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Scrubs ad that insulted women and DOs pulled after outcry
A video that advertised scrubs but denigrated women and DOs has been removed from the company’s website after fierce backlash.
On Tuesday Kevin Klauer, DO, EJD, directed this tweet to the medical uniform company Figs: “@wearfigs REMOVE YOUR DO offensive web ad immediately or the @AOAforDOs will proceed promptly with a defamation lawsuit on behalf of our members and profession.”
Also on Tuesday, the American Association of Colleges of Osteopathic Medicine demanded a public apology.
The video ad featured a woman carrying a “Medical Terminology for Dummies” book upside down while modeling the pink scrubs from all angles and dancing. At one point in the ad, the camera zooms in on the badge clipped to her waistband that read “DO.”
Agnieszka Solberg, MD, a vascular and interventional radiologist and assistant clinical professor at the University of North Dakota in Grand Forks, was among those voicing pointed criticism on social media.
“This was another hit for our DO colleagues,” she said in an interview, emphasizing that MDs and DOs provide the same level of care.
AACOM tweeted: “We are outraged women physicians & doctors of osteopathic medicine are still attacked in ignorant marketing campaigns. A company like @wearfigs should be ashamed for promoting these stereotypes. We demand the respect we’ve earned AND a public apology.”
Dr. Solberg says this is not the first offense by the company. She said she had stopped buying the company’s scrubs a year ago because the ads “have been portraying female providers as dumb and silly. This was the final straw.”
She said the timing of the ad is suspect as DOs had been swept into a storm of negativity earlier this month, as Medscape Medical News reported, when some questioned the qualifications of President Donald Trump’s physician, Sean Conley, who is a DO.
The scrubs ad ignited criticism across specialties, provider levels, and genders.
Jessica K. Willett, MD, tweeted: “As women physicians in 2020, we still struggle to be taken seriously compared to our male counterparts, as we battle stereotypes like THIS EXACT ONE. We expect the brands we support to reflect the badasses we are.”
The company responded to her tweet: “Thank you so much for the feedback! Totally not our intent – we’re taking down both the men’s and women’s versions of this ASAP! I really appreciate you taking the time to share this.”
The company did not respond to a request for comment but issued an apology on social media: “A lot of you guys have pointed out an insensitive video we had on our site – we are incredibly sorry for any hurt this has caused you, especially our female DOs (who are amazing!) FIGS is a female founded company whose only mission is to make you guys feel awesome.”
The Los Angeles–based company, which Forbes estimated will make $250 million in sales this year, was founded by co-CEOs Heather Hasson and Trina Spear.
A med student wrote on Twitter: “As a female and a DO student, how would I ever “feel awesome” about myself knowing that this is how you view me??? And how you want others to view me??? Women and DO’s have fought stereotypes way too long for you to go ahead and put this out there. Do better.”
Even the company’s apology was tinged with disrespect, some noted, with the use of “you guys” and for what it didn’t include.
As Liesl Young, MD, tweeted: “We are not “guys”, we are women. MD = DO. We stand together.”
Dr. Solberg said the apology came across as an apology that feelings were hurt. It should have detailed the changes the company would make to prevent another incident and address the processes that led to the video.
Dr. Solberg said she is seeing something positive come from the whole incident in that, “women are taking up the torch of feminism in such a volatile and divisive time.”
Dr. Solberg reported no relevant financial relationships.
This article first appeared on Medscape.com.
A video that advertised scrubs but denigrated women and DOs has been removed from the company’s website after fierce backlash.
On Tuesday Kevin Klauer, DO, EJD, directed this tweet to the medical uniform company Figs: “@wearfigs REMOVE YOUR DO offensive web ad immediately or the @AOAforDOs will proceed promptly with a defamation lawsuit on behalf of our members and profession.”
Also on Tuesday, the American Association of Colleges of Osteopathic Medicine demanded a public apology.
The video ad featured a woman carrying a “Medical Terminology for Dummies” book upside down while modeling the pink scrubs from all angles and dancing. At one point in the ad, the camera zooms in on the badge clipped to her waistband that read “DO.”
Agnieszka Solberg, MD, a vascular and interventional radiologist and assistant clinical professor at the University of North Dakota in Grand Forks, was among those voicing pointed criticism on social media.
“This was another hit for our DO colleagues,” she said in an interview, emphasizing that MDs and DOs provide the same level of care.
AACOM tweeted: “We are outraged women physicians & doctors of osteopathic medicine are still attacked in ignorant marketing campaigns. A company like @wearfigs should be ashamed for promoting these stereotypes. We demand the respect we’ve earned AND a public apology.”
Dr. Solberg says this is not the first offense by the company. She said she had stopped buying the company’s scrubs a year ago because the ads “have been portraying female providers as dumb and silly. This was the final straw.”
She said the timing of the ad is suspect as DOs had been swept into a storm of negativity earlier this month, as Medscape Medical News reported, when some questioned the qualifications of President Donald Trump’s physician, Sean Conley, who is a DO.
The scrubs ad ignited criticism across specialties, provider levels, and genders.
Jessica K. Willett, MD, tweeted: “As women physicians in 2020, we still struggle to be taken seriously compared to our male counterparts, as we battle stereotypes like THIS EXACT ONE. We expect the brands we support to reflect the badasses we are.”
The company responded to her tweet: “Thank you so much for the feedback! Totally not our intent – we’re taking down both the men’s and women’s versions of this ASAP! I really appreciate you taking the time to share this.”
The company did not respond to a request for comment but issued an apology on social media: “A lot of you guys have pointed out an insensitive video we had on our site – we are incredibly sorry for any hurt this has caused you, especially our female DOs (who are amazing!) FIGS is a female founded company whose only mission is to make you guys feel awesome.”
The Los Angeles–based company, which Forbes estimated will make $250 million in sales this year, was founded by co-CEOs Heather Hasson and Trina Spear.
A med student wrote on Twitter: “As a female and a DO student, how would I ever “feel awesome” about myself knowing that this is how you view me??? And how you want others to view me??? Women and DO’s have fought stereotypes way too long for you to go ahead and put this out there. Do better.”
Even the company’s apology was tinged with disrespect, some noted, with the use of “you guys” and for what it didn’t include.
As Liesl Young, MD, tweeted: “We are not “guys”, we are women. MD = DO. We stand together.”
Dr. Solberg said the apology came across as an apology that feelings were hurt. It should have detailed the changes the company would make to prevent another incident and address the processes that led to the video.
Dr. Solberg said she is seeing something positive come from the whole incident in that, “women are taking up the torch of feminism in such a volatile and divisive time.”
Dr. Solberg reported no relevant financial relationships.
This article first appeared on Medscape.com.
A video that advertised scrubs but denigrated women and DOs has been removed from the company’s website after fierce backlash.
On Tuesday Kevin Klauer, DO, EJD, directed this tweet to the medical uniform company Figs: “@wearfigs REMOVE YOUR DO offensive web ad immediately or the @AOAforDOs will proceed promptly with a defamation lawsuit on behalf of our members and profession.”
Also on Tuesday, the American Association of Colleges of Osteopathic Medicine demanded a public apology.
The video ad featured a woman carrying a “Medical Terminology for Dummies” book upside down while modeling the pink scrubs from all angles and dancing. At one point in the ad, the camera zooms in on the badge clipped to her waistband that read “DO.”
Agnieszka Solberg, MD, a vascular and interventional radiologist and assistant clinical professor at the University of North Dakota in Grand Forks, was among those voicing pointed criticism on social media.
“This was another hit for our DO colleagues,” she said in an interview, emphasizing that MDs and DOs provide the same level of care.
AACOM tweeted: “We are outraged women physicians & doctors of osteopathic medicine are still attacked in ignorant marketing campaigns. A company like @wearfigs should be ashamed for promoting these stereotypes. We demand the respect we’ve earned AND a public apology.”
Dr. Solberg says this is not the first offense by the company. She said she had stopped buying the company’s scrubs a year ago because the ads “have been portraying female providers as dumb and silly. This was the final straw.”
She said the timing of the ad is suspect as DOs had been swept into a storm of negativity earlier this month, as Medscape Medical News reported, when some questioned the qualifications of President Donald Trump’s physician, Sean Conley, who is a DO.
The scrubs ad ignited criticism across specialties, provider levels, and genders.
Jessica K. Willett, MD, tweeted: “As women physicians in 2020, we still struggle to be taken seriously compared to our male counterparts, as we battle stereotypes like THIS EXACT ONE. We expect the brands we support to reflect the badasses we are.”
The company responded to her tweet: “Thank you so much for the feedback! Totally not our intent – we’re taking down both the men’s and women’s versions of this ASAP! I really appreciate you taking the time to share this.”
The company did not respond to a request for comment but issued an apology on social media: “A lot of you guys have pointed out an insensitive video we had on our site – we are incredibly sorry for any hurt this has caused you, especially our female DOs (who are amazing!) FIGS is a female founded company whose only mission is to make you guys feel awesome.”
The Los Angeles–based company, which Forbes estimated will make $250 million in sales this year, was founded by co-CEOs Heather Hasson and Trina Spear.
A med student wrote on Twitter: “As a female and a DO student, how would I ever “feel awesome” about myself knowing that this is how you view me??? And how you want others to view me??? Women and DO’s have fought stereotypes way too long for you to go ahead and put this out there. Do better.”
Even the company’s apology was tinged with disrespect, some noted, with the use of “you guys” and for what it didn’t include.
As Liesl Young, MD, tweeted: “We are not “guys”, we are women. MD = DO. We stand together.”
Dr. Solberg said the apology came across as an apology that feelings were hurt. It should have detailed the changes the company would make to prevent another incident and address the processes that led to the video.
Dr. Solberg said she is seeing something positive come from the whole incident in that, “women are taking up the torch of feminism in such a volatile and divisive time.”
Dr. Solberg reported no relevant financial relationships.
This article first appeared on Medscape.com.
Latest week brings 44,000 more children with COVID-19
in the United States, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
The total number of COVID-19 cases among children was 741,891 as of Oct. 15, which puts the cumulative proportion at 10.9% of the 6.8 million cases reported in all ages by 49 states (New York does not report ages), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP and CHA said in their weekly COVID-19 report.
The 44,258 new cases in children represented 13.3% of all cases reported during the week ending Oct. 15, down from 14.6% the previous week (children make up almost 23% of the total U.S. population), the AAP/CHA data show.
Those data also indicate that there have been almost 986 cases of COVID-19 per 100,000 children in the United States. Corresponding rates among the states range from 181 per 100,000 in Vermont to 2,581 per 100,000 in North Dakota. Tennessee (2,277) and South Carolina (2,212) are the only other states above 2,000, according to the report.
California has reported the most child cases, 89,843 (1,010 per 100,000 children), so far, followed by Florida (44,199), Illinois (42,132), and Tennessee (40,137). Seven other states have had over 20,000 cases each, the AAP and CHA noted.
Measures of severe illness continue to be low, although the data are less comprehensive. Children represent only 1.7% of all COVID-19 hospitalizations (24 states and N.Y.C. reporting) and 0.07% of all deaths (42 states and N.Y.C. reporting). Thirteen states and D.C. have had no deaths yet, while Texas has reported three times as many (27) as any other state (Arizona is next with 9, although N.Y.C. has had 15), the AAP/CHA report said.
in the United States, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
The total number of COVID-19 cases among children was 741,891 as of Oct. 15, which puts the cumulative proportion at 10.9% of the 6.8 million cases reported in all ages by 49 states (New York does not report ages), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP and CHA said in their weekly COVID-19 report.
The 44,258 new cases in children represented 13.3% of all cases reported during the week ending Oct. 15, down from 14.6% the previous week (children make up almost 23% of the total U.S. population), the AAP/CHA data show.
Those data also indicate that there have been almost 986 cases of COVID-19 per 100,000 children in the United States. Corresponding rates among the states range from 181 per 100,000 in Vermont to 2,581 per 100,000 in North Dakota. Tennessee (2,277) and South Carolina (2,212) are the only other states above 2,000, according to the report.
California has reported the most child cases, 89,843 (1,010 per 100,000 children), so far, followed by Florida (44,199), Illinois (42,132), and Tennessee (40,137). Seven other states have had over 20,000 cases each, the AAP and CHA noted.
Measures of severe illness continue to be low, although the data are less comprehensive. Children represent only 1.7% of all COVID-19 hospitalizations (24 states and N.Y.C. reporting) and 0.07% of all deaths (42 states and N.Y.C. reporting). Thirteen states and D.C. have had no deaths yet, while Texas has reported three times as many (27) as any other state (Arizona is next with 9, although N.Y.C. has had 15), the AAP/CHA report said.
in the United States, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
The total number of COVID-19 cases among children was 741,891 as of Oct. 15, which puts the cumulative proportion at 10.9% of the 6.8 million cases reported in all ages by 49 states (New York does not report ages), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP and CHA said in their weekly COVID-19 report.
The 44,258 new cases in children represented 13.3% of all cases reported during the week ending Oct. 15, down from 14.6% the previous week (children make up almost 23% of the total U.S. population), the AAP/CHA data show.
Those data also indicate that there have been almost 986 cases of COVID-19 per 100,000 children in the United States. Corresponding rates among the states range from 181 per 100,000 in Vermont to 2,581 per 100,000 in North Dakota. Tennessee (2,277) and South Carolina (2,212) are the only other states above 2,000, according to the report.
California has reported the most child cases, 89,843 (1,010 per 100,000 children), so far, followed by Florida (44,199), Illinois (42,132), and Tennessee (40,137). Seven other states have had over 20,000 cases each, the AAP and CHA noted.
Measures of severe illness continue to be low, although the data are less comprehensive. Children represent only 1.7% of all COVID-19 hospitalizations (24 states and N.Y.C. reporting) and 0.07% of all deaths (42 states and N.Y.C. reporting). Thirteen states and D.C. have had no deaths yet, while Texas has reported three times as many (27) as any other state (Arizona is next with 9, although N.Y.C. has had 15), the AAP/CHA report said.
Is patient suicide in psychiatry a medical error?
When Rodney Vivian, MD, a psychiatrist in Cincinnati, was sued for medical malpractice after a psychiatric inpatient died by suicide, he recalls being naive about the process and how difficult it would be. “I was thinking that truth and common sense would prevail. How stupid I was,” he said.
Although Dr. Vivian, who was at the time the medical director of a hospital psychiatric unit in Ohio, was found not liable in two appeals, the legal process dragged on for 6 years, creating an emotional roller coaster of sadness, fear, vulnerability, and anxiety.
“The lawsuit took a big chunk out of me, and there was a sense of unfairness. It was incredibly humiliating and destructive; and it did not make me a better person or psychiatrist,” Dr. Vivian said.
Dr. Vivian is just one of the many psychiatrists who have had their world turned upside down after a patient suicide. When such events occur, grief-stricken families often point the finger at the treating psychiatrist. Although lawsuits are rare in psychiatry, patient suicide can lead to a myriad of emotional, legal, and career consequences.
Tyler Black, MD, child and adolescent psychiatrist and assistant clinical professor at the University of British Columbia, Vancouver, likens patient suicide to “a nuclear bomb” but emphasizes the importance of not classifying such events as a medical error or assigning blame.
“Starting with the assumption that suicide is always avoidable is not evidence based,” Dr. Black said.
Although patient suicide can occur across medicine, the odds are alarmingly high in psychiatry.
“There’s at least a 50-50 chance that a psychiatrist is going to face the suicide of a patient,” said Eric Plakun, MD, medical director/CEO at the Austen Riggs Center, Stockbridge, Mass. a hospital-based facility that offers a continuum of psychiatric treatment. Quoting forensic psychiatrist Robert Simon, Dr. Plakun said: “There are two kinds of psychiatrists – those who have had a patient die by suicide, and those who will.”
Research from 2015 shows that, among specialists, psychiatrists are among the least likely to be sued. A 2007/2008 Physician Survey from the American Medical Association showed that 22.2% of psychiatrists had been sued for malpractice; the probability that they would face a claim each year was only 2.6%. However, failure to prevent suicide is one of the top reasons for lawsuits.
One report from 2008 suggests that 20%-68% of psychiatrists will lose a patient to suicide. A report cowritten by Dr. Plakun in 2005 notes that about one in six psychiatric interns and one in three psychiatric residents will experience a patient suicide some time during their training. The authors added that 50% of all psychiatrists will have a patient die by suicide during their career. That risk stays at about 50% for future patients even after a clinician experiences the death of a previous patient.
Although mental health professionals prevail in up to 80% of suicide-related malpractice cases, such events are still emotionally devastating for everyone involved.
When a patient dies by suicide, it is a huge event, he noted. “It fuels a lot of fear and a lot of guilt, worry, and sadness.”
Paul S. Appelbaum, MD, past president of the American Psychiatric Association and Dollard Professor of Psychiatry, Medicine, and Law at Columbia University, New York, noted that patient suicide will happen.
The problem with many administrators who talk about a target of “zero suicide” is that when suicide does occur, it can lead to the erroneous conclusion that someone is to blame, said Dr. Appelbaum, who is also director of the Center for Law, Ethics, and Psychiatry at Columbia University. “That’s not necessarily true and contributes to finger-pointing.”
Stopping the blame game
Dr. Black’s first experience as a psychiatry resident was arriving at the hospital and finding the body of a patient who had died by suicide by hanging. Although he did not know the patient, Dr. Black said he had a strong emotional response that was coupled with an intense and sometimes confusing reaction by the hospital administration, including what he called “nonsensical banning” of pencils on the ward.
Dr. Black is now the medical director of emergency psychiatry at BC Children’s Hospital in Vancouver and specializes in suicidology and emergency/crisis youth mental health care. He said during a recent live chat on Twitter that he does not predict suicide but instead “assesses risk,” meaning he examines potential risk factors in his patients.
“If systems and administrators (and consulting doctors) could recognize this, the ‘blame game’ would severely decrease. From the advocacy end, we have to stop seeing suicide as a ‘medical error,’ ” Dr. Black tweeted.
“There’s a strong administrative push, especially in the face of suicide, to dive into the [occurrence] as if it must be that an error was made,” he said in an interview.
To help counteract any potential finger-pointing, Dr. Black created a free-to-download patient risk assessment document called the Assessment of Suicide and Risk Inventory (ASARI) for use at every patient visit.
“ASARI was designed to walk an assessor through their thinking process such that they can put all of their thoughts down on one piece of paper. It makes it a better communication document, and it’s definitely better medicolegal documentation,” he said.
Dr. Appelbaum noted that, although having documentation is beneficial, “I don’t think that you necessarily need to separate actions that are ‘protective’ from actions that are intended to help a patient.”
However, he pointed out that, if a psychiatrist conforms to or exceeds the standard of care, including conducting appropriate suicide risk assessments, developing an appropriate treatment plan, and keeping comprehensive documentation, these measures “should provide an effective defense to claims of malpractice or negligence.”
‘Horrendous event’
Dr. Vivian said that, during his 40-year career in psychiatry, there have been about 12 “office patients” who died by suicide. However, nothing prepared him for the fallout from a lawsuit.
In 2010, a patient who had overdosed was transferred to the psychiatric unit of Mercy Health–Clermont (Ohio) Hospital, where Dr. Vivian was the admitting physician. Although the hospital staff was ordered to check on her every 15 minutes, her husband found her unconscious from a hanging attempt when he came to visit the next evening. After she was transferred to the ICU, she was taken off life support and died a few days later.
“It was a horrendous event,” Dr. Vivian said.
The family sued the hospital, and the matter was settled out of court without Dr. Vivian’s knowledge. The family also filed a separate lawsuit against Dr. Vivian, which went to trial 3 years later.
“My insurance company’s claims person was very supportive and wanted me to not settle. She agreed that I didn’t do anything wrong and that I needed to face this,” he added.
In the first trial, a jury found Dr. Vivian not liable. Six months later, the plaintiff’s attorney filed an appeal. A year after the first trial, the court of appeals also came back with a new ruling in his favor and, in a subsequent appeal, the Ohio Supreme Court also ruled in his favor.
Dr. Vivian noted that there really are no winners in these situations. “Even though the jury ruled in my favor, there was never a sense of ‘success.’ I could never feel good about what happened.” He was told the insurance company spent more than $300,000 on his defense.
Although he no longer performs psychiatric inpatient admissions, Dr. Vivian continues to work in private practice and provides psychiatric consultation to patients at a local medical center.
“I consider my work as a blessing in my life, and I continue to learn from my patients,” he said.
‘Will I be sued?’
Dr. Appelbaum noted there is a difference between a malpractice claim that may be filed and a “payout” to plaintiffs because of a negotiated resolution of a case or an award that is made at trial.
Malpractice insurers may raise the rates of a physician who has been found at fault in one or more legal actions in which financial settlements have been paid out, he said.
The issue in any malpractice case is whether the psychiatrist met the standard of care, which is traditionally defined as “skill and learning that is ordinarily possessed and exercised by members of that profession in good standing.”
“No physician is expected to be the guarantor of a good outcome of a case. Sometimes things go wrong. Merely because there’s a bad outcome, merely because a suicide has occurred, doesn’t mean that the psychiatrist was negligent,” Dr. Appelbaum said.
He believes all large centers should have a “clear-cut plan” in place to assist clinicians in the event of a patient suicide. Such plans should help in dealing with stress from losing a patient and should provide guidance about how to handle any potential lawsuit.
For those worried that a patient’s suicide will shadow them through their career, Dr. Appelbaum said that it can happen, especially in cases involving a financial settlement against the clinician.
Such cases must be reported to the national practitioner data bank, where they can be accessed by any licensing body in any state when physicians apply for a medical license.
In addition, Dr. Appelbaum pointed out that licensure, medical staff, and malpractice applications typically require disclosure of a history of successful or unsuccessful claims filed against a physician. Although that may be limited to the past 10 years, the requirement can go on indefinitely.
Beware how you share
Dr. Plakun noted that there is a sense of isolation for a clinician in cases of patient suicide and that physicians often turn inward. He added that, although it is important to talk with others, in institutions, this is best done in a “peer-review, protected space” – and perhaps with a lawyer present.
However, Dr. Appelbaum warned that sharing information, even in this type of setting, may not offer legal protection. Talking to others in order to get some emotional support is permitted once the statute of limitations for filing a claim has lapsed or if a claim has been closed.
Discussing a case of patient suicide with peers prior to that can have serious legal implications, he added. Colleagues can be called to testify in any resulting legal case and disclose what was said during such conversations.
“The typical advice that a risk manager, a claims manager, or an attorney would give to a clinician is, don’t talk to other people about it other than the lawyer or claims manager who’s dealing with the case,” he noted.
That said, there are three general exceptions to this rule. These include attorney-client privilege, any matters discussed with the physician’s own therapist, and, “depending on the state, there are varying protections for what’s considered ‘peer review.’ ”
For instance, when hospitals implement a formal review process after an event, what is said during discovery may be protected. However, not all states have such protection. That’s why it is important to understand what the law is in your particular state, said Dr. Appelbaum.
Support for psychiatrists
Kaz J. Nelson, MD, psychiatrist and associate professor at the University of Minnesota, Minneapolis, also works with high-risk populations, including those with acute suicidality and self-injury.
During a recent chat on patient suicide, Dr. Nelson tweeted: “Sadly in our field, suicide is not an IF but a WHEN. Don’t keep the inevitable shame and sadness to yourself.”
