Background: Occupational burnout is more prevalent among physicians than among the general population, and physician burnout is associated with several negative clinical outcomes. However, little is known about the economic cost of this widespread issue.

Dr. Suojanen is a hospitalist at Vanderbilt University Medical Center, Nashville, Tenn.

Background: Occupational burnout is more prevalent among physicians than among the general population, and physician burnout is associated with several negative clinical outcomes. However, little is known about the economic cost of this widespread issue.

Dr. Suojanen is a hospitalist at Vanderbilt University Medical Center, Nashville, Tenn.

Background: Occupational burnout is more prevalent among physicians than among the general population, and physician burnout is associated with several negative clinical outcomes. However, little is known about the economic cost of this widespread issue.

Dr. Suojanen is a hospitalist at Vanderbilt University Medical Center, Nashville, Tenn.

Within minutes of her arrival at Community North Hospital in Indianapolis, Ramya Yeleti’s vital signs plummeted; her pulse was at 45 beats per minute and her ejection fraction was hovering near 10%. “I definitely thought there was a chance I would close my eyes and never open them again, but I only had a few seconds to process that,” she recalled. Then everything went black. Ramya fell unconscious as shock pads were positioned and a swarm of clinicians prepared to insert an Impella heart pump through a catheter into her aorta.

The third-year medical student and aspiring psychiatrist had been doing in-person neurology rotations in July when she began to experience fever and uncontrolled vomiting. Her initial thought was that she must have caught the flu from a patient.

After all, Ramya, along with her father Ram Yeleti, MD, mother Indira, and twin sister Divya, had all weathered COVID-19 in previous months and later tested positive for SARS-CoV-2 antibodies. The only family member who had been spared was her younger brother Rohith.

Indira suffered a severe case, requiring ICU care for 2 days but no ventilator; the others experienced mostly mild symptoms. Ramya — who was studying for her third-year board exams after classes at Marian University College of Osteopathic Medicine in Indianapolis went virtual in March — was left with lingering fatigue; however, her cough and muscle aches abated and her sense of taste and smell returned. When she started rotations, she thought her life was getting back to normal.

Ramya’s flu symptoms did not improve. A university-mandated rapid COVID test came back negative, but 2 more days of vomiting started to worry both her and her father, who is a cardiologist and chief physician executive at Community Health Network in Indianapolis. After Ramya felt some chest pain, she asked her father to listen to her heart. All sounded normal, and Ram prescribed ondansetron for her nausea.

But the antiemetic didn’t work, and by the next morning both father and daughter were convinced that they needed to head to the emergency department.

“I wanted to double-check if I was missing something about her being dehydrated,” Ram told Medscape Medical News. “Several things can cause protracted nausea, like hepatitis, appendicitis, or another infection. I feel terribly guilty I didn’t realize she had a heart condition.”
 

A surprising turn for the worst

Ramya’s subtle symptoms quickly gave way to the dramatic cardiac crisis that unfolded just after her arrival at Community North. “Her EKG looked absolutely horrendous, like a 75-year-old having a heart attack,” Ram said.

As a cardiologist, he knew his daughter’s situation was growing dire when he heard physicians shouting that the Impella wasn’t working and she needed extracorporeal membrane oxygenation (ECMO).

“At that point, I didn’t think she’d survive,” her father recalled. “We had 10 physicians in the room who worked on her for 5 hours to get her stabilized.”

“It was especially traumatic because, obviously, I knew exactly what was happening,” he added. “You can’t sugarcoat anything.”

After being connected to the heart–lung equipment, Ramya was transferred to IU Health Methodist Hospital, also in Indianapolis, where she was tested again for COVID-19. Unlike the rapid test administered just days earlier, the PCR assay came back positive.

“I knew she had acute myocarditis, but coronavirus never crossed my mind,” said Ram.

“As we were dealing with her heart, we were also dealing with this challenge: she was coming back positive for COVID-19 again,” said Roopa Rao, MD, the heart failure transplant cardiologist at IU Health who treated Ramya.

“We weren’t sure whether we were dealing with an active infection or dead virus” from her previous infection, Rao said, “so we started treating her like she had active COVID-19 and gave her remdesivir, convalescent plasma, and steroids, which was the protocol in our hospital.”

A biopsy of Ramya’s heart tissue, along with blood tests, indicated a past parvovirus infection. It’s possible that Ramya’s previous coronavirus infection made her susceptible to heart damage from a newer parvovirus infection, said Rao. Either virus, or both together, could have been responsible for the calamity.

Although it was unheard of during Ramya’s cardiac crisis in early August, evolving evidence now raises the possibility that she is one of a handful of people in the world to be reinfected with SARS-CoV-2. Also emerging are cases of COVID-related myocarditis and other extreme heart complications, particularly in young people.

“At the time, it wasn’t really clear if people could have another infection so quickly,” Rao told Medscape Medical News. “It is possible she is one of these rare individuals to have COVID-19 twice. I’m hoping at some point we will have some clarity.”

“I would favor a coinfection as probably the triggering factor for her sickness,” she said. “It may take some time, but like any other disease — and it doesn’t look like COVID will go away magically — I hope we’ll have some answers down the road.”
 

Another wrinkle

The next 48 hours brought astonishing news: Ramya’s heart function had rebounded to nearly normal, and her ejection fraction increased to about 45%. Heart transplantation wouldn’t be necessary, although Rao stood poised to follow through if ECMO only sustained, rather than improved, Ramya’s prognosis.

“Ramya was so sick that if she didn’t recover, the only option would be a heart transplant,” said Rao. “But we wanted to do everything to keep that heart.”

After steroid and COVID treatment, Ramya’s heart started to come back. “It didn’t make sense to me,” said Rao. “I don’t know what helped. If we hadn’t done ECMO, her heart probably wouldn’t have recovered, so I would say we have to support these patients and give them time for the heart to recover, even to the point of ECMO.”

Despite the good news, Ramya’s survival still hung in the balance. When she was disconnected from ECMO, clinicians discovered that the Impella device had caused a rare complication, damaging her mitral valve. The valve could be repaired surgically, but both Rao and Ram felt great trepidation at the prospect of cardiopulmonary bypass during the open-heart procedure.

“They would need to stop her heart and restart it, and I was concerned it would not restart,” Ram explained. “I didn’t like the idea of open-heart surgery, but my biggest fear was she was not going to survive it because of a really fresh, sick heart.”

The cardiologists’ fears did, in fact, come to pass: it took an hour to coax Ramya’s heart back at the end of surgery. But, just as the surgeon was preparing to reconnect Ramya to ECMO in desperation, “her heart recovered again,” Rao reported.

“Some things you never forget in life,” she said. “I can’t describe how everyone in the OR felt, all taking care of her. I told Ramya, ‘you are a fighter’.”
 

New strength

Six days would pass before Ramya woke up and learned of the astounding series of events that saved her. She knew “something was really wrong” because of the incision at the center of her chest, but learning she’d been on ECMO and the heart transplant list drove home how close to death she’d actually come.

“Most people don’t get off ECMO; they die on it,” she said. “And the chances of dying on the heart transplant list are very high. It was very strange to me that this was my story all of a sudden, when a week and a half earlier I was on rotation.”

Ongoing physical therapy over the past 3 months has transformed Ramya from a state of profound physical weakness to a place of relative strength. The now-fourth-year med student is turning 26 in November and is hungry to restart in-person rotations. Her downtime has been filled in part with researching myocarditis and collaborating with Rao on her own case study for journal publication.

But the mental trauma from her experience has girded her in ways she knows will make her stronger personally and professionally in the years ahead.

“It’s still very hard. I’m still recovering,” she acknowledged. “I described it to my therapist as an invisible wound on my brain.”

“When I came out of the hospital, I still had ECMO wounds, deep gashes on my legs that affected how fast and how long I could walk,” she said. “I felt like the same thing was going on my brain — a huge cut no one could see.”

Her intention to specialize in psychiatry has become more pressing now that Ramya has realized the impact of trauma on mental health.

“My body failing me was awful, but I could handle it,” she said. “Losing any part of my mind would have been way worse. I want to take care of that in my patients.”

This article first appeared on Medscape.com.

Within minutes of her arrival at Community North Hospital in Indianapolis, Ramya Yeleti’s vital signs plummeted; her pulse was at 45 beats per minute and her ejection fraction was hovering near 10%. “I definitely thought there was a chance I would close my eyes and never open them again, but I only had a few seconds to process that,” she recalled. Then everything went black. Ramya fell unconscious as shock pads were positioned and a swarm of clinicians prepared to insert an Impella heart pump through a catheter into her aorta.

The third-year medical student and aspiring psychiatrist had been doing in-person neurology rotations in July when she began to experience fever and uncontrolled vomiting. Her initial thought was that she must have caught the flu from a patient.

After all, Ramya, along with her father Ram Yeleti, MD, mother Indira, and twin sister Divya, had all weathered COVID-19 in previous months and later tested positive for SARS-CoV-2 antibodies. The only family member who had been spared was her younger brother Rohith.

Indira suffered a severe case, requiring ICU care for 2 days but no ventilator; the others experienced mostly mild symptoms. Ramya — who was studying for her third-year board exams after classes at Marian University College of Osteopathic Medicine in Indianapolis went virtual in March — was left with lingering fatigue; however, her cough and muscle aches abated and her sense of taste and smell returned. When she started rotations, she thought her life was getting back to normal.

Ramya’s flu symptoms did not improve. A university-mandated rapid COVID test came back negative, but 2 more days of vomiting started to worry both her and her father, who is a cardiologist and chief physician executive at Community Health Network in Indianapolis. After Ramya felt some chest pain, she asked her father to listen to her heart. All sounded normal, and Ram prescribed ondansetron for her nausea.

But the antiemetic didn’t work, and by the next morning both father and daughter were convinced that they needed to head to the emergency department.

“I wanted to double-check if I was missing something about her being dehydrated,” Ram told Medscape Medical News. “Several things can cause protracted nausea, like hepatitis, appendicitis, or another infection. I feel terribly guilty I didn’t realize she had a heart condition.”
 

A surprising turn for the worst

Ramya’s subtle symptoms quickly gave way to the dramatic cardiac crisis that unfolded just after her arrival at Community North. “Her EKG looked absolutely horrendous, like a 75-year-old having a heart attack,” Ram said.

As a cardiologist, he knew his daughter’s situation was growing dire when he heard physicians shouting that the Impella wasn’t working and she needed extracorporeal membrane oxygenation (ECMO).

“At that point, I didn’t think she’d survive,” her father recalled. “We had 10 physicians in the room who worked on her for 5 hours to get her stabilized.”

“It was especially traumatic because, obviously, I knew exactly what was happening,” he added. “You can’t sugarcoat anything.”

After being connected to the heart–lung equipment, Ramya was transferred to IU Health Methodist Hospital, also in Indianapolis, where she was tested again for COVID-19. Unlike the rapid test administered just days earlier, the PCR assay came back positive.

“I knew she had acute myocarditis, but coronavirus never crossed my mind,” said Ram.

“As we were dealing with her heart, we were also dealing with this challenge: she was coming back positive for COVID-19 again,” said Roopa Rao, MD, the heart failure transplant cardiologist at IU Health who treated Ramya.

“We weren’t sure whether we were dealing with an active infection or dead virus” from her previous infection, Rao said, “so we started treating her like she had active COVID-19 and gave her remdesivir, convalescent plasma, and steroids, which was the protocol in our hospital.”

A biopsy of Ramya’s heart tissue, along with blood tests, indicated a past parvovirus infection. It’s possible that Ramya’s previous coronavirus infection made her susceptible to heart damage from a newer parvovirus infection, said Rao. Either virus, or both together, could have been responsible for the calamity.

Although it was unheard of during Ramya’s cardiac crisis in early August, evolving evidence now raises the possibility that she is one of a handful of people in the world to be reinfected with SARS-CoV-2. Also emerging are cases of COVID-related myocarditis and other extreme heart complications, particularly in young people.

“At the time, it wasn’t really clear if people could have another infection so quickly,” Rao told Medscape Medical News. “It is possible she is one of these rare individuals to have COVID-19 twice. I’m hoping at some point we will have some clarity.”

“I would favor a coinfection as probably the triggering factor for her sickness,” she said. “It may take some time, but like any other disease — and it doesn’t look like COVID will go away magically — I hope we’ll have some answers down the road.”
 

Another wrinkle

The next 48 hours brought astonishing news: Ramya’s heart function had rebounded to nearly normal, and her ejection fraction increased to about 45%. Heart transplantation wouldn’t be necessary, although Rao stood poised to follow through if ECMO only sustained, rather than improved, Ramya’s prognosis.

“Ramya was so sick that if she didn’t recover, the only option would be a heart transplant,” said Rao. “But we wanted to do everything to keep that heart.”

After steroid and COVID treatment, Ramya’s heart started to come back. “It didn’t make sense to me,” said Rao. “I don’t know what helped. If we hadn’t done ECMO, her heart probably wouldn’t have recovered, so I would say we have to support these patients and give them time for the heart to recover, even to the point of ECMO.”

Despite the good news, Ramya’s survival still hung in the balance. When she was disconnected from ECMO, clinicians discovered that the Impella device had caused a rare complication, damaging her mitral valve. The valve could be repaired surgically, but both Rao and Ram felt great trepidation at the prospect of cardiopulmonary bypass during the open-heart procedure.

“They would need to stop her heart and restart it, and I was concerned it would not restart,” Ram explained. “I didn’t like the idea of open-heart surgery, but my biggest fear was she was not going to survive it because of a really fresh, sick heart.”

The cardiologists’ fears did, in fact, come to pass: it took an hour to coax Ramya’s heart back at the end of surgery. But, just as the surgeon was preparing to reconnect Ramya to ECMO in desperation, “her heart recovered again,” Rao reported.

“Some things you never forget in life,” she said. “I can’t describe how everyone in the OR felt, all taking care of her. I told Ramya, ‘you are a fighter’.”
 

New strength

Six days would pass before Ramya woke up and learned of the astounding series of events that saved her. She knew “something was really wrong” because of the incision at the center of her chest, but learning she’d been on ECMO and the heart transplant list drove home how close to death she’d actually come.

“Most people don’t get off ECMO; they die on it,” she said. “And the chances of dying on the heart transplant list are very high. It was very strange to me that this was my story all of a sudden, when a week and a half earlier I was on rotation.”

Ongoing physical therapy over the past 3 months has transformed Ramya from a state of profound physical weakness to a place of relative strength. The now-fourth-year med student is turning 26 in November and is hungry to restart in-person rotations. Her downtime has been filled in part with researching myocarditis and collaborating with Rao on her own case study for journal publication.

But the mental trauma from her experience has girded her in ways she knows will make her stronger personally and professionally in the years ahead.

“It’s still very hard. I’m still recovering,” she acknowledged. “I described it to my therapist as an invisible wound on my brain.”

“When I came out of the hospital, I still had ECMO wounds, deep gashes on my legs that affected how fast and how long I could walk,” she said. “I felt like the same thing was going on my brain — a huge cut no one could see.”

Her intention to specialize in psychiatry has become more pressing now that Ramya has realized the impact of trauma on mental health.

“My body failing me was awful, but I could handle it,” she said. “Losing any part of my mind would have been way worse. I want to take care of that in my patients.”

This article first appeared on Medscape.com.

Within minutes of her arrival at Community North Hospital in Indianapolis, Ramya Yeleti’s vital signs plummeted; her pulse was at 45 beats per minute and her ejection fraction was hovering near 10%. “I definitely thought there was a chance I would close my eyes and never open them again, but I only had a few seconds to process that,” she recalled. Then everything went black. Ramya fell unconscious as shock pads were positioned and a swarm of clinicians prepared to insert an Impella heart pump through a catheter into her aorta.

The third-year medical student and aspiring psychiatrist had been doing in-person neurology rotations in July when she began to experience fever and uncontrolled vomiting. Her initial thought was that she must have caught the flu from a patient.

After all, Ramya, along with her father Ram Yeleti, MD, mother Indira, and twin sister Divya, had all weathered COVID-19 in previous months and later tested positive for SARS-CoV-2 antibodies. The only family member who had been spared was her younger brother Rohith.

Indira suffered a severe case, requiring ICU care for 2 days but no ventilator; the others experienced mostly mild symptoms. Ramya — who was studying for her third-year board exams after classes at Marian University College of Osteopathic Medicine in Indianapolis went virtual in March — was left with lingering fatigue; however, her cough and muscle aches abated and her sense of taste and smell returned. When she started rotations, she thought her life was getting back to normal.

Ramya’s flu symptoms did not improve. A university-mandated rapid COVID test came back negative, but 2 more days of vomiting started to worry both her and her father, who is a cardiologist and chief physician executive at Community Health Network in Indianapolis. After Ramya felt some chest pain, she asked her father to listen to her heart. All sounded normal, and Ram prescribed ondansetron for her nausea.

But the antiemetic didn’t work, and by the next morning both father and daughter were convinced that they needed to head to the emergency department.

“I wanted to double-check if I was missing something about her being dehydrated,” Ram told Medscape Medical News. “Several things can cause protracted nausea, like hepatitis, appendicitis, or another infection. I feel terribly guilty I didn’t realize she had a heart condition.”
 

A surprising turn for the worst

Ramya’s subtle symptoms quickly gave way to the dramatic cardiac crisis that unfolded just after her arrival at Community North. “Her EKG looked absolutely horrendous, like a 75-year-old having a heart attack,” Ram said.

As a cardiologist, he knew his daughter’s situation was growing dire when he heard physicians shouting that the Impella wasn’t working and she needed extracorporeal membrane oxygenation (ECMO).

“At that point, I didn’t think she’d survive,” her father recalled. “We had 10 physicians in the room who worked on her for 5 hours to get her stabilized.”

“It was especially traumatic because, obviously, I knew exactly what was happening,” he added. “You can’t sugarcoat anything.”

After being connected to the heart–lung equipment, Ramya was transferred to IU Health Methodist Hospital, also in Indianapolis, where she was tested again for COVID-19. Unlike the rapid test administered just days earlier, the PCR assay came back positive.

“I knew she had acute myocarditis, but coronavirus never crossed my mind,” said Ram.

“As we were dealing with her heart, we were also dealing with this challenge: she was coming back positive for COVID-19 again,” said Roopa Rao, MD, the heart failure transplant cardiologist at IU Health who treated Ramya.

“We weren’t sure whether we were dealing with an active infection or dead virus” from her previous infection, Rao said, “so we started treating her like she had active COVID-19 and gave her remdesivir, convalescent plasma, and steroids, which was the protocol in our hospital.”

A biopsy of Ramya’s heart tissue, along with blood tests, indicated a past parvovirus infection. It’s possible that Ramya’s previous coronavirus infection made her susceptible to heart damage from a newer parvovirus infection, said Rao. Either virus, or both together, could have been responsible for the calamity.

Although it was unheard of during Ramya’s cardiac crisis in early August, evolving evidence now raises the possibility that she is one of a handful of people in the world to be reinfected with SARS-CoV-2. Also emerging are cases of COVID-related myocarditis and other extreme heart complications, particularly in young people.

“At the time, it wasn’t really clear if people could have another infection so quickly,” Rao told Medscape Medical News. “It is possible she is one of these rare individuals to have COVID-19 twice. I’m hoping at some point we will have some clarity.”

“I would favor a coinfection as probably the triggering factor for her sickness,” she said. “It may take some time, but like any other disease — and it doesn’t look like COVID will go away magically — I hope we’ll have some answers down the road.”
 

Another wrinkle

The next 48 hours brought astonishing news: Ramya’s heart function had rebounded to nearly normal, and her ejection fraction increased to about 45%. Heart transplantation wouldn’t be necessary, although Rao stood poised to follow through if ECMO only sustained, rather than improved, Ramya’s prognosis.

“Ramya was so sick that if she didn’t recover, the only option would be a heart transplant,” said Rao. “But we wanted to do everything to keep that heart.”

After steroid and COVID treatment, Ramya’s heart started to come back. “It didn’t make sense to me,” said Rao. “I don’t know what helped. If we hadn’t done ECMO, her heart probably wouldn’t have recovered, so I would say we have to support these patients and give them time for the heart to recover, even to the point of ECMO.”

Despite the good news, Ramya’s survival still hung in the balance. When she was disconnected from ECMO, clinicians discovered that the Impella device had caused a rare complication, damaging her mitral valve. The valve could be repaired surgically, but both Rao and Ram felt great trepidation at the prospect of cardiopulmonary bypass during the open-heart procedure.

“They would need to stop her heart and restart it, and I was concerned it would not restart,” Ram explained. “I didn’t like the idea of open-heart surgery, but my biggest fear was she was not going to survive it because of a really fresh, sick heart.”

The cardiologists’ fears did, in fact, come to pass: it took an hour to coax Ramya’s heart back at the end of surgery. But, just as the surgeon was preparing to reconnect Ramya to ECMO in desperation, “her heart recovered again,” Rao reported.

“Some things you never forget in life,” she said. “I can’t describe how everyone in the OR felt, all taking care of her. I told Ramya, ‘you are a fighter’.”
 

New strength

Six days would pass before Ramya woke up and learned of the astounding series of events that saved her. She knew “something was really wrong” because of the incision at the center of her chest, but learning she’d been on ECMO and the heart transplant list drove home how close to death she’d actually come.

“Most people don’t get off ECMO; they die on it,” she said. “And the chances of dying on the heart transplant list are very high. It was very strange to me that this was my story all of a sudden, when a week and a half earlier I was on rotation.”

Ongoing physical therapy over the past 3 months has transformed Ramya from a state of profound physical weakness to a place of relative strength. The now-fourth-year med student is turning 26 in November and is hungry to restart in-person rotations. Her downtime has been filled in part with researching myocarditis and collaborating with Rao on her own case study for journal publication.

But the mental trauma from her experience has girded her in ways she knows will make her stronger personally and professionally in the years ahead.

“It’s still very hard. I’m still recovering,” she acknowledged. “I described it to my therapist as an invisible wound on my brain.”

“When I came out of the hospital, I still had ECMO wounds, deep gashes on my legs that affected how fast and how long I could walk,” she said. “I felt like the same thing was going on my brain — a huge cut no one could see.”

Her intention to specialize in psychiatry has become more pressing now that Ramya has realized the impact of trauma on mental health.

“My body failing me was awful, but I could handle it,” she said. “Losing any part of my mind would have been way worse. I want to take care of that in my patients.”

This article first appeared on Medscape.com.

Telehealth has been steadily gaining mainstream use throughout the last decade, but the practice was recently shoved, almost overnight, into the forefront of the health care profession. Telehealth is now used more frequently by medical groups and physicians than ever before. General reports before the COVID-19 pandemic approximated 90% of health care organizations used or planned to use telehealth in the future. This future may already be a reality, with a McKinsey & Company report estimating that physicians saw 50-175 times more patients over telehealth platforms since the pandemic’s start.¹

In general, telehealth includes use of electronic communication and information technologies to deliver long-distance or remote health care. A physician’s use of telemedicine (clinical services) is one of the most common uses, but the industry also includes other professionals, such as pharmacists and nurses.

• Increased access to health care.
• Increased access to medical specialists in small and rural communities.
• Improved long-term care from the comfort of patients’ homes.
• Improved platforms to document patient care outside regular business hours.

But along with these benefits, telehealth carries the disadvantage of potential increased liability. This increased liability could stem from:

• Breached standards of care.
• Inadequate or improper licensing.
• Limited care options.
• Decision making without a proper physical exam.
• Increased informed consent requirements.
• Restricted prescription access.

Before expanding any practice into telemedicine, awareness of potential legal issues is crucial.

Standard of care

Currently, telehealth laws and regulations vary significantly from state to state. But one rule is consistent across the board – that the standard of care for practicing medicine through telemedicine is identical to the standard of care required for practicing medicine during physical practice. It still requires the appropriate examination, testing, labs, imaging, and consultations that any in-person diagnosis needs. For physicians, it also includes supervising nonphysician clinicians, where state law requires supervision.

The American Telemedicine Association currently determines the primary governing standards and guidelines for telemedicine. These can help physicians understand best practices in meeting the standard of care through telemedicine. The American Gastroenterological Association provides coding guidelines and other resources to help physicians with telehealth and e-visits. Other professional societies, such as the American College of Radiology and the American Academy of Dermatology, offer guidelines specific to their medical specialties’ standards of care. These standards still vary from state to state, so medical professionals must be aware of any differences before treating patients in multiple states.
 

Licensing

Licensing is one of telemedicine’s most confusing legal issues. All states require a license to practice medicine (traditional or telehealth) within their borders. Without that license, practicing medicine in the state is a crime. On top of being criminal, unlicensed practice can affect insurance, liability, billing, and malpractice coverage. When in a brick-and-mortar clinic, a physician’s confidence in practicing within the licensed jurisdiction is easy. Now, the distinction is not so clear. Patients and physicians no longer have to be in the same room, city, or even state, meaning there could be unknown conflicting laws between the two locations. With rare exceptions, standards of care are based on the patient’s location, not the physician’s location. This increases the risk of practicing without being correctly licensed to higher than ever.

Because licensing is a significant roadblock in providing telemedicine, efforts are underway to make the process simpler and more streamlined. The Federation of State Medical Boards developed the Interstate Medical Licensure Compact (IMLC).² This can qualify physicians to practice medicine across state lines within the compact so long as they meet specific eligibility requirements. The IMLC creates a fast-track option for physicians to fill out one application and receive licenses from multiple states at once. Currently, the compact includes 32 states, the District of Columbia, and Guam.³

Informed consent

Telemedicine health care still requires informed consent from patients. In fact, in some states, the requirements for care provided through telehealth are actually stricter than requirements for informed consent obtained in person.

Most informed consent laws require physicians to cover the risks and benefits of a recommended course of treatment and all feasible and reasonable material alternatives. On top of this traditional informed consent, physicians must get additional consent to receive care over a telehealth platform. This unique requirement explains what telehealth is, possible risks and expected benefits, and security measures used to protect patient information. States vary regarding when verbal consent is sufficient, and when written consent is required.
 

Prescriptions

Telemedicine is still a relatively new industry, and few legal opinions specifically address telemedicine malpractice. However, prescribing medication based on telemedicine information is among the few issues the courts have addressed. A 2008 decision found that a physician review of patient questionnaires submitted over the Internet was insufficient to prescribe medication without a physical examination determining patient health.⁴ This cautious approach stemmed from telehealth’s early concern about the absence of patient-physician relationships and potential online pharmacy abuse. Since this decision, many states require an “in-person” visit with a patient before prescribing medication. The definition of what qualifies as an in-person visit varies from state to state – some still consider the use of real-time, audiovisual conferencing sufficient.

The law is still evolving for prescriptions. Some states don’t allow any prescriptions, while others allow physicians to prescribe their patients’ medications as part of an appropriate treatment plan according to their professional discretion. Almost every state prohibits the prescription of controlled substances based on telemedicine.
 

Conclusion

Telemedicine is becoming an increasingly significant part of both physician-patient relationships and the broader health care industry. Used appropriately, it can be an incredibly effective method of care for physicians and patients. Physicians should learn the laws governing telemedicine in every state they want to practice and continue to stay current on any changes. The Center for Connected Health Policy offers a report, updated semiannually, to help physicians stay up to date on their state laws. These efforts will help prevent physicians from exposure to liability and medical malpractice claims.

Mr. Hyde is a partner at Younker Hyde Macfarlane, a law firm that focuses on prosecuting medical malpractice claims on behalf of injured patients. Ms. Johnson is an associate attorney with the firm. You can find them at YHMLaw.com.

References

1. Bestsennyy O, Harris A, Rost J. Telehealth: A quarter-trillion-dollar post-COVID-19 reality? Mckinsey & Company, May 29, 2020.

2. FSMB: Draft Interstate Compact for Physician Licensure Nears Completion, 2014.

3. Interstate Medical Licensure Compact: U.S. State Participation in the Compact.

4. See, Low Cost Pharm., Inc. v. Ariz. State Bd. Of Pharm, 2008 Ariz. App. Unpub. LEXIS 790, referencing conclusion of Arizona Medical Board.

Telehealth has been steadily gaining mainstream use throughout the last decade, but the practice was recently shoved, almost overnight, into the forefront of the health care profession. Telehealth is now used more frequently by medical groups and physicians than ever before. General reports before the COVID-19 pandemic approximated 90% of health care organizations used or planned to use telehealth in the future. This future may already be a reality, with a McKinsey & Company report estimating that physicians saw 50-175 times more patients over telehealth platforms since the pandemic’s start.¹

In general, telehealth includes use of electronic communication and information technologies to deliver long-distance or remote health care. A physician’s use of telemedicine (clinical services) is one of the most common uses, but the industry also includes other professionals, such as pharmacists and nurses.

• Increased access to health care.
• Increased access to medical specialists in small and rural communities.
• Improved long-term care from the comfort of patients’ homes.
• Improved platforms to document patient care outside regular business hours.

But along with these benefits, telehealth carries the disadvantage of potential increased liability. This increased liability could stem from:

• Breached standards of care.
• Inadequate or improper licensing.
• Limited care options.
• Decision making without a proper physical exam.
• Increased informed consent requirements.
• Restricted prescription access.

Before expanding any practice into telemedicine, awareness of potential legal issues is crucial.

Standard of care

Currently, telehealth laws and regulations vary significantly from state to state. But one rule is consistent across the board – that the standard of care for practicing medicine through telemedicine is identical to the standard of care required for practicing medicine during physical practice. It still requires the appropriate examination, testing, labs, imaging, and consultations that any in-person diagnosis needs. For physicians, it also includes supervising nonphysician clinicians, where state law requires supervision.

The American Telemedicine Association currently determines the primary governing standards and guidelines for telemedicine. These can help physicians understand best practices in meeting the standard of care through telemedicine. The American Gastroenterological Association provides coding guidelines and other resources to help physicians with telehealth and e-visits. Other professional societies, such as the American College of Radiology and the American Academy of Dermatology, offer guidelines specific to their medical specialties’ standards of care. These standards still vary from state to state, so medical professionals must be aware of any differences before treating patients in multiple states.
 

Licensing

Licensing is one of telemedicine’s most confusing legal issues. All states require a license to practice medicine (traditional or telehealth) within their borders. Without that license, practicing medicine in the state is a crime. On top of being criminal, unlicensed practice can affect insurance, liability, billing, and malpractice coverage. When in a brick-and-mortar clinic, a physician’s confidence in practicing within the licensed jurisdiction is easy. Now, the distinction is not so clear. Patients and physicians no longer have to be in the same room, city, or even state, meaning there could be unknown conflicting laws between the two locations. With rare exceptions, standards of care are based on the patient’s location, not the physician’s location. This increases the risk of practicing without being correctly licensed to higher than ever.

Because licensing is a significant roadblock in providing telemedicine, efforts are underway to make the process simpler and more streamlined. The Federation of State Medical Boards developed the Interstate Medical Licensure Compact (IMLC).² This can qualify physicians to practice medicine across state lines within the compact so long as they meet specific eligibility requirements. The IMLC creates a fast-track option for physicians to fill out one application and receive licenses from multiple states at once. Currently, the compact includes 32 states, the District of Columbia, and Guam.³

Informed consent

Telemedicine health care still requires informed consent from patients. In fact, in some states, the requirements for care provided through telehealth are actually stricter than requirements for informed consent obtained in person.

Most informed consent laws require physicians to cover the risks and benefits of a recommended course of treatment and all feasible and reasonable material alternatives. On top of this traditional informed consent, physicians must get additional consent to receive care over a telehealth platform. This unique requirement explains what telehealth is, possible risks and expected benefits, and security measures used to protect patient information. States vary regarding when verbal consent is sufficient, and when written consent is required.
 

Prescriptions

Telemedicine is still a relatively new industry, and few legal opinions specifically address telemedicine malpractice. However, prescribing medication based on telemedicine information is among the few issues the courts have addressed. A 2008 decision found that a physician review of patient questionnaires submitted over the Internet was insufficient to prescribe medication without a physical examination determining patient health.⁴ This cautious approach stemmed from telehealth’s early concern about the absence of patient-physician relationships and potential online pharmacy abuse. Since this decision, many states require an “in-person” visit with a patient before prescribing medication. The definition of what qualifies as an in-person visit varies from state to state – some still consider the use of real-time, audiovisual conferencing sufficient.

The law is still evolving for prescriptions. Some states don’t allow any prescriptions, while others allow physicians to prescribe their patients’ medications as part of an appropriate treatment plan according to their professional discretion. Almost every state prohibits the prescription of controlled substances based on telemedicine.
 

Conclusion

Telemedicine is becoming an increasingly significant part of both physician-patient relationships and the broader health care industry. Used appropriately, it can be an incredibly effective method of care for physicians and patients. Physicians should learn the laws governing telemedicine in every state they want to practice and continue to stay current on any changes. The Center for Connected Health Policy offers a report, updated semiannually, to help physicians stay up to date on their state laws. These efforts will help prevent physicians from exposure to liability and medical malpractice claims.

Mr. Hyde is a partner at Younker Hyde Macfarlane, a law firm that focuses on prosecuting medical malpractice claims on behalf of injured patients. Ms. Johnson is an associate attorney with the firm. You can find them at YHMLaw.com.

References

1. Bestsennyy O, Harris A, Rost J. Telehealth: A quarter-trillion-dollar post-COVID-19 reality? Mckinsey & Company, May 29, 2020.

2. FSMB: Draft Interstate Compact for Physician Licensure Nears Completion, 2014.

3. Interstate Medical Licensure Compact: U.S. State Participation in the Compact.

4. See, Low Cost Pharm., Inc. v. Ariz. State Bd. Of Pharm, 2008 Ariz. App. Unpub. LEXIS 790, referencing conclusion of Arizona Medical Board.

Telehealth has been steadily gaining mainstream use throughout the last decade, but the practice was recently shoved, almost overnight, into the forefront of the health care profession. Telehealth is now used more frequently by medical groups and physicians than ever before. General reports before the COVID-19 pandemic approximated 90% of health care organizations used or planned to use telehealth in the future. This future may already be a reality, with a McKinsey & Company report estimating that physicians saw 50-175 times more patients over telehealth platforms since the pandemic’s start.¹

In general, telehealth includes use of electronic communication and information technologies to deliver long-distance or remote health care. A physician’s use of telemedicine (clinical services) is one of the most common uses, but the industry also includes other professionals, such as pharmacists and nurses.

• Increased access to health care.
• Increased access to medical specialists in small and rural communities.
• Improved long-term care from the comfort of patients’ homes.
• Improved platforms to document patient care outside regular business hours.

But along with these benefits, telehealth carries the disadvantage of potential increased liability. This increased liability could stem from:

• Breached standards of care.
• Inadequate or improper licensing.
• Limited care options.
• Decision making without a proper physical exam.
• Increased informed consent requirements.
• Restricted prescription access.

Before expanding any practice into telemedicine, awareness of potential legal issues is crucial.

Standard of care

Currently, telehealth laws and regulations vary significantly from state to state. But one rule is consistent across the board – that the standard of care for practicing medicine through telemedicine is identical to the standard of care required for practicing medicine during physical practice. It still requires the appropriate examination, testing, labs, imaging, and consultations that any in-person diagnosis needs. For physicians, it also includes supervising nonphysician clinicians, where state law requires supervision.

The American Telemedicine Association currently determines the primary governing standards and guidelines for telemedicine. These can help physicians understand best practices in meeting the standard of care through telemedicine. The American Gastroenterological Association provides coding guidelines and other resources to help physicians with telehealth and e-visits. Other professional societies, such as the American College of Radiology and the American Academy of Dermatology, offer guidelines specific to their medical specialties’ standards of care. These standards still vary from state to state, so medical professionals must be aware of any differences before treating patients in multiple states.
 

Licensing

Licensing is one of telemedicine’s most confusing legal issues. All states require a license to practice medicine (traditional or telehealth) within their borders. Without that license, practicing medicine in the state is a crime. On top of being criminal, unlicensed practice can affect insurance, liability, billing, and malpractice coverage. When in a brick-and-mortar clinic, a physician’s confidence in practicing within the licensed jurisdiction is easy. Now, the distinction is not so clear. Patients and physicians no longer have to be in the same room, city, or even state, meaning there could be unknown conflicting laws between the two locations. With rare exceptions, standards of care are based on the patient’s location, not the physician’s location. This increases the risk of practicing without being correctly licensed to higher than ever.

