Detection of Epstein-Barr virus DNA in plasma reliably signaled “a broad range” of EBV+ diseases, according to investigators.

In contrast, the presence of EBV DNA in peripheral blood mononuclear cells did not reliably predict EBV diseases, said Dr. Jennifer A. Kanakry and her associates at Johns Hopkins University, Baltimore. Patients without EBV diseases can have EBV DNA in their PBMCs, particularly if they are immunocompromised, the researchers observed.

National Cancer Institute/Public Domain

Latent EBV infection is associated with lymphomas, lymphoproliferative disorders, hemophagocytic lymphohistiocytosis, solid tumors, and other diseases. To characterize the relationship between these diseases and EBV DNA, the researchers studied viral quantitative real-time polymerase chain reaction assays of plasma and PBMCs from 2,146 patients tested at Johns Hopkins over 5 years. Patients were usually immunocompromised and hospitalized, the investigators noted (Blood 2016;127:2007-17).

A total of 535 patients (25%) had EBV detected in plasma or PBMCs. Notably, 69% of patients who did not have EBV diseases had EBV in PBMCs, but not in plasma. Among 105 patients with active systemic EBV+ diseases, 99% had EBV DNA in plasma, but only 54% had EBV in PBMCs. Furthermore, the number of copies of EBV DNA distinguished untreated EBV+ lymphoma, remitted EBV+ lymphoma, and EBV- lymphoma, and also distinguished untreated, EBV+ post-transplantation lymphoproliferative disorder (PTLD), EBV+ PTLD in remission, and EBV– PTLD.

“Cell-free (plasma) EBV DNA performs better than cellular EBV DNA as a marker of a broad range of EBV+ diseases,” the investigators concluded. “Within a largely immunocompromised and hospitalized cohort, detection of EBV DNA in plasma is uncommon in the absence of EBV+ disease.”

The National Cancer Institute, National Institutes of Health, and Center for AIDS Research funded the study. The researchers had no disclosures.

Detection of Epstein-Barr virus DNA in plasma reliably signaled “a broad range” of EBV+ diseases, according to investigators.

In contrast, the presence of EBV DNA in peripheral blood mononuclear cells did not reliably predict EBV diseases, said Dr. Jennifer A. Kanakry and her associates at Johns Hopkins University, Baltimore. Patients without EBV diseases can have EBV DNA in their PBMCs, particularly if they are immunocompromised, the researchers observed.

National Cancer Institute/Public Domain

Latent EBV infection is associated with lymphomas, lymphoproliferative disorders, hemophagocytic lymphohistiocytosis, solid tumors, and other diseases. To characterize the relationship between these diseases and EBV DNA, the researchers studied viral quantitative real-time polymerase chain reaction assays of plasma and PBMCs from 2,146 patients tested at Johns Hopkins over 5 years. Patients were usually immunocompromised and hospitalized, the investigators noted (Blood 2016;127:2007-17).

A total of 535 patients (25%) had EBV detected in plasma or PBMCs. Notably, 69% of patients who did not have EBV diseases had EBV in PBMCs, but not in plasma. Among 105 patients with active systemic EBV+ diseases, 99% had EBV DNA in plasma, but only 54% had EBV in PBMCs. Furthermore, the number of copies of EBV DNA distinguished untreated EBV+ lymphoma, remitted EBV+ lymphoma, and EBV- lymphoma, and also distinguished untreated, EBV+ post-transplantation lymphoproliferative disorder (PTLD), EBV+ PTLD in remission, and EBV– PTLD.

“Cell-free (plasma) EBV DNA performs better than cellular EBV DNA as a marker of a broad range of EBV+ diseases,” the investigators concluded. “Within a largely immunocompromised and hospitalized cohort, detection of EBV DNA in plasma is uncommon in the absence of EBV+ disease.”

The National Cancer Institute, National Institutes of Health, and Center for AIDS Research funded the study. The researchers had no disclosures.

Detection of Epstein-Barr virus DNA in plasma reliably signaled “a broad range” of EBV+ diseases, according to investigators.

In contrast, the presence of EBV DNA in peripheral blood mononuclear cells did not reliably predict EBV diseases, said Dr. Jennifer A. Kanakry and her associates at Johns Hopkins University, Baltimore. Patients without EBV diseases can have EBV DNA in their PBMCs, particularly if they are immunocompromised, the researchers observed.

National Cancer Institute/Public Domain

Latent EBV infection is associated with lymphomas, lymphoproliferative disorders, hemophagocytic lymphohistiocytosis, solid tumors, and other diseases. To characterize the relationship between these diseases and EBV DNA, the researchers studied viral quantitative real-time polymerase chain reaction assays of plasma and PBMCs from 2,146 patients tested at Johns Hopkins over 5 years. Patients were usually immunocompromised and hospitalized, the investigators noted (Blood 2016;127:2007-17).

A total of 535 patients (25%) had EBV detected in plasma or PBMCs. Notably, 69% of patients who did not have EBV diseases had EBV in PBMCs, but not in plasma. Among 105 patients with active systemic EBV+ diseases, 99% had EBV DNA in plasma, but only 54% had EBV in PBMCs. Furthermore, the number of copies of EBV DNA distinguished untreated EBV+ lymphoma, remitted EBV+ lymphoma, and EBV- lymphoma, and also distinguished untreated, EBV+ post-transplantation lymphoproliferative disorder (PTLD), EBV+ PTLD in remission, and EBV– PTLD.

“Cell-free (plasma) EBV DNA performs better than cellular EBV DNA as a marker of a broad range of EBV+ diseases,” the investigators concluded. “Within a largely immunocompromised and hospitalized cohort, detection of EBV DNA in plasma is uncommon in the absence of EBV+ disease.”

The National Cancer Institute, National Institutes of Health, and Center for AIDS Research funded the study. The researchers had no disclosures.

Olanzapine can cause a rare but serious skin reaction that can affect other parts of the body, according to a Food and Drug Administration safety alert released May 10.

The condition linked to all products containing the second-generation antipsychotic is called Drug Reaction with Eosinophilia and Systemic Symptoms, or DRESS. Symptoms of DRESS include a rash that can spread to all parts of the body, fever, swollen lymph nodes, and swelling. In addition, DRESS can result in injury to the liver, kidneys, lungs, heart, or pancreas, and it also can lead to death. The mortality tied to DRESS can reach 10%, the FDA said.

The FDA Adverse Event Reporting System database has identified 23 cases worldwide of DRESS resulting from olanzapine since 1996, including one patient who died. Currently, the only way to treat DRESS is to withdraw the drug promptly. “Health care professionals should immediately stop treatment with olanzapine if DRESS is suspected,” the safety alert states. “The important ways to manage DRESS are early recognition of the syndrome, discontinuation of the offending agent as soon as possible, and supportive care.”

Olanzapine, used to treat schizophrenia and manic episodes of bipolar disorder, is available in generic versions. The medication also is available under the brand names Zyprexa, Zyprexa Zydis, Zyprexa Relprevv, and Symbyax. The agency said it would add a warning describing DRESS to the labels of drugs containing olanzapine.

Read the full safety alert on the FDA website.

[email protected]

Olanzapine can cause a rare but serious skin reaction that can affect other parts of the body, according to a Food and Drug Administration safety alert released May 10.

The condition linked to all products containing the second-generation antipsychotic is called Drug Reaction with Eosinophilia and Systemic Symptoms, or DRESS. Symptoms of DRESS include a rash that can spread to all parts of the body, fever, swollen lymph nodes, and swelling. In addition, DRESS can result in injury to the liver, kidneys, lungs, heart, or pancreas, and it also can lead to death. The mortality tied to DRESS can reach 10%, the FDA said.

The FDA Adverse Event Reporting System database has identified 23 cases worldwide of DRESS resulting from olanzapine since 1996, including one patient who died. Currently, the only way to treat DRESS is to withdraw the drug promptly. “Health care professionals should immediately stop treatment with olanzapine if DRESS is suspected,” the safety alert states. “The important ways to manage DRESS are early recognition of the syndrome, discontinuation of the offending agent as soon as possible, and supportive care.”

Olanzapine, used to treat schizophrenia and manic episodes of bipolar disorder, is available in generic versions. The medication also is available under the brand names Zyprexa, Zyprexa Zydis, Zyprexa Relprevv, and Symbyax. The agency said it would add a warning describing DRESS to the labels of drugs containing olanzapine.

Read the full safety alert on the FDA website.

[email protected]

Olanzapine can cause a rare but serious skin reaction that can affect other parts of the body, according to a Food and Drug Administration safety alert released May 10.

The condition linked to all products containing the second-generation antipsychotic is called Drug Reaction with Eosinophilia and Systemic Symptoms, or DRESS. Symptoms of DRESS include a rash that can spread to all parts of the body, fever, swollen lymph nodes, and swelling. In addition, DRESS can result in injury to the liver, kidneys, lungs, heart, or pancreas, and it also can lead to death. The mortality tied to DRESS can reach 10%, the FDA said.

The FDA Adverse Event Reporting System database has identified 23 cases worldwide of DRESS resulting from olanzapine since 1996, including one patient who died. Currently, the only way to treat DRESS is to withdraw the drug promptly. “Health care professionals should immediately stop treatment with olanzapine if DRESS is suspected,” the safety alert states. “The important ways to manage DRESS are early recognition of the syndrome, discontinuation of the offending agent as soon as possible, and supportive care.”

Olanzapine, used to treat schizophrenia and manic episodes of bipolar disorder, is available in generic versions. The medication also is available under the brand names Zyprexa, Zyprexa Zydis, Zyprexa Relprevv, and Symbyax. The agency said it would add a warning describing DRESS to the labels of drugs containing olanzapine.

Read the full safety alert on the FDA website.

[email protected]

A 70-year-old man is seen for “broken blood vessels” on his face. The lesions were recently noted by a relative who had not seen him in years.

The patient has a pronounced history of sun overexposure as a result of his job and his hobbies, which include fishing and hunting. As a younger man, he enjoyed waterskiing and going to the lake almost every weekend during the warmer months.

He is in decent health apart from the lesions and has no other skin complaints.

EXAMINATION
The sides of the patient’s face are covered with linear, red, dilated blood vessels running in jagged patterns. The lesions are asymptomatic and range from 0.5 to 1.0 mm in diameter; some are several centimeters long. They are readily blanchable with digital pressure, though none are palpable.

Far more blood vessels are seen on the patient’s left side than on his right. The underlying skin is quite fair and thin. In some locations (eg, the lateral forehead), there are patches of white skin free of surface adnexa (ie pores, skin lines, or hair follicles).

His dorsal arms are very rough, with hundreds of solar lentigines, while the skin on his volar arms is relatively unaffected.

What is the diagnosis?

DISCUSSION
This collection of findings is called dermatoheliosis (DHe), literally “sun-skin condition,” caused by overexposure to UV light. Telangiectasias, one manifestation, have many potential causes, but sun exposure is the most common—especially in those whose skin burns easily and frequently.

These blood vessels are simply normal surface vasculature made more obvious by two factors: First, chronic sun exposure overheats the skin for prolonged periods, leading to persistent vasodilatation that eventually becomes fixed. Second, solar atrophy may occur when the skin thins from sun overexposure, making typically invisible structures apparent.

DHe can also manifest as actinic keratosis, weathering of the skin, solar elastosis, and sun-caused skin cancers (basal and squamous cell carcinomas, melanoma, etc). The condition is incredibly common.

Many causes of telangiectasias are unrelated to sun exposure. Other processes that thin the skin—such as radiation therapy or injudicious use of topical steroids—may produce telangiectasias. Further examples include spider vessels on legs due to venous insufficiency and newly acquired vascular lesions resulting from pregnancy or liver cirrhosis. There are also two unusual but significant conditions that involve telangiectasias: a variant of systemic sclerosis called CREST syndrome (calcinosis, Raynaud’s, esophageal dysmotility, sclerodactyly, and telangiectasias) and hereditary hemorrhagic telangiectasias (also known eponymically as Osler-Weber-Rendu syndrome).

Treatment for sun-caused telangiectasias includes laser and electrodessication.

TAKE-HOME LEARNING POINTS
• Telangiectasias are permanently dilated surface vasculature usually seen on the most prominently sun-exposed areas of the skin. The left face and arm are often more heavily affected than the right, since they are closer to the car window during driving.

• Telangiectasias are only one of a number of sun-caused skin changes that are collectively termed dermatoheliosis (DHe).

• Telangiectasias are important because they identify patients at risk for sun-caused skin cancers, such as basal or squamous cell carcinomas and melanoma.

• Other potential causes of telangiectasias include injudicious use of topical steroids, focal radiation therapy, pregnancy, liver disease, and rare conditions such as CREST syndrome and hereditary hemorrhagic telangiectasias.

A 70-year-old man is seen for “broken blood vessels” on his face. The lesions were recently noted by a relative who had not seen him in years.

The patient has a pronounced history of sun overexposure as a result of his job and his hobbies, which include fishing and hunting. As a younger man, he enjoyed waterskiing and going to the lake almost every weekend during the warmer months.

He is in decent health apart from the lesions and has no other skin complaints.

EXAMINATION
The sides of the patient’s face are covered with linear, red, dilated blood vessels running in jagged patterns. The lesions are asymptomatic and range from 0.5 to 1.0 mm in diameter; some are several centimeters long. They are readily blanchable with digital pressure, though none are palpable.

Far more blood vessels are seen on the patient’s left side than on his right. The underlying skin is quite fair and thin. In some locations (eg, the lateral forehead), there are patches of white skin free of surface adnexa (ie pores, skin lines, or hair follicles).

His dorsal arms are very rough, with hundreds of solar lentigines, while the skin on his volar arms is relatively unaffected.

What is the diagnosis?

DISCUSSION
This collection of findings is called dermatoheliosis (DHe), literally “sun-skin condition,” caused by overexposure to UV light. Telangiectasias, one manifestation, have many potential causes, but sun exposure is the most common—especially in those whose skin burns easily and frequently.

These blood vessels are simply normal surface vasculature made more obvious by two factors: First, chronic sun exposure overheats the skin for prolonged periods, leading to persistent vasodilatation that eventually becomes fixed. Second, solar atrophy may occur when the skin thins from sun overexposure, making typically invisible structures apparent.

DHe can also manifest as actinic keratosis, weathering of the skin, solar elastosis, and sun-caused skin cancers (basal and squamous cell carcinomas, melanoma, etc). The condition is incredibly common.

Many causes of telangiectasias are unrelated to sun exposure. Other processes that thin the skin—such as radiation therapy or injudicious use of topical steroids—may produce telangiectasias. Further examples include spider vessels on legs due to venous insufficiency and newly acquired vascular lesions resulting from pregnancy or liver cirrhosis. There are also two unusual but significant conditions that involve telangiectasias: a variant of systemic sclerosis called CREST syndrome (calcinosis, Raynaud’s, esophageal dysmotility, sclerodactyly, and telangiectasias) and hereditary hemorrhagic telangiectasias (also known eponymically as Osler-Weber-Rendu syndrome).

Treatment for sun-caused telangiectasias includes laser and electrodessication.

TAKE-HOME LEARNING POINTS
• Telangiectasias are permanently dilated surface vasculature usually seen on the most prominently sun-exposed areas of the skin. The left face and arm are often more heavily affected than the right, since they are closer to the car window during driving.