Dr. Nelson agreed with Dr. Black that it’s important to look into these occurrences as a quality improvement measure, but not as a way to assign blame. Preparing for potential patient loss “and having very solid, very supportive, very inclusive ‘postvention’ procedures” is critical, she noted. “When you don’t have these policies and procedures in place and have them very transparent, it creates a culture of silence around the issue.”
Dr. Plakun reiterated the importance of not staying silent. “We can’t simply surrender to the idea of not talking about patient suicide. We have to find a way to speak.”
A version of this story originally appeared on Medscape.com.
When Rodney Vivian, MD, a psychiatrist in Cincinnati, was sued for medical malpractice after a psychiatric inpatient died by suicide, he recalls being naive about the process and how difficult it would be. “I was thinking that truth and common sense would prevail. How stupid I was,” he said.
Although Dr. Vivian, who was at the time the medical director of a hospital psychiatric unit in Ohio, was found not liable in two appeals, the legal process dragged on for 6 years, creating an emotional roller coaster of sadness, fear, vulnerability, and anxiety.
“The lawsuit took a big chunk out of me, and there was a sense of unfairness. It was incredibly humiliating and destructive; and it did not make me a better person or psychiatrist,” Dr. Vivian said.
Dr. Vivian is just one of the many psychiatrists who have had their world turned upside down after a patient suicide. When such events occur, grief-stricken families often point the finger at the treating psychiatrist. Although lawsuits are rare in psychiatry, patient suicide can lead to a myriad of emotional, legal, and career consequences.
Tyler Black, MD, child and adolescent psychiatrist and assistant clinical professor at the University of British Columbia, Vancouver, likens patient suicide to “a nuclear bomb” but emphasizes the importance of not classifying such events as a medical error or assigning blame.
“Starting with the assumption that suicide is always avoidable is not evidence based,” Dr. Black said.
Although patient suicide can occur across medicine, the odds are alarmingly high in psychiatry.
“There’s at least a 50-50 chance that a psychiatrist is going to face the suicide of a patient,” said Eric Plakun, MD, medical director/CEO at the Austen Riggs Center, Stockbridge, Mass. a hospital-based facility that offers a continuum of psychiatric treatment. Quoting forensic psychiatrist Robert Simon, Dr. Plakun said: “There are two kinds of psychiatrists – those who have had a patient die by suicide, and those who will.”
Research from 2015 shows that, among specialists, psychiatrists are among the least likely to be sued. A 2007/2008 Physician Survey from the American Medical Association showed that 22.2% of psychiatrists had been sued for malpractice; the probability that they would face a claim each year was only 2.6%. However, failure to prevent suicide is one of the top reasons for lawsuits.
One report from 2008 suggests that 20%-68% of psychiatrists will lose a patient to suicide. A report cowritten by Dr. Plakun in 2005 notes that about one in six psychiatric interns and one in three psychiatric residents will experience a patient suicide some time during their training. The authors added that 50% of all psychiatrists will have a patient die by suicide during their career. That risk stays at about 50% for future patients even after a clinician experiences the death of a previous patient.
Although mental health professionals prevail in up to 80% of suicide-related malpractice cases, such events are still emotionally devastating for everyone involved.
When a patient dies by suicide, it is a huge event, he noted. “It fuels a lot of fear and a lot of guilt, worry, and sadness.”
Paul S. Appelbaum, MD, past president of the American Psychiatric Association and Dollard Professor of Psychiatry, Medicine, and Law at Columbia University, New York, noted that patient suicide will happen.
The problem with many administrators who talk about a target of “zero suicide” is that when suicide does occur, it can lead to the erroneous conclusion that someone is to blame, said Dr. Appelbaum, who is also director of the Center for Law, Ethics, and Psychiatry at Columbia University. “That’s not necessarily true and contributes to finger-pointing.”
Stopping the blame game
Dr. Black’s first experience as a psychiatry resident was arriving at the hospital and finding the body of a patient who had died by suicide by hanging. Although he did not know the patient, Dr. Black said he had a strong emotional response that was coupled with an intense and sometimes confusing reaction by the hospital administration, including what he called “nonsensical banning” of pencils on the ward.
Dr. Black is now the medical director of emergency psychiatry at BC Children’s Hospital in Vancouver and specializes in suicidology and emergency/crisis youth mental health care. He said during a recent live chat on Twitter that he does not predict suicide but instead “assesses risk,” meaning he examines potential risk factors in his patients.
“If systems and administrators (and consulting doctors) could recognize this, the ‘blame game’ would severely decrease. From the advocacy end, we have to stop seeing suicide as a ‘medical error,’ ” Dr. Black tweeted.
“There’s a strong administrative push, especially in the face of suicide, to dive into the [occurrence] as if it must be that an error was made,” he said in an interview.
To help counteract any potential finger-pointing, Dr. Black created a free-to-download patient risk assessment document called the Assessment of Suicide and Risk Inventory (ASARI) for use at every patient visit.
“ASARI was designed to walk an assessor through their thinking process such that they can put all of their thoughts down on one piece of paper. It makes it a better communication document, and it’s definitely better medicolegal documentation,” he said.
Dr. Appelbaum noted that, although having documentation is beneficial, “I don’t think that you necessarily need to separate actions that are ‘protective’ from actions that are intended to help a patient.”
However, he pointed out that, if a psychiatrist conforms to or exceeds the standard of care, including conducting appropriate suicide risk assessments, developing an appropriate treatment plan, and keeping comprehensive documentation, these measures “should provide an effective defense to claims of malpractice or negligence.”
‘Horrendous event’
Dr. Vivian said that, during his 40-year career in psychiatry, there have been about 12 “office patients” who died by suicide. However, nothing prepared him for the fallout from a lawsuit.
In 2010, a patient who had overdosed was transferred to the psychiatric unit of Mercy Health–Clermont (Ohio) Hospital, where Dr. Vivian was the admitting physician. Although the hospital staff was ordered to check on her every 15 minutes, her husband found her unconscious from a hanging attempt when he came to visit the next evening. After she was transferred to the ICU, she was taken off life support and died a few days later.
“It was a horrendous event,” Dr. Vivian said.
The family sued the hospital, and the matter was settled out of court without Dr. Vivian’s knowledge. The family also filed a separate lawsuit against Dr. Vivian, which went to trial 3 years later.
“My insurance company’s claims person was very supportive and wanted me to not settle. She agreed that I didn’t do anything wrong and that I needed to face this,” he added.
In the first trial, a jury found Dr. Vivian not liable. Six months later, the plaintiff’s attorney filed an appeal. A year after the first trial, the court of appeals also came back with a new ruling in his favor and, in a subsequent appeal, the Ohio Supreme Court also ruled in his favor.
Dr. Vivian noted that there really are no winners in these situations. “Even though the jury ruled in my favor, there was never a sense of ‘success.’ I could never feel good about what happened.” He was told the insurance company spent more than $300,000 on his defense.
Although he no longer performs psychiatric inpatient admissions, Dr. Vivian continues to work in private practice and provides psychiatric consultation to patients at a local medical center.
“I consider my work as a blessing in my life, and I continue to learn from my patients,” he said.
‘Will I be sued?’
Dr. Appelbaum noted there is a difference between a malpractice claim that may be filed and a “payout” to plaintiffs because of a negotiated resolution of a case or an award that is made at trial.
Malpractice insurers may raise the rates of a physician who has been found at fault in one or more legal actions in which financial settlements have been paid out, he said.
The issue in any malpractice case is whether the psychiatrist met the standard of care, which is traditionally defined as “skill and learning that is ordinarily possessed and exercised by members of that profession in good standing.”
“No physician is expected to be the guarantor of a good outcome of a case. Sometimes things go wrong. Merely because there’s a bad outcome, merely because a suicide has occurred, doesn’t mean that the psychiatrist was negligent,” Dr. Appelbaum said.
He believes all large centers should have a “clear-cut plan” in place to assist clinicians in the event of a patient suicide. Such plans should help in dealing with stress from losing a patient and should provide guidance about how to handle any potential lawsuit.
For those worried that a patient’s suicide will shadow them through their career, Dr. Appelbaum said that it can happen, especially in cases involving a financial settlement against the clinician.
Such cases must be reported to the national practitioner data bank, where they can be accessed by any licensing body in any state when physicians apply for a medical license.
In addition, Dr. Appelbaum pointed out that licensure, medical staff, and malpractice applications typically require disclosure of a history of successful or unsuccessful claims filed against a physician. Although that may be limited to the past 10 years, the requirement can go on indefinitely.
Beware how you share
Dr. Plakun noted that there is a sense of isolation for a clinician in cases of patient suicide and that physicians often turn inward. He added that, although it is important to talk with others, in institutions, this is best done in a “peer-review, protected space” – and perhaps with a lawyer present.
However, Dr. Appelbaum warned that sharing information, even in this type of setting, may not offer legal protection. Talking to others in order to get some emotional support is permitted once the statute of limitations for filing a claim has lapsed or if a claim has been closed.
Discussing a case of patient suicide with peers prior to that can have serious legal implications, he added. Colleagues can be called to testify in any resulting legal case and disclose what was said during such conversations.
“The typical advice that a risk manager, a claims manager, or an attorney would give to a clinician is, don’t talk to other people about it other than the lawyer or claims manager who’s dealing with the case,” he noted.
That said, there are three general exceptions to this rule. These include attorney-client privilege, any matters discussed with the physician’s own therapist, and, “depending on the state, there are varying protections for what’s considered ‘peer review.’ ”
For instance, when hospitals implement a formal review process after an event, what is said during discovery may be protected. However, not all states have such protection. That’s why it is important to understand what the law is in your particular state, said Dr. Appelbaum.
Support for psychiatrists
Kaz J. Nelson, MD, psychiatrist and associate professor at the University of Minnesota, Minneapolis, also works with high-risk populations, including those with acute suicidality and self-injury.
During a recent chat on patient suicide, Dr. Nelson tweeted: “Sadly in our field, suicide is not an IF but a WHEN. Don’t keep the inevitable shame and sadness to yourself.”
Dr. Nelson agreed with Dr. Black that it’s important to look into these occurrences as a quality improvement measure, but not as a way to assign blame. Preparing for potential patient loss “and having very solid, very supportive, very inclusive ‘postvention’ procedures” is critical, she noted. “When you don’t have these policies and procedures in place and have them very transparent, it creates a culture of silence around the issue.”
Dr. Plakun reiterated the importance of not staying silent. “We can’t simply surrender to the idea of not talking about patient suicide. We have to find a way to speak.”
A version of this story originally appeared on Medscape.com.
When Rodney Vivian, MD, a psychiatrist in Cincinnati, was sued for medical malpractice after a psychiatric inpatient died by suicide, he recalls being naive about the process and how difficult it would be. “I was thinking that truth and common sense would prevail. How stupid I was,” he said.
Although Dr. Vivian, who was at the time the medical director of a hospital psychiatric unit in Ohio, was found not liable in two appeals, the legal process dragged on for 6 years, creating an emotional roller coaster of sadness, fear, vulnerability, and anxiety.
“The lawsuit took a big chunk out of me, and there was a sense of unfairness. It was incredibly humiliating and destructive; and it did not make me a better person or psychiatrist,” Dr. Vivian said.
Dr. Vivian is just one of the many psychiatrists who have had their world turned upside down after a patient suicide. When such events occur, grief-stricken families often point the finger at the treating psychiatrist. Although lawsuits are rare in psychiatry, patient suicide can lead to a myriad of emotional, legal, and career consequences.
Tyler Black, MD, child and adolescent psychiatrist and assistant clinical professor at the University of British Columbia, Vancouver, likens patient suicide to “a nuclear bomb” but emphasizes the importance of not classifying such events as a medical error or assigning blame.
“Starting with the assumption that suicide is always avoidable is not evidence based,” Dr. Black said.
Although patient suicide can occur across medicine, the odds are alarmingly high in psychiatry.
“There’s at least a 50-50 chance that a psychiatrist is going to face the suicide of a patient,” said Eric Plakun, MD, medical director/CEO at the Austen Riggs Center, Stockbridge, Mass. a hospital-based facility that offers a continuum of psychiatric treatment. Quoting forensic psychiatrist Robert Simon, Dr. Plakun said: “There are two kinds of psychiatrists – those who have had a patient die by suicide, and those who will.”
Research from 2015 shows that, among specialists, psychiatrists are among the least likely to be sued. A 2007/2008 Physician Survey from the American Medical Association showed that 22.2% of psychiatrists had been sued for malpractice; the probability that they would face a claim each year was only 2.6%. However, failure to prevent suicide is one of the top reasons for lawsuits.
One report from 2008 suggests that 20%-68% of psychiatrists will lose a patient to suicide. A report cowritten by Dr. Plakun in 2005 notes that about one in six psychiatric interns and one in three psychiatric residents will experience a patient suicide some time during their training. The authors added that 50% of all psychiatrists will have a patient die by suicide during their career. That risk stays at about 50% for future patients even after a clinician experiences the death of a previous patient.
Although mental health professionals prevail in up to 80% of suicide-related malpractice cases, such events are still emotionally devastating for everyone involved.
When a patient dies by suicide, it is a huge event, he noted. “It fuels a lot of fear and a lot of guilt, worry, and sadness.”
Paul S. Appelbaum, MD, past president of the American Psychiatric Association and Dollard Professor of Psychiatry, Medicine, and Law at Columbia University, New York, noted that patient suicide will happen.
The problem with many administrators who talk about a target of “zero suicide” is that when suicide does occur, it can lead to the erroneous conclusion that someone is to blame, said Dr. Appelbaum, who is also director of the Center for Law, Ethics, and Psychiatry at Columbia University. “That’s not necessarily true and contributes to finger-pointing.”
Stopping the blame game
Dr. Black’s first experience as a psychiatry resident was arriving at the hospital and finding the body of a patient who had died by suicide by hanging. Although he did not know the patient, Dr. Black said he had a strong emotional response that was coupled with an intense and sometimes confusing reaction by the hospital administration, including what he called “nonsensical banning” of pencils on the ward.
Dr. Black is now the medical director of emergency psychiatry at BC Children’s Hospital in Vancouver and specializes in suicidology and emergency/crisis youth mental health care. He said during a recent live chat on Twitter that he does not predict suicide but instead “assesses risk,” meaning he examines potential risk factors in his patients.
“If systems and administrators (and consulting doctors) could recognize this, the ‘blame game’ would severely decrease. From the advocacy end, we have to stop seeing suicide as a ‘medical error,’ ” Dr. Black tweeted.
“There’s a strong administrative push, especially in the face of suicide, to dive into the [occurrence] as if it must be that an error was made,” he said in an interview.
To help counteract any potential finger-pointing, Dr. Black created a free-to-download patient risk assessment document called the Assessment of Suicide and Risk Inventory (ASARI) for use at every patient visit.
“ASARI was designed to walk an assessor through their thinking process such that they can put all of their thoughts down on one piece of paper. It makes it a better communication document, and it’s definitely better medicolegal documentation,” he said.
Dr. Appelbaum noted that, although having documentation is beneficial, “I don’t think that you necessarily need to separate actions that are ‘protective’ from actions that are intended to help a patient.”
However, he pointed out that, if a psychiatrist conforms to or exceeds the standard of care, including conducting appropriate suicide risk assessments, developing an appropriate treatment plan, and keeping comprehensive documentation, these measures “should provide an effective defense to claims of malpractice or negligence.”
‘Horrendous event’
Dr. Vivian said that, during his 40-year career in psychiatry, there have been about 12 “office patients” who died by suicide. However, nothing prepared him for the fallout from a lawsuit.
In 2010, a patient who had overdosed was transferred to the psychiatric unit of Mercy Health–Clermont (Ohio) Hospital, where Dr. Vivian was the admitting physician. Although the hospital staff was ordered to check on her every 15 minutes, her husband found her unconscious from a hanging attempt when he came to visit the next evening. After she was transferred to the ICU, she was taken off life support and died a few days later.
“It was a horrendous event,” Dr. Vivian said.
The family sued the hospital, and the matter was settled out of court without Dr. Vivian’s knowledge. The family also filed a separate lawsuit against Dr. Vivian, which went to trial 3 years later.
“My insurance company’s claims person was very supportive and wanted me to not settle. She agreed that I didn’t do anything wrong and that I needed to face this,” he added.
In the first trial, a jury found Dr. Vivian not liable. Six months later, the plaintiff’s attorney filed an appeal. A year after the first trial, the court of appeals also came back with a new ruling in his favor and, in a subsequent appeal, the Ohio Supreme Court also ruled in his favor.
Dr. Vivian noted that there really are no winners in these situations. “Even though the jury ruled in my favor, there was never a sense of ‘success.’ I could never feel good about what happened.” He was told the insurance company spent more than $300,000 on his defense.
Although he no longer performs psychiatric inpatient admissions, Dr. Vivian continues to work in private practice and provides psychiatric consultation to patients at a local medical center.
“I consider my work as a blessing in my life, and I continue to learn from my patients,” he said.
‘Will I be sued?’
Dr. Appelbaum noted there is a difference between a malpractice claim that may be filed and a “payout” to plaintiffs because of a negotiated resolution of a case or an award that is made at trial.
Malpractice insurers may raise the rates of a physician who has been found at fault in one or more legal actions in which financial settlements have been paid out, he said.
The issue in any malpractice case is whether the psychiatrist met the standard of care, which is traditionally defined as “skill and learning that is ordinarily possessed and exercised by members of that profession in good standing.”
“No physician is expected to be the guarantor of a good outcome of a case. Sometimes things go wrong. Merely because there’s a bad outcome, merely because a suicide has occurred, doesn’t mean that the psychiatrist was negligent,” Dr. Appelbaum said.
He believes all large centers should have a “clear-cut plan” in place to assist clinicians in the event of a patient suicide. Such plans should help in dealing with stress from losing a patient and should provide guidance about how to handle any potential lawsuit.
For those worried that a patient’s suicide will shadow them through their career, Dr. Appelbaum said that it can happen, especially in cases involving a financial settlement against the clinician.
Such cases must be reported to the national practitioner data bank, where they can be accessed by any licensing body in any state when physicians apply for a medical license.
In addition, Dr. Appelbaum pointed out that licensure, medical staff, and malpractice applications typically require disclosure of a history of successful or unsuccessful claims filed against a physician. Although that may be limited to the past 10 years, the requirement can go on indefinitely.
Beware how you share
Dr. Plakun noted that there is a sense of isolation for a clinician in cases of patient suicide and that physicians often turn inward. He added that, although it is important to talk with others, in institutions, this is best done in a “peer-review, protected space” – and perhaps with a lawyer present.
However, Dr. Appelbaum warned that sharing information, even in this type of setting, may not offer legal protection. Talking to others in order to get some emotional support is permitted once the statute of limitations for filing a claim has lapsed or if a claim has been closed.
Discussing a case of patient suicide with peers prior to that can have serious legal implications, he added. Colleagues can be called to testify in any resulting legal case and disclose what was said during such conversations.
“The typical advice that a risk manager, a claims manager, or an attorney would give to a clinician is, don’t talk to other people about it other than the lawyer or claims manager who’s dealing with the case,” he noted.
That said, there are three general exceptions to this rule. These include attorney-client privilege, any matters discussed with the physician’s own therapist, and, “depending on the state, there are varying protections for what’s considered ‘peer review.’ ”
For instance, when hospitals implement a formal review process after an event, what is said during discovery may be protected. However, not all states have such protection. That’s why it is important to understand what the law is in your particular state, said Dr. Appelbaum.
Support for psychiatrists
Kaz J. Nelson, MD, psychiatrist and associate professor at the University of Minnesota, Minneapolis, also works with high-risk populations, including those with acute suicidality and self-injury.
During a recent chat on patient suicide, Dr. Nelson tweeted: “Sadly in our field, suicide is not an IF but a WHEN. Don’t keep the inevitable shame and sadness to yourself.”
Dr. Nelson agreed with Dr. Black that it’s important to look into these occurrences as a quality improvement measure, but not as a way to assign blame. Preparing for potential patient loss “and having very solid, very supportive, very inclusive ‘postvention’ procedures” is critical, she noted. “When you don’t have these policies and procedures in place and have them very transparent, it creates a culture of silence around the issue.”
Dr. Plakun reiterated the importance of not staying silent. “We can’t simply surrender to the idea of not talking about patient suicide. We have to find a way to speak.”
A version of this story originally appeared on Medscape.com.
Cancer researchers cross over to COVID-19 clinical trials
When the first reports emerged of “cytokine storm” in patients with severe COVID-19, all eyes turned to cancer research. Oncologists have years of experience reigning in “cytokine release syndrome” (CRS) in patients treated with chimeric antigen receptor (CAR) therapies for advanced blood cancers.
There was hope that drugs used to quell CRS in patients with cancer would be effective in patients with severe COVID. But the promise of a quick fix with oncology medications has yet to be fully realized.
Part of the problem is that the two conditions, while analogous, are “not the same,” said Nirali Shah, MD, head of the hematologic malignancies section in the pediatric oncology branch at the National Cancer Institute.
“You have to understand the underlying pathophysiology, what triggers the inflammation,” Dr. Shah said.
CAR T–related CRS is caused by activated T cells in patients with cancer who often do not have an infection, she explained. In contrast, cytokine storm in COVID-19 is triggered by a viral pathogen that can drive “out of control” inflammation. These differences may explain why drugs work in the first instance, but not in the second, she added. Drugs that inhibit interleukin-6 (such as tocilizumab, sarilumab, and siltuximab) are used with great success to dampen down the CRS in patients receiving CAR therapy for blood cancers. And although trials of these agents in patients with COVID are still ongoing, initial results are disappointing.
The first global, phase 3 randomized controlled trial of tocilizumab in severe COVID-19 failed to meet its primary endpoint of improved clinical status, and it did not meet its secondary endpoint of improved mortality at week 4.
In its recent recommendations, the National Institutes of Health noted a lack of data to support the efficacy of IL-6 inhibitors in COVID-19, and recommended against their use, except as part of a clinical trial.
Trimming the tree vs. cutting it down
As researchers have begun to decode the immune process underlying severe COVID-19, they have turned to other cancer drugs to tame cytokine storm.
Louis Staudt, MD, PhD, and Wyndham Wilson, MD, PhD, both at the NCI, think that cytokine storm in COVID-19 is driven by macrophages, which trigger release of multiple cytokines.
For years, the pair have been studying lymphoid tumors. Dr. Staudt is chief of the lymphoid malignancies branch at the NCI, and Wilson is head of the lymphoma therapeutics section. In past work, Dr. Staudt discovered that inhibiting an enzyme called bruton tyrosine kinase (BTK) dampens macrophage function.
When the pandemic began, Dr. Staudt and Dr. Wilson realized that singling out just one cytokine like IL-6 may not be enough. They thought that a more effective approach may be to target macrophages with a BTK inhibitor called acalabrutinib (Calquence), which would inhibit multiple cytokines at the same time.
Dr. Staudt likens the immune response to a tree, with the macrophages composing the tree trunk and the limbs made up of individual cytokines.
“Targeting macrophages is getting at the trunk of the problem,” he said. “You’re only cutting off the limbs with tocilizumab.”
