Expert Commentary

With the decision by Astora Women’s Health to discontinue operations as of March 31, 2016, we have lost midurethral slings and pelvic organ prolapse repair mesh, technologies and kits that have been among the most widely used and studied (Steve Blum, Senior Vice President and General Manager, Astora Women’s Health, and Kathie J. Lenzen, Senior Vice President and General Manager, Endo Device Operations, e-mail communication to physician customers, February 29, 2016). US Food and Drug Administration (FDA)−mandated 522 postmarket surveillance studies on these products have stopped enrolling patients, and we will therefore never glean the full science from fully enrolled and completed studies. This is a horrible precedent. How did this happen, and what do we need to do now to prevent further loss of helpful innovative technologies that benefit our patients with pelvic floor disorders?

Liability challenges precipitated shut downEndo Pharmaceuticals, the parent company of Astora (previously American Medical Systems Women’s Health division), last year offered $1.5 billion to settle a majority of its pending mesh litigation cases. I was told that the company wanted to put all of the negative noise from the relentless plaintiff attorney public media campaign behind it and refocus its attention on helping women with pelvic floor disorders.

Over the past year, 4 interested and capable buyers have been in discussions with the company to purchase and continue its product line. The company’s recent decision to not sell its product line and discontinue all operations was based on “the current legal environment and the ongoing challenges associated with vaginal mesh product liability” (Astora Women’s Health, e-mail communication to physician customers, February 29, 2016). If it had chosen to sell its product line, the company always would have remained a potential deep-pocketed codefendant in any future litigation against the company that purchased its products, technologies, and intellectual properties.

This is a frightening scenario that threatens existing companies that want to remain in the prolapse and incontinence product space. This is a threat to all future innovation for pelvic floor disorder therapies, and it discourages anyone or any company to invest in innovative products that may help our patients. In addition, it is a threat to our mission as physicians and surgeons to provide the very best therapies to our patients who deserve and expect us to do so.

Let me be crystal clear: Currently available midurethral slings are also in the crosshairs of plaintiff attorneys, and we are at risk of losing them as well if we do not act quickly, decisively, and as a unified force. More than 60% of the mesh lawsuits have been against midurethral slings, not the prolapse mesh kits focused on in the FDA Public Health notice of July 2011.¹ In their class action lawsuits, plaintiff attorneys lumped together any procedure involving mesh in the pelvis to increase the number of their patient clients involved, which can drive up settlement awards, and they succeeded. In 2014, 128,030 sling procedures for incontinence were performed. Does anyone truly believe that the scientific literature supports that these patients would have been best served by 128,030 Burch procedures?

Some believe that Endo Pharmaceuticals’ placement of $1.5 billion in settlement funds was an error, “threw blood in the water,” and led to what has happened. Some believe that companies should fight every lawsuit to win and not settle. By the companies winning cases, the plaintiff attorneys lose their incentives to advertise and file more cases, as they only receive money if they win (or get a settlement) and are out of pocket for their costs and time if they lose.

Plaintiff attorneys have a responsibility to zealously advocate for their patient clients. Defense attorneys have a responsibility to zealously defend their corporate clients. We surgeons must realize that we have a responsibility to zealously advocate for our patients and do whatever is needed to best serve them and to protect the use (and development) of innovative products and therapies that give them value and a better quality of life.

Proactive steps surgeons can take

Implement expert oversight for litigation. Some of the large plaintiff awards were assisted by expert testimony based on a highly questionable scientific foundation. Judges give expert witnesses great latitude in their testimony, relying on the jury to discern the truth. I recommend that professional societies, such as the American College of Obstetricians and Gynecologists (ACOG), AmericanUrological Association (AUA), American Urogynecologic Society (AUGS), Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction (SUFU), and Society of Gynecologic Surgeons (SGS), establish a panel to review and carefully evaluate plaintiff expert testimony that has a questionable scientific foundation. If such a panel finds the scientific basis of testimony to be biased, untruthful, or unethical, the societies must publicly reprimand and sanction these experts. Only then would these experts no longer be used by the plaintiff attorneys.

Such an expert panel also could serve to educate the judges in federal and state courts on real science and not manufactured opinions.

We need juries that can understand the science so they truly can decide on cases involving complex technologies.

Support professional leadership efforts. I am encouraged that AUGS is working to establish guidelines for the management of mesh complications. I have seen cases in which a small amount of mesh exposure, best treated by limited local excision of the exposed mesh, instead has been treated by complete excision of every polypropylene fiber placed, resulting in an unnecessarily morbid surgery that leaves a scarred and small vagina. Notably, some of the surgeons who excise every polypropylene fiber are also working as plaintiff experts, who may then testify that the scarred, small vagina was caused by the mesh and the implanting surgeon.

Our professional society leadership and volunteer committees, especially from AUGS, have done a tremendous amount of work in assisting with the FDA-required 522 postmarket surveillance study research design; establishing a Pelvic Floor Disorders Registry (http://www.pfdr.org/) and a sling registry; and developing credentialing guidelines for sacrocolpopexy, transvaginal mesh, and slings. They deserve our gratitude and our participation in the registries. It would be a tragedy if all of this work does not lead to fully enrolled and completed 522 studies so that we can scientifically make decisions on products before any more treatment options are removed from the market.

Use video to scrutinize surgical outcomes data. The surgical literature shows extreme variance in outcomes and complications for vaginal mesh surgery, including exposure rates from 1% to 20% with the same mesh products. This only can be explained by depth of surgical dissection and implanting technique. Surgical outcomes have been shown to be related directly to surgical volumes and experience.² I propose that going forward, any authors who publish their study outcomes and complication data on a surgical procedure must submit a surgical video that demonstrates exactly how the surgery was done.

Best serve the patient. We all need to rigorously follow our own surgery results, improve our techniques, and keep within our surgical skill sets. We need to share our outcome and complication data with our patients during the informed consent process, since we, and not the surgical literature, are performing their surgeries.

We need to be transparent and respectful of our colleagues with different skill sets, putting what is best for patients ahead of everything else. We must be mindful of our inherent biases toward surgeries we are personally very good at and comfortable with. We must respect that other surgeons may achieve better clinical outcomes than us with the same surgery. We need to teach each other the best reproducible surgical techniques to maximize outcomes and minimize complications.

We must humbly accept that not every surgeon can do every surgery (and should not try). If a patient would be best served with a surgery we are not skilled in, we must refer that patient to a colleague who is.

Encourage industry’s part in training. As new technologies are developed, we must be brutally honest with ourselves about whether or not we have the skill sets to use them. Industry must gauge the complexity of the surgical skill set necessary to use their products and limit attendance at their teaching labs to surgeons who have the skills required to obtain good outcomes and minimize complications.

We have reached the tipping pointWe have seen the enemy, and it is us. We now need to advocate zealously for our patients. We will succeed only if we keep what is best for our patients at the forefront of everything we do. We must today decide to lead or be led. If we do not lead, we will be led by others—to places that may not best serve our patients. Make no mistake, this is a tipping point. The future of midurethral slings and potential future innovations lie in our hands right now.

Notably, just days prior to Astora’s letter to its physician customers announcing the decision to discontinue all of its operations, the transobturator postanal sling system (TOPAS) for fecal incontinence, a product in the pipeline at Astora, received 3 unanimous 8-0 votes from an FDA device advisory panel on safety, efficacy, and benefit outweighing risk.³ The future of this technology is now uncertain as well.

I ask Endo Pharmaceuticals to reconsider abandoning all of its products and intellectual properties. I ask it to entertain discussions with large companies that want its technologies and intellectual properties and can indemnify it from future litigation. While there never is a guarantee of complete indemnification and the company does have a fiduciary responsibility to its shareholders, industry also has a responsibility to patients and surgeons to allow helpful technologies to persist.

According to Astora’s letter to its physician customers, “Patient health has always been our number one priority. As such, the business closure has been expedited so that you and your patients have the opportunity to assess alternative treatment options as soon as possible.”

That letter was dated February 29. I do not feel that 31 days’ notice is enough time for surgeons to assess—let alone learn and master—new treatment options. It would have been helpful if Endo Pharmaceuticals had given more notice and would at least have allowed other interested companies the option to purchase useful technologies and intellectual property to mitigate its rapid departure from the space. The company remains in the health care arena with its pharmaceutical products, and how it behaves leaving the surgical space will be noted and impact its brand and reputation.

Lessons from the morcellation situationHow quickly the power morcellator disappeared is a lesson to note very carefully, and it has important parallels to what we now face. I highly recommend that you read and study Lisa Rosenbaum’s article in New England Journal of Medicine, “N-of-1 policymaking—tragedy, trade-offs, and the demise of morcellation.”⁴ She eloquently discusses how decisions to terminate technologies based on passionate anecdotal stories and media campaigns, and not scientific study, does not serve the greater good. She explores lessons learned from the silicone breast implant saga as well, stating “the tendency to focus on eliminating an immediate harm while failing to consider potentially greater harms caused by that reaction is heightened by the power of tragic stories.”⁴

We need a calmer, less emotional, and balanced scientific approach to evaluate technologies. We need to consider what harm is done by not allowing new technologies to be adequately studied, improved, and implemented. Dr. Rosenbaum discusses what Cass Sunstein and Timur Kuran call the “availability cascade,” “a phenomenon whereby stories inform public perceptions and anyone challenging those perceptions is vilified.”^4,5

No technology will ever be risk free, and there always will be some risks and complications that could be significant and chilling. However, patient autonomy requires a full discussion of a risk/benefit ratio that is based on science, and these scientific data must be allowed to be collected and learned. There even can be more significant and chilling complications from not using a technology as well.

It is challenging to speak science to emotion that is driven by tragic outcomes, but we can remain compassionate as we seek the science that will serve the greater good. Condemning proponents of carefully studied and properly implemented technologies as immoral is neither helpful nor constructive. Crushing the ability to thoroughly and scientifically study new technologies is not in the best interest of our patients with pelvic floor disorders.

It is time to reawaken the better angels of our natureWill we do the necessary work now no matter how uncomfortable it may make us feel? Or will we be intimidated and remain silent and disjointed? Will we participate in the registries and follow best clinical practice and credentialing guidelines? Will we hold ourselves and our colleagues accountable? It is time to remember why we became surgeons, and to start acting on our convictions.

To that end, we must ask ourselves, will we:

• honor the Hippocratic Oath that we took in medical school and “respect the hard-won scientific gains of those physicians in whose steps I walk, and gladly share such knowledge as is mine with those who are to follow”⁶
• “not be ashamed to say ‘I know not,’ nor will I fail to call in my colleagues when the skills of another are needed for a patient’s recovery”⁶
• zealously advocate for our patients to ensure we can offer them the very best therapies
• honor and respect the sacred trust patients place in us when we take them to the operating room
• lead or be led?

This is personal for me. My mother struggled with pelvic floor disorders. I always felt it grossly unfair that women who chose to give us life could suffer for the rest of theirs for that decision. These women deserve our very best. The 40 million women with pelvic floor disorders deserve—and expect—that we lead. Will we?

I am hopeful that we will. I believe we will rise to today’s challenges and protect and fight for our patients. I believe that years from now we will look back and be proud that we did the right thing, and in so doing protected and encouraged innovations that significantly enhanced the quality of our patients’ lives. I believe patients will recognize our genuine efforts and in so doing give our profession the respect and trust that I feel has been diminished.

I believe we will draw the needed courage and resolve from the oath we recited in medical school and remember that, “If I do not violate this oath, may I enjoy life and art, respected while I live and remembered with affection thereafter. May I always act so as to preserve the finest traditions of my calling and may I long experience the joy of healing those who seek my help.”⁶

I do believe we will.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

With the decision by Astora Women’s Health to discontinue operations as of March 31, 2016, we have lost midurethral slings and pelvic organ prolapse repair mesh, technologies and kits that have been among the most widely used and studied (Steve Blum, Senior Vice President and General Manager, Astora Women’s Health, and Kathie J. Lenzen, Senior Vice President and General Manager, Endo Device Operations, e-mail communication to physician customers, February 29, 2016). US Food and Drug Administration (FDA)−mandated 522 postmarket surveillance studies on these products have stopped enrolling patients, and we will therefore never glean the full science from fully enrolled and completed studies. This is a horrible precedent. How did this happen, and what do we need to do now to prevent further loss of helpful innovative technologies that benefit our patients with pelvic floor disorders?

Liability challenges precipitated shut downEndo Pharmaceuticals, the parent company of Astora (previously American Medical Systems Women’s Health division), last year offered $1.5 billion to settle a majority of its pending mesh litigation cases. I was told that the company wanted to put all of the negative noise from the relentless plaintiff attorney public media campaign behind it and refocus its attention on helping women with pelvic floor disorders.

Over the past year, 4 interested and capable buyers have been in discussions with the company to purchase and continue its product line. The company’s recent decision to not sell its product line and discontinue all operations was based on “the current legal environment and the ongoing challenges associated with vaginal mesh product liability” (Astora Women’s Health, e-mail communication to physician customers, February 29, 2016). If it had chosen to sell its product line, the company always would have remained a potential deep-pocketed codefendant in any future litigation against the company that purchased its products, technologies, and intellectual properties.

This is a frightening scenario that threatens existing companies that want to remain in the prolapse and incontinence product space. This is a threat to all future innovation for pelvic floor disorder therapies, and it discourages anyone or any company to invest in innovative products that may help our patients. In addition, it is a threat to our mission as physicians and surgeons to provide the very best therapies to our patients who deserve and expect us to do so.

Let me be crystal clear: Currently available midurethral slings are also in the crosshairs of plaintiff attorneys, and we are at risk of losing them as well if we do not act quickly, decisively, and as a unified force. More than 60% of the mesh lawsuits have been against midurethral slings, not the prolapse mesh kits focused on in the FDA Public Health notice of July 2011.¹ In their class action lawsuits, plaintiff attorneys lumped together any procedure involving mesh in the pelvis to increase the number of their patient clients involved, which can drive up settlement awards, and they succeeded. In 2014, 128,030 sling procedures for incontinence were performed. Does anyone truly believe that the scientific literature supports that these patients would have been best served by 128,030 Burch procedures?

Some believe that Endo Pharmaceuticals’ placement of $1.5 billion in settlement funds was an error, “threw blood in the water,” and led to what has happened. Some believe that companies should fight every lawsuit to win and not settle. By the companies winning cases, the plaintiff attorneys lose their incentives to advertise and file more cases, as they only receive money if they win (or get a settlement) and are out of pocket for their costs and time if they lose.

Plaintiff attorneys have a responsibility to zealously advocate for their patient clients. Defense attorneys have a responsibility to zealously defend their corporate clients. We surgeons must realize that we have a responsibility to zealously advocate for our patients and do whatever is needed to best serve them and to protect the use (and development) of innovative products and therapies that give them value and a better quality of life.

Proactive steps surgeons can take

Implement expert oversight for litigation. Some of the large plaintiff awards were assisted by expert testimony based on a highly questionable scientific foundation. Judges give expert witnesses great latitude in their testimony, relying on the jury to discern the truth. I recommend that professional societies, such as the American College of Obstetricians and Gynecologists (ACOG), AmericanUrological Association (AUA), American Urogynecologic Society (AUGS), Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction (SUFU), and Society of Gynecologic Surgeons (SGS), establish a panel to review and carefully evaluate plaintiff expert testimony that has a questionable scientific foundation. If such a panel finds the scientific basis of testimony to be biased, untruthful, or unethical, the societies must publicly reprimand and sanction these experts. Only then would these experts no longer be used by the plaintiff attorneys.

Such an expert panel also could serve to educate the judges in federal and state courts on real science and not manufactured opinions.

We need juries that can understand the science so they truly can decide on cases involving complex technologies.

Support professional leadership efforts. I am encouraged that AUGS is working to establish guidelines for the management of mesh complications. I have seen cases in which a small amount of mesh exposure, best treated by limited local excision of the exposed mesh, instead has been treated by complete excision of every polypropylene fiber placed, resulting in an unnecessarily morbid surgery that leaves a scarred and small vagina. Notably, some of the surgeons who excise every polypropylene fiber are also working as plaintiff experts, who may then testify that the scarred, small vagina was caused by the mesh and the implanting surgeon.

Our professional society leadership and volunteer committees, especially from AUGS, have done a tremendous amount of work in assisting with the FDA-required 522 postmarket surveillance study research design; establishing a Pelvic Floor Disorders Registry (http://www.pfdr.org/) and a sling registry; and developing credentialing guidelines for sacrocolpopexy, transvaginal mesh, and slings. They deserve our gratitude and our participation in the registries. It would be a tragedy if all of this work does not lead to fully enrolled and completed 522 studies so that we can scientifically make decisions on products before any more treatment options are removed from the market.

Use video to scrutinize surgical outcomes data. The surgical literature shows extreme variance in outcomes and complications for vaginal mesh surgery, including exposure rates from 1% to 20% with the same mesh products. This only can be explained by depth of surgical dissection and implanting technique. Surgical outcomes have been shown to be related directly to surgical volumes and experience.² I propose that going forward, any authors who publish their study outcomes and complication data on a surgical procedure must submit a surgical video that demonstrates exactly how the surgery was done.

Best serve the patient. We all need to rigorously follow our own surgery results, improve our techniques, and keep within our surgical skill sets. We need to share our outcome and complication data with our patients during the informed consent process, since we, and not the surgical literature, are performing their surgeries.

We need to be transparent and respectful of our colleagues with different skill sets, putting what is best for patients ahead of everything else. We must be mindful of our inherent biases toward surgeries we are personally very good at and comfortable with. We must respect that other surgeons may achieve better clinical outcomes than us with the same surgery. We need to teach each other the best reproducible surgical techniques to maximize outcomes and minimize complications.

We must humbly accept that not every surgeon can do every surgery (and should not try). If a patient would be best served with a surgery we are not skilled in, we must refer that patient to a colleague who is.

Encourage industry’s part in training. As new technologies are developed, we must be brutally honest with ourselves about whether or not we have the skill sets to use them. Industry must gauge the complexity of the surgical skill set necessary to use their products and limit attendance at their teaching labs to surgeons who have the skills required to obtain good outcomes and minimize complications.

We have reached the tipping pointWe have seen the enemy, and it is us. We now need to advocate zealously for our patients. We will succeed only if we keep what is best for our patients at the forefront of everything we do. We must today decide to lead or be led. If we do not lead, we will be led by others—to places that may not best serve our patients. Make no mistake, this is a tipping point. The future of midurethral slings and potential future innovations lie in our hands right now.

Notably, just days prior to Astora’s letter to its physician customers announcing the decision to discontinue all of its operations, the transobturator postanal sling system (TOPAS) for fecal incontinence, a product in the pipeline at Astora, received 3 unanimous 8-0 votes from an FDA device advisory panel on safety, efficacy, and benefit outweighing risk.³ The future of this technology is now uncertain as well.

I ask Endo Pharmaceuticals to reconsider abandoning all of its products and intellectual properties. I ask it to entertain discussions with large companies that want its technologies and intellectual properties and can indemnify it from future litigation. While there never is a guarantee of complete indemnification and the company does have a fiduciary responsibility to its shareholders, industry also has a responsibility to patients and surgeons to allow helpful technologies to persist.

According to Astora’s letter to its physician customers, “Patient health has always been our number one priority. As such, the business closure has been expedited so that you and your patients have the opportunity to assess alternative treatment options as soon as possible.”

That letter was dated February 29. I do not feel that 31 days’ notice is enough time for surgeons to assess—let alone learn and master—new treatment options. It would have been helpful if Endo Pharmaceuticals had given more notice and would at least have allowed other interested companies the option to purchase useful technologies and intellectual property to mitigate its rapid departure from the space. The company remains in the health care arena with its pharmaceutical products, and how it behaves leaving the surgical space will be noted and impact its brand and reputation.