Because licensing is a significant roadblock in providing telemedicine, efforts are underway to make the process simpler and more streamlined. The Federation of State Medical Boards developed the Interstate Medical Licensure Compact (IMLC).² This can qualify physicians to practice medicine across state lines within the compact so long as they meet specific eligibility requirements. The IMLC creates a fast-track option for physicians to fill out one application and receive licenses from multiple states at once. Currently, the compact includes 32 states, the District of Columbia, and Guam.³

Informed consent

Telemedicine health care still requires informed consent from patients. In fact, in some states, the requirements for care provided through telehealth are actually stricter than requirements for informed consent obtained in person.

Most informed consent laws require physicians to cover the risks and benefits of a recommended course of treatment and all feasible and reasonable material alternatives. On top of this traditional informed consent, physicians must get additional consent to receive care over a telehealth platform. This unique requirement explains what telehealth is, possible risks and expected benefits, and security measures used to protect patient information. States vary regarding when verbal consent is sufficient, and when written consent is required.
 

Prescriptions

Telemedicine is still a relatively new industry, and few legal opinions specifically address telemedicine malpractice. However, prescribing medication based on telemedicine information is among the few issues the courts have addressed. A 2008 decision found that a physician review of patient questionnaires submitted over the Internet was insufficient to prescribe medication without a physical examination determining patient health.⁴ This cautious approach stemmed from telehealth’s early concern about the absence of patient-physician relationships and potential online pharmacy abuse. Since this decision, many states require an “in-person” visit with a patient before prescribing medication. The definition of what qualifies as an in-person visit varies from state to state – some still consider the use of real-time, audiovisual conferencing sufficient.

The law is still evolving for prescriptions. Some states don’t allow any prescriptions, while others allow physicians to prescribe their patients’ medications as part of an appropriate treatment plan according to their professional discretion. Almost every state prohibits the prescription of controlled substances based on telemedicine.
 

Conclusion

Telemedicine is becoming an increasingly significant part of both physician-patient relationships and the broader health care industry. Used appropriately, it can be an incredibly effective method of care for physicians and patients. Physicians should learn the laws governing telemedicine in every state they want to practice and continue to stay current on any changes. The Center for Connected Health Policy offers a report, updated semiannually, to help physicians stay up to date on their state laws. These efforts will help prevent physicians from exposure to liability and medical malpractice claims.

Mr. Hyde is a partner at Younker Hyde Macfarlane, a law firm that focuses on prosecuting medical malpractice claims on behalf of injured patients. Ms. Johnson is an associate attorney with the firm. You can find them at YHMLaw.com.

References

1. Bestsennyy O, Harris A, Rost J. Telehealth: A quarter-trillion-dollar post-COVID-19 reality? Mckinsey & Company, May 29, 2020.

2. FSMB: Draft Interstate Compact for Physician Licensure Nears Completion, 2014.

3. Interstate Medical Licensure Compact: U.S. State Participation in the Compact.

4. See, Low Cost Pharm., Inc. v. Ariz. State Bd. Of Pharm, 2008 Ariz. App. Unpub. LEXIS 790, referencing conclusion of Arizona Medical Board.

For reasons unknown, about one in six people who recovered from COVID-19 subsequently retested positive at least 2 weeks later, researchers reported in a study in Italy.

Sore throat and rhinitis were the only symptoms associated with a positive result. “Patients who continued to have respiratory symptoms, especially, were more likely to have a new positive test result,” lead author Francesco Landi, MD, PhD, said in an interview.

“This suggests the persistence of respiratory symptoms should not be underestimated and should be adequately assessed in all patients considered recovered from COVID-19,” he said.

“The study results are interesting,” Akiko Iwasaki, PhD, an immunobiologist at Yale University and the Howard Hughes Medical Institute, both in New Haven, Conn.,, said in an interview. “There are other reports of RNA detection postdischarge, but this study ... found that only two symptoms out of many – sore throat and rhinitis – were higher in those with PCR [polymerase chain reaction]-positive status.”

The study was published online Sept. 18 in the American Journal of Preventive Medicine.

The findings could carry important implications for people who continue to be symptomatic. “It is reasonable to be cautious and avoid close contact with others, wear a face mask, and possibly undergo an additional nasopharyngeal swab,” said Dr. Landi, associate professor of internal medicine at Catholic University of the Sacred Heart in Rome.

“One of most interesting findings is that persistent symptoms do not correlate with PCR positivity, suggesting that symptoms are in many cases not due to ongoing viral replication,” Jonathan Karn, PhD, professor and chair of the department of molecular biology and microbiology at Case Western Reserve University, Cleveland, said in an interview.

“The key technical problem, which they have discussed, is that a viral RNA signal in the PCR assay does not necessarily mean that infectious virus is present,” Dr. Karn said. He added that new comprehensive viral RNA analyses would be needed to answer this question.
 

Official COVID-19 recovery

To identify risk factors and COVID-19 survivors more likely to retest positive, Dr. Landi and members of the Gemelli Against COVID-19 Post-Acute Care Study Group evaluated 131 people after hospital discharge.

All participants met World Health Organization criteria for release from isolation, including two negative test results at least 24 hours apart, and were studied between April 21 and May 21. Mean age was 56 and 39% were women. Only a slightly higher mean body mass index of 27.6 kg/m² in the positive group versus 25.9 in the negative group, was significant.

Although 51% of survivors reported fatigue, 44% had dyspnea, and 17% were coughing, the rates did not differ significantly between groups. In contrast, 18% of positive survivors and 4% of negative survivors had a sore throat (P = .04), and 27% versus 12%, respectively, reported rhinitis (P = .05).

People returned for follow-up visits a mean 17 days after the second negative swab test.
 

Asymptomatic COVID-19 carriers

“These findings indicate that a noteworthy rate of recovered patients with COVID-19 could still be asymptomatic carriers of the virus,” the researchers noted in the paper. “Even in the absence of specific guidelines, the 22 patients who tested positive for COVID-19 again were suggested to quarantine for a second time.”

No family member or close contact of the positive survivors reported SARS-CoV-2 infection. All patients continued to wear masks and observe social distancing recommendations, which makes it “very difficult to affirm whether these patients were really contagious,” the researchers noted.
 

Next steps

Evaluating all COVID-19 survivors to identify any who retest positive “will be a crucial contribution to a better understanding of both the natural history of COVID-19 as well as the public health implications of viral shedding,” the authors wrote.

One study limitation is that the reverse transcriptase–PCR test reveals genetic sequences specific to COVID-19. “It is important to underline that this is not a viral culture and cannot determine whether the virus is viable and transmissible,” the researchers noted.

“In this respect, we are trying to better understand if the persistence of long-time positive [reverse transcriptase]–PCR test for COVID-19 is really correlated to a potential contagiousness,” they added.

Dr. Landi and colleagues said their findings should be considered preliminary, and larger data samples are warranted to validate the results.

Dr. Landi and Dr. Karn disclosed no relevant financial relationships. Dr. Iwasaki disclosed a research grant from Condair, a 5% or greater equity interest in RIGImmune, and income of $250 or more from PureTec.

A version of this article originally appeared on Medscape.com.

For reasons unknown, about one in six people who recovered from COVID-19 subsequently retested positive at least 2 weeks later, researchers reported in a study in Italy.

Sore throat and rhinitis were the only symptoms associated with a positive result. “Patients who continued to have respiratory symptoms, especially, were more likely to have a new positive test result,” lead author Francesco Landi, MD, PhD, said in an interview.

“This suggests the persistence of respiratory symptoms should not be underestimated and should be adequately assessed in all patients considered recovered from COVID-19,” he said.

“The study results are interesting,” Akiko Iwasaki, PhD, an immunobiologist at Yale University and the Howard Hughes Medical Institute, both in New Haven, Conn.,, said in an interview. “There are other reports of RNA detection postdischarge, but this study ... found that only two symptoms out of many – sore throat and rhinitis – were higher in those with PCR [polymerase chain reaction]-positive status.”

The study was published online Sept. 18 in the American Journal of Preventive Medicine.

The findings could carry important implications for people who continue to be symptomatic. “It is reasonable to be cautious and avoid close contact with others, wear a face mask, and possibly undergo an additional nasopharyngeal swab,” said Dr. Landi, associate professor of internal medicine at Catholic University of the Sacred Heart in Rome.

“One of most interesting findings is that persistent symptoms do not correlate with PCR positivity, suggesting that symptoms are in many cases not due to ongoing viral replication,” Jonathan Karn, PhD, professor and chair of the department of molecular biology and microbiology at Case Western Reserve University, Cleveland, said in an interview.

“The key technical problem, which they have discussed, is that a viral RNA signal in the PCR assay does not necessarily mean that infectious virus is present,” Dr. Karn said. He added that new comprehensive viral RNA analyses would be needed to answer this question.
 

Official COVID-19 recovery

To identify risk factors and COVID-19 survivors more likely to retest positive, Dr. Landi and members of the Gemelli Against COVID-19 Post-Acute Care Study Group evaluated 131 people after hospital discharge.

All participants met World Health Organization criteria for release from isolation, including two negative test results at least 24 hours apart, and were studied between April 21 and May 21. Mean age was 56 and 39% were women. Only a slightly higher mean body mass index of 27.6 kg/m² in the positive group versus 25.9 in the negative group, was significant.

Although 51% of survivors reported fatigue, 44% had dyspnea, and 17% were coughing, the rates did not differ significantly between groups. In contrast, 18% of positive survivors and 4% of negative survivors had a sore throat (P = .04), and 27% versus 12%, respectively, reported rhinitis (P = .05).

People returned for follow-up visits a mean 17 days after the second negative swab test.
 

Asymptomatic COVID-19 carriers

“These findings indicate that a noteworthy rate of recovered patients with COVID-19 could still be asymptomatic carriers of the virus,” the researchers noted in the paper. “Even in the absence of specific guidelines, the 22 patients who tested positive for COVID-19 again were suggested to quarantine for a second time.”

No family member or close contact of the positive survivors reported SARS-CoV-2 infection. All patients continued to wear masks and observe social distancing recommendations, which makes it “very difficult to affirm whether these patients were really contagious,” the researchers noted.
 

Next steps

Evaluating all COVID-19 survivors to identify any who retest positive “will be a crucial contribution to a better understanding of both the natural history of COVID-19 as well as the public health implications of viral shedding,” the authors wrote.

One study limitation is that the reverse transcriptase–PCR test reveals genetic sequences specific to COVID-19. “It is important to underline that this is not a viral culture and cannot determine whether the virus is viable and transmissible,” the researchers noted.

“In this respect, we are trying to better understand if the persistence of long-time positive [reverse transcriptase]–PCR test for COVID-19 is really correlated to a potential contagiousness,” they added.

Dr. Landi and colleagues said their findings should be considered preliminary, and larger data samples are warranted to validate the results.

Dr. Landi and Dr. Karn disclosed no relevant financial relationships. Dr. Iwasaki disclosed a research grant from Condair, a 5% or greater equity interest in RIGImmune, and income of $250 or more from PureTec.

A version of this article originally appeared on Medscape.com.

For reasons unknown, about one in six people who recovered from COVID-19 subsequently retested positive at least 2 weeks later, researchers reported in a study in Italy.

Sore throat and rhinitis were the only symptoms associated with a positive result. “Patients who continued to have respiratory symptoms, especially, were more likely to have a new positive test result,” lead author Francesco Landi, MD, PhD, said in an interview.

“This suggests the persistence of respiratory symptoms should not be underestimated and should be adequately assessed in all patients considered recovered from COVID-19,” he said.

“The study results are interesting,” Akiko Iwasaki, PhD, an immunobiologist at Yale University and the Howard Hughes Medical Institute, both in New Haven, Conn.,, said in an interview. “There are other reports of RNA detection postdischarge, but this study ... found that only two symptoms out of many – sore throat and rhinitis – were higher in those with PCR [polymerase chain reaction]-positive status.”

The study was published online Sept. 18 in the American Journal of Preventive Medicine.

The findings could carry important implications for people who continue to be symptomatic. “It is reasonable to be cautious and avoid close contact with others, wear a face mask, and possibly undergo an additional nasopharyngeal swab,” said Dr. Landi, associate professor of internal medicine at Catholic University of the Sacred Heart in Rome.

“One of most interesting findings is that persistent symptoms do not correlate with PCR positivity, suggesting that symptoms are in many cases not due to ongoing viral replication,” Jonathan Karn, PhD, professor and chair of the department of molecular biology and microbiology at Case Western Reserve University, Cleveland, said in an interview.

“The key technical problem, which they have discussed, is that a viral RNA signal in the PCR assay does not necessarily mean that infectious virus is present,” Dr. Karn said. He added that new comprehensive viral RNA analyses would be needed to answer this question.
 

Official COVID-19 recovery

To identify risk factors and COVID-19 survivors more likely to retest positive, Dr. Landi and members of the Gemelli Against COVID-19 Post-Acute Care Study Group evaluated 131 people after hospital discharge.

All participants met World Health Organization criteria for release from isolation, including two negative test results at least 24 hours apart, and were studied between April 21 and May 21. Mean age was 56 and 39% were women. Only a slightly higher mean body mass index of 27.6 kg/m² in the positive group versus 25.9 in the negative group, was significant.

Although 51% of survivors reported fatigue, 44% had dyspnea, and 17% were coughing, the rates did not differ significantly between groups. In contrast, 18% of positive survivors and 4% of negative survivors had a sore throat (P = .04), and 27% versus 12%, respectively, reported rhinitis (P = .05).

People returned for follow-up visits a mean 17 days after the second negative swab test.
 

Asymptomatic COVID-19 carriers

“These findings indicate that a noteworthy rate of recovered patients with COVID-19 could still be asymptomatic carriers of the virus,” the researchers noted in the paper. “Even in the absence of specific guidelines, the 22 patients who tested positive for COVID-19 again were suggested to quarantine for a second time.”

No family member or close contact of the positive survivors reported SARS-CoV-2 infection. All patients continued to wear masks and observe social distancing recommendations, which makes it “very difficult to affirm whether these patients were really contagious,” the researchers noted.
 

Next steps

Evaluating all COVID-19 survivors to identify any who retest positive “will be a crucial contribution to a better understanding of both the natural history of COVID-19 as well as the public health implications of viral shedding,” the authors wrote.

One study limitation is that the reverse transcriptase–PCR test reveals genetic sequences specific to COVID-19. “It is important to underline that this is not a viral culture and cannot determine whether the virus is viable and transmissible,” the researchers noted.

“In this respect, we are trying to better understand if the persistence of long-time positive [reverse transcriptase]–PCR test for COVID-19 is really correlated to a potential contagiousness,” they added.

Dr. Landi and colleagues said their findings should be considered preliminary, and larger data samples are warranted to validate the results.

Dr. Landi and Dr. Karn disclosed no relevant financial relationships. Dr. Iwasaki disclosed a research grant from Condair, a 5% or greater equity interest in RIGImmune, and income of $250 or more from PureTec.

A version of this article originally appeared on Medscape.com.

Federal advisers who will help determine which Americans get the first COVID vaccines took an in-depth look Oct. 30 at the challenges they face in selecting priority groups.

The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) will face two key decisions once a COVID vaccine wins clearance from the US Food and Drug Administration (FDA).

ACIP will need to decide whether to recommend its use in adults (the age group in which vaccines are currently being tested). The group will also need to offer direction on which groups should get priority in vaccine allocation, inasmuch as early supplies will not be sufficient to vaccinate everyone.

At the Oct. 30 meeting, CDC’s Kathleen Dooling, MD, MPH, suggested that ACIP plan on tackling these issues as two separate questions when it comes time to weigh in on an approved vaccine. Although there was no formal vote among ACIP members at the meeting, Dooling’s proposal for tackling a future recommendation in a two-part fashion drew positive feedback.

ACIP member Katherine A. Poehling, MD, MPH, suggested that the panel and CDC be ready to reexamine the situation frequently regarding COVID vaccination. “Perhaps we could think about reviewing data on a monthly basis and updating the recommendation, so that we can account for the concerns and balance both the benefits and the [potential] harm,” Poehling said.

Dooling agreed. “Both the vaccine recommendation and allocation will be revisited in what is a very dynamic situation,” Dooling replied to Poehling. “So all new evidence will be brought to ACIP, and certainly the allocation as vaccine distribution proceeds will need to be adjusted accordingly.”
 

Ethics and limited evidence

During the meeting, ACIP members repeatedly expressed discomfort with the prospect of having to weigh in on widespread use of COVID vaccines on the basis of limited evidence.

Within months, FDA may opt for a special clearance, known as an emergency use authorization (EUA), for one or more of the experimental COVID vaccines now in advanced testing. Many of FDA’s past EUA clearances were granted for test kits. For those EUA approvals, the agency considered risks of false results but not longer-term, direct harm to patients from these products.

With a COVID vaccine, there will be strong pressure to distribute doses as quickly as possible with the hope of curbing the pandemic, which has already led to more than 229,000 deaths in the United States alone and has disrupted lives and economies around the world. But questions will persist about the possibility of serious complications from these vaccines, ACIP members noted.

“My personal struggle is the ethical side and how to balance these two,” said ACIP member Robert L. Atmar, MD, of Baylor College of Medicine, Houston, Texas, who noted that he expects his fellow panelists to share this concern.

Currently, four experimental COVID vaccines likely to be used in the United States have advanced to phase 3 testing. Pfizer Inc and BioNtech have enrolled more than 42,000 participants in a test of their candidate, BNT162b2 vaccine, and rival Moderna has enrolled about 30,000 participants in a test of its mRNA-1273 vaccine, CDC staff said.

The other two advanced COVID vaccine candidates have overcome recent hurdles. AstraZeneca Plc on Oct. 23 announced that FDA had removed a hold on the testing of its AZD1222 vaccine candidate; the trial will enroll approximately 30,000 people. Johnson & Johnson’s Janssen unit also announced that day the lifting of a safety pause for its Ad26.COV2.S vaccine; the phase 3 trial for that vaccine will enroll approximately 60,000 volunteers. Federal agencies, states, and territories have developed plans for future distribution of COVID vaccines, CDC staff said in briefing materials for today’s ACIP meeting.

Several ACIP members raised many of the same concerns that members of an FDA advisory committee raised at a meeting earlier in October. ACIP and FDA advisers honed in on the FDA’s decision to set a median follow-up duration of 2 months in phase 3 trials in connection with expected EUA applications for COVID-19 vaccines.

“I struggle with following people for 2 months after their second vaccination as a time point to start making final decisions about safety,” said ACIP member Sharon E. Frey, MD, a professor at St. Louis University School of Medicine, St. Louis, Missouri. “I just want to put that out there.”
 

Medical front line, then who?

There is consensus that healthcare workers be in the first stage ― Phase 1 ― of distribution. That recommendation was made in a report from the National Academies of Sciences, Engineering, and Medicine (NASEM). Phase 1A would include first responders; Phase 1B might include people of all ages who have two or more comorbidities that put them at significantly higher risk for COVID-19 or death, as well as older adults living in congregate or overcrowded settings, the NASEM report said.

A presentation from the CDC’s Matthew Biggerstaff, ScD, MPH, underscored challenges in distributing what are expected to be limited initial supplies of COVID vaccines.

Biggerstaff showed several scenarios the CDC’s Data, Analytics, and Modeling Task Force had studied. The initial allocation of vaccines would be for healthcare workers, followed by what the CDC called Phase 1B.

Choices for a rollout may include next giving COVID vaccines to people at high risk, such as persons who have one or more chronic medical conditions, including heart disease, diabetes, kidney disease, or obesity. Other options for the rollout could be to vaccinate people aged 65 years and older or essential workers whose employment puts them in contact with the public, thus raising the risk of contracting the virus.

The CDC’s research found that the greatest impact in preventing death was to initially vaccinate adults aged 65 and older in Phase 1B. The agency staff described this approach as likely to result in an about “1 to 11% increase in averted deaths across the scenarios.”

Initially vaccinating essential workers or high-risk adults in Phase 1B would avert the most infections. The agency staff described this approach as yielding about “1 to 5% increase in averted infections across the scenarios,” Biggerstaff said during his presentation.

The following are other findings of the CDC staff:

The earlier the vaccine rollout relative to increasing transmission, the greater the averted percentage and differences between the strategies.

Differences were not substantial in some scenarios.

The need to continue efforts to slow the spread of COVID-19 should be emphasized.

Adverse effects

ACIP members also heard about strategies for tracking potential side effects of future vaccines. A presentation by Tom Shimabukuro, MD, MPH, MBA, from the CDC’s COVID-19 Vaccine Task Force/Vaccine Safety Team, included details about a new smartphone-based active surveillance program for COVID-19 vaccine safety.

Known as v-safe, this system would use Web-based survey monitoring and incorporate text messaging. It would conduct electronic health checks on vaccine recipients, which would occur daily during the first week post vaccination and weekly thereafter for 6 weeks from the time of vaccination.

Clinicians “can play an important role in helping CDC enroll patients in v-safe at the time of vaccination,” Shimabukuro noted in his presentation. This would add another task, though, for clinicians, the CDC staff noted.
 

Pregnancy and breastfeeding are special concerns

Of special concern with the rollout of a COVID vaccine are recommendations regarding pregnancy and breastfeeding. Women constitute about 75% of the healthcare workforce, CDC staff noted.

At the time the initial ACIP COVID vaccination recommendations are made, there could be approximately 330,000 healthcare personnel who are pregnant or who have recently given birth. Available data indicate potentially increased risks for severe maternal illness and preterm birth associated with SARS-CoV-2 infection, said CDC’s Megan Wallace, DrPH, MPH, in a presentation for the Friday meeting.

In an Oct. 27 letter to ACIP, Chair Jose Romero, the American College of Obstetricians and Gynecologists (ACOG), urged the panel to ensure that pregnant women and new mothers in the healthcare workforce have priority access to a COVID vaccine. Pregnant and lactating women were “noticeably and alarmingly absent from the NASEM vaccine allocation plan for COVID-19,” wrote Christopher M. Zahn, MD, vice president for practice activities at ACOG, in the letter to Romero.

“ACOG urges ACIP to incorporate pregnant and lactating women clearly and explicitly into its COVID-19 vaccine allocation and prioritization framework,” Zahn wrote. “Should an Emergency Use Authorization be executed for one or more COVID-19 vaccines and provide a permissive recommendation for pregnant and lactating women, pregnant health care workers, pregnant first responders, and pregnant individuals with underlying conditions should be prioritized for vaccination alongside their non-pregnant peers.”

This article first appeared on Medscape.com.

Federal advisers who will help determine which Americans get the first COVID vaccines took an in-depth look Oct. 30 at the challenges they face in selecting priority groups.

The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) will face two key decisions once a COVID vaccine wins clearance from the US Food and Drug Administration (FDA).

ACIP will need to decide whether to recommend its use in adults (the age group in which vaccines are currently being tested). The group will also need to offer direction on which groups should get priority in vaccine allocation, inasmuch as early supplies will not be sufficient to vaccinate everyone.

At the Oct. 30 meeting, CDC’s Kathleen Dooling, MD, MPH, suggested that ACIP plan on tackling these issues as two separate questions when it comes time to weigh in on an approved vaccine. Although there was no formal vote among ACIP members at the meeting, Dooling’s proposal for tackling a future recommendation in a two-part fashion drew positive feedback.

ACIP member Katherine A. Poehling, MD, MPH, suggested that the panel and CDC be ready to reexamine the situation frequently regarding COVID vaccination. “Perhaps we could think about reviewing data on a monthly basis and updating the recommendation, so that we can account for the concerns and balance both the benefits and the [potential] harm,” Poehling said.

Dooling agreed. “Both the vaccine recommendation and allocation will be revisited in what is a very dynamic situation,” Dooling replied to Poehling. “So all new evidence will be brought to ACIP, and certainly the allocation as vaccine distribution proceeds will need to be adjusted accordingly.”
 

Ethics and limited evidence

During the meeting, ACIP members repeatedly expressed discomfort with the prospect of having to weigh in on widespread use of COVID vaccines on the basis of limited evidence.

Within months, FDA may opt for a special clearance, known as an emergency use authorization (EUA), for one or more of the experimental COVID vaccines now in advanced testing. Many of FDA’s past EUA clearances were granted for test kits. For those EUA approvals, the agency considered risks of false results but not longer-term, direct harm to patients from these products.

With a COVID vaccine, there will be strong pressure to distribute doses as quickly as possible with the hope of curbing the pandemic, which has already led to more than 229,000 deaths in the United States alone and has disrupted lives and economies around the world. But questions will persist about the possibility of serious complications from these vaccines, ACIP members noted.

“My personal struggle is the ethical side and how to balance these two,” said ACIP member Robert L. Atmar, MD, of Baylor College of Medicine, Houston, Texas, who noted that he expects his fellow panelists to share this concern.

Currently, four experimental COVID vaccines likely to be used in the United States have advanced to phase 3 testing. Pfizer Inc and BioNtech have enrolled more than 42,000 participants in a test of their candidate, BNT162b2 vaccine, and rival Moderna has enrolled about 30,000 participants in a test of its mRNA-1273 vaccine, CDC staff said.

The other two advanced COVID vaccine candidates have overcome recent hurdles. AstraZeneca Plc on Oct. 23 announced that FDA had removed a hold on the testing of its AZD1222 vaccine candidate; the trial will enroll approximately 30,000 people. Johnson & Johnson’s Janssen unit also announced that day the lifting of a safety pause for its Ad26.COV2.S vaccine; the phase 3 trial for that vaccine will enroll approximately 60,000 volunteers. Federal agencies, states, and territories have developed plans for future distribution of COVID vaccines, CDC staff said in briefing materials for today’s ACIP meeting.

Several ACIP members raised many of the same concerns that members of an FDA advisory committee raised at a meeting earlier in October. ACIP and FDA advisers honed in on the FDA’s decision to set a median follow-up duration of 2 months in phase 3 trials in connection with expected EUA applications for COVID-19 vaccines.

“I struggle with following people for 2 months after their second vaccination as a time point to start making final decisions about safety,” said ACIP member Sharon E. Frey, MD, a professor at St. Louis University School of Medicine, St. Louis, Missouri. “I just want to put that out there.”
 

Medical front line, then who?

There is consensus that healthcare workers be in the first stage ― Phase 1 ― of distribution. That recommendation was made in a report from the National Academies of Sciences, Engineering, and Medicine (NASEM). Phase 1A would include first responders; Phase 1B might include people of all ages who have two or more comorbidities that put them at significantly higher risk for COVID-19 or death, as well as older adults living in congregate or overcrowded settings, the NASEM report said.

A presentation from the CDC’s Matthew Biggerstaff, ScD, MPH, underscored challenges in distributing what are expected to be limited initial supplies of COVID vaccines.

Biggerstaff showed several scenarios the CDC’s Data, Analytics, and Modeling Task Force had studied. The initial allocation of vaccines would be for healthcare workers, followed by what the CDC called Phase 1B.

Choices for a rollout may include next giving COVID vaccines to people at high risk, such as persons who have one or more chronic medical conditions, including heart disease, diabetes, kidney disease, or obesity. Other options for the rollout could be to vaccinate people aged 65 years and older or essential workers whose employment puts them in contact with the public, thus raising the risk of contracting the virus.

The CDC’s research found that the greatest impact in preventing death was to initially vaccinate adults aged 65 and older in Phase 1B. The agency staff described this approach as likely to result in an about “1 to 11% increase in averted deaths across the scenarios.”

Initially vaccinating essential workers or high-risk adults in Phase 1B would avert the most infections. The agency staff described this approach as yielding about “1 to 5% increase in averted infections across the scenarios,” Biggerstaff said during his presentation.

The following are other findings of the CDC staff:

The earlier the vaccine rollout relative to increasing transmission, the greater the averted percentage and differences between the strategies.

Differences were not substantial in some scenarios.

The need to continue efforts to slow the spread of COVID-19 should be emphasized.

Adverse effects

ACIP members also heard about strategies for tracking potential side effects of future vaccines. A presentation by Tom Shimabukuro, MD, MPH, MBA, from the CDC’s COVID-19 Vaccine Task Force/Vaccine Safety Team, included details about a new smartphone-based active surveillance program for COVID-19 vaccine safety.

Known as v-safe, this system would use Web-based survey monitoring and incorporate text messaging. It would conduct electronic health checks on vaccine recipients, which would occur daily during the first week post vaccination and weekly thereafter for 6 weeks from the time of vaccination.

Clinicians “can play an important role in helping CDC enroll patients in v-safe at the time of vaccination,” Shimabukuro noted in his presentation. This would add another task, though, for clinicians, the CDC staff noted.
 

Pregnancy and breastfeeding are special concerns

Of special concern with the rollout of a COVID vaccine are recommendations regarding pregnancy and breastfeeding. Women constitute about 75% of the healthcare workforce, CDC staff noted.

At the time the initial ACIP COVID vaccination recommendations are made, there could be approximately 330,000 healthcare personnel who are pregnant or who have recently given birth. Available data indicate potentially increased risks for severe maternal illness and preterm birth associated with SARS-CoV-2 infection, said CDC’s Megan Wallace, DrPH, MPH, in a presentation for the Friday meeting.

In an Oct. 27 letter to ACIP, Chair Jose Romero, the American College of Obstetricians and Gynecologists (ACOG), urged the panel to ensure that pregnant women and new mothers in the healthcare workforce have priority access to a COVID vaccine. Pregnant and lactating women were “noticeably and alarmingly absent from the NASEM vaccine allocation plan for COVID-19,” wrote Christopher M. Zahn, MD, vice president for practice activities at ACOG, in the letter to Romero.

“ACOG urges ACIP to incorporate pregnant and lactating women clearly and explicitly into its COVID-19 vaccine allocation and prioritization framework,” Zahn wrote. “Should an Emergency Use Authorization be executed for one or more COVID-19 vaccines and provide a permissive recommendation for pregnant and lactating women, pregnant health care workers, pregnant first responders, and pregnant individuals with underlying conditions should be prioritized for vaccination alongside their non-pregnant peers.”

This article first appeared on Medscape.com.

Federal advisers who will help determine which Americans get the first COVID vaccines took an in-depth look Oct. 30 at the challenges they face in selecting priority groups.

The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) will face two key decisions once a COVID vaccine wins clearance from the US Food and Drug Administration (FDA).

ACIP will need to decide whether to recommend its use in adults (the age group in which vaccines are currently being tested). The group will also need to offer direction on which groups should get priority in vaccine allocation, inasmuch as early supplies will not be sufficient to vaccinate everyone.

At the Oct. 30 meeting, CDC’s Kathleen Dooling, MD, MPH, suggested that ACIP plan on tackling these issues as two separate questions when it comes time to weigh in on an approved vaccine. Although there was no formal vote among ACIP members at the meeting, Dooling’s proposal for tackling a future recommendation in a two-part fashion drew positive feedback.

ACIP member Katherine A. Poehling, MD, MPH, suggested that the panel and CDC be ready to reexamine the situation frequently regarding COVID vaccination. “Perhaps we could think about reviewing data on a monthly basis and updating the recommendation, so that we can account for the concerns and balance both the benefits and the [potential] harm,” Poehling said.

Dooling agreed. “Both the vaccine recommendation and allocation will be revisited in what is a very dynamic situation,” Dooling replied to Poehling. “So all new evidence will be brought to ACIP, and certainly the allocation as vaccine distribution proceeds will need to be adjusted accordingly.”
 

Ethics and limited evidence

During the meeting, ACIP members repeatedly expressed discomfort with the prospect of having to weigh in on widespread use of COVID vaccines on the basis of limited evidence.

Within months, FDA may opt for a special clearance, known as an emergency use authorization (EUA), for one or more of the experimental COVID vaccines now in advanced testing. Many of FDA’s past EUA clearances were granted for test kits. For those EUA approvals, the agency considered risks of false results but not longer-term, direct harm to patients from these products.

With a COVID vaccine, there will be strong pressure to distribute doses as quickly as possible with the hope of curbing the pandemic, which has already led to more than 229,000 deaths in the United States alone and has disrupted lives and economies around the world. But questions will persist about the possibility of serious complications from these vaccines, ACIP members noted.

“My personal struggle is the ethical side and how to balance these two,” said ACIP member Robert L. Atmar, MD, of Baylor College of Medicine, Houston, Texas, who noted that he expects his fellow panelists to share this concern.

Currently, four experimental COVID vaccines likely to be used in the United States have advanced to phase 3 testing. Pfizer Inc and BioNtech have enrolled more than 42,000 participants in a test of their candidate, BNT162b2 vaccine, and rival Moderna has enrolled about 30,000 participants in a test of its mRNA-1273 vaccine, CDC staff said.

The other two advanced COVID vaccine candidates have overcome recent hurdles. AstraZeneca Plc on Oct. 23 announced that FDA had removed a hold on the testing of its AZD1222 vaccine candidate; the trial will enroll approximately 30,000 people. Johnson & Johnson’s Janssen unit also announced that day the lifting of a safety pause for its Ad26.COV2.S vaccine; the phase 3 trial for that vaccine will enroll approximately 60,000 volunteers. Federal agencies, states, and territories have developed plans for future distribution of COVID vaccines, CDC staff said in briefing materials for today’s ACIP meeting.

Several ACIP members raised many of the same concerns that members of an FDA advisory committee raised at a meeting earlier in October. ACIP and FDA advisers honed in on the FDA’s decision to set a median follow-up duration of 2 months in phase 3 trials in connection with expected EUA applications for COVID-19 vaccines.

“I struggle with following people for 2 months after their second vaccination as a time point to start making final decisions about safety,” said ACIP member Sharon E. Frey, MD, a professor at St. Louis University School of Medicine, St. Louis, Missouri. “I just want to put that out there.”
 

Medical front line, then who?

There is consensus that healthcare workers be in the first stage ― Phase 1 ― of distribution. That recommendation was made in a report from the National Academies of Sciences, Engineering, and Medicine (NASEM). Phase 1A would include first responders; Phase 1B might include people of all ages who have two or more comorbidities that put them at significantly higher risk for COVID-19 or death, as well as older adults living in congregate or overcrowded settings, the NASEM report said.

A presentation from the CDC’s Matthew Biggerstaff, ScD, MPH, underscored challenges in distributing what are expected to be limited initial supplies of COVID vaccines.

Biggerstaff showed several scenarios the CDC’s Data, Analytics, and Modeling Task Force had studied. The initial allocation of vaccines would be for healthcare workers, followed by what the CDC called Phase 1B.

Choices for a rollout may include next giving COVID vaccines to people at high risk, such as persons who have one or more chronic medical conditions, including heart disease, diabetes, kidney disease, or obesity. Other options for the rollout could be to vaccinate people aged 65 years and older or essential workers whose employment puts them in contact with the public, thus raising the risk of contracting the virus.

The CDC’s research found that the greatest impact in preventing death was to initially vaccinate adults aged 65 and older in Phase 1B. The agency staff described this approach as likely to result in an about “1 to 11% increase in averted deaths across the scenarios.”

Initially vaccinating essential workers or high-risk adults in Phase 1B would avert the most infections. The agency staff described this approach as yielding about “1 to 5% increase in averted infections across the scenarios,” Biggerstaff said during his presentation.

The following are other findings of the CDC staff:

The earlier the vaccine rollout relative to increasing transmission, the greater the averted percentage and differences between the strategies.

Differences were not substantial in some scenarios.

The need to continue efforts to slow the spread of COVID-19 should be emphasized.

Adverse effects

ACIP members also heard about strategies for tracking potential side effects of future vaccines. A presentation by Tom Shimabukuro, MD, MPH, MBA, from the CDC’s COVID-19 Vaccine Task Force/Vaccine Safety Team, included details about a new smartphone-based active surveillance program for COVID-19 vaccine safety.

Known as v-safe, this system would use Web-based survey monitoring and incorporate text messaging. It would conduct electronic health checks on vaccine recipients, which would occur daily during the first week post vaccination and weekly thereafter for 6 weeks from the time of vaccination.

Clinicians “can play an important role in helping CDC enroll patients in v-safe at the time of vaccination,” Shimabukuro noted in his presentation. This would add another task, though, for clinicians, the CDC staff noted.
 

Pregnancy and breastfeeding are special concerns

Of special concern with the rollout of a COVID vaccine are recommendations regarding pregnancy and breastfeeding. Women constitute about 75% of the healthcare workforce, CDC staff noted.

At the time the initial ACIP COVID vaccination recommendations are made, there could be approximately 330,000 healthcare personnel who are pregnant or who have recently given birth. Available data indicate potentially increased risks for severe maternal illness and preterm birth associated with SARS-CoV-2 infection, said CDC’s Megan Wallace, DrPH, MPH, in a presentation for the Friday meeting.

