Kari Oakes

AUSTIN, TEXAS – When the check box for ordering formula for newborns was removed as a standard newborn order option in the electronic health record (EHR), rates of exclusive breastfeeding climbed significantly in Los Angeles County hospitals, according to a recent study.

“The saying, ‘out of sight, out of mind’ cannot be overstated when it comes to physician order entry,” wrote Ramy Eskander, MD, and his colleagues in the poster accompanying the presentation at the annual clinical and scientific sessions of the American College of Obstetricians and Gynecologists.

In a video interview, Dr. Eskander said that he and his colleagues at the University of California, Los Angeles, were looking for an intervention that would use the EHR as a quality improvement tool.

What they decided to do was to see “how could we possibly ‘get in the way’ and have an intervention between the provider and the patient that didn’t necessarily involve much work on the provider’s end, that had a significant impact on the back end,” he said. What they ended up doing was remove the order to request formula for mothers from the physician order set in the EHR.

Study data were collected in three stages for the academic tertiary care hospital within the Los Angeles County Department of Health Services system.

First, Dr. Eskander and his colleagues collected baseline data from January to July of 2016. Then, data were collected from July to the end of 2016, while a campaign was underway to bring staff and patients up to speed on the benefits of exclusive breastfeeding. There were no statistically significant differences in the rates of exclusive breastfeeding on discharge between these two time periods, when rates hovered between 30% and 40%.

The final data collection period began in January 2017. At that time, the option to order formula for a newborn was removed as an option for the EHR newborn order set.

“When we did that, providers weren’t looking at the possibility of having that easy check box right there to fill in … and we know that when people have to go through more steps, they invariably don’t do it,” Dr. Eskander said.

He and his colleagues saw an almost immediate leap in rates of exclusive breastfeeding once clinicians had to click through an additional set of screens to reach the formula order. Once the formula order was removed, breastfeeding rates rose from 40.57% to 53.90% (P less than .001). Rates have been sustained since the removal of the EHR option for formula.

There was no difference in how infants fared after the intervention, said Dr. Eskander. “The outcomes for those infants was identical. There were no increased NICU admissions, there were no increased poor outcomes.”

Length of stay remained the same as well. “The babies were being discharged in the same state of health, just more of them were getting breast milk only, and we know the benefits that tends to portend,” he added.

There was some initial grumbling when the formula order was pulled from the newborn order set, he conceded. “The providers were not very happy about having to look for the newborn order for formula.” However, it took just about a month for the new workflow to seem normal, he said.

Dr. Eskander envisions a future where the EHR is “smart” enough to prompt appropriate orders and interventions for serious conditions such as preeclampsia. The electronic record, he said, could recognize the maternal diagnosis “and immediately create a system and structure around that mother to be able to help protect her and her baby. ... then having those diagnoses be able to drive outcomes can be very significant.”

Dr. Eskander reported no relevant financial disclosures.

[email protected]

SOURCE: Eskander, R et al. ACOG 2018, Abstract 31I.

AUSTIN, TEXAS – When the check box for ordering formula for newborns was removed as a standard newborn order option in the electronic health record (EHR), rates of exclusive breastfeeding climbed significantly in Los Angeles County hospitals, according to a recent study.

“The saying, ‘out of sight, out of mind’ cannot be overstated when it comes to physician order entry,” wrote Ramy Eskander, MD, and his colleagues in the poster accompanying the presentation at the annual clinical and scientific sessions of the American College of Obstetricians and Gynecologists.

In a video interview, Dr. Eskander said that he and his colleagues at the University of California, Los Angeles, were looking for an intervention that would use the EHR as a quality improvement tool.

What they decided to do was to see “how could we possibly ‘get in the way’ and have an intervention between the provider and the patient that didn’t necessarily involve much work on the provider’s end, that had a significant impact on the back end,” he said. What they ended up doing was remove the order to request formula for mothers from the physician order set in the EHR.

Study data were collected in three stages for the academic tertiary care hospital within the Los Angeles County Department of Health Services system.

First, Dr. Eskander and his colleagues collected baseline data from January to July of 2016. Then, data were collected from July to the end of 2016, while a campaign was underway to bring staff and patients up to speed on the benefits of exclusive breastfeeding. There were no statistically significant differences in the rates of exclusive breastfeeding on discharge between these two time periods, when rates hovered between 30% and 40%.

The final data collection period began in January 2017. At that time, the option to order formula for a newborn was removed as an option for the EHR newborn order set.

“When we did that, providers weren’t looking at the possibility of having that easy check box right there to fill in … and we know that when people have to go through more steps, they invariably don’t do it,” Dr. Eskander said.

He and his colleagues saw an almost immediate leap in rates of exclusive breastfeeding once clinicians had to click through an additional set of screens to reach the formula order. Once the formula order was removed, breastfeeding rates rose from 40.57% to 53.90% (P less than .001). Rates have been sustained since the removal of the EHR option for formula.

There was no difference in how infants fared after the intervention, said Dr. Eskander. “The outcomes for those infants was identical. There were no increased NICU admissions, there were no increased poor outcomes.”

Length of stay remained the same as well. “The babies were being discharged in the same state of health, just more of them were getting breast milk only, and we know the benefits that tends to portend,” he added.

There was some initial grumbling when the formula order was pulled from the newborn order set, he conceded. “The providers were not very happy about having to look for the newborn order for formula.” However, it took just about a month for the new workflow to seem normal, he said.

Dr. Eskander envisions a future where the EHR is “smart” enough to prompt appropriate orders and interventions for serious conditions such as preeclampsia. The electronic record, he said, could recognize the maternal diagnosis “and immediately create a system and structure around that mother to be able to help protect her and her baby. ... then having those diagnoses be able to drive outcomes can be very significant.”

Dr. Eskander reported no relevant financial disclosures.

[email protected]

SOURCE: Eskander, R et al. ACOG 2018, Abstract 31I.

AUSTIN, TEXAS – When the check box for ordering formula for newborns was removed as a standard newborn order option in the electronic health record (EHR), rates of exclusive breastfeeding climbed significantly in Los Angeles County hospitals, according to a recent study.

“The saying, ‘out of sight, out of mind’ cannot be overstated when it comes to physician order entry,” wrote Ramy Eskander, MD, and his colleagues in the poster accompanying the presentation at the annual clinical and scientific sessions of the American College of Obstetricians and Gynecologists.

In a video interview, Dr. Eskander said that he and his colleagues at the University of California, Los Angeles, were looking for an intervention that would use the EHR as a quality improvement tool.

What they decided to do was to see “how could we possibly ‘get in the way’ and have an intervention between the provider and the patient that didn’t necessarily involve much work on the provider’s end, that had a significant impact on the back end,” he said. What they ended up doing was remove the order to request formula for mothers from the physician order set in the EHR.

Study data were collected in three stages for the academic tertiary care hospital within the Los Angeles County Department of Health Services system.

First, Dr. Eskander and his colleagues collected baseline data from January to July of 2016. Then, data were collected from July to the end of 2016, while a campaign was underway to bring staff and patients up to speed on the benefits of exclusive breastfeeding. There were no statistically significant differences in the rates of exclusive breastfeeding on discharge between these two time periods, when rates hovered between 30% and 40%.

The final data collection period began in January 2017. At that time, the option to order formula for a newborn was removed as an option for the EHR newborn order set.

“When we did that, providers weren’t looking at the possibility of having that easy check box right there to fill in … and we know that when people have to go through more steps, they invariably don’t do it,” Dr. Eskander said.

He and his colleagues saw an almost immediate leap in rates of exclusive breastfeeding once clinicians had to click through an additional set of screens to reach the formula order. Once the formula order was removed, breastfeeding rates rose from 40.57% to 53.90% (P less than .001). Rates have been sustained since the removal of the EHR option for formula.

There was no difference in how infants fared after the intervention, said Dr. Eskander. “The outcomes for those infants was identical. There were no increased NICU admissions, there were no increased poor outcomes.”

Length of stay remained the same as well. “The babies were being discharged in the same state of health, just more of them were getting breast milk only, and we know the benefits that tends to portend,” he added.

There was some initial grumbling when the formula order was pulled from the newborn order set, he conceded. “The providers were not very happy about having to look for the newborn order for formula.” However, it took just about a month for the new workflow to seem normal, he said.

Dr. Eskander envisions a future where the EHR is “smart” enough to prompt appropriate orders and interventions for serious conditions such as preeclampsia. The electronic record, he said, could recognize the maternal diagnosis “and immediately create a system and structure around that mother to be able to help protect her and her baby. ... then having those diagnoses be able to drive outcomes can be very significant.”

Dr. Eskander reported no relevant financial disclosures.

[email protected]

SOURCE: Eskander, R et al. ACOG 2018, Abstract 31I.

AUSTIN, TEXAS – The experiences of one safety net hospital showed the feasibility of delivering prenatal care to low-risk, uninsured women in a prepaid, bundled package.

Women with low-risk pregnancies saw quality of care better than that provided with Medicaid coverage when receiving bundled care. The adjusted odds ratio for predefined adequacy of care was 3.75 for the low-risk bundled care recipients compared with those on Medicaid (P = .015), according to the experience at Grady Memorial Hospital, Atlanta, presented at the annual clinical and scientific sessions of the American College of Obstetricians and Gynecologists.

For hospitals with large numbers of undocumented patients and others who are uninsured but ineligible for Medicaid, considerable cost savings could be realized, said Erin Duncan, MD, who completed the work while in training at Emory University.

“Using data from previous studies, Grady Memorial Hospital could see a savings of over $1 million per year by providing care to its undocumented population,” she and her collaborators wrote in the poster accompanying the presentation.

Dr. Duncan said that since implementation in 2010, about 40% of deliveries at the facility have occurred under the “Grady Healthy Baby” (GHB) bundle.

The one-payment package of bundled prenatal care was developed assuming that most participants would have low-risk pregnancies, said Dr. Duncan, who is currently an ob.gyn. in private practice in the Atlanta area.

To look further into maternal and pregnancy characteristics of GHB participants and compare them with those on Medicaid, Dr. Duncan and her collaborators performed a retrospective cohort study. Examining viable singleton pregnancies delivered at Grady between 2011 and 2014, the investigators compared 100 randomly selected GHB participants with 100 randomly selected Medicaid participants.

Comparing patients receiving care under GHB and Medicaid, Dr. Duncan and her colleagues found that “GHB participants were older, more likely to be Hispanic, and less likely to be black compared to Medicaid recipients (P less than .001 for all,)” they wrote in the poster accompanying the presentation.

Hispanic patients made up 59% of the GHB group, compared with 8% of the Medicaid group, said Dr. Duncan, adding in an interview that over half of Hispanics in the state of Georgia during the study period were undocumented.