Lessons from the morcellation situationHow quickly the power morcellator disappeared is a lesson to note very carefully, and it has important parallels to what we now face. I highly recommend that you read and study Lisa Rosenbaum’s article in New England Journal of Medicine, “N-of-1 policymaking—tragedy, trade-offs, and the demise of morcellation.”⁴ She eloquently discusses how decisions to terminate technologies based on passionate anecdotal stories and media campaigns, and not scientific study, does not serve the greater good. She explores lessons learned from the silicone breast implant saga as well, stating “the tendency to focus on eliminating an immediate harm while failing to consider potentially greater harms caused by that reaction is heightened by the power of tragic stories.”⁴

We need a calmer, less emotional, and balanced scientific approach to evaluate technologies. We need to consider what harm is done by not allowing new technologies to be adequately studied, improved, and implemented. Dr. Rosenbaum discusses what Cass Sunstein and Timur Kuran call the “availability cascade,” “a phenomenon whereby stories inform public perceptions and anyone challenging those perceptions is vilified.”^4,5

No technology will ever be risk free, and there always will be some risks and complications that could be significant and chilling. However, patient autonomy requires a full discussion of a risk/benefit ratio that is based on science, and these scientific data must be allowed to be collected and learned. There even can be more significant and chilling complications from not using a technology as well.

It is challenging to speak science to emotion that is driven by tragic outcomes, but we can remain compassionate as we seek the science that will serve the greater good. Condemning proponents of carefully studied and properly implemented technologies as immoral is neither helpful nor constructive. Crushing the ability to thoroughly and scientifically study new technologies is not in the best interest of our patients with pelvic floor disorders.

It is time to reawaken the better angels of our natureWill we do the necessary work now no matter how uncomfortable it may make us feel? Or will we be intimidated and remain silent and disjointed? Will we participate in the registries and follow best clinical practice and credentialing guidelines? Will we hold ourselves and our colleagues accountable? It is time to remember why we became surgeons, and to start acting on our convictions.

To that end, we must ask ourselves, will we:

• honor the Hippocratic Oath that we took in medical school and “respect the hard-won scientific gains of those physicians in whose steps I walk, and gladly share such knowledge as is mine with those who are to follow”⁶
• “not be ashamed to say ‘I know not,’ nor will I fail to call in my colleagues when the skills of another are needed for a patient’s recovery”⁶
• zealously advocate for our patients to ensure we can offer them the very best therapies
• honor and respect the sacred trust patients place in us when we take them to the operating room
• lead or be led?

This is personal for me. My mother struggled with pelvic floor disorders. I always felt it grossly unfair that women who chose to give us life could suffer for the rest of theirs for that decision. These women deserve our very best. The 40 million women with pelvic floor disorders deserve—and expect—that we lead. Will we?

I am hopeful that we will. I believe we will rise to today’s challenges and protect and fight for our patients. I believe that years from now we will look back and be proud that we did the right thing, and in so doing protected and encouraged innovations that significantly enhanced the quality of our patients’ lives. I believe patients will recognize our genuine efforts and in so doing give our profession the respect and trust that I feel has been diminished.

I believe we will draw the needed courage and resolve from the oath we recited in medical school and remember that, “If I do not violate this oath, may I enjoy life and art, respected while I live and remembered with affection thereafter. May I always act so as to preserve the finest traditions of my calling and may I long experience the joy of healing those who seek my help.”⁶

I do believe we will.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

With the decision by Astora Women’s Health to discontinue operations as of March 31, 2016, we have lost midurethral slings and pelvic organ prolapse repair mesh, technologies and kits that have been among the most widely used and studied (Steve Blum, Senior Vice President and General Manager, Astora Women’s Health, and Kathie J. Lenzen, Senior Vice President and General Manager, Endo Device Operations, e-mail communication to physician customers, February 29, 2016). US Food and Drug Administration (FDA)−mandated 522 postmarket surveillance studies on these products have stopped enrolling patients, and we will therefore never glean the full science from fully enrolled and completed studies. This is a horrible precedent. How did this happen, and what do we need to do now to prevent further loss of helpful innovative technologies that benefit our patients with pelvic floor disorders?

Liability challenges precipitated shut downEndo Pharmaceuticals, the parent company of Astora (previously American Medical Systems Women’s Health division), last year offered $1.5 billion to settle a majority of its pending mesh litigation cases. I was told that the company wanted to put all of the negative noise from the relentless plaintiff attorney public media campaign behind it and refocus its attention on helping women with pelvic floor disorders.

Over the past year, 4 interested and capable buyers have been in discussions with the company to purchase and continue its product line. The company’s recent decision to not sell its product line and discontinue all operations was based on “the current legal environment and the ongoing challenges associated with vaginal mesh product liability” (Astora Women’s Health, e-mail communication to physician customers, February 29, 2016). If it had chosen to sell its product line, the company always would have remained a potential deep-pocketed codefendant in any future litigation against the company that purchased its products, technologies, and intellectual properties.

This is a frightening scenario that threatens existing companies that want to remain in the prolapse and incontinence product space. This is a threat to all future innovation for pelvic floor disorder therapies, and it discourages anyone or any company to invest in innovative products that may help our patients. In addition, it is a threat to our mission as physicians and surgeons to provide the very best therapies to our patients who deserve and expect us to do so.

Let me be crystal clear: Currently available midurethral slings are also in the crosshairs of plaintiff attorneys, and we are at risk of losing them as well if we do not act quickly, decisively, and as a unified force. More than 60% of the mesh lawsuits have been against midurethral slings, not the prolapse mesh kits focused on in the FDA Public Health notice of July 2011.¹ In their class action lawsuits, plaintiff attorneys lumped together any procedure involving mesh in the pelvis to increase the number of their patient clients involved, which can drive up settlement awards, and they succeeded. In 2014, 128,030 sling procedures for incontinence were performed. Does anyone truly believe that the scientific literature supports that these patients would have been best served by 128,030 Burch procedures?

Some believe that Endo Pharmaceuticals’ placement of $1.5 billion in settlement funds was an error, “threw blood in the water,” and led to what has happened. Some believe that companies should fight every lawsuit to win and not settle. By the companies winning cases, the plaintiff attorneys lose their incentives to advertise and file more cases, as they only receive money if they win (or get a settlement) and are out of pocket for their costs and time if they lose.

Plaintiff attorneys have a responsibility to zealously advocate for their patient clients. Defense attorneys have a responsibility to zealously defend their corporate clients. We surgeons must realize that we have a responsibility to zealously advocate for our patients and do whatever is needed to best serve them and to protect the use (and development) of innovative products and therapies that give them value and a better quality of life.

Proactive steps surgeons can take

Implement expert oversight for litigation. Some of the large plaintiff awards were assisted by expert testimony based on a highly questionable scientific foundation. Judges give expert witnesses great latitude in their testimony, relying on the jury to discern the truth. I recommend that professional societies, such as the American College of Obstetricians and Gynecologists (ACOG), AmericanUrological Association (AUA), American Urogynecologic Society (AUGS), Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction (SUFU), and Society of Gynecologic Surgeons (SGS), establish a panel to review and carefully evaluate plaintiff expert testimony that has a questionable scientific foundation. If such a panel finds the scientific basis of testimony to be biased, untruthful, or unethical, the societies must publicly reprimand and sanction these experts. Only then would these experts no longer be used by the plaintiff attorneys.

Such an expert panel also could serve to educate the judges in federal and state courts on real science and not manufactured opinions.

We need juries that can understand the science so they truly can decide on cases involving complex technologies.

Support professional leadership efforts. I am encouraged that AUGS is working to establish guidelines for the management of mesh complications. I have seen cases in which a small amount of mesh exposure, best treated by limited local excision of the exposed mesh, instead has been treated by complete excision of every polypropylene fiber placed, resulting in an unnecessarily morbid surgery that leaves a scarred and small vagina. Notably, some of the surgeons who excise every polypropylene fiber are also working as plaintiff experts, who may then testify that the scarred, small vagina was caused by the mesh and the implanting surgeon.

Our professional society leadership and volunteer committees, especially from AUGS, have done a tremendous amount of work in assisting with the FDA-required 522 postmarket surveillance study research design; establishing a Pelvic Floor Disorders Registry (http://www.pfdr.org/) and a sling registry; and developing credentialing guidelines for sacrocolpopexy, transvaginal mesh, and slings. They deserve our gratitude and our participation in the registries. It would be a tragedy if all of this work does not lead to fully enrolled and completed 522 studies so that we can scientifically make decisions on products before any more treatment options are removed from the market.

Use video to scrutinize surgical outcomes data. The surgical literature shows extreme variance in outcomes and complications for vaginal mesh surgery, including exposure rates from 1% to 20% with the same mesh products. This only can be explained by depth of surgical dissection and implanting technique. Surgical outcomes have been shown to be related directly to surgical volumes and experience.² I propose that going forward, any authors who publish their study outcomes and complication data on a surgical procedure must submit a surgical video that demonstrates exactly how the surgery was done.

Best serve the patient. We all need to rigorously follow our own surgery results, improve our techniques, and keep within our surgical skill sets. We need to share our outcome and complication data with our patients during the informed consent process, since we, and not the surgical literature, are performing their surgeries.

We need to be transparent and respectful of our colleagues with different skill sets, putting what is best for patients ahead of everything else. We must be mindful of our inherent biases toward surgeries we are personally very good at and comfortable with. We must respect that other surgeons may achieve better clinical outcomes than us with the same surgery. We need to teach each other the best reproducible surgical techniques to maximize outcomes and minimize complications.

We must humbly accept that not every surgeon can do every surgery (and should not try). If a patient would be best served with a surgery we are not skilled in, we must refer that patient to a colleague who is.

Encourage industry’s part in training. As new technologies are developed, we must be brutally honest with ourselves about whether or not we have the skill sets to use them. Industry must gauge the complexity of the surgical skill set necessary to use their products and limit attendance at their teaching labs to surgeons who have the skills required to obtain good outcomes and minimize complications.

We have reached the tipping pointWe have seen the enemy, and it is us. We now need to advocate zealously for our patients. We will succeed only if we keep what is best for our patients at the forefront of everything we do. We must today decide to lead or be led. If we do not lead, we will be led by others—to places that may not best serve our patients. Make no mistake, this is a tipping point. The future of midurethral slings and potential future innovations lie in our hands right now.

Notably, just days prior to Astora’s letter to its physician customers announcing the decision to discontinue all of its operations, the transobturator postanal sling system (TOPAS) for fecal incontinence, a product in the pipeline at Astora, received 3 unanimous 8-0 votes from an FDA device advisory panel on safety, efficacy, and benefit outweighing risk.³ The future of this technology is now uncertain as well.

I ask Endo Pharmaceuticals to reconsider abandoning all of its products and intellectual properties. I ask it to entertain discussions with large companies that want its technologies and intellectual properties and can indemnify it from future litigation. While there never is a guarantee of complete indemnification and the company does have a fiduciary responsibility to its shareholders, industry also has a responsibility to patients and surgeons to allow helpful technologies to persist.

According to Astora’s letter to its physician customers, “Patient health has always been our number one priority. As such, the business closure has been expedited so that you and your patients have the opportunity to assess alternative treatment options as soon as possible.”

That letter was dated February 29. I do not feel that 31 days’ notice is enough time for surgeons to assess—let alone learn and master—new treatment options. It would have been helpful if Endo Pharmaceuticals had given more notice and would at least have allowed other interested companies the option to purchase useful technologies and intellectual property to mitigate its rapid departure from the space. The company remains in the health care arena with its pharmaceutical products, and how it behaves leaving the surgical space will be noted and impact its brand and reputation.

Lessons from the morcellation situationHow quickly the power morcellator disappeared is a lesson to note very carefully, and it has important parallels to what we now face. I highly recommend that you read and study Lisa Rosenbaum’s article in New England Journal of Medicine, “N-of-1 policymaking—tragedy, trade-offs, and the demise of morcellation.”⁴ She eloquently discusses how decisions to terminate technologies based on passionate anecdotal stories and media campaigns, and not scientific study, does not serve the greater good. She explores lessons learned from the silicone breast implant saga as well, stating “the tendency to focus on eliminating an immediate harm while failing to consider potentially greater harms caused by that reaction is heightened by the power of tragic stories.”⁴

We need a calmer, less emotional, and balanced scientific approach to evaluate technologies. We need to consider what harm is done by not allowing new technologies to be adequately studied, improved, and implemented. Dr. Rosenbaum discusses what Cass Sunstein and Timur Kuran call the “availability cascade,” “a phenomenon whereby stories inform public perceptions and anyone challenging those perceptions is vilified.”^4,5

No technology will ever be risk free, and there always will be some risks and complications that could be significant and chilling. However, patient autonomy requires a full discussion of a risk/benefit ratio that is based on science, and these scientific data must be allowed to be collected and learned. There even can be more significant and chilling complications from not using a technology as well.

It is challenging to speak science to emotion that is driven by tragic outcomes, but we can remain compassionate as we seek the science that will serve the greater good. Condemning proponents of carefully studied and properly implemented technologies as immoral is neither helpful nor constructive. Crushing the ability to thoroughly and scientifically study new technologies is not in the best interest of our patients with pelvic floor disorders.

It is time to reawaken the better angels of our natureWill we do the necessary work now no matter how uncomfortable it may make us feel? Or will we be intimidated and remain silent and disjointed? Will we participate in the registries and follow best clinical practice and credentialing guidelines? Will we hold ourselves and our colleagues accountable? It is time to remember why we became surgeons, and to start acting on our convictions.

To that end, we must ask ourselves, will we:

• honor the Hippocratic Oath that we took in medical school and “respect the hard-won scientific gains of those physicians in whose steps I walk, and gladly share such knowledge as is mine with those who are to follow”⁶
• “not be ashamed to say ‘I know not,’ nor will I fail to call in my colleagues when the skills of another are needed for a patient’s recovery”⁶
• zealously advocate for our patients to ensure we can offer them the very best therapies
• honor and respect the sacred trust patients place in us when we take them to the operating room
• lead or be led?

This is personal for me. My mother struggled with pelvic floor disorders. I always felt it grossly unfair that women who chose to give us life could suffer for the rest of theirs for that decision. These women deserve our very best. The 40 million women with pelvic floor disorders deserve—and expect—that we lead. Will we?

I am hopeful that we will. I believe we will rise to today’s challenges and protect and fight for our patients. I believe that years from now we will look back and be proud that we did the right thing, and in so doing protected and encouraged innovations that significantly enhanced the quality of our patients’ lives. I believe patients will recognize our genuine efforts and in so doing give our profession the respect and trust that I feel has been diminished.

I believe we will draw the needed courage and resolve from the oath we recited in medical school and remember that, “If I do not violate this oath, may I enjoy life and art, respected while I live and remembered with affection thereafter. May I always act so as to preserve the finest traditions of my calling and may I long experience the joy of healing those who seek my help.”⁶

I do believe we will.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

As readers of OBG Management, you are very familiar with the name Janelle Yates. Janelle was an editor and writer for the journal for more than 15 years. Her byline has graced articles on, among other topics, obstetrics, liability, menopause, and tissue extraction. You may recall the 3-part series on endometriosis she authored beginning in April 2015.¹ She worked with several expert surgeons to deliver an in-depth look at diagnosis, treatment, and related infertility. She interviewed presidents of the American Congress of Obstetricians and Gynecologists (ACOG)² and worked with ACOG staff, including Lucia DiVenere, MA, on legislative articles for OBG Management, helping to bring new policies and practice changes to the forefront for readers.^3,4

One topic that was of particular, personal interest to Janelle was breast cancer. She lived on and off with, but always under the shadow of, breast cancer for more than 8 years. This past December, Janelle developed a rare and incurable cancer of the nervous system, which took her life in January.

Janelle’s contributions to OBG Management Janelle worked closely with Robert L. Barbieri, MD, and the OBG Management Board of Editors on writing and editing projects. In fact, Janelle began as Senior Associate Editor with the journal in 2000, only a few months after Dr. Barbieri was inaugurated as Editor in Chief.

“Janelle was exceptionally skillful in polishing a rough manuscript into a superbly crafted article,” says Dr. Barbieri. “The physician authors with whom she collaborated were in awe of her talent and recognized the value of her contributions to advancing women’s health care.”

“Janelle approached the craft of writing like an artist, always searching for an additional layer of deeper meaning and insight. Her strength of character and myriad life experiences gave her unique skills in exploring, questioning, and improving the content that was brought forth.”

“She and I had an ongoing conversation on the pros and cons of being concise,” says Dr. Barbieri. “I would ask her the hypothetical, ‘If an author could effectively deliver his or her core message in a 1-page article, why take 3 pages to do so?’ As a counterpoint, her perspective was that if you could concisely make your point in 3 pages, it might be even better for an author to expand their article to 9 pages to help the reader achieve a deeper level of understanding and insight.”

In May 2013, Barbara S. Levy, MD, after serving for 17 years as an OBG Management Board of Editors member, assumed the position of Vice President for Health Policy at ACOG, and resigned her position on the journal’s editorial board. Janelle collaborated with Dr. Levy on an article commemorating her lifetime of service to women.⁵ Dr. Levy recalls that article, and the numerous others she partnered on with Janelle:

“She was the quintessential professional. We are professional doctors, but Janelle was a professional writer and editor. She had an ability to, when speaking with us, get the best out of us, and take what we said and translate that into a cogent, crisp presentation that was really meaningful to readers. Having her perspective as a partner in writing helped me reach a core in readers that I believe I otherwise would not have been able to reach.”

Andrew M. Kaunitz, MD, Board of Editors member since 2006, describes Janelle as “a wonderful colleague and person.”

“My early perceptions of Janelle,” he says, “relate to her tremendous skills as a medical writer. Over time, however, I recognized that, in addition to her wonderful talents as a writer, she brought what I can only call a sense of grace to each interaction that I had with her. I continue to find it hard to imagine a world without her.”

“During my 15-year excursion as the Editor in Chief of OBG Management,” says Dr. Barbieri, “Janelle was the perfect guide and travel companion. She will always be in my thoughts and heart.”

Janelle’s memory enduresJanelle’s colleagues at the journal office and the Board of Editors honor her dedication to OBG Management, and truly to women’s health in general, in a permanent way in the pages of OBG Management. Janelle’s name has been added to the journal’s staff masthead with the title, “Editor Emeritus.” We feel this is a small but sincere gesture from those of us who have had the immense pleasure and incredible honor to work with Janelle over the years. 

John Baranowski, who served as Editor of OBG Management from 2008 until mid-2012, eloquently states: “As her supervisor for several years, I was the initial recipient of tens of thousands of her well-ordered, well-chosen, and insightful words. At this time, it is hard for me to find words to offer on her behalf. Her outsized skill, her easeful manner, and her certain success at improving the care that physicians provide—those are humbling, silencing remembrances; things of such great value that words just do not work as tribute.”

Dianne Reynolds, Publisher of OBG Management, has known Janelle since 2008 and says that she feels blessed and fortunate to have had Janelle in her life on more than just a professional level. “I will cherish her memory forever,” she says.

OBG Management Managing Editor Deborah Reale joined the journal staff in 2010. “Words connected Janelle and I not only in our editorial work but also personally, through our shared love of poetry,” she says. Unbeknownst to many, Janelle was a published poet. She also wrote two biographies, of Woodie Guthrie and Zora Neale Hurston, while working many years ago as an editor for Ward Hill Press.

Like so many others, I feel privileged to have worked with Janelle. Her work was fearless. Whether it was an audio interview with gynecologic oncologist Eva Chalas, MD, on preserving minimally invasive approaches to gynecologic surgery⁶ or a Q&A article on liability claims in obstetrics,⁷ Janelle did it brilliantly. She applied her years of knowledge and experience to each piece she wrote or edited, always bringing an expert’s best voice forward. In fact, Dianne Reynolds says, “Janelle once told me that she had dreamed of being a doctor, and she imagined herself pushing through hospital doors on her way to treat patients. Instead, Janelle used her acquired medical knowledge in women’s health and writing acumen to assist physicians in explaining their techniques for the benefit of their colleagues.”

Janelle’s siblings Diana and Kent Yates, and her daughter Adrienne Cano, say they have been aware of how supportive the OBG Management extended team has been to Janelle. In speaking with Board of Editors member, Cheryl B. Iglesia, MD, Diana says, “This was such a blessing in her life. It was a rare thing, the kind of relationship she had with all of you. We appreciate so very much your nurturing of her talents and of her as a person.”

Janelle meant a great deal to her colleagues, of course because of her superb work and wise perspective, but also because of her warmth and gentle ease. Simply put, Janelle was a wonderful person to be near.

“She was absolutely amazing and will be greatly missed both personally and professionally,” says 10-year OBG Management board member JoAnn V. Pinkerton, MD.

