but stimulant-prescribing rates were higher for men in five states.

Opioid use was highest in people aged 55-64 years, though use spiked dramatically past the age of 25. People in Louisiana aged 55-64 receiving opioids had the highest controlled substance prescription rate of any measured age group, at 1,715.7 per 1,000 people. Benzodiazepine use was most common in people over 65 years, and stimulant prescriptions were highest in people younger than 18, likely because of the prevalence of childhood attention-deficit/hyperactivity disorder, the CDC investigators said.

The MMWR report used data collected by the Prescription Behavior Surveillance System. The eight states were included because they submitted data to the Prescription Behavior Surveillance System in time for the report, and they represent about one-quarter of the U.S. population.

[email protected]

In December 2014, The Wall Street Journal ran an article about a young mother who wanted a vaginal birth after C-section (VBAC) for her second child. After her hospital stopped offering VBACs, the woman had to find another place to deliver. She did have a successful VBAC, but her story is not unique – many women may not receive adequate consultations about or provider support for VBAC as a delivery option.

According to the article, a lack of clinical support was the reason the hospital discontinued VBACs. Although the hospital’s decision may have frustrated the mother, this ensured that she would not be promised a birthing option that the hospital could not deliver – in all senses of this word. Successful VBAC requires proper patient selection, appropriate consent and adequate provisions in case of emergencies.

Not every hospital has made such a choice. Based on studies of a trial of labor after cesarean, conducted after the 1960s, the rate of VBACs increased. As VBACs became more common, the approach to the procedure became more relaxed. VBACs went from only being performed in tertiary care hospitals with appropriate support for emergencies, to community hospitals with no backup. Patient selection became less rigorous, and the rate of complications went up, which, in turn, caused the number of associated legal claims to rise. Hospitals started discouraging VBACs, and ob.gyns. no longer counseled their patients about this option. The VBAC rate decreased, and the C-section rate increased.

Today, many women want to pursue a trial of labor after cesarean. Data from large clinical studies have demonstrated the safety and success of VBAC with proper care. Because of the storied history and a revival of interest in VBACs, we have invited Dr. Mark Landon, the Richard L. Meiling Professor and chairman of the department of obstetrics and gynecology at the Ohio State University, and the lead on one of the recent seminal VBAC studies, to address this topic.

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece reported having no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].

In December 2014, The Wall Street Journal ran an article about a young mother who wanted a vaginal birth after C-section (VBAC) for her second child. After her hospital stopped offering VBACs, the woman had to find another place to deliver. She did have a successful VBAC, but her story is not unique – many women may not receive adequate consultations about or provider support for VBAC as a delivery option.

According to the article, a lack of clinical support was the reason the hospital discontinued VBACs. Although the hospital’s decision may have frustrated the mother, this ensured that she would not be promised a birthing option that the hospital could not deliver – in all senses of this word. Successful VBAC requires proper patient selection, appropriate consent and adequate provisions in case of emergencies.

Not every hospital has made such a choice. Based on studies of a trial of labor after cesarean, conducted after the 1960s, the rate of VBACs increased. As VBACs became more common, the approach to the procedure became more relaxed. VBACs went from only being performed in tertiary care hospitals with appropriate support for emergencies, to community hospitals with no backup. Patient selection became less rigorous, and the rate of complications went up, which, in turn, caused the number of associated legal claims to rise. Hospitals started discouraging VBACs, and ob.gyns. no longer counseled their patients about this option. The VBAC rate decreased, and the C-section rate increased.

Today, many women want to pursue a trial of labor after cesarean. Data from large clinical studies have demonstrated the safety and success of VBAC with proper care. Because of the storied history and a revival of interest in VBACs, we have invited Dr. Mark Landon, the Richard L. Meiling Professor and chairman of the department of obstetrics and gynecology at the Ohio State University, and the lead on one of the recent seminal VBAC studies, to address this topic.

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece reported having no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].

In December 2014, The Wall Street Journal ran an article about a young mother who wanted a vaginal birth after C-section (VBAC) for her second child. After her hospital stopped offering VBACs, the woman had to find another place to deliver. She did have a successful VBAC, but her story is not unique – many women may not receive adequate consultations about or provider support for VBAC as a delivery option.

According to the article, a lack of clinical support was the reason the hospital discontinued VBACs. Although the hospital’s decision may have frustrated the mother, this ensured that she would not be promised a birthing option that the hospital could not deliver – in all senses of this word. Successful VBAC requires proper patient selection, appropriate consent and adequate provisions in case of emergencies.

Not every hospital has made such a choice. Based on studies of a trial of labor after cesarean, conducted after the 1960s, the rate of VBACs increased. As VBACs became more common, the approach to the procedure became more relaxed. VBACs went from only being performed in tertiary care hospitals with appropriate support for emergencies, to community hospitals with no backup. Patient selection became less rigorous, and the rate of complications went up, which, in turn, caused the number of associated legal claims to rise. Hospitals started discouraging VBACs, and ob.gyns. no longer counseled their patients about this option. The VBAC rate decreased, and the C-section rate increased.

Today, many women want to pursue a trial of labor after cesarean. Data from large clinical studies have demonstrated the safety and success of VBAC with proper care. Because of the storied history and a revival of interest in VBACs, we have invited Dr. Mark Landon, the Richard L. Meiling Professor and chairman of the department of obstetrics and gynecology at the Ohio State University, and the lead on one of the recent seminal VBAC studies, to address this topic.

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece reported having no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].

The relative safety of vaginal birth after cesarean (VBAC) has been documented in several large-scale studies in the past 15 years, and was affirmed in 2010 through a National Institutes of Health consensus development conference and a practice bulletin from the American College of Obstetricians and Gynecologists. Yet, despite all this research and review, rates of a trial of labor after cesarean (TOLAC) have increased only modestly in the last several years.

Approximately 20% of all births in 2013 in women with a history of one cesarean section involved a trial of labor, according to a recent report from the Centers for Disease Control and Prevention. This represents only a small increase from 2006, when the TOLAC rate had plummeted to approximately 15%.

The limited change is concerning because up to two-thirds of women with a prior cesarean delivery are candidates for a trial of labor, and many of them are excellent candidates. In total, 70% of the women who attempted labor in 2013 after a previous cesarean had successful VBACs, the CDC data shows.

Several European countries have TOLAC rates between 50% and 70%, but in the United States, as evidenced by the recent CDC data, there continues to be an underutilization of attempted VBAC. We must ask ourselves, are women truly able to choose TOLAC, or are they being dissuaded by the health care system?

I believe that the barriers are still pervasive. Too often, women who are TOLAC candidates are not receiving appropriate counseling – and too often, women are not even being presented the option of a trial of labor, even when staff are immediately available to provide emergency care if needed.

Rupture concerns in perspective

When the NIH consensus development panel reviewed VBAC in 2010, it concluded that TOLAC is a reasonable option for many women with a prior cesarean. The panel found that restricted access to VBAC/TOLAC stemmed from existing practice guidelines and the medical liability climate, and it called upon providers and others to “mitigate or even eliminate” the barriers that women face in finding clinicians and facilities able and willing to offer TOLAC.

ACOG’s 2010 practice bulletin also acknowledged the problem of limited access. ACOG recommended, as it had in an earlier bulletin, that TOLAC-VBAC be undertaken in facilities where staff are immediately available for emergency care. It added, however, that when such resources are not available, the best alternative may be to refer patients to a facility with available resources. Health care providers and insurance carriers “should do all they can to facilitate transfer of care or comanagement in support of a desired TOLAC,” ACOG’s document states.

Why, given such recommendations, are we still falling so short of where we should be?

A number of nonclinical factors are involved, but clearly, as both the NIH and ACOG have stated, the fear of litigation in cases of uterine rupture is a contributing factor. A ruptured uterus is indeed the principal risk associated with TOLAC, and it can have serious sequelae including perinatal death, hypoxic ischemic encephalopathy (HIE), and hysterectomy.

We must appreciate, however, that the absolute rates of uterine rupture and of serious adverse outcomes are quite low. The rupture rate in 2013 among women who underwent TOLAC but ultimately had a repeat cesarean section – the highest-risk group – was 495 per 100,000 live births, according to the CDC. This rate of approximately 0.5% is consistent with the level of risk reported in the literature for several decades.

In one of the two large observational studies done in the United States that have shed light on TOLAC outcomes, the rate of uterine rupture among women who underwent TOLAC was 0.7% for women with a prior low transverse incision, 2.0% for those with a prior low vertical incision, and 0.5% for those with an unknown type of prior incision. Overall, the rate of uterine rupture in this study’s cohort of 17,898 women who underwent TOLAC was 0.7% (N Engl J Med. 2004 Dec 16;351[25]:2581-9). The study was conducted at 19 medical centers belonging to the Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Maternal-Fetal Medical Units (MFMU) Network.

The second large study conducted in the United States – a multicenter observational study in which records of approximately 25,000 women with a prior low-transverse cesarean section were reviewed – also showed rates of uterine rupture less than 1% (Am J Obstet Gynecol. 2005 Nov;193[5]:1656-62).

The attributable risk for perinatal death or HIE at term appears to be 1 per 2,000 TOLAC, according to the MFMU Network study.

Failed trials of labor resulting in repeat cesarean deliveries have consistently been associated with higher morbidity than scheduled repeat cesarean deliveries, with the greatest difference in rates for ruptured uterus. In the first MFMU Network study, there were no cases of uterine rupture among a cohort of 15,801 women who underwent elective repeat cesarean delivery, and in the second multicenter study of 25,000 women, this patient group had a rupture rate of 0.004%.

Yet, as ACOG points out, neither elective repeat cesarean deliveries nor TOLAC are without maternal or neonatal risk. Women who have successful VBAC delivery, on the other hand, have significantly lower morbidity and better outcomes than women who do not attempt labor. Women who undergo VBAC also avoid exposure to the significant risks of repeat cesarean deliveries in the long term.

Research unequivocally shows that the risk of placenta accreta, hysterectomy, hemorrhage, and other serious maternal morbidity increases progressively with each repeat cesarean delivery. Rates of placenta accreta have, in fact, been rising in the United States – a trend that should prompt us to think more about TOLAC.

Moreover, TOLAC is being shown to be a cost-effective strategy. In one analysis, TOLAC in a second pregnancy was cost-effective as long as the chance of VBAC exceeded approximately 74% (Obstet Gynecol. 2001 Jun;97[6]:932-41). More recently, TOLAC was found to be cost-effective across a wide variety of circumstances, including when a woman had a probability of VBAC as low as 43%. The model in this analysis, which used probability estimates from the MFMU Cesarean Registry, took a longer-term view by including probabilities of outcomes throughout a woman’s reproductive life that were contingent upon her initial choice regarding TOLAC (Am J Perinatol. 2013 Jan;30[1]:11-20).

Likelihood of success

Evaluating and discussing the likelihood of success with TOLAC is therefore key to the counseling process. The higher the likelihood of achieving VBAC, the more favorable the risk-benefit ratio will be and the more appealing it will be to consider.

According to one analysis, if a woman undergoing a TOLAC has at least a 60%-70% chance of VBAC, her chance of having major or minor morbidity is no greater than a woman undergoing a planned repeat cesarean delivery (Am J Obstet Gynecol 2009;200:56.e1-e6).

There are several prediction tools available that can be used at the first prenatal visit and in early labor to give a reasonably good estimate of success. One of these tools is available at the MFMU Network website (http://mfmu.bsc.gwu.edu). The tools take into account factors such as prior indication for cesarean delivery; history of vaginal delivery; demographic characteristics such as maternal age and body mass index; the occurrence of spontaneous labor; and cervical status at admission.

Prior vaginal delivery is one of the strongest predictors of a successful TOLAC. Research has consistently shown that women with a prior vaginal delivery – including a vaginal delivery predating an unsuccessful TOLAC – have significantly higher TOLAC success rates than women who did not have any prior vaginal delivery.

The indication for a prior cesarean delivery also clearly affects the likelihood of a successful TOLAC. Women whose first cesarean delivery was performed for a nonrecurring indication, such as breech presentation or low intolerance of labor, have TOLAC success rates that are similar to vaginal delivery rates for nulliparous women. Success rates for these women may exceed 85%. On the other hand, women who had a prior cesarean delivery for cephalopelvic disproportion or failure to progress have been shown to have lower TOLAC success rates ranging from 50%-67%.

Labor induction should be approached cautiously, as women who undergo induction of labor in TOLAC have an increased risk of repeat cesarean delivery. Still, success rates with induction are high. Data from the MFMU Cesarean Registry showed that about 66% of women undergoing induction after one prior cesarean delivery achieved VBAC versus 76% of women entering TOLAC spontaneously (Obstet Gynecol. 2007 Feb;109[2 Pt 1]:262-9). Another study of women undergoing induction after one prior cesarean reported an overall success rate of 78% (Obstet Gynecol. 2004 Mar;103[3]:534-8).