In just 3 days, Dr. Staudt and Dr. Wilson went from concept to approval to launching a prospective, observational study. The study took place at five centers in the US, and included 19 patients hospitalized with COVID-19; the results were published in Science Immunology. Over a treatment course of 14 days, the majority of patients treated off-label with acalabrutinib improved, some within 24 hours. Eight of 11 patients on supplemental oxygen were discharged on room air. Four of eight patients on ventilators were extubated, with two of these discharged on room air. Two patients on ventilators died. No discernible toxicity was noted.
Analyses also showed increased BTK activity and elevated IL-6 levels in monocytes – precursors of macrophages – in patients with severe COVID-19, compared with healthy volunteers.
“We showed that the target of acalabrutinib was active in the immune cells of patients with severe COVID-19,” Dr. Staudt said. “So we have the target. We have the drug to hit the target. And we have an apparent clinical benefit.”
Those three things were compelling enough to launch the CALAVI phase 2 trial, an open-label, randomized, controlled trial, sponsored by AstraZeneca and the NCI, that is being conducted in the United States and internationally. It is testing acalabrutinib with best supportive care versus BSC alone in people hospitalized with COVID-19. The trial is scheduled to be completed on Nov. 26.
Preliminary insights from this trial are expected soon. “These are not insights that we will likely publish, but they are important insights that will lead to the launch of a definitive double-blind, randomized, phase 3 trial, which we hope to launch in the next month or so,” Dr. Wilson said.
Targeting inflammation and infection simultaneously
Other scientists are investigating inhibitors of Janus kinase (JAK), a family of enzymes that play a key role in orchestrating immune responses, particularly cytokines. Interest in JAK inhibition to control hyperinflammation in cancer goes back at least 15 years, and drugs that act as JAK inhibitors are already approved for use in the treatment of myelofibrosis (ruxolitinib [Jakafi], fedratinib [Inrebic]) and also for rheumatoid arthritis (upadacitinib [Rinvoq], baricitinib [Olumiant]).
“It wasn’t a huge leap for those of us with a lot of understanding of JAK inhibitors to propose taking them into the clinic to treat patients with COVID-19,” commented John Mascarenhas, MD, the leader of clinical investigation in the myeloproliferative disorders program at the Icahn School of Medicine at Mount Sinai, New York.
Dr. Mascarenhas is also principal investigator of the PRE-VENT trial, which is comparing the investigational JAK2 inhibitor pacritinib plus standard of care to standard of care alone in patients hospitalized with severe COVID-19, with and without cancer. The trial is sponsored by CTI BioPharma (manufacturer of pacritinib), and is taking place at 10 sites in the United States.
In a move that may raise eyebrows, PRE-VENT skipped phase 1 and 2 and went straight to phase 3. Pacritinib has yet to receive FDA approval and has mostly been studied in myelofibrosis, an intensely inflammatory disease.
The decision was based on trials of pacritinib in hematologic malignancies and also on results from a phase 2 study in China that found possible clinical benefit for the JAK 1/2 inhibitor ruxolitinib in 43 patients hospitalized with severe COVID-19, although results were not statistically significant, Dr. Mascarenhas explained.
Recent results from Lilly’s ACTT-2 study have provided further support for the role of JAK inhibitors in treating cytokine storm. ACTT-2 is a phase 3, double-blind, placebo-controlled, randomized, controlled trial sponsored by the NIH and NIAID comparing the JAK 1/2 inhibitor baricitinib plus the antiviral remdesivir with remdesivir alone in patients hospitalized with COVID-19. In September, Lilly announced that the trial met its primary endpoint of decreased time to recovery in patients who received baricitinib in combination with remdesivir.
But pacritinib’s mechanism of action may take things a step further. The drug selectively inhibits JAK2 and spares JAK1, which is important for antiviral activity in the immune system. Also, in vitro data suggests pacritinib may simultaneously reduce inflammation and fight off the virus by selectively inhibiting two additional enzymes and two other receptors.
“The rationale to me is very strong for using pacritinib,” Dr. Mascarenhas said. “I think this approach was bold but appropriate.”
The main safety concern with pacritinib could be bleeding, especially among patients on anticoagulants, Dr. Mascarenhas said. Because some patients with severe COVID-19 tend to develop blood clots, anticoagulation has become the standard of care at many institutions.
Because the trial is just beginning – only a minority of the total planned population of 358 patients has been enrolled – no interim results are available.
Right drug, wrong time?
IL-6 inhibition could still have a role to play in COVID-19, but the trick could be in the timing. Most of the trials so far have studied tocilizumab in patients with severe COVID-19, many of whom were already on ventilators. At that point, it may be too late to reverse the damage that has already taken place.
One of the main reasons tocilizumab works so well in CRS after CAR T therapy is that oncologists have learned how to use it early, often within 24 hours of fever onset. Oncologists use the American Society for Transplantation and Cellular Therapy consensus grading system, which helps them identify CRS when it is easier to control.
But applying the ASTCT grading system to COVID-19 is problematic. “Almost by definition, patients hospitalized with COVID-19 have low oxygen levels, which throws off the scale,” said Joshua Hill, MD, an infectious disease specialist at Fred Hutchinson Cancer Research Center in Seattle, who has research expertise in infectious complications after CAR T therapy.
“The key is to intervene earlier to prevent damage to the lungs and other end organs. We don’t have anything magical that will reverse that damage,” Dr. Hill said.
Results from the phase 3 trial EMPACTA trial (sponsored by Genentech) seem to bear this out. EMPACTA is evaluating use of tocilizumab in hospitalized patients with less severe COVID-19 who do not yet require mechanical ventilation. The trial is notable for being the first global phase 3 trial to demonstrate efficacy for tocilizumab vs placebo in hospitalized patients with COVID-19 pneumonia, and for including a high percentage of racial/ethnic minorities (85% of 389 participants), who have been hard hit by the pandemic and have historically been underrepresented in drug trials.
Last month, Roche announced that EMPACTA met its primary endpoint. Results showed that patients hospitalized with COVID-19 pneumonia who received tocilizumab plus standard of care were 44% less likely to go on mechanical ventilation or die, compared with those who received placebo plus standard of care (P = .0348), although there were no statistically significant differences in death by day 28 between tocilizumab and placebo (10.4% vs. 8.6%, P = .5146).
However, earlier administration of tocilizumab raises another issue. IL-6 and its pathway are important for clearing viral infections. Using tocilizumab in the context of an ongoing infection could raise safety issues.
Also, tocilizumab sticks around in the body for a relatively long time. In the treatment of rheumatoid arthritis, it is dosed once a month, and it carries a black box warning for reactivation of tuberculosis.
Whereas results from EMPACTA showed similar rates of infection associated with tocilizumab and placebo (10% vs. 11%), at least one other study has found increased rates of superinfection in patients with severe COVID-19 who received tocilizumab. Overall, though, the drug was associated with decreased risk of death in the latter study.
A phase 2 trial called COVIDOSE is tackling the safety issue. COVIDOSE is evaluating whether low-dose tocilizumab is effective in noncritical COVID-19 patients, with the idea that lower doses could be safer. Early results published as a preprint before peer review indicated that low-dose tocilizumab (ranging from 40 mg to 200 mg) was associated with clinical improvement in 32 noncritical patients hospitalized with COVID-19.
Five patients (15.6%) developed bacterial superinfections, and five (15.6%) died by 28-day follow-up, although there wasn’t a perfect “overlap” between these groups of patients. Bacterial superinfection was not the cause of death in all five patients who died, and not all patients who died developed bacterial superinfections, according to senior author Pankti Reid, MD, MPH, an assistant professor of medicine at the University of Chicago.
Results from COVIDOSE also showed that treatment with tocilizumab did not seem to affect the ability of patients to develop antibodies against COVID-19. The results set the stage for a larger randomized, controlled trial (still ongoing) to determine the optimal dose of tocilizumab.
Still, Dr. Hill urges caution.
Many of these immunomodulators have been used only in the context of a clinical trial, or only for patients with terminal cancer and no other treatment options. In patients with cancer, these drugs have been studied and have shown an “acceptable safety profile,” according to Dr. Shah.
But this is a different situation, and when it comes to repurposing them to relatively healthy patients with COVID-19, Dr. Hill emphasized the need for careful research.
“We’re always very concerned about giving drugs that suppress the immune response if people have active infections,” Dr. Hill said. “Often times we think it makes things worse, and it typically does.”
Dr. Mascarenhas reported institutional research funding from CTI Biopharma. Dr. Hill, Dr. Staudt, Dr. Wilson, and Dr. Shah disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
When the first reports emerged of “cytokine storm” in patients with severe COVID-19, all eyes turned to cancer research. Oncologists have years of experience reigning in “cytokine release syndrome” (CRS) in patients treated with chimeric antigen receptor (CAR) therapies for advanced blood cancers.
There was hope that drugs used to quell CRS in patients with cancer would be effective in patients with severe COVID. But the promise of a quick fix with oncology medications has yet to be fully realized.
Part of the problem is that the two conditions, while analogous, are “not the same,” said Nirali Shah, MD, head of the hematologic malignancies section in the pediatric oncology branch at the National Cancer Institute.
“You have to understand the underlying pathophysiology, what triggers the inflammation,” Dr. Shah said.
CAR T–related CRS is caused by activated T cells in patients with cancer who often do not have an infection, she explained. In contrast, cytokine storm in COVID-19 is triggered by a viral pathogen that can drive “out of control” inflammation. These differences may explain why drugs work in the first instance, but not in the second, she added. Drugs that inhibit interleukin-6 (such as tocilizumab, sarilumab, and siltuximab) are used with great success to dampen down the CRS in patients receiving CAR therapy for blood cancers. And although trials of these agents in patients with COVID are still ongoing, initial results are disappointing.
The first global, phase 3 randomized controlled trial of tocilizumab in severe COVID-19 failed to meet its primary endpoint of improved clinical status, and it did not meet its secondary endpoint of improved mortality at week 4.
In its recent recommendations, the National Institutes of Health noted a lack of data to support the efficacy of IL-6 inhibitors in COVID-19, and recommended against their use, except as part of a clinical trial.
Trimming the tree vs. cutting it down
As researchers have begun to decode the immune process underlying severe COVID-19, they have turned to other cancer drugs to tame cytokine storm.
Louis Staudt, MD, PhD, and Wyndham Wilson, MD, PhD, both at the NCI, think that cytokine storm in COVID-19 is driven by macrophages, which trigger release of multiple cytokines.
For years, the pair have been studying lymphoid tumors. Dr. Staudt is chief of the lymphoid malignancies branch at the NCI, and Wilson is head of the lymphoma therapeutics section. In past work, Dr. Staudt discovered that inhibiting an enzyme called bruton tyrosine kinase (BTK) dampens macrophage function.
When the pandemic began, Dr. Staudt and Dr. Wilson realized that singling out just one cytokine like IL-6 may not be enough. They thought that a more effective approach may be to target macrophages with a BTK inhibitor called acalabrutinib (Calquence), which would inhibit multiple cytokines at the same time.
Dr. Staudt likens the immune response to a tree, with the macrophages composing the tree trunk and the limbs made up of individual cytokines.
“Targeting macrophages is getting at the trunk of the problem,” he said. “You’re only cutting off the limbs with tocilizumab.”
In just 3 days, Dr. Staudt and Dr. Wilson went from concept to approval to launching a prospective, observational study. The study took place at five centers in the US, and included 19 patients hospitalized with COVID-19; the results were published in Science Immunology. Over a treatment course of 14 days, the majority of patients treated off-label with acalabrutinib improved, some within 24 hours. Eight of 11 patients on supplemental oxygen were discharged on room air. Four of eight patients on ventilators were extubated, with two of these discharged on room air. Two patients on ventilators died. No discernible toxicity was noted.
Analyses also showed increased BTK activity and elevated IL-6 levels in monocytes – precursors of macrophages – in patients with severe COVID-19, compared with healthy volunteers.
“We showed that the target of acalabrutinib was active in the immune cells of patients with severe COVID-19,” Dr. Staudt said. “So we have the target. We have the drug to hit the target. And we have an apparent clinical benefit.”
Those three things were compelling enough to launch the CALAVI phase 2 trial, an open-label, randomized, controlled trial, sponsored by AstraZeneca and the NCI, that is being conducted in the United States and internationally. It is testing acalabrutinib with best supportive care versus BSC alone in people hospitalized with COVID-19. The trial is scheduled to be completed on Nov. 26.
Preliminary insights from this trial are expected soon. “These are not insights that we will likely publish, but they are important insights that will lead to the launch of a definitive double-blind, randomized, phase 3 trial, which we hope to launch in the next month or so,” Dr. Wilson said.
Targeting inflammation and infection simultaneously
Other scientists are investigating inhibitors of Janus kinase (JAK), a family of enzymes that play a key role in orchestrating immune responses, particularly cytokines. Interest in JAK inhibition to control hyperinflammation in cancer goes back at least 15 years, and drugs that act as JAK inhibitors are already approved for use in the treatment of myelofibrosis (ruxolitinib [Jakafi], fedratinib [Inrebic]) and also for rheumatoid arthritis (upadacitinib [Rinvoq], baricitinib [Olumiant]).
“It wasn’t a huge leap for those of us with a lot of understanding of JAK inhibitors to propose taking them into the clinic to treat patients with COVID-19,” commented John Mascarenhas, MD, the leader of clinical investigation in the myeloproliferative disorders program at the Icahn School of Medicine at Mount Sinai, New York.
Dr. Mascarenhas is also principal investigator of the PRE-VENT trial, which is comparing the investigational JAK2 inhibitor pacritinib plus standard of care to standard of care alone in patients hospitalized with severe COVID-19, with and without cancer. The trial is sponsored by CTI BioPharma (manufacturer of pacritinib), and is taking place at 10 sites in the United States.
In a move that may raise eyebrows, PRE-VENT skipped phase 1 and 2 and went straight to phase 3. Pacritinib has yet to receive FDA approval and has mostly been studied in myelofibrosis, an intensely inflammatory disease.
The decision was based on trials of pacritinib in hematologic malignancies and also on results from a phase 2 study in China that found possible clinical benefit for the JAK 1/2 inhibitor ruxolitinib in 43 patients hospitalized with severe COVID-19, although results were not statistically significant, Dr. Mascarenhas explained.
Recent results from Lilly’s ACTT-2 study have provided further support for the role of JAK inhibitors in treating cytokine storm. ACTT-2 is a phase 3, double-blind, placebo-controlled, randomized, controlled trial sponsored by the NIH and NIAID comparing the JAK 1/2 inhibitor baricitinib plus the antiviral remdesivir with remdesivir alone in patients hospitalized with COVID-19. In September, Lilly announced that the trial met its primary endpoint of decreased time to recovery in patients who received baricitinib in combination with remdesivir.
But pacritinib’s mechanism of action may take things a step further. The drug selectively inhibits JAK2 and spares JAK1, which is important for antiviral activity in the immune system. Also, in vitro data suggests pacritinib may simultaneously reduce inflammation and fight off the virus by selectively inhibiting two additional enzymes and two other receptors.
“The rationale to me is very strong for using pacritinib,” Dr. Mascarenhas said. “I think this approach was bold but appropriate.”
The main safety concern with pacritinib could be bleeding, especially among patients on anticoagulants, Dr. Mascarenhas said. Because some patients with severe COVID-19 tend to develop blood clots, anticoagulation has become the standard of care at many institutions.
Because the trial is just beginning – only a minority of the total planned population of 358 patients has been enrolled – no interim results are available.
Right drug, wrong time?
IL-6 inhibition could still have a role to play in COVID-19, but the trick could be in the timing. Most of the trials so far have studied tocilizumab in patients with severe COVID-19, many of whom were already on ventilators. At that point, it may be too late to reverse the damage that has already taken place.
One of the main reasons tocilizumab works so well in CRS after CAR T therapy is that oncologists have learned how to use it early, often within 24 hours of fever onset. Oncologists use the American Society for Transplantation and Cellular Therapy consensus grading system, which helps them identify CRS when it is easier to control.
But applying the ASTCT grading system to COVID-19 is problematic. “Almost by definition, patients hospitalized with COVID-19 have low oxygen levels, which throws off the scale,” said Joshua Hill, MD, an infectious disease specialist at Fred Hutchinson Cancer Research Center in Seattle, who has research expertise in infectious complications after CAR T therapy.
“The key is to intervene earlier to prevent damage to the lungs and other end organs. We don’t have anything magical that will reverse that damage,” Dr. Hill said.
Results from the phase 3 trial EMPACTA trial (sponsored by Genentech) seem to bear this out. EMPACTA is evaluating use of tocilizumab in hospitalized patients with less severe COVID-19 who do not yet require mechanical ventilation. The trial is notable for being the first global phase 3 trial to demonstrate efficacy for tocilizumab vs placebo in hospitalized patients with COVID-19 pneumonia, and for including a high percentage of racial/ethnic minorities (85% of 389 participants), who have been hard hit by the pandemic and have historically been underrepresented in drug trials.
Last month, Roche announced that EMPACTA met its primary endpoint. Results showed that patients hospitalized with COVID-19 pneumonia who received tocilizumab plus standard of care were 44% less likely to go on mechanical ventilation or die, compared with those who received placebo plus standard of care (P = .0348), although there were no statistically significant differences in death by day 28 between tocilizumab and placebo (10.4% vs. 8.6%, P = .5146).
However, earlier administration of tocilizumab raises another issue. IL-6 and its pathway are important for clearing viral infections. Using tocilizumab in the context of an ongoing infection could raise safety issues.
Also, tocilizumab sticks around in the body for a relatively long time. In the treatment of rheumatoid arthritis, it is dosed once a month, and it carries a black box warning for reactivation of tuberculosis.
Whereas results from EMPACTA showed similar rates of infection associated with tocilizumab and placebo (10% vs. 11%), at least one other study has found increased rates of superinfection in patients with severe COVID-19 who received tocilizumab. Overall, though, the drug was associated with decreased risk of death in the latter study.
A phase 2 trial called COVIDOSE is tackling the safety issue. COVIDOSE is evaluating whether low-dose tocilizumab is effective in noncritical COVID-19 patients, with the idea that lower doses could be safer. Early results published as a preprint before peer review indicated that low-dose tocilizumab (ranging from 40 mg to 200 mg) was associated with clinical improvement in 32 noncritical patients hospitalized with COVID-19.
Five patients (15.6%) developed bacterial superinfections, and five (15.6%) died by 28-day follow-up, although there wasn’t a perfect “overlap” between these groups of patients. Bacterial superinfection was not the cause of death in all five patients who died, and not all patients who died developed bacterial superinfections, according to senior author Pankti Reid, MD, MPH, an assistant professor of medicine at the University of Chicago.
Results from COVIDOSE also showed that treatment with tocilizumab did not seem to affect the ability of patients to develop antibodies against COVID-19. The results set the stage for a larger randomized, controlled trial (still ongoing) to determine the optimal dose of tocilizumab.
Still, Dr. Hill urges caution.
Many of these immunomodulators have been used only in the context of a clinical trial, or only for patients with terminal cancer and no other treatment options. In patients with cancer, these drugs have been studied and have shown an “acceptable safety profile,” according to Dr. Shah.
But this is a different situation, and when it comes to repurposing them to relatively healthy patients with COVID-19, Dr. Hill emphasized the need for careful research.
“We’re always very concerned about giving drugs that suppress the immune response if people have active infections,” Dr. Hill said. “Often times we think it makes things worse, and it typically does.”
Dr. Mascarenhas reported institutional research funding from CTI Biopharma. Dr. Hill, Dr. Staudt, Dr. Wilson, and Dr. Shah disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
When the first reports emerged of “cytokine storm” in patients with severe COVID-19, all eyes turned to cancer research. Oncologists have years of experience reigning in “cytokine release syndrome” (CRS) in patients treated with chimeric antigen receptor (CAR) therapies for advanced blood cancers.
There was hope that drugs used to quell CRS in patients with cancer would be effective in patients with severe COVID. But the promise of a quick fix with oncology medications has yet to be fully realized.
Part of the problem is that the two conditions, while analogous, are “not the same,” said Nirali Shah, MD, head of the hematologic malignancies section in the pediatric oncology branch at the National Cancer Institute.
“You have to understand the underlying pathophysiology, what triggers the inflammation,” Dr. Shah said.
CAR T–related CRS is caused by activated T cells in patients with cancer who often do not have an infection, she explained. In contrast, cytokine storm in COVID-19 is triggered by a viral pathogen that can drive “out of control” inflammation. These differences may explain why drugs work in the first instance, but not in the second, she added. Drugs that inhibit interleukin-6 (such as tocilizumab, sarilumab, and siltuximab) are used with great success to dampen down the CRS in patients receiving CAR therapy for blood cancers. And although trials of these agents in patients with COVID are still ongoing, initial results are disappointing.
The first global, phase 3 randomized controlled trial of tocilizumab in severe COVID-19 failed to meet its primary endpoint of improved clinical status, and it did not meet its secondary endpoint of improved mortality at week 4.
In its recent recommendations, the National Institutes of Health noted a lack of data to support the efficacy of IL-6 inhibitors in COVID-19, and recommended against their use, except as part of a clinical trial.
Trimming the tree vs. cutting it down
As researchers have begun to decode the immune process underlying severe COVID-19, they have turned to other cancer drugs to tame cytokine storm.
Louis Staudt, MD, PhD, and Wyndham Wilson, MD, PhD, both at the NCI, think that cytokine storm in COVID-19 is driven by macrophages, which trigger release of multiple cytokines.
For years, the pair have been studying lymphoid tumors. Dr. Staudt is chief of the lymphoid malignancies branch at the NCI, and Wilson is head of the lymphoma therapeutics section. In past work, Dr. Staudt discovered that inhibiting an enzyme called bruton tyrosine kinase (BTK) dampens macrophage function.
When the pandemic began, Dr. Staudt and Dr. Wilson realized that singling out just one cytokine like IL-6 may not be enough. They thought that a more effective approach may be to target macrophages with a BTK inhibitor called acalabrutinib (Calquence), which would inhibit multiple cytokines at the same time.
Dr. Staudt likens the immune response to a tree, with the macrophages composing the tree trunk and the limbs made up of individual cytokines.
“Targeting macrophages is getting at the trunk of the problem,” he said. “You’re only cutting off the limbs with tocilizumab.”
In just 3 days, Dr. Staudt and Dr. Wilson went from concept to approval to launching a prospective, observational study. The study took place at five centers in the US, and included 19 patients hospitalized with COVID-19; the results were published in Science Immunology. Over a treatment course of 14 days, the majority of patients treated off-label with acalabrutinib improved, some within 24 hours. Eight of 11 patients on supplemental oxygen were discharged on room air. Four of eight patients on ventilators were extubated, with two of these discharged on room air. Two patients on ventilators died. No discernible toxicity was noted.
Analyses also showed increased BTK activity and elevated IL-6 levels in monocytes – precursors of macrophages – in patients with severe COVID-19, compared with healthy volunteers.
“We showed that the target of acalabrutinib was active in the immune cells of patients with severe COVID-19,” Dr. Staudt said. “So we have the target. We have the drug to hit the target. And we have an apparent clinical benefit.”
Those three things were compelling enough to launch the CALAVI phase 2 trial, an open-label, randomized, controlled trial, sponsored by AstraZeneca and the NCI, that is being conducted in the United States and internationally. It is testing acalabrutinib with best supportive care versus BSC alone in people hospitalized with COVID-19. The trial is scheduled to be completed on Nov. 26.