Dr. Iglesia asserts, “Janelle never will be forgotten. She truly has left a legacy of very important articles for many generations.”

Janelle, we can only hope that with your name on the masthead, readers of OBG Management in future generations will have the privilege of your touch. May that touch bring them the gift of journalistic accuracy, professional integrity, spot-on syntax and, above all, compelling reading. 

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

As readers of OBG Management, you are very familiar with the name Janelle Yates. Janelle was an editor and writer for the journal for more than 15 years. Her byline has graced articles on, among other topics, obstetrics, liability, menopause, and tissue extraction. You may recall the 3-part series on endometriosis she authored beginning in April 2015.¹ She worked with several expert surgeons to deliver an in-depth look at diagnosis, treatment, and related infertility. She interviewed presidents of the American Congress of Obstetricians and Gynecologists (ACOG)² and worked with ACOG staff, including Lucia DiVenere, MA, on legislative articles for OBG Management, helping to bring new policies and practice changes to the forefront for readers.^3,4

One topic that was of particular, personal interest to Janelle was breast cancer. She lived on and off with, but always under the shadow of, breast cancer for more than 8 years. This past December, Janelle developed a rare and incurable cancer of the nervous system, which took her life in January.

Janelle’s contributions to OBG Management Janelle worked closely with Robert L. Barbieri, MD, and the OBG Management Board of Editors on writing and editing projects. In fact, Janelle began as Senior Associate Editor with the journal in 2000, only a few months after Dr. Barbieri was inaugurated as Editor in Chief.

“Janelle was exceptionally skillful in polishing a rough manuscript into a superbly crafted article,” says Dr. Barbieri. “The physician authors with whom she collaborated were in awe of her talent and recognized the value of her contributions to advancing women’s health care.”

“Janelle approached the craft of writing like an artist, always searching for an additional layer of deeper meaning and insight. Her strength of character and myriad life experiences gave her unique skills in exploring, questioning, and improving the content that was brought forth.”

“She and I had an ongoing conversation on the pros and cons of being concise,” says Dr. Barbieri. “I would ask her the hypothetical, ‘If an author could effectively deliver his or her core message in a 1-page article, why take 3 pages to do so?’ As a counterpoint, her perspective was that if you could concisely make your point in 3 pages, it might be even better for an author to expand their article to 9 pages to help the reader achieve a deeper level of understanding and insight.”

In May 2013, Barbara S. Levy, MD, after serving for 17 years as an OBG Management Board of Editors member, assumed the position of Vice President for Health Policy at ACOG, and resigned her position on the journal’s editorial board. Janelle collaborated with Dr. Levy on an article commemorating her lifetime of service to women.⁵ Dr. Levy recalls that article, and the numerous others she partnered on with Janelle:

“She was the quintessential professional. We are professional doctors, but Janelle was a professional writer and editor. She had an ability to, when speaking with us, get the best out of us, and take what we said and translate that into a cogent, crisp presentation that was really meaningful to readers. Having her perspective as a partner in writing helped me reach a core in readers that I believe I otherwise would not have been able to reach.”

Andrew M. Kaunitz, MD, Board of Editors member since 2006, describes Janelle as “a wonderful colleague and person.”

“My early perceptions of Janelle,” he says, “relate to her tremendous skills as a medical writer. Over time, however, I recognized that, in addition to her wonderful talents as a writer, she brought what I can only call a sense of grace to each interaction that I had with her. I continue to find it hard to imagine a world without her.”

“During my 15-year excursion as the Editor in Chief of OBG Management,” says Dr. Barbieri, “Janelle was the perfect guide and travel companion. She will always be in my thoughts and heart.”

Janelle’s memory enduresJanelle’s colleagues at the journal office and the Board of Editors honor her dedication to OBG Management, and truly to women’s health in general, in a permanent way in the pages of OBG Management. Janelle’s name has been added to the journal’s staff masthead with the title, “Editor Emeritus.” We feel this is a small but sincere gesture from those of us who have had the immense pleasure and incredible honor to work with Janelle over the years. 

John Baranowski, who served as Editor of OBG Management from 2008 until mid-2012, eloquently states: “As her supervisor for several years, I was the initial recipient of tens of thousands of her well-ordered, well-chosen, and insightful words. At this time, it is hard for me to find words to offer on her behalf. Her outsized skill, her easeful manner, and her certain success at improving the care that physicians provide—those are humbling, silencing remembrances; things of such great value that words just do not work as tribute.”

Dianne Reynolds, Publisher of OBG Management, has known Janelle since 2008 and says that she feels blessed and fortunate to have had Janelle in her life on more than just a professional level. “I will cherish her memory forever,” she says.

OBG Management Managing Editor Deborah Reale joined the journal staff in 2010. “Words connected Janelle and I not only in our editorial work but also personally, through our shared love of poetry,” she says. Unbeknownst to many, Janelle was a published poet. She also wrote two biographies, of Woodie Guthrie and Zora Neale Hurston, while working many years ago as an editor for Ward Hill Press.

Like so many others, I feel privileged to have worked with Janelle. Her work was fearless. Whether it was an audio interview with gynecologic oncologist Eva Chalas, MD, on preserving minimally invasive approaches to gynecologic surgery⁶ or a Q&A article on liability claims in obstetrics,⁷ Janelle did it brilliantly. She applied her years of knowledge and experience to each piece she wrote or edited, always bringing an expert’s best voice forward. In fact, Dianne Reynolds says, “Janelle once told me that she had dreamed of being a doctor, and she imagined herself pushing through hospital doors on her way to treat patients. Instead, Janelle used her acquired medical knowledge in women’s health and writing acumen to assist physicians in explaining their techniques for the benefit of their colleagues.”

Janelle’s siblings Diana and Kent Yates, and her daughter Adrienne Cano, say they have been aware of how supportive the OBG Management extended team has been to Janelle. In speaking with Board of Editors member, Cheryl B. Iglesia, MD, Diana says, “This was such a blessing in her life. It was a rare thing, the kind of relationship she had with all of you. We appreciate so very much your nurturing of her talents and of her as a person.”

Janelle meant a great deal to her colleagues, of course because of her superb work and wise perspective, but also because of her warmth and gentle ease. Simply put, Janelle was a wonderful person to be near.

“She was absolutely amazing and will be greatly missed both personally and professionally,” says 10-year OBG Management board member JoAnn V. Pinkerton, MD.

Dr. Iglesia asserts, “Janelle never will be forgotten. She truly has left a legacy of very important articles for many generations.”

Janelle, we can only hope that with your name on the masthead, readers of OBG Management in future generations will have the privilege of your touch. May that touch bring them the gift of journalistic accuracy, professional integrity, spot-on syntax and, above all, compelling reading. 

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

As readers of OBG Management, you are very familiar with the name Janelle Yates. Janelle was an editor and writer for the journal for more than 15 years. Her byline has graced articles on, among other topics, obstetrics, liability, menopause, and tissue extraction. You may recall the 3-part series on endometriosis she authored beginning in April 2015.¹ She worked with several expert surgeons to deliver an in-depth look at diagnosis, treatment, and related infertility. She interviewed presidents of the American Congress of Obstetricians and Gynecologists (ACOG)² and worked with ACOG staff, including Lucia DiVenere, MA, on legislative articles for OBG Management, helping to bring new policies and practice changes to the forefront for readers.^3,4

One topic that was of particular, personal interest to Janelle was breast cancer. She lived on and off with, but always under the shadow of, breast cancer for more than 8 years. This past December, Janelle developed a rare and incurable cancer of the nervous system, which took her life in January.

Janelle’s contributions to OBG Management Janelle worked closely with Robert L. Barbieri, MD, and the OBG Management Board of Editors on writing and editing projects. In fact, Janelle began as Senior Associate Editor with the journal in 2000, only a few months after Dr. Barbieri was inaugurated as Editor in Chief.

“Janelle was exceptionally skillful in polishing a rough manuscript into a superbly crafted article,” says Dr. Barbieri. “The physician authors with whom she collaborated were in awe of her talent and recognized the value of her contributions to advancing women’s health care.”

“Janelle approached the craft of writing like an artist, always searching for an additional layer of deeper meaning and insight. Her strength of character and myriad life experiences gave her unique skills in exploring, questioning, and improving the content that was brought forth.”

“She and I had an ongoing conversation on the pros and cons of being concise,” says Dr. Barbieri. “I would ask her the hypothetical, ‘If an author could effectively deliver his or her core message in a 1-page article, why take 3 pages to do so?’ As a counterpoint, her perspective was that if you could concisely make your point in 3 pages, it might be even better for an author to expand their article to 9 pages to help the reader achieve a deeper level of understanding and insight.”

In May 2013, Barbara S. Levy, MD, after serving for 17 years as an OBG Management Board of Editors member, assumed the position of Vice President for Health Policy at ACOG, and resigned her position on the journal’s editorial board. Janelle collaborated with Dr. Levy on an article commemorating her lifetime of service to women.⁵ Dr. Levy recalls that article, and the numerous others she partnered on with Janelle:

“She was the quintessential professional. We are professional doctors, but Janelle was a professional writer and editor. She had an ability to, when speaking with us, get the best out of us, and take what we said and translate that into a cogent, crisp presentation that was really meaningful to readers. Having her perspective as a partner in writing helped me reach a core in readers that I believe I otherwise would not have been able to reach.”

Andrew M. Kaunitz, MD, Board of Editors member since 2006, describes Janelle as “a wonderful colleague and person.”

“My early perceptions of Janelle,” he says, “relate to her tremendous skills as a medical writer. Over time, however, I recognized that, in addition to her wonderful talents as a writer, she brought what I can only call a sense of grace to each interaction that I had with her. I continue to find it hard to imagine a world without her.”

“During my 15-year excursion as the Editor in Chief of OBG Management,” says Dr. Barbieri, “Janelle was the perfect guide and travel companion. She will always be in my thoughts and heart.”

Janelle’s memory enduresJanelle’s colleagues at the journal office and the Board of Editors honor her dedication to OBG Management, and truly to women’s health in general, in a permanent way in the pages of OBG Management. Janelle’s name has been added to the journal’s staff masthead with the title, “Editor Emeritus.” We feel this is a small but sincere gesture from those of us who have had the immense pleasure and incredible honor to work with Janelle over the years. 

John Baranowski, who served as Editor of OBG Management from 2008 until mid-2012, eloquently states: “As her supervisor for several years, I was the initial recipient of tens of thousands of her well-ordered, well-chosen, and insightful words. At this time, it is hard for me to find words to offer on her behalf. Her outsized skill, her easeful manner, and her certain success at improving the care that physicians provide—those are humbling, silencing remembrances; things of such great value that words just do not work as tribute.”

Dianne Reynolds, Publisher of OBG Management, has known Janelle since 2008 and says that she feels blessed and fortunate to have had Janelle in her life on more than just a professional level. “I will cherish her memory forever,” she says.

OBG Management Managing Editor Deborah Reale joined the journal staff in 2010. “Words connected Janelle and I not only in our editorial work but also personally, through our shared love of poetry,” she says. Unbeknownst to many, Janelle was a published poet. She also wrote two biographies, of Woodie Guthrie and Zora Neale Hurston, while working many years ago as an editor for Ward Hill Press.

Like so many others, I feel privileged to have worked with Janelle. Her work was fearless. Whether it was an audio interview with gynecologic oncologist Eva Chalas, MD, on preserving minimally invasive approaches to gynecologic surgery⁶ or a Q&A article on liability claims in obstetrics,⁷ Janelle did it brilliantly. She applied her years of knowledge and experience to each piece she wrote or edited, always bringing an expert’s best voice forward. In fact, Dianne Reynolds says, “Janelle once told me that she had dreamed of being a doctor, and she imagined herself pushing through hospital doors on her way to treat patients. Instead, Janelle used her acquired medical knowledge in women’s health and writing acumen to assist physicians in explaining their techniques for the benefit of their colleagues.”

Janelle’s siblings Diana and Kent Yates, and her daughter Adrienne Cano, say they have been aware of how supportive the OBG Management extended team has been to Janelle. In speaking with Board of Editors member, Cheryl B. Iglesia, MD, Diana says, “This was such a blessing in her life. It was a rare thing, the kind of relationship she had with all of you. We appreciate so very much your nurturing of her talents and of her as a person.”

Janelle meant a great deal to her colleagues, of course because of her superb work and wise perspective, but also because of her warmth and gentle ease. Simply put, Janelle was a wonderful person to be near.

“She was absolutely amazing and will be greatly missed both personally and professionally,” says 10-year OBG Management board member JoAnn V. Pinkerton, MD.

Dr. Iglesia asserts, “Janelle never will be forgotten. She truly has left a legacy of very important articles for many generations.”

Janelle, we can only hope that with your name on the masthead, readers of OBG Management in future generations will have the privilege of your touch. May that touch bring them the gift of journalistic accuracy, professional integrity, spot-on syntax and, above all, compelling reading. 

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Presently it seems that anything a pregnant woman ingests can be correlated with a teratology or an unfortunate neurobehavioral outcome. In an era when up to 15% of pregnant women are taking antidepressant therapy, antidepressants are obvious drugs to be correlated with an untoward fetal outcome, despite the fact that untreated maternal depression itself is significantly worse.1

A recent retrospective secondary end point study by Boukhris and colleagues on antidepressant use in pregnancy and the risk of autism spectrum disorder (ASD) in children is an example of correlation without substantive evidence of causation. Although this study received media attention,² it is a “data-dredge” study. While the authors correctly note that the database is derived from a prospective registry-based population-based cohort study (the Quebec Pregnancy/Children Cohort), their study’s design more closely resembles a post hoc nested case-control study.

Details of the study
Researchers evaluated data from 145,456 singleton full-term infants born alive between January 1, 1998, and December 31, 2009, with antidepressant exposure during pregnancy defined according to trimester and specific antidepressant classes. Children were considered as having autism if they had received at least 1 autism diagnosis between their date of birth and the last date of follow-up.

We perceive several problems in the study’s design and the authors’ conclusions.

Shortcomings of study design
The study results are based on a post hoc analysis. Autism spectrum disorder was not the primary end point of interest in this database. Accordingly, in a secondary end point study, the risk for bias and confounding is substantial. This study design cannot prove causation.^3–5

Exposure is defined by number of antidepressant prescriptions filled. No data regarding adherence (true exposure) are provided. Many women will not take antidepressant drugs as prescribed during pregnancy. It has been reported that antidepressants dispensed to pregnant women during the last 2 trimesters of pregnancy were taken by only 55% of the women.⁶

The specific antidepressant agents and dosages used were not identified, and the study provided no good sense of duration of use. Is it biologically plausible, therefore, to suggest that all antidepressants—with their disparate structures and mechanisms, in all doses, and for various durations of use—have a uniform effect on fetal neurodevelopment?

Notably, in another prescription drug study of 668,468 pregnancies in 2013, investigators found no significant association between prenatal exposure to antidepressants and ASD.⁷

Some data suggest that ASD and depression may share preexisting risk factors.⁸ The increased risk for ASD proposed by Boukhris and colleagues’ study cannot likely be separated from the well-described genetic risk of ASD that might be shared with that of depression.^9,10

The stated hazard ratios (HRs) are all <2.2. Given this study’s design, it is plausible that various biases and confounders account for these findings. True significance of these HRs are suspect unless they exceed 3.0, and there is a greater probability of avoiding a type I error when the risk ratios are greater than 4 to 5.^3,4

What this evidence means for practice
In this registry-based study of an ongoing population-based cohort, the authors suggest a sensational 87% increased risk of ASD with use of antidepressants during pregnancy. While technically correct, the absolute risk (if real) is really less than 1%. Using sound epidemiologic principles, we would advise against speculating on a number needed to harm based on this study design. Such a projection would require a prospective randomized trial.
—Robert P. Kauffman, MD; Teresa Baker, MD; and Thomas W. Hale, PhD

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Presently it seems that anything a pregnant woman ingests can be correlated with a teratology or an unfortunate neurobehavioral outcome. In an era when up to 15% of pregnant women are taking antidepressant therapy, antidepressants are obvious drugs to be correlated with an untoward fetal outcome, despite the fact that untreated maternal depression itself is significantly worse.1

A recent retrospective secondary end point study by Boukhris and colleagues on antidepressant use in pregnancy and the risk of autism spectrum disorder (ASD) in children is an example of correlation without substantive evidence of causation. Although this study received media attention,² it is a “data-dredge” study. While the authors correctly note that the database is derived from a prospective registry-based population-based cohort study (the Quebec Pregnancy/Children Cohort), their study’s design more closely resembles a post hoc nested case-control study.

Details of the study
Researchers evaluated data from 145,456 singleton full-term infants born alive between January 1, 1998, and December 31, 2009, with antidepressant exposure during pregnancy defined according to trimester and specific antidepressant classes. Children were considered as having autism if they had received at least 1 autism diagnosis between their date of birth and the last date of follow-up.

We perceive several problems in the study’s design and the authors’ conclusions.

Shortcomings of study design
The study results are based on a post hoc analysis. Autism spectrum disorder was not the primary end point of interest in this database. Accordingly, in a secondary end point study, the risk for bias and confounding is substantial. This study design cannot prove causation.^3–5

Exposure is defined by number of antidepressant prescriptions filled. No data regarding adherence (true exposure) are provided. Many women will not take antidepressant drugs as prescribed during pregnancy. It has been reported that antidepressants dispensed to pregnant women during the last 2 trimesters of pregnancy were taken by only 55% of the women.⁶

The specific antidepressant agents and dosages used were not identified, and the study provided no good sense of duration of use. Is it biologically plausible, therefore, to suggest that all antidepressants—with their disparate structures and mechanisms, in all doses, and for various durations of use—have a uniform effect on fetal neurodevelopment?

Notably, in another prescription drug study of 668,468 pregnancies in 2013, investigators found no significant association between prenatal exposure to antidepressants and ASD.⁷

Some data suggest that ASD and depression may share preexisting risk factors.⁸ The increased risk for ASD proposed by Boukhris and colleagues’ study cannot likely be separated from the well-described genetic risk of ASD that might be shared with that of depression.^9,10

The stated hazard ratios (HRs) are all <2.2. Given this study’s design, it is plausible that various biases and confounders account for these findings. True significance of these HRs are suspect unless they exceed 3.0, and there is a greater probability of avoiding a type I error when the risk ratios are greater than 4 to 5.^3,4

What this evidence means for practice
In this registry-based study of an ongoing population-based cohort, the authors suggest a sensational 87% increased risk of ASD with use of antidepressants during pregnancy. While technically correct, the absolute risk (if real) is really less than 1%. Using sound epidemiologic principles, we would advise against speculating on a number needed to harm based on this study design. Such a projection would require a prospective randomized trial.
—Robert P. Kauffman, MD; Teresa Baker, MD; and Thomas W. Hale, PhD

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Presently it seems that anything a pregnant woman ingests can be correlated with a teratology or an unfortunate neurobehavioral outcome. In an era when up to 15% of pregnant women are taking antidepressant therapy, antidepressants are obvious drugs to be correlated with an untoward fetal outcome, despite the fact that untreated maternal depression itself is significantly worse.1

A recent retrospective secondary end point study by Boukhris and colleagues on antidepressant use in pregnancy and the risk of autism spectrum disorder (ASD) in children is an example of correlation without substantive evidence of causation. Although this study received media attention,² it is a “data-dredge” study. While the authors correctly note that the database is derived from a prospective registry-based population-based cohort study (the Quebec Pregnancy/Children Cohort), their study’s design more closely resembles a post hoc nested case-control study.

Details of the study
Researchers evaluated data from 145,456 singleton full-term infants born alive between January 1, 1998, and December 31, 2009, with antidepressant exposure during pregnancy defined according to trimester and specific antidepressant classes. Children were considered as having autism if they had received at least 1 autism diagnosis between their date of birth and the last date of follow-up.

We perceive several problems in the study’s design and the authors’ conclusions.

Shortcomings of study design
The study results are based on a post hoc analysis. Autism spectrum disorder was not the primary end point of interest in this database. Accordingly, in a secondary end point study, the risk for bias and confounding is substantial. This study design cannot prove causation.^3–5

Exposure is defined by number of antidepressant prescriptions filled. No data regarding adherence (true exposure) are provided. Many women will not take antidepressant drugs as prescribed during pregnancy. It has been reported that antidepressants dispensed to pregnant women during the last 2 trimesters of pregnancy were taken by only 55% of the women.⁶

The specific antidepressant agents and dosages used were not identified, and the study provided no good sense of duration of use. Is it biologically plausible, therefore, to suggest that all antidepressants—with their disparate structures and mechanisms, in all doses, and for various durations of use—have a uniform effect on fetal neurodevelopment?