Whether induction specifically increases the risk for uterine rupture in TOLAC, compared with expectant management, is unclear. There also are conflicting data as to whether particular induction methods increase this risk.

Based on available data, ACOG considers induction of labor for either maternal or fetal indications to be an option for women undergoing TOLAC. Oxytocin may be used for induction as well as augmentation, but caution should be exercised at higher doses. While there is no clear dosing threshold for increased risk of rupture, research has suggested that higher doses of oxytocin are best avoided.

The use of prostaglandins is more controversial: Based on evidence from several small studies, ACOG concluded in its 2010 bulletin that misoprostol (prostaglandin E₁) for cervical ripening is contraindicated in women undergoing TOLAC. It appears likely that rupture risk increases in patients who received both prostaglandins and oxytocin, so ACOG has advised avoiding their sequential use when prostaglandin E₂ is used. This of course limits the options for the practitioner. Therefore, utilizing a Foley catheter followed by pitocin has been an approach advocated in some cases.

Uterine rupture is not predictable, and it is far more difficult to assess an individual’s risk of this complication than it is to assess the likelihood of VBAC. Still, there is value to discussing with the patient whether there are any other modifiers that could potentially influence the risk of rupture.

Since rates of uterine rupture are highest in women with previous classical or T-shaped incision, for example, it is important to try to ascertain what type of incision was previously used. It is widely appreciated that low-transverse uterine incisions are most favorable, but findings are mixed in regard to low-vertical incisions. Some research shows that women with a previous low-vertical incision do not have significantly lower VBAC success rates or higher risks of uterine rupture. TOLAC should therefore not be ruled out in these cases.

Additionally, TOLAC should not be ruled out for women who have had more than one cesarean delivery. Several studies have shown an increased risk of uterine rupture after two prior cesarean deliveries, compared with one, and one meta-analysis suggested a more than twofold increased risk (BJOG. 2010 Jan;117(1):5-19.).

In contrast, an analysis of the MFMU Cesarean Registry found no significant difference in rupture rates in women with one prior cesarean versus multiple prior cesareans (Obstet Gynecol. 2006 Jul;108[1]:12-20.).

It appears, therefore, that even if having more than one prior cesarean section is associated with an increased risk of rupture, the magnitude of this increase is small.

Just as women with a prior vaginal delivery have the highest chance of VBAC success, they also have the lowest rates of rupture among all women undergoing TOLAC.

Patient counseling

We must inform our patients who have had a cesarean section in the past of their options for childbirth in an unbiased manner.

The complications of both TOLAC and elective repeat cesarean section should be discussed, and every attempt should be made to individually assess both the likelihood of a successful VBAC and the comparative risk of maternal and perinatal morbidity. A shared decision-making process should be adopted, and whenever possible, the patient’s preference should be respected. In the end, a woman undergoing TOLAC should be truly motivated to pursue a trial of labor, because there are inherent risks.

One thing I’ve learned from my clinical practice and research on this issue is that the desire to undergo a vaginal delivery is powerful for some women. Many of my patients have self-referred for consultation about TOLAC after their ob.gyn. informed them that their hospital is not equipped, and they should therefore have a scheduled repeat operation. In many cases they discover that TOLAC is an option if they are willing to travel a half-hour or so.

We need to honor this desire and inform our patients of the option, and help facilitate delivery at another nearby hospital when our own facility is not equipped for TOLAC.

Dr. Landon is the Richard L. Meiling Professor and chairman of the department of obstetrics and gynecology at the Ohio State University, Columbus. He served for more than 25 years as Ohio State’s coinvestigator for the National Institutes of Child Health and Human Development Maternal Fetal Medicine Units Network. He reported having no relevant financial disclosures.

The relative safety of vaginal birth after cesarean (VBAC) has been documented in several large-scale studies in the past 15 years, and was affirmed in 2010 through a National Institutes of Health consensus development conference and a practice bulletin from the American College of Obstetricians and Gynecologists. Yet, despite all this research and review, rates of a trial of labor after cesarean (TOLAC) have increased only modestly in the last several years.

Approximately 20% of all births in 2013 in women with a history of one cesarean section involved a trial of labor, according to a recent report from the Centers for Disease Control and Prevention. This represents only a small increase from 2006, when the TOLAC rate had plummeted to approximately 15%.

The limited change is concerning because up to two-thirds of women with a prior cesarean delivery are candidates for a trial of labor, and many of them are excellent candidates. In total, 70% of the women who attempted labor in 2013 after a previous cesarean had successful VBACs, the CDC data shows.

Several European countries have TOLAC rates between 50% and 70%, but in the United States, as evidenced by the recent CDC data, there continues to be an underutilization of attempted VBAC. We must ask ourselves, are women truly able to choose TOLAC, or are they being dissuaded by the health care system?

I believe that the barriers are still pervasive. Too often, women who are TOLAC candidates are not receiving appropriate counseling – and too often, women are not even being presented the option of a trial of labor, even when staff are immediately available to provide emergency care if needed.

Rupture concerns in perspective

When the NIH consensus development panel reviewed VBAC in 2010, it concluded that TOLAC is a reasonable option for many women with a prior cesarean. The panel found that restricted access to VBAC/TOLAC stemmed from existing practice guidelines and the medical liability climate, and it called upon providers and others to “mitigate or even eliminate” the barriers that women face in finding clinicians and facilities able and willing to offer TOLAC.

ACOG’s 2010 practice bulletin also acknowledged the problem of limited access. ACOG recommended, as it had in an earlier bulletin, that TOLAC-VBAC be undertaken in facilities where staff are immediately available for emergency care. It added, however, that when such resources are not available, the best alternative may be to refer patients to a facility with available resources. Health care providers and insurance carriers “should do all they can to facilitate transfer of care or comanagement in support of a desired TOLAC,” ACOG’s document states.

Why, given such recommendations, are we still falling so short of where we should be?

A number of nonclinical factors are involved, but clearly, as both the NIH and ACOG have stated, the fear of litigation in cases of uterine rupture is a contributing factor. A ruptured uterus is indeed the principal risk associated with TOLAC, and it can have serious sequelae including perinatal death, hypoxic ischemic encephalopathy (HIE), and hysterectomy.

We must appreciate, however, that the absolute rates of uterine rupture and of serious adverse outcomes are quite low. The rupture rate in 2013 among women who underwent TOLAC but ultimately had a repeat cesarean section – the highest-risk group – was 495 per 100,000 live births, according to the CDC. This rate of approximately 0.5% is consistent with the level of risk reported in the literature for several decades.

In one of the two large observational studies done in the United States that have shed light on TOLAC outcomes, the rate of uterine rupture among women who underwent TOLAC was 0.7% for women with a prior low transverse incision, 2.0% for those with a prior low vertical incision, and 0.5% for those with an unknown type of prior incision. Overall, the rate of uterine rupture in this study’s cohort of 17,898 women who underwent TOLAC was 0.7% (N Engl J Med. 2004 Dec 16;351[25]:2581-9). The study was conducted at 19 medical centers belonging to the Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Maternal-Fetal Medical Units (MFMU) Network.

The second large study conducted in the United States – a multicenter observational study in which records of approximately 25,000 women with a prior low-transverse cesarean section were reviewed – also showed rates of uterine rupture less than 1% (Am J Obstet Gynecol. 2005 Nov;193[5]:1656-62).

The attributable risk for perinatal death or HIE at term appears to be 1 per 2,000 TOLAC, according to the MFMU Network study.

Failed trials of labor resulting in repeat cesarean deliveries have consistently been associated with higher morbidity than scheduled repeat cesarean deliveries, with the greatest difference in rates for ruptured uterus. In the first MFMU Network study, there were no cases of uterine rupture among a cohort of 15,801 women who underwent elective repeat cesarean delivery, and in the second multicenter study of 25,000 women, this patient group had a rupture rate of 0.004%.

Yet, as ACOG points out, neither elective repeat cesarean deliveries nor TOLAC are without maternal or neonatal risk. Women who have successful VBAC delivery, on the other hand, have significantly lower morbidity and better outcomes than women who do not attempt labor. Women who undergo VBAC also avoid exposure to the significant risks of repeat cesarean deliveries in the long term.

Research unequivocally shows that the risk of placenta accreta, hysterectomy, hemorrhage, and other serious maternal morbidity increases progressively with each repeat cesarean delivery. Rates of placenta accreta have, in fact, been rising in the United States – a trend that should prompt us to think more about TOLAC.

Moreover, TOLAC is being shown to be a cost-effective strategy. In one analysis, TOLAC in a second pregnancy was cost-effective as long as the chance of VBAC exceeded approximately 74% (Obstet Gynecol. 2001 Jun;97[6]:932-41). More recently, TOLAC was found to be cost-effective across a wide variety of circumstances, including when a woman had a probability of VBAC as low as 43%. The model in this analysis, which used probability estimates from the MFMU Cesarean Registry, took a longer-term view by including probabilities of outcomes throughout a woman’s reproductive life that were contingent upon her initial choice regarding TOLAC (Am J Perinatol. 2013 Jan;30[1]:11-20).

Likelihood of success

Evaluating and discussing the likelihood of success with TOLAC is therefore key to the counseling process. The higher the likelihood of achieving VBAC, the more favorable the risk-benefit ratio will be and the more appealing it will be to consider.

According to one analysis, if a woman undergoing a TOLAC has at least a 60%-70% chance of VBAC, her chance of having major or minor morbidity is no greater than a woman undergoing a planned repeat cesarean delivery (Am J Obstet Gynecol 2009;200:56.e1-e6).

There are several prediction tools available that can be used at the first prenatal visit and in early labor to give a reasonably good estimate of success. One of these tools is available at the MFMU Network website (http://mfmu.bsc.gwu.edu). The tools take into account factors such as prior indication for cesarean delivery; history of vaginal delivery; demographic characteristics such as maternal age and body mass index; the occurrence of spontaneous labor; and cervical status at admission.

Prior vaginal delivery is one of the strongest predictors of a successful TOLAC. Research has consistently shown that women with a prior vaginal delivery – including a vaginal delivery predating an unsuccessful TOLAC – have significantly higher TOLAC success rates than women who did not have any prior vaginal delivery.

The indication for a prior cesarean delivery also clearly affects the likelihood of a successful TOLAC. Women whose first cesarean delivery was performed for a nonrecurring indication, such as breech presentation or low intolerance of labor, have TOLAC success rates that are similar to vaginal delivery rates for nulliparous women. Success rates for these women may exceed 85%. On the other hand, women who had a prior cesarean delivery for cephalopelvic disproportion or failure to progress have been shown to have lower TOLAC success rates ranging from 50%-67%.

Labor induction should be approached cautiously, as women who undergo induction of labor in TOLAC have an increased risk of repeat cesarean delivery. Still, success rates with induction are high. Data from the MFMU Cesarean Registry showed that about 66% of women undergoing induction after one prior cesarean delivery achieved VBAC versus 76% of women entering TOLAC spontaneously (Obstet Gynecol. 2007 Feb;109[2 Pt 1]:262-9). Another study of women undergoing induction after one prior cesarean reported an overall success rate of 78% (Obstet Gynecol. 2004 Mar;103[3]:534-8).

Whether induction specifically increases the risk for uterine rupture in TOLAC, compared with expectant management, is unclear. There also are conflicting data as to whether particular induction methods increase this risk.

Based on available data, ACOG considers induction of labor for either maternal or fetal indications to be an option for women undergoing TOLAC. Oxytocin may be used for induction as well as augmentation, but caution should be exercised at higher doses. While there is no clear dosing threshold for increased risk of rupture, research has suggested that higher doses of oxytocin are best avoided.

The use of prostaglandins is more controversial: Based on evidence from several small studies, ACOG concluded in its 2010 bulletin that misoprostol (prostaglandin E₁) for cervical ripening is contraindicated in women undergoing TOLAC. It appears likely that rupture risk increases in patients who received both prostaglandins and oxytocin, so ACOG has advised avoiding their sequential use when prostaglandin E₂ is used. This of course limits the options for the practitioner. Therefore, utilizing a Foley catheter followed by pitocin has been an approach advocated in some cases.

Uterine rupture is not predictable, and it is far more difficult to assess an individual’s risk of this complication than it is to assess the likelihood of VBAC. Still, there is value to discussing with the patient whether there are any other modifiers that could potentially influence the risk of rupture.

