SNOWMASS, COLO. – Multifaceted progress in mechanical circulatory support as long-term therapy in end-stage heart failure is happening at a brisk pace, Y. Joseph C. Woo, MD, reported at the Annual Cardiovascular Conference at Snowmass.

“I believe mechanical circulatory support will ultimately surpass heart transplantation,” declared Dr. Woo, professor and chair of the department of cardiothoracic surgery at Stanford (Calif.) University.

That’s quite a prediction, especially considering the source: Stanford is where the late Dr. Norman Shumway – widely considered “the father of heart transplantation” – performed the first adult heart transplant in the United States in 1968.

In comparing the pros and cons of heart transplantation versus mechanical circulatory support, it’s obvious that device therapy is the winning strategy, Dr. Woo said. The only two areas where heart transplantation now has an edge are that it doesn’t entail lifelong anticoagulation or need for a driveline passing through the skin. But change is coming. Wireless energy transfer technology for left ventricular assist devices (LVADs) is in an advanced stage of development, and ongoing research into blood/device interactions is likely to yield solutions that obviate the need for long-term anticoagulation in patients on mechanical circulatory support (MCS), he predicted.

Dr. Woo was coauthor of an American Heart Association policy statement on the future of cardiovascular disease in the United States, which forecast a 25% increase in heart failure between 2010 and 2030 (Circulation. 2011 Mar 1;123[8]:933-44). There is simply no way that heart transplantation can begin to meet the projected growing need for effective therapy in patients with end-stage disease.

Bruce Jancin/Frontline Medical News

Indeed, as a result of the perpetual donor shortage, only about 4,500 heart transplants are done annually worldwide. In North America the annual number has been essentially flat since 1990. Dr. Woo and his coworkers have managed to put a small dent in the donor organ shortage by developing novel techniques for surgical repair of donor hearts previously rejected by multiple transplant centers due to isolated aortic or mitral valve disease. The ex vivo valve repairs are done rapidly while the donor heart is sitting in an ice bucket prior to transplantation. But these and other efforts to enhance donor heart utilization can’t meet the growing demand.

Here’s what Dr. Woo sees as the future of MCS:

Minimally invasive implantation

At Stanford, LVAD implantations are now routinely done off-pump on a beating heart.

“We clamp only when there is a sound reason, like the presence of left ventricular thrombus, where you run the risk of embolization without the cross clamp,” the surgeon said.

Concomitant valvular surgery

At Stanford and other centers of excellence, surgeons perform additional procedures as warranted while they implant an LVAD, including atrial fibrillation ablation, revascularization of the right heart coronaries, patent foramen ovale closure, and repair of the tricuspid, pulmonic, or aortic valves.

Enhanced right ventricular management

Survival is greatly impaired if a patient with an LVAD later requires the addition of a right ventricular assist device. This realization has led to the development of multiple preoperative risk scoring systems by the Stanford group (Ann Thorac Surg. 2013 Sep;96[3]:857-63) and others, including investigators at the Deutsche Herzzentrum Berlin, the world’s busiest heart transplant center. The purpose is to identify upfront those patients who are likely to later develop right heart failure so they can receive biventricular MCS from the start.

Adjunctive biologic therapies

Intramyocardial injection of 25 million allogeneic mesenchymal precursor cells during LVAD implantation appeared to be safe and showed a promising efficacy signal in a 30-patient, multicenter, double-blind, placebo-controlled, National Institutes of Health–sponsored proof of concept study in which Dr. Woo was a coinvestigator (Circulation. 2014 Jun 3;129[22]:2287-96).

The goal of this research effort is to provide a cell therapy assist to the LVAD as a bridge to recovery of left ventricular function such that the device might eventually no longer be needed, he explained.

These cells are immune privileged. They can be transplanted into recipients without need for immunosuppressive therapy or HLA matching, basically as an off the shelf product. Rather than transforming into cardiomyocytes, it appears that the mechanism by which the donor cells enhance cardiac performance in heart failure is via secretion of a shower of growth and angiogenic factors.

Based upon the encouraging results of the initial study, a 90-patient, phase II, double-blind clinical trial is underway. In order to better evaluate efficacy, this time the patients will receive 150 million mesenchymal precursor cells rather than 25 million.

 

New technologies

The developmental pipeline is chock full of MCS devices. The trend is to go smaller and simpler. HeartWare is developing a miniaturized version of its approved continuous flow centrifugal force LVAD. The ReliantHeart aVAD, an intraventricular device less than 2.5 cm in diameter, is approved in Europe and under study in the U.S. The Thoratec HeartMate III is a smaller version of the HeartMate II, which is FDA-approved as destination therapy. And the Circulite Synergy micropump, designed to provide partial circulatory support to patients who don’t require a full-force LVAD, is the size of a AA battery.

Dr. Woo reported having no financial conflicts.

[email protected]

SNOWMASS, COLO. – Multifaceted progress in mechanical circulatory support as long-term therapy in end-stage heart failure is happening at a brisk pace, Y. Joseph C. Woo, MD, reported at the Annual Cardiovascular Conference at Snowmass.

“I believe mechanical circulatory support will ultimately surpass heart transplantation,” declared Dr. Woo, professor and chair of the department of cardiothoracic surgery at Stanford (Calif.) University.

That’s quite a prediction, especially considering the source: Stanford is where the late Dr. Norman Shumway – widely considered “the father of heart transplantation” – performed the first adult heart transplant in the United States in 1968.

In comparing the pros and cons of heart transplantation versus mechanical circulatory support, it’s obvious that device therapy is the winning strategy, Dr. Woo said. The only two areas where heart transplantation now has an edge are that it doesn’t entail lifelong anticoagulation or need for a driveline passing through the skin. But change is coming. Wireless energy transfer technology for left ventricular assist devices (LVADs) is in an advanced stage of development, and ongoing research into blood/device interactions is likely to yield solutions that obviate the need for long-term anticoagulation in patients on mechanical circulatory support (MCS), he predicted.

Dr. Woo was coauthor of an American Heart Association policy statement on the future of cardiovascular disease in the United States, which forecast a 25% increase in heart failure between 2010 and 2030 (Circulation. 2011 Mar 1;123[8]:933-44). There is simply no way that heart transplantation can begin to meet the projected growing need for effective therapy in patients with end-stage disease.

Bruce Jancin/Frontline Medical News

Indeed, as a result of the perpetual donor shortage, only about 4,500 heart transplants are done annually worldwide. In North America the annual number has been essentially flat since 1990. Dr. Woo and his coworkers have managed to put a small dent in the donor organ shortage by developing novel techniques for surgical repair of donor hearts previously rejected by multiple transplant centers due to isolated aortic or mitral valve disease. The ex vivo valve repairs are done rapidly while the donor heart is sitting in an ice bucket prior to transplantation. But these and other efforts to enhance donor heart utilization can’t meet the growing demand.

Here’s what Dr. Woo sees as the future of MCS:

Minimally invasive implantation

At Stanford, LVAD implantations are now routinely done off-pump on a beating heart.

“We clamp only when there is a sound reason, like the presence of left ventricular thrombus, where you run the risk of embolization without the cross clamp,” the surgeon said.

Concomitant valvular surgery

At Stanford and other centers of excellence, surgeons perform additional procedures as warranted while they implant an LVAD, including atrial fibrillation ablation, revascularization of the right heart coronaries, patent foramen ovale closure, and repair of the tricuspid, pulmonic, or aortic valves.

Enhanced right ventricular management

Survival is greatly impaired if a patient with an LVAD later requires the addition of a right ventricular assist device. This realization has led to the development of multiple preoperative risk scoring systems by the Stanford group (Ann Thorac Surg. 2013 Sep;96[3]:857-63) and others, including investigators at the Deutsche Herzzentrum Berlin, the world’s busiest heart transplant center. The purpose is to identify upfront those patients who are likely to later develop right heart failure so they can receive biventricular MCS from the start.

Adjunctive biologic therapies

Intramyocardial injection of 25 million allogeneic mesenchymal precursor cells during LVAD implantation appeared to be safe and showed a promising efficacy signal in a 30-patient, multicenter, double-blind, placebo-controlled, National Institutes of Health–sponsored proof of concept study in which Dr. Woo was a coinvestigator (Circulation. 2014 Jun 3;129[22]:2287-96).

The goal of this research effort is to provide a cell therapy assist to the LVAD as a bridge to recovery of left ventricular function such that the device might eventually no longer be needed, he explained.

These cells are immune privileged. They can be transplanted into recipients without need for immunosuppressive therapy or HLA matching, basically as an off the shelf product. Rather than transforming into cardiomyocytes, it appears that the mechanism by which the donor cells enhance cardiac performance in heart failure is via secretion of a shower of growth and angiogenic factors.

Based upon the encouraging results of the initial study, a 90-patient, phase II, double-blind clinical trial is underway. In order to better evaluate efficacy, this time the patients will receive 150 million mesenchymal precursor cells rather than 25 million.

 

New technologies

The developmental pipeline is chock full of MCS devices. The trend is to go smaller and simpler. HeartWare is developing a miniaturized version of its approved continuous flow centrifugal force LVAD. The ReliantHeart aVAD, an intraventricular device less than 2.5 cm in diameter, is approved in Europe and under study in the U.S. The Thoratec HeartMate III is a smaller version of the HeartMate II, which is FDA-approved as destination therapy. And the Circulite Synergy micropump, designed to provide partial circulatory support to patients who don’t require a full-force LVAD, is the size of a AA battery.

Dr. Woo reported having no financial conflicts.

[email protected]

SNOWMASS, COLO. – Multifaceted progress in mechanical circulatory support as long-term therapy in end-stage heart failure is happening at a brisk pace, Y. Joseph C. Woo, MD, reported at the Annual Cardiovascular Conference at Snowmass.

“I believe mechanical circulatory support will ultimately surpass heart transplantation,” declared Dr. Woo, professor and chair of the department of cardiothoracic surgery at Stanford (Calif.) University.

That’s quite a prediction, especially considering the source: Stanford is where the late Dr. Norman Shumway – widely considered “the father of heart transplantation” – performed the first adult heart transplant in the United States in 1968.

In comparing the pros and cons of heart transplantation versus mechanical circulatory support, it’s obvious that device therapy is the winning strategy, Dr. Woo said. The only two areas where heart transplantation now has an edge are that it doesn’t entail lifelong anticoagulation or need for a driveline passing through the skin. But change is coming. Wireless energy transfer technology for left ventricular assist devices (LVADs) is in an advanced stage of development, and ongoing research into blood/device interactions is likely to yield solutions that obviate the need for long-term anticoagulation in patients on mechanical circulatory support (MCS), he predicted.

Dr. Woo was coauthor of an American Heart Association policy statement on the future of cardiovascular disease in the United States, which forecast a 25% increase in heart failure between 2010 and 2030 (Circulation. 2011 Mar 1;123[8]:933-44). There is simply no way that heart transplantation can begin to meet the projected growing need for effective therapy in patients with end-stage disease.

Bruce Jancin/Frontline Medical News

Indeed, as a result of the perpetual donor shortage, only about 4,500 heart transplants are done annually worldwide. In North America the annual number has been essentially flat since 1990. Dr. Woo and his coworkers have managed to put a small dent in the donor organ shortage by developing novel techniques for surgical repair of donor hearts previously rejected by multiple transplant centers due to isolated aortic or mitral valve disease. The ex vivo valve repairs are done rapidly while the donor heart is sitting in an ice bucket prior to transplantation. But these and other efforts to enhance donor heart utilization can’t meet the growing demand.

Here’s what Dr. Woo sees as the future of MCS:

Minimally invasive implantation

At Stanford, LVAD implantations are now routinely done off-pump on a beating heart.

“We clamp only when there is a sound reason, like the presence of left ventricular thrombus, where you run the risk of embolization without the cross clamp,” the surgeon said.

Concomitant valvular surgery

At Stanford and other centers of excellence, surgeons perform additional procedures as warranted while they implant an LVAD, including atrial fibrillation ablation, revascularization of the right heart coronaries, patent foramen ovale closure, and repair of the tricuspid, pulmonic, or aortic valves.

Enhanced right ventricular management

Survival is greatly impaired if a patient with an LVAD later requires the addition of a right ventricular assist device. This realization has led to the development of multiple preoperative risk scoring systems by the Stanford group (Ann Thorac Surg. 2013 Sep;96[3]:857-63) and others, including investigators at the Deutsche Herzzentrum Berlin, the world’s busiest heart transplant center. The purpose is to identify upfront those patients who are likely to later develop right heart failure so they can receive biventricular MCS from the start.

Adjunctive biologic therapies

Intramyocardial injection of 25 million allogeneic mesenchymal precursor cells during LVAD implantation appeared to be safe and showed a promising efficacy signal in a 30-patient, multicenter, double-blind, placebo-controlled, National Institutes of Health–sponsored proof of concept study in which Dr. Woo was a coinvestigator (Circulation. 2014 Jun 3;129[22]:2287-96).

The goal of this research effort is to provide a cell therapy assist to the LVAD as a bridge to recovery of left ventricular function such that the device might eventually no longer be needed, he explained.

These cells are immune privileged. They can be transplanted into recipients without need for immunosuppressive therapy or HLA matching, basically as an off the shelf product. Rather than transforming into cardiomyocytes, it appears that the mechanism by which the donor cells enhance cardiac performance in heart failure is via secretion of a shower of growth and angiogenic factors.

Based upon the encouraging results of the initial study, a 90-patient, phase II, double-blind clinical trial is underway. In order to better evaluate efficacy, this time the patients will receive 150 million mesenchymal precursor cells rather than 25 million.

 

New technologies

The developmental pipeline is chock full of MCS devices. The trend is to go smaller and simpler. HeartWare is developing a miniaturized version of its approved continuous flow centrifugal force LVAD. The ReliantHeart aVAD, an intraventricular device less than 2.5 cm in diameter, is approved in Europe and under study in the U.S. The Thoratec HeartMate III is a smaller version of the HeartMate II, which is FDA-approved as destination therapy. And the Circulite Synergy micropump, designed to provide partial circulatory support to patients who don’t require a full-force LVAD, is the size of a AA battery.

Dr. Woo reported having no financial conflicts.

[email protected]

 

EXPERT ANALYSIS AT THE NPA PSYCHOPHARMACOLOGY UPDATE

LAS VEGAS – Michael F. Myers, MD, found a common thread in interviews with loved ones, friends, and colleagues of physicians who have taken their own lives: About 10%-15% of the decedents never sought help beforehand.

“They’ve gone from illness to death without any care,” Dr. Myers, a psychiatrist, said at the annual psychopharmacology update held by the Nevada Psychiatric Association.

Courtesy Dr. Michael Myers

“I was shocked about this finding because we tend to know about the ones who do knock on our door to receive some type of treatment and then die by suicide. But to know that there are significant numbers of doctors out there who have received no treatment at all is unprecedented. We tend to delay going to physicians for help when we notice things in ourselves. It has been especially devastating for families. They want something to change in the world of medicine that will make it easier for doctors to go for help.”