Parity was similar between the two groups, as were gestational age at delivery and mode of delivery.

In their analysis, Dr. Duncan and her collaborators looked at both complexity and adequacy of care for the 200 patients studied. They found that there was no significant difference in the number of patients in each care group who remained low risk throughout their pregnancies, transitioned from low risk to high risk, or entered prenatal care with a high risk pregnancy, a circumstance that occurred in about 1 in 10 pregnancies.

For the approximately 50% of patients who remained low risk through their pregnancies, care under the GHB model was significantly more likely to be assessed as adequate throughout pregnancy than for those patients on Medicaid (61.7% vs 35.5%, P = .001).

Patients who became high risk during prenatal care were no more likely to receive adequate care under one model than the other.

For high risk patients, delivery of adequate care happened only under the Medicaid care model. Numbers in this group were small; 7 of 100 GHB and 15 of 100 Medicaid patients entered prenatal care with high risk pregnancies. However, no high risk GHB patients received adequate care, while that standard was met for 80% of the Medicaid patients (P less than .001).

Adequacy of care was assessed using the Kotelchuck index for low-risk pregnancies; this model assumes care is “adequate” when 80% of the number of expected visits were attended by the woman receiving prenatal care. Additionally, care was deemed adequate for high-risk pregnancies if at least 80% of the number of expected ultrasound appointments were attended.

“In the current political climate, this study has implications for all pregnancies that begin as uninsured, regardless of maternal documentation status,” wrote Dr. Duncan and her colleagues.

Dr. Duncan reported no conflicts of interest.

[email protected]

SOURCE: Duncan, E et al. ACOG 2018, Abstract 28C.

AUSTIN, TEXAS – The experiences of one safety net hospital showed the feasibility of delivering prenatal care to low-risk, uninsured women in a prepaid, bundled package.

Women with low-risk pregnancies saw quality of care better than that provided with Medicaid coverage when receiving bundled care. The adjusted odds ratio for predefined adequacy of care was 3.75 for the low-risk bundled care recipients compared with those on Medicaid (P = .015), according to the experience at Grady Memorial Hospital, Atlanta, presented at the annual clinical and scientific sessions of the American College of Obstetricians and Gynecologists.

For hospitals with large numbers of undocumented patients and others who are uninsured but ineligible for Medicaid, considerable cost savings could be realized, said Erin Duncan, MD, who completed the work while in training at Emory University.

“Using data from previous studies, Grady Memorial Hospital could see a savings of over $1 million per year by providing care to its undocumented population,” she and her collaborators wrote in the poster accompanying the presentation.

Dr. Duncan said that since implementation in 2010, about 40% of deliveries at the facility have occurred under the “Grady Healthy Baby” (GHB) bundle.

The one-payment package of bundled prenatal care was developed assuming that most participants would have low-risk pregnancies, said Dr. Duncan, who is currently an ob.gyn. in private practice in the Atlanta area.

To look further into maternal and pregnancy characteristics of GHB participants and compare them with those on Medicaid, Dr. Duncan and her collaborators performed a retrospective cohort study. Examining viable singleton pregnancies delivered at Grady between 2011 and 2014, the investigators compared 100 randomly selected GHB participants with 100 randomly selected Medicaid participants.

Comparing patients receiving care under GHB and Medicaid, Dr. Duncan and her colleagues found that “GHB participants were older, more likely to be Hispanic, and less likely to be black compared to Medicaid recipients (P less than .001 for all,)” they wrote in the poster accompanying the presentation.

Hispanic patients made up 59% of the GHB group, compared with 8% of the Medicaid group, said Dr. Duncan, adding in an interview that over half of Hispanics in the state of Georgia during the study period were undocumented.

Parity was similar between the two groups, as were gestational age at delivery and mode of delivery.

In their analysis, Dr. Duncan and her collaborators looked at both complexity and adequacy of care for the 200 patients studied. They found that there was no significant difference in the number of patients in each care group who remained low risk throughout their pregnancies, transitioned from low risk to high risk, or entered prenatal care with a high risk pregnancy, a circumstance that occurred in about 1 in 10 pregnancies.

For the approximately 50% of patients who remained low risk through their pregnancies, care under the GHB model was significantly more likely to be assessed as adequate throughout pregnancy than for those patients on Medicaid (61.7% vs 35.5%, P = .001).

Patients who became high risk during prenatal care were no more likely to receive adequate care under one model than the other.

For high risk patients, delivery of adequate care happened only under the Medicaid care model. Numbers in this group were small; 7 of 100 GHB and 15 of 100 Medicaid patients entered prenatal care with high risk pregnancies. However, no high risk GHB patients received adequate care, while that standard was met for 80% of the Medicaid patients (P less than .001).

Adequacy of care was assessed using the Kotelchuck index for low-risk pregnancies; this model assumes care is “adequate” when 80% of the number of expected visits were attended by the woman receiving prenatal care. Additionally, care was deemed adequate for high-risk pregnancies if at least 80% of the number of expected ultrasound appointments were attended.

“In the current political climate, this study has implications for all pregnancies that begin as uninsured, regardless of maternal documentation status,” wrote Dr. Duncan and her colleagues.

Dr. Duncan reported no conflicts of interest.

[email protected]

SOURCE: Duncan, E et al. ACOG 2018, Abstract 28C.

AUSTIN, TEXAS – The experiences of one safety net hospital showed the feasibility of delivering prenatal care to low-risk, uninsured women in a prepaid, bundled package.

Women with low-risk pregnancies saw quality of care better than that provided with Medicaid coverage when receiving bundled care. The adjusted odds ratio for predefined adequacy of care was 3.75 for the low-risk bundled care recipients compared with those on Medicaid (P = .015), according to the experience at Grady Memorial Hospital, Atlanta, presented at the annual clinical and scientific sessions of the American College of Obstetricians and Gynecologists.

For hospitals with large numbers of undocumented patients and others who are uninsured but ineligible for Medicaid, considerable cost savings could be realized, said Erin Duncan, MD, who completed the work while in training at Emory University.

“Using data from previous studies, Grady Memorial Hospital could see a savings of over $1 million per year by providing care to its undocumented population,” she and her collaborators wrote in the poster accompanying the presentation.

Dr. Duncan said that since implementation in 2010, about 40% of deliveries at the facility have occurred under the “Grady Healthy Baby” (GHB) bundle.

The one-payment package of bundled prenatal care was developed assuming that most participants would have low-risk pregnancies, said Dr. Duncan, who is currently an ob.gyn. in private practice in the Atlanta area.

To look further into maternal and pregnancy characteristics of GHB participants and compare them with those on Medicaid, Dr. Duncan and her collaborators performed a retrospective cohort study. Examining viable singleton pregnancies delivered at Grady between 2011 and 2014, the investigators compared 100 randomly selected GHB participants with 100 randomly selected Medicaid participants.

Comparing patients receiving care under GHB and Medicaid, Dr. Duncan and her colleagues found that “GHB participants were older, more likely to be Hispanic, and less likely to be black compared to Medicaid recipients (P less than .001 for all,)” they wrote in the poster accompanying the presentation.

Hispanic patients made up 59% of the GHB group, compared with 8% of the Medicaid group, said Dr. Duncan, adding in an interview that over half of Hispanics in the state of Georgia during the study period were undocumented.

Parity was similar between the two groups, as were gestational age at delivery and mode of delivery.

In their analysis, Dr. Duncan and her collaborators looked at both complexity and adequacy of care for the 200 patients studied. They found that there was no significant difference in the number of patients in each care group who remained low risk throughout their pregnancies, transitioned from low risk to high risk, or entered prenatal care with a high risk pregnancy, a circumstance that occurred in about 1 in 10 pregnancies.

For the approximately 50% of patients who remained low risk through their pregnancies, care under the GHB model was significantly more likely to be assessed as adequate throughout pregnancy than for those patients on Medicaid (61.7% vs 35.5%, P = .001).

Patients who became high risk during prenatal care were no more likely to receive adequate care under one model than the other.

For high risk patients, delivery of adequate care happened only under the Medicaid care model. Numbers in this group were small; 7 of 100 GHB and 15 of 100 Medicaid patients entered prenatal care with high risk pregnancies. However, no high risk GHB patients received adequate care, while that standard was met for 80% of the Medicaid patients (P less than .001).

Adequacy of care was assessed using the Kotelchuck index for low-risk pregnancies; this model assumes care is “adequate” when 80% of the number of expected visits were attended by the woman receiving prenatal care. Additionally, care was deemed adequate for high-risk pregnancies if at least 80% of the number of expected ultrasound appointments were attended.

“In the current political climate, this study has implications for all pregnancies that begin as uninsured, regardless of maternal documentation status,” wrote Dr. Duncan and her colleagues.

Dr. Duncan reported no conflicts of interest.

[email protected]

SOURCE: Duncan, E et al. ACOG 2018, Abstract 28C.

CHICAGO – Management of fertility and reproduction for women with prolactin-secreting pituitary tumors is a balancing act, often in the absence of robust data to support clinical decision making. So judgment, communication, and paying attention to the patient become paramount considerations, said endocrinologist Mark Molitch, MD, speaking at the annual meeting of the Endocrine Society.

The first step: restoring fertility

“Remember that our patients that have hyperprolactinemia are generally infertile,” said Dr. Molitch, Martha Leland Sherwin Professor of Medicine at Northwestern University, Chicago. “You really need to restore prolactin levels to close to normal, or normal, to allow ovulation to occur,” he said.

Dr. Molitch noted that up to 94% of women with hyperprolactinemia will initially have anovulation, amenorrhea, and infertility, but restoration of normal prolactin levels usually corrects these.

“If you have a patient where you are unable to restore prolactin levels to normal, there are other methods” to consider. Patients may end up using clomiphene, gonadotropin-releasing hormone (GnRH) or gonadotropins, or even moving to in vitro fertilization in these cases, said Dr. Molitch.

Preferable to any of these, though, is achieving normal prolactin levels. “The critical thing is to think about what’s going on here, and then to try to lower the prolactin,” Dr. Molitch said.

In patients who are hyperprolactinemic, “the major action is occurring at the hypothalamic level,” with decreases in pulsatile secretion of GnRH, said Dr. Molitch. Next, there are resultant decreases in gonadotropin secretion, which in turn interrupt the ovary’s normal physiology. “There’s also an interruption in positive estrogen feedback in this cycle,” he said.

“So what’s new in this area is kisspeptin,” Dr. Molitch said, adding that the peptide activates the G-protein coupled receptor GPR54, found in the hypothalamus and pituitary. Infusion of kisspeptin stimulates secretion of luteinizing hormone, follicle stimulating hormone, and testosterone. Conversely, mutations that inactivate GPR43 result in hypogonadotropic hypogonadism, while activating mutations are associated with centrally caused precocious puberty (Biol Reprod. 2011 Oct;85[4]:650-60; Mol Cell Endocrinol. 2011 Oct 22;346[1-2]:29-3).