Notably, in another prescription drug study of 668,468 pregnancies in 2013, investigators found no significant association between prenatal exposure to antidepressants and ASD.⁷

Some data suggest that ASD and depression may share preexisting risk factors.⁸ The increased risk for ASD proposed by Boukhris and colleagues’ study cannot likely be separated from the well-described genetic risk of ASD that might be shared with that of depression.^9,10

The stated hazard ratios (HRs) are all <2.2. Given this study’s design, it is plausible that various biases and confounders account for these findings. True significance of these HRs are suspect unless they exceed 3.0, and there is a greater probability of avoiding a type I error when the risk ratios are greater than 4 to 5.^3,4

What this evidence means for practice
In this registry-based study of an ongoing population-based cohort, the authors suggest a sensational 87% increased risk of ASD with use of antidepressants during pregnancy. While technically correct, the absolute risk (if real) is really less than 1%. Using sound epidemiologic principles, we would advise against speculating on a number needed to harm based on this study design. Such a projection would require a prospective randomized trial.
—Robert P. Kauffman, MD; Teresa Baker, MD; and Thomas W. Hale, PhD

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Editor’s note: Second in a three-part series.

This month continues my list of important issues that help position your hospitalist group for greatest success. SHM’s “Key Principles and Characteristics of an Effective Hospital Medicine Group” is the definitive list, and this is my much smaller list. Last month, I discussed a culture (or mindset) of practice ownership, a formal system of group decision-making, and the importance of hospitalists themselves playing an active role in recruitment.

Policy and Procedure Manual

New protocols and decisions are being implemented every day. It is impossible to keep track of them, especially the ones that come into play infrequently. For example, many adult hospitalist groups have reached decisions about whether to admit teenagers (e.g., admit only 16 and older or 18 and older, etc.) and whether a hospitalist or obstetrician serves as attending for pregnant women admitted for a medical problem like asthma or pneumonia. But ask everyone in your group to recite the policies, and I bet the answers will differ.

My experience is that only about 20% to 25% of hospitalist groups have written these things down in one place, but all should. It doesn’t need to be fancy and could just start as a Word document in which the lead hospitalist or other designated person writes down a handful of policies and then updates them on an ongoing basis. For example, if a group meeting results in adopting a new policy, it could be added to the document as soon as the meeting adjourns. In some cases, a policy is communicated by email; it would be fine to just copy the body of that email into the manual.

This “living” document could be maintained on a shared computer drive accessible from anywhere in or out of the hospital. That way, when the solo night doctor thinks, “Do we admit 17-year-olds or not?,” she has a place to find the answer right away. And the manual will be a real asset to orient new providers to your practice.

You could start the policy and procedure manual by listing categories, including human resource issues like sick-day policy, how to request days off or scheduling changes, clinical policies like which hip fractures are admitted by hospitalists versus orthopedics, billing and coding practices such as always turn in charges at end of each day, and so on.

I’ve seen useful manuals that are about 10 pages and others that run more than 50 pages.

An Effective Performance Dashboard

Every hospitalist group should have some sort of routine performance report (dashboard) provided in the same format at regular intervals, yet in my experience many, or even most, don’t. It is worth the sometimes considerable effort to develop a meaningful dashboard, and in 2006, SHM published a helpful guide. Even though it is getting old, most of the advice is still very relevant even if the metrics we care most about have changed.

I’m a big believer in providing unblinded performance data to all in the hospitalist group. For example, a report of individual work relative value unit (wRVU) productivity would show productivity for each doctor by name. I think it is healthy to be transparent and ensure all in the group know how others are performing. There is nothing like finding out you are a performance outlier to spark an interest in understanding why and what should be done about it.

Roles for NPs and PAs

Nurse practitioners (NPs) and physician assistants (PAs) can be valuable contributors to a successful hospitalist program, and according to the 2014 State of Hospital Medicine Report, 65% of hospitalist groups nationally had at least one such clinician—an increase over prior years.

While the idea of NP/PAs contributing to the practice is a sound one, my experience is that many groups execute the idea poorly and end up creating a role that can be both professionally unsatisfying and not serve as a platform to contribute effectively to the group. A common scenario is a hospitalist group has trouble with recruiting physicians, so it turns to NP/PAs because they are more readily available. But so often the group has thought little about the precise role NP/PAs will serve (nothing more than “they will help out the docs”). Too often the result is NP/PAs who will say many physician hospitalists simply repeat all the work on each patient, which certainly isn’t a rewarding or cost-effective role.

All should be convinced that the practice is better off in terms of increased overall productivity and/or other benefits by investing in NP/PAs than if those same dollars were instead invested in physician staffing. So one economic model to consider is to calculate the total cost (salary, benefits, malpractice, etc.) for an NP/PA and divide that by those costs for a physician. Let’s say that shows an NP/PA costs half as much as a physician (ranges 40% to 60% in my experience). That staffing cost could be considered in “physician FTE equivalents” so that, for example, a practice with four NP/PAs each costing 50% as much as a physician, or two physician equivalents, could be said to have a total of two physician-equivalent FTEs of staffing. Is the practice better off configured that way, or would it be better to have two physicians instead of the four NP/PAs? The answer will vary, but I think every practice should look at NP/PA staffing through this lens, as well as other considerations, to determine whether they’ve made the best choice.

Having NP/PAs and physicians share rounding duties can be tricky to do efficiently. In my experience, NP/PAs can be better positioned to contribute optimally and find greater professional satisfaction if responsible for a specific portion of the group’s work. For example, at a large hospital, NP/PAs might see all orthopedic consults or psych unit admissions reasonably independently, though with physician backup available. Or NP/PAs could serve as evening (“swing”) shift staffing and manage cross-cover and some admissions. In these roles, the division of labor between NP/PAs and physicians is clearer and allows NP/PAs to contribute most effectively. TH

Editor’s note: Second in a three-part series.

This month continues my list of important issues that help position your hospitalist group for greatest success. SHM’s “Key Principles and Characteristics of an Effective Hospital Medicine Group” is the definitive list, and this is my much smaller list. Last month, I discussed a culture (or mindset) of practice ownership, a formal system of group decision-making, and the importance of hospitalists themselves playing an active role in recruitment.

Policy and Procedure Manual

New protocols and decisions are being implemented every day. It is impossible to keep track of them, especially the ones that come into play infrequently. For example, many adult hospitalist groups have reached decisions about whether to admit teenagers (e.g., admit only 16 and older or 18 and older, etc.) and whether a hospitalist or obstetrician serves as attending for pregnant women admitted for a medical problem like asthma or pneumonia. But ask everyone in your group to recite the policies, and I bet the answers will differ.

My experience is that only about 20% to 25% of hospitalist groups have written these things down in one place, but all should. It doesn’t need to be fancy and could just start as a Word document in which the lead hospitalist or other designated person writes down a handful of policies and then updates them on an ongoing basis. For example, if a group meeting results in adopting a new policy, it could be added to the document as soon as the meeting adjourns. In some cases, a policy is communicated by email; it would be fine to just copy the body of that email into the manual.

This “living” document could be maintained on a shared computer drive accessible from anywhere in or out of the hospital. That way, when the solo night doctor thinks, “Do we admit 17-year-olds or not?,” she has a place to find the answer right away. And the manual will be a real asset to orient new providers to your practice.

You could start the policy and procedure manual by listing categories, including human resource issues like sick-day policy, how to request days off or scheduling changes, clinical policies like which hip fractures are admitted by hospitalists versus orthopedics, billing and coding practices such as always turn in charges at end of each day, and so on.

I’ve seen useful manuals that are about 10 pages and others that run more than 50 pages.

An Effective Performance Dashboard

Every hospitalist group should have some sort of routine performance report (dashboard) provided in the same format at regular intervals, yet in my experience many, or even most, don’t. It is worth the sometimes considerable effort to develop a meaningful dashboard, and in 2006, SHM published a helpful guide. Even though it is getting old, most of the advice is still very relevant even if the metrics we care most about have changed.

I’m a big believer in providing unblinded performance data to all in the hospitalist group. For example, a report of individual work relative value unit (wRVU) productivity would show productivity for each doctor by name. I think it is healthy to be transparent and ensure all in the group know how others are performing. There is nothing like finding out you are a performance outlier to spark an interest in understanding why and what should be done about it.

Roles for NPs and PAs

Nurse practitioners (NPs) and physician assistants (PAs) can be valuable contributors to a successful hospitalist program, and according to the 2014 State of Hospital Medicine Report, 65% of hospitalist groups nationally had at least one such clinician—an increase over prior years.

While the idea of NP/PAs contributing to the practice is a sound one, my experience is that many groups execute the idea poorly and end up creating a role that can be both professionally unsatisfying and not serve as a platform to contribute effectively to the group. A common scenario is a hospitalist group has trouble with recruiting physicians, so it turns to NP/PAs because they are more readily available. But so often the group has thought little about the precise role NP/PAs will serve (nothing more than “they will help out the docs”). Too often the result is NP/PAs who will say many physician hospitalists simply repeat all the work on each patient, which certainly isn’t a rewarding or cost-effective role.

All should be convinced that the practice is better off in terms of increased overall productivity and/or other benefits by investing in NP/PAs than if those same dollars were instead invested in physician staffing. So one economic model to consider is to calculate the total cost (salary, benefits, malpractice, etc.) for an NP/PA and divide that by those costs for a physician. Let’s say that shows an NP/PA costs half as much as a physician (ranges 40% to 60% in my experience). That staffing cost could be considered in “physician FTE equivalents” so that, for example, a practice with four NP/PAs each costing 50% as much as a physician, or two physician equivalents, could be said to have a total of two physician-equivalent FTEs of staffing. Is the practice better off configured that way, or would it be better to have two physicians instead of the four NP/PAs? The answer will vary, but I think every practice should look at NP/PA staffing through this lens, as well as other considerations, to determine whether they’ve made the best choice.

Having NP/PAs and physicians share rounding duties can be tricky to do efficiently. In my experience, NP/PAs can be better positioned to contribute optimally and find greater professional satisfaction if responsible for a specific portion of the group’s work. For example, at a large hospital, NP/PAs might see all orthopedic consults or psych unit admissions reasonably independently, though with physician backup available. Or NP/PAs could serve as evening (“swing”) shift staffing and manage cross-cover and some admissions. In these roles, the division of labor between NP/PAs and physicians is clearer and allows NP/PAs to contribute most effectively. TH

Editor’s note: Second in a three-part series.

This month continues my list of important issues that help position your hospitalist group for greatest success. SHM’s “Key Principles and Characteristics of an Effective Hospital Medicine Group” is the definitive list, and this is my much smaller list. Last month, I discussed a culture (or mindset) of practice ownership, a formal system of group decision-making, and the importance of hospitalists themselves playing an active role in recruitment.

Policy and Procedure Manual

New protocols and decisions are being implemented every day. It is impossible to keep track of them, especially the ones that come into play infrequently. For example, many adult hospitalist groups have reached decisions about whether to admit teenagers (e.g., admit only 16 and older or 18 and older, etc.) and whether a hospitalist or obstetrician serves as attending for pregnant women admitted for a medical problem like asthma or pneumonia. But ask everyone in your group to recite the policies, and I bet the answers will differ.

My experience is that only about 20% to 25% of hospitalist groups have written these things down in one place, but all should. It doesn’t need to be fancy and could just start as a Word document in which the lead hospitalist or other designated person writes down a handful of policies and then updates them on an ongoing basis. For example, if a group meeting results in adopting a new policy, it could be added to the document as soon as the meeting adjourns. In some cases, a policy is communicated by email; it would be fine to just copy the body of that email into the manual.

This “living” document could be maintained on a shared computer drive accessible from anywhere in or out of the hospital. That way, when the solo night doctor thinks, “Do we admit 17-year-olds or not?,” she has a place to find the answer right away. And the manual will be a real asset to orient new providers to your practice.

You could start the policy and procedure manual by listing categories, including human resource issues like sick-day policy, how to request days off or scheduling changes, clinical policies like which hip fractures are admitted by hospitalists versus orthopedics, billing and coding practices such as always turn in charges at end of each day, and so on.

I’ve seen useful manuals that are about 10 pages and others that run more than 50 pages.

An Effective Performance Dashboard

Every hospitalist group should have some sort of routine performance report (dashboard) provided in the same format at regular intervals, yet in my experience many, or even most, don’t. It is worth the sometimes considerable effort to develop a meaningful dashboard, and in 2006, SHM published a helpful guide. Even though it is getting old, most of the advice is still very relevant even if the metrics we care most about have changed.

I’m a big believer in providing unblinded performance data to all in the hospitalist group. For example, a report of individual work relative value unit (wRVU) productivity would show productivity for each doctor by name. I think it is healthy to be transparent and ensure all in the group know how others are performing. There is nothing like finding out you are a performance outlier to spark an interest in understanding why and what should be done about it.

Roles for NPs and PAs

Nurse practitioners (NPs) and physician assistants (PAs) can be valuable contributors to a successful hospitalist program, and according to the 2014 State of Hospital Medicine Report, 65% of hospitalist groups nationally had at least one such clinician—an increase over prior years.

While the idea of NP/PAs contributing to the practice is a sound one, my experience is that many groups execute the idea poorly and end up creating a role that can be both professionally unsatisfying and not serve as a platform to contribute effectively to the group. A common scenario is a hospitalist group has trouble with recruiting physicians, so it turns to NP/PAs because they are more readily available. But so often the group has thought little about the precise role NP/PAs will serve (nothing more than “they will help out the docs”). Too often the result is NP/PAs who will say many physician hospitalists simply repeat all the work on each patient, which certainly isn’t a rewarding or cost-effective role.

All should be convinced that the practice is better off in terms of increased overall productivity and/or other benefits by investing in NP/PAs than if those same dollars were instead invested in physician staffing. So one economic model to consider is to calculate the total cost (salary, benefits, malpractice, etc.) for an NP/PA and divide that by those costs for a physician. Let’s say that shows an NP/PA costs half as much as a physician (ranges 40% to 60% in my experience). That staffing cost could be considered in “physician FTE equivalents” so that, for example, a practice with four NP/PAs each costing 50% as much as a physician, or two physician equivalents, could be said to have a total of two physician-equivalent FTEs of staffing. Is the practice better off configured that way, or would it be better to have two physicians instead of the four NP/PAs? The answer will vary, but I think every practice should look at NP/PA staffing through this lens, as well as other considerations, to determine whether they’ve made the best choice.

Having NP/PAs and physicians share rounding duties can be tricky to do efficiently. In my experience, NP/PAs can be better positioned to contribute optimally and find greater professional satisfaction if responsible for a specific portion of the group’s work. For example, at a large hospital, NP/PAs might see all orthopedic consults or psych unit admissions reasonably independently, though with physician backup available. Or NP/PAs could serve as evening (“swing”) shift staffing and manage cross-cover and some admissions. In these roles, the division of labor between NP/PAs and physicians is clearer and allows NP/PAs to contribute most effectively. TH

SAN DIEGO – Prescription medications are a major contributor to unnecessary health care spending.

According to data from the Centers for Medicare & Medicaid Services, retail spending on prescription drugs grew 12.2% to $297.7 billion in 2014, compared with the 2.4% growth in 2013. That’s one key reason why medication reconciliation should be performed at every inpatient and outpatient visit and prior to every hospital discharge, Dr. Aparna Kamath said in a video interview at the annual meeting of the Society of Hospital Medicine. “The focus should be on clear indications for each medication prescribed, substitution of generics when possible, and consideration of an individual patient’s insurance formulary and ability to meet out-of-pocket costs.”

A recent article in JAMA Internal Medicine discussed the practice of “deprescribing” in an effort to reduce the number of prescribed drugs (2015;175[5]:827-34). According to Dr. Kamath of the department of medicine at Duke University Health System, Durham, N.C., who was not involved with the article, deprescribing “means safely narrowing, discontinuing, or withdrawing medications for our patients. It has been shown that deprescribing might actually improve outpatient outcomes by making the medication list safer for our patients and hopefully also improve medication adherence by making them more affordable for our patients.”

The study authors proposed a five-step protocol for deprescribing:

• Ascertain all drugs the patient is currently taking and the reasons for each one.

• Consider overall risk of drug-induced harm in individual patients in determining the required intensity of deprescribing intervention.

• Assess each drug in regard to its current or future benefit potential, compared with current or future harm or burden potential.

• Prioritize drugs for discontinuation that have the lowest benefit-harm ratio and lowest likelihood of adverse withdrawal reactions or disease rebound syndromes.

• Implement a discontinuation regimen and monitor patients closely for improvement in outcomes or onset of adverse effects.

According to Dr. Kamath, other medication reconciliation strategies include referring patients to a social worker to inquire about drug assistance programs; following up with the patient’s primary care or prescribing physician; partnering with pharmacists; and educating patients about variance in prescription drug prices. “I think it’s important to inform the patients that these drugs are priced differently in different pharmacies,” she said. “According to Consumer Reports, we should ask the patient to shop around, maybe call the medication pharmacies in their local area to find out where they can find the drugs at a most affordable price. We can also advise our patients to ask for discounts or coupons, and check for monthly price changes,” Dr. Kamath said. She recommended the following websites, which allow patients to compare costs and/or inquire about discounts:

• www.goodrx.com.

• https://www.rxpricequotes.com.

• www.needymeds.org.

• www.pparx.org.

• www.rxoutreach.org.

• https://www.blinkhealth.com.

Dr. Kamath reported having no financial disclosures.

dbrunk@frontlinemedcom.com

SAN DIEGO – Prescription medications are a major contributor to unnecessary health care spending.

According to data from the Centers for Medicare & Medicaid Services, retail spending on prescription drugs grew 12.2% to $297.7 billion in 2014, compared with the 2.4% growth in 2013. That’s one key reason why medication reconciliation should be performed at every inpatient and outpatient visit and prior to every hospital discharge, Dr. Aparna Kamath said in a video interview at the annual meeting of the Society of Hospital Medicine. “The focus should be on clear indications for each medication prescribed, substitution of generics when possible, and consideration of an individual patient’s insurance formulary and ability to meet out-of-pocket costs.”

A recent article in JAMA Internal Medicine discussed the practice of “deprescribing” in an effort to reduce the number of prescribed drugs (2015;175[5]:827-34). According to Dr. Kamath of the department of medicine at Duke University Health System, Durham, N.C., who was not involved with the article, deprescribing “means safely narrowing, discontinuing, or withdrawing medications for our patients. It has been shown that deprescribing might actually improve outpatient outcomes by making the medication list safer for our patients and hopefully also improve medication adherence by making them more affordable for our patients.”

The study authors proposed a five-step protocol for deprescribing:

• Ascertain all drugs the patient is currently taking and the reasons for each one.

• Consider overall risk of drug-induced harm in individual patients in determining the required intensity of deprescribing intervention.

• Assess each drug in regard to its current or future benefit potential, compared with current or future harm or burden potential.

• Prioritize drugs for discontinuation that have the lowest benefit-harm ratio and lowest likelihood of adverse withdrawal reactions or disease rebound syndromes.

• Implement a discontinuation regimen and monitor patients closely for improvement in outcomes or onset of adverse effects.

According to Dr. Kamath, other medication reconciliation strategies include referring patients to a social worker to inquire about drug assistance programs; following up with the patient’s primary care or prescribing physician; partnering with pharmacists; and educating patients about variance in prescription drug prices. “I think it’s important to inform the patients that these drugs are priced differently in different pharmacies,” she said. “According to Consumer Reports, we should ask the patient to shop around, maybe call the medication pharmacies in their local area to find out where they can find the drugs at a most affordable price. We can also advise our patients to ask for discounts or coupons, and check for monthly price changes,” Dr. Kamath said. She recommended the following websites, which allow patients to compare costs and/or inquire about discounts:

• www.goodrx.com.

• https://www.rxpricequotes.com.

• www.needymeds.org.

• www.pparx.org.

• www.rxoutreach.org.

• https://www.blinkhealth.com.