• Telangiectasias are only one of a number of sun-caused skin changes that are collectively termed dermatoheliosis (DHe).

• Telangiectasias are important because they identify patients at risk for sun-caused skin cancers, such as basal or squamous cell carcinomas and melanoma.

• Other potential causes of telangiectasias include injudicious use of topical steroids, focal radiation therapy, pregnancy, liver disease, and rare conditions such as CREST syndrome and hereditary hemorrhagic telangiectasias.

A 70-year-old man is seen for “broken blood vessels” on his face. The lesions were recently noted by a relative who had not seen him in years.

The patient has a pronounced history of sun overexposure as a result of his job and his hobbies, which include fishing and hunting. As a younger man, he enjoyed waterskiing and going to the lake almost every weekend during the warmer months.

He is in decent health apart from the lesions and has no other skin complaints.

EXAMINATION
The sides of the patient’s face are covered with linear, red, dilated blood vessels running in jagged patterns. The lesions are asymptomatic and range from 0.5 to 1.0 mm in diameter; some are several centimeters long. They are readily blanchable with digital pressure, though none are palpable.

Far more blood vessels are seen on the patient’s left side than on his right. The underlying skin is quite fair and thin. In some locations (eg, the lateral forehead), there are patches of white skin free of surface adnexa (ie pores, skin lines, or hair follicles).

His dorsal arms are very rough, with hundreds of solar lentigines, while the skin on his volar arms is relatively unaffected.

What is the diagnosis?

DISCUSSION
This collection of findings is called dermatoheliosis (DHe), literally “sun-skin condition,” caused by overexposure to UV light. Telangiectasias, one manifestation, have many potential causes, but sun exposure is the most common—especially in those whose skin burns easily and frequently.

These blood vessels are simply normal surface vasculature made more obvious by two factors: First, chronic sun exposure overheats the skin for prolonged periods, leading to persistent vasodilatation that eventually becomes fixed. Second, solar atrophy may occur when the skin thins from sun overexposure, making typically invisible structures apparent.

DHe can also manifest as actinic keratosis, weathering of the skin, solar elastosis, and sun-caused skin cancers (basal and squamous cell carcinomas, melanoma, etc). The condition is incredibly common.

Many causes of telangiectasias are unrelated to sun exposure. Other processes that thin the skin—such as radiation therapy or injudicious use of topical steroids—may produce telangiectasias. Further examples include spider vessels on legs due to venous insufficiency and newly acquired vascular lesions resulting from pregnancy or liver cirrhosis. There are also two unusual but significant conditions that involve telangiectasias: a variant of systemic sclerosis called CREST syndrome (calcinosis, Raynaud’s, esophageal dysmotility, sclerodactyly, and telangiectasias) and hereditary hemorrhagic telangiectasias (also known eponymically as Osler-Weber-Rendu syndrome).

Treatment for sun-caused telangiectasias includes laser and electrodessication.

TAKE-HOME LEARNING POINTS
• Telangiectasias are permanently dilated surface vasculature usually seen on the most prominently sun-exposed areas of the skin. The left face and arm are often more heavily affected than the right, since they are closer to the car window during driving.

• Telangiectasias are only one of a number of sun-caused skin changes that are collectively termed dermatoheliosis (DHe).

• Telangiectasias are important because they identify patients at risk for sun-caused skin cancers, such as basal or squamous cell carcinomas and melanoma.

• Other potential causes of telangiectasias include injudicious use of topical steroids, focal radiation therapy, pregnancy, liver disease, and rare conditions such as CREST syndrome and hereditary hemorrhagic telangiectasias.

MAUI, HAWAII – The consensus among gastroenterologists with expertise in inflammatory bowel disease is that continuation of biologics or immunomodulators in affected women throughout pregnancy and breastfeeding poses no increased risks to the fetus – and therein lies a message for rheumatologists and obstetricians, Dr. Uma Mahadevan said at the 2016 Rheumatology Winter Clinical Symposium.

“The risk of uncontrolled disease must be weighed against the risk of medical therapy. And this is something that is often missed,” according to Dr. Mahadevan, professor of medicine and co–medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.

Gastroenterologists – at least, those whose practices focus on inflammatory bowel disease (IBD) – have led the way within medicine in terms of establishing the safety of biologics and immunomodulators such as azathioprine in pregnant women with chronic inflammatory diseases and their babies. And having accomplished that, they have been ahead of the curve in terms of continuing such therapy throughout pregnancy and breastfeeding. That’s because active Crohn’s disease and ulcerative colitis are particularly common in women during their childbearing years. And a disease flare during pregnancy is associated with a markedly increased risk of preterm birth and other adverse outcomes.

Gastroenterologists’ longstanding interest in the safety to mother and fetus of continued use of effective, potent medications throughout pregnancy was the impetus for the ongoing prospective U.S. Pregnancy in Inflammatory Bowel Disease and Neonatal Outcomes (PIANO) study, now in its ninth year, with an enrollment of roughly 1,500 women with IBD. The study has included comparisons of outcomes of women on different medications during pregnancy versus unmedicated women.

In multiple publications, Dr. Mahadevan and other PIANO investigators have established that increased IBD activity adversely affects pregnancy outcomes, and that stabilization of disease and effective maintenance therapy throughout pregnancy is important. The PIANO group has demonstrated that IBD medication exposure well into the third trimester in patients in sustained remission was not associated with an increase in congenital anomalies, spontaneous abortions, intrauterine growth restriction, or low birth weight.

To the surprise of many gastroenterologists, the PIANO study has shown that women with Crohn’s disease generally have smoother pregnancies than do those with ulcerative colitis, who tend to get sicker and have more complications.

Since PIANO data show an increased rate of preterm birth and low birth weight in IBD patients on combination therapy with azathioprine plus a biologic throughout pregnancy, Dr. Mahadevan and others try to discontinue the azathioprine, even though the need for combination therapy is a marker for patients with more severe disease.

Anti-TNF-alpha use during third trimester

Of particular interest to rheumatologists, who rely heavily on many of the same biologic agents gastroenterologists use to treat IBD, the use of anti–tumor necrosis factor–alpha biologics in the third trimester was not associated with an increase in preterm birth or maternal disease activity in the third trimester or the first 4 months post partum. When women on certolizumab pegol (Cimzia) during the third trimester were excluded from the analysis, since this biologic uniquely does not cross the placenta at all, the most recent PIANO data show a modest yet statistically significant 35% increase in infections in infants at age 12 months whose mothers were on other biologics in the third trimester. But Dr. Mahadevan said she doesn’t yet consider this finding definitive.

“It’s still a small group of patients, and every year when we update the results the infant infection risk goes back and forth from statistically significant to nonsignificant. I think there’s a signal here; we just need to keep collecting more data,” she said.

Particularly reassuring is the finding that the offspring of PIANO participants who had in utero exposure to biologics and immunomodulators didn’t have any developmental delay, compared with unexposed babies, according to the validated Ages and Stages Questionnaire at ages 1, 2, 3, and 4 years and Denver Childhood Developmental Score at months 4, 9, and 12.

“These kids do great later in life. Actually, they have better scores than unexposed kids. Not to say that biologics make your kid smarter. It probably has to do with better IBD control,” Dr. Mahadevan said.

Effects while breastfeeding

Breastfeeding while on biologics or azathioprine didn’t adversely affect infant growth, infection rate, or developmental milestones. More specifically, levels of biologics in the mothers, babies, or cord serum were not associated with the likelihood of a neonatal intensive care unit stay, an increase in infant infections, or achievement of developmental milestones.

“Almost all the agents are detectable in breast milk, but only at the nanogram level. We tell all our patients on biologics they can breastfeed. It doesn’t matter when their last dose was, don’t worry about it,” the gastroenterologist said.

Importance of preconception counseling

Key practical lessons she has learned in taking care of large numbers of patients with severe IBD referred to her tertiary center include the importance of preconception counseling. A woman should stop methotrexate at least 3 months prior to conception. Providing information on medication safety and the risks of poorly controlled disease helps in adherence.

It’s best to communicate with the patient’s obstetrician about the importance of continuing her IBD therapy during pregnancy before she becomes pregnant.

“It’s better to have this discussion ahead of time and have a plan in place. Once a patient is pregnant it’s very difficult if her doula or someone else has told them to stop a medication to convince them to continue it,” said Dr. Mahadevan.

All women with IBD should be followed as high-risk pregnancies. Mode of delivery is at the discretion of the obstetrician unless the patient has an open rectovaginal fistula; even if it’s inactive, cesarean delivery is preferable in that situation, she said.

Steps taken in the third trimester

In the third trimester, she routinely sends a letter to the patient’s pediatrician requesting no live virus vaccines in the coming baby’s first 6 months – in the United States, that’s the rotavirus vaccine – if the infant was exposed in utero to a biologic other than certolizumab pegol, but that all other vaccines can be given on schedule. She also asks that the pediatrician monitor an exposed baby for infections.

“That being said, there have been 20-plus exposures to rotavirus vaccine in the first 6 months of life recorded in the PIANO registry in the infants of mothers on biologics and we haven’t seen any adverse events. So maybe the CDC is overstating the risk, but at this point the rule is still no live virus vaccines,” she said.

She tries to time her last dose of biologic agents during pregnancy as follows: at week 30-32 for infliximab or vedolizumab and week 36-38 for adalimumab or golimumab. As for certolizumab pegol, “they can take that on their way to labor and delivery,” she quipped.

“I give the next dose of a biologic agent soon after delivery, often while the patient is still in the hospital, 24 hours after vaginal delivery and 48 hours after a C-section, assuming no infection,” Dr. Mahadevan said.

The elements of her approach to management of the pregnant patient with IBD are in accord with a recent report, The Toronto Consensus Statements for the Management of Inflammatory Bowel Disease in Pregnancy, in which she participated (Gastroenterology. 2016 Mar;150[3]:734-57).

Rheumatologists’ habits with biologics in pregnancy

Dr. John J. Cush rose from the audience to observe that the situation in rheumatology with regard to biologics in pregnancy is quite a bit different from what’s going on in gastroenterology.

“I think a lot of rheumatologists don’t let their patients get pregnant on biologics for fear of what may happen. And that’s because they don’t know the data. I think you’ve shown very clearly that you can get pregnant on biologics and do well. But for many of us who do allow our patients to get pregnant on biologic monotherapy, the practice is to stop it once they get pregnant. The idea is we want them to be in a very deep remission to increase the odds of getting pregnant and having a successful pregnancy, but then we stop the drug and we assume the disease state is going to stay the same. Often, though, it doesn’t stay the same, it gets worse. Yet this is a common practice in rheumatology. What’s your response?” asked Dr. Cush, professor of medicine and rheumatology at Baylor University Medical Center, Dallas, and director of clinical rheumatology at the Baylor Research Institute.

“I think in IBD it’s very clear that patients with active disease in pregnancy do much, much worse,” Dr. Mahadevan replied. “They have preterm birth, they get very sick, they’re hospitalized and placed on steroids. So for us, the benefit is very clear. I don’t know the data in rheumatoid arthritis – whether active disease leads to increased complication rates – but I do know from colleagues that in the postpartum period women with poorly controlled rheumatoid arthritis can’t take care of their baby because their hands are so damaged. And that’s a big deal.

“So when you see that the drugs are not associated with an increased risk of birth defects and on monotherapy there’s no increase in infections and other complications, you’d think that in the right patient continuing treatment until the late third trimester would be the way to go, especially since if you’ve put the patient on a biologic it must mean she has severe disease,” the gastroenterologist observed.

Dr. Roy Fleischmann of the University of Texas, Dallas, asked why gastroenterologists don’t put all IBD patients of childbearing age on certolizumab pegol if they need biologic therapy, since it doesn’t cross the placenta.

“Maybe IBD is different, but our biologics don’t necessarily have the longest persistence,” Dr. Mahadevan replied. “If you start a woman on certolizumab pegol at age 20 the chances of her still being on it at 28 are probably pretty low.”

Conference director Dr. Arthur Kavanaugh, professor of medicine at the University of California, San Diego, asked if the message regarding management of IBD in pregnancy being put forth by Dr. Mahadevan and the IBD in Pregnancy Consensus Group has gained wide acceptance by gastroenterologists across the country.

“I think the people who do IBD as a concentrated practice, whether in private or academic practice, are very aware of this literature,” she said.

“In general, IBD has become more and more centered among a group of people who want to take care of IBD. If you look at the big private practices, they have a hepatitis C person, an IBD person, and everyone else just wants to scope. I think the message is getting across to non-IBD gastroenterologists, but there is some confusion because the Europeans are very firm about stopping biologics at 22 weeks’ gestation if the patient is in deep remission and we in North America continue treatment,” said Dr. Mahadevan.

Her work with the PIANO study is funded by the Crohn’s and Colitis Foundation of America. In addition, Dr. Mahadevan disclosed ties to more than half a dozen pharmaceutical companies.

[email protected]

MAUI, HAWAII – The consensus among gastroenterologists with expertise in inflammatory bowel disease is that continuation of biologics or immunomodulators in affected women throughout pregnancy and breastfeeding poses no increased risks to the fetus – and therein lies a message for rheumatologists and obstetricians, Dr. Uma Mahadevan said at the 2016 Rheumatology Winter Clinical Symposium.

“The risk of uncontrolled disease must be weighed against the risk of medical therapy. And this is something that is often missed,” according to Dr. Mahadevan, professor of medicine and co–medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.

Gastroenterologists – at least, those whose practices focus on inflammatory bowel disease (IBD) – have led the way within medicine in terms of establishing the safety of biologics and immunomodulators such as azathioprine in pregnant women with chronic inflammatory diseases and their babies. And having accomplished that, they have been ahead of the curve in terms of continuing such therapy throughout pregnancy and breastfeeding. That’s because active Crohn’s disease and ulcerative colitis are particularly common in women during their childbearing years. And a disease flare during pregnancy is associated with a markedly increased risk of preterm birth and other adverse outcomes.

Gastroenterologists’ longstanding interest in the safety to mother and fetus of continued use of effective, potent medications throughout pregnancy was the impetus for the ongoing prospective U.S. Pregnancy in Inflammatory Bowel Disease and Neonatal Outcomes (PIANO) study, now in its ninth year, with an enrollment of roughly 1,500 women with IBD. The study has included comparisons of outcomes of women on different medications during pregnancy versus unmedicated women.

In multiple publications, Dr. Mahadevan and other PIANO investigators have established that increased IBD activity adversely affects pregnancy outcomes, and that stabilization of disease and effective maintenance therapy throughout pregnancy is important. The PIANO group has demonstrated that IBD medication exposure well into the third trimester in patients in sustained remission was not associated with an increase in congenital anomalies, spontaneous abortions, intrauterine growth restriction, or low birth weight.

To the surprise of many gastroenterologists, the PIANO study has shown that women with Crohn’s disease generally have smoother pregnancies than do those with ulcerative colitis, who tend to get sicker and have more complications.

Since PIANO data show an increased rate of preterm birth and low birth weight in IBD patients on combination therapy with azathioprine plus a biologic throughout pregnancy, Dr. Mahadevan and others try to discontinue the azathioprine, even though the need for combination therapy is a marker for patients with more severe disease.