In a new book based on the interviews, “Why Physicians Die by Suicide: Lessons Learned From Their Families and Others Who Cared” (Amazon, 2017), Dr. Myers combined stories from his own clinical practice and qualitative interviews with about 75 men and women to explore reasons why physicians might choose to take their own lives. “Our nonpsychiatric medical colleagues are really anxious to have information from us, because we’re living in an age of burnout; roughly 50% of U.S. physicians suffer from burnout,” he said. In addition to perspectives from bereaved loved ones and former medical colleagues, the book includes insights from others who are affected when doctors die by suicide: their medical training directors, employers, medical students, treating psychiatrists, and patients.

According to the American Foundation for Suicide Prevention, 300-400 physicians take their own lives every year, the equivalent of two to three medical school classes. “That’s a doctor a day we lose to suicide,” said Dr. Myers, a professor of clinical psychiatry at State University of New York, Brooklyn, who specializes in physician health. Compared with the general population, the suicide rate ratio is 2.27 among female physicians and 1.41 among male physicians (Am J Psychiatry. 2004;161[12]:2295-2302), and an estimated 85%-90% of those who carry out a suicide have a psychiatric illness such as major depressive disorder, bipolar disorder, alcohol use and substance use disorder, and borderline personality disorder. Other triggers common to physicians, Dr. Myers said, include other kinds of personality disorders, burnout, untreated anxiety disorders, substance/medication-induced depressive disorder (especially in clinicians who have been self-medicating), and posttraumatic stress disorder.

Additional risk considerations to keep in mind for physician patients include a family history of mood disorders, a sense of professional isolation, coping with lawsuits and/or medical license investigations, previous history of a depressive episode, and a previous suicide attempt. “Sometimes, it’s hard to get this information from a new physician who’s sitting opposite you,” Dr. Myers noted. “We mustn’t forget that there’s a lot of shame, embarrassment, and guilt that’s attached to previous suicide attempts.”

Suicide risk also is elevated for physicians with treatment-refractory psychiatric illness. “It troubles me when a physician is being treated by a generalist, the patient is not doing well, and he or she is not being referred for a second opinion or has never been referred to a psychopharmacologist,” he said. “It’s important that be done, because you know how difficult many of your patients can be. It’s important to have the expertise of a psychopharmacologist. I believe that physician patients will welcome that [second opinion], even if they have to travel 200 miles for it.”

The list of risk considerations for suicidal physicians also includes undiagnosed and untreated bipolar I or II disorder, rapid cycling bipolar disorder, and mixed affective states. “These are important things that can make our patients ill very quickly,” he said. Impulsivity is another consideration, as are severe sleep deprivation, circadian rhythm disturbances, and acute suicidal affective disturbance, which has emerged as a condition to consider in future revisions of DSM-5. “What you see in this condition is an individual becoming suicidal within minutes or hours,” Dr. Myers explained. “It’s usually an agitated state with insomnia and overvalued ideas or delusions that they are completely untreatable and hopeless. Physicians are no different than anyone else in that kind of state.” He emphasized that the stigma attached to mental illness in physicians is pernicious, because untreated mental illness is a key driver of suicide. After one of Dr. Myers’s patients took his own life, his son told Dr. Myers, “My father just hated being a patient. He felt so ashamed. I tried hard, too, but my support wasn’t enough.”

Inadequate treatment can occur for physician patients because of transference and countertransference dynamics “that muddle the treatment dyad,” Dr. Myers added. “We must be mindful of the many issues that are going on when we treat our own.”

In his 2005 book “Why People Die By Suicide,” psychologist Thomas Joiner, PhD, described three key reasons why people choose to take their own lives. The first is “perceived burdensomeness,” or a sense that one is a burden on others. “When I see it in my physician patients, it’s when they have a sense of being a burden on their family and feel they are no longer serving a purpose,” Dr. Myers said. The second reason is “failed belongingness,” or a sense that one does not belong to a valued social group. “This resonates with me,” Dr. Myers said. “Sometimes in therapy sessions, my physician patients will say ‘Don’t call me Dr. Smith anymore; I’m Mr. Smith.’ They’ve removed themselves from the field because they don’t feel like they belong anymore. That’s the unworthiness that physicians can feel.”

The third reason is “learned fearlessness,” or the acquired capability to enact self-injury. Dr. Myers likened it to “the kind of exposure to pain and fear that people also might learn through such experiences as mountain climbing, performing surgery, fighting in wars, or being afflicted with anorexia.”

If you suspect that a physician patient is engaged in suicidal thinking and planning, Dr. Myers advises framing your mental health assessment in the context of trust and mutual respect. “Please don’t be seduced by somebody who’s squeaky clean in the area of suicidality,” he said. “That individual may just not be sharing with you yet. You’re going to have to be firm and parental at times. There’s a lot of terror and shame that can lurk behind those symptomatic behaviors. That’s where you’ll use your expertise. I have found that there are many physicians out there who welcome you to go in that ‘dark place’ with them. For them to be able to share those scary thoughts with someone can enhance the therapeutic alliance.” The inquiry should include questions about potential means and methods, including access to firearms, stockpiled and/or self-prescribed medications, and medications ordered online or stolen/diverted from the workplace. Timely and careful documentation are essential, he said.

The plan for treating suicidal physicians should include obtaining old records and speaking with former treating professionals. “If you get pushback from the patient, say, ‘This is about me wanting to be thorough in my assessment and treatment plan with you,’ ” Dr. Myers said. “There is no substitute for a detailed mental status evaluation, collateral information, clinical intuition, experience, and consultation.” Hospitalizing the physician patient should be judicious and in consultation with others. “If you’re not sure, get a second opinion, because it can be life-saving,” he said, “but if done inappropriately, you can turn them off psychiatry for the rest of their lives. Make sure you’re not just panicking and worrying about some sort of medical-legal risk.”

In cases of split treatment, ensure regular contact with the psychotherapist and document all communication and any changes in status, medication, or psychotherapy modality change.

Dr. Myers cited many ways that psychiatrists can educate their colleagues about burnout, depression, and the risk of suicide. These include offering to give grand rounds or a lecture on the topic, serving on your local CME planning committee, joining your institute’s physician wellness team, serving on your state’s physician health program, and offering to facilitate a group for physicians after a physician colleague has died by suicide. “Postvention is prevention for the next generation,” Dr. Myers said, quoting Edwin S. Shneidman, PhD, founder of the American Association of Suicidology. “By taking care of ourselves and accepting the painful reality of physician suicide, we reach out to those left behind and make a difference. You become a change agent – someone who is part of the movement to stop doctors from killing themselves.”

Dr. Myers disclosed that he has received funding from the Medical Education Speakers Network.

 

[email protected]

 

EXPERT ANALYSIS AT THE NPA PSYCHOPHARMACOLOGY UPDATE

LAS VEGAS – Michael F. Myers, MD, found a common thread in interviews with loved ones, friends, and colleagues of physicians who have taken their own lives: About 10%-15% of the decedents never sought help beforehand.

“They’ve gone from illness to death without any care,” Dr. Myers, a psychiatrist, said at the annual psychopharmacology update held by the Nevada Psychiatric Association.

Courtesy Dr. Michael Myers

“I was shocked about this finding because we tend to know about the ones who do knock on our door to receive some type of treatment and then die by suicide. But to know that there are significant numbers of doctors out there who have received no treatment at all is unprecedented. We tend to delay going to physicians for help when we notice things in ourselves. It has been especially devastating for families. They want something to change in the world of medicine that will make it easier for doctors to go for help.”

In a new book based on the interviews, “Why Physicians Die by Suicide: Lessons Learned From Their Families and Others Who Cared” (Amazon, 2017), Dr. Myers combined stories from his own clinical practice and qualitative interviews with about 75 men and women to explore reasons why physicians might choose to take their own lives. “Our nonpsychiatric medical colleagues are really anxious to have information from us, because we’re living in an age of burnout; roughly 50% of U.S. physicians suffer from burnout,” he said. In addition to perspectives from bereaved loved ones and former medical colleagues, the book includes insights from others who are affected when doctors die by suicide: their medical training directors, employers, medical students, treating psychiatrists, and patients.

According to the American Foundation for Suicide Prevention, 300-400 physicians take their own lives every year, the equivalent of two to three medical school classes. “That’s a doctor a day we lose to suicide,” said Dr. Myers, a professor of clinical psychiatry at State University of New York, Brooklyn, who specializes in physician health. Compared with the general population, the suicide rate ratio is 2.27 among female physicians and 1.41 among male physicians (Am J Psychiatry. 2004;161[12]:2295-2302), and an estimated 85%-90% of those who carry out a suicide have a psychiatric illness such as major depressive disorder, bipolar disorder, alcohol use and substance use disorder, and borderline personality disorder. Other triggers common to physicians, Dr. Myers said, include other kinds of personality disorders, burnout, untreated anxiety disorders, substance/medication-induced depressive disorder (especially in clinicians who have been self-medicating), and posttraumatic stress disorder.

Additional risk considerations to keep in mind for physician patients include a family history of mood disorders, a sense of professional isolation, coping with lawsuits and/or medical license investigations, previous history of a depressive episode, and a previous suicide attempt. “Sometimes, it’s hard to get this information from a new physician who’s sitting opposite you,” Dr. Myers noted. “We mustn’t forget that there’s a lot of shame, embarrassment, and guilt that’s attached to previous suicide attempts.”

Suicide risk also is elevated for physicians with treatment-refractory psychiatric illness. “It troubles me when a physician is being treated by a generalist, the patient is not doing well, and he or she is not being referred for a second opinion or has never been referred to a psychopharmacologist,” he said. “It’s important that be done, because you know how difficult many of your patients can be. It’s important to have the expertise of a psychopharmacologist. I believe that physician patients will welcome that [second opinion], even if they have to travel 200 miles for it.”

The list of risk considerations for suicidal physicians also includes undiagnosed and untreated bipolar I or II disorder, rapid cycling bipolar disorder, and mixed affective states. “These are important things that can make our patients ill very quickly,” he said. Impulsivity is another consideration, as are severe sleep deprivation, circadian rhythm disturbances, and acute suicidal affective disturbance, which has emerged as a condition to consider in future revisions of DSM-5. “What you see in this condition is an individual becoming suicidal within minutes or hours,” Dr. Myers explained. “It’s usually an agitated state with insomnia and overvalued ideas or delusions that they are completely untreatable and hopeless. Physicians are no different than anyone else in that kind of state.” He emphasized that the stigma attached to mental illness in physicians is pernicious, because untreated mental illness is a key driver of suicide. After one of Dr. Myers’s patients took his own life, his son told Dr. Myers, “My father just hated being a patient. He felt so ashamed. I tried hard, too, but my support wasn’t enough.”

Inadequate treatment can occur for physician patients because of transference and countertransference dynamics “that muddle the treatment dyad,” Dr. Myers added. “We must be mindful of the many issues that are going on when we treat our own.”

In his 2005 book “Why People Die By Suicide,” psychologist Thomas Joiner, PhD, described three key reasons why people choose to take their own lives. The first is “perceived burdensomeness,” or a sense that one is a burden on others. “When I see it in my physician patients, it’s when they have a sense of being a burden on their family and feel they are no longer serving a purpose,” Dr. Myers said. The second reason is “failed belongingness,” or a sense that one does not belong to a valued social group. “This resonates with me,” Dr. Myers said. “Sometimes in therapy sessions, my physician patients will say ‘Don’t call me Dr. Smith anymore; I’m Mr. Smith.’ They’ve removed themselves from the field because they don’t feel like they belong anymore. That’s the unworthiness that physicians can feel.”

The third reason is “learned fearlessness,” or the acquired capability to enact self-injury. Dr. Myers likened it to “the kind of exposure to pain and fear that people also might learn through such experiences as mountain climbing, performing surgery, fighting in wars, or being afflicted with anorexia.”

If you suspect that a physician patient is engaged in suicidal thinking and planning, Dr. Myers advises framing your mental health assessment in the context of trust and mutual respect. “Please don’t be seduced by somebody who’s squeaky clean in the area of suicidality,” he said. “That individual may just not be sharing with you yet. You’re going to have to be firm and parental at times. There’s a lot of terror and shame that can lurk behind those symptomatic behaviors. That’s where you’ll use your expertise. I have found that there are many physicians out there who welcome you to go in that ‘dark place’ with them. For them to be able to share those scary thoughts with someone can enhance the therapeutic alliance.” The inquiry should include questions about potential means and methods, including access to firearms, stockpiled and/or self-prescribed medications, and medications ordered online or stolen/diverted from the workplace. Timely and careful documentation are essential, he said.

The plan for treating suicidal physicians should include obtaining old records and speaking with former treating professionals. “If you get pushback from the patient, say, ‘This is about me wanting to be thorough in my assessment and treatment plan with you,’ ” Dr. Myers said. “There is no substitute for a detailed mental status evaluation, collateral information, clinical intuition, experience, and consultation.” Hospitalizing the physician patient should be judicious and in consultation with others. “If you’re not sure, get a second opinion, because it can be life-saving,” he said, “but if done inappropriately, you can turn them off psychiatry for the rest of their lives. Make sure you’re not just panicking and worrying about some sort of medical-legal risk.”

In cases of split treatment, ensure regular contact with the psychotherapist and document all communication and any changes in status, medication, or psychotherapy modality change.

Dr. Myers cited many ways that psychiatrists can educate their colleagues about burnout, depression, and the risk of suicide. These include offering to give grand rounds or a lecture on the topic, serving on your local CME planning committee, joining your institute’s physician wellness team, serving on your state’s physician health program, and offering to facilitate a group for physicians after a physician colleague has died by suicide. “Postvention is prevention for the next generation,” Dr. Myers said, quoting Edwin S. Shneidman, PhD, founder of the American Association of Suicidology. “By taking care of ourselves and accepting the painful reality of physician suicide, we reach out to those left behind and make a difference. You become a change agent – someone who is part of the movement to stop doctors from killing themselves.”

Dr. Myers disclosed that he has received funding from the Medical Education Speakers Network.

 

[email protected]

 

EXPERT ANALYSIS AT THE NPA PSYCHOPHARMACOLOGY UPDATE

LAS VEGAS – Michael F. Myers, MD, found a common thread in interviews with loved ones, friends, and colleagues of physicians who have taken their own lives: About 10%-15% of the decedents never sought help beforehand.

“They’ve gone from illness to death without any care,” Dr. Myers, a psychiatrist, said at the annual psychopharmacology update held by the Nevada Psychiatric Association.

Courtesy Dr. Michael Myers

“I was shocked about this finding because we tend to know about the ones who do knock on our door to receive some type of treatment and then die by suicide. But to know that there are significant numbers of doctors out there who have received no treatment at all is unprecedented. We tend to delay going to physicians for help when we notice things in ourselves. It has been especially devastating for families. They want something to change in the world of medicine that will make it easier for doctors to go for help.”

