To the Editor:

Zinc chloride originally was used by Dr. Frederic Mohs as an in vivo tissue fixative during the early phases of Mohs micrographic surgery.¹ Although this technique has since been replaced with fresh frozen tissue fixation, zinc chloride still is found in topical preparations that are readily available to patients. Specifically, black salve describes variably composed topical preparations that share the common ingredients zinc chloride and Sanguinaria canadensis (bloodroot).² Patients self-treat with these unregulated compounds, but the majority do not have their lesions evaluated by a clinician prior to use and are unaware of the potential risks.^3-5 Products containing zinc chloride and S canadensis that are not marketed as black salve present a new problem for the dermatology community.

A 73-year-old man presented to our dermatology clinic for the focused evaluation of scaly lesions on the face and nose. At this visit, it was recommended he undergo a total-body skin examination for skin cancer screening given his age and substantial photodamage.

Physical examination revealed more than 20 superficial, 3- to 10-mm scars predominantly over the trunk. One scar over the left mid-back had a large, 1.2-cm peripheral rim of dark brown pigment that was clinically concerning for a melanocytic neoplasm. Shave removal of this lesion was performed. Histologic examination showed melanoma in situ with a central scar. The central scar spanned the depth of the dermis, and the melanocytic component was absent in this area, raising the question if prior biopsy or treatment had been performed on this lesion. During a discussion of the results with the patient, he was questioned about prior biopsy or treatment of this lesion. He reported prior use of a topical all-natural cream containing zinc chloride and S canadensis that he purchased online, which he had used to treat this lesion as well as numerous presumed moles.

The trend of at-home mole removal products containing the traditional ingredients in black salve seems to be one of rapidly shifting product availability as well as a departure from marketing items as black salve. Many prior black salve products are no longer available.⁴ The product that our patient used is a topical cream marketed as a treatment for moles and skin tags.⁶ Despite not being marketed as black salve, it does contain zinc chloride and S canadensis. The product’s website highlights these ingredients as being a safe and effective treatment for mole removal, with claims that the product will remove the mole or skin tag without irritating the surrounding skin and can be safely used anywhere on the body without scarring.⁶ A Google search at the time this article was written using the term skin tag remover revealed similar products marketed as all-natural “skin tag remover and mole corrector creams.” These similar products containing zinc chloride and S canadensis were available in the United States at the time of our initial research but have since been removed and only are available outside of the United States.⁷

Prior reports of melanoma masked by zinc chloride and S canadensis described the use of topical agents marketed as black salve. This new wave of products marketed as all-natural creams makes continued education on the available products and their associated risks necessary for clinicians. The lack of US Food and Drug Administration oversight for these products and their frequent introduction and discontinuation in the market makes keeping updated even more challenging. Because many patients self-treat without prior evaluation by a health care provider, treatment with these products can lead to a delay in diagnosis or inaccurate staging due to scars from the chemical destruction, both of which may have occurred in our patient.⁵ Until these products become regulated by the US Food and Drug Administration, it is imperative that clinicians continue to educate their patients on the lack of documented benefit and clear risks of their use as well as remain up-to-date on product trends.

To the Editor:

Zinc chloride originally was used by Dr. Frederic Mohs as an in vivo tissue fixative during the early phases of Mohs micrographic surgery.¹ Although this technique has since been replaced with fresh frozen tissue fixation, zinc chloride still is found in topical preparations that are readily available to patients. Specifically, black salve describes variably composed topical preparations that share the common ingredients zinc chloride and Sanguinaria canadensis (bloodroot).² Patients self-treat with these unregulated compounds, but the majority do not have their lesions evaluated by a clinician prior to use and are unaware of the potential risks.^3-5 Products containing zinc chloride and S canadensis that are not marketed as black salve present a new problem for the dermatology community.

A 73-year-old man presented to our dermatology clinic for the focused evaluation of scaly lesions on the face and nose. At this visit, it was recommended he undergo a total-body skin examination for skin cancer screening given his age and substantial photodamage.

Physical examination revealed more than 20 superficial, 3- to 10-mm scars predominantly over the trunk. One scar over the left mid-back had a large, 1.2-cm peripheral rim of dark brown pigment that was clinically concerning for a melanocytic neoplasm. Shave removal of this lesion was performed. Histologic examination showed melanoma in situ with a central scar. The central scar spanned the depth of the dermis, and the melanocytic component was absent in this area, raising the question if prior biopsy or treatment had been performed on this lesion. During a discussion of the results with the patient, he was questioned about prior biopsy or treatment of this lesion. He reported prior use of a topical all-natural cream containing zinc chloride and S canadensis that he purchased online, which he had used to treat this lesion as well as numerous presumed moles.

The trend of at-home mole removal products containing the traditional ingredients in black salve seems to be one of rapidly shifting product availability as well as a departure from marketing items as black salve. Many prior black salve products are no longer available.⁴ The product that our patient used is a topical cream marketed as a treatment for moles and skin tags.⁶ Despite not being marketed as black salve, it does contain zinc chloride and S canadensis. The product’s website highlights these ingredients as being a safe and effective treatment for mole removal, with claims that the product will remove the mole or skin tag without irritating the surrounding skin and can be safely used anywhere on the body without scarring.⁶ A Google search at the time this article was written using the term skin tag remover revealed similar products marketed as all-natural “skin tag remover and mole corrector creams.” These similar products containing zinc chloride and S canadensis were available in the United States at the time of our initial research but have since been removed and only are available outside of the United States.⁷

Prior reports of melanoma masked by zinc chloride and S canadensis described the use of topical agents marketed as black salve. This new wave of products marketed as all-natural creams makes continued education on the available products and their associated risks necessary for clinicians. The lack of US Food and Drug Administration oversight for these products and their frequent introduction and discontinuation in the market makes keeping updated even more challenging. Because many patients self-treat without prior evaluation by a health care provider, treatment with these products can lead to a delay in diagnosis or inaccurate staging due to scars from the chemical destruction, both of which may have occurred in our patient.⁵ Until these products become regulated by the US Food and Drug Administration, it is imperative that clinicians continue to educate their patients on the lack of documented benefit and clear risks of their use as well as remain up-to-date on product trends.

To the Editor:

Zinc chloride originally was used by Dr. Frederic Mohs as an in vivo tissue fixative during the early phases of Mohs micrographic surgery.¹ Although this technique has since been replaced with fresh frozen tissue fixation, zinc chloride still is found in topical preparations that are readily available to patients. Specifically, black salve describes variably composed topical preparations that share the common ingredients zinc chloride and Sanguinaria canadensis (bloodroot).² Patients self-treat with these unregulated compounds, but the majority do not have their lesions evaluated by a clinician prior to use and are unaware of the potential risks.^3-5 Products containing zinc chloride and S canadensis that are not marketed as black salve present a new problem for the dermatology community.

A 73-year-old man presented to our dermatology clinic for the focused evaluation of scaly lesions on the face and nose. At this visit, it was recommended he undergo a total-body skin examination for skin cancer screening given his age and substantial photodamage.

Physical examination revealed more than 20 superficial, 3- to 10-mm scars predominantly over the trunk. One scar over the left mid-back had a large, 1.2-cm peripheral rim of dark brown pigment that was clinically concerning for a melanocytic neoplasm. Shave removal of this lesion was performed. Histologic examination showed melanoma in situ with a central scar. The central scar spanned the depth of the dermis, and the melanocytic component was absent in this area, raising the question if prior biopsy or treatment had been performed on this lesion. During a discussion of the results with the patient, he was questioned about prior biopsy or treatment of this lesion. He reported prior use of a topical all-natural cream containing zinc chloride and S canadensis that he purchased online, which he had used to treat this lesion as well as numerous presumed moles.

The trend of at-home mole removal products containing the traditional ingredients in black salve seems to be one of rapidly shifting product availability as well as a departure from marketing items as black salve. Many prior black salve products are no longer available.⁴ The product that our patient used is a topical cream marketed as a treatment for moles and skin tags.⁶ Despite not being marketed as black salve, it does contain zinc chloride and S canadensis. The product’s website highlights these ingredients as being a safe and effective treatment for mole removal, with claims that the product will remove the mole or skin tag without irritating the surrounding skin and can be safely used anywhere on the body without scarring.⁶ A Google search at the time this article was written using the term skin tag remover revealed similar products marketed as all-natural “skin tag remover and mole corrector creams.” These similar products containing zinc chloride and S canadensis were available in the United States at the time of our initial research but have since been removed and only are available outside of the United States.⁷

Prior reports of melanoma masked by zinc chloride and S canadensis described the use of topical agents marketed as black salve. This new wave of products marketed as all-natural creams makes continued education on the available products and their associated risks necessary for clinicians. The lack of US Food and Drug Administration oversight for these products and their frequent introduction and discontinuation in the market makes keeping updated even more challenging. Because many patients self-treat without prior evaluation by a health care provider, treatment with these products can lead to a delay in diagnosis or inaccurate staging due to scars from the chemical destruction, both of which may have occurred in our patient.⁵ Until these products become regulated by the US Food and Drug Administration, it is imperative that clinicians continue to educate their patients on the lack of documented benefit and clear risks of their use as well as remain up-to-date on product trends.

An appeals court has upheld a family’s $9.5 million jury award after a physician left an 18-inch sponge in a patient’s abdomen that remained in her stomach for 5 years.

Carolyn Boerste underwent aortobifemoral bypass surgery at the University of Louisville (Ky.) Hospital in March 2011 to improve circulation in her lower extremities. She had a history of peripheral vascular disease, hypertension, and diabetes, which caused a wound on her toe to become infected and gangrenous, according to court records.

Courtesy Bo Bolus of Bolus Law Offices, Louisville, Ky.

During the surgery, performed by Marvin Morris, MD, the surgical team left a laparotomy sponge in Ms. Boerste’s abdomen. Because of its size, Ms. Boerste’s attorneys characterized the 18-by-18-inch object as “more like a towel,” according to court documents.

During the years that the sponge went undetected, the object eroded via transmural migration from Ms. Boerste’s abdomen into her intestine, causing diarrhea, vomiting, and nausea. In March 2015, Ms. Boerste was transferred by ambulance to an emergency department because of abdominal pain. An emergency physician ordered an abdominal CT scan, which showed the x-ray detectable sponge marker inside Ms. Boerste’s intestine, according to her complaint.

Although the radiologist called the emergency physician to advise him of the sponge marker, the information was not shared with Ms. Boerste and she was discharged from the hospital with a urinary tract infection diagnosis. The emergency physician later testified he had no memory of the call with the radiologist.

The CT scan was faxed to Ms. Boerste’s family physician. She testified that she read the report but did not mention the sponge marker to Ms. Boerste because she believed the issue had been handled by the emergency physician. Thus the sponge remained inside Ms. Boerste for another 20 months.

In November 2016, Ms. Boerste returned to the same emergency department with more intense gastrointestinal issues. Another CT scan was ordered, which revealed the sponge. The object was removed by exploratory laparotomy later that month. In her complaint, Ms. Boerste claimed that the removal surgery resulted in amputation of her leg because of wounds developed on her lower extremities while she was bedridden during recovery.

In 2017, she filed a negligence lawsuit against Dr. Morris, the hospital, and several others involved in her care. On the first day of trial in December 2019, the hospital conceded liability. The trial continued against Dr. Morris and the other defendants as to liability and damages and proceeded against the hospital as to damages.

At trial, evidence showed there was significant confusion among nurses on how to document sponge counts, according to the appellate decision. In general, nurses used a perioperative nursing record to document the surgical procedure, and that record had a place to document some but not all sponge counts required by hospital policy. The nursing record did not have a place to document sponge counts required to be recorded at every break, lunch, and shift change. Nurses also used a worksheet to track sponge counts, but that worksheet was not part of the medical record.

Dr. Morris testified that he relies on nurses regarding sponge counts, but that he also performs a visual and tactile inspection of the abdominal cavity. He acknowledged during trial that the standard of care required him to keep track of the sponges before closing. Dr. Morris also testified that the surgeon and nurses are a team, and “the entire team did not count the sponges correctly when finishing the bypass surgery,” according to the appellate decision.

After a 10-day trial, jurors found Dr. Morris and several other defendants liable. They apportioned 60% liability to the hospital, 10% to Morris, 15% to the family physician, 0% to the emergency physician, and 15% to the rehabilitation center. Ms. Boerste was awarded $9.5 million in damages and an additional $1 million in punitive damages, for a total of $10.5 million.

Dr. Morris and the hospital appealed to the Commonwealth of Kentucky Court of Appeals. As the appeal was pending, Ms. Boerste died, and her son took over the plaintiff’s role.

In their appeal, Dr. Morris and the hospital said they should be granted a new trial for a number of reasons, including that the pain and suffering award was grossly excessive and reflected improper jury sympathy, that the punitive damages award should be vacated because jurors were not properly instructed on the issue, and that the judgment against Dr. Morris should be overturned because there was no evidence he deviated from the standard of care.

The defendants also argued that they were entitled to instructions on “apportionment of fault and mitigation of damages against Boerste.” The mitigation of damages doctrine prevents an injured plaintiff from recovering unreasonable expenses associated with the injury if they could have been avoided through reasonable efforts. Specifically, attorneys for Dr. Morris emphasized that Ms. Boerste failed to follow medical advice for follow-up care, to obtain recommended podiatrist care, and to make necessary efforts to control her diabetes. Had Ms. Boerste taken more proactive steps to manage her health, leg amputation may not have been needed because the sponge may have been found during other treatment, they contended.

