NATIONAL HARBOR, MD. – Gastric bypass and sleeve gastrectomy procedures for weight loss should not be denied to patients older than 60 years, despite a slight increase in unadjusted mortality rates, according to an analysis of data from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP).

Based on data that was collected in 2015 and submitted to MBSAQIP, “bariatric surgery is safe in the elderly, even in those 70 years old and older,” reported Tallal Zeni, MD, director of the Michigan Bariatric Institute in Livonia.

NATIONAL HARBOR, MD. – Gastric bypass and sleeve gastrectomy procedures for weight loss should not be denied to patients older than 60 years, despite a slight increase in unadjusted mortality rates, according to an analysis of data from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP).

Based on data that was collected in 2015 and submitted to MBSAQIP, “bariatric surgery is safe in the elderly, even in those 70 years old and older,” reported Tallal Zeni, MD, director of the Michigan Bariatric Institute in Livonia.

NATIONAL HARBOR, MD. – Gastric bypass and sleeve gastrectomy procedures for weight loss should not be denied to patients older than 60 years, despite a slight increase in unadjusted mortality rates, according to an analysis of data from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP).

Based on data that was collected in 2015 and submitted to MBSAQIP, “bariatric surgery is safe in the elderly, even in those 70 years old and older,” reported Tallal Zeni, MD, director of the Michigan Bariatric Institute in Livonia.

ANAHEIM, CALIF. – Patients with symptomatic peripheral artery disease or a high-risk history of MI got the biggest bang for the buck from aggressive LDL cholesterol lowering with evolocumab in two new prespecified subgroup analyses from the landmark FOURIER trial presented at the American Heart Association scientific sessions.

“At the end of the day, not all of our patients with ASCVD [atherosclerotic cardiovascular disease] can have these expensive medications. These subgroup analyses will help clinicians to target use of PCSK9 inhibitors to the patients who will benefit the most,” Lynne T. Braun, PhD, commented in her role as discussant of the two secondary analyses, presented back to back in a late-breaking science session. Dr. Braun is a professor in the department of internal medicine at Rush University, Chicago.

The FOURIER trial included 27,564 high-risk patients with prior MI, stroke, and/or symptomatic peripheral arterial disease (PAD) who had an LDL cholesterol level of 70 mg/dL or more on high- or moderate-intensity statin therapy. They were randomized in double-blind fashion to add-on subcutaneous evolocumab (Repatha) at either 140 mg every 2 weeks or 420 mg/month or to placebo, for a median of 2.5 years of follow-up. The evolocumab group experienced a 59% reduction in LDL cholesterol, compared with the controls on background statin therapy plus placebo, down to a mean LDL cholesterol level of just 30 mg/dL.

As previously reported, the risk of the primary composite endpoint – comprising cardiovascular death, MI, stroke, unstable angina, or coronary revascularization – was reduced by 15% in the evolocumab group at 3 years. The secondary endpoint of cardiovascular death, MI, or stroke was reduced by 20%, from 9.9% to 7.9% (N Engl J Med. 2017;376:1713-22).
 

Evolocumab tamed PAD

At the AHA scientific sessions, Marc P. Bonaca, MD, presented a secondary analysis restricted to the 3,642 FOURIER participants with symptomatic PAD. The goal was to answer two unresolved questions: Does LDL cholesterol lowering beyond what’s achievable with a statin further reduce PAD patients’ cardiovascular risk? And does it reduce their risk of major adverse leg events (MALE), defined as a composite of acute limb ischemia, major amputation, and urgent revascularization?

Bruce Jancin/Frontline Medical News

Spotting the patients with a history of MI who’re at highest risk

Marc S. Sabatine, MD, presented the subanalysis involving the 22,351 FOURIER patients with a prior MI. He and his coinvestigators identified three high-risk features within this group: an MI within the past 2 years, a history of two or more MIs, and residual multivessel CAD. Each of these three features was individually associated with a 34%-90% increased risk of MACE during follow-up. All told, 63% of FOURIER participants with prior MI had one or more of the high-risk features.

Bruce Jancin/Frontline Medical News

Lingering questions

Dr. Braun was particularly impressed that the absolute risk reduction in MACE was even larger in patients with baseline PAD but no history of stroke or MI than in PAD patients with such a history. She added that, while she recognizes the value of selecting objectively assessable hard clinical MACE as the primary endpoint in FOURIER, her own patients care even more about other outcomes.

“What my patients with PAD care most about is whether profound LDL lowering translates to less claudication, improved quality of life, and greater physical activity tolerance. These were prespecified secondary outcomes in FOURIER, and I look forward to future reports addressing those issues,” she said.

Another unanswered question involves the mechanism by which intensive LDL cholesterol lowering results in fewer MACE and MALE events in high-risk subgroups. The possibilities include the plaque regression that was documented in the GLAGOV trial, an anti-inflammatory plaque-stabilizing effect being exerted through PCSK9 inhibition, or perhaps the PCSK9 inhibitors’ ability to moderately lower lipoprotein(a) cholesterol levels.

Simultaneous with Dr. Bonaca’s presentation at the AHA, the FOURIER PAD analysis was published online in Circulation (2017 Nov 13; doi: 10.1161/CIRCULATIONAHA.117.032235).

The FOURIER trial was sponsored by Amgen. Dr. Bonaca and Dr. Sabatine reported receiving research grants from and serving as consultants to Amgen and other companies.

[email protected]
 

ANAHEIM, CALIF. – Patients with symptomatic peripheral artery disease or a high-risk history of MI got the biggest bang for the buck from aggressive LDL cholesterol lowering with evolocumab in two new prespecified subgroup analyses from the landmark FOURIER trial presented at the American Heart Association scientific sessions.

“At the end of the day, not all of our patients with ASCVD [atherosclerotic cardiovascular disease] can have these expensive medications. These subgroup analyses will help clinicians to target use of PCSK9 inhibitors to the patients who will benefit the most,” Lynne T. Braun, PhD, commented in her role as discussant of the two secondary analyses, presented back to back in a late-breaking science session. Dr. Braun is a professor in the department of internal medicine at Rush University, Chicago.

The FOURIER trial included 27,564 high-risk patients with prior MI, stroke, and/or symptomatic peripheral arterial disease (PAD) who had an LDL cholesterol level of 70 mg/dL or more on high- or moderate-intensity statin therapy. They were randomized in double-blind fashion to add-on subcutaneous evolocumab (Repatha) at either 140 mg every 2 weeks or 420 mg/month or to placebo, for a median of 2.5 years of follow-up. The evolocumab group experienced a 59% reduction in LDL cholesterol, compared with the controls on background statin therapy plus placebo, down to a mean LDL cholesterol level of just 30 mg/dL.

As previously reported, the risk of the primary composite endpoint – comprising cardiovascular death, MI, stroke, unstable angina, or coronary revascularization – was reduced by 15% in the evolocumab group at 3 years. The secondary endpoint of cardiovascular death, MI, or stroke was reduced by 20%, from 9.9% to 7.9% (N Engl J Med. 2017;376:1713-22).
 

Evolocumab tamed PAD

At the AHA scientific sessions, Marc P. Bonaca, MD, presented a secondary analysis restricted to the 3,642 FOURIER participants with symptomatic PAD. The goal was to answer two unresolved questions: Does LDL cholesterol lowering beyond what’s achievable with a statin further reduce PAD patients’ cardiovascular risk? And does it reduce their risk of major adverse leg events (MALE), defined as a composite of acute limb ischemia, major amputation, and urgent revascularization?

Bruce Jancin/Frontline Medical News

Spotting the patients with a history of MI who’re at highest risk

Marc S. Sabatine, MD, presented the subanalysis involving the 22,351 FOURIER patients with a prior MI. He and his coinvestigators identified three high-risk features within this group: an MI within the past 2 years, a history of two or more MIs, and residual multivessel CAD. Each of these three features was individually associated with a 34%-90% increased risk of MACE during follow-up. All told, 63% of FOURIER participants with prior MI had one or more of the high-risk features.

Bruce Jancin/Frontline Medical News

Lingering questions

Dr. Braun was particularly impressed that the absolute risk reduction in MACE was even larger in patients with baseline PAD but no history of stroke or MI than in PAD patients with such a history. She added that, while she recognizes the value of selecting objectively assessable hard clinical MACE as the primary endpoint in FOURIER, her own patients care even more about other outcomes.

“What my patients with PAD care most about is whether profound LDL lowering translates to less claudication, improved quality of life, and greater physical activity tolerance. These were prespecified secondary outcomes in FOURIER, and I look forward to future reports addressing those issues,” she said.

Another unanswered question involves the mechanism by which intensive LDL cholesterol lowering results in fewer MACE and MALE events in high-risk subgroups. The possibilities include the plaque regression that was documented in the GLAGOV trial, an anti-inflammatory plaque-stabilizing effect being exerted through PCSK9 inhibition, or perhaps the PCSK9 inhibitors’ ability to moderately lower lipoprotein(a) cholesterol levels.

Simultaneous with Dr. Bonaca’s presentation at the AHA, the FOURIER PAD analysis was published online in Circulation (2017 Nov 13; doi: 10.1161/CIRCULATIONAHA.117.032235).

The FOURIER trial was sponsored by Amgen. Dr. Bonaca and Dr. Sabatine reported receiving research grants from and serving as consultants to Amgen and other companies.

[email protected]
 

ANAHEIM, CALIF. – Patients with symptomatic peripheral artery disease or a high-risk history of MI got the biggest bang for the buck from aggressive LDL cholesterol lowering with evolocumab in two new prespecified subgroup analyses from the landmark FOURIER trial presented at the American Heart Association scientific sessions.

“At the end of the day, not all of our patients with ASCVD [atherosclerotic cardiovascular disease] can have these expensive medications. These subgroup analyses will help clinicians to target use of PCSK9 inhibitors to the patients who will benefit the most,” Lynne T. Braun, PhD, commented in her role as discussant of the two secondary analyses, presented back to back in a late-breaking science session. Dr. Braun is a professor in the department of internal medicine at Rush University, Chicago.

The FOURIER trial included 27,564 high-risk patients with prior MI, stroke, and/or symptomatic peripheral arterial disease (PAD) who had an LDL cholesterol level of 70 mg/dL or more on high- or moderate-intensity statin therapy. They were randomized in double-blind fashion to add-on subcutaneous evolocumab (Repatha) at either 140 mg every 2 weeks or 420 mg/month or to placebo, for a median of 2.5 years of follow-up. The evolocumab group experienced a 59% reduction in LDL cholesterol, compared with the controls on background statin therapy plus placebo, down to a mean LDL cholesterol level of just 30 mg/dL.

As previously reported, the risk of the primary composite endpoint – comprising cardiovascular death, MI, stroke, unstable angina, or coronary revascularization – was reduced by 15% in the evolocumab group at 3 years. The secondary endpoint of cardiovascular death, MI, or stroke was reduced by 20%, from 9.9% to 7.9% (N Engl J Med. 2017;376:1713-22).
 

Evolocumab tamed PAD

At the AHA scientific sessions, Marc P. Bonaca, MD, presented a secondary analysis restricted to the 3,642 FOURIER participants with symptomatic PAD. The goal was to answer two unresolved questions: Does LDL cholesterol lowering beyond what’s achievable with a statin further reduce PAD patients’ cardiovascular risk? And does it reduce their risk of major adverse leg events (MALE), defined as a composite of acute limb ischemia, major amputation, and urgent revascularization?

Bruce Jancin/Frontline Medical News

Spotting the patients with a history of MI who’re at highest risk

Marc S. Sabatine, MD, presented the subanalysis involving the 22,351 FOURIER patients with a prior MI. He and his coinvestigators identified three high-risk features within this group: an MI within the past 2 years, a history of two or more MIs, and residual multivessel CAD. Each of these three features was individually associated with a 34%-90% increased risk of MACE during follow-up. All told, 63% of FOURIER participants with prior MI had one or more of the high-risk features.

Bruce Jancin/Frontline Medical News

Lingering questions

Dr. Braun was particularly impressed that the absolute risk reduction in MACE was even larger in patients with baseline PAD but no history of stroke or MI than in PAD patients with such a history. She added that, while she recognizes the value of selecting objectively assessable hard clinical MACE as the primary endpoint in FOURIER, her own patients care even more about other outcomes.

“What my patients with PAD care most about is whether profound LDL lowering translates to less claudication, improved quality of life, and greater physical activity tolerance. These were prespecified secondary outcomes in FOURIER, and I look forward to future reports addressing those issues,” she said.

Another unanswered question involves the mechanism by which intensive LDL cholesterol lowering results in fewer MACE and MALE events in high-risk subgroups. The possibilities include the plaque regression that was documented in the GLAGOV trial, an anti-inflammatory plaque-stabilizing effect being exerted through PCSK9 inhibition, or perhaps the PCSK9 inhibitors’ ability to moderately lower lipoprotein(a) cholesterol levels.

Simultaneous with Dr. Bonaca’s presentation at the AHA, the FOURIER PAD analysis was published online in Circulation (2017 Nov 13; doi: 10.1161/CIRCULATIONAHA.117.032235).

The FOURIER trial was sponsored by Amgen. Dr. Bonaca and Dr. Sabatine reported receiving research grants from and serving as consultants to Amgen and other companies.