Preliminary insights from this trial are expected soon. “These are not insights that we will likely publish, but they are important insights that will lead to the launch of a definitive double-blind, randomized, phase 3 trial, which we hope to launch in the next month or so,” Dr. Wilson said.
Targeting inflammation and infection simultaneously
Other scientists are investigating inhibitors of Janus kinase (JAK), a family of enzymes that play a key role in orchestrating immune responses, particularly cytokines. Interest in JAK inhibition to control hyperinflammation in cancer goes back at least 15 years, and drugs that act as JAK inhibitors are already approved for use in the treatment of myelofibrosis (ruxolitinib [Jakafi], fedratinib [Inrebic]) and also for rheumatoid arthritis (upadacitinib [Rinvoq], baricitinib [Olumiant]).
“It wasn’t a huge leap for those of us with a lot of understanding of JAK inhibitors to propose taking them into the clinic to treat patients with COVID-19,” commented John Mascarenhas, MD, the leader of clinical investigation in the myeloproliferative disorders program at the Icahn School of Medicine at Mount Sinai, New York.
Dr. Mascarenhas is also principal investigator of the PRE-VENT trial, which is comparing the investigational JAK2 inhibitor pacritinib plus standard of care to standard of care alone in patients hospitalized with severe COVID-19, with and without cancer. The trial is sponsored by CTI BioPharma (manufacturer of pacritinib), and is taking place at 10 sites in the United States.
In a move that may raise eyebrows, PRE-VENT skipped phase 1 and 2 and went straight to phase 3. Pacritinib has yet to receive FDA approval and has mostly been studied in myelofibrosis, an intensely inflammatory disease.
The decision was based on trials of pacritinib in hematologic malignancies and also on results from a phase 2 study in China that found possible clinical benefit for the JAK 1/2 inhibitor ruxolitinib in 43 patients hospitalized with severe COVID-19, although results were not statistically significant, Dr. Mascarenhas explained.
Recent results from Lilly’s ACTT-2 study have provided further support for the role of JAK inhibitors in treating cytokine storm. ACTT-2 is a phase 3, double-blind, placebo-controlled, randomized, controlled trial sponsored by the NIH and NIAID comparing the JAK 1/2 inhibitor baricitinib plus the antiviral remdesivir with remdesivir alone in patients hospitalized with COVID-19. In September, Lilly announced that the trial met its primary endpoint of decreased time to recovery in patients who received baricitinib in combination with remdesivir.
But pacritinib’s mechanism of action may take things a step further. The drug selectively inhibits JAK2 and spares JAK1, which is important for antiviral activity in the immune system. Also, in vitro data suggests pacritinib may simultaneously reduce inflammation and fight off the virus by selectively inhibiting two additional enzymes and two other receptors.
“The rationale to me is very strong for using pacritinib,” Dr. Mascarenhas said. “I think this approach was bold but appropriate.”
The main safety concern with pacritinib could be bleeding, especially among patients on anticoagulants, Dr. Mascarenhas said. Because some patients with severe COVID-19 tend to develop blood clots, anticoagulation has become the standard of care at many institutions.
Because the trial is just beginning – only a minority of the total planned population of 358 patients has been enrolled – no interim results are available.
Right drug, wrong time?
IL-6 inhibition could still have a role to play in COVID-19, but the trick could be in the timing. Most of the trials so far have studied tocilizumab in patients with severe COVID-19, many of whom were already on ventilators. At that point, it may be too late to reverse the damage that has already taken place.
One of the main reasons tocilizumab works so well in CRS after CAR T therapy is that oncologists have learned how to use it early, often within 24 hours of fever onset. Oncologists use the American Society for Transplantation and Cellular Therapy consensus grading system, which helps them identify CRS when it is easier to control.
But applying the ASTCT grading system to COVID-19 is problematic. “Almost by definition, patients hospitalized with COVID-19 have low oxygen levels, which throws off the scale,” said Joshua Hill, MD, an infectious disease specialist at Fred Hutchinson Cancer Research Center in Seattle, who has research expertise in infectious complications after CAR T therapy.
“The key is to intervene earlier to prevent damage to the lungs and other end organs. We don’t have anything magical that will reverse that damage,” Dr. Hill said.
Results from the phase 3 trial EMPACTA trial (sponsored by Genentech) seem to bear this out. EMPACTA is evaluating use of tocilizumab in hospitalized patients with less severe COVID-19 who do not yet require mechanical ventilation. The trial is notable for being the first global phase 3 trial to demonstrate efficacy for tocilizumab vs placebo in hospitalized patients with COVID-19 pneumonia, and for including a high percentage of racial/ethnic minorities (85% of 389 participants), who have been hard hit by the pandemic and have historically been underrepresented in drug trials.
Last month, Roche announced that EMPACTA met its primary endpoint. Results showed that patients hospitalized with COVID-19 pneumonia who received tocilizumab plus standard of care were 44% less likely to go on mechanical ventilation or die, compared with those who received placebo plus standard of care (P = .0348), although there were no statistically significant differences in death by day 28 between tocilizumab and placebo (10.4% vs. 8.6%, P = .5146).
However, earlier administration of tocilizumab raises another issue. IL-6 and its pathway are important for clearing viral infections. Using tocilizumab in the context of an ongoing infection could raise safety issues.
Also, tocilizumab sticks around in the body for a relatively long time. In the treatment of rheumatoid arthritis, it is dosed once a month, and it carries a black box warning for reactivation of tuberculosis.
Whereas results from EMPACTA showed similar rates of infection associated with tocilizumab and placebo (10% vs. 11%), at least one other study has found increased rates of superinfection in patients with severe COVID-19 who received tocilizumab. Overall, though, the drug was associated with decreased risk of death in the latter study.
A phase 2 trial called COVIDOSE is tackling the safety issue. COVIDOSE is evaluating whether low-dose tocilizumab is effective in noncritical COVID-19 patients, with the idea that lower doses could be safer. Early results published as a preprint before peer review indicated that low-dose tocilizumab (ranging from 40 mg to 200 mg) was associated with clinical improvement in 32 noncritical patients hospitalized with COVID-19.
Five patients (15.6%) developed bacterial superinfections, and five (15.6%) died by 28-day follow-up, although there wasn’t a perfect “overlap” between these groups of patients. Bacterial superinfection was not the cause of death in all five patients who died, and not all patients who died developed bacterial superinfections, according to senior author Pankti Reid, MD, MPH, an assistant professor of medicine at the University of Chicago.
Results from COVIDOSE also showed that treatment with tocilizumab did not seem to affect the ability of patients to develop antibodies against COVID-19. The results set the stage for a larger randomized, controlled trial (still ongoing) to determine the optimal dose of tocilizumab.
Still, Dr. Hill urges caution.
Many of these immunomodulators have been used only in the context of a clinical trial, or only for patients with terminal cancer and no other treatment options. In patients with cancer, these drugs have been studied and have shown an “acceptable safety profile,” according to Dr. Shah.
But this is a different situation, and when it comes to repurposing them to relatively healthy patients with COVID-19, Dr. Hill emphasized the need for careful research.
“We’re always very concerned about giving drugs that suppress the immune response if people have active infections,” Dr. Hill said. “Often times we think it makes things worse, and it typically does.”
Dr. Mascarenhas reported institutional research funding from CTI Biopharma. Dr. Hill, Dr. Staudt, Dr. Wilson, and Dr. Shah disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Sleepless nights, hair loss, and cracked teeth: Pandemic stress takes its toll
In late March, shortly after New York state closed nonessential businesses and asked people to stay home, Ashley Laderer began waking each morning with a throbbing headache.
“The pressure was so intense it felt like my head was going to explode,” recalled the 27-year-old freelance writer from Long Island.
She tried spending less time on the computer and taking over-the-counter pain medication, but the pounding kept breaking through – a constant drumbeat to accompany her equally incessant worries about COVID-19.
“Every day I lived in fear that I was going to get it and I was going to infect my whole family,” she said.
After a month and a half, Ms. Laderer decided to visit a neurologist, who ordered an MRI. But the doctor found no physical cause. The scan was clear.
Then he asked: “Are you under a lot of stress?”
excruciating headaches, episodes of hair loss, upset stomach for weeks on end, sudden outbreaks of shingles, and flare-ups of autoimmune disorders. The disparate symptoms, often in otherwise-healthy individuals, have puzzled doctors and patients alike, sometimes resulting in a series of visits to specialists with few answers. But it turns out there’s a common thread among many of these conditions, one that has been months in the making: chronic stress.
Although people often underestimate the influence of the mind on the body, a growing catalog of research shows that high levels of stress over an extended time can drastically alter physical function and affect nearly every organ system.
Now, at least 8 months into the pandemic, alongside a divisive election cycle and racial unrest, those effects are showing up in a variety of symptoms.
“The mental health component of COVID is starting to come like a tsunami,” said Jennifer Love, MD, a California-based psychiatrist and coauthor of an upcoming book on how to heal from chronic stress.
Nationwide, surveys have found increasing rates of depression, anxiety and suicidal thoughts during the pandemic. But many medical experts said it’s too soon to measure the related physical symptoms, since they generally appear months after the stress begins.
Still, some early research, such as a small Chinese study and an online survey of more than 500 people in Turkey, points to an uptick.
In the United States, data from FAIR Health, a nonprofit database that provides cost information to the health industry and consumers, showed slight to moderate increases in the percentage of medical claims related to conditions triggered or exacerbated by stress, like multiple sclerosis and shingles. The portion of claims for the autoimmune disease lupus, for example, showed one of the biggest increases – 12% this year – compared with the same period last year (January to August).
Express Scripts, a major pharmacy benefit manager, reported that prescriptions for anti-insomnia medications increased 15% early in the pandemic.
Perhaps the strongest indicator comes from doctors reporting a growing number of patients with physical symptoms for which they can’t determine a cause.
Shilpi Khetarpal, MD, a dermatologist at the Cleveland Clinic, used to see about five patients a week with stress-related hair loss. Since mid-June, that number has jumped to 20 or 25. Mostly women, ages 20-80, are reporting hair coming out in fistfuls, Dr. Khetarpal said.
In Houston, at least a dozen patients have told fertility specialist Rashmi Kudesia, MD, they’re having irregular menstrual cycles, changes in cervical discharge and breast tenderness, despite normal hormone levels.
Stress is also the culprit dentists are pointing to for the rapid increase in patients with teeth grinding, teeth fractures, and temporomandibular joint dysfunction.
“We, as humans, like to have the idea that we are in control of our minds and that stress isn’t a big deal,” Dr. Love said. “But it’s simply not true.”
How mental stress becomes physical
Stress causes physical changes in the body that can affect nearly every organ system.
Although symptoms of chronic stress are often dismissed as being in one’s head, the pain is very real, said Kate Harkness, PhD, a professor of psychology and psychiatry at Queen’s University, Kingston, Ont.
When the body feels unsafe – whether it’s a physical threat of attack or a psychological fear of losing a job or catching a disease – the brain signals adrenal glands to pump stress hormones. Adrenaline and cortisol flood the body, activating the fight-or-flight response. They also disrupt bodily functions that aren’t necessary for immediate survival, like digestion and reproduction.
When the danger is over, the hormones return to normal levels. But during times of chronic stress, like a pandemic, the body keeps pumping out stress hormones until it tires itself out. This leads to increased inflammation throughout the body and brain, and a poorly functioning immune system.
Studies link chronic stress to heart disease, muscle tension, gastrointestinal issues and even physical shrinking of the hippocampus, an area of the brain associated with memory and learning. As the immune system acts up, some people can even develop new allergic reactions, Dr. Harkness said.
The good news is that many of these symptoms are reversible. But it’s important to recognize them early, especially when it comes to the brain, said Barbara Sahakian, FBA, FMedSci, a professor of clinical neuropsychology at the University of Cambridge (England).
“The brain is plastic, so we can to some extent modify it,” Dr. Sahakian said. “But we don’t know if there’s a cliff beyond which you can’t reverse a change. So the sooner you catch something, the better.”
The day-to-day impact
In some ways, mental health awareness has increased during the pandemic. TV shows are flush with ads for therapy and meditation apps, like Talkspace and Calm, and companies are announcing mental health days off for staff. But those spurts of attention fail to reveal the full impact of poor mental health on people’s daily lives.
For Alex Kostka, pandemic-related stress has brought on mood swings, nightmares, and jaw pain.
He’d been working at a Whole Foods coffee bar in New York City for only about a month before the pandemic hit, suddenly anointing him an essential worker. As deaths in the city soared, Mr. Kostka continued riding the subway to work, interacting with coworkers in the store and working longer hours for just a $2-per-hour wage increase. (Months later, he’d get a $500 bonus.) It left the 28-year-old feeling constantly unsafe and helpless.
“It was hard not to break down on the subway the minute I got on it,” Mr. Kostka said.
Soon he began waking in the middle of the night with pain from clenching his jaw so tightly. Often his teeth grinding and chomping were loud enough to wake his girlfriend.
Mr. Kostka tried Talkspace, but found texting about his troubles felt impersonal. By the end of the summer, he decided to start using the seven free counseling sessions offered by his employer. That’s helped, he said. But as the sessions run out, he worries the symptoms might return if he’s unable to find a new therapist covered by his insurance.
“Eventually, I will be able to leave this behind me, but it will take time,” Mr. Kostka said. “I’m still very much a work in progress.”
How to mitigate chronic stress
When it comes to chronic stress, seeing a doctor for stomach pain, headaches, or skin rashes may address those physical symptoms. But the root cause is mental, medical experts said.
That means the solution will often involve stress-management techniques. And there’s plenty we can do to feel better:
- Exercise. Even low- to moderate-intensity physical activity can help counteract stress-induced inflammation in the body. It can also increase neuronal connections in the brain.
- Meditation and mindfulness. Research shows this can lead to positive, structural, and functional changes in the brain.
- Fostering social connections. Talking to family and friends, even virtually, or staring into a pet’s eyes can release a hormone that may counteract inflammation.
- Learning something new. Whether it’s a formal class or taking up a casual hobby, learning supports brain plasticity, the ability to change and adapt as a result of experience, which can be protective against depression and other mental illness.
“We shouldn’t think of this stressful situation as a negative sentence for the brain,” said Dr. Harkness. “Because stress changes the brain, that means positive stuff can change the brain, too. And there is plenty we can do to help ourselves feel better in the face of adversity.”
KHN (Kaiser Health News) is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.
In late March, shortly after New York state closed nonessential businesses and asked people to stay home, Ashley Laderer began waking each morning with a throbbing headache.
“The pressure was so intense it felt like my head was going to explode,” recalled the 27-year-old freelance writer from Long Island.
She tried spending less time on the computer and taking over-the-counter pain medication, but the pounding kept breaking through – a constant drumbeat to accompany her equally incessant worries about COVID-19.
“Every day I lived in fear that I was going to get it and I was going to infect my whole family,” she said.
After a month and a half, Ms. Laderer decided to visit a neurologist, who ordered an MRI. But the doctor found no physical cause. The scan was clear.
Then he asked: “Are you under a lot of stress?”
excruciating headaches, episodes of hair loss, upset stomach for weeks on end, sudden outbreaks of shingles, and flare-ups of autoimmune disorders. The disparate symptoms, often in otherwise-healthy individuals, have puzzled doctors and patients alike, sometimes resulting in a series of visits to specialists with few answers. But it turns out there’s a common thread among many of these conditions, one that has been months in the making: chronic stress.
Although people often underestimate the influence of the mind on the body, a growing catalog of research shows that high levels of stress over an extended time can drastically alter physical function and affect nearly every organ system.
Now, at least 8 months into the pandemic, alongside a divisive election cycle and racial unrest, those effects are showing up in a variety of symptoms.
“The mental health component of COVID is starting to come like a tsunami,” said Jennifer Love, MD, a California-based psychiatrist and coauthor of an upcoming book on how to heal from chronic stress.
Nationwide, surveys have found increasing rates of depression, anxiety and suicidal thoughts during the pandemic. But many medical experts said it’s too soon to measure the related physical symptoms, since they generally appear months after the stress begins.
Still, some early research, such as a small Chinese study and an online survey of more than 500 people in Turkey, points to an uptick.
In the United States, data from FAIR Health, a nonprofit database that provides cost information to the health industry and consumers, showed slight to moderate increases in the percentage of medical claims related to conditions triggered or exacerbated by stress, like multiple sclerosis and shingles. The portion of claims for the autoimmune disease lupus, for example, showed one of the biggest increases – 12% this year – compared with the same period last year (January to August).
Express Scripts, a major pharmacy benefit manager, reported that prescriptions for anti-insomnia medications increased 15% early in the pandemic.
Perhaps the strongest indicator comes from doctors reporting a growing number of patients with physical symptoms for which they can’t determine a cause.
Shilpi Khetarpal, MD, a dermatologist at the Cleveland Clinic, used to see about five patients a week with stress-related hair loss. Since mid-June, that number has jumped to 20 or 25. Mostly women, ages 20-80, are reporting hair coming out in fistfuls, Dr. Khetarpal said.
In Houston, at least a dozen patients have told fertility specialist Rashmi Kudesia, MD, they’re having irregular menstrual cycles, changes in cervical discharge and breast tenderness, despite normal hormone levels.
Stress is also the culprit dentists are pointing to for the rapid increase in patients with teeth grinding, teeth fractures, and temporomandibular joint dysfunction.
“We, as humans, like to have the idea that we are in control of our minds and that stress isn’t a big deal,” Dr. Love said. “But it’s simply not true.”
How mental stress becomes physical
Stress causes physical changes in the body that can affect nearly every organ system.
Although symptoms of chronic stress are often dismissed as being in one’s head, the pain is very real, said Kate Harkness, PhD, a professor of psychology and psychiatry at Queen’s University, Kingston, Ont.
When the body feels unsafe – whether it’s a physical threat of attack or a psychological fear of losing a job or catching a disease – the brain signals adrenal glands to pump stress hormones. Adrenaline and cortisol flood the body, activating the fight-or-flight response. They also disrupt bodily functions that aren’t necessary for immediate survival, like digestion and reproduction.
When the danger is over, the hormones return to normal levels. But during times of chronic stress, like a pandemic, the body keeps pumping out stress hormones until it tires itself out. This leads to increased inflammation throughout the body and brain, and a poorly functioning immune system.
Studies link chronic stress to heart disease, muscle tension, gastrointestinal issues and even physical shrinking of the hippocampus, an area of the brain associated with memory and learning. As the immune system acts up, some people can even develop new allergic reactions, Dr. Harkness said.
The good news is that many of these symptoms are reversible. But it’s important to recognize them early, especially when it comes to the brain, said Barbara Sahakian, FBA, FMedSci, a professor of clinical neuropsychology at the University of Cambridge (England).
“The brain is plastic, so we can to some extent modify it,” Dr. Sahakian said. “But we don’t know if there’s a cliff beyond which you can’t reverse a change. So the sooner you catch something, the better.”
The day-to-day impact
In some ways, mental health awareness has increased during the pandemic. TV shows are flush with ads for therapy and meditation apps, like Talkspace and Calm, and companies are announcing mental health days off for staff. But those spurts of attention fail to reveal the full impact of poor mental health on people’s daily lives.
For Alex Kostka, pandemic-related stress has brought on mood swings, nightmares, and jaw pain.
He’d been working at a Whole Foods coffee bar in New York City for only about a month before the pandemic hit, suddenly anointing him an essential worker. As deaths in the city soared, Mr. Kostka continued riding the subway to work, interacting with coworkers in the store and working longer hours for just a $2-per-hour wage increase. (Months later, he’d get a $500 bonus.) It left the 28-year-old feeling constantly unsafe and helpless.
“It was hard not to break down on the subway the minute I got on it,” Mr. Kostka said.
Soon he began waking in the middle of the night with pain from clenching his jaw so tightly. Often his teeth grinding and chomping were loud enough to wake his girlfriend.
Mr. Kostka tried Talkspace, but found texting about his troubles felt impersonal. By the end of the summer, he decided to start using the seven free counseling sessions offered by his employer. That’s helped, he said. But as the sessions run out, he worries the symptoms might return if he’s unable to find a new therapist covered by his insurance.
“Eventually, I will be able to leave this behind me, but it will take time,” Mr. Kostka said. “I’m still very much a work in progress.”
How to mitigate chronic stress
When it comes to chronic stress, seeing a doctor for stomach pain, headaches, or skin rashes may address those physical symptoms. But the root cause is mental, medical experts said.
That means the solution will often involve stress-management techniques. And there’s plenty we can do to feel better:
- Exercise. Even low- to moderate-intensity physical activity can help counteract stress-induced inflammation in the body. It can also increase neuronal connections in the brain.
- Meditation and mindfulness. Research shows this can lead to positive, structural, and functional changes in the brain.
- Fostering social connections. Talking to family and friends, even virtually, or staring into a pet’s eyes can release a hormone that may counteract inflammation.
- Learning something new. Whether it’s a formal class or taking up a casual hobby, learning supports brain plasticity, the ability to change and adapt as a result of experience, which can be protective against depression and other mental illness.
“We shouldn’t think of this stressful situation as a negative sentence for the brain,” said Dr. Harkness. “Because stress changes the brain, that means positive stuff can change the brain, too. And there is plenty we can do to help ourselves feel better in the face of adversity.”
KHN (Kaiser Health News) is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.
In late March, shortly after New York state closed nonessential businesses and asked people to stay home, Ashley Laderer began waking each morning with a throbbing headache.
“The pressure was so intense it felt like my head was going to explode,” recalled the 27-year-old freelance writer from Long Island.
She tried spending less time on the computer and taking over-the-counter pain medication, but the pounding kept breaking through – a constant drumbeat to accompany her equally incessant worries about COVID-19.
“Every day I lived in fear that I was going to get it and I was going to infect my whole family,” she said.
After a month and a half, Ms. Laderer decided to visit a neurologist, who ordered an MRI. But the doctor found no physical cause. The scan was clear.
Then he asked: “Are you under a lot of stress?”
excruciating headaches, episodes of hair loss, upset stomach for weeks on end, sudden outbreaks of shingles, and flare-ups of autoimmune disorders. The disparate symptoms, often in otherwise-healthy individuals, have puzzled doctors and patients alike, sometimes resulting in a series of visits to specialists with few answers. But it turns out there’s a common thread among many of these conditions, one that has been months in the making: chronic stress.
Although people often underestimate the influence of the mind on the body, a growing catalog of research shows that high levels of stress over an extended time can drastically alter physical function and affect nearly every organ system.
Now, at least 8 months into the pandemic, alongside a divisive election cycle and racial unrest, those effects are showing up in a variety of symptoms.
“The mental health component of COVID is starting to come like a tsunami,” said Jennifer Love, MD, a California-based psychiatrist and coauthor of an upcoming book on how to heal from chronic stress.
Nationwide, surveys have found increasing rates of depression, anxiety and suicidal thoughts during the pandemic. But many medical experts said it’s too soon to measure the related physical symptoms, since they generally appear months after the stress begins.
Still, some early research, such as a small Chinese study and an online survey of more than 500 people in Turkey, points to an uptick.