From this and other work, endocrinologists now know that kisspeptin is “very likely involved in puberty initiation and in response to fasting,” said Dr. Molitch. It’s now thought that high prolactin levels alter kisspeptin levels, “which then causes the further downstream effects,” said Dr. Molitch.

Dopamine agonists and pregnancy

Dopamine agonists are the primary therapies used for patients with prolactinomas and hyperprolactinemia. In patients seeking fertility, the dopamine agonist is usually continued just through the first few weeks of pregnancy, until the patient misses her first menstrual period, he said.

Establishing the menstrual interval is key to knowing when to stop the dopamine agonist, though. “We often use barrier contraceptives, so we can tell what the menstrual interval is – so we can tell when somebody’s missed her period,” Dr. Molitch explained.

“Most of the safety data on these drugs … are based on that relatively short period of exposure,” said Dr. Molitch. “As far as long-term use during pregnancy, only about 100 patients who took bromocriptine throughout pregnancy have been reported,” with two minor fetal anomalies reported from this series of patients, he said.

Though fewer than 20 cases have been reported of cabergoline being continued throughout a pregnancy, “there have not been any problems with that,” said Dr. Molitch.

Overall, over 6,000 pregnancies with bromocriptine exposure, as well as over 1,000 with cabergoline, have now been reported.

Dr. Molitch summarized the aggregate safety data for each dopamine agonist: “When we look at the adverse outcomes that occurred with either of these drugs, as far as spontaneous abortions or terminations, premature deliveries, multiple births, and, of course, the most important thing here being major malformations … in neither drug is there an increase in these adverse outcomes” (J Endocrinol Invest. 2018 Jan;41[1]:129-41).

“In my own mind now, I think that the number of cases with cabergoline now is quite sufficient to justify the safety of its use during pregnancy,” Dr. Molitch said. “However, this is sort of an individualized decision between you – the clinician – as well as your patient to make”: whether to trust the 1,000-case–strong data for cabergoline. “I no longer change patients from cabergoline to bromocriptine because of safety concerns. I think that cabergoline is perfectly safe,” he added.

What if the tumor grows in pregnancy?

During pregnancy, high estrogen levels from the placenta can stimulate prolactinoma growth, and the dopamine agonist’s inhibitory effect is gone once that medication’s been stopped. This means that “We have both a ‘push’ and a decrease in the ‘pull’ here, so you may have tumor enlargement,” said Dr. Molitch.

The risk for tumor enlargement in microadenomas is about 2.4%, and ranges to about 16% for enlargement of macroadenomas during pregnancy. For macroadenomas, “you might consider a prepregnancy debulking of the tumor,” Dr. Molitch said.

It’s reasonable to stop a dopamine agonist once pregnancy’s been established in a patient with a prolactinoma, and “follow the patient symptomatically every few months,” letting suspicious new symptoms like visual changes or headaches be the prompt for visual field exam and magnetic resonance imaging without contrast, said Dr. Molitch.

Though it’s not FDA approved, consideration can be given to continuing a dopamine agonist in a patient with a large prepregnancy adenoma throughout pregnancy – and if the tumor is enlarging significantly, the dopamine agonist should be restarted if it’s been withheld, said Dr. Molitch. Finally, surgery is the option if an enlarging tumor doesn’t respond to a dopamine agonist, unless the pregnancy is far enough along that delivery is a safe option.

“It’s important to actually document that there’s tumor enlargement, because if you’re going to do something like restarting a drug or even surgery, you really want to make sure that it’s the enlarging tumor that’s causing the problem,” said Dr. Molitch.

Postpartum prolactinoma considerations

Postpartum, even though prolactin secretion is upped by nursing, “there are no data to show that lactation stimulates tumor growth,” said Dr. Molitch. “I don’t see that there’s any problem with somebody nursing if they choose to do so.” However, “You certainly cannot restart the dopamine agonist, because that will lower prolactin levels and prevent that person from being able to nurse,” he said.

For reasons that are not clear, prolactin levels often drop post partum. Accordingly, it’s a reasonable approach in a nursing mother with mildly elevated prolactin levels to wait until nursing is done to see if menses resume spontaneously before restarting the dopamine agonist, said Dr. Molitch.

Dr. Molitch reported receiving fees and research funding from several pharmaceutical companies. He also disclosed that his spouse holds stock in Amgen.

[email protected]

SOURCE: Molitch M ENDO 2018. Abstract M02-2.

CHICAGO – Management of fertility and reproduction for women with prolactin-secreting pituitary tumors is a balancing act, often in the absence of robust data to support clinical decision making. So judgment, communication, and paying attention to the patient become paramount considerations, said endocrinologist Mark Molitch, MD, speaking at the annual meeting of the Endocrine Society.

The first step: restoring fertility

“Remember that our patients that have hyperprolactinemia are generally infertile,” said Dr. Molitch, Martha Leland Sherwin Professor of Medicine at Northwestern University, Chicago. “You really need to restore prolactin levels to close to normal, or normal, to allow ovulation to occur,” he said.

Dr. Molitch noted that up to 94% of women with hyperprolactinemia will initially have anovulation, amenorrhea, and infertility, but restoration of normal prolactin levels usually corrects these.

“If you have a patient where you are unable to restore prolactin levels to normal, there are other methods” to consider. Patients may end up using clomiphene, gonadotropin-releasing hormone (GnRH) or gonadotropins, or even moving to in vitro fertilization in these cases, said Dr. Molitch.

Preferable to any of these, though, is achieving normal prolactin levels. “The critical thing is to think about what’s going on here, and then to try to lower the prolactin,” Dr. Molitch said.

In patients who are hyperprolactinemic, “the major action is occurring at the hypothalamic level,” with decreases in pulsatile secretion of GnRH, said Dr. Molitch. Next, there are resultant decreases in gonadotropin secretion, which in turn interrupt the ovary’s normal physiology. “There’s also an interruption in positive estrogen feedback in this cycle,” he said.

“So what’s new in this area is kisspeptin,” Dr. Molitch said, adding that the peptide activates the G-protein coupled receptor GPR54, found in the hypothalamus and pituitary. Infusion of kisspeptin stimulates secretion of luteinizing hormone, follicle stimulating hormone, and testosterone. Conversely, mutations that inactivate GPR43 result in hypogonadotropic hypogonadism, while activating mutations are associated with centrally caused precocious puberty (Biol Reprod. 2011 Oct;85[4]:650-60; Mol Cell Endocrinol. 2011 Oct 22;346[1-2]:29-3).

From this and other work, endocrinologists now know that kisspeptin is “very likely involved in puberty initiation and in response to fasting,” said Dr. Molitch. It’s now thought that high prolactin levels alter kisspeptin levels, “which then causes the further downstream effects,” said Dr. Molitch.

Dopamine agonists and pregnancy

Dopamine agonists are the primary therapies used for patients with prolactinomas and hyperprolactinemia. In patients seeking fertility, the dopamine agonist is usually continued just through the first few weeks of pregnancy, until the patient misses her first menstrual period, he said.

Establishing the menstrual interval is key to knowing when to stop the dopamine agonist, though. “We often use barrier contraceptives, so we can tell what the menstrual interval is – so we can tell when somebody’s missed her period,” Dr. Molitch explained.

“Most of the safety data on these drugs … are based on that relatively short period of exposure,” said Dr. Molitch. “As far as long-term use during pregnancy, only about 100 patients who took bromocriptine throughout pregnancy have been reported,” with two minor fetal anomalies reported from this series of patients, he said.

Though fewer than 20 cases have been reported of cabergoline being continued throughout a pregnancy, “there have not been any problems with that,” said Dr. Molitch.

Overall, over 6,000 pregnancies with bromocriptine exposure, as well as over 1,000 with cabergoline, have now been reported.

Dr. Molitch summarized the aggregate safety data for each dopamine agonist: “When we look at the adverse outcomes that occurred with either of these drugs, as far as spontaneous abortions or terminations, premature deliveries, multiple births, and, of course, the most important thing here being major malformations … in neither drug is there an increase in these adverse outcomes” (J Endocrinol Invest. 2018 Jan;41[1]:129-41).

“In my own mind now, I think that the number of cases with cabergoline now is quite sufficient to justify the safety of its use during pregnancy,” Dr. Molitch said. “However, this is sort of an individualized decision between you – the clinician – as well as your patient to make”: whether to trust the 1,000-case–strong data for cabergoline. “I no longer change patients from cabergoline to bromocriptine because of safety concerns. I think that cabergoline is perfectly safe,” he added.

What if the tumor grows in pregnancy?

During pregnancy, high estrogen levels from the placenta can stimulate prolactinoma growth, and the dopamine agonist’s inhibitory effect is gone once that medication’s been stopped. This means that “We have both a ‘push’ and a decrease in the ‘pull’ here, so you may have tumor enlargement,” said Dr. Molitch.

The risk for tumor enlargement in microadenomas is about 2.4%, and ranges to about 16% for enlargement of macroadenomas during pregnancy. For macroadenomas, “you might consider a prepregnancy debulking of the tumor,” Dr. Molitch said.

It’s reasonable to stop a dopamine agonist once pregnancy’s been established in a patient with a prolactinoma, and “follow the patient symptomatically every few months,” letting suspicious new symptoms like visual changes or headaches be the prompt for visual field exam and magnetic resonance imaging without contrast, said Dr. Molitch.

Though it’s not FDA approved, consideration can be given to continuing a dopamine agonist in a patient with a large prepregnancy adenoma throughout pregnancy – and if the tumor is enlarging significantly, the dopamine agonist should be restarted if it’s been withheld, said Dr. Molitch. Finally, surgery is the option if an enlarging tumor doesn’t respond to a dopamine agonist, unless the pregnancy is far enough along that delivery is a safe option.

“It’s important to actually document that there’s tumor enlargement, because if you’re going to do something like restarting a drug or even surgery, you really want to make sure that it’s the enlarging tumor that’s causing the problem,” said Dr. Molitch.

Postpartum prolactinoma considerations

Postpartum, even though prolactin secretion is upped by nursing, “there are no data to show that lactation stimulates tumor growth,” said Dr. Molitch. “I don’t see that there’s any problem with somebody nursing if they choose to do so.” However, “You certainly cannot restart the dopamine agonist, because that will lower prolactin levels and prevent that person from being able to nurse,” he said.

For reasons that are not clear, prolactin levels often drop post partum. Accordingly, it’s a reasonable approach in a nursing mother with mildly elevated prolactin levels to wait until nursing is done to see if menses resume spontaneously before restarting the dopamine agonist, said Dr. Molitch.