Anti-TNF-alpha use during third trimester

Of particular interest to rheumatologists, who rely heavily on many of the same biologic agents gastroenterologists use to treat IBD, the use of anti–tumor necrosis factor–alpha biologics in the third trimester was not associated with an increase in preterm birth or maternal disease activity in the third trimester or the first 4 months post partum. When women on certolizumab pegol (Cimzia) during the third trimester were excluded from the analysis, since this biologic uniquely does not cross the placenta at all, the most recent PIANO data show a modest yet statistically significant 35% increase in infections in infants at age 12 months whose mothers were on other biologics in the third trimester. But Dr. Mahadevan said she doesn’t yet consider this finding definitive.

“It’s still a small group of patients, and every year when we update the results the infant infection risk goes back and forth from statistically significant to nonsignificant. I think there’s a signal here; we just need to keep collecting more data,” she said.

Particularly reassuring is the finding that the offspring of PIANO participants who had in utero exposure to biologics and immunomodulators didn’t have any developmental delay, compared with unexposed babies, according to the validated Ages and Stages Questionnaire at ages 1, 2, 3, and 4 years and Denver Childhood Developmental Score at months 4, 9, and 12.

“These kids do great later in life. Actually, they have better scores than unexposed kids. Not to say that biologics make your kid smarter. It probably has to do with better IBD control,” Dr. Mahadevan said.

Effects while breastfeeding

Breastfeeding while on biologics or azathioprine didn’t adversely affect infant growth, infection rate, or developmental milestones. More specifically, levels of biologics in the mothers, babies, or cord serum were not associated with the likelihood of a neonatal intensive care unit stay, an increase in infant infections, or achievement of developmental milestones.

“Almost all the agents are detectable in breast milk, but only at the nanogram level. We tell all our patients on biologics they can breastfeed. It doesn’t matter when their last dose was, don’t worry about it,” the gastroenterologist said.

Importance of preconception counseling

Key practical lessons she has learned in taking care of large numbers of patients with severe IBD referred to her tertiary center include the importance of preconception counseling. A woman should stop methotrexate at least 3 months prior to conception. Providing information on medication safety and the risks of poorly controlled disease helps in adherence.

It’s best to communicate with the patient’s obstetrician about the importance of continuing her IBD therapy during pregnancy before she becomes pregnant.

“It’s better to have this discussion ahead of time and have a plan in place. Once a patient is pregnant it’s very difficult if her doula or someone else has told them to stop a medication to convince them to continue it,” said Dr. Mahadevan.

All women with IBD should be followed as high-risk pregnancies. Mode of delivery is at the discretion of the obstetrician unless the patient has an open rectovaginal fistula; even if it’s inactive, cesarean delivery is preferable in that situation, she said.

Steps taken in the third trimester

In the third trimester, she routinely sends a letter to the patient’s pediatrician requesting no live virus vaccines in the coming baby’s first 6 months – in the United States, that’s the rotavirus vaccine – if the infant was exposed in utero to a biologic other than certolizumab pegol, but that all other vaccines can be given on schedule. She also asks that the pediatrician monitor an exposed baby for infections.

“That being said, there have been 20-plus exposures to rotavirus vaccine in the first 6 months of life recorded in the PIANO registry in the infants of mothers on biologics and we haven’t seen any adverse events. So maybe the CDC is overstating the risk, but at this point the rule is still no live virus vaccines,” she said.

She tries to time her last dose of biologic agents during pregnancy as follows: at week 30-32 for infliximab or vedolizumab and week 36-38 for adalimumab or golimumab. As for certolizumab pegol, “they can take that on their way to labor and delivery,” she quipped.

“I give the next dose of a biologic agent soon after delivery, often while the patient is still in the hospital, 24 hours after vaginal delivery and 48 hours after a C-section, assuming no infection,” Dr. Mahadevan said.

The elements of her approach to management of the pregnant patient with IBD are in accord with a recent report, The Toronto Consensus Statements for the Management of Inflammatory Bowel Disease in Pregnancy, in which she participated (Gastroenterology. 2016 Mar;150[3]:734-57).

Rheumatologists’ habits with biologics in pregnancy

Dr. John J. Cush rose from the audience to observe that the situation in rheumatology with regard to biologics in pregnancy is quite a bit different from what’s going on in gastroenterology.

“I think a lot of rheumatologists don’t let their patients get pregnant on biologics for fear of what may happen. And that’s because they don’t know the data. I think you’ve shown very clearly that you can get pregnant on biologics and do well. But for many of us who do allow our patients to get pregnant on biologic monotherapy, the practice is to stop it once they get pregnant. The idea is we want them to be in a very deep remission to increase the odds of getting pregnant and having a successful pregnancy, but then we stop the drug and we assume the disease state is going to stay the same. Often, though, it doesn’t stay the same, it gets worse. Yet this is a common practice in rheumatology. What’s your response?” asked Dr. Cush, professor of medicine and rheumatology at Baylor University Medical Center, Dallas, and director of clinical rheumatology at the Baylor Research Institute.

“I think in IBD it’s very clear that patients with active disease in pregnancy do much, much worse,” Dr. Mahadevan replied. “They have preterm birth, they get very sick, they’re hospitalized and placed on steroids. So for us, the benefit is very clear. I don’t know the data in rheumatoid arthritis – whether active disease leads to increased complication rates – but I do know from colleagues that in the postpartum period women with poorly controlled rheumatoid arthritis can’t take care of their baby because their hands are so damaged. And that’s a big deal.

“So when you see that the drugs are not associated with an increased risk of birth defects and on monotherapy there’s no increase in infections and other complications, you’d think that in the right patient continuing treatment until the late third trimester would be the way to go, especially since if you’ve put the patient on a biologic it must mean she has severe disease,” the gastroenterologist observed.

Dr. Roy Fleischmann of the University of Texas, Dallas, asked why gastroenterologists don’t put all IBD patients of childbearing age on certolizumab pegol if they need biologic therapy, since it doesn’t cross the placenta.

“Maybe IBD is different, but our biologics don’t necessarily have the longest persistence,” Dr. Mahadevan replied. “If you start a woman on certolizumab pegol at age 20 the chances of her still being on it at 28 are probably pretty low.”

Conference director Dr. Arthur Kavanaugh, professor of medicine at the University of California, San Diego, asked if the message regarding management of IBD in pregnancy being put forth by Dr. Mahadevan and the IBD in Pregnancy Consensus Group has gained wide acceptance by gastroenterologists across the country.

“I think the people who do IBD as a concentrated practice, whether in private or academic practice, are very aware of this literature,” she said.

“In general, IBD has become more and more centered among a group of people who want to take care of IBD. If you look at the big private practices, they have a hepatitis C person, an IBD person, and everyone else just wants to scope. I think the message is getting across to non-IBD gastroenterologists, but there is some confusion because the Europeans are very firm about stopping biologics at 22 weeks’ gestation if the patient is in deep remission and we in North America continue treatment,” said Dr. Mahadevan.

Her work with the PIANO study is funded by the Crohn’s and Colitis Foundation of America. In addition, Dr. Mahadevan disclosed ties to more than half a dozen pharmaceutical companies.

[email protected]

MAUI, HAWAII – The consensus among gastroenterologists with expertise in inflammatory bowel disease is that continuation of biologics or immunomodulators in affected women throughout pregnancy and breastfeeding poses no increased risks to the fetus – and therein lies a message for rheumatologists and obstetricians, Dr. Uma Mahadevan said at the 2016 Rheumatology Winter Clinical Symposium.

“The risk of uncontrolled disease must be weighed against the risk of medical therapy. And this is something that is often missed,” according to Dr. Mahadevan, professor of medicine and co–medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.

Gastroenterologists – at least, those whose practices focus on inflammatory bowel disease (IBD) – have led the way within medicine in terms of establishing the safety of biologics and immunomodulators such as azathioprine in pregnant women with chronic inflammatory diseases and their babies. And having accomplished that, they have been ahead of the curve in terms of continuing such therapy throughout pregnancy and breastfeeding. That’s because active Crohn’s disease and ulcerative colitis are particularly common in women during their childbearing years. And a disease flare during pregnancy is associated with a markedly increased risk of preterm birth and other adverse outcomes.

Gastroenterologists’ longstanding interest in the safety to mother and fetus of continued use of effective, potent medications throughout pregnancy was the impetus for the ongoing prospective U.S. Pregnancy in Inflammatory Bowel Disease and Neonatal Outcomes (PIANO) study, now in its ninth year, with an enrollment of roughly 1,500 women with IBD. The study has included comparisons of outcomes of women on different medications during pregnancy versus unmedicated women.

In multiple publications, Dr. Mahadevan and other PIANO investigators have established that increased IBD activity adversely affects pregnancy outcomes, and that stabilization of disease and effective maintenance therapy throughout pregnancy is important. The PIANO group has demonstrated that IBD medication exposure well into the third trimester in patients in sustained remission was not associated with an increase in congenital anomalies, spontaneous abortions, intrauterine growth restriction, or low birth weight.

To the surprise of many gastroenterologists, the PIANO study has shown that women with Crohn’s disease generally have smoother pregnancies than do those with ulcerative colitis, who tend to get sicker and have more complications.

Since PIANO data show an increased rate of preterm birth and low birth weight in IBD patients on combination therapy with azathioprine plus a biologic throughout pregnancy, Dr. Mahadevan and others try to discontinue the azathioprine, even though the need for combination therapy is a marker for patients with more severe disease.

Anti-TNF-alpha use during third trimester

Of particular interest to rheumatologists, who rely heavily on many of the same biologic agents gastroenterologists use to treat IBD, the use of anti–tumor necrosis factor–alpha biologics in the third trimester was not associated with an increase in preterm birth or maternal disease activity in the third trimester or the first 4 months post partum. When women on certolizumab pegol (Cimzia) during the third trimester were excluded from the analysis, since this biologic uniquely does not cross the placenta at all, the most recent PIANO data show a modest yet statistically significant 35% increase in infections in infants at age 12 months whose mothers were on other biologics in the third trimester. But Dr. Mahadevan said she doesn’t yet consider this finding definitive.

“It’s still a small group of patients, and every year when we update the results the infant infection risk goes back and forth from statistically significant to nonsignificant. I think there’s a signal here; we just need to keep collecting more data,” she said.

Particularly reassuring is the finding that the offspring of PIANO participants who had in utero exposure to biologics and immunomodulators didn’t have any developmental delay, compared with unexposed babies, according to the validated Ages and Stages Questionnaire at ages 1, 2, 3, and 4 years and Denver Childhood Developmental Score at months 4, 9, and 12.

“These kids do great later in life. Actually, they have better scores than unexposed kids. Not to say that biologics make your kid smarter. It probably has to do with better IBD control,” Dr. Mahadevan said.

Effects while breastfeeding

Breastfeeding while on biologics or azathioprine didn’t adversely affect infant growth, infection rate, or developmental milestones. More specifically, levels of biologics in the mothers, babies, or cord serum were not associated with the likelihood of a neonatal intensive care unit stay, an increase in infant infections, or achievement of developmental milestones.

“Almost all the agents are detectable in breast milk, but only at the nanogram level. We tell all our patients on biologics they can breastfeed. It doesn’t matter when their last dose was, don’t worry about it,” the gastroenterologist said.

Importance of preconception counseling

Key practical lessons she has learned in taking care of large numbers of patients with severe IBD referred to her tertiary center include the importance of preconception counseling. A woman should stop methotrexate at least 3 months prior to conception. Providing information on medication safety and the risks of poorly controlled disease helps in adherence.

It’s best to communicate with the patient’s obstetrician about the importance of continuing her IBD therapy during pregnancy before she becomes pregnant.

“It’s better to have this discussion ahead of time and have a plan in place. Once a patient is pregnant it’s very difficult if her doula or someone else has told them to stop a medication to convince them to continue it,” said Dr. Mahadevan.

All women with IBD should be followed as high-risk pregnancies. Mode of delivery is at the discretion of the obstetrician unless the patient has an open rectovaginal fistula; even if it’s inactive, cesarean delivery is preferable in that situation, she said.

Steps taken in the third trimester

In the third trimester, she routinely sends a letter to the patient’s pediatrician requesting no live virus vaccines in the coming baby’s first 6 months – in the United States, that’s the rotavirus vaccine – if the infant was exposed in utero to a biologic other than certolizumab pegol, but that all other vaccines can be given on schedule. She also asks that the pediatrician monitor an exposed baby for infections.

“That being said, there have been 20-plus exposures to rotavirus vaccine in the first 6 months of life recorded in the PIANO registry in the infants of mothers on biologics and we haven’t seen any adverse events. So maybe the CDC is overstating the risk, but at this point the rule is still no live virus vaccines,” she said.

She tries to time her last dose of biologic agents during pregnancy as follows: at week 30-32 for infliximab or vedolizumab and week 36-38 for adalimumab or golimumab. As for certolizumab pegol, “they can take that on their way to labor and delivery,” she quipped.

“I give the next dose of a biologic agent soon after delivery, often while the patient is still in the hospital, 24 hours after vaginal delivery and 48 hours after a C-section, assuming no infection,” Dr. Mahadevan said.

The elements of her approach to management of the pregnant patient with IBD are in accord with a recent report, The Toronto Consensus Statements for the Management of Inflammatory Bowel Disease in Pregnancy, in which she participated (Gastroenterology. 2016 Mar;150[3]:734-57).

Rheumatologists’ habits with biologics in pregnancy

Dr. John J. Cush rose from the audience to observe that the situation in rheumatology with regard to biologics in pregnancy is quite a bit different from what’s going on in gastroenterology.

“I think a lot of rheumatologists don’t let their patients get pregnant on biologics for fear of what may happen. And that’s because they don’t know the data. I think you’ve shown very clearly that you can get pregnant on biologics and do well. But for many of us who do allow our patients to get pregnant on biologic monotherapy, the practice is to stop it once they get pregnant. The idea is we want them to be in a very deep remission to increase the odds of getting pregnant and having a successful pregnancy, but then we stop the drug and we assume the disease state is going to stay the same. Often, though, it doesn’t stay the same, it gets worse. Yet this is a common practice in rheumatology. What’s your response?” asked Dr. Cush, professor of medicine and rheumatology at Baylor University Medical Center, Dallas, and director of clinical rheumatology at the Baylor Research Institute.

“I think in IBD it’s very clear that patients with active disease in pregnancy do much, much worse,” Dr. Mahadevan replied. “They have preterm birth, they get very sick, they’re hospitalized and placed on steroids. So for us, the benefit is very clear. I don’t know the data in rheumatoid arthritis – whether active disease leads to increased complication rates – but I do know from colleagues that in the postpartum period women with poorly controlled rheumatoid arthritis can’t take care of their baby because their hands are so damaged. And that’s a big deal.

“So when you see that the drugs are not associated with an increased risk of birth defects and on monotherapy there’s no increase in infections and other complications, you’d think that in the right patient continuing treatment until the late third trimester would be the way to go, especially since if you’ve put the patient on a biologic it must mean she has severe disease,” the gastroenterologist observed.

Dr. Roy Fleischmann of the University of Texas, Dallas, asked why gastroenterologists don’t put all IBD patients of childbearing age on certolizumab pegol if they need biologic therapy, since it doesn’t cross the placenta.