Since rates of uterine rupture are highest in women with previous classical or T-shaped incision, for example, it is important to try to ascertain what type of incision was previously used. It is widely appreciated that low-transverse uterine incisions are most favorable, but findings are mixed in regard to low-vertical incisions. Some research shows that women with a previous low-vertical incision do not have significantly lower VBAC success rates or higher risks of uterine rupture. TOLAC should therefore not be ruled out in these cases.

Additionally, TOLAC should not be ruled out for women who have had more than one cesarean delivery. Several studies have shown an increased risk of uterine rupture after two prior cesarean deliveries, compared with one, and one meta-analysis suggested a more than twofold increased risk (BJOG. 2010 Jan;117(1):5-19.).

In contrast, an analysis of the MFMU Cesarean Registry found no significant difference in rupture rates in women with one prior cesarean versus multiple prior cesareans (Obstet Gynecol. 2006 Jul;108[1]:12-20.).

It appears, therefore, that even if having more than one prior cesarean section is associated with an increased risk of rupture, the magnitude of this increase is small.

Just as women with a prior vaginal delivery have the highest chance of VBAC success, they also have the lowest rates of rupture among all women undergoing TOLAC.

Patient counseling

We must inform our patients who have had a cesarean section in the past of their options for childbirth in an unbiased manner.

The complications of both TOLAC and elective repeat cesarean section should be discussed, and every attempt should be made to individually assess both the likelihood of a successful VBAC and the comparative risk of maternal and perinatal morbidity. A shared decision-making process should be adopted, and whenever possible, the patient’s preference should be respected. In the end, a woman undergoing TOLAC should be truly motivated to pursue a trial of labor, because there are inherent risks.

One thing I’ve learned from my clinical practice and research on this issue is that the desire to undergo a vaginal delivery is powerful for some women. Many of my patients have self-referred for consultation about TOLAC after their ob.gyn. informed them that their hospital is not equipped, and they should therefore have a scheduled repeat operation. In many cases they discover that TOLAC is an option if they are willing to travel a half-hour or so.

We need to honor this desire and inform our patients of the option, and help facilitate delivery at another nearby hospital when our own facility is not equipped for TOLAC.

Dr. Landon is the Richard L. Meiling Professor and chairman of the department of obstetrics and gynecology at the Ohio State University, Columbus. He served for more than 25 years as Ohio State’s coinvestigator for the National Institutes of Child Health and Human Development Maternal Fetal Medicine Units Network. He reported having no relevant financial disclosures.

The relative safety of vaginal birth after cesarean (VBAC) has been documented in several large-scale studies in the past 15 years, and was affirmed in 2010 through a National Institutes of Health consensus development conference and a practice bulletin from the American College of Obstetricians and Gynecologists. Yet, despite all this research and review, rates of a trial of labor after cesarean (TOLAC) have increased only modestly in the last several years.

Approximately 20% of all births in 2013 in women with a history of one cesarean section involved a trial of labor, according to a recent report from the Centers for Disease Control and Prevention. This represents only a small increase from 2006, when the TOLAC rate had plummeted to approximately 15%.

The limited change is concerning because up to two-thirds of women with a prior cesarean delivery are candidates for a trial of labor, and many of them are excellent candidates. In total, 70% of the women who attempted labor in 2013 after a previous cesarean had successful VBACs, the CDC data shows.

Several European countries have TOLAC rates between 50% and 70%, but in the United States, as evidenced by the recent CDC data, there continues to be an underutilization of attempted VBAC. We must ask ourselves, are women truly able to choose TOLAC, or are they being dissuaded by the health care system?

I believe that the barriers are still pervasive. Too often, women who are TOLAC candidates are not receiving appropriate counseling – and too often, women are not even being presented the option of a trial of labor, even when staff are immediately available to provide emergency care if needed.

Rupture concerns in perspective

When the NIH consensus development panel reviewed VBAC in 2010, it concluded that TOLAC is a reasonable option for many women with a prior cesarean. The panel found that restricted access to VBAC/TOLAC stemmed from existing practice guidelines and the medical liability climate, and it called upon providers and others to “mitigate or even eliminate” the barriers that women face in finding clinicians and facilities able and willing to offer TOLAC.

ACOG’s 2010 practice bulletin also acknowledged the problem of limited access. ACOG recommended, as it had in an earlier bulletin, that TOLAC-VBAC be undertaken in facilities where staff are immediately available for emergency care. It added, however, that when such resources are not available, the best alternative may be to refer patients to a facility with available resources. Health care providers and insurance carriers “should do all they can to facilitate transfer of care or comanagement in support of a desired TOLAC,” ACOG’s document states.

Why, given such recommendations, are we still falling so short of where we should be?

A number of nonclinical factors are involved, but clearly, as both the NIH and ACOG have stated, the fear of litigation in cases of uterine rupture is a contributing factor. A ruptured uterus is indeed the principal risk associated with TOLAC, and it can have serious sequelae including perinatal death, hypoxic ischemic encephalopathy (HIE), and hysterectomy.

We must appreciate, however, that the absolute rates of uterine rupture and of serious adverse outcomes are quite low. The rupture rate in 2013 among women who underwent TOLAC but ultimately had a repeat cesarean section – the highest-risk group – was 495 per 100,000 live births, according to the CDC. This rate of approximately 0.5% is consistent with the level of risk reported in the literature for several decades.

In one of the two large observational studies done in the United States that have shed light on TOLAC outcomes, the rate of uterine rupture among women who underwent TOLAC was 0.7% for women with a prior low transverse incision, 2.0% for those with a prior low vertical incision, and 0.5% for those with an unknown type of prior incision. Overall, the rate of uterine rupture in this study’s cohort of 17,898 women who underwent TOLAC was 0.7% (N Engl J Med. 2004 Dec 16;351[25]:2581-9). The study was conducted at 19 medical centers belonging to the Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Maternal-Fetal Medical Units (MFMU) Network.

The second large study conducted in the United States – a multicenter observational study in which records of approximately 25,000 women with a prior low-transverse cesarean section were reviewed – also showed rates of uterine rupture less than 1% (Am J Obstet Gynecol. 2005 Nov;193[5]:1656-62).

The attributable risk for perinatal death or HIE at term appears to be 1 per 2,000 TOLAC, according to the MFMU Network study.

Failed trials of labor resulting in repeat cesarean deliveries have consistently been associated with higher morbidity than scheduled repeat cesarean deliveries, with the greatest difference in rates for ruptured uterus. In the first MFMU Network study, there were no cases of uterine rupture among a cohort of 15,801 women who underwent elective repeat cesarean delivery, and in the second multicenter study of 25,000 women, this patient group had a rupture rate of 0.004%.

Yet, as ACOG points out, neither elective repeat cesarean deliveries nor TOLAC are without maternal or neonatal risk. Women who have successful VBAC delivery, on the other hand, have significantly lower morbidity and better outcomes than women who do not attempt labor. Women who undergo VBAC also avoid exposure to the significant risks of repeat cesarean deliveries in the long term.

Research unequivocally shows that the risk of placenta accreta, hysterectomy, hemorrhage, and other serious maternal morbidity increases progressively with each repeat cesarean delivery. Rates of placenta accreta have, in fact, been rising in the United States – a trend that should prompt us to think more about TOLAC.

Moreover, TOLAC is being shown to be a cost-effective strategy. In one analysis, TOLAC in a second pregnancy was cost-effective as long as the chance of VBAC exceeded approximately 74% (Obstet Gynecol. 2001 Jun;97[6]:932-41). More recently, TOLAC was found to be cost-effective across a wide variety of circumstances, including when a woman had a probability of VBAC as low as 43%. The model in this analysis, which used probability estimates from the MFMU Cesarean Registry, took a longer-term view by including probabilities of outcomes throughout a woman’s reproductive life that were contingent upon her initial choice regarding TOLAC (Am J Perinatol. 2013 Jan;30[1]:11-20).

Likelihood of success

Evaluating and discussing the likelihood of success with TOLAC is therefore key to the counseling process. The higher the likelihood of achieving VBAC, the more favorable the risk-benefit ratio will be and the more appealing it will be to consider.

According to one analysis, if a woman undergoing a TOLAC has at least a 60%-70% chance of VBAC, her chance of having major or minor morbidity is no greater than a woman undergoing a planned repeat cesarean delivery (Am J Obstet Gynecol 2009;200:56.e1-e6).

There are several prediction tools available that can be used at the first prenatal visit and in early labor to give a reasonably good estimate of success. One of these tools is available at the MFMU Network website (http://mfmu.bsc.gwu.edu). The tools take into account factors such as prior indication for cesarean delivery; history of vaginal delivery; demographic characteristics such as maternal age and body mass index; the occurrence of spontaneous labor; and cervical status at admission.

Prior vaginal delivery is one of the strongest predictors of a successful TOLAC. Research has consistently shown that women with a prior vaginal delivery – including a vaginal delivery predating an unsuccessful TOLAC – have significantly higher TOLAC success rates than women who did not have any prior vaginal delivery.

The indication for a prior cesarean delivery also clearly affects the likelihood of a successful TOLAC. Women whose first cesarean delivery was performed for a nonrecurring indication, such as breech presentation or low intolerance of labor, have TOLAC success rates that are similar to vaginal delivery rates for nulliparous women. Success rates for these women may exceed 85%. On the other hand, women who had a prior cesarean delivery for cephalopelvic disproportion or failure to progress have been shown to have lower TOLAC success rates ranging from 50%-67%.

Labor induction should be approached cautiously, as women who undergo induction of labor in TOLAC have an increased risk of repeat cesarean delivery. Still, success rates with induction are high. Data from the MFMU Cesarean Registry showed that about 66% of women undergoing induction after one prior cesarean delivery achieved VBAC versus 76% of women entering TOLAC spontaneously (Obstet Gynecol. 2007 Feb;109[2 Pt 1]:262-9). Another study of women undergoing induction after one prior cesarean reported an overall success rate of 78% (Obstet Gynecol. 2004 Mar;103[3]:534-8).

Whether induction specifically increases the risk for uterine rupture in TOLAC, compared with expectant management, is unclear. There also are conflicting data as to whether particular induction methods increase this risk.

Based on available data, ACOG considers induction of labor for either maternal or fetal indications to be an option for women undergoing TOLAC. Oxytocin may be used for induction as well as augmentation, but caution should be exercised at higher doses. While there is no clear dosing threshold for increased risk of rupture, research has suggested that higher doses of oxytocin are best avoided.

The use of prostaglandins is more controversial: Based on evidence from several small studies, ACOG concluded in its 2010 bulletin that misoprostol (prostaglandin E₁) for cervical ripening is contraindicated in women undergoing TOLAC. It appears likely that rupture risk increases in patients who received both prostaglandins and oxytocin, so ACOG has advised avoiding their sequential use when prostaglandin E₂ is used. This of course limits the options for the practitioner. Therefore, utilizing a Foley catheter followed by pitocin has been an approach advocated in some cases.

Uterine rupture is not predictable, and it is far more difficult to assess an individual’s risk of this complication than it is to assess the likelihood of VBAC. Still, there is value to discussing with the patient whether there are any other modifiers that could potentially influence the risk of rupture.

Since rates of uterine rupture are highest in women with previous classical or T-shaped incision, for example, it is important to try to ascertain what type of incision was previously used. It is widely appreciated that low-transverse uterine incisions are most favorable, but findings are mixed in regard to low-vertical incisions. Some research shows that women with a previous low-vertical incision do not have significantly lower VBAC success rates or higher risks of uterine rupture. TOLAC should therefore not be ruled out in these cases.

Additionally, TOLAC should not be ruled out for women who have had more than one cesarean delivery. Several studies have shown an increased risk of uterine rupture after two prior cesarean deliveries, compared with one, and one meta-analysis suggested a more than twofold increased risk (BJOG. 2010 Jan;117(1):5-19.).

In contrast, an analysis of the MFMU Cesarean Registry found no significant difference in rupture rates in women with one prior cesarean versus multiple prior cesareans (Obstet Gynecol. 2006 Jul;108[1]:12-20.).

It appears, therefore, that even if having more than one prior cesarean section is associated with an increased risk of rupture, the magnitude of this increase is small.

Just as women with a prior vaginal delivery have the highest chance of VBAC success, they also have the lowest rates of rupture among all women undergoing TOLAC.

Patient counseling

We must inform our patients who have had a cesarean section in the past of their options for childbirth in an unbiased manner.

The complications of both TOLAC and elective repeat cesarean section should be discussed, and every attempt should be made to individually assess both the likelihood of a successful VBAC and the comparative risk of maternal and perinatal morbidity. A shared decision-making process should be adopted, and whenever possible, the patient’s preference should be respected. In the end, a woman undergoing TOLAC should be truly motivated to pursue a trial of labor, because there are inherent risks.