Dr. Molitch reported receiving fees and research funding from several pharmaceutical companies. He also disclosed that his spouse holds stock in Amgen.

[email protected]

SOURCE: Molitch M ENDO 2018. Abstract M02-2.

CHICAGO – Management of fertility and reproduction for women with prolactin-secreting pituitary tumors is a balancing act, often in the absence of robust data to support clinical decision making. So judgment, communication, and paying attention to the patient become paramount considerations, said endocrinologist Mark Molitch, MD, speaking at the annual meeting of the Endocrine Society.

The first step: restoring fertility

“Remember that our patients that have hyperprolactinemia are generally infertile,” said Dr. Molitch, Martha Leland Sherwin Professor of Medicine at Northwestern University, Chicago. “You really need to restore prolactin levels to close to normal, or normal, to allow ovulation to occur,” he said.

Dr. Molitch noted that up to 94% of women with hyperprolactinemia will initially have anovulation, amenorrhea, and infertility, but restoration of normal prolactin levels usually corrects these.

“If you have a patient where you are unable to restore prolactin levels to normal, there are other methods” to consider. Patients may end up using clomiphene, gonadotropin-releasing hormone (GnRH) or gonadotropins, or even moving to in vitro fertilization in these cases, said Dr. Molitch.

Preferable to any of these, though, is achieving normal prolactin levels. “The critical thing is to think about what’s going on here, and then to try to lower the prolactin,” Dr. Molitch said.

In patients who are hyperprolactinemic, “the major action is occurring at the hypothalamic level,” with decreases in pulsatile secretion of GnRH, said Dr. Molitch. Next, there are resultant decreases in gonadotropin secretion, which in turn interrupt the ovary’s normal physiology. “There’s also an interruption in positive estrogen feedback in this cycle,” he said.

“So what’s new in this area is kisspeptin,” Dr. Molitch said, adding that the peptide activates the G-protein coupled receptor GPR54, found in the hypothalamus and pituitary. Infusion of kisspeptin stimulates secretion of luteinizing hormone, follicle stimulating hormone, and testosterone. Conversely, mutations that inactivate GPR43 result in hypogonadotropic hypogonadism, while activating mutations are associated with centrally caused precocious puberty (Biol Reprod. 2011 Oct;85[4]:650-60; Mol Cell Endocrinol. 2011 Oct 22;346[1-2]:29-3).

From this and other work, endocrinologists now know that kisspeptin is “very likely involved in puberty initiation and in response to fasting,” said Dr. Molitch. It’s now thought that high prolactin levels alter kisspeptin levels, “which then causes the further downstream effects,” said Dr. Molitch.

Dopamine agonists and pregnancy

Dopamine agonists are the primary therapies used for patients with prolactinomas and hyperprolactinemia. In patients seeking fertility, the dopamine agonist is usually continued just through the first few weeks of pregnancy, until the patient misses her first menstrual period, he said.

Establishing the menstrual interval is key to knowing when to stop the dopamine agonist, though. “We often use barrier contraceptives, so we can tell what the menstrual interval is – so we can tell when somebody’s missed her period,” Dr. Molitch explained.

“Most of the safety data on these drugs … are based on that relatively short period of exposure,” said Dr. Molitch. “As far as long-term use during pregnancy, only about 100 patients who took bromocriptine throughout pregnancy have been reported,” with two minor fetal anomalies reported from this series of patients, he said.

Though fewer than 20 cases have been reported of cabergoline being continued throughout a pregnancy, “there have not been any problems with that,” said Dr. Molitch.

Overall, over 6,000 pregnancies with bromocriptine exposure, as well as over 1,000 with cabergoline, have now been reported.

Dr. Molitch summarized the aggregate safety data for each dopamine agonist: “When we look at the adverse outcomes that occurred with either of these drugs, as far as spontaneous abortions or terminations, premature deliveries, multiple births, and, of course, the most important thing here being major malformations … in neither drug is there an increase in these adverse outcomes” (J Endocrinol Invest. 2018 Jan;41[1]:129-41).

“In my own mind now, I think that the number of cases with cabergoline now is quite sufficient to justify the safety of its use during pregnancy,” Dr. Molitch said. “However, this is sort of an individualized decision between you – the clinician – as well as your patient to make”: whether to trust the 1,000-case–strong data for cabergoline. “I no longer change patients from cabergoline to bromocriptine because of safety concerns. I think that cabergoline is perfectly safe,” he added.

What if the tumor grows in pregnancy?

During pregnancy, high estrogen levels from the placenta can stimulate prolactinoma growth, and the dopamine agonist’s inhibitory effect is gone once that medication’s been stopped. This means that “We have both a ‘push’ and a decrease in the ‘pull’ here, so you may have tumor enlargement,” said Dr. Molitch.

The risk for tumor enlargement in microadenomas is about 2.4%, and ranges to about 16% for enlargement of macroadenomas during pregnancy. For macroadenomas, “you might consider a prepregnancy debulking of the tumor,” Dr. Molitch said.

It’s reasonable to stop a dopamine agonist once pregnancy’s been established in a patient with a prolactinoma, and “follow the patient symptomatically every few months,” letting suspicious new symptoms like visual changes or headaches be the prompt for visual field exam and magnetic resonance imaging without contrast, said Dr. Molitch.

Though it’s not FDA approved, consideration can be given to continuing a dopamine agonist in a patient with a large prepregnancy adenoma throughout pregnancy – and if the tumor is enlarging significantly, the dopamine agonist should be restarted if it’s been withheld, said Dr. Molitch. Finally, surgery is the option if an enlarging tumor doesn’t respond to a dopamine agonist, unless the pregnancy is far enough along that delivery is a safe option.

“It’s important to actually document that there’s tumor enlargement, because if you’re going to do something like restarting a drug or even surgery, you really want to make sure that it’s the enlarging tumor that’s causing the problem,” said Dr. Molitch.

Postpartum prolactinoma considerations

Postpartum, even though prolactin secretion is upped by nursing, “there are no data to show that lactation stimulates tumor growth,” said Dr. Molitch. “I don’t see that there’s any problem with somebody nursing if they choose to do so.” However, “You certainly cannot restart the dopamine agonist, because that will lower prolactin levels and prevent that person from being able to nurse,” he said.

For reasons that are not clear, prolactin levels often drop post partum. Accordingly, it’s a reasonable approach in a nursing mother with mildly elevated prolactin levels to wait until nursing is done to see if menses resume spontaneously before restarting the dopamine agonist, said Dr. Molitch.

Dr. Molitch reported receiving fees and research funding from several pharmaceutical companies. He also disclosed that his spouse holds stock in Amgen.

[email protected]

SOURCE: Molitch M ENDO 2018. Abstract M02-2.

CHICAGO – A scoring system that addresses severity of metabolic syndrome successfully predicted risk for future coronary heart disease in individuals with type 2 diabetes; the system identified the association independent of hemoglobin A_1c levels, according to work presented at the annual meeting of the Endocrine Society.

The findings may point toward an additional surveillance tool for coronary heart disease (CHD) in patients who have type 2 diabetes, according to Mark D. DeBoer, MD, and his coauthors, who had not previously applied the metabolic syndrome severity scoring system to individuals with diabetes.

Bruce Jancin/MDedge News

When broken down by quartile, increasing severity of metabolic syndrome for individuals with type 2 diabetes was associated with an increased risk of future cardiovascular disease, even when blood glucose levels were not included in calculation of metabolic syndrome (P less than .001 with glucose levels and P = .001 without glucose levels).

Dr. DeBoer, of the department of pediatrics and the Child Health Research Center at the University of Virginia, Charlottesville, and his coinvestigators, had previously developed the continuous scoring system for metabolic syndrome. The system incorporates the components that form the diagnostic criteria for metabolic syndrome – waist circumference, systolic blood pressure, and levels of HDL cholesterol, triglycerides, and blood glucose.

However, rather than using cutoffs for a dichotomous score of 0 or 1 for each criterion, the investigators developed sex- and race/ethnicity-specific scores of severity. This approach may identify metabolic dysregulation that would not be apparent if measures of several different criteria were just short of missing the cutoff, for example.

“These scores are standardized like z scores such that 2.0 is two standard deviations above the mean,” wrote Dr. DeBoer and his colleagues. Thus, the scores are dubbed “MetS z scores;” a free online calculator is available.

In developing the model, the investigators performed single-factor confirmatory factor analyses using data from 6,870 adults from the National Health and Nutrition Examination Survey cohort, developing scores specific for non-Hispanic whites, non-Hispanic blacks, and Hispanics.

In the present work, MetS z scores were applied to data from the Atherosclerosis Risk in Communities (ARIC) study, which followed 8,660 participants aged 45-64 years for 12 years, with adjudicated follow-up for cardiovascular incidents up to 20 years. Only participants with no baseline CHD and with complete metabolic syndrome risk factor data were included.

Dr. DeBoer and his collaborators compared MetS z scores for patients who were never diagnosed with diabetes, those who had diabetes at baseline, and those who had an incident diagnosis of type 2 diabetes at the second, third, or fourth ARIC study visit. They found that individuals who entered ARIC with diabetes had the highest z scores, while those with incident type 2 diabetes had higher baseline scores, compared with those who never had a diabetes diagnosis. The difference in z scores was lowest for white men, while black men and women “exhibited increased scores after diagnosis, suggesting inadequate treatment,” wrote Dr. DeBoer and his colleagues.

The investigators also looked for an association between MetS z scores and the primary outcome measure, time to incident CHD, calculating the z score both with and without the inclusion of glucose levels.

Dr. DeBoer and his colleagues analyzed the association between MetS z score and CHD for patients with and without type 2 diabetes. They found metabolic syndrome severity as assessed by MetS z score was independently associated with increased risk for CHD in participants with diabetes (P = .001).

“We additionally assessed whether the [metabolic syndrome] z score predicted future CHD following adjustment for HbA_1c and when using a similar score derived without glucose as a component,” wrote Dr. DeBoer and his collaborators.

When metabolic syndrome severity as assessed by z score was broken into quartiles, “increasing MetS severity (by quartile) increased the risk of future CVD [cardiovascular disease], both using the traditional 5-component MetS z score and the no-glucose score,” wrote Dr. DeBoer and his colleagues. “This continuous MetS severity z score confers risk for future CHD among individuals with type 2 diabetes, both with the traditional MetS score and a score without glucose. These findings were independent of HbA_1c and may relate to risk associated with the pathophysiologic processes underlying MetS.”

The investigators plan to integrate an automated metabolic syndrome severity score calculator into the electronic medical record “to identify and track risk in individuals over time and identify those who may benefit from increased intervention,” wrote Dr. DeBoer and his collaborators.