[email protected]
 

The Food and Drug Administration has approved the first drug in the United States with a digital ingestion tracking system. Abilify MyCite (aripiprazole tablets with sensor) has an ingestible sensor embedded in the pill that records that the medication was taken. The product is approved for the treatment of schizophrenia, acute treatment of manic and mixed episodes associated with bipolar I disorder, and for use as an add-on treatment for depression in adults.

The system works by sending a message from the pill’s sensor to a wearable patch, according to a statement issued by the FDA. The patch transmits the information to a mobile application so that patients can track the ingestion of the medication on their smartphones. Patients can also permit their caregivers and physician to access the information through a web-based portal.

[polldaddy:9874958]

The Food and Drug Administration has approved the first drug in the United States with a digital ingestion tracking system. Abilify MyCite (aripiprazole tablets with sensor) has an ingestible sensor embedded in the pill that records that the medication was taken. The product is approved for the treatment of schizophrenia, acute treatment of manic and mixed episodes associated with bipolar I disorder, and for use as an add-on treatment for depression in adults.

The system works by sending a message from the pill’s sensor to a wearable patch, according to a statement issued by the FDA. The patch transmits the information to a mobile application so that patients can track the ingestion of the medication on their smartphones. Patients can also permit their caregivers and physician to access the information through a web-based portal.

[polldaddy:9874958]

The Food and Drug Administration has approved the first drug in the United States with a digital ingestion tracking system. Abilify MyCite (aripiprazole tablets with sensor) has an ingestible sensor embedded in the pill that records that the medication was taken. The product is approved for the treatment of schizophrenia, acute treatment of manic and mixed episodes associated with bipolar I disorder, and for use as an add-on treatment for depression in adults.

The system works by sending a message from the pill’s sensor to a wearable patch, according to a statement issued by the FDA. The patch transmits the information to a mobile application so that patients can track the ingestion of the medication on their smartphones. Patients can also permit their caregivers and physician to access the information through a web-based portal.

[polldaddy:9874958]

SAN DIEGO – Healthy individuals can show signs of spinal and pelvic inflammation on MRI, but these scans can be misleading if relied on to make a diagnosis of axial spondyloarthritis, according to findings from three separate studies at the annual meeting of the American College of Rheumatology.

“Don’t rely on MRI alone is our message,” said Robert Landewé, MD, PhD, of the University of Amsterdam, who was a coauthor of one of the three studies. “A positive MRI may occur in individuals that are completely healthy. We need to make sure that not too many patients with chronic lower back pain are diagnosed with a disease they don’t have.”

The axial form of spondyloarthritis (axSpA) affects the spinal and pelvic joints of an estimated 1.4% of the U.S. population, and the term encompasses the diagnosis of ankylosing spondylitis (0.5% of U.S. population) in which advanced sacroiliitis is seen on conventional radiography, according to the ACR. Axial SpA is particularly common in young people, especially males, in their teens and 20s.

Researchers believe that MRI scans can misleadingly suggest that patients have the condition. “We know that MRI is a sensitive method, but there’s a lack of data regarding its specificity,” Thomas Renson, MD, of Ghent (Belgium) University, said at a press conference during the meeting.

Dr. Landewé led a study that compared MRIs of sacroiliac joints in 47 healthy people, 47 axSpA patients matched for gender and age, 47 chronic back pain patients, 7 women with postpartum back pain, and 24 frequent runners. Positive MRIs were common in the axSpA patients (43 of 47), but they were also found in healthy people (11 of 47), chronic back pain patients (3 of 47), frequent runners (3 of 24), and women with postpartum back pain (4 of 7).

In another study, Dr. Renson and his colleagues sought to understand whether a sustained period of intense physical activity affected spinal findings in 22 healthy military recruits who did not have SpA.

However, there was a statistically significant increase of combined structural and inflammatory lesions (P = .038) from baseline to post training.

The findings underscore “the importance of interpretation of imaging in the right clinical context,” Dr. Renson said, since they point to the possibility of an incorrect diagnosis “even in a young, active population.”

Another study, led by Ulrich Weber, MD, of King Christian 10th Hospital for Rheumatic Diseases, Gråsten, Denmark, sought to understand levels of normal low-grade BME in 20 amateur runners (8 men) and 22 professional Danish hockey players (all men). On average, the researchers found signs of BME in 3.1 sacroiliac joint quadrants in the runners before and after they ran a race. Hockey players were scanned at the end of the competitive season and showed signs of BME in an average of 3.6 sacroiliac joint quadrants.

In an interview, Dr. Landewé said the studies point to how common positive MRIs are in healthy people. “It was far higher than we would have thought 10 years ago,” he said.

Are MRIs still useful then? Dr. Weber said MRI scans are still helpful in axSpA diagnoses even though they have major limitations. “The imaging method is the only one that’s halfway reliable,” he said. “These joints are deep in the body, so we have virtually no clinical ways to diagnose this.”

However, Dr. Landewé said, “you should do it only when you have sufficient suspicion of spondyloarthritis” – due to accompanying conditions such as positive family history, acute anterior uveitis, psoriasis, or peripheral arthritis – and not just when a patient has chronic back pain.

Dr. Renson reported having no relevant disclosures; two of his coauthors reported extensive disclosures. Dr. Weber and his coauthors reported having no relevant disclosures. Dr. Landewé reported having no relevant disclosures; several of his coauthors reported various disclosures. Funding for the studies was not reported.

SAN DIEGO – Healthy individuals can show signs of spinal and pelvic inflammation on MRI, but these scans can be misleading if relied on to make a diagnosis of axial spondyloarthritis, according to findings from three separate studies at the annual meeting of the American College of Rheumatology.

“Don’t rely on MRI alone is our message,” said Robert Landewé, MD, PhD, of the University of Amsterdam, who was a coauthor of one of the three studies. “A positive MRI may occur in individuals that are completely healthy. We need to make sure that not too many patients with chronic lower back pain are diagnosed with a disease they don’t have.”

The axial form of spondyloarthritis (axSpA) affects the spinal and pelvic joints of an estimated 1.4% of the U.S. population, and the term encompasses the diagnosis of ankylosing spondylitis (0.5% of U.S. population) in which advanced sacroiliitis is seen on conventional radiography, according to the ACR. Axial SpA is particularly common in young people, especially males, in their teens and 20s.

Researchers believe that MRI scans can misleadingly suggest that patients have the condition. “We know that MRI is a sensitive method, but there’s a lack of data regarding its specificity,” Thomas Renson, MD, of Ghent (Belgium) University, said at a press conference during the meeting.

Dr. Landewé led a study that compared MRIs of sacroiliac joints in 47 healthy people, 47 axSpA patients matched for gender and age, 47 chronic back pain patients, 7 women with postpartum back pain, and 24 frequent runners. Positive MRIs were common in the axSpA patients (43 of 47), but they were also found in healthy people (11 of 47), chronic back pain patients (3 of 47), frequent runners (3 of 24), and women with postpartum back pain (4 of 7).

In another study, Dr. Renson and his colleagues sought to understand whether a sustained period of intense physical activity affected spinal findings in 22 healthy military recruits who did not have SpA.

However, there was a statistically significant increase of combined structural and inflammatory lesions (P = .038) from baseline to post training.

The findings underscore “the importance of interpretation of imaging in the right clinical context,” Dr. Renson said, since they point to the possibility of an incorrect diagnosis “even in a young, active population.”

Another study, led by Ulrich Weber, MD, of King Christian 10th Hospital for Rheumatic Diseases, Gråsten, Denmark, sought to understand levels of normal low-grade BME in 20 amateur runners (8 men) and 22 professional Danish hockey players (all men). On average, the researchers found signs of BME in 3.1 sacroiliac joint quadrants in the runners before and after they ran a race. Hockey players were scanned at the end of the competitive season and showed signs of BME in an average of 3.6 sacroiliac joint quadrants.

In an interview, Dr. Landewé said the studies point to how common positive MRIs are in healthy people. “It was far higher than we would have thought 10 years ago,” he said.

Are MRIs still useful then? Dr. Weber said MRI scans are still helpful in axSpA diagnoses even though they have major limitations. “The imaging method is the only one that’s halfway reliable,” he said. “These joints are deep in the body, so we have virtually no clinical ways to diagnose this.”

However, Dr. Landewé said, “you should do it only when you have sufficient suspicion of spondyloarthritis” – due to accompanying conditions such as positive family history, acute anterior uveitis, psoriasis, or peripheral arthritis – and not just when a patient has chronic back pain.

Dr. Renson reported having no relevant disclosures; two of his coauthors reported extensive disclosures. Dr. Weber and his coauthors reported having no relevant disclosures. Dr. Landewé reported having no relevant disclosures; several of his coauthors reported various disclosures. Funding for the studies was not reported.

SAN DIEGO – Healthy individuals can show signs of spinal and pelvic inflammation on MRI, but these scans can be misleading if relied on to make a diagnosis of axial spondyloarthritis, according to findings from three separate studies at the annual meeting of the American College of Rheumatology.

“Don’t rely on MRI alone is our message,” said Robert Landewé, MD, PhD, of the University of Amsterdam, who was a coauthor of one of the three studies. “A positive MRI may occur in individuals that are completely healthy. We need to make sure that not too many patients with chronic lower back pain are diagnosed with a disease they don’t have.”

The axial form of spondyloarthritis (axSpA) affects the spinal and pelvic joints of an estimated 1.4% of the U.S. population, and the term encompasses the diagnosis of ankylosing spondylitis (0.5% of U.S. population) in which advanced sacroiliitis is seen on conventional radiography, according to the ACR. Axial SpA is particularly common in young people, especially males, in their teens and 20s.

Researchers believe that MRI scans can misleadingly suggest that patients have the condition. “We know that MRI is a sensitive method, but there’s a lack of data regarding its specificity,” Thomas Renson, MD, of Ghent (Belgium) University, said at a press conference during the meeting.

Dr. Landewé led a study that compared MRIs of sacroiliac joints in 47 healthy people, 47 axSpA patients matched for gender and age, 47 chronic back pain patients, 7 women with postpartum back pain, and 24 frequent runners. Positive MRIs were common in the axSpA patients (43 of 47), but they were also found in healthy people (11 of 47), chronic back pain patients (3 of 47), frequent runners (3 of 24), and women with postpartum back pain (4 of 7).

In another study, Dr. Renson and his colleagues sought to understand whether a sustained period of intense physical activity affected spinal findings in 22 healthy military recruits who did not have SpA.

However, there was a statistically significant increase of combined structural and inflammatory lesions (P = .038) from baseline to post training.

The findings underscore “the importance of interpretation of imaging in the right clinical context,” Dr. Renson said, since they point to the possibility of an incorrect diagnosis “even in a young, active population.”

Another study, led by Ulrich Weber, MD, of King Christian 10th Hospital for Rheumatic Diseases, Gråsten, Denmark, sought to understand levels of normal low-grade BME in 20 amateur runners (8 men) and 22 professional Danish hockey players (all men). On average, the researchers found signs of BME in 3.1 sacroiliac joint quadrants in the runners before and after they ran a race. Hockey players were scanned at the end of the competitive season and showed signs of BME in an average of 3.6 sacroiliac joint quadrants.

In an interview, Dr. Landewé said the studies point to how common positive MRIs are in healthy people. “It was far higher than we would have thought 10 years ago,” he said.

Are MRIs still useful then? Dr. Weber said MRI scans are still helpful in axSpA diagnoses even though they have major limitations. “The imaging method is the only one that’s halfway reliable,” he said. “These joints are deep in the body, so we have virtually no clinical ways to diagnose this.”

However, Dr. Landewé said, “you should do it only when you have sufficient suspicion of spondyloarthritis” – due to accompanying conditions such as positive family history, acute anterior uveitis, psoriasis, or peripheral arthritis – and not just when a patient has chronic back pain.

Dr. Renson reported having no relevant disclosures; two of his coauthors reported extensive disclosures. Dr. Weber and his coauthors reported having no relevant disclosures. Dr. Landewé reported having no relevant disclosures; several of his coauthors reported various disclosures. Funding for the studies was not reported.

NATIONAL HARBOR, MD. – Women undergoing hysterectomy or myomectomy for benign indications, who also had fibroids, were less likely to have a malignant diagnosis, according to a study presented at the AAGL Global Congress.

These findings could change the conversation when it comes to counseling patients about the risks associated with morcellation, a procedure that was strongly discouraged by the FDA in 2014 due to the concern that it might have the potential to spread malignancy.

“There’s a lot of things going on in the media about morcellation and risk of malignancy at the time of benign fibroid surgery, but this research actually makes apparent the higher risk of malignancy when fibroids are not present,” Farah Alvi, MD, a second-year fellow at Northwestern University, Chicago, said in an interview. Despite the concerns regarding morcellation and malignancy, this research suggests that patients who have fibroids at time of surgery may have a lower chance of malignancy, compared with patients who have other indications for surgery, she explained.

Dr. Alvi and her colleagues studied 2,987 hysterectomy or myomectomy patients with benign indications between January 2005 and December 2014.