In the United States, data from FAIR Health, a nonprofit database that provides cost information to the health industry and consumers, showed slight to moderate increases in the percentage of medical claims related to conditions triggered or exacerbated by stress, like multiple sclerosis and shingles. The portion of claims for the autoimmune disease lupus, for example, showed one of the biggest increases – 12% this year – compared with the same period last year (January to August).
Express Scripts, a major pharmacy benefit manager, reported that prescriptions for anti-insomnia medications increased 15% early in the pandemic.
Perhaps the strongest indicator comes from doctors reporting a growing number of patients with physical symptoms for which they can’t determine a cause.
Shilpi Khetarpal, MD, a dermatologist at the Cleveland Clinic, used to see about five patients a week with stress-related hair loss. Since mid-June, that number has jumped to 20 or 25. Mostly women, ages 20-80, are reporting hair coming out in fistfuls, Dr. Khetarpal said.
In Houston, at least a dozen patients have told fertility specialist Rashmi Kudesia, MD, they’re having irregular menstrual cycles, changes in cervical discharge and breast tenderness, despite normal hormone levels.
Stress is also the culprit dentists are pointing to for the rapid increase in patients with teeth grinding, teeth fractures, and temporomandibular joint dysfunction.
“We, as humans, like to have the idea that we are in control of our minds and that stress isn’t a big deal,” Dr. Love said. “But it’s simply not true.”
How mental stress becomes physical
Stress causes physical changes in the body that can affect nearly every organ system.
Although symptoms of chronic stress are often dismissed as being in one’s head, the pain is very real, said Kate Harkness, PhD, a professor of psychology and psychiatry at Queen’s University, Kingston, Ont.
When the body feels unsafe – whether it’s a physical threat of attack or a psychological fear of losing a job or catching a disease – the brain signals adrenal glands to pump stress hormones. Adrenaline and cortisol flood the body, activating the fight-or-flight response. They also disrupt bodily functions that aren’t necessary for immediate survival, like digestion and reproduction.
When the danger is over, the hormones return to normal levels. But during times of chronic stress, like a pandemic, the body keeps pumping out stress hormones until it tires itself out. This leads to increased inflammation throughout the body and brain, and a poorly functioning immune system.
Studies link chronic stress to heart disease, muscle tension, gastrointestinal issues and even physical shrinking of the hippocampus, an area of the brain associated with memory and learning. As the immune system acts up, some people can even develop new allergic reactions, Dr. Harkness said.
The good news is that many of these symptoms are reversible. But it’s important to recognize them early, especially when it comes to the brain, said Barbara Sahakian, FBA, FMedSci, a professor of clinical neuropsychology at the University of Cambridge (England).
“The brain is plastic, so we can to some extent modify it,” Dr. Sahakian said. “But we don’t know if there’s a cliff beyond which you can’t reverse a change. So the sooner you catch something, the better.”
The day-to-day impact
In some ways, mental health awareness has increased during the pandemic. TV shows are flush with ads for therapy and meditation apps, like Talkspace and Calm, and companies are announcing mental health days off for staff. But those spurts of attention fail to reveal the full impact of poor mental health on people’s daily lives.
For Alex Kostka, pandemic-related stress has brought on mood swings, nightmares, and jaw pain.
He’d been working at a Whole Foods coffee bar in New York City for only about a month before the pandemic hit, suddenly anointing him an essential worker. As deaths in the city soared, Mr. Kostka continued riding the subway to work, interacting with coworkers in the store and working longer hours for just a $2-per-hour wage increase. (Months later, he’d get a $500 bonus.) It left the 28-year-old feeling constantly unsafe and helpless.
“It was hard not to break down on the subway the minute I got on it,” Mr. Kostka said.
Soon he began waking in the middle of the night with pain from clenching his jaw so tightly. Often his teeth grinding and chomping were loud enough to wake his girlfriend.
Mr. Kostka tried Talkspace, but found texting about his troubles felt impersonal. By the end of the summer, he decided to start using the seven free counseling sessions offered by his employer. That’s helped, he said. But as the sessions run out, he worries the symptoms might return if he’s unable to find a new therapist covered by his insurance.
“Eventually, I will be able to leave this behind me, but it will take time,” Mr. Kostka said. “I’m still very much a work in progress.”
How to mitigate chronic stress
When it comes to chronic stress, seeing a doctor for stomach pain, headaches, or skin rashes may address those physical symptoms. But the root cause is mental, medical experts said.
That means the solution will often involve stress-management techniques. And there’s plenty we can do to feel better:
- Exercise. Even low- to moderate-intensity physical activity can help counteract stress-induced inflammation in the body. It can also increase neuronal connections in the brain.
- Meditation and mindfulness. Research shows this can lead to positive, structural, and functional changes in the brain.
- Fostering social connections. Talking to family and friends, even virtually, or staring into a pet’s eyes can release a hormone that may counteract inflammation.
- Learning something new. Whether it’s a formal class or taking up a casual hobby, learning supports brain plasticity, the ability to change and adapt as a result of experience, which can be protective against depression and other mental illness.
“We shouldn’t think of this stressful situation as a negative sentence for the brain,” said Dr. Harkness. “Because stress changes the brain, that means positive stuff can change the brain, too. And there is plenty we can do to help ourselves feel better in the face of adversity.”
KHN (Kaiser Health News) is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.
Survey: Doctors lonely, burned out in COVID-19
Patrick Ross, MD, a critical care physician at Children’s Hospital of Los Angeles, was plagued with increasing worry about his health and that of his family, patients, and colleagues. While distancing from his wife and daughter, he became terrified of falling ill and dying alone.
As he grew more anxious, Ross withdrew from family, colleagues, and friends, although his clinical and academic responsibilities were unaffected. He barely ate; his weight plummeted, and he began to have suicidal thoughts.
Rebecca Margolis, DO, a pediatric anesthesiologist whom Ross was mentoring, noticed something was amiss and suggested that he go to a therapist. That suggestion may have saved him.
“Once I started therapy, I no longer had suicidal ideations, but I still remained anxious on a day-to-day basis,” said Ross, who is an associate professor of clinical anesthesiology and pediatrics at the University of Southern California, Los Angeles. “As soon as I learned to manage or mitigate the anxiety, I was no longer consumed to the degree I had been by the sense of day-to-day threat.”
Ross openly shares his story because “many other physicians may be going through versions of what I experienced, and I want to encourage them to get help if they’re feeling stressed, anxious, lonely, depressed, or burned out, and to recognize that they are not alone.”
Physicians feel a sense of betrayal
Ross’ experience, although extreme, is not unique. According to a Medscape survey of almost 7,500 physicians, about two-thirds (64%) of U.S. physicians reported experiencing more intense burnout, and close to half (46%) reported feeling more lonely and isolated during the pandemic.
“We know that stress, which was already significant in physicians, has increased dramatically for many physicians during the pandemic. That’s understandable, given the circumstances they’ve been working under,” said Christine A. Sinsky, MD, vice president of professional satisfaction at the American Medical Association.
Physicians are stressed about potentially contracting the virus or infecting family members; being overworked and fatigued; witnessing wrenching scenes of patients dying alone; grieving the loss of patients, colleagues, or family members; and sometimes lacking adequate personal protective equipment (PPE), she said.
Lack of PPE has been identified as one of the most significant contributors to burnout and stress among physicians and other health care professionals. In all eight countries surveyed by Medscape, a significant number of respondents reported lacking appropriate PPE “sometimes,” “often,” or “always” when treating COVID-19 patients. Only 54% of U.S. respondents said they were always adequately protected.
The PPE shortage not only jeopardizes physical health but also has a negative effect on mental health and morale. A U.S.-based rheumatologist said, “The fact that we were sent to take care of infectious patients without proper PPE makes me feel we were betrayed in this fight.”
Not what they signed up for
Many physicians expressed fear regarding their personal safety, but that was often superseded by concern for family – especially elderly relatives or young children. (Medscape’s survey found that 9% of US respondents had immediate family members who had been diagnosed with COVID-19.)
Larissa Thomas, MD, MPH, University of California, San Francisco, said her greatest fear was bringing the virus home to her new baby and other vulnerable family members. Thomas is associate clinical professor of medicine and is a faculty hospitalist at Zuckerberg San Francisco General Hospital.
“Although physicians assume risk in our work, we didn’t sign up to care for patients without adequate protection, and our families certainly didn’t sign up for that risk, so the concern was acutely stressful,” said Thomas, who is also associate program director for the UCSF Internal Medicine Residency Program and is director of well-being for UCSF Graduate Medical Education.
The impact of stay-at-home restrictions on family members’ mental health also affected many physicians.
David Marcus, MD, residency director of the Combined Program in Emergency/Internal/Critical Care Medicine and chair of the GME Physician Wellbeing Committee at Northwell Health, Long Island, New York, said that a large stressor during the pandemic was having an elderly father with multiple comorbidities who lived alone and was unable to go out because of stay-at-home restrictions.
“I was worried not only for his physical health but also that his cognition might slip due to lack of socialization,” said Marcus.
Marcus was also worried about his preschool-age daughter, who seemed to be regressing and becoming desocialized from no longer being at school. “Fortunately, school has reopened, but it was a constant weight on my wife and me to see the impact of the lockdown on her development,” he said.
New situations create more anxiety
Being redeployed to new clinical roles in settings such as the emergency department or intensive care, which were not in their area of specialty, created much stress for physicians, Thomas said.
Physicians in private practice also had to adjust to new ways of practicing. In Medscape’s survey, 39% of U.S. physicians reported that their medical practice never closed during the pandemic. Keeping a practice open often meant learning to see patients virtually or becoming extremely vigilant about reducing the risk for contagion when seeing patients in person.
Relationships became more challenging
Social distancing during the pandemic had a negative effect on personal relationships for 44% of respondents, both in the United States and abroad.
One physician described her relationship with her partner as “more stressful” and argumentative. A rheumatologist reported experiencing frustration at having college-aged children living at home. Another respondent said that being with young children 24/7 left her “short-tempered,” and an emergency medicine physician respondent said she and her family were “driving each other crazy.”
Social distancing was not the only challenge to relationships. An orthopedist identified long, taxing work hours as contributing to a “decline in spousal harmony.”
On the other hand, some physicians said their relationships improved by developing shared insight. An emergency medicine physician wrote that he and his wife were “having more quarrels” but were “trying very hard and succeeding at understanding that much of this is due to the changes in our living situation.”
As a volunteer with New York City’s Medical Reserve Corps, Wilfrid Noel Raby, PhD, MD, adjunct clinical professor of psychiatry, Albert Einstein College of Medicine, New York City, chose to keep his Teaneck, New Jersey–based office open and was taking overnight shifts at Lincoln Hospital in New York City during the acute physician shortage. “After my regular hospital job treating psychiatric patients and seeing patients in my private practice, I sometimes pulled 12-hour nights caring for very ill patients. It was grueling, and I came home drained and exhausted,” he recalled.
Raby’s wife, a surgical nurse, had been redeployed to care for COVID-19 patients in the ICU – a situation she found grueling as well. Adding to the stress were the “rigorous distancing and sanitation precautions we needed to practice at home.” Fear of contagion, together with exhaustion, resulted in “occasional moments of friction,” Raby acknowledged.
Still, some physicians managed to find a bit of a silver lining. “We tried to relax, get as much sleep as possible, and keep things simple, not taking on extra tasks that could be postponed,” Raby said. “It helped that we both recognized how difficult it was to reassure each other when we were stressed and scared, so we faced the crisis together, and I think it ultimately brought us closer.”
Thomas said that the pandemic has helped her to recognize what she can and cannot control and how to take things one day at a time.
“When my husband and I can both work from home, we are grateful to have that ability and grateful for the things that we do have. These small moments of gratitude have sustained us day to day,” Thomas said.
Socializing outside the box
Several physicians expressed a sense of loneliness because stay-at-home guidelines and social distancing prevented them from socializing with friends. In all countries, physician respondents to the Medscape survey reported feeling “more lonely” than prior to the pandemic. Over half (51%) of Portuguese physicians reported feeling lonelier; 48% of physicians in Brazil felt that way. The United States came in third, at 46%.
Many physicians feel cut off, even from other physicians, and are reluctant to share feelings of distress.
“Talking to colleagues about distress is an important human connection,” Margolis emphasized. “We need to rely on each other to commiserate and receive validation and comfort.”
Some institutions have formalized this process by instituting a “battle buddy” model – a term borrowed from the military – which involves pairing clinicians of similar specialty, career stage, and life circumstances to provide mutual peer support, Margolis said. A partner who notices concerning signs in the other partner can refer the person to resources for help.
Sinsky said that an organization called PeerRxMed offers physicians a chance to sign up for a “buddy,” even outside their own institution.
The importance of ‘fixing’ the workplace
Close to half (43%) of U.S. respondents to Medscape’s survey reported that their workplace offers activities to help physicians deal with grief and stress, but 39% said that their workplace does not offer this type of support, and 18% were not sure whether these services were offered.
At times of crisis, organizations need to offer “stress first aid,” Sinsky said. This includes providing for basic needs, such as child care, transportation, and healthy food, and having “open, transparent, and honest communication” from leadership regarding what is known and not known about the pandemic, clinician responsibilities, and stress reduction measures.
Marcus notes that, at his institution, psychiatric residents and other members of the psychiatry department have “stepped up and crafted process groups and peer support contexts to debrief, engage, explore productive outlets for feelings, and facilitate communication.” In particular, residents have found cognitive-behavioral therapy to be useful.
Despite the difficult situation, seeking help can be challenging for some physicians. One reason, Marcus says, is that doctors tend to think of themselves as being at the giving rather than the receiving end of help – especially during a crisis. “We do what we need to do, and we often don’t see the toll it takes on us,” he noted. Moreover, the pressure to be at the “giving” end can lead to stigma in acknowledging vulnerability.
Ross said he hopes his story will help to destigmatize reaching out for help. “It is possible that a silver lining of this terrible crisis is to normalize physicians receiving help for mental health issues.”
Marcus likewise openly shares his own experiences about struggles with burnout and depressive symptoms. “As a physician educator, I think it’s important for me to be public about these things, which validates help-seeking for residents and colleagues.”
For physicians seeking help not offered in their workplace, the Physician Support Line is a useful resource, added Margolis. She noted that its services are free and confidential.
This article first appeared on Medscape.com.
Patrick Ross, MD, a critical care physician at Children’s Hospital of Los Angeles, was plagued with increasing worry about his health and that of his family, patients, and colleagues. While distancing from his wife and daughter, he became terrified of falling ill and dying alone.
As he grew more anxious, Ross withdrew from family, colleagues, and friends, although his clinical and academic responsibilities were unaffected. He barely ate; his weight plummeted, and he began to have suicidal thoughts.
Rebecca Margolis, DO, a pediatric anesthesiologist whom Ross was mentoring, noticed something was amiss and suggested that he go to a therapist. That suggestion may have saved him.
“Once I started therapy, I no longer had suicidal ideations, but I still remained anxious on a day-to-day basis,” said Ross, who is an associate professor of clinical anesthesiology and pediatrics at the University of Southern California, Los Angeles. “As soon as I learned to manage or mitigate the anxiety, I was no longer consumed to the degree I had been by the sense of day-to-day threat.”
Ross openly shares his story because “many other physicians may be going through versions of what I experienced, and I want to encourage them to get help if they’re feeling stressed, anxious, lonely, depressed, or burned out, and to recognize that they are not alone.”
Physicians feel a sense of betrayal
Ross’ experience, although extreme, is not unique. According to a Medscape survey of almost 7,500 physicians, about two-thirds (64%) of U.S. physicians reported experiencing more intense burnout, and close to half (46%) reported feeling more lonely and isolated during the pandemic.
“We know that stress, which was already significant in physicians, has increased dramatically for many physicians during the pandemic. That’s understandable, given the circumstances they’ve been working under,” said Christine A. Sinsky, MD, vice president of professional satisfaction at the American Medical Association.
Physicians are stressed about potentially contracting the virus or infecting family members; being overworked and fatigued; witnessing wrenching scenes of patients dying alone; grieving the loss of patients, colleagues, or family members; and sometimes lacking adequate personal protective equipment (PPE), she said.
Lack of PPE has been identified as one of the most significant contributors to burnout and stress among physicians and other health care professionals. In all eight countries surveyed by Medscape, a significant number of respondents reported lacking appropriate PPE “sometimes,” “often,” or “always” when treating COVID-19 patients. Only 54% of U.S. respondents said they were always adequately protected.
The PPE shortage not only jeopardizes physical health but also has a negative effect on mental health and morale. A U.S.-based rheumatologist said, “The fact that we were sent to take care of infectious patients without proper PPE makes me feel we were betrayed in this fight.”
Not what they signed up for
Many physicians expressed fear regarding their personal safety, but that was often superseded by concern for family – especially elderly relatives or young children. (Medscape’s survey found that 9% of US respondents had immediate family members who had been diagnosed with COVID-19.)
Larissa Thomas, MD, MPH, University of California, San Francisco, said her greatest fear was bringing the virus home to her new baby and other vulnerable family members. Thomas is associate clinical professor of medicine and is a faculty hospitalist at Zuckerberg San Francisco General Hospital.
“Although physicians assume risk in our work, we didn’t sign up to care for patients without adequate protection, and our families certainly didn’t sign up for that risk, so the concern was acutely stressful,” said Thomas, who is also associate program director for the UCSF Internal Medicine Residency Program and is director of well-being for UCSF Graduate Medical Education.
The impact of stay-at-home restrictions on family members’ mental health also affected many physicians.
David Marcus, MD, residency director of the Combined Program in Emergency/Internal/Critical Care Medicine and chair of the GME Physician Wellbeing Committee at Northwell Health, Long Island, New York, said that a large stressor during the pandemic was having an elderly father with multiple comorbidities who lived alone and was unable to go out because of stay-at-home restrictions.
“I was worried not only for his physical health but also that his cognition might slip due to lack of socialization,” said Marcus.
Marcus was also worried about his preschool-age daughter, who seemed to be regressing and becoming desocialized from no longer being at school. “Fortunately, school has reopened, but it was a constant weight on my wife and me to see the impact of the lockdown on her development,” he said.
New situations create more anxiety
Being redeployed to new clinical roles in settings such as the emergency department or intensive care, which were not in their area of specialty, created much stress for physicians, Thomas said.
Physicians in private practice also had to adjust to new ways of practicing. In Medscape’s survey, 39% of U.S. physicians reported that their medical practice never closed during the pandemic. Keeping a practice open often meant learning to see patients virtually or becoming extremely vigilant about reducing the risk for contagion when seeing patients in person.
Relationships became more challenging
Social distancing during the pandemic had a negative effect on personal relationships for 44% of respondents, both in the United States and abroad.
One physician described her relationship with her partner as “more stressful” and argumentative. A rheumatologist reported experiencing frustration at having college-aged children living at home. Another respondent said that being with young children 24/7 left her “short-tempered,” and an emergency medicine physician respondent said she and her family were “driving each other crazy.”
Social distancing was not the only challenge to relationships. An orthopedist identified long, taxing work hours as contributing to a “decline in spousal harmony.”
On the other hand, some physicians said their relationships improved by developing shared insight. An emergency medicine physician wrote that he and his wife were “having more quarrels” but were “trying very hard and succeeding at understanding that much of this is due to the changes in our living situation.”
As a volunteer with New York City’s Medical Reserve Corps, Wilfrid Noel Raby, PhD, MD, adjunct clinical professor of psychiatry, Albert Einstein College of Medicine, New York City, chose to keep his Teaneck, New Jersey–based office open and was taking overnight shifts at Lincoln Hospital in New York City during the acute physician shortage. “After my regular hospital job treating psychiatric patients and seeing patients in my private practice, I sometimes pulled 12-hour nights caring for very ill patients. It was grueling, and I came home drained and exhausted,” he recalled.
Raby’s wife, a surgical nurse, had been redeployed to care for COVID-19 patients in the ICU – a situation she found grueling as well. Adding to the stress were the “rigorous distancing and sanitation precautions we needed to practice at home.” Fear of contagion, together with exhaustion, resulted in “occasional moments of friction,” Raby acknowledged.
Still, some physicians managed to find a bit of a silver lining. “We tried to relax, get as much sleep as possible, and keep things simple, not taking on extra tasks that could be postponed,” Raby said. “It helped that we both recognized how difficult it was to reassure each other when we were stressed and scared, so we faced the crisis together, and I think it ultimately brought us closer.”
Thomas said that the pandemic has helped her to recognize what she can and cannot control and how to take things one day at a time.
“When my husband and I can both work from home, we are grateful to have that ability and grateful for the things that we do have. These small moments of gratitude have sustained us day to day,” Thomas said.
Socializing outside the box
Several physicians expressed a sense of loneliness because stay-at-home guidelines and social distancing prevented them from socializing with friends. In all countries, physician respondents to the Medscape survey reported feeling “more lonely” than prior to the pandemic. Over half (51%) of Portuguese physicians reported feeling lonelier; 48% of physicians in Brazil felt that way. The United States came in third, at 46%.
Many physicians feel cut off, even from other physicians, and are reluctant to share feelings of distress.
“Talking to colleagues about distress is an important human connection,” Margolis emphasized. “We need to rely on each other to commiserate and receive validation and comfort.”
Some institutions have formalized this process by instituting a “battle buddy” model – a term borrowed from the military – which involves pairing clinicians of similar specialty, career stage, and life circumstances to provide mutual peer support, Margolis said. A partner who notices concerning signs in the other partner can refer the person to resources for help.
Sinsky said that an organization called PeerRxMed offers physicians a chance to sign up for a “buddy,” even outside their own institution.
The importance of ‘fixing’ the workplace
Close to half (43%) of U.S. respondents to Medscape’s survey reported that their workplace offers activities to help physicians deal with grief and stress, but 39% said that their workplace does not offer this type of support, and 18% were not sure whether these services were offered.
At times of crisis, organizations need to offer “stress first aid,” Sinsky said. This includes providing for basic needs, such as child care, transportation, and healthy food, and having “open, transparent, and honest communication” from leadership regarding what is known and not known about the pandemic, clinician responsibilities, and stress reduction measures.
Marcus notes that, at his institution, psychiatric residents and other members of the psychiatry department have “stepped up and crafted process groups and peer support contexts to debrief, engage, explore productive outlets for feelings, and facilitate communication.” In particular, residents have found cognitive-behavioral therapy to be useful.
Despite the difficult situation, seeking help can be challenging for some physicians. One reason, Marcus says, is that doctors tend to think of themselves as being at the giving rather than the receiving end of help – especially during a crisis. “We do what we need to do, and we often don’t see the toll it takes on us,” he noted. Moreover, the pressure to be at the “giving” end can lead to stigma in acknowledging vulnerability.
Ross said he hopes his story will help to destigmatize reaching out for help. “It is possible that a silver lining of this terrible crisis is to normalize physicians receiving help for mental health issues.”
Marcus likewise openly shares his own experiences about struggles with burnout and depressive symptoms. “As a physician educator, I think it’s important for me to be public about these things, which validates help-seeking for residents and colleagues.”
For physicians seeking help not offered in their workplace, the Physician Support Line is a useful resource, added Margolis. She noted that its services are free and confidential.
This article first appeared on Medscape.com.
Patrick Ross, MD, a critical care physician at Children’s Hospital of Los Angeles, was plagued with increasing worry about his health and that of his family, patients, and colleagues. While distancing from his wife and daughter, he became terrified of falling ill and dying alone.