The National Institutes of Health funded the study. Dr. DeBoer reported no relevant conflicts of interest.

[email protected]

SOURCE: DeBoer MD et al. ENDO 2018, Abstract SAT-015.

CHICAGO – A scoring system that addresses severity of metabolic syndrome successfully predicted risk for future coronary heart disease in individuals with type 2 diabetes; the system identified the association independent of hemoglobin A_1c levels, according to work presented at the annual meeting of the Endocrine Society.

The findings may point toward an additional surveillance tool for coronary heart disease (CHD) in patients who have type 2 diabetes, according to Mark D. DeBoer, MD, and his coauthors, who had not previously applied the metabolic syndrome severity scoring system to individuals with diabetes.

Bruce Jancin/MDedge News

When broken down by quartile, increasing severity of metabolic syndrome for individuals with type 2 diabetes was associated with an increased risk of future cardiovascular disease, even when blood glucose levels were not included in calculation of metabolic syndrome (P less than .001 with glucose levels and P = .001 without glucose levels).

Dr. DeBoer, of the department of pediatrics and the Child Health Research Center at the University of Virginia, Charlottesville, and his coinvestigators, had previously developed the continuous scoring system for metabolic syndrome. The system incorporates the components that form the diagnostic criteria for metabolic syndrome – waist circumference, systolic blood pressure, and levels of HDL cholesterol, triglycerides, and blood glucose.

However, rather than using cutoffs for a dichotomous score of 0 or 1 for each criterion, the investigators developed sex- and race/ethnicity-specific scores of severity. This approach may identify metabolic dysregulation that would not be apparent if measures of several different criteria were just short of missing the cutoff, for example.

“These scores are standardized like z scores such that 2.0 is two standard deviations above the mean,” wrote Dr. DeBoer and his colleagues. Thus, the scores are dubbed “MetS z scores;” a free online calculator is available.

In developing the model, the investigators performed single-factor confirmatory factor analyses using data from 6,870 adults from the National Health and Nutrition Examination Survey cohort, developing scores specific for non-Hispanic whites, non-Hispanic blacks, and Hispanics.

In the present work, MetS z scores were applied to data from the Atherosclerosis Risk in Communities (ARIC) study, which followed 8,660 participants aged 45-64 years for 12 years, with adjudicated follow-up for cardiovascular incidents up to 20 years. Only participants with no baseline CHD and with complete metabolic syndrome risk factor data were included.

Dr. DeBoer and his collaborators compared MetS z scores for patients who were never diagnosed with diabetes, those who had diabetes at baseline, and those who had an incident diagnosis of type 2 diabetes at the second, third, or fourth ARIC study visit. They found that individuals who entered ARIC with diabetes had the highest z scores, while those with incident type 2 diabetes had higher baseline scores, compared with those who never had a diabetes diagnosis. The difference in z scores was lowest for white men, while black men and women “exhibited increased scores after diagnosis, suggesting inadequate treatment,” wrote Dr. DeBoer and his colleagues.

The investigators also looked for an association between MetS z scores and the primary outcome measure, time to incident CHD, calculating the z score both with and without the inclusion of glucose levels.

Dr. DeBoer and his colleagues analyzed the association between MetS z score and CHD for patients with and without type 2 diabetes. They found metabolic syndrome severity as assessed by MetS z score was independently associated with increased risk for CHD in participants with diabetes (P = .001).

“We additionally assessed whether the [metabolic syndrome] z score predicted future CHD following adjustment for HbA_1c and when using a similar score derived without glucose as a component,” wrote Dr. DeBoer and his collaborators.

When metabolic syndrome severity as assessed by z score was broken into quartiles, “increasing MetS severity (by quartile) increased the risk of future CVD [cardiovascular disease], both using the traditional 5-component MetS z score and the no-glucose score,” wrote Dr. DeBoer and his colleagues. “This continuous MetS severity z score confers risk for future CHD among individuals with type 2 diabetes, both with the traditional MetS score and a score without glucose. These findings were independent of HbA_1c and may relate to risk associated with the pathophysiologic processes underlying MetS.”

The investigators plan to integrate an automated metabolic syndrome severity score calculator into the electronic medical record “to identify and track risk in individuals over time and identify those who may benefit from increased intervention,” wrote Dr. DeBoer and his collaborators.

The National Institutes of Health funded the study. Dr. DeBoer reported no relevant conflicts of interest.

[email protected]

SOURCE: DeBoer MD et al. ENDO 2018, Abstract SAT-015.

CHICAGO – A scoring system that addresses severity of metabolic syndrome successfully predicted risk for future coronary heart disease in individuals with type 2 diabetes; the system identified the association independent of hemoglobin A_1c levels, according to work presented at the annual meeting of the Endocrine Society.

The findings may point toward an additional surveillance tool for coronary heart disease (CHD) in patients who have type 2 diabetes, according to Mark D. DeBoer, MD, and his coauthors, who had not previously applied the metabolic syndrome severity scoring system to individuals with diabetes.

Bruce Jancin/MDedge News

When broken down by quartile, increasing severity of metabolic syndrome for individuals with type 2 diabetes was associated with an increased risk of future cardiovascular disease, even when blood glucose levels were not included in calculation of metabolic syndrome (P less than .001 with glucose levels and P = .001 without glucose levels).

Dr. DeBoer, of the department of pediatrics and the Child Health Research Center at the University of Virginia, Charlottesville, and his coinvestigators, had previously developed the continuous scoring system for metabolic syndrome. The system incorporates the components that form the diagnostic criteria for metabolic syndrome – waist circumference, systolic blood pressure, and levels of HDL cholesterol, triglycerides, and blood glucose.

However, rather than using cutoffs for a dichotomous score of 0 or 1 for each criterion, the investigators developed sex- and race/ethnicity-specific scores of severity. This approach may identify metabolic dysregulation that would not be apparent if measures of several different criteria were just short of missing the cutoff, for example.

“These scores are standardized like z scores such that 2.0 is two standard deviations above the mean,” wrote Dr. DeBoer and his colleagues. Thus, the scores are dubbed “MetS z scores;” a free online calculator is available.

In developing the model, the investigators performed single-factor confirmatory factor analyses using data from 6,870 adults from the National Health and Nutrition Examination Survey cohort, developing scores specific for non-Hispanic whites, non-Hispanic blacks, and Hispanics.

In the present work, MetS z scores were applied to data from the Atherosclerosis Risk in Communities (ARIC) study, which followed 8,660 participants aged 45-64 years for 12 years, with adjudicated follow-up for cardiovascular incidents up to 20 years. Only participants with no baseline CHD and with complete metabolic syndrome risk factor data were included.

Dr. DeBoer and his collaborators compared MetS z scores for patients who were never diagnosed with diabetes, those who had diabetes at baseline, and those who had an incident diagnosis of type 2 diabetes at the second, third, or fourth ARIC study visit. They found that individuals who entered ARIC with diabetes had the highest z scores, while those with incident type 2 diabetes had higher baseline scores, compared with those who never had a diabetes diagnosis. The difference in z scores was lowest for white men, while black men and women “exhibited increased scores after diagnosis, suggesting inadequate treatment,” wrote Dr. DeBoer and his colleagues.

The investigators also looked for an association between MetS z scores and the primary outcome measure, time to incident CHD, calculating the z score both with and without the inclusion of glucose levels.

Dr. DeBoer and his colleagues analyzed the association between MetS z score and CHD for patients with and without type 2 diabetes. They found metabolic syndrome severity as assessed by MetS z score was independently associated with increased risk for CHD in participants with diabetes (P = .001).

“We additionally assessed whether the [metabolic syndrome] z score predicted future CHD following adjustment for HbA_1c and when using a similar score derived without glucose as a component,” wrote Dr. DeBoer and his collaborators.

When metabolic syndrome severity as assessed by z score was broken into quartiles, “increasing MetS severity (by quartile) increased the risk of future CVD [cardiovascular disease], both using the traditional 5-component MetS z score and the no-glucose score,” wrote Dr. DeBoer and his colleagues. “This continuous MetS severity z score confers risk for future CHD among individuals with type 2 diabetes, both with the traditional MetS score and a score without glucose. These findings were independent of HbA_1c and may relate to risk associated with the pathophysiologic processes underlying MetS.”

The investigators plan to integrate an automated metabolic syndrome severity score calculator into the electronic medical record “to identify and track risk in individuals over time and identify those who may benefit from increased intervention,” wrote Dr. DeBoer and his collaborators.

The National Institutes of Health funded the study. Dr. DeBoer reported no relevant conflicts of interest.

[email protected]

SOURCE: DeBoer MD et al. ENDO 2018, Abstract SAT-015.

CHICAGO – Consumption of a sucralose-laden beverage stimulated appetite centers of the brain in individuals with obesity but not in lean participants of a recent study, even though hunger and satiety hormone levels didn’t change. Those with obesity also consumed more calories after ingesting the artificial sweetener, though lean participants did not.

The study compared acute effects of consuming a set amount of glucose, sucralose, or water as the control, finding that sucralose consumption resulted in a significant increase in blood flow to certain areas of the brains of study participants with obesity but not in lean individuals (2.10 mL/100g per min vs. –.079 mL/100g per min; P = .002).

Kari Oakes/MDedge News

Participants had three scans, spaced at least 2 days apart and occurring after a 12-hour overnight fast. A scan with arterial spin labeling acquisition was taken before and 10 minutes after participants drank a 300-mL beverage consisting of just water, or either a 75-g glucose solution or 2 mmol/L sucralose.

Twenty-five of the participants had blood drawn at 0, 40, and 60 minutes after drinking the study beverage, to track levels of serum insulin, ghrelin, GLP-1, and peptide YY – all hormones that help regulate appetite and satiety.

Hormone levels for individuals who had the non–glucose beverages were similar, regardless of BMI. However, there were significant differences in cerebral blood flow between obese and nonobese participants. Mr. Ge, an undergraduate student, and his collaborators looked at the contributions of the individual brain structures to the significantly higher activation seen after sucralose consumption by the high-BMI participants. Individuals with obesity had significantly more activity in the amygdala than did the lean participants (P = .0088) after drinking the sucralose beverage; also, in lean individuals, hypothalamic activity decreased after sucralose consumption, while activity increased slightly in the high-BMI participants (P = .017).

Eating behavior after drinking the various beverages also differed depending on beverage type and BMI status. After the overnight fast and study beverage consumption, participants were offered unlimited access to a buffet-style meal. The beverage type had no significant effect on calorie consumption at the buffet for the lean study participants. However, obese individuals consumed significantly more calories than did lean individuals after ingesting sucralose (1,191 kcal vs. 731 kcal; P = .01). Caloric intake was not significantly different between the high- and low-BMI groups after consumption of water or glucose.