In a new book based on the interviews, “Why Physicians Die by Suicide: Lessons Learned From Their Families and Others Who Cared” (Amazon, 2017), Dr. Myers combined stories from his own clinical practice and qualitative interviews with about 75 men and women to explore reasons why physicians might choose to take their own lives. “Our nonpsychiatric medical colleagues are really anxious to have information from us, because we’re living in an age of burnout; roughly 50% of U.S. physicians suffer from burnout,” he said. In addition to perspectives from bereaved loved ones and former medical colleagues, the book includes insights from others who are affected when doctors die by suicide: their medical training directors, employers, medical students, treating psychiatrists, and patients.

According to the American Foundation for Suicide Prevention, 300-400 physicians take their own lives every year, the equivalent of two to three medical school classes. “That’s a doctor a day we lose to suicide,” said Dr. Myers, a professor of clinical psychiatry at State University of New York, Brooklyn, who specializes in physician health. Compared with the general population, the suicide rate ratio is 2.27 among female physicians and 1.41 among male physicians (Am J Psychiatry. 2004;161[12]:2295-2302), and an estimated 85%-90% of those who carry out a suicide have a psychiatric illness such as major depressive disorder, bipolar disorder, alcohol use and substance use disorder, and borderline personality disorder. Other triggers common to physicians, Dr. Myers said, include other kinds of personality disorders, burnout, untreated anxiety disorders, substance/medication-induced depressive disorder (especially in clinicians who have been self-medicating), and posttraumatic stress disorder.

Additional risk considerations to keep in mind for physician patients include a family history of mood disorders, a sense of professional isolation, coping with lawsuits and/or medical license investigations, previous history of a depressive episode, and a previous suicide attempt. “Sometimes, it’s hard to get this information from a new physician who’s sitting opposite you,” Dr. Myers noted. “We mustn’t forget that there’s a lot of shame, embarrassment, and guilt that’s attached to previous suicide attempts.”

Suicide risk also is elevated for physicians with treatment-refractory psychiatric illness. “It troubles me when a physician is being treated by a generalist, the patient is not doing well, and he or she is not being referred for a second opinion or has never been referred to a psychopharmacologist,” he said. “It’s important that be done, because you know how difficult many of your patients can be. It’s important to have the expertise of a psychopharmacologist. I believe that physician patients will welcome that [second opinion], even if they have to travel 200 miles for it.”

The list of risk considerations for suicidal physicians also includes undiagnosed and untreated bipolar I or II disorder, rapid cycling bipolar disorder, and mixed affective states. “These are important things that can make our patients ill very quickly,” he said. Impulsivity is another consideration, as are severe sleep deprivation, circadian rhythm disturbances, and acute suicidal affective disturbance, which has emerged as a condition to consider in future revisions of DSM-5. “What you see in this condition is an individual becoming suicidal within minutes or hours,” Dr. Myers explained. “It’s usually an agitated state with insomnia and overvalued ideas or delusions that they are completely untreatable and hopeless. Physicians are no different than anyone else in that kind of state.” He emphasized that the stigma attached to mental illness in physicians is pernicious, because untreated mental illness is a key driver of suicide. After one of Dr. Myers’s patients took his own life, his son told Dr. Myers, “My father just hated being a patient. He felt so ashamed. I tried hard, too, but my support wasn’t enough.”

Inadequate treatment can occur for physician patients because of transference and countertransference dynamics “that muddle the treatment dyad,” Dr. Myers added. “We must be mindful of the many issues that are going on when we treat our own.”

In his 2005 book “Why People Die By Suicide,” psychologist Thomas Joiner, PhD, described three key reasons why people choose to take their own lives. The first is “perceived burdensomeness,” or a sense that one is a burden on others. “When I see it in my physician patients, it’s when they have a sense of being a burden on their family and feel they are no longer serving a purpose,” Dr. Myers said. The second reason is “failed belongingness,” or a sense that one does not belong to a valued social group. “This resonates with me,” Dr. Myers said. “Sometimes in therapy sessions, my physician patients will say ‘Don’t call me Dr. Smith anymore; I’m Mr. Smith.’ They’ve removed themselves from the field because they don’t feel like they belong anymore. That’s the unworthiness that physicians can feel.”

The third reason is “learned fearlessness,” or the acquired capability to enact self-injury. Dr. Myers likened it to “the kind of exposure to pain and fear that people also might learn through such experiences as mountain climbing, performing surgery, fighting in wars, or being afflicted with anorexia.”

If you suspect that a physician patient is engaged in suicidal thinking and planning, Dr. Myers advises framing your mental health assessment in the context of trust and mutual respect. “Please don’t be seduced by somebody who’s squeaky clean in the area of suicidality,” he said. “That individual may just not be sharing with you yet. You’re going to have to be firm and parental at times. There’s a lot of terror and shame that can lurk behind those symptomatic behaviors. That’s where you’ll use your expertise. I have found that there are many physicians out there who welcome you to go in that ‘dark place’ with them. For them to be able to share those scary thoughts with someone can enhance the therapeutic alliance.” The inquiry should include questions about potential means and methods, including access to firearms, stockpiled and/or self-prescribed medications, and medications ordered online or stolen/diverted from the workplace. Timely and careful documentation are essential, he said.

The plan for treating suicidal physicians should include obtaining old records and speaking with former treating professionals. “If you get pushback from the patient, say, ‘This is about me wanting to be thorough in my assessment and treatment plan with you,’ ” Dr. Myers said. “There is no substitute for a detailed mental status evaluation, collateral information, clinical intuition, experience, and consultation.” Hospitalizing the physician patient should be judicious and in consultation with others. “If you’re not sure, get a second opinion, because it can be life-saving,” he said, “but if done inappropriately, you can turn them off psychiatry for the rest of their lives. Make sure you’re not just panicking and worrying about some sort of medical-legal risk.”

In cases of split treatment, ensure regular contact with the psychotherapist and document all communication and any changes in status, medication, or psychotherapy modality change.

Dr. Myers cited many ways that psychiatrists can educate their colleagues about burnout, depression, and the risk of suicide. These include offering to give grand rounds or a lecture on the topic, serving on your local CME planning committee, joining your institute’s physician wellness team, serving on your state’s physician health program, and offering to facilitate a group for physicians after a physician colleague has died by suicide. “Postvention is prevention for the next generation,” Dr. Myers said, quoting Edwin S. Shneidman, PhD, founder of the American Association of Suicidology. “By taking care of ourselves and accepting the painful reality of physician suicide, we reach out to those left behind and make a difference. You become a change agent – someone who is part of the movement to stop doctors from killing themselves.”

Dr. Myers disclosed that he has received funding from the Medical Education Speakers Network.

 

[email protected]

ORLANDO – A composite score based on day 28 plasma levels of the angiogenic factors follistatin and endoglin predicts 1-year nonrelapse mortality in patients who have undergone myeloablative allogeneic hematopoietic cell transplantation, based on findings from the randomized Blood and Marrow Transplant Clinical Trials Network acute graft-versus-host prophylaxis study 0402 (BMT CTN 0402).

Elevations in these factors at day 28 may reflect susceptibility to regimen-related and other toxicities that adversely affect tissue repair and survival, Shernan Holtan, MD, said at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

Sharon Worcester/Frontline Medical News

“Without important trophic angiogenic factors, the body may not be able to heal well after injury such as graft-versus-host disease [GVHD]. We previously reported that such angiogenic factors are indeed altered at the onset of acute graft-versus-host disease based upon samples from BMT CTN 0302 and 0802,” said Dr. Holtan of the University of Minnesota, Minneapolis. “Specifically, we found that repair factors of epidermal growth factor and VEGF-A are low at the onset of acute GVHD, and that damage-associated angiogenic factors are high at the onset of acute graft-versus-host disease.”

These damage-associated factors include follistatin, endoglin, placental growth factor, and angiopoietin-2, she added.

Based on the previous results, Dr. Holtan and her colleagues hypothesized that a pattern of tissue damage as illustrated by these markers at 28 days after treatment would be associated with 1-year nonrelapse mortality.

Of 221 patients from BMT CTN 0402 with pretreatment and day 28 plasma samples available for analysis, 25 had died at 1 year of causes unrelated to relapse. In a univariate analysis, nonrelapse mortality was associated with levels of follistatin, endoglin, and angiopoietin-2. When combined to assess for an overall pattern of damage, only follistatin and endoglin were significantly associated with nonrelapse mortality.

The relative risk of death unrelated to relapse was 4.5-fold higher in patients with the highest score (score of 3) on multivariate regression analysis of follistatin and endoglin levels. Grade II-IV acute GVHD was not significantly associated with 1-year nonrelapse mortality in multivariate analyses, but age over 50 years was.

“Notably, the composite score was a better predictor than any factor alone,” Dr. Holtan said.

The composite score was also predictive of the development of acute GVHD.

“We found that a moderate score of 2 was associated with a 2.3-fold increased risk of acute GVHD prior to day 100. Interestingly, the higher score [3] was not associated with acute GVHD. There was no association of the composite score with chronic GVHD,” she said.

The risk of nonrelapse mortality was less than 10% in patients with a composite score of 1.

Among patients in the study with a score of 3, more than half of the deaths were related to organ toxicity, including liver failure and respiratory failure, which were predominantly infection-related. Those with a low composite score had very few deaths associated with organ toxicity, she noted.

While there are many unanswered questions, these findings highlight possible opportunities to improve survival after allogeneic hematopoietic cell transplantation that warrant further study, she said.

“We need to learn how to constrain this angiogenic inflammatory response with the ultimate goal of hopefully identifying novel treatment strategies to mitigate nonrelapse mortality in our patients,” she concluded.

Dr. Holtan is an investigator for Alexion and is site principal investigator on the GI GVHD clinical trial.

[email protected]

ORLANDO – A composite score based on day 28 plasma levels of the angiogenic factors follistatin and endoglin predicts 1-year nonrelapse mortality in patients who have undergone myeloablative allogeneic hematopoietic cell transplantation, based on findings from the randomized Blood and Marrow Transplant Clinical Trials Network acute graft-versus-host prophylaxis study 0402 (BMT CTN 0402).

Elevations in these factors at day 28 may reflect susceptibility to regimen-related and other toxicities that adversely affect tissue repair and survival, Shernan Holtan, MD, said at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

Sharon Worcester/Frontline Medical News

“Without important trophic angiogenic factors, the body may not be able to heal well after injury such as graft-versus-host disease [GVHD]. We previously reported that such angiogenic factors are indeed altered at the onset of acute graft-versus-host disease based upon samples from BMT CTN 0302 and 0802,” said Dr. Holtan of the University of Minnesota, Minneapolis. “Specifically, we found that repair factors of epidermal growth factor and VEGF-A are low at the onset of acute GVHD, and that damage-associated angiogenic factors are high at the onset of acute graft-versus-host disease.”

These damage-associated factors include follistatin, endoglin, placental growth factor, and angiopoietin-2, she added.

Based on the previous results, Dr. Holtan and her colleagues hypothesized that a pattern of tissue damage as illustrated by these markers at 28 days after treatment would be associated with 1-year nonrelapse mortality.

Of 221 patients from BMT CTN 0402 with pretreatment and day 28 plasma samples available for analysis, 25 had died at 1 year of causes unrelated to relapse. In a univariate analysis, nonrelapse mortality was associated with levels of follistatin, endoglin, and angiopoietin-2. When combined to assess for an overall pattern of damage, only follistatin and endoglin were significantly associated with nonrelapse mortality.

The relative risk of death unrelated to relapse was 4.5-fold higher in patients with the highest score (score of 3) on multivariate regression analysis of follistatin and endoglin levels. Grade II-IV acute GVHD was not significantly associated with 1-year nonrelapse mortality in multivariate analyses, but age over 50 years was.

“Notably, the composite score was a better predictor than any factor alone,” Dr. Holtan said.

The composite score was also predictive of the development of acute GVHD.

“We found that a moderate score of 2 was associated with a 2.3-fold increased risk of acute GVHD prior to day 100. Interestingly, the higher score [3] was not associated with acute GVHD. There was no association of the composite score with chronic GVHD,” she said.

The risk of nonrelapse mortality was less than 10% in patients with a composite score of 1.

Among patients in the study with a score of 3, more than half of the deaths were related to organ toxicity, including liver failure and respiratory failure, which were predominantly infection-related. Those with a low composite score had very few deaths associated with organ toxicity, she noted.

While there are many unanswered questions, these findings highlight possible opportunities to improve survival after allogeneic hematopoietic cell transplantation that warrant further study, she said.

“We need to learn how to constrain this angiogenic inflammatory response with the ultimate goal of hopefully identifying novel treatment strategies to mitigate nonrelapse mortality in our patients,” she concluded.

Dr. Holtan is an investigator for Alexion and is site principal investigator on the GI GVHD clinical trial.

[email protected]

ORLANDO – A composite score based on day 28 plasma levels of the angiogenic factors follistatin and endoglin predicts 1-year nonrelapse mortality in patients who have undergone myeloablative allogeneic hematopoietic cell transplantation, based on findings from the randomized Blood and Marrow Transplant Clinical Trials Network acute graft-versus-host prophylaxis study 0402 (BMT CTN 0402).

Elevations in these factors at day 28 may reflect susceptibility to regimen-related and other toxicities that adversely affect tissue repair and survival, Shernan Holtan, MD, said at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

Sharon Worcester/Frontline Medical News

“Without important trophic angiogenic factors, the body may not be able to heal well after injury such as graft-versus-host disease [GVHD]. We previously reported that such angiogenic factors are indeed altered at the onset of acute graft-versus-host disease based upon samples from BMT CTN 0302 and 0802,” said Dr. Holtan of the University of Minnesota, Minneapolis. “Specifically, we found that repair factors of epidermal growth factor and VEGF-A are low at the onset of acute GVHD, and that damage-associated angiogenic factors are high at the onset of acute graft-versus-host disease.”

These damage-associated factors include follistatin, endoglin, placental growth factor, and angiopoietin-2, she added.

Based on the previous results, Dr. Holtan and her colleagues hypothesized that a pattern of tissue damage as illustrated by these markers at 28 days after treatment would be associated with 1-year nonrelapse mortality.

Of 221 patients from BMT CTN 0402 with pretreatment and day 28 plasma samples available for analysis, 25 had died at 1 year of causes unrelated to relapse. In a univariate analysis, nonrelapse mortality was associated with levels of follistatin, endoglin, and angiopoietin-2. When combined to assess for an overall pattern of damage, only follistatin and endoglin were significantly associated with nonrelapse mortality.

The relative risk of death unrelated to relapse was 4.5-fold higher in patients with the highest score (score of 3) on multivariate regression analysis of follistatin and endoglin levels. Grade II-IV acute GVHD was not significantly associated with 1-year nonrelapse mortality in multivariate analyses, but age over 50 years was.

“Notably, the composite score was a better predictor than any factor alone,” Dr. Holtan said.