As he grew more anxious, Ross withdrew from family, colleagues, and friends, although his clinical and academic responsibilities were unaffected. He barely ate; his weight plummeted, and he began to have suicidal thoughts.
Rebecca Margolis, DO, a pediatric anesthesiologist whom Ross was mentoring, noticed something was amiss and suggested that he go to a therapist. That suggestion may have saved him.
“Once I started therapy, I no longer had suicidal ideations, but I still remained anxious on a day-to-day basis,” said Ross, who is an associate professor of clinical anesthesiology and pediatrics at the University of Southern California, Los Angeles. “As soon as I learned to manage or mitigate the anxiety, I was no longer consumed to the degree I had been by the sense of day-to-day threat.”
Ross openly shares his story because “many other physicians may be going through versions of what I experienced, and I want to encourage them to get help if they’re feeling stressed, anxious, lonely, depressed, or burned out, and to recognize that they are not alone.”
Physicians feel a sense of betrayal
Ross’ experience, although extreme, is not unique. According to a Medscape survey of almost 7,500 physicians, about two-thirds (64%) of U.S. physicians reported experiencing more intense burnout, and close to half (46%) reported feeling more lonely and isolated during the pandemic.
“We know that stress, which was already significant in physicians, has increased dramatically for many physicians during the pandemic. That’s understandable, given the circumstances they’ve been working under,” said Christine A. Sinsky, MD, vice president of professional satisfaction at the American Medical Association.
Physicians are stressed about potentially contracting the virus or infecting family members; being overworked and fatigued; witnessing wrenching scenes of patients dying alone; grieving the loss of patients, colleagues, or family members; and sometimes lacking adequate personal protective equipment (PPE), she said.
Lack of PPE has been identified as one of the most significant contributors to burnout and stress among physicians and other health care professionals. In all eight countries surveyed by Medscape, a significant number of respondents reported lacking appropriate PPE “sometimes,” “often,” or “always” when treating COVID-19 patients. Only 54% of U.S. respondents said they were always adequately protected.
The PPE shortage not only jeopardizes physical health but also has a negative effect on mental health and morale. A U.S.-based rheumatologist said, “The fact that we were sent to take care of infectious patients without proper PPE makes me feel we were betrayed in this fight.”
Not what they signed up for
Many physicians expressed fear regarding their personal safety, but that was often superseded by concern for family – especially elderly relatives or young children. (Medscape’s survey found that 9% of US respondents had immediate family members who had been diagnosed with COVID-19.)
Larissa Thomas, MD, MPH, University of California, San Francisco, said her greatest fear was bringing the virus home to her new baby and other vulnerable family members. Thomas is associate clinical professor of medicine and is a faculty hospitalist at Zuckerberg San Francisco General Hospital.
“Although physicians assume risk in our work, we didn’t sign up to care for patients without adequate protection, and our families certainly didn’t sign up for that risk, so the concern was acutely stressful,” said Thomas, who is also associate program director for the UCSF Internal Medicine Residency Program and is director of well-being for UCSF Graduate Medical Education.
The impact of stay-at-home restrictions on family members’ mental health also affected many physicians.
David Marcus, MD, residency director of the Combined Program in Emergency/Internal/Critical Care Medicine and chair of the GME Physician Wellbeing Committee at Northwell Health, Long Island, New York, said that a large stressor during the pandemic was having an elderly father with multiple comorbidities who lived alone and was unable to go out because of stay-at-home restrictions.
“I was worried not only for his physical health but also that his cognition might slip due to lack of socialization,” said Marcus.
Marcus was also worried about his preschool-age daughter, who seemed to be regressing and becoming desocialized from no longer being at school. “Fortunately, school has reopened, but it was a constant weight on my wife and me to see the impact of the lockdown on her development,” he said.
New situations create more anxiety
Being redeployed to new clinical roles in settings such as the emergency department or intensive care, which were not in their area of specialty, created much stress for physicians, Thomas said.
Physicians in private practice also had to adjust to new ways of practicing. In Medscape’s survey, 39% of U.S. physicians reported that their medical practice never closed during the pandemic. Keeping a practice open often meant learning to see patients virtually or becoming extremely vigilant about reducing the risk for contagion when seeing patients in person.
Relationships became more challenging
Social distancing during the pandemic had a negative effect on personal relationships for 44% of respondents, both in the United States and abroad.
One physician described her relationship with her partner as “more stressful” and argumentative. A rheumatologist reported experiencing frustration at having college-aged children living at home. Another respondent said that being with young children 24/7 left her “short-tempered,” and an emergency medicine physician respondent said she and her family were “driving each other crazy.”
Social distancing was not the only challenge to relationships. An orthopedist identified long, taxing work hours as contributing to a “decline in spousal harmony.”
On the other hand, some physicians said their relationships improved by developing shared insight. An emergency medicine physician wrote that he and his wife were “having more quarrels” but were “trying very hard and succeeding at understanding that much of this is due to the changes in our living situation.”
As a volunteer with New York City’s Medical Reserve Corps, Wilfrid Noel Raby, PhD, MD, adjunct clinical professor of psychiatry, Albert Einstein College of Medicine, New York City, chose to keep his Teaneck, New Jersey–based office open and was taking overnight shifts at Lincoln Hospital in New York City during the acute physician shortage. “After my regular hospital job treating psychiatric patients and seeing patients in my private practice, I sometimes pulled 12-hour nights caring for very ill patients. It was grueling, and I came home drained and exhausted,” he recalled.
Raby’s wife, a surgical nurse, had been redeployed to care for COVID-19 patients in the ICU – a situation she found grueling as well. Adding to the stress were the “rigorous distancing and sanitation precautions we needed to practice at home.” Fear of contagion, together with exhaustion, resulted in “occasional moments of friction,” Raby acknowledged.
Still, some physicians managed to find a bit of a silver lining. “We tried to relax, get as much sleep as possible, and keep things simple, not taking on extra tasks that could be postponed,” Raby said. “It helped that we both recognized how difficult it was to reassure each other when we were stressed and scared, so we faced the crisis together, and I think it ultimately brought us closer.”
Thomas said that the pandemic has helped her to recognize what she can and cannot control and how to take things one day at a time.
“When my husband and I can both work from home, we are grateful to have that ability and grateful for the things that we do have. These small moments of gratitude have sustained us day to day,” Thomas said.
Socializing outside the box
Several physicians expressed a sense of loneliness because stay-at-home guidelines and social distancing prevented them from socializing with friends. In all countries, physician respondents to the Medscape survey reported feeling “more lonely” than prior to the pandemic. Over half (51%) of Portuguese physicians reported feeling lonelier; 48% of physicians in Brazil felt that way. The United States came in third, at 46%.
Many physicians feel cut off, even from other physicians, and are reluctant to share feelings of distress.
“Talking to colleagues about distress is an important human connection,” Margolis emphasized. “We need to rely on each other to commiserate and receive validation and comfort.”
Some institutions have formalized this process by instituting a “battle buddy” model – a term borrowed from the military – which involves pairing clinicians of similar specialty, career stage, and life circumstances to provide mutual peer support, Margolis said. A partner who notices concerning signs in the other partner can refer the person to resources for help.
Sinsky said that an organization called PeerRxMed offers physicians a chance to sign up for a “buddy,” even outside their own institution.
The importance of ‘fixing’ the workplace
Close to half (43%) of U.S. respondents to Medscape’s survey reported that their workplace offers activities to help physicians deal with grief and stress, but 39% said that their workplace does not offer this type of support, and 18% were not sure whether these services were offered.
At times of crisis, organizations need to offer “stress first aid,” Sinsky said. This includes providing for basic needs, such as child care, transportation, and healthy food, and having “open, transparent, and honest communication” from leadership regarding what is known and not known about the pandemic, clinician responsibilities, and stress reduction measures.
Marcus notes that, at his institution, psychiatric residents and other members of the psychiatry department have “stepped up and crafted process groups and peer support contexts to debrief, engage, explore productive outlets for feelings, and facilitate communication.” In particular, residents have found cognitive-behavioral therapy to be useful.
Despite the difficult situation, seeking help can be challenging for some physicians. One reason, Marcus says, is that doctors tend to think of themselves as being at the giving rather than the receiving end of help – especially during a crisis. “We do what we need to do, and we often don’t see the toll it takes on us,” he noted. Moreover, the pressure to be at the “giving” end can lead to stigma in acknowledging vulnerability.
Ross said he hopes his story will help to destigmatize reaching out for help. “It is possible that a silver lining of this terrible crisis is to normalize physicians receiving help for mental health issues.”
Marcus likewise openly shares his own experiences about struggles with burnout and depressive symptoms. “As a physician educator, I think it’s important for me to be public about these things, which validates help-seeking for residents and colleagues.”
For physicians seeking help not offered in their workplace, the Physician Support Line is a useful resource, added Margolis. She noted that its services are free and confidential.
This article first appeared on Medscape.com.
What’s in a number? 697,633 children with COVID-19
according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
For the week, 14.6% of all COVID-19 cases reported in the United States occurred in children, after 2 consecutive weeks of declines that saw the proportion drop from 16.9% to 12.3%. The cumulative rate of child cases for the entire pandemic is 10.7%, with total child cases in the United States now up to 697,633 and cases among all ages at just over 6.5 million, the AAP and the CHA said Oct. 12 in their weekly COVID-19 report.
Nationally, there were 927 cases reported per 100,000 children as of Oct. 8, with rates at the state level varying from 176 per 100,000 in Vermont to 2,221 per 100,000 in North Dakota. Two other states were over 2,000 cases per 100,000 children: Tennessee (2,155) and South Carolina (2,116), based on data from the health departments of 49 states (New York does not report age distribution), as well as the District of Columbia, New York City, Puerto Rico, and Guam.
Severe illness continues to be rare in children, and national (25 states and New York City) hospitalization rates dropped in the last week. The proportion of hospitalizations occurring in children slipped from a pandemic high of 1.8% the previous week to 1.7% during the week of Oct. 8, and the rate of hospitalizations for children with COVID-19 was down to 1.4% from 1.6% the week before and 1.9% on Sept. 3, the AAP and the CHA said.
Mortality data from 42 states and New York City also show a decline. For the third consecutive week, children represented just 0.06% of all COVID-19 deaths in the United States, down from a high of 0.07% on Sept. 17. Only 0.02% of all cases in children have resulted in death, and that figure has been dropping since early June, when it reached 0.06%, according to the AAP/CHA report. As of Oct. 8, there have been 115 total deaths reported in children.
according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
For the week, 14.6% of all COVID-19 cases reported in the United States occurred in children, after 2 consecutive weeks of declines that saw the proportion drop from 16.9% to 12.3%. The cumulative rate of child cases for the entire pandemic is 10.7%, with total child cases in the United States now up to 697,633 and cases among all ages at just over 6.5 million, the AAP and the CHA said Oct. 12 in their weekly COVID-19 report.
Nationally, there were 927 cases reported per 100,000 children as of Oct. 8, with rates at the state level varying from 176 per 100,000 in Vermont to 2,221 per 100,000 in North Dakota. Two other states were over 2,000 cases per 100,000 children: Tennessee (2,155) and South Carolina (2,116), based on data from the health departments of 49 states (New York does not report age distribution), as well as the District of Columbia, New York City, Puerto Rico, and Guam.
Severe illness continues to be rare in children, and national (25 states and New York City) hospitalization rates dropped in the last week. The proportion of hospitalizations occurring in children slipped from a pandemic high of 1.8% the previous week to 1.7% during the week of Oct. 8, and the rate of hospitalizations for children with COVID-19 was down to 1.4% from 1.6% the week before and 1.9% on Sept. 3, the AAP and the CHA said.
Mortality data from 42 states and New York City also show a decline. For the third consecutive week, children represented just 0.06% of all COVID-19 deaths in the United States, down from a high of 0.07% on Sept. 17. Only 0.02% of all cases in children have resulted in death, and that figure has been dropping since early June, when it reached 0.06%, according to the AAP/CHA report. As of Oct. 8, there have been 115 total deaths reported in children.
according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
For the week, 14.6% of all COVID-19 cases reported in the United States occurred in children, after 2 consecutive weeks of declines that saw the proportion drop from 16.9% to 12.3%. The cumulative rate of child cases for the entire pandemic is 10.7%, with total child cases in the United States now up to 697,633 and cases among all ages at just over 6.5 million, the AAP and the CHA said Oct. 12 in their weekly COVID-19 report.
Nationally, there were 927 cases reported per 100,000 children as of Oct. 8, with rates at the state level varying from 176 per 100,000 in Vermont to 2,221 per 100,000 in North Dakota. Two other states were over 2,000 cases per 100,000 children: Tennessee (2,155) and South Carolina (2,116), based on data from the health departments of 49 states (New York does not report age distribution), as well as the District of Columbia, New York City, Puerto Rico, and Guam.
Severe illness continues to be rare in children, and national (25 states and New York City) hospitalization rates dropped in the last week. The proportion of hospitalizations occurring in children slipped from a pandemic high of 1.8% the previous week to 1.7% during the week of Oct. 8, and the rate of hospitalizations for children with COVID-19 was down to 1.4% from 1.6% the week before and 1.9% on Sept. 3, the AAP and the CHA said.
Mortality data from 42 states and New York City also show a decline. For the third consecutive week, children represented just 0.06% of all COVID-19 deaths in the United States, down from a high of 0.07% on Sept. 17. Only 0.02% of all cases in children have resulted in death, and that figure has been dropping since early June, when it reached 0.06%, according to the AAP/CHA report. As of Oct. 8, there have been 115 total deaths reported in children.
A uniquely patient-focused take on treating AML in older adults
A diagnosis of acute myeloid leukemia (AML) is particularly challenging in older adults, whose age makes them highly susceptible to the disease and treatment-related toxicity. To help patients and practitioners navigate the clinical decision-making process, the American Society of Hematology convened a panel of experts who conducted a thorough review of the literature. The result of their work can be found in a new set of guidelines for the treatment of newly diagnosed AML in older adults.
In an interview, Mikkael Sekeres, MD, chair of the ASH AML guideline panel and director of the Leukemia Program at Cleveland Clinic Taussig Cancer Institute in Cleveland, Ohio, shared the rationale behind the panel’s key recommendations and the importance of keeping the patient’s goals in mind.
Question: What is the average life expectancy of a 75-year-old developing AML compared with someone of the same age without AML?
Dr. Sekeres: A 75-year-old developing AML has an average life expectancy measured in fewer than 6 months. Somebody who is 75 without leukemia in the United States has a life expectancy that can be measured in a decade or more. AML is a really serious diagnosis when someone is older and significantly truncates expected survival.
Q: What is the median age at AML diagnosis in the United States?
Dr. Sekeres: About 67 years.
Q: What are the biological underpinnings for poor outcomes in older AML patients?
Dr. Sekeres: There are a few of them. Older adults with AML tend to have a leukemia that has evolved from a known or unknown previous bone marrow condition such as myelodysplastic syndrome. Older adults also have worse genetics driving their leukemia, which makes the leukemia cells more resistant to chemotherapy. And the leukemia cells may even have drug efflux pumps that extrude chemotherapy that tries to enter the cell. Finally, older adults are more likely to have comorbidities that make their ability to tolerate chemotherapy much lower than for younger adults.
Q: In someone who is newly diagnosed with AML, what initial options are they routinely given?
Dr. Sekeres: For someone who is older, we divide those options into three main categories.
The first is to take intensive chemotherapy, which requires a 4-6 week hospitalization and has a chance of getting somebody who is older into a remission of approximately 50%-60%. But this also carries with it significant treatment-related mortality that may be as high as 10%-20%. So I have to look my older patients in the eyes when I talk about intensive chemotherapy and say, “There is a 1 in 10 or 1 in 5 chance that you might not make it out of the hospital alive.”
The second prong is lower-dose therapy. While the more-intensive therapy requiring hospitalization does have a low, but real, chance of curing that person, less-intensive therapy is not curative. Our best hope with less-intensive therapy is that our patients enter a remission and live longer. With less-intensive therapy, the chance that someone will go into remission is probably around 20%, but again it is not curative. The flip side to that is that it improves a person’s immediate quality of life because they’re not in the hospital for 4-6 weeks.
The final prong is to discuss palliative care or hospice upfront. We designed these guidelines to be focused on a patient’s goals of therapy and to constantly revisit those goals to make sure that the treatment options we are offering are aligning with them.
Q: The panel’s first recommendation is to offer antileukemic therapy over best supportive care in patients who are appropriate candidates. Can you provide some context for this recommendation?
Dr. Sekeres: Doesn’t that strike you as funny that we even have to make a recommendation about getting chemotherapy? Some database studies conducted over the past 2 decades show that, as recently as 15 years ago, only one-third of patients who were over the age of 65 years received any type of chemotherapy for AML. More recently, as we have had a few more drugs available that allow us to use lower-dose approaches, that number has crept up to probably about 50%. We still have half the patients offered no therapy at all. So we felt that we had to deliberately make a recommendation saying that, if it aligns with the patients’ goals, they should be offered chemotherapy.
Q: The second recommendation is that patients considered candidates for intensive antileukemic therapy should receive it over less-intensive antileukemic therapy. How did you get to that recommendation?
Dr. Sekeres: There is a debate in our field about whether older adults should be offered intensive inpatient chemotherapy at all or whether we should be treating all of them with less-intensive therapy. There is not a huge amount of high-quality studies out there to answer some of these questions, in particular whether intensive chemotherapy should be recommended over less-intensive therapy. But with the available evidence, what we believe is that patients live longer if they are offered intensive antileukemic chemotherapy. So again, if it aligns with a patient’s goals, we support that patient receiving more-intensive therapy in the hospital.
Q: What does the panel recommend for patients who achieve remission after at least a single cycle of intensive antileukemic therapy and who are not candidates for allogeneic hematopoietic stem cell transplantation?
Dr. Sekeres: Once again, this may seem at first blush to be an obvious recommendation. The standard treatment of someone who is younger with AML is to offer intensive inpatient chemotherapy to induce remission. This is followed by a few cycles of chemotherapy, mostly in an outpatient setting, to consolidate that remission.
Q: What is the underlying philosophy for this approach?
Dr. Sekeres: Every time we give chemotherapy, we probably get about a 3-4 log kill of leukemia cells. Imagine when patients first present with AML, they may have 10 billion leukemia cells in their body. We are reducing that 3-4 log with the first course of chemotherapy.
When we then look at a bone marrow biopsy, it may appear to be normal. When leukemia is at a lower level in the body, we simply can’t see it using standard techniques. But that doesn’t mean the leukemia is gone. For younger patients, we give another cycle of chemotherapy, then another, then another, and then even another to reduce the number of leukemia cells left over in the body until that person has a durable remission and hopefully cure.
For someone who is older, the data are less clear. While some studies have shown that, if you give too much chemotherapy after the initial course, it doesn’t help that much, there is a paucity of studies that show that any chemotherapy at all after the first induction course is helpful. Consequently, we have to use indirect data. Older people who are long-term survivors from their acute leukemia always seem to have gotten more than one course of chemotherapy. In other words, the initial course of chemotherapy that a patient receives in the hospital isn’t enough. They should receive more than that.
Q: What about older adults with AML considered appropriate for antileukemic therapy but not for intensive antileukemic therapy?
Dr. Sekeres: This again gets to the question of what are a patient’s goals. It takes a very involved conversation with patients at the time of their AML diagnosis to determine whether they would want to pursue an aggressive approach or a less-aggressive approach. If a patients want a less-aggressive approach, and want nothing to do with a hospital stay, then they are also prioritizing initial quality of life. In this recommendation, based on existing studies, we didn’t have a preference for which of the available less-aggressive chemotherapies a person selects.
There’s also debate about what to do in those considered appropriate for antileukemic therapy, such as hypomethylating agents (azacitidine and decitabine) or low-dose cytarabine, but not for intensive antileukemic therapy. What did the available evidence seem to indicate about this issue?
There has been a lot of studies trying to add two drugs together to see if those do better than one drug alone in patients who are older and who choose less-intensive therapy. The majority of those studies have shown no advantage to getting two drugs over one drug.
Our recommendation is that in these situations a patient gets one drug, not two, but there are a couple of caveats. One caveat is that there has been a small study showing the effectiveness of one of those low-dose chemotherapies combined with the drug glasdegib. The second caveat is that there have been results presented combining one of these low-dose chemotherapies with the drug venetoclax. One of those was a negative study, and another was a positive study showing a survival advantage to the combination vs. the low-dose therapy alone. We had to couch our recommendation a little bit because we knew this other study had been presented at a conference, but it hadn’t come out in final form yet. It did recently, however, and we will now revisit this recommendation.
The other complicated aspect to this is that we weren’t 100% convinced that the combination of venetoclax with one of these lower-dose therapies is truly less-intensive therapy. We think it is starting to creep up toward more-intensive chemotherapy, even though it is commonly given to patients in the outpatient setting. It gets into the very complicated area of what are we defining as more-intensive therapy and less-intensive therapy.
Q: Is there a recommended strategy for older adults with AML who achieve a response after receiving less-intensive therapy?
Dr. Sekeres: This is also challenging because there are no randomized studies in which patients received less-intensive therapy for a finite period of time vs. receiving those therapies ad infinitum. Given the lack of data and also given a lot of anecdotal data out there about patients who stopped a certain therapy and relapsed thereafter, we recommended that patients continue the less-intensive therapy ad infinitum. So as long as they are receiving a response to that therapy, they continue on the drug.
Q: Of course, there are also unique considerations faced by older patients who are no longer receiving antileukemic therapy and have moved on to receiving end-of-life care or hospice care. What advice do the guidelines offer in this situation?
Dr. Sekeres: There are a lot of aspects of these recommendations that I think are special. The first is the focus on patient goals of care at every point in these guidelines. The second is that the guidelines follow the real disease course and a real conversation that doctors and patients have at every step of the way to help guide the decisions that have to be made in real time.
A problem we have in the United States is that once patients enter a hospice, most will not allow blood transfusions. One reason is that some say it is antithetical to their philosophy and consider it aggressive care. The second reason is that, to be completely blunt, economically it doesn’t make sense for hospices to allow blood transfusions. The amount that they are reimbursed by Medicare is much lower than the cost of receiving blood in an infusion center.
We wanted to make a clear recommendation that we consider transfusions in a patient who is in a palliative care or hospice mode to be supportive and necessary, and that these should be provided to patients even if they are in hospice and, as always, if consistent with a patient’s goals of care.
Q: How does a patient’s age inform the discussion surrounding what intensity treatment to offer?
Dr. Sekeres: With younger adults, this is not as complicated a conversation. A younger person has a better chance of being cured with intensive chemotherapy and is much more likely to tolerate that intensive chemotherapy. For someone who is younger, we offer intensive chemotherapy and the chance of going into remission is higher, at 70%-80%. The chance of dying is lower, usually less than 5%. It is an easy decision to make.
For an older adult, the risk-benefit ratio shifts and it becomes a more complicated option. Less-intensive therapy or best supportive care or hospice become viable.
Q: Are there other factors confounding the treatment decision-making process in older adults with AML that practitioners should consider?
Dr. Sekeres: Someone who is older is making a different decision than I would. I have school-aged children and believe that my job as a parent is to successfully get them to adulthood, so I would take any treatment under the sun to make sure that happens. People who have lived a longer life than I have may have children and even grandchildren who are adults, and they might have different goals of care. My goals are not going to be the same as my patient’s goals.