Among patients studied, researchers found 33 confirmed malignant or borderline tumors, 16 of 1,790 (0.89%) in the leiomyoma group and 17 of 1,197 (1.42%) in the group with other indications (P = 0.04). The malignancies/borderline tumors included three leiomyosarcomas, two endometrial sarcomas, two endometrioid adenocarcinomas, one granulose cell tumor, three smooth muscle tumors of uncertain malignant potential, three atypical leiomyoma, and one serous papillary borderline ovarian tumor.

Of those with leiomyomata, 1 in 600 patients were diagnosed with leiomyosarcoma, compared with a risk of 1 in 350 for unanticipated malignancy in general.

Patients with surgical indications of symptomatic leiomyoma had an odds ratio of 0.63 (P = .18) for diagnosis of an unanticipated malignancy, compared with those without leiomyoma, according to Dr. Alvi. The odds of malignancy were also reduced in patients with uterine sizes of 15-20 weeks (OR, 0.65; P = .43) and those with specimen sizes of 250-500 grams (OR, 0.68; P = .64).

These findings will have implications for how physicians counsel women undergoing minimally invasive hysterectomy or myomectomy, Dr. Alvi said.

“In counseling patients about morcellation, we often have quoted them an estimated risk of 1 in 458 for leiomyosarcoma, based on the FDA morcellation warnings, and one thing we can learn is that risk is actually much lower than we think it is,” Dr. Alvi said.

The findings also suggest a shift in focus toward identifying the factors that put women at higher risk for malignancy. For example, older age is one of the most significant risk factors identified in the study, she added.

Dr. Alvi reported having no relevant financial disclosures.

[email protected]

On Twitter @eaztweets

NATIONAL HARBOR, MD. – Women undergoing hysterectomy or myomectomy for benign indications, who also had fibroids, were less likely to have a malignant diagnosis, according to a study presented at the AAGL Global Congress.

These findings could change the conversation when it comes to counseling patients about the risks associated with morcellation, a procedure that was strongly discouraged by the FDA in 2014 due to the concern that it might have the potential to spread malignancy.

“There’s a lot of things going on in the media about morcellation and risk of malignancy at the time of benign fibroid surgery, but this research actually makes apparent the higher risk of malignancy when fibroids are not present,” Farah Alvi, MD, a second-year fellow at Northwestern University, Chicago, said in an interview. Despite the concerns regarding morcellation and malignancy, this research suggests that patients who have fibroids at time of surgery may have a lower chance of malignancy, compared with patients who have other indications for surgery, she explained.

Dr. Alvi and her colleagues studied 2,987 hysterectomy or myomectomy patients with benign indications between January 2005 and December 2014.

Among patients studied, researchers found 33 confirmed malignant or borderline tumors, 16 of 1,790 (0.89%) in the leiomyoma group and 17 of 1,197 (1.42%) in the group with other indications (P = 0.04). The malignancies/borderline tumors included three leiomyosarcomas, two endometrial sarcomas, two endometrioid adenocarcinomas, one granulose cell tumor, three smooth muscle tumors of uncertain malignant potential, three atypical leiomyoma, and one serous papillary borderline ovarian tumor.

Of those with leiomyomata, 1 in 600 patients were diagnosed with leiomyosarcoma, compared with a risk of 1 in 350 for unanticipated malignancy in general.

Patients with surgical indications of symptomatic leiomyoma had an odds ratio of 0.63 (P = .18) for diagnosis of an unanticipated malignancy, compared with those without leiomyoma, according to Dr. Alvi. The odds of malignancy were also reduced in patients with uterine sizes of 15-20 weeks (OR, 0.65; P = .43) and those with specimen sizes of 250-500 grams (OR, 0.68; P = .64).

These findings will have implications for how physicians counsel women undergoing minimally invasive hysterectomy or myomectomy, Dr. Alvi said.

“In counseling patients about morcellation, we often have quoted them an estimated risk of 1 in 458 for leiomyosarcoma, based on the FDA morcellation warnings, and one thing we can learn is that risk is actually much lower than we think it is,” Dr. Alvi said.

The findings also suggest a shift in focus toward identifying the factors that put women at higher risk for malignancy. For example, older age is one of the most significant risk factors identified in the study, she added.

Dr. Alvi reported having no relevant financial disclosures.

[email protected]

On Twitter @eaztweets

NATIONAL HARBOR, MD. – Women undergoing hysterectomy or myomectomy for benign indications, who also had fibroids, were less likely to have a malignant diagnosis, according to a study presented at the AAGL Global Congress.

These findings could change the conversation when it comes to counseling patients about the risks associated with morcellation, a procedure that was strongly discouraged by the FDA in 2014 due to the concern that it might have the potential to spread malignancy.

“There’s a lot of things going on in the media about morcellation and risk of malignancy at the time of benign fibroid surgery, but this research actually makes apparent the higher risk of malignancy when fibroids are not present,” Farah Alvi, MD, a second-year fellow at Northwestern University, Chicago, said in an interview. Despite the concerns regarding morcellation and malignancy, this research suggests that patients who have fibroids at time of surgery may have a lower chance of malignancy, compared with patients who have other indications for surgery, she explained.

Dr. Alvi and her colleagues studied 2,987 hysterectomy or myomectomy patients with benign indications between January 2005 and December 2014.

Among patients studied, researchers found 33 confirmed malignant or borderline tumors, 16 of 1,790 (0.89%) in the leiomyoma group and 17 of 1,197 (1.42%) in the group with other indications (P = 0.04). The malignancies/borderline tumors included three leiomyosarcomas, two endometrial sarcomas, two endometrioid adenocarcinomas, one granulose cell tumor, three smooth muscle tumors of uncertain malignant potential, three atypical leiomyoma, and one serous papillary borderline ovarian tumor.

Of those with leiomyomata, 1 in 600 patients were diagnosed with leiomyosarcoma, compared with a risk of 1 in 350 for unanticipated malignancy in general.

Patients with surgical indications of symptomatic leiomyoma had an odds ratio of 0.63 (P = .18) for diagnosis of an unanticipated malignancy, compared with those without leiomyoma, according to Dr. Alvi. The odds of malignancy were also reduced in patients with uterine sizes of 15-20 weeks (OR, 0.65; P = .43) and those with specimen sizes of 250-500 grams (OR, 0.68; P = .64).

These findings will have implications for how physicians counsel women undergoing minimally invasive hysterectomy or myomectomy, Dr. Alvi said.

“In counseling patients about morcellation, we often have quoted them an estimated risk of 1 in 458 for leiomyosarcoma, based on the FDA morcellation warnings, and one thing we can learn is that risk is actually much lower than we think it is,” Dr. Alvi said.

The findings also suggest a shift in focus toward identifying the factors that put women at higher risk for malignancy. For example, older age is one of the most significant risk factors identified in the study, she added.

Dr. Alvi reported having no relevant financial disclosures.

[email protected]

On Twitter @eaztweets

NATIONAL HARBOR, MD. – Single-port laparoscopy is both safe and feasible, and has the potential to decrease surgical complications and increase efficiency, according to findings presented at the AAGL Global Congress.

Ahmed N. Al-Niaimi, MD, of the University of Wisconsin–Madison, and his colleagues, conducted a retrospective cohort study analyzing 587 consecutive patients who underwent single-port laparoscopy from March 2012 to December 2016. Of the 587 patients, there were 27 clinically-relevant complications among 18 patients (3%). The complications included intensive care unit admission, reoperation, end organ damage, organ space surgical site infection, and readmission.

“Those factors leading to those complications are similar to the factors that cause complications in any other surgery,” Dr. Al-Niaimi said in an interview before the meeting.

Body mass index was found to be a primary contributor to surgical complications. Patients with a BMI of more than 30 kg/m² experienced a 1% increase in the risk of surgical complications per unit value increase of BMI. This is significant because the median BMI of the patient population in the study was 33.9 kg/m² and 57% of the study participants were considered obese or morbidly obese.

“The heavier the patient, the higher the complication rate,” Dr. Al-Niaimi said.

Surgeons who are learning single-port laparoscopy should choose patients with lower BMIs to gain efficiency in using the new technique, Dr. Al-Niaimi suggested. This will allow patients to decrease their risk of surgical complications while allowing surgeons to hone their abilities in a new surgical technique, he said.

The other prime contributor to surgical complications is the length of surgical time. The average time of surgery during the study was 156 minutes. Dr. Al-Niaimi and his colleagues found that for each 10-minute increase in surgical time, the risk of complications increased by 2%.

While the results of the study demonstrate safety in the single-port approach, Dr. Al-Niaimi said a randomized controlled trial is needed to validate the findings and determine whether single-port laparoscopy is more effective than multi-port laparoscopy.

Dr. Al-Niaimi reported having no financial disclosures.

[email protected]

NATIONAL HARBOR, MD. – Single-port laparoscopy is both safe and feasible, and has the potential to decrease surgical complications and increase efficiency, according to findings presented at the AAGL Global Congress.

Ahmed N. Al-Niaimi, MD, of the University of Wisconsin–Madison, and his colleagues, conducted a retrospective cohort study analyzing 587 consecutive patients who underwent single-port laparoscopy from March 2012 to December 2016. Of the 587 patients, there were 27 clinically-relevant complications among 18 patients (3%). The complications included intensive care unit admission, reoperation, end organ damage, organ space surgical site infection, and readmission.

“Those factors leading to those complications are similar to the factors that cause complications in any other surgery,” Dr. Al-Niaimi said in an interview before the meeting.

Body mass index was found to be a primary contributor to surgical complications. Patients with a BMI of more than 30 kg/m² experienced a 1% increase in the risk of surgical complications per unit value increase of BMI. This is significant because the median BMI of the patient population in the study was 33.9 kg/m² and 57% of the study participants were considered obese or morbidly obese.

“The heavier the patient, the higher the complication rate,” Dr. Al-Niaimi said.

Surgeons who are learning single-port laparoscopy should choose patients with lower BMIs to gain efficiency in using the new technique, Dr. Al-Niaimi suggested. This will allow patients to decrease their risk of surgical complications while allowing surgeons to hone their abilities in a new surgical technique, he said.

The other prime contributor to surgical complications is the length of surgical time. The average time of surgery during the study was 156 minutes. Dr. Al-Niaimi and his colleagues found that for each 10-minute increase in surgical time, the risk of complications increased by 2%.

While the results of the study demonstrate safety in the single-port approach, Dr. Al-Niaimi said a randomized controlled trial is needed to validate the findings and determine whether single-port laparoscopy is more effective than multi-port laparoscopy.

Dr. Al-Niaimi reported having no financial disclosures.

[email protected]

NATIONAL HARBOR, MD. – Single-port laparoscopy is both safe and feasible, and has the potential to decrease surgical complications and increase efficiency, according to findings presented at the AAGL Global Congress.

Ahmed N. Al-Niaimi, MD, of the University of Wisconsin–Madison, and his colleagues, conducted a retrospective cohort study analyzing 587 consecutive patients who underwent single-port laparoscopy from March 2012 to December 2016. Of the 587 patients, there were 27 clinically-relevant complications among 18 patients (3%). The complications included intensive care unit admission, reoperation, end organ damage, organ space surgical site infection, and readmission.

“Those factors leading to those complications are similar to the factors that cause complications in any other surgery,” Dr. Al-Niaimi said in an interview before the meeting.

Body mass index was found to be a primary contributor to surgical complications. Patients with a BMI of more than 30 kg/m² experienced a 1% increase in the risk of surgical complications per unit value increase of BMI. This is significant because the median BMI of the patient population in the study was 33.9 kg/m² and 57% of the study participants were considered obese or morbidly obese.

“The heavier the patient, the higher the complication rate,” Dr. Al-Niaimi said.

Surgeons who are learning single-port laparoscopy should choose patients with lower BMIs to gain efficiency in using the new technique, Dr. Al-Niaimi suggested. This will allow patients to decrease their risk of surgical complications while allowing surgeons to hone their abilities in a new surgical technique, he said.

The other prime contributor to surgical complications is the length of surgical time. The average time of surgery during the study was 156 minutes. Dr. Al-Niaimi and his colleagues found that for each 10-minute increase in surgical time, the risk of complications increased by 2%.

While the results of the study demonstrate safety in the single-port approach, Dr. Al-Niaimi said a randomized controlled trial is needed to validate the findings and determine whether single-port laparoscopy is more effective than multi-port laparoscopy.

Dr. Al-Niaimi reported having no financial disclosures.

[email protected]

ANAHEIM, CALIF. – Whether direct oral anticoagulants are continued or interrupted for device placement in atrial fibrillation patients, the risk of device pocket hematoma or stroke is very low, based on results of the BRUISE CONTROL–2 trial in more than 600 subjects.

Either strategy is reasonable depending on the clinical scenario, coprincipal investigator David Birnie, MD, said in presenting the results at the American Heart Association scientific sessions.

When atrial fibrillation (AF) patients on direct oral anticoagulants (DOACs) present for device surgery, there’s concern that keeping them on the drugs will increase the bleeding risk, but that taking them off will increase the stroke risk. “We sought to resolve this dilemma,” said Dr. Birnie, an electrophysiologist and director of the arrhythmia service at the University of Ottawa Heart Institute.