Dr. Kamath reported having no financial disclosures.

dbrunk@frontlinemedcom.com

SAN DIEGO – Prescription medications are a major contributor to unnecessary health care spending.

According to data from the Centers for Medicare & Medicaid Services, retail spending on prescription drugs grew 12.2% to $297.7 billion in 2014, compared with the 2.4% growth in 2013. That’s one key reason why medication reconciliation should be performed at every inpatient and outpatient visit and prior to every hospital discharge, Dr. Aparna Kamath said in a video interview at the annual meeting of the Society of Hospital Medicine. “The focus should be on clear indications for each medication prescribed, substitution of generics when possible, and consideration of an individual patient’s insurance formulary and ability to meet out-of-pocket costs.”

A recent article in JAMA Internal Medicine discussed the practice of “deprescribing” in an effort to reduce the number of prescribed drugs (2015;175[5]:827-34). According to Dr. Kamath of the department of medicine at Duke University Health System, Durham, N.C., who was not involved with the article, deprescribing “means safely narrowing, discontinuing, or withdrawing medications for our patients. It has been shown that deprescribing might actually improve outpatient outcomes by making the medication list safer for our patients and hopefully also improve medication adherence by making them more affordable for our patients.”

The study authors proposed a five-step protocol for deprescribing:

• Ascertain all drugs the patient is currently taking and the reasons for each one.

• Consider overall risk of drug-induced harm in individual patients in determining the required intensity of deprescribing intervention.

• Assess each drug in regard to its current or future benefit potential, compared with current or future harm or burden potential.

• Prioritize drugs for discontinuation that have the lowest benefit-harm ratio and lowest likelihood of adverse withdrawal reactions or disease rebound syndromes.

• Implement a discontinuation regimen and monitor patients closely for improvement in outcomes or onset of adverse effects.

According to Dr. Kamath, other medication reconciliation strategies include referring patients to a social worker to inquire about drug assistance programs; following up with the patient’s primary care or prescribing physician; partnering with pharmacists; and educating patients about variance in prescription drug prices. “I think it’s important to inform the patients that these drugs are priced differently in different pharmacies,” she said. “According to Consumer Reports, we should ask the patient to shop around, maybe call the medication pharmacies in their local area to find out where they can find the drugs at a most affordable price. We can also advise our patients to ask for discounts or coupons, and check for monthly price changes,” Dr. Kamath said. She recommended the following websites, which allow patients to compare costs and/or inquire about discounts:

• www.goodrx.com.

• https://www.rxpricequotes.com.

• www.needymeds.org.

• www.pparx.org.

• www.rxoutreach.org.

• https://www.blinkhealth.com.

Dr. Kamath reported having no financial disclosures.

dbrunk@frontlinemedcom.com

It has been two years since the “Key Characteristics” was published in the Journal of Hospital Medicine.1 The SHM board of directors envisions the Key Characteristics as a tool to improve the performance of hospital medicine groups (HMGs) and “raise the bar” for the specialty.

At SHM’s annual meeting (www.hospitalmedicine2016.org) next month in San Diego, the Key Characteristics will provide the framework for the Practice Management Pre-Course (Sunday, March 6). The pre-course faculty, of which I am a member, will address all 10 principles of the Key Characteristics (see Table 1), including case studies and practical ideas for performance improvement. As a preview, I will cover Principle 6 and provide a few practical tips that you can implement in your practice.

For a more comprehensive discussion of all the Key Characteristics and how to use them, visit the SHM website (visit www.hospitalmedicine.org, then click on the “Practice Management” icon at the top of the landing page).

Characteristic 6.1

The HMG has systems in place to ensure effective and reliable communication with the patient’s primary care physician and/or other provider(s) involved in the patient’s care in the non-acute-care setting.

Practical tip: Your practice probably has administrative procedures in place to notify PCPs that their patient has been admitted to the hospital, using the electronic health record or secure email, if available, or messaging by fax/phone. But are you receiving vital information from the PCP’s office or from the nursing facility? Establish a protocol for obtaining key history, medication, and diagnostic testing information from these sources. One approach is to request this information when notifying the PCP of the patient’s admission.

Practical tip: Use the “grocery store test” to determine when to contact the PCP during the hospital stay. For example, if the PCP were to run into a family member of the patient in the grocery store, would the PCP want to have learned of a change in the patient’s condition in advance of the family member encounter?

Practical tip: Because reaching skilling nursing facility (SNF) physicians/providers (SNFists) can be challenging, hold an annual social event so that they can meet the hospitalists in your practice face-to-face. At the event, exchange cellphone or beeper numbers with the SNFists, and establish an explicit understanding of how handoffs will occur, especially for high-risk patients.

Characteristic 6.2

The HMG contributes in meaningful ways to the hospital’s efforts to improve care transitions.

Because of readmissions penalties, every hospital in the country is concerned with care transitions and avoiding readmissions. But HMGs want to know which interventions reliably decrease readmissions. The Commonwealth Fund recently released the results of a study of 428 hospitals that participated in national efforts to reduce readmissions, including the State Action on Avoidable Rehospitalizations (STAAR) and Hospital to Home (H2H) initiatives. The study’s primary conclusions were as follows:

• The only strategy consistently associated with reduced risk-standardized readmissions was discharging patients with their appointments already made.2 No other single strategy was reliably associated with a reduction.
• Hospitals that implemented three or more readmission reduction strategies showed a significant decrease in risk-standardized readmissions versus those implementing fewer than three.

Practical tip: Ensure patients leave the hospital with a PCP follow-up appointment made and in hand.

Practical tip: Work with your hospital on at least three definitive strategies to reduce readmissions.

Implement to Improve Your HMG

The basic and updated 2015 versions of the “Key Principles and Characteristics of an Effective Hospital Medicine Group” can be downloaded from the SHM website (visit www.hospitalmedicine.org, then click on the “Practice Management” icon at the top of the landing page). The updated 2015 version provides definitions and requirements and suggested approaches to demonstrating the characteristic that enables the HMG to conduct a comprehensive self-assessment.

In addition, there is a new tool intended for use by hospitalist practice administrators that cross-references the Key Characteristics with another tool, The Core Competencies for a Hospitalist Practice Administrator. TH

References

1. Cawley P, Deitelzweig S, Flores L, et al. The key principles and characteristics of an effective hospital medicine group: an assessment guide for hospitals and hospitalists. J Hosp Med. 2014;9(2):123-128.
2. Bradley EH, Brewster A, Curry L. National campaigns to reduce readmissions: what have we learned? The Commonwealth Fund website. Available at: commonwealthfund.org/publications/blog/2015/oct/national-campaigns-to-reduce-readmissions. Accessed December 28, 2015.

It has been two years since the “Key Characteristics” was published in the Journal of Hospital Medicine.1 The SHM board of directors envisions the Key Characteristics as a tool to improve the performance of hospital medicine groups (HMGs) and “raise the bar” for the specialty.

At SHM’s annual meeting (www.hospitalmedicine2016.org) next month in San Diego, the Key Characteristics will provide the framework for the Practice Management Pre-Course (Sunday, March 6). The pre-course faculty, of which I am a member, will address all 10 principles of the Key Characteristics (see Table 1), including case studies and practical ideas for performance improvement. As a preview, I will cover Principle 6 and provide a few practical tips that you can implement in your practice.

For a more comprehensive discussion of all the Key Characteristics and how to use them, visit the SHM website (visit www.hospitalmedicine.org, then click on the “Practice Management” icon at the top of the landing page).

Characteristic 6.1

The HMG has systems in place to ensure effective and reliable communication with the patient’s primary care physician and/or other provider(s) involved in the patient’s care in the non-acute-care setting.

Practical tip: Your practice probably has administrative procedures in place to notify PCPs that their patient has been admitted to the hospital, using the electronic health record or secure email, if available, or messaging by fax/phone. But are you receiving vital information from the PCP’s office or from the nursing facility? Establish a protocol for obtaining key history, medication, and diagnostic testing information from these sources. One approach is to request this information when notifying the PCP of the patient’s admission.

Practical tip: Use the “grocery store test” to determine when to contact the PCP during the hospital stay. For example, if the PCP were to run into a family member of the patient in the grocery store, would the PCP want to have learned of a change in the patient’s condition in advance of the family member encounter?

Practical tip: Because reaching skilling nursing facility (SNF) physicians/providers (SNFists) can be challenging, hold an annual social event so that they can meet the hospitalists in your practice face-to-face. At the event, exchange cellphone or beeper numbers with the SNFists, and establish an explicit understanding of how handoffs will occur, especially for high-risk patients.

Characteristic 6.2

The HMG contributes in meaningful ways to the hospital’s efforts to improve care transitions.

Because of readmissions penalties, every hospital in the country is concerned with care transitions and avoiding readmissions. But HMGs want to know which interventions reliably decrease readmissions. The Commonwealth Fund recently released the results of a study of 428 hospitals that participated in national efforts to reduce readmissions, including the State Action on Avoidable Rehospitalizations (STAAR) and Hospital to Home (H2H) initiatives. The study’s primary conclusions were as follows:

• The only strategy consistently associated with reduced risk-standardized readmissions was discharging patients with their appointments already made.2 No other single strategy was reliably associated with a reduction.
• Hospitals that implemented three or more readmission reduction strategies showed a significant decrease in risk-standardized readmissions versus those implementing fewer than three.

Practical tip: Ensure patients leave the hospital with a PCP follow-up appointment made and in hand.

Practical tip: Work with your hospital on at least three definitive strategies to reduce readmissions.

Implement to Improve Your HMG

The basic and updated 2015 versions of the “Key Principles and Characteristics of an Effective Hospital Medicine Group” can be downloaded from the SHM website (visit www.hospitalmedicine.org, then click on the “Practice Management” icon at the top of the landing page). The updated 2015 version provides definitions and requirements and suggested approaches to demonstrating the characteristic that enables the HMG to conduct a comprehensive self-assessment.

In addition, there is a new tool intended for use by hospitalist practice administrators that cross-references the Key Characteristics with another tool, The Core Competencies for a Hospitalist Practice Administrator. TH

References

1. Cawley P, Deitelzweig S, Flores L, et al. The key principles and characteristics of an effective hospital medicine group: an assessment guide for hospitals and hospitalists. J Hosp Med. 2014;9(2):123-128.
2. Bradley EH, Brewster A, Curry L. National campaigns to reduce readmissions: what have we learned? The Commonwealth Fund website. Available at: commonwealthfund.org/publications/blog/2015/oct/national-campaigns-to-reduce-readmissions. Accessed December 28, 2015.

It has been two years since the “Key Characteristics” was published in the Journal of Hospital Medicine.1 The SHM board of directors envisions the Key Characteristics as a tool to improve the performance of hospital medicine groups (HMGs) and “raise the bar” for the specialty.

At SHM’s annual meeting (www.hospitalmedicine2016.org) next month in San Diego, the Key Characteristics will provide the framework for the Practice Management Pre-Course (Sunday, March 6). The pre-course faculty, of which I am a member, will address all 10 principles of the Key Characteristics (see Table 1), including case studies and practical ideas for performance improvement. As a preview, I will cover Principle 6 and provide a few practical tips that you can implement in your practice.

For a more comprehensive discussion of all the Key Characteristics and how to use them, visit the SHM website (visit www.hospitalmedicine.org, then click on the “Practice Management” icon at the top of the landing page).

Characteristic 6.1

The HMG has systems in place to ensure effective and reliable communication with the patient’s primary care physician and/or other provider(s) involved in the patient’s care in the non-acute-care setting.

Practical tip: Your practice probably has administrative procedures in place to notify PCPs that their patient has been admitted to the hospital, using the electronic health record or secure email, if available, or messaging by fax/phone. But are you receiving vital information from the PCP’s office or from the nursing facility? Establish a protocol for obtaining key history, medication, and diagnostic testing information from these sources. One approach is to request this information when notifying the PCP of the patient’s admission.

Practical tip: Use the “grocery store test” to determine when to contact the PCP during the hospital stay. For example, if the PCP were to run into a family member of the patient in the grocery store, would the PCP want to have learned of a change in the patient’s condition in advance of the family member encounter?

Practical tip: Because reaching skilling nursing facility (SNF) physicians/providers (SNFists) can be challenging, hold an annual social event so that they can meet the hospitalists in your practice face-to-face. At the event, exchange cellphone or beeper numbers with the SNFists, and establish an explicit understanding of how handoffs will occur, especially for high-risk patients.

Characteristic 6.2

The HMG contributes in meaningful ways to the hospital’s efforts to improve care transitions.

Because of readmissions penalties, every hospital in the country is concerned with care transitions and avoiding readmissions. But HMGs want to know which interventions reliably decrease readmissions. The Commonwealth Fund recently released the results of a study of 428 hospitals that participated in national efforts to reduce readmissions, including the State Action on Avoidable Rehospitalizations (STAAR) and Hospital to Home (H2H) initiatives. The study’s primary conclusions were as follows:

• The only strategy consistently associated with reduced risk-standardized readmissions was discharging patients with their appointments already made.2 No other single strategy was reliably associated with a reduction.
• Hospitals that implemented three or more readmission reduction strategies showed a significant decrease in risk-standardized readmissions versus those implementing fewer than three.

Practical tip: Ensure patients leave the hospital with a PCP follow-up appointment made and in hand.

Practical tip: Work with your hospital on at least three definitive strategies to reduce readmissions.

Implement to Improve Your HMG

The basic and updated 2015 versions of the “Key Principles and Characteristics of an Effective Hospital Medicine Group” can be downloaded from the SHM website (visit www.hospitalmedicine.org, then click on the “Practice Management” icon at the top of the landing page). The updated 2015 version provides definitions and requirements and suggested approaches to demonstrating the characteristic that enables the HMG to conduct a comprehensive self-assessment.

In addition, there is a new tool intended for use by hospitalist practice administrators that cross-references the Key Characteristics with another tool, The Core Competencies for a Hospitalist Practice Administrator. TH

References

1. Cawley P, Deitelzweig S, Flores L, et al. The key principles and characteristics of an effective hospital medicine group: an assessment guide for hospitals and hospitalists. J Hosp Med. 2014;9(2):123-128.
2. Bradley EH, Brewster A, Curry L. National campaigns to reduce readmissions: what have we learned? The Commonwealth Fund website. Available at: commonwealthfund.org/publications/blog/2015/oct/national-campaigns-to-reduce-readmissions. Accessed December 28, 2015.

LOS ANGELES – The use of endovascular thrombectomy in the United States to treat appropriate patients with acute ischemic stroke mushroomed during the past year, following several early-2015 reports that collectively documented the dramatic clinical benefit of the treatment.

As endovascular thrombectomy use grows, stroke centers are also refining and reshaping delivery of the treatment in concert with administration of intravenous tissue plasminogen activator (TPA; alteplase; Activase), which remains a key partner in producing best outcomes for acute ischemic-stroke patients with a proximal occlusion of a large cerebral artery. Collapsing delivery of the two treatments into a more seamless and streamlined process shaves critical minutes to treatment delivery, an approach called parallel processing. Recent findings have also emboldened stroke specialists to seriously consider simplifying the brain imaging that stroke patients receive prior to these treatments, a step that could further cut time to intervention while also making thrombectomy even more widely available.

Use of thrombectomy surges

The biggest endovascular thrombectomy news of the past year is how it has taken off for treating selected patients with acute ischemic stroke. “The rollout over the past year has been explosive. Everything pretty much shut down after the negative trial results in 2013, but now more hospitals are offering thrombectomy,” said Dr. Thomas A. Kent, professor of neurology and director of stroke research and education at Baylor College of Medicine in Houston, in an interview at the International Stroke Conference sponsored by the American Heart Association.

The best documentation of this surge came in a poster presented at the conference by researchers at the University of California, San Francisco. They analyzed data on treatment of 357,973 patients with acute ischemic stroke who were hospitalized at any one of 161 U.S. academic medical centers during October 2009-July 2015 and included in the University Healthsystem Consortium database. They tracked the percentage of patients treated endovascularly during each calendar quarter of the study period.

During 2009-2013, use of endovascular treatment rose steadily but gradually, from 1.5% of stroke patients in 2009 to 3.1% during the fourth quarter of 2012. Then, following three reports of no benefit from endovascular treatment presented at the International Stroke Conference in February 2013 – the IMS III, MR RESCUE, and SYNTHESIS trials – the endovascular rate dropped immediately and quickly bottomed out at a level of 2.6% that remained steady through the third quarter of 2014. But when the positive endovascular results from the MR CLEAN study became public in the final week of 2014, endovascular use began to quickly rise again, and then began to skyrocket during the first quarter of 2015 with three additional positive trial results reported during the Stroke Conference in February 2015. By the end of the second quarter of 2015, usage stood at 4.7%, representing a projected year-over-year increase of about 150% for all of 2015, compared with 2014, reported Dr. Anthony S. Kim, a vascular neurologist and medical director of the Stroke Center at the University of California, San Francisco, and his associates.

To put these percentages in perspective, experts estimate that roughly 10%-15% of all stroke patients qualify for thrombectomy intervention.

Their data also showed that the percentage of hospitals included in the database that performed endovascular therapies for stroke rose steadily from about 40% of centers in 2009 to nearly 60% by mid-2015.

“Endovascular therapy with newer-generation devices is increasingly part of standard treatment for acute ischemic stroke,” they said in their poster. In addition, they cited a “new urgency to evaluate regional access to embolectomy [another name for thrombectomy] nationally and to identify system-based solutions to improve access in underserved areas.”

Several stroke experts interviewed at the conference added their own anecdotal view of thrombectomy’s rapidly expanding use for appropriate acute ischemic stroke patients during 2015, and the need for continued effort to broaden its U.S. availability.

“The number of thrombectomies fell off after the negative 2013 trials and stayed flat until a year ago, but then jumped up. It has been very dramatic,” said Dr. Wade S. Smith, professor of neurology and director of the neurovascular service at the University of California, San Francisco.

“Thrombectomy use tremendously increased since February 2015,” said Dr. Mark J. Alberts, professor of neurology and medical director of the neurology service at the University of Texas Southwestern Medical Center in Dallas, in a video interview during the conference. But despite this growth, “the major challenge [today] is geography;” that is, reaching patients in suburban and rural areas who are not as close to the primarily urban medical centers that currently offer the procedure.

“We now have about 100 certified comprehensive stroke centers in the U.S.,” and by definition comprehensive stroke centers have the capability of treating patients with endovascular thrombectomy, noted Dr. Jeffrey Saver, professor of neurology and director of the stroke unit at the University of California, Los Angeles.

“Certification of these centers did not begin until about 2-3 years ago. But we probably need 300-400 of these centers” to provide thrombectomy to most U.S. stroke patients, he said. “A lot of additional hospitals are close to certification. I anticipate that over the next 1-2 years we will be in the neighborhood of having the number of centers we need,” Dr. Saver said in an interview.

Making thrombectomy better

In addition to expanding availability, the specifics of how endovascular thrombectomy gets delivered is evolving. A major trend is movement toward a “parallel processing” model, in which patients with an acute clinical presentation of a stroke amenable for endovascular treatment simultaneously undergo CT angiography to confirm and localize the large-artery clot causing their stroke, receive intravenous TPA, and undergo preparation for the endovascular access needed to remove the clot.

A pooled analysis of the recent, positive endovascular thrombectomy trials that was presented at the conference showed how quick you need to be to obtain a benefit from the procedures. “This gives us a starting point to further improve the target metrics for imaging and puncture times,” Dr. Saver said. “We want to shorten door-to-needle times for TPA and door-to-puncture times for thrombectomy, and the processes that need to be addressed for rapid delivery of both of these are very similar. We need for patients to only make a pit stop in the ED; we need to have the catheterization team ready to go in the thrombectomy suite within 30 minutes; and we need to emphasize speed in access to the target clot rather than time-consuming diagnostic angiography.”

“We now face the issue of how to best integrate TPA treatment and clot removal.” Dr. Kent said. “People are still trying to work that out. With parallel processing there is some overuse of resources: Some patients recover with TPA alone and don’t need thrombectomy. We are getting closer to the cardiology model of MI treatment. It’s now clear that there needs to be a simple, safe, effective way to do both TPA treatment and thrombectomy. We need to model ourselves on the cardiology experience.”