One thing I’ve learned from my clinical practice and research on this issue is that the desire to undergo a vaginal delivery is powerful for some women. Many of my patients have self-referred for consultation about TOLAC after their ob.gyn. informed them that their hospital is not equipped, and they should therefore have a scheduled repeat operation. In many cases they discover that TOLAC is an option if they are willing to travel a half-hour or so.

We need to honor this desire and inform our patients of the option, and help facilitate delivery at another nearby hospital when our own facility is not equipped for TOLAC.

Dr. Landon is the Richard L. Meiling Professor and chairman of the department of obstetrics and gynecology at the Ohio State University, Columbus. He served for more than 25 years as Ohio State’s coinvestigator for the National Institutes of Child Health and Human Development Maternal Fetal Medicine Units Network. He reported having no relevant financial disclosures.

When screening for bipolar disorders, Mood Disorders Questionnaire scores proved more sensitive – but showed less specificity – in an inpatient mood disorders setting than an outpatient psychiatric population, a retrospective study shows. The results suggest that the MDQ can be used effectively on an inpatient psychiatry mood disorders unit, reported Dr. Simon Kung and his associates.

Dr. Kung of the Mayo Clinic in Rochester, Minn., and his associates evaluated 1,330 patients who checked into a mood disorders unit and administered the MDQ upon entry. After excluding patients with diagnoses that were neither unipolar or bipolar, 860 MDQs were ultimately used. Sensitivity and specificity were calculated for each number of questionnaire items checked positive.

The researchers determined that the optimal cutoff score for MDQs was 8, resulting in a sensitivity/specificity of 86%/71%, compared with 92%/64% using the recommended outpatient cutoff of 7.

Read the full article here: (J Affect Disord. 201515;188:97-100. doi:10.1016/j.jad.2015.08.060)

[email protected]

When screening for bipolar disorders, Mood Disorders Questionnaire scores proved more sensitive – but showed less specificity – in an inpatient mood disorders setting than an outpatient psychiatric population, a retrospective study shows. The results suggest that the MDQ can be used effectively on an inpatient psychiatry mood disorders unit, reported Dr. Simon Kung and his associates.

Dr. Kung of the Mayo Clinic in Rochester, Minn., and his associates evaluated 1,330 patients who checked into a mood disorders unit and administered the MDQ upon entry. After excluding patients with diagnoses that were neither unipolar or bipolar, 860 MDQs were ultimately used. Sensitivity and specificity were calculated for each number of questionnaire items checked positive.

The researchers determined that the optimal cutoff score for MDQs was 8, resulting in a sensitivity/specificity of 86%/71%, compared with 92%/64% using the recommended outpatient cutoff of 7.

Read the full article here: (J Affect Disord. 201515;188:97-100. doi:10.1016/j.jad.2015.08.060)

[email protected]

When screening for bipolar disorders, Mood Disorders Questionnaire scores proved more sensitive – but showed less specificity – in an inpatient mood disorders setting than an outpatient psychiatric population, a retrospective study shows. The results suggest that the MDQ can be used effectively on an inpatient psychiatry mood disorders unit, reported Dr. Simon Kung and his associates.

Dr. Kung of the Mayo Clinic in Rochester, Minn., and his associates evaluated 1,330 patients who checked into a mood disorders unit and administered the MDQ upon entry. After excluding patients with diagnoses that were neither unipolar or bipolar, 860 MDQs were ultimately used. Sensitivity and specificity were calculated for each number of questionnaire items checked positive.

The researchers determined that the optimal cutoff score for MDQs was 8, resulting in a sensitivity/specificity of 86%/71%, compared with 92%/64% using the recommended outpatient cutoff of 7.

Read the full article here: (J Affect Disord. 201515;188:97-100. doi:10.1016/j.jad.2015.08.060)

[email protected]

Half of U.S. physicians are experiencing some of the symptoms of burnout, with even higher rates for general internists. Implementation of the electronic health record (EHR) has been cited as the biggest driver of physician job dissatisfaction, Christine Sinsky, MD, a former hospitalist and currently vice president of professional satisfaction at the American Medical Association (AMA), told attendees at the 19th Management of the Hospitalized Patient Conference, presented by the University of California-San Francisco.¹

Dr. Sinsky deemed physician discontent “the canary in the coal mine” for a dysfunctional healthcare system. After visiting 23 high-functioning medical teams, Dr. Sinsky said she had found that 70% to 80% of physician work output could be considered waste, defined as work that doesn’t need to be done and doesn’t add value to the patient. The AMA, she said, has made a commitment to addressing physicians’ dissatisfaction and burnout.

Dr. Sinsky offered a number of suggestions for physicians and the larger system. Among them was the suggestion for medical teams to employ a documentation specialist, or scribe, to accompany physicians on patient rounds to help with the clerical tasks that divert physicians from patient care. She also cited David Reuben, MD, a gerontologist at UCLA whose JAMA IM study documented his training of physician “practice partners,” often medical or nursing students, who help queue up orders in the EHR, and the improved patient satisfaction that resulted.²

“Be bold,” she advised hospitalists. “The patient care delivery modes of the future can’t be met with staffing models from the past.” TH

References

1. Friedberg M, Chen PG, Van Busum KR, et al. Factors affecting physician professional satisfaction and their implications for patient care, health systems, and health policy. Santa Monica, Calif.: RAND Corporation, 2013. http://www.rand.org/pubs/research_reports/RR439. Also available in print form.
2. Reuben DB, Knudsen J, Senelick W, Glazier E, Koretz BK. The effect of a physician partner program on physician efficiency and patient satisfaction. JAMA Intern Med. 2014;174(7):1190–1193.

Half of U.S. physicians are experiencing some of the symptoms of burnout, with even higher rates for general internists. Implementation of the electronic health record (EHR) has been cited as the biggest driver of physician job dissatisfaction, Christine Sinsky, MD, a former hospitalist and currently vice president of professional satisfaction at the American Medical Association (AMA), told attendees at the 19th Management of the Hospitalized Patient Conference, presented by the University of California-San Francisco.¹

Dr. Sinsky deemed physician discontent “the canary in the coal mine” for a dysfunctional healthcare system. After visiting 23 high-functioning medical teams, Dr. Sinsky said she had found that 70% to 80% of physician work output could be considered waste, defined as work that doesn’t need to be done and doesn’t add value to the patient. The AMA, she said, has made a commitment to addressing physicians’ dissatisfaction and burnout.

Dr. Sinsky offered a number of suggestions for physicians and the larger system. Among them was the suggestion for medical teams to employ a documentation specialist, or scribe, to accompany physicians on patient rounds to help with the clerical tasks that divert physicians from patient care. She also cited David Reuben, MD, a gerontologist at UCLA whose JAMA IM study documented his training of physician “practice partners,” often medical or nursing students, who help queue up orders in the EHR, and the improved patient satisfaction that resulted.²

“Be bold,” she advised hospitalists. “The patient care delivery modes of the future can’t be met with staffing models from the past.” TH

References

1. Friedberg M, Chen PG, Van Busum KR, et al. Factors affecting physician professional satisfaction and their implications for patient care, health systems, and health policy. Santa Monica, Calif.: RAND Corporation, 2013. http://www.rand.org/pubs/research_reports/RR439. Also available in print form.
2. Reuben DB, Knudsen J, Senelick W, Glazier E, Koretz BK. The effect of a physician partner program on physician efficiency and patient satisfaction. JAMA Intern Med. 2014;174(7):1190–1193.

Half of U.S. physicians are experiencing some of the symptoms of burnout, with even higher rates for general internists. Implementation of the electronic health record (EHR) has been cited as the biggest driver of physician job dissatisfaction, Christine Sinsky, MD, a former hospitalist and currently vice president of professional satisfaction at the American Medical Association (AMA), told attendees at the 19th Management of the Hospitalized Patient Conference, presented by the University of California-San Francisco.¹

Dr. Sinsky deemed physician discontent “the canary in the coal mine” for a dysfunctional healthcare system. After visiting 23 high-functioning medical teams, Dr. Sinsky said she had found that 70% to 80% of physician work output could be considered waste, defined as work that doesn’t need to be done and doesn’t add value to the patient. The AMA, she said, has made a commitment to addressing physicians’ dissatisfaction and burnout.

Dr. Sinsky offered a number of suggestions for physicians and the larger system. Among them was the suggestion for medical teams to employ a documentation specialist, or scribe, to accompany physicians on patient rounds to help with the clerical tasks that divert physicians from patient care. She also cited David Reuben, MD, a gerontologist at UCLA whose JAMA IM study documented his training of physician “practice partners,” often medical or nursing students, who help queue up orders in the EHR, and the improved patient satisfaction that resulted.²

“Be bold,” she advised hospitalists. “The patient care delivery modes of the future can’t be met with staffing models from the past.” TH

References

1. Friedberg M, Chen PG, Van Busum KR, et al. Factors affecting physician professional satisfaction and their implications for patient care, health systems, and health policy. Santa Monica, Calif.: RAND Corporation, 2013. http://www.rand.org/pubs/research_reports/RR439. Also available in print form.
2. Reuben DB, Knudsen J, Senelick W, Glazier E, Koretz BK. The effect of a physician partner program on physician efficiency and patient satisfaction. JAMA Intern Med. 2014;174(7):1190–1193.

 

 

Radiation therapist preparing

woman for radiotherapy

Photo by Rhoda Baer

 

SAN ANTONIO—A new study indicates that patients with early stage follicular lymphoma (FL) are increasingly receiving no treatment or single-agent chemotherapy, despite evidence suggesting that radiation therapy can produce better outcomes.

Guidelines from the National Comprehensive Cancer Network and the European Society for Medical Oncology both list radiation therapy as the preferred treatment for low-grade FL.

However, investigators found that, in recent years, radiation has been replaced by alternative strategies.

“Our study highlights the increasing omission of radiation therapy in [FL] and its associated negative effect on overall survival at a national level,” said John Austin Vargo, MD, of the University of Pittsburg Cancer Institute in Pennsylvania.

“This increasing bias towards the omission of radiation therapy is despite proven efficacy and increasing adoption of lower radiation therapy doses and more modern radiation therapy techniques which decrease risk of side effects.”

Dr Vargo presented these findings at the 57th Annual Meeting of the American Society for Radiation Oncology (presentation #183).

He and his colleagues analyzed patterns of care and survival outcomes for 35,961 patients diagnosed with early stage FL as listed in the National Cancer Data Base. A majority of patients were older than 60 (61%), and most had stage I disease (63%).

The use of radiation therapy in this group of patients decreased from 37% in 1999 to 24% in 2012 (P<0.0001).

The use of observation increased from 34% in 1998 to 44% in 2012 (P<0.0001). And the use of single-agent chemotherapy increased from 5.4% in 1999 to 11.7% in 2006 (P=0.01).

The 5-year overall survival rate was 86% in patients who received radiation and 74% in those who did not (P<0.0001). Ten-year overall survival rates were 68% and 54%, respectively (P<0.0001).

In multivariate analysis, radiation therapy remained significantly associated with improved overall survival (P<0.0001).

 

 

Radiation therapist preparing

woman for radiotherapy

Photo by Rhoda Baer

 

SAN ANTONIO—A new study indicates that patients with early stage follicular lymphoma (FL) are increasingly receiving no treatment or single-agent chemotherapy, despite evidence suggesting that radiation therapy can produce better outcomes.

Guidelines from the National Comprehensive Cancer Network and the European Society for Medical Oncology both list radiation therapy as the preferred treatment for low-grade FL.

However, investigators found that, in recent years, radiation has been replaced by alternative strategies.

“Our study highlights the increasing omission of radiation therapy in [FL] and its associated negative effect on overall survival at a national level,” said John Austin Vargo, MD, of the University of Pittsburg Cancer Institute in Pennsylvania.

“This increasing bias towards the omission of radiation therapy is despite proven efficacy and increasing adoption of lower radiation therapy doses and more modern radiation therapy techniques which decrease risk of side effects.”

Dr Vargo presented these findings at the 57th Annual Meeting of the American Society for Radiation Oncology (presentation #183).

He and his colleagues analyzed patterns of care and survival outcomes for 35,961 patients diagnosed with early stage FL as listed in the National Cancer Data Base. A majority of patients were older than 60 (61%), and most had stage I disease (63%).

The use of radiation therapy in this group of patients decreased from 37% in 1999 to 24% in 2012 (P<0.0001).

The use of observation increased from 34% in 1998 to 44% in 2012 (P<0.0001). And the use of single-agent chemotherapy increased from 5.4% in 1999 to 11.7% in 2006 (P=0.01).