None of the study authors reported conflicts of interest.

[email protected]

SOURCE: Ge B et al. ENDO 2018, Abstract SUN-070.

CHICAGO – Consumption of a sucralose-laden beverage stimulated appetite centers of the brain in individuals with obesity but not in lean participants of a recent study, even though hunger and satiety hormone levels didn’t change. Those with obesity also consumed more calories after ingesting the artificial sweetener, though lean participants did not.

The study compared acute effects of consuming a set amount of glucose, sucralose, or water as the control, finding that sucralose consumption resulted in a significant increase in blood flow to certain areas of the brains of study participants with obesity but not in lean individuals (2.10 mL/100g per min vs. –.079 mL/100g per min; P = .002).

Kari Oakes/MDedge News

Participants had three scans, spaced at least 2 days apart and occurring after a 12-hour overnight fast. A scan with arterial spin labeling acquisition was taken before and 10 minutes after participants drank a 300-mL beverage consisting of just water, or either a 75-g glucose solution or 2 mmol/L sucralose.

Twenty-five of the participants had blood drawn at 0, 40, and 60 minutes after drinking the study beverage, to track levels of serum insulin, ghrelin, GLP-1, and peptide YY – all hormones that help regulate appetite and satiety.

Hormone levels for individuals who had the non–glucose beverages were similar, regardless of BMI. However, there were significant differences in cerebral blood flow between obese and nonobese participants. Mr. Ge, an undergraduate student, and his collaborators looked at the contributions of the individual brain structures to the significantly higher activation seen after sucralose consumption by the high-BMI participants. Individuals with obesity had significantly more activity in the amygdala than did the lean participants (P = .0088) after drinking the sucralose beverage; also, in lean individuals, hypothalamic activity decreased after sucralose consumption, while activity increased slightly in the high-BMI participants (P = .017).

Eating behavior after drinking the various beverages also differed depending on beverage type and BMI status. After the overnight fast and study beverage consumption, participants were offered unlimited access to a buffet-style meal. The beverage type had no significant effect on calorie consumption at the buffet for the lean study participants. However, obese individuals consumed significantly more calories than did lean individuals after ingesting sucralose (1,191 kcal vs. 731 kcal; P = .01). Caloric intake was not significantly different between the high- and low-BMI groups after consumption of water or glucose.

None of the study authors reported conflicts of interest.

[email protected]

SOURCE: Ge B et al. ENDO 2018, Abstract SUN-070.

CHICAGO – Consumption of a sucralose-laden beverage stimulated appetite centers of the brain in individuals with obesity but not in lean participants of a recent study, even though hunger and satiety hormone levels didn’t change. Those with obesity also consumed more calories after ingesting the artificial sweetener, though lean participants did not.

The study compared acute effects of consuming a set amount of glucose, sucralose, or water as the control, finding that sucralose consumption resulted in a significant increase in blood flow to certain areas of the brains of study participants with obesity but not in lean individuals (2.10 mL/100g per min vs. –.079 mL/100g per min; P = .002).

Kari Oakes/MDedge News

Participants had three scans, spaced at least 2 days apart and occurring after a 12-hour overnight fast. A scan with arterial spin labeling acquisition was taken before and 10 minutes after participants drank a 300-mL beverage consisting of just water, or either a 75-g glucose solution or 2 mmol/L sucralose.

Twenty-five of the participants had blood drawn at 0, 40, and 60 minutes after drinking the study beverage, to track levels of serum insulin, ghrelin, GLP-1, and peptide YY – all hormones that help regulate appetite and satiety.

Hormone levels for individuals who had the non–glucose beverages were similar, regardless of BMI. However, there were significant differences in cerebral blood flow between obese and nonobese participants. Mr. Ge, an undergraduate student, and his collaborators looked at the contributions of the individual brain structures to the significantly higher activation seen after sucralose consumption by the high-BMI participants. Individuals with obesity had significantly more activity in the amygdala than did the lean participants (P = .0088) after drinking the sucralose beverage; also, in lean individuals, hypothalamic activity decreased after sucralose consumption, while activity increased slightly in the high-BMI participants (P = .017).

Eating behavior after drinking the various beverages also differed depending on beverage type and BMI status. After the overnight fast and study beverage consumption, participants were offered unlimited access to a buffet-style meal. The beverage type had no significant effect on calorie consumption at the buffet for the lean study participants. However, obese individuals consumed significantly more calories than did lean individuals after ingesting sucralose (1,191 kcal vs. 731 kcal; P = .01). Caloric intake was not significantly different between the high- and low-BMI groups after consumption of water or glucose.

None of the study authors reported conflicts of interest.

[email protected]

SOURCE: Ge B et al. ENDO 2018, Abstract SUN-070.

Most beta thalassemia patients were off transfusions at a median of 26 months after receiving gene therapy via a lentiviral vector, according to new results of two phase 1/2 studies regarding the use of LentiGlobin in transfusion-dependent beta thalassemia.

Of 13 patients who did not have the most severe beta⁰/beta⁰ genotype, all but 1 has become transfusion independent post transplant. Among patients who either had the beta⁰/beta⁰ genotype or had two copies of the IVS1-110 mutation, transfusions were down a median 73% annually, and three of these patients with more severe thalassemia became transfusion independent.

At the time of last data collection, hemoglobin levels in individual patients ranged from 8.2-13.7 g/dL.

“No clonal dominance related to vector integration was observed,” wrote Alexis Thompson, MD, and her collaborators, and replication-competent lentivirus had not been found in any patients.

Hematopoietic cell transplant (HCT) is an option primarily for younger beta thalassemia patients who have an HLA-matched sibling donor, the researchers wrote in the New England Journal of Medicine. Gene therapy represents an alternative to the current standard of care for patients who are not candidates for allogeneic HCT, which – without a good match – carries increased risk for rejection and graft-versus-host disease.

Patients with beta thalassemia aged 35 years or younger and without advanced organ damage were enrolled in the two studies, one conducted internationally and one conducted at a single site in France.

There were some protocol differences between the two studies; notably, the French study used enhanced red cell transfusion for 3 or more months before stem cell mobilization “to enrich for bona fide hematopoietic stem cells in the harvested CD34+ cell compartment by suppressing the erythroid lineage expansion and the skewing that is seen in beta thalassemia,” wrote Dr. Thompson, professor of pediatrics at Northwestern University, Chicago, and her colleagues.

[email protected]

SOURCE: Thompson A et al. N Engl J Med 2018;378:1479-93

Most beta thalassemia patients were off transfusions at a median of 26 months after receiving gene therapy via a lentiviral vector, according to new results of two phase 1/2 studies regarding the use of LentiGlobin in transfusion-dependent beta thalassemia.

Of 13 patients who did not have the most severe beta⁰/beta⁰ genotype, all but 1 has become transfusion independent post transplant. Among patients who either had the beta⁰/beta⁰ genotype or had two copies of the IVS1-110 mutation, transfusions were down a median 73% annually, and three of these patients with more severe thalassemia became transfusion independent.

At the time of last data collection, hemoglobin levels in individual patients ranged from 8.2-13.7 g/dL.

“No clonal dominance related to vector integration was observed,” wrote Alexis Thompson, MD, and her collaborators, and replication-competent lentivirus had not been found in any patients.

Hematopoietic cell transplant (HCT) is an option primarily for younger beta thalassemia patients who have an HLA-matched sibling donor, the researchers wrote in the New England Journal of Medicine. Gene therapy represents an alternative to the current standard of care for patients who are not candidates for allogeneic HCT, which – without a good match – carries increased risk for rejection and graft-versus-host disease.

Patients with beta thalassemia aged 35 years or younger and without advanced organ damage were enrolled in the two studies, one conducted internationally and one conducted at a single site in France.

There were some protocol differences between the two studies; notably, the French study used enhanced red cell transfusion for 3 or more months before stem cell mobilization “to enrich for bona fide hematopoietic stem cells in the harvested CD34+ cell compartment by suppressing the erythroid lineage expansion and the skewing that is seen in beta thalassemia,” wrote Dr. Thompson, professor of pediatrics at Northwestern University, Chicago, and her colleagues.

[email protected]

SOURCE: Thompson A et al. N Engl J Med 2018;378:1479-93

Most beta thalassemia patients were off transfusions at a median of 26 months after receiving gene therapy via a lentiviral vector, according to new results of two phase 1/2 studies regarding the use of LentiGlobin in transfusion-dependent beta thalassemia.

Of 13 patients who did not have the most severe beta⁰/beta⁰ genotype, all but 1 has become transfusion independent post transplant. Among patients who either had the beta⁰/beta⁰ genotype or had two copies of the IVS1-110 mutation, transfusions were down a median 73% annually, and three of these patients with more severe thalassemia became transfusion independent.

At the time of last data collection, hemoglobin levels in individual patients ranged from 8.2-13.7 g/dL.

“No clonal dominance related to vector integration was observed,” wrote Alexis Thompson, MD, and her collaborators, and replication-competent lentivirus had not been found in any patients.

Hematopoietic cell transplant (HCT) is an option primarily for younger beta thalassemia patients who have an HLA-matched sibling donor, the researchers wrote in the New England Journal of Medicine. Gene therapy represents an alternative to the current standard of care for patients who are not candidates for allogeneic HCT, which – without a good match – carries increased risk for rejection and graft-versus-host disease.

Patients with beta thalassemia aged 35 years or younger and without advanced organ damage were enrolled in the two studies, one conducted internationally and one conducted at a single site in France.

There were some protocol differences between the two studies; notably, the French study used enhanced red cell transfusion for 3 or more months before stem cell mobilization “to enrich for bona fide hematopoietic stem cells in the harvested CD34+ cell compartment by suppressing the erythroid lineage expansion and the skewing that is seen in beta thalassemia,” wrote Dr. Thompson, professor of pediatrics at Northwestern University, Chicago, and her colleagues.

[email protected]

SOURCE: Thompson A et al. N Engl J Med 2018;378:1479-93

Advisors to the Food and Drug Administration have found a generally favorable benefit-risk profile for cannabidiol oil solution in the treatment of two forms of severe pediatric seizure disorders. The drug is under expedited review by the agency.

In a unanimous vote, the 13 members of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee found that the benefit-risk profile of cannabidiol is favorable for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) in patients 2 years of age and older.

If the FDA supports this recommendation, cannabidiol oral solution would be the first cannabis-based medication approved in the United States.

“At this point, this is a spectacular advance,” said committee member John Mendelson, MD, chief medical officer of Ria Health, San Francisco.