The subjects were on dabigatran, rivaroxaban, or apixaban, about a third in each group; 328 were randomized to continue their daily dosing, including on the day of surgery. The other 334 were randomized to interrupted treatment. For rivaroxaban and apixaban, that meant taking their last dose 2 days before surgery. Dabigatran patients discontinued the drug 1-2 days beforehand, depending on glomerular filtration rate. Patients resumed treatment about 24 hours after surgery. CHA2DS2-VASc scores were a mean of 3.9 in both arms, and at least 2 in all participants.

The rate of clinically significant hematoma – the primary outcome in the study, defined as a hematoma requiring prolonged hospitalization, interrupted postoperative anticoagulation, or reoperation to evacuate – was identical in both arms, 2.1% (seven patients each). There were two ischemic strokes, one in each arm. There was one delayed cardiac tamponade in the continuation arm and one pericardial effusion in the interrupted arm. The three deaths in the trial were not related to device placement.

So, what to do depends on the clinical scenario, Dr. Birnie said in an interview. If someone needs urgent placement and there’s no time to wait for DOAC washout, “it’s quite reasonable to go ahead.” Also, “if somebody is at extremely high risk for stroke, then it’s very reasonable to continue the drug.”

On the other hand, “if someone has a much lower stroke risk, then the risk-benefit ratio is probably in the opposite direction, so temporarily discontinuing the drug is the right thing to do,” he said.

Dr. Birnie cautioned that although continued DOAC may reduce the risk of thromboembolism, “this study was not designed with power to answer this.”

“We are already putting these findings into practice” in Ottawa, he said. “Our protocol” – as in many places – “ was always to stop anticoagulation for 2 or 3 days, but now, for very high-risk patients – high-risk AF, unstable temporary pacing, that type of thing – we are very comfortable continuing it,” he said. The study follows up a previous randomized trial by Dr. Birnie and his colleagues that pitted continued warfarin against heparin bridging for AF device placement. There were far fewer device pocket hematomas with uninterrupted warfarin (N Engl J Med. 2013 May 30;368[22]:2084-93).

The team wanted to repeat the study using DOACs, since their use has grown substantially, with the majority of AF patients now on them.

The arms in BRUISE CONTROL–2 (Strategy of Continued Versus Interrupted Novel Oral Anticoagulant at Time of Device Surgery in Patients With Moderate to High Risk of Arterial Thromboembolic Events) were well matched, with a mean age of about 74 years; men made up more than 70% of the subjects in both arms. About 17% of the participants were on chronic aspirin therapy and about 4% were on clopidogrel, in each arm. The uninterrupted DOAC group went about 14 hours between their last preop and first postop DOAC dose. The interrupted group went about 72 hours.

BRUISE CONTROL–2 was funded by the Heart and Stroke Foundation of Canada, Boehringer Ingelheim, Bayer, Pfizer, and Bristol-Myers Squibb, among others. Dr. Birnie had no relevant financial disclosures.

[email protected]

ANAHEIM, CALIF. – Whether direct oral anticoagulants are continued or interrupted for device placement in atrial fibrillation patients, the risk of device pocket hematoma or stroke is very low, based on results of the BRUISE CONTROL–2 trial in more than 600 subjects.

Either strategy is reasonable depending on the clinical scenario, coprincipal investigator David Birnie, MD, said in presenting the results at the American Heart Association scientific sessions.

When atrial fibrillation (AF) patients on direct oral anticoagulants (DOACs) present for device surgery, there’s concern that keeping them on the drugs will increase the bleeding risk, but that taking them off will increase the stroke risk. “We sought to resolve this dilemma,” said Dr. Birnie, an electrophysiologist and director of the arrhythmia service at the University of Ottawa Heart Institute.

The subjects were on dabigatran, rivaroxaban, or apixaban, about a third in each group; 328 were randomized to continue their daily dosing, including on the day of surgery. The other 334 were randomized to interrupted treatment. For rivaroxaban and apixaban, that meant taking their last dose 2 days before surgery. Dabigatran patients discontinued the drug 1-2 days beforehand, depending on glomerular filtration rate. Patients resumed treatment about 24 hours after surgery. CHA2DS2-VASc scores were a mean of 3.9 in both arms, and at least 2 in all participants.

The rate of clinically significant hematoma – the primary outcome in the study, defined as a hematoma requiring prolonged hospitalization, interrupted postoperative anticoagulation, or reoperation to evacuate – was identical in both arms, 2.1% (seven patients each). There were two ischemic strokes, one in each arm. There was one delayed cardiac tamponade in the continuation arm and one pericardial effusion in the interrupted arm. The three deaths in the trial were not related to device placement.

So, what to do depends on the clinical scenario, Dr. Birnie said in an interview. If someone needs urgent placement and there’s no time to wait for DOAC washout, “it’s quite reasonable to go ahead.” Also, “if somebody is at extremely high risk for stroke, then it’s very reasonable to continue the drug.”

On the other hand, “if someone has a much lower stroke risk, then the risk-benefit ratio is probably in the opposite direction, so temporarily discontinuing the drug is the right thing to do,” he said.

Dr. Birnie cautioned that although continued DOAC may reduce the risk of thromboembolism, “this study was not designed with power to answer this.”

“We are already putting these findings into practice” in Ottawa, he said. “Our protocol” – as in many places – “ was always to stop anticoagulation for 2 or 3 days, but now, for very high-risk patients – high-risk AF, unstable temporary pacing, that type of thing – we are very comfortable continuing it,” he said. The study follows up a previous randomized trial by Dr. Birnie and his colleagues that pitted continued warfarin against heparin bridging for AF device placement. There were far fewer device pocket hematomas with uninterrupted warfarin (N Engl J Med. 2013 May 30;368[22]:2084-93).

The team wanted to repeat the study using DOACs, since their use has grown substantially, with the majority of AF patients now on them.

The arms in BRUISE CONTROL–2 (Strategy of Continued Versus Interrupted Novel Oral Anticoagulant at Time of Device Surgery in Patients With Moderate to High Risk of Arterial Thromboembolic Events) were well matched, with a mean age of about 74 years; men made up more than 70% of the subjects in both arms. About 17% of the participants were on chronic aspirin therapy and about 4% were on clopidogrel, in each arm. The uninterrupted DOAC group went about 14 hours between their last preop and first postop DOAC dose. The interrupted group went about 72 hours.

BRUISE CONTROL–2 was funded by the Heart and Stroke Foundation of Canada, Boehringer Ingelheim, Bayer, Pfizer, and Bristol-Myers Squibb, among others. Dr. Birnie had no relevant financial disclosures.

[email protected]

ANAHEIM, CALIF. – Whether direct oral anticoagulants are continued or interrupted for device placement in atrial fibrillation patients, the risk of device pocket hematoma or stroke is very low, based on results of the BRUISE CONTROL–2 trial in more than 600 subjects.

Either strategy is reasonable depending on the clinical scenario, coprincipal investigator David Birnie, MD, said in presenting the results at the American Heart Association scientific sessions.

When atrial fibrillation (AF) patients on direct oral anticoagulants (DOACs) present for device surgery, there’s concern that keeping them on the drugs will increase the bleeding risk, but that taking them off will increase the stroke risk. “We sought to resolve this dilemma,” said Dr. Birnie, an electrophysiologist and director of the arrhythmia service at the University of Ottawa Heart Institute.

The subjects were on dabigatran, rivaroxaban, or apixaban, about a third in each group; 328 were randomized to continue their daily dosing, including on the day of surgery. The other 334 were randomized to interrupted treatment. For rivaroxaban and apixaban, that meant taking their last dose 2 days before surgery. Dabigatran patients discontinued the drug 1-2 days beforehand, depending on glomerular filtration rate. Patients resumed treatment about 24 hours after surgery. CHA2DS2-VASc scores were a mean of 3.9 in both arms, and at least 2 in all participants.

The rate of clinically significant hematoma – the primary outcome in the study, defined as a hematoma requiring prolonged hospitalization, interrupted postoperative anticoagulation, or reoperation to evacuate – was identical in both arms, 2.1% (seven patients each). There were two ischemic strokes, one in each arm. There was one delayed cardiac tamponade in the continuation arm and one pericardial effusion in the interrupted arm. The three deaths in the trial were not related to device placement.

So, what to do depends on the clinical scenario, Dr. Birnie said in an interview. If someone needs urgent placement and there’s no time to wait for DOAC washout, “it’s quite reasonable to go ahead.” Also, “if somebody is at extremely high risk for stroke, then it’s very reasonable to continue the drug.”

On the other hand, “if someone has a much lower stroke risk, then the risk-benefit ratio is probably in the opposite direction, so temporarily discontinuing the drug is the right thing to do,” he said.

Dr. Birnie cautioned that although continued DOAC may reduce the risk of thromboembolism, “this study was not designed with power to answer this.”

“We are already putting these findings into practice” in Ottawa, he said. “Our protocol” – as in many places – “ was always to stop anticoagulation for 2 or 3 days, but now, for very high-risk patients – high-risk AF, unstable temporary pacing, that type of thing – we are very comfortable continuing it,” he said. The study follows up a previous randomized trial by Dr. Birnie and his colleagues that pitted continued warfarin against heparin bridging for AF device placement. There were far fewer device pocket hematomas with uninterrupted warfarin (N Engl J Med. 2013 May 30;368[22]:2084-93).

The team wanted to repeat the study using DOACs, since their use has grown substantially, with the majority of AF patients now on them.

The arms in BRUISE CONTROL–2 (Strategy of Continued Versus Interrupted Novel Oral Anticoagulant at Time of Device Surgery in Patients With Moderate to High Risk of Arterial Thromboembolic Events) were well matched, with a mean age of about 74 years; men made up more than 70% of the subjects in both arms. About 17% of the participants were on chronic aspirin therapy and about 4% were on clopidogrel, in each arm. The uninterrupted DOAC group went about 14 hours between their last preop and first postop DOAC dose. The interrupted group went about 72 hours.

BRUISE CONTROL–2 was funded by the Heart and Stroke Foundation of Canada, Boehringer Ingelheim, Bayer, Pfizer, and Bristol-Myers Squibb, among others. Dr. Birnie had no relevant financial disclosures.

[email protected]

NATIONAL HARBOR, MD. – Second-generation endometrial ablations performed for an indication related to pain were significantly more likely to fail, according to findings presented at the AAGL Global Congress.

“We know that endometrial ablation carries a reasonable risk of failure – meaning a second ablation or hysterectomy procedure – and that rate can vary institutionally,” Matthew Hoffman, MD, chair of obstetrics and gynecology at Christiana Care Health Center, Newark, Del., said in an interview prior to the meeting. “Part of our goal is to examine patients who had pain as an indication for their procedure and to better understand if that served as an independent risk factor for women who would ultimately require additional surgical intervention.”

In a retrospective study, researchers identified 5,818 women who had undergone an ablation between October 2003 and March 2016 at a community hospital affiliated with the Christina Care Health System. Patients had either a radiofrequency ablation (3,706), hydrothermablation (1,786), or uterine balloon ablation (326).

The majority of the patients were white. Pain indications included pelvic pain, dysmenorrhea, dyspareunia, lower abdominal pain, endometriosis, and adenomyosis.

Investigators found a hysterectomy rate of 19.2% among the 437 patients who had pain as an indication for ablation, compared with 13.5% of patients with different indications (P = .001).

Secondary outcomes showed older women who underwent ablation for pain were still less likely to fail than were younger patients (odds ratio, 0.96, 95% confidence interval, .95-.97). “Older age, especially age 50 years or older, with the indication of pain, was actually protective against hysterectomy,” Meagan Cramer, MD, a resident physician at Christina Care Health System and one of the study researchers, said in an interview. “So even though pain itself was a risk factor, if you were in pain and older than 50 you were less likely to need a hysterectomy.”

The data used were collected at a single center, potentially limiting the generalizability of the findings.

Dr. Hoffman and Dr. Cramer suggested using hormonal IUDs as an alternative treatment when counseling patients who may be at risk for a failed ablation.

“This is a call for folks to look at a diverse number of risk factors and to look at this data to better counsel patients in how they choose and select procedures to get to the endpoints that you want,” Dr. Hoffman said.

The researchers reported no relevant financial disclosures.

[email protected]

On Twitter @eaztweets

NATIONAL HARBOR, MD. – Second-generation endometrial ablations performed for an indication related to pain were significantly more likely to fail, according to findings presented at the AAGL Global Congress.

“We know that endometrial ablation carries a reasonable risk of failure – meaning a second ablation or hysterectomy procedure – and that rate can vary institutionally,” Matthew Hoffman, MD, chair of obstetrics and gynecology at Christiana Care Health Center, Newark, Del., said in an interview prior to the meeting. “Part of our goal is to examine patients who had pain as an indication for their procedure and to better understand if that served as an independent risk factor for women who would ultimately require additional surgical intervention.”

In a retrospective study, researchers identified 5,818 women who had undergone an ablation between October 2003 and March 2016 at a community hospital affiliated with the Christina Care Health System. Patients had either a radiofrequency ablation (3,706), hydrothermablation (1,786), or uterine balloon ablation (326).

The majority of the patients were white. Pain indications included pelvic pain, dysmenorrhea, dyspareunia, lower abdominal pain, endometriosis, and adenomyosis.

Investigators found a hysterectomy rate of 19.2% among the 437 patients who had pain as an indication for ablation, compared with 13.5% of patients with different indications (P = .001).