It is also harder because patients who are older may feel that they have lived a good life and don’t need to go through heroic measures to try to be around as long as possible, and those goals may not align with the goals of that person’s children who want their parent to be around as long as possible. One of the confounding factors in this is navigating the different goals of the different family members.
Dr. Sekeres has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
A diagnosis of acute myeloid leukemia (AML) is particularly challenging in older adults, whose age makes them highly susceptible to the disease and treatment-related toxicity. To help patients and practitioners navigate the clinical decision-making process, the American Society of Hematology convened a panel of experts who conducted a thorough review of the literature. The result of their work can be found in a new set of guidelines for the treatment of newly diagnosed AML in older adults.
In an interview, Mikkael Sekeres, MD, chair of the ASH AML guideline panel and director of the Leukemia Program at Cleveland Clinic Taussig Cancer Institute in Cleveland, Ohio, shared the rationale behind the panel’s key recommendations and the importance of keeping the patient’s goals in mind.
Question: What is the average life expectancy of a 75-year-old developing AML compared with someone of the same age without AML?
Dr. Sekeres: A 75-year-old developing AML has an average life expectancy measured in fewer than 6 months. Somebody who is 75 without leukemia in the United States has a life expectancy that can be measured in a decade or more. AML is a really serious diagnosis when someone is older and significantly truncates expected survival.
Q: What is the median age at AML diagnosis in the United States?
Dr. Sekeres: About 67 years.
Q: What are the biological underpinnings for poor outcomes in older AML patients?
Dr. Sekeres: There are a few of them. Older adults with AML tend to have a leukemia that has evolved from a known or unknown previous bone marrow condition such as myelodysplastic syndrome. Older adults also have worse genetics driving their leukemia, which makes the leukemia cells more resistant to chemotherapy. And the leukemia cells may even have drug efflux pumps that extrude chemotherapy that tries to enter the cell. Finally, older adults are more likely to have comorbidities that make their ability to tolerate chemotherapy much lower than for younger adults.
Q: In someone who is newly diagnosed with AML, what initial options are they routinely given?
Dr. Sekeres: For someone who is older, we divide those options into three main categories.
The first is to take intensive chemotherapy, which requires a 4-6 week hospitalization and has a chance of getting somebody who is older into a remission of approximately 50%-60%. But this also carries with it significant treatment-related mortality that may be as high as 10%-20%. So I have to look my older patients in the eyes when I talk about intensive chemotherapy and say, “There is a 1 in 10 or 1 in 5 chance that you might not make it out of the hospital alive.”
The second prong is lower-dose therapy. While the more-intensive therapy requiring hospitalization does have a low, but real, chance of curing that person, less-intensive therapy is not curative. Our best hope with less-intensive therapy is that our patients enter a remission and live longer. With less-intensive therapy, the chance that someone will go into remission is probably around 20%, but again it is not curative. The flip side to that is that it improves a person’s immediate quality of life because they’re not in the hospital for 4-6 weeks.
The final prong is to discuss palliative care or hospice upfront. We designed these guidelines to be focused on a patient’s goals of therapy and to constantly revisit those goals to make sure that the treatment options we are offering are aligning with them.
Q: The panel’s first recommendation is to offer antileukemic therapy over best supportive care in patients who are appropriate candidates. Can you provide some context for this recommendation?
Dr. Sekeres: Doesn’t that strike you as funny that we even have to make a recommendation about getting chemotherapy? Some database studies conducted over the past 2 decades show that, as recently as 15 years ago, only one-third of patients who were over the age of 65 years received any type of chemotherapy for AML. More recently, as we have had a few more drugs available that allow us to use lower-dose approaches, that number has crept up to probably about 50%. We still have half the patients offered no therapy at all. So we felt that we had to deliberately make a recommendation saying that, if it aligns with the patients’ goals, they should be offered chemotherapy.
Q: The second recommendation is that patients considered candidates for intensive antileukemic therapy should receive it over less-intensive antileukemic therapy. How did you get to that recommendation?
Dr. Sekeres: There is a debate in our field about whether older adults should be offered intensive inpatient chemotherapy at all or whether we should be treating all of them with less-intensive therapy. There is not a huge amount of high-quality studies out there to answer some of these questions, in particular whether intensive chemotherapy should be recommended over less-intensive therapy. But with the available evidence, what we believe is that patients live longer if they are offered intensive antileukemic chemotherapy. So again, if it aligns with a patient’s goals, we support that patient receiving more-intensive therapy in the hospital.
Q: What does the panel recommend for patients who achieve remission after at least a single cycle of intensive antileukemic therapy and who are not candidates for allogeneic hematopoietic stem cell transplantation?
Dr. Sekeres: Once again, this may seem at first blush to be an obvious recommendation. The standard treatment of someone who is younger with AML is to offer intensive inpatient chemotherapy to induce remission. This is followed by a few cycles of chemotherapy, mostly in an outpatient setting, to consolidate that remission.
Q: What is the underlying philosophy for this approach?
Dr. Sekeres: Every time we give chemotherapy, we probably get about a 3-4 log kill of leukemia cells. Imagine when patients first present with AML, they may have 10 billion leukemia cells in their body. We are reducing that 3-4 log with the first course of chemotherapy.
When we then look at a bone marrow biopsy, it may appear to be normal. When leukemia is at a lower level in the body, we simply can’t see it using standard techniques. But that doesn’t mean the leukemia is gone. For younger patients, we give another cycle of chemotherapy, then another, then another, and then even another to reduce the number of leukemia cells left over in the body until that person has a durable remission and hopefully cure.
For someone who is older, the data are less clear. While some studies have shown that, if you give too much chemotherapy after the initial course, it doesn’t help that much, there is a paucity of studies that show that any chemotherapy at all after the first induction course is helpful. Consequently, we have to use indirect data. Older people who are long-term survivors from their acute leukemia always seem to have gotten more than one course of chemotherapy. In other words, the initial course of chemotherapy that a patient receives in the hospital isn’t enough. They should receive more than that.
Q: What about older adults with AML considered appropriate for antileukemic therapy but not for intensive antileukemic therapy?
Dr. Sekeres: This again gets to the question of what are a patient’s goals. It takes a very involved conversation with patients at the time of their AML diagnosis to determine whether they would want to pursue an aggressive approach or a less-aggressive approach. If a patients want a less-aggressive approach, and want nothing to do with a hospital stay, then they are also prioritizing initial quality of life. In this recommendation, based on existing studies, we didn’t have a preference for which of the available less-aggressive chemotherapies a person selects.
There’s also debate about what to do in those considered appropriate for antileukemic therapy, such as hypomethylating agents (azacitidine and decitabine) or low-dose cytarabine, but not for intensive antileukemic therapy. What did the available evidence seem to indicate about this issue?
There has been a lot of studies trying to add two drugs together to see if those do better than one drug alone in patients who are older and who choose less-intensive therapy. The majority of those studies have shown no advantage to getting two drugs over one drug.
Our recommendation is that in these situations a patient gets one drug, not two, but there are a couple of caveats. One caveat is that there has been a small study showing the effectiveness of one of those low-dose chemotherapies combined with the drug glasdegib. The second caveat is that there have been results presented combining one of these low-dose chemotherapies with the drug venetoclax. One of those was a negative study, and another was a positive study showing a survival advantage to the combination vs. the low-dose therapy alone. We had to couch our recommendation a little bit because we knew this other study had been presented at a conference, but it hadn’t come out in final form yet. It did recently, however, and we will now revisit this recommendation.
The other complicated aspect to this is that we weren’t 100% convinced that the combination of venetoclax with one of these lower-dose therapies is truly less-intensive therapy. We think it is starting to creep up toward more-intensive chemotherapy, even though it is commonly given to patients in the outpatient setting. It gets into the very complicated area of what are we defining as more-intensive therapy and less-intensive therapy.
Q: Is there a recommended strategy for older adults with AML who achieve a response after receiving less-intensive therapy?
Dr. Sekeres: This is also challenging because there are no randomized studies in which patients received less-intensive therapy for a finite period of time vs. receiving those therapies ad infinitum. Given the lack of data and also given a lot of anecdotal data out there about patients who stopped a certain therapy and relapsed thereafter, we recommended that patients continue the less-intensive therapy ad infinitum. So as long as they are receiving a response to that therapy, they continue on the drug.
Q: Of course, there are also unique considerations faced by older patients who are no longer receiving antileukemic therapy and have moved on to receiving end-of-life care or hospice care. What advice do the guidelines offer in this situation?
Dr. Sekeres: There are a lot of aspects of these recommendations that I think are special. The first is the focus on patient goals of care at every point in these guidelines. The second is that the guidelines follow the real disease course and a real conversation that doctors and patients have at every step of the way to help guide the decisions that have to be made in real time.
A problem we have in the United States is that once patients enter a hospice, most will not allow blood transfusions. One reason is that some say it is antithetical to their philosophy and consider it aggressive care. The second reason is that, to be completely blunt, economically it doesn’t make sense for hospices to allow blood transfusions. The amount that they are reimbursed by Medicare is much lower than the cost of receiving blood in an infusion center.
We wanted to make a clear recommendation that we consider transfusions in a patient who is in a palliative care or hospice mode to be supportive and necessary, and that these should be provided to patients even if they are in hospice and, as always, if consistent with a patient’s goals of care.
Q: How does a patient’s age inform the discussion surrounding what intensity treatment to offer?
Dr. Sekeres: With younger adults, this is not as complicated a conversation. A younger person has a better chance of being cured with intensive chemotherapy and is much more likely to tolerate that intensive chemotherapy. For someone who is younger, we offer intensive chemotherapy and the chance of going into remission is higher, at 70%-80%. The chance of dying is lower, usually less than 5%. It is an easy decision to make.
For an older adult, the risk-benefit ratio shifts and it becomes a more complicated option. Less-intensive therapy or best supportive care or hospice become viable.
Q: Are there other factors confounding the treatment decision-making process in older adults with AML that practitioners should consider?
Dr. Sekeres: Someone who is older is making a different decision than I would. I have school-aged children and believe that my job as a parent is to successfully get them to adulthood, so I would take any treatment under the sun to make sure that happens. People who have lived a longer life than I have may have children and even grandchildren who are adults, and they might have different goals of care. My goals are not going to be the same as my patient’s goals.
It is also harder because patients who are older may feel that they have lived a good life and don’t need to go through heroic measures to try to be around as long as possible, and those goals may not align with the goals of that person’s children who want their parent to be around as long as possible. One of the confounding factors in this is navigating the different goals of the different family members.
Dr. Sekeres has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
A diagnosis of acute myeloid leukemia (AML) is particularly challenging in older adults, whose age makes them highly susceptible to the disease and treatment-related toxicity. To help patients and practitioners navigate the clinical decision-making process, the American Society of Hematology convened a panel of experts who conducted a thorough review of the literature. The result of their work can be found in a new set of guidelines for the treatment of newly diagnosed AML in older adults.
In an interview, Mikkael Sekeres, MD, chair of the ASH AML guideline panel and director of the Leukemia Program at Cleveland Clinic Taussig Cancer Institute in Cleveland, Ohio, shared the rationale behind the panel’s key recommendations and the importance of keeping the patient’s goals in mind.
Question: What is the average life expectancy of a 75-year-old developing AML compared with someone of the same age without AML?
Dr. Sekeres: A 75-year-old developing AML has an average life expectancy measured in fewer than 6 months. Somebody who is 75 without leukemia in the United States has a life expectancy that can be measured in a decade or more. AML is a really serious diagnosis when someone is older and significantly truncates expected survival.
Q: What is the median age at AML diagnosis in the United States?
Dr. Sekeres: About 67 years.
Q: What are the biological underpinnings for poor outcomes in older AML patients?
Dr. Sekeres: There are a few of them. Older adults with AML tend to have a leukemia that has evolved from a known or unknown previous bone marrow condition such as myelodysplastic syndrome. Older adults also have worse genetics driving their leukemia, which makes the leukemia cells more resistant to chemotherapy. And the leukemia cells may even have drug efflux pumps that extrude chemotherapy that tries to enter the cell. Finally, older adults are more likely to have comorbidities that make their ability to tolerate chemotherapy much lower than for younger adults.
Q: In someone who is newly diagnosed with AML, what initial options are they routinely given?
Dr. Sekeres: For someone who is older, we divide those options into three main categories.
The first is to take intensive chemotherapy, which requires a 4-6 week hospitalization and has a chance of getting somebody who is older into a remission of approximately 50%-60%. But this also carries with it significant treatment-related mortality that may be as high as 10%-20%. So I have to look my older patients in the eyes when I talk about intensive chemotherapy and say, “There is a 1 in 10 or 1 in 5 chance that you might not make it out of the hospital alive.”
The second prong is lower-dose therapy. While the more-intensive therapy requiring hospitalization does have a low, but real, chance of curing that person, less-intensive therapy is not curative. Our best hope with less-intensive therapy is that our patients enter a remission and live longer. With less-intensive therapy, the chance that someone will go into remission is probably around 20%, but again it is not curative. The flip side to that is that it improves a person’s immediate quality of life because they’re not in the hospital for 4-6 weeks.
The final prong is to discuss palliative care or hospice upfront. We designed these guidelines to be focused on a patient’s goals of therapy and to constantly revisit those goals to make sure that the treatment options we are offering are aligning with them.
Q: The panel’s first recommendation is to offer antileukemic therapy over best supportive care in patients who are appropriate candidates. Can you provide some context for this recommendation?
Dr. Sekeres: Doesn’t that strike you as funny that we even have to make a recommendation about getting chemotherapy? Some database studies conducted over the past 2 decades show that, as recently as 15 years ago, only one-third of patients who were over the age of 65 years received any type of chemotherapy for AML. More recently, as we have had a few more drugs available that allow us to use lower-dose approaches, that number has crept up to probably about 50%. We still have half the patients offered no therapy at all. So we felt that we had to deliberately make a recommendation saying that, if it aligns with the patients’ goals, they should be offered chemotherapy.
Q: The second recommendation is that patients considered candidates for intensive antileukemic therapy should receive it over less-intensive antileukemic therapy. How did you get to that recommendation?
Dr. Sekeres: There is a debate in our field about whether older adults should be offered intensive inpatient chemotherapy at all or whether we should be treating all of them with less-intensive therapy. There is not a huge amount of high-quality studies out there to answer some of these questions, in particular whether intensive chemotherapy should be recommended over less-intensive therapy. But with the available evidence, what we believe is that patients live longer if they are offered intensive antileukemic chemotherapy. So again, if it aligns with a patient’s goals, we support that patient receiving more-intensive therapy in the hospital.
Q: What does the panel recommend for patients who achieve remission after at least a single cycle of intensive antileukemic therapy and who are not candidates for allogeneic hematopoietic stem cell transplantation?
Dr. Sekeres: Once again, this may seem at first blush to be an obvious recommendation. The standard treatment of someone who is younger with AML is to offer intensive inpatient chemotherapy to induce remission. This is followed by a few cycles of chemotherapy, mostly in an outpatient setting, to consolidate that remission.
Q: What is the underlying philosophy for this approach?
Dr. Sekeres: Every time we give chemotherapy, we probably get about a 3-4 log kill of leukemia cells. Imagine when patients first present with AML, they may have 10 billion leukemia cells in their body. We are reducing that 3-4 log with the first course of chemotherapy.
When we then look at a bone marrow biopsy, it may appear to be normal. When leukemia is at a lower level in the body, we simply can’t see it using standard techniques. But that doesn’t mean the leukemia is gone. For younger patients, we give another cycle of chemotherapy, then another, then another, and then even another to reduce the number of leukemia cells left over in the body until that person has a durable remission and hopefully cure.
For someone who is older, the data are less clear. While some studies have shown that, if you give too much chemotherapy after the initial course, it doesn’t help that much, there is a paucity of studies that show that any chemotherapy at all after the first induction course is helpful. Consequently, we have to use indirect data. Older people who are long-term survivors from their acute leukemia always seem to have gotten more than one course of chemotherapy. In other words, the initial course of chemotherapy that a patient receives in the hospital isn’t enough. They should receive more than that.
Q: What about older adults with AML considered appropriate for antileukemic therapy but not for intensive antileukemic therapy?
Dr. Sekeres: This again gets to the question of what are a patient’s goals. It takes a very involved conversation with patients at the time of their AML diagnosis to determine whether they would want to pursue an aggressive approach or a less-aggressive approach. If a patients want a less-aggressive approach, and want nothing to do with a hospital stay, then they are also prioritizing initial quality of life. In this recommendation, based on existing studies, we didn’t have a preference for which of the available less-aggressive chemotherapies a person selects.
There’s also debate about what to do in those considered appropriate for antileukemic therapy, such as hypomethylating agents (azacitidine and decitabine) or low-dose cytarabine, but not for intensive antileukemic therapy. What did the available evidence seem to indicate about this issue?
There has been a lot of studies trying to add two drugs together to see if those do better than one drug alone in patients who are older and who choose less-intensive therapy. The majority of those studies have shown no advantage to getting two drugs over one drug.
Our recommendation is that in these situations a patient gets one drug, not two, but there are a couple of caveats. One caveat is that there has been a small study showing the effectiveness of one of those low-dose chemotherapies combined with the drug glasdegib. The second caveat is that there have been results presented combining one of these low-dose chemotherapies with the drug venetoclax. One of those was a negative study, and another was a positive study showing a survival advantage to the combination vs. the low-dose therapy alone. We had to couch our recommendation a little bit because we knew this other study had been presented at a conference, but it hadn’t come out in final form yet. It did recently, however, and we will now revisit this recommendation.
The other complicated aspect to this is that we weren’t 100% convinced that the combination of venetoclax with one of these lower-dose therapies is truly less-intensive therapy. We think it is starting to creep up toward more-intensive chemotherapy, even though it is commonly given to patients in the outpatient setting. It gets into the very complicated area of what are we defining as more-intensive therapy and less-intensive therapy.
Q: Is there a recommended strategy for older adults with AML who achieve a response after receiving less-intensive therapy?
Dr. Sekeres: This is also challenging because there are no randomized studies in which patients received less-intensive therapy for a finite period of time vs. receiving those therapies ad infinitum. Given the lack of data and also given a lot of anecdotal data out there about patients who stopped a certain therapy and relapsed thereafter, we recommended that patients continue the less-intensive therapy ad infinitum. So as long as they are receiving a response to that therapy, they continue on the drug.
Q: Of course, there are also unique considerations faced by older patients who are no longer receiving antileukemic therapy and have moved on to receiving end-of-life care or hospice care. What advice do the guidelines offer in this situation?
Dr. Sekeres: There are a lot of aspects of these recommendations that I think are special. The first is the focus on patient goals of care at every point in these guidelines. The second is that the guidelines follow the real disease course and a real conversation that doctors and patients have at every step of the way to help guide the decisions that have to be made in real time.
A problem we have in the United States is that once patients enter a hospice, most will not allow blood transfusions. One reason is that some say it is antithetical to their philosophy and consider it aggressive care. The second reason is that, to be completely blunt, economically it doesn’t make sense for hospices to allow blood transfusions. The amount that they are reimbursed by Medicare is much lower than the cost of receiving blood in an infusion center.
We wanted to make a clear recommendation that we consider transfusions in a patient who is in a palliative care or hospice mode to be supportive and necessary, and that these should be provided to patients even if they are in hospice and, as always, if consistent with a patient’s goals of care.
Q: How does a patient’s age inform the discussion surrounding what intensity treatment to offer?
Dr. Sekeres: With younger adults, this is not as complicated a conversation. A younger person has a better chance of being cured with intensive chemotherapy and is much more likely to tolerate that intensive chemotherapy. For someone who is younger, we offer intensive chemotherapy and the chance of going into remission is higher, at 70%-80%. The chance of dying is lower, usually less than 5%. It is an easy decision to make.
For an older adult, the risk-benefit ratio shifts and it becomes a more complicated option. Less-intensive therapy or best supportive care or hospice become viable.
Q: Are there other factors confounding the treatment decision-making process in older adults with AML that practitioners should consider?
Dr. Sekeres: Someone who is older is making a different decision than I would. I have school-aged children and believe that my job as a parent is to successfully get them to adulthood, so I would take any treatment under the sun to make sure that happens. People who have lived a longer life than I have may have children and even grandchildren who are adults, and they might have different goals of care. My goals are not going to be the same as my patient’s goals.
It is also harder because patients who are older may feel that they have lived a good life and don’t need to go through heroic measures to try to be around as long as possible, and those goals may not align with the goals of that person’s children who want their parent to be around as long as possible. One of the confounding factors in this is navigating the different goals of the different family members.
Dr. Sekeres has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
A 31-year-old with a 3-week history of a waxing and waning, mildly pruritic eruption on his neck, chest, and back
Prurigo pigmentosa is an inflammatory disorder of uncertain etiology characterized by the eruption of erythematous, markedly pruritic, urticaria-like papules and vesicles on the posterior neck, mid- to upper back, and chest. Crops of papules appear rapidly and then involute within days, leaving behind postinflammatory hyperpigmentation in a netlike configuration. New papules may appear prior to resolution of hyperpigmented macules, resulting in a mixed presentation of erythematous papules overlying reticulated hyperpigmentation.1
The condition was initially described in Japanese individuals, and to date, most cases have occurred in this population.2 However, the incidence of prurigo pigmentosa is increasing worldwide, including in the United States, which has led to the identification of several metabolic risk factors including diabetes mellitus, fasting, and dieting, with the common etiologic endpoint of ketosis.3With the increasing popularity of diets with strict carbohydrate limits, often with the goal of ketosis, dermatologists should be aware of the clinical appearance and common history of this rash to facilitate prompt diagnosis and treatment.
Clinical exam with appropriate history is usually sufficient for diagnosis. However, biopsy with histopathologic analysis can be utilized to confirm atypical cases. Histopathologic findings depend on the stage of the lesion biopsied. The earliest finding is a shallow perivascular neutrophilic infiltrate, neutrophil exocytosis, and epidermal and superficial dermal edema. As lesions progress, the prominent findings include epidermal vesiculation with necrotic keratinocytes and a lichenoid infiltrate dominated by lymphocytes and eosinophils. In the final stages, lesions demonstrate variable parakeratosis and acanthosis, as well as prominent dermal melanophagia.1
Treatment of prurigo pigmentosa includes modification of the patient’s underlying health issues to avoid ketosis, and in the case of diet-induced ketosis, reinstitution of a more balanced diet with sufficient carbohydrates. In the case of the patient presented here, rash resolved 1 week following instruction to include more carbohydrates in his diet. For recalcitrant cases or those without a clear precipitating factor, the addition of oral antibiotics is often helpful. Tetracyclines or dapsone are typically employed, usually in courses of 1-2 months.3,4
Dr. Johnson is a PGY-4 dermatology resident at Carilion Clinic in Roanoke, Va. He provided the case and photos. Donna Bilu Martin, MD, is the editor of the column.