In an Oct. 27 letter to ACIP, Chair Jose Romero, the American College of Obstetricians and Gynecologists (ACOG), urged the panel to ensure that pregnant women and new mothers in the healthcare workforce have priority access to a COVID vaccine. Pregnant and lactating women were “noticeably and alarmingly absent from the NASEM vaccine allocation plan for COVID-19,” wrote Christopher M. Zahn, MD, vice president for practice activities at ACOG, in the letter to Romero.

“ACOG urges ACIP to incorporate pregnant and lactating women clearly and explicitly into its COVID-19 vaccine allocation and prioritization framework,” Zahn wrote. “Should an Emergency Use Authorization be executed for one or more COVID-19 vaccines and provide a permissive recommendation for pregnant and lactating women, pregnant health care workers, pregnant first responders, and pregnant individuals with underlying conditions should be prioritized for vaccination alongside their non-pregnant peers.”

This article first appeared on Medscape.com.

“I disapprove of what you say, but I will defend to the death your right to say it.” The choice of the secretary general of the European Association for Cardio-Thoracic Surgery to open with this quote was the first hint that the next presentation at the 2019 annual meeting would be anything but dull. The session chair followed with a reminder to keep the discussion polite and civil.

Presenter David Taggart, MD, PhD, did not disappoint. The professor of cardiovascular surgery at the University of Oxford (England) began with the announcement that he had withdrawn his name from a recent paper in the New England Journal of Medicine. He then proceeded to accuse his coinvestigators of misrepresenting the findings of a major clinical trial.

Dr. Taggart was chair of the surgical committee for the Abbott-sponsored EXCEL trial, which compared two procedures for patients who had blockages in their left main coronary artery: percutaneous coronary intervention (PCI) using coronary stents, and coronary artery bypass graft surgery (CABG). The investigators designed the trial to compare outcomes for the two treatments using a composite endpoint of death, stroke, and MI. The 3-year follow-up data had been published in NEJM without controversy – or, at least, without public controversy.

But when it came time to publish the 5-year follow-up, there was a significantly higher rate of death in the stent group, and both Dr. Taggart and the journal editors were concerned that this finding was being downplayed in the manuscript.

In their comments to the authors, the journal editors had recommended including the mortality difference (unless clearly trivial) ‘”in the concluding statement in the final paragraph.” Yet, the concluding statement of the published paper read that there “was no significant difference between PCI and CABG.”

In Dr. Taggart’s view, that claim was dangerous for patients, and so he was left with no choice but to remove himself as an author, a first for the academic with over 300 scientific papers to his name.

Earlier publications from the EXCEL trial had influenced European treatment guidelines. But subsequent allegations of misconduct and hidden data spurred the EACTS to repudiate those guidelines out of concern “that some results in the EXCEL trial appear to have been concealed and that some patients may therefore have received the wrong clinical advice.”

The controversy pitted cardiothoracic surgeons against interventional cardiologists, who were seen as increasingly encroaching on the surgeons’ turf. Dr. Taggart was a long-time critic of the subspecialty.

Surgeons demanded an independent analysis of the EXCEL trial data – a demand that the investigators have yet to satisfy. Dr. Taggart was the first to speak publicly, but others had major reservations about the trial reporting and conduct years earlier.
 

Mortality data held back

One such person was Lars Wallentin, MD, a professor of cardiology at Uppsala (Sweden) University Hospital, who chaired the independent committee that monitored the safety and scientific validity of the EXCEL trial.

The committee, known as the data and safety monitoring board (DSMB), received a report on March 23, 2016, that showed that increasingly more patients who had received stents were dying, compared with the group of patients that had undergone CABG. A graph of the survival curves showed the gap between the two groups widening after 3 years (Figure 1).

By September of that year, Dr. Wallentin and other members of the DSMB were anxious to share the concerning mortality difference with the broader medical community.

They were aware that EACTS and the European Society of Cardiology had started the process of updating their guidelines on myocardial revascularization, and were keen for the guideline writing committee to see all of the data.

Meanwhile, the trial investigators, led by principal investigator Gregg Stone, MD, then at New York–Presbyterian Hospital and Columbia University Medical Center, were preparing to publish a report of the 3-year outcomes. Recruitment for EXCEL started in September 2010, so at the time of the 3-year analysis in 2016, some patients had been followed up for over 5 years. But the data, published in NEJM in October 2016, were capped at 3 years (Figure 2). It didn’t show the widening gap in late mortality that Dr. Wallentin and the rest of the DSMB had seen.

When asked about this, the investigators said they were transparent about their plans to cap the data at 3 years in an amendment to the study protocol. Stone’s coprincipal investigators were interventional cardiologist Patrick Serruys, MD, then of Imperial College London; and two surgeons: Joseph Sabik, MD, then of the Cleveland Clinic Foundation, and A. Pieter Kappetein, MD, PhD, then at Erasmus Medical Center, Rotterdam. The four principal investigators all declared financial payments from stent manufacturers either to themselves or their institutions.

Study sponsor Abbott has distanced itself from the decisions made and has referred all questions about the trial to the EXCEL investigators. Charles Simonton, chief medical officer at Abbott (now at Abiomed) was a coauthor on both the 3- and 5-year papers. Dr. Wallentin believes that the sponsor must have been aware of the DSMB’s concerns.
 

Continuing DSMB concerns

A year later, the DSMB was still troubled. Dr. Wallentin emailed Dr. Stone in September 2017 asking for an updated analysis of the mortality data without any capping in time.

Dr. Wallentin added that he didn’t think that unblinding the mortality results would be an issue at that stage because these were late deaths in a trial where the interventions were long completed. But, he warned, “it might be very concerning if, in the future, suspicions were raised that already available information on mortality was withheld from the cardiology and thoracic surgery community.”

The investigators took a month to respond. They declined the request, saying that the trial was not statistically powered to measure mortality. In his email to Dr. Wallentin, Dr. Stone stressed that they were committed to complete disclosure of all of the EXCEL data and that the responsible time point to unblind was after 4 years. His coprincipal investigators (Dr. Serruys, Dr. Sabik, and Dr. Kappetein) as well as EXCEL statistical committee chair Stuart Pocock, PhD, and Mr. Simonton were all copied on the email.

Dr. Wallentin deferred to the principal investigators’ arguments.
 

Missing MI data

Death was not the only outcome of the EXCEL trial to draw scrutiny.

The EXCEL investigators used a unique definition of MI that was almost exclusively based on a rise in the cardiac biomarker CK-MB. This protocol definition of MI was later adapted into the Society for Cardiovascular Angiography and Interventions definition in a paper coauthored by Dr. Stone. The investigators agreed to also measure MIs that met the more commonly used Third Universal Definition as a secondary endpoint. The Third Universal Definition of Myocardial Infarction uses a change in biomarkers – preferably troponin or alternatively CK-MB – coupled with other clinical signs.

It is standard practice to report secondary endpoints in any analysis of the main findings of a study. Yet, the EXCEL investigators did not report the universal definition of MI in either the 3-year or 5-year publications.

This is critical because MI according to one definition may not count according to the other, and the final tally could tip the trial results positive, negative, or neutral for coronary stents.

In Dr. Taggart’s opinion, the protocol definition puts CABG at a disadvantage because it uses the same biomarker threshold for procedural-related MI for both PCI and CABG. Because surgery involves more manipulation of the heart, cardiac enzyme levels will naturally be higher after CABG than PCI. These procedure-related enzyme elevations are not “true clinical MIs,” according to Dr. Taggart and others.

Late last year, a dataset containing the 3-year follow-up of EXCEL, including the information on the universal definition of MI, was leaked to the BBC. Working with biostatisticians, the BBC confirmed that according to this definition, there were more MIs in the stent group.

Originally, the investigators disputed the finding, calling the BBC data “imaginary.” They claimed that they were unable to calculate a rate of MI according to the universal definition because they lacked routine collection of troponins, although the universal definition also allows use of CK-MB. They have since published an analysis of 5-year MI data according to the universal definition, which showed twice the rate of MI in the PCI group.

From the leaked data, the BBC calculated the main composite endpoint of death, stroke, and MI using the universal definition of MI. Now the results swung in favor of CABG.
 

Impact on guidelines

None of this was known at the time the European cardiology societies convened a committee to write their new guidelines on myocardial revascularization. The writing panel disagreed about whether PCI and CABG were equivalent for patients with left main coronary artery disease (CAD).

Besides EXCEL, another study, the NOBLE trial, compared PCI and CABG in left main CAD and came to opposite conclusions – conclusions that matched the leaked data. In that trial, European investigators chose a slightly different primary endpoint: a composite of death, MI, stroke, and the need for a repeat procedure. They used the universal definition of MI exclusively, and notably, they omitted procedural MI from their clinical event count. The results, published at the same time as the EXCEL 3-year findings, suggested that CABG was better.

Given the discrepant findings of two large trials, the guideline committee considered all of the available data comparing the two methods of revascularization for left main CAD. But even then, things weren’t clear-cut. One draft meta-analysis, supported by the National Institute for Health Research, suggested that results were worse for first- and second-generation drug-eluting coronary stents – including those used in EXCEL – compared with surgery.

Another meta-analysis, later published in The Lancet, drew a different conclusion and found that PCI was just as good as surgery. The main author, Stuart Head, a cardiothoracic surgeon on the ESC/EACTS guideline committee, was a research fellow with EXCEL investigator Dr. Kappetein at Erasmus. EXCEL investigators Dr. Stone, Dr. Kappetein, and Dr. Serruys were coauthors of the Lancet meta-analysis.

There was heated discussion about the committee’s draft recommendations, which gave both CABG and PCI a Class IA recommendation in patients with left main CAD and low anatomical complexity. In October 2017, the ESC commissioned an anonymous external reviewer to weigh in. James Brophy, MD, PhD, a cardiologist and professor of medicine and epidemiology at McGill University, Montreal, confirmed that he was the reviewer after he published an updated version in June 2020.

Looking at all of the data available at the time comparing the procedures for left main CAD, Dr. Brophy’s analysis suggested a 73% chance that the excess in death, stroke, or MI represents at least two excess events per 100 patients treated with PCI rather than CABG.

Dr. Brophy thought that most patients would find these differences clinically meaningful and advised against giving both procedures the same class of recommendation. He was also concerned that many readers will skip to the summary recommendation table without reading the entire guideline document.

“I feel this is misleading in its present form,” he wrote in 2017.

Despite Dr. Brophy’s review, the guideline committee stuck with its original recommendations. The final 2018 ESC/EACTS Guidelines on myocardial revascularization gave equal weight to both CABG and PCI in patients with left main CAD and low anatomical complexity. In contrast, US guidelines do not put PCI and CABG on the same footing for any group of patients with left main CAD.

The lead author of the ESC/EACTS guidelines section on left main disease, and around a third of those on the writing task force, all declared financial payments from stent manufacturers either to themselves or their institutions. The EXCEL principal investigator, Dr. Kappetein, was secretary general of EACTS and oversaw the guidelines process for the surgical organization. He left to work for Medtronic midway through the process and was later joined there by his former research fellow, Stuart Head.

Dr. Brophy said in an interview that given the final guideline recommendations, he assumed that the committee had other reviews and went with the majority opinion.

But not everyone involved in the guidelines saw Dr. Brophy’s review. Nick Freemantle, a statistical reviewer appointed by EACTS, expected to see it but didn’t. This omission calls into question the neutrality of the whole process, in his view.

Mr. Freemantle believes that the deck was stacked so that he only saw the pieces of evidence that supported the conclusions that were already decided and that he was not shown “the bits that don’t fit that neatly.”

“And without that narrative, it all feels a bit grubby, to be honest,” he said.

Professor Barbara Casadei, ESC president, disputed this, saying that the guidelines were approved by all surgical members, including the EACTS council.

Missing from Dr. Brophy’s review were the later data from EXCEL. As he had told the DSMB in 2017, Stone presented the 4-year data from EXCEL at the TCT conference in September 2018. At this point, the analysis showed that 10.3% of people had died after PCI and 7.4% after CABG.

But this presentation was not given much prominence at the conference, which Dr. Stone organized, and occurred during a didactic session in a small room rather than on one of the main stages where the 3-year data from EXCEL were announced with much fanfare. The presentation also took place 3 weeks after the European guidelines were published.
 

Surgeons withdraw support

After the BBC report last year that the universal definition of MI data had been collected but not published in the 3-year follow-up manuscript, and showed more MI in the PCI group than the protocol definition, the EACTS withdrew its support for the guidelines. The ESC continued to uphold the guidelines «until there is robust scientific evidence (as opposed to allegations) indicating we should do otherwise,” said Ms. Casadei.

A spokesperson for NEJM said the journal stood by the EXCEL papers because “there is no credible harm to patients from the publication of the paper and accurate reporting of trial results.” NEJM has since conducted a review and published a series of letters in response. The letters have reinvigorated rather than appeased the dissenters, as reported by Medscape.

A number of cardiologists and researchers started a petition on change.org to revise the EACTS/ESC left main CAD guidelines, and surgical societies across the globe have written to the editor of NEJM asking him to retract or amend the EXCEL papers.

This has not happened. The journal’s editor maintains that the letters containing the analyses are “sufficient information” to allow readers and guideline authors to “evaluate the trial findings.”

Dr. Taggart was dismissive of that response. “There is still no recognition or acknowledgment that failure to publish these data in 2016 ‘misled’ the guideline writers for the ESC/EACTS guidelines, and there is still no formal correction of the 2016 and 2019 NEJM manuscripts.”

Over a year after the BBC received the leaked data, the EXCEL investigators published an analysis of the primary outcome using the universal definition of MI data in the Journal of the American College of Cardiology.

It shows 141 events in the PCI arm, compared with 102 in the CABG arm. The investigators acknowledge that the rates of procedural MI differ depending on the definition used. According to their analysis, the protocol definition was predictive of mortality after both treatments, whereas the universal definition of procedural MI was predictive of mortality only after CABG. Not everyone agrees with this interpretation, and an accompanying editorial questioned these conclusions.

For Dr. Wallentin, it’s a relief that these data are in the public domain so that their interpretation and clinical consequences can be “openly discussed.” He hoped that the whole experience will result in something constructive and useful for the future.

As for the guidelines, the tide may be turning.

In a joint statement with EACTS on Oct. 6, 2020, the ESC agreed to review its guidelines for left main disease in the light of emerging, longer-term outcome data from the trials of CABG versus PCI.

Dr. Taggart has no regrets about speaking out despite this being “an exceedingly painful and bruising experience.”

The saga, he said, “reflects very badly on our specialty, the investigators, industry, and the world’s ‘leading’ medical journal.”

This article first appeared on Medscape.com.

“I disapprove of what you say, but I will defend to the death your right to say it.” The choice of the secretary general of the European Association for Cardio-Thoracic Surgery to open with this quote was the first hint that the next presentation at the 2019 annual meeting would be anything but dull. The session chair followed with a reminder to keep the discussion polite and civil.

Presenter David Taggart, MD, PhD, did not disappoint. The professor of cardiovascular surgery at the University of Oxford (England) began with the announcement that he had withdrawn his name from a recent paper in the New England Journal of Medicine. He then proceeded to accuse his coinvestigators of misrepresenting the findings of a major clinical trial.

Dr. Taggart was chair of the surgical committee for the Abbott-sponsored EXCEL trial, which compared two procedures for patients who had blockages in their left main coronary artery: percutaneous coronary intervention (PCI) using coronary stents, and coronary artery bypass graft surgery (CABG). The investigators designed the trial to compare outcomes for the two treatments using a composite endpoint of death, stroke, and MI. The 3-year follow-up data had been published in NEJM without controversy – or, at least, without public controversy.

But when it came time to publish the 5-year follow-up, there was a significantly higher rate of death in the stent group, and both Dr. Taggart and the journal editors were concerned that this finding was being downplayed in the manuscript.

In their comments to the authors, the journal editors had recommended including the mortality difference (unless clearly trivial) ‘”in the concluding statement in the final paragraph.” Yet, the concluding statement of the published paper read that there “was no significant difference between PCI and CABG.”

In Dr. Taggart’s view, that claim was dangerous for patients, and so he was left with no choice but to remove himself as an author, a first for the academic with over 300 scientific papers to his name.

Earlier publications from the EXCEL trial had influenced European treatment guidelines. But subsequent allegations of misconduct and hidden data spurred the EACTS to repudiate those guidelines out of concern “that some results in the EXCEL trial appear to have been concealed and that some patients may therefore have received the wrong clinical advice.”

The controversy pitted cardiothoracic surgeons against interventional cardiologists, who were seen as increasingly encroaching on the surgeons’ turf. Dr. Taggart was a long-time critic of the subspecialty.

Surgeons demanded an independent analysis of the EXCEL trial data – a demand that the investigators have yet to satisfy. Dr. Taggart was the first to speak publicly, but others had major reservations about the trial reporting and conduct years earlier.
 

Mortality data held back

One such person was Lars Wallentin, MD, a professor of cardiology at Uppsala (Sweden) University Hospital, who chaired the independent committee that monitored the safety and scientific validity of the EXCEL trial.

The committee, known as the data and safety monitoring board (DSMB), received a report on March 23, 2016, that showed that increasingly more patients who had received stents were dying, compared with the group of patients that had undergone CABG. A graph of the survival curves showed the gap between the two groups widening after 3 years (Figure 1).

By September of that year, Dr. Wallentin and other members of the DSMB were anxious to share the concerning mortality difference with the broader medical community.

They were aware that EACTS and the European Society of Cardiology had started the process of updating their guidelines on myocardial revascularization, and were keen for the guideline writing committee to see all of the data.

Meanwhile, the trial investigators, led by principal investigator Gregg Stone, MD, then at New York–Presbyterian Hospital and Columbia University Medical Center, were preparing to publish a report of the 3-year outcomes. Recruitment for EXCEL started in September 2010, so at the time of the 3-year analysis in 2016, some patients had been followed up for over 5 years. But the data, published in NEJM in October 2016, were capped at 3 years (Figure 2). It didn’t show the widening gap in late mortality that Dr. Wallentin and the rest of the DSMB had seen.

When asked about this, the investigators said they were transparent about their plans to cap the data at 3 years in an amendment to the study protocol. Stone’s coprincipal investigators were interventional cardiologist Patrick Serruys, MD, then of Imperial College London; and two surgeons: Joseph Sabik, MD, then of the Cleveland Clinic Foundation, and A. Pieter Kappetein, MD, PhD, then at Erasmus Medical Center, Rotterdam. The four principal investigators all declared financial payments from stent manufacturers either to themselves or their institutions.

Study sponsor Abbott has distanced itself from the decisions made and has referred all questions about the trial to the EXCEL investigators. Charles Simonton, chief medical officer at Abbott (now at Abiomed) was a coauthor on both the 3- and 5-year papers. Dr. Wallentin believes that the sponsor must have been aware of the DSMB’s concerns.
 

Continuing DSMB concerns

A year later, the DSMB was still troubled. Dr. Wallentin emailed Dr. Stone in September 2017 asking for an updated analysis of the mortality data without any capping in time.

Dr. Wallentin added that he didn’t think that unblinding the mortality results would be an issue at that stage because these were late deaths in a trial where the interventions were long completed. But, he warned, “it might be very concerning if, in the future, suspicions were raised that already available information on mortality was withheld from the cardiology and thoracic surgery community.”

The investigators took a month to respond. They declined the request, saying that the trial was not statistically powered to measure mortality. In his email to Dr. Wallentin, Dr. Stone stressed that they were committed to complete disclosure of all of the EXCEL data and that the responsible time point to unblind was after 4 years. His coprincipal investigators (Dr. Serruys, Dr. Sabik, and Dr. Kappetein) as well as EXCEL statistical committee chair Stuart Pocock, PhD, and Mr. Simonton were all copied on the email.

Dr. Wallentin deferred to the principal investigators’ arguments.
 

Missing MI data

Death was not the only outcome of the EXCEL trial to draw scrutiny.

The EXCEL investigators used a unique definition of MI that was almost exclusively based on a rise in the cardiac biomarker CK-MB. This protocol definition of MI was later adapted into the Society for Cardiovascular Angiography and Interventions definition in a paper coauthored by Dr. Stone. The investigators agreed to also measure MIs that met the more commonly used Third Universal Definition as a secondary endpoint. The Third Universal Definition of Myocardial Infarction uses a change in biomarkers – preferably troponin or alternatively CK-MB – coupled with other clinical signs.

It is standard practice to report secondary endpoints in any analysis of the main findings of a study. Yet, the EXCEL investigators did not report the universal definition of MI in either the 3-year or 5-year publications.

This is critical because MI according to one definition may not count according to the other, and the final tally could tip the trial results positive, negative, or neutral for coronary stents.

In Dr. Taggart’s opinion, the protocol definition puts CABG at a disadvantage because it uses the same biomarker threshold for procedural-related MI for both PCI and CABG. Because surgery involves more manipulation of the heart, cardiac enzyme levels will naturally be higher after CABG than PCI. These procedure-related enzyme elevations are not “true clinical MIs,” according to Dr. Taggart and others.

Late last year, a dataset containing the 3-year follow-up of EXCEL, including the information on the universal definition of MI, was leaked to the BBC. Working with biostatisticians, the BBC confirmed that according to this definition, there were more MIs in the stent group.

Originally, the investigators disputed the finding, calling the BBC data “imaginary.” They claimed that they were unable to calculate a rate of MI according to the universal definition because they lacked routine collection of troponins, although the universal definition also allows use of CK-MB. They have since published an analysis of 5-year MI data according to the universal definition, which showed twice the rate of MI in the PCI group.

From the leaked data, the BBC calculated the main composite endpoint of death, stroke, and MI using the universal definition of MI. Now the results swung in favor of CABG.
 

Impact on guidelines

None of this was known at the time the European cardiology societies convened a committee to write their new guidelines on myocardial revascularization. The writing panel disagreed about whether PCI and CABG were equivalent for patients with left main coronary artery disease (CAD).

Besides EXCEL, another study, the NOBLE trial, compared PCI and CABG in left main CAD and came to opposite conclusions – conclusions that matched the leaked data. In that trial, European investigators chose a slightly different primary endpoint: a composite of death, MI, stroke, and the need for a repeat procedure. They used the universal definition of MI exclusively, and notably, they omitted procedural MI from their clinical event count. The results, published at the same time as the EXCEL 3-year findings, suggested that CABG was better.

Given the discrepant findings of two large trials, the guideline committee considered all of the available data comparing the two methods of revascularization for left main CAD. But even then, things weren’t clear-cut. One draft meta-analysis, supported by the National Institute for Health Research, suggested that results were worse for first- and second-generation drug-eluting coronary stents – including those used in EXCEL – compared with surgery.

Another meta-analysis, later published in The Lancet, drew a different conclusion and found that PCI was just as good as surgery. The main author, Stuart Head, a cardiothoracic surgeon on the ESC/EACTS guideline committee, was a research fellow with EXCEL investigator Dr. Kappetein at Erasmus. EXCEL investigators Dr. Stone, Dr. Kappetein, and Dr. Serruys were coauthors of the Lancet meta-analysis.

There was heated discussion about the committee’s draft recommendations, which gave both CABG and PCI a Class IA recommendation in patients with left main CAD and low anatomical complexity. In October 2017, the ESC commissioned an anonymous external reviewer to weigh in. James Brophy, MD, PhD, a cardiologist and professor of medicine and epidemiology at McGill University, Montreal, confirmed that he was the reviewer after he published an updated version in June 2020.

Looking at all of the data available at the time comparing the procedures for left main CAD, Dr. Brophy’s analysis suggested a 73% chance that the excess in death, stroke, or MI represents at least two excess events per 100 patients treated with PCI rather than CABG.

Dr. Brophy thought that most patients would find these differences clinically meaningful and advised against giving both procedures the same class of recommendation. He was also concerned that many readers will skip to the summary recommendation table without reading the entire guideline document.

“I feel this is misleading in its present form,” he wrote in 2017.

Despite Dr. Brophy’s review, the guideline committee stuck with its original recommendations. The final 2018 ESC/EACTS Guidelines on myocardial revascularization gave equal weight to both CABG and PCI in patients with left main CAD and low anatomical complexity. In contrast, US guidelines do not put PCI and CABG on the same footing for any group of patients with left main CAD.

The lead author of the ESC/EACTS guidelines section on left main disease, and around a third of those on the writing task force, all declared financial payments from stent manufacturers either to themselves or their institutions. The EXCEL principal investigator, Dr. Kappetein, was secretary general of EACTS and oversaw the guidelines process for the surgical organization. He left to work for Medtronic midway through the process and was later joined there by his former research fellow, Stuart Head.

Dr. Brophy said in an interview that given the final guideline recommendations, he assumed that the committee had other reviews and went with the majority opinion.

But not everyone involved in the guidelines saw Dr. Brophy’s review. Nick Freemantle, a statistical reviewer appointed by EACTS, expected to see it but didn’t. This omission calls into question the neutrality of the whole process, in his view.

Mr. Freemantle believes that the deck was stacked so that he only saw the pieces of evidence that supported the conclusions that were already decided and that he was not shown “the bits that don’t fit that neatly.”

“And without that narrative, it all feels a bit grubby, to be honest,” he said.

Professor Barbara Casadei, ESC president, disputed this, saying that the guidelines were approved by all surgical members, including the EACTS council.

Missing from Dr. Brophy’s review were the later data from EXCEL. As he had told the DSMB in 2017, Stone presented the 4-year data from EXCEL at the TCT conference in September 2018. At this point, the analysis showed that 10.3% of people had died after PCI and 7.4% after CABG.

But this presentation was not given much prominence at the conference, which Dr. Stone organized, and occurred during a didactic session in a small room rather than on one of the main stages where the 3-year data from EXCEL were announced with much fanfare. The presentation also took place 3 weeks after the European guidelines were published.
 

Surgeons withdraw support

After the BBC report last year that the universal definition of MI data had been collected but not published in the 3-year follow-up manuscript, and showed more MI in the PCI group than the protocol definition, the EACTS withdrew its support for the guidelines. The ESC continued to uphold the guidelines «until there is robust scientific evidence (as opposed to allegations) indicating we should do otherwise,” said Ms. Casadei.

A spokesperson for NEJM said the journal stood by the EXCEL papers because “there is no credible harm to patients from the publication of the paper and accurate reporting of trial results.” NEJM has since conducted a review and published a series of letters in response. The letters have reinvigorated rather than appeased the dissenters, as reported by Medscape.

A number of cardiologists and researchers started a petition on change.org to revise the EACTS/ESC left main CAD guidelines, and surgical societies across the globe have written to the editor of NEJM asking him to retract or amend the EXCEL papers.

This has not happened. The journal’s editor maintains that the letters containing the analyses are “sufficient information” to allow readers and guideline authors to “evaluate the trial findings.”

Dr. Taggart was dismissive of that response. “There is still no recognition or acknowledgment that failure to publish these data in 2016 ‘misled’ the guideline writers for the ESC/EACTS guidelines, and there is still no formal correction of the 2016 and 2019 NEJM manuscripts.”

Over a year after the BBC received the leaked data, the EXCEL investigators published an analysis of the primary outcome using the universal definition of MI data in the Journal of the American College of Cardiology.

It shows 141 events in the PCI arm, compared with 102 in the CABG arm. The investigators acknowledge that the rates of procedural MI differ depending on the definition used. According to their analysis, the protocol definition was predictive of mortality after both treatments, whereas the universal definition of procedural MI was predictive of mortality only after CABG. Not everyone agrees with this interpretation, and an accompanying editorial questioned these conclusions.

For Dr. Wallentin, it’s a relief that these data are in the public domain so that their interpretation and clinical consequences can be “openly discussed.” He hoped that the whole experience will result in something constructive and useful for the future.

As for the guidelines, the tide may be turning.

In a joint statement with EACTS on Oct. 6, 2020, the ESC agreed to review its guidelines for left main disease in the light of emerging, longer-term outcome data from the trials of CABG versus PCI.

Dr. Taggart has no regrets about speaking out despite this being “an exceedingly painful and bruising experience.”

The saga, he said, “reflects very badly on our specialty, the investigators, industry, and the world’s ‘leading’ medical journal.”

This article first appeared on Medscape.com.

“I disapprove of what you say, but I will defend to the death your right to say it.” The choice of the secretary general of the European Association for Cardio-Thoracic Surgery to open with this quote was the first hint that the next presentation at the 2019 annual meeting would be anything but dull. The session chair followed with a reminder to keep the discussion polite and civil.

Presenter David Taggart, MD, PhD, did not disappoint. The professor of cardiovascular surgery at the University of Oxford (England) began with the announcement that he had withdrawn his name from a recent paper in the New England Journal of Medicine. He then proceeded to accuse his coinvestigators of misrepresenting the findings of a major clinical trial.

Dr. Taggart was chair of the surgical committee for the Abbott-sponsored EXCEL trial, which compared two procedures for patients who had blockages in their left main coronary artery: percutaneous coronary intervention (PCI) using coronary stents, and coronary artery bypass graft surgery (CABG). The investigators designed the trial to compare outcomes for the two treatments using a composite endpoint of death, stroke, and MI. The 3-year follow-up data had been published in NEJM without controversy – or, at least, without public controversy.

But when it came time to publish the 5-year follow-up, there was a significantly higher rate of death in the stent group, and both Dr. Taggart and the journal editors were concerned that this finding was being downplayed in the manuscript.

In their comments to the authors, the journal editors had recommended including the mortality difference (unless clearly trivial) ‘”in the concluding statement in the final paragraph.” Yet, the concluding statement of the published paper read that there “was no significant difference between PCI and CABG.”

In Dr. Taggart’s view, that claim was dangerous for patients, and so he was left with no choice but to remove himself as an author, a first for the academic with over 300 scientific papers to his name.

Earlier publications from the EXCEL trial had influenced European treatment guidelines. But subsequent allegations of misconduct and hidden data spurred the EACTS to repudiate those guidelines out of concern “that some results in the EXCEL trial appear to have been concealed and that some patients may therefore have received the wrong clinical advice.”

The controversy pitted cardiothoracic surgeons against interventional cardiologists, who were seen as increasingly encroaching on the surgeons’ turf. Dr. Taggart was a long-time critic of the subspecialty.

Surgeons demanded an independent analysis of the EXCEL trial data – a demand that the investigators have yet to satisfy. Dr. Taggart was the first to speak publicly, but others had major reservations about the trial reporting and conduct years earlier.
 

Mortality data held back

One such person was Lars Wallentin, MD, a professor of cardiology at Uppsala (Sweden) University Hospital, who chaired the independent committee that monitored the safety and scientific validity of the EXCEL trial.

The committee, known as the data and safety monitoring board (DSMB), received a report on March 23, 2016, that showed that increasingly more patients who had received stents were dying, compared with the group of patients that had undergone CABG. A graph of the survival curves showed the gap between the two groups widening after 3 years (Figure 1).

By September of that year, Dr. Wallentin and other members of the DSMB were anxious to share the concerning mortality difference with the broader medical community.

They were aware that EACTS and the European Society of Cardiology had started the process of updating their guidelines on myocardial revascularization, and were keen for the guideline writing committee to see all of the data.

Meanwhile, the trial investigators, led by principal investigator Gregg Stone, MD, then at New York–Presbyterian Hospital and Columbia University Medical Center, were preparing to publish a report of the 3-year outcomes. Recruitment for EXCEL started in September 2010, so at the time of the 3-year analysis in 2016, some patients had been followed up for over 5 years. But the data, published in NEJM in October 2016, were capped at 3 years (Figure 2). It didn’t show the widening gap in late mortality that Dr. Wallentin and the rest of the DSMB had seen.

When asked about this, the investigators said they were transparent about their plans to cap the data at 3 years in an amendment to the study protocol. Stone’s coprincipal investigators were interventional cardiologist Patrick Serruys, MD, then of Imperial College London; and two surgeons: Joseph Sabik, MD, then of the Cleveland Clinic Foundation, and A. Pieter Kappetein, MD, PhD, then at Erasmus Medical Center, Rotterdam. The four principal investigators all declared financial payments from stent manufacturers either to themselves or their institutions.

Study sponsor Abbott has distanced itself from the decisions made and has referred all questions about the trial to the EXCEL investigators. Charles Simonton, chief medical officer at Abbott (now at Abiomed) was a coauthor on both the 3- and 5-year papers. Dr. Wallentin believes that the sponsor must have been aware of the DSMB’s concerns.
 

Continuing DSMB concerns

A year later, the DSMB was still troubled. Dr. Wallentin emailed Dr. Stone in September 2017 asking for an updated analysis of the mortality data without any capping in time.

Dr. Wallentin added that he didn’t think that unblinding the mortality results would be an issue at that stage because these were late deaths in a trial where the interventions were long completed. But, he warned, “it might be very concerning if, in the future, suspicions were raised that already available information on mortality was withheld from the cardiology and thoracic surgery community.”

The investigators took a month to respond. They declined the request, saying that the trial was not statistically powered to measure mortality. In his email to Dr. Wallentin, Dr. Stone stressed that they were committed to complete disclosure of all of the EXCEL data and that the responsible time point to unblind was after 4 years. His coprincipal investigators (Dr. Serruys, Dr. Sabik, and Dr. Kappetein) as well as EXCEL statistical committee chair Stuart Pocock, PhD, and Mr. Simonton were all copied on the email.

Dr. Wallentin deferred to the principal investigators’ arguments.
 

Missing MI data

Death was not the only outcome of the EXCEL trial to draw scrutiny.

The EXCEL investigators used a unique definition of MI that was almost exclusively based on a rise in the cardiac biomarker CK-MB. This protocol definition of MI was later adapted into the Society for Cardiovascular Angiography and Interventions definition in a paper coauthored by Dr. Stone. The investigators agreed to also measure MIs that met the more commonly used Third Universal Definition as a secondary endpoint. The Third Universal Definition of Myocardial Infarction uses a change in biomarkers – preferably troponin or alternatively CK-MB – coupled with other clinical signs.

It is standard practice to report secondary endpoints in any analysis of the main findings of a study. Yet, the EXCEL investigators did not report the universal definition of MI in either the 3-year or 5-year publications.

This is critical because MI according to one definition may not count according to the other, and the final tally could tip the trial results positive, negative, or neutral for coronary stents.

In Dr. Taggart’s opinion, the protocol definition puts CABG at a disadvantage because it uses the same biomarker threshold for procedural-related MI for both PCI and CABG. Because surgery involves more manipulation of the heart, cardiac enzyme levels will naturally be higher after CABG than PCI. These procedure-related enzyme elevations are not “true clinical MIs,” according to Dr. Taggart and others.

Late last year, a dataset containing the 3-year follow-up of EXCEL, including the information on the universal definition of MI, was leaked to the BBC. Working with biostatisticians, the BBC confirmed that according to this definition, there were more MIs in the stent group.

Originally, the investigators disputed the finding, calling the BBC data “imaginary.” They claimed that they were unable to calculate a rate of MI according to the universal definition because they lacked routine collection of troponins, although the universal definition also allows use of CK-MB. They have since published an analysis of 5-year MI data according to the universal definition, which showed twice the rate of MI in the PCI group.

From the leaked data, the BBC calculated the main composite endpoint of death, stroke, and MI using the universal definition of MI. Now the results swung in favor of CABG.
 

Impact on guidelines

None of this was known at the time the European cardiology societies convened a committee to write their new guidelines on myocardial revascularization. The writing panel disagreed about whether PCI and CABG were equivalent for patients with left main coronary artery disease (CAD).

Besides EXCEL, another study, the NOBLE trial, compared PCI and CABG in left main CAD and came to opposite conclusions – conclusions that matched the leaked data. In that trial, European investigators chose a slightly different primary endpoint: a composite of death, MI, stroke, and the need for a repeat procedure. They used the universal definition of MI exclusively, and notably, they omitted procedural MI from their clinical event count. The results, published at the same time as the EXCEL 3-year findings, suggested that CABG was better.

Given the discrepant findings of two large trials, the guideline committee considered all of the available data comparing the two methods of revascularization for left main CAD. But even then, things weren’t clear-cut. One draft meta-analysis, supported by the National Institute for Health Research, suggested that results were worse for first- and second-generation drug-eluting coronary stents – including those used in EXCEL – compared with surgery.