Secondary outcomes showed older women who underwent ablation for pain were still less likely to fail than were younger patients (odds ratio, 0.96, 95% confidence interval, .95-.97). “Older age, especially age 50 years or older, with the indication of pain, was actually protective against hysterectomy,” Meagan Cramer, MD, a resident physician at Christina Care Health System and one of the study researchers, said in an interview. “So even though pain itself was a risk factor, if you were in pain and older than 50 you were less likely to need a hysterectomy.”

The data used were collected at a single center, potentially limiting the generalizability of the findings.

Dr. Hoffman and Dr. Cramer suggested using hormonal IUDs as an alternative treatment when counseling patients who may be at risk for a failed ablation.

“This is a call for folks to look at a diverse number of risk factors and to look at this data to better counsel patients in how they choose and select procedures to get to the endpoints that you want,” Dr. Hoffman said.

The researchers reported no relevant financial disclosures.

[email protected]

On Twitter @eaztweets

NATIONAL HARBOR, MD. – Second-generation endometrial ablations performed for an indication related to pain were significantly more likely to fail, according to findings presented at the AAGL Global Congress.

“We know that endometrial ablation carries a reasonable risk of failure – meaning a second ablation or hysterectomy procedure – and that rate can vary institutionally,” Matthew Hoffman, MD, chair of obstetrics and gynecology at Christiana Care Health Center, Newark, Del., said in an interview prior to the meeting. “Part of our goal is to examine patients who had pain as an indication for their procedure and to better understand if that served as an independent risk factor for women who would ultimately require additional surgical intervention.”

In a retrospective study, researchers identified 5,818 women who had undergone an ablation between October 2003 and March 2016 at a community hospital affiliated with the Christina Care Health System. Patients had either a radiofrequency ablation (3,706), hydrothermablation (1,786), or uterine balloon ablation (326).

The majority of the patients were white. Pain indications included pelvic pain, dysmenorrhea, dyspareunia, lower abdominal pain, endometriosis, and adenomyosis.

Investigators found a hysterectomy rate of 19.2% among the 437 patients who had pain as an indication for ablation, compared with 13.5% of patients with different indications (P = .001).

Secondary outcomes showed older women who underwent ablation for pain were still less likely to fail than were younger patients (odds ratio, 0.96, 95% confidence interval, .95-.97). “Older age, especially age 50 years or older, with the indication of pain, was actually protective against hysterectomy,” Meagan Cramer, MD, a resident physician at Christina Care Health System and one of the study researchers, said in an interview. “So even though pain itself was a risk factor, if you were in pain and older than 50 you were less likely to need a hysterectomy.”

The data used were collected at a single center, potentially limiting the generalizability of the findings.

Dr. Hoffman and Dr. Cramer suggested using hormonal IUDs as an alternative treatment when counseling patients who may be at risk for a failed ablation.

“This is a call for folks to look at a diverse number of risk factors and to look at this data to better counsel patients in how they choose and select procedures to get to the endpoints that you want,” Dr. Hoffman said.

The researchers reported no relevant financial disclosures.

[email protected]

On Twitter @eaztweets

CHICAGO – Nearly one in five people who take prescription medications also take herbal or mineral supplements, so it’s essential to make herbs, vitamins, and other supplements part of every patient medication history, emphasized Cora Breuner, MD, MPH, a professor of pediatrics at the University of Washington in Seattle.

“In chronically ill children, almost 80% to 90% of kids are using supplements, so it’s really almost imperative that this be asked when you’re taking your histories, not in the social history, but when you’re asking about medications,” Dr. Breuner told attendees at the annual meeting of the American Academy of Pediatrics. “Remember to ask it, and remember to ask it every time because it makes the patient actually realize it’s something like a medication, and so you can get the drug-herb interactions.”

Providers also should be familiar with the evidence base for complementary and alternative medicine (CAM). According to the 2012 U.S. National Health Interview Survey, which included 10,218 youths, 11.6% of those aged 4-17 years had taken or used some type of complementary health product within the previous year. Fish oil/omega-3 fatty acid supplements, melatonin, probiotics/prebiotics, and echinacea topped the list.

“For children, complementary approaches were most often used for back or neck pain, other musculoskeletal conditions, head or chest colds, anxiety or stress, attention-deficit hyperactivity disorder [ADHD], and insomnia or trouble sleeping,” Dr. Breuner said.
 

Regulation of herbal and other supplements

Dietary supplements, including vitamins, minerals, and herbal remedies, are regulated under the Dietary Supplement Health and Education Act of 1994 (DSHEA) – not the Food and Drug Administration. Not only can products enter the market without any testing for efficacy, but companies only have to provide “reasonable assurance” of a product’s safety, not proof.

“Supplements do not have to be manufactured according to any standards,” Dr. Breuner said, although reputable manufacturers support standards. “It’s basically up to the company that manufactures it to make sure the product is not contaminated and that the product is basically consistent. There’s no need whatsoever for the company to make sure it works.”

Yet many patients and parents don’t realize that, she said.

“It’s important for people to be aware that this is not a regulated industry per se by the federal government,” she said. “Patients really do think that it is.”

One voluntary quality indicator is the United States Pharmacopeia Dietary Supplement Verification Program, identified by a USP “dietary supplement verified” logo. ConsumerLab.com also provides an “approved quality” logo, tests samples voluntarily sent by manufacturers, and rates the quality of different brands.

“Supplements may not claim to cure or prevent a disease, but they can say how it affects the body’s structure and function,” she said, and companies do not need FDA approval for packaging or marketing claims. In this low regulatory environment, substantial variations exist in the quality and quantity of biological ingredients in marketed supplements.
 

Risks from herbal supplements

Dr. Breuner cited a 2011 study finding that 75% of 68 products tested had no key safety messages, including all 12 ginkgo products and all but 1 of the 21 garlic and seven Asian ginseng products tested. Most of the 13 echinacea products also lacked safety messages, but two-thirds of the 12 St John’s wort products did have safety information.

Risks can include contamination, inadequate packaging information, and unknown toxicities and interactions. Adverse reactions should be reported to the Food and Drug Administration’s MedWatch at 800-FDA-1088 (fax: 800-FDA-0178) and to Poison Control at 800-222-1222.

Two popular herbal remedies that are unsafe for children include licorice and ephedra. Although it is used for peptic ulcers, licorice lacks much evidence backing it and also shouldn’t be used (or eaten) during pregnancy. Ephedra (ma huang), an appetite suppressant and decongestant, can cause heart palpitations, heart attacks, and death.

“You can still get ephedra over the Internet, but it’s very, very dangerous,” Dr. Breuner said.

Dr. Breuner listed other herbal products available online but deemed unsafe for children: aconite (also known as bushi), species from the genus Aristolochia, belladonna, blue cohosh, borage, broom, calamus, chaparral, coltsfoot, comfrey, germander, life root, lobelia, pennyroyal, poke root, sassafras, skullcap, tansy ragwort, and wormwood.

Another set of herbs can be dangerous prior to surgery, she said, noting that an estimated 26% of patients scheduled for surgery use herbal products.

“Many, many of the herbs cause platelet aggregation issues,” Dr. Breuner said, so it’s very important to ask about different herbs before surgeries. Patients should discontinue echinacea, ephedra, garlic, ginkgo, ginseng, kava, St. John’s wort, and valerian before surgery. Risks include cardiovascular instability, prolonged sedation, bleeding, electrolyte disturbances, and immunosuppression. Additionally, four supplements also adversely interact with warfarin: garlic, ginger, and feverfew have additive effects (although small dietary amounts of ginger and garlic are fine), and St. John’s wort can decrease warfarin’s effects.

Dr. Breuner urged attendees to use resources like PubMed Dietary Supplement Subset to find out more about supplements; this subset limits results of a PubMed search of citations and abstracts to just those related to dietary supplements. It was created through a partnership between the Office of Dietary Supplements and the National Library of Medicine, both parts of the National Institutes of Health.
 

Information on specific herbs

 Ginkgo. Although commonly used to boost memory and concentration, only limited studies in adults shows some potential benefit from ginkgo at 40 mg three times a day. “There isn’t any evidence to show any reason to use it in children,” Dr. Breuner said. Adverse effects can include gastrointestinal irritation, headache, bleeding, and contact dermatitis.

 Echinacea. Although people use echinacea to treat or prevent the common cold or upper respiratory infections, the evidence does not show significant reductions of incidence, duration, or severity of upper respiratory infections and common colds. Anyone immunocompromised with an allergy or autoimmune disease should not take it.

 Zinc. Some evidence from a pediatric Cochrane Review, albeit with heterogeneous studies, supports using 75 mg of zinc a day to reduce duration of common cold and sore throat symptoms in healthy people. Adverse effects include a bad taste, nausea, and anosmia.

 Valerian. Children can take 400 mg nightly of valerian to help with sleep, although there are some caveats.

“The problem with Valerian is that it takes 2-6 weeks before it has any effect,” Breuner said. “It tastes terrible, and it’s only in a capsule form. It isn’t dosed for age at all, so you have to be careful about this, and it’s not like Ambien,” she added. It does not work instantaneously, and stopping it abruptly can cause withdrawal symptoms, although she would recommend it over melatonin. Despite its use for sleep, it can have adverse effects, such as anxiety, restlessness, and heart palpitations, and it can interfere with barbiturates.

 St. John’s wort. No one is quite sure how it works, but research has shown St. John’s wort extracts can treat mild to moderate depression about as well as standard antidepressants. However, the dose is 300 mg three times a day. “There’s no St. John’s XL,” Dr. Breuner joked. It can also interfere with a wide range of prescribed medications, including oral contraception.

 Butterbur. Those taking pyrrolizidine alkaloids should avoid butterbur, but it otherwise can help prevent migraine when dosed at 50-75 mg daily divided up into 2-3 for ages 8-9 years and 100-150 mg daily divided up into 2-3 for ages 10-17 years. “Most of the neurologists at my institution are recommending butterbur,” Dr. Breuner said. “It’s not an abortive, but it’s a preventive, with decreased intensity and severity in childhood migraine 6 weeks after using it. This is absolutely something to consider in your patients with chronic headaches.” Adverse effects include diarrhea, stomach upset, belching, and dermal and allergic symptoms, such as itchy eyes, asthma, and rash.

 Magnesium. Also recommended by pediatric neurologists at her institution, 300-500 mg daily of magnesium can reduce migraine incidence, but doses should be titrated up at first. “Don’t start with the higher doses,” she said. “You have to be careful about starting at too high of a dose because of diarrhea,” which is its primary adverse effect. Magnesium also can interfere with bisphosphonates, antibiotics, and diuretics; proton pump inhibitors may reduce magnesium levels.

 Melatonin. Unlike most supplements that are herbal or mineral, melatonin is a synthetic hormone, but Dr. Breuner said many patients don’t realize that. “Because it’s a hormone, I’m very, very careful about it,” she said, never recommending more than 0.5 to 5 mg a night for help falling asleep. “I’m really not a fan of melatonin,” she said. “You develop a tolerance to it, and this is not something parents or children should be taking chronically because we do not know long-term outcomes at all. It’s not benign even though you can just toss it into your grocery basket.”

She briefly wrapped up with mentions of omega-3 fatty acid supplements (docosahexaenoic acid and eicosapentaenoic acid); most of the evidence for these supplements comes from adults with psychiatric disorders. However, one study showed reduced tics in children with Tourette’s – if they can stand the fishy taste. It also can cause belching, nosebleeds, nausea, loose stools, and, at higher doses, decreased blood coagulation.

Peppermint can be used to reduce nausea, coughs, anxiety, and irritable bowel syndrome symptoms, but it needs to be taken as 1-2 enteric capsules, not as tea or another form.

“Chamomile is very helpful for generalized colic and also for those with chronic anxiety,” Dr. Breuner said, and arnica can be used topically for bruising. Ginger also can be used to reduce nausea but can cause heartburn. A combination of peppermint, chamomile, arnica, and ginger may be appropriate to address various chemotherapy symptoms in a child, she said.

Several articles are useful for looking up interactions between herbs and drugs, including Pediatrics. 2017. doi: 10.1542/peds.2010-2720C; J Emerg Med. 2005 Apr;28(3):267-71; and Clin Med (Lond). 2013 Feb;13(1):7-12.

No funding was used for this presentation, and Dr. Breuner reported having no disclosures.

CHICAGO – Nearly one in five people who take prescription medications also take herbal or mineral supplements, so it’s essential to make herbs, vitamins, and other supplements part of every patient medication history, emphasized Cora Breuner, MD, MPH, a professor of pediatrics at the University of Washington in Seattle.

“In chronically ill children, almost 80% to 90% of kids are using supplements, so it’s really almost imperative that this be asked when you’re taking your histories, not in the social history, but when you’re asking about medications,” Dr. Breuner told attendees at the annual meeting of the American Academy of Pediatrics. “Remember to ask it, and remember to ask it every time because it makes the patient actually realize it’s something like a medication, and so you can get the drug-herb interactions.”

Providers also should be familiar with the evidence base for complementary and alternative medicine (CAM). According to the 2012 U.S. National Health Interview Survey, which included 10,218 youths, 11.6% of those aged 4-17 years had taken or used some type of complementary health product within the previous year. Fish oil/omega-3 fatty acid supplements, melatonin, probiotics/prebiotics, and echinacea topped the list.