“Maybe IBD is different, but our biologics don’t necessarily have the longest persistence,” Dr. Mahadevan replied. “If you start a woman on certolizumab pegol at age 20 the chances of her still being on it at 28 are probably pretty low.”

Conference director Dr. Arthur Kavanaugh, professor of medicine at the University of California, San Diego, asked if the message regarding management of IBD in pregnancy being put forth by Dr. Mahadevan and the IBD in Pregnancy Consensus Group has gained wide acceptance by gastroenterologists across the country.

“I think the people who do IBD as a concentrated practice, whether in private or academic practice, are very aware of this literature,” she said.

“In general, IBD has become more and more centered among a group of people who want to take care of IBD. If you look at the big private practices, they have a hepatitis C person, an IBD person, and everyone else just wants to scope. I think the message is getting across to non-IBD gastroenterologists, but there is some confusion because the Europeans are very firm about stopping biologics at 22 weeks’ gestation if the patient is in deep remission and we in North America continue treatment,” said Dr. Mahadevan.

Her work with the PIANO study is funded by the Crohn’s and Colitis Foundation of America. In addition, Dr. Mahadevan disclosed ties to more than half a dozen pharmaceutical companies.

[email protected]

CHICAGO – Prompt, effective treatment for depression in the primary care setting appears to swiftly reduce the elevated cardiovascular risk known to be tied to the mood disorder, Heidi Thomas May, Ph.D., reported at the annual meeting of the American College of Cardiology.

“We know that depression is a risk factor for long-term adverse cardiovascular outcomes. Our study shows that it can also have immediate effects on someone’s cardiovascular health. I think our study highlights the importance of screening for depression in the primary care setting – and if someone’s depressed, they need to be treated,” said Dr. May, a cardiovascular and genetic epidemiologist at Intermountain Medical Center in Murray, Utah.

Bruce Jancin/Frontline Medical News

She presented an observational study of the electronic medical records of 7,559 Intermountain Healthcare patients over age 40 years who completed the Patient Health Questionnaire-9 (PHQ-9) depression screening tool during a visit to an Intermountain primary care clinic for any reason. They completed another PHQ-9 a median of 2.7 years later. Under the Intermountain system, a PHQ-9 score of 10 or more triggers implementation of a depression treatment pathway, the specifics of which vary depending upon the severity of symptoms.

On the basis of their two PHQ-9 scores, all patients were classified into one of four groups: The “nondepressed” group of 3,286 patients had a score of 9 or less on both occasions; the “remained depressed” cohort of 1,987 patients scored 10 or more on both PHQ-9s; the “no longer depressed” group of 1,542 patients scored at least 10 but subsequently improved by at least 5 points to a score of 9 or less; and the 735 patients in the “became depressed” group first scored 9 or less on the PHQ-9 but subsequently had at least a 5-point increase to a score of 10 or more.

The subjects were then followed for major adverse cardiovascular events, or MACE – defined as a composite of death, diagnosis of coronary artery disease, acute MI, stroke, and heart failure hospitalization – for a median of 208 days after completing their second PHQ-9.

The MACE rate was 4.8% in the nondepressed group and similar at 4.6% in the “no longer depressed” group, Dr. May reported. Both groups fared significantly better than the “remained depressed” and “became depressed” groups, which had MACE rates of 6% and 6.4%, respectively.

In a multivariate regression analysis adjusted for demographics, cardiovascular risk factors, prior disease diagnoses, medications, and other potential confounders, the “remained depressed” group was 33% more likely to experience a cardiovascular event than was the nondepressed group, she said. The “became depressed” group had a 44% increase in risk, compared with the nondepressed individuals. In contrast, the MACE risk in patients in the “no longer depressed” group was not significantly different from that of patients who weren’t depressed at either time point. And the MACE risk of patients who became depressed during the course of the study was no different from that of patients who remained depressed at both time points.

This is the first study of its kind, Dr. May said. Hence, the results require confirmation, ideally in a randomized clinical trial.

She reported having no financial conflicts regarding the study, which was supported by Intermountain Healthcare.

[email protected]

CHICAGO – Prompt, effective treatment for depression in the primary care setting appears to swiftly reduce the elevated cardiovascular risk known to be tied to the mood disorder, Heidi Thomas May, Ph.D., reported at the annual meeting of the American College of Cardiology.

“We know that depression is a risk factor for long-term adverse cardiovascular outcomes. Our study shows that it can also have immediate effects on someone’s cardiovascular health. I think our study highlights the importance of screening for depression in the primary care setting – and if someone’s depressed, they need to be treated,” said Dr. May, a cardiovascular and genetic epidemiologist at Intermountain Medical Center in Murray, Utah.

Bruce Jancin/Frontline Medical News

She presented an observational study of the electronic medical records of 7,559 Intermountain Healthcare patients over age 40 years who completed the Patient Health Questionnaire-9 (PHQ-9) depression screening tool during a visit to an Intermountain primary care clinic for any reason. They completed another PHQ-9 a median of 2.7 years later. Under the Intermountain system, a PHQ-9 score of 10 or more triggers implementation of a depression treatment pathway, the specifics of which vary depending upon the severity of symptoms.

On the basis of their two PHQ-9 scores, all patients were classified into one of four groups: The “nondepressed” group of 3,286 patients had a score of 9 or less on both occasions; the “remained depressed” cohort of 1,987 patients scored 10 or more on both PHQ-9s; the “no longer depressed” group of 1,542 patients scored at least 10 but subsequently improved by at least 5 points to a score of 9 or less; and the 735 patients in the “became depressed” group first scored 9 or less on the PHQ-9 but subsequently had at least a 5-point increase to a score of 10 or more.

The subjects were then followed for major adverse cardiovascular events, or MACE – defined as a composite of death, diagnosis of coronary artery disease, acute MI, stroke, and heart failure hospitalization – for a median of 208 days after completing their second PHQ-9.

The MACE rate was 4.8% in the nondepressed group and similar at 4.6% in the “no longer depressed” group, Dr. May reported. Both groups fared significantly better than the “remained depressed” and “became depressed” groups, which had MACE rates of 6% and 6.4%, respectively.

In a multivariate regression analysis adjusted for demographics, cardiovascular risk factors, prior disease diagnoses, medications, and other potential confounders, the “remained depressed” group was 33% more likely to experience a cardiovascular event than was the nondepressed group, she said. The “became depressed” group had a 44% increase in risk, compared with the nondepressed individuals. In contrast, the MACE risk in patients in the “no longer depressed” group was not significantly different from that of patients who weren’t depressed at either time point. And the MACE risk of patients who became depressed during the course of the study was no different from that of patients who remained depressed at both time points.

This is the first study of its kind, Dr. May said. Hence, the results require confirmation, ideally in a randomized clinical trial.

She reported having no financial conflicts regarding the study, which was supported by Intermountain Healthcare.

[email protected]

CHICAGO – Prompt, effective treatment for depression in the primary care setting appears to swiftly reduce the elevated cardiovascular risk known to be tied to the mood disorder, Heidi Thomas May, Ph.D., reported at the annual meeting of the American College of Cardiology.

“We know that depression is a risk factor for long-term adverse cardiovascular outcomes. Our study shows that it can also have immediate effects on someone’s cardiovascular health. I think our study highlights the importance of screening for depression in the primary care setting – and if someone’s depressed, they need to be treated,” said Dr. May, a cardiovascular and genetic epidemiologist at Intermountain Medical Center in Murray, Utah.

Bruce Jancin/Frontline Medical News

She presented an observational study of the electronic medical records of 7,559 Intermountain Healthcare patients over age 40 years who completed the Patient Health Questionnaire-9 (PHQ-9) depression screening tool during a visit to an Intermountain primary care clinic for any reason. They completed another PHQ-9 a median of 2.7 years later. Under the Intermountain system, a PHQ-9 score of 10 or more triggers implementation of a depression treatment pathway, the specifics of which vary depending upon the severity of symptoms.

On the basis of their two PHQ-9 scores, all patients were classified into one of four groups: The “nondepressed” group of 3,286 patients had a score of 9 or less on both occasions; the “remained depressed” cohort of 1,987 patients scored 10 or more on both PHQ-9s; the “no longer depressed” group of 1,542 patients scored at least 10 but subsequently improved by at least 5 points to a score of 9 or less; and the 735 patients in the “became depressed” group first scored 9 or less on the PHQ-9 but subsequently had at least a 5-point increase to a score of 10 or more.

The subjects were then followed for major adverse cardiovascular events, or MACE – defined as a composite of death, diagnosis of coronary artery disease, acute MI, stroke, and heart failure hospitalization – for a median of 208 days after completing their second PHQ-9.

The MACE rate was 4.8% in the nondepressed group and similar at 4.6% in the “no longer depressed” group, Dr. May reported. Both groups fared significantly better than the “remained depressed” and “became depressed” groups, which had MACE rates of 6% and 6.4%, respectively.

In a multivariate regression analysis adjusted for demographics, cardiovascular risk factors, prior disease diagnoses, medications, and other potential confounders, the “remained depressed” group was 33% more likely to experience a cardiovascular event than was the nondepressed group, she said. The “became depressed” group had a 44% increase in risk, compared with the nondepressed individuals. In contrast, the MACE risk in patients in the “no longer depressed” group was not significantly different from that of patients who weren’t depressed at either time point. And the MACE risk of patients who became depressed during the course of the study was no different from that of patients who remained depressed at both time points.

This is the first study of its kind, Dr. May said. Hence, the results require confirmation, ideally in a randomized clinical trial.

She reported having no financial conflicts regarding the study, which was supported by Intermountain Healthcare.

[email protected]

A consolidated registry system designed to increase access to the second-generation antipsychotic clozapine is plagued with glitches, delays, and excess red tape more than 8 months after its initial launch, according to clinicians and pharmacists who are attempting to use it.

The problems include psychiatrists receiving information from the registry on patients not in their care, a breach of Health Insurance Portability and Accountability Act privacy rules. And some said they fear that clozapine, the only Food and Drug Administration–approved drug for treatment-resistant schizophrenia, will end up underprescribed as a result of difficulties complying with the new registry’s demands.

The psychiatric community lauded the FDA’s decision in September 2015 to change the monitoring requirements for clozapine. One rare but dangerous adverse effect of the drug is severe neutropenia, and patients on clozapine must be monitored through regular blood screening. This means that every clozapine script requires careful coordination among the prescriber, patient, laboratory, and pharmacy.

Now, instead of looking at white blood cell counts as before, the FDA said, absolute neutrophil count (ANC) will be the lab measure used to determine whether a patient can be started or continued on clozapine, and new lowered ANC thresholds will allow more patients to be initiated. The new lowered ANC thresholds may pertain to people of African and Middle Eastern heritage with a naturally lower ANC called “benign ethnic neutropenia” and who previously might not have been able to receive the drug.

At the same time it announced the new monitoring rules, the FDA also said the six existing manufacturer registries of clozapine would be consolidated into one, called the Clozapine Risk Evaluation and Mitigation Strategies, or Clozapine REMS. The REMS is managed jointly by the manufacturers. Prescribers and pharmacies dealing with clozapine must become certified under the REMS if they wish patients to receive the drug. Though certification was supposed to have been completed by this month, the agency now is saying providers have until year-end.

REMS applauded early on

Originally, psychiatrists welcomed the news of the REMS, as it promised to make it easier for a patient to continue on clozapine even if the drug supplier changed – when transitioning from an inpatient to outpatient setting, for example.

However, when it launched in the fall of 2015, the Clozapine REMS website was full of glitches, and calls to the toll-free number weren’t picked up. “I couldn’t even get onto [the registry], as they wouldn’t answer the phone,” said Dr. Ira D. Glick, professor emeritus of psychiatry and behavioral sciences and psychopharmacology at Stanford (Calif.) University, who has prescribed clozapine for decades. More recently, he said, the response time has improved.

The FDA has acknowledged providers’ complaints, and mainly characterizes the registry’s problems as growing pains. “As with any new IT system, and large data migration and reconciliation effort, there are challenges,” an agency spokesperson said in an interview about the REMS. “Merging six previous clozapine registries was a huge undertaking for the manufacturers that encompassed merging data from over 50,000 prescribers, 28,000 pharmacies, and 200,000 patient records.” 

The FDA has been working “to address the issues identified when the Clozapine REMS Program was initially implemented,” the representative said. “We believe that most of the issues have been resolved.” The FDA did not directly respond to questions about confidentiality breaches.

Providers said in interviews, however, that the issues continue, including mix-ups of confidential health information.

“I’m now registered as a provider designee for several clozapine prescribers here at my hospital,” said Megan Maroney, Pharm.D., of Monmouth Medical Center in Long Branch, N.J. “One of our prescribers also has a private practice, and those patients are popping up on my list, but they’re not my patients.” Dr. Maroney said she contacted the Clozapine REMS about the problem. “They haven’t yet come up with a good way to deal with it,” she said.

Courtesy Dr. Jean-Pierre Lindenmayer

Dr. Jean-Pierre Lindenmayer, clinical professor in the department of psychiatry at New York University, said he, too, receives information about patients who are not his. “I’m still getting faxed notifications on patients I have no idea who they are, saying they’re due for a blood test. It’s incredible that they keep doing this.” The REMS never responded to his complaints about privacy breaches, he said.

Problems ‘causing confusion’

Providers say the Clozapine REMS website remains filled with glitches and that deadlines are being extended until these can be resolved. “We’re trying to follow the intended rules with the understanding that if issues come up, we’re supposed to use our clinical judgment and not delay care to the patient. But it’s causing a lot of confusion among my staff, because whenever we try to use it, we encounter some kind of glitch,” Dr. Maroney said.

Another of the providers’ key concerns is the extra red-tape burdens imposed by the REMS, which, they say, have the potential to dampen the prescribing of clozapine – the exact opposite of its intended effect.

By mandating that only registered prescribers can write for clozapine, the REMS can cause problems for hospitals. “If a patient comes in for a medical reason and happens to be on clozapine, it’s impossible for us to get our internal medicine physicians registered just so they can prescribe it for their one patient who comes through,” Dr. Maroney said. Her workaround has been to make sure all the hospital’s psychiatrists are registered and that patients on clozapine have a psych consult, regardless of the reason they’re hospitalized. This, she acknowledged, could drive up costs.

“Here at my hospital, I tend to work out the issues for my prescribers so that they can start patients and continue them, and I think we’ve been doing a pretty good job. But I wonder about places without the manpower to do that or that don’t have a psych pharmacist who can work with them,” she said.

The REMS “is a major obstacle, and it’s more complicated now than it was before,” said Dr. Lindenmayer, who also is affiliated with the Manhattan Psychiatric Center in New York, an institution that manages about 100 patients on clozapine. “The excessive registry demands, and sending doctors letters about all the potential terrible side effects, will discourage providers. Clozapine is already difficult to prescribe: You have to have a pharmacy lined up, you have to have a lab lined up, you have to have a patient that gets the prescription and the blood test in a timely manner, and you are not being reimbursed at any higher rate by having a clozapine patient.”

Dr. Glick agreed. “Clozapine is one of our best drugs, but the most difficult to manage – as it takes a lot of time and effort. This is one more step making it more complicated.”