Another meta-analysis, later published in The Lancet, drew a different conclusion and found that PCI was just as good as surgery. The main author, Stuart Head, a cardiothoracic surgeon on the ESC/EACTS guideline committee, was a research fellow with EXCEL investigator Dr. Kappetein at Erasmus. EXCEL investigators Dr. Stone, Dr. Kappetein, and Dr. Serruys were coauthors of the Lancet meta-analysis.

There was heated discussion about the committee’s draft recommendations, which gave both CABG and PCI a Class IA recommendation in patients with left main CAD and low anatomical complexity. In October 2017, the ESC commissioned an anonymous external reviewer to weigh in. James Brophy, MD, PhD, a cardiologist and professor of medicine and epidemiology at McGill University, Montreal, confirmed that he was the reviewer after he published an updated version in June 2020.

Looking at all of the data available at the time comparing the procedures for left main CAD, Dr. Brophy’s analysis suggested a 73% chance that the excess in death, stroke, or MI represents at least two excess events per 100 patients treated with PCI rather than CABG.

Dr. Brophy thought that most patients would find these differences clinically meaningful and advised against giving both procedures the same class of recommendation. He was also concerned that many readers will skip to the summary recommendation table without reading the entire guideline document.

“I feel this is misleading in its present form,” he wrote in 2017.

Despite Dr. Brophy’s review, the guideline committee stuck with its original recommendations. The final 2018 ESC/EACTS Guidelines on myocardial revascularization gave equal weight to both CABG and PCI in patients with left main CAD and low anatomical complexity. In contrast, US guidelines do not put PCI and CABG on the same footing for any group of patients with left main CAD.

The lead author of the ESC/EACTS guidelines section on left main disease, and around a third of those on the writing task force, all declared financial payments from stent manufacturers either to themselves or their institutions. The EXCEL principal investigator, Dr. Kappetein, was secretary general of EACTS and oversaw the guidelines process for the surgical organization. He left to work for Medtronic midway through the process and was later joined there by his former research fellow, Stuart Head.

Dr. Brophy said in an interview that given the final guideline recommendations, he assumed that the committee had other reviews and went with the majority opinion.

But not everyone involved in the guidelines saw Dr. Brophy’s review. Nick Freemantle, a statistical reviewer appointed by EACTS, expected to see it but didn’t. This omission calls into question the neutrality of the whole process, in his view.

Mr. Freemantle believes that the deck was stacked so that he only saw the pieces of evidence that supported the conclusions that were already decided and that he was not shown “the bits that don’t fit that neatly.”

“And without that narrative, it all feels a bit grubby, to be honest,” he said.

Professor Barbara Casadei, ESC president, disputed this, saying that the guidelines were approved by all surgical members, including the EACTS council.

Missing from Dr. Brophy’s review were the later data from EXCEL. As he had told the DSMB in 2017, Stone presented the 4-year data from EXCEL at the TCT conference in September 2018. At this point, the analysis showed that 10.3% of people had died after PCI and 7.4% after CABG.

But this presentation was not given much prominence at the conference, which Dr. Stone organized, and occurred during a didactic session in a small room rather than on one of the main stages where the 3-year data from EXCEL were announced with much fanfare. The presentation also took place 3 weeks after the European guidelines were published.
 

Surgeons withdraw support

After the BBC report last year that the universal definition of MI data had been collected but not published in the 3-year follow-up manuscript, and showed more MI in the PCI group than the protocol definition, the EACTS withdrew its support for the guidelines. The ESC continued to uphold the guidelines «until there is robust scientific evidence (as opposed to allegations) indicating we should do otherwise,” said Ms. Casadei.

A spokesperson for NEJM said the journal stood by the EXCEL papers because “there is no credible harm to patients from the publication of the paper and accurate reporting of trial results.” NEJM has since conducted a review and published a series of letters in response. The letters have reinvigorated rather than appeased the dissenters, as reported by Medscape.

A number of cardiologists and researchers started a petition on change.org to revise the EACTS/ESC left main CAD guidelines, and surgical societies across the globe have written to the editor of NEJM asking him to retract or amend the EXCEL papers.

This has not happened. The journal’s editor maintains that the letters containing the analyses are “sufficient information” to allow readers and guideline authors to “evaluate the trial findings.”

Dr. Taggart was dismissive of that response. “There is still no recognition or acknowledgment that failure to publish these data in 2016 ‘misled’ the guideline writers for the ESC/EACTS guidelines, and there is still no formal correction of the 2016 and 2019 NEJM manuscripts.”

Over a year after the BBC received the leaked data, the EXCEL investigators published an analysis of the primary outcome using the universal definition of MI data in the Journal of the American College of Cardiology.

It shows 141 events in the PCI arm, compared with 102 in the CABG arm. The investigators acknowledge that the rates of procedural MI differ depending on the definition used. According to their analysis, the protocol definition was predictive of mortality after both treatments, whereas the universal definition of procedural MI was predictive of mortality only after CABG. Not everyone agrees with this interpretation, and an accompanying editorial questioned these conclusions.

For Dr. Wallentin, it’s a relief that these data are in the public domain so that their interpretation and clinical consequences can be “openly discussed.” He hoped that the whole experience will result in something constructive and useful for the future.

As for the guidelines, the tide may be turning.

In a joint statement with EACTS on Oct. 6, 2020, the ESC agreed to review its guidelines for left main disease in the light of emerging, longer-term outcome data from the trials of CABG versus PCI.

Dr. Taggart has no regrets about speaking out despite this being “an exceedingly painful and bruising experience.”

The saga, he said, “reflects very badly on our specialty, the investigators, industry, and the world’s ‘leading’ medical journal.”

This article first appeared on Medscape.com.

After years of dormancy, psychiatric drug development is showing signs of life. There is the novel antipsychotic lumateperone, recently approved for adults with schizophrenia. Brexanolone was approved last year for postpartum depression. And perhaps generating the most attention lately among psychiatrists – and people with depression – is the use of ketamine and esketamine for depression.

Columbia psychiatrist J. John Mann, MD, a professor of translational neuroscience and a mood disorder specialist, has been involved in several notable studies of ketamine in patients with depression. He and his colleagues’ recent research efforts include a randomized study into ketamine’s ability to reduce suicidal thoughts in bipolar depression and an MRI analysis illuminating the role that dosing plays in antidepressant effects.

Dr. Mann sat down with his Columbia colleague Lloyd I. Sederer, MD, to discuss how, nearly a year after its approval, ketamine fits into mental health care.
 

Dr. Sederer: Nearly 20 million people in this country alone suffer from clinical depression every year. That means they have a functional impairment in addition to their suffering and are at risk of taking their own lives. Depression is a very prevalent, painful, and disabling condition. The psychopharmacologic treatments we’ve had have been more or less the same for the past 20 or 30 years.

We’ve asked Dr. Mann to … talk to us about ketamine and its nasal preparation esketamine, which is a novel psychopharmacologic treatment. Dr. Mann, please tell us about ketamine, its utility, and the yet-to-be-answered questions.

Dr. Mann: Ketamine and esketamine, which is a component of ketamine itself, is different from traditional antidepressant medications in three fundamental ways.

The first is that it acts very quickly. Traditional antidepressants take 4, 6, 8 weeks to work. This means that the patient has to put up with a great deal of suffering while waiting for a response. And the probability of the medication working isn’t that high. About 50%-70% of individuals will respond eventually at the end of this ride. But ketamine, when it works, does so in 2 hours. That’s a totally different timescale.

The second aspect is that, when it does work, it often works very robustly, even though it’s a quick-acting antidepressant. The patient often quickly feels distinctly better.

Very often when you’re using traditional antidepressants, it takes a while for the improvement to reach the point that the patient is confident that they are clearly better, and too often that does not happen.

Dr. Sederer: As the treating doctor, you’re trying to keep that patient’s hope alive, even though we don’t have substantial evidence that they’re going to respond.

Dr. Mann: Exactly. One of the difficulties of keeping patients on track with traditional antidepressants is that, after the first dose or two, they have all the side effects and yet no benefit has emerged. In many ways patients sometimes feel that they’re going backwards. They have all of their depression plus the side effects of the medication.

But with ketamine, it’s rather different. You come in, you have the treatment, and many patients feel improved in a couple of hours. And not just a bit improved, but in many cases distinctly improved.

It’s very important for clinicians to appreciate that ketamine will work in patients who have a classically described treatment-resistant depression, meaning they’ve tried several other types of antidepressant medications that haven’t worked.

A prerequisite for treatment with ketamine is that they have had a number of treatment failures. The labeling for the intranasal esketamine states that you should try the other antidepressants first and then use this if they don’t work. The fact that ketamine can work even when the other medications have failed is a huge advantage.

Dr. Sederer: There is another feature of ketamine, in that it also has a pronounced benefit for suicidal ideation, which your research has reported on.

Dr. Mann: Yes, we’ve learned over the years that depression and suicidality are in some ways comorbid conditions. That both have to be addressed in order to keep somebody alive so that they can respond to treatment.

That’s a very important point. If the patient is suffering from depression and the antidepressant takes weeks to work, they may lose hope during that time. They may become overwhelmed by the suicidal ideation, no longer able to control or resist the impulse to take their life. A lot of the management is therefore to try to help support the patient (and family) so that these thoughts never become too compelling. Often we have to consider hospitalization to protect these patients so that they can stay alive long enough for the antidepressant to work. But ketamine not only has this very rapid effect for their depression, it also has a partly independent effect on suicidal ideation that is equally rapid and robust, which can render the patient safer.

Dr. Sederer: In other words, it’s effective and rapidly so for depression, with a bonus of reducing suicidality? This sounds almost too good to be true.

Dr. Mann: There are some limitations that we have to keep in mind. One limitation is that a single administration of ketamine will produce this robust improvement but it will only persist for most people for 5-7 days.

Dr. Sederer: Is the same duration true for scheduling the next treatment as well?

Dr. Mann: Yes, it is. The patient will gradually begin to deteriorate if you do not repeat the treatment. But as we showed in our randomized controlled clinical study, with ketamine for suicidal ideation, if you continue to deliver the medication, you can sustain the benefit.

Dr. Sederer: Can a person receive both ketamine and a conventional antidepressant at the same time?

Dr. Mann: Yes. In this study, half of the patients were actually continued on their previous medication while we added the ketamine on top of that. It worked very well.

In practice, people use two approaches. One approach used by most ketamine clinics is to give six doses of ketamine at a frequency of about two per week. Then they will reduce the frequency down to once a week for a few more doses and then once a month.

Dr. Sederer:: And this is a ketamine infusion?

Dr. Mann: Yes, this generally has been a ketamine infusion. This approach seems to work quite well. But that may not be necessary.

Another strategy is to give one, two, or three doses of ketamine. If the patient doesn’t respond robustly to two or three doses, they’re not going to respond to subsequent doses.

Dr. Sederer: So, initial responses are a predictor of future response?

Dr. Mann: Exactly. Now, if they haven’t done well with two or three doses, then you’ve got to use other treatments. But if they do well with the two or three, then you’ve got a choice: You can either complete the treatment course with ketamine and then continue them on antidepressant medications, or simply treat them with ketamine alone. What we tend to do is to treat with only antidepressant medications after a small number of ketamine treatments. We also use ketamine as a kind of “rescue medication” if they relapse into severe depression, though this is true for only a minority of patients.

Dr. Sederer: One of the things that we’ve learned is that antidepressants have a very beneficial effect for some people, but then they wear out and the person starts to relapse. Should ketamine be studied as an intervention for people who are no longer responding to the antidepressant(s) that they are on?

Dr. Mann: We do not really know the answer to that question. My experience treating very seriously ill patients is that sometimes the ketamine will work very well the first time or the second time but then in the future, if you try to use it as a rescue medication, it might not work that well. There is some clinical experience that suggests that that may be true for some people. But we have no idea about the frequency or timing with which this might happen. That’s all uncertain.

Moreover, most of our control clinical trial data come from either one dose of ketamine or from a few trials where people have received multiple doses of ketamine, followed by a bit of a taper. But there are very, very few of those types of studies. We’re still learning about the use of this medication.

Dr. Sederer: Importantly, you referenced the side effects of antidepressants. What are the side effects and risks of ketamine?

Dr. Mann: We know a lot more about the immediate short-term side effects of a single dose or a few doses of ketamine. Most people will get a kind of tripping experience. They’ll feel a bit unreal, or their circumstances or experiences of the world feel a bit distorted.

Some patients develop strange ideas. Most patients don’t enjoy those symptoms, even though I know ketamine is used as a party drug, and so on and so forth.

Dr. Sederer: It seems that the context is what matters.

Dr. Mann: Yes. And in a clinic context, most patients simply don’t enjoy these types of dissociative experiences, but they put up with them. They’re not severe, in general.

Dr. Sederer: Is part of the preparation of the patient telling them that this may happen?

Dr. Mann: Yes. We try to explain the potential for these symptoms and that most people get them. These side effects almost invariably terminate with the cessation of the administration.

Dr. Sederer: What’s the typical duration of the infusion you use?

Dr. Mann: Traditionally, infusion is 40 minutes and always in a clinic setting.

Dr. Sederer: And that’s because of the concern that a patient may have these symptoms?

Dr. Mann: Exactly. They may have dissociative effects that they’re disturbed by, and we need to monitor that. They’re probably going to remain under observation in the clinic for about the same amount of time because it takes about the same time for these effects to wear off.

The other consideration is that some people get a little nausea. In our experience with the intravenous ketamine, there’s also a problematic side effect that their blood pressure will be slightly raised. Therefore, it’s good to know that the person’s blood pressure is under control before they begin the treatments and that you’re monitoring it during administration.

Dr. Sederer: What are the differences you’re discovering between esketamine and ketamine?

Dr. Mann: It is a bit different. We’ve just completed a very important National Institutes of Health–funded clinical trial here at Columbia showing that with esketamine or ketamine itself, the dose and the blood levels are very closely related to the robustness of the clinical response.

When you give a drug intravenously, you give a very reliable dose. When you give the drug over 40 minutes, you’re spreading the dose administration over a period of time so that it doesn’t peak very high. The side effects appear to be proportional to the peak dose.

When you give it intranasally, you give the drug over a much shorter period of time. Even if you use more than one intranasal administration to give the whole dose, it’s still a relatively shorter time, compared with the 40 minutes.

Dr. Sederer: This means that to get the equivalent dose intranasally, the patient is going to have to experience a higher peak. Can you predict that those patients who are treated intranasally are going to have more side effects?

Dr. Mann: Right. And that should be explained to the patient. You will not need an intravenous line inserted, which some people might find highly appealing and advantageous, but you will probably have more side effects.

Also, in general, intranasal absorption of drugs is more variable. The predictability of the blood level and, therefore, the degree of antidepressant effect is not as good intranasally as intravenously.

Now, all of this is anecdotal clinical experience, based on theoretical pharmacology, because nobody has actually done a head-to-head control comparison.

Dr. Sederer: What about the cost of both of these preparations?

Dr. Mann: There is a bit of a range in pricing between ketamine clinics around the country. It’s always important to find out what they charge per administration. And then it makes a difference whether you have two or three administrations versus six plus further tapered administration. Clearly, the cost can vary a great deal.

Dr. Sederer: But it’s generally not covered by insurance, so most people are paying out of pocket.

Dr. Mann: Yes. The intranasal ketamine is still in negotiation at the moment, but it should be resolved before it’s fully marketed.

Dr. Sederer: Ketamine is used for major depression. Does it have utility in bipolar depression?

Dr. Mann: We and some others have done initial studies in bipolar depression. In our view, it’s probably going to be as effective in bipolar disorder as it is in major depressive disorder, unipolar depression.

We haven’t seen any manic episodes triggered, but we don’t give repeated doses. We allow research patients to stay on anticonvulsants or mood stabilizers, so that’s helpful. Generally, people with bipolar disorder who come for ketamine treatment for their depression are coming on a mood stabilizer, because that and perhaps other conventional antidepressants have not proven to be effective. So, I think that ketamine plus mood stabilizers seems to be very promising.

Dr. Sederer: I want to return to the antisuicidal properties that you had previously mentioned. I heard from a colleague about a patient who had been admitted to a psychiatric inpatient unit. The patient was in her 20s; she did not have major depression but was persistently suicidal, constantly trying to hurt herself in any way she could. But that seemed to be more a product of borderline personality disorder, with its impulsive and self-destructive problems.

In the end, they tried intranasal ketamine. The response was, just as you described, robust. Her self-injurious behavior dropped in a very pronounced way within a day or two. But she then did require administrations a couple of times a week in order to keep that suicidality at bay.

Based on that example, I’m wondering whether there is an application here for people who are suicidal yet who may not have features of major depression or bipolar depression.

Dr. Mann: It’s a very interesting suggestion for which we have no data-based answer. However, we have a clue from the study that we published in the American Journal of Psychiatry and have since published further analyses on.

The reasons that people die by suicide, or make suicide attempts, are not entirely attributable to the fact that they suffer from a mood disorder.

Dr. Sederer: Yes, because only a minority of individuals with a mood disorder ever make suicide attempts. But there is a subgroup at risk.

Dr. Mann: Here at Columbia, we’ve promulgated the stress-diathesis model for suicidal behavior. A stressor could be external life events, but the internal stressor would be something like an acute episode of depression.

But predisposition also plays an important role, which has several elements to it. One is decision-making. These are patients with a propensity to go for a short-term, quick relief. In other words, a patient would be seeking immediate relief rather than waiting for the delayed improvement from an antidepressant. They’re more prone to act on the pain of the depression and terminate their lives – to try to end their pain – rather than wait and hope that, in time, there’s a chance that the antidepressant will work.

Dr. Sederer: What else do you want to share with our viewers about this medication and how it’s used?

Dr. Mann: My goal in treating patients is to try to use the least amount of medication possible. We do not really know yet the long-term safety of ketamine treatment.

It’s been used for many decades in anesthesia, but people don’t get repeated anesthetic doses of ketamine. And higher doses of ketamine given repeatedly have been shown in preclinical studies to produce little lesions in the brain, which is not good. But we’re using much lower doses.

As we potentially move into a time when we could be giving multiple doses of ketamine to patients, we should remember that we need to be cautious about that. If we don’t need to give them more doses, we shouldn’t. We should know that there is a potential downside that we don’t fully understand yet to giving ketamine repeatedly.

And that’s aside from its abuse potential. We know that people have employed ketamine for physical and emotional pain, and when they administer it themselves, they tend to get dependent on it. In a clinic setting it’s given in a very formal and structured fashion, a bit like the administration of opioids. In that setting, it is much safer and the risk for abuse and diversion is minimized. But we need to remember that this drug does have abuse potential and perhaps not yet fully measurable neurotoxic effects.

Dr. Sederer: If physicians, nurses, and other professional clinicians want to learn more about this medication, what are the accurate, reliable sources of information to which you suggest they turn?

Dr. Mann: The National Institute of Mental Health’s website offers good and reliable information for patients and their families. It is an unbiased, scientific, and thoughtful source of information, and better than just trolling the Internet for information.

People are much more sophisticated now than they were 20 years ago in these matters, and scientific papers are much more accessible to the public. Reading papers in recognized journals is also a useful way to gain information.

For example, one of the major papers that we published in the American Journal of Psychiatry is available to anybody on the Internet to read. So, I encourage people to make their own inquiries and talk to more than one doctor. Informed patients and families are the best partners a doctor can ever have. We encourage that in all of our patients.

Dr. Sederer: I want to thank you very much, Dr. Mann, for your work in this area and for joining us here at Medscape and Columbia Psychiatry to teach us so much about what is truly a novel psychopharmacologic agent, yet one where we still have a lot more to learn.

A version of this article originally appeared on Medscape.com.

After years of dormancy, psychiatric drug development is showing signs of life. There is the novel antipsychotic lumateperone, recently approved for adults with schizophrenia. Brexanolone was approved last year for postpartum depression. And perhaps generating the most attention lately among psychiatrists – and people with depression – is the use of ketamine and esketamine for depression.

Columbia psychiatrist J. John Mann, MD, a professor of translational neuroscience and a mood disorder specialist, has been involved in several notable studies of ketamine in patients with depression. He and his colleagues’ recent research efforts include a randomized study into ketamine’s ability to reduce suicidal thoughts in bipolar depression and an MRI analysis illuminating the role that dosing plays in antidepressant effects.

Dr. Mann sat down with his Columbia colleague Lloyd I. Sederer, MD, to discuss how, nearly a year after its approval, ketamine fits into mental health care.
 

Dr. Sederer: Nearly 20 million people in this country alone suffer from clinical depression every year. That means they have a functional impairment in addition to their suffering and are at risk of taking their own lives. Depression is a very prevalent, painful, and disabling condition. The psychopharmacologic treatments we’ve had have been more or less the same for the past 20 or 30 years.

We’ve asked Dr. Mann to … talk to us about ketamine and its nasal preparation esketamine, which is a novel psychopharmacologic treatment. Dr. Mann, please tell us about ketamine, its utility, and the yet-to-be-answered questions.

Dr. Mann: Ketamine and esketamine, which is a component of ketamine itself, is different from traditional antidepressant medications in three fundamental ways.

The first is that it acts very quickly. Traditional antidepressants take 4, 6, 8 weeks to work. This means that the patient has to put up with a great deal of suffering while waiting for a response. And the probability of the medication working isn’t that high. About 50%-70% of individuals will respond eventually at the end of this ride. But ketamine, when it works, does so in 2 hours. That’s a totally different timescale.

The second aspect is that, when it does work, it often works very robustly, even though it’s a quick-acting antidepressant. The patient often quickly feels distinctly better.

Very often when you’re using traditional antidepressants, it takes a while for the improvement to reach the point that the patient is confident that they are clearly better, and too often that does not happen.

Dr. Sederer: As the treating doctor, you’re trying to keep that patient’s hope alive, even though we don’t have substantial evidence that they’re going to respond.

Dr. Mann: Exactly. One of the difficulties of keeping patients on track with traditional antidepressants is that, after the first dose or two, they have all the side effects and yet no benefit has emerged. In many ways patients sometimes feel that they’re going backwards. They have all of their depression plus the side effects of the medication.

But with ketamine, it’s rather different. You come in, you have the treatment, and many patients feel improved in a couple of hours. And not just a bit improved, but in many cases distinctly improved.

It’s very important for clinicians to appreciate that ketamine will work in patients who have a classically described treatment-resistant depression, meaning they’ve tried several other types of antidepressant medications that haven’t worked.

A prerequisite for treatment with ketamine is that they have had a number of treatment failures. The labeling for the intranasal esketamine states that you should try the other antidepressants first and then use this if they don’t work. The fact that ketamine can work even when the other medications have failed is a huge advantage.

Dr. Sederer: There is another feature of ketamine, in that it also has a pronounced benefit for suicidal ideation, which your research has reported on.

Dr. Mann: Yes, we’ve learned over the years that depression and suicidality are in some ways comorbid conditions. That both have to be addressed in order to keep somebody alive so that they can respond to treatment.

That’s a very important point. If the patient is suffering from depression and the antidepressant takes weeks to work, they may lose hope during that time. They may become overwhelmed by the suicidal ideation, no longer able to control or resist the impulse to take their life. A lot of the management is therefore to try to help support the patient (and family) so that these thoughts never become too compelling. Often we have to consider hospitalization to protect these patients so that they can stay alive long enough for the antidepressant to work. But ketamine not only has this very rapid effect for their depression, it also has a partly independent effect on suicidal ideation that is equally rapid and robust, which can render the patient safer.

Dr. Sederer: In other words, it’s effective and rapidly so for depression, with a bonus of reducing suicidality? This sounds almost too good to be true.

Dr. Mann: There are some limitations that we have to keep in mind. One limitation is that a single administration of ketamine will produce this robust improvement but it will only persist for most people for 5-7 days.

Dr. Sederer: Is the same duration true for scheduling the next treatment as well?

Dr. Mann: Yes, it is. The patient will gradually begin to deteriorate if you do not repeat the treatment. But as we showed in our randomized controlled clinical study, with ketamine for suicidal ideation, if you continue to deliver the medication, you can sustain the benefit.

Dr. Sederer: Can a person receive both ketamine and a conventional antidepressant at the same time?

Dr. Mann: Yes. In this study, half of the patients were actually continued on their previous medication while we added the ketamine on top of that. It worked very well.

In practice, people use two approaches. One approach used by most ketamine clinics is to give six doses of ketamine at a frequency of about two per week. Then they will reduce the frequency down to once a week for a few more doses and then once a month.

Dr. Sederer:: And this is a ketamine infusion?

Dr. Mann: Yes, this generally has been a ketamine infusion. This approach seems to work quite well. But that may not be necessary.

Another strategy is to give one, two, or three doses of ketamine. If the patient doesn’t respond robustly to two or three doses, they’re not going to respond to subsequent doses.

Dr. Sederer: So, initial responses are a predictor of future response?

Dr. Mann: Exactly. Now, if they haven’t done well with two or three doses, then you’ve got to use other treatments. But if they do well with the two or three, then you’ve got a choice: You can either complete the treatment course with ketamine and then continue them on antidepressant medications, or simply treat them with ketamine alone. What we tend to do is to treat with only antidepressant medications after a small number of ketamine treatments. We also use ketamine as a kind of “rescue medication” if they relapse into severe depression, though this is true for only a minority of patients.

Dr. Sederer: One of the things that we’ve learned is that antidepressants have a very beneficial effect for some people, but then they wear out and the person starts to relapse. Should ketamine be studied as an intervention for people who are no longer responding to the antidepressant(s) that they are on?

Dr. Mann: We do not really know the answer to that question. My experience treating very seriously ill patients is that sometimes the ketamine will work very well the first time or the second time but then in the future, if you try to use it as a rescue medication, it might not work that well. There is some clinical experience that suggests that that may be true for some people. But we have no idea about the frequency or timing with which this might happen. That’s all uncertain.

Moreover, most of our control clinical trial data come from either one dose of ketamine or from a few trials where people have received multiple doses of ketamine, followed by a bit of a taper. But there are very, very few of those types of studies. We’re still learning about the use of this medication.

Dr. Sederer: Importantly, you referenced the side effects of antidepressants. What are the side effects and risks of ketamine?

Dr. Mann: We know a lot more about the immediate short-term side effects of a single dose or a few doses of ketamine. Most people will get a kind of tripping experience. They’ll feel a bit unreal, or their circumstances or experiences of the world feel a bit distorted.

Some patients develop strange ideas. Most patients don’t enjoy those symptoms, even though I know ketamine is used as a party drug, and so on and so forth.

Dr. Sederer: It seems that the context is what matters.

Dr. Mann: Yes. And in a clinic context, most patients simply don’t enjoy these types of dissociative experiences, but they put up with them. They’re not severe, in general.

Dr. Sederer: Is part of the preparation of the patient telling them that this may happen?

Dr. Mann: Yes. We try to explain the potential for these symptoms and that most people get them. These side effects almost invariably terminate with the cessation of the administration.

Dr. Sederer: What’s the typical duration of the infusion you use?

Dr. Mann: Traditionally, infusion is 40 minutes and always in a clinic setting.

Dr. Sederer: And that’s because of the concern that a patient may have these symptoms?

Dr. Mann: Exactly. They may have dissociative effects that they’re disturbed by, and we need to monitor that. They’re probably going to remain under observation in the clinic for about the same amount of time because it takes about the same time for these effects to wear off.

The other consideration is that some people get a little nausea. In our experience with the intravenous ketamine, there’s also a problematic side effect that their blood pressure will be slightly raised. Therefore, it’s good to know that the person’s blood pressure is under control before they begin the treatments and that you’re monitoring it during administration.

Dr. Sederer: What are the differences you’re discovering between esketamine and ketamine?

Dr. Mann: It is a bit different. We’ve just completed a very important National Institutes of Health–funded clinical trial here at Columbia showing that with esketamine or ketamine itself, the dose and the blood levels are very closely related to the robustness of the clinical response.

When you give a drug intravenously, you give a very reliable dose. When you give the drug over 40 minutes, you’re spreading the dose administration over a period of time so that it doesn’t peak very high. The side effects appear to be proportional to the peak dose.

When you give it intranasally, you give the drug over a much shorter period of time. Even if you use more than one intranasal administration to give the whole dose, it’s still a relatively shorter time, compared with the 40 minutes.

Dr. Sederer: This means that to get the equivalent dose intranasally, the patient is going to have to experience a higher peak. Can you predict that those patients who are treated intranasally are going to have more side effects?

Dr. Mann: Right. And that should be explained to the patient. You will not need an intravenous line inserted, which some people might find highly appealing and advantageous, but you will probably have more side effects.

Also, in general, intranasal absorption of drugs is more variable. The predictability of the blood level and, therefore, the degree of antidepressant effect is not as good intranasally as intravenously.

Now, all of this is anecdotal clinical experience, based on theoretical pharmacology, because nobody has actually done a head-to-head control comparison.

Dr. Sederer: What about the cost of both of these preparations?

Dr. Mann: There is a bit of a range in pricing between ketamine clinics around the country. It’s always important to find out what they charge per administration. And then it makes a difference whether you have two or three administrations versus six plus further tapered administration. Clearly, the cost can vary a great deal.

Dr. Sederer: But it’s generally not covered by insurance, so most people are paying out of pocket.

Dr. Mann: Yes. The intranasal ketamine is still in negotiation at the moment, but it should be resolved before it’s fully marketed.

Dr. Sederer: Ketamine is used for major depression. Does it have utility in bipolar depression?

Dr. Mann: We and some others have done initial studies in bipolar depression. In our view, it’s probably going to be as effective in bipolar disorder as it is in major depressive disorder, unipolar depression.

We haven’t seen any manic episodes triggered, but we don’t give repeated doses. We allow research patients to stay on anticonvulsants or mood stabilizers, so that’s helpful. Generally, people with bipolar disorder who come for ketamine treatment for their depression are coming on a mood stabilizer, because that and perhaps other conventional antidepressants have not proven to be effective. So, I think that ketamine plus mood stabilizers seems to be very promising.

Dr. Sederer: I want to return to the antisuicidal properties that you had previously mentioned. I heard from a colleague about a patient who had been admitted to a psychiatric inpatient unit. The patient was in her 20s; she did not have major depression but was persistently suicidal, constantly trying to hurt herself in any way she could. But that seemed to be more a product of borderline personality disorder, with its impulsive and self-destructive problems.

In the end, they tried intranasal ketamine. The response was, just as you described, robust. Her self-injurious behavior dropped in a very pronounced way within a day or two. But she then did require administrations a couple of times a week in order to keep that suicidality at bay.

Based on that example, I’m wondering whether there is an application here for people who are suicidal yet who may not have features of major depression or bipolar depression.

Dr. Mann: It’s a very interesting suggestion for which we have no data-based answer. However, we have a clue from the study that we published in the American Journal of Psychiatry and have since published further analyses on.

The reasons that people die by suicide, or make suicide attempts, are not entirely attributable to the fact that they suffer from a mood disorder.

Dr. Sederer: Yes, because only a minority of individuals with a mood disorder ever make suicide attempts. But there is a subgroup at risk.

Dr. Mann: Here at Columbia, we’ve promulgated the stress-diathesis model for suicidal behavior. A stressor could be external life events, but the internal stressor would be something like an acute episode of depression.

But predisposition also plays an important role, which has several elements to it. One is decision-making. These are patients with a propensity to go for a short-term, quick relief. In other words, a patient would be seeking immediate relief rather than waiting for the delayed improvement from an antidepressant. They’re more prone to act on the pain of the depression and terminate their lives – to try to end their pain – rather than wait and hope that, in time, there’s a chance that the antidepressant will work.

Dr. Sederer: What else do you want to share with our viewers about this medication and how it’s used?

Dr. Mann: My goal in treating patients is to try to use the least amount of medication possible. We do not really know yet the long-term safety of ketamine treatment.

It’s been used for many decades in anesthesia, but people don’t get repeated anesthetic doses of ketamine. And higher doses of ketamine given repeatedly have been shown in preclinical studies to produce little lesions in the brain, which is not good. But we’re using much lower doses.

As we potentially move into a time when we could be giving multiple doses of ketamine to patients, we should remember that we need to be cautious about that. If we don’t need to give them more doses, we shouldn’t. We should know that there is a potential downside that we don’t fully understand yet to giving ketamine repeatedly.

And that’s aside from its abuse potential. We know that people have employed ketamine for physical and emotional pain, and when they administer it themselves, they tend to get dependent on it. In a clinic setting it’s given in a very formal and structured fashion, a bit like the administration of opioids. In that setting, it is much safer and the risk for abuse and diversion is minimized. But we need to remember that this drug does have abuse potential and perhaps not yet fully measurable neurotoxic effects.

Dr. Sederer: If physicians, nurses, and other professional clinicians want to learn more about this medication, what are the accurate, reliable sources of information to which you suggest they turn?

Dr. Mann: The National Institute of Mental Health’s website offers good and reliable information for patients and their families. It is an unbiased, scientific, and thoughtful source of information, and better than just trolling the Internet for information.

People are much more sophisticated now than they were 20 years ago in these matters, and scientific papers are much more accessible to the public. Reading papers in recognized journals is also a useful way to gain information.

For example, one of the major papers that we published in the American Journal of Psychiatry is available to anybody on the Internet to read. So, I encourage people to make their own inquiries and talk to more than one doctor. Informed patients and families are the best partners a doctor can ever have. We encourage that in all of our patients.

Dr. Sederer: I want to thank you very much, Dr. Mann, for your work in this area and for joining us here at Medscape and Columbia Psychiatry to teach us so much about what is truly a novel psychopharmacologic agent, yet one where we still have a lot more to learn.

A version of this article originally appeared on Medscape.com.

After years of dormancy, psychiatric drug development is showing signs of life. There is the novel antipsychotic lumateperone, recently approved for adults with schizophrenia. Brexanolone was approved last year for postpartum depression. And perhaps generating the most attention lately among psychiatrists – and people with depression – is the use of ketamine and esketamine for depression.

Columbia psychiatrist J. John Mann, MD, a professor of translational neuroscience and a mood disorder specialist, has been involved in several notable studies of ketamine in patients with depression. He and his colleagues’ recent research efforts include a randomized study into ketamine’s ability to reduce suicidal thoughts in bipolar depression and an MRI analysis illuminating the role that dosing plays in antidepressant effects.

Dr. Mann sat down with his Columbia colleague Lloyd I. Sederer, MD, to discuss how, nearly a year after its approval, ketamine fits into mental health care.
 

Dr. Sederer: Nearly 20 million people in this country alone suffer from clinical depression every year. That means they have a functional impairment in addition to their suffering and are at risk of taking their own lives. Depression is a very prevalent, painful, and disabling condition. The psychopharmacologic treatments we’ve had have been more or less the same for the past 20 or 30 years.

We’ve asked Dr. Mann to … talk to us about ketamine and its nasal preparation esketamine, which is a novel psychopharmacologic treatment. Dr. Mann, please tell us about ketamine, its utility, and the yet-to-be-answered questions.

Dr. Mann: Ketamine and esketamine, which is a component of ketamine itself, is different from traditional antidepressant medications in three fundamental ways.

The first is that it acts very quickly. Traditional antidepressants take 4, 6, 8 weeks to work. This means that the patient has to put up with a great deal of suffering while waiting for a response. And the probability of the medication working isn’t that high. About 50%-70% of individuals will respond eventually at the end of this ride. But ketamine, when it works, does so in 2 hours. That’s a totally different timescale.

The second aspect is that, when it does work, it often works very robustly, even though it’s a quick-acting antidepressant. The patient often quickly feels distinctly better.

Very often when you’re using traditional antidepressants, it takes a while for the improvement to reach the point that the patient is confident that they are clearly better, and too often that does not happen.

Dr. Sederer: As the treating doctor, you’re trying to keep that patient’s hope alive, even though we don’t have substantial evidence that they’re going to respond.

Dr. Mann: Exactly. One of the difficulties of keeping patients on track with traditional antidepressants is that, after the first dose or two, they have all the side effects and yet no benefit has emerged. In many ways patients sometimes feel that they’re going backwards. They have all of their depression plus the side effects of the medication.

But with ketamine, it’s rather different. You come in, you have the treatment, and many patients feel improved in a couple of hours. And not just a bit improved, but in many cases distinctly improved.

It’s very important for clinicians to appreciate that ketamine will work in patients who have a classically described treatment-resistant depression, meaning they’ve tried several other types of antidepressant medications that haven’t worked.

A prerequisite for treatment with ketamine is that they have had a number of treatment failures. The labeling for the intranasal esketamine states that you should try the other antidepressants first and then use this if they don’t work. The fact that ketamine can work even when the other medications have failed is a huge advantage.