The 5-year overall survival rate was 86% in patients who received radiation and 74% in those who did not (P<0.0001). Ten-year overall survival rates were 68% and 54%, respectively (P<0.0001).

In multivariate analysis, radiation therapy remained significantly associated with improved overall survival (P<0.0001).

 

 

Radiation therapist preparing

woman for radiotherapy

Photo by Rhoda Baer

 

SAN ANTONIO—A new study indicates that patients with early stage follicular lymphoma (FL) are increasingly receiving no treatment or single-agent chemotherapy, despite evidence suggesting that radiation therapy can produce better outcomes.

Guidelines from the National Comprehensive Cancer Network and the European Society for Medical Oncology both list radiation therapy as the preferred treatment for low-grade FL.

However, investigators found that, in recent years, radiation has been replaced by alternative strategies.

“Our study highlights the increasing omission of radiation therapy in [FL] and its associated negative effect on overall survival at a national level,” said John Austin Vargo, MD, of the University of Pittsburg Cancer Institute in Pennsylvania.

“This increasing bias towards the omission of radiation therapy is despite proven efficacy and increasing adoption of lower radiation therapy doses and more modern radiation therapy techniques which decrease risk of side effects.”

Dr Vargo presented these findings at the 57th Annual Meeting of the American Society for Radiation Oncology (presentation #183).

He and his colleagues analyzed patterns of care and survival outcomes for 35,961 patients diagnosed with early stage FL as listed in the National Cancer Data Base. A majority of patients were older than 60 (61%), and most had stage I disease (63%).

The use of radiation therapy in this group of patients decreased from 37% in 1999 to 24% in 2012 (P<0.0001).

The use of observation increased from 34% in 1998 to 44% in 2012 (P<0.0001). And the use of single-agent chemotherapy increased from 5.4% in 1999 to 11.7% in 2006 (P=0.01).

The 5-year overall survival rate was 86% in patients who received radiation and 74% in those who did not (P<0.0001). Ten-year overall survival rates were 68% and 54%, respectively (P<0.0001).

In multivariate analysis, radiation therapy remained significantly associated with improved overall survival (P<0.0001).

Lab mouse

A small-molecule compound that has previously shown activity against Ewing sarcoma and prostate cancer may fight leukemia as well, according to preclinical research published in Oncotarget.

The compound, YK-4-279, inhibits the oncogenic activity of the fusion protein EWS-FLI1.

“EWS-FLI1 is already known to drive a rare but deadly bone cancer called Ewing sarcoma,” said study author Aykut Üren, MD, of Georgetown University Medical Center in Washington, DC.

“It also appears to drive cancer cell growth in some prostate cancers.”

ETS family fusion proteins are found in patients with acute myeloid leukemia and acute lymphoblastic leukemia as well.

So Dr Üren and his colleagues decided to create a mouse model of EWS-FLI1-induced leukemia and assess the activity of YK-4-279 in this model.

Mice with EWS-FLI1-induced leukemia presented with severe hepatomegaly, splenomegaly, and anemia, followed by rapid death.

The investigators treated these mice with injections of YK-4-279 five days a week for 2 weeks or vehicle intraperitoneal injections on the same schedule.

The team said treatment with YK-4-279 significantly reduced white blood cell counts, nucleated erythroblasts in the peripheral blood, splenomegaly, and hepatomegaly.

They noted that mice experienced reductions in the weight of their spleens and livers without experiencing reductions in total body weight.

In addition, mice that received YK-4-279 had significantly better overall survival than control mice. The median survival times were 60.5 days and 21 days, respectively.

The investigators also noted that treated mice did not exhibit overt toxicity in the liver, spleen, or bone marrow.

“The fact that treated mice did not get sick from the YK-4-279 gives us an early indication that it might be safe to use in humans, but that is a question that can’t be answered until we conduct clinical trials,” Dr Üren said.

Nevertheless, he and his colleagues believe these results support the continued preclinical development of YK-4-279 for Ewing sarcoma, prostate cancers, and leukemias with highly homologous translocation products or with a clear ETS-driven gene signature.

Lab mouse

A small-molecule compound that has previously shown activity against Ewing sarcoma and prostate cancer may fight leukemia as well, according to preclinical research published in Oncotarget.

The compound, YK-4-279, inhibits the oncogenic activity of the fusion protein EWS-FLI1.

“EWS-FLI1 is already known to drive a rare but deadly bone cancer called Ewing sarcoma,” said study author Aykut Üren, MD, of Georgetown University Medical Center in Washington, DC.

“It also appears to drive cancer cell growth in some prostate cancers.”

ETS family fusion proteins are found in patients with acute myeloid leukemia and acute lymphoblastic leukemia as well.

So Dr Üren and his colleagues decided to create a mouse model of EWS-FLI1-induced leukemia and assess the activity of YK-4-279 in this model.

Mice with EWS-FLI1-induced leukemia presented with severe hepatomegaly, splenomegaly, and anemia, followed by rapid death.

The investigators treated these mice with injections of YK-4-279 five days a week for 2 weeks or vehicle intraperitoneal injections on the same schedule.

The team said treatment with YK-4-279 significantly reduced white blood cell counts, nucleated erythroblasts in the peripheral blood, splenomegaly, and hepatomegaly.

They noted that mice experienced reductions in the weight of their spleens and livers without experiencing reductions in total body weight.

In addition, mice that received YK-4-279 had significantly better overall survival than control mice. The median survival times were 60.5 days and 21 days, respectively.

The investigators also noted that treated mice did not exhibit overt toxicity in the liver, spleen, or bone marrow.

“The fact that treated mice did not get sick from the YK-4-279 gives us an early indication that it might be safe to use in humans, but that is a question that can’t be answered until we conduct clinical trials,” Dr Üren said.

Nevertheless, he and his colleagues believe these results support the continued preclinical development of YK-4-279 for Ewing sarcoma, prostate cancers, and leukemias with highly homologous translocation products or with a clear ETS-driven gene signature.

Lab mouse

A small-molecule compound that has previously shown activity against Ewing sarcoma and prostate cancer may fight leukemia as well, according to preclinical research published in Oncotarget.

The compound, YK-4-279, inhibits the oncogenic activity of the fusion protein EWS-FLI1.

“EWS-FLI1 is already known to drive a rare but deadly bone cancer called Ewing sarcoma,” said study author Aykut Üren, MD, of Georgetown University Medical Center in Washington, DC.

“It also appears to drive cancer cell growth in some prostate cancers.”

ETS family fusion proteins are found in patients with acute myeloid leukemia and acute lymphoblastic leukemia as well.

So Dr Üren and his colleagues decided to create a mouse model of EWS-FLI1-induced leukemia and assess the activity of YK-4-279 in this model.

Mice with EWS-FLI1-induced leukemia presented with severe hepatomegaly, splenomegaly, and anemia, followed by rapid death.

The investigators treated these mice with injections of YK-4-279 five days a week for 2 weeks or vehicle intraperitoneal injections on the same schedule.

The team said treatment with YK-4-279 significantly reduced white blood cell counts, nucleated erythroblasts in the peripheral blood, splenomegaly, and hepatomegaly.

They noted that mice experienced reductions in the weight of their spleens and livers without experiencing reductions in total body weight.

In addition, mice that received YK-4-279 had significantly better overall survival than control mice. The median survival times were 60.5 days and 21 days, respectively.

The investigators also noted that treated mice did not exhibit overt toxicity in the liver, spleen, or bone marrow.

“The fact that treated mice did not get sick from the YK-4-279 gives us an early indication that it might be safe to use in humans, but that is a question that can’t be answered until we conduct clinical trials,” Dr Üren said.

Nevertheless, he and his colleagues believe these results support the continued preclinical development of YK-4-279 for Ewing sarcoma, prostate cancers, and leukemias with highly homologous translocation products or with a clear ETS-driven gene signature.

Red blood cells

Researchers say they can increase the production of red blood cells (RBCs) in the lab by targeting a single gene—SH2B3.

The team used RNA interference (RNAi) to turn down SH2B3 in human hematopoietic stem and progenitor cells (HSPCs) and increased the yield of RBCs about 3- to 7-fold.

They also used CRISPR/Cas9 genome editing to shut off SH2B3 in human embryonic stem cell (hESC) lines, increasing the yield of RBCs about 3-fold.

The researchers noted that the method involving hESCs would be easier to use for large-scale production of RBCs.

Vijay Sankaran, MD, PhD, of the Broad Institute in Cambridge, Massachusetts, and his colleagues conducted this research and reported the results in Cell Stem Cell.

The researchers homed in on their target gene, SH2B3, after genome sequencing data revealed naturally occurring variations in SH2B3. These variations reduce the gene’s activity and increase RBC production.

“There’s a variation in SH2B3 found in about 40% of people that leads to modestly higher red blood cell counts,” Dr Sankaran said. “But if you look at people with really high red blood cell levels, they often have rare SH2B3 mutations. That said to us that here is a target where you can partially or completely eliminate its function as a way of increasing red blood cells robustly.”

So Dr Sankaran and his colleagues set out to see if they could use SH2B3 as a target to increase the yield of lab-based RBC production processes (as opposed to tweaking cells in culture by adding cytokines and other factors).

To do this, they first used RNAi to turn down SH2B3 in donated adult HSPCs and HSPCs from umbilical cord blood.

The team’s data confirmed that shutting off SH2B3 with RNAi skews an HSPC’s profile of cell production to favor RBCs. Adult HSPCs treated with RNAi produced 3- to 5-fold more RBCs than controls. And RNAi-treated HSPCs from cord blood produced 5- to 7-fold more RBCs than controls.

Using multiple tests, the researchers found the RBCs produced by RNAi were essentially indistinguishable from control cells.

Dr Sankaran and his colleagues recognized that this approach would be very difficult to scale up to a level that could impact the clinical need for RBCs. So, in a separate set of experiments, they used CRISPR to permanently shut off SH2B3 in hESC lines, which can be readily renewed in a lab.

The team then treated the edited cells with a cocktail of factors known to encourage blood cell production. Under these conditions, the edited hESCs produced 3 times more RBCs than controls. Again, the team could find no significant differences between RBCs from the edited stem cells and controls.

Dr Sankaran believes that SH2B3 enforces some kind of upper limit on how much RBC precursors respond to calls for more RBC production.

“This is a nice approach because it removes the brakes that normally keep cells restrained and limit how much red blood cell precursors respond to different laboratory conditions,” he said.

Dr Sankaran also believes that, with further development, the combination of CRISPR and hESCs could increase the yields and reduce the costs of producing RBCs in the lab to the level where commercial-scale manufacture could be feasible.

“This is allowing us to get close to the cost of normal donor-derived blood units,” he said. “If we can get the costs down to about $2000 per unit, that’s a reasonable cost.”

Previous research has shown it is possible to produce transfusion-grade RBCs, but the costs ranged from $8000 to $15,000 per unit of blood.

Red blood cells

Researchers say they can increase the production of red blood cells (RBCs) in the lab by targeting a single gene—SH2B3.

The team used RNA interference (RNAi) to turn down SH2B3 in human hematopoietic stem and progenitor cells (HSPCs) and increased the yield of RBCs about 3- to 7-fold.

They also used CRISPR/Cas9 genome editing to shut off SH2B3 in human embryonic stem cell (hESC) lines, increasing the yield of RBCs about 3-fold.

The researchers noted that the method involving hESCs would be easier to use for large-scale production of RBCs.

Vijay Sankaran, MD, PhD, of the Broad Institute in Cambridge, Massachusetts, and his colleagues conducted this research and reported the results in Cell Stem Cell.

The researchers homed in on their target gene, SH2B3, after genome sequencing data revealed naturally occurring variations in SH2B3. These variations reduce the gene’s activity and increase RBC production.

“There’s a variation in SH2B3 found in about 40% of people that leads to modestly higher red blood cell counts,” Dr Sankaran said. “But if you look at people with really high red blood cell levels, they often have rare SH2B3 mutations. That said to us that here is a target where you can partially or completely eliminate its function as a way of increasing red blood cells robustly.”

So Dr Sankaran and his colleagues set out to see if they could use SH2B3 as a target to increase the yield of lab-based RBC production processes (as opposed to tweaking cells in culture by adding cytokines and other factors).

To do this, they first used RNAi to turn down SH2B3 in donated adult HSPCs and HSPCs from umbilical cord blood.

The team’s data confirmed that shutting off SH2B3 with RNAi skews an HSPC’s profile of cell production to favor RBCs. Adult HSPCs treated with RNAi produced 3- to 5-fold more RBCs than controls. And RNAi-treated HSPCs from cord blood produced 5- to 7-fold more RBCs than controls.