Dr. Maroney said that at her institution, she’s already seen a chilling effect from the REMS. Recently, she said, “my prescribers and I were going over all the changes and some of them said, ‘Just forget it, I’ll put [patients] on something else.’ And I said, ‘No – the whole point of a lot of the changes was to make [clozapine] more accessible.’ ”

Dr. Lindenmayer said he considers the REMS – or at least the extra layers of bureaucracy and certification it imposes – to have been a misguided move by the FDA. “I am not aware that there have been more deaths recently due to clozapine prescribing, and haven’t seen any upsurge of morbidity and mortality in the literature, which I follow closely.” Relatively few prescribers use clozapine, he said, and those who do “are fairly careful and knowledgeable about what they’re doing. So they’re preaching to the choir,” he said.

Yet Dr. Maroney said she remains optimistic that the REMS and the providers will be able to reach common ground – eventually: “The College of Psychiatric and Neurologic Pharmacists has been communicating with the FDA to hammer out these issues. I think it should get better. I just don’t know when that will occur and how many of these issues will be completely addressed.”

The FDA spokesperson confirmed that the agency was seeking provider input to improve the Clozapine REMS, and that several changes already had been made in response to provider concerns.

A consolidated registry system designed to increase access to the second-generation antipsychotic clozapine is plagued with glitches, delays, and excess red tape more than 8 months after its initial launch, according to clinicians and pharmacists who are attempting to use it.

The problems include psychiatrists receiving information from the registry on patients not in their care, a breach of Health Insurance Portability and Accountability Act privacy rules. And some said they fear that clozapine, the only Food and Drug Administration–approved drug for treatment-resistant schizophrenia, will end up underprescribed as a result of difficulties complying with the new registry’s demands.

The psychiatric community lauded the FDA’s decision in September 2015 to change the monitoring requirements for clozapine. One rare but dangerous adverse effect of the drug is severe neutropenia, and patients on clozapine must be monitored through regular blood screening. This means that every clozapine script requires careful coordination among the prescriber, patient, laboratory, and pharmacy.

Now, instead of looking at white blood cell counts as before, the FDA said, absolute neutrophil count (ANC) will be the lab measure used to determine whether a patient can be started or continued on clozapine, and new lowered ANC thresholds will allow more patients to be initiated. The new lowered ANC thresholds may pertain to people of African and Middle Eastern heritage with a naturally lower ANC called “benign ethnic neutropenia” and who previously might not have been able to receive the drug.

At the same time it announced the new monitoring rules, the FDA also said the six existing manufacturer registries of clozapine would be consolidated into one, called the Clozapine Risk Evaluation and Mitigation Strategies, or Clozapine REMS. The REMS is managed jointly by the manufacturers. Prescribers and pharmacies dealing with clozapine must become certified under the REMS if they wish patients to receive the drug. Though certification was supposed to have been completed by this month, the agency now is saying providers have until year-end.

REMS applauded early on

Originally, psychiatrists welcomed the news of the REMS, as it promised to make it easier for a patient to continue on clozapine even if the drug supplier changed – when transitioning from an inpatient to outpatient setting, for example.

However, when it launched in the fall of 2015, the Clozapine REMS website was full of glitches, and calls to the toll-free number weren’t picked up. “I couldn’t even get onto [the registry], as they wouldn’t answer the phone,” said Dr. Ira D. Glick, professor emeritus of psychiatry and behavioral sciences and psychopharmacology at Stanford (Calif.) University, who has prescribed clozapine for decades. More recently, he said, the response time has improved.

The FDA has acknowledged providers’ complaints, and mainly characterizes the registry’s problems as growing pains. “As with any new IT system, and large data migration and reconciliation effort, there are challenges,” an agency spokesperson said in an interview about the REMS. “Merging six previous clozapine registries was a huge undertaking for the manufacturers that encompassed merging data from over 50,000 prescribers, 28,000 pharmacies, and 200,000 patient records.” 

The FDA has been working “to address the issues identified when the Clozapine REMS Program was initially implemented,” the representative said. “We believe that most of the issues have been resolved.” The FDA did not directly respond to questions about confidentiality breaches.

Providers said in interviews, however, that the issues continue, including mix-ups of confidential health information.

“I’m now registered as a provider designee for several clozapine prescribers here at my hospital,” said Megan Maroney, Pharm.D., of Monmouth Medical Center in Long Branch, N.J. “One of our prescribers also has a private practice, and those patients are popping up on my list, but they’re not my patients.” Dr. Maroney said she contacted the Clozapine REMS about the problem. “They haven’t yet come up with a good way to deal with it,” she said.

Courtesy Dr. Jean-Pierre Lindenmayer

Dr. Jean-Pierre Lindenmayer, clinical professor in the department of psychiatry at New York University, said he, too, receives information about patients who are not his. “I’m still getting faxed notifications on patients I have no idea who they are, saying they’re due for a blood test. It’s incredible that they keep doing this.” The REMS never responded to his complaints about privacy breaches, he said.

Problems ‘causing confusion’

Providers say the Clozapine REMS website remains filled with glitches and that deadlines are being extended until these can be resolved. “We’re trying to follow the intended rules with the understanding that if issues come up, we’re supposed to use our clinical judgment and not delay care to the patient. But it’s causing a lot of confusion among my staff, because whenever we try to use it, we encounter some kind of glitch,” Dr. Maroney said.

Another of the providers’ key concerns is the extra red-tape burdens imposed by the REMS, which, they say, have the potential to dampen the prescribing of clozapine – the exact opposite of its intended effect.

By mandating that only registered prescribers can write for clozapine, the REMS can cause problems for hospitals. “If a patient comes in for a medical reason and happens to be on clozapine, it’s impossible for us to get our internal medicine physicians registered just so they can prescribe it for their one patient who comes through,” Dr. Maroney said. Her workaround has been to make sure all the hospital’s psychiatrists are registered and that patients on clozapine have a psych consult, regardless of the reason they’re hospitalized. This, she acknowledged, could drive up costs.

“Here at my hospital, I tend to work out the issues for my prescribers so that they can start patients and continue them, and I think we’ve been doing a pretty good job. But I wonder about places without the manpower to do that or that don’t have a psych pharmacist who can work with them,” she said.

The REMS “is a major obstacle, and it’s more complicated now than it was before,” said Dr. Lindenmayer, who also is affiliated with the Manhattan Psychiatric Center in New York, an institution that manages about 100 patients on clozapine. “The excessive registry demands, and sending doctors letters about all the potential terrible side effects, will discourage providers. Clozapine is already difficult to prescribe: You have to have a pharmacy lined up, you have to have a lab lined up, you have to have a patient that gets the prescription and the blood test in a timely manner, and you are not being reimbursed at any higher rate by having a clozapine patient.”

Dr. Glick agreed. “Clozapine is one of our best drugs, but the most difficult to manage – as it takes a lot of time and effort. This is one more step making it more complicated.”

Dr. Maroney said that at her institution, she’s already seen a chilling effect from the REMS. Recently, she said, “my prescribers and I were going over all the changes and some of them said, ‘Just forget it, I’ll put [patients] on something else.’ And I said, ‘No – the whole point of a lot of the changes was to make [clozapine] more accessible.’ ”

Dr. Lindenmayer said he considers the REMS – or at least the extra layers of bureaucracy and certification it imposes – to have been a misguided move by the FDA. “I am not aware that there have been more deaths recently due to clozapine prescribing, and haven’t seen any upsurge of morbidity and mortality in the literature, which I follow closely.” Relatively few prescribers use clozapine, he said, and those who do “are fairly careful and knowledgeable about what they’re doing. So they’re preaching to the choir,” he said.

Yet Dr. Maroney said she remains optimistic that the REMS and the providers will be able to reach common ground – eventually: “The College of Psychiatric and Neurologic Pharmacists has been communicating with the FDA to hammer out these issues. I think it should get better. I just don’t know when that will occur and how many of these issues will be completely addressed.”

The FDA spokesperson confirmed that the agency was seeking provider input to improve the Clozapine REMS, and that several changes already had been made in response to provider concerns.

A consolidated registry system designed to increase access to the second-generation antipsychotic clozapine is plagued with glitches, delays, and excess red tape more than 8 months after its initial launch, according to clinicians and pharmacists who are attempting to use it.

The problems include psychiatrists receiving information from the registry on patients not in their care, a breach of Health Insurance Portability and Accountability Act privacy rules. And some said they fear that clozapine, the only Food and Drug Administration–approved drug for treatment-resistant schizophrenia, will end up underprescribed as a result of difficulties complying with the new registry’s demands.

The psychiatric community lauded the FDA’s decision in September 2015 to change the monitoring requirements for clozapine. One rare but dangerous adverse effect of the drug is severe neutropenia, and patients on clozapine must be monitored through regular blood screening. This means that every clozapine script requires careful coordination among the prescriber, patient, laboratory, and pharmacy.

Now, instead of looking at white blood cell counts as before, the FDA said, absolute neutrophil count (ANC) will be the lab measure used to determine whether a patient can be started or continued on clozapine, and new lowered ANC thresholds will allow more patients to be initiated. The new lowered ANC thresholds may pertain to people of African and Middle Eastern heritage with a naturally lower ANC called “benign ethnic neutropenia” and who previously might not have been able to receive the drug.

At the same time it announced the new monitoring rules, the FDA also said the six existing manufacturer registries of clozapine would be consolidated into one, called the Clozapine Risk Evaluation and Mitigation Strategies, or Clozapine REMS. The REMS is managed jointly by the manufacturers. Prescribers and pharmacies dealing with clozapine must become certified under the REMS if they wish patients to receive the drug. Though certification was supposed to have been completed by this month, the agency now is saying providers have until year-end.

REMS applauded early on

Originally, psychiatrists welcomed the news of the REMS, as it promised to make it easier for a patient to continue on clozapine even if the drug supplier changed – when transitioning from an inpatient to outpatient setting, for example.

However, when it launched in the fall of 2015, the Clozapine REMS website was full of glitches, and calls to the toll-free number weren’t picked up. “I couldn’t even get onto [the registry], as they wouldn’t answer the phone,” said Dr. Ira D. Glick, professor emeritus of psychiatry and behavioral sciences and psychopharmacology at Stanford (Calif.) University, who has prescribed clozapine for decades. More recently, he said, the response time has improved.

The FDA has acknowledged providers’ complaints, and mainly characterizes the registry’s problems as growing pains. “As with any new IT system, and large data migration and reconciliation effort, there are challenges,” an agency spokesperson said in an interview about the REMS. “Merging six previous clozapine registries was a huge undertaking for the manufacturers that encompassed merging data from over 50,000 prescribers, 28,000 pharmacies, and 200,000 patient records.” 

The FDA has been working “to address the issues identified when the Clozapine REMS Program was initially implemented,” the representative said. “We believe that most of the issues have been resolved.” The FDA did not directly respond to questions about confidentiality breaches.

Providers said in interviews, however, that the issues continue, including mix-ups of confidential health information.

“I’m now registered as a provider designee for several clozapine prescribers here at my hospital,” said Megan Maroney, Pharm.D., of Monmouth Medical Center in Long Branch, N.J. “One of our prescribers also has a private practice, and those patients are popping up on my list, but they’re not my patients.” Dr. Maroney said she contacted the Clozapine REMS about the problem. “They haven’t yet come up with a good way to deal with it,” she said.

Courtesy Dr. Jean-Pierre Lindenmayer

Dr. Jean-Pierre Lindenmayer, clinical professor in the department of psychiatry at New York University, said he, too, receives information about patients who are not his. “I’m still getting faxed notifications on patients I have no idea who they are, saying they’re due for a blood test. It’s incredible that they keep doing this.” The REMS never responded to his complaints about privacy breaches, he said.

Problems ‘causing confusion’

Providers say the Clozapine REMS website remains filled with glitches and that deadlines are being extended until these can be resolved. “We’re trying to follow the intended rules with the understanding that if issues come up, we’re supposed to use our clinical judgment and not delay care to the patient. But it’s causing a lot of confusion among my staff, because whenever we try to use it, we encounter some kind of glitch,” Dr. Maroney said.

Another of the providers’ key concerns is the extra red-tape burdens imposed by the REMS, which, they say, have the potential to dampen the prescribing of clozapine – the exact opposite of its intended effect.

By mandating that only registered prescribers can write for clozapine, the REMS can cause problems for hospitals. “If a patient comes in for a medical reason and happens to be on clozapine, it’s impossible for us to get our internal medicine physicians registered just so they can prescribe it for their one patient who comes through,” Dr. Maroney said. Her workaround has been to make sure all the hospital’s psychiatrists are registered and that patients on clozapine have a psych consult, regardless of the reason they’re hospitalized. This, she acknowledged, could drive up costs.

“Here at my hospital, I tend to work out the issues for my prescribers so that they can start patients and continue them, and I think we’ve been doing a pretty good job. But I wonder about places without the manpower to do that or that don’t have a psych pharmacist who can work with them,” she said.

The REMS “is a major obstacle, and it’s more complicated now than it was before,” said Dr. Lindenmayer, who also is affiliated with the Manhattan Psychiatric Center in New York, an institution that manages about 100 patients on clozapine. “The excessive registry demands, and sending doctors letters about all the potential terrible side effects, will discourage providers. Clozapine is already difficult to prescribe: You have to have a pharmacy lined up, you have to have a lab lined up, you have to have a patient that gets the prescription and the blood test in a timely manner, and you are not being reimbursed at any higher rate by having a clozapine patient.”

Dr. Glick agreed. “Clozapine is one of our best drugs, but the most difficult to manage – as it takes a lot of time and effort. This is one more step making it more complicated.”

Dr. Maroney said that at her institution, she’s already seen a chilling effect from the REMS. Recently, she said, “my prescribers and I were going over all the changes and some of them said, ‘Just forget it, I’ll put [patients] on something else.’ And I said, ‘No – the whole point of a lot of the changes was to make [clozapine] more accessible.’ ”

Dr. Lindenmayer said he considers the REMS – or at least the extra layers of bureaucracy and certification it imposes – to have been a misguided move by the FDA. “I am not aware that there have been more deaths recently due to clozapine prescribing, and haven’t seen any upsurge of morbidity and mortality in the literature, which I follow closely.” Relatively few prescribers use clozapine, he said, and those who do “are fairly careful and knowledgeable about what they’re doing. So they’re preaching to the choir,” he said.

Yet Dr. Maroney said she remains optimistic that the REMS and the providers will be able to reach common ground – eventually: “The College of Psychiatric and Neurologic Pharmacists has been communicating with the FDA to hammer out these issues. I think it should get better. I just don’t know when that will occur and how many of these issues will be completely addressed.”

The FDA spokesperson confirmed that the agency was seeking provider input to improve the Clozapine REMS, and that several changes already had been made in response to provider concerns.

Well, UnitedHealthcare has announced that it’s pulling out of the health insurance exchanges because of huge losses. This may be the mortal wound. It is apparent that health care reform is undergoing a slow-motion implosion. Most of the Affordable Care Act has been delayed or canceled, including the individual and employer mandates, the independent payment advisory board (thank goodness), Medicare Advantage payment cuts, the Cadillac health insurance tax, and auto enrollment. Half the insurance co-ops have failed, and the remainder are running at a deficit. The exchange-plan premiums are increasing dramatically. In fact, with 71 cancellations and delays, health care reform has already effectively been repealed.