Dr. Sederer: There is another feature of ketamine, in that it also has a pronounced benefit for suicidal ideation, which your research has reported on.

Dr. Mann: Yes, we’ve learned over the years that depression and suicidality are in some ways comorbid conditions. That both have to be addressed in order to keep somebody alive so that they can respond to treatment.

That’s a very important point. If the patient is suffering from depression and the antidepressant takes weeks to work, they may lose hope during that time. They may become overwhelmed by the suicidal ideation, no longer able to control or resist the impulse to take their life. A lot of the management is therefore to try to help support the patient (and family) so that these thoughts never become too compelling. Often we have to consider hospitalization to protect these patients so that they can stay alive long enough for the antidepressant to work. But ketamine not only has this very rapid effect for their depression, it also has a partly independent effect on suicidal ideation that is equally rapid and robust, which can render the patient safer.

Dr. Sederer: In other words, it’s effective and rapidly so for depression, with a bonus of reducing suicidality? This sounds almost too good to be true.

Dr. Mann: There are some limitations that we have to keep in mind. One limitation is that a single administration of ketamine will produce this robust improvement but it will only persist for most people for 5-7 days.

Dr. Sederer: Is the same duration true for scheduling the next treatment as well?

Dr. Mann: Yes, it is. The patient will gradually begin to deteriorate if you do not repeat the treatment. But as we showed in our randomized controlled clinical study, with ketamine for suicidal ideation, if you continue to deliver the medication, you can sustain the benefit.

Dr. Sederer: Can a person receive both ketamine and a conventional antidepressant at the same time?

Dr. Mann: Yes. In this study, half of the patients were actually continued on their previous medication while we added the ketamine on top of that. It worked very well.

In practice, people use two approaches. One approach used by most ketamine clinics is to give six doses of ketamine at a frequency of about two per week. Then they will reduce the frequency down to once a week for a few more doses and then once a month.

Dr. Sederer:: And this is a ketamine infusion?

Dr. Mann: Yes, this generally has been a ketamine infusion. This approach seems to work quite well. But that may not be necessary.

Another strategy is to give one, two, or three doses of ketamine. If the patient doesn’t respond robustly to two or three doses, they’re not going to respond to subsequent doses.

Dr. Sederer: So, initial responses are a predictor of future response?

Dr. Mann: Exactly. Now, if they haven’t done well with two or three doses, then you’ve got to use other treatments. But if they do well with the two or three, then you’ve got a choice: You can either complete the treatment course with ketamine and then continue them on antidepressant medications, or simply treat them with ketamine alone. What we tend to do is to treat with only antidepressant medications after a small number of ketamine treatments. We also use ketamine as a kind of “rescue medication” if they relapse into severe depression, though this is true for only a minority of patients.

Dr. Sederer: One of the things that we’ve learned is that antidepressants have a very beneficial effect for some people, but then they wear out and the person starts to relapse. Should ketamine be studied as an intervention for people who are no longer responding to the antidepressant(s) that they are on?

Dr. Mann: We do not really know the answer to that question. My experience treating very seriously ill patients is that sometimes the ketamine will work very well the first time or the second time but then in the future, if you try to use it as a rescue medication, it might not work that well. There is some clinical experience that suggests that that may be true for some people. But we have no idea about the frequency or timing with which this might happen. That’s all uncertain.

Moreover, most of our control clinical trial data come from either one dose of ketamine or from a few trials where people have received multiple doses of ketamine, followed by a bit of a taper. But there are very, very few of those types of studies. We’re still learning about the use of this medication.

Dr. Sederer: Importantly, you referenced the side effects of antidepressants. What are the side effects and risks of ketamine?

Dr. Mann: We know a lot more about the immediate short-term side effects of a single dose or a few doses of ketamine. Most people will get a kind of tripping experience. They’ll feel a bit unreal, or their circumstances or experiences of the world feel a bit distorted.

Some patients develop strange ideas. Most patients don’t enjoy those symptoms, even though I know ketamine is used as a party drug, and so on and so forth.

Dr. Sederer: It seems that the context is what matters.

Dr. Mann: Yes. And in a clinic context, most patients simply don’t enjoy these types of dissociative experiences, but they put up with them. They’re not severe, in general.

Dr. Sederer: Is part of the preparation of the patient telling them that this may happen?

Dr. Mann: Yes. We try to explain the potential for these symptoms and that most people get them. These side effects almost invariably terminate with the cessation of the administration.

Dr. Sederer: What’s the typical duration of the infusion you use?

Dr. Mann: Traditionally, infusion is 40 minutes and always in a clinic setting.

Dr. Sederer: And that’s because of the concern that a patient may have these symptoms?

Dr. Mann: Exactly. They may have dissociative effects that they’re disturbed by, and we need to monitor that. They’re probably going to remain under observation in the clinic for about the same amount of time because it takes about the same time for these effects to wear off.

The other consideration is that some people get a little nausea. In our experience with the intravenous ketamine, there’s also a problematic side effect that their blood pressure will be slightly raised. Therefore, it’s good to know that the person’s blood pressure is under control before they begin the treatments and that you’re monitoring it during administration.

Dr. Sederer: What are the differences you’re discovering between esketamine and ketamine?

Dr. Mann: It is a bit different. We’ve just completed a very important National Institutes of Health–funded clinical trial here at Columbia showing that with esketamine or ketamine itself, the dose and the blood levels are very closely related to the robustness of the clinical response.

When you give a drug intravenously, you give a very reliable dose. When you give the drug over 40 minutes, you’re spreading the dose administration over a period of time so that it doesn’t peak very high. The side effects appear to be proportional to the peak dose.

When you give it intranasally, you give the drug over a much shorter period of time. Even if you use more than one intranasal administration to give the whole dose, it’s still a relatively shorter time, compared with the 40 minutes.

Dr. Sederer: This means that to get the equivalent dose intranasally, the patient is going to have to experience a higher peak. Can you predict that those patients who are treated intranasally are going to have more side effects?

Dr. Mann: Right. And that should be explained to the patient. You will not need an intravenous line inserted, which some people might find highly appealing and advantageous, but you will probably have more side effects.

Also, in general, intranasal absorption of drugs is more variable. The predictability of the blood level and, therefore, the degree of antidepressant effect is not as good intranasally as intravenously.

Now, all of this is anecdotal clinical experience, based on theoretical pharmacology, because nobody has actually done a head-to-head control comparison.

Dr. Sederer: What about the cost of both of these preparations?

Dr. Mann: There is a bit of a range in pricing between ketamine clinics around the country. It’s always important to find out what they charge per administration. And then it makes a difference whether you have two or three administrations versus six plus further tapered administration. Clearly, the cost can vary a great deal.

Dr. Sederer: But it’s generally not covered by insurance, so most people are paying out of pocket.

Dr. Mann: Yes. The intranasal ketamine is still in negotiation at the moment, but it should be resolved before it’s fully marketed.

Dr. Sederer: Ketamine is used for major depression. Does it have utility in bipolar depression?

Dr. Mann: We and some others have done initial studies in bipolar depression. In our view, it’s probably going to be as effective in bipolar disorder as it is in major depressive disorder, unipolar depression.

We haven’t seen any manic episodes triggered, but we don’t give repeated doses. We allow research patients to stay on anticonvulsants or mood stabilizers, so that’s helpful. Generally, people with bipolar disorder who come for ketamine treatment for their depression are coming on a mood stabilizer, because that and perhaps other conventional antidepressants have not proven to be effective. So, I think that ketamine plus mood stabilizers seems to be very promising.

Dr. Sederer: I want to return to the antisuicidal properties that you had previously mentioned. I heard from a colleague about a patient who had been admitted to a psychiatric inpatient unit. The patient was in her 20s; she did not have major depression but was persistently suicidal, constantly trying to hurt herself in any way she could. But that seemed to be more a product of borderline personality disorder, with its impulsive and self-destructive problems.

In the end, they tried intranasal ketamine. The response was, just as you described, robust. Her self-injurious behavior dropped in a very pronounced way within a day or two. But she then did require administrations a couple of times a week in order to keep that suicidality at bay.

Based on that example, I’m wondering whether there is an application here for people who are suicidal yet who may not have features of major depression or bipolar depression.

Dr. Mann: It’s a very interesting suggestion for which we have no data-based answer. However, we have a clue from the study that we published in the American Journal of Psychiatry and have since published further analyses on.

The reasons that people die by suicide, or make suicide attempts, are not entirely attributable to the fact that they suffer from a mood disorder.

Dr. Sederer: Yes, because only a minority of individuals with a mood disorder ever make suicide attempts. But there is a subgroup at risk.

Dr. Mann: Here at Columbia, we’ve promulgated the stress-diathesis model for suicidal behavior. A stressor could be external life events, but the internal stressor would be something like an acute episode of depression.

But predisposition also plays an important role, which has several elements to it. One is decision-making. These are patients with a propensity to go for a short-term, quick relief. In other words, a patient would be seeking immediate relief rather than waiting for the delayed improvement from an antidepressant. They’re more prone to act on the pain of the depression and terminate their lives – to try to end their pain – rather than wait and hope that, in time, there’s a chance that the antidepressant will work.

Dr. Sederer: What else do you want to share with our viewers about this medication and how it’s used?

Dr. Mann: My goal in treating patients is to try to use the least amount of medication possible. We do not really know yet the long-term safety of ketamine treatment.

It’s been used for many decades in anesthesia, but people don’t get repeated anesthetic doses of ketamine. And higher doses of ketamine given repeatedly have been shown in preclinical studies to produce little lesions in the brain, which is not good. But we’re using much lower doses.

As we potentially move into a time when we could be giving multiple doses of ketamine to patients, we should remember that we need to be cautious about that. If we don’t need to give them more doses, we shouldn’t. We should know that there is a potential downside that we don’t fully understand yet to giving ketamine repeatedly.

And that’s aside from its abuse potential. We know that people have employed ketamine for physical and emotional pain, and when they administer it themselves, they tend to get dependent on it. In a clinic setting it’s given in a very formal and structured fashion, a bit like the administration of opioids. In that setting, it is much safer and the risk for abuse and diversion is minimized. But we need to remember that this drug does have abuse potential and perhaps not yet fully measurable neurotoxic effects.

Dr. Sederer: If physicians, nurses, and other professional clinicians want to learn more about this medication, what are the accurate, reliable sources of information to which you suggest they turn?

Dr. Mann: The National Institute of Mental Health’s website offers good and reliable information for patients and their families. It is an unbiased, scientific, and thoughtful source of information, and better than just trolling the Internet for information.

People are much more sophisticated now than they were 20 years ago in these matters, and scientific papers are much more accessible to the public. Reading papers in recognized journals is also a useful way to gain information.

For example, one of the major papers that we published in the American Journal of Psychiatry is available to anybody on the Internet to read. So, I encourage people to make their own inquiries and talk to more than one doctor. Informed patients and families are the best partners a doctor can ever have. We encourage that in all of our patients.

Dr. Sederer: I want to thank you very much, Dr. Mann, for your work in this area and for joining us here at Medscape and Columbia Psychiatry to teach us so much about what is truly a novel psychopharmacologic agent, yet one where we still have a lot more to learn.

A version of this article originally appeared on Medscape.com.

Dr. G, a New York surgeon, was only a couple years into practice when he faced his first lawsuit.

After undergoing liposuction surgery on the area of her calf and ankle, a patient claimed she had developed a severe allergic reaction, characterized by small areas of necrosis on the lower extremities, said Dr. G, who asked to remain anonymous. However, the alleged injury seemed suspicious, said Dr. G, considering that 3 weeks after the surgery, the area had shown a successful result with minimal swelling.

Six months into the suit, Dr. G received a shocking phone call. It was the patient’s estranged husband, who revealed that his wife was having an affair with another man, a physician. In recorded phone calls, the patient and her paramour had discussed causing an injury near the patient’s calf in an attempt to sue and get rich, the husband relayed. Dr. G immediately contacted his insurance carrier with the news, but his attorney said the information would not be admissible in court. Instead, the insurer settled with the patient, who received about $125,000.

At the time, Dr. G did not have a consent-to-settle clause in his contract, so the insurer was able to settle without his approval.

In legal practice, a frivolous claim is defined as one that lacks a supporting legal argument or any factual basis. A claim issued with the intent of disturbing, annoying, or harassing the opposing party can also be described as legally frivolous, said Michael Stinson, vice president of government relations and public policy for the Medical Professional Liability Association (MPL Association), a trade association for medical liability insurers.

However, when most physicians refer to “frivolous claims,” they often mean a claim in which there is no attributable negligence. Such suits represent a second category of claims – nonmeritorious lawsuits.

“I think people intermix nonmeritorious and frivolous all the time,” Mr. Stinson said. “In the vast majority of nonmeritorious claims, the patient has suffered an adverse outcome, it’s just that it wasn’t the result of negligence, whereas with a frivolous lawsuit, they really haven’t suffered any damage, so they’ve got no business filing a lawsuit on any level.”

A third type of so-called frivolous suit is that of a fraudulent or fake claim, in which, as Dr. G experienced, a patient causes a self-injury or lies about a condition to craft a false claim against a physician.

If a patient files a claim that the patient knows is false, the patient commits fraud and may be subject to counterclaims for malicious prosecution or abuse of process, said Jeffrey Segal, MD, JD, a neurosurgeon and health law attorney. Further, the patient would be testifying under oath, and such testimony can be considered perjury, a criminal offense with criminal penalties.

Sadly, Dr. G was the target of another frivolous lawsuit years later. In that suit, a patient claimed the surgeon had left a piece of sponge in her breast cavity during surgery. The case was dismissed when medical records proved the patient knew that the foreign body resulted from an unrelated procedure she had undergone years earlier.

“There is so much abuse in the court system,” Dr. G said. “You really don’t think stuff like that will happen to you, especially if you honor the profession. It’s unfortunate. It’s left a very bitter taste in my mouth.”

Frivolous claims have long been a subject of debate. Tort reform advocates often contend that such claims are pervasive. They cite them as key reasons for high health care costs and say that they have led to the rise of defensive medicine. Plaintiffs’ attorneys counter that the rate of frivolous claims is widely exaggerated and argue that the pursuit of frivolous claims would be “bad business” for legal firms. The debate begs the question: Do frivolous cases still exist, and if so, how common are they?

“I have never seen a frivolous malpractice claim,” says Malcolm P. McConnell III, JD, a Richmond, Va., medical malpractice attorney and chair of the Medical Malpractice Legislative Subcommittee for the Virginia Trial Lawyers Association. “I cannot say that such things never happen, but any lawyer bringing such a thing is foolish, because there is no reward for it.”
 

Are shotgun lawsuits frivolous?

To many physicians, being dragged into a lawsuit over a complaint or medical outcome in which they were not involved is frivolous, said Stanislaw Stawicki, MD, a trauma surgeon and researcher based in Bethlehem, Pa. Dr. Stawicki was named in a lawsuit along with a long list of medical staff who interacted in some way with the plaintiff. Dr. Stawicki himself saw the patient once and made a note in the chart but had nothing to do with the patient’s surgery or with any critical decisions regarding his care, he said.

“Nothing really prepares you for seeing your name on a legal complaint,” Dr. Stawicki said. “It’s traumatic. I had to block out entire days to give depositions, which were really kind of pointless. Questions like, ‘Is this really your name? Where did you train? Were you there that morning?’ Stuff that was really not consequential to the fact that someone had surgery a month earlier and had some sort of complication.”

Dr. Stawicki was eventually dropped from the claim, but not before a nearly year-long ordeal of legal proceedings, meetings, and paperwork.

It is common practice for plaintiffs’ attorneys to add codefendants in the early stages of a claim, said David M. Studdert, ScD, a leading health law researcher and a professor of law at Stanford (Calif.) Law School. Defendants are gradually dismissed as the case moves forward and details of the incident become clearer, he said.

“Plaintiffs’ attorneys have strong incentives to try and choose claims that will be successful,” Dr. Studdert said. “However, in the early point in the process, neither the patient nor the attorney may have a good idea what has actually happened with care. So sometimes, filing a lawsuit may be the only way to begin the process of opening up that information.”

A study by Dr. Studdert in which medical malpractice claims, errors, and compensation payments were analyzed found that, out of 1,452 claims, about one-third (37%) did not involve errors.

“Many physicians might call those frivolous lawsuits, but in fact, most of those don’t go on to receive compensation,” he said. “We suspect that in many instances, those claims are simply dropped once it becomes apparent that there wasn’t error involved.

“They can still be burdensome, anxiety provoking, and time consuming for physicians who are named in those suits, so I don’t want to suggest that claims that don’t involve errors are not a problem,” said Dr. Studdert. “However, I think it’s wrong to assume, as many people do when they use the term ‘frivolous lawsuit,’ that this is really an extortionary effort by a plaintiffs’ attorney to try to get money out of a hospital or a physician for care that was really unproblematic.”
 

Certain ‘frivolous’ cases more common than others

Nonmeritorious claims still occur relatively frequently today, according to data from the Medical Professional Liability Association’s Data Sharing Project. Of about 18,000 liability claims reported from 2016 to 2018, 65% were dropped, withdrawn, or dismissed. Of the 6% of claims that went before a jury, more than 85% resulted in a verdict for the defendant, the researchers found.

“Basically, any claim that does not result in a payment because the underlying claim of negligence on the part of a health professional had been demonstrated, proven, or adjudicated false is one we would describe as nonmeritorious,” Mr. Stinson said.

The MPL Association does not track cases that meet the legal definition of frivolous, said Mr. Stinson, and they “don’t see truly frivolous lawsuits very often.”

Malpractice claims are risky, expensive, and aggressively defended, says Mr. McConnell, the plaintiffs’ attorney. Mr. McConnell, who has been practicing for 30 years, said his own claim selection process is very rigorous and that he cannot afford to pursue claims that aren’t well supported by science and medicine.

“Pursuing frivolous cases would bankrupt me and ruin my reputation,” he said. “A lawyer I know once said he would write a check for $10,000 to anyone who could show him a lawyer who makes a living pursuing frivolous medical malpractice cases. It’s a fair challenge. The economics and the practices of liability carriers and defense lawyers make frivolous cases a dead end for plaintiff lawyers.”

Most medical malpractice cases are taken on a contingency fee basis, Mr. McConnell noted, meaning that the plaintiff’s lawyer is not paid unless the claim is successful.

“This means that the plaintiff’s lawyer is risking 2 years of intensive labor on a case which may yield no fee at all,” he said. “Obviously, any reasonable lawyer is going to want to minimize that risk. The only way to minimize that risk is for the case to be solid, not weak, and certainly not frivolous.”

But Dr. Segal, the health law attorney, says that plenty of frivolous liability claims are levied each year, with attorneys willing to pursue them.

It’s true that seasoned plaintiffs’ attorneys generally screen for merit and damages, Dr. Segal said, but in some instances, attorneys who are not trained in malpractice law accept frivolous claims and take them forward. In some cases, they are slip-and-fall accident attorneys accustomed to receiving modest amounts from insurance companies quickly, said Dr. Segal, founder of Medical Justice, a company that helps deter frivolous lawsuits against physicians.

“If we lived in a perfectly rational universe where plaintiffs’ attorneys screened cases well and only took the meritorious cases forward, we would see less frivolous cases filed, but that’s not the universe I live in,” Dr. Segal said. “There are well over a million attorneys in this country, and some are hungrier than others. The attorneys may frequently get burned in the end, and maybe that attorney won’t move another malpractice case forward, but there’s always someone else willing to take their place.”

Medical Justice has twice run a Most Frivolous Lawsuit Contest on its website, one in 2008 and one in late 2018. The first contest drew 30 entries, and the second garnered nearly 40 submissions, primarily from physicians who were defendants in the cases, according to Dr. Segal. (Dr. G’s lawsuit was highlighted in the most recent contest.)

In one case, an emergency physician was drawn into litigation by the family of a deceased patient. The patient experienced sudden cardiac arrythmia at home, and paramedics were unable to intubate her or establish IV access. She was transferred to the hospital, where resuscitation efforts continued, but she remained in asystole and was pronounced dead after 15 minutes.

At the hospital, blood tests were conducted. They showed that her serum potassium concentration was elevated to about 12 mEq/L, Dr. Segal said. The family initiated a claim in which they accused the emergency physician of failure to diagnose hyperkalemia. They alleged that had the hyperkalemia been discovered sooner, the patient’s death could have been prevented.

“If you had no other facts about this, you would wonder how a person with potassium that high would even be alive,” Dr. Segal said. “But what they were looking at was the body decomposing and all the potassium in the cells being released into the bloodstream. It wasn’t the cause of the problem, it was an effect of the problem. She really was dead on arrival, and she was probably dead at home.”

The case was eventually dropped.

Although the outcome for the patient was tragic, says Dr. Segal, the case is one of many types of frivolous claims that exist today.

“Yes, frivolous cases are out there,” he said.
 

Fraudulent claims uncommon

As for fraudulent medical liability claims, legal experts say they’re rare. J. Richard Moore, JD, an Indianapolis-based medical liability defense attorney, said he’s never personally encountered a medical malpractice claim in which he believed a plaintiff caused an injury or an illness and attempted to blame it on a physician.

However, Mr. Moore has defended many claims in which the illness or condition the plaintiff claimed was caused or was made worse through medical negligence was actually a preexisting condition or a preexisting condition that worsened and was not related to any medical negligence, Mr. Moore said.

“Although I have often felt in such cases that the plaintiff really knew that the condition was not affected by any alleged medical negligence, I would not put that in the ‘fraudulent claim’ category because it can be very difficult to establish a person’s subjective state of mind,” he said. “Usually in those cases, the plaintiff just denies memory of previous medical records or claims that the previous doctor who treated him or her for the same condition ‘got it wrong.’ In those cases, it is generally left to the jury whether to believe the plaintiff or not.”

Mr. Stinson also says he has not come across a truly fraudulent medical liability case. He noted that such a claim might be similar to a person falsely claiming a soft-tissue injury following an alleged slip-and-fall accident.

“Clearly, a fraudulent claim could be viewed as riskier from the plaintiff’s perspective because they could face criminal prosecution for insurance fraud, whereas if a claim is merely frivolous, they probably only run the risk of court-issued fine, if even that. That may be why we don’t often see fraudulent MPL claims.”
 

Ways to prevent or fight frivolous lawsuits

Since Dr. Stawicki’s legal nightmare as a resident, rules have tightened in Pennsylvania, and it is now more difficult to file frivolous claims, he said.

Pennsylvania is one of at least 28 states that require a certificate of merit in order for a medical liability claim to move forward. The provisions generally state that an appropriately licensed professional must supply a written statement attesting that the care the patient received failed to meet acceptable professional standards and that such conduct was a cause in the alleged harm.

“There is now a much greater burden of proof regarding what can proceed,” Dr. Stawicki said. “I’ve been involved in a couple cases that did not proceed because there was no certificate of merit.”

Although these reforms may help, not all merit rules are created equal. Some states require that the expert who signs the affidavit be knowledgeable in the relevant issues involved in the action. Other states have looser requirements. In one of the cases featured in Medical Justice’s Most Frivolous Lawsuit Contest, a podiatrist signed a supporting declaration for a claim related to obstetric care.

For physicians facing a frivolous claim, fighting it out in court depends on a number of factors. Without a consent-to-settle clause in the contract, an insurer can make the final decision on whether to defend or settle a case.

Resolving a malpractice claim is generally a business decision for the insurer, Dr. Studdert said.

“When the claim is for a relatively low amount of money, the costs of moving forward to defend that claim may be much more than the costs of simply settling it would be,” he said. “On the other hand, liability insurers and their lawyers are repeat players here, as are the plaintiffs’ attorneys. They don’t want to incentivize plaintiffs’ attorneys to bring questionable claims, and if they settle quickly, that may do so.”

Mr. Stinson, of the MPL Association, said a truly frivolous claim – one with no legal basis – is highly unlikely to be settled, “especially by MPL Association members who go beyond having a purely financial interest in their insureds to also focus on their professional reputation/integrity.” MPL Association members insure nearly 2 million health care professionals globally, including 2,500 hospitals and more than two-thirds of America’s physicians who are in private practice.

Physicians should make sure they know what is and what is not included in their policy, Dr. Segal said.

“The broker should sit down with the doctor, ideally before initial purchase or renewal, and explain in clear terms what the carrier’s obligations are and what the physician’s obligations are,” he said. “Know what type of protection is being purchased and what conditions might trigger a surprising and unhappy outcome.”
 

Should I countersue?

For truly frivolous claims, physicians have the legal right to sue for damages caused by the unfounded complaint.

Perhaps the most well-known case of a successful malpractice countersuit is that of Louisville neurosurgeon John Guarnaschelli, MD, who in 2000 won $72,000 in damages against a plaintiffs’ attorney for malicious prosecution.

The physician’s countersuit followed the dismissal of a negligence claim against Dr. Guarnaschelli by a patient who contracted meningitis. The plaintiffs’ attorney had made little effort to gather evidence to connect Dr. Guarnaschelli to the patient’s injuries and had consulted only one other physician, a client of his, before filing the lawsuit, according to a summary of the case in the American Bar Association Journal.

Malicious prosecution is the most common legal theory of recovery for physicians in countersuits, according to a review of successful countersuits by doctors. Dr. Stawicki is a coauthor of that review. Other legal theories that physicians can raise include abuse of process, negligence, defamation, invasion of privacy, and infliction of emotional distress. Of the 13 cases evaluated in the article by Dr. Stawicki and colleagues, damages awarded to physicians ranged from about $13,000 to $125,000.

Although some doctors have success, pursuing a counterclaim can be a difficult feat, said Benjamin Braslow, MD, a trauma surgeon and professor of clinical surgery at the University of Pennsylvania in Philadelphia.

“The main takeaways were it’s an uphill battle often met with not only resistance but diminishing returns to countersue,” said Dr. Braslow, a coauthor of the countersuits analysis. “You have to meet very specific criteria regarding leveling the suit, and it may end up being a costly, time-consuming battle.”

To prove malicious prosecution, for example, a physician must show that a claim was instituted without probable cause, that the suing party acted maliciously in instituting the action, and that the doctor was damaged by the action, among other essential elements.

As for Dr. G, the surgeon, he now has a contract with a consent-to-settle clause and has taken other legal precautions since his lawsuits. He requires that his patients sign an agreement that any negligence claims they levy go to arbitration. If an arbitrator finds in the patient’s favor, the case may proceed to court, he said. However, he requires another agreement such that if patients lose in court, they are responsible for his legal fees.

“I’m just more careful,” he said. “I ask all my staff in the office to use their judgment, however superficial, if they feel something is wrong with an individual to tell me so. I’d rather send them away than operate on them and have it result in a lawsuit.”
 

A version of this article originally appeared on Medscape.com.

Dr. G, a New York surgeon, was only a couple years into practice when he faced his first lawsuit.

After undergoing liposuction surgery on the area of her calf and ankle, a patient claimed she had developed a severe allergic reaction, characterized by small areas of necrosis on the lower extremities, said Dr. G, who asked to remain anonymous. However, the alleged injury seemed suspicious, said Dr. G, considering that 3 weeks after the surgery, the area had shown a successful result with minimal swelling.

Six months into the suit, Dr. G received a shocking phone call. It was the patient’s estranged husband, who revealed that his wife was having an affair with another man, a physician. In recorded phone calls, the patient and her paramour had discussed causing an injury near the patient’s calf in an attempt to sue and get rich, the husband relayed. Dr. G immediately contacted his insurance carrier with the news, but his attorney said the information would not be admissible in court. Instead, the insurer settled with the patient, who received about $125,000.

At the time, Dr. G did not have a consent-to-settle clause in his contract, so the insurer was able to settle without his approval.

In legal practice, a frivolous claim is defined as one that lacks a supporting legal argument or any factual basis. A claim issued with the intent of disturbing, annoying, or harassing the opposing party can also be described as legally frivolous, said Michael Stinson, vice president of government relations and public policy for the Medical Professional Liability Association (MPL Association), a trade association for medical liability insurers.

However, when most physicians refer to “frivolous claims,” they often mean a claim in which there is no attributable negligence. Such suits represent a second category of claims – nonmeritorious lawsuits.

“I think people intermix nonmeritorious and frivolous all the time,” Mr. Stinson said. “In the vast majority of nonmeritorious claims, the patient has suffered an adverse outcome, it’s just that it wasn’t the result of negligence, whereas with a frivolous lawsuit, they really haven’t suffered any damage, so they’ve got no business filing a lawsuit on any level.”

A third type of so-called frivolous suit is that of a fraudulent or fake claim, in which, as Dr. G experienced, a patient causes a self-injury or lies about a condition to craft a false claim against a physician.

If a patient files a claim that the patient knows is false, the patient commits fraud and may be subject to counterclaims for malicious prosecution or abuse of process, said Jeffrey Segal, MD, JD, a neurosurgeon and health law attorney. Further, the patient would be testifying under oath, and such testimony can be considered perjury, a criminal offense with criminal penalties.

Sadly, Dr. G was the target of another frivolous lawsuit years later. In that suit, a patient claimed the surgeon had left a piece of sponge in her breast cavity during surgery. The case was dismissed when medical records proved the patient knew that the foreign body resulted from an unrelated procedure she had undergone years earlier.

“There is so much abuse in the court system,” Dr. G said. “You really don’t think stuff like that will happen to you, especially if you honor the profession. It’s unfortunate. It’s left a very bitter taste in my mouth.”

Frivolous claims have long been a subject of debate. Tort reform advocates often contend that such claims are pervasive. They cite them as key reasons for high health care costs and say that they have led to the rise of defensive medicine. Plaintiffs’ attorneys counter that the rate of frivolous claims is widely exaggerated and argue that the pursuit of frivolous claims would be “bad business” for legal firms. The debate begs the question: Do frivolous cases still exist, and if so, how common are they?

“I have never seen a frivolous malpractice claim,” says Malcolm P. McConnell III, JD, a Richmond, Va., medical malpractice attorney and chair of the Medical Malpractice Legislative Subcommittee for the Virginia Trial Lawyers Association. “I cannot say that such things never happen, but any lawyer bringing such a thing is foolish, because there is no reward for it.”
 

Are shotgun lawsuits frivolous?

To many physicians, being dragged into a lawsuit over a complaint or medical outcome in which they were not involved is frivolous, said Stanislaw Stawicki, MD, a trauma surgeon and researcher based in Bethlehem, Pa. Dr. Stawicki was named in a lawsuit along with a long list of medical staff who interacted in some way with the plaintiff. Dr. Stawicki himself saw the patient once and made a note in the chart but had nothing to do with the patient’s surgery or with any critical decisions regarding his care, he said.

“Nothing really prepares you for seeing your name on a legal complaint,” Dr. Stawicki said. “It’s traumatic. I had to block out entire days to give depositions, which were really kind of pointless. Questions like, ‘Is this really your name? Where did you train? Were you there that morning?’ Stuff that was really not consequential to the fact that someone had surgery a month earlier and had some sort of complication.”

Dr. Stawicki was eventually dropped from the claim, but not before a nearly year-long ordeal of legal proceedings, meetings, and paperwork.

It is common practice for plaintiffs’ attorneys to add codefendants in the early stages of a claim, said David M. Studdert, ScD, a leading health law researcher and a professor of law at Stanford (Calif.) Law School. Defendants are gradually dismissed as the case moves forward and details of the incident become clearer, he said.

“Plaintiffs’ attorneys have strong incentives to try and choose claims that will be successful,” Dr. Studdert said. “However, in the early point in the process, neither the patient nor the attorney may have a good idea what has actually happened with care. So sometimes, filing a lawsuit may be the only way to begin the process of opening up that information.”

A study by Dr. Studdert in which medical malpractice claims, errors, and compensation payments were analyzed found that, out of 1,452 claims, about one-third (37%) did not involve errors.

“Many physicians might call those frivolous lawsuits, but in fact, most of those don’t go on to receive compensation,” he said. “We suspect that in many instances, those claims are simply dropped once it becomes apparent that there wasn’t error involved.

“They can still be burdensome, anxiety provoking, and time consuming for physicians who are named in those suits, so I don’t want to suggest that claims that don’t involve errors are not a problem,” said Dr. Studdert. “However, I think it’s wrong to assume, as many people do when they use the term ‘frivolous lawsuit,’ that this is really an extortionary effort by a plaintiffs’ attorney to try to get money out of a hospital or a physician for care that was really unproblematic.”
 

Certain ‘frivolous’ cases more common than others

Nonmeritorious claims still occur relatively frequently today, according to data from the Medical Professional Liability Association’s Data Sharing Project. Of about 18,000 liability claims reported from 2016 to 2018, 65% were dropped, withdrawn, or dismissed. Of the 6% of claims that went before a jury, more than 85% resulted in a verdict for the defendant, the researchers found.

“Basically, any claim that does not result in a payment because the underlying claim of negligence on the part of a health professional had been demonstrated, proven, or adjudicated false is one we would describe as nonmeritorious,” Mr. Stinson said.

The MPL Association does not track cases that meet the legal definition of frivolous, said Mr. Stinson, and they “don’t see truly frivolous lawsuits very often.”

Malpractice claims are risky, expensive, and aggressively defended, says Mr. McConnell, the plaintiffs’ attorney. Mr. McConnell, who has been practicing for 30 years, said his own claim selection process is very rigorous and that he cannot afford to pursue claims that aren’t well supported by science and medicine.

“Pursuing frivolous cases would bankrupt me and ruin my reputation,” he said. “A lawyer I know once said he would write a check for $10,000 to anyone who could show him a lawyer who makes a living pursuing frivolous medical malpractice cases. It’s a fair challenge. The economics and the practices of liability carriers and defense lawyers make frivolous cases a dead end for plaintiff lawyers.”

Most medical malpractice cases are taken on a contingency fee basis, Mr. McConnell noted, meaning that the plaintiff’s lawyer is not paid unless the claim is successful.

“This means that the plaintiff’s lawyer is risking 2 years of intensive labor on a case which may yield no fee at all,” he said. “Obviously, any reasonable lawyer is going to want to minimize that risk. The only way to minimize that risk is for the case to be solid, not weak, and certainly not frivolous.”

But Dr. Segal, the health law attorney, says that plenty of frivolous liability claims are levied each year, with attorneys willing to pursue them.

It’s true that seasoned plaintiffs’ attorneys generally screen for merit and damages, Dr. Segal said, but in some instances, attorneys who are not trained in malpractice law accept frivolous claims and take them forward. In some cases, they are slip-and-fall accident attorneys accustomed to receiving modest amounts from insurance companies quickly, said Dr. Segal, founder of Medical Justice, a company that helps deter frivolous lawsuits against physicians.

“If we lived in a perfectly rational universe where plaintiffs’ attorneys screened cases well and only took the meritorious cases forward, we would see less frivolous cases filed, but that’s not the universe I live in,” Dr. Segal said. “There are well over a million attorneys in this country, and some are hungrier than others. The attorneys may frequently get burned in the end, and maybe that attorney won’t move another malpractice case forward, but there’s always someone else willing to take their place.”

Medical Justice has twice run a Most Frivolous Lawsuit Contest on its website, one in 2008 and one in late 2018. The first contest drew 30 entries, and the second garnered nearly 40 submissions, primarily from physicians who were defendants in the cases, according to Dr. Segal. (Dr. G’s lawsuit was highlighted in the most recent contest.)

In one case, an emergency physician was drawn into litigation by the family of a deceased patient. The patient experienced sudden cardiac arrythmia at home, and paramedics were unable to intubate her or establish IV access. She was transferred to the hospital, where resuscitation efforts continued, but she remained in asystole and was pronounced dead after 15 minutes.

At the hospital, blood tests were conducted. They showed that her serum potassium concentration was elevated to about 12 mEq/L, Dr. Segal said. The family initiated a claim in which they accused the emergency physician of failure to diagnose hyperkalemia. They alleged that had the hyperkalemia been discovered sooner, the patient’s death could have been prevented.

“If you had no other facts about this, you would wonder how a person with potassium that high would even be alive,” Dr. Segal said. “But what they were looking at was the body decomposing and all the potassium in the cells being released into the bloodstream. It wasn’t the cause of the problem, it was an effect of the problem. She really was dead on arrival, and she was probably dead at home.”

The case was eventually dropped.

Although the outcome for the patient was tragic, says Dr. Segal, the case is one of many types of frivolous claims that exist today.

“Yes, frivolous cases are out there,” he said.
 