The composite score was also predictive of the development of acute GVHD.

“We found that a moderate score of 2 was associated with a 2.3-fold increased risk of acute GVHD prior to day 100. Interestingly, the higher score [3] was not associated with acute GVHD. There was no association of the composite score with chronic GVHD,” she said.

The risk of nonrelapse mortality was less than 10% in patients with a composite score of 1.

Among patients in the study with a score of 3, more than half of the deaths were related to organ toxicity, including liver failure and respiratory failure, which were predominantly infection-related. Those with a low composite score had very few deaths associated with organ toxicity, she noted.

While there are many unanswered questions, these findings highlight possible opportunities to improve survival after allogeneic hematopoietic cell transplantation that warrant further study, she said.

“We need to learn how to constrain this angiogenic inflammatory response with the ultimate goal of hopefully identifying novel treatment strategies to mitigate nonrelapse mortality in our patients,” she concluded.

Dr. Holtan is an investigator for Alexion and is site principal investigator on the GI GVHD clinical trial.

[email protected]

 

SCOTTSDALE, ARIZ. – Whether or not the Affordable Care Act (ACA) is repealed, replaced, reviled, or revered should not deter psychiatrists and primary care physicians from seeking to work together, according to a leading expert on integrating mental health care in medical practice.

“Community-based psychiatrists should be focused on finding ways to help create integrated models of care, both in health systems and in other settings, to provide mental health specialty support for primary care providers, regardless of whatever else is going on [in Washington],” Paul Summergrad, MD, said in an interview at the annual meeting of the American College of Psychiatrists.

designer491/Thinkstock

In a premeeting session on the future of integrated care, Dr. Summergrad, the Dr. Frances S. Arkin Professor and chairman of psychiatry at Tufts University, Boston, pointed to two current trends in Washington that are affecting mental health care. The first is a clamor for repeal of the ACA, which includes pressure from employers who are unhappy with the mandate to provide health insurance to employees; the second is a desire on the part of some lawmakers to slow the growth of state Medicaid budgets by rolling back the federal program’s expansion under the ACA and replacing it with block grants. In opposition, the recent passage of the bipartisan and highly pro–mental health care 21st Century Cures Act calls for more block grants for services for the seriously mentally ill, including those who currently are incarcerated with serious mental illness and substance use disorders, as well as for increased training programs to expand the behavioral health workforce, among other measures.

“If Medicaid expansion is replaced with block grants, that would lead to less care in general for Medicaid recipients,” Dr. Summergrad said in the interview. “It depends on how the states would view their costs of care, and how they would view the medical psychiatric issues.”

Since Medicaid is the largest payer of mental and behavioral health services in the country with reimbursable models of collaborative care, cutting funding for those services would sting. “There’s evidence that addressing mental and behavioral health issues keeps medical costs low,” said Dr. Summergrad, a past president of the American Psychiatric Association.

In his talk, Dr. Summergrad pointed to the now decade-old IMPACT study (Improving Mood: Promoting Access to Collaborative Treatment) which showed that patients screened for depression when presenting with chronic medical issues had lower overall medical costs over time.

He also referred to a more recent study in a large Utah health system that showed overall cost savings, far-fewer emergency department admissions, and better patient outcomes across a wide range of medical issues, which were achieved when mental health services were integrated into routine care: in all, a $12 million investment resulted in $52 million in savings after 4 years (JAMA. 2016;316[8]:826-34). “Utah is not exactly a blue state, but it worked for them,” Dr. Summergrad said. The key was that physicians “embraced normalizing mental health care,” he said.

As for how any changes to the Medicare Access and CHIP Reauthorization Act, which is predicated largely on team-based care for higher reimbursements, Dr. Summergrad said cash-only psychiatrists should be thinking about how to collaborate with primary care providers. “I think the important message at this point is that, however this works, we’ll have to think about integrated care.”

In an interview, Lee H. Beecher, MD, agreed. In fact, Dr. Beecher said that, in his state of Minnesota, engaging with patients on a cash-only basis is the only way a psychiatrist can have a private practice and provide valuable, essential communication with primary care physicians. “Direct-pay physicians are uniquely able to actively facilitate communication,” said Dr. Beecher, president of the nonprofit Minnesota Physician-Patient Alliance. “Most of this is done by phone, directly, with the primary care clinician – rather than inputting and sending an electronic health record.”

Dr. Summergrad had no relevant disclosures.

[email protected]

On Twitter @whitneymcknight

 

SCOTTSDALE, ARIZ. – Whether or not the Affordable Care Act (ACA) is repealed, replaced, reviled, or revered should not deter psychiatrists and primary care physicians from seeking to work together, according to a leading expert on integrating mental health care in medical practice.

“Community-based psychiatrists should be focused on finding ways to help create integrated models of care, both in health systems and in other settings, to provide mental health specialty support for primary care providers, regardless of whatever else is going on [in Washington],” Paul Summergrad, MD, said in an interview at the annual meeting of the American College of Psychiatrists.

designer491/Thinkstock

In a premeeting session on the future of integrated care, Dr. Summergrad, the Dr. Frances S. Arkin Professor and chairman of psychiatry at Tufts University, Boston, pointed to two current trends in Washington that are affecting mental health care. The first is a clamor for repeal of the ACA, which includes pressure from employers who are unhappy with the mandate to provide health insurance to employees; the second is a desire on the part of some lawmakers to slow the growth of state Medicaid budgets by rolling back the federal program’s expansion under the ACA and replacing it with block grants. In opposition, the recent passage of the bipartisan and highly pro–mental health care 21st Century Cures Act calls for more block grants for services for the seriously mentally ill, including those who currently are incarcerated with serious mental illness and substance use disorders, as well as for increased training programs to expand the behavioral health workforce, among other measures.

“If Medicaid expansion is replaced with block grants, that would lead to less care in general for Medicaid recipients,” Dr. Summergrad said in the interview. “It depends on how the states would view their costs of care, and how they would view the medical psychiatric issues.”

Since Medicaid is the largest payer of mental and behavioral health services in the country with reimbursable models of collaborative care, cutting funding for those services would sting. “There’s evidence that addressing mental and behavioral health issues keeps medical costs low,” said Dr. Summergrad, a past president of the American Psychiatric Association.

In his talk, Dr. Summergrad pointed to the now decade-old IMPACT study (Improving Mood: Promoting Access to Collaborative Treatment) which showed that patients screened for depression when presenting with chronic medical issues had lower overall medical costs over time.

He also referred to a more recent study in a large Utah health system that showed overall cost savings, far-fewer emergency department admissions, and better patient outcomes across a wide range of medical issues, which were achieved when mental health services were integrated into routine care: in all, a $12 million investment resulted in $52 million in savings after 4 years (JAMA. 2016;316[8]:826-34). “Utah is not exactly a blue state, but it worked for them,” Dr. Summergrad said. The key was that physicians “embraced normalizing mental health care,” he said.

As for how any changes to the Medicare Access and CHIP Reauthorization Act, which is predicated largely on team-based care for higher reimbursements, Dr. Summergrad said cash-only psychiatrists should be thinking about how to collaborate with primary care providers. “I think the important message at this point is that, however this works, we’ll have to think about integrated care.”

In an interview, Lee H. Beecher, MD, agreed. In fact, Dr. Beecher said that, in his state of Minnesota, engaging with patients on a cash-only basis is the only way a psychiatrist can have a private practice and provide valuable, essential communication with primary care physicians. “Direct-pay physicians are uniquely able to actively facilitate communication,” said Dr. Beecher, president of the nonprofit Minnesota Physician-Patient Alliance. “Most of this is done by phone, directly, with the primary care clinician – rather than inputting and sending an electronic health record.”

Dr. Summergrad had no relevant disclosures.

[email protected]

On Twitter @whitneymcknight

 

SCOTTSDALE, ARIZ. – Whether or not the Affordable Care Act (ACA) is repealed, replaced, reviled, or revered should not deter psychiatrists and primary care physicians from seeking to work together, according to a leading expert on integrating mental health care in medical practice.

“Community-based psychiatrists should be focused on finding ways to help create integrated models of care, both in health systems and in other settings, to provide mental health specialty support for primary care providers, regardless of whatever else is going on [in Washington],” Paul Summergrad, MD, said in an interview at the annual meeting of the American College of Psychiatrists.

designer491/Thinkstock

In a premeeting session on the future of integrated care, Dr. Summergrad, the Dr. Frances S. Arkin Professor and chairman of psychiatry at Tufts University, Boston, pointed to two current trends in Washington that are affecting mental health care. The first is a clamor for repeal of the ACA, which includes pressure from employers who are unhappy with the mandate to provide health insurance to employees; the second is a desire on the part of some lawmakers to slow the growth of state Medicaid budgets by rolling back the federal program’s expansion under the ACA and replacing it with block grants. In opposition, the recent passage of the bipartisan and highly pro–mental health care 21st Century Cures Act calls for more block grants for services for the seriously mentally ill, including those who currently are incarcerated with serious mental illness and substance use disorders, as well as for increased training programs to expand the behavioral health workforce, among other measures.

“If Medicaid expansion is replaced with block grants, that would lead to less care in general for Medicaid recipients,” Dr. Summergrad said in the interview. “It depends on how the states would view their costs of care, and how they would view the medical psychiatric issues.”

Since Medicaid is the largest payer of mental and behavioral health services in the country with reimbursable models of collaborative care, cutting funding for those services would sting. “There’s evidence that addressing mental and behavioral health issues keeps medical costs low,” said Dr. Summergrad, a past president of the American Psychiatric Association.

In his talk, Dr. Summergrad pointed to the now decade-old IMPACT study (Improving Mood: Promoting Access to Collaborative Treatment) which showed that patients screened for depression when presenting with chronic medical issues had lower overall medical costs over time.

He also referred to a more recent study in a large Utah health system that showed overall cost savings, far-fewer emergency department admissions, and better patient outcomes across a wide range of medical issues, which were achieved when mental health services were integrated into routine care: in all, a $12 million investment resulted in $52 million in savings after 4 years (JAMA. 2016;316[8]:826-34). “Utah is not exactly a blue state, but it worked for them,” Dr. Summergrad said. The key was that physicians “embraced normalizing mental health care,” he said.

As for how any changes to the Medicare Access and CHIP Reauthorization Act, which is predicated largely on team-based care for higher reimbursements, Dr. Summergrad said cash-only psychiatrists should be thinking about how to collaborate with primary care providers. “I think the important message at this point is that, however this works, we’ll have to think about integrated care.”

In an interview, Lee H. Beecher, MD, agreed. In fact, Dr. Beecher said that, in his state of Minnesota, engaging with patients on a cash-only basis is the only way a psychiatrist can have a private practice and provide valuable, essential communication with primary care physicians. “Direct-pay physicians are uniquely able to actively facilitate communication,” said Dr. Beecher, president of the nonprofit Minnesota Physician-Patient Alliance. “Most of this is done by phone, directly, with the primary care clinician – rather than inputting and sending an electronic health record.”

Dr. Summergrad had no relevant disclosures.

[email protected]

On Twitter @whitneymcknight

 

While using sublay mesh continues to be standard practice when performing ventral hernia repair (VHR), a recent study shows that using onlay mesh placement with adhesive can be just as safe, at least in the short term.

“While the use of mesh during VHR is well accepted, the ideal location of mesh placement remains heavily debated,” wrote the study’s authors, adding that the “paucity of high-level data has led the choice of mesh location to reside primarily on the preference of the surgeon rather than grounded in clinical outcomes.”

castillodominici/Thinkstock

The study was led by Ivy Haskins, MD, a clinical research fellow at the Cleveland Clinic, and was published online in the Journal of the American College of Surgeons (J Am Coll Surg. 2017 Feb 2doi: 10.1016/j.jamcollsurg.2017.01.048).

The investigators identified patients in the Americas Hernia Society Quality Collaborative national registry who were undergoing open, elective VHR and had clean wounds and a wound class I designation based on Centers for Disease Control and Prevention guidelines at any point between January 2013 and January 2016. A total of 1,854 individuals were ultimately selected for inclusion in the study and were divided into two groups: one that received traditional VHR with sublay mesh and one that received onlay mesh with adhesive.

All subjects’ data were analyzed within 30 days for any adverse events related to the wounds from the surgery. These events were surgical site infections, surgical site occurrences – which could include an infection and any skin or soft tissue ischemia, necrosis, or other events – and surgical site occurrences that required procedural intervention, which were defined as any occurrences that required “opening of the wound, wound debridement, suture excision, percutaneous drainage, or partial or complete mesh removal.”

The sublay cohort numbered 1,761 (95.0%), compared with 93 (5.0%) who received the onlay technique. There was no significant difference found in the rate of 30-day adverse incidents between the two cohorts. For surgical site infections, the sublay cohort rate was 2.9%, while the onlay cohort had a 5.5% rate (P = .30). Surgical site occurrences happened in 15.2% of sublay patients versus 7.7% of those in the other group (P = .08), while surgical site occurrences that required procedural intervention were 8.2% in sublay patients but 5.5% in onlay patients (P = .42).

While both approaches fared similarly in terms of comorbidities and average Ventral Hernia Working Group grade, the investigators recommend that “the Chevrel onlay technique be used in nonobese patients without significant comorbidities, with moderate hernia defects, and whose abdominal wall vasculatures are without risk of compromise.” The data were generalizable because of the number of surgeons performing VHR and because the data sample allowed the investigators to control for the hernia width, defect size, and patient comorbidities this case, leading to this conclusion.

“Additional studies are needed to determine the long-term benefits of both approaches with respect to mesh infection rates and hernia recurrence rates, as well as the ideal mesh location for ventral hernia repairs in higher-risk patients,” the authors concluded.

No funding source was disclosed for this study. The investigators reported no relevant financial disclosures.
 

[email protected]

 

While using sublay mesh continues to be standard practice when performing ventral hernia repair (VHR), a recent study shows that using onlay mesh placement with adhesive can be just as safe, at least in the short term.

“While the use of mesh during VHR is well accepted, the ideal location of mesh placement remains heavily debated,” wrote the study’s authors, adding that the “paucity of high-level data has led the choice of mesh location to reside primarily on the preference of the surgeon rather than grounded in clinical outcomes.”

castillodominici/Thinkstock

The study was led by Ivy Haskins, MD, a clinical research fellow at the Cleveland Clinic, and was published online in the Journal of the American College of Surgeons (J Am Coll Surg. 2017 Feb 2doi: 10.1016/j.jamcollsurg.2017.01.048).

The investigators identified patients in the Americas Hernia Society Quality Collaborative national registry who were undergoing open, elective VHR and had clean wounds and a wound class I designation based on Centers for Disease Control and Prevention guidelines at any point between January 2013 and January 2016. A total of 1,854 individuals were ultimately selected for inclusion in the study and were divided into two groups: one that received traditional VHR with sublay mesh and one that received onlay mesh with adhesive.