“For children, complementary approaches were most often used for back or neck pain, other musculoskeletal conditions, head or chest colds, anxiety or stress, attention-deficit hyperactivity disorder [ADHD], and insomnia or trouble sleeping,” Dr. Breuner said.
 

Regulation of herbal and other supplements

Dietary supplements, including vitamins, minerals, and herbal remedies, are regulated under the Dietary Supplement Health and Education Act of 1994 (DSHEA) – not the Food and Drug Administration. Not only can products enter the market without any testing for efficacy, but companies only have to provide “reasonable assurance” of a product’s safety, not proof.

“Supplements do not have to be manufactured according to any standards,” Dr. Breuner said, although reputable manufacturers support standards. “It’s basically up to the company that manufactures it to make sure the product is not contaminated and that the product is basically consistent. There’s no need whatsoever for the company to make sure it works.”

Yet many patients and parents don’t realize that, she said.

“It’s important for people to be aware that this is not a regulated industry per se by the federal government,” she said. “Patients really do think that it is.”

One voluntary quality indicator is the United States Pharmacopeia Dietary Supplement Verification Program, identified by a USP “dietary supplement verified” logo. ConsumerLab.com also provides an “approved quality” logo, tests samples voluntarily sent by manufacturers, and rates the quality of different brands.

“Supplements may not claim to cure or prevent a disease, but they can say how it affects the body’s structure and function,” she said, and companies do not need FDA approval for packaging or marketing claims. In this low regulatory environment, substantial variations exist in the quality and quantity of biological ingredients in marketed supplements.
 

Risks from herbal supplements

Dr. Breuner cited a 2011 study finding that 75% of 68 products tested had no key safety messages, including all 12 ginkgo products and all but 1 of the 21 garlic and seven Asian ginseng products tested. Most of the 13 echinacea products also lacked safety messages, but two-thirds of the 12 St John’s wort products did have safety information.

Risks can include contamination, inadequate packaging information, and unknown toxicities and interactions. Adverse reactions should be reported to the Food and Drug Administration’s MedWatch at 800-FDA-1088 (fax: 800-FDA-0178) and to Poison Control at 800-222-1222.

Two popular herbal remedies that are unsafe for children include licorice and ephedra. Although it is used for peptic ulcers, licorice lacks much evidence backing it and also shouldn’t be used (or eaten) during pregnancy. Ephedra (ma huang), an appetite suppressant and decongestant, can cause heart palpitations, heart attacks, and death.

“You can still get ephedra over the Internet, but it’s very, very dangerous,” Dr. Breuner said.

Dr. Breuner listed other herbal products available online but deemed unsafe for children: aconite (also known as bushi), species from the genus Aristolochia, belladonna, blue cohosh, borage, broom, calamus, chaparral, coltsfoot, comfrey, germander, life root, lobelia, pennyroyal, poke root, sassafras, skullcap, tansy ragwort, and wormwood.

Another set of herbs can be dangerous prior to surgery, she said, noting that an estimated 26% of patients scheduled for surgery use herbal products.

“Many, many of the herbs cause platelet aggregation issues,” Dr. Breuner said, so it’s very important to ask about different herbs before surgeries. Patients should discontinue echinacea, ephedra, garlic, ginkgo, ginseng, kava, St. John’s wort, and valerian before surgery. Risks include cardiovascular instability, prolonged sedation, bleeding, electrolyte disturbances, and immunosuppression. Additionally, four supplements also adversely interact with warfarin: garlic, ginger, and feverfew have additive effects (although small dietary amounts of ginger and garlic are fine), and St. John’s wort can decrease warfarin’s effects.

Dr. Breuner urged attendees to use resources like PubMed Dietary Supplement Subset to find out more about supplements; this subset limits results of a PubMed search of citations and abstracts to just those related to dietary supplements. It was created through a partnership between the Office of Dietary Supplements and the National Library of Medicine, both parts of the National Institutes of Health.
 

Information on specific herbs

 Ginkgo. Although commonly used to boost memory and concentration, only limited studies in adults shows some potential benefit from ginkgo at 40 mg three times a day. “There isn’t any evidence to show any reason to use it in children,” Dr. Breuner said. Adverse effects can include gastrointestinal irritation, headache, bleeding, and contact dermatitis.

 Echinacea. Although people use echinacea to treat or prevent the common cold or upper respiratory infections, the evidence does not show significant reductions of incidence, duration, or severity of upper respiratory infections and common colds. Anyone immunocompromised with an allergy or autoimmune disease should not take it.

 Zinc. Some evidence from a pediatric Cochrane Review, albeit with heterogeneous studies, supports using 75 mg of zinc a day to reduce duration of common cold and sore throat symptoms in healthy people. Adverse effects include a bad taste, nausea, and anosmia.

 Valerian. Children can take 400 mg nightly of valerian to help with sleep, although there are some caveats.

“The problem with Valerian is that it takes 2-6 weeks before it has any effect,” Breuner said. “It tastes terrible, and it’s only in a capsule form. It isn’t dosed for age at all, so you have to be careful about this, and it’s not like Ambien,” she added. It does not work instantaneously, and stopping it abruptly can cause withdrawal symptoms, although she would recommend it over melatonin. Despite its use for sleep, it can have adverse effects, such as anxiety, restlessness, and heart palpitations, and it can interfere with barbiturates.

 St. John’s wort. No one is quite sure how it works, but research has shown St. John’s wort extracts can treat mild to moderate depression about as well as standard antidepressants. However, the dose is 300 mg three times a day. “There’s no St. John’s XL,” Dr. Breuner joked. It can also interfere with a wide range of prescribed medications, including oral contraception.

 Butterbur. Those taking pyrrolizidine alkaloids should avoid butterbur, but it otherwise can help prevent migraine when dosed at 50-75 mg daily divided up into 2-3 for ages 8-9 years and 100-150 mg daily divided up into 2-3 for ages 10-17 years. “Most of the neurologists at my institution are recommending butterbur,” Dr. Breuner said. “It’s not an abortive, but it’s a preventive, with decreased intensity and severity in childhood migraine 6 weeks after using it. This is absolutely something to consider in your patients with chronic headaches.” Adverse effects include diarrhea, stomach upset, belching, and dermal and allergic symptoms, such as itchy eyes, asthma, and rash.

 Magnesium. Also recommended by pediatric neurologists at her institution, 300-500 mg daily of magnesium can reduce migraine incidence, but doses should be titrated up at first. “Don’t start with the higher doses,” she said. “You have to be careful about starting at too high of a dose because of diarrhea,” which is its primary adverse effect. Magnesium also can interfere with bisphosphonates, antibiotics, and diuretics; proton pump inhibitors may reduce magnesium levels.

 Melatonin. Unlike most supplements that are herbal or mineral, melatonin is a synthetic hormone, but Dr. Breuner said many patients don’t realize that. “Because it’s a hormone, I’m very, very careful about it,” she said, never recommending more than 0.5 to 5 mg a night for help falling asleep. “I’m really not a fan of melatonin,” she said. “You develop a tolerance to it, and this is not something parents or children should be taking chronically because we do not know long-term outcomes at all. It’s not benign even though you can just toss it into your grocery basket.”

She briefly wrapped up with mentions of omega-3 fatty acid supplements (docosahexaenoic acid and eicosapentaenoic acid); most of the evidence for these supplements comes from adults with psychiatric disorders. However, one study showed reduced tics in children with Tourette’s – if they can stand the fishy taste. It also can cause belching, nosebleeds, nausea, loose stools, and, at higher doses, decreased blood coagulation.

Peppermint can be used to reduce nausea, coughs, anxiety, and irritable bowel syndrome symptoms, but it needs to be taken as 1-2 enteric capsules, not as tea or another form.

“Chamomile is very helpful for generalized colic and also for those with chronic anxiety,” Dr. Breuner said, and arnica can be used topically for bruising. Ginger also can be used to reduce nausea but can cause heartburn. A combination of peppermint, chamomile, arnica, and ginger may be appropriate to address various chemotherapy symptoms in a child, she said.

Several articles are useful for looking up interactions between herbs and drugs, including Pediatrics. 2017. doi: 10.1542/peds.2010-2720C; J Emerg Med. 2005 Apr;28(3):267-71; and Clin Med (Lond). 2013 Feb;13(1):7-12.

No funding was used for this presentation, and Dr. Breuner reported having no disclosures.

CHICAGO – Nearly one in five people who take prescription medications also take herbal or mineral supplements, so it’s essential to make herbs, vitamins, and other supplements part of every patient medication history, emphasized Cora Breuner, MD, MPH, a professor of pediatrics at the University of Washington in Seattle.

“In chronically ill children, almost 80% to 90% of kids are using supplements, so it’s really almost imperative that this be asked when you’re taking your histories, not in the social history, but when you’re asking about medications,” Dr. Breuner told attendees at the annual meeting of the American Academy of Pediatrics. “Remember to ask it, and remember to ask it every time because it makes the patient actually realize it’s something like a medication, and so you can get the drug-herb interactions.”

Providers also should be familiar with the evidence base for complementary and alternative medicine (CAM). According to the 2012 U.S. National Health Interview Survey, which included 10,218 youths, 11.6% of those aged 4-17 years had taken or used some type of complementary health product within the previous year. Fish oil/omega-3 fatty acid supplements, melatonin, probiotics/prebiotics, and echinacea topped the list.

“For children, complementary approaches were most often used for back or neck pain, other musculoskeletal conditions, head or chest colds, anxiety or stress, attention-deficit hyperactivity disorder [ADHD], and insomnia or trouble sleeping,” Dr. Breuner said.
 

Regulation of herbal and other supplements

Dietary supplements, including vitamins, minerals, and herbal remedies, are regulated under the Dietary Supplement Health and Education Act of 1994 (DSHEA) – not the Food and Drug Administration. Not only can products enter the market without any testing for efficacy, but companies only have to provide “reasonable assurance” of a product’s safety, not proof.

“Supplements do not have to be manufactured according to any standards,” Dr. Breuner said, although reputable manufacturers support standards. “It’s basically up to the company that manufactures it to make sure the product is not contaminated and that the product is basically consistent. There’s no need whatsoever for the company to make sure it works.”

Yet many patients and parents don’t realize that, she said.

“It’s important for people to be aware that this is not a regulated industry per se by the federal government,” she said. “Patients really do think that it is.”

One voluntary quality indicator is the United States Pharmacopeia Dietary Supplement Verification Program, identified by a USP “dietary supplement verified” logo. ConsumerLab.com also provides an “approved quality” logo, tests samples voluntarily sent by manufacturers, and rates the quality of different brands.

“Supplements may not claim to cure or prevent a disease, but they can say how it affects the body’s structure and function,” she said, and companies do not need FDA approval for packaging or marketing claims. In this low regulatory environment, substantial variations exist in the quality and quantity of biological ingredients in marketed supplements.
 

Risks from herbal supplements

Dr. Breuner cited a 2011 study finding that 75% of 68 products tested had no key safety messages, including all 12 ginkgo products and all but 1 of the 21 garlic and seven Asian ginseng products tested. Most of the 13 echinacea products also lacked safety messages, but two-thirds of the 12 St John’s wort products did have safety information.

Risks can include contamination, inadequate packaging information, and unknown toxicities and interactions. Adverse reactions should be reported to the Food and Drug Administration’s MedWatch at 800-FDA-1088 (fax: 800-FDA-0178) and to Poison Control at 800-222-1222.

Two popular herbal remedies that are unsafe for children include licorice and ephedra. Although it is used for peptic ulcers, licorice lacks much evidence backing it and also shouldn’t be used (or eaten) during pregnancy. Ephedra (ma huang), an appetite suppressant and decongestant, can cause heart palpitations, heart attacks, and death.

“You can still get ephedra over the Internet, but it’s very, very dangerous,” Dr. Breuner said.

Dr. Breuner listed other herbal products available online but deemed unsafe for children: aconite (also known as bushi), species from the genus Aristolochia, belladonna, blue cohosh, borage, broom, calamus, chaparral, coltsfoot, comfrey, germander, life root, lobelia, pennyroyal, poke root, sassafras, skullcap, tansy ragwort, and wormwood.

Another set of herbs can be dangerous prior to surgery, she said, noting that an estimated 26% of patients scheduled for surgery use herbal products.

“Many, many of the herbs cause platelet aggregation issues,” Dr. Breuner said, so it’s very important to ask about different herbs before surgeries. Patients should discontinue echinacea, ephedra, garlic, ginkgo, ginseng, kava, St. John’s wort, and valerian before surgery. Risks include cardiovascular instability, prolonged sedation, bleeding, electrolyte disturbances, and immunosuppression. Additionally, four supplements also adversely interact with warfarin: garlic, ginger, and feverfew have additive effects (although small dietary amounts of ginger and garlic are fine), and St. John’s wort can decrease warfarin’s effects.

Dr. Breuner urged attendees to use resources like PubMed Dietary Supplement Subset to find out more about supplements; this subset limits results of a PubMed search of citations and abstracts to just those related to dietary supplements. It was created through a partnership between the Office of Dietary Supplements and the National Library of Medicine, both parts of the National Institutes of Health.
 