Fraudulent claims uncommon

As for fraudulent medical liability claims, legal experts say they’re rare. J. Richard Moore, JD, an Indianapolis-based medical liability defense attorney, said he’s never personally encountered a medical malpractice claim in which he believed a plaintiff caused an injury or an illness and attempted to blame it on a physician.

However, Mr. Moore has defended many claims in which the illness or condition the plaintiff claimed was caused or was made worse through medical negligence was actually a preexisting condition or a preexisting condition that worsened and was not related to any medical negligence, Mr. Moore said.

“Although I have often felt in such cases that the plaintiff really knew that the condition was not affected by any alleged medical negligence, I would not put that in the ‘fraudulent claim’ category because it can be very difficult to establish a person’s subjective state of mind,” he said. “Usually in those cases, the plaintiff just denies memory of previous medical records or claims that the previous doctor who treated him or her for the same condition ‘got it wrong.’ In those cases, it is generally left to the jury whether to believe the plaintiff or not.”

Mr. Stinson also says he has not come across a truly fraudulent medical liability case. He noted that such a claim might be similar to a person falsely claiming a soft-tissue injury following an alleged slip-and-fall accident.

“Clearly, a fraudulent claim could be viewed as riskier from the plaintiff’s perspective because they could face criminal prosecution for insurance fraud, whereas if a claim is merely frivolous, they probably only run the risk of court-issued fine, if even that. That may be why we don’t often see fraudulent MPL claims.”
 

Ways to prevent or fight frivolous lawsuits

Since Dr. Stawicki’s legal nightmare as a resident, rules have tightened in Pennsylvania, and it is now more difficult to file frivolous claims, he said.

Pennsylvania is one of at least 28 states that require a certificate of merit in order for a medical liability claim to move forward. The provisions generally state that an appropriately licensed professional must supply a written statement attesting that the care the patient received failed to meet acceptable professional standards and that such conduct was a cause in the alleged harm.

“There is now a much greater burden of proof regarding what can proceed,” Dr. Stawicki said. “I’ve been involved in a couple cases that did not proceed because there was no certificate of merit.”

Although these reforms may help, not all merit rules are created equal. Some states require that the expert who signs the affidavit be knowledgeable in the relevant issues involved in the action. Other states have looser requirements. In one of the cases featured in Medical Justice’s Most Frivolous Lawsuit Contest, a podiatrist signed a supporting declaration for a claim related to obstetric care.

For physicians facing a frivolous claim, fighting it out in court depends on a number of factors. Without a consent-to-settle clause in the contract, an insurer can make the final decision on whether to defend or settle a case.

Resolving a malpractice claim is generally a business decision for the insurer, Dr. Studdert said.

“When the claim is for a relatively low amount of money, the costs of moving forward to defend that claim may be much more than the costs of simply settling it would be,” he said. “On the other hand, liability insurers and their lawyers are repeat players here, as are the plaintiffs’ attorneys. They don’t want to incentivize plaintiffs’ attorneys to bring questionable claims, and if they settle quickly, that may do so.”

Mr. Stinson, of the MPL Association, said a truly frivolous claim – one with no legal basis – is highly unlikely to be settled, “especially by MPL Association members who go beyond having a purely financial interest in their insureds to also focus on their professional reputation/integrity.” MPL Association members insure nearly 2 million health care professionals globally, including 2,500 hospitals and more than two-thirds of America’s physicians who are in private practice.

Physicians should make sure they know what is and what is not included in their policy, Dr. Segal said.

“The broker should sit down with the doctor, ideally before initial purchase or renewal, and explain in clear terms what the carrier’s obligations are and what the physician’s obligations are,” he said. “Know what type of protection is being purchased and what conditions might trigger a surprising and unhappy outcome.”
 

Should I countersue?

For truly frivolous claims, physicians have the legal right to sue for damages caused by the unfounded complaint.

Perhaps the most well-known case of a successful malpractice countersuit is that of Louisville neurosurgeon John Guarnaschelli, MD, who in 2000 won $72,000 in damages against a plaintiffs’ attorney for malicious prosecution.

The physician’s countersuit followed the dismissal of a negligence claim against Dr. Guarnaschelli by a patient who contracted meningitis. The plaintiffs’ attorney had made little effort to gather evidence to connect Dr. Guarnaschelli to the patient’s injuries and had consulted only one other physician, a client of his, before filing the lawsuit, according to a summary of the case in the American Bar Association Journal.

Malicious prosecution is the most common legal theory of recovery for physicians in countersuits, according to a review of successful countersuits by doctors. Dr. Stawicki is a coauthor of that review. Other legal theories that physicians can raise include abuse of process, negligence, defamation, invasion of privacy, and infliction of emotional distress. Of the 13 cases evaluated in the article by Dr. Stawicki and colleagues, damages awarded to physicians ranged from about $13,000 to $125,000.

Although some doctors have success, pursuing a counterclaim can be a difficult feat, said Benjamin Braslow, MD, a trauma surgeon and professor of clinical surgery at the University of Pennsylvania in Philadelphia.

“The main takeaways were it’s an uphill battle often met with not only resistance but diminishing returns to countersue,” said Dr. Braslow, a coauthor of the countersuits analysis. “You have to meet very specific criteria regarding leveling the suit, and it may end up being a costly, time-consuming battle.”

To prove malicious prosecution, for example, a physician must show that a claim was instituted without probable cause, that the suing party acted maliciously in instituting the action, and that the doctor was damaged by the action, among other essential elements.

As for Dr. G, the surgeon, he now has a contract with a consent-to-settle clause and has taken other legal precautions since his lawsuits. He requires that his patients sign an agreement that any negligence claims they levy go to arbitration. If an arbitrator finds in the patient’s favor, the case may proceed to court, he said. However, he requires another agreement such that if patients lose in court, they are responsible for his legal fees.

“I’m just more careful,” he said. “I ask all my staff in the office to use their judgment, however superficial, if they feel something is wrong with an individual to tell me so. I’d rather send them away than operate on them and have it result in a lawsuit.”
 

A version of this article originally appeared on Medscape.com.

Dr. G, a New York surgeon, was only a couple years into practice when he faced his first lawsuit.

After undergoing liposuction surgery on the area of her calf and ankle, a patient claimed she had developed a severe allergic reaction, characterized by small areas of necrosis on the lower extremities, said Dr. G, who asked to remain anonymous. However, the alleged injury seemed suspicious, said Dr. G, considering that 3 weeks after the surgery, the area had shown a successful result with minimal swelling.

Six months into the suit, Dr. G received a shocking phone call. It was the patient’s estranged husband, who revealed that his wife was having an affair with another man, a physician. In recorded phone calls, the patient and her paramour had discussed causing an injury near the patient’s calf in an attempt to sue and get rich, the husband relayed. Dr. G immediately contacted his insurance carrier with the news, but his attorney said the information would not be admissible in court. Instead, the insurer settled with the patient, who received about $125,000.

At the time, Dr. G did not have a consent-to-settle clause in his contract, so the insurer was able to settle without his approval.

In legal practice, a frivolous claim is defined as one that lacks a supporting legal argument or any factual basis. A claim issued with the intent of disturbing, annoying, or harassing the opposing party can also be described as legally frivolous, said Michael Stinson, vice president of government relations and public policy for the Medical Professional Liability Association (MPL Association), a trade association for medical liability insurers.

However, when most physicians refer to “frivolous claims,” they often mean a claim in which there is no attributable negligence. Such suits represent a second category of claims – nonmeritorious lawsuits.

“I think people intermix nonmeritorious and frivolous all the time,” Mr. Stinson said. “In the vast majority of nonmeritorious claims, the patient has suffered an adverse outcome, it’s just that it wasn’t the result of negligence, whereas with a frivolous lawsuit, they really haven’t suffered any damage, so they’ve got no business filing a lawsuit on any level.”

A third type of so-called frivolous suit is that of a fraudulent or fake claim, in which, as Dr. G experienced, a patient causes a self-injury or lies about a condition to craft a false claim against a physician.

If a patient files a claim that the patient knows is false, the patient commits fraud and may be subject to counterclaims for malicious prosecution or abuse of process, said Jeffrey Segal, MD, JD, a neurosurgeon and health law attorney. Further, the patient would be testifying under oath, and such testimony can be considered perjury, a criminal offense with criminal penalties.

Sadly, Dr. G was the target of another frivolous lawsuit years later. In that suit, a patient claimed the surgeon had left a piece of sponge in her breast cavity during surgery. The case was dismissed when medical records proved the patient knew that the foreign body resulted from an unrelated procedure she had undergone years earlier.

“There is so much abuse in the court system,” Dr. G said. “You really don’t think stuff like that will happen to you, especially if you honor the profession. It’s unfortunate. It’s left a very bitter taste in my mouth.”

Frivolous claims have long been a subject of debate. Tort reform advocates often contend that such claims are pervasive. They cite them as key reasons for high health care costs and say that they have led to the rise of defensive medicine. Plaintiffs’ attorneys counter that the rate of frivolous claims is widely exaggerated and argue that the pursuit of frivolous claims would be “bad business” for legal firms. The debate begs the question: Do frivolous cases still exist, and if so, how common are they?

“I have never seen a frivolous malpractice claim,” says Malcolm P. McConnell III, JD, a Richmond, Va., medical malpractice attorney and chair of the Medical Malpractice Legislative Subcommittee for the Virginia Trial Lawyers Association. “I cannot say that such things never happen, but any lawyer bringing such a thing is foolish, because there is no reward for it.”
 

Are shotgun lawsuits frivolous?

To many physicians, being dragged into a lawsuit over a complaint or medical outcome in which they were not involved is frivolous, said Stanislaw Stawicki, MD, a trauma surgeon and researcher based in Bethlehem, Pa. Dr. Stawicki was named in a lawsuit along with a long list of medical staff who interacted in some way with the plaintiff. Dr. Stawicki himself saw the patient once and made a note in the chart but had nothing to do with the patient’s surgery or with any critical decisions regarding his care, he said.

“Nothing really prepares you for seeing your name on a legal complaint,” Dr. Stawicki said. “It’s traumatic. I had to block out entire days to give depositions, which were really kind of pointless. Questions like, ‘Is this really your name? Where did you train? Were you there that morning?’ Stuff that was really not consequential to the fact that someone had surgery a month earlier and had some sort of complication.”

Dr. Stawicki was eventually dropped from the claim, but not before a nearly year-long ordeal of legal proceedings, meetings, and paperwork.

It is common practice for plaintiffs’ attorneys to add codefendants in the early stages of a claim, said David M. Studdert, ScD, a leading health law researcher and a professor of law at Stanford (Calif.) Law School. Defendants are gradually dismissed as the case moves forward and details of the incident become clearer, he said.

“Plaintiffs’ attorneys have strong incentives to try and choose claims that will be successful,” Dr. Studdert said. “However, in the early point in the process, neither the patient nor the attorney may have a good idea what has actually happened with care. So sometimes, filing a lawsuit may be the only way to begin the process of opening up that information.”

A study by Dr. Studdert in which medical malpractice claims, errors, and compensation payments were analyzed found that, out of 1,452 claims, about one-third (37%) did not involve errors.

“Many physicians might call those frivolous lawsuits, but in fact, most of those don’t go on to receive compensation,” he said. “We suspect that in many instances, those claims are simply dropped once it becomes apparent that there wasn’t error involved.

“They can still be burdensome, anxiety provoking, and time consuming for physicians who are named in those suits, so I don’t want to suggest that claims that don’t involve errors are not a problem,” said Dr. Studdert. “However, I think it’s wrong to assume, as many people do when they use the term ‘frivolous lawsuit,’ that this is really an extortionary effort by a plaintiffs’ attorney to try to get money out of a hospital or a physician for care that was really unproblematic.”
 

Certain ‘frivolous’ cases more common than others

Nonmeritorious claims still occur relatively frequently today, according to data from the Medical Professional Liability Association’s Data Sharing Project. Of about 18,000 liability claims reported from 2016 to 2018, 65% were dropped, withdrawn, or dismissed. Of the 6% of claims that went before a jury, more than 85% resulted in a verdict for the defendant, the researchers found.

“Basically, any claim that does not result in a payment because the underlying claim of negligence on the part of a health professional had been demonstrated, proven, or adjudicated false is one we would describe as nonmeritorious,” Mr. Stinson said.

The MPL Association does not track cases that meet the legal definition of frivolous, said Mr. Stinson, and they “don’t see truly frivolous lawsuits very often.”

Malpractice claims are risky, expensive, and aggressively defended, says Mr. McConnell, the plaintiffs’ attorney. Mr. McConnell, who has been practicing for 30 years, said his own claim selection process is very rigorous and that he cannot afford to pursue claims that aren’t well supported by science and medicine.

“Pursuing frivolous cases would bankrupt me and ruin my reputation,” he said. “A lawyer I know once said he would write a check for $10,000 to anyone who could show him a lawyer who makes a living pursuing frivolous medical malpractice cases. It’s a fair challenge. The economics and the practices of liability carriers and defense lawyers make frivolous cases a dead end for plaintiff lawyers.”

Most medical malpractice cases are taken on a contingency fee basis, Mr. McConnell noted, meaning that the plaintiff’s lawyer is not paid unless the claim is successful.

“This means that the plaintiff’s lawyer is risking 2 years of intensive labor on a case which may yield no fee at all,” he said. “Obviously, any reasonable lawyer is going to want to minimize that risk. The only way to minimize that risk is for the case to be solid, not weak, and certainly not frivolous.”

But Dr. Segal, the health law attorney, says that plenty of frivolous liability claims are levied each year, with attorneys willing to pursue them.

It’s true that seasoned plaintiffs’ attorneys generally screen for merit and damages, Dr. Segal said, but in some instances, attorneys who are not trained in malpractice law accept frivolous claims and take them forward. In some cases, they are slip-and-fall accident attorneys accustomed to receiving modest amounts from insurance companies quickly, said Dr. Segal, founder of Medical Justice, a company that helps deter frivolous lawsuits against physicians.

“If we lived in a perfectly rational universe where plaintiffs’ attorneys screened cases well and only took the meritorious cases forward, we would see less frivolous cases filed, but that’s not the universe I live in,” Dr. Segal said. “There are well over a million attorneys in this country, and some are hungrier than others. The attorneys may frequently get burned in the end, and maybe that attorney won’t move another malpractice case forward, but there’s always someone else willing to take their place.”

Medical Justice has twice run a Most Frivolous Lawsuit Contest on its website, one in 2008 and one in late 2018. The first contest drew 30 entries, and the second garnered nearly 40 submissions, primarily from physicians who were defendants in the cases, according to Dr. Segal. (Dr. G’s lawsuit was highlighted in the most recent contest.)

In one case, an emergency physician was drawn into litigation by the family of a deceased patient. The patient experienced sudden cardiac arrythmia at home, and paramedics were unable to intubate her or establish IV access. She was transferred to the hospital, where resuscitation efforts continued, but she remained in asystole and was pronounced dead after 15 minutes.

At the hospital, blood tests were conducted. They showed that her serum potassium concentration was elevated to about 12 mEq/L, Dr. Segal said. The family initiated a claim in which they accused the emergency physician of failure to diagnose hyperkalemia. They alleged that had the hyperkalemia been discovered sooner, the patient’s death could have been prevented.

“If you had no other facts about this, you would wonder how a person with potassium that high would even be alive,” Dr. Segal said. “But what they were looking at was the body decomposing and all the potassium in the cells being released into the bloodstream. It wasn’t the cause of the problem, it was an effect of the problem. She really was dead on arrival, and she was probably dead at home.”

The case was eventually dropped.

Although the outcome for the patient was tragic, says Dr. Segal, the case is one of many types of frivolous claims that exist today.

“Yes, frivolous cases are out there,” he said.
 

Fraudulent claims uncommon

As for fraudulent medical liability claims, legal experts say they’re rare. J. Richard Moore, JD, an Indianapolis-based medical liability defense attorney, said he’s never personally encountered a medical malpractice claim in which he believed a plaintiff caused an injury or an illness and attempted to blame it on a physician.

However, Mr. Moore has defended many claims in which the illness or condition the plaintiff claimed was caused or was made worse through medical negligence was actually a preexisting condition or a preexisting condition that worsened and was not related to any medical negligence, Mr. Moore said.

“Although I have often felt in such cases that the plaintiff really knew that the condition was not affected by any alleged medical negligence, I would not put that in the ‘fraudulent claim’ category because it can be very difficult to establish a person’s subjective state of mind,” he said. “Usually in those cases, the plaintiff just denies memory of previous medical records or claims that the previous doctor who treated him or her for the same condition ‘got it wrong.’ In those cases, it is generally left to the jury whether to believe the plaintiff or not.”

Mr. Stinson also says he has not come across a truly fraudulent medical liability case. He noted that such a claim might be similar to a person falsely claiming a soft-tissue injury following an alleged slip-and-fall accident.

“Clearly, a fraudulent claim could be viewed as riskier from the plaintiff’s perspective because they could face criminal prosecution for insurance fraud, whereas if a claim is merely frivolous, they probably only run the risk of court-issued fine, if even that. That may be why we don’t often see fraudulent MPL claims.”
 

Ways to prevent or fight frivolous lawsuits

Since Dr. Stawicki’s legal nightmare as a resident, rules have tightened in Pennsylvania, and it is now more difficult to file frivolous claims, he said.

Pennsylvania is one of at least 28 states that require a certificate of merit in order for a medical liability claim to move forward. The provisions generally state that an appropriately licensed professional must supply a written statement attesting that the care the patient received failed to meet acceptable professional standards and that such conduct was a cause in the alleged harm.

“There is now a much greater burden of proof regarding what can proceed,” Dr. Stawicki said. “I’ve been involved in a couple cases that did not proceed because there was no certificate of merit.”

Although these reforms may help, not all merit rules are created equal. Some states require that the expert who signs the affidavit be knowledgeable in the relevant issues involved in the action. Other states have looser requirements. In one of the cases featured in Medical Justice’s Most Frivolous Lawsuit Contest, a podiatrist signed a supporting declaration for a claim related to obstetric care.

For physicians facing a frivolous claim, fighting it out in court depends on a number of factors. Without a consent-to-settle clause in the contract, an insurer can make the final decision on whether to defend or settle a case.

Resolving a malpractice claim is generally a business decision for the insurer, Dr. Studdert said.

“When the claim is for a relatively low amount of money, the costs of moving forward to defend that claim may be much more than the costs of simply settling it would be,” he said. “On the other hand, liability insurers and their lawyers are repeat players here, as are the plaintiffs’ attorneys. They don’t want to incentivize plaintiffs’ attorneys to bring questionable claims, and if they settle quickly, that may do so.”

Mr. Stinson, of the MPL Association, said a truly frivolous claim – one with no legal basis – is highly unlikely to be settled, “especially by MPL Association members who go beyond having a purely financial interest in their insureds to also focus on their professional reputation/integrity.” MPL Association members insure nearly 2 million health care professionals globally, including 2,500 hospitals and more than two-thirds of America’s physicians who are in private practice.

Physicians should make sure they know what is and what is not included in their policy, Dr. Segal said.

“The broker should sit down with the doctor, ideally before initial purchase or renewal, and explain in clear terms what the carrier’s obligations are and what the physician’s obligations are,” he said. “Know what type of protection is being purchased and what conditions might trigger a surprising and unhappy outcome.”
 

Should I countersue?

For truly frivolous claims, physicians have the legal right to sue for damages caused by the unfounded complaint.

Perhaps the most well-known case of a successful malpractice countersuit is that of Louisville neurosurgeon John Guarnaschelli, MD, who in 2000 won $72,000 in damages against a plaintiffs’ attorney for malicious prosecution.

The physician’s countersuit followed the dismissal of a negligence claim against Dr. Guarnaschelli by a patient who contracted meningitis. The plaintiffs’ attorney had made little effort to gather evidence to connect Dr. Guarnaschelli to the patient’s injuries and had consulted only one other physician, a client of his, before filing the lawsuit, according to a summary of the case in the American Bar Association Journal.

Malicious prosecution is the most common legal theory of recovery for physicians in countersuits, according to a review of successful countersuits by doctors. Dr. Stawicki is a coauthor of that review. Other legal theories that physicians can raise include abuse of process, negligence, defamation, invasion of privacy, and infliction of emotional distress. Of the 13 cases evaluated in the article by Dr. Stawicki and colleagues, damages awarded to physicians ranged from about $13,000 to $125,000.

Although some doctors have success, pursuing a counterclaim can be a difficult feat, said Benjamin Braslow, MD, a trauma surgeon and professor of clinical surgery at the University of Pennsylvania in Philadelphia.

“The main takeaways were it’s an uphill battle often met with not only resistance but diminishing returns to countersue,” said Dr. Braslow, a coauthor of the countersuits analysis. “You have to meet very specific criteria regarding leveling the suit, and it may end up being a costly, time-consuming battle.”

To prove malicious prosecution, for example, a physician must show that a claim was instituted without probable cause, that the suing party acted maliciously in instituting the action, and that the doctor was damaged by the action, among other essential elements.

As for Dr. G, the surgeon, he now has a contract with a consent-to-settle clause and has taken other legal precautions since his lawsuits. He requires that his patients sign an agreement that any negligence claims they levy go to arbitration. If an arbitrator finds in the patient’s favor, the case may proceed to court, he said. However, he requires another agreement such that if patients lose in court, they are responsible for his legal fees.

“I’m just more careful,” he said. “I ask all my staff in the office to use their judgment, however superficial, if they feel something is wrong with an individual to tell me so. I’d rather send them away than operate on them and have it result in a lawsuit.”
 

A version of this article originally appeared on Medscape.com.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus that is causing the ongoing coronavirus disease 2019 (COVID-19) pandemic, was first reported in late 2019.¹ As of mid-October 2020, >39 million confirmed cases of COVID-19 had been reported worldwide, and the United States was the most affected country with >8 million confirmed cases.² Although the reported symptoms of COVID-19 are primarily respiratory with acute respiratory distress syndrome, SARS-CoV-2 has also been shown to affect other organs, including the brain, and there are emerging reports of neurologic symptoms due to COVID-19.³

Psychological endurance will be a challenge that many individuals will continue to face during and after the pandemic. Physical and social isolation, the disruption of daily routines, financial stress, food insecurity, and numerous other potential triggers for stress response have all been intensified due to this pandemic, creating a situation in which many individuals’ mental well-being and stability is likely to be threatened. The uncertain environment is likely to increase the frequency and/or severity of mental health problems worldwide. Psychiatric symptoms such as anxiety and depression have been reported among patients with SARS-CoV-1 during the previous severe acute respiratory syndrome (SARS) epidemic.⁴

In this article, we summarize 8 recent studies, systematic reviews, and meta-analyses to provide an overview of the psychiatric consequences of COVID-19. These studies are summarized in the Table.^5-12 Clearly, the studies reviewed here are preliminary evidence, and our understanding of COVID-19’s effects on mental health, particularly its long-term sequelae, is certain to evolve with future research. However, these 8 studies describe how COVID-19 is currently affecting mental health among health care workers, patients, and the general public.

1. Vindegaard N, Benros ME. COVID-19 pandemic and mental health consequences: systematic review of the current evidence. Brain Behav Immun. 2020;89:531-542. 

Vindegaard and Benros⁵ conducted a systematic review of the literature to characterize the impact of COVID-19–related psychiatric complications and COVID-19’s effect on the mental health of patients infected with COVID-19, as well as non-infected individuals.

Study design

• This systematic review included 43 studies that measured psychiatric disorders or symptoms in patients with COVID-19 and in a non-infected group.
• The non-infected group consisted of psychiatric patients, health care workers, and the general population.
• The review excluded studies with participants who were children, adolescents, or older adults, or had substance abuse or somatic disorders.

Outcomes

• Only 2 studies included patients with confirmed COVID-19 infection. Of the remaining 41 studies, 2 studies examined the indirect effects of the pandemic on psychiatric patients, 20 studies examined health care workers, and 19 studies examined the general population. Eighteen of the studies were case-control studies and 25 had no control group

Patients with confirmed COVID-19 infection. One case-control study showed an increased prevalence of depression in patients with COVID-19 who had recently recovered (29.2%) compared with participants who were in quarantine (9.8%). The other study showed posttraumatic stress symptoms in 96% of hospitalized patients with COVID-19 who were stable.

Continue to: Patients with preexisting psychiatric disorders

Patients with preexisting psychiatric disorders. Two studies found increased symptoms of psychiatric disorders.

Health care workers. Depression (6 studies) and anxiety symptoms (8 studies) were increased among health care workers compared with the general public or administrative staff. However, 2 studies found no difference in these symptoms among health care workers compared with the general public. Poor sleep quality and more obsessive-compulsive symptoms were reported in health care workers compared with the general public.

General public. Compared to before the COVID-19 pandemic, lower psychological well-being and increased rates of depression and anxiety were noted among the general public. Higher rates of anxiety and depression were also found in parents of children who were hospitalized during the pandemic compared with prior to the pandemic. One study found no difference between being in quarantine or not.

• Current or prior medical illness was associated with higher rates of anxiety and depression. One study found higher social media exposure was associated with increased anxiety and depression. Female health care workers had higher rates of anxiety and depression symptoms.

Conclusions/limitations

This systematic review included 39 studies from Asia and 4 from Europe, but none from other continents, which may affect the external validity of the results. Most of the studies included were not case-controlled, which limits the ability to comment on association. Because there is little research on this topic, only 2 of the studies focused on psychiatric symptoms in patients with COVID-19. In most studies, the reporting of psychiatric dis­orders was vague and only a few studies used assessment tools, such as the General Anxiety Disorder-7 or the Patient Health Questionnaire-9, for reporting depression and anxiety.

2. Pappa S, Ntella V, Giannakas T, et al. Prevalence of depression, anxiety, and insomnia among healthcare workers during the COVID-19 pandemic: a systematic review and meta-analysis. Brain Behav Immun. 2020;88:901-907.

Pappa et al⁶ examined the effects of the COVID-19 pandemic on the mental health of health care workers, with specific focus on the prevalence of anxiety, depression, and insomnia.

Continue to: Study design

• Researchers searched for studies on PubMed, Medline, and Google Scholar. A random effect meta-analysis was used on the included 13 cross-sectional studies with a total of 33,062 participants. Twelve of the included studies were conducted in China and 1 in Singapore.
• Evaluation of the risk of bias of included studies was assessed using a modified form of the Newcastle-Ottawa Scale (NOS), with a score >3 considered as low risk of bias.

Outcomes

• Results were categorized by gender, rating scales, severity of depression, and professional groups for subgroup analysis.
• The primary outcomes were prevalence (p), confidence intervals (CI), and percentage prevalence (p × 100%). Studies with a low risk of bias were sub-analyzed again (n = 9).
• Anxiety was evaluated in 12 studies, depression in 10 studies, and insomnia in 5 studies (all 5 studies had a low risk of bias).
• There was a pooled prevalence of 23.2% for anxiety (29% female, 20.9% male), 22.8% for depression (26.87% female, 20.3% male), and 38.9% for insomnia. Female participants showed higher rates of anxiety and depression, while no subgroup analysis was performed for insomnia.
• The subgroup analysis of pooled data after excluding each study showed that no single study had >2% effect on the pooled analysis.
• The subgroup analysis by gender, professional group, and severity suggested that there was an increased prevalence of anxiety and depression in female health care workers, which was consistent with the increased prevalence in the general population.

Conclusions/limitations

There was a questionable effect of between-study heterogeneity. Different studies used different rating scales and different cutoff points on the same scales, which might make the results of pooled analysis unreliable, or might be assumed to increase the confidence. Despite the use of different scales and cutoff points, there was still a high prevalence of anxiety, depression, and insomnia. All studies were conducted in a single geographical region (12 in China and 1 in Singapore). None of the included studies had a control group, either from the general population or compared with pre-COVID-19 rates of depression, anxiety, and insomnia in health care workers.

3. Loades ME, Chatburn E, Higson-Sweeney N, et al. Rapid systematic review: the impact of social isolation and loneliness on the mental health of children and adolescents in the context of COVID-19 [published online June 3, 2020]. J Am Acad Child Adolesc Psychiatry. 2020;S0890-8567(20)30337-3. doi: 10.1016/j.jaac.2020.05.009.

The COVID-19 pandemic has led to long periods of isolation/quarantine, social distancing, and school closures, all which have resulted in significant upheaval of the lives of children and adolescents. Loades et al⁷ explored the impact of loneliness and disease-containment measures related to the COVID-19 pandemic on children and adolescents.

Study design

• Researchers conducted a systematic review of 63 studies examining the impact of loneliness or disease-containment measures on healthy children and adolescents. located through a search of Medline, PsycINFO, and Web of Science. Sixty-one studies were observational, and 2 were interventional.
• The search yielded studies published between 1946 and March 29, 2020.
• The quality of studies was assessed using the National Institutes of Health quality assessment tool.

Continue to: Outcomes

• Results by mental health symptom or disorder were categorized as follows:

Depression. Forty-five studies examined depressive symptoms and loneliness; only 6 studies included children age <10. Most reported a moderate to large correlation (0.12 ≤ r ≤ 0.81), and most of them included a measure of depressive symptoms. The association was stronger in older and female participants. Loneliness was associated with depression in 12 longitudinal studies that followed participants for 1 to 3 years. However, 3 studies (2 in children and 1 in adolescents) found no association between loneliness and depression at follow-up.

Anxiety. Twenty-three studies examined symptoms of anxiety and found a small to moderate correlation between loneliness/social isolation and anxiety (0.18 ≤ r ≤ 0.54), with duration of loneliness being more strongly associated with anxiety than intensity of loneliness. However, social anxiety or generalized anxiety were associated more with loneliness ([0.33 ≤ r ≤ 0.72] and [r = 0.37, 0.40], respectively). Three longitudinal studies found associations between loneliness and subsequent anxiety, and 1 study did not find an association between loneliness at age 5 and increased anxiety at age 12.

Mental health and well-being. Two studies found negative associations between social isolation/loneliness and well-being and mental health.

Conclusions/limitations

There is decent evidence of a strong association between loneliness/social isolation in childhood/adolescence and the development of depression, with some suggestion of increased rates in females. However, there was a small to moderate association with anxiety with increased rates in males. The length of social isolation was a strong predictor of future mental illness. Children who experienced enforced quarantine were 5 times more likely to require mental health services for posttraumatic stress symptoms.

Continue to: The compiled evidence presented in this study...

The compiled evidence presented in this study looked at previous similar scenarios of enforced social isolations; however, it cannot necessarily predict the effect of COVID-19–associated social distancing measures. Most of the studies included were cross-sectional studies and did not control for confounders. Social isolation in childhood or adolescence may be associated with developing mental health problems later in life and should be considered when implementing school closures and switching to online classes. Loades et al⁷ suggested that the increased rate of electronic communication and use of social media in children and adolescents may mitigate this predicted effect of social isolation.

4. Rogers JP, Chesney E, Oliver D, et al. Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic. Lancet Psychiatry. 2020;7(7):611-627.

To identify possible psychiatric and neuro­psychiatric implications of the COVID-19 pandemic, Rogers et al⁸ examined 2 previous coronavirus epidemics, SARS and Middle East respiratory syndrome (MERS), and COVID-19.

Study design

• Researchers conducted a random-effects model meta-analysis and systematic review of 65 studies and 7 preprints from 10 countries, including approximately 3,559 case studies of psychiatric and neuropsychiatric symptoms in participants infected with the 3 major coronavirus-induced illnesses (SARS, MERS, and COVID-19).
• Pure neurologic complications and indirect effects of the epidemics were excluded.
• The systematic review followed PRISMA guidelines.
• The quality of the studies was assessed using the NOS.

Outcomes

• Outcomes measured were psychiatric signs or symptoms; symptom severity; diagnoses based on ICD-10, DSM-IV, the Chinese Classification of Mental Disorders (third edition), or psychometric scales; quality of life; and employment.
• Results were stratified as acute or post-illness:

Acute illness. Delirium was the most frequently reported symptom in all 3 coronavirus infections. Depression, anxiety, or insomnia were also reported in MERS and SARS infections. Mania was described in SARS, but it was almost entirely present in cases treated with high-dose corticosteroids, which are not used routinely for COVID-19.

Continue to: Post-illness

Post-illness. There was increased incidence of depression, anxiety, fatigue, and posttraumatic stress disorder (PTSD) in the post-illness stage of previous coronavirus epidemics (SARS and MERS), but there was no control group for comparison. There was not enough data available for COVID-19.

Conclusions/limitations

Three studies were deemed to be of high quality, 32 were low quality, and 30 were moderate quality. Despite the high incidence of psychiatric symptoms in previous coronavirus infections, it was difficult to draw conclusions due to a lack of adequate control groups and predominantly low-quality studies. The difference in treatment strategies, such as the use of high-dose corticosteroids for MERS and SARS, but not for COVID-19, made it difficult to accurately predict a response for COVID-19 based on previous epidemics.

5. Shiozawa P, Uchida RR. An updated systematic review on the coronavirus pandemic: lessons for psychiatry. Braz J Psychiatry. 2020;42(3):330-331.

Schiozawa et al⁹ conducted a systematic review of articles to identify psychiatric issues during the COVID-19 pandemic.

Study design

• Researchers conducted a systematic review of 10 articles (7 articles from China, 1 from the United States, 1 from Japan, and 1 from Korea) that described strategies for coping with the COVID-19 pandemic and/or provided a descriptive analysis of the clinical scenario, with an emphasis on psychiatric comorbidities.
• The study used PRISMA guidelines to summarize the findings of those 10 studies. There were no pre-set outcomes or inclusion criteria.

Outcomes

• The compiled results of the 10 studies showed high rates of new-onset insomnia, anxiety, and relapse of underlying conditions such as depression.
• One study found increased hospital visits and misinterpretations of any symptom in patients with health anxiety (health anxiety was not defined).
• One study found some benefit from multidisciplinary psychological care and online counseling for both patients and health care workers.

Continue to: Conclusions/limitations

Conclusions/limitations

Because each of the 10 studies examined extremely different outcomes, researchers were unable to compile data from all studies to draw a conclusion.

6. Salari N, Hosseinian-Far A, Jalali R, et al. Prevalence of stress, anxiety, depression among the general population during the COVID-19 pandemic: a systematic review and meta-analysis. Global Health. 2020;16(1):57.

Salari et al¹⁰ examined the prevalence of stress, anxiety, and depression in the general population during the COVID-19 pandemic.

Study design

• Researchers conducted a systematic review and meta-analysis of 17 observational studies examining the prevalence of anxiety and stress in the general population during the COVID-19 pandemic. The STROBE checklist was used to assess the quality of studies.
• Only studies judged as medium to high quality were included in the analysis.

Outcomes

• The prevalence of stress was 29.6% (5 studies, sample size 9,074 individuals).
• The prevalence of anxiety was 31.9% (17 studies, sample size 63,439 individuals).
• The prevalence of depression was 33.7% (14 studies, sample size of 44,531 individuals).
• A sub-analysis of rates by continent revealed that Asia had highest prevalence of anxiety and depression (32.9% and 35.3%, respectively). Europe had the highest rates of stress (31.9%).

Conclusions/limitations

There is an increased prevalence of anxiety, stress, and depression in the general population amid the COVID-19 pandemic. None of the included studies compared rates to before the pandemic. Most studies used online surveys, which increased the chance of sample bias. Most studies originated from China and Iran, which had the highest rates of infection when this review was conducted.

Continue to: #7

Preti et al¹¹ performed a review of the literature to determine the impact of epidemic/pandemic outbreaks on health care workers’ mental health.

Study design

• Researchers conducted a rapid systematic review of 44 studies examining the psychological impact of epidemic/pandemic outbreaks on health care workers.
• Of the 44 studies, 27 (62%) referred to the SARS outbreak, 5 (11%) referred to the MERS outbreak, 5 (11%) referred to the COVID-19 outbreak, 3 (7%) referred to the influenza A virus subtype H1N1 outbreak, 3 (7%) referred to the Ebola virus disease outbreak, and 1 (2%) referred to the Asian lineage avian influenza outbreak.

Outcomes

• During these outbreaks, insomnia was found in 34% to 36.1% of health care workers, and severe anxiety symptoms in 45%.
• The prevalence of PTSD-like symptoms among health care workers during the outbreaks was 11% to 73.4%. Studies of the COVID-19 pandemic reported the highest prevalence of PTSD-like symptoms (71.5% to 73%). After 1 to 3 years following an outbreak, 10% to 40% of health care workers still had significant PTSD-like symptoms.
• Anxiety was reported in 45% of health care workers during the COVID-19 pandemic.
• A sub-analysis revealed a positive association between anxiety, PTSD, and stress symptoms and being female gender, being a nurse, and working on high-risk units.
• Perceived organizational support and confidence in protective measures were negatively associated with psychological symptoms.