Fellow committee member Mark Green, MD, concurred. “It is clearly an honor to be making a decision based on science and public interest, rather than political discussion,” said Dr. Green, professor of neurology, anesthesiology, and rehabilitation medicine at Icahn School of Medicine, Mt Sinai, New York.

Patients with LGS taking cannabidiol oral solution at 20 mg/kg/day in two clinical trials saw a 42%-44% reduction in drop seizure frequency over a 14-week treatment period (P = .0047 and P = .0135, compared to placebo). A 50% reduction of drop seizure frequency was seen in 40% and 44% of LGS patients in the two clinical trials.

For patients with DS, 20 mg/kg/day of cannabidiol oral solution resulted in a 39% decrease in convulsive seizure frequency during a 14-week treatment period (P less than .05). There was a numeric, but not statistically significant, increase in the number of DS patients who saw a 50% reduction in convulsive seizure frequency on this dose.

Sustained efficacy for both seizure disorders has been seen during an extended open-label follow-on study.

This article was updated 4/19/18.

[email protected]

Advisors to the Food and Drug Administration have found a generally favorable benefit-risk profile for cannabidiol oil solution in the treatment of two forms of severe pediatric seizure disorders. The drug is under expedited review by the agency.

In a unanimous vote, the 13 members of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee found that the benefit-risk profile of cannabidiol is favorable for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) in patients 2 years of age and older.

If the FDA supports this recommendation, cannabidiol oral solution would be the first cannabis-based medication approved in the United States.

“At this point, this is a spectacular advance,” said committee member John Mendelson, MD, chief medical officer of Ria Health, San Francisco.

Fellow committee member Mark Green, MD, concurred. “It is clearly an honor to be making a decision based on science and public interest, rather than political discussion,” said Dr. Green, professor of neurology, anesthesiology, and rehabilitation medicine at Icahn School of Medicine, Mt Sinai, New York.

Patients with LGS taking cannabidiol oral solution at 20 mg/kg/day in two clinical trials saw a 42%-44% reduction in drop seizure frequency over a 14-week treatment period (P = .0047 and P = .0135, compared to placebo). A 50% reduction of drop seizure frequency was seen in 40% and 44% of LGS patients in the two clinical trials.

For patients with DS, 20 mg/kg/day of cannabidiol oral solution resulted in a 39% decrease in convulsive seizure frequency during a 14-week treatment period (P less than .05). There was a numeric, but not statistically significant, increase in the number of DS patients who saw a 50% reduction in convulsive seizure frequency on this dose.

Sustained efficacy for both seizure disorders has been seen during an extended open-label follow-on study.

This article was updated 4/19/18.

[email protected]

Advisors to the Food and Drug Administration have found a generally favorable benefit-risk profile for cannabidiol oil solution in the treatment of two forms of severe pediatric seizure disorders. The drug is under expedited review by the agency.

In a unanimous vote, the 13 members of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee found that the benefit-risk profile of cannabidiol is favorable for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) in patients 2 years of age and older.

If the FDA supports this recommendation, cannabidiol oral solution would be the first cannabis-based medication approved in the United States.

“At this point, this is a spectacular advance,” said committee member John Mendelson, MD, chief medical officer of Ria Health, San Francisco.

Fellow committee member Mark Green, MD, concurred. “It is clearly an honor to be making a decision based on science and public interest, rather than political discussion,” said Dr. Green, professor of neurology, anesthesiology, and rehabilitation medicine at Icahn School of Medicine, Mt Sinai, New York.

Patients with LGS taking cannabidiol oral solution at 20 mg/kg/day in two clinical trials saw a 42%-44% reduction in drop seizure frequency over a 14-week treatment period (P = .0047 and P = .0135, compared to placebo). A 50% reduction of drop seizure frequency was seen in 40% and 44% of LGS patients in the two clinical trials.

For patients with DS, 20 mg/kg/day of cannabidiol oral solution resulted in a 39% decrease in convulsive seizure frequency during a 14-week treatment period (P less than .05). There was a numeric, but not statistically significant, increase in the number of DS patients who saw a 50% reduction in convulsive seizure frequency on this dose.

Sustained efficacy for both seizure disorders has been seen during an extended open-label follow-on study.

This article was updated 4/19/18.

[email protected]

The Food and Drug Administration has approved burosumab to treat X-linked hypophosphatemia, a rare, heritable form of rickets, in adults and children at least 1 year of age. Burosumab received expedited review by the FDA as a breakthrough therapy, and it also has been designated an orphan drug.

X-linked hypophosphatemia (XLH) “differs from other forms of rickets in that vitamin D therapy is not effective. This is the first FDA-approved medication for the treatment of XLH and a real breakthrough for those living with this serious disease,” said Julie Beitz, MD, in an FDA press release announcing the approval of the fully human monoclonal antibody. Dr. Beitz is director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research.

Four clinical trials formed the basis for the FDA’s approval of burosumab. A pivotal randomized, placebo-controlled, double-blind study of adults with XLH that randomized 134 patients 1:1 to subcutaneous burosumab or placebo found that normal phosphorus levels were achieved in 94% of adults receiving burosumab, compared with 8% of those who received placebo.

For children, biweekly burosumab resulted in normal phosphorus levels for 94%-100% of participants. Significant skeletal radiographic improvement also was seen for adults and children taking burosumab.

In both adults and children, burosumab had a good safety profile, with no significant changes in serum or urine levels of calcium or in serum levels of intact parathyroid hormone.

X-linked hypophosphatemia is variable in severity; many patients with XLH will have bone pain, bowed legs, and a waddling gait; enthesopathy with associated joint pain; and dental problems and pain. Many also have short stature and, unlike rickets caused by dietary deficiency and some malabsorption problems, XLH is not improved by conventional vitamin D therapy.

The rare disorder, affecting about 3,000 children and 12,000 adults in the United States, is caused by a mutation in the PHEX gene, with resultant overactivity of fibroblast growth factor 23 (FGF23). Burosumab binds FGF23, increasing renal tubular reabsorption of phosphorus and 1,25-dihydroxycholecalciferol, also called calcitriol.

Previously, XLH had been treated by frequent oral supplementation with phosphate and calcitriol. Burosumab will be marketed by Ultragenyx Pharmaceutical as Crysvita. It is given as a once-monthly or biweekly subcutaneous injection.

[email protected]

The Food and Drug Administration has approved burosumab to treat X-linked hypophosphatemia, a rare, heritable form of rickets, in adults and children at least 1 year of age. Burosumab received expedited review by the FDA as a breakthrough therapy, and it also has been designated an orphan drug.

X-linked hypophosphatemia (XLH) “differs from other forms of rickets in that vitamin D therapy is not effective. This is the first FDA-approved medication for the treatment of XLH and a real breakthrough for those living with this serious disease,” said Julie Beitz, MD, in an FDA press release announcing the approval of the fully human monoclonal antibody. Dr. Beitz is director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research.

Four clinical trials formed the basis for the FDA’s approval of burosumab. A pivotal randomized, placebo-controlled, double-blind study of adults with XLH that randomized 134 patients 1:1 to subcutaneous burosumab or placebo found that normal phosphorus levels were achieved in 94% of adults receiving burosumab, compared with 8% of those who received placebo.

For children, biweekly burosumab resulted in normal phosphorus levels for 94%-100% of participants. Significant skeletal radiographic improvement also was seen for adults and children taking burosumab.

In both adults and children, burosumab had a good safety profile, with no significant changes in serum or urine levels of calcium or in serum levels of intact parathyroid hormone.

X-linked hypophosphatemia is variable in severity; many patients with XLH will have bone pain, bowed legs, and a waddling gait; enthesopathy with associated joint pain; and dental problems and pain. Many also have short stature and, unlike rickets caused by dietary deficiency and some malabsorption problems, XLH is not improved by conventional vitamin D therapy.

The rare disorder, affecting about 3,000 children and 12,000 adults in the United States, is caused by a mutation in the PHEX gene, with resultant overactivity of fibroblast growth factor 23 (FGF23). Burosumab binds FGF23, increasing renal tubular reabsorption of phosphorus and 1,25-dihydroxycholecalciferol, also called calcitriol.

Previously, XLH had been treated by frequent oral supplementation with phosphate and calcitriol. Burosumab will be marketed by Ultragenyx Pharmaceutical as Crysvita. It is given as a once-monthly or biweekly subcutaneous injection.

[email protected]

The Food and Drug Administration has approved burosumab to treat X-linked hypophosphatemia, a rare, heritable form of rickets, in adults and children at least 1 year of age. Burosumab received expedited review by the FDA as a breakthrough therapy, and it also has been designated an orphan drug.

X-linked hypophosphatemia (XLH) “differs from other forms of rickets in that vitamin D therapy is not effective. This is the first FDA-approved medication for the treatment of XLH and a real breakthrough for those living with this serious disease,” said Julie Beitz, MD, in an FDA press release announcing the approval of the fully human monoclonal antibody. Dr. Beitz is director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research.

Four clinical trials formed the basis for the FDA’s approval of burosumab. A pivotal randomized, placebo-controlled, double-blind study of adults with XLH that randomized 134 patients 1:1 to subcutaneous burosumab or placebo found that normal phosphorus levels were achieved in 94% of adults receiving burosumab, compared with 8% of those who received placebo.

For children, biweekly burosumab resulted in normal phosphorus levels for 94%-100% of participants. Significant skeletal radiographic improvement also was seen for adults and children taking burosumab.

In both adults and children, burosumab had a good safety profile, with no significant changes in serum or urine levels of calcium or in serum levels of intact parathyroid hormone.

X-linked hypophosphatemia is variable in severity; many patients with XLH will have bone pain, bowed legs, and a waddling gait; enthesopathy with associated joint pain; and dental problems and pain. Many also have short stature and, unlike rickets caused by dietary deficiency and some malabsorption problems, XLH is not improved by conventional vitamin D therapy.

The rare disorder, affecting about 3,000 children and 12,000 adults in the United States, is caused by a mutation in the PHEX gene, with resultant overactivity of fibroblast growth factor 23 (FGF23). Burosumab binds FGF23, increasing renal tubular reabsorption of phosphorus and 1,25-dihydroxycholecalciferol, also called calcitriol.

Previously, XLH had been treated by frequent oral supplementation with phosphate and calcitriol. Burosumab will be marketed by Ultragenyx Pharmaceutical as Crysvita. It is given as a once-monthly or biweekly subcutaneous injection.

[email protected]

SALT LAKE CITY – Recipients of hematopoietic cell transplant with umbilical cord blood CD34+ cells expanded with an aryl hydrocarbon receptor (AHR) antagonist had a significantly higher rate of engraftment and comparable survival to a historical cohort of umbilical cord blood recipients.