Information on specific herbs

 Ginkgo. Although commonly used to boost memory and concentration, only limited studies in adults shows some potential benefit from ginkgo at 40 mg three times a day. “There isn’t any evidence to show any reason to use it in children,” Dr. Breuner said. Adverse effects can include gastrointestinal irritation, headache, bleeding, and contact dermatitis.

 Echinacea. Although people use echinacea to treat or prevent the common cold or upper respiratory infections, the evidence does not show significant reductions of incidence, duration, or severity of upper respiratory infections and common colds. Anyone immunocompromised with an allergy or autoimmune disease should not take it.

 Zinc. Some evidence from a pediatric Cochrane Review, albeit with heterogeneous studies, supports using 75 mg of zinc a day to reduce duration of common cold and sore throat symptoms in healthy people. Adverse effects include a bad taste, nausea, and anosmia.

 Valerian. Children can take 400 mg nightly of valerian to help with sleep, although there are some caveats.

“The problem with Valerian is that it takes 2-6 weeks before it has any effect,” Breuner said. “It tastes terrible, and it’s only in a capsule form. It isn’t dosed for age at all, so you have to be careful about this, and it’s not like Ambien,” she added. It does not work instantaneously, and stopping it abruptly can cause withdrawal symptoms, although she would recommend it over melatonin. Despite its use for sleep, it can have adverse effects, such as anxiety, restlessness, and heart palpitations, and it can interfere with barbiturates.

 St. John’s wort. No one is quite sure how it works, but research has shown St. John’s wort extracts can treat mild to moderate depression about as well as standard antidepressants. However, the dose is 300 mg three times a day. “There’s no St. John’s XL,” Dr. Breuner joked. It can also interfere with a wide range of prescribed medications, including oral contraception.

 Butterbur. Those taking pyrrolizidine alkaloids should avoid butterbur, but it otherwise can help prevent migraine when dosed at 50-75 mg daily divided up into 2-3 for ages 8-9 years and 100-150 mg daily divided up into 2-3 for ages 10-17 years. “Most of the neurologists at my institution are recommending butterbur,” Dr. Breuner said. “It’s not an abortive, but it’s a preventive, with decreased intensity and severity in childhood migraine 6 weeks after using it. This is absolutely something to consider in your patients with chronic headaches.” Adverse effects include diarrhea, stomach upset, belching, and dermal and allergic symptoms, such as itchy eyes, asthma, and rash.

 Magnesium. Also recommended by pediatric neurologists at her institution, 300-500 mg daily of magnesium can reduce migraine incidence, but doses should be titrated up at first. “Don’t start with the higher doses,” she said. “You have to be careful about starting at too high of a dose because of diarrhea,” which is its primary adverse effect. Magnesium also can interfere with bisphosphonates, antibiotics, and diuretics; proton pump inhibitors may reduce magnesium levels.

 Melatonin. Unlike most supplements that are herbal or mineral, melatonin is a synthetic hormone, but Dr. Breuner said many patients don’t realize that. “Because it’s a hormone, I’m very, very careful about it,” she said, never recommending more than 0.5 to 5 mg a night for help falling asleep. “I’m really not a fan of melatonin,” she said. “You develop a tolerance to it, and this is not something parents or children should be taking chronically because we do not know long-term outcomes at all. It’s not benign even though you can just toss it into your grocery basket.”

She briefly wrapped up with mentions of omega-3 fatty acid supplements (docosahexaenoic acid and eicosapentaenoic acid); most of the evidence for these supplements comes from adults with psychiatric disorders. However, one study showed reduced tics in children with Tourette’s – if they can stand the fishy taste. It also can cause belching, nosebleeds, nausea, loose stools, and, at higher doses, decreased blood coagulation.

Peppermint can be used to reduce nausea, coughs, anxiety, and irritable bowel syndrome symptoms, but it needs to be taken as 1-2 enteric capsules, not as tea or another form.

“Chamomile is very helpful for generalized colic and also for those with chronic anxiety,” Dr. Breuner said, and arnica can be used topically for bruising. Ginger also can be used to reduce nausea but can cause heartburn. A combination of peppermint, chamomile, arnica, and ginger may be appropriate to address various chemotherapy symptoms in a child, she said.

Several articles are useful for looking up interactions between herbs and drugs, including Pediatrics. 2017. doi: 10.1542/peds.2010-2720C; J Emerg Med. 2005 Apr;28(3):267-71; and Clin Med (Lond). 2013 Feb;13(1):7-12.

No funding was used for this presentation, and Dr. Breuner reported having no disclosures.

WASHINGTON – The American College of Obstetricians and Gynecologists’ conclusion that insulin should be considered the first-line pharmacologic treatment for gestational diabetes came under fire at a recent meeting on diabetes in pregnancy, indicating the extent to which controversy persists over the use of oral antidiabetic medications in pregnancy.

“Like many others, I’m perplexed by the strong endorsement,” Mark Landon, MD, professor and chair of the department of obstetrics and gynecology at Ohio State University, Columbus, said during an open discussion of oral hypoglycemic agents held at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

Dr. Landon and several other researchers and experts in diabetes in pregnancy expressed discontent with any firm prioritization of the drugs most commonly used for gestational diabetes, saying that there are not yet enough data to do so.

Current recommendations

In its practice bulletin, ACOG noted that oral antidiabetic medications, such as glyburide and metformin, are increasingly used among women with GDM, despite not being approved by the Food and Drug Administration for this indication and even though insulin continues to be the recommended as first-line therapy by the American Diabetes Association (ADA).

The ADA, in a summary of its 2017 guideline on the management of diabetes in pregnancy, stated that insulin is the “preferred medication for treating hyperglycemia in gestational diabetes mellitus, as it does not cross the placenta to a measurable extent.” Metformin and glyburide are options, “but both cross the placenta to the fetus, with metformin likely crossing to a greater extent than glyburide” (Diabetes Care. 2017 Jan;40[Suppl 1]:S114- 9).Regarding metformin, the ACOG bulletin cited two trials that randomized women to metformin or insulin – one in which both groups experienced similar rates of a composite outcome of perinatal morbidity, and another in which women receiving metformin had lower mean glucose levels, less gestational weight gain, and neonates with lower rates of hypoglycemia.

ACOG also cited a meta-analysis, that found “minimal differences” between neonates of women randomized to metformin versus insulin, but also noted that “interestingly, women randomized to metformin experienced a higher rate of preterm birth” and a lower rate of gestational hypertension (BMJ. 2015;350:h102).

With respect to glyburide, the ACOG bulletin said that two recent meta-analyses had demonstrated worse neonatal outcomes with glyburide, compared with insulin, and that observational studies have shown higher rates of preeclampsia, hyperbilirubinemia, and stillbirth with the use of glyburide, compared with insulin. However, many other outcomes have not been statistically significantly different, according to the practice bulletin.

Additionally, at least 4%-16% of women eventually require the addition of insulin when glyburide is used as initial treatment, as do 26%-46% of women who take metformin, according to ACOG.

Regarding placental transfer, ACOG’s bulletin said that while one study that analyzed umbilical cord blood revealed no detectable glyburide in exposed pregnancies, another study demonstrated that glyburide does cross the placenta. Metformin has also been found to cross the placenta, with the fetus exposed to concentrations similar to maternal levels, the bulletin noted.

“Although current data demonstrate no adverse short-term effects on maternal or neonatal health from oral diabetic therapy during pregnancy, long-term outcomes are not yet available,” ACOG wrote in the practice bulletin.

Concerns about research

As Thomas Moore, MD, sees it, the quality of available data is insufficient to recommend insulin over oral agents, or one oral agent over another. “We really need to focus [the National Institutes of Health] on putting together proper studies,” he said at the meeting.

In a later interview, Dr. Moore referred to two recent Cochrane reviews. One review, published in January 2017, analyzed eight studies of oral antidiabetic therapies for GDM and concluded there was “insufficient high-quality evidence to be able to draw any meaningful conclusions as to the benefits of one oral antidiabetic pharmacological therapy over another” (Cochrane Database Syst Rev. 2017 Jan 25;1:CD011967).

The other Cochrane review, published in November 2017, concluded that insulin and oral antidiabetic agents have similar effects on key health outcomes, and that each one has minimal harms. The quality of evidence, the authors said, ranged from “very low to moderate, with downgrading decisions due to imprecision, risk of bias, and inconsistency” (Cochrane Database Syst Rev. 2017 Nov 5;11:CD012037).

Dr. Moore, professor of maternal-fetal medicine at the University of California, San Diego, cautioned against presuming that placental transfer of an antidiabetic drug is “ipso facto dangerous or terrible.” Moreover, he said that it’s not yet clear whether glyburide crosses the placenta in the first place.

Dr. Moore, Dr. Landon, and others at the meeting said they are eagerly awaiting long-term follow-up data from the Metformin in Gestational Diabetes (MiG) trial underway in Australia. The prospective randomized trial is designed to compare metformin with insulin and finished recruiting women in 2006. A recently published analysis found similar neurodevelopmental outcomes in offspring at 2 years, but it’s the longer-term data looking into early puberty that experts now want to see (Arch Dis Child Fetal Neonatal Ed. 2016 Feb 24. doi: 10.1136/archdischild-2015-309602).

In the meantime, Dr. Landon said the “short-term safety record for oral antidiabetic medications is actually pretty good.” There are studies “suggesting an increased risk for large babies with glyburide, but these are very small RCTs [randomized controlled trials],” he said in an interview.

Data from population-based studies, moreover, are “flawed in as much as we don’t know the thresholds for initiating glyburide treatment, nor do we know whether the women were really good candidates for this therapy,” Dr. Landon said. “It’s conceivable, and it’s been my experience, that glyburide has been overprescribed and inappropriately prescribed in certain women with GDM who really should receive insulin therapy.”

Whether glyburide and metformin are being prescribed for GDM in optimal doses is another growing question – one that interests Steve N. Caritis, MD. The drugs are typically prescribed to be taken twice a day every 12 hours, but he said he is finding that some patients may need more frequent, individually tailored dosing.

“We may have come to conclusions in [the studies published thus far] that may not be the correct conclusions,” Dr. Caritis, who coleads obstetric pharmacology research at the Magee-Womens Research Institute in Pittsburgh, said at the DPSG meeting. “The question is, If the dosing were appropriate, would we have the same outcomes?”

Individualizing drug choice

Dosing aside, there may be populations of women who respond poorly to a medication because of the underlying pathophysiology of their GDM, said Maisa N. Feghali, MD, assistant professor of obstetrics, gynecology, and reproductive sciences at the University of Pittsburgh.

A study published in 2016 demonstrated the heterogeneity of the physiologic processes underlying hyperglycemia in 67 women with GDM. Almost one-third of women with GDM had predominant insulin secretion deficit, one-half had predominant insulin resistance, and the remaining 20% had a mixed “metabolic profile” (Diabetes Care. 2016 Jun;39[6]:1052-5).

This study prompted Dr. Feghali and her colleagues to design a pilot study aimed at testing an individualized approach that matches treatment to GDM mechanism. “We [currently] have the expectation that all glucose-lowering agents will be similarly effective despite significant variation in underlying GDM pathophysiology,” she said during a presentation at the DPSG meeting. “But I think we have a mismatch between variations in GDM and the uniformity of treatment.”

In her pilot study, women diagnosed with GDM who fail dietary control will be randomized into usual treatment or matched treatment (metformin for predominant insulin resistance, glyburide or insulin for predominant insulin secretion defects, and one of the three for combined insulin resistance and insulin secretion defects).

The MATCh-GDM study (Metabolic Analysis for Treatment Choice of GDM) is just getting underway. Patients will be monitored for consistency of GDM mechanism and glucose control, and routine clinical variables (hypertensive diseases, cesarean delivery, and birth weight) will be studied, as well as neonatal body composition, cord blood glucose, and cord blood C-peptide.

WASHINGTON – The American College of Obstetricians and Gynecologists’ conclusion that insulin should be considered the first-line pharmacologic treatment for gestational diabetes came under fire at a recent meeting on diabetes in pregnancy, indicating the extent to which controversy persists over the use of oral antidiabetic medications in pregnancy.

“Like many others, I’m perplexed by the strong endorsement,” Mark Landon, MD, professor and chair of the department of obstetrics and gynecology at Ohio State University, Columbus, said during an open discussion of oral hypoglycemic agents held at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

Dr. Landon and several other researchers and experts in diabetes in pregnancy expressed discontent with any firm prioritization of the drugs most commonly used for gestational diabetes, saying that there are not yet enough data to do so.

Current recommendations

In its practice bulletin, ACOG noted that oral antidiabetic medications, such as glyburide and metformin, are increasingly used among women with GDM, despite not being approved by the Food and Drug Administration for this indication and even though insulin continues to be the recommended as first-line therapy by the American Diabetes Association (ADA).

The ADA, in a summary of its 2017 guideline on the management of diabetes in pregnancy, stated that insulin is the “preferred medication for treating hyperglycemia in gestational diabetes mellitus, as it does not cross the placenta to a measurable extent.” Metformin and glyburide are options, “but both cross the placenta to the fetus, with metformin likely crossing to a greater extent than glyburide” (Diabetes Care. 2017 Jan;40[Suppl 1]:S114- 9).Regarding metformin, the ACOG bulletin cited two trials that randomized women to metformin or insulin – one in which both groups experienced similar rates of a composite outcome of perinatal morbidity, and another in which women receiving metformin had lower mean glucose levels, less gestational weight gain, and neonates with lower rates of hypoglycemia.