Using multiple tests, the researchers found the RBCs produced by RNAi were essentially indistinguishable from control cells.

Dr Sankaran and his colleagues recognized that this approach would be very difficult to scale up to a level that could impact the clinical need for RBCs. So, in a separate set of experiments, they used CRISPR to permanently shut off SH2B3 in hESC lines, which can be readily renewed in a lab.

The team then treated the edited cells with a cocktail of factors known to encourage blood cell production. Under these conditions, the edited hESCs produced 3 times more RBCs than controls. Again, the team could find no significant differences between RBCs from the edited stem cells and controls.

Dr Sankaran believes that SH2B3 enforces some kind of upper limit on how much RBC precursors respond to calls for more RBC production.

“This is a nice approach because it removes the brakes that normally keep cells restrained and limit how much red blood cell precursors respond to different laboratory conditions,” he said.

Dr Sankaran also believes that, with further development, the combination of CRISPR and hESCs could increase the yields and reduce the costs of producing RBCs in the lab to the level where commercial-scale manufacture could be feasible.

“This is allowing us to get close to the cost of normal donor-derived blood units,” he said. “If we can get the costs down to about $2000 per unit, that’s a reasonable cost.”

Previous research has shown it is possible to produce transfusion-grade RBCs, but the costs ranged from $8000 to $15,000 per unit of blood.

Red blood cells

Researchers say they can increase the production of red blood cells (RBCs) in the lab by targeting a single gene—SH2B3.

The team used RNA interference (RNAi) to turn down SH2B3 in human hematopoietic stem and progenitor cells (HSPCs) and increased the yield of RBCs about 3- to 7-fold.

They also used CRISPR/Cas9 genome editing to shut off SH2B3 in human embryonic stem cell (hESC) lines, increasing the yield of RBCs about 3-fold.

The researchers noted that the method involving hESCs would be easier to use for large-scale production of RBCs.

Vijay Sankaran, MD, PhD, of the Broad Institute in Cambridge, Massachusetts, and his colleagues conducted this research and reported the results in Cell Stem Cell.

The researchers homed in on their target gene, SH2B3, after genome sequencing data revealed naturally occurring variations in SH2B3. These variations reduce the gene’s activity and increase RBC production.

“There’s a variation in SH2B3 found in about 40% of people that leads to modestly higher red blood cell counts,” Dr Sankaran said. “But if you look at people with really high red blood cell levels, they often have rare SH2B3 mutations. That said to us that here is a target where you can partially or completely eliminate its function as a way of increasing red blood cells robustly.”

So Dr Sankaran and his colleagues set out to see if they could use SH2B3 as a target to increase the yield of lab-based RBC production processes (as opposed to tweaking cells in culture by adding cytokines and other factors).

To do this, they first used RNAi to turn down SH2B3 in donated adult HSPCs and HSPCs from umbilical cord blood.

The team’s data confirmed that shutting off SH2B3 with RNAi skews an HSPC’s profile of cell production to favor RBCs. Adult HSPCs treated with RNAi produced 3- to 5-fold more RBCs than controls. And RNAi-treated HSPCs from cord blood produced 5- to 7-fold more RBCs than controls.

Using multiple tests, the researchers found the RBCs produced by RNAi were essentially indistinguishable from control cells.

Dr Sankaran and his colleagues recognized that this approach would be very difficult to scale up to a level that could impact the clinical need for RBCs. So, in a separate set of experiments, they used CRISPR to permanently shut off SH2B3 in hESC lines, which can be readily renewed in a lab.

The team then treated the edited cells with a cocktail of factors known to encourage blood cell production. Under these conditions, the edited hESCs produced 3 times more RBCs than controls. Again, the team could find no significant differences between RBCs from the edited stem cells and controls.

Dr Sankaran believes that SH2B3 enforces some kind of upper limit on how much RBC precursors respond to calls for more RBC production.

“This is a nice approach because it removes the brakes that normally keep cells restrained and limit how much red blood cell precursors respond to different laboratory conditions,” he said.

Dr Sankaran also believes that, with further development, the combination of CRISPR and hESCs could increase the yields and reduce the costs of producing RBCs in the lab to the level where commercial-scale manufacture could be feasible.

“This is allowing us to get close to the cost of normal donor-derived blood units,” he said. “If we can get the costs down to about $2000 per unit, that’s a reasonable cost.”

Previous research has shown it is possible to produce transfusion-grade RBCs, but the costs ranged from $8000 to $15,000 per unit of blood.

Child receiving RTS,S

Photo by Caitlin Kleiboer

Results of a genomic sequencing analysis appear to explain why the malaria vaccine candidate RTS,S/AS01 (Mosquirix) is more effective in some children than others.

Researchers sequenced nearly 5000 patient samples and discovered that genetic variation in the protein targeted by RTS,S influences the vaccine’s ability to ward off malaria in young children.

The variation did not appear to affect the vaccine’s efficacy for infants.

Daniel E. Neafsey, PhD, of the Broad Institute in Cambridge, Massachusetts, and his colleagues reported these findings in NEJM.

RTS,S is designed to target a fragment of the protein circumsporozoite (CS), which sits on the surface of the Plasmodium falciparum parasite.

The CS protein is capable of provoking an immune response that can prevent parasites from infecting the liver, where they typically mature and reproduce before dispersing and invading red blood cells, leading to symptomatic malaria.

RTS,S aims to trigger that response as a way to protect against the disease. However, the CS protein is genetically diverse—perhaps due to its evolutionary role in the immune response—and RTS,S includes only one allele of the protein.

With their study, Dr Neafsey and his colleagues sought to test whether alleles of CS that matched the one targeted by RTS,S were linked with better vaccine protection.

The team obtained blood samples from 4985 of the approximately 15,000 infants and children who participated in the vaccine’s phase 3 trial between 2009 and 2013.

The researchers were sent samples when the first symptomatic cases appeared in those vaccinated, as well as samples from all participants at month 14 and month 20 following vaccination.

The team used polymerase chain reaction-based next-generation sequencing of DNA extracted from the samples to survey CS protein polymorphisms. And they set out to determine whether polymorphic positions and haplotypic regions within CS had any effect on the vaccine’s efficacy against first episodes of malaria within a year of vaccination.

The researchers found that RTS,S provided at least partial protection against all strains of P falciparum. However, the vaccine was significantly more effective at preventing malaria in children with matched allele parasites than those with mismatched allele parasites.

Among children who were 5 months to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% against malaria in which parasites matched the vaccine in the entire CS protein C-terminal, compared to 33.4% against mismatched malaria (P=0.04).

The same effect was not noted in infants. Among infants 6 weeks to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy.

Previous genetic studies conducted during RTS,S’s phase 2 trials had not detected an allele-specific effect for this vaccine candidate. The current study had a larger sample size, and recent technological advances made it possible to read the genetic samples with greater sensitivity.

“This is the first study that was big enough and used a methodology that was sufficiently sensitive to detect this phenomenon,” Dr Neafsey said. “Now that we know that it exists, it contributes to our understanding of how RTS,S confers protection and informs future vaccine development efforts.”

RTS,S is the first malaria vaccine candidate to complete phase 3 trials and receive a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use.

The vaccine was originally designed by scientists at GlaxoSmithKline in 1987. It is now being developed via a public-private partnership between GlaxoSmithKline and PATH Malaria Vaccine Initiative.

The current study was supported by the National Institute of Allergy and Infectious Diseases, the Bill & Melinda Gates Foundation, and the PATH Malaria Vaccine Initiative.

Child receiving RTS,S

Photo by Caitlin Kleiboer

Results of a genomic sequencing analysis appear to explain why the malaria vaccine candidate RTS,S/AS01 (Mosquirix) is more effective in some children than others.

Researchers sequenced nearly 5000 patient samples and discovered that genetic variation in the protein targeted by RTS,S influences the vaccine’s ability to ward off malaria in young children.

The variation did not appear to affect the vaccine’s efficacy for infants.

Daniel E. Neafsey, PhD, of the Broad Institute in Cambridge, Massachusetts, and his colleagues reported these findings in NEJM.

RTS,S is designed to target a fragment of the protein circumsporozoite (CS), which sits on the surface of the Plasmodium falciparum parasite.

The CS protein is capable of provoking an immune response that can prevent parasites from infecting the liver, where they typically mature and reproduce before dispersing and invading red blood cells, leading to symptomatic malaria.

RTS,S aims to trigger that response as a way to protect against the disease. However, the CS protein is genetically diverse—perhaps due to its evolutionary role in the immune response—and RTS,S includes only one allele of the protein.

With their study, Dr Neafsey and his colleagues sought to test whether alleles of CS that matched the one targeted by RTS,S were linked with better vaccine protection.

The team obtained blood samples from 4985 of the approximately 15,000 infants and children who participated in the vaccine’s phase 3 trial between 2009 and 2013.

The researchers were sent samples when the first symptomatic cases appeared in those vaccinated, as well as samples from all participants at month 14 and month 20 following vaccination.

The team used polymerase chain reaction-based next-generation sequencing of DNA extracted from the samples to survey CS protein polymorphisms. And they set out to determine whether polymorphic positions and haplotypic regions within CS had any effect on the vaccine’s efficacy against first episodes of malaria within a year of vaccination.

The researchers found that RTS,S provided at least partial protection against all strains of P falciparum. However, the vaccine was significantly more effective at preventing malaria in children with matched allele parasites than those with mismatched allele parasites.

Among children who were 5 months to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% against malaria in which parasites matched the vaccine in the entire CS protein C-terminal, compared to 33.4% against mismatched malaria (P=0.04).

The same effect was not noted in infants. Among infants 6 weeks to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy.

Previous genetic studies conducted during RTS,S’s phase 2 trials had not detected an allele-specific effect for this vaccine candidate. The current study had a larger sample size, and recent technological advances made it possible to read the genetic samples with greater sensitivity.

“This is the first study that was big enough and used a methodology that was sufficiently sensitive to detect this phenomenon,” Dr Neafsey said. “Now that we know that it exists, it contributes to our understanding of how RTS,S confers protection and informs future vaccine development efforts.”

RTS,S is the first malaria vaccine candidate to complete phase 3 trials and receive a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use.

The vaccine was originally designed by scientists at GlaxoSmithKline in 1987. It is now being developed via a public-private partnership between GlaxoSmithKline and PATH Malaria Vaccine Initiative.

The current study was supported by the National Institute of Allergy and Infectious Diseases, the Bill & Melinda Gates Foundation, and the PATH Malaria Vaccine Initiative.

Child receiving RTS,S

Photo by Caitlin Kleiboer

Results of a genomic sequencing analysis appear to explain why the malaria vaccine candidate RTS,S/AS01 (Mosquirix) is more effective in some children than others.

Researchers sequenced nearly 5000 patient samples and discovered that genetic variation in the protein targeted by RTS,S influences the vaccine’s ability to ward off malaria in young children.

The variation did not appear to affect the vaccine’s efficacy for infants.

Daniel E. Neafsey, PhD, of the Broad Institute in Cambridge, Massachusetts, and his colleagues reported these findings in NEJM.

RTS,S is designed to target a fragment of the protein circumsporozoite (CS), which sits on the surface of the Plasmodium falciparum parasite.

The CS protein is capable of provoking an immune response that can prevent parasites from infecting the liver, where they typically mature and reproduce before dispersing and invading red blood cells, leading to symptomatic malaria.

RTS,S aims to trigger that response as a way to protect against the disease. However, the CS protein is genetically diverse—perhaps due to its evolutionary role in the immune response—and RTS,S includes only one allele of the protein.

With their study, Dr Neafsey and his colleagues sought to test whether alleles of CS that matched the one targeted by RTS,S were linked with better vaccine protection.

The team obtained blood samples from 4985 of the approximately 15,000 infants and children who participated in the vaccine’s phase 3 trial between 2009 and 2013.

The researchers were sent samples when the first symptomatic cases appeared in those vaccinated, as well as samples from all participants at month 14 and month 20 following vaccination.

The team used polymerase chain reaction-based next-generation sequencing of DNA extracted from the samples to survey CS protein polymorphisms. And they set out to determine whether polymorphic positions and haplotypic regions within CS had any effect on the vaccine’s efficacy against first episodes of malaria within a year of vaccination.

The researchers found that RTS,S provided at least partial protection against all strains of P falciparum. However, the vaccine was significantly more effective at preventing malaria in children with matched allele parasites than those with mismatched allele parasites.

Among children who were 5 months to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% against malaria in which parasites matched the vaccine in the entire CS protein C-terminal, compared to 33.4% against mismatched malaria (P=0.04).