In its Jan. 7, 2022, opinion, the appeals court upheld the majority of the jury award. Judges wrote that Dr. Morris’ testimony alone was sufficient for the jury to determine whether he breached the standard of care, and that the defendants are not entitled to a new trial on pain and suffering damages. In addition, judges rejected mitigation of damages.  

“The fact that Boerste was a poor patient who failed to properly treat her diabetes is irrelevant,” the panel wrote in their decision. “She was a poor patient prior to the bypass surgery, and Appellants knew Boerste might ultimately need to have her lower leg amputated at the time of the bypass surgery. Therefore, we hold Appellants were not entitled to instructions on apportionment of fault or mitigation of damages.”

The appeals court, however, vacated the $1 million punitive damages award, ruling that the lower court did not give a proper instruction to the jury on punitive damages. The appeals court sent the case back to the lower court for a retrial as it pertains to punitive damages.

Attorneys for Dr. Morris and the hospital did not return messages seeking comment.

Bo Bolus, an attorney for Ms. Boerste’s family, said there will be no retrial on punitive damages, and that the plaintiff is satisfied with the outcome of the case.

“While we are pleased that Carolyn’s family and, equally importantly, her memory, now finally have closure on this extremely trying matter, our pleasure is severely tempered by the loss of Carolyn in November of last year,” Mr. Bolus said. “After having endured all she did, it is, frankly, painful for all concerned that she will not reap the reward of the jury’s verdict.”

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

An appeals court has upheld a family’s $9.5 million jury award after a physician left an 18-inch sponge in a patient’s abdomen that remained in her stomach for 5 years.

Carolyn Boerste underwent aortobifemoral bypass surgery at the University of Louisville (Ky.) Hospital in March 2011 to improve circulation in her lower extremities. She had a history of peripheral vascular disease, hypertension, and diabetes, which caused a wound on her toe to become infected and gangrenous, according to court records.

Courtesy Bo Bolus of Bolus Law Offices, Louisville, Ky.

During the surgery, performed by Marvin Morris, MD, the surgical team left a laparotomy sponge in Ms. Boerste’s abdomen. Because of its size, Ms. Boerste’s attorneys characterized the 18-by-18-inch object as “more like a towel,” according to court documents.

During the years that the sponge went undetected, the object eroded via transmural migration from Ms. Boerste’s abdomen into her intestine, causing diarrhea, vomiting, and nausea. In March 2015, Ms. Boerste was transferred by ambulance to an emergency department because of abdominal pain. An emergency physician ordered an abdominal CT scan, which showed the x-ray detectable sponge marker inside Ms. Boerste’s intestine, according to her complaint.

Although the radiologist called the emergency physician to advise him of the sponge marker, the information was not shared with Ms. Boerste and she was discharged from the hospital with a urinary tract infection diagnosis. The emergency physician later testified he had no memory of the call with the radiologist.

The CT scan was faxed to Ms. Boerste’s family physician. She testified that she read the report but did not mention the sponge marker to Ms. Boerste because she believed the issue had been handled by the emergency physician. Thus the sponge remained inside Ms. Boerste for another 20 months.

In November 2016, Ms. Boerste returned to the same emergency department with more intense gastrointestinal issues. Another CT scan was ordered, which revealed the sponge. The object was removed by exploratory laparotomy later that month. In her complaint, Ms. Boerste claimed that the removal surgery resulted in amputation of her leg because of wounds developed on her lower extremities while she was bedridden during recovery.

In 2017, she filed a negligence lawsuit against Dr. Morris, the hospital, and several others involved in her care. On the first day of trial in December 2019, the hospital conceded liability. The trial continued against Dr. Morris and the other defendants as to liability and damages and proceeded against the hospital as to damages.

At trial, evidence showed there was significant confusion among nurses on how to document sponge counts, according to the appellate decision. In general, nurses used a perioperative nursing record to document the surgical procedure, and that record had a place to document some but not all sponge counts required by hospital policy. The nursing record did not have a place to document sponge counts required to be recorded at every break, lunch, and shift change. Nurses also used a worksheet to track sponge counts, but that worksheet was not part of the medical record.

Dr. Morris testified that he relies on nurses regarding sponge counts, but that he also performs a visual and tactile inspection of the abdominal cavity. He acknowledged during trial that the standard of care required him to keep track of the sponges before closing. Dr. Morris also testified that the surgeon and nurses are a team, and “the entire team did not count the sponges correctly when finishing the bypass surgery,” according to the appellate decision.

After a 10-day trial, jurors found Dr. Morris and several other defendants liable. They apportioned 60% liability to the hospital, 10% to Morris, 15% to the family physician, 0% to the emergency physician, and 15% to the rehabilitation center. Ms. Boerste was awarded $9.5 million in damages and an additional $1 million in punitive damages, for a total of $10.5 million.

Dr. Morris and the hospital appealed to the Commonwealth of Kentucky Court of Appeals. As the appeal was pending, Ms. Boerste died, and her son took over the plaintiff’s role.

In their appeal, Dr. Morris and the hospital said they should be granted a new trial for a number of reasons, including that the pain and suffering award was grossly excessive and reflected improper jury sympathy, that the punitive damages award should be vacated because jurors were not properly instructed on the issue, and that the judgment against Dr. Morris should be overturned because there was no evidence he deviated from the standard of care.

The defendants also argued that they were entitled to instructions on “apportionment of fault and mitigation of damages against Boerste.” The mitigation of damages doctrine prevents an injured plaintiff from recovering unreasonable expenses associated with the injury if they could have been avoided through reasonable efforts. Specifically, attorneys for Dr. Morris emphasized that Ms. Boerste failed to follow medical advice for follow-up care, to obtain recommended podiatrist care, and to make necessary efforts to control her diabetes. Had Ms. Boerste taken more proactive steps to manage her health, leg amputation may not have been needed because the sponge may have been found during other treatment, they contended.

In its Jan. 7, 2022, opinion, the appeals court upheld the majority of the jury award. Judges wrote that Dr. Morris’ testimony alone was sufficient for the jury to determine whether he breached the standard of care, and that the defendants are not entitled to a new trial on pain and suffering damages. In addition, judges rejected mitigation of damages.  

“The fact that Boerste was a poor patient who failed to properly treat her diabetes is irrelevant,” the panel wrote in their decision. “She was a poor patient prior to the bypass surgery, and Appellants knew Boerste might ultimately need to have her lower leg amputated at the time of the bypass surgery. Therefore, we hold Appellants were not entitled to instructions on apportionment of fault or mitigation of damages.”

The appeals court, however, vacated the $1 million punitive damages award, ruling that the lower court did not give a proper instruction to the jury on punitive damages. The appeals court sent the case back to the lower court for a retrial as it pertains to punitive damages.

Attorneys for Dr. Morris and the hospital did not return messages seeking comment.

Bo Bolus, an attorney for Ms. Boerste’s family, said there will be no retrial on punitive damages, and that the plaintiff is satisfied with the outcome of the case.

“While we are pleased that Carolyn’s family and, equally importantly, her memory, now finally have closure on this extremely trying matter, our pleasure is severely tempered by the loss of Carolyn in November of last year,” Mr. Bolus said. “After having endured all she did, it is, frankly, painful for all concerned that she will not reap the reward of the jury’s verdict.”

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

An appeals court has upheld a family’s $9.5 million jury award after a physician left an 18-inch sponge in a patient’s abdomen that remained in her stomach for 5 years.

Carolyn Boerste underwent aortobifemoral bypass surgery at the University of Louisville (Ky.) Hospital in March 2011 to improve circulation in her lower extremities. She had a history of peripheral vascular disease, hypertension, and diabetes, which caused a wound on her toe to become infected and gangrenous, according to court records.

Courtesy Bo Bolus of Bolus Law Offices, Louisville, Ky.

During the surgery, performed by Marvin Morris, MD, the surgical team left a laparotomy sponge in Ms. Boerste’s abdomen. Because of its size, Ms. Boerste’s attorneys characterized the 18-by-18-inch object as “more like a towel,” according to court documents.

During the years that the sponge went undetected, the object eroded via transmural migration from Ms. Boerste’s abdomen into her intestine, causing diarrhea, vomiting, and nausea. In March 2015, Ms. Boerste was transferred by ambulance to an emergency department because of abdominal pain. An emergency physician ordered an abdominal CT scan, which showed the x-ray detectable sponge marker inside Ms. Boerste’s intestine, according to her complaint.

Although the radiologist called the emergency physician to advise him of the sponge marker, the information was not shared with Ms. Boerste and she was discharged from the hospital with a urinary tract infection diagnosis. The emergency physician later testified he had no memory of the call with the radiologist.

The CT scan was faxed to Ms. Boerste’s family physician. She testified that she read the report but did not mention the sponge marker to Ms. Boerste because she believed the issue had been handled by the emergency physician. Thus the sponge remained inside Ms. Boerste for another 20 months.

In November 2016, Ms. Boerste returned to the same emergency department with more intense gastrointestinal issues. Another CT scan was ordered, which revealed the sponge. The object was removed by exploratory laparotomy later that month. In her complaint, Ms. Boerste claimed that the removal surgery resulted in amputation of her leg because of wounds developed on her lower extremities while she was bedridden during recovery.

In 2017, she filed a negligence lawsuit against Dr. Morris, the hospital, and several others involved in her care. On the first day of trial in December 2019, the hospital conceded liability. The trial continued against Dr. Morris and the other defendants as to liability and damages and proceeded against the hospital as to damages.

At trial, evidence showed there was significant confusion among nurses on how to document sponge counts, according to the appellate decision. In general, nurses used a perioperative nursing record to document the surgical procedure, and that record had a place to document some but not all sponge counts required by hospital policy. The nursing record did not have a place to document sponge counts required to be recorded at every break, lunch, and shift change. Nurses also used a worksheet to track sponge counts, but that worksheet was not part of the medical record.

Dr. Morris testified that he relies on nurses regarding sponge counts, but that he also performs a visual and tactile inspection of the abdominal cavity. He acknowledged during trial that the standard of care required him to keep track of the sponges before closing. Dr. Morris also testified that the surgeon and nurses are a team, and “the entire team did not count the sponges correctly when finishing the bypass surgery,” according to the appellate decision.

After a 10-day trial, jurors found Dr. Morris and several other defendants liable. They apportioned 60% liability to the hospital, 10% to Morris, 15% to the family physician, 0% to the emergency physician, and 15% to the rehabilitation center. Ms. Boerste was awarded $9.5 million in damages and an additional $1 million in punitive damages, for a total of $10.5 million.

Dr. Morris and the hospital appealed to the Commonwealth of Kentucky Court of Appeals. As the appeal was pending, Ms. Boerste died, and her son took over the plaintiff’s role.

In their appeal, Dr. Morris and the hospital said they should be granted a new trial for a number of reasons, including that the pain and suffering award was grossly excessive and reflected improper jury sympathy, that the punitive damages award should be vacated because jurors were not properly instructed on the issue, and that the judgment against Dr. Morris should be overturned because there was no evidence he deviated from the standard of care.

The defendants also argued that they were entitled to instructions on “apportionment of fault and mitigation of damages against Boerste.” The mitigation of damages doctrine prevents an injured plaintiff from recovering unreasonable expenses associated with the injury if they could have been avoided through reasonable efforts. Specifically, attorneys for Dr. Morris emphasized that Ms. Boerste failed to follow medical advice for follow-up care, to obtain recommended podiatrist care, and to make necessary efforts to control her diabetes. Had Ms. Boerste taken more proactive steps to manage her health, leg amputation may not have been needed because the sponge may have been found during other treatment, they contended.

In its Jan. 7, 2022, opinion, the appeals court upheld the majority of the jury award. Judges wrote that Dr. Morris’ testimony alone was sufficient for the jury to determine whether he breached the standard of care, and that the defendants are not entitled to a new trial on pain and suffering damages. In addition, judges rejected mitigation of damages.  

“The fact that Boerste was a poor patient who failed to properly treat her diabetes is irrelevant,” the panel wrote in their decision. “She was a poor patient prior to the bypass surgery, and Appellants knew Boerste might ultimately need to have her lower leg amputated at the time of the bypass surgery. Therefore, we hold Appellants were not entitled to instructions on apportionment of fault or mitigation of damages.”

The appeals court, however, vacated the $1 million punitive damages award, ruling that the lower court did not give a proper instruction to the jury on punitive damages. The appeals court sent the case back to the lower court for a retrial as it pertains to punitive damages.

Attorneys for Dr. Morris and the hospital did not return messages seeking comment.

Bo Bolus, an attorney for Ms. Boerste’s family, said there will be no retrial on punitive damages, and that the plaintiff is satisfied with the outcome of the case.

“While we are pleased that Carolyn’s family and, equally importantly, her memory, now finally have closure on this extremely trying matter, our pleasure is severely tempered by the loss of Carolyn in November of last year,” Mr. Bolus said. “After having endured all she did, it is, frankly, painful for all concerned that she will not reap the reward of the jury’s verdict.”

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

The American College of Rheumatology and the American Association of Hip and Knee Surgeons have released updated guidelines regarding whether to withhold drugs such as biologics and immunosuppressives for patients with inflammatory rheumatic disease who are scheduled to undergo elective total hip or knee replacement surgery.

The guidelines, published in a summary by the societies on Feb. 28, include revised and new recommendations about biologics and Janus kinase (JAK) inhibitors for patients with several types of inflammatory arthritis and systemic lupus erythematosus (SLE). In general, the guidelines recommend that the most powerful medications be withheld prior to surgery except for patients whose SLE is so severe that it threatens organs. They also recommend a shorter period of withholding drugs – 3 days instead of 7 – for JAK inhibitors.
 