Conclusions/limitations

Lessons from previous outbreaks and early data from the COVID-19 pandemic suggest that health care workers experience higher levels of psychological symptoms during outbreaks. Findings of this study suggest that organizational support and confidence in protective measures can mitigate this effect. To help preserve the well-being of health care workers, adequate training should be provided, appropriate personal protective equipment should be readily available, and support services should be well established.

8. Varatharaj A, Thomas N, Ellul MA, et al. Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study. Lancet Psychiatry. 2020;7(10):875-882.

Varatharaj et al¹² conducted a surveillance study in patients in the United Kingdom to understand the breadth of neurologic complications of COVID-19.

Continue to: Study design

• Researchers performed a cross-sectional analysis of the prevalence of psychiatric and neurologic complications in patients with COVID-19 across multiple centers in United Kingdom. Data were collected through the anonymous online reporting portals of several major neurology and psychiatric associations. Retrospective reporting was allowed.
• Evidence of SARS-CoV-2 infection was defined as:

Confirmed COVID-19 (114 cases) if polymerase chain reaction (PCR) of respiratory samples (eg, nasal or throat swab) or CSF was positive for viral RNA or if serology was positive for anti-SARS-CoV-2 immunoglobulin M (IgM) or immunoglobulin G (IgG).

Probable COVID-19 (6 cases) if a chest radiograph or chest CT was consistent with COVID-19 but PCR and serology were negative or not performed.

Possible COVID-19 (5 cases) if the disease was suspected on clinical grounds by the notifying clinician, but PCR, serology, and chest imaging were negative or not performed.

Outcomes

• Sixty-two percent of patients presented with cerebrovascular events (intracerebral hemorrhage, ischemic stroke, vasculitis, or other). Thirty-one percent of patients presented with altered mental status (AMS), and 5% had peripheral neurologic disorders.
• Of those with AMS, 18% (7 patients) had encephalitis, 23% (9 patients) had unspecified encephalopathy, and 59% (23 patients) had a psychiatric diagnosis as classified by the notifying psychiatrist or neuropsychiatrist. Ten patients (43%) of the 23 patients with neuropsychiatric disorders had new-onset psychosis, while only 2 patients had an exacerbation of a preexisting mental illness.

Continue to: Conclusions/limitations

This study had an over-representation of older adults. There was no control group for comparison, and the definition of confirmed COVID-19 included a positive IgM or IgG without a positive PCR or chest imaging. Although all psychiatric conditions reported were confirmed by a psychiatrist or neuropsychiatrist, there were no pre-defined criteria used for reported diagnoses.

Bottom Line

Evidence from studies of previous outbreaks and early data from the coronavirus disease 2019 (COVID-19) pandemic suggest that during outbreaks, health care workers experience higher levels of psychological symptoms than the general population. There has been an increased prevalence of anxiety, stress, poor sleep quality, obsessive-compulsive symptoms, and depression among the general population during the pandemic. COVID-19 can also impact the CNS directly and result in delirium, cerebrovascular events, encephalitis, unspecified encephalopathy, altered mental status, or peripheral neurologic disorders. Patients with preexisting psychiatric disorders are likely to have increased symptoms and should be monitored for breakthrough symptoms and acute exacerbations.

Related Resources

• Ryznar E. Evaluating patients’ decision-making capacity during COVID-19. Current Psychiatry. 2020;19(10):34-40.
• Freudenreich O, Kontos N, Querques J. COVID-19 and patients with serious mental illness. 2020;19(9):24-27,33-39.
• Esterwood E, Saeed SA. Past epidemics, natural disasters, COVID19, and mental health: learning from history as we deal with the present and prepare for the future [published online August 16, 2020]. Psychiatr Q. 2020:1-13. doi: 10.1007/s11126-020-09808-4.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus that is causing the ongoing coronavirus disease 2019 (COVID-19) pandemic, was first reported in late 2019.¹ As of mid-October 2020, >39 million confirmed cases of COVID-19 had been reported worldwide, and the United States was the most affected country with >8 million confirmed cases.² Although the reported symptoms of COVID-19 are primarily respiratory with acute respiratory distress syndrome, SARS-CoV-2 has also been shown to affect other organs, including the brain, and there are emerging reports of neurologic symptoms due to COVID-19.³

Psychological endurance will be a challenge that many individuals will continue to face during and after the pandemic. Physical and social isolation, the disruption of daily routines, financial stress, food insecurity, and numerous other potential triggers for stress response have all been intensified due to this pandemic, creating a situation in which many individuals’ mental well-being and stability is likely to be threatened. The uncertain environment is likely to increase the frequency and/or severity of mental health problems worldwide. Psychiatric symptoms such as anxiety and depression have been reported among patients with SARS-CoV-1 during the previous severe acute respiratory syndrome (SARS) epidemic.⁴

In this article, we summarize 8 recent studies, systematic reviews, and meta-analyses to provide an overview of the psychiatric consequences of COVID-19. These studies are summarized in the Table.^5-12 Clearly, the studies reviewed here are preliminary evidence, and our understanding of COVID-19’s effects on mental health, particularly its long-term sequelae, is certain to evolve with future research. However, these 8 studies describe how COVID-19 is currently affecting mental health among health care workers, patients, and the general public.

1. Vindegaard N, Benros ME. COVID-19 pandemic and mental health consequences: systematic review of the current evidence. Brain Behav Immun. 2020;89:531-542. 

Vindegaard and Benros⁵ conducted a systematic review of the literature to characterize the impact of COVID-19–related psychiatric complications and COVID-19’s effect on the mental health of patients infected with COVID-19, as well as non-infected individuals.

Study design

• This systematic review included 43 studies that measured psychiatric disorders or symptoms in patients with COVID-19 and in a non-infected group.
• The non-infected group consisted of psychiatric patients, health care workers, and the general population.
• The review excluded studies with participants who were children, adolescents, or older adults, or had substance abuse or somatic disorders.

Outcomes

• Only 2 studies included patients with confirmed COVID-19 infection. Of the remaining 41 studies, 2 studies examined the indirect effects of the pandemic on psychiatric patients, 20 studies examined health care workers, and 19 studies examined the general population. Eighteen of the studies were case-control studies and 25 had no control group

Patients with confirmed COVID-19 infection. One case-control study showed an increased prevalence of depression in patients with COVID-19 who had recently recovered (29.2%) compared with participants who were in quarantine (9.8%). The other study showed posttraumatic stress symptoms in 96% of hospitalized patients with COVID-19 who were stable.

Continue to: Patients with preexisting psychiatric disorders

Patients with preexisting psychiatric disorders. Two studies found increased symptoms of psychiatric disorders.

Health care workers. Depression (6 studies) and anxiety symptoms (8 studies) were increased among health care workers compared with the general public or administrative staff. However, 2 studies found no difference in these symptoms among health care workers compared with the general public. Poor sleep quality and more obsessive-compulsive symptoms were reported in health care workers compared with the general public.

General public. Compared to before the COVID-19 pandemic, lower psychological well-being and increased rates of depression and anxiety were noted among the general public. Higher rates of anxiety and depression were also found in parents of children who were hospitalized during the pandemic compared with prior to the pandemic. One study found no difference between being in quarantine or not.

• Current or prior medical illness was associated with higher rates of anxiety and depression. One study found higher social media exposure was associated with increased anxiety and depression. Female health care workers had higher rates of anxiety and depression symptoms.

Conclusions/limitations

This systematic review included 39 studies from Asia and 4 from Europe, but none from other continents, which may affect the external validity of the results. Most of the studies included were not case-controlled, which limits the ability to comment on association. Because there is little research on this topic, only 2 of the studies focused on psychiatric symptoms in patients with COVID-19. In most studies, the reporting of psychiatric dis­orders was vague and only a few studies used assessment tools, such as the General Anxiety Disorder-7 or the Patient Health Questionnaire-9, for reporting depression and anxiety.

2. Pappa S, Ntella V, Giannakas T, et al. Prevalence of depression, anxiety, and insomnia among healthcare workers during the COVID-19 pandemic: a systematic review and meta-analysis. Brain Behav Immun. 2020;88:901-907.

Pappa et al⁶ examined the effects of the COVID-19 pandemic on the mental health of health care workers, with specific focus on the prevalence of anxiety, depression, and insomnia.

Continue to: Study design

• Researchers searched for studies on PubMed, Medline, and Google Scholar. A random effect meta-analysis was used on the included 13 cross-sectional studies with a total of 33,062 participants. Twelve of the included studies were conducted in China and 1 in Singapore.
• Evaluation of the risk of bias of included studies was assessed using a modified form of the Newcastle-Ottawa Scale (NOS), with a score >3 considered as low risk of bias.

Outcomes

• Results were categorized by gender, rating scales, severity of depression, and professional groups for subgroup analysis.
• The primary outcomes were prevalence (p), confidence intervals (CI), and percentage prevalence (p × 100%). Studies with a low risk of bias were sub-analyzed again (n = 9).
• Anxiety was evaluated in 12 studies, depression in 10 studies, and insomnia in 5 studies (all 5 studies had a low risk of bias).
• There was a pooled prevalence of 23.2% for anxiety (29% female, 20.9% male), 22.8% for depression (26.87% female, 20.3% male), and 38.9% for insomnia. Female participants showed higher rates of anxiety and depression, while no subgroup analysis was performed for insomnia.
• The subgroup analysis of pooled data after excluding each study showed that no single study had >2% effect on the pooled analysis.
• The subgroup analysis by gender, professional group, and severity suggested that there was an increased prevalence of anxiety and depression in female health care workers, which was consistent with the increased prevalence in the general population.

Conclusions/limitations

There was a questionable effect of between-study heterogeneity. Different studies used different rating scales and different cutoff points on the same scales, which might make the results of pooled analysis unreliable, or might be assumed to increase the confidence. Despite the use of different scales and cutoff points, there was still a high prevalence of anxiety, depression, and insomnia. All studies were conducted in a single geographical region (12 in China and 1 in Singapore). None of the included studies had a control group, either from the general population or compared with pre-COVID-19 rates of depression, anxiety, and insomnia in health care workers.

3. Loades ME, Chatburn E, Higson-Sweeney N, et al. Rapid systematic review: the impact of social isolation and loneliness on the mental health of children and adolescents in the context of COVID-19 [published online June 3, 2020]. J Am Acad Child Adolesc Psychiatry. 2020;S0890-8567(20)30337-3. doi: 10.1016/j.jaac.2020.05.009.

The COVID-19 pandemic has led to long periods of isolation/quarantine, social distancing, and school closures, all which have resulted in significant upheaval of the lives of children and adolescents. Loades et al⁷ explored the impact of loneliness and disease-containment measures related to the COVID-19 pandemic on children and adolescents.

Study design

• Researchers conducted a systematic review of 63 studies examining the impact of loneliness or disease-containment measures on healthy children and adolescents. located through a search of Medline, PsycINFO, and Web of Science. Sixty-one studies were observational, and 2 were interventional.
• The search yielded studies published between 1946 and March 29, 2020.
• The quality of studies was assessed using the National Institutes of Health quality assessment tool.

Continue to: Outcomes

• Results by mental health symptom or disorder were categorized as follows:

Depression. Forty-five studies examined depressive symptoms and loneliness; only 6 studies included children age <10. Most reported a moderate to large correlation (0.12 ≤ r ≤ 0.81), and most of them included a measure of depressive symptoms. The association was stronger in older and female participants. Loneliness was associated with depression in 12 longitudinal studies that followed participants for 1 to 3 years. However, 3 studies (2 in children and 1 in adolescents) found no association between loneliness and depression at follow-up.

Anxiety. Twenty-three studies examined symptoms of anxiety and found a small to moderate correlation between loneliness/social isolation and anxiety (0.18 ≤ r ≤ 0.54), with duration of loneliness being more strongly associated with anxiety than intensity of loneliness. However, social anxiety or generalized anxiety were associated more with loneliness ([0.33 ≤ r ≤ 0.72] and [r = 0.37, 0.40], respectively). Three longitudinal studies found associations between loneliness and subsequent anxiety, and 1 study did not find an association between loneliness at age 5 and increased anxiety at age 12.

Mental health and well-being. Two studies found negative associations between social isolation/loneliness and well-being and mental health.

Conclusions/limitations

There is decent evidence of a strong association between loneliness/social isolation in childhood/adolescence and the development of depression, with some suggestion of increased rates in females. However, there was a small to moderate association with anxiety with increased rates in males. The length of social isolation was a strong predictor of future mental illness. Children who experienced enforced quarantine were 5 times more likely to require mental health services for posttraumatic stress symptoms.

Continue to: The compiled evidence presented in this study...

The compiled evidence presented in this study looked at previous similar scenarios of enforced social isolations; however, it cannot necessarily predict the effect of COVID-19–associated social distancing measures. Most of the studies included were cross-sectional studies and did not control for confounders. Social isolation in childhood or adolescence may be associated with developing mental health problems later in life and should be considered when implementing school closures and switching to online classes. Loades et al⁷ suggested that the increased rate of electronic communication and use of social media in children and adolescents may mitigate this predicted effect of social isolation.

4. Rogers JP, Chesney E, Oliver D, et al. Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic. Lancet Psychiatry. 2020;7(7):611-627.

To identify possible psychiatric and neuro­psychiatric implications of the COVID-19 pandemic, Rogers et al⁸ examined 2 previous coronavirus epidemics, SARS and Middle East respiratory syndrome (MERS), and COVID-19.

Study design

• Researchers conducted a random-effects model meta-analysis and systematic review of 65 studies and 7 preprints from 10 countries, including approximately 3,559 case studies of psychiatric and neuropsychiatric symptoms in participants infected with the 3 major coronavirus-induced illnesses (SARS, MERS, and COVID-19).
• Pure neurologic complications and indirect effects of the epidemics were excluded.
• The systematic review followed PRISMA guidelines.
• The quality of the studies was assessed using the NOS.

Outcomes

• Outcomes measured were psychiatric signs or symptoms; symptom severity; diagnoses based on ICD-10, DSM-IV, the Chinese Classification of Mental Disorders (third edition), or psychometric scales; quality of life; and employment.
• Results were stratified as acute or post-illness:

Acute illness. Delirium was the most frequently reported symptom in all 3 coronavirus infections. Depression, anxiety, or insomnia were also reported in MERS and SARS infections. Mania was described in SARS, but it was almost entirely present in cases treated with high-dose corticosteroids, which are not used routinely for COVID-19.

Continue to: Post-illness

Post-illness. There was increased incidence of depression, anxiety, fatigue, and posttraumatic stress disorder (PTSD) in the post-illness stage of previous coronavirus epidemics (SARS and MERS), but there was no control group for comparison. There was not enough data available for COVID-19.

Conclusions/limitations

Three studies were deemed to be of high quality, 32 were low quality, and 30 were moderate quality. Despite the high incidence of psychiatric symptoms in previous coronavirus infections, it was difficult to draw conclusions due to a lack of adequate control groups and predominantly low-quality studies. The difference in treatment strategies, such as the use of high-dose corticosteroids for MERS and SARS, but not for COVID-19, made it difficult to accurately predict a response for COVID-19 based on previous epidemics.

5. Shiozawa P, Uchida RR. An updated systematic review on the coronavirus pandemic: lessons for psychiatry. Braz J Psychiatry. 2020;42(3):330-331.

Schiozawa et al⁹ conducted a systematic review of articles to identify psychiatric issues during the COVID-19 pandemic.

Study design

• Researchers conducted a systematic review of 10 articles (7 articles from China, 1 from the United States, 1 from Japan, and 1 from Korea) that described strategies for coping with the COVID-19 pandemic and/or provided a descriptive analysis of the clinical scenario, with an emphasis on psychiatric comorbidities.
• The study used PRISMA guidelines to summarize the findings of those 10 studies. There were no pre-set outcomes or inclusion criteria.

Outcomes

• The compiled results of the 10 studies showed high rates of new-onset insomnia, anxiety, and relapse of underlying conditions such as depression.
• One study found increased hospital visits and misinterpretations of any symptom in patients with health anxiety (health anxiety was not defined).
• One study found some benefit from multidisciplinary psychological care and online counseling for both patients and health care workers.

Continue to: Conclusions/limitations

Conclusions/limitations

Because each of the 10 studies examined extremely different outcomes, researchers were unable to compile data from all studies to draw a conclusion.

6. Salari N, Hosseinian-Far A, Jalali R, et al. Prevalence of stress, anxiety, depression among the general population during the COVID-19 pandemic: a systematic review and meta-analysis. Global Health. 2020;16(1):57.

Salari et al¹⁰ examined the prevalence of stress, anxiety, and depression in the general population during the COVID-19 pandemic.

Study design

• Researchers conducted a systematic review and meta-analysis of 17 observational studies examining the prevalence of anxiety and stress in the general population during the COVID-19 pandemic. The STROBE checklist was used to assess the quality of studies.
• Only studies judged as medium to high quality were included in the analysis.

Outcomes

• The prevalence of stress was 29.6% (5 studies, sample size 9,074 individuals).
• The prevalence of anxiety was 31.9% (17 studies, sample size 63,439 individuals).
• The prevalence of depression was 33.7% (14 studies, sample size of 44,531 individuals).
• A sub-analysis of rates by continent revealed that Asia had highest prevalence of anxiety and depression (32.9% and 35.3%, respectively). Europe had the highest rates of stress (31.9%).

Conclusions/limitations

There is an increased prevalence of anxiety, stress, and depression in the general population amid the COVID-19 pandemic. None of the included studies compared rates to before the pandemic. Most studies used online surveys, which increased the chance of sample bias. Most studies originated from China and Iran, which had the highest rates of infection when this review was conducted.

Continue to: #7

Preti et al¹¹ performed a review of the literature to determine the impact of epidemic/pandemic outbreaks on health care workers’ mental health.

Study design

• Researchers conducted a rapid systematic review of 44 studies examining the psychological impact of epidemic/pandemic outbreaks on health care workers.
• Of the 44 studies, 27 (62%) referred to the SARS outbreak, 5 (11%) referred to the MERS outbreak, 5 (11%) referred to the COVID-19 outbreak, 3 (7%) referred to the influenza A virus subtype H1N1 outbreak, 3 (7%) referred to the Ebola virus disease outbreak, and 1 (2%) referred to the Asian lineage avian influenza outbreak.

Outcomes

• During these outbreaks, insomnia was found in 34% to 36.1% of health care workers, and severe anxiety symptoms in 45%.
• The prevalence of PTSD-like symptoms among health care workers during the outbreaks was 11% to 73.4%. Studies of the COVID-19 pandemic reported the highest prevalence of PTSD-like symptoms (71.5% to 73%). After 1 to 3 years following an outbreak, 10% to 40% of health care workers still had significant PTSD-like symptoms.
• Anxiety was reported in 45% of health care workers during the COVID-19 pandemic.
• A sub-analysis revealed a positive association between anxiety, PTSD, and stress symptoms and being female gender, being a nurse, and working on high-risk units.
• Perceived organizational support and confidence in protective measures were negatively associated with psychological symptoms.

Conclusions/limitations

Lessons from previous outbreaks and early data from the COVID-19 pandemic suggest that health care workers experience higher levels of psychological symptoms during outbreaks. Findings of this study suggest that organizational support and confidence in protective measures can mitigate this effect. To help preserve the well-being of health care workers, adequate training should be provided, appropriate personal protective equipment should be readily available, and support services should be well established.

8. Varatharaj A, Thomas N, Ellul MA, et al. Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study. Lancet Psychiatry. 2020;7(10):875-882.

Varatharaj et al¹² conducted a surveillance study in patients in the United Kingdom to understand the breadth of neurologic complications of COVID-19.

Continue to: Study design

• Researchers performed a cross-sectional analysis of the prevalence of psychiatric and neurologic complications in patients with COVID-19 across multiple centers in United Kingdom. Data were collected through the anonymous online reporting portals of several major neurology and psychiatric associations. Retrospective reporting was allowed.
• Evidence of SARS-CoV-2 infection was defined as:

Confirmed COVID-19 (114 cases) if polymerase chain reaction (PCR) of respiratory samples (eg, nasal or throat swab) or CSF was positive for viral RNA or if serology was positive for anti-SARS-CoV-2 immunoglobulin M (IgM) or immunoglobulin G (IgG).

Probable COVID-19 (6 cases) if a chest radiograph or chest CT was consistent with COVID-19 but PCR and serology were negative or not performed.

Possible COVID-19 (5 cases) if the disease was suspected on clinical grounds by the notifying clinician, but PCR, serology, and chest imaging were negative or not performed.

Outcomes

• Sixty-two percent of patients presented with cerebrovascular events (intracerebral hemorrhage, ischemic stroke, vasculitis, or other). Thirty-one percent of patients presented with altered mental status (AMS), and 5% had peripheral neurologic disorders.
• Of those with AMS, 18% (7 patients) had encephalitis, 23% (9 patients) had unspecified encephalopathy, and 59% (23 patients) had a psychiatric diagnosis as classified by the notifying psychiatrist or neuropsychiatrist. Ten patients (43%) of the 23 patients with neuropsychiatric disorders had new-onset psychosis, while only 2 patients had an exacerbation of a preexisting mental illness.

Continue to: Conclusions/limitations

This study had an over-representation of older adults. There was no control group for comparison, and the definition of confirmed COVID-19 included a positive IgM or IgG without a positive PCR or chest imaging. Although all psychiatric conditions reported were confirmed by a psychiatrist or neuropsychiatrist, there were no pre-defined criteria used for reported diagnoses.

Bottom Line

Evidence from studies of previous outbreaks and early data from the coronavirus disease 2019 (COVID-19) pandemic suggest that during outbreaks, health care workers experience higher levels of psychological symptoms than the general population. There has been an increased prevalence of anxiety, stress, poor sleep quality, obsessive-compulsive symptoms, and depression among the general population during the pandemic. COVID-19 can also impact the CNS directly and result in delirium, cerebrovascular events, encephalitis, unspecified encephalopathy, altered mental status, or peripheral neurologic disorders. Patients with preexisting psychiatric disorders are likely to have increased symptoms and should be monitored for breakthrough symptoms and acute exacerbations.

Related Resources

• Ryznar E. Evaluating patients’ decision-making capacity during COVID-19. Current Psychiatry. 2020;19(10):34-40.
• Freudenreich O, Kontos N, Querques J. COVID-19 and patients with serious mental illness. 2020;19(9):24-27,33-39.
• Esterwood E, Saeed SA. Past epidemics, natural disasters, COVID19, and mental health: learning from history as we deal with the present and prepare for the future [published online August 16, 2020]. Psychiatr Q. 2020:1-13. doi: 10.1007/s11126-020-09808-4.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus that is causing the ongoing coronavirus disease 2019 (COVID-19) pandemic, was first reported in late 2019.¹ As of mid-October 2020, >39 million confirmed cases of COVID-19 had been reported worldwide, and the United States was the most affected country with >8 million confirmed cases.² Although the reported symptoms of COVID-19 are primarily respiratory with acute respiratory distress syndrome, SARS-CoV-2 has also been shown to affect other organs, including the brain, and there are emerging reports of neurologic symptoms due to COVID-19.³

Psychological endurance will be a challenge that many individuals will continue to face during and after the pandemic. Physical and social isolation, the disruption of daily routines, financial stress, food insecurity, and numerous other potential triggers for stress response have all been intensified due to this pandemic, creating a situation in which many individuals’ mental well-being and stability is likely to be threatened. The uncertain environment is likely to increase the frequency and/or severity of mental health problems worldwide. Psychiatric symptoms such as anxiety and depression have been reported among patients with SARS-CoV-1 during the previous severe acute respiratory syndrome (SARS) epidemic.⁴

In this article, we summarize 8 recent studies, systematic reviews, and meta-analyses to provide an overview of the psychiatric consequences of COVID-19. These studies are summarized in the Table.^5-12 Clearly, the studies reviewed here are preliminary evidence, and our understanding of COVID-19’s effects on mental health, particularly its long-term sequelae, is certain to evolve with future research. However, these 8 studies describe how COVID-19 is currently affecting mental health among health care workers, patients, and the general public.

1. Vindegaard N, Benros ME. COVID-19 pandemic and mental health consequences: systematic review of the current evidence. Brain Behav Immun. 2020;89:531-542. 

Vindegaard and Benros⁵ conducted a systematic review of the literature to characterize the impact of COVID-19–related psychiatric complications and COVID-19’s effect on the mental health of patients infected with COVID-19, as well as non-infected individuals.

Study design

• This systematic review included 43 studies that measured psychiatric disorders or symptoms in patients with COVID-19 and in a non-infected group.
• The non-infected group consisted of psychiatric patients, health care workers, and the general population.
• The review excluded studies with participants who were children, adolescents, or older adults, or had substance abuse or somatic disorders.

Outcomes

• Only 2 studies included patients with confirmed COVID-19 infection. Of the remaining 41 studies, 2 studies examined the indirect effects of the pandemic on psychiatric patients, 20 studies examined health care workers, and 19 studies examined the general population. Eighteen of the studies were case-control studies and 25 had no control group

Patients with confirmed COVID-19 infection. One case-control study showed an increased prevalence of depression in patients with COVID-19 who had recently recovered (29.2%) compared with participants who were in quarantine (9.8%). The other study showed posttraumatic stress symptoms in 96% of hospitalized patients with COVID-19 who were stable.

Continue to: Patients with preexisting psychiatric disorders

Patients with preexisting psychiatric disorders. Two studies found increased symptoms of psychiatric disorders.

Health care workers. Depression (6 studies) and anxiety symptoms (8 studies) were increased among health care workers compared with the general public or administrative staff. However, 2 studies found no difference in these symptoms among health care workers compared with the general public. Poor sleep quality and more obsessive-compulsive symptoms were reported in health care workers compared with the general public.

General public. Compared to before the COVID-19 pandemic, lower psychological well-being and increased rates of depression and anxiety were noted among the general public. Higher rates of anxiety and depression were also found in parents of children who were hospitalized during the pandemic compared with prior to the pandemic. One study found no difference between being in quarantine or not.

• Current or prior medical illness was associated with higher rates of anxiety and depression. One study found higher social media exposure was associated with increased anxiety and depression. Female health care workers had higher rates of anxiety and depression symptoms.

Conclusions/limitations

This systematic review included 39 studies from Asia and 4 from Europe, but none from other continents, which may affect the external validity of the results. Most of the studies included were not case-controlled, which limits the ability to comment on association. Because there is little research on this topic, only 2 of the studies focused on psychiatric symptoms in patients with COVID-19. In most studies, the reporting of psychiatric dis­orders was vague and only a few studies used assessment tools, such as the General Anxiety Disorder-7 or the Patient Health Questionnaire-9, for reporting depression and anxiety.

2. Pappa S, Ntella V, Giannakas T, et al. Prevalence of depression, anxiety, and insomnia among healthcare workers during the COVID-19 pandemic: a systematic review and meta-analysis. Brain Behav Immun. 2020;88:901-907.

Pappa et al⁶ examined the effects of the COVID-19 pandemic on the mental health of health care workers, with specific focus on the prevalence of anxiety, depression, and insomnia.

Continue to: Study design

• Researchers searched for studies on PubMed, Medline, and Google Scholar. A random effect meta-analysis was used on the included 13 cross-sectional studies with a total of 33,062 participants. Twelve of the included studies were conducted in China and 1 in Singapore.
• Evaluation of the risk of bias of included studies was assessed using a modified form of the Newcastle-Ottawa Scale (NOS), with a score >3 considered as low risk of bias.

Outcomes

• Results were categorized by gender, rating scales, severity of depression, and professional groups for subgroup analysis.
• The primary outcomes were prevalence (p), confidence intervals (CI), and percentage prevalence (p × 100%). Studies with a low risk of bias were sub-analyzed again (n = 9).
• Anxiety was evaluated in 12 studies, depression in 10 studies, and insomnia in 5 studies (all 5 studies had a low risk of bias).
• There was a pooled prevalence of 23.2% for anxiety (29% female, 20.9% male), 22.8% for depression (26.87% female, 20.3% male), and 38.9% for insomnia. Female participants showed higher rates of anxiety and depression, while no subgroup analysis was performed for insomnia.
• The subgroup analysis of pooled data after excluding each study showed that no single study had >2% effect on the pooled analysis.
• The subgroup analysis by gender, professional group, and severity suggested that there was an increased prevalence of anxiety and depression in female health care workers, which was consistent with the increased prevalence in the general population.

Conclusions/limitations

There was a questionable effect of between-study heterogeneity. Different studies used different rating scales and different cutoff points on the same scales, which might make the results of pooled analysis unreliable, or might be assumed to increase the confidence. Despite the use of different scales and cutoff points, there was still a high prevalence of anxiety, depression, and insomnia. All studies were conducted in a single geographical region (12 in China and 1 in Singapore). None of the included studies had a control group, either from the general population or compared with pre-COVID-19 rates of depression, anxiety, and insomnia in health care workers.

3. Loades ME, Chatburn E, Higson-Sweeney N, et al. Rapid systematic review: the impact of social isolation and loneliness on the mental health of children and adolescents in the context of COVID-19 [published online June 3, 2020]. J Am Acad Child Adolesc Psychiatry. 2020;S0890-8567(20)30337-3. doi: 10.1016/j.jaac.2020.05.009.

The COVID-19 pandemic has led to long periods of isolation/quarantine, social distancing, and school closures, all which have resulted in significant upheaval of the lives of children and adolescents. Loades et al⁷ explored the impact of loneliness and disease-containment measures related to the COVID-19 pandemic on children and adolescents.

Study design

• Researchers conducted a systematic review of 63 studies examining the impact of loneliness or disease-containment measures on healthy children and adolescents. located through a search of Medline, PsycINFO, and Web of Science. Sixty-one studies were observational, and 2 were interventional.
• The search yielded studies published between 1946 and March 29, 2020.
• The quality of studies was assessed using the National Institutes of Health quality assessment tool.

Continue to: Outcomes

• Results by mental health symptom or disorder were categorized as follows:

Depression. Forty-five studies examined depressive symptoms and loneliness; only 6 studies included children age <10. Most reported a moderate to large correlation (0.12 ≤ r ≤ 0.81), and most of them included a measure of depressive symptoms. The association was stronger in older and female participants. Loneliness was associated with depression in 12 longitudinal studies that followed participants for 1 to 3 years. However, 3 studies (2 in children and 1 in adolescents) found no association between loneliness and depression at follow-up.

Anxiety. Twenty-three studies examined symptoms of anxiety and found a small to moderate correlation between loneliness/social isolation and anxiety (0.18 ≤ r ≤ 0.54), with duration of loneliness being more strongly associated with anxiety than intensity of loneliness. However, social anxiety or generalized anxiety were associated more with loneliness ([0.33 ≤ r ≤ 0.72] and [r = 0.37, 0.40], respectively). Three longitudinal studies found associations between loneliness and subsequent anxiety, and 1 study did not find an association between loneliness at age 5 and increased anxiety at age 12.

Mental health and well-being. Two studies found negative associations between social isolation/loneliness and well-being and mental health.

Conclusions/limitations

There is decent evidence of a strong association between loneliness/social isolation in childhood/adolescence and the development of depression, with some suggestion of increased rates in females. However, there was a small to moderate association with anxiety with increased rates in males. The length of social isolation was a strong predictor of future mental illness. Children who experienced enforced quarantine were 5 times more likely to require mental health services for posttraumatic stress symptoms.

Continue to: The compiled evidence presented in this study...

The compiled evidence presented in this study looked at previous similar scenarios of enforced social isolations; however, it cannot necessarily predict the effect of COVID-19–associated social distancing measures. Most of the studies included were cross-sectional studies and did not control for confounders. Social isolation in childhood or adolescence may be associated with developing mental health problems later in life and should be considered when implementing school closures and switching to online classes. Loades et al⁷ suggested that the increased rate of electronic communication and use of social media in children and adolescents may mitigate this predicted effect of social isolation.

4. Rogers JP, Chesney E, Oliver D, et al. Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic. Lancet Psychiatry. 2020;7(7):611-627.

To identify possible psychiatric and neuro­psychiatric implications of the COVID-19 pandemic, Rogers et al⁸ examined 2 previous coronavirus epidemics, SARS and Middle East respiratory syndrome (MERS), and COVID-19.

Study design

• Researchers conducted a random-effects model meta-analysis and systematic review of 65 studies and 7 preprints from 10 countries, including approximately 3,559 case studies of psychiatric and neuropsychiatric symptoms in participants infected with the 3 major coronavirus-induced illnesses (SARS, MERS, and COVID-19).
• Pure neurologic complications and indirect effects of the epidemics were excluded.
• The systematic review followed PRISMA guidelines.
• The quality of the studies was assessed using the NOS.

Outcomes

• Outcomes measured were psychiatric signs or symptoms; symptom severity; diagnoses based on ICD-10, DSM-IV, the Chinese Classification of Mental Disorders (third edition), or psychometric scales; quality of life; and employment.
• Results were stratified as acute or post-illness:

Acute illness. Delirium was the most frequently reported symptom in all 3 coronavirus infections. Depression, anxiety, or insomnia were also reported in MERS and SARS infections. Mania was described in SARS, but it was almost entirely present in cases treated with high-dose corticosteroids, which are not used routinely for COVID-19.

Continue to: Post-illness

Post-illness. There was increased incidence of depression, anxiety, fatigue, and posttraumatic stress disorder (PTSD) in the post-illness stage of previous coronavirus epidemics (SARS and MERS), but there was no control group for comparison. There was not enough data available for COVID-19.

Conclusions/limitations

Three studies were deemed to be of high quality, 32 were low quality, and 30 were moderate quality. Despite the high incidence of psychiatric symptoms in previous coronavirus infections, it was difficult to draw conclusions due to a lack of adequate control groups and predominantly low-quality studies. The difference in treatment strategies, such as the use of high-dose corticosteroids for MERS and SARS, but not for COVID-19, made it difficult to accurately predict a response for COVID-19 based on previous epidemics.

5. Shiozawa P, Uchida RR. An updated systematic review on the coronavirus pandemic: lessons for psychiatry. Braz J Psychiatry. 2020;42(3):330-331.

Schiozawa et al⁹ conducted a systematic review of articles to identify psychiatric issues during the COVID-19 pandemic.

Study design

• Researchers conducted a systematic review of 10 articles (7 articles from China, 1 from the United States, 1 from Japan, and 1 from Korea) that described strategies for coping with the COVID-19 pandemic and/or provided a descriptive analysis of the clinical scenario, with an emphasis on psychiatric comorbidities.
• The study used PRISMA guidelines to summarize the findings of those 10 studies. There were no pre-set outcomes or inclusion criteria.

Outcomes

• The compiled results of the 10 studies showed high rates of new-onset insomnia, anxiety, and relapse of underlying conditions such as depression.
• One study found increased hospital visits and misinterpretations of any symptom in patients with health anxiety (health anxiety was not defined).
• One study found some benefit from multidisciplinary psychological care and online counseling for both patients and health care workers.

Continue to: Conclusions/limitations

Conclusions/limitations

Because each of the 10 studies examined extremely different outcomes, researchers were unable to compile data from all studies to draw a conclusion.

6. Salari N, Hosseinian-Far A, Jalali R, et al. Prevalence of stress, anxiety, depression among the general population during the COVID-19 pandemic: a systematic review and meta-analysis. Global Health. 2020;16(1):57.

Salari et al¹⁰ examined the prevalence of stress, anxiety, and depression in the general population during the COVID-19 pandemic.

Study design

• Researchers conducted a systematic review and meta-analysis of 17 observational studies examining the prevalence of anxiety and stress in the general population during the COVID-19 pandemic. The STROBE checklist was used to assess the quality of studies.
• Only studies judged as medium to high quality were included in the analysis.

Outcomes

• The prevalence of stress was 29.6% (5 studies, sample size 9,074 individuals).
• The prevalence of anxiety was 31.9% (17 studies, sample size 63,439 individuals).
• The prevalence of depression was 33.7% (14 studies, sample size of 44,531 individuals).
• A sub-analysis of rates by continent revealed that Asia had highest prevalence of anxiety and depression (32.9% and 35.3%, respectively). Europe had the highest rates of stress (31.9%).