ACOG also cited a meta-analysis, that found “minimal differences” between neonates of women randomized to metformin versus insulin, but also noted that “interestingly, women randomized to metformin experienced a higher rate of preterm birth” and a lower rate of gestational hypertension (BMJ. 2015;350:h102).

With respect to glyburide, the ACOG bulletin said that two recent meta-analyses had demonstrated worse neonatal outcomes with glyburide, compared with insulin, and that observational studies have shown higher rates of preeclampsia, hyperbilirubinemia, and stillbirth with the use of glyburide, compared with insulin. However, many other outcomes have not been statistically significantly different, according to the practice bulletin.

Additionally, at least 4%-16% of women eventually require the addition of insulin when glyburide is used as initial treatment, as do 26%-46% of women who take metformin, according to ACOG.

Regarding placental transfer, ACOG’s bulletin said that while one study that analyzed umbilical cord blood revealed no detectable glyburide in exposed pregnancies, another study demonstrated that glyburide does cross the placenta. Metformin has also been found to cross the placenta, with the fetus exposed to concentrations similar to maternal levels, the bulletin noted.

“Although current data demonstrate no adverse short-term effects on maternal or neonatal health from oral diabetic therapy during pregnancy, long-term outcomes are not yet available,” ACOG wrote in the practice bulletin.

Concerns about research

As Thomas Moore, MD, sees it, the quality of available data is insufficient to recommend insulin over oral agents, or one oral agent over another. “We really need to focus [the National Institutes of Health] on putting together proper studies,” he said at the meeting.

In a later interview, Dr. Moore referred to two recent Cochrane reviews. One review, published in January 2017, analyzed eight studies of oral antidiabetic therapies for GDM and concluded there was “insufficient high-quality evidence to be able to draw any meaningful conclusions as to the benefits of one oral antidiabetic pharmacological therapy over another” (Cochrane Database Syst Rev. 2017 Jan 25;1:CD011967).

The other Cochrane review, published in November 2017, concluded that insulin and oral antidiabetic agents have similar effects on key health outcomes, and that each one has minimal harms. The quality of evidence, the authors said, ranged from “very low to moderate, with downgrading decisions due to imprecision, risk of bias, and inconsistency” (Cochrane Database Syst Rev. 2017 Nov 5;11:CD012037).

Dr. Moore, professor of maternal-fetal medicine at the University of California, San Diego, cautioned against presuming that placental transfer of an antidiabetic drug is “ipso facto dangerous or terrible.” Moreover, he said that it’s not yet clear whether glyburide crosses the placenta in the first place.

Dr. Moore, Dr. Landon, and others at the meeting said they are eagerly awaiting long-term follow-up data from the Metformin in Gestational Diabetes (MiG) trial underway in Australia. The prospective randomized trial is designed to compare metformin with insulin and finished recruiting women in 2006. A recently published analysis found similar neurodevelopmental outcomes in offspring at 2 years, but it’s the longer-term data looking into early puberty that experts now want to see (Arch Dis Child Fetal Neonatal Ed. 2016 Feb 24. doi: 10.1136/archdischild-2015-309602).

In the meantime, Dr. Landon said the “short-term safety record for oral antidiabetic medications is actually pretty good.” There are studies “suggesting an increased risk for large babies with glyburide, but these are very small RCTs [randomized controlled trials],” he said in an interview.

Data from population-based studies, moreover, are “flawed in as much as we don’t know the thresholds for initiating glyburide treatment, nor do we know whether the women were really good candidates for this therapy,” Dr. Landon said. “It’s conceivable, and it’s been my experience, that glyburide has been overprescribed and inappropriately prescribed in certain women with GDM who really should receive insulin therapy.”

Whether glyburide and metformin are being prescribed for GDM in optimal doses is another growing question – one that interests Steve N. Caritis, MD. The drugs are typically prescribed to be taken twice a day every 12 hours, but he said he is finding that some patients may need more frequent, individually tailored dosing.

“We may have come to conclusions in [the studies published thus far] that may not be the correct conclusions,” Dr. Caritis, who coleads obstetric pharmacology research at the Magee-Womens Research Institute in Pittsburgh, said at the DPSG meeting. “The question is, If the dosing were appropriate, would we have the same outcomes?”

Individualizing drug choice

Dosing aside, there may be populations of women who respond poorly to a medication because of the underlying pathophysiology of their GDM, said Maisa N. Feghali, MD, assistant professor of obstetrics, gynecology, and reproductive sciences at the University of Pittsburgh.

A study published in 2016 demonstrated the heterogeneity of the physiologic processes underlying hyperglycemia in 67 women with GDM. Almost one-third of women with GDM had predominant insulin secretion deficit, one-half had predominant insulin resistance, and the remaining 20% had a mixed “metabolic profile” (Diabetes Care. 2016 Jun;39[6]:1052-5).

This study prompted Dr. Feghali and her colleagues to design a pilot study aimed at testing an individualized approach that matches treatment to GDM mechanism. “We [currently] have the expectation that all glucose-lowering agents will be similarly effective despite significant variation in underlying GDM pathophysiology,” she said during a presentation at the DPSG meeting. “But I think we have a mismatch between variations in GDM and the uniformity of treatment.”

In her pilot study, women diagnosed with GDM who fail dietary control will be randomized into usual treatment or matched treatment (metformin for predominant insulin resistance, glyburide or insulin for predominant insulin secretion defects, and one of the three for combined insulin resistance and insulin secretion defects).

The MATCh-GDM study (Metabolic Analysis for Treatment Choice of GDM) is just getting underway. Patients will be monitored for consistency of GDM mechanism and glucose control, and routine clinical variables (hypertensive diseases, cesarean delivery, and birth weight) will be studied, as well as neonatal body composition, cord blood glucose, and cord blood C-peptide.

WASHINGTON – The American College of Obstetricians and Gynecologists’ conclusion that insulin should be considered the first-line pharmacologic treatment for gestational diabetes came under fire at a recent meeting on diabetes in pregnancy, indicating the extent to which controversy persists over the use of oral antidiabetic medications in pregnancy.

“Like many others, I’m perplexed by the strong endorsement,” Mark Landon, MD, professor and chair of the department of obstetrics and gynecology at Ohio State University, Columbus, said during an open discussion of oral hypoglycemic agents held at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

Dr. Landon and several other researchers and experts in diabetes in pregnancy expressed discontent with any firm prioritization of the drugs most commonly used for gestational diabetes, saying that there are not yet enough data to do so.

Current recommendations

In its practice bulletin, ACOG noted that oral antidiabetic medications, such as glyburide and metformin, are increasingly used among women with GDM, despite not being approved by the Food and Drug Administration for this indication and even though insulin continues to be the recommended as first-line therapy by the American Diabetes Association (ADA).

The ADA, in a summary of its 2017 guideline on the management of diabetes in pregnancy, stated that insulin is the “preferred medication for treating hyperglycemia in gestational diabetes mellitus, as it does not cross the placenta to a measurable extent.” Metformin and glyburide are options, “but both cross the placenta to the fetus, with metformin likely crossing to a greater extent than glyburide” (Diabetes Care. 2017 Jan;40[Suppl 1]:S114- 9).Regarding metformin, the ACOG bulletin cited two trials that randomized women to metformin or insulin – one in which both groups experienced similar rates of a composite outcome of perinatal morbidity, and another in which women receiving metformin had lower mean glucose levels, less gestational weight gain, and neonates with lower rates of hypoglycemia.

ACOG also cited a meta-analysis, that found “minimal differences” between neonates of women randomized to metformin versus insulin, but also noted that “interestingly, women randomized to metformin experienced a higher rate of preterm birth” and a lower rate of gestational hypertension (BMJ. 2015;350:h102).

With respect to glyburide, the ACOG bulletin said that two recent meta-analyses had demonstrated worse neonatal outcomes with glyburide, compared with insulin, and that observational studies have shown higher rates of preeclampsia, hyperbilirubinemia, and stillbirth with the use of glyburide, compared with insulin. However, many other outcomes have not been statistically significantly different, according to the practice bulletin.

Additionally, at least 4%-16% of women eventually require the addition of insulin when glyburide is used as initial treatment, as do 26%-46% of women who take metformin, according to ACOG.

Regarding placental transfer, ACOG’s bulletin said that while one study that analyzed umbilical cord blood revealed no detectable glyburide in exposed pregnancies, another study demonstrated that glyburide does cross the placenta. Metformin has also been found to cross the placenta, with the fetus exposed to concentrations similar to maternal levels, the bulletin noted.

“Although current data demonstrate no adverse short-term effects on maternal or neonatal health from oral diabetic therapy during pregnancy, long-term outcomes are not yet available,” ACOG wrote in the practice bulletin.

Concerns about research

As Thomas Moore, MD, sees it, the quality of available data is insufficient to recommend insulin over oral agents, or one oral agent over another. “We really need to focus [the National Institutes of Health] on putting together proper studies,” he said at the meeting.

In a later interview, Dr. Moore referred to two recent Cochrane reviews. One review, published in January 2017, analyzed eight studies of oral antidiabetic therapies for GDM and concluded there was “insufficient high-quality evidence to be able to draw any meaningful conclusions as to the benefits of one oral antidiabetic pharmacological therapy over another” (Cochrane Database Syst Rev. 2017 Jan 25;1:CD011967).

The other Cochrane review, published in November 2017, concluded that insulin and oral antidiabetic agents have similar effects on key health outcomes, and that each one has minimal harms. The quality of evidence, the authors said, ranged from “very low to moderate, with downgrading decisions due to imprecision, risk of bias, and inconsistency” (Cochrane Database Syst Rev. 2017 Nov 5;11:CD012037).

Dr. Moore, professor of maternal-fetal medicine at the University of California, San Diego, cautioned against presuming that placental transfer of an antidiabetic drug is “ipso facto dangerous or terrible.” Moreover, he said that it’s not yet clear whether glyburide crosses the placenta in the first place.

Dr. Moore, Dr. Landon, and others at the meeting said they are eagerly awaiting long-term follow-up data from the Metformin in Gestational Diabetes (MiG) trial underway in Australia. The prospective randomized trial is designed to compare metformin with insulin and finished recruiting women in 2006. A recently published analysis found similar neurodevelopmental outcomes in offspring at 2 years, but it’s the longer-term data looking into early puberty that experts now want to see (Arch Dis Child Fetal Neonatal Ed. 2016 Feb 24. doi: 10.1136/archdischild-2015-309602).

In the meantime, Dr. Landon said the “short-term safety record for oral antidiabetic medications is actually pretty good.” There are studies “suggesting an increased risk for large babies with glyburide, but these are very small RCTs [randomized controlled trials],” he said in an interview.

Data from population-based studies, moreover, are “flawed in as much as we don’t know the thresholds for initiating glyburide treatment, nor do we know whether the women were really good candidates for this therapy,” Dr. Landon said. “It’s conceivable, and it’s been my experience, that glyburide has been overprescribed and inappropriately prescribed in certain women with GDM who really should receive insulin therapy.”

Whether glyburide and metformin are being prescribed for GDM in optimal doses is another growing question – one that interests Steve N. Caritis, MD. The drugs are typically prescribed to be taken twice a day every 12 hours, but he said he is finding that some patients may need more frequent, individually tailored dosing.

“We may have come to conclusions in [the studies published thus far] that may not be the correct conclusions,” Dr. Caritis, who coleads obstetric pharmacology research at the Magee-Womens Research Institute in Pittsburgh, said at the DPSG meeting. “The question is, If the dosing were appropriate, would we have the same outcomes?”

Individualizing drug choice

Dosing aside, there may be populations of women who respond poorly to a medication because of the underlying pathophysiology of their GDM, said Maisa N. Feghali, MD, assistant professor of obstetrics, gynecology, and reproductive sciences at the University of Pittsburgh.

A study published in 2016 demonstrated the heterogeneity of the physiologic processes underlying hyperglycemia in 67 women with GDM. Almost one-third of women with GDM had predominant insulin secretion deficit, one-half had predominant insulin resistance, and the remaining 20% had a mixed “metabolic profile” (Diabetes Care. 2016 Jun;39[6]:1052-5).

This study prompted Dr. Feghali and her colleagues to design a pilot study aimed at testing an individualized approach that matches treatment to GDM mechanism. “We [currently] have the expectation that all glucose-lowering agents will be similarly effective despite significant variation in underlying GDM pathophysiology,” she said during a presentation at the DPSG meeting. “But I think we have a mismatch between variations in GDM and the uniformity of treatment.”

In her pilot study, women diagnosed with GDM who fail dietary control will be randomized into usual treatment or matched treatment (metformin for predominant insulin resistance, glyburide or insulin for predominant insulin secretion defects, and one of the three for combined insulin resistance and insulin secretion defects).

The MATCh-GDM study (Metabolic Analysis for Treatment Choice of GDM) is just getting underway. Patients will be monitored for consistency of GDM mechanism and glucose control, and routine clinical variables (hypertensive diseases, cesarean delivery, and birth weight) will be studied, as well as neonatal body composition, cord blood glucose, and cord blood C-peptide.