All subjects’ data were analyzed within 30 days for any adverse events related to the wounds from the surgery. These events were surgical site infections, surgical site occurrences – which could include an infection and any skin or soft tissue ischemia, necrosis, or other events – and surgical site occurrences that required procedural intervention, which were defined as any occurrences that required “opening of the wound, wound debridement, suture excision, percutaneous drainage, or partial or complete mesh removal.”

The sublay cohort numbered 1,761 (95.0%), compared with 93 (5.0%) who received the onlay technique. There was no significant difference found in the rate of 30-day adverse incidents between the two cohorts. For surgical site infections, the sublay cohort rate was 2.9%, while the onlay cohort had a 5.5% rate (P = .30). Surgical site occurrences happened in 15.2% of sublay patients versus 7.7% of those in the other group (P = .08), while surgical site occurrences that required procedural intervention were 8.2% in sublay patients but 5.5% in onlay patients (P = .42).

While both approaches fared similarly in terms of comorbidities and average Ventral Hernia Working Group grade, the investigators recommend that “the Chevrel onlay technique be used in nonobese patients without significant comorbidities, with moderate hernia defects, and whose abdominal wall vasculatures are without risk of compromise.” The data were generalizable because of the number of surgeons performing VHR and because the data sample allowed the investigators to control for the hernia width, defect size, and patient comorbidities this case, leading to this conclusion.

“Additional studies are needed to determine the long-term benefits of both approaches with respect to mesh infection rates and hernia recurrence rates, as well as the ideal mesh location for ventral hernia repairs in higher-risk patients,” the authors concluded.

No funding source was disclosed for this study. The investigators reported no relevant financial disclosures.
 

[email protected]

 

While using sublay mesh continues to be standard practice when performing ventral hernia repair (VHR), a recent study shows that using onlay mesh placement with adhesive can be just as safe, at least in the short term.

“While the use of mesh during VHR is well accepted, the ideal location of mesh placement remains heavily debated,” wrote the study’s authors, adding that the “paucity of high-level data has led the choice of mesh location to reside primarily on the preference of the surgeon rather than grounded in clinical outcomes.”

castillodominici/Thinkstock

The study was led by Ivy Haskins, MD, a clinical research fellow at the Cleveland Clinic, and was published online in the Journal of the American College of Surgeons (J Am Coll Surg. 2017 Feb 2doi: 10.1016/j.jamcollsurg.2017.01.048).

The investigators identified patients in the Americas Hernia Society Quality Collaborative national registry who were undergoing open, elective VHR and had clean wounds and a wound class I designation based on Centers for Disease Control and Prevention guidelines at any point between January 2013 and January 2016. A total of 1,854 individuals were ultimately selected for inclusion in the study and were divided into two groups: one that received traditional VHR with sublay mesh and one that received onlay mesh with adhesive.

All subjects’ data were analyzed within 30 days for any adverse events related to the wounds from the surgery. These events were surgical site infections, surgical site occurrences – which could include an infection and any skin or soft tissue ischemia, necrosis, or other events – and surgical site occurrences that required procedural intervention, which were defined as any occurrences that required “opening of the wound, wound debridement, suture excision, percutaneous drainage, or partial or complete mesh removal.”

The sublay cohort numbered 1,761 (95.0%), compared with 93 (5.0%) who received the onlay technique. There was no significant difference found in the rate of 30-day adverse incidents between the two cohorts. For surgical site infections, the sublay cohort rate was 2.9%, while the onlay cohort had a 5.5% rate (P = .30). Surgical site occurrences happened in 15.2% of sublay patients versus 7.7% of those in the other group (P = .08), while surgical site occurrences that required procedural intervention were 8.2% in sublay patients but 5.5% in onlay patients (P = .42).

While both approaches fared similarly in terms of comorbidities and average Ventral Hernia Working Group grade, the investigators recommend that “the Chevrel onlay technique be used in nonobese patients without significant comorbidities, with moderate hernia defects, and whose abdominal wall vasculatures are without risk of compromise.” The data were generalizable because of the number of surgeons performing VHR and because the data sample allowed the investigators to control for the hernia width, defect size, and patient comorbidities this case, leading to this conclusion.

“Additional studies are needed to determine the long-term benefits of both approaches with respect to mesh infection rates and hernia recurrence rates, as well as the ideal mesh location for ventral hernia repairs in higher-risk patients,” the authors concluded.

No funding source was disclosed for this study. The investigators reported no relevant financial disclosures.
 

[email protected]

Primary Cutaneous Cryptococcosis

Natasha Cowan, University of California, San Diego, and Brooke Resh Sateesh, MD, San Diego Family Dermatology

Cryptococcal skin lesions may present in a variety of manifestations, including cellulitis, ulcers, pustules, granulomata, abscesses, herpetiform or molluscum contagium-like lesions. Primary cutaneous cryptococcosis (PCC) differs from its secondary counterpart in that it occurs due to local inoculation of the fungus as opposed to dissemination from a distant site of infection. Secondary cryptococcal skin lesions are more common than PCC. Cryptococcus neoformans is responsible for the majority of cases of PCC. This yeast is ubiquitous in the environment worldwide. Infection with Cryptococcus is more common in immunocompromised individuals; however, cryptococcal infection can occur in immunocompetent hosts as well.

The differential diagnosis upon initial examination may be wide.  Patients generally present with a new skin lesion that proves to be refractory to conservative or traditional therapy. The upper extremities are the most common site of PCC. In almost all cases, a previous injury at the site of inoculation can be identified. Risk factors for exposure to Cryptococcus include residence in a rural area and contact with soil contaminated by avian droppings. The average time between skin injury and onset of symptoms has been reported as 2.5 days. Although rare, it is possible for a patient to present with multiple sites of infection in the absence of dissemination. This is almost exclusively seen in immunocompromised hosts.

Because of its widely variable clinical manifestations, PCC is a diagnosis made by culture and histology. Histopathology reveals numerous yeasts and a giant cell inflammatory process. In PCC, serology should not demonstrate Cryptococcus antigen, as the disease is localized to the skin. Patients diagnosed with PCC should undergo proper work-up to rule out the possibility of an underlying immunosuppressive condition, such as infection or malignancy.

Therapy for PCC can be solely medical or a combination of medical and surgical treatments. Surgical de-bulking in combination with 6-12 months of fluconazole is often used. Early treatment is essential, as cases of Cryptococcus dissemination secondary to PCC have been reported.

This patient's workup did not reveal any underlying immunodeficiencies.  He worked with heating, ventilation and air condition (HVAC) in Spain.  He was referred to infectious disease and admitted to the hospital for intravenous antifungal therapy. 

Case and photo courtesy of: Natasha Cowan, BS, UCSD School of Medicine, and Brooke Resh Sateesh, MD, San Deigo Family Dermatology

Donna Bilu Martin, MD, is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at edermatologynews.com. To submit a case for possible publication, send an email to [email protected].

 

Primary Cutaneous Cryptococcosis

Natasha Cowan, University of California, San Diego, and Brooke Resh Sateesh, MD, San Diego Family Dermatology

Cryptococcal skin lesions may present in a variety of manifestations, including cellulitis, ulcers, pustules, granulomata, abscesses, herpetiform or molluscum contagium-like lesions. Primary cutaneous cryptococcosis (PCC) differs from its secondary counterpart in that it occurs due to local inoculation of the fungus as opposed to dissemination from a distant site of infection. Secondary cryptococcal skin lesions are more common than PCC. Cryptococcus neoformans is responsible for the majority of cases of PCC. This yeast is ubiquitous in the environment worldwide. Infection with Cryptococcus is more common in immunocompromised individuals; however, cryptococcal infection can occur in immunocompetent hosts as well.

The differential diagnosis upon initial examination may be wide.  Patients generally present with a new skin lesion that proves to be refractory to conservative or traditional therapy. The upper extremities are the most common site of PCC. In almost all cases, a previous injury at the site of inoculation can be identified. Risk factors for exposure to Cryptococcus include residence in a rural area and contact with soil contaminated by avian droppings. The average time between skin injury and onset of symptoms has been reported as 2.5 days. Although rare, it is possible for a patient to present with multiple sites of infection in the absence of dissemination. This is almost exclusively seen in immunocompromised hosts.

Because of its widely variable clinical manifestations, PCC is a diagnosis made by culture and histology. Histopathology reveals numerous yeasts and a giant cell inflammatory process. In PCC, serology should not demonstrate Cryptococcus antigen, as the disease is localized to the skin. Patients diagnosed with PCC should undergo proper work-up to rule out the possibility of an underlying immunosuppressive condition, such as infection or malignancy.

Therapy for PCC can be solely medical or a combination of medical and surgical treatments. Surgical de-bulking in combination with 6-12 months of fluconazole is often used. Early treatment is essential, as cases of Cryptococcus dissemination secondary to PCC have been reported.

This patient's workup did not reveal any underlying immunodeficiencies.  He worked with heating, ventilation and air condition (HVAC) in Spain.  He was referred to infectious disease and admitted to the hospital for intravenous antifungal therapy. 

Case and photo courtesy of: Natasha Cowan, BS, UCSD School of Medicine, and Brooke Resh Sateesh, MD, San Deigo Family Dermatology

Donna Bilu Martin, MD, is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at edermatologynews.com. To submit a case for possible publication, send an email to [email protected].

 

Primary Cutaneous Cryptococcosis

Natasha Cowan, University of California, San Diego, and Brooke Resh Sateesh, MD, San Diego Family Dermatology

Cryptococcal skin lesions may present in a variety of manifestations, including cellulitis, ulcers, pustules, granulomata, abscesses, herpetiform or molluscum contagium-like lesions. Primary cutaneous cryptococcosis (PCC) differs from its secondary counterpart in that it occurs due to local inoculation of the fungus as opposed to dissemination from a distant site of infection. Secondary cryptococcal skin lesions are more common than PCC. Cryptococcus neoformans is responsible for the majority of cases of PCC. This yeast is ubiquitous in the environment worldwide. Infection with Cryptococcus is more common in immunocompromised individuals; however, cryptococcal infection can occur in immunocompetent hosts as well.

The differential diagnosis upon initial examination may be wide.  Patients generally present with a new skin lesion that proves to be refractory to conservative or traditional therapy. The upper extremities are the most common site of PCC. In almost all cases, a previous injury at the site of inoculation can be identified. Risk factors for exposure to Cryptococcus include residence in a rural area and contact with soil contaminated by avian droppings. The average time between skin injury and onset of symptoms has been reported as 2.5 days. Although rare, it is possible for a patient to present with multiple sites of infection in the absence of dissemination. This is almost exclusively seen in immunocompromised hosts.

Because of its widely variable clinical manifestations, PCC is a diagnosis made by culture and histology. Histopathology reveals numerous yeasts and a giant cell inflammatory process. In PCC, serology should not demonstrate Cryptococcus antigen, as the disease is localized to the skin. Patients diagnosed with PCC should undergo proper work-up to rule out the possibility of an underlying immunosuppressive condition, such as infection or malignancy.

Therapy for PCC can be solely medical or a combination of medical and surgical treatments. Surgical de-bulking in combination with 6-12 months of fluconazole is often used. Early treatment is essential, as cases of Cryptococcus dissemination secondary to PCC have been reported.

This patient's workup did not reveal any underlying immunodeficiencies.  He worked with heating, ventilation and air condition (HVAC) in Spain.  He was referred to infectious disease and admitted to the hospital for intravenous antifungal therapy. 

Case and photo courtesy of: Natasha Cowan, BS, UCSD School of Medicine, and Brooke Resh Sateesh, MD, San Deigo Family Dermatology

Donna Bilu Martin, MD, is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at edermatologynews.com. To submit a case for possible publication, send an email to [email protected].

 

 

The burden of serious infection is quite high among children who have systemic lupus erythematosus, with a “striking” preponderance of bacterial pneumonia, according to a report published in Arthritis Care & Research.

Infections are known to be commonplace among systemic lupus erythematosus (SLE) patients in general, and the increased risk is attributed both to the disease and to immunosuppressant therapies. However, most information on this topic comes from studies of adult patients seen at individual academic medical centers, said Linda T. Hiraki, MD, ScD, of the division of rheumatology at The Hospital for Sick Children, Toronto, and her associates.

To examine the nationwide prevalence of serious infections among children with SLE, they analyzed administrative data from a Medicaid database. They focused on 3,500 patients aged 5-18 years, including 1,297 who also had lupus nephritis, who were enrolled in Medicaid during 2000-2006 and followed for a mean of 2.6 years. This yielded a cumulative follow-up of more than 10,100 person-years (Arthritis Care Res. 2017 Feb 19. doi: 10.1002/acr.23219).

Courtesy Wikimedia Commons/doktorinternet/Creative Commons License

A total of 593 of these children had 1,053 serious infections requiring hospitalization during the study period, including 326 children with concurrent lupus nephritis who had 624 infections. A total of 17% of the entire study population and 25% of the subset with lupus nephritis developed at least one such infection. A substantial proportion – 18% of the overall cohort and 21% of those with lupus nephritis – had three or more serious infections requiring hospitalization during the relatively short follow-up, Dr. Hiraki and her associates noted.

The overall incidence was 10.4 serious infections per 100 person-years, and it was 17.65 per 100 person-years in the subset of patients who had lupus nephritis. By comparison, this overall rate is nearly four times higher than that reported for children with juvenile idiopathic arthritis, and the incidence among children with concomitant lupus nephritis is more than six times higher.

Infection rates were markedly higher among African American (incidence rate ratio [IRR], 1.83) and Native American (IRR, 1.81) children, compared with white children. They also were higher in early adolescence (ages 9-12 years) than earlier in childhood (ages 5-8 years), the investigators said.

Most of the infections (87%) were bacterial, whereas 11% were viral and 1.3% were fungal. (The remaining amount was unknown in the data because of too few numbers for federal reporting.) The most frequent bacterial infections were pneumonia (438 cases), followed by bacteremia (274 cases) and cellulitis (272 cases). Herpes zoster was the most frequent viral infection, accounting for 81 cases. The investigators noted that the low rate of fungal infections may be an artifact of the study protocol, which excluded, for technical reasons, cases of systemic candidiasis.

Not surprisingly, the rate of serious infection was higher among children with a high comorbidity burden than among healthier children.

Overall, the risk of serious infection was 59% higher for SLE patients who took corticosteroids during the study’s 6-month baseline period, in which 67% of patients took them (minimum of 20 mg/day of prednisone equivalent). However, the risk of serious infection was no different between those who used immunosuppressants (31%) or didn’t use them during that period.

A total of 26 children died within 30 days of hospital admission for a serious infection, for an overall mortality of 4.4% among children who developed serious infections. In comparison, 1.6% in the total cohort of 3,500 died. More than half of the children who died had concomitant lupus nephritis. In addition, 77% of those who died were taking corticosteroids when they developed the infections.

It is difficult to distinguish whether the high infection rate could be attributed to SLE itself or to its treatments. More studies are needed to further investigate this, as well as to address the disproportionate incidence among nonwhite children and any potential benefits from prophylactic use of antibiotics and vaccinations, Dr. Hiraki and her associates said.