The previous guidelines were published in 2017.

“These recommendations seek to balance flares of disease that are likely when medications are stopped vs. the risk of infection,” Susan M. Goodman, MD, a rheumatologist at the Hospital for Special Surgery, New York, and co–principal investigator of the guideline, told this news organization. “Patients and physicians may want to be either more conservative or more aggressive with their medications, depending on their personal priorities or specific medical history.”

According to Dr. Goodman, patients with inflammatory rheumatic diseases are especially likely to undergo joint replacement surgery because the conditions can damage the joints. “While the introduction of potent biologics has been linked to a decrease in surgery of soft tissues and small joints, there has been little impact on large-joint surgeries,” she said.

The risk of infection in these patients is about 50% higher than in the general population, she said. However, “it is hard to determine the magnitude of the effect of withholding medications, given the low rate of infection. In fact, using pharmaco-epidemiologic methods in large Medicare databases, no difference was seen in patients whose immunosuppressant medication infusions were close to the time of surgery compared to those patients whose medication infusions were months prior to surgery.”

The guidelines add a recommendation for the first time for apremilast (Otezla), saying that when it is administered twice daily it is okay to schedule surgery at any time.

Withholding drugs in patients with SLE

“We now recommend continuing biologics used to treat SLE – rituximab and belimumab – in patients with severe SLE but continue to recommend withholding them in less severe cases where there is little risk of organ damage,” Bryan D. Springer, MD, an orthopedic surgeon in Charlotte, N.C., first vice president of the AAHKS, and co–principal investigator of the new guidelines, told this news organization.

In severe SLE cases, the guidelines recommend timing total joint replacement surgery for 4-6 months after the latest IV dose of rituximab (Rituxan), which is given every 4-6 months. For patients taking belimumab (Benlysta), time surgery anytime when weekly subcutaneous doses are administered or at week 4 when monthly IV doses are given.

The guidelines also make recommendations regarding two new drugs for the treatment of severe SLE:

• Anifrolumab (Saphnelo): Time surgery at week 4 when IV treatment is given every 4 weeks.
• Voclosporin (Lupkynis): Continue doses when they’re given twice daily.

An ACR statement cautions that there are no published, peer-reviewed data regarding the use of these two drugs prior to total joint surgery. “The medications do increase the risk of infection,” the statement says, “and therefore their use in patients with severe SLE would merit review by the treating rheumatologist in consideration of surgery.”

Timing of stopping and restarting medication

The guidelines also recommend that certain drugs be withheld for patients with rheumatoid arthritis, ankylosing spondylitis, or any type of SLE and then “restarting the antirheumatic therapy once the wound shows evidence of healing, any sutures/staples are out, there is no significant swelling, erythema, or drainage, and there is no ongoing nonsurgical site infection, which is typically about 14 days.”

In regard to biologics, “we continue to recommend withholding biologic medications in patients with inflammatory arthritis, withholding the medication for a dosing cycle prior to surgery, and scheduling the surgery after that dose would be due,” Dr. Springer said. “For example, if a patient takes the medication every 4 weeks, the patient would withhold the dose of the medication and schedule surgery in the 5th week.”

The new recommendations for biologics suggest scheduling surgery at week 5 when the interleukin (IL)-17 inhibitor ixekizumab (Taltz) is given once every 4 weeks and at week 9 when the IL-23 inhibitor guselkumab (Tremfya) is given every 8 weeks.

The guidelines also revise the previous recommendation about tofacitinib (Xeljanz): Surgery should be scheduled on day 4 when the drug is given once or twice daily. New recommendations for fellow JAK inhibitors baricitinib (Olumiant, daily) and upadacitinib (Rinvoq, daily) are the same: Withhold for 3 days prior to surgery and perform surgery on the 4th day.

“We shortened the time between the last dose of JAK inhibitors and surgery to 3 days from 7 based on trial data demonstrating early flares when the drug was withheld, suggesting the immunosuppressant effect wears off sooner than we previously thought,” Dr. Springer said.

The guidelines caution that the recommendations for JAK inhibitors are for infection risk but do not consider the risk of cardiac events or venous thromboembolism.

In patients with nonsevere SLE, the guidelines revise the recommendations for mycophenolate mofetil (twice daily), cyclosporine (twice daily), and tacrolimus (twice daily, IV and oral). The new advice is to withhold the drugs for 1 week after last dose prior to surgery. New recommendations offer the same advice for belimumab, both IV and subcutaneous: Withhold for 1 week after last dose prior to surgery.

The board of the ACR approved the guidelines summary; the full manuscript has been submitted for peer review with an eye toward later publication in the journals Arthritis and Rheumatology and Arthritis Care and Research.

The ACR and AAHKS funded the guidelines. Dr. Goodman and Dr. Springer report no relevant financial relationships.

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

The American College of Rheumatology and the American Association of Hip and Knee Surgeons have released updated guidelines regarding whether to withhold drugs such as biologics and immunosuppressives for patients with inflammatory rheumatic disease who are scheduled to undergo elective total hip or knee replacement surgery.

The guidelines, published in a summary by the societies on Feb. 28, include revised and new recommendations about biologics and Janus kinase (JAK) inhibitors for patients with several types of inflammatory arthritis and systemic lupus erythematosus (SLE). In general, the guidelines recommend that the most powerful medications be withheld prior to surgery except for patients whose SLE is so severe that it threatens organs. They also recommend a shorter period of withholding drugs – 3 days instead of 7 – for JAK inhibitors.
 

The previous guidelines were published in 2017.

“These recommendations seek to balance flares of disease that are likely when medications are stopped vs. the risk of infection,” Susan M. Goodman, MD, a rheumatologist at the Hospital for Special Surgery, New York, and co–principal investigator of the guideline, told this news organization. “Patients and physicians may want to be either more conservative or more aggressive with their medications, depending on their personal priorities or specific medical history.”

According to Dr. Goodman, patients with inflammatory rheumatic diseases are especially likely to undergo joint replacement surgery because the conditions can damage the joints. “While the introduction of potent biologics has been linked to a decrease in surgery of soft tissues and small joints, there has been little impact on large-joint surgeries,” she said.

The risk of infection in these patients is about 50% higher than in the general population, she said. However, “it is hard to determine the magnitude of the effect of withholding medications, given the low rate of infection. In fact, using pharmaco-epidemiologic methods in large Medicare databases, no difference was seen in patients whose immunosuppressant medication infusions were close to the time of surgery compared to those patients whose medication infusions were months prior to surgery.”

The guidelines add a recommendation for the first time for apremilast (Otezla), saying that when it is administered twice daily it is okay to schedule surgery at any time.

Withholding drugs in patients with SLE

“We now recommend continuing biologics used to treat SLE – rituximab and belimumab – in patients with severe SLE but continue to recommend withholding them in less severe cases where there is little risk of organ damage,” Bryan D. Springer, MD, an orthopedic surgeon in Charlotte, N.C., first vice president of the AAHKS, and co–principal investigator of the new guidelines, told this news organization.

In severe SLE cases, the guidelines recommend timing total joint replacement surgery for 4-6 months after the latest IV dose of rituximab (Rituxan), which is given every 4-6 months. For patients taking belimumab (Benlysta), time surgery anytime when weekly subcutaneous doses are administered or at week 4 when monthly IV doses are given.

The guidelines also make recommendations regarding two new drugs for the treatment of severe SLE:

• Anifrolumab (Saphnelo): Time surgery at week 4 when IV treatment is given every 4 weeks.
• Voclosporin (Lupkynis): Continue doses when they’re given twice daily.

An ACR statement cautions that there are no published, peer-reviewed data regarding the use of these two drugs prior to total joint surgery. “The medications do increase the risk of infection,” the statement says, “and therefore their use in patients with severe SLE would merit review by the treating rheumatologist in consideration of surgery.”

Timing of stopping and restarting medication

The guidelines also recommend that certain drugs be withheld for patients with rheumatoid arthritis, ankylosing spondylitis, or any type of SLE and then “restarting the antirheumatic therapy once the wound shows evidence of healing, any sutures/staples are out, there is no significant swelling, erythema, or drainage, and there is no ongoing nonsurgical site infection, which is typically about 14 days.”

In regard to biologics, “we continue to recommend withholding biologic medications in patients with inflammatory arthritis, withholding the medication for a dosing cycle prior to surgery, and scheduling the surgery after that dose would be due,” Dr. Springer said. “For example, if a patient takes the medication every 4 weeks, the patient would withhold the dose of the medication and schedule surgery in the 5th week.”

The new recommendations for biologics suggest scheduling surgery at week 5 when the interleukin (IL)-17 inhibitor ixekizumab (Taltz) is given once every 4 weeks and at week 9 when the IL-23 inhibitor guselkumab (Tremfya) is given every 8 weeks.

The guidelines also revise the previous recommendation about tofacitinib (Xeljanz): Surgery should be scheduled on day 4 when the drug is given once or twice daily. New recommendations for fellow JAK inhibitors baricitinib (Olumiant, daily) and upadacitinib (Rinvoq, daily) are the same: Withhold for 3 days prior to surgery and perform surgery on the 4th day.

“We shortened the time between the last dose of JAK inhibitors and surgery to 3 days from 7 based on trial data demonstrating early flares when the drug was withheld, suggesting the immunosuppressant effect wears off sooner than we previously thought,” Dr. Springer said.

The guidelines caution that the recommendations for JAK inhibitors are for infection risk but do not consider the risk of cardiac events or venous thromboembolism.

In patients with nonsevere SLE, the guidelines revise the recommendations for mycophenolate mofetil (twice daily), cyclosporine (twice daily), and tacrolimus (twice daily, IV and oral). The new advice is to withhold the drugs for 1 week after last dose prior to surgery. New recommendations offer the same advice for belimumab, both IV and subcutaneous: Withhold for 1 week after last dose prior to surgery.

The board of the ACR approved the guidelines summary; the full manuscript has been submitted for peer review with an eye toward later publication in the journals Arthritis and Rheumatology and Arthritis Care and Research.

The ACR and AAHKS funded the guidelines. Dr. Goodman and Dr. Springer report no relevant financial relationships.

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

The American College of Rheumatology and the American Association of Hip and Knee Surgeons have released updated guidelines regarding whether to withhold drugs such as biologics and immunosuppressives for patients with inflammatory rheumatic disease who are scheduled to undergo elective total hip or knee replacement surgery.

The guidelines, published in a summary by the societies on Feb. 28, include revised and new recommendations about biologics and Janus kinase (JAK) inhibitors for patients with several types of inflammatory arthritis and systemic lupus erythematosus (SLE). In general, the guidelines recommend that the most powerful medications be withheld prior to surgery except for patients whose SLE is so severe that it threatens organs. They also recommend a shorter period of withholding drugs – 3 days instead of 7 – for JAK inhibitors.
 

The previous guidelines were published in 2017.

“These recommendations seek to balance flares of disease that are likely when medications are stopped vs. the risk of infection,” Susan M. Goodman, MD, a rheumatologist at the Hospital for Special Surgery, New York, and co–principal investigator of the guideline, told this news organization. “Patients and physicians may want to be either more conservative or more aggressive with their medications, depending on their personal priorities or specific medical history.”

According to Dr. Goodman, patients with inflammatory rheumatic diseases are especially likely to undergo joint replacement surgery because the conditions can damage the joints. “While the introduction of potent biologics has been linked to a decrease in surgery of soft tissues and small joints, there has been little impact on large-joint surgeries,” she said.

The risk of infection in these patients is about 50% higher than in the general population, she said. However, “it is hard to determine the magnitude of the effect of withholding medications, given the low rate of infection. In fact, using pharmaco-epidemiologic methods in large Medicare databases, no difference was seen in patients whose immunosuppressant medication infusions were close to the time of surgery compared to those patients whose medication infusions were months prior to surgery.”

The guidelines add a recommendation for the first time for apremilast (Otezla), saying that when it is administered twice daily it is okay to schedule surgery at any time.

Withholding drugs in patients with SLE

“We now recommend continuing biologics used to treat SLE – rituximab and belimumab – in patients with severe SLE but continue to recommend withholding them in less severe cases where there is little risk of organ damage,” Bryan D. Springer, MD, an orthopedic surgeon in Charlotte, N.C., first vice president of the AAHKS, and co–principal investigator of the new guidelines, told this news organization.

In severe SLE cases, the guidelines recommend timing total joint replacement surgery for 4-6 months after the latest IV dose of rituximab (Rituxan), which is given every 4-6 months. For patients taking belimumab (Benlysta), time surgery anytime when weekly subcutaneous doses are administered or at week 4 when monthly IV doses are given.

The guidelines also make recommendations regarding two new drugs for the treatment of severe SLE:

• Anifrolumab (Saphnelo): Time surgery at week 4 when IV treatment is given every 4 weeks.
• Voclosporin (Lupkynis): Continue doses when they’re given twice daily.

An ACR statement cautions that there are no published, peer-reviewed data regarding the use of these two drugs prior to total joint surgery. “The medications do increase the risk of infection,” the statement says, “and therefore their use in patients with severe SLE would merit review by the treating rheumatologist in consideration of surgery.”

Timing of stopping and restarting medication

The guidelines also recommend that certain drugs be withheld for patients with rheumatoid arthritis, ankylosing spondylitis, or any type of SLE and then “restarting the antirheumatic therapy once the wound shows evidence of healing, any sutures/staples are out, there is no significant swelling, erythema, or drainage, and there is no ongoing nonsurgical site infection, which is typically about 14 days.”