The same effect was not noted in infants. Among infants 6 weeks to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy.

Previous genetic studies conducted during RTS,S’s phase 2 trials had not detected an allele-specific effect for this vaccine candidate. The current study had a larger sample size, and recent technological advances made it possible to read the genetic samples with greater sensitivity.

“This is the first study that was big enough and used a methodology that was sufficiently sensitive to detect this phenomenon,” Dr Neafsey said. “Now that we know that it exists, it contributes to our understanding of how RTS,S confers protection and informs future vaccine development efforts.”

RTS,S is the first malaria vaccine candidate to complete phase 3 trials and receive a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use.

The vaccine was originally designed by scientists at GlaxoSmithKline in 1987. It is now being developed via a public-private partnership between GlaxoSmithKline and PATH Malaria Vaccine Initiative.

The current study was supported by the National Institute of Allergy and Infectious Diseases, the Bill & Melinda Gates Foundation, and the PATH Malaria Vaccine Initiative.

When the American Cancer Society (ACS) updated its guidelines for screening mammography earlier this week,¹ the effect was that of a stone being tossed into a tranquil pond, generating ripples in all directions.

The new guidelines focus on women at average risk for breast cancer (TABLE 1) and were updated for the first time since 2003, based on new evidence, a new emphasis on eliminating as many screening harms as possible, and a goal of “supporting the interplay among values, preferences, informed decision making, and recommendations.”¹ Earlier ACS guidelines recommended annual screening starting at age 40.
 

The new guidelines are graded according to the strength of the rec ommendation as being either “strong” or “qualified.” The ACS defines a “strong” recommendation as one that most individuals should follow. “Adherence to this recommendation according to the guideline could be used as a quality criterion or performance indicator,” the guidelines note.¹

A “qualified” recommendation indicates that “Clinicians should acknowledge that different choices will be appropriate for different patients and that clinicians must help each patient arrive at a management decision consistent with her or his values and preferences.”¹

The recommendations are:

ACOG weighs in
Shortly after publication of the new ACS guidelines, the American College of Obstetricians and Gynecologists (ACOG) issued a formal statement in response²:

Response of the USPSTF
The US Preventive Services Task Force (USPSTF) also issued a statement in response to the new ACS guidelines:

The USPSTF currently recommends biennial screening beginning at age 50.

A leader in breast health cites pros and cons of ACS recommendations
Mark Pearlman, MD, professor of obstetrics and gynecology at the University of Michigan health system, is a nationally recognized expert on breast cancer screening. He sits on the National Comprehensive Cancer Network (NCCN) breast cancer screening and diagnosis group, helped author ACOG guidelines on mammography screening, and serves as a Contributing Editor to OBG Management.

“I believe the overall ACS mammography benefit evidence synthesis is reasonable and is in keeping with both NCCN and ACOG’s current recommendations. NCCN and ACOG mammography screening recommendations have both valued lives saved more highly than the ‘harms’ such as recalls and needle biopsies,” Dr. Pearlman says.

“If one combines ACS ‘strong’ and ‘qualified’ recommendations, ACS recommendations are similar to current ACOG and NCCN recommendations for mammography,” he adds.

Dr. Pearlman finds 7 areas of agreement between NCCN/ACOG and ACS recommendations, using both strong and qualified recommendations:

Where the ACS and ACOG/NCCN disagree is over the issue of the physical exam (abandoning CBE in average-risk women).

In regard to this last item, Dr. Pearlman says, “The ACS made a qualified recommendation against clinical breast exam. There is no high-level data to support such a marked change in practice. For example, when recommendations against breast self-examinations (BSE) were made, there were randomized controlled trials (RCTs) showing a lack of benefit and significant harms with BSE. With RCT-level data, it made sense to make a recommendation against the long-taught practice of SBE in average-risk women. That was not the case here. In fact, there are small amounts of data showing benefits of clinical breast exam.”

“One of my biggest concerns is not just the recommendation against CBE,” says Dr. Pearlman, “but that this may lead many women to interpret [this statement] as if they do not need to see their health care provider anymore. As you may recall, the American College of Physicians (ACP) recommended against annual pelvic examinations in asymptomatic patients. The ACS recommendation statement—taken together with the ACP statement—basically suggests that average-risk women don’t ever need to see a provider for a pelvic or breast examination except every 5 years for a Pap smear. That thinking does not recognize the importance of the clinical encounter (not just the CBE or pelvic exam), which is the opportunity to perform risk assessment and provide risk-reduction recommendations and healthy lifestyle recommendations.”

Radiologists resist new recommendations
Although the American College of Radiology (ACR) and the Society of Breast Imaging (SBI) agree with the ACS that mammography screening saves lives and should be available to women aged 40 and older, the 2 imaging organizations continue to recommend that annual screening begin at age 40. Their rationale: The latest ACS breast cancer screening guidelines, and earlier data used by the USPSTF to create its recommendations, both note that starting annual mammography at age 40 “saves the most lives.”

Where the organizations differ from the ACR is summed up by a formal statement on the ACR Web site: “The ACR and SBI strongly encourage women to obtain the maximum lifesaving benefits from mammography by continuing to get annual screening.”⁴

When OBG Management touched base with radiologist Barbara Monsees, MD, professor of radiology and Evens Professor of Women’s Health at Washington University Medical Center in St. Louis, Missouri, she expressed dismay at early news reports on the ACS guidelines.

“I’m dismayed that the headlines don’t seem to correlate with what the ACS actually recommended. The ACS did not state that women should wait until age 45 to begin screening. I believe the ACS was going for a more nuanced approach, but since that’s a bit complicated, I think that reporters have misconstrued what was intended,” Dr. Monsees says.

“The ACS guideline says that women between 40 and 44 years should have the opportunity to begin annual screening,” she says, noting that this recommendation was graded as “qualified.”

“The ACS states that a qualified recommendation indicates that ‘there is clear evidence of benefit of screening, but less certainty about the balance of benefits and harms, or about patients’ values and preferences, which could lead to different decisions about screening.’” The guideline also articulates the view “that the meaning of a qualified recommendation for patients is that the ‘majority of individuals in this situation would want the suggested course of action, but many would not.’ Therefore, I find it mind-boggling that this has been interpreted to mean that women should not begin screening until age 45.”¹

“It is my opinion that it is clear that if women want to achieve the most lifesaving benefit from screening, they should adhere to a schedule of yearly mammograms beginning at age 40,” says Dr. Monsees. However, she also agrees with the ACS notation that clinicians should acknowledge that “different choices will be appropriate for different patients and that clinicians must help each patient arrive at a management decision consistent with her values and preferences.”¹

The word from an expert ObGyn
“By changing its guidance to begin screening at age 45 instead of 40, and in recommending biennial rather than annual screens in women 55 years of age and older, the updated ACS guidance will reduce harms (overdiagnosis and unnecessary additional imaging and biopsies) and moves closer to USPSTF guidance,” says Andrew M. Kaunitz, MD. He is University of Florida Research Foundation Professor and Associate Chairman, Department of Obstetrics and Gynecology, at the University of Florida College of Medicine–Jacksonville. He also serves on the OBG Management Board of Editors.

“As one editorialist points out, the ACS recommendation that women begin screening at age 45 years is based on observational comparisons of screened and unscreened cohorts—a type of analysis which the USPSTF does not consider due to concerns regarding bias,” notes Dr. Kaunitz.⁵

“The ACS recommendation for annual screening in women aged 45 to 54 is largely based on the findings of a report showing that, for premenopausal (but not postmenopausal) women, tumor stage was higher and size larger for screen-detected lesions among women undergoing biennial screens."⁶

As for the recommendation against screening CBE, Dr. Kaunitz considers that “a dramatic change from prior guidance. It is based on the absence of data finding benefits with CBE (alone or with screening mammography). Furthermore, the updated ACS guidance does not change its 2003 guidance, which does not support routine performance of or instruction regarding SBE.”

“These updated ACS guidelines should result in more women starting screening mammograms later in life, and they endorse biennial screening for many women, meaning that patients following ACS guidance will have fewer lifetime screens than with earlier recommendations,” says Dr. Kaunitz.

“Another plus is that performing fewer breast examinations during well-woman visits will allow us more time to assess family history and other risk factors for breast cancer, and to discuss screening recommendations.”

The bottom line
What is one to make of the many viewpoints on screening? For now, it probably is best to adhere to either the new ACS guidelines or current ACOG guidelines (TABLE 2), says OBG Management Editor in Chief Robert L. Barbieri, MD. He is chief of the Department of Obstetrics and Gynecology at Brigham and Women’s Hospital in Boston, and Kate Macy Ladd Professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School.
 

ACOG recommends screening mammography every year for women starting at age 40. ACOG also states that “breast self-awareness has the potential to detect palpable breast cancer and can be recommended”; it also recommends CBE every year for women aged 19 or older.

These recommendations may change early next year, after ACOG convenes a consensus conference on the subject. The aim: “To develop a consistent set of uniform guidelines for breast cancer screening that can be implemented nationwide. Major organizations and providers of women’s health care, including ACS, will gather to evaluate and interpret the data in greater detail.”²

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

When the American Cancer Society (ACS) updated its guidelines for screening mammography earlier this week,¹ the effect was that of a stone being tossed into a tranquil pond, generating ripples in all directions.

The new guidelines focus on women at average risk for breast cancer (TABLE 1) and were updated for the first time since 2003, based on new evidence, a new emphasis on eliminating as many screening harms as possible, and a goal of “supporting the interplay among values, preferences, informed decision making, and recommendations.”¹ Earlier ACS guidelines recommended annual screening starting at age 40.
 

The new guidelines are graded according to the strength of the rec ommendation as being either “strong” or “qualified.” The ACS defines a “strong” recommendation as one that most individuals should follow. “Adherence to this recommendation according to the guideline could be used as a quality criterion or performance indicator,” the guidelines note.¹

A “qualified” recommendation indicates that “Clinicians should acknowledge that different choices will be appropriate for different patients and that clinicians must help each patient arrive at a management decision consistent with her or his values and preferences.”¹

The recommendations are:

ACOG weighs in
Shortly after publication of the new ACS guidelines, the American College of Obstetricians and Gynecologists (ACOG) issued a formal statement in response²:

Response of the USPSTF
The US Preventive Services Task Force (USPSTF) also issued a statement in response to the new ACS guidelines:

The USPSTF currently recommends biennial screening beginning at age 50.

A leader in breast health cites pros and cons of ACS recommendations
Mark Pearlman, MD, professor of obstetrics and gynecology at the University of Michigan health system, is a nationally recognized expert on breast cancer screening. He sits on the National Comprehensive Cancer Network (NCCN) breast cancer screening and diagnosis group, helped author ACOG guidelines on mammography screening, and serves as a Contributing Editor to OBG Management.

“I believe the overall ACS mammography benefit evidence synthesis is reasonable and is in keeping with both NCCN and ACOG’s current recommendations. NCCN and ACOG mammography screening recommendations have both valued lives saved more highly than the ‘harms’ such as recalls and needle biopsies,” Dr. Pearlman says.

“If one combines ACS ‘strong’ and ‘qualified’ recommendations, ACS recommendations are similar to current ACOG and NCCN recommendations for mammography,” he adds.

Dr. Pearlman finds 7 areas of agreement between NCCN/ACOG and ACS recommendations, using both strong and qualified recommendations:

Where the ACS and ACOG/NCCN disagree is over the issue of the physical exam (abandoning CBE in average-risk women).

In regard to this last item, Dr. Pearlman says, “The ACS made a qualified recommendation against clinical breast exam. There is no high-level data to support such a marked change in practice. For example, when recommendations against breast self-examinations (BSE) were made, there were randomized controlled trials (RCTs) showing a lack of benefit and significant harms with BSE. With RCT-level data, it made sense to make a recommendation against the long-taught practice of SBE in average-risk women. That was not the case here. In fact, there are small amounts of data showing benefits of clinical breast exam.”

“One of my biggest concerns is not just the recommendation against CBE,” says Dr. Pearlman, “but that this may lead many women to interpret [this statement] as if they do not need to see their health care provider anymore. As you may recall, the American College of Physicians (ACP) recommended against annual pelvic examinations in asymptomatic patients. The ACS recommendation statement—taken together with the ACP statement—basically suggests that average-risk women don’t ever need to see a provider for a pelvic or breast examination except every 5 years for a Pap smear. That thinking does not recognize the importance of the clinical encounter (not just the CBE or pelvic exam), which is the opportunity to perform risk assessment and provide risk-reduction recommendations and healthy lifestyle recommendations.”