Conclusions/limitations

There is an increased prevalence of anxiety, stress, and depression in the general population amid the COVID-19 pandemic. None of the included studies compared rates to before the pandemic. Most studies used online surveys, which increased the chance of sample bias. Most studies originated from China and Iran, which had the highest rates of infection when this review was conducted.

Continue to: #7

Preti et al¹¹ performed a review of the literature to determine the impact of epidemic/pandemic outbreaks on health care workers’ mental health.

Study design

• Researchers conducted a rapid systematic review of 44 studies examining the psychological impact of epidemic/pandemic outbreaks on health care workers.
• Of the 44 studies, 27 (62%) referred to the SARS outbreak, 5 (11%) referred to the MERS outbreak, 5 (11%) referred to the COVID-19 outbreak, 3 (7%) referred to the influenza A virus subtype H1N1 outbreak, 3 (7%) referred to the Ebola virus disease outbreak, and 1 (2%) referred to the Asian lineage avian influenza outbreak.

Outcomes

• During these outbreaks, insomnia was found in 34% to 36.1% of health care workers, and severe anxiety symptoms in 45%.
• The prevalence of PTSD-like symptoms among health care workers during the outbreaks was 11% to 73.4%. Studies of the COVID-19 pandemic reported the highest prevalence of PTSD-like symptoms (71.5% to 73%). After 1 to 3 years following an outbreak, 10% to 40% of health care workers still had significant PTSD-like symptoms.
• Anxiety was reported in 45% of health care workers during the COVID-19 pandemic.
• A sub-analysis revealed a positive association between anxiety, PTSD, and stress symptoms and being female gender, being a nurse, and working on high-risk units.
• Perceived organizational support and confidence in protective measures were negatively associated with psychological symptoms.

Conclusions/limitations

Lessons from previous outbreaks and early data from the COVID-19 pandemic suggest that health care workers experience higher levels of psychological symptoms during outbreaks. Findings of this study suggest that organizational support and confidence in protective measures can mitigate this effect. To help preserve the well-being of health care workers, adequate training should be provided, appropriate personal protective equipment should be readily available, and support services should be well established.

8. Varatharaj A, Thomas N, Ellul MA, et al. Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study. Lancet Psychiatry. 2020;7(10):875-882.

Varatharaj et al¹² conducted a surveillance study in patients in the United Kingdom to understand the breadth of neurologic complications of COVID-19.

Continue to: Study design

• Researchers performed a cross-sectional analysis of the prevalence of psychiatric and neurologic complications in patients with COVID-19 across multiple centers in United Kingdom. Data were collected through the anonymous online reporting portals of several major neurology and psychiatric associations. Retrospective reporting was allowed.
• Evidence of SARS-CoV-2 infection was defined as:

Confirmed COVID-19 (114 cases) if polymerase chain reaction (PCR) of respiratory samples (eg, nasal or throat swab) or CSF was positive for viral RNA or if serology was positive for anti-SARS-CoV-2 immunoglobulin M (IgM) or immunoglobulin G (IgG).

Probable COVID-19 (6 cases) if a chest radiograph or chest CT was consistent with COVID-19 but PCR and serology were negative or not performed.

Possible COVID-19 (5 cases) if the disease was suspected on clinical grounds by the notifying clinician, but PCR, serology, and chest imaging were negative or not performed.

Outcomes

• Sixty-two percent of patients presented with cerebrovascular events (intracerebral hemorrhage, ischemic stroke, vasculitis, or other). Thirty-one percent of patients presented with altered mental status (AMS), and 5% had peripheral neurologic disorders.
• Of those with AMS, 18% (7 patients) had encephalitis, 23% (9 patients) had unspecified encephalopathy, and 59% (23 patients) had a psychiatric diagnosis as classified by the notifying psychiatrist or neuropsychiatrist. Ten patients (43%) of the 23 patients with neuropsychiatric disorders had new-onset psychosis, while only 2 patients had an exacerbation of a preexisting mental illness.

Continue to: Conclusions/limitations

This study had an over-representation of older adults. There was no control group for comparison, and the definition of confirmed COVID-19 included a positive IgM or IgG without a positive PCR or chest imaging. Although all psychiatric conditions reported were confirmed by a psychiatrist or neuropsychiatrist, there were no pre-defined criteria used for reported diagnoses.

Bottom Line

Evidence from studies of previous outbreaks and early data from the coronavirus disease 2019 (COVID-19) pandemic suggest that during outbreaks, health care workers experience higher levels of psychological symptoms than the general population. There has been an increased prevalence of anxiety, stress, poor sleep quality, obsessive-compulsive symptoms, and depression among the general population during the pandemic. COVID-19 can also impact the CNS directly and result in delirium, cerebrovascular events, encephalitis, unspecified encephalopathy, altered mental status, or peripheral neurologic disorders. Patients with preexisting psychiatric disorders are likely to have increased symptoms and should be monitored for breakthrough symptoms and acute exacerbations.

Related Resources

• Ryznar E. Evaluating patients’ decision-making capacity during COVID-19. Current Psychiatry. 2020;19(10):34-40.
• Freudenreich O, Kontos N, Querques J. COVID-19 and patients with serious mental illness. 2020;19(9):24-27,33-39.
• Esterwood E, Saeed SA. Past epidemics, natural disasters, COVID19, and mental health: learning from history as we deal with the present and prepare for the future [published online August 16, 2020]. Psychiatr Q. 2020:1-13. doi: 10.1007/s11126-020-09808-4.

Mr. T, age 26, presents to the psychiatric emergency department with acutely worsening symptoms of schizophrenia. The treating team decides to admit him to the inpatient psychiatry unit. The patient agrees to admission bloodwork, but adamantly refuses a coronavirus disease 2019 (COVID-19) nasal swab, stating that he does not consent to “having COVID-19 injected into his nose.” His nurse pages the psychiatry resident on call, asking her for seclusion orders to be placed for the patient in order to quarantine him.

This case illustrates a quandary that has arisen during the COVID-19 era. Traditionally, the use of seclusion in inpatient psychiatry wards has been restricted to the management of violent or self-destructive behavior. Most guidelines advise that seclusion should be used only to ensure the immediate physical safety of a patient, staff members, or other patients.¹ Using seclusion for other purposes, such as to quarantine patients suspected of having an infectious disease, raises ethical questions.

What is seclusion?

To best understand the questions that arise from the above scenario, a thorough understanding of the terminology used is needed. Although the terms “isolation,” “quarantine,” and “seclusion” are often used interchangeably, each has a distinct definition and unique history.

Isolation in a medical context refers to the practice of isolating people confirmed to have a disease from the general population. The earliest description of medical isolation dates back to the 7th century BC in the Book of Leviticus, which mentions a protocol for separating individuals infected with leprosy from those who are healthy.²

Quarantine hearkens back to the most fatal pandemic recorded in human history, the Black Death. In 1377, on the advice of the city’s chief physician, the Mediterranean seaport of Ragusa passed a law establishing an isolation period for all visitors from plague-endemic lands.² Initially a 30-day isolation period (a trentino), this was extended to 40 days (a quarantino). Distinct from isolation, quarantine is the practice of limiting movements of apparently healthy individuals who may have been exposed to a disease but do not have a confirmed diagnosis.

Seclusion, a term used most often in psychiatry, is defined as “the involuntary confinement of a patient alone in a room or area from which the patient is physically prevented from leaving.”³ The use of seclusion rooms in psychiatric facilities was originally championed by the 19th century British psychiatrist John Conolly.⁴ In The Treatment of the Insane without Mechanical Restraints, Conolly argued that a padded seclusion room was far more humane and effective in calming a violent patient than mechanical restraints. After exhausting less restrictive measures, seclusion is one of the most common means of restraining violent patients in inpatient psychiatric facilities.

Why consider seclusion?

The discussion of using seclusion as a means of quarantine has arisen recently due to the COVID-19 pandemic. This infectious disease was first identified in December 2019 in Wuhan, China.⁵ Since then, it has spread rapidly across the world. As of mid-October 2020, >39 million cases across 189 countries had been reported.⁶ The primary means by which the virus is spread is through respiratory droplets released from infected individuals through coughing, sneezing, or talking.⁷ These droplets can remain airborne or fall onto surfaces that become fomites. Transmission is possible before symptoms appear in an infected individual or even from individuals who are asymptomatic.⁸

Continue to: The typical layout and requirements...

The typical layout and requirements of an inpatient psychiatric ward intensify the risk of COVID-19 transmission.⁹ Unlike most medical specialty wards, psychiatric wards are set up with a therapeutic milieu where patients have the opportunity to mingle and interact with each other and staff members. Patients are allowed to walk around the unit, spend time in group therapy, eat meals with each other, and have visitation hours. The therapeutic benefit of such a milieu, however, must be weighed against the risks that patients pose to staff members and other patients. While many facilities have restricted some of these activities to limit COVID-19 exposure, the overall risk of transmission is still elevated. Early in course of the pandemic, the virus spread to an inpatient psychiatric ward in South Korea. Although health officials put the ward on lockdown, given the heightened risk of transmission, the virus quickly spread from patient to patient. Out of 103 inpatients, 101 contracted COVID-19.¹⁰

To mitigate this risk, many inpatient psychiatric facilities have mandated that all newly admitted patients be tested for COVID-19. By obtaining COVID-19 testing, facilities are better able to risk stratify their patient population and appropriately protect all patients. A dilemma arises, however, when a patient refuses to consent to COVID-19 testing. In such cases, the infectious risk of the patient remains unknown. Given the potentially disastrous consequences of an unchecked COVID-19 infection running rampant in an inpatient ward, some facilities have elected to use seclusion as a means of quarantining the patient.

Is seclusion justifiable?

There are legitimate objections to using seclusion as a means of quarantine. Most guidelines state that the only time seclusion is ethical is when it is used to prevent immediate physical danger, either to the patient or others.¹¹ Involuntary confinement entails considerable restriction of a patient’s rights and thus should be used only after all other options have been exhausted. People opposed to the use of seclusion point out that outside of the hospital, people are not forcibly restrained in order to enforce social distancing,¹² so by extension, those who are inside the hospital should not be forced to seclude.

Seclusion also comes with potentially harmful effects. For the 14 days that a patient is in quarantine, they are cut off from most social contact, which is the opposite of the intended purpose of the therapeutic milieu in inpatient psychiatric wards. Several quantitative studies have shown that individuals who are quarantined tend to report a high prevalence of symptoms of psychological distress, including low mood, irritability, depression, stress, anger, and posttraumatic stress disorder.¹³

Furthermore, there is considerable evidence that a negative test does not definitively rule out a COVID-19 infection. Nasal swabs for COVID-19 have a false-negative rate of 27%.¹⁴ In other words, patients on an inpatient psychiatry ward who are free to walk around the unit and interact with others are only probably COVID-19 free, not definitively. This fact throws into question the original justification for seclusion—to protect other patients from COVID-19.

Continue to: Support for using seclusion as quarantine

Despite these objections, there are clear arguments in favor of using seclusion as a means of quarantine. First, the danger posed by an unidentified COVID-19 infection to the inpatient psychiatric population is not small. As of mid-October 2020, >217,000 Americans had died of COVID-19.⁶ Psychiatric patients, especially those who are acutely decompensated and hospitalized, have a heightened risk.¹⁵ Those with underlying medical issues are more likely to be seriously affected by an infection. Patients with serious mental illness have higher rates of medical comorbidities¹⁶ and premature death.¹⁷ The risk of a patient contracting and then dying from COVID-19 is elevated in an inpatient psychiatric ward. Even if a test is not 100% sensitive or specific, the balance of probability it provides is sufficient to make an informed decision about transmission risk.

In choosing to seclude a patient who refuses COVID-19 testing, the treating team must weigh one person’s autonomy against the safety of every other individual on the ward. From a purely utilitarian perspective, the lives of the many outweigh the discomfort of one. Addressing this balance, the American Medical Association (AMA) Code of Ethics states “Although physicians’ primary ethical obligation is to their individual patients, they also have a long-recognized public health responsibility. In the context of infectious disease, this may include the use of quarantine and isolation to reduce the transmission of disease and protect the health of the public. In such situations, physicians have a further responsibility to protect their own health to ensure that they remain able to provide care. These responsibilities potentially conflict with patients’ rights of self-determination and with physicians’ duty to advocate for the best interests of individual patients and to provide care in emergencies.”¹⁸

The AMA Code of Ethics further mentions that physicians should “support mandatory quarantine and isolation when a patient fails to adhere voluntarily.” Medical evidence supports both quarantine¹⁹ and enacting isolation measures for COVID-19–positive hospitalized patients.²⁰ Table 1^21-24 summarizes the recommendations of major medical societies regarding isolation on hospital units.

Further, public health officials and law enforcement officials do in fact have the authority²⁵ to enforce quarantine and restrict a citizen’s movement outside a hospital setting. Recent cases have illustrated how this has been enforced, particularly with the use of electronic monitoring units and even criminal sanctions.^26,27

It is also important to consider that when used as quarantine, seclusion is not an indefinite action. Current recommendations suggest the longest period of time a patient would need to be in seclusion is 14 days. A patient could potentially reduce this period by agreeing to COVID-19 testing and obtaining a negative test result.

Continue to: Enacting inpatient quarantine

In Mr. T’s case, the resident physician was asked to make a decision regarding seclusion on the spot. Prudent facilities will set policies and educate clinicians before they need to face this conundrum. The following practical considerations may guide implementation of seclusion as a measure of quarantine on an inpatient psychiatric unit:

• given the risk of asymptomatic carriers, all admitted patients should be tested for COVID-19
• patients who refuse a test should be evaluated by the psychiatrist on duty to determine if the patient has the capacity to make this decision
• if a patient demonstrates capacity to refuse and continues to refuse testing, seclusion orders should then be placed
• the facility should create a protocol to ensure consistent application of seclusion orders.

So that they can make an informed decision, patients should be educated about the risks of not undergoing testing. It is important to correctly frame a seclusion decision to the patient. Explain that seclusion is not a punitive measure, but rather a means of respecting the patient’s right to refuse testing while ensuring other patients’ right to be protected from COVID-19 transmission.

It is crucial to not allow psychiatric care to be diminished because a patient is isolated due to COVID-19. Psychiatrists have legal duties to provide care when a patient is admitted to their unit,^28-30 and state laws generally outline patients’ rights while they are hospitalized.³¹ The use of technology can ensure these duties are fulfilled. Patient rounds and group treatment can be conducted through telehealth.^10,32 When in-person interaction is required, caretakers should don proper personal protective equipment and interact with the patient as often as they would if the patient were not in seclusion. Table 2^33-36 summarizes further ethical considerations when implementing quarantine measures on a psychiatry unit.

The contemporary inpatient unit

The ideal design to optimize care and safety is to create designated COVID-19 psychiatric units. Indeed, the US Substance Abuse and Mental Health Services Administration recommends segregating floors based on infection status where possible.³⁷ This minimizes the risk of transmission to other patients while maintaining the same standards of psychiatric treatment, including milieu and group therapy (which may also require adjustments). Such a unit already has precedent.³⁸ Although designated COVID-19 psychiatric units present clinical and administrative hurdles,³⁹ they may become more commonplace as the number of COVID-19–positive inpatients continues to rise.

Bottom Line

The coronavirus disease 2019 (COVID-19) pandemic has created challenges for inpatient psychiatric facilities. Although seclusion is a serious decision and should not be undertaken lightly, there are clear ethical and practical justifications for using it as a means of quarantine for patients who are COVID-19–positive or refuse testing.

Related Resources

• Askew L, Fisher P, Beazley P. What are adult psychiatric inpatients’ experience of seclusion: a systematic review of qualitative studies. J Psychiatr Ment Health Nurs. 2019; 26(7-8):274-285.
• Komrad MS. Medical ethics in the time of COVID-19. Current Psychiatry. 2020;19(7):29-32,46.

Mr. T, age 26, presents to the psychiatric emergency department with acutely worsening symptoms of schizophrenia. The treating team decides to admit him to the inpatient psychiatry unit. The patient agrees to admission bloodwork, but adamantly refuses a coronavirus disease 2019 (COVID-19) nasal swab, stating that he does not consent to “having COVID-19 injected into his nose.” His nurse pages the psychiatry resident on call, asking her for seclusion orders to be placed for the patient in order to quarantine him.

This case illustrates a quandary that has arisen during the COVID-19 era. Traditionally, the use of seclusion in inpatient psychiatry wards has been restricted to the management of violent or self-destructive behavior. Most guidelines advise that seclusion should be used only to ensure the immediate physical safety of a patient, staff members, or other patients.¹ Using seclusion for other purposes, such as to quarantine patients suspected of having an infectious disease, raises ethical questions.

What is seclusion?

To best understand the questions that arise from the above scenario, a thorough understanding of the terminology used is needed. Although the terms “isolation,” “quarantine,” and “seclusion” are often used interchangeably, each has a distinct definition and unique history.

Isolation in a medical context refers to the practice of isolating people confirmed to have a disease from the general population. The earliest description of medical isolation dates back to the 7th century BC in the Book of Leviticus, which mentions a protocol for separating individuals infected with leprosy from those who are healthy.²

Quarantine hearkens back to the most fatal pandemic recorded in human history, the Black Death. In 1377, on the advice of the city’s chief physician, the Mediterranean seaport of Ragusa passed a law establishing an isolation period for all visitors from plague-endemic lands.² Initially a 30-day isolation period (a trentino), this was extended to 40 days (a quarantino). Distinct from isolation, quarantine is the practice of limiting movements of apparently healthy individuals who may have been exposed to a disease but do not have a confirmed diagnosis.

Seclusion, a term used most often in psychiatry, is defined as “the involuntary confinement of a patient alone in a room or area from which the patient is physically prevented from leaving.”³ The use of seclusion rooms in psychiatric facilities was originally championed by the 19th century British psychiatrist John Conolly.⁴ In The Treatment of the Insane without Mechanical Restraints, Conolly argued that a padded seclusion room was far more humane and effective in calming a violent patient than mechanical restraints. After exhausting less restrictive measures, seclusion is one of the most common means of restraining violent patients in inpatient psychiatric facilities.

Why consider seclusion?

The discussion of using seclusion as a means of quarantine has arisen recently due to the COVID-19 pandemic. This infectious disease was first identified in December 2019 in Wuhan, China.⁵ Since then, it has spread rapidly across the world. As of mid-October 2020, >39 million cases across 189 countries had been reported.⁶ The primary means by which the virus is spread is through respiratory droplets released from infected individuals through coughing, sneezing, or talking.⁷ These droplets can remain airborne or fall onto surfaces that become fomites. Transmission is possible before symptoms appear in an infected individual or even from individuals who are asymptomatic.⁸

Continue to: The typical layout and requirements...

The typical layout and requirements of an inpatient psychiatric ward intensify the risk of COVID-19 transmission.⁹ Unlike most medical specialty wards, psychiatric wards are set up with a therapeutic milieu where patients have the opportunity to mingle and interact with each other and staff members. Patients are allowed to walk around the unit, spend time in group therapy, eat meals with each other, and have visitation hours. The therapeutic benefit of such a milieu, however, must be weighed against the risks that patients pose to staff members and other patients. While many facilities have restricted some of these activities to limit COVID-19 exposure, the overall risk of transmission is still elevated. Early in course of the pandemic, the virus spread to an inpatient psychiatric ward in South Korea. Although health officials put the ward on lockdown, given the heightened risk of transmission, the virus quickly spread from patient to patient. Out of 103 inpatients, 101 contracted COVID-19.¹⁰

To mitigate this risk, many inpatient psychiatric facilities have mandated that all newly admitted patients be tested for COVID-19. By obtaining COVID-19 testing, facilities are better able to risk stratify their patient population and appropriately protect all patients. A dilemma arises, however, when a patient refuses to consent to COVID-19 testing. In such cases, the infectious risk of the patient remains unknown. Given the potentially disastrous consequences of an unchecked COVID-19 infection running rampant in an inpatient ward, some facilities have elected to use seclusion as a means of quarantining the patient.

Is seclusion justifiable?

There are legitimate objections to using seclusion as a means of quarantine. Most guidelines state that the only time seclusion is ethical is when it is used to prevent immediate physical danger, either to the patient or others.¹¹ Involuntary confinement entails considerable restriction of a patient’s rights and thus should be used only after all other options have been exhausted. People opposed to the use of seclusion point out that outside of the hospital, people are not forcibly restrained in order to enforce social distancing,¹² so by extension, those who are inside the hospital should not be forced to seclude.

Seclusion also comes with potentially harmful effects. For the 14 days that a patient is in quarantine, they are cut off from most social contact, which is the opposite of the intended purpose of the therapeutic milieu in inpatient psychiatric wards. Several quantitative studies have shown that individuals who are quarantined tend to report a high prevalence of symptoms of psychological distress, including low mood, irritability, depression, stress, anger, and posttraumatic stress disorder.¹³

Furthermore, there is considerable evidence that a negative test does not definitively rule out a COVID-19 infection. Nasal swabs for COVID-19 have a false-negative rate of 27%.¹⁴ In other words, patients on an inpatient psychiatry ward who are free to walk around the unit and interact with others are only probably COVID-19 free, not definitively. This fact throws into question the original justification for seclusion—to protect other patients from COVID-19.

Continue to: Support for using seclusion as quarantine

Despite these objections, there are clear arguments in favor of using seclusion as a means of quarantine. First, the danger posed by an unidentified COVID-19 infection to the inpatient psychiatric population is not small. As of mid-October 2020, >217,000 Americans had died of COVID-19.⁶ Psychiatric patients, especially those who are acutely decompensated and hospitalized, have a heightened risk.¹⁵ Those with underlying medical issues are more likely to be seriously affected by an infection. Patients with serious mental illness have higher rates of medical comorbidities¹⁶ and premature death.¹⁷ The risk of a patient contracting and then dying from COVID-19 is elevated in an inpatient psychiatric ward. Even if a test is not 100% sensitive or specific, the balance of probability it provides is sufficient to make an informed decision about transmission risk.

In choosing to seclude a patient who refuses COVID-19 testing, the treating team must weigh one person’s autonomy against the safety of every other individual on the ward. From a purely utilitarian perspective, the lives of the many outweigh the discomfort of one. Addressing this balance, the American Medical Association (AMA) Code of Ethics states “Although physicians’ primary ethical obligation is to their individual patients, they also have a long-recognized public health responsibility. In the context of infectious disease, this may include the use of quarantine and isolation to reduce the transmission of disease and protect the health of the public. In such situations, physicians have a further responsibility to protect their own health to ensure that they remain able to provide care. These responsibilities potentially conflict with patients’ rights of self-determination and with physicians’ duty to advocate for the best interests of individual patients and to provide care in emergencies.”¹⁸

The AMA Code of Ethics further mentions that physicians should “support mandatory quarantine and isolation when a patient fails to adhere voluntarily.” Medical evidence supports both quarantine¹⁹ and enacting isolation measures for COVID-19–positive hospitalized patients.²⁰ Table 1^21-24 summarizes the recommendations of major medical societies regarding isolation on hospital units.

Further, public health officials and law enforcement officials do in fact have the authority²⁵ to enforce quarantine and restrict a citizen’s movement outside a hospital setting. Recent cases have illustrated how this has been enforced, particularly with the use of electronic monitoring units and even criminal sanctions.^26,27

It is also important to consider that when used as quarantine, seclusion is not an indefinite action. Current recommendations suggest the longest period of time a patient would need to be in seclusion is 14 days. A patient could potentially reduce this period by agreeing to COVID-19 testing and obtaining a negative test result.

Continue to: Enacting inpatient quarantine

In Mr. T’s case, the resident physician was asked to make a decision regarding seclusion on the spot. Prudent facilities will set policies and educate clinicians before they need to face this conundrum. The following practical considerations may guide implementation of seclusion as a measure of quarantine on an inpatient psychiatric unit:

• given the risk of asymptomatic carriers, all admitted patients should be tested for COVID-19
• patients who refuse a test should be evaluated by the psychiatrist on duty to determine if the patient has the capacity to make this decision
• if a patient demonstrates capacity to refuse and continues to refuse testing, seclusion orders should then be placed
• the facility should create a protocol to ensure consistent application of seclusion orders.

So that they can make an informed decision, patients should be educated about the risks of not undergoing testing. It is important to correctly frame a seclusion decision to the patient. Explain that seclusion is not a punitive measure, but rather a means of respecting the patient’s right to refuse testing while ensuring other patients’ right to be protected from COVID-19 transmission.

It is crucial to not allow psychiatric care to be diminished because a patient is isolated due to COVID-19. Psychiatrists have legal duties to provide care when a patient is admitted to their unit,^28-30 and state laws generally outline patients’ rights while they are hospitalized.³¹ The use of technology can ensure these duties are fulfilled. Patient rounds and group treatment can be conducted through telehealth.^10,32 When in-person interaction is required, caretakers should don proper personal protective equipment and interact with the patient as often as they would if the patient were not in seclusion. Table 2^33-36 summarizes further ethical considerations when implementing quarantine measures on a psychiatry unit.

The contemporary inpatient unit

The ideal design to optimize care and safety is to create designated COVID-19 psychiatric units. Indeed, the US Substance Abuse and Mental Health Services Administration recommends segregating floors based on infection status where possible.³⁷ This minimizes the risk of transmission to other patients while maintaining the same standards of psychiatric treatment, including milieu and group therapy (which may also require adjustments). Such a unit already has precedent.³⁸ Although designated COVID-19 psychiatric units present clinical and administrative hurdles,³⁹ they may become more commonplace as the number of COVID-19–positive inpatients continues to rise.

Bottom Line

The coronavirus disease 2019 (COVID-19) pandemic has created challenges for inpatient psychiatric facilities. Although seclusion is a serious decision and should not be undertaken lightly, there are clear ethical and practical justifications for using it as a means of quarantine for patients who are COVID-19–positive or refuse testing.

Related Resources

• Askew L, Fisher P, Beazley P. What are adult psychiatric inpatients’ experience of seclusion: a systematic review of qualitative studies. J Psychiatr Ment Health Nurs. 2019; 26(7-8):274-285.
• Komrad MS. Medical ethics in the time of COVID-19. Current Psychiatry. 2020;19(7):29-32,46.

Mr. T, age 26, presents to the psychiatric emergency department with acutely worsening symptoms of schizophrenia. The treating team decides to admit him to the inpatient psychiatry unit. The patient agrees to admission bloodwork, but adamantly refuses a coronavirus disease 2019 (COVID-19) nasal swab, stating that he does not consent to “having COVID-19 injected into his nose.” His nurse pages the psychiatry resident on call, asking her for seclusion orders to be placed for the patient in order to quarantine him.

This case illustrates a quandary that has arisen during the COVID-19 era. Traditionally, the use of seclusion in inpatient psychiatry wards has been restricted to the management of violent or self-destructive behavior. Most guidelines advise that seclusion should be used only to ensure the immediate physical safety of a patient, staff members, or other patients.¹ Using seclusion for other purposes, such as to quarantine patients suspected of having an infectious disease, raises ethical questions.

What is seclusion?

To best understand the questions that arise from the above scenario, a thorough understanding of the terminology used is needed. Although the terms “isolation,” “quarantine,” and “seclusion” are often used interchangeably, each has a distinct definition and unique history.

Isolation in a medical context refers to the practice of isolating people confirmed to have a disease from the general population. The earliest description of medical isolation dates back to the 7th century BC in the Book of Leviticus, which mentions a protocol for separating individuals infected with leprosy from those who are healthy.²

Quarantine hearkens back to the most fatal pandemic recorded in human history, the Black Death. In 1377, on the advice of the city’s chief physician, the Mediterranean seaport of Ragusa passed a law establishing an isolation period for all visitors from plague-endemic lands.² Initially a 30-day isolation period (a trentino), this was extended to 40 days (a quarantino). Distinct from isolation, quarantine is the practice of limiting movements of apparently healthy individuals who may have been exposed to a disease but do not have a confirmed diagnosis.

Seclusion, a term used most often in psychiatry, is defined as “the involuntary confinement of a patient alone in a room or area from which the patient is physically prevented from leaving.”³ The use of seclusion rooms in psychiatric facilities was originally championed by the 19th century British psychiatrist John Conolly.⁴ In The Treatment of the Insane without Mechanical Restraints, Conolly argued that a padded seclusion room was far more humane and effective in calming a violent patient than mechanical restraints. After exhausting less restrictive measures, seclusion is one of the most common means of restraining violent patients in inpatient psychiatric facilities.

Why consider seclusion?

The discussion of using seclusion as a means of quarantine has arisen recently due to the COVID-19 pandemic. This infectious disease was first identified in December 2019 in Wuhan, China.⁵ Since then, it has spread rapidly across the world. As of mid-October 2020, >39 million cases across 189 countries had been reported.⁶ The primary means by which the virus is spread is through respiratory droplets released from infected individuals through coughing, sneezing, or talking.⁷ These droplets can remain airborne or fall onto surfaces that become fomites. Transmission is possible before symptoms appear in an infected individual or even from individuals who are asymptomatic.⁸

Continue to: The typical layout and requirements...

The typical layout and requirements of an inpatient psychiatric ward intensify the risk of COVID-19 transmission.⁹ Unlike most medical specialty wards, psychiatric wards are set up with a therapeutic milieu where patients have the opportunity to mingle and interact with each other and staff members. Patients are allowed to walk around the unit, spend time in group therapy, eat meals with each other, and have visitation hours. The therapeutic benefit of such a milieu, however, must be weighed against the risks that patients pose to staff members and other patients. While many facilities have restricted some of these activities to limit COVID-19 exposure, the overall risk of transmission is still elevated. Early in course of the pandemic, the virus spread to an inpatient psychiatric ward in South Korea. Although health officials put the ward on lockdown, given the heightened risk of transmission, the virus quickly spread from patient to patient. Out of 103 inpatients, 101 contracted COVID-19.¹⁰

To mitigate this risk, many inpatient psychiatric facilities have mandated that all newly admitted patients be tested for COVID-19. By obtaining COVID-19 testing, facilities are better able to risk stratify their patient population and appropriately protect all patients. A dilemma arises, however, when a patient refuses to consent to COVID-19 testing. In such cases, the infectious risk of the patient remains unknown. Given the potentially disastrous consequences of an unchecked COVID-19 infection running rampant in an inpatient ward, some facilities have elected to use seclusion as a means of quarantining the patient.

Is seclusion justifiable?

There are legitimate objections to using seclusion as a means of quarantine. Most guidelines state that the only time seclusion is ethical is when it is used to prevent immediate physical danger, either to the patient or others.¹¹ Involuntary confinement entails considerable restriction of a patient’s rights and thus should be used only after all other options have been exhausted. People opposed to the use of seclusion point out that outside of the hospital, people are not forcibly restrained in order to enforce social distancing,¹² so by extension, those who are inside the hospital should not be forced to seclude.

Seclusion also comes with potentially harmful effects. For the 14 days that a patient is in quarantine, they are cut off from most social contact, which is the opposite of the intended purpose of the therapeutic milieu in inpatient psychiatric wards. Several quantitative studies have shown that individuals who are quarantined tend to report a high prevalence of symptoms of psychological distress, including low mood, irritability, depression, stress, anger, and posttraumatic stress disorder.¹³

Furthermore, there is considerable evidence that a negative test does not definitively rule out a COVID-19 infection. Nasal swabs for COVID-19 have a false-negative rate of 27%.¹⁴ In other words, patients on an inpatient psychiatry ward who are free to walk around the unit and interact with others are only probably COVID-19 free, not definitively. This fact throws into question the original justification for seclusion—to protect other patients from COVID-19.

Continue to: Support for using seclusion as quarantine

Despite these objections, there are clear arguments in favor of using seclusion as a means of quarantine. First, the danger posed by an unidentified COVID-19 infection to the inpatient psychiatric population is not small. As of mid-October 2020, >217,000 Americans had died of COVID-19.⁶ Psychiatric patients, especially those who are acutely decompensated and hospitalized, have a heightened risk.¹⁵ Those with underlying medical issues are more likely to be seriously affected by an infection. Patients with serious mental illness have higher rates of medical comorbidities¹⁶ and premature death.¹⁷ The risk of a patient contracting and then dying from COVID-19 is elevated in an inpatient psychiatric ward. Even if a test is not 100% sensitive or specific, the balance of probability it provides is sufficient to make an informed decision about transmission risk.

In choosing to seclude a patient who refuses COVID-19 testing, the treating team must weigh one person’s autonomy against the safety of every other individual on the ward. From a purely utilitarian perspective, the lives of the many outweigh the discomfort of one. Addressing this balance, the American Medical Association (AMA) Code of Ethics states “Although physicians’ primary ethical obligation is to their individual patients, they also have a long-recognized public health responsibility. In the context of infectious disease, this may include the use of quarantine and isolation to reduce the transmission of disease and protect the health of the public. In such situations, physicians have a further responsibility to protect their own health to ensure that they remain able to provide care. These responsibilities potentially conflict with patients’ rights of self-determination and with physicians’ duty to advocate for the best interests of individual patients and to provide care in emergencies.”¹⁸

The AMA Code of Ethics further mentions that physicians should “support mandatory quarantine and isolation when a patient fails to adhere voluntarily.” Medical evidence supports both quarantine¹⁹ and enacting isolation measures for COVID-19–positive hospitalized patients.²⁰ Table 1^21-24 summarizes the recommendations of major medical societies regarding isolation on hospital units.

Further, public health officials and law enforcement officials do in fact have the authority²⁵ to enforce quarantine and restrict a citizen’s movement outside a hospital setting. Recent cases have illustrated how this has been enforced, particularly with the use of electronic monitoring units and even criminal sanctions.^26,27

It is also important to consider that when used as quarantine, seclusion is not an indefinite action. Current recommendations suggest the longest period of time a patient would need to be in seclusion is 14 days. A patient could potentially reduce this period by agreeing to COVID-19 testing and obtaining a negative test result.

Continue to: Enacting inpatient quarantine

In Mr. T’s case, the resident physician was asked to make a decision regarding seclusion on the spot. Prudent facilities will set policies and educate clinicians before they need to face this conundrum. The following practical considerations may guide implementation of seclusion as a measure of quarantine on an inpatient psychiatric unit:

• given the risk of asymptomatic carriers, all admitted patients should be tested for COVID-19
• patients who refuse a test should be evaluated by the psychiatrist on duty to determine if the patient has the capacity to make this decision
• if a patient demonstrates capacity to refuse and continues to refuse testing, seclusion orders should then be placed
• the facility should create a protocol to ensure consistent application of seclusion orders.

So that they can make an informed decision, patients should be educated about the risks of not undergoing testing. It is important to correctly frame a seclusion decision to the patient. Explain that seclusion is not a punitive measure, but rather a means of respecting the patient’s right to refuse testing while ensuring other patients’ right to be protected from COVID-19 transmission.

It is crucial to not allow psychiatric care to be diminished because a patient is isolated due to COVID-19. Psychiatrists have legal duties to provide care when a patient is admitted to their unit,^28-30 and state laws generally outline patients’ rights while they are hospitalized.³¹ The use of technology can ensure these duties are fulfilled. Patient rounds and group treatment can be conducted through telehealth.^10,32 When in-person interaction is required, caretakers should don proper personal protective equipment and interact with the patient as often as they would if the patient were not in seclusion. Table 2^33-36 summarizes further ethical considerations when implementing quarantine measures on a psychiatry unit.

The contemporary inpatient unit

The ideal design to optimize care and safety is to create designated COVID-19 psychiatric units. Indeed, the US Substance Abuse and Mental Health Services Administration recommends segregating floors based on infection status where possible.³⁷ This minimizes the risk of transmission to other patients while maintaining the same standards of psychiatric treatment, including milieu and group therapy (which may also require adjustments). Such a unit already has precedent.³⁸ Although designated COVID-19 psychiatric units present clinical and administrative hurdles,³⁹ they may become more commonplace as the number of COVID-19–positive inpatients continues to rise.

Bottom Line

The coronavirus disease 2019 (COVID-19) pandemic has created challenges for inpatient psychiatric facilities. Although seclusion is a serious decision and should not be undertaken lightly, there are clear ethical and practical justifications for using it as a means of quarantine for patients who are COVID-19–positive or refuse testing.

Related Resources

• Askew L, Fisher P, Beazley P. What are adult psychiatric inpatients’ experience of seclusion: a systematic review of qualitative studies. J Psychiatr Ment Health Nurs. 2019; 26(7-8):274-285.
• Komrad MS. Medical ethics in the time of COVID-19. Current Psychiatry. 2020;19(7):29-32,46.