In regard to biologics, “we continue to recommend withholding biologic medications in patients with inflammatory arthritis, withholding the medication for a dosing cycle prior to surgery, and scheduling the surgery after that dose would be due,” Dr. Springer said. “For example, if a patient takes the medication every 4 weeks, the patient would withhold the dose of the medication and schedule surgery in the 5th week.”

The new recommendations for biologics suggest scheduling surgery at week 5 when the interleukin (IL)-17 inhibitor ixekizumab (Taltz) is given once every 4 weeks and at week 9 when the IL-23 inhibitor guselkumab (Tremfya) is given every 8 weeks.

The guidelines also revise the previous recommendation about tofacitinib (Xeljanz): Surgery should be scheduled on day 4 when the drug is given once or twice daily. New recommendations for fellow JAK inhibitors baricitinib (Olumiant, daily) and upadacitinib (Rinvoq, daily) are the same: Withhold for 3 days prior to surgery and perform surgery on the 4th day.

“We shortened the time between the last dose of JAK inhibitors and surgery to 3 days from 7 based on trial data demonstrating early flares when the drug was withheld, suggesting the immunosuppressant effect wears off sooner than we previously thought,” Dr. Springer said.

The guidelines caution that the recommendations for JAK inhibitors are for infection risk but do not consider the risk of cardiac events or venous thromboembolism.

In patients with nonsevere SLE, the guidelines revise the recommendations for mycophenolate mofetil (twice daily), cyclosporine (twice daily), and tacrolimus (twice daily, IV and oral). The new advice is to withhold the drugs for 1 week after last dose prior to surgery. New recommendations offer the same advice for belimumab, both IV and subcutaneous: Withhold for 1 week after last dose prior to surgery.

The board of the ACR approved the guidelines summary; the full manuscript has been submitted for peer review with an eye toward later publication in the journals Arthritis and Rheumatology and Arthritis Care and Research.

The ACR and AAHKS funded the guidelines. Dr. Goodman and Dr. Springer report no relevant financial relationships.

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

The COVID-19 pandemic continues to take a toll on the happiness, wellness, and lifestyles of many segments of the population, but especially those in the health care field, including gastroenterologists.

The newly released Medscape Gastroenterologist Lifestyle, Happiness & Burnout Report 2022 explores gastroenterologists’ level of happiness in their personal and professional lives and how they maintain their mental and physical health.

Prior to the global pandemic, 8 in 10 (80%) gastroenterologists said they were “very” or “somewhat” happy outside of work, similar to physicians overall (81%).

But as the pandemic has worn on, feelings have shifted, and there are clear signs of stress and strain on those in the health care field.

Now, the percentage of gastroenterologists who say they are currently “very” or “somewhat” happy outside of work has dropped to 60%, about the same as physicians overall (59%).
 

Buried in paperwork

In 2021’s report, 42% of gastroenterologists reported burnout; that’s risen to 47% this year.

When it comes to burnout, gastroenterologists remain in the middle range of burned-out physicians.

Perhaps not surprising given the challenges of the COVID-19 pandemic, burnout rates are highest among emergency medicine and critical care specialists.

About half of gastroenterologists (52%) report being more burned out now than during the initial quarantine months of the pandemic, similar to physicians overall (55%). About 4 in 10 (39%) said their burnout was the same.

Female gastroenterologists report burnout at a greater rate than their male colleagues – 57% versus 46%.

“There’s no question that women have reported far more role strain during the pandemic than men,” said Carol A. Bernstein, MD, a psychiatrist at Montefiore Health System and professor and vice chair for faculty development and well-being at Albert Einstein College of Medicine, New York.

“Often women assumed more of the childcare and home-schooling responsibilities in their households. As [a] result, we know that more women dropped out of the workforce. Also, past studies indicate that women are more likely to report feelings of burnout than men,” Dr. Bernstein noted.

The volume of bureaucratic tasks is the main driver of gastroenterologist burnout, similar to that for physicians overall. Lack of respect from colleagues and more time devoted to electronic health records were also selected as major factors in this year’s report.

Gastroenterologists’ top ways to quell burnout are reducing their hours on the job (24%), changing workflow or staffing to ease their workload (23%), and taking advantage of meditation or other stress-reduction methods (18%) – similar to physicians overall.

Roughly one-third (34%) of gastroenterologists feel that their personality type contributes to their burnout, similar to physicians overall. Six in 10 gastroenterologists (60%) say burnout affects their relationships, similar to physicians overall (68%).
 

Seeking better work-life balance

More than half of gastroenterologists (57%) said they are willing to take a cut in pay in order to achieve a better work-life balance or have more free time – similar among physicians overall (55%).

About 16% of gastroenterologists reported clinical depression (severe depression lasting some time and not caused by grief), while 71% reported colloquial depression (feeling down, blue, sad).

About half (53%) of depressed gastroenterologists said their depression does not have an impact on relationships with patients.

Among those who saw an impact, the major behaviors they reported included being easily exasperated with patients (44%) and feeling less motivated to take patient notes carefully (20%).

To maintain well-being, gastroenterologists often choose to spend their time with their loved ones (59%), do the things they enjoy (58%), exercise (57%), get plenty of sleep (42%), and eat right (35%).

Perhaps not surprisingly, more gastroenterologists were happy with their work-life balance before the pandemic than now (70% vs. 44%). The same holds for physicians overall.

Before the pandemic, 22% of gastroenterologists reported being unhappy with their work-life balance. That has risen to 39% this year.

Most gastroenterologists are currently in a committed relationship, with 90% either married or living with a partner, a somewhat higher percentage than physicians overall (83%).

About 83% of gastroenterologists say they are in a “very good” or “good” marriage. This is down somewhat from the 2021 report (89%).

Nearly 6 in 10 gastroenterologists have partners who do not work in medicine. This is similar to the proportion among all physicians.

Findings from Medscape’s latest happiness, wellness, and lifestyle survey are based on 13,069 Medscape member physicians (61% male) practicing in the United States who completed an online survey conducted between June 29, 2021, and Sept. 26, 2021. Most respondents were between 35 and 64 years old.

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

The COVID-19 pandemic continues to take a toll on the happiness, wellness, and lifestyles of many segments of the population, but especially those in the health care field, including gastroenterologists.

The newly released Medscape Gastroenterologist Lifestyle, Happiness & Burnout Report 2022 explores gastroenterologists’ level of happiness in their personal and professional lives and how they maintain their mental and physical health.

Prior to the global pandemic, 8 in 10 (80%) gastroenterologists said they were “very” or “somewhat” happy outside of work, similar to physicians overall (81%).

But as the pandemic has worn on, feelings have shifted, and there are clear signs of stress and strain on those in the health care field.

Now, the percentage of gastroenterologists who say they are currently “very” or “somewhat” happy outside of work has dropped to 60%, about the same as physicians overall (59%).
 

Buried in paperwork

In 2021’s report, 42% of gastroenterologists reported burnout; that’s risen to 47% this year.

When it comes to burnout, gastroenterologists remain in the middle range of burned-out physicians.

Perhaps not surprising given the challenges of the COVID-19 pandemic, burnout rates are highest among emergency medicine and critical care specialists.

About half of gastroenterologists (52%) report being more burned out now than during the initial quarantine months of the pandemic, similar to physicians overall (55%). About 4 in 10 (39%) said their burnout was the same.

Female gastroenterologists report burnout at a greater rate than their male colleagues – 57% versus 46%.

“There’s no question that women have reported far more role strain during the pandemic than men,” said Carol A. Bernstein, MD, a psychiatrist at Montefiore Health System and professor and vice chair for faculty development and well-being at Albert Einstein College of Medicine, New York.

“Often women assumed more of the childcare and home-schooling responsibilities in their households. As [a] result, we know that more women dropped out of the workforce. Also, past studies indicate that women are more likely to report feelings of burnout than men,” Dr. Bernstein noted.

The volume of bureaucratic tasks is the main driver of gastroenterologist burnout, similar to that for physicians overall. Lack of respect from colleagues and more time devoted to electronic health records were also selected as major factors in this year’s report.

Gastroenterologists’ top ways to quell burnout are reducing their hours on the job (24%), changing workflow or staffing to ease their workload (23%), and taking advantage of meditation or other stress-reduction methods (18%) – similar to physicians overall.

Roughly one-third (34%) of gastroenterologists feel that their personality type contributes to their burnout, similar to physicians overall. Six in 10 gastroenterologists (60%) say burnout affects their relationships, similar to physicians overall (68%).
 

Seeking better work-life balance

More than half of gastroenterologists (57%) said they are willing to take a cut in pay in order to achieve a better work-life balance or have more free time – similar among physicians overall (55%).

About 16% of gastroenterologists reported clinical depression (severe depression lasting some time and not caused by grief), while 71% reported colloquial depression (feeling down, blue, sad).

About half (53%) of depressed gastroenterologists said their depression does not have an impact on relationships with patients.

Among those who saw an impact, the major behaviors they reported included being easily exasperated with patients (44%) and feeling less motivated to take patient notes carefully (20%).

To maintain well-being, gastroenterologists often choose to spend their time with their loved ones (59%), do the things they enjoy (58%), exercise (57%), get plenty of sleep (42%), and eat right (35%).

Perhaps not surprisingly, more gastroenterologists were happy with their work-life balance before the pandemic than now (70% vs. 44%). The same holds for physicians overall.

Before the pandemic, 22% of gastroenterologists reported being unhappy with their work-life balance. That has risen to 39% this year.

Most gastroenterologists are currently in a committed relationship, with 90% either married or living with a partner, a somewhat higher percentage than physicians overall (83%).

About 83% of gastroenterologists say they are in a “very good” or “good” marriage. This is down somewhat from the 2021 report (89%).

Nearly 6 in 10 gastroenterologists have partners who do not work in medicine. This is similar to the proportion among all physicians.

Findings from Medscape’s latest happiness, wellness, and lifestyle survey are based on 13,069 Medscape member physicians (61% male) practicing in the United States who completed an online survey conducted between June 29, 2021, and Sept. 26, 2021. Most respondents were between 35 and 64 years old.

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

The COVID-19 pandemic continues to take a toll on the happiness, wellness, and lifestyles of many segments of the population, but especially those in the health care field, including gastroenterologists.

The newly released Medscape Gastroenterologist Lifestyle, Happiness & Burnout Report 2022 explores gastroenterologists’ level of happiness in their personal and professional lives and how they maintain their mental and physical health.

Prior to the global pandemic, 8 in 10 (80%) gastroenterologists said they were “very” or “somewhat” happy outside of work, similar to physicians overall (81%).

But as the pandemic has worn on, feelings have shifted, and there are clear signs of stress and strain on those in the health care field.

Now, the percentage of gastroenterologists who say they are currently “very” or “somewhat” happy outside of work has dropped to 60%, about the same as physicians overall (59%).
 

Buried in paperwork

In 2021’s report, 42% of gastroenterologists reported burnout; that’s risen to 47% this year.

When it comes to burnout, gastroenterologists remain in the middle range of burned-out physicians.

Perhaps not surprising given the challenges of the COVID-19 pandemic, burnout rates are highest among emergency medicine and critical care specialists.

About half of gastroenterologists (52%) report being more burned out now than during the initial quarantine months of the pandemic, similar to physicians overall (55%). About 4 in 10 (39%) said their burnout was the same.

Female gastroenterologists report burnout at a greater rate than their male colleagues – 57% versus 46%.

“There’s no question that women have reported far more role strain during the pandemic than men,” said Carol A. Bernstein, MD, a psychiatrist at Montefiore Health System and professor and vice chair for faculty development and well-being at Albert Einstein College of Medicine, New York.

“Often women assumed more of the childcare and home-schooling responsibilities in their households. As [a] result, we know that more women dropped out of the workforce. Also, past studies indicate that women are more likely to report feelings of burnout than men,” Dr. Bernstein noted.

The volume of bureaucratic tasks is the main driver of gastroenterologist burnout, similar to that for physicians overall. Lack of respect from colleagues and more time devoted to electronic health records were also selected as major factors in this year’s report.

Gastroenterologists’ top ways to quell burnout are reducing their hours on the job (24%), changing workflow or staffing to ease their workload (23%), and taking advantage of meditation or other stress-reduction methods (18%) – similar to physicians overall.

Roughly one-third (34%) of gastroenterologists feel that their personality type contributes to their burnout, similar to physicians overall. Six in 10 gastroenterologists (60%) say burnout affects their relationships, similar to physicians overall (68%).
 

Seeking better work-life balance

More than half of gastroenterologists (57%) said they are willing to take a cut in pay in order to achieve a better work-life balance or have more free time – similar among physicians overall (55%).

About 16% of gastroenterologists reported clinical depression (severe depression lasting some time and not caused by grief), while 71% reported colloquial depression (feeling down, blue, sad).

About half (53%) of depressed gastroenterologists said their depression does not have an impact on relationships with patients.

Among those who saw an impact, the major behaviors they reported included being easily exasperated with patients (44%) and feeling less motivated to take patient notes carefully (20%).

To maintain well-being, gastroenterologists often choose to spend their time with their loved ones (59%), do the things they enjoy (58%), exercise (57%), get plenty of sleep (42%), and eat right (35%).

Perhaps not surprisingly, more gastroenterologists were happy with their work-life balance before the pandemic than now (70% vs. 44%). The same holds for physicians overall.

Before the pandemic, 22% of gastroenterologists reported being unhappy with their work-life balance. That has risen to 39% this year.