The Canadian Institutes of Health Research, the Lupus Foundation of America, the Rheumatology Research Foundation, and the National Institutes of Health supported the study. Dr. Hiraki and her associates reported having no relevant disclosures.

 

 

The burden of serious infection is quite high among children who have systemic lupus erythematosus, with a “striking” preponderance of bacterial pneumonia, according to a report published in Arthritis Care & Research.

Infections are known to be commonplace among systemic lupus erythematosus (SLE) patients in general, and the increased risk is attributed both to the disease and to immunosuppressant therapies. However, most information on this topic comes from studies of adult patients seen at individual academic medical centers, said Linda T. Hiraki, MD, ScD, of the division of rheumatology at The Hospital for Sick Children, Toronto, and her associates.

To examine the nationwide prevalence of serious infections among children with SLE, they analyzed administrative data from a Medicaid database. They focused on 3,500 patients aged 5-18 years, including 1,297 who also had lupus nephritis, who were enrolled in Medicaid during 2000-2006 and followed for a mean of 2.6 years. This yielded a cumulative follow-up of more than 10,100 person-years (Arthritis Care Res. 2017 Feb 19. doi: 10.1002/acr.23219).

Courtesy Wikimedia Commons/doktorinternet/Creative Commons License

A total of 593 of these children had 1,053 serious infections requiring hospitalization during the study period, including 326 children with concurrent lupus nephritis who had 624 infections. A total of 17% of the entire study population and 25% of the subset with lupus nephritis developed at least one such infection. A substantial proportion – 18% of the overall cohort and 21% of those with lupus nephritis – had three or more serious infections requiring hospitalization during the relatively short follow-up, Dr. Hiraki and her associates noted.

The overall incidence was 10.4 serious infections per 100 person-years, and it was 17.65 per 100 person-years in the subset of patients who had lupus nephritis. By comparison, this overall rate is nearly four times higher than that reported for children with juvenile idiopathic arthritis, and the incidence among children with concomitant lupus nephritis is more than six times higher.

Infection rates were markedly higher among African American (incidence rate ratio [IRR], 1.83) and Native American (IRR, 1.81) children, compared with white children. They also were higher in early adolescence (ages 9-12 years) than earlier in childhood (ages 5-8 years), the investigators said.

Most of the infections (87%) were bacterial, whereas 11% were viral and 1.3% were fungal. (The remaining amount was unknown in the data because of too few numbers for federal reporting.) The most frequent bacterial infections were pneumonia (438 cases), followed by bacteremia (274 cases) and cellulitis (272 cases). Herpes zoster was the most frequent viral infection, accounting for 81 cases. The investigators noted that the low rate of fungal infections may be an artifact of the study protocol, which excluded, for technical reasons, cases of systemic candidiasis.

Not surprisingly, the rate of serious infection was higher among children with a high comorbidity burden than among healthier children.

Overall, the risk of serious infection was 59% higher for SLE patients who took corticosteroids during the study’s 6-month baseline period, in which 67% of patients took them (minimum of 20 mg/day of prednisone equivalent). However, the risk of serious infection was no different between those who used immunosuppressants (31%) or didn’t use them during that period.

A total of 26 children died within 30 days of hospital admission for a serious infection, for an overall mortality of 4.4% among children who developed serious infections. In comparison, 1.6% in the total cohort of 3,500 died. More than half of the children who died had concomitant lupus nephritis. In addition, 77% of those who died were taking corticosteroids when they developed the infections.

It is difficult to distinguish whether the high infection rate could be attributed to SLE itself or to its treatments. More studies are needed to further investigate this, as well as to address the disproportionate incidence among nonwhite children and any potential benefits from prophylactic use of antibiotics and vaccinations, Dr. Hiraki and her associates said.

The Canadian Institutes of Health Research, the Lupus Foundation of America, the Rheumatology Research Foundation, and the National Institutes of Health supported the study. Dr. Hiraki and her associates reported having no relevant disclosures.

 

 

The burden of serious infection is quite high among children who have systemic lupus erythematosus, with a “striking” preponderance of bacterial pneumonia, according to a report published in Arthritis Care & Research.

Infections are known to be commonplace among systemic lupus erythematosus (SLE) patients in general, and the increased risk is attributed both to the disease and to immunosuppressant therapies. However, most information on this topic comes from studies of adult patients seen at individual academic medical centers, said Linda T. Hiraki, MD, ScD, of the division of rheumatology at The Hospital for Sick Children, Toronto, and her associates.

To examine the nationwide prevalence of serious infections among children with SLE, they analyzed administrative data from a Medicaid database. They focused on 3,500 patients aged 5-18 years, including 1,297 who also had lupus nephritis, who were enrolled in Medicaid during 2000-2006 and followed for a mean of 2.6 years. This yielded a cumulative follow-up of more than 10,100 person-years (Arthritis Care Res. 2017 Feb 19. doi: 10.1002/acr.23219).

Courtesy Wikimedia Commons/doktorinternet/Creative Commons License

A total of 593 of these children had 1,053 serious infections requiring hospitalization during the study period, including 326 children with concurrent lupus nephritis who had 624 infections. A total of 17% of the entire study population and 25% of the subset with lupus nephritis developed at least one such infection. A substantial proportion – 18% of the overall cohort and 21% of those with lupus nephritis – had three or more serious infections requiring hospitalization during the relatively short follow-up, Dr. Hiraki and her associates noted.

The overall incidence was 10.4 serious infections per 100 person-years, and it was 17.65 per 100 person-years in the subset of patients who had lupus nephritis. By comparison, this overall rate is nearly four times higher than that reported for children with juvenile idiopathic arthritis, and the incidence among children with concomitant lupus nephritis is more than six times higher.

Infection rates were markedly higher among African American (incidence rate ratio [IRR], 1.83) and Native American (IRR, 1.81) children, compared with white children. They also were higher in early adolescence (ages 9-12 years) than earlier in childhood (ages 5-8 years), the investigators said.

Most of the infections (87%) were bacterial, whereas 11% were viral and 1.3% were fungal. (The remaining amount was unknown in the data because of too few numbers for federal reporting.) The most frequent bacterial infections were pneumonia (438 cases), followed by bacteremia (274 cases) and cellulitis (272 cases). Herpes zoster was the most frequent viral infection, accounting for 81 cases. The investigators noted that the low rate of fungal infections may be an artifact of the study protocol, which excluded, for technical reasons, cases of systemic candidiasis.

Not surprisingly, the rate of serious infection was higher among children with a high comorbidity burden than among healthier children.

Overall, the risk of serious infection was 59% higher for SLE patients who took corticosteroids during the study’s 6-month baseline period, in which 67% of patients took them (minimum of 20 mg/day of prednisone equivalent). However, the risk of serious infection was no different between those who used immunosuppressants (31%) or didn’t use them during that period.

A total of 26 children died within 30 days of hospital admission for a serious infection, for an overall mortality of 4.4% among children who developed serious infections. In comparison, 1.6% in the total cohort of 3,500 died. More than half of the children who died had concomitant lupus nephritis. In addition, 77% of those who died were taking corticosteroids when they developed the infections.

It is difficult to distinguish whether the high infection rate could be attributed to SLE itself or to its treatments. More studies are needed to further investigate this, as well as to address the disproportionate incidence among nonwhite children and any potential benefits from prophylactic use of antibiotics and vaccinations, Dr. Hiraki and her associates said.

The Canadian Institutes of Health Research, the Lupus Foundation of America, the Rheumatology Research Foundation, and the National Institutes of Health supported the study. Dr. Hiraki and her associates reported having no relevant disclosures.

 

 

The overall national measure of outpatient flu activity was down for the week ending Feb. 18, and the number of states at the highest level of activity dropped from 25 to 24, according to the Centers for Disease Control and Prevention.

The national proportion of outpatient visits for influenza-like illness (ILI) decreased from 5.2% the previous week to 4.8% for the week ending Feb. 18, the CDC reported.

In addition to the 24 states at level 10 on the CDC’s 1-10 scale of ILI activity, three other states were in the “high” range (8-10): Alaska, Michigan, and Wyoming were all at level 8, data from the U.S. Outpatient Influenza-like Illness Surveillance Network show.

There were 5 ILI-related pediatric deaths reported during the week, bringing the total to 34 for the season so far, but none of the 5 occurred in the current week, the CDC said. There were 89 pediatric deaths reported during the 2015-2016 season, with the peak week occurring in late March/early April (11 deaths). During the 2014-2015 season, there were 148 deaths reported, and 111 were reported in 2013-2014.

[email protected]

 

The overall national measure of outpatient flu activity was down for the week ending Feb. 18, and the number of states at the highest level of activity dropped from 25 to 24, according to the Centers for Disease Control and Prevention.

The national proportion of outpatient visits for influenza-like illness (ILI) decreased from 5.2% the previous week to 4.8% for the week ending Feb. 18, the CDC reported.

In addition to the 24 states at level 10 on the CDC’s 1-10 scale of ILI activity, three other states were in the “high” range (8-10): Alaska, Michigan, and Wyoming were all at level 8, data from the U.S. Outpatient Influenza-like Illness Surveillance Network show.

There were 5 ILI-related pediatric deaths reported during the week, bringing the total to 34 for the season so far, but none of the 5 occurred in the current week, the CDC said. There were 89 pediatric deaths reported during the 2015-2016 season, with the peak week occurring in late March/early April (11 deaths). During the 2014-2015 season, there were 148 deaths reported, and 111 were reported in 2013-2014.

[email protected]

 

The overall national measure of outpatient flu activity was down for the week ending Feb. 18, and the number of states at the highest level of activity dropped from 25 to 24, according to the Centers for Disease Control and Prevention.

The national proportion of outpatient visits for influenza-like illness (ILI) decreased from 5.2% the previous week to 4.8% for the week ending Feb. 18, the CDC reported.

In addition to the 24 states at level 10 on the CDC’s 1-10 scale of ILI activity, three other states were in the “high” range (8-10): Alaska, Michigan, and Wyoming were all at level 8, data from the U.S. Outpatient Influenza-like Illness Surveillance Network show.

There were 5 ILI-related pediatric deaths reported during the week, bringing the total to 34 for the season so far, but none of the 5 occurred in the current week, the CDC said. There were 89 pediatric deaths reported during the 2015-2016 season, with the peak week occurring in late March/early April (11 deaths). During the 2014-2015 season, there were 148 deaths reported, and 111 were reported in 2013-2014.

[email protected]

Phenylephrine, a sympathomimetic drug, is commonly used in eye exams to dilate the pupil of the eye and to differentiate scleritis from episcleritis. Common adverse effects (AEs) of phenylephrine include subjective burning, stinging with lacrimation, rebound hyperemia, and liberation of iris pigment into the anterior chamber. Less common, systemic AEs include tachycardia and elevation of systemic blood pressure. Although instances of allergic reactions are rare, phenylephrine has been reported to cause contact dermatitis, blepharoconjunctivitis, and as in this case, keratoconjunctivitis.

Case Report

An 83-year-old white male presented for a red eye evaluation 2 days after having undergone a comprehensive eye exam with dilation at the Malcom Randall VAMC clinic in Gainesville, Florida. The patient reported onset of blurred vision, which he described as looking through a fog. He further compared the feeling to pins sticking in his eyes. The patient noted he had experienced similar symptoms on a few other occasions following eye exams. At the most recent eye exam, proparacaine and fluorescein had been used for tonometry, and phenylephrine 2.5% and tropicamide 0.5% had been used for pupillary dilation.

The patient’s best-corrected visual acuity was counting fingers at 2 feet in the right eye (OD) and left eye (OS). The best-corrected visual acuity 2 days prior had been 20/20 OD and OS. Pupils and extraocular motilities were unremarkable. Intraocular pressures were not obtained due to concern for a possible adverse reaction to proparacaine.

Slit-lamp evaluation revealed the lids to be lax, erythematous, and edematous in both eyes (Figure 1).

A marked papillary reaction and 3+ bulbar conjunctival injection in both eyes (OU) also was evident. The corneas had 2+ filamentous strands with dense superficial punctate keratitis bilaterally (Figures 2a & 2b).

Anterior chamber angles were open, but it was difficult to assess for cells and flare through the hazy corneas. Irides were flat and clear OU. Lens exam revealed modest nuclear sclerosis OU. Due to concern for allergic reaction to tropicamide or phenylephrine, the patient was not redilated. The level of vision loss was consistent with the degree of keratitis observed OU.

The initial diagnosis was acute chemical conjunctivitis most likely due to an AE to proparacaine. The plan was to start the patient on antibiotic eye drops qid OU, prednisolone qid OU, and artificial tears every hour OU. The patient was scheduled to return to clinic 4 days later for an anterior segment follow-up.

At the follow-up visit, the patient reported significant visual improvement. His best-corrected visual acuity was 20/40-2 without improvement on pinhole OD and 20/50-2 with improvement to 20/30+ on pinhole OS. Slit-lamp evaluation revealed 1+ bulbar conjunctival injection OU, intact corneal epithelium OU, and no cells or flare in the anterior chambers OU. Due to improving punctate epitheliopathy, the frequency of the antibiotic drops, the prednisolone, and the artificial tears was reduced to bid. After 3 days, he was instructed to discontinue them. The patient was scheduled to return in 2 weeks for an anterior segment follow-up.

At the next follow-up visit, the patient reported that his vision had returned to normal, and he had no further ocular AEs. His best-corrected visual acuity was 20/20-2 OD and 20/20 OS. Slit-lamp evaluation revealed mild blepharitis OU, trace bulbar conjunctival injection OU, and complete resolution of the keratitis OU. The assessment was acute allergic conjunctivitis thought to be secondary to an AE to proparacaine OU, yet the need to rule out hypersensitivity to tropicamide and/or phenylephrine remained. The plan was to educate the patient of the possibility of allergic reaction on future visits and to recommend continued use of artificial tears as needed.

Through a careful and extensive chart review of all past visits, it was suspected that phenylephrine might be to blame rather than proparacaine. At the subsequent visit, the patient agreed to undergo testing to determine the culprit via instillation of proparacaine in one eye and tropicamide in the other. The patient had no reaction to either drop (checked 45 minutes after instillation and the following day). By process of elimination, phenylephrine was determined to be the offending agent.

Discussion

Following a thorough review of the patient’s chart, it was found that on other occasions he had presented with suspected allergic reactions following routine eye examinations. The patient reported he had experienced a reaction in 2007 but could not recall what drops were instilled in his eyes at the time. In addition, there was no documentation in his medical record of the subsequent reaction following that visit. Another reaction occurred in July 2010 with instillation of tropicamide 1%, phenylephrine 2.5%, and Fluress (fluorescein sodium and benoxinate hydrochloride ophthalmic solution USP). In October 2013, when tropicamide 0.5%, proparacaine, and fluorescein strips were instilled, there was no reaction. The next reaction occurred in October 2014, when tropicamide 0.5%, phenylephrine 2.5%, proparacaine, and fluorescein strips were instilled.