Insurance coverage has increased by about 8% (10 million more into Medicaid, 80% of all new insureds), particularly of the poor. On the flip side, millions have lost their old insurance, now have very high deductibles, and have lost their doctors. High-deductible insurance means that patients really aren’t going to be able to use their insurance, unless they have a catastrophic event and are hospitalized.

High-deductible insurance that pays at Medicaid rates, and Medicaid, are a particularly bad mix for dermatologists. Medicaid does not even cover the cost of overhead in the office setting, and many patients cannot afford their high deductibles. Almost all of the cost-efficient in-office curative procedures we offer cost less than the deductible. We are all seeing patients delay and delay treatment until the end of the year, hoping they won’t have to meet their deductible.

Many patients, excited that they finally have health insurance, are bitterly disappointed to find that they really don’t, except for their annual physical exam and the emergency room. The doctor is put in the poisonous position of explaining insurance policy limitations, and being collection agent. Poor Medicaid patients, who get free care at the hospital, go to the emergency room for minor complaints that would be much more efficiently handled in the office setting. This clogs emergency rooms, and is ferociously expensive. This is the opposite of what health care reform was supposed to do.

Insurance premiums are rising rapidly because somebody has to pay for coverage of the millions who could not formerly qualify for health insurance because of preexisting conditions. The current exchanges allow dropping in and out of insurance coverage and, with the elimination of preexisting conditions, this allows patients to game the system and wait until they fall ill to buy insurance. Historically, almost all were in the pool of insureds and the risk was predictable.

There is no way for politicians to go back and remove millions of chronically ill from the coverage rolls. Imagine the nightly news. As a physician, it is impossible not to feel compassion for these chronically ill patients, but it would have cost a lot less to just make them eligible for Medicaid to begin with.

OK, it is easy to complain, but what are possible solutions? Patients need health care savings accounts for a sizable portion of their deductibles. Physician rosters need to be real time and accurate. Networks need to be adequate (another column, another day). Medicaid rates need to increase to Medicare levels, as they did for the initial 2-year teaser period for primary care physicians. Exchange plan payment rates need to match their commercial insurance wrappers, instead of Medicaid rates, so physicians can afford to accept them. Stricter enrollment periods are needed, so patients cannot game the system, signing up only when they get sick or want a joint replaced. If you are going to provide health insurance for all, then make sure the health insurance is real, not hollow.

Dr. Coldiron is a past president of the American Academy of Dermatology. He is currently in private practice, but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. Write to him at [email protected].

Well, UnitedHealthcare has announced that it’s pulling out of the health insurance exchanges because of huge losses. This may be the mortal wound. It is apparent that health care reform is undergoing a slow-motion implosion. Most of the Affordable Care Act has been delayed or canceled, including the individual and employer mandates, the independent payment advisory board (thank goodness), Medicare Advantage payment cuts, the Cadillac health insurance tax, and auto enrollment. Half the insurance co-ops have failed, and the remainder are running at a deficit. The exchange-plan premiums are increasing dramatically. In fact, with 71 cancellations and delays, health care reform has already effectively been repealed.

Insurance coverage has increased by about 8% (10 million more into Medicaid, 80% of all new insureds), particularly of the poor. On the flip side, millions have lost their old insurance, now have very high deductibles, and have lost their doctors. High-deductible insurance means that patients really aren’t going to be able to use their insurance, unless they have a catastrophic event and are hospitalized.

High-deductible insurance that pays at Medicaid rates, and Medicaid, are a particularly bad mix for dermatologists. Medicaid does not even cover the cost of overhead in the office setting, and many patients cannot afford their high deductibles. Almost all of the cost-efficient in-office curative procedures we offer cost less than the deductible. We are all seeing patients delay and delay treatment until the end of the year, hoping they won’t have to meet their deductible.

Many patients, excited that they finally have health insurance, are bitterly disappointed to find that they really don’t, except for their annual physical exam and the emergency room. The doctor is put in the poisonous position of explaining insurance policy limitations, and being collection agent. Poor Medicaid patients, who get free care at the hospital, go to the emergency room for minor complaints that would be much more efficiently handled in the office setting. This clogs emergency rooms, and is ferociously expensive. This is the opposite of what health care reform was supposed to do.

Insurance premiums are rising rapidly because somebody has to pay for coverage of the millions who could not formerly qualify for health insurance because of preexisting conditions. The current exchanges allow dropping in and out of insurance coverage and, with the elimination of preexisting conditions, this allows patients to game the system and wait until they fall ill to buy insurance. Historically, almost all were in the pool of insureds and the risk was predictable.

There is no way for politicians to go back and remove millions of chronically ill from the coverage rolls. Imagine the nightly news. As a physician, it is impossible not to feel compassion for these chronically ill patients, but it would have cost a lot less to just make them eligible for Medicaid to begin with.

OK, it is easy to complain, but what are possible solutions? Patients need health care savings accounts for a sizable portion of their deductibles. Physician rosters need to be real time and accurate. Networks need to be adequate (another column, another day). Medicaid rates need to increase to Medicare levels, as they did for the initial 2-year teaser period for primary care physicians. Exchange plan payment rates need to match their commercial insurance wrappers, instead of Medicaid rates, so physicians can afford to accept them. Stricter enrollment periods are needed, so patients cannot game the system, signing up only when they get sick or want a joint replaced. If you are going to provide health insurance for all, then make sure the health insurance is real, not hollow.

Dr. Coldiron is a past president of the American Academy of Dermatology. He is currently in private practice, but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. Write to him at [email protected].

Well, UnitedHealthcare has announced that it’s pulling out of the health insurance exchanges because of huge losses. This may be the mortal wound. It is apparent that health care reform is undergoing a slow-motion implosion. Most of the Affordable Care Act has been delayed or canceled, including the individual and employer mandates, the independent payment advisory board (thank goodness), Medicare Advantage payment cuts, the Cadillac health insurance tax, and auto enrollment. Half the insurance co-ops have failed, and the remainder are running at a deficit. The exchange-plan premiums are increasing dramatically. In fact, with 71 cancellations and delays, health care reform has already effectively been repealed.

Insurance coverage has increased by about 8% (10 million more into Medicaid, 80% of all new insureds), particularly of the poor. On the flip side, millions have lost their old insurance, now have very high deductibles, and have lost their doctors. High-deductible insurance means that patients really aren’t going to be able to use their insurance, unless they have a catastrophic event and are hospitalized.

High-deductible insurance that pays at Medicaid rates, and Medicaid, are a particularly bad mix for dermatologists. Medicaid does not even cover the cost of overhead in the office setting, and many patients cannot afford their high deductibles. Almost all of the cost-efficient in-office curative procedures we offer cost less than the deductible. We are all seeing patients delay and delay treatment until the end of the year, hoping they won’t have to meet their deductible.

Many patients, excited that they finally have health insurance, are bitterly disappointed to find that they really don’t, except for their annual physical exam and the emergency room. The doctor is put in the poisonous position of explaining insurance policy limitations, and being collection agent. Poor Medicaid patients, who get free care at the hospital, go to the emergency room for minor complaints that would be much more efficiently handled in the office setting. This clogs emergency rooms, and is ferociously expensive. This is the opposite of what health care reform was supposed to do.

Insurance premiums are rising rapidly because somebody has to pay for coverage of the millions who could not formerly qualify for health insurance because of preexisting conditions. The current exchanges allow dropping in and out of insurance coverage and, with the elimination of preexisting conditions, this allows patients to game the system and wait until they fall ill to buy insurance. Historically, almost all were in the pool of insureds and the risk was predictable.

There is no way for politicians to go back and remove millions of chronically ill from the coverage rolls. Imagine the nightly news. As a physician, it is impossible not to feel compassion for these chronically ill patients, but it would have cost a lot less to just make them eligible for Medicaid to begin with.

OK, it is easy to complain, but what are possible solutions? Patients need health care savings accounts for a sizable portion of their deductibles. Physician rosters need to be real time and accurate. Networks need to be adequate (another column, another day). Medicaid rates need to increase to Medicare levels, as they did for the initial 2-year teaser period for primary care physicians. Exchange plan payment rates need to match their commercial insurance wrappers, instead of Medicaid rates, so physicians can afford to accept them. Stricter enrollment periods are needed, so patients cannot game the system, signing up only when they get sick or want a joint replaced. If you are going to provide health insurance for all, then make sure the health insurance is real, not hollow.

Dr. Coldiron is a past president of the American Academy of Dermatology. He is currently in private practice, but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. Write to him at [email protected].

Dr. Gloria E. Sarto was one of just six women in her medical school graduating class of 76 in 1958 – a time when many medical schools, she recalled, had quota systems for women and minorities. Later, she became the first female ob.gyn. resident at the University of Wisconsin–Madison.

“When I was interviewing for a residency position, the department chair told me ‘I’m going to treat you like one of the boys,’” the 86-year-old professor emeritus said. “And I said, ‘If you do that, it will be just fine.’”

Courtesy of the University of Wisconsin, Madison

Yet she still had to lobby sometimes for equal treatment – convincing the department chief in one instance that sleeping on a delivery table during hospital duty because there weren’t any rooms for women was not being treated “like one of the boys.” And she was often bothered by her observation that, in general, “the women [residents] weren’t noticed... they weren’t being recognized.”

Dr. Sarto has since chaired two ob.gyn. departments and was the first woman president of the American Gynecological and Obstetrical Society. Today, however, as she continues mentoring junior faculty and works to ensure the smooth succession of programs she founded, she sees a much different field – one in which women not only command more respect but where they make up a majority of ob.gyns.

Impact on women’s health

In 2014, 62% of all ob.gyns. were women (Obstet Gynecol. 2016 Jan;127[1]:148-52). The majority has been years in the making; more women than men have been entering the specialty since 1993. And if current trends continue, the percentage of women active in the specialty will only increase further. In 2010, women comprised more than 80% of all ob.gyn. residents/fellows, more than any other specialty, according to data from the Association of American Medical Colleges.

Such numerical strength is significant, but for Dr. Sarto and other leaders in the specialty who spoke about their experiences as female ob.gyns., it’s the impact that women physicians have had on women’s health that’s most important.

Dr. Sarto helped to start Lamaze classes in a hospital basement amidst widespread opposition from the male-dominated leadership and staff who felt that women didn’t need such help with labor. She also takes pride in her collaboration with Dr. Florence Haseltine, Phyllis Greenberger, and several other women to address biases in biomedical research. Their work with Congress led to a federal audit of National Institutes of Health policies and practices.

“We knew that when that report came out [in 1990], it would hit every newspaper in the country,” Dr. Sarto said. It just about did, and soon after that, the NIH Office of Research on Women’s Health was established to ensure that women were included in clinical trials and that gaps in knowledge of women’s health were addressed.

Dr. Barbara Levy, who left a private practice and two medical directorships in 2012 to become Vice President for Health Policy at the American College of Obstetricians and Gynecologists, recalls feeling early in her career that women’s health needed to be approached much more holistically.

“What I was seeing and experiencing didn’t match the textbooks,” she said. “The connection, for instance, between chronic pelvic pain and women who’d been victims of sexual abuse – there wasn’t anything in the literature. I’d see women with the same kinds of physical characteristics on their exams... and patients were willing to share with me things that they wouldn’t have been willing to share with my colleagues.”

Dr. Levy graduated from Princeton University in 1974 with the second class of admitted women, and after a year off, went west for medical school. She graduated in 1979 from the University of California, San Diego, with nine other women in a class of 110.

Her desire to care for the “whole patient” had her leaning toward family medicine until a beloved mentor, Dr. Donna Brooks, “reminded me that there were so few women to take care of women... and that as an ob.gyn. I could follow women through pregnancy, delivery, surgeries, hormone issues, and so many [other facets of their health].”

Dr. Levy, who served as president of the American Association of Gynecologic Laparoscopists in 1995, recalls a world “that was very tolerant of sexual harassment” and remembers the energy she needed to expend to be taken seriously and to correct unconscious bias.

When she applied for fellowship in the American College of Surgeons in the late 1980s, the committee members who conducted an interview “told me right away that I couldn’t expect to be a fellow if I hadn’t done my duty [serving on hospital committees],” Dr. Levy said.

“I told them I had volunteered for more than three committees every single year I’d been on staff, and had never been asked to serve,” she said. “They had no idea. Their assumption was that I had children at home and I wasn’t taking the time.”

Entering leadership

When it comes to leadership, a look at academic medicine suggests that women ob.gyns. have made significant strides. In 2013, compared with other major specialties, obstetrics and gynecology had the highest proportion of department leaders who were women. Yet the picture is mixed. According to an analysis published earlier in 2016, women in ob.gyn. and nine other major specialties “were not represented in the proportions in which they entered their fields” (Obstet Gynecol. 2016 Mar;127[3]:442-7).

Women comprised 57% of all faculty in departments of ob.gyn. in 2013. And, according to the analysis, they comprised 62% of ob.gyn. residency program directors, 30% of division directors, and 24% of department chairs.

The high numbers of women serving as residency program directors raises concern because such positions “do not result in advancement in the same way,” said Dr. Levy, adding that women have excelled in such positions and may desire them, but should be mentored early on about what tracks have the potential for upper-level leadership roles.

Courtesy Women & Infants Hospital

Dr. Maureen Phipps, who in 2013 was appointed as chair of ob.gyn. and assistant dean in the Warren Albert Medical School of Brown University in Providence, said she carries with her the fact that women are not yet proportionally represented at the upper levels. “I know that my being in this position and in other positions I’ve held is important for women to see,” she said.

Dr. Phipps graduated from the University of Vermont’s College of Medicine in 1994 as a part of a class in which men and women were fairly evenly represented. In addition to her role as department chair and assistant dean, she is also now chief of ob.gyn. at Women & Infants Hospital of Rhode Island, where she did her residency, and executive chief of ob.gyn for the Care New England Health System.

“I’ve had amazing male leaders and mentors in my career – the people who’ve gone to bat for me have been men,” said Dr. Phipps. Yet, “it’s important to have women in leadership... It’s known that we think differently and approach things differently. Having balance and a variety of different lenses will allow us to [further] grow the field.”

Gender pay gap

Both in academic medicine and in practice, a gender pay gap still reportedly affects women physicians across the board. Various reports and analyses have shown women earning disproportionately less than their male colleagues in similar positions.

Notably, a 2011 analysis in Health Affairs found a nearly $17,000 gap between the starting salaries for men and women physicians. This differential accounted for variables such as patient care hours, practice type, and location. It is possible, the study authors reported, that practices “may now be offering greater flexibility and family-friendly attributes that are more appealing but that come at the price of commensurately lower pay” (Health Aff. 2011:30;193-201).

The American Medical Women’s Association, which promotes advocacy on a gender pay gap, said in a statement about the study, however, that “gender discrimination still exists within the echelons of medicine, and gender stereotyping frequently leads to the devaluation of women physicians.”

From her perspective, Dr. Levy said it’s “complicated” to tease apart and understand all the factors that may be involved.

The challenges of balancing work and family/caregiving and are “still really tough” for women ob.gyns., she said, especially those who want to practice obstetrics. Dr. Levy said she gave up obstetrics when it became apparent that she and her husband would need to hire an additional child care provider.

While the hospitalist-laborist model has been a valuable addition to obstetrics, Dr. Phipps said, “it’s our challenge to continue to think creatively about how we can keep clinicians engaged when they’re in the earlier parts of their careers and challenged by family responsibilities and other commitments.”