“If you can deal with the TPA decision in the same room without moving patients from room to room, from a scanner to a catheterization suite, you can really shorten the time to treatment,” Dr. Smith explained. “This is identical to the model that cardiologists have developed. We should now consider taking stroke patients directly to the angiography room in addition to administering TPA. We still need cross-sectional imaging, but the quality of the image from an angiography suite is probably sufficient to make a TPA decision. So you can start TPA while you are getting arterial access. The idea is simultaneous approaches to the patient instead of serial.”

“The whole system moves at the same time to eliminate wasted time,” Dr. Alberts summed up.

One of the big questions that has come up in this effort to speed up treatment and carve the quickest route to endovascular thrombectomy is whether TPA remains necessary. The skeptics’ position is, why waste time administering TPA if you’re also going to take out the offending clot?

The answer, at least for now, is that all signs indicate that giving TPA helps and is worth delivering.

“The 2015 thrombectomy trials had big differences among them in the dosage of TPA administered, and in the percentage of patients who received TPA. When 100% of patients received TPA they had the best outcomes,” Dr. Kent said. “There was a clear synergistic relationship between thrombectomy and TPA. There has been a trend to think about sending patients straight to thrombectomy and skipping TPA, but my colleagues and I think that we need to hold off on doing that. For now, if a patient is eligible to receive TPA they should get it and then quickly move to endovascular therapy. We are not yet ready to know it’s okay to go straight to endovascular treatment. In SWIFT-PRIME, it was pretty clear that the good outcomes were attributable to both [thrombectomy plus TPA]. Treating patients with TPA helps soften the clot to make it easier to remove, and improves flow through collateral arteries.”

“Our data in Memphis show that patients do better with thrombectomy plus intravenous TPA than on TPA alone,” agreed Dr. Lucas Elijovich, a neurologist at the University of Tennessee Health Science Center in Memphis, in an interview.

Simpler imaging also saves time

Although it’s not yet proven, another new wrinkle in working up acute ischemic-stroke patients for TPA and thrombectomy treatment is the idea that simpler and more widely available CT imaging, especially CT angiography of cerebral arteries, may suffice for confirming and localizing the culprit clot.

This concept received a significant boost at the International Stroke Conference in data reported from the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) trial, yet another study that compared treatment with TPA alone with TPA plus endovascular thrombectomy, this time in 65 randomized patients treated at any of 11 U.K. centers. PISTE had a low enrollment level because the trial stopped prematurely, in July 2015, following the news that several fully completed trials had collectively established the superiority of endovascular thrombectomy plus TPA, thereby making it unethical to continue yet another randomized study.

This premature stoppage prevented PISTE from itself producing a statistically significant difference for its primary efficacy endpoint in favor of the combined treatment, although the results did show a nominal advantage to using thrombectomy plus TPA over TPA alone that was fully consistent with the other studies, Dr. Keith W. Muir reported at the conference.

But what made the PISTE results especially notable was that the trial achieved this consistent outcome with a “simpler” imaging protocol for patients during their workup that used only CT angiography, avoiding the cerebral CT perfusion imaging or MRI used in several of the other TPA-plus-thrombectomy versus TPA-only trials, noted Dr. Muir, professor of neuroscience and head of the stroke imaging group at the University of Glasgow.

“PISTE raises the question of how much imaging is necessary,” Dr. Kent commented.

“The PISTE results are exciting. A lot of us believe that all we need to know is that there is a blockage in a target vessel,” Dr. Smith said. “If we have that information, then we can identify a population of patients who will benefit from [thrombectomy]. CT angiography is simple and can easily fit into work flows.”

“PISTE used a very simple imaging system that makes thrombectomy even more applicable and generalizable to less resourced health systems,” Dr. Saver said. “Although the results from PISTE were not internally statistically significant because the trial ended early, the results were consistent with the external studies of thrombectomy, so it provides further evidence for benefit from thrombectomy.” And because the consistent results were achieved with simpler imaging it suggests simpler imaging may be all that’s needed.

“That’s a major question to wrestle with,” Dr. Saver suggested. “We need addition trials with a head-to-head comparison of simpler and more sophisticated imaging so we can tailor treatment to patients who would benefit from simpler and faster imaging.”

Dr. Kent had no disclosures. Dr. Kim has received research funding from SanBio and Biogen. Dr. Smith served on the data safety and monitoring board for a trial funded by Stryker. Dr. Alberts has been a consultant to Genentech. Dr. Saver has been a consultant to Stryker, Neuravi, Cognition Medical, Boehringer Ingelheim, and Medtronic. Dr. Elijovich has been a consultant to Stryker and Codman and received research support from Siemens. Dr. Muir has received research support from ReNeuron and unrestricted grants from Codman and Covidien.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

LOS ANGELES – The use of endovascular thrombectomy in the United States to treat appropriate patients with acute ischemic stroke mushroomed during the past year, following several early-2015 reports that collectively documented the dramatic clinical benefit of the treatment.

As endovascular thrombectomy use grows, stroke centers are also refining and reshaping delivery of the treatment in concert with administration of intravenous tissue plasminogen activator (TPA; alteplase; Activase), which remains a key partner in producing best outcomes for acute ischemic-stroke patients with a proximal occlusion of a large cerebral artery. Collapsing delivery of the two treatments into a more seamless and streamlined process shaves critical minutes to treatment delivery, an approach called parallel processing. Recent findings have also emboldened stroke specialists to seriously consider simplifying the brain imaging that stroke patients receive prior to these treatments, a step that could further cut time to intervention while also making thrombectomy even more widely available.

Use of thrombectomy surges

The biggest endovascular thrombectomy news of the past year is how it has taken off for treating selected patients with acute ischemic stroke. “The rollout over the past year has been explosive. Everything pretty much shut down after the negative trial results in 2013, but now more hospitals are offering thrombectomy,” said Dr. Thomas A. Kent, professor of neurology and director of stroke research and education at Baylor College of Medicine in Houston, in an interview at the International Stroke Conference sponsored by the American Heart Association.

The best documentation of this surge came in a poster presented at the conference by researchers at the University of California, San Francisco. They analyzed data on treatment of 357,973 patients with acute ischemic stroke who were hospitalized at any one of 161 U.S. academic medical centers during October 2009-July 2015 and included in the University Healthsystem Consortium database. They tracked the percentage of patients treated endovascularly during each calendar quarter of the study period.

During 2009-2013, use of endovascular treatment rose steadily but gradually, from 1.5% of stroke patients in 2009 to 3.1% during the fourth quarter of 2012. Then, following three reports of no benefit from endovascular treatment presented at the International Stroke Conference in February 2013 – the IMS III, MR RESCUE, and SYNTHESIS trials – the endovascular rate dropped immediately and quickly bottomed out at a level of 2.6% that remained steady through the third quarter of 2014. But when the positive endovascular results from the MR CLEAN study became public in the final week of 2014, endovascular use began to quickly rise again, and then began to skyrocket during the first quarter of 2015 with three additional positive trial results reported during the Stroke Conference in February 2015. By the end of the second quarter of 2015, usage stood at 4.7%, representing a projected year-over-year increase of about 150% for all of 2015, compared with 2014, reported Dr. Anthony S. Kim, a vascular neurologist and medical director of the Stroke Center at the University of California, San Francisco, and his associates.

To put these percentages in perspective, experts estimate that roughly 10%-15% of all stroke patients qualify for thrombectomy intervention.

Their data also showed that the percentage of hospitals included in the database that performed endovascular therapies for stroke rose steadily from about 40% of centers in 2009 to nearly 60% by mid-2015.

“Endovascular therapy with newer-generation devices is increasingly part of standard treatment for acute ischemic stroke,” they said in their poster. In addition, they cited a “new urgency to evaluate regional access to embolectomy [another name for thrombectomy] nationally and to identify system-based solutions to improve access in underserved areas.”

Several stroke experts interviewed at the conference added their own anecdotal view of thrombectomy’s rapidly expanding use for appropriate acute ischemic stroke patients during 2015, and the need for continued effort to broaden its U.S. availability.

“The number of thrombectomies fell off after the negative 2013 trials and stayed flat until a year ago, but then jumped up. It has been very dramatic,” said Dr. Wade S. Smith, professor of neurology and director of the neurovascular service at the University of California, San Francisco.

“Thrombectomy use tremendously increased since February 2015,” said Dr. Mark J. Alberts, professor of neurology and medical director of the neurology service at the University of Texas Southwestern Medical Center in Dallas, in a video interview during the conference. But despite this growth, “the major challenge [today] is geography;” that is, reaching patients in suburban and rural areas who are not as close to the primarily urban medical centers that currently offer the procedure.

“We now have about 100 certified comprehensive stroke centers in the U.S.,” and by definition comprehensive stroke centers have the capability of treating patients with endovascular thrombectomy, noted Dr. Jeffrey Saver, professor of neurology and director of the stroke unit at the University of California, Los Angeles.

“Certification of these centers did not begin until about 2-3 years ago. But we probably need 300-400 of these centers” to provide thrombectomy to most U.S. stroke patients, he said. “A lot of additional hospitals are close to certification. I anticipate that over the next 1-2 years we will be in the neighborhood of having the number of centers we need,” Dr. Saver said in an interview.

Making thrombectomy better

In addition to expanding availability, the specifics of how endovascular thrombectomy gets delivered is evolving. A major trend is movement toward a “parallel processing” model, in which patients with an acute clinical presentation of a stroke amenable for endovascular treatment simultaneously undergo CT angiography to confirm and localize the large-artery clot causing their stroke, receive intravenous TPA, and undergo preparation for the endovascular access needed to remove the clot.

A pooled analysis of the recent, positive endovascular thrombectomy trials that was presented at the conference showed how quick you need to be to obtain a benefit from the procedures. “This gives us a starting point to further improve the target metrics for imaging and puncture times,” Dr. Saver said. “We want to shorten door-to-needle times for TPA and door-to-puncture times for thrombectomy, and the processes that need to be addressed for rapid delivery of both of these are very similar. We need for patients to only make a pit stop in the ED; we need to have the catheterization team ready to go in the thrombectomy suite within 30 minutes; and we need to emphasize speed in access to the target clot rather than time-consuming diagnostic angiography.”

“We now face the issue of how to best integrate TPA treatment and clot removal.” Dr. Kent said. “People are still trying to work that out. With parallel processing there is some overuse of resources: Some patients recover with TPA alone and don’t need thrombectomy. We are getting closer to the cardiology model of MI treatment. It’s now clear that there needs to be a simple, safe, effective way to do both TPA treatment and thrombectomy. We need to model ourselves on the cardiology experience.”

“If you can deal with the TPA decision in the same room without moving patients from room to room, from a scanner to a catheterization suite, you can really shorten the time to treatment,” Dr. Smith explained. “This is identical to the model that cardiologists have developed. We should now consider taking stroke patients directly to the angiography room in addition to administering TPA. We still need cross-sectional imaging, but the quality of the image from an angiography suite is probably sufficient to make a TPA decision. So you can start TPA while you are getting arterial access. The idea is simultaneous approaches to the patient instead of serial.”

“The whole system moves at the same time to eliminate wasted time,” Dr. Alberts summed up.

One of the big questions that has come up in this effort to speed up treatment and carve the quickest route to endovascular thrombectomy is whether TPA remains necessary. The skeptics’ position is, why waste time administering TPA if you’re also going to take out the offending clot?

The answer, at least for now, is that all signs indicate that giving TPA helps and is worth delivering.

“The 2015 thrombectomy trials had big differences among them in the dosage of TPA administered, and in the percentage of patients who received TPA. When 100% of patients received TPA they had the best outcomes,” Dr. Kent said. “There was a clear synergistic relationship between thrombectomy and TPA. There has been a trend to think about sending patients straight to thrombectomy and skipping TPA, but my colleagues and I think that we need to hold off on doing that. For now, if a patient is eligible to receive TPA they should get it and then quickly move to endovascular therapy. We are not yet ready to know it’s okay to go straight to endovascular treatment. In SWIFT-PRIME, it was pretty clear that the good outcomes were attributable to both [thrombectomy plus TPA]. Treating patients with TPA helps soften the clot to make it easier to remove, and improves flow through collateral arteries.”

“Our data in Memphis show that patients do better with thrombectomy plus intravenous TPA than on TPA alone,” agreed Dr. Lucas Elijovich, a neurologist at the University of Tennessee Health Science Center in Memphis, in an interview.

Simpler imaging also saves time

Although it’s not yet proven, another new wrinkle in working up acute ischemic-stroke patients for TPA and thrombectomy treatment is the idea that simpler and more widely available CT imaging, especially CT angiography of cerebral arteries, may suffice for confirming and localizing the culprit clot.

This concept received a significant boost at the International Stroke Conference in data reported from the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) trial, yet another study that compared treatment with TPA alone with TPA plus endovascular thrombectomy, this time in 65 randomized patients treated at any of 11 U.K. centers. PISTE had a low enrollment level because the trial stopped prematurely, in July 2015, following the news that several fully completed trials had collectively established the superiority of endovascular thrombectomy plus TPA, thereby making it unethical to continue yet another randomized study.

This premature stoppage prevented PISTE from itself producing a statistically significant difference for its primary efficacy endpoint in favor of the combined treatment, although the results did show a nominal advantage to using thrombectomy plus TPA over TPA alone that was fully consistent with the other studies, Dr. Keith W. Muir reported at the conference.

But what made the PISTE results especially notable was that the trial achieved this consistent outcome with a “simpler” imaging protocol for patients during their workup that used only CT angiography, avoiding the cerebral CT perfusion imaging or MRI used in several of the other TPA-plus-thrombectomy versus TPA-only trials, noted Dr. Muir, professor of neuroscience and head of the stroke imaging group at the University of Glasgow.

“PISTE raises the question of how much imaging is necessary,” Dr. Kent commented.

“The PISTE results are exciting. A lot of us believe that all we need to know is that there is a blockage in a target vessel,” Dr. Smith said. “If we have that information, then we can identify a population of patients who will benefit from [thrombectomy]. CT angiography is simple and can easily fit into work flows.”

“PISTE used a very simple imaging system that makes thrombectomy even more applicable and generalizable to less resourced health systems,” Dr. Saver said. “Although the results from PISTE were not internally statistically significant because the trial ended early, the results were consistent with the external studies of thrombectomy, so it provides further evidence for benefit from thrombectomy.” And because the consistent results were achieved with simpler imaging it suggests simpler imaging may be all that’s needed.

“That’s a major question to wrestle with,” Dr. Saver suggested. “We need addition trials with a head-to-head comparison of simpler and more sophisticated imaging so we can tailor treatment to patients who would benefit from simpler and faster imaging.”

Dr. Kent had no disclosures. Dr. Kim has received research funding from SanBio and Biogen. Dr. Smith served on the data safety and monitoring board for a trial funded by Stryker. Dr. Alberts has been a consultant to Genentech. Dr. Saver has been a consultant to Stryker, Neuravi, Cognition Medical, Boehringer Ingelheim, and Medtronic. Dr. Elijovich has been a consultant to Stryker and Codman and received research support from Siemens. Dr. Muir has received research support from ReNeuron and unrestricted grants from Codman and Covidien.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

LOS ANGELES – The use of endovascular thrombectomy in the United States to treat appropriate patients with acute ischemic stroke mushroomed during the past year, following several early-2015 reports that collectively documented the dramatic clinical benefit of the treatment.

As endovascular thrombectomy use grows, stroke centers are also refining and reshaping delivery of the treatment in concert with administration of intravenous tissue plasminogen activator (TPA; alteplase; Activase), which remains a key partner in producing best outcomes for acute ischemic-stroke patients with a proximal occlusion of a large cerebral artery. Collapsing delivery of the two treatments into a more seamless and streamlined process shaves critical minutes to treatment delivery, an approach called parallel processing. Recent findings have also emboldened stroke specialists to seriously consider simplifying the brain imaging that stroke patients receive prior to these treatments, a step that could further cut time to intervention while also making thrombectomy even more widely available.

Use of thrombectomy surges

The biggest endovascular thrombectomy news of the past year is how it has taken off for treating selected patients with acute ischemic stroke. “The rollout over the past year has been explosive. Everything pretty much shut down after the negative trial results in 2013, but now more hospitals are offering thrombectomy,” said Dr. Thomas A. Kent, professor of neurology and director of stroke research and education at Baylor College of Medicine in Houston, in an interview at the International Stroke Conference sponsored by the American Heart Association.

The best documentation of this surge came in a poster presented at the conference by researchers at the University of California, San Francisco. They analyzed data on treatment of 357,973 patients with acute ischemic stroke who were hospitalized at any one of 161 U.S. academic medical centers during October 2009-July 2015 and included in the University Healthsystem Consortium database. They tracked the percentage of patients treated endovascularly during each calendar quarter of the study period.

During 2009-2013, use of endovascular treatment rose steadily but gradually, from 1.5% of stroke patients in 2009 to 3.1% during the fourth quarter of 2012. Then, following three reports of no benefit from endovascular treatment presented at the International Stroke Conference in February 2013 – the IMS III, MR RESCUE, and SYNTHESIS trials – the endovascular rate dropped immediately and quickly bottomed out at a level of 2.6% that remained steady through the third quarter of 2014. But when the positive endovascular results from the MR CLEAN study became public in the final week of 2014, endovascular use began to quickly rise again, and then began to skyrocket during the first quarter of 2015 with three additional positive trial results reported during the Stroke Conference in February 2015. By the end of the second quarter of 2015, usage stood at 4.7%, representing a projected year-over-year increase of about 150% for all of 2015, compared with 2014, reported Dr. Anthony S. Kim, a vascular neurologist and medical director of the Stroke Center at the University of California, San Francisco, and his associates.

To put these percentages in perspective, experts estimate that roughly 10%-15% of all stroke patients qualify for thrombectomy intervention.

Their data also showed that the percentage of hospitals included in the database that performed endovascular therapies for stroke rose steadily from about 40% of centers in 2009 to nearly 60% by mid-2015.

“Endovascular therapy with newer-generation devices is increasingly part of standard treatment for acute ischemic stroke,” they said in their poster. In addition, they cited a “new urgency to evaluate regional access to embolectomy [another name for thrombectomy] nationally and to identify system-based solutions to improve access in underserved areas.”

Several stroke experts interviewed at the conference added their own anecdotal view of thrombectomy’s rapidly expanding use for appropriate acute ischemic stroke patients during 2015, and the need for continued effort to broaden its U.S. availability.

“The number of thrombectomies fell off after the negative 2013 trials and stayed flat until a year ago, but then jumped up. It has been very dramatic,” said Dr. Wade S. Smith, professor of neurology and director of the neurovascular service at the University of California, San Francisco.

“Thrombectomy use tremendously increased since February 2015,” said Dr. Mark J. Alberts, professor of neurology and medical director of the neurology service at the University of Texas Southwestern Medical Center in Dallas, in a video interview during the conference. But despite this growth, “the major challenge [today] is geography;” that is, reaching patients in suburban and rural areas who are not as close to the primarily urban medical centers that currently offer the procedure.

“We now have about 100 certified comprehensive stroke centers in the U.S.,” and by definition comprehensive stroke centers have the capability of treating patients with endovascular thrombectomy, noted Dr. Jeffrey Saver, professor of neurology and director of the stroke unit at the University of California, Los Angeles.

“Certification of these centers did not begin until about 2-3 years ago. But we probably need 300-400 of these centers” to provide thrombectomy to most U.S. stroke patients, he said. “A lot of additional hospitals are close to certification. I anticipate that over the next 1-2 years we will be in the neighborhood of having the number of centers we need,” Dr. Saver said in an interview.

Making thrombectomy better

In addition to expanding availability, the specifics of how endovascular thrombectomy gets delivered is evolving. A major trend is movement toward a “parallel processing” model, in which patients with an acute clinical presentation of a stroke amenable for endovascular treatment simultaneously undergo CT angiography to confirm and localize the large-artery clot causing their stroke, receive intravenous TPA, and undergo preparation for the endovascular access needed to remove the clot.

A pooled analysis of the recent, positive endovascular thrombectomy trials that was presented at the conference showed how quick you need to be to obtain a benefit from the procedures. “This gives us a starting point to further improve the target metrics for imaging and puncture times,” Dr. Saver said. “We want to shorten door-to-needle times for TPA and door-to-puncture times for thrombectomy, and the processes that need to be addressed for rapid delivery of both of these are very similar. We need for patients to only make a pit stop in the ED; we need to have the catheterization team ready to go in the thrombectomy suite within 30 minutes; and we need to emphasize speed in access to the target clot rather than time-consuming diagnostic angiography.”