 

This careful review of past exam notes revealed that phenylephrine and Fluress were the only drops that had not been instilled at the October 2013 visit when no AE was reported. However, Fluress was an unlikely culprit since it was not instilled in October 2014, and the patient still experienced an AE. Therefore, the agent most likely responsible for the allergic reaction in the patient, as confirmed by a review of the past notes and by the aforementioned pharmacologic test, was deemed to be phenylephrine (Table).

Adverse reactions to topical ocular medications and specifically to diagnostic eye drops have long been recognized. Mathias, Camarasa, Barber, Ducombs, and Monsálvezhave reported on variations of conjunctivitis and periorbital erythema with positive patch testing to phenylephrine.^1-5 Geyer and colleagues reported on a study of 21 patients who had blepharoconjunctivitis after instillation of phenylephrine.⁶ In this case study patient, severe keratoconjunctivitis was the clinical manifestation observed.

Villarreal and colleagues studied 31 patients who had a previous reaction to mydriatic drops. The study found that phenylephrine was the drug that most frequently caused an AE (93.5%).⁷ One patient reacted to the preservative thimerosal, and 1 patient reacted to benoxiprocaine. Tropicamide was demonstrated to be very well tolerated as none of the patients tested positive on either the patch test or the pharmacologic test.

Tropicamide is a nonselective muscarinic antagonist commonly used for mydriasis due to its fast onset and short duration.⁸ Adverse reactions to tropicamide are rare. Three studies reported on patients who had a positive patch test to tropicamide.^9-11 However, the reaction was not provoked by direct instillation of tropicamide into the eye.

Common in-office topical anesthetics, proparacaine, tetracaine, benoxinate, and lidocaine also can cause AEs. Corneal toxicity is a well-known complication with topical anesthetic abuse, whereas allergic reactions are considered rare. The most common symptoms include stingingand discomfort upon instillation. Common signs include punctate corneal epithelial erosionsresulting indirectly from a decrease in reflex tearing, infrequent blinking, and increased tear evaporation.¹² Topical anesthetics also inhibit the migration of corneal epithelial cells and cause direct damage to the cells that are present, leading to impaired healing and epithelial defects.¹³

Manifestations of allergic reaction to topical anesthetics can include conjunctival hyperemia and edema, edematous eyelids, and lacrimation. One published case described a 60-year-old woman who developed eczematous dermatitis of the eyelids after ophthalmic anesthetic drops were instilled prior to laser surgery. Patch testing showed a positive response to benzocaine 5%, proparacaine, and tetracaine 0.5%.¹⁴

Preservatives, in general, can cause an allergic reaction. Benzalkonium chloride’s (BAK) cytotoxic sequelae include possible trabecular cell death in glaucoma patients, disruption of tear film stability (even at low concentrations), and immune-allergenic properties. One article reported BAK as one of the 30 most frequent allergens causing allergic periorbital dermatitis.¹⁵ Benzalkonium chloride is used in most brands of phenylephrine. However, preservatives in this patient’s case were ruled out as instigating agents since both phenylephrine and tropicamide contain the same preservative, BAK 0.01%, yet this patient did not develop a reaction to tropicamide when used without phenylephrine. Expired medications also were not considered to be a factor as none of the medications used on the patient were indeed expired (the Malcom Randall VAMC clinic maintains a strict policy of discarding medications 28 days after being opened).

Although uncommon, phenylephrine sometimes has been found to cause a type 4 hypersensitivity reaction, also known as cell-mediated or delayed-type hypersensitivity.¹⁶ First, helper T cells secrete cytokines. Activation of cytokines recruits and activates cytotoxic T cells, monocytes, and macrophages, leading to inflammation of the surrounding tissue. Examples of cell-mediated hypersensitivity include reactions to the tuberculin skin test and to poison ivy.

Type 1 hypersensitivity reactions, also known as immediate or anaphylactic hypersensitivity reactions, are not triggered by phenylephrine. In this type of reaction, IgE binds to the mast cell on initial exposure to an allergen. On second exposure, the allergen binds to the IgE, causing the mast cell to release mediators of inflammation, triggering physiologic responses. Examples of this type of hypersensitivity include those seen with penicillin, bee stings, hay fever, bronchial asthma, and food allergies, for example, to shellfish.

A toxic reaction’s mechanism differs from that of a type 4 hypersensitivity reaction. Toxic reactions occur due to direct cytotoxicity of a drug caused by a low or high pH and either hyper- or hypo-osmolarity. Toxicity can lead to corneal and conjunctival cell necrosis or induce apoptosis, stimulating inflammatory reactions. Clinically, toxic reactions will present with follicles, whereas allergic reactions will present with papillae.

The definitive diagnostic methods used to determine the allergic agent causing ocular or periocular AEs are patch testing and conjunctival challenge.⁷ Mathias, Camarasa, Barber, Ducombs,and Monsálvezused patch testing to confirm phenylephrine as the allergic agent in their series of cases. Patch testing entails the application of a small amount of an allergic agent that is taped onto the skin. The allergic agent is confirmed if the patient has a dermal reaction, wherein the area patched will become erythematous. When patch testing is negative or inconclusive, a conjunctival challenge is performed by instillation of the suspected allergic agent into the eye with subsequent observation to determine whether a reaction occurs. The sequelae found in Villarreal’s study included itching, lacrimation, edema, erythema, and sometimes blepharitis.⁷

A direct conjunctival challenge with the suspected culprit was not pursued in this patient’s case due to the known severity of the potential resulting reaction. The authors instead chose an indirect method of determining the implicating agent and used the process of elimination to whittle down the most likely suspect. A challenge with the medications suspected not to be likely offenders was undertaken. This spared the patient a likely repeat of the AE he had just recovered from.

 

Management

Allergic reactions can resolve without medical intervention. The first step is to remove the allergen. For delayed hypersensitivity reactions, treatments may include topical decongestants, cool compresses, and corticosteroids.⁸ The treatment for immediate hypersensitivity reaction differs from that of delayed hypersensitivity reaction in that antihistamines are used.^17,18

This patient reported receiving no treatment for his ocular symptoms following eye examinations in the past, yet he experienced complete resolution after each AE. In this case, both a steroid and a prophylactic antibiotic to facilitate a more rapid improvement were used.

Conclusion

Although uncommon, cases of allergic reaction to phenylephrine can occur. The incidence of phenylephrine allergy is 0.6%.6 The case study patient presented with a severe keratoconjunctivitis following routine eye examination with an accompanying history of adverse ocular signs and symptoms following multiple past exams.

It is important for all eye care clinicians to realize that AEs to diagnostic eye drops are possible and can occur following the most routine of visits. Such reactions can be caused by dilating agents, anesthetics, or preservatives, and these may be allergic or toxic. Clinicians should take special care to identify the instigating agent, and if possible, to avoid using such agents on patients during future exams. Clinicians also should understand how best to manage iatrogenic AEs when they encounter them in order to restore a patient’s visual function as quickly as possible.

Phenylephrine, a sympathomimetic drug, is commonly used in eye exams to dilate the pupil of the eye and to differentiate scleritis from episcleritis. Common adverse effects (AEs) of phenylephrine include subjective burning, stinging with lacrimation, rebound hyperemia, and liberation of iris pigment into the anterior chamber. Less common, systemic AEs include tachycardia and elevation of systemic blood pressure. Although instances of allergic reactions are rare, phenylephrine has been reported to cause contact dermatitis, blepharoconjunctivitis, and as in this case, keratoconjunctivitis.

Case Report

An 83-year-old white male presented for a red eye evaluation 2 days after having undergone a comprehensive eye exam with dilation at the Malcom Randall VAMC clinic in Gainesville, Florida. The patient reported onset of blurred vision, which he described as looking through a fog. He further compared the feeling to pins sticking in his eyes. The patient noted he had experienced similar symptoms on a few other occasions following eye exams. At the most recent eye exam, proparacaine and fluorescein had been used for tonometry, and phenylephrine 2.5% and tropicamide 0.5% had been used for pupillary dilation.

The patient’s best-corrected visual acuity was counting fingers at 2 feet in the right eye (OD) and left eye (OS). The best-corrected visual acuity 2 days prior had been 20/20 OD and OS. Pupils and extraocular motilities were unremarkable. Intraocular pressures were not obtained due to concern for a possible adverse reaction to proparacaine.

Slit-lamp evaluation revealed the lids to be lax, erythematous, and edematous in both eyes (Figure 1).

A marked papillary reaction and 3+ bulbar conjunctival injection in both eyes (OU) also was evident. The corneas had 2+ filamentous strands with dense superficial punctate keratitis bilaterally (Figures 2a & 2b).

Anterior chamber angles were open, but it was difficult to assess for cells and flare through the hazy corneas. Irides were flat and clear OU. Lens exam revealed modest nuclear sclerosis OU. Due to concern for allergic reaction to tropicamide or phenylephrine, the patient was not redilated. The level of vision loss was consistent with the degree of keratitis observed OU.

The initial diagnosis was acute chemical conjunctivitis most likely due to an AE to proparacaine. The plan was to start the patient on antibiotic eye drops qid OU, prednisolone qid OU, and artificial tears every hour OU. The patient was scheduled to return to clinic 4 days later for an anterior segment follow-up.

At the follow-up visit, the patient reported significant visual improvement. His best-corrected visual acuity was 20/40-2 without improvement on pinhole OD and 20/50-2 with improvement to 20/30+ on pinhole OS. Slit-lamp evaluation revealed 1+ bulbar conjunctival injection OU, intact corneal epithelium OU, and no cells or flare in the anterior chambers OU. Due to improving punctate epitheliopathy, the frequency of the antibiotic drops, the prednisolone, and the artificial tears was reduced to bid. After 3 days, he was instructed to discontinue them. The patient was scheduled to return in 2 weeks for an anterior segment follow-up.

At the next follow-up visit, the patient reported that his vision had returned to normal, and he had no further ocular AEs. His best-corrected visual acuity was 20/20-2 OD and 20/20 OS. Slit-lamp evaluation revealed mild blepharitis OU, trace bulbar conjunctival injection OU, and complete resolution of the keratitis OU. The assessment was acute allergic conjunctivitis thought to be secondary to an AE to proparacaine OU, yet the need to rule out hypersensitivity to tropicamide and/or phenylephrine remained. The plan was to educate the patient of the possibility of allergic reaction on future visits and to recommend continued use of artificial tears as needed.

Through a careful and extensive chart review of all past visits, it was suspected that phenylephrine might be to blame rather than proparacaine. At the subsequent visit, the patient agreed to undergo testing to determine the culprit via instillation of proparacaine in one eye and tropicamide in the other. The patient had no reaction to either drop (checked 45 minutes after instillation and the following day). By process of elimination, phenylephrine was determined to be the offending agent.

Discussion

Following a thorough review of the patient’s chart, it was found that on other occasions he had presented with suspected allergic reactions following routine eye examinations. The patient reported he had experienced a reaction in 2007 but could not recall what drops were instilled in his eyes at the time. In addition, there was no documentation in his medical record of the subsequent reaction following that visit. Another reaction occurred in July 2010 with instillation of tropicamide 1%, phenylephrine 2.5%, and Fluress (fluorescein sodium and benoxinate hydrochloride ophthalmic solution USP). In October 2013, when tropicamide 0.5%, proparacaine, and fluorescein strips were instilled, there was no reaction. The next reaction occurred in October 2014, when tropicamide 0.5%, phenylephrine 2.5%, proparacaine, and fluorescein strips were instilled.

 

This careful review of past exam notes revealed that phenylephrine and Fluress were the only drops that had not been instilled at the October 2013 visit when no AE was reported. However, Fluress was an unlikely culprit since it was not instilled in October 2014, and the patient still experienced an AE. Therefore, the agent most likely responsible for the allergic reaction in the patient, as confirmed by a review of the past notes and by the aforementioned pharmacologic test, was deemed to be phenylephrine (Table).

Adverse reactions to topical ocular medications and specifically to diagnostic eye drops have long been recognized. Mathias, Camarasa, Barber, Ducombs, and Monsálvezhave reported on variations of conjunctivitis and periorbital erythema with positive patch testing to phenylephrine.^1-5 Geyer and colleagues reported on a study of 21 patients who had blepharoconjunctivitis after instillation of phenylephrine.⁶ In this case study patient, severe keratoconjunctivitis was the clinical manifestation observed.

Villarreal and colleagues studied 31 patients who had a previous reaction to mydriatic drops. The study found that phenylephrine was the drug that most frequently caused an AE (93.5%).⁷ One patient reacted to the preservative thimerosal, and 1 patient reacted to benoxiprocaine. Tropicamide was demonstrated to be very well tolerated as none of the patients tested positive on either the patch test or the pharmacologic test.

Tropicamide is a nonselective muscarinic antagonist commonly used for mydriasis due to its fast onset and short duration.⁸ Adverse reactions to tropicamide are rare. Three studies reported on patients who had a positive patch test to tropicamide.^9-11 However, the reaction was not provoked by direct instillation of tropicamide into the eye.

Common in-office topical anesthetics, proparacaine, tetracaine, benoxinate, and lidocaine also can cause AEs. Corneal toxicity is a well-known complication with topical anesthetic abuse, whereas allergic reactions are considered rare. The most common symptoms include stingingand discomfort upon instillation. Common signs include punctate corneal epithelial erosionsresulting indirectly from a decrease in reflex tearing, infrequent blinking, and increased tear evaporation.¹² Topical anesthetics also inhibit the migration of corneal epithelial cells and cause direct damage to the cells that are present, leading to impaired healing and epithelial defects.¹³

Manifestations of allergic reaction to topical anesthetics can include conjunctival hyperemia and edema, edematous eyelids, and lacrimation. One published case described a 60-year-old woman who developed eczematous dermatitis of the eyelids after ophthalmic anesthetic drops were instilled prior to laser surgery. Patch testing showed a positive response to benzocaine 5%, proparacaine, and tetracaine 0.5%.¹⁴

Preservatives, in general, can cause an allergic reaction. Benzalkonium chloride’s (BAK) cytotoxic sequelae include possible trabecular cell death in glaucoma patients, disruption of tear film stability (even at low concentrations), and immune-allergenic properties. One article reported BAK as one of the 30 most frequent allergens causing allergic periorbital dermatitis.¹⁵ Benzalkonium chloride is used in most brands of phenylephrine. However, preservatives in this patient’s case were ruled out as instigating agents since both phenylephrine and tropicamide contain the same preservative, BAK 0.01%, yet this patient did not develop a reaction to tropicamide when used without phenylephrine. Expired medications also were not considered to be a factor as none of the medications used on the patient were indeed expired (the Malcom Randall VAMC clinic maintains a strict policy of discarding medications 28 days after being opened).