Radiologists resist new recommendations
Although the American College of Radiology (ACR) and the Society of Breast Imaging (SBI) agree with the ACS that mammography screening saves lives and should be available to women aged 40 and older, the 2 imaging organizations continue to recommend that annual screening begin at age 40. Their rationale: The latest ACS breast cancer screening guidelines, and earlier data used by the USPSTF to create its recommendations, both note that starting annual mammography at age 40 “saves the most lives.”

Where the organizations differ from the ACR is summed up by a formal statement on the ACR Web site: “The ACR and SBI strongly encourage women to obtain the maximum lifesaving benefits from mammography by continuing to get annual screening.”⁴

When OBG Management touched base with radiologist Barbara Monsees, MD, professor of radiology and Evens Professor of Women’s Health at Washington University Medical Center in St. Louis, Missouri, she expressed dismay at early news reports on the ACS guidelines.

“I’m dismayed that the headlines don’t seem to correlate with what the ACS actually recommended. The ACS did not state that women should wait until age 45 to begin screening. I believe the ACS was going for a more nuanced approach, but since that’s a bit complicated, I think that reporters have misconstrued what was intended,” Dr. Monsees says.

“The ACS guideline says that women between 40 and 44 years should have the opportunity to begin annual screening,” she says, noting that this recommendation was graded as “qualified.”

“The ACS states that a qualified recommendation indicates that ‘there is clear evidence of benefit of screening, but less certainty about the balance of benefits and harms, or about patients’ values and preferences, which could lead to different decisions about screening.’” The guideline also articulates the view “that the meaning of a qualified recommendation for patients is that the ‘majority of individuals in this situation would want the suggested course of action, but many would not.’ Therefore, I find it mind-boggling that this has been interpreted to mean that women should not begin screening until age 45.”¹

“It is my opinion that it is clear that if women want to achieve the most lifesaving benefit from screening, they should adhere to a schedule of yearly mammograms beginning at age 40,” says Dr. Monsees. However, she also agrees with the ACS notation that clinicians should acknowledge that “different choices will be appropriate for different patients and that clinicians must help each patient arrive at a management decision consistent with her values and preferences.”¹

The word from an expert ObGyn
“By changing its guidance to begin screening at age 45 instead of 40, and in recommending biennial rather than annual screens in women 55 years of age and older, the updated ACS guidance will reduce harms (overdiagnosis and unnecessary additional imaging and biopsies) and moves closer to USPSTF guidance,” says Andrew M. Kaunitz, MD. He is University of Florida Research Foundation Professor and Associate Chairman, Department of Obstetrics and Gynecology, at the University of Florida College of Medicine–Jacksonville. He also serves on the OBG Management Board of Editors.

“As one editorialist points out, the ACS recommendation that women begin screening at age 45 years is based on observational comparisons of screened and unscreened cohorts—a type of analysis which the USPSTF does not consider due to concerns regarding bias,” notes Dr. Kaunitz.⁵

“The ACS recommendation for annual screening in women aged 45 to 54 is largely based on the findings of a report showing that, for premenopausal (but not postmenopausal) women, tumor stage was higher and size larger for screen-detected lesions among women undergoing biennial screens."⁶

As for the recommendation against screening CBE, Dr. Kaunitz considers that “a dramatic change from prior guidance. It is based on the absence of data finding benefits with CBE (alone or with screening mammography). Furthermore, the updated ACS guidance does not change its 2003 guidance, which does not support routine performance of or instruction regarding SBE.”

“These updated ACS guidelines should result in more women starting screening mammograms later in life, and they endorse biennial screening for many women, meaning that patients following ACS guidance will have fewer lifetime screens than with earlier recommendations,” says Dr. Kaunitz.

“Another plus is that performing fewer breast examinations during well-woman visits will allow us more time to assess family history and other risk factors for breast cancer, and to discuss screening recommendations.”

The bottom line
What is one to make of the many viewpoints on screening? For now, it probably is best to adhere to either the new ACS guidelines or current ACOG guidelines (TABLE 2), says OBG Management Editor in Chief Robert L. Barbieri, MD. He is chief of the Department of Obstetrics and Gynecology at Brigham and Women’s Hospital in Boston, and Kate Macy Ladd Professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School.
 

ACOG recommends screening mammography every year for women starting at age 40. ACOG also states that “breast self-awareness has the potential to detect palpable breast cancer and can be recommended”; it also recommends CBE every year for women aged 19 or older.

These recommendations may change early next year, after ACOG convenes a consensus conference on the subject. The aim: “To develop a consistent set of uniform guidelines for breast cancer screening that can be implemented nationwide. Major organizations and providers of women’s health care, including ACS, will gather to evaluate and interpret the data in greater detail.”²

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

When the American Cancer Society (ACS) updated its guidelines for screening mammography earlier this week,¹ the effect was that of a stone being tossed into a tranquil pond, generating ripples in all directions.

The new guidelines focus on women at average risk for breast cancer (TABLE 1) and were updated for the first time since 2003, based on new evidence, a new emphasis on eliminating as many screening harms as possible, and a goal of “supporting the interplay among values, preferences, informed decision making, and recommendations.”¹ Earlier ACS guidelines recommended annual screening starting at age 40.
 

The new guidelines are graded according to the strength of the rec ommendation as being either “strong” or “qualified.” The ACS defines a “strong” recommendation as one that most individuals should follow. “Adherence to this recommendation according to the guideline could be used as a quality criterion or performance indicator,” the guidelines note.¹

A “qualified” recommendation indicates that “Clinicians should acknowledge that different choices will be appropriate for different patients and that clinicians must help each patient arrive at a management decision consistent with her or his values and preferences.”¹

The recommendations are:

ACOG weighs in
Shortly after publication of the new ACS guidelines, the American College of Obstetricians and Gynecologists (ACOG) issued a formal statement in response²:

Response of the USPSTF
The US Preventive Services Task Force (USPSTF) also issued a statement in response to the new ACS guidelines:

The USPSTF currently recommends biennial screening beginning at age 50.

A leader in breast health cites pros and cons of ACS recommendations
Mark Pearlman, MD, professor of obstetrics and gynecology at the University of Michigan health system, is a nationally recognized expert on breast cancer screening. He sits on the National Comprehensive Cancer Network (NCCN) breast cancer screening and diagnosis group, helped author ACOG guidelines on mammography screening, and serves as a Contributing Editor to OBG Management.

“I believe the overall ACS mammography benefit evidence synthesis is reasonable and is in keeping with both NCCN and ACOG’s current recommendations. NCCN and ACOG mammography screening recommendations have both valued lives saved more highly than the ‘harms’ such as recalls and needle biopsies,” Dr. Pearlman says.

“If one combines ACS ‘strong’ and ‘qualified’ recommendations, ACS recommendations are similar to current ACOG and NCCN recommendations for mammography,” he adds.

Dr. Pearlman finds 7 areas of agreement between NCCN/ACOG and ACS recommendations, using both strong and qualified recommendations:

Where the ACS and ACOG/NCCN disagree is over the issue of the physical exam (abandoning CBE in average-risk women).

In regard to this last item, Dr. Pearlman says, “The ACS made a qualified recommendation against clinical breast exam. There is no high-level data to support such a marked change in practice. For example, when recommendations against breast self-examinations (BSE) were made, there were randomized controlled trials (RCTs) showing a lack of benefit and significant harms with BSE. With RCT-level data, it made sense to make a recommendation against the long-taught practice of SBE in average-risk women. That was not the case here. In fact, there are small amounts of data showing benefits of clinical breast exam.”

“One of my biggest concerns is not just the recommendation against CBE,” says Dr. Pearlman, “but that this may lead many women to interpret [this statement] as if they do not need to see their health care provider anymore. As you may recall, the American College of Physicians (ACP) recommended against annual pelvic examinations in asymptomatic patients. The ACS recommendation statement—taken together with the ACP statement—basically suggests that average-risk women don’t ever need to see a provider for a pelvic or breast examination except every 5 years for a Pap smear. That thinking does not recognize the importance of the clinical encounter (not just the CBE or pelvic exam), which is the opportunity to perform risk assessment and provide risk-reduction recommendations and healthy lifestyle recommendations.”

Radiologists resist new recommendations
Although the American College of Radiology (ACR) and the Society of Breast Imaging (SBI) agree with the ACS that mammography screening saves lives and should be available to women aged 40 and older, the 2 imaging organizations continue to recommend that annual screening begin at age 40. Their rationale: The latest ACS breast cancer screening guidelines, and earlier data used by the USPSTF to create its recommendations, both note that starting annual mammography at age 40 “saves the most lives.”

Where the organizations differ from the ACR is summed up by a formal statement on the ACR Web site: “The ACR and SBI strongly encourage women to obtain the maximum lifesaving benefits from mammography by continuing to get annual screening.”⁴

When OBG Management touched base with radiologist Barbara Monsees, MD, professor of radiology and Evens Professor of Women’s Health at Washington University Medical Center in St. Louis, Missouri, she expressed dismay at early news reports on the ACS guidelines.

“I’m dismayed that the headlines don’t seem to correlate with what the ACS actually recommended. The ACS did not state that women should wait until age 45 to begin screening. I believe the ACS was going for a more nuanced approach, but since that’s a bit complicated, I think that reporters have misconstrued what was intended,” Dr. Monsees says.

“The ACS guideline says that women between 40 and 44 years should have the opportunity to begin annual screening,” she says, noting that this recommendation was graded as “qualified.”

“The ACS states that a qualified recommendation indicates that ‘there is clear evidence of benefit of screening, but less certainty about the balance of benefits and harms, or about patients’ values and preferences, which could lead to different decisions about screening.’” The guideline also articulates the view “that the meaning of a qualified recommendation for patients is that the ‘majority of individuals in this situation would want the suggested course of action, but many would not.’ Therefore, I find it mind-boggling that this has been interpreted to mean that women should not begin screening until age 45.”¹

“It is my opinion that it is clear that if women want to achieve the most lifesaving benefit from screening, they should adhere to a schedule of yearly mammograms beginning at age 40,” says Dr. Monsees. However, she also agrees with the ACS notation that clinicians should acknowledge that “different choices will be appropriate for different patients and that clinicians must help each patient arrive at a management decision consistent with her values and preferences.”¹

The word from an expert ObGyn
“By changing its guidance to begin screening at age 45 instead of 40, and in recommending biennial rather than annual screens in women 55 years of age and older, the updated ACS guidance will reduce harms (overdiagnosis and unnecessary additional imaging and biopsies) and moves closer to USPSTF guidance,” says Andrew M. Kaunitz, MD. He is University of Florida Research Foundation Professor and Associate Chairman, Department of Obstetrics and Gynecology, at the University of Florida College of Medicine–Jacksonville. He also serves on the OBG Management Board of Editors.

“As one editorialist points out, the ACS recommendation that women begin screening at age 45 years is based on observational comparisons of screened and unscreened cohorts—a type of analysis which the USPSTF does not consider due to concerns regarding bias,” notes Dr. Kaunitz.⁵

“The ACS recommendation for annual screening in women aged 45 to 54 is largely based on the findings of a report showing that, for premenopausal (but not postmenopausal) women, tumor stage was higher and size larger for screen-detected lesions among women undergoing biennial screens."⁶

As for the recommendation against screening CBE, Dr. Kaunitz considers that “a dramatic change from prior guidance. It is based on the absence of data finding benefits with CBE (alone or with screening mammography). Furthermore, the updated ACS guidance does not change its 2003 guidance, which does not support routine performance of or instruction regarding SBE.”

“These updated ACS guidelines should result in more women starting screening mammograms later in life, and they endorse biennial screening for many women, meaning that patients following ACS guidance will have fewer lifetime screens than with earlier recommendations,” says Dr. Kaunitz.

“Another plus is that performing fewer breast examinations during well-woman visits will allow us more time to assess family history and other risk factors for breast cancer, and to discuss screening recommendations.”

The bottom line
What is one to make of the many viewpoints on screening? For now, it probably is best to adhere to either the new ACS guidelines or current ACOG guidelines (TABLE 2), says OBG Management Editor in Chief Robert L. Barbieri, MD. He is chief of the Department of Obstetrics and Gynecology at Brigham and Women’s Hospital in Boston, and Kate Macy Ladd Professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School.
 

ACOG recommends screening mammography every year for women starting at age 40. ACOG also states that “breast self-awareness has the potential to detect palpable breast cancer and can be recommended”; it also recommends CBE every year for women aged 19 or older.

These recommendations may change early next year, after ACOG convenes a consensus conference on the subject. The aim: “To develop a consistent set of uniform guidelines for breast cancer screening that can be implemented nationwide. Major organizations and providers of women’s health care, including ACS, will gather to evaluate and interpret the data in greater detail.”²

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.