Both she and Dr. Levy emphasized their concerns about burnout and their desire to keep career satisfaction high – especially now that women are such a big part of ob.gyn. – and both spoke of the importance of making time for whatever activities help women “recharge.”

“We should be doing what we’re doing because we love it,” Dr. Levy said. “We should focus on that every day. Our patients trust us. We need to remind ourselves of what incredible connections we have.”

Throughout 2016, Ob.Gyn. News will celebrate its 50th anniversary with exclusive articles looking at the evolution of the specialty, including the history of contraception, changes in gynecologic surgery, and the transformation of the well-woman visit. Look for these articles and more special features in the pages of Ob.Gyn. News and online at obgynnews.com.

Dr. Gloria E. Sarto was one of just six women in her medical school graduating class of 76 in 1958 – a time when many medical schools, she recalled, had quota systems for women and minorities. Later, she became the first female ob.gyn. resident at the University of Wisconsin–Madison.

“When I was interviewing for a residency position, the department chair told me ‘I’m going to treat you like one of the boys,’” the 86-year-old professor emeritus said. “And I said, ‘If you do that, it will be just fine.’”

Courtesy of the University of Wisconsin, Madison

Yet she still had to lobby sometimes for equal treatment – convincing the department chief in one instance that sleeping on a delivery table during hospital duty because there weren’t any rooms for women was not being treated “like one of the boys.” And she was often bothered by her observation that, in general, “the women [residents] weren’t noticed... they weren’t being recognized.”

Dr. Sarto has since chaired two ob.gyn. departments and was the first woman president of the American Gynecological and Obstetrical Society. Today, however, as she continues mentoring junior faculty and works to ensure the smooth succession of programs she founded, she sees a much different field – one in which women not only command more respect but where they make up a majority of ob.gyns.

Impact on women’s health

In 2014, 62% of all ob.gyns. were women (Obstet Gynecol. 2016 Jan;127[1]:148-52). The majority has been years in the making; more women than men have been entering the specialty since 1993. And if current trends continue, the percentage of women active in the specialty will only increase further. In 2010, women comprised more than 80% of all ob.gyn. residents/fellows, more than any other specialty, according to data from the Association of American Medical Colleges.

Such numerical strength is significant, but for Dr. Sarto and other leaders in the specialty who spoke about their experiences as female ob.gyns., it’s the impact that women physicians have had on women’s health that’s most important.

Dr. Sarto helped to start Lamaze classes in a hospital basement amidst widespread opposition from the male-dominated leadership and staff who felt that women didn’t need such help with labor. She also takes pride in her collaboration with Dr. Florence Haseltine, Phyllis Greenberger, and several other women to address biases in biomedical research. Their work with Congress led to a federal audit of National Institutes of Health policies and practices.

“We knew that when that report came out [in 1990], it would hit every newspaper in the country,” Dr. Sarto said. It just about did, and soon after that, the NIH Office of Research on Women’s Health was established to ensure that women were included in clinical trials and that gaps in knowledge of women’s health were addressed.

Dr. Barbara Levy, who left a private practice and two medical directorships in 2012 to become Vice President for Health Policy at the American College of Obstetricians and Gynecologists, recalls feeling early in her career that women’s health needed to be approached much more holistically.

“What I was seeing and experiencing didn’t match the textbooks,” she said. “The connection, for instance, between chronic pelvic pain and women who’d been victims of sexual abuse – there wasn’t anything in the literature. I’d see women with the same kinds of physical characteristics on their exams... and patients were willing to share with me things that they wouldn’t have been willing to share with my colleagues.”

Dr. Levy graduated from Princeton University in 1974 with the second class of admitted women, and after a year off, went west for medical school. She graduated in 1979 from the University of California, San Diego, with nine other women in a class of 110.

Her desire to care for the “whole patient” had her leaning toward family medicine until a beloved mentor, Dr. Donna Brooks, “reminded me that there were so few women to take care of women... and that as an ob.gyn. I could follow women through pregnancy, delivery, surgeries, hormone issues, and so many [other facets of their health].”

Dr. Levy, who served as president of the American Association of Gynecologic Laparoscopists in 1995, recalls a world “that was very tolerant of sexual harassment” and remembers the energy she needed to expend to be taken seriously and to correct unconscious bias.

When she applied for fellowship in the American College of Surgeons in the late 1980s, the committee members who conducted an interview “told me right away that I couldn’t expect to be a fellow if I hadn’t done my duty [serving on hospital committees],” Dr. Levy said.

“I told them I had volunteered for more than three committees every single year I’d been on staff, and had never been asked to serve,” she said. “They had no idea. Their assumption was that I had children at home and I wasn’t taking the time.”

Entering leadership

When it comes to leadership, a look at academic medicine suggests that women ob.gyns. have made significant strides. In 2013, compared with other major specialties, obstetrics and gynecology had the highest proportion of department leaders who were women. Yet the picture is mixed. According to an analysis published earlier in 2016, women in ob.gyn. and nine other major specialties “were not represented in the proportions in which they entered their fields” (Obstet Gynecol. 2016 Mar;127[3]:442-7).

Women comprised 57% of all faculty in departments of ob.gyn. in 2013. And, according to the analysis, they comprised 62% of ob.gyn. residency program directors, 30% of division directors, and 24% of department chairs.

The high numbers of women serving as residency program directors raises concern because such positions “do not result in advancement in the same way,” said Dr. Levy, adding that women have excelled in such positions and may desire them, but should be mentored early on about what tracks have the potential for upper-level leadership roles.

Courtesy Women & Infants Hospital

Dr. Maureen Phipps, who in 2013 was appointed as chair of ob.gyn. and assistant dean in the Warren Albert Medical School of Brown University in Providence, said she carries with her the fact that women are not yet proportionally represented at the upper levels. “I know that my being in this position and in other positions I’ve held is important for women to see,” she said.

Dr. Phipps graduated from the University of Vermont’s College of Medicine in 1994 as a part of a class in which men and women were fairly evenly represented. In addition to her role as department chair and assistant dean, she is also now chief of ob.gyn. at Women & Infants Hospital of Rhode Island, where she did her residency, and executive chief of ob.gyn for the Care New England Health System.

“I’ve had amazing male leaders and mentors in my career – the people who’ve gone to bat for me have been men,” said Dr. Phipps. Yet, “it’s important to have women in leadership... It’s known that we think differently and approach things differently. Having balance and a variety of different lenses will allow us to [further] grow the field.”

Gender pay gap

Both in academic medicine and in practice, a gender pay gap still reportedly affects women physicians across the board. Various reports and analyses have shown women earning disproportionately less than their male colleagues in similar positions.

Notably, a 2011 analysis in Health Affairs found a nearly $17,000 gap between the starting salaries for men and women physicians. This differential accounted for variables such as patient care hours, practice type, and location. It is possible, the study authors reported, that practices “may now be offering greater flexibility and family-friendly attributes that are more appealing but that come at the price of commensurately lower pay” (Health Aff. 2011:30;193-201).

The American Medical Women’s Association, which promotes advocacy on a gender pay gap, said in a statement about the study, however, that “gender discrimination still exists within the echelons of medicine, and gender stereotyping frequently leads to the devaluation of women physicians.”

From her perspective, Dr. Levy said it’s “complicated” to tease apart and understand all the factors that may be involved.

The challenges of balancing work and family/caregiving and are “still really tough” for women ob.gyns., she said, especially those who want to practice obstetrics. Dr. Levy said she gave up obstetrics when it became apparent that she and her husband would need to hire an additional child care provider.

While the hospitalist-laborist model has been a valuable addition to obstetrics, Dr. Phipps said, “it’s our challenge to continue to think creatively about how we can keep clinicians engaged when they’re in the earlier parts of their careers and challenged by family responsibilities and other commitments.”

Both she and Dr. Levy emphasized their concerns about burnout and their desire to keep career satisfaction high – especially now that women are such a big part of ob.gyn. – and both spoke of the importance of making time for whatever activities help women “recharge.”

“We should be doing what we’re doing because we love it,” Dr. Levy said. “We should focus on that every day. Our patients trust us. We need to remind ourselves of what incredible connections we have.”

Throughout 2016, Ob.Gyn. News will celebrate its 50th anniversary with exclusive articles looking at the evolution of the specialty, including the history of contraception, changes in gynecologic surgery, and the transformation of the well-woman visit. Look for these articles and more special features in the pages of Ob.Gyn. News and online at obgynnews.com.

Dr. Gloria E. Sarto was one of just six women in her medical school graduating class of 76 in 1958 – a time when many medical schools, she recalled, had quota systems for women and minorities. Later, she became the first female ob.gyn. resident at the University of Wisconsin–Madison.

“When I was interviewing for a residency position, the department chair told me ‘I’m going to treat you like one of the boys,’” the 86-year-old professor emeritus said. “And I said, ‘If you do that, it will be just fine.’”

Courtesy of the University of Wisconsin, Madison

Yet she still had to lobby sometimes for equal treatment – convincing the department chief in one instance that sleeping on a delivery table during hospital duty because there weren’t any rooms for women was not being treated “like one of the boys.” And she was often bothered by her observation that, in general, “the women [residents] weren’t noticed... they weren’t being recognized.”

Dr. Sarto has since chaired two ob.gyn. departments and was the first woman president of the American Gynecological and Obstetrical Society. Today, however, as she continues mentoring junior faculty and works to ensure the smooth succession of programs she founded, she sees a much different field – one in which women not only command more respect but where they make up a majority of ob.gyns.

Impact on women’s health

In 2014, 62% of all ob.gyns. were women (Obstet Gynecol. 2016 Jan;127[1]:148-52). The majority has been years in the making; more women than men have been entering the specialty since 1993. And if current trends continue, the percentage of women active in the specialty will only increase further. In 2010, women comprised more than 80% of all ob.gyn. residents/fellows, more than any other specialty, according to data from the Association of American Medical Colleges.

Such numerical strength is significant, but for Dr. Sarto and other leaders in the specialty who spoke about their experiences as female ob.gyns., it’s the impact that women physicians have had on women’s health that’s most important.

Dr. Sarto helped to start Lamaze classes in a hospital basement amidst widespread opposition from the male-dominated leadership and staff who felt that women didn’t need such help with labor. She also takes pride in her collaboration with Dr. Florence Haseltine, Phyllis Greenberger, and several other women to address biases in biomedical research. Their work with Congress led to a federal audit of National Institutes of Health policies and practices.

“We knew that when that report came out [in 1990], it would hit every newspaper in the country,” Dr. Sarto said. It just about did, and soon after that, the NIH Office of Research on Women’s Health was established to ensure that women were included in clinical trials and that gaps in knowledge of women’s health were addressed.

Dr. Barbara Levy, who left a private practice and two medical directorships in 2012 to become Vice President for Health Policy at the American College of Obstetricians and Gynecologists, recalls feeling early in her career that women’s health needed to be approached much more holistically.

“What I was seeing and experiencing didn’t match the textbooks,” she said. “The connection, for instance, between chronic pelvic pain and women who’d been victims of sexual abuse – there wasn’t anything in the literature. I’d see women with the same kinds of physical characteristics on their exams... and patients were willing to share with me things that they wouldn’t have been willing to share with my colleagues.”

Dr. Levy graduated from Princeton University in 1974 with the second class of admitted women, and after a year off, went west for medical school. She graduated in 1979 from the University of California, San Diego, with nine other women in a class of 110.

Her desire to care for the “whole patient” had her leaning toward family medicine until a beloved mentor, Dr. Donna Brooks, “reminded me that there were so few women to take care of women... and that as an ob.gyn. I could follow women through pregnancy, delivery, surgeries, hormone issues, and so many [other facets of their health].”

Dr. Levy, who served as president of the American Association of Gynecologic Laparoscopists in 1995, recalls a world “that was very tolerant of sexual harassment” and remembers the energy she needed to expend to be taken seriously and to correct unconscious bias.

When she applied for fellowship in the American College of Surgeons in the late 1980s, the committee members who conducted an interview “told me right away that I couldn’t expect to be a fellow if I hadn’t done my duty [serving on hospital committees],” Dr. Levy said.

“I told them I had volunteered for more than three committees every single year I’d been on staff, and had never been asked to serve,” she said. “They had no idea. Their assumption was that I had children at home and I wasn’t taking the time.”

Entering leadership

When it comes to leadership, a look at academic medicine suggests that women ob.gyns. have made significant strides. In 2013, compared with other major specialties, obstetrics and gynecology had the highest proportion of department leaders who were women. Yet the picture is mixed. According to an analysis published earlier in 2016, women in ob.gyn. and nine other major specialties “were not represented in the proportions in which they entered their fields” (Obstet Gynecol. 2016 Mar;127[3]:442-7).

Women comprised 57% of all faculty in departments of ob.gyn. in 2013. And, according to the analysis, they comprised 62% of ob.gyn. residency program directors, 30% of division directors, and 24% of department chairs.

The high numbers of women serving as residency program directors raises concern because such positions “do not result in advancement in the same way,” said Dr. Levy, adding that women have excelled in such positions and may desire them, but should be mentored early on about what tracks have the potential for upper-level leadership roles.

Courtesy Women & Infants Hospital

Dr. Maureen Phipps, who in 2013 was appointed as chair of ob.gyn. and assistant dean in the Warren Albert Medical School of Brown University in Providence, said she carries with her the fact that women are not yet proportionally represented at the upper levels. “I know that my being in this position and in other positions I’ve held is important for women to see,” she said.

Dr. Phipps graduated from the University of Vermont’s College of Medicine in 1994 as a part of a class in which men and women were fairly evenly represented. In addition to her role as department chair and assistant dean, she is also now chief of ob.gyn. at Women & Infants Hospital of Rhode Island, where she did her residency, and executive chief of ob.gyn for the Care New England Health System.

“I’ve had amazing male leaders and mentors in my career – the people who’ve gone to bat for me have been men,” said Dr. Phipps. Yet, “it’s important to have women in leadership... It’s known that we think differently and approach things differently. Having balance and a variety of different lenses will allow us to [further] grow the field.”

Gender pay gap

Both in academic medicine and in practice, a gender pay gap still reportedly affects women physicians across the board. Various reports and analyses have shown women earning disproportionately less than their male colleagues in similar positions.

Notably, a 2011 analysis in Health Affairs found a nearly $17,000 gap between the starting salaries for men and women physicians. This differential accounted for variables such as patient care hours, practice type, and location. It is possible, the study authors reported, that practices “may now be offering greater flexibility and family-friendly attributes that are more appealing but that come at the price of commensurately lower pay” (Health Aff. 2011:30;193-201).

The American Medical Women’s Association, which promotes advocacy on a gender pay gap, said in a statement about the study, however, that “gender discrimination still exists within the echelons of medicine, and gender stereotyping frequently leads to the devaluation of women physicians.”

From her perspective, Dr. Levy said it’s “complicated” to tease apart and understand all the factors that may be involved.

The challenges of balancing work and family/caregiving and are “still really tough” for women ob.gyns., she said, especially those who want to practice obstetrics. Dr. Levy said she gave up obstetrics when it became apparent that she and her husband would need to hire an additional child care provider.