Most gastroenterologists are currently in a committed relationship, with 90% either married or living with a partner, a somewhat higher percentage than physicians overall (83%).

About 83% of gastroenterologists say they are in a “very good” or “good” marriage. This is down somewhat from the 2021 report (89%).

Nearly 6 in 10 gastroenterologists have partners who do not work in medicine. This is similar to the proportion among all physicians.

Findings from Medscape’s latest happiness, wellness, and lifestyle survey are based on 13,069 Medscape member physicians (61% male) practicing in the United States who completed an online survey conducted between June 29, 2021, and Sept. 26, 2021. Most respondents were between 35 and 64 years old.

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

The prevalence of metabolic syndrome varies according to how it is defined, but approximately 30% of psoriatic arthritis (PsA) patients met the criteria in a cohort study of 724 individuals, as did approximately 23%-63% of patients across multiple studies, investigators from Spain report.

Previous studies of people with PsA in particular suggest they are at an increased risk of cardiovascular disease and have a higher prevalence of metabolic syndrome, prompting recommendations on cardiovascular risk management for patients with PsA, wrote the authors, Ana Urruticoechea-Arana, MD, of the department of rheumatology, Hospital Can Misses, Ibiza, Spain, and colleagues.

However, assessing the prevalence of metabolic syndrome remains a challenge because the definition varies across studies, they noted.

For a more thorough assessment of the prevalence of metabolic syndrome in this population, the researchers conducted a study using two sources: a systematic literature review of 18 studies published up to March 2019, and data on patients with PsA enrolled in the CARMA (Spanish Cardiovascular in Rheumatology) project, a longitudinal cohort observational study of adults with inflammatory diseases in Spain. The findings were published March 1 in the Journal of Clinical Rheumatology.

The literature review included a total of a total of 2,452 patients with PsA, with a mean age between 42 and 59 years, and a mean disease duration ranging from 3 to 14 years.

The definitions of metabolic syndrome varied; the most common was the definition from the National Cholesterol Education Program (NECP ATP III). Other definitions used in the studies included those issued by the International Diabetes Federation, the World Health Organization, and the American Heart Association.

Across these studies, the rate of metabolic syndrome ranged from 23.5% to 62.9%. Prevalence was similar between men and women. One study that included patients with a PsA disease duration of only 3 years showed a prevalence of 38%, similar to the average prevalence overall. Another study showed a significantly higher prevalence of metabolic syndrome in patients with PsA and cutaneous psoriasis, compared with those without psoriasis (40.8% vs. 13.16%; P = .006).

The CARMA study included 724 patients with PsA; 45.4% were women and 21.8% were smokers. The mean age of the population in this study was 51 years, and the mean disease duration was 9 years. Overall, 222 patients (30.7%) met at least three criteria for metabolic syndrome, based on the NCEP ATP III definition. The most common abnormal findings for traditional cardiovascular risk factors in the CARMA cohort were high blood pressure (66.8%), hyperglycemia (42.6%), and hypertriglyceridemia (30.6%).

Despite the variation in prevalence of metabolic syndrome, depending on the definition used, the authors wrote, “It can be stated that the rate of [metabolic syndrome] in patients with PsA is in general very high, especially if we take into account the mean age of patients included in the studies.”

“These findings support the hypotheses that this increase in the inflammatory pathway in PsA may contribute a higher risk of cardiovascular events and [metabolic syndrome] in patients with PsA than patients with psoriasis alone, the risk being even higher in severe PsA,” and that insulin resistance, metabolic syndrome, and atherosclerotic events “may have a common inflammatory basis,” the researchers wrote in their discussion of the results.

The study findings were limited by several factors, most importantly the variation in definitions of metabolic syndrome in the literature review, which limits the generalizability of the results, the researchers said. Limitations of the CARMA study include the focus only on patients who were being cared for in hospitals, which might yield an overestimation of metabolic syndrome, they added.

However, the results support findings from previous studies and highlight the need for proper assessment of body weight and cardiovascular risk factors in patients with PsA at the onset of disease, they said.

“Furthermore, it is necessary to conduct more research to standardize (and modify as appropriate) the definition of [metabolic syndrome] and establish the best strategy for managing it in these patients,” they concluded.

The study was funded by an independent grant from UCB Pharma. One author disclosed receiving grants from Pfizer, Abbvie, Novartis, Roche, UCB, Sanofi, BMS, Lilly, MSD, and Janssen. Lead author Dr. Urruticoechea-Arana and the other authors had no disclosures.

The prevalence of metabolic syndrome varies according to how it is defined, but approximately 30% of psoriatic arthritis (PsA) patients met the criteria in a cohort study of 724 individuals, as did approximately 23%-63% of patients across multiple studies, investigators from Spain report.

Previous studies of people with PsA in particular suggest they are at an increased risk of cardiovascular disease and have a higher prevalence of metabolic syndrome, prompting recommendations on cardiovascular risk management for patients with PsA, wrote the authors, Ana Urruticoechea-Arana, MD, of the department of rheumatology, Hospital Can Misses, Ibiza, Spain, and colleagues.

However, assessing the prevalence of metabolic syndrome remains a challenge because the definition varies across studies, they noted.

For a more thorough assessment of the prevalence of metabolic syndrome in this population, the researchers conducted a study using two sources: a systematic literature review of 18 studies published up to March 2019, and data on patients with PsA enrolled in the CARMA (Spanish Cardiovascular in Rheumatology) project, a longitudinal cohort observational study of adults with inflammatory diseases in Spain. The findings were published March 1 in the Journal of Clinical Rheumatology.

The literature review included a total of a total of 2,452 patients with PsA, with a mean age between 42 and 59 years, and a mean disease duration ranging from 3 to 14 years.

The definitions of metabolic syndrome varied; the most common was the definition from the National Cholesterol Education Program (NECP ATP III). Other definitions used in the studies included those issued by the International Diabetes Federation, the World Health Organization, and the American Heart Association.

Across these studies, the rate of metabolic syndrome ranged from 23.5% to 62.9%. Prevalence was similar between men and women. One study that included patients with a PsA disease duration of only 3 years showed a prevalence of 38%, similar to the average prevalence overall. Another study showed a significantly higher prevalence of metabolic syndrome in patients with PsA and cutaneous psoriasis, compared with those without psoriasis (40.8% vs. 13.16%; P = .006).

The CARMA study included 724 patients with PsA; 45.4% were women and 21.8% were smokers. The mean age of the population in this study was 51 years, and the mean disease duration was 9 years. Overall, 222 patients (30.7%) met at least three criteria for metabolic syndrome, based on the NCEP ATP III definition. The most common abnormal findings for traditional cardiovascular risk factors in the CARMA cohort were high blood pressure (66.8%), hyperglycemia (42.6%), and hypertriglyceridemia (30.6%).

Despite the variation in prevalence of metabolic syndrome, depending on the definition used, the authors wrote, “It can be stated that the rate of [metabolic syndrome] in patients with PsA is in general very high, especially if we take into account the mean age of patients included in the studies.”

“These findings support the hypotheses that this increase in the inflammatory pathway in PsA may contribute a higher risk of cardiovascular events and [metabolic syndrome] in patients with PsA than patients with psoriasis alone, the risk being even higher in severe PsA,” and that insulin resistance, metabolic syndrome, and atherosclerotic events “may have a common inflammatory basis,” the researchers wrote in their discussion of the results.

The study findings were limited by several factors, most importantly the variation in definitions of metabolic syndrome in the literature review, which limits the generalizability of the results, the researchers said. Limitations of the CARMA study include the focus only on patients who were being cared for in hospitals, which might yield an overestimation of metabolic syndrome, they added.

However, the results support findings from previous studies and highlight the need for proper assessment of body weight and cardiovascular risk factors in patients with PsA at the onset of disease, they said.

“Furthermore, it is necessary to conduct more research to standardize (and modify as appropriate) the definition of [metabolic syndrome] and establish the best strategy for managing it in these patients,” they concluded.

The study was funded by an independent grant from UCB Pharma. One author disclosed receiving grants from Pfizer, Abbvie, Novartis, Roche, UCB, Sanofi, BMS, Lilly, MSD, and Janssen. Lead author Dr. Urruticoechea-Arana and the other authors had no disclosures.

The prevalence of metabolic syndrome varies according to how it is defined, but approximately 30% of psoriatic arthritis (PsA) patients met the criteria in a cohort study of 724 individuals, as did approximately 23%-63% of patients across multiple studies, investigators from Spain report.

Previous studies of people with PsA in particular suggest they are at an increased risk of cardiovascular disease and have a higher prevalence of metabolic syndrome, prompting recommendations on cardiovascular risk management for patients with PsA, wrote the authors, Ana Urruticoechea-Arana, MD, of the department of rheumatology, Hospital Can Misses, Ibiza, Spain, and colleagues.

However, assessing the prevalence of metabolic syndrome remains a challenge because the definition varies across studies, they noted.

For a more thorough assessment of the prevalence of metabolic syndrome in this population, the researchers conducted a study using two sources: a systematic literature review of 18 studies published up to March 2019, and data on patients with PsA enrolled in the CARMA (Spanish Cardiovascular in Rheumatology) project, a longitudinal cohort observational study of adults with inflammatory diseases in Spain. The findings were published March 1 in the Journal of Clinical Rheumatology.

The literature review included a total of a total of 2,452 patients with PsA, with a mean age between 42 and 59 years, and a mean disease duration ranging from 3 to 14 years.

The definitions of metabolic syndrome varied; the most common was the definition from the National Cholesterol Education Program (NECP ATP III). Other definitions used in the studies included those issued by the International Diabetes Federation, the World Health Organization, and the American Heart Association.

Across these studies, the rate of metabolic syndrome ranged from 23.5% to 62.9%. Prevalence was similar between men and women. One study that included patients with a PsA disease duration of only 3 years showed a prevalence of 38%, similar to the average prevalence overall. Another study showed a significantly higher prevalence of metabolic syndrome in patients with PsA and cutaneous psoriasis, compared with those without psoriasis (40.8% vs. 13.16%; P = .006).

The CARMA study included 724 patients with PsA; 45.4% were women and 21.8% were smokers. The mean age of the population in this study was 51 years, and the mean disease duration was 9 years. Overall, 222 patients (30.7%) met at least three criteria for metabolic syndrome, based on the NCEP ATP III definition. The most common abnormal findings for traditional cardiovascular risk factors in the CARMA cohort were high blood pressure (66.8%), hyperglycemia (42.6%), and hypertriglyceridemia (30.6%).

Despite the variation in prevalence of metabolic syndrome, depending on the definition used, the authors wrote, “It can be stated that the rate of [metabolic syndrome] in patients with PsA is in general very high, especially if we take into account the mean age of patients included in the studies.”

“These findings support the hypotheses that this increase in the inflammatory pathway in PsA may contribute a higher risk of cardiovascular events and [metabolic syndrome] in patients with PsA than patients with psoriasis alone, the risk being even higher in severe PsA,” and that insulin resistance, metabolic syndrome, and atherosclerotic events “may have a common inflammatory basis,” the researchers wrote in their discussion of the results.

The study findings were limited by several factors, most importantly the variation in definitions of metabolic syndrome in the literature review, which limits the generalizability of the results, the researchers said. Limitations of the CARMA study include the focus only on patients who were being cared for in hospitals, which might yield an overestimation of metabolic syndrome, they added.

However, the results support findings from previous studies and highlight the need for proper assessment of body weight and cardiovascular risk factors in patients with PsA at the onset of disease, they said.

“Furthermore, it is necessary to conduct more research to standardize (and modify as appropriate) the definition of [metabolic syndrome] and establish the best strategy for managing it in these patients,” they concluded.

The study was funded by an independent grant from UCB Pharma. One author disclosed receiving grants from Pfizer, Abbvie, Novartis, Roche, UCB, Sanofi, BMS, Lilly, MSD, and Janssen. Lead author Dr. Urruticoechea-Arana and the other authors had no disclosures.

“Living with diabetes is not smooth sailing…From the onset of the disease in a child or adolescent through all the days that follow, there is nothing ordinary about it,” according to Aide aux Jeunes Diabétiques (AJD), a French association providing support for children and adolescents with diabetes. What is the psychological impact of the disease on patients and their loved ones? When we look at the life of a person with diabetes, are there key stages that call for more focused attention?

Nadine Hoffmeister, a psychologist at AJD, offers support to patients with diabetes and their parents as they navigate and deal with in-patient treatment for the disease. She recently spoke with this news organization.

Q: Are psychological issues more prevalent in patients with type 1 diabetes (T1D) than in the general population?

Dr. Hoffmeister: Having a chronic disease is not something that should be viewed as automatically making the person more susceptible to psychological issues. When we think about kids with T1D, it’s important to keep in mind that the risk for depression and the risk for eating disorders are, in general, higher in adolescence.

Of course, it can’t be denied that having diabetes can make one more vulnerable to experiencing mental distress. Clearly, the risk for eating disorders is there, given the constant focus on managing one’s diet. And there’s a greater risk for depression, because life with diabetes can really be trying. That said, how much impact the disease has depends in large part on the environment, the monitoring, and the collaboration of everyone involved.
 

Q: Are there key stages in the life of patients with T1D that call for targeted psychological support? 

Dr. Hoffmeister: The thing about T1D is that it can affect anyone at any age – a small child, a teenager, a young adult. So, in that sense, all ‘firsts’ are key stages. They start, of course, with the first ‘first’: diagnosis. For children diagnosed at an early age, there’s the first day of nursery school or kindergarten, the first piece of birthday cake. Then we get to kids starting middle school and high school, places where they’re now left to their own devices. This is when, for the first time, they’ll have an opportunity to take a trip without their parents and siblings, to go to a party.

And then, there’s the first time using a particular treatment. For example, switching from injections to a pump requires not only an adjustment in terms of physically operating a new device, but a reorientation in terms of mentally settling into a new routine, a new way of administering medication, and so on. They have to learn how to get along with this machine that’s attached to them all the time. They have to view it as being a part of them, view it as a partner, a teammate, a friend. It’s not that easy.

Later on, one of the major stages is, of course, adolescence. Critical developments in the separation–individuation process are taking place. They start to feel the need to break free, to become autonomous, as they seek to fully come to terms with their disease.

Parents usually worry about this stage, adolescence. They’re scared that their child won’t be as vigilant, that they’ll be scatterbrained or careless when it comes to staying on top of all those things that need to be done to keep T1D under control. Most of the time, this stage goes better than they thought. Still, the fact remains that it’s difficult to find a happy medium between adolescence and diabetes. Indeed, there’s a bit of a paradox here. On the one hand, we have adolescence which, by definition, is a time of spontaneity, independence, of trying new things. On the other hand, we have diabetes and its limits and constraints, its care and treatment, day in and day out. We have to pay close attention to how the child navigates and makes their way through this stage of their life.

During adolescence, there’s also a heightened awareness and concern about how others look at you, see you – everywhere, not only in classrooms and hallways. If the way someone looks at them seems aggressive or intrusive, the child may start to feel scared. The risk then becomes that they’ll start feeling awkward or ashamed or embarrassed. We have to keep this in mind and help lead the child away from those feelings. Otherwise, they can end up with low self-esteem, they can start to withdraw.

It can sometimes get to the point where they choose to neglect their treatment so as to conform to the way others see them. Adults can easily lose sight of these kinds of things. So, it’s imperative that we talk to the child. If they’re having trouble following their treatment plan, maybe there’s something going on at school. So, let’s ask them: “How do you like your classes and teachers?” “How are you doing with your injections? Are you finding that they’re getting easier and easier to do?” And always keeping in mind the real possibility that the child may be feeling awkward, ashamed, embarrassed.
 

Q: Is enough being done to pick up on and address these children’s needs?

Dr. Hoffmeister: I think that these efforts are becoming more and more widespread. Still, there are disparities. When it comes to patients with chronic diseases, it’s not always easy to implement mental health care into the treatment plan. In some cases, there might not be a hospital nearby. And as we know, there are no spots available in medical and psychiatric centers. Of course, outside of hospital settings, we’re seeing the unfortunate situation of fewer and fewer middle schools and high schools having nurses on site.

And then, what options there are for getting support vary greatly from hospital to hospital. Some don’t have psychologists. Others have full schedules and not enough staff. That said, more and more teams are trying to set up regular appointments right from the time of diagnosis. This is a really good approach to take, even though the circumstances may not be ideal. After all, the person has just been told that they have diabetes; they’re not really in the best state of mind to have any kind of discussion.
 

Q: And so, it makes sense that AJD would offer the kind of mental health support that you’re now providing there.

Dr. Hoffmeister: Exactly. My position was created 4 years ago. I’m not at the hospital. I’m an external. The goal is to be able to offer this psychological support to everyone. I do consultations over the phone so that no matter where a person is in France, they’ll have access to this support. There’s great demand, and the requests are only increasing. I think this has to do with the fact that people are being diagnosed younger and younger. It’s a very complicated situation for the parents. No matter how young their child is, they want to get that support underway as soon as possible.

Q: You speak about the patients getting support. But doesn’t some kind of help have to be given to their parents and loved ones as well?

Dr. Hoffmeister: Yes. I’d say that 60% to 70% of the work I do at AJD is for parents. I also have some older adolescents and some younger kids whom I call to keep up with. But children aren’t very interested in discussing plans over the phone. For parents, the thing about diabetes is that they find themselves in these situations where their child is in the hospital for, say, a week, then is discharged, and all of a sudden, they find themselves at home as the ones in charge of their child’s treatment.

When it’s a little kid, the parents are the ones who are taking care of all the steps, the injections, the pumps. They’re dealing with the distress of a child going through episodes of nocturnal hypoglycemia. They’re experiencing varying degrees of anxiety in carrying out all of these responsibilities and, at the same time, the bond they have with their child is becoming stronger and stronger. So, there’s that anxiety. In this situation, parents may also feel a need for control. And they’re also feeling exhausted; the mental load of dealing with diabetes is very, very intense. To work through all this, many parents reach out for psychological support.

Then later on, when the child has gotten a little older, the parents find it difficult to get to the point of being able to just let go. But once the parents get to know their child better, get to know how their child experiences diabetes, they’ll get to that point. What they come to learn is that the child can take care of things, the child can feel what’s going on in their body, the child can be trusted.
 

Q: How can we help and support children with diabetes?

Dr. Hoffmeister: One of the most important things is to teach the child to come to terms with the disease and how it affects their body. In other words, the idea here is to adapt diabetes to one’s life, not the other way around. The goal is to not let diabetes take over.

When faced with standardized medical protocols, during a session with a psychologist, the child can talk about their life, give an idea of what a day in their life looks like. For example, the school cafeteria is a place where children get the opportunity to socialize and interact with their peers. We want to have that lunch period be as normal as possible for the child with diabetes. In some schools, lunchtime becomes a challenge. So, not seeing any other solution, mom stops working so the child can come home to eat. These are the kinds of situations where efforts to make the child feel included have failed. They’re tough to deal with, all around. And so this is why we do all we can to keep things as normal as possible for these children.
 

Q: What would you say is the one initiative out there that’s giving young patients with T1D the most help and support?

Dr. Hoffmeister: AJD offers stays at Care Management and Rehabilitation (SSR) sites. For kids and teenagers with diabetes, these places are like summer camps where every aspect of treatment is taken care of.

There’s a medical team monitoring their disease and a team of counselors always on hand. It’s a time when children may very well bring up things that are on their mind. All in all, the children have a safe and welcoming environment where treatment is provided and they can feel free to open up and talk.

If a problem crops up, I’m always on call to jump online. And throughout the stay, the medical team is keeping in touch to discuss the child’s care.

AJD is also an interdisciplinary association. We regularly organize practice exchange groups that bring together health care professionals and families from all over France. In this way, we’re able to collaborate and come up with resources, such as information packets and kits – for the newly diagnosed, for those starting intensive insulin therapy, and so on. These resources take into account medical protocols related to diabetes. They’re also designed with family life in mind. And having this set of resources works toward standardizing treatments.

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

“Living with diabetes is not smooth sailing…From the onset of the disease in a child or adolescent through all the days that follow, there is nothing ordinary about it,” according to Aide aux Jeunes Diabétiques (AJD), a French association providing support for children and adolescents with diabetes. What is the psychological impact of the disease on patients and their loved ones? When we look at the life of a person with diabetes, are there key stages that call for more focused attention?

Nadine Hoffmeister, a psychologist at AJD, offers support to patients with diabetes and their parents as they navigate and deal with in-patient treatment for the disease. She recently spoke with this news organization.

Q: Are psychological issues more prevalent in patients with type 1 diabetes (T1D) than in the general population?

Dr. Hoffmeister: Having a chronic disease is not something that should be viewed as automatically making the person more susceptible to psychological issues. When we think about kids with T1D, it’s important to keep in mind that the risk for depression and the risk for eating disorders are, in general, higher in adolescence.

Of course, it can’t be denied that having diabetes can make one more vulnerable to experiencing mental distress. Clearly, the risk for eating disorders is there, given the constant focus on managing one’s diet. And there’s a greater risk for depression, because life with diabetes can really be trying. That said, how much impact the disease has depends in large part on the environment, the monitoring, and the collaboration of everyone involved.
 

Q: Are there key stages in the life of patients with T1D that call for targeted psychological support? 

Dr. Hoffmeister: The thing about T1D is that it can affect anyone at any age – a small child, a teenager, a young adult. So, in that sense, all ‘firsts’ are key stages. They start, of course, with the first ‘first’: diagnosis. For children diagnosed at an early age, there’s the first day of nursery school or kindergarten, the first piece of birthday cake. Then we get to kids starting middle school and high school, places where they’re now left to their own devices. This is when, for the first time, they’ll have an opportunity to take a trip without their parents and siblings, to go to a party.

And then, there’s the first time using a particular treatment. For example, switching from injections to a pump requires not only an adjustment in terms of physically operating a new device, but a reorientation in terms of mentally settling into a new routine, a new way of administering medication, and so on. They have to learn how to get along with this machine that’s attached to them all the time. They have to view it as being a part of them, view it as a partner, a teammate, a friend. It’s not that easy.

Later on, one of the major stages is, of course, adolescence. Critical developments in the separation–individuation process are taking place. They start to feel the need to break free, to become autonomous, as they seek to fully come to terms with their disease.

Parents usually worry about this stage, adolescence. They’re scared that their child won’t be as vigilant, that they’ll be scatterbrained or careless when it comes to staying on top of all those things that need to be done to keep T1D under control. Most of the time, this stage goes better than they thought. Still, the fact remains that it’s difficult to find a happy medium between adolescence and diabetes. Indeed, there’s a bit of a paradox here. On the one hand, we have adolescence which, by definition, is a time of spontaneity, independence, of trying new things. On the other hand, we have diabetes and its limits and constraints, its care and treatment, day in and day out. We have to pay close attention to how the child navigates and makes their way through this stage of their life.

During adolescence, there’s also a heightened awareness and concern about how others look at you, see you – everywhere, not only in classrooms and hallways. If the way someone looks at them seems aggressive or intrusive, the child may start to feel scared. The risk then becomes that they’ll start feeling awkward or ashamed or embarrassed. We have to keep this in mind and help lead the child away from those feelings. Otherwise, they can end up with low self-esteem, they can start to withdraw.

It can sometimes get to the point where they choose to neglect their treatment so as to conform to the way others see them. Adults can easily lose sight of these kinds of things. So, it’s imperative that we talk to the child. If they’re having trouble following their treatment plan, maybe there’s something going on at school. So, let’s ask them: “How do you like your classes and teachers?” “How are you doing with your injections? Are you finding that they’re getting easier and easier to do?” And always keeping in mind the real possibility that the child may be feeling awkward, ashamed, embarrassed.
 

Q: Is enough being done to pick up on and address these children’s needs?

Dr. Hoffmeister: I think that these efforts are becoming more and more widespread. Still, there are disparities. When it comes to patients with chronic diseases, it’s not always easy to implement mental health care into the treatment plan. In some cases, there might not be a hospital nearby. And as we know, there are no spots available in medical and psychiatric centers. Of course, outside of hospital settings, we’re seeing the unfortunate situation of fewer and fewer middle schools and high schools having nurses on site.

And then, what options there are for getting support vary greatly from hospital to hospital. Some don’t have psychologists. Others have full schedules and not enough staff. That said, more and more teams are trying to set up regular appointments right from the time of diagnosis. This is a really good approach to take, even though the circumstances may not be ideal. After all, the person has just been told that they have diabetes; they’re not really in the best state of mind to have any kind of discussion.
 

Q: And so, it makes sense that AJD would offer the kind of mental health support that you’re now providing there.

Dr. Hoffmeister: Exactly. My position was created 4 years ago. I’m not at the hospital. I’m an external. The goal is to be able to offer this psychological support to everyone. I do consultations over the phone so that no matter where a person is in France, they’ll have access to this support. There’s great demand, and the requests are only increasing. I think this has to do with the fact that people are being diagnosed younger and younger. It’s a very complicated situation for the parents. No matter how young their child is, they want to get that support underway as soon as possible.

Q: You speak about the patients getting support. But doesn’t some kind of help have to be given to their parents and loved ones as well?

Dr. Hoffmeister: Yes. I’d say that 60% to 70% of the work I do at AJD is for parents. I also have some older adolescents and some younger kids whom I call to keep up with. But children aren’t very interested in discussing plans over the phone. For parents, the thing about diabetes is that they find themselves in these situations where their child is in the hospital for, say, a week, then is discharged, and all of a sudden, they find themselves at home as the ones in charge of their child’s treatment.

When it’s a little kid, the parents are the ones who are taking care of all the steps, the injections, the pumps. They’re dealing with the distress of a child going through episodes of nocturnal hypoglycemia. They’re experiencing varying degrees of anxiety in carrying out all of these responsibilities and, at the same time, the bond they have with their child is becoming stronger and stronger. So, there’s that anxiety. In this situation, parents may also feel a need for control. And they’re also feeling exhausted; the mental load of dealing with diabetes is very, very intense. To work through all this, many parents reach out for psychological support.

Then later on, when the child has gotten a little older, the parents find it difficult to get to the point of being able to just let go. But once the parents get to know their child better, get to know how their child experiences diabetes, they’ll get to that point. What they come to learn is that the child can take care of things, the child can feel what’s going on in their body, the child can be trusted.
 

Q: How can we help and support children with diabetes?

Dr. Hoffmeister: One of the most important things is to teach the child to come to terms with the disease and how it affects their body. In other words, the idea here is to adapt diabetes to one’s life, not the other way around. The goal is to not let diabetes take over.

When faced with standardized medical protocols, during a session with a psychologist, the child can talk about their life, give an idea of what a day in their life looks like. For example, the school cafeteria is a place where children get the opportunity to socialize and interact with their peers. We want to have that lunch period be as normal as possible for the child with diabetes. In some schools, lunchtime becomes a challenge. So, not seeing any other solution, mom stops working so the child can come home to eat. These are the kinds of situations where efforts to make the child feel included have failed. They’re tough to deal with, all around. And so this is why we do all we can to keep things as normal as possible for these children.
 

Q: What would you say is the one initiative out there that’s giving young patients with T1D the most help and support?

Dr. Hoffmeister: AJD offers stays at Care Management and Rehabilitation (SSR) sites. For kids and teenagers with diabetes, these places are like summer camps where every aspect of treatment is taken care of.

There’s a medical team monitoring their disease and a team of counselors always on hand. It’s a time when children may very well bring up things that are on their mind. All in all, the children have a safe and welcoming environment where treatment is provided and they can feel free to open up and talk.

If a problem crops up, I’m always on call to jump online. And throughout the stay, the medical team is keeping in touch to discuss the child’s care.

AJD is also an interdisciplinary association. We regularly organize practice exchange groups that bring together health care professionals and families from all over France. In this way, we’re able to collaborate and come up with resources, such as information packets and kits – for the newly diagnosed, for those starting intensive insulin therapy, and so on. These resources take into account medical protocols related to diabetes. They’re also designed with family life in mind. And having this set of resources works toward standardizing treatments.

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

“Living with diabetes is not smooth sailing…From the onset of the disease in a child or adolescent through all the days that follow, there is nothing ordinary about it,” according to Aide aux Jeunes Diabétiques (AJD), a French association providing support for children and adolescents with diabetes. What is the psychological impact of the disease on patients and their loved ones? When we look at the life of a person with diabetes, are there key stages that call for more focused attention?

Nadine Hoffmeister, a psychologist at AJD, offers support to patients with diabetes and their parents as they navigate and deal with in-patient treatment for the disease. She recently spoke with this news organization.

Q: Are psychological issues more prevalent in patients with type 1 diabetes (T1D) than in the general population?

Dr. Hoffmeister: Having a chronic disease is not something that should be viewed as automatically making the person more susceptible to psychological issues. When we think about kids with T1D, it’s important to keep in mind that the risk for depression and the risk for eating disorders are, in general, higher in adolescence.

Of course, it can’t be denied that having diabetes can make one more vulnerable to experiencing mental distress. Clearly, the risk for eating disorders is there, given the constant focus on managing one’s diet. And there’s a greater risk for depression, because life with diabetes can really be trying. That said, how much impact the disease has depends in large part on the environment, the monitoring, and the collaboration of everyone involved.
 

Q: Are there key stages in the life of patients with T1D that call for targeted psychological support? 

Dr. Hoffmeister: The thing about T1D is that it can affect anyone at any age – a small child, a teenager, a young adult. So, in that sense, all ‘firsts’ are key stages. They start, of course, with the first ‘first’: diagnosis. For children diagnosed at an early age, there’s the first day of nursery school or kindergarten, the first piece of birthday cake. Then we get to kids starting middle school and high school, places where they’re now left to their own devices. This is when, for the first time, they’ll have an opportunity to take a trip without their parents and siblings, to go to a party.

And then, there’s the first time using a particular treatment. For example, switching from injections to a pump requires not only an adjustment in terms of physically operating a new device, but a reorientation in terms of mentally settling into a new routine, a new way of administering medication, and so on. They have to learn how to get along with this machine that’s attached to them all the time. They have to view it as being a part of them, view it as a partner, a teammate, a friend. It’s not that easy.

Later on, one of the major stages is, of course, adolescence. Critical developments in the separation–individuation process are taking place. They start to feel the need to break free, to become autonomous, as they seek to fully come to terms with their disease.

Parents usually worry about this stage, adolescence. They’re scared that their child won’t be as vigilant, that they’ll be scatterbrained or careless when it comes to staying on top of all those things that need to be done to keep T1D under control. Most of the time, this stage goes better than they thought. Still, the fact remains that it’s difficult to find a happy medium between adolescence and diabetes. Indeed, there’s a bit of a paradox here. On the one hand, we have adolescence which, by definition, is a time of spontaneity, independence, of trying new things. On the other hand, we have diabetes and its limits and constraints, its care and treatment, day in and day out. We have to pay close attention to how the child navigates and makes their way through this stage of their life.

During adolescence, there’s also a heightened awareness and concern about how others look at you, see you – everywhere, not only in classrooms and hallways. If the way someone looks at them seems aggressive or intrusive, the child may start to feel scared. The risk then becomes that they’ll start feeling awkward or ashamed or embarrassed. We have to keep this in mind and help lead the child away from those feelings. Otherwise, they can end up with low self-esteem, they can start to withdraw.

It can sometimes get to the point where they choose to neglect their treatment so as to conform to the way others see them. Adults can easily lose sight of these kinds of things. So, it’s imperative that we talk to the child. If they’re having trouble following their treatment plan, maybe there’s something going on at school. So, let’s ask them: “How do you like your classes and teachers?” “How are you doing with your injections? Are you finding that they’re getting easier and easier to do?” And always keeping in mind the real possibility that the child may be feeling awkward, ashamed, embarrassed.
 

Q: Is enough being done to pick up on and address these children’s needs?

Dr. Hoffmeister: I think that these efforts are becoming more and more widespread. Still, there are disparities. When it comes to patients with chronic diseases, it’s not always easy to implement mental health care into the treatment plan. In some cases, there might not be a hospital nearby. And as we know, there are no spots available in medical and psychiatric centers. Of course, outside of hospital settings, we’re seeing the unfortunate situation of fewer and fewer middle schools and high schools having nurses on site.

And then, what options there are for getting support vary greatly from hospital to hospital. Some don’t have psychologists. Others have full schedules and not enough staff. That said, more and more teams are trying to set up regular appointments right from the time of diagnosis. This is a really good approach to take, even though the circumstances may not be ideal. After all, the person has just been told that they have diabetes; they’re not really in the best state of mind to have any kind of discussion.
 

Q: And so, it makes sense that AJD would offer the kind of mental health support that you’re now providing there.

Dr. Hoffmeister: Exactly. My position was created 4 years ago. I’m not at the hospital. I’m an external. The goal is to be able to offer this psychological support to everyone. I do consultations over the phone so that no matter where a person is in France, they’ll have access to this support. There’s great demand, and the requests are only increasing. I think this has to do with the fact that people are being diagnosed younger and younger. It’s a very complicated situation for the parents. No matter how young their child is, they want to get that support underway as soon as possible.

Q: You speak about the patients getting support. But doesn’t some kind of help have to be given to their parents and loved ones as well?

Dr. Hoffmeister: Yes. I’d say that 60% to 70% of the work I do at AJD is for parents. I also have some older adolescents and some younger kids whom I call to keep up with. But children aren’t very interested in discussing plans over the phone. For parents, the thing about diabetes is that they find themselves in these situations where their child is in the hospital for, say, a week, then is discharged, and all of a sudden, they find themselves at home as the ones in charge of their child’s treatment.

When it’s a little kid, the parents are the ones who are taking care of all the steps, the injections, the pumps. They’re dealing with the distress of a child going through episodes of nocturnal hypoglycemia. They’re experiencing varying degrees of anxiety in carrying out all of these responsibilities and, at the same time, the bond they have with their child is becoming stronger and stronger. So, there’s that anxiety. In this situation, parents may also feel a need for control. And they’re also feeling exhausted; the mental load of dealing with diabetes is very, very intense. To work through all this, many parents reach out for psychological support.

Then later on, when the child has gotten a little older, the parents find it difficult to get to the point of being able to just let go. But once the parents get to know their child better, get to know how their child experiences diabetes, they’ll get to that point. What they come to learn is that the child can take care of things, the child can feel what’s going on in their body, the child can be trusted.
 

Q: How can we help and support children with diabetes?

Dr. Hoffmeister: One of the most important things is to teach the child to come to terms with the disease and how it affects their body. In other words, the idea here is to adapt diabetes to one’s life, not the other way around. The goal is to not let diabetes take over.

When faced with standardized medical protocols, during a session with a psychologist, the child can talk about their life, give an idea of what a day in their life looks like. For example, the school cafeteria is a place where children get the opportunity to socialize and interact with their peers. We want to have that lunch period be as normal as possible for the child with diabetes. In some schools, lunchtime becomes a challenge. So, not seeing any other solution, mom stops working so the child can come home to eat. These are the kinds of situations where efforts to make the child feel included have failed. They’re tough to deal with, all around. And so this is why we do all we can to keep things as normal as possible for these children.
 

Q: What would you say is the one initiative out there that’s giving young patients with T1D the most help and support?

Dr. Hoffmeister: AJD offers stays at Care Management and Rehabilitation (SSR) sites. For kids and teenagers with diabetes, these places are like summer camps where every aspect of treatment is taken care of.

There’s a medical team monitoring their disease and a team of counselors always on hand. It’s a time when children may very well bring up things that are on their mind. All in all, the children have a safe and welcoming environment where treatment is provided and they can feel free to open up and talk.

If a problem crops up, I’m always on call to jump online. And throughout the stay, the medical team is keeping in touch to discuss the child’s care.

AJD is also an interdisciplinary association. We regularly organize practice exchange groups that bring together health care professionals and families from all over France. In this way, we’re able to collaborate and come up with resources, such as information packets and kits – for the newly diagnosed, for those starting intensive insulin therapy, and so on. These resources take into account medical protocols related to diabetes. They’re also designed with family life in mind. And having this set of resources works toward standardizing treatments.

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

Children who survive an episode of acute respiratory failure that requires invasive mechanical ventilation may be at risk for slightly lower long-term neurocognitive function, new research suggests.

Investigators found lower IQs in children without previous neurocognitive problems who survived pediatric intensive care unit admission for acute respiratory failure, compared with their biological siblings.

Although this magnitude of difference was small on average, more than twice as many patients as siblings had an IQ of ≤85, and children hospitalized at the youngest ages did worse than their siblings.

“Children surviving acute respiratory failure may benefit from routine evaluation of neurocognitive function after hospital discharge and may require serial evaluation to identify deficits that emerge over the course of child’s continued development to facilitate early intervention to prevent disability and optimize school performance,” study investigator R. Scott Watson, MD, MPH, professor of pediatrics, University of Washington, Seattle, told this news organization.

The study was published online March 1 in JAMA.
 

Unknown long-term effects

“Approximately 23,700 U.S. children undergo invasive mechanical ventilation for acute respiratory failure annually, with unknown long-term effects on neurocognitive function,” the authors write.

“With improvements in pediatric critical care over the past several decades, critical illness–associated mortality has improved dramatically [but] as survivorship has increased, we are starting to learn that many patients and their families suffer from long-term morbidity associated with the illness and its treatment,” said Dr. Watson, who is the associate division chief, pediatric critical care medicine, Seattle Children’s Hospital, Center for Child Health, Behavior, and Development.

Animal studies “have found that some sedative medications commonly used to keep children safe during mechanical ventilation may have detrimental neurologic effects, particularly in the developing brain,” Dr. Watson added.

To gain a better understanding of this potential association, the researchers turned to a subset of participants in the previously conducted Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) trial of pediatric patients receiving mechanical ventilation for acute respiratory failure.

For the current study (RESTORE-Cognition), multiple domains of neurocognitive function were assessed 3-8 years after hospital discharge in trial patients who did not have a history of neurocognitive dysfunction, as well as matched, healthy siblings.

To be included in the study, the children had to be ≤8 years old at trial enrollment, have a Pediatric Cerebral Performance Category (PCPC) score of 1 (normal) prior to PICU admission, and have no worse than moderate neurocognitive dysfunction at PICU discharge.

Siblings of enrolled patients were required to be between 4 and 16 years old at the time of neurocognitive testing, have a PCPC score of 1, have the same biological parents as the patient, and live with the patient.

The primary outcome was IQ, estimated by the age-appropriate Vocabulary and Block Design subtests of the Wechsler Intelligence Scale. Secondary outcomes included attention, processing speed, learning and memory, visuospatial skills, motor skills, language, and executive function. Enough time was allowed after hospitalization “for transient deficits to resolve and longer-lasting neurocognitive sequelae to manifest.”
 

‘Uncertain’ clinical importance

Of the 121 sibling pairs (67% non-Hispanic White, 47% from families in which one or both parents worked full-time), 116 were included in the primary outcome analysis, and 66-19 were included in analyses of secondary outcomes.

Patients had been in the PICU at a median (interquartile range [IQR]) age of 1.0 (0.2-3.2) years and had received a median of 5.5 (3.1-7.7) days of invasive mechanical ventilation.

The median age at testing for patients and matched siblings was 6.6 (5.4-9.1) and 8.4 (7.0-10.2) years, respectively. Interviews with parents and testing of patients were conducted a median (IQR) of 3.8 (3.2-5.2) and 5.2 (4.3-6.1) years, respectively, after hospitalization.

The most common etiologies of respiratory failure were bronchiolitis and asthma and pneumonia (44% and 37%, respectively). Beyond respiratory failure, most patients (72%) also had experienced multiple organ dysfunction syndrome.

Patients had a lower mean estimated IQ, compared with the matched siblings (101.5 vs. 104.3; mean difference, –2.8 [95% confidence interval, –5.4 to –0.2]), and more patients than siblings had an estimated IQ of ≤5 but not of ≤70.

Patients also had significantly lower scores on nonverbal memory, visuospatial skills, and fine motor control (mean differences, –0.9 [–1.6 to –0.3]; –0.9 [–1.8 to –.1]; and –-3.1 [–4.9 to –1.4], respectively), compared with matched siblings. They also had significantly higher scores on processing speed (mean difference, 4.4 [0.2-8.5]). There were no significant differences in the other secondary outcomes.

Differences in scores between patients and siblings varied significantly by age at hospitalization in several tests – for example, Block Design scores in patients were lower than those of siblings for patients hospitalized at <1 year old, versus those hospitalized between ages 4 and 8 years.

“When adjusting for patient age at PICU admission, patient age at testing, sibling age at testing, and duration between hospital discharge and testing, the difference in estimated IQ between patients and siblings remained statistically significantly different,” the authors note.

The investigators point out several limitations, including the fact that “little is known about sibling outcomes after critical illness, nor about whether parenting of siblings or child development differs based on birth order or on relationship between patient critical illness and the birth of siblings. ... If siblings also incur negative effects related to the critical illness, differences between critically ill children and the control siblings would be blunted.”

Despite the statistical significance of the difference between the patients and the matched controls, ultimately, the magnitude of the difference was “small and of uncertain clinical importance,” the authors conclude.
 

Filling a research gap

Commenting on the findings, Alexandre T. Rotta, MD, professor of pediatrics and chief of the division of pediatric critical care medicine, Duke University Medical Center, Durham, N.C., said the study “addresses an important yet vastly understudied gap: long-term neurocognitive morbidity in children exposed to critical care.”

Dr. Rotta, who is also a coauthor of an accompanying editorial, noted that the fact that the “vast majority of children with an IQ significantly lower than their siblings were under the age of 4 years suggests that the developing immature brain may be particularly susceptible to the effects of critical illness and therapies required to treat it.”

The study “underscores the need to include assessments of long-term morbidity as part of any future trial evaluating interventions in pediatric critical care,” he added.

The study was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development for RESTORE-Cognition and by grants for the RESTORE trial from the National Heart, Lung, and Blood Institute and the National Institute of Nursing Research, National Institutes of Health. Dr. Watson and coauthors report no relevant financial relationships. Dr. Rotta has received personal fees from Vapotherm for lecturing and development of educational materials and from Breas US for participation in a scientific advisory board, as well as royalties from Elsevier for editorial work outside the submitted work. His coauthor reports no relevant financial relationships.

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

Children who survive an episode of acute respiratory failure that requires invasive mechanical ventilation may be at risk for slightly lower long-term neurocognitive function, new research suggests.

Investigators found lower IQs in children without previous neurocognitive problems who survived pediatric intensive care unit admission for acute respiratory failure, compared with their biological siblings.

Although this magnitude of difference was small on average, more than twice as many patients as siblings had an IQ of ≤85, and children hospitalized at the youngest ages did worse than their siblings.

“Children surviving acute respiratory failure may benefit from routine evaluation of neurocognitive function after hospital discharge and may require serial evaluation to identify deficits that emerge over the course of child’s continued development to facilitate early intervention to prevent disability and optimize school performance,” study investigator R. Scott Watson, MD, MPH, professor of pediatrics, University of Washington, Seattle, told this news organization.

The study was published online March 1 in JAMA.
 

Unknown long-term effects

“Approximately 23,700 U.S. children undergo invasive mechanical ventilation for acute respiratory failure annually, with unknown long-term effects on neurocognitive function,” the authors write.

“With improvements in pediatric critical care over the past several decades, critical illness–associated mortality has improved dramatically [but] as survivorship has increased, we are starting to learn that many patients and their families suffer from long-term morbidity associated with the illness and its treatment,” said Dr. Watson, who is the associate division chief, pediatric critical care medicine, Seattle Children’s Hospital, Center for Child Health, Behavior, and Development.

Animal studies “have found that some sedative medications commonly used to keep children safe during mechanical ventilation may have detrimental neurologic effects, particularly in the developing brain,” Dr. Watson added.

To gain a better understanding of this potential association, the researchers turned to a subset of participants in the previously conducted Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) trial of pediatric patients receiving mechanical ventilation for acute respiratory failure.

For the current study (RESTORE-Cognition), multiple domains of neurocognitive function were assessed 3-8 years after hospital discharge in trial patients who did not have a history of neurocognitive dysfunction, as well as matched, healthy siblings.

To be included in the study, the children had to be ≤8 years old at trial enrollment, have a Pediatric Cerebral Performance Category (PCPC) score of 1 (normal) prior to PICU admission, and have no worse than moderate neurocognitive dysfunction at PICU discharge.

Siblings of enrolled patients were required to be between 4 and 16 years old at the time of neurocognitive testing, have a PCPC score of 1, have the same biological parents as the patient, and live with the patient.

The primary outcome was IQ, estimated by the age-appropriate Vocabulary and Block Design subtests of the Wechsler Intelligence Scale. Secondary outcomes included attention, processing speed, learning and memory, visuospatial skills, motor skills, language, and executive function. Enough time was allowed after hospitalization “for transient deficits to resolve and longer-lasting neurocognitive sequelae to manifest.”
 

‘Uncertain’ clinical importance

Of the 121 sibling pairs (67% non-Hispanic White, 47% from families in which one or both parents worked full-time), 116 were included in the primary outcome analysis, and 66-19 were included in analyses of secondary outcomes.

Patients had been in the PICU at a median (interquartile range [IQR]) age of 1.0 (0.2-3.2) years and had received a median of 5.5 (3.1-7.7) days of invasive mechanical ventilation.

The median age at testing for patients and matched siblings was 6.6 (5.4-9.1) and 8.4 (7.0-10.2) years, respectively. Interviews with parents and testing of patients were conducted a median (IQR) of 3.8 (3.2-5.2) and 5.2 (4.3-6.1) years, respectively, after hospitalization.

The most common etiologies of respiratory failure were bronchiolitis and asthma and pneumonia (44% and 37%, respectively). Beyond respiratory failure, most patients (72%) also had experienced multiple organ dysfunction syndrome.

Patients had a lower mean estimated IQ, compared with the matched siblings (101.5 vs. 104.3; mean difference, –2.8 [95% confidence interval, –5.4 to –0.2]), and more patients than siblings had an estimated IQ of ≤5 but not of ≤70.

Patients also had significantly lower scores on nonverbal memory, visuospatial skills, and fine motor control (mean differences, –0.9 [–1.6 to –0.3]; –0.9 [–1.8 to –.1]; and –-3.1 [–4.9 to –1.4], respectively), compared with matched siblings. They also had significantly higher scores on processing speed (mean difference, 4.4 [0.2-8.5]). There were no significant differences in the other secondary outcomes.

Differences in scores between patients and siblings varied significantly by age at hospitalization in several tests – for example, Block Design scores in patients were lower than those of siblings for patients hospitalized at <1 year old, versus those hospitalized between ages 4 and 8 years.

“When adjusting for patient age at PICU admission, patient age at testing, sibling age at testing, and duration between hospital discharge and testing, the difference in estimated IQ between patients and siblings remained statistically significantly different,” the authors note.

The investigators point out several limitations, including the fact that “little is known about sibling outcomes after critical illness, nor about whether parenting of siblings or child development differs based on birth order or on relationship between patient critical illness and the birth of siblings. ... If siblings also incur negative effects related to the critical illness, differences between critically ill children and the control siblings would be blunted.”

Despite the statistical significance of the difference between the patients and the matched controls, ultimately, the magnitude of the difference was “small and of uncertain clinical importance,” the authors conclude.
 

Filling a research gap

Commenting on the findings, Alexandre T. Rotta, MD, professor of pediatrics and chief of the division of pediatric critical care medicine, Duke University Medical Center, Durham, N.C., said the study “addresses an important yet vastly understudied gap: long-term neurocognitive morbidity in children exposed to critical care.”

Dr. Rotta, who is also a coauthor of an accompanying editorial, noted that the fact that the “vast majority of children with an IQ significantly lower than their siblings were under the age of 4 years suggests that the developing immature brain may be particularly susceptible to the effects of critical illness and therapies required to treat it.”

The study “underscores the need to include assessments of long-term morbidity as part of any future trial evaluating interventions in pediatric critical care,” he added.

The study was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development for RESTORE-Cognition and by grants for the RESTORE trial from the National Heart, Lung, and Blood Institute and the National Institute of Nursing Research, National Institutes of Health. Dr. Watson and coauthors report no relevant financial relationships. Dr. Rotta has received personal fees from Vapotherm for lecturing and development of educational materials and from Breas US for participation in a scientific advisory board, as well as royalties from Elsevier for editorial work outside the submitted work. His coauthor reports no relevant financial relationships.

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

Children who survive an episode of acute respiratory failure that requires invasive mechanical ventilation may be at risk for slightly lower long-term neurocognitive function, new research suggests.

Investigators found lower IQs in children without previous neurocognitive problems who survived pediatric intensive care unit admission for acute respiratory failure, compared with their biological siblings.

Although this magnitude of difference was small on average, more than twice as many patients as siblings had an IQ of ≤85, and children hospitalized at the youngest ages did worse than their siblings.

“Children surviving acute respiratory failure may benefit from routine evaluation of neurocognitive function after hospital discharge and may require serial evaluation to identify deficits that emerge over the course of child’s continued development to facilitate early intervention to prevent disability and optimize school performance,” study investigator R. Scott Watson, MD, MPH, professor of pediatrics, University of Washington, Seattle, told this news organization.

The study was published online March 1 in JAMA.
 

Unknown long-term effects

“Approximately 23,700 U.S. children undergo invasive mechanical ventilation for acute respiratory failure annually, with unknown long-term effects on neurocognitive function,” the authors write.

“With improvements in pediatric critical care over the past several decades, critical illness–associated mortality has improved dramatically [but] as survivorship has increased, we are starting to learn that many patients and their families suffer from long-term morbidity associated with the illness and its treatment,” said Dr. Watson, who is the associate division chief, pediatric critical care medicine, Seattle Children’s Hospital, Center for Child Health, Behavior, and Development.

Animal studies “have found that some sedative medications commonly used to keep children safe during mechanical ventilation may have detrimental neurologic effects, particularly in the developing brain,” Dr. Watson added.

To gain a better understanding of this potential association, the researchers turned to a subset of participants in the previously conducted Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) trial of pediatric patients receiving mechanical ventilation for acute respiratory failure.

For the current study (RESTORE-Cognition), multiple domains of neurocognitive function were assessed 3-8 years after hospital discharge in trial patients who did not have a history of neurocognitive dysfunction, as well as matched, healthy siblings.

To be included in the study, the children had to be ≤8 years old at trial enrollment, have a Pediatric Cerebral Performance Category (PCPC) score of 1 (normal) prior to PICU admission, and have no worse than moderate neurocognitive dysfunction at PICU discharge.

Siblings of enrolled patients were required to be between 4 and 16 years old at the time of neurocognitive testing, have a PCPC score of 1, have the same biological parents as the patient, and live with the patient.

The primary outcome was IQ, estimated by the age-appropriate Vocabulary and Block Design subtests of the Wechsler Intelligence Scale. Secondary outcomes included attention, processing speed, learning and memory, visuospatial skills, motor skills, language, and executive function. Enough time was allowed after hospitalization “for transient deficits to resolve and longer-lasting neurocognitive sequelae to manifest.”
 

‘Uncertain’ clinical importance

Of the 121 sibling pairs (67% non-Hispanic White, 47% from families in which one or both parents worked full-time), 116 were included in the primary outcome analysis, and 66-19 were included in analyses of secondary outcomes.

Patients had been in the PICU at a median (interquartile range [IQR]) age of 1.0 (0.2-3.2) years and had received a median of 5.5 (3.1-7.7) days of invasive mechanical ventilation.

The median age at testing for patients and matched siblings was 6.6 (5.4-9.1) and 8.4 (7.0-10.2) years, respectively. Interviews with parents and testing of patients were conducted a median (IQR) of 3.8 (3.2-5.2) and 5.2 (4.3-6.1) years, respectively, after hospitalization.

The most common etiologies of respiratory failure were bronchiolitis and asthma and pneumonia (44% and 37%, respectively). Beyond respiratory failure, most patients (72%) also had experienced multiple organ dysfunction syndrome.

Patients had a lower mean estimated IQ, compared with the matched siblings (101.5 vs. 104.3; mean difference, –2.8 [95% confidence interval, –5.4 to –0.2]), and more patients than siblings had an estimated IQ of ≤5 but not of ≤70.

Patients also had significantly lower scores on nonverbal memory, visuospatial skills, and fine motor control (mean differences, –0.9 [–1.6 to –0.3]; –0.9 [–1.8 to –.1]; and –-3.1 [–4.9 to –1.4], respectively), compared with matched siblings. They also had significantly higher scores on processing speed (mean difference, 4.4 [0.2-8.5]). There were no significant differences in the other secondary outcomes.

Differences in scores between patients and siblings varied significantly by age at hospitalization in several tests – for example, Block Design scores in patients were lower than those of siblings for patients hospitalized at <1 year old, versus those hospitalized between ages 4 and 8 years.

“When adjusting for patient age at PICU admission, patient age at testing, sibling age at testing, and duration between hospital discharge and testing, the difference in estimated IQ between patients and siblings remained statistically significantly different,” the authors note.

The investigators point out several limitations, including the fact that “little is known about sibling outcomes after critical illness, nor about whether parenting of siblings or child development differs based on birth order or on relationship between patient critical illness and the birth of siblings. ... If siblings also incur negative effects related to the critical illness, differences between critically ill children and the control siblings would be blunted.”

Despite the statistical significance of the difference between the patients and the matched controls, ultimately, the magnitude of