Although uncommon, phenylephrine sometimes has been found to cause a type 4 hypersensitivity reaction, also known as cell-mediated or delayed-type hypersensitivity.¹⁶ First, helper T cells secrete cytokines. Activation of cytokines recruits and activates cytotoxic T cells, monocytes, and macrophages, leading to inflammation of the surrounding tissue. Examples of cell-mediated hypersensitivity include reactions to the tuberculin skin test and to poison ivy.

Type 1 hypersensitivity reactions, also known as immediate or anaphylactic hypersensitivity reactions, are not triggered by phenylephrine. In this type of reaction, IgE binds to the mast cell on initial exposure to an allergen. On second exposure, the allergen binds to the IgE, causing the mast cell to release mediators of inflammation, triggering physiologic responses. Examples of this type of hypersensitivity include those seen with penicillin, bee stings, hay fever, bronchial asthma, and food allergies, for example, to shellfish.

A toxic reaction’s mechanism differs from that of a type 4 hypersensitivity reaction. Toxic reactions occur due to direct cytotoxicity of a drug caused by a low or high pH and either hyper- or hypo-osmolarity. Toxicity can lead to corneal and conjunctival cell necrosis or induce apoptosis, stimulating inflammatory reactions. Clinically, toxic reactions will present with follicles, whereas allergic reactions will present with papillae.

The definitive diagnostic methods used to determine the allergic agent causing ocular or periocular AEs are patch testing and conjunctival challenge.⁷ Mathias, Camarasa, Barber, Ducombs,and Monsálvezused patch testing to confirm phenylephrine as the allergic agent in their series of cases. Patch testing entails the application of a small amount of an allergic agent that is taped onto the skin. The allergic agent is confirmed if the patient has a dermal reaction, wherein the area patched will become erythematous. When patch testing is negative or inconclusive, a conjunctival challenge is performed by instillation of the suspected allergic agent into the eye with subsequent observation to determine whether a reaction occurs. The sequelae found in Villarreal’s study included itching, lacrimation, edema, erythema, and sometimes blepharitis.⁷

A direct conjunctival challenge with the suspected culprit was not pursued in this patient’s case due to the known severity of the potential resulting reaction. The authors instead chose an indirect method of determining the implicating agent and used the process of elimination to whittle down the most likely suspect. A challenge with the medications suspected not to be likely offenders was undertaken. This spared the patient a likely repeat of the AE he had just recovered from.

 

Management

Allergic reactions can resolve without medical intervention. The first step is to remove the allergen. For delayed hypersensitivity reactions, treatments may include topical decongestants, cool compresses, and corticosteroids.⁸ The treatment for immediate hypersensitivity reaction differs from that of delayed hypersensitivity reaction in that antihistamines are used.^17,18

This patient reported receiving no treatment for his ocular symptoms following eye examinations in the past, yet he experienced complete resolution after each AE. In this case, both a steroid and a prophylactic antibiotic to facilitate a more rapid improvement were used.

Conclusion

Although uncommon, cases of allergic reaction to phenylephrine can occur. The incidence of phenylephrine allergy is 0.6%.6 The case study patient presented with a severe keratoconjunctivitis following routine eye examination with an accompanying history of adverse ocular signs and symptoms following multiple past exams.

It is important for all eye care clinicians to realize that AEs to diagnostic eye drops are possible and can occur following the most routine of visits. Such reactions can be caused by dilating agents, anesthetics, or preservatives, and these may be allergic or toxic. Clinicians should take special care to identify the instigating agent, and if possible, to avoid using such agents on patients during future exams. Clinicians also should understand how best to manage iatrogenic AEs when they encounter them in order to restore a patient’s visual function as quickly as possible.

Phenylephrine, a sympathomimetic drug, is commonly used in eye exams to dilate the pupil of the eye and to differentiate scleritis from episcleritis. Common adverse effects (AEs) of phenylephrine include subjective burning, stinging with lacrimation, rebound hyperemia, and liberation of iris pigment into the anterior chamber. Less common, systemic AEs include tachycardia and elevation of systemic blood pressure. Although instances of allergic reactions are rare, phenylephrine has been reported to cause contact dermatitis, blepharoconjunctivitis, and as in this case, keratoconjunctivitis.

Case Report

An 83-year-old white male presented for a red eye evaluation 2 days after having undergone a comprehensive eye exam with dilation at the Malcom Randall VAMC clinic in Gainesville, Florida. The patient reported onset of blurred vision, which he described as looking through a fog. He further compared the feeling to pins sticking in his eyes. The patient noted he had experienced similar symptoms on a few other occasions following eye exams. At the most recent eye exam, proparacaine and fluorescein had been used for tonometry, and phenylephrine 2.5% and tropicamide 0.5% had been used for pupillary dilation.

The patient’s best-corrected visual acuity was counting fingers at 2 feet in the right eye (OD) and left eye (OS). The best-corrected visual acuity 2 days prior had been 20/20 OD and OS. Pupils and extraocular motilities were unremarkable. Intraocular pressures were not obtained due to concern for a possible adverse reaction to proparacaine.

Slit-lamp evaluation revealed the lids to be lax, erythematous, and edematous in both eyes (Figure 1).

A marked papillary reaction and 3+ bulbar conjunctival injection in both eyes (OU) also was evident. The corneas had 2+ filamentous strands with dense superficial punctate keratitis bilaterally (Figures 2a & 2b).

Anterior chamber angles were open, but it was difficult to assess for cells and flare through the hazy corneas. Irides were flat and clear OU. Lens exam revealed modest nuclear sclerosis OU. Due to concern for allergic reaction to tropicamide or phenylephrine, the patient was not redilated. The level of vision loss was consistent with the degree of keratitis observed OU.

The initial diagnosis was acute chemical conjunctivitis most likely due to an AE to proparacaine. The plan was to start the patient on antibiotic eye drops qid OU, prednisolone qid OU, and artificial tears every hour OU. The patient was scheduled to return to clinic 4 days later for an anterior segment follow-up.

At the follow-up visit, the patient reported significant visual improvement. His best-corrected visual acuity was 20/40-2 without improvement on pinhole OD and 20/50-2 with improvement to 20/30+ on pinhole OS. Slit-lamp evaluation revealed 1+ bulbar conjunctival injection OU, intact corneal epithelium OU, and no cells or flare in the anterior chambers OU. Due to improving punctate epitheliopathy, the frequency of the antibiotic drops, the prednisolone, and the artificial tears was reduced to bid. After 3 days, he was instructed to discontinue them. The patient was scheduled to return in 2 weeks for an anterior segment follow-up.

At the next follow-up visit, the patient reported that his vision had returned to normal, and he had no further ocular AEs. His best-corrected visual acuity was 20/20-2 OD and 20/20 OS. Slit-lamp evaluation revealed mild blepharitis OU, trace bulbar conjunctival injection OU, and complete resolution of the keratitis OU. The assessment was acute allergic conjunctivitis thought to be secondary to an AE to proparacaine OU, yet the need to rule out hypersensitivity to tropicamide and/or phenylephrine remained. The plan was to educate the patient of the possibility of allergic reaction on future visits and to recommend continued use of artificial tears as needed.

Through a careful and extensive chart review of all past visits, it was suspected that phenylephrine might be to blame rather than proparacaine. At the subsequent visit, the patient agreed to undergo testing to determine the culprit via instillation of proparacaine in one eye and tropicamide in the other. The patient had no reaction to either drop (checked 45 minutes after instillation and the following day). By process of elimination, phenylephrine was determined to be the offending agent.

Discussion

Following a thorough review of the patient’s chart, it was found that on other occasions he had presented with suspected allergic reactions following routine eye examinations. The patient reported he had experienced a reaction in 2007 but could not recall what drops were instilled in his eyes at the time. In addition, there was no documentation in his medical record of the subsequent reaction following that visit. Another reaction occurred in July 2010 with instillation of tropicamide 1%, phenylephrine 2.5%, and Fluress (fluorescein sodium and benoxinate hydrochloride ophthalmic solution USP). In October 2013, when tropicamide 0.5%, proparacaine, and fluorescein strips were instilled, there was no reaction. The next reaction occurred in October 2014, when tropicamide 0.5%, phenylephrine 2.5%, proparacaine, and fluorescein strips were instilled.

 

This careful review of past exam notes revealed that phenylephrine and Fluress were the only drops that had not been instilled at the October 2013 visit when no AE was reported. However, Fluress was an unlikely culprit since it was not instilled in October 2014, and the patient still experienced an AE. Therefore, the agent most likely responsible for the allergic reaction in the patient, as confirmed by a review of the past notes and by the aforementioned pharmacologic test, was deemed to be phenylephrine (Table).

Adverse reactions to topical ocular medications and specifically to diagnostic eye drops have long been recognized. Mathias, Camarasa, Barber, Ducombs, and Monsálvezhave reported on variations of conjunctivitis and periorbital erythema with positive patch testing to phenylephrine.^1-5 Geyer and colleagues reported on a study of 21 patients who had blepharoconjunctivitis after instillation of phenylephrine.⁶ In this case study patient, severe keratoconjunctivitis was the clinical manifestation observed.

Villarreal and colleagues studied 31 patients who had a previous reaction to mydriatic drops. The study found that phenylephrine was the drug that most frequently caused an AE (93.5%).⁷ One patient reacted to the preservative thimerosal, and 1 patient reacted to benoxiprocaine. Tropicamide was demonstrated to be very well tolerated as none of the patients tested positive on either the patch test or the pharmacologic test.

Tropicamide is a nonselective muscarinic antagonist commonly used for mydriasis due to its fast onset and short duration.⁸ Adverse reactions to tropicamide are rare. Three studies reported on patients who had a positive patch test to tropicamide.^9-11 However, the reaction was not provoked by direct instillation of tropicamide into the eye.

Common in-office topical anesthetics, proparacaine, tetracaine, benoxinate, and lidocaine also can cause AEs. Corneal toxicity is a well-known complication with topical anesthetic abuse, whereas allergic reactions are considered rare. The most common symptoms include stingingand discomfort upon instillation. Common signs include punctate corneal epithelial erosionsresulting indirectly from a decrease in reflex tearing, infrequent blinking, and increased tear evaporation.¹² Topical anesthetics also inhibit the migration of corneal epithelial cells and cause direct damage to the cells that are present, leading to impaired healing and epithelial defects.¹³

Manifestations of allergic reaction to topical anesthetics can include conjunctival hyperemia and edema, edematous eyelids, and lacrimation. One published case described a 60-year-old woman who developed eczematous dermatitis of the eyelids after ophthalmic anesthetic drops were instilled prior to laser surgery. Patch testing showed a positive response to benzocaine 5%, proparacaine, and tetracaine 0.5%.¹⁴

Preservatives, in general, can cause an allergic reaction. Benzalkonium chloride’s (BAK) cytotoxic sequelae include possible trabecular cell death in glaucoma patients, disruption of tear film stability (even at low concentrations), and immune-allergenic properties. One article reported BAK as one of the 30 most frequent allergens causing allergic periorbital dermatitis.¹⁵ Benzalkonium chloride is used in most brands of phenylephrine. However, preservatives in this patient’s case were ruled out as instigating agents since both phenylephrine and tropicamide contain the same preservative, BAK 0.01%, yet this patient did not develop a reaction to tropicamide when used without phenylephrine. Expired medications also were not considered to be a factor as none of the medications used on the patient were indeed expired (the Malcom Randall VAMC clinic maintains a strict policy of discarding medications 28 days after being opened).

Although uncommon, phenylephrine sometimes has been found to cause a type 4 hypersensitivity reaction, also known as cell-mediated or delayed-type hypersensitivity.¹⁶ First, helper T cells secrete cytokines. Activation of cytokines recruits and activates cytotoxic T cells, monocytes, and macrophages, leading to inflammation of the surrounding tissue. Examples of cell-mediated hypersensitivity include reactions to the tuberculin skin test and to poison ivy.

Type 1 hypersensitivity reactions, also known as immediate or anaphylactic hypersensitivity reactions, are not triggered by phenylephrine. In this type of reaction, IgE binds to the mast cell on initial exposure to an allergen. On second exposure, the allergen binds to the IgE, causing the mast cell to release mediators of inflammation, triggering physiologic responses. Examples of this type of hypersensitivity include those seen with penicillin, bee stings, hay fever, bronchial asthma, and food allergies, for example, to shellfish.

A toxic reaction’s mechanism differs from that of a type 4 hypersensitivity reaction. Toxic reactions occur due to direct cytotoxicity of a drug caused by a low or high pH and either hyper- or hypo-osmolarity. Toxicity can lead to corneal and conjunctival cell necrosis or induce apoptosis, stimulating inflammatory reactions. Clinically, toxic reactions will present with follicles, whereas allergic reactions will present with papillae.

The definitive diagnostic methods used to determine the allergic agent causing ocular or periocular AEs are patch testing and conjunctival challenge.⁷ Mathias, Camarasa, Barber, Ducombs,and Monsálvezused patch testing to confirm phenylephrine as the allergic agent in their series of cases. Patch testing entails the application of a small amount of an allergic agent that is taped onto the skin. The allergic agent is confirmed if the patient has a dermal reaction, wherein the area patched will become erythematous. When patch testing is negative or inconclusive, a conjunctival challenge is performed by instillation of the suspected allergic agent into the eye with subsequent observation to determine whether a reaction occurs. The sequelae found in Villarreal’s study included itching, lacrimation, edema, erythema, and sometimes blepharitis.⁷

A direct conjunctival challenge with the suspected culprit was not pursued in this patient’s case due to the known severity of the potential resulting reaction. The authors instead chose an indirect method of determining the implicating agent and used the process of elimination to whittle down the most likely suspect. A challenge with the medications suspected not to be likely offenders was undertaken. This spared the patient a likely repeat of the AE he had just recovered from.

 

Management

Allergic reactions can resolve without medical intervention. The first step is to remove the allergen. For delayed hypersensitivity reactions, treatments may include topical decongestants, cool compresses, and corticosteroids.⁸ The treatment for immediate hypersensitivity reaction differs from that of delayed hypersensitivity reaction in that antihistamines are used.^17,18

This patient reported receiving no treatment for his ocular symptoms following eye examinations in the past, yet he experienced complete resolution after each AE. In this case, both a steroid and a prophylactic antibiotic to facilitate a more rapid improvement were used.

Conclusion

Although uncommon, cases of allergic reaction to phenylephrine can occur. The incidence of phenylephrine allergy is 0.6%.6 The case study patient presented with a severe keratoconjunctivitis following routine eye examination with an accompanying history of adverse ocular signs and symptoms following multiple past exams.

It is important for all eye care clinicians to realize that AEs to diagnostic eye drops are possible and can occur following the most routine of visits. Such reactions can be caused by dilating agents, anesthetics, or preservatives, and these may be allergic or toxic. Clinicians should take special care to identify the instigating agent, and if possible, to avoid using such agents on patients during future exams. Clinicians also should understand how best to manage iatrogenic AEs when they encounter them in order to restore a patient’s visual function as quickly as possible.