While the hospitalist-laborist model has been a valuable addition to obstetrics, Dr. Phipps said, “it’s our challenge to continue to think creatively about how we can keep clinicians engaged when they’re in the earlier parts of their careers and challenged by family responsibilities and other commitments.”

Both she and Dr. Levy emphasized their concerns about burnout and their desire to keep career satisfaction high – especially now that women are such a big part of ob.gyn. – and both spoke of the importance of making time for whatever activities help women “recharge.”

“We should be doing what we’re doing because we love it,” Dr. Levy said. “We should focus on that every day. Our patients trust us. We need to remind ourselves of what incredible connections we have.”

Throughout 2016, Ob.Gyn. News will celebrate its 50th anniversary with exclusive articles looking at the evolution of the specialty, including the history of contraception, changes in gynecologic surgery, and the transformation of the well-woman visit. Look for these articles and more special features in the pages of Ob.Gyn. News and online at obgynnews.com.

NEW YORK (Reuters Health) - Implanted cardioverter-defibrillators (ICDs) carry a high risk of long-term complications, especially for younger patients, women, and blacks, researchers report.

Early implantation-related risks such as device malfunction are well known, but longer-term risks -- especially beyond the first year after implantation -- are poorly defined, Dr. Isuru Ranasinghe of Queen Elizabeth Hospital in South Australia and colleagues observed in an article online May 2 in Annals of

Internal Medicine.

"Knowing the long-term risks is important for patients to make an informed choice, because (implantation) is a lifelong treatment," Dr. Ranasinghe told Reuters Health by email.  "Moreover, more than two-thirds of patients who receive an ICD for prevention of future events never require treatment from the ICD, although they continue to be at risk for device-related harms."

To investigate, the researchers analyzed data from the American College of Cardiology Foundation's National Cardiovascular Data Registry ICD Registry and Medicare claims to assess the long-term nonfatal risks for ICD-related complications among 114,484 patients at 1,437 U.S. centers with first-time implantations.

Implanted devices included single-chamber ICDs (19.8% of patients); dual-chamber ICDs (41.3%), and cardiac resynchronization therapy with a defibrillator (CRT-D; 38.9%).

During a median follow-up of 2.7 years, 40,072 patients died, representing 12.6 deaths per 100 patient years of followup. After accounting for the deaths, "there were 6.1 ICD-related complications per 100 patient years where the patient required an acute hospitalization or a reoperation," Dr. Ranasinghe said.

"In addition, there were 3.9 device reoperations per 100 patient years for reasons other than complications. Typically performed to replace the ICD battery, these reoperations are somewhat expected with time. Nevertheless, these surgical procedures are important for patients, as they carry a risk of patient harm," he observed.

Those more likely to experience long-term complications were women (16% higher risk), blacks (14% higher risk), and patients ages 65-69 at implantation (55% higher risk compared with those 85 and older) -- findings that require further investigation, according to Dr. Ranasinghe.

"Patients were 38% more likely to experience a complication if they had the more complex CRT-D compared with a simpler (single-chamber) device. A patient with a CRT-D device was also four times more likely to require a reoperation for reasons other than complications compared with a single-chamber ICD during the study period," he said.

Dr Ranasinghe added, "The rate of complications is substantial and higher than previously reported. The continued occurrence of complications long after the initial implantation indicates the need for vigilance and ongoing surveillance of ICD-related complications."

"There is considerable debate as to the added benefit of more complex devices compared with simpler single-chamber ICDs. Where possible, using a simpler device may reduce the risk of ICD-related harm," he said.

Dr. Paul J. Hauptman of Saint Louis University School of Medicine in Missouri, told Reuters Health by email, "The study adds to a rich literature that highlights the need for clinicians and patients to carefully consider the potential risks and benefits of implantable defibrillators and CRT devices."

"Although (this was) not a primary focus of the paper, I was struck by the 35% mortality at a median of 2.7 years (in addition to a significant ICD-related complication rate)," said Dr. Hauptman, who has done work in this area. "By linking registry and Medicare data, the authors succeed in providing meaningful insight into what happens to real patients in the real world. We would be abrogating our role as physicians if we ignore analyses like this one."

The study was funded by the American College of Cardiology Foundation's National Cardiovascular Data Registry and other organizations. Five coauthors reported disclosures.

NEW YORK (Reuters Health) - Implanted cardioverter-defibrillators (ICDs) carry a high risk of long-term complications, especially for younger patients, women, and blacks, researchers report.

Early implantation-related risks such as device malfunction are well known, but longer-term risks -- especially beyond the first year after implantation -- are poorly defined, Dr. Isuru Ranasinghe of Queen Elizabeth Hospital in South Australia and colleagues observed in an article online May 2 in Annals of

Internal Medicine.

"Knowing the long-term risks is important for patients to make an informed choice, because (implantation) is a lifelong treatment," Dr. Ranasinghe told Reuters Health by email.  "Moreover, more than two-thirds of patients who receive an ICD for prevention of future events never require treatment from the ICD, although they continue to be at risk for device-related harms."

To investigate, the researchers analyzed data from the American College of Cardiology Foundation's National Cardiovascular Data Registry ICD Registry and Medicare claims to assess the long-term nonfatal risks for ICD-related complications among 114,484 patients at 1,437 U.S. centers with first-time implantations.

Implanted devices included single-chamber ICDs (19.8% of patients); dual-chamber ICDs (41.3%), and cardiac resynchronization therapy with a defibrillator (CRT-D; 38.9%).

During a median follow-up of 2.7 years, 40,072 patients died, representing 12.6 deaths per 100 patient years of followup. After accounting for the deaths, "there were 6.1 ICD-related complications per 100 patient years where the patient required an acute hospitalization or a reoperation," Dr. Ranasinghe said.

"In addition, there were 3.9 device reoperations per 100 patient years for reasons other than complications. Typically performed to replace the ICD battery, these reoperations are somewhat expected with time. Nevertheless, these surgical procedures are important for patients, as they carry a risk of patient harm," he observed.

Those more likely to experience long-term complications were women (16% higher risk), blacks (14% higher risk), and patients ages 65-69 at implantation (55% higher risk compared with those 85 and older) -- findings that require further investigation, according to Dr. Ranasinghe.

"Patients were 38% more likely to experience a complication if they had the more complex CRT-D compared with a simpler (single-chamber) device. A patient with a CRT-D device was also four times more likely to require a reoperation for reasons other than complications compared with a single-chamber ICD during the study period," he said.

Dr Ranasinghe added, "The rate of complications is substantial and higher than previously reported. The continued occurrence of complications long after the initial implantation indicates the need for vigilance and ongoing surveillance of ICD-related complications."

"There is considerable debate as to the added benefit of more complex devices compared with simpler single-chamber ICDs. Where possible, using a simpler device may reduce the risk of ICD-related harm," he said.

Dr. Paul J. Hauptman of Saint Louis University School of Medicine in Missouri, told Reuters Health by email, "The study adds to a rich literature that highlights the need for clinicians and patients to carefully consider the potential risks and benefits of implantable defibrillators and CRT devices."

"Although (this was) not a primary focus of the paper, I was struck by the 35% mortality at a median of 2.7 years (in addition to a significant ICD-related complication rate)," said Dr. Hauptman, who has done work in this area. "By linking registry and Medicare data, the authors succeed in providing meaningful insight into what happens to real patients in the real world. We would be abrogating our role as physicians if we ignore analyses like this one."

The study was funded by the American College of Cardiology Foundation's National Cardiovascular Data Registry and other organizations. Five coauthors reported disclosures.

NEW YORK (Reuters Health) - Implanted cardioverter-defibrillators (ICDs) carry a high risk of long-term complications, especially for younger patients, women, and blacks, researchers report.

Early implantation-related risks such as device malfunction are well known, but longer-term risks -- especially beyond the first year after implantation -- are poorly defined, Dr. Isuru Ranasinghe of Queen Elizabeth Hospital in South Australia and colleagues observed in an article online May 2 in Annals of

Internal Medicine.

"Knowing the long-term risks is important for patients to make an informed choice, because (implantation) is a lifelong treatment," Dr. Ranasinghe told Reuters Health by email.  "Moreover, more than two-thirds of patients who receive an ICD for prevention of future events never require treatment from the ICD, although they continue to be at risk for device-related harms."

To investigate, the researchers analyzed data from the American College of Cardiology Foundation's National Cardiovascular Data Registry ICD Registry and Medicare claims to assess the long-term nonfatal risks for ICD-related complications among 114,484 patients at 1,437 U.S. centers with first-time implantations.

Implanted devices included single-chamber ICDs (19.8% of patients); dual-chamber ICDs (41.3%), and cardiac resynchronization therapy with a defibrillator (CRT-D; 38.9%).

During a median follow-up of 2.7 years, 40,072 patients died, representing 12.6 deaths per 100 patient years of followup. After accounting for the deaths, "there were 6.1 ICD-related complications per 100 patient years where the patient required an acute hospitalization or a reoperation," Dr. Ranasinghe said.

"In addition, there were 3.9 device reoperations per 100 patient years for reasons other than complications. Typically performed to replace the ICD battery, these reoperations are somewhat expected with time. Nevertheless, these surgical procedures are important for patients, as they carry a risk of patient harm," he observed.

Those more likely to experience long-term complications were women (16% higher risk), blacks (14% higher risk), and patients ages 65-69 at implantation (55% higher risk compared with those 85 and older) -- findings that require further investigation, according to Dr. Ranasinghe.

"Patients were 38% more likely to experience a complication if they had the more complex CRT-D compared with a simpler (single-chamber) device. A patient with a CRT-D device was also four times more likely to require a reoperation for reasons other than complications compared with a single-chamber ICD during the study period," he said.

Dr Ranasinghe added, "The rate of complications is substantial and higher than previously reported. The continued occurrence of complications long after the initial implantation indicates the need for vigilance and ongoing surveillance of ICD-related complications."

"There is considerable debate as to the added benefit of more complex devices compared with simpler single-chamber ICDs. Where possible, using a simpler device may reduce the risk of ICD-related harm," he said.

Dr. Paul J. Hauptman of Saint Louis University School of Medicine in Missouri, told Reuters Health by email, "The study adds to a rich literature that highlights the need for clinicians and patients to carefully consider the potential risks and benefits of implantable defibrillators and CRT devices."

"Although (this was) not a primary focus of the paper, I was struck by the 35% mortality at a median of 2.7 years (in addition to a significant ICD-related complication rate)," said Dr. Hauptman, who has done work in this area. "By linking registry and Medicare data, the authors succeed in providing meaningful insight into what happens to real patients in the real world. We would be abrogating our role as physicians if we ignore analyses like this one."

The study was funded by the American College of Cardiology Foundation's National Cardiovascular Data Registry and other organizations. Five coauthors reported disclosures.

Blood samples

Photo by Graham Colm

A new technique provides a way to keep blood samples stable for long periods at high temperatures, according to research published in PNAS.

Investigators found they could keep blood samples stable for nearly 3 months at temperatures as high as 113 degrees F by encapsulating them in air-dried silk protein.

The team believes this technique could have broad applications for clinical care and research.

“This approach should facilitate outpatient blood collection for disease screening and monitoring, particularly for underserved populations, and also serve needs of researchers and clinicians without access to centralized testing facilities,” said study author David L. Kaplan, PhD, of the Department of Biomedical Engineering at Tufts University in Medford, Massachusetts.

For this approach, Dr Kaplan and his colleagues mixed a solution or a powder of purified silk fibroin protein extracted from silkworm cocoons with blood or plasma and air-dried the mixture.

The air-dried silk films were stored at temperatures between 22 and 45 degrees C (71.6 to 113 degrees F). At set intervals, the researchers recovered the encapsulated blood samples by dissolving the films in water and analyzed them.

“We found that biomarkers could be successfully analyzed even after storage for 84 days at temperatures up to 113 degrees F,” said study author Jonathan A. Kluge, PhD, formerly of Tufts University but now at Vaxess Technologies in Cambridge, Massachusetts.

“Encapsulation of samples in silk provided better protection than the traditional approach of drying on paper, especially at these elevated temperatures, which a shipment might encounter during overseas or summer transport.”

The investigators noted that the silk-based technique requires accurate starting volumes of the blood or other specimens to be known, and salts or other buffers are needed to reconstitute samples for accurate testing of certain markers.

Blood samples

Photo by Graham Colm

A new technique provides a way to keep blood samples stable for long periods at high temperatures, according to research published in PNAS.

Investigators found they could keep blood samples stable for nearly 3 months at temperatures as high as 113 degrees F by encapsulating them in air-dried silk protein.

The team believes this technique could have broad applications for clinical care and research.

“This approach should facilitate outpatient blood collection for disease screening and monitoring, particularly for underserved populations, and also serve needs of researchers and clinicians without access to centralized testing facilities,” said study author David L. Kaplan, PhD, of the Department of Biomedical Engineering at Tufts University in Medford, Massachusetts.

For this approach, Dr Kaplan and his colleagues mixed a solution or a powder of purified silk fibroin protein extracted from silkworm cocoons with blood or plasma and air-dried the mixture.

The air-dried silk films were stored at temperatures between 22 and 45 degrees C (71.6 to 113 degrees F). At set intervals, the researchers recovered the encapsulated blood samples by dissolving the films in water and analyzed them.

“We found that biomarkers could be successfully analyzed even after storage for 84 days at temperatures up to 113 degrees F,” said study author Jonathan A. Kluge, PhD, formerly of Tufts University but now at Vaxess Technologies in Cambridge, Massachusetts.

“Encapsulation of samples in silk provided better protection than the traditional approach of drying on paper, especially at these elevated temperatures, which a shipment might encounter during overseas or summer transport.”

The investigators noted that the silk-based technique requires accurate starting volumes of the blood or other specimens to be known, and salts or other buffers are needed to reconstitute samples for accurate testing of certain markers.

Blood samples

Photo by Graham Colm

A new technique provides a way to keep blood samples stable for long periods at high temperatures, according to research published in PNAS.

Investigators found they could keep blood samples stable for nearly 3 months at temperatures as high as 113 degrees F by encapsulating them in air-dried silk protein.

The team believes this technique could have broad applications for clinical care and research.

“This approach should facilitate outpatient blood collection for disease screening and monitoring, particularly for underserved populations, and also serve needs of researchers and clinicians without access to centralized testing facilities,” said study author David L. Kaplan, PhD, of the Department of Biomedical Engineering at Tufts University in Medford, Massachusetts.

For this approach, Dr Kaplan and his colleagues mixed a solution or a powder of purified silk fibroin protein extracted from silkworm cocoons with blood or plasma and air-dried the mixture.

The air-dried silk films were stored at temperatures between 22 and 45 degrees C (71.6 to 113 degrees F). At set intervals, the researchers recovered the encapsulated blood samples by dissolving the films in water and analyzed them.

“We found that biomarkers could be successfully analyzed even after storage for 84 days at temperatures up to 113 degrees F,” said study author Jonathan A. Kluge, PhD, formerly of Tufts University but now at Vaxess Technologies in Cambridge, Massachusetts.

“Encapsulation of samples in silk provided better protection than the traditional approach of drying on paper, especially at these elevated temperatures, which a shipment might encounter during overseas or summer transport.”

The investigators noted that the silk-based technique requires accurate starting volumes of the blood or other specimens to be known, and salts or other buffers are needed to reconstitute samples for accurate testing of certain markers.