“We now face the issue of how to best integrate TPA treatment and clot removal.” Dr. Kent said. “People are still trying to work that out. With parallel processing there is some overuse of resources: Some patients recover with TPA alone and don’t need thrombectomy. We are getting closer to the cardiology model of MI treatment. It’s now clear that there needs to be a simple, safe, effective way to do both TPA treatment and thrombectomy. We need to model ourselves on the cardiology experience.”

“If you can deal with the TPA decision in the same room without moving patients from room to room, from a scanner to a catheterization suite, you can really shorten the time to treatment,” Dr. Smith explained. “This is identical to the model that cardiologists have developed. We should now consider taking stroke patients directly to the angiography room in addition to administering TPA. We still need cross-sectional imaging, but the quality of the image from an angiography suite is probably sufficient to make a TPA decision. So you can start TPA while you are getting arterial access. The idea is simultaneous approaches to the patient instead of serial.”

“The whole system moves at the same time to eliminate wasted time,” Dr. Alberts summed up.

One of the big questions that has come up in this effort to speed up treatment and carve the quickest route to endovascular thrombectomy is whether TPA remains necessary. The skeptics’ position is, why waste time administering TPA if you’re also going to take out the offending clot?

The answer, at least for now, is that all signs indicate that giving TPA helps and is worth delivering.

“The 2015 thrombectomy trials had big differences among them in the dosage of TPA administered, and in the percentage of patients who received TPA. When 100% of patients received TPA they had the best outcomes,” Dr. Kent said. “There was a clear synergistic relationship between thrombectomy and TPA. There has been a trend to think about sending patients straight to thrombectomy and skipping TPA, but my colleagues and I think that we need to hold off on doing that. For now, if a patient is eligible to receive TPA they should get it and then quickly move to endovascular therapy. We are not yet ready to know it’s okay to go straight to endovascular treatment. In SWIFT-PRIME, it was pretty clear that the good outcomes were attributable to both [thrombectomy plus TPA]. Treating patients with TPA helps soften the clot to make it easier to remove, and improves flow through collateral arteries.”

“Our data in Memphis show that patients do better with thrombectomy plus intravenous TPA than on TPA alone,” agreed Dr. Lucas Elijovich, a neurologist at the University of Tennessee Health Science Center in Memphis, in an interview.

Simpler imaging also saves time

Although it’s not yet proven, another new wrinkle in working up acute ischemic-stroke patients for TPA and thrombectomy treatment is the idea that simpler and more widely available CT imaging, especially CT angiography of cerebral arteries, may suffice for confirming and localizing the culprit clot.

This concept received a significant boost at the International Stroke Conference in data reported from the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) trial, yet another study that compared treatment with TPA alone with TPA plus endovascular thrombectomy, this time in 65 randomized patients treated at any of 11 U.K. centers. PISTE had a low enrollment level because the trial stopped prematurely, in July 2015, following the news that several fully completed trials had collectively established the superiority of endovascular thrombectomy plus TPA, thereby making it unethical to continue yet another randomized study.

This premature stoppage prevented PISTE from itself producing a statistically significant difference for its primary efficacy endpoint in favor of the combined treatment, although the results did show a nominal advantage to using thrombectomy plus TPA over TPA alone that was fully consistent with the other studies, Dr. Keith W. Muir reported at the conference.

But what made the PISTE results especially notable was that the trial achieved this consistent outcome with a “simpler” imaging protocol for patients during their workup that used only CT angiography, avoiding the cerebral CT perfusion imaging or MRI used in several of the other TPA-plus-thrombectomy versus TPA-only trials, noted Dr. Muir, professor of neuroscience and head of the stroke imaging group at the University of Glasgow.

“PISTE raises the question of how much imaging is necessary,” Dr. Kent commented.

“The PISTE results are exciting. A lot of us believe that all we need to know is that there is a blockage in a target vessel,” Dr. Smith said. “If we have that information, then we can identify a population of patients who will benefit from [thrombectomy]. CT angiography is simple and can easily fit into work flows.”

“PISTE used a very simple imaging system that makes thrombectomy even more applicable and generalizable to less resourced health systems,” Dr. Saver said. “Although the results from PISTE were not internally statistically significant because the trial ended early, the results were consistent with the external studies of thrombectomy, so it provides further evidence for benefit from thrombectomy.” And because the consistent results were achieved with simpler imaging it suggests simpler imaging may be all that’s needed.

“That’s a major question to wrestle with,” Dr. Saver suggested. “We need addition trials with a head-to-head comparison of simpler and more sophisticated imaging so we can tailor treatment to patients who would benefit from simpler and faster imaging.”

Dr. Kent had no disclosures. Dr. Kim has received research funding from SanBio and Biogen. Dr. Smith served on the data safety and monitoring board for a trial funded by Stryker. Dr. Alberts has been a consultant to Genentech. Dr. Saver has been a consultant to Stryker, Neuravi, Cognition Medical, Boehringer Ingelheim, and Medtronic. Dr. Elijovich has been a consultant to Stryker and Codman and received research support from Siemens. Dr. Muir has received research support from ReNeuron and unrestricted grants from Codman and Covidien.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

Preterm premature rupture of membranes (PPROM) refers to rupture of membranes prior to the onset of labor before 37 weeks’ gestation. It accounts for one-third of all preterm births.¹ Pregnancy complications associated with PPROM include intrauterine infection (chorioamnionitis), preterm labor, and placental abruption. Should such complications develop, immediate delivery is indicated. When to recommend elective delivery in the absence of complications, however, remains controversial.

The American College of Obstetricians and Gynecologists (ACOG) currently recommends elective delivery at or after 34 weeks’ gestation,² because the prevailing evidence suggests that the risk of pregnancy-related complications (especially ascending infection) exceeds the risks of iatrogenic prematurity at this gestational age. However, ACOG acknowledges that this recommendation is based on “limited and inconsistent scientific evidence.”² To address deficiencies in the literature, investigators designed the PPROMT (preterm prelabor rupture of the membranes close to term) trial to study women with ruptured membranes before the onset of labor between 34 and 37 weeks’ gestation.

PPROMT study designMorris and colleagues present results of their multicenter, international, randomized controlled trial (RCT) of expectant management versus planned delivery in pregnancies complicated by PPROM at 34 0/7 through 36 6/7 weeks’ gestation carried out in 65 centers across 11 countries. A total of 1,839 women not requiring urgent delivery were randomly assigned to either immediate delivery (n = 924) or expectant management (n = 915).

No difference was noted in the primary outcome of neonatal sepsis between the immediate birth (n = 23 [2%]) and expectant management groups (n = 29 [3%]; relative risk [RR], 0.8; 95% confidence interval [CI], 0.5–1.3). This also was true in the subgroup of women who were colonized with group B streptococcus (RR, 0.9; 95% CI, 0.2–4.5).

There also was no difference in the secondary outcome measure, a composite metric including sepsis, ventilation for 24 or more hours, or death (73 [8%] in the immediate delivery group vs 61 [7%] in the expectant management group; RR, 1.2; 95% CI, 0.9–1.6). However, infants born to women randomly assigned to immediate delivery, versus expectant management, had a significantly higher rate of respiratory distress syndrome (RR, 1.6; 95% CI, 1.1–2.3) and mechanical ventilation (RR, 1.4; 95% CI, 1.0–1.8). In addition, the immediate-delivery infants had a longer median stay in the special care nursery/neonatal intensive care unit (4.0 days, interquartile range [IQR], 0.0–10.0 vs 2.0 days, IQR, 0.0–7.0) and total hospital stay (6.0 days, IQR, 3.0–10.0 vs 4.0 days, IQR, 3.0–8.0). As expected, women in the expectant management group had a significantly longer hospital stay than women in the immediate delivery group, because 75% (688/912) were managed as inpatients. Interestingly, women in the immediate delivery group had a higher cesarean delivery rate than those in the expectant management group (239 [26%] vs 169 [19%], respectively; RR, 1.4; 95% CI, 1.2–1.7), although no explanation was offered.

Strengths and limitationsMajor strengths of this study include the large sample size and superior study design. It is by far the largest RCT to address this question. Because this was a pragmatic RCT, certain practices (such as the choice of latency antibiotic regimen) varied across centers, although randomization would be expected to minimize the effect of such variables on study outcome.

A major limitation is that participant recruitment occurred over a period of more than 10 years, during which time antenatal and neonatal intensive care unit practices likely would have changed.

What this evidence means for practiceFew clinical studies have the potential to significantly change obstetric management. This report by Morris and colleagues is one such study. It was well designed, well executed, and powered to look at the most clinically relevant outcome, namely, neonatal sepsis. While these study results do call into question the current American College of Obstetricians and Gynecologists recommendations to electively deliver patients with PPROM at or after 34 weeks’ gestation, additional discussion is needed at the national level before these recommendations can be changed.
—Denis A. Vaughan, MBBCh, BAO, MRCPI, and Errol R. Norwitz, MD, PhD

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Preterm premature rupture of membranes (PPROM) refers to rupture of membranes prior to the onset of labor before 37 weeks’ gestation. It accounts for one-third of all preterm births.¹ Pregnancy complications associated with PPROM include intrauterine infection (chorioamnionitis), preterm labor, and placental abruption. Should such complications develop, immediate delivery is indicated. When to recommend elective delivery in the absence of complications, however, remains controversial.

The American College of Obstetricians and Gynecologists (ACOG) currently recommends elective delivery at or after 34 weeks’ gestation,² because the prevailing evidence suggests that the risk of pregnancy-related complications (especially ascending infection) exceeds the risks of iatrogenic prematurity at this gestational age. However, ACOG acknowledges that this recommendation is based on “limited and inconsistent scientific evidence.”² To address deficiencies in the literature, investigators designed the PPROMT (preterm prelabor rupture of the membranes close to term) trial to study women with ruptured membranes before the onset of labor between 34 and 37 weeks’ gestation.

PPROMT study designMorris and colleagues present results of their multicenter, international, randomized controlled trial (RCT) of expectant management versus planned delivery in pregnancies complicated by PPROM at 34 0/7 through 36 6/7 weeks’ gestation carried out in 65 centers across 11 countries. A total of 1,839 women not requiring urgent delivery were randomly assigned to either immediate delivery (n = 924) or expectant management (n = 915).

No difference was noted in the primary outcome of neonatal sepsis between the immediate birth (n = 23 [2%]) and expectant management groups (n = 29 [3%]; relative risk [RR], 0.8; 95% confidence interval [CI], 0.5–1.3). This also was true in the subgroup of women who were colonized with group B streptococcus (RR, 0.9; 95% CI, 0.2–4.5).

There also was no difference in the secondary outcome measure, a composite metric including sepsis, ventilation for 24 or more hours, or death (73 [8%] in the immediate delivery group vs 61 [7%] in the expectant management group; RR, 1.2; 95% CI, 0.9–1.6). However, infants born to women randomly assigned to immediate delivery, versus expectant management, had a significantly higher rate of respiratory distress syndrome (RR, 1.6; 95% CI, 1.1–2.3) and mechanical ventilation (RR, 1.4; 95% CI, 1.0–1.8). In addition, the immediate-delivery infants had a longer median stay in the special care nursery/neonatal intensive care unit (4.0 days, interquartile range [IQR], 0.0–10.0 vs 2.0 days, IQR, 0.0–7.0) and total hospital stay (6.0 days, IQR, 3.0–10.0 vs 4.0 days, IQR, 3.0–8.0). As expected, women in the expectant management group had a significantly longer hospital stay than women in the immediate delivery group, because 75% (688/912) were managed as inpatients. Interestingly, women in the immediate delivery group had a higher cesarean delivery rate than those in the expectant management group (239 [26%] vs 169 [19%], respectively; RR, 1.4; 95% CI, 1.2–1.7), although no explanation was offered.

Strengths and limitationsMajor strengths of this study include the large sample size and superior study design. It is by far the largest RCT to address this question. Because this was a pragmatic RCT, certain practices (such as the choice of latency antibiotic regimen) varied across centers, although randomization would be expected to minimize the effect of such variables on study outcome.

A major limitation is that participant recruitment occurred over a period of more than 10 years, during which time antenatal and neonatal intensive care unit practices likely would have changed.

What this evidence means for practiceFew clinical studies have the potential to significantly change obstetric management. This report by Morris and colleagues is one such study. It was well designed, well executed, and powered to look at the most clinically relevant outcome, namely, neonatal sepsis. While these study results do call into question the current American College of Obstetricians and Gynecologists recommendations to electively deliver patients with PPROM at or after 34 weeks’ gestation, additional discussion is needed at the national level before these recommendations can be changed.
—Denis A. Vaughan, MBBCh, BAO, MRCPI, and Errol R. Norwitz, MD, PhD

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Preterm premature rupture of membranes (PPROM) refers to rupture of membranes prior to the onset of labor before 37 weeks’ gestation. It accounts for one-third of all preterm births.¹ Pregnancy complications associated with PPROM include intrauterine infection (chorioamnionitis), preterm labor, and placental abruption. Should such complications develop, immediate delivery is indicated. When to recommend elective delivery in the absence of complications, however, remains controversial.

The American College of Obstetricians and Gynecologists (ACOG) currently recommends elective delivery at or after 34 weeks’ gestation,² because the prevailing evidence suggests that the risk of pregnancy-related complications (especially ascending infection) exceeds the risks of iatrogenic prematurity at this gestational age. However, ACOG acknowledges that this recommendation is based on “limited and inconsistent scientific evidence.”² To address deficiencies in the literature, investigators designed the PPROMT (preterm prelabor rupture of the membranes close to term) trial to study women with ruptured membranes before the onset of labor between 34 and 37 weeks’ gestation.

PPROMT study designMorris and colleagues present results of their multicenter, international, randomized controlled trial (RCT) of expectant management versus planned delivery in pregnancies complicated by PPROM at 34 0/7 through 36 6/7 weeks’ gestation carried out in 65 centers across 11 countries. A total of 1,839 women not requiring urgent delivery were randomly assigned to either immediate delivery (n = 924) or expectant management (n = 915).

No difference was noted in the primary outcome of neonatal sepsis between the immediate birth (n = 23 [2%]) and expectant management groups (n = 29 [3%]; relative risk [RR], 0.8; 95% confidence interval [CI], 0.5–1.3). This also was true in the subgroup of women who were colonized with group B streptococcus (RR, 0.9; 95% CI, 0.2–4.5).

There also was no difference in the secondary outcome measure, a composite metric including sepsis, ventilation for 24 or more hours, or death (73 [8%] in the immediate delivery group vs 61 [7%] in the expectant management group; RR, 1.2; 95% CI, 0.9–1.6). However, infants born to women randomly assigned to immediate delivery, versus expectant management, had a significantly higher rate of respiratory distress syndrome (RR, 1.6; 95% CI, 1.1–2.3) and mechanical ventilation (RR, 1.4; 95% CI, 1.0–1.8). In addition, the immediate-delivery infants had a longer median stay in the special care nursery/neonatal intensive care unit (4.0 days, interquartile range [IQR], 0.0–10.0 vs 2.0 days, IQR, 0.0–7.0) and total hospital stay (6.0 days, IQR, 3.0–10.0 vs 4.0 days, IQR, 3.0–8.0). As expected, women in the expectant management group had a significantly longer hospital stay than women in the immediate delivery group, because 75% (688/912) were managed as inpatients. Interestingly, women in the immediate delivery group had a higher cesarean delivery rate than those in the expectant management group (239 [26%] vs 169 [19%], respectively; RR, 1.4; 95% CI, 1.2–1.7), although no explanation was offered.

Strengths and limitationsMajor strengths of this study include the large sample size and superior study design. It is by far the largest RCT to address this question. Because this was a pragmatic RCT, certain practices (such as the choice of latency antibiotic regimen) varied across centers, although randomization would be expected to minimize the effect of such variables on study outcome.

A major limitation is that participant recruitment occurred over a period of more than 10 years, during which time antenatal and neonatal intensive care unit practices likely would have changed.

What this evidence means for practiceFew clinical studies have the potential to significantly change obstetric management. This report by Morris and colleagues is one such study. It was well designed, well executed, and powered to look at the most clinically relevant outcome, namely, neonatal sepsis. While these study results do call into question the current American College of Obstetricians and Gynecologists recommendations to electively deliver patients with PPROM at or after 34 weeks’ gestation, additional discussion is needed at the national level before these recommendations can be changed.
—Denis A. Vaughan, MBBCh, BAO, MRCPI, and Errol R. Norwitz, MD, PhD

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Access Dr. Burkman's Webcasts on contraception:

• Obesity and contraceptive efficacy and risks 
• How to use the CDC's online tools to manage complex cases in contraception

Helpful resource for your practice:

• Guttmacher Institute Fact Sheet: Contraceptive Use in the United States, October 2015    

Access Dr. Burkman's Webcasts on contraception:

• Obesity and contraceptive efficacy and risks 
• How to use the CDC's online tools to manage complex cases in contraception

Helpful resource for your practice:

• Guttmacher Institute Fact Sheet: Contraceptive Use in the United States, October 2015    

Access Dr. Burkman's Webcasts on contraception:

• Obesity and contraceptive efficacy and risks 
• How to use the CDC's online tools to manage complex cases in contraception

Helpful resource for your practice:

• Guttmacher Institute Fact Sheet: Contraceptive Use in the United States, October 2015    

The results of the highly anticipated Antenatal Late Preterm Study recently have become available.¹ Data from this randomized controlled trial, conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network, demonstrated that administration of betamethasone to women at risk for preterm delivery between 34 weeks 0 days and 36 weeks 6 days of gestation significantly reduces the rate of neonatal respiratory complications. It may represent the largest study of antenatal corticosteroids (ACS) to date, with 2,827 infants studied, and its results inevitably lead to the logical practical question: Should ACS use be extended beyond the 34 weeks’ gestation limit previously recommended by professional guidelines in the United States²?

There are some issues that bear discussion before such a significant change in standard of care should be promoted.²

Antenatal Late Preterm Study outcomesThe primary outcome in the study was a composite end point describing the need for respiratory support within 72 hours after birth. Based on a pilot study, the investigators had anticipated a 33% decrease in the rate of the primary outcome; however, the reduction was only 20% (relative risk [RR], 0.80; 95% confidence interval [CI], 0.66−0.97). Although the effect size was statistically significant, one could question the clinical relevance of such a small difference.

A 33% reduction effect, more consistent with the preliminary expectations, was noted in the prespecified secondary composite outcome of severe respiratory complications (RR, 0.67; 95% CI, 0.53−0.84). Occurrences included in the secondary composite outcome that also showed significant rate reductions were:

The reported reduction in bronchopulmonary dysplasia (RR, 0.22; 95% CI, 0.02−0.92) cannot plausibly be attributed to ACS. Randomized data aggregated by the Cochrane Database of Systematic Reviews³ do not show improvement in chronic lung disease with ACS use. Moreover, the authors recognize that the assessment for bronchopulmonary dysplasia at only 28 days of life is only partially informative and that longer childhood follow-up is required to confirm the finding.

We recommend caution before changing current practiceWe propose prudence with ACS use after 34 weeks’ gestation for the following reasons: the increased risk for neonatal hypoglycemia associated with ACS, the increased risk for ACS-related harm in term-born babies, and safety concerns with ACS in the late preterm period.

Evidence shows an increased risk for neonatal hypoglycemiaThe most profound effect modification observed in the study was an adverse effect—namely, a 60% increase in neonatal hypoglycemia with ACS administration (RR, 1.6; 95% CI, 1.37−1.87). The rate of neonatal hypoglycemia was 24% in the ACS group, compared with 15% in the placebo group.

Results of prior studies have demonstrated either no increased risk of hypoglycemia with ACS use⁴⁻⁷ or a much smaller increase (from 4.2% to 5.7%).⁸ The higher rate of neonatal hypoglycemia seen in this study suggests the possibility that the late preterm population may be more vulnerable to the negative impact of ACS on neonatal glucose/insulin homeostasis. Presumed mechanisms of action are either maternal hyperglycemia or fetal adrenal suppression or both, with potential for fetal adrenal suppression resulting from betamethasone exposure to affect long-term metabolic outcomes.⁹

Of note, women with pregestational diabetes were excluded from the study and, in routine practice, inclusion of such patients may further increase the risk of neonatal hypoglycemia.