The robust expansion of donor umbilical cord blood seen with the new technique opens the door for better use of umbilical cord blood inventory with superior human leukocyte antigen (HLA) matching, John Wagner, MD, said at a top abstracts session of the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

The new technique still shared the benefits of low rates of graft-versus-host disease (GVHD) and high survival that have been seen in previous umbilical cord blood transplants, with no significant difference in overall survival, relapse, or acute or chronic GVHD.

Compared to historical controls (n = 151), patients receiving the AHR antagonist–expanded umbilical cord blood (UCB) cells with myeloablative conditioning (n = 9) saw complete and more rapid engraftment (100% vs. 89% engraftment at a median 14 days vs. 23 days; P less than .01), reported Dr. Wagner of the University of Minnesota, Minneapolis.

These and other results came from two arms of a phase 2 trial of MGTA-456 (the working name of the AHR-expanded UCB cells). Twenty patients were to receive MGTA-456 derived from partially matched umbilical cord blood units after either myeloablative or nonmyeloablative conditioning; one patient in each arm had low expansion of UCB, so a total of 18 patients received MGTA-456. Each intervention arm was compared with a historical control arm that had received conventional UCB units.

In the myeloablative arm, patient demographics and disease characteristics were similar to the control cohort except that the MGTA-456 patients were significantly heavier (93.8 kg vs. 66.7 kg; P less than .04).

[email protected]

SOURCE: Wagner J et al. 2018 BMT Tandem Meetings, Abstract 4.

SALT LAKE CITY – Recipients of hematopoietic cell transplant with umbilical cord blood CD34+ cells expanded with an aryl hydrocarbon receptor (AHR) antagonist had a significantly higher rate of engraftment and comparable survival to a historical cohort of umbilical cord blood recipients.

The robust expansion of donor umbilical cord blood seen with the new technique opens the door for better use of umbilical cord blood inventory with superior human leukocyte antigen (HLA) matching, John Wagner, MD, said at a top abstracts session of the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

The new technique still shared the benefits of low rates of graft-versus-host disease (GVHD) and high survival that have been seen in previous umbilical cord blood transplants, with no significant difference in overall survival, relapse, or acute or chronic GVHD.

Compared to historical controls (n = 151), patients receiving the AHR antagonist–expanded umbilical cord blood (UCB) cells with myeloablative conditioning (n = 9) saw complete and more rapid engraftment (100% vs. 89% engraftment at a median 14 days vs. 23 days; P less than .01), reported Dr. Wagner of the University of Minnesota, Minneapolis.

These and other results came from two arms of a phase 2 trial of MGTA-456 (the working name of the AHR-expanded UCB cells). Twenty patients were to receive MGTA-456 derived from partially matched umbilical cord blood units after either myeloablative or nonmyeloablative conditioning; one patient in each arm had low expansion of UCB, so a total of 18 patients received MGTA-456. Each intervention arm was compared with a historical control arm that had received conventional UCB units.

In the myeloablative arm, patient demographics and disease characteristics were similar to the control cohort except that the MGTA-456 patients were significantly heavier (93.8 kg vs. 66.7 kg; P less than .04).

[email protected]

SOURCE: Wagner J et al. 2018 BMT Tandem Meetings, Abstract 4.

SALT LAKE CITY – Recipients of hematopoietic cell transplant with umbilical cord blood CD34+ cells expanded with an aryl hydrocarbon receptor (AHR) antagonist had a significantly higher rate of engraftment and comparable survival to a historical cohort of umbilical cord blood recipients.

The robust expansion of donor umbilical cord blood seen with the new technique opens the door for better use of umbilical cord blood inventory with superior human leukocyte antigen (HLA) matching, John Wagner, MD, said at a top abstracts session of the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

The new technique still shared the benefits of low rates of graft-versus-host disease (GVHD) and high survival that have been seen in previous umbilical cord blood transplants, with no significant difference in overall survival, relapse, or acute or chronic GVHD.

Compared to historical controls (n = 151), patients receiving the AHR antagonist–expanded umbilical cord blood (UCB) cells with myeloablative conditioning (n = 9) saw complete and more rapid engraftment (100% vs. 89% engraftment at a median 14 days vs. 23 days; P less than .01), reported Dr. Wagner of the University of Minnesota, Minneapolis.

These and other results came from two arms of a phase 2 trial of MGTA-456 (the working name of the AHR-expanded UCB cells). Twenty patients were to receive MGTA-456 derived from partially matched umbilical cord blood units after either myeloablative or nonmyeloablative conditioning; one patient in each arm had low expansion of UCB, so a total of 18 patients received MGTA-456. Each intervention arm was compared with a historical control arm that had received conventional UCB units.

In the myeloablative arm, patient demographics and disease characteristics were similar to the control cohort except that the MGTA-456 patients were significantly heavier (93.8 kg vs. 66.7 kg; P less than .04).

[email protected]

SOURCE: Wagner J et al. 2018 BMT Tandem Meetings, Abstract 4.

How do you summarize a year’s worth of hospitalist-relevant research in an hour? If you’re Cynthia Cooper, MD, and Barbara Slawski, MD, MS, SFHM, you do it with teamwork, rigor, and style.

When the two physicians signed on for the 2018 “Update in Hospital Medicine” talk, they knew the bar was high. The updates talk is a perennial crowd favorite at the Society of Hospital Medicine annual conferences, and this year’s talk, which touched on topics from #MeToo to kidney injury, didn’t disappoint.

MDedge News

Among the highlights of the 20 studies reviewed in concise fashion by Dr. Cooper and Dr. Slawski was work that revealed a startling amount of gender bias when speakers are introduced at medical grand rounds. “One of the things that made the news a lot this last year is gender bias, so we thought we’d start out with that,” said Dr. Slawski, chief of the section of perioperative medicine at the Medical College of Wisconsin in Milwaukee.

In a retrospective observational study, the investigators looked at archived grand rounds video to see how often speakers with doctoral degrees were introduced by title, rather than by first name. Mixed-gender evaluators found that females were much more likely than were males to introduce either females or males by title (P less than .001).

“Have any of you ever had this experience? Me, too,” said Dr. Slawski, to wide and prolonged applause.

Females introducing males were almost twice as likely to use the speaker’s title as when males introduced females (95% vs. 49%; P less than .001). These revelations, said Dr. Slawski, present an “opportunity for improving professional interactions in an environment of mutual respect,” a comment that the room again greeted with a round of applause.

The inpatient syncope evaluation was made a little easier with another top study presented by Dr. Slawski. Using a large multinational database, investigators looked at a subgroup of patients with syncope who were admitted to the hospital. They found that fewer than 2% of patients with syncope were diagnosed with pulmonary embolus (PE) or deep venous thrombosis within 90 days of the index admission. For Dr. Slawski, this means clinicians may be able to relax their worry about thromboembolic events just a bit: “Although this diagnosis should be considered, not all patients need evaluation,” she said.

How do you summarize a year’s worth of hospitalist-relevant research in an hour? If you’re Cynthia Cooper, MD, and Barbara Slawski, MD, MS, SFHM, you do it with teamwork, rigor, and style.

When the two physicians signed on for the 2018 “Update in Hospital Medicine” talk, they knew the bar was high. The updates talk is a perennial crowd favorite at the Society of Hospital Medicine annual conferences, and this year’s talk, which touched on topics from #MeToo to kidney injury, didn’t disappoint.

MDedge News

Among the highlights of the 20 studies reviewed in concise fashion by Dr. Cooper and Dr. Slawski was work that revealed a startling amount of gender bias when speakers are introduced at medical grand rounds. “One of the things that made the news a lot this last year is gender bias, so we thought we’d start out with that,” said Dr. Slawski, chief of the section of perioperative medicine at the Medical College of Wisconsin in Milwaukee.

In a retrospective observational study, the investigators looked at archived grand rounds video to see how often speakers with doctoral degrees were introduced by title, rather than by first name. Mixed-gender evaluators found that females were much more likely than were males to introduce either females or males by title (P less than .001).

“Have any of you ever had this experience? Me, too,” said Dr. Slawski, to wide and prolonged applause.

Females introducing males were almost twice as likely to use the speaker’s title as when males introduced females (95% vs. 49%; P less than .001). These revelations, said Dr. Slawski, present an “opportunity for improving professional interactions in an environment of mutual respect,” a comment that the room again greeted with a round of applause.

The inpatient syncope evaluation was made a little easier with another top study presented by Dr. Slawski. Using a large multinational database, investigators looked at a subgroup of patients with syncope who were admitted to the hospital. They found that fewer than 2% of patients with syncope were diagnosed with pulmonary embolus (PE) or deep venous thrombosis within 90 days of the index admission. For Dr. Slawski, this means clinicians may be able to relax their worry about thromboembolic events just a bit: “Although this diagnosis should be considered, not all patients need evaluation,” she said.

How do you summarize a year’s worth of hospitalist-relevant research in an hour? If you’re Cynthia Cooper, MD, and Barbara Slawski, MD, MS, SFHM, you do it with teamwork, rigor, and style.

When the two physicians signed on for the 2018 “Update in Hospital Medicine” talk, they knew the bar was high. The updates talk is a perennial crowd favorite at the Society of Hospital Medicine annual conferences, and this year’s talk, which touched on topics from #MeToo to kidney injury, didn’t disappoint.

MDedge News

Among the highlights of the 20 studies reviewed in concise fashion by Dr. Cooper and Dr. Slawski was work that revealed a startling amount of gender bias when speakers are introduced at medical grand rounds. “One of the things that made the news a lot this last year is gender bias, so we thought we’d start out with that,” said Dr. Slawski, chief of the section of perioperative medicine at the Medical College of Wisconsin in Milwaukee.

In a retrospective observational study, the investigators looked at archived grand rounds video to see how often speakers with doctoral degrees were introduced by title, rather than by first name. Mixed-gender evaluators found that females were much more likely than were males to introduce either females or males by title (P less than .001).

“Have any of you ever had this experience? Me, too,” said Dr. Slawski, to wide and prolonged applause.

Females introducing males were almost twice as likely to use the speaker’s title as when males introduced females (95% vs. 49%; P less than .001). These revelations, said Dr. Slawski, present an “opportunity for improving professional interactions in an environment of mutual respect,” a comment that the room again greeted with a round of applause.

The inpatient syncope evaluation was made a little easier with another top study presented by Dr. Slawski. Using a large multinational database, investigators looked at a subgroup of patients with syncope who were admitted to the hospital. They found that fewer than 2% of patients with syncope were diagnosed with pulmonary embolus (PE) or deep venous thrombosis within 90 days of the index admission. For Dr. Slawski, this means clinicians may be able to relax their worry about thromboembolic events just a bit: “Although this diagnosis should be considered, not all patients need evaluation,” she said.