References
1. Boer A et al. Am J Dermatopathol. 2003 Apr;25(2):117-292.
2. Satter E et al. J Cutan Pathol. 2016 Oct;43(10):809-14.
3. Alshaya M et al. JAAD Case Rep. 2019 Jun 8;5(6):504-7.
4. Hartman M et al. Cutis. 2019 Mar;103(3):E10-3.
Prurigo pigmentosa is an inflammatory disorder of uncertain etiology characterized by the eruption of erythematous, markedly pruritic, urticaria-like papules and vesicles on the posterior neck, mid- to upper back, and chest. Crops of papules appear rapidly and then involute within days, leaving behind postinflammatory hyperpigmentation in a netlike configuration. New papules may appear prior to resolution of hyperpigmented macules, resulting in a mixed presentation of erythematous papules overlying reticulated hyperpigmentation.1
The condition was initially described in Japanese individuals, and to date, most cases have occurred in this population.2 However, the incidence of prurigo pigmentosa is increasing worldwide, including in the United States, which has led to the identification of several metabolic risk factors including diabetes mellitus, fasting, and dieting, with the common etiologic endpoint of ketosis.3With the increasing popularity of diets with strict carbohydrate limits, often with the goal of ketosis, dermatologists should be aware of the clinical appearance and common history of this rash to facilitate prompt diagnosis and treatment.
Clinical exam with appropriate history is usually sufficient for diagnosis. However, biopsy with histopathologic analysis can be utilized to confirm atypical cases. Histopathologic findings depend on the stage of the lesion biopsied. The earliest finding is a shallow perivascular neutrophilic infiltrate, neutrophil exocytosis, and epidermal and superficial dermal edema. As lesions progress, the prominent findings include epidermal vesiculation with necrotic keratinocytes and a lichenoid infiltrate dominated by lymphocytes and eosinophils. In the final stages, lesions demonstrate variable parakeratosis and acanthosis, as well as prominent dermal melanophagia.1
Treatment of prurigo pigmentosa includes modification of the patient’s underlying health issues to avoid ketosis, and in the case of diet-induced ketosis, reinstitution of a more balanced diet with sufficient carbohydrates. In the case of the patient presented here, rash resolved 1 week following instruction to include more carbohydrates in his diet. For recalcitrant cases or those without a clear precipitating factor, the addition of oral antibiotics is often helpful. Tetracyclines or dapsone are typically employed, usually in courses of 1-2 months.3,4
Dr. Johnson is a PGY-4 dermatology resident at Carilion Clinic in Roanoke, Va. He provided the case and photos. Donna Bilu Martin, MD, is the editor of the column.
References
1. Boer A et al. Am J Dermatopathol. 2003 Apr;25(2):117-292.
2. Satter E et al. J Cutan Pathol. 2016 Oct;43(10):809-14.
3. Alshaya M et al. JAAD Case Rep. 2019 Jun 8;5(6):504-7.
4. Hartman M et al. Cutis. 2019 Mar;103(3):E10-3.
Prurigo pigmentosa is an inflammatory disorder of uncertain etiology characterized by the eruption of erythematous, markedly pruritic, urticaria-like papules and vesicles on the posterior neck, mid- to upper back, and chest. Crops of papules appear rapidly and then involute within days, leaving behind postinflammatory hyperpigmentation in a netlike configuration. New papules may appear prior to resolution of hyperpigmented macules, resulting in a mixed presentation of erythematous papules overlying reticulated hyperpigmentation.1
The condition was initially described in Japanese individuals, and to date, most cases have occurred in this population.2 However, the incidence of prurigo pigmentosa is increasing worldwide, including in the United States, which has led to the identification of several metabolic risk factors including diabetes mellitus, fasting, and dieting, with the common etiologic endpoint of ketosis.3With the increasing popularity of diets with strict carbohydrate limits, often with the goal of ketosis, dermatologists should be aware of the clinical appearance and common history of this rash to facilitate prompt diagnosis and treatment.
Clinical exam with appropriate history is usually sufficient for diagnosis. However, biopsy with histopathologic analysis can be utilized to confirm atypical cases. Histopathologic findings depend on the stage of the lesion biopsied. The earliest finding is a shallow perivascular neutrophilic infiltrate, neutrophil exocytosis, and epidermal and superficial dermal edema. As lesions progress, the prominent findings include epidermal vesiculation with necrotic keratinocytes and a lichenoid infiltrate dominated by lymphocytes and eosinophils. In the final stages, lesions demonstrate variable parakeratosis and acanthosis, as well as prominent dermal melanophagia.1
Treatment of prurigo pigmentosa includes modification of the patient’s underlying health issues to avoid ketosis, and in the case of diet-induced ketosis, reinstitution of a more balanced diet with sufficient carbohydrates. In the case of the patient presented here, rash resolved 1 week following instruction to include more carbohydrates in his diet. For recalcitrant cases or those without a clear precipitating factor, the addition of oral antibiotics is often helpful. Tetracyclines or dapsone are typically employed, usually in courses of 1-2 months.3,4
Dr. Johnson is a PGY-4 dermatology resident at Carilion Clinic in Roanoke, Va. He provided the case and photos. Donna Bilu Martin, MD, is the editor of the column.
References
1. Boer A et al. Am J Dermatopathol. 2003 Apr;25(2):117-292.
2. Satter E et al. J Cutan Pathol. 2016 Oct;43(10):809-14.
3. Alshaya M et al. JAAD Case Rep. 2019 Jun 8;5(6):504-7.
4. Hartman M et al. Cutis. 2019 Mar;103(3):E10-3.
Adrenal vein sampling looms as choke point for aldosteronism assessment of hypertensives
At a time when new evidence strongly suggests that roughly a fifth of patents with hypertension have primary aldosteronism as the cause, other recent findings suggest that many of these possibly tens of millions of patients with aldosterone-driven high blood pressure may as a consequence need an expensive and not-widely-available diagnostic test – adrenal vein sampling – to determine whether they are candidates for a definitive surgical cure to their aldosteronism.
Some endocrinologists worry the worldwide infrastructure for running adrenal vein sampling (AVS) isn’t close to being in place to deliver on this looming need for patients with primary aldosteronism (PA), especially given the burgeoning numbers now being cited for PA prevalence.
“The system could be overwhelmed,” warned Robert M. Carey, MD, a cardiovascular endocrinologist and professor of medicine at the University of Virginia in Charlottesville. “Right now, adrenal vein sampling [AVS] is the gold standard,” for distinguishing unilateral and bilateral excess aldosterone secretion, “but not every radiologist can do AVS. Until we find a surrogate biomarker that can distinguish unilateral and bilateral PA” many patients will need AVS, Dr. Carey said in an interview.
“AVS is important for accurate lateralization of aldosterone excess in patients, but it may not be feasible for all patients with PA to undergo AVS. If the prevalence of PA truly is on the order of 15% [of all patients with hypertension] then health systems would be stretched to offer all of them AVS, which is technically challenging and requires dedicated training and is therefore limited to expert centers,” commented Jun Yang, MBBS, a cardiovascular endocrinologist at the Hudson Institute of Medical Research and a hypertension researcher at Monash University, both in Melbourne. “At Monash, our interventional radiologists have increased their [AVS] success rate from 40% to more than 90% during the past 10 years, and our waiting list for patients scheduled for AVS is now 3-4 months long,” Dr. Yang said in an interview.
Finding a unilateral adrenal nodule as the cause of PA means that surgical removal is an option, a step that often fully resolves the PA and normalizes blood pressure. Patients with a bilateral source of the aldosterone are not candidates for surgical cure and must be managed with medical treatment, usually a mineralocorticoid receptor antagonist such as spironolactone that can neutralize or at least reduce the impact of hyperaldosteronism.
AVS finds unilateral adenomas when imaging can’t
The evidence that raised concerns about the reliability of imaging as an easier and noninvasive means to identify hypertensive patients with PA and a unilateral adrenal nodule that makes them candidates for surgical removal to resolve their PA and hypertension came out in May 2020 in a review of 174 PA patients who underwent AVS at a single center in Calgary, Alta., during 2006-2018.
The review included 366 patients with PA referred to the University of Calgary for assessment, of whom 179 had no adrenal nodule visible with either CT or MRI imaging, with 174 of these patients also undergoing successful AVS. The procedure revealed 70 patients (40%) had unilateral aldosterone secretion (Can J Cardiol. 2020 May 16. doi: 10.1016/j.cjca.2020.05.013).
In an editorial about this report that appeared a few weeks later, Ross D. Feldman, MD, a hypertension-management researcher and professor of medicine at the University of Manitoba in Winnipeg, Man., said the finding was “amazing,” and “confirms that lateralization of aldosterone secretion in a patient with PA but without an identifiable mass on that side is not a zebra,” but instead a presentation that “occurs in almost half of patients with PA and no discernible adenoma on the side that lateralizes.” (Can J. Cardiol. 2020 Jul 3. doi: 10.1016/j.cjca.2020.06.022).
Although this was just one center’s experience, the authors are not alone in making this finding, although prior reports seem to have been largely forgotten or ignored until now.
“The discordance between AVS and adrenal imaging has been documented by numerous groups, and in our own experience [in Melbourne] around 40% of patients with unilateral aldosterone excess do not have a distinct unilateral adenoma on CT,” said Dr. Yang.
“Here’s the problem,” summed up Dr. Feldman in an interview. “Nearly half of patients with hyperaldosteronism don’t localize based on a CT or MRI, so you have to do AVS, but AVS is not generally available; it’s only at tertiary centers; and you have to do a lot of them,” to do them well. “It’s a half-day procedure, and you have to hit the correct adrenal vein.”
AVS for millions?
Compounding the challenge is the other bit of bombshell news recently dropped on the endocrinology and hypertension communities: PA may be much more prevalent that previously suspected, occurring in roughly 20% of patients with hypertension, according to study results that also came out in 2020 (Ann Int Med. 2020 Jul 7;173[1]:10-20).
The upshot, according to Dr. Feldman and others, is that researchers will need to find reliable criteria besides imaging for identifying PA patients with an increased likelihood of having a lateralized source for their excess aldosterone production. That’s “the only hope,” said Dr. Feldman, “so we won’t have to do AVS on 20 million Americans.”
Unfortunately, the path toward a successful screen to winnow down candidates for AVS has been long and not especially fruitful, with efforts dating back at least 50 years, and with one of the most recent efforts at stratifying PA patients by certain laboratory measures getting dismissed as producing a benefit that “might not be substantial,” wrote Michael Stowasser, MBBS, in a published commentary (J Hypertension. 2020 Jul;38[7]:1259-61).
In contrast to Dr. Feldman, Dr. Stowasser was more optimistic about the prospects for avoiding an immediate crisis in AVS assessment of PA patients, mostly because so few patients with PA are now identified by clinicians. Given the poor record clinicians have historically rung up diagnosing PA, “it would seem unlikely that we are going to be flooded with AVS requests any time soon,” he wrote. There is also reason to hope that increased demand for AVS will help broaden availability, and innovative testing methods promise to speed up the procedure, said Dr. Stowasser, a professor of medicine at the University of Queensland in Brisbane, Australia and director of the Endocrine Hypertension Research Centre at Greenslopes and Princess Alexandra Hospitals in Brisbane, in an interview.
But regardless of whether AVS testing becomes more available or streamlined, recent events suggest there will be little way to avoid eventually having to run millions of these diagnostic procedures.
Patients with PA “who decide they will not want surgery do not need AVS. For all other patients with PA, you need AVS. The medical system will just have to respond,” Dr. Carey concluded.
Dr. Carey, Dr. Yang, Dr. Feldman, and Dr. Stowasser had no relevant disclosures.
At a time when new evidence strongly suggests that roughly a fifth of patents with hypertension have primary aldosteronism as the cause, other recent findings suggest that many of these possibly tens of millions of patients with aldosterone-driven high blood pressure may as a consequence need an expensive and not-widely-available diagnostic test – adrenal vein sampling – to determine whether they are candidates for a definitive surgical cure to their aldosteronism.
Some endocrinologists worry the worldwide infrastructure for running adrenal vein sampling (AVS) isn’t close to being in place to deliver on this looming need for patients with primary aldosteronism (PA), especially given the burgeoning numbers now being cited for PA prevalence.
“The system could be overwhelmed,” warned Robert M. Carey, MD, a cardiovascular endocrinologist and professor of medicine at the University of Virginia in Charlottesville. “Right now, adrenal vein sampling [AVS] is the gold standard,” for distinguishing unilateral and bilateral excess aldosterone secretion, “but not every radiologist can do AVS. Until we find a surrogate biomarker that can distinguish unilateral and bilateral PA” many patients will need AVS, Dr. Carey said in an interview.
“AVS is important for accurate lateralization of aldosterone excess in patients, but it may not be feasible for all patients with PA to undergo AVS. If the prevalence of PA truly is on the order of 15% [of all patients with hypertension] then health systems would be stretched to offer all of them AVS, which is technically challenging and requires dedicated training and is therefore limited to expert centers,” commented Jun Yang, MBBS, a cardiovascular endocrinologist at the Hudson Institute of Medical Research and a hypertension researcher at Monash University, both in Melbourne. “At Monash, our interventional radiologists have increased their [AVS] success rate from 40% to more than 90% during the past 10 years, and our waiting list for patients scheduled for AVS is now 3-4 months long,” Dr. Yang said in an interview.
Finding a unilateral adrenal nodule as the cause of PA means that surgical removal is an option, a step that often fully resolves the PA and normalizes blood pressure. Patients with a bilateral source of the aldosterone are not candidates for surgical cure and must be managed with medical treatment, usually a mineralocorticoid receptor antagonist such as spironolactone that can neutralize or at least reduce the impact of hyperaldosteronism.
AVS finds unilateral adenomas when imaging can’t
The evidence that raised concerns about the reliability of imaging as an easier and noninvasive means to identify hypertensive patients with PA and a unilateral adrenal nodule that makes them candidates for surgical removal to resolve their PA and hypertension came out in May 2020 in a review of 174 PA patients who underwent AVS at a single center in Calgary, Alta., during 2006-2018.
The review included 366 patients with PA referred to the University of Calgary for assessment, of whom 179 had no adrenal nodule visible with either CT or MRI imaging, with 174 of these patients also undergoing successful AVS. The procedure revealed 70 patients (40%) had unilateral aldosterone secretion (Can J Cardiol. 2020 May 16. doi: 10.1016/j.cjca.2020.05.013).
In an editorial about this report that appeared a few weeks later, Ross D. Feldman, MD, a hypertension-management researcher and professor of medicine at the University of Manitoba in Winnipeg, Man., said the finding was “amazing,” and “confirms that lateralization of aldosterone secretion in a patient with PA but without an identifiable mass on that side is not a zebra,” but instead a presentation that “occurs in almost half of patients with PA and no discernible adenoma on the side that lateralizes.” (Can J. Cardiol. 2020 Jul 3. doi: 10.1016/j.cjca.2020.06.022).
Although this was just one center’s experience, the authors are not alone in making this finding, although prior reports seem to have been largely forgotten or ignored until now.
“The discordance between AVS and adrenal imaging has been documented by numerous groups, and in our own experience [in Melbourne] around 40% of patients with unilateral aldosterone excess do not have a distinct unilateral adenoma on CT,” said Dr. Yang.
“Here’s the problem,” summed up Dr. Feldman in an interview. “Nearly half of patients with hyperaldosteronism don’t localize based on a CT or MRI, so you have to do AVS, but AVS is not generally available; it’s only at tertiary centers; and you have to do a lot of them,” to do them well. “It’s a half-day procedure, and you have to hit the correct adrenal vein.”
AVS for millions?
Compounding the challenge is the other bit of bombshell news recently dropped on the endocrinology and hypertension communities: PA may be much more prevalent that previously suspected, occurring in roughly 20% of patients with hypertension, according to study results that also came out in 2020 (Ann Int Med. 2020 Jul 7;173[1]:10-20).
The upshot, according to Dr. Feldman and others, is that researchers will need to find reliable criteria besides imaging for identifying PA patients with an increased likelihood of having a lateralized source for their excess aldosterone production. That’s “the only hope,” said Dr. Feldman, “so we won’t have to do AVS on 20 million Americans.”
Unfortunately, the path toward a successful screen to winnow down candidates for AVS has been long and not especially fruitful, with efforts dating back at least 50 years, and with one of the most recent efforts at stratifying PA patients by certain laboratory measures getting dismissed as producing a benefit that “might not be substantial,” wrote Michael Stowasser, MBBS, in a published commentary (J Hypertension. 2020 Jul;38[7]:1259-61).
In contrast to Dr. Feldman, Dr. Stowasser was more optimistic about the prospects for avoiding an immediate crisis in AVS assessment of PA patients, mostly because so few patients with PA are now identified by clinicians. Given the poor record clinicians have historically rung up diagnosing PA, “it would seem unlikely that we are going to be flooded with AVS requests any time soon,” he wrote. There is also reason to hope that increased demand for AVS will help broaden availability, and innovative testing methods promise to speed up the procedure, said Dr. Stowasser, a professor of medicine at the University of Queensland in Brisbane, Australia and director of the Endocrine Hypertension Research Centre at Greenslopes and Princess Alexandra Hospitals in Brisbane, in an interview.
But regardless of whether AVS testing becomes more available or streamlined, recent events suggest there will be little way to avoid eventually having to run millions of these diagnostic procedures.
Patients with PA “who decide they will not want surgery do not need AVS. For all other patients with PA, you need AVS. The medical system will just have to respond,” Dr. Carey concluded.
Dr. Carey, Dr. Yang, Dr. Feldman, and Dr. Stowasser had no relevant disclosures.
At a time when new evidence strongly suggests that roughly a fifth of patents with hypertension have primary aldosteronism as the cause, other recent findings suggest that many of these possibly tens of millions of patients with aldosterone-driven high blood pressure may as a consequence need an expensive and not-widely-available diagnostic test – adrenal vein sampling – to determine whether they are candidates for a definitive surgical cure to their aldosteronism.
Some endocrinologists worry the worldwide infrastructure for running adrenal vein sampling (AVS) isn’t close to being in place to deliver on this looming need for patients with primary aldosteronism (PA), especially given the burgeoning numbers now being cited for PA prevalence.
“The system could be overwhelmed,” warned Robert M. Carey, MD, a cardiovascular endocrinologist and professor of medicine at the University of Virginia in Charlottesville. “Right now, adrenal vein sampling [AVS] is the gold standard,” for distinguishing unilateral and bilateral excess aldosterone secretion, “but not every radiologist can do AVS. Until we find a surrogate biomarker that can distinguish unilateral and bilateral PA” many patients will need AVS, Dr. Carey said in an interview.
“AVS is important for accurate lateralization of aldosterone excess in patients, but it may not be feasible for all patients with PA to undergo AVS. If the prevalence of PA truly is on the order of 15% [of all patients with hypertension] then health systems would be stretched to offer all of them AVS, which is technically challenging and requires dedicated training and is therefore limited to expert centers,” commented Jun Yang, MBBS, a cardiovascular endocrinologist at the Hudson Institute of Medical Research and a hypertension researcher at Monash University, both in Melbourne. “At Monash, our interventional radiologists have increased their [AVS] success rate from 40% to more than 90% during the past 10 years, and our waiting list for patients scheduled for AVS is now 3-4 months long,” Dr. Yang said in an interview.
Finding a unilateral adrenal nodule as the cause of PA means that surgical removal is an option, a step that often fully resolves the PA and normalizes blood pressure. Patients with a bilateral source of the aldosterone are not candidates for surgical cure and must be managed with medical treatment, usually a mineralocorticoid receptor antagonist such as spironolactone that can neutralize or at least reduce the impact of hyperaldosteronism.
AVS finds unilateral adenomas when imaging can’t
The evidence that raised concerns about the reliability of imaging as an easier and noninvasive means to identify hypertensive patients with PA and a unilateral adrenal nodule that makes them candidates for surgical removal to resolve their PA and hypertension came out in May 2020 in a review of 174 PA patients who underwent AVS at a single center in Calgary, Alta., during 2006-2018.
The review included 366 patients with PA referred to the University of Calgary for assessment, of whom 179 had no adrenal nodule visible with either CT or MRI imaging, with 174 of these patients also undergoing successful AVS. The procedure revealed 70 patients (40%) had unilateral aldosterone secretion (Can J Cardiol. 2020 May 16. doi: 10.1016/j.cjca.2020.05.013).
In an editorial about this report that appeared a few weeks later, Ross D. Feldman, MD, a hypertension-management researcher and professor of medicine at the University of Manitoba in Winnipeg, Man., said the finding was “amazing,” and “confirms that lateralization of aldosterone secretion in a patient with PA but without an identifiable mass on that side is not a zebra,” but instead a presentation that “occurs in almost half of patients with PA and no discernible adenoma on the side that lateralizes.” (Can J. Cardiol. 2020 Jul 3. doi: 10.1016/j.cjca.2020.06.022).
Although this was just one center’s experience, the authors are not alone in making this finding, although prior reports seem to have been largely forgotten or ignored until now.
“The discordance between AVS and adrenal imaging has been documented by numerous groups, and in our own experience [in Melbourne] around 40% of patients with unilateral aldosterone excess do not have a distinct unilateral adenoma on CT,” said Dr. Yang.
“Here’s the problem,” summed up Dr. Feldman in an interview. “Nearly half of patients with hyperaldosteronism don’t localize based on a CT or MRI, so you have to do AVS, but AVS is not generally available; it’s only at tertiary centers; and you have to do a lot of them,” to do them well. “It’s a half-day procedure, and you have to hit the correct adrenal vein.”
AVS for millions?
Compounding the challenge is the other bit of bombshell news recently dropped on the endocrinology and hypertension communities: PA may be much more prevalent that previously suspected, occurring in roughly 20% of patients with hypertension, according to study results that also came out in 2020 (Ann Int Med. 2020 Jul 7;173[1]:10-20).
The upshot, according to Dr. Feldman and others, is that researchers will need to find reliable criteria besides imaging for identifying PA patients with an increased likelihood of having a lateralized source for their excess aldosterone production. That’s “the only hope,” said Dr. Feldman, “so we won’t have to do AVS on 20 million Americans.”
Unfortunately, the path toward a successful screen to winnow down candidates for AVS has been long and not especially fruitful, with efforts dating back at least 50 years, and with one of the most recent efforts at stratifying PA patients by certain laboratory measures getting dismissed as producing a benefit that “might not be substantial,” wrote Michael Stowasser, MBBS, in a published commentary (J Hypertension. 2020 Jul;38[7]:1259-61).
In contrast to Dr. Feldman, Dr. Stowasser was more optimistic about the prospects for avoiding an immediate crisis in AVS assessment of PA patients, mostly because so few patients with PA are now identified by clinicians. Given the poor record clinicians have historically rung up diagnosing PA, “it would seem unlikely that we are going to be flooded with AVS requests any time soon,” he wrote. There is also reason to hope that increased demand for AVS will help broaden availability, and innovative testing methods promise to speed up the procedure, said Dr. Stowasser, a professor of medicine at the University of Queensland in Brisbane, Australia and director of the Endocrine Hypertension Research Centre at Greenslopes and Princess Alexandra Hospitals in Brisbane, in an interview.
But regardless of whether AVS testing becomes more available or streamlined, recent events suggest there will be little way to avoid eventually having to run millions of these diagnostic procedures.
Patients with PA “who decide they will not want surgery do not need AVS. For all other patients with PA, you need AVS. The medical system will just have to respond,” Dr. Carey concluded.
Dr. Carey, Dr. Yang, Dr. Feldman, and Dr. Stowasser had no relevant disclosures.