There are few data on the prognostic significance of neonatal hypoglycemia in preterm infants, with the exception of a single study, the results of which show that it is associated with adverse neurodevelopment at 18 months of age.¹⁰

Data reveal increased risk for harm in term-born babiesIn spite of strict protocol specifications to increase the probability of delivery before 37 weeks’ gestation, 16% of women in the trial delivered at term. Investigators of prior randomized studies of ACS, aimed at reducing the risks of prematurity, have reported a rate of term delivery of about one-third,^4,11 and in routine practice, administration of ACS after 34 weeks may be associated with even higher rates of term delivery.

This is important because recent evidence shows an unfavorable impact of ACS exposure in term-born children.¹² The 5-year follow-up of the largest randomized trial in which multiple ACS courses were used noted that babies born at term had a 4-fold increased odds ratio for neurosensory disability.¹¹ There was no dose−response interaction, with the same adverse odds ratio after 1 or 4 additional ACS courses. This observation was consistent with a previously reported Swedish national cohort, pointing to an unfavorable impact of even a single course of ACS in term-born children, with a greater likelihood of harm than benefit.¹³

In a UK follow-up of children aged 8 to 15 years who were enrolled in an RCT of ACS before cesarean delivery at term, low academic achievement was significantly more common in the group whose mothers had received ACS.¹⁴ In another study of 304 children born at term after exposure to a single course of ACS, investigators noted significantly increased cortisol reactivity to acute psychological stress at ages 6 to 11 years in the ACS-exposed patients, compared with 212 babies of women with threatened preterm labor who did not receive ACS and 372 babies from uncomplicated term pregnancies.¹⁵

The relevance of such study findings extends beyond childhood given the fact that elevated hypothalamic-pituitary-adrenal (HPA) axis reactivity has been linked to the pathogenesis of metabolic syndrome and depression in adult life.¹⁶ As recently as 2015, investigators of a randomized trial of ACS in 6 low- and middle-income countries highlighted their concern regarding “potentially harmful use of antenatal corticosteroids for infants not delivered preterm.”¹⁷

There are safety concerns with ACS in the late preterm periodThe effects of ACS are more pleiotropic than those reflected in a lower incidence of respiratory difficulties. Knowledge of the overall consequences of ACS exposure in infants born late-preterm or at term is still limited. The close-to-term fetus exposed to exogenous corticosteroids is also exposed to the physiologic endogenous surge of cortisol known to occur in the maternal circulation in late pregnancy, which reaches levels 3 times higher than those seen in nonpregnant women.¹⁸ Although placental 11 beta-hydroxysteroid dehydrogenase type 2 plays a protective role by allowing no more than 10% to 20% of maternal corticosteroids to cross the placenta, fetal overexposure from concomitant exogenous maternal corticosteroid administration remains a theoretical concern close to term. This is especially worrisome if there is a gestational age−related increase in the sensitivity to corticosteroid-induced in utero fetal programming. It has been reported that fetal overexposure to corticosteroids in late pregnancy can permanently increase the activity of the HPA-axis, with likely consequences in adult life.¹⁹

Another concern relates to oligodendrocytes development. Although the neuronal division process in humans usually is completed by 24 weeks’ gestation, the most rapid growth for oligodendrocytes occurs between 34 and 36 weeks’ gestation; these are the cells responsible for the synthesis of myelin. Overexposure to corticosteroids at this vulnerable time in the late preterm fetus potentially may have unanticipated negative neurologic consequences.²⁰

Where should future studies focus?There is clear neonatal benefit from a single course of ACS given to women who will deliver before 34 weeks’ gestation. It is widely accepted, based on the evidence provided by the 30-year follow-up of the cohort of 534 participants from the Auckland trial (the longest follow-up for any pregnancy trial), that administration of ACS at less than 34 weeks’ gestation is not associated with any obvious major developmental risk.²¹⁻²³

However, the reassurances provided by the Auckland cohort should be neither directly extrapolated to the administration of ACS in the late preterm period nor applied to term-born babies exposed to ACS, for the simple reason that these subgroups never have been analyzed separately. The risk:benefit ratio of ACS use in the late-preterm period is as yet unknown, and in term-born babies the ratio may be unfavorable.

Follow-up studies are neededWe consider that there is a vital need for long-term follow-up studies. The focus of research on the effects of ACS no longer is on the immediate neonatal outcomes and now is on safety and the long-term outcomes of this exposure.

Bottom lineWe regard the large, high-quality study conducted by the NICHD MFMU Network¹ as an opportunity to answer current concerns. It is hoped that the resources necessaryfor in-depth follow-up of the children involved in this study will be provided to the investigators and to the NICHD. It is only with such follow-up that mid- and long-term adverse effects can be assessed. We believe that, at a minimum, mid-term follow-up data should be available before it is wise to make any definitive recommendations for a sweeping change in clinical practice.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

The results of the highly anticipated Antenatal Late Preterm Study recently have become available.¹ Data from this randomized controlled trial, conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network, demonstrated that administration of betamethasone to women at risk for preterm delivery between 34 weeks 0 days and 36 weeks 6 days of gestation significantly reduces the rate of neonatal respiratory complications. It may represent the largest study of antenatal corticosteroids (ACS) to date, with 2,827 infants studied, and its results inevitably lead to the logical practical question: Should ACS use be extended beyond the 34 weeks’ gestation limit previously recommended by professional guidelines in the United States²?

There are some issues that bear discussion before such a significant change in standard of care should be promoted.²

Antenatal Late Preterm Study outcomesThe primary outcome in the study was a composite end point describing the need for respiratory support within 72 hours after birth. Based on a pilot study, the investigators had anticipated a 33% decrease in the rate of the primary outcome; however, the reduction was only 20% (relative risk [RR], 0.80; 95% confidence interval [CI], 0.66−0.97). Although the effect size was statistically significant, one could question the clinical relevance of such a small difference.

A 33% reduction effect, more consistent with the preliminary expectations, was noted in the prespecified secondary composite outcome of severe respiratory complications (RR, 0.67; 95% CI, 0.53−0.84). Occurrences included in the secondary composite outcome that also showed significant rate reductions were:

The reported reduction in bronchopulmonary dysplasia (RR, 0.22; 95% CI, 0.02−0.92) cannot plausibly be attributed to ACS. Randomized data aggregated by the Cochrane Database of Systematic Reviews³ do not show improvement in chronic lung disease with ACS use. Moreover, the authors recognize that the assessment for bronchopulmonary dysplasia at only 28 days of life is only partially informative and that longer childhood follow-up is required to confirm the finding.

We recommend caution before changing current practiceWe propose prudence with ACS use after 34 weeks’ gestation for the following reasons: the increased risk for neonatal hypoglycemia associated with ACS, the increased risk for ACS-related harm in term-born babies, and safety concerns with ACS in the late preterm period.

Evidence shows an increased risk for neonatal hypoglycemiaThe most profound effect modification observed in the study was an adverse effect—namely, a 60% increase in neonatal hypoglycemia with ACS administration (RR, 1.6; 95% CI, 1.37−1.87). The rate of neonatal hypoglycemia was 24% in the ACS group, compared with 15% in the placebo group.

Results of prior studies have demonstrated either no increased risk of hypoglycemia with ACS use⁴⁻⁷ or a much smaller increase (from 4.2% to 5.7%).⁸ The higher rate of neonatal hypoglycemia seen in this study suggests the possibility that the late preterm population may be more vulnerable to the negative impact of ACS on neonatal glucose/insulin homeostasis. Presumed mechanisms of action are either maternal hyperglycemia or fetal adrenal suppression or both, with potential for fetal adrenal suppression resulting from betamethasone exposure to affect long-term metabolic outcomes.⁹

Of note, women with pregestational diabetes were excluded from the study and, in routine practice, inclusion of such patients may further increase the risk of neonatal hypoglycemia.

There are few data on the prognostic significance of neonatal hypoglycemia in preterm infants, with the exception of a single study, the results of which show that it is associated with adverse neurodevelopment at 18 months of age.¹⁰

Data reveal increased risk for harm in term-born babiesIn spite of strict protocol specifications to increase the probability of delivery before 37 weeks’ gestation, 16% of women in the trial delivered at term. Investigators of prior randomized studies of ACS, aimed at reducing the risks of prematurity, have reported a rate of term delivery of about one-third,^4,11 and in routine practice, administration of ACS after 34 weeks may be associated with even higher rates of term delivery.

This is important because recent evidence shows an unfavorable impact of ACS exposure in term-born children.¹² The 5-year follow-up of the largest randomized trial in which multiple ACS courses were used noted that babies born at term had a 4-fold increased odds ratio for neurosensory disability.¹¹ There was no dose−response interaction, with the same adverse odds ratio after 1 or 4 additional ACS courses. This observation was consistent with a previously reported Swedish national cohort, pointing to an unfavorable impact of even a single course of ACS in term-born children, with a greater likelihood of harm than benefit.¹³

In a UK follow-up of children aged 8 to 15 years who were enrolled in an RCT of ACS before cesarean delivery at term, low academic achievement was significantly more common in the group whose mothers had received ACS.¹⁴ In another study of 304 children born at term after exposure to a single course of ACS, investigators noted significantly increased cortisol reactivity to acute psychological stress at ages 6 to 11 years in the ACS-exposed patients, compared with 212 babies of women with threatened preterm labor who did not receive ACS and 372 babies from uncomplicated term pregnancies.¹⁵

The relevance of such study findings extends beyond childhood given the fact that elevated hypothalamic-pituitary-adrenal (HPA) axis reactivity has been linked to the pathogenesis of metabolic syndrome and depression in adult life.¹⁶ As recently as 2015, investigators of a randomized trial of ACS in 6 low- and middle-income countries highlighted their concern regarding “potentially harmful use of antenatal corticosteroids for infants not delivered preterm.”¹⁷

There are safety concerns with ACS in the late preterm periodThe effects of ACS are more pleiotropic than those reflected in a lower incidence of respiratory difficulties. Knowledge of the overall consequences of ACS exposure in infants born late-preterm or at term is still limited. The close-to-term fetus exposed to exogenous corticosteroids is also exposed to the physiologic endogenous surge of cortisol known to occur in the maternal circulation in late pregnancy, which reaches levels 3 times higher than those seen in nonpregnant women.¹⁸ Although placental 11 beta-hydroxysteroid dehydrogenase type 2 plays a protective role by allowing no more than 10% to 20% of maternal corticosteroids to cross the placenta, fetal overexposure from concomitant exogenous maternal corticosteroid administration remains a theoretical concern close to term. This is especially worrisome if there is a gestational age−related increase in the sensitivity to corticosteroid-induced in utero fetal programming. It has been reported that fetal overexposure to corticosteroids in late pregnancy can permanently increase the activity of the HPA-axis, with likely consequences in adult life.¹⁹

Another concern relates to oligodendrocytes development. Although the neuronal division process in humans usually is completed by 24 weeks’ gestation, the most rapid growth for oligodendrocytes occurs between 34 and 36 weeks’ gestation; these are the cells responsible for the synthesis of myelin. Overexposure to corticosteroids at this vulnerable time in the late preterm fetus potentially may have unanticipated negative neurologic consequences.²⁰

Where should future studies focus?There is clear neonatal benefit from a single course of ACS given to women who will deliver before 34 weeks’ gestation. It is widely accepted, based on the evidence provided by the 30-year follow-up of the cohort of 534 participants from the Auckland trial (the longest follow-up for any pregnancy trial), that administration of ACS at less than 34 weeks’ gestation is not associated with any obvious major developmental risk.²¹⁻²³

However, the reassurances provided by the Auckland cohort should be neither directly extrapolated to the administration of ACS in the late preterm period nor applied to term-born babies exposed to ACS, for the simple reason that these subgroups never have been analyzed separately. The risk:benefit ratio of ACS use in the late-preterm period is as yet unknown, and in term-born babies the ratio may be unfavorable.

Follow-up studies are neededWe consider that there is a vital need for long-term follow-up studies. The focus of research on the effects of ACS no longer is on the immediate neonatal outcomes and now is on safety and the long-term outcomes of this exposure.

Bottom lineWe regard the large, high-quality study conducted by the NICHD MFMU Network¹ as an opportunity to answer current concerns. It is hoped that the resources necessaryfor in-depth follow-up of the children involved in this study will be provided to the investigators and to the NICHD. It is only with such follow-up that mid- and long-term adverse effects can be assessed. We believe that, at a minimum, mid-term follow-up data should be available before it is wise to make any definitive recommendations for a sweeping change in clinical practice.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

The results of the highly anticipated Antenatal Late Preterm Study recently have become available.¹ Data from this randomized controlled trial, conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network, demonstrated that administration of betamethasone to women at risk for preterm delivery between 34 weeks 0 days and 36 weeks 6 days of gestation significantly reduces the rate of neonatal respiratory complications. It may represent the largest study of antenatal corticosteroids (ACS) to date, with 2,827 infants studied, and its results inevitably lead to the logical practical question: Should ACS use be extended beyond the 34 weeks’ gestation limit previously recommended by professional guidelines in the United States²?

There are some issues that bear discussion before such a significant change in standard of care should be promoted.²

Antenatal Late Preterm Study outcomesThe primary outcome in the study was a composite end point describing the need for respiratory support within 72 hours after birth. Based on a pilot study, the investigators had anticipated a 33% decrease in the rate of the primary outcome; however, the reduction was only 20% (relative risk [RR], 0.80; 95% confidence interval [CI], 0.66−0.97). Although the effect size was statistically significant, one could question the clinical relevance of such a small difference.

A 33% reduction effect, more consistent with the preliminary expectations, was noted in the prespecified secondary composite outcome of severe respiratory complications (RR, 0.67; 95% CI, 0.53−0.84). Occurrences included in the secondary composite outcome that also showed significant rate reductions were:

The reported reduction in bronchopulmonary dysplasia (RR, 0.22; 95% CI, 0.02−0.92) cannot plausibly be attributed to ACS. Randomized data aggregated by the Cochrane Database of Systematic Reviews³ do not show improvement in chronic lung disease with ACS use. Moreover, the authors recognize that the assessment for bronchopulmonary dysplasia at only 28 days of life is only partially informative and that longer childhood follow-up is required to confirm the finding.

We recommend caution before changing current practiceWe propose prudence with ACS use after 34 weeks’ gestation for the following reasons: the increased risk for neonatal hypoglycemia associated with ACS, the increased risk for ACS-related harm in term-born babies, and safety concerns with ACS in the late preterm period.

Evidence shows an increased risk for neonatal hypoglycemiaThe most profound effect modification observed in the study was an adverse effect—namely, a 60% increase in neonatal hypoglycemia with ACS administration (RR, 1.6; 95% CI, 1.37−1.87). The rate of neonatal hypoglycemia was 24% in the ACS group, compared with 15% in the placebo group.

Results of prior studies have demonstrated either no increased risk of hypoglycemia with ACS use⁴⁻⁷ or a much smaller increase (from 4.2% to 5.7%).⁸ The higher rate of neonatal hypoglycemia seen in this study suggests the possibility that the late preterm population may be more vulnerable to the negative impact of ACS on neonatal glucose/insulin homeostasis. Presumed mechanisms of action are either maternal hyperglycemia or fetal adrenal suppression or both, with potential for fetal adrenal suppression resulting from betamethasone exposure to affect long-term metabolic outcomes.⁹

Of note, women with pregestational diabetes were excluded from the study and, in routine practice, inclusion of such patients may further increase the risk of neonatal hypoglycemia.

There are few data on the prognostic significance of neonatal hypoglycemia in preterm infants, with the exception of a single study, the results of which show that it is associated with adverse neurodevelopment at 18 months of age.¹⁰

Data reveal increased risk for harm in term-born babiesIn spite of strict protocol specifications to increase the probability of delivery before 37 weeks’ gestation, 16% of women in the trial delivered at term. Investigators of prior randomized studies of ACS, aimed at reducing the risks of prematurity, have reported a rate of term delivery of about one-third,^4,11 and in routine practice, administration of ACS after 34 weeks may be associated with even higher rates of term delivery.

This is important because recent evidence shows an unfavorable impact of ACS exposure in term-born children.¹² The 5-year follow-up of the largest randomized trial in which multiple ACS courses were used noted that babies born at term had a 4-fold increased odds ratio for neurosensory disability.¹¹ There was no dose−response interaction, with the same adverse odds ratio after 1 or 4 additional ACS courses. This observation was consistent with a previously reported Swedish national cohort, pointing to an unfavorable impact of even a single course of ACS in term-born children, with a greater likelihood of harm than benefit.¹³

In a UK follow-up of children aged 8 to 15 years who were enrolled in an RCT of ACS before cesarean delivery at term, low academic achievement was significantly more common in the group whose mothers had received ACS.¹⁴ In another study of 304 children born at term after exposure to a single course of ACS, investigators noted significantly increased cortisol reactivity to acute psychological stress at ages 6 to 11 years in the ACS-exposed patients, compared with 212 babies of women with threatened preterm labor who did not receive ACS and 372 babies from uncomplicated term pregnancies.¹⁵

The relevance of such study findings extends beyond childhood given the fact that elevated hypothalamic-pituitary-adrenal (HPA) axis reactivity has been linked to the pathogenesis of metabolic syndrome and depression in adult life.¹⁶ As recently as 2015, investigators of a randomized trial of ACS in 6 low- and middle-income countries highlighted their concern regarding “potentially harmful use of antenatal corticosteroids for infants not delivered preterm.”¹⁷

There are safety concerns with ACS in the late preterm periodThe effects of ACS are more pleiotropic than those reflected in a lower incidence of respiratory difficulties. Knowledge of the overall consequences of ACS exposure in infants born late-preterm or at term is still limited. The close-to-term fetus exposed to exogenous corticosteroids is also exposed to the physiologic endogenous surge of cortisol known to occur in the maternal circulation in late pregnancy, which reaches levels 3 times higher than those seen in nonpregnant women.¹⁸ Although placental 11 beta-hydroxysteroid dehydrogenase type 2 plays a protective role by allowing no more than 10% to 20% of maternal corticosteroids to cross the placenta, fetal overexposure from concomitant exogenous maternal corticosteroid administration remains a theoretical concern close to term. This is especially worrisome if there is a gestational age−related increase in the sensitivity to corticosteroid-induced in utero fetal programming. It has been reported that fetal overexposure to corticosteroids in late pregnancy can permanently increase the activity of the HPA-axis, with likely consequences in adult life.¹⁹

Another concern relates to oligodendrocytes development. Although the neuronal division process in humans usually is completed by 24 weeks’ gestation, the most rapid growth for oligodendrocytes occurs between 34 and 36 weeks’ gestation; these are the cells responsible for the synthesis of myelin. Overexposure to corticosteroids at this vulnerable time in the late preterm fetus potentially may have unanticipated negative neurologic consequences.²⁰

Where should future studies focus?There is clear neonatal benefit from a single course of ACS given to women who will deliver before 34 weeks’ gestation. It is widely accepted, based on the evidence provided by the 30-year follow-up of the cohort of 534 participants from the Auckland trial (the longest follow-up for any pregnancy trial), that administration of ACS at less than 34 weeks’ gestation is not associated with any obvious major developmental risk.²¹⁻²³

However, the reassurances provided by the Auckland cohort should be neither directly extrapolated to the administration of ACS in the late preterm period nor applied to term-born babies exposed to ACS, for the simple reason that these subgroups never have been analyzed separately. The risk:benefit ratio of ACS use in the late-preterm period is as yet unknown, and in term-born babies the ratio may be unfavorable.

Follow-up studies are neededWe consider that there is a vital need for long-term follow-up studies. The focus of research on the effects of ACS no longer is on the immediate neonatal outcomes and now is on safety and the long-term outcomes of this exposure.

Bottom lineWe regard the large, high-quality study conducted by the NICHD MFMU Network¹ as an opportunity to answer current concerns. It is hoped that the resources necessaryfor in-depth follow-up of the children involved in this study will be provided to the investigators and to the NICHD. It is only with such follow-up that mid- and long-term adverse effects can be assessed. We believe that, at a minimum, mid-term follow-up data should be available before it is wise to make any definitive recommendations for a sweeping change in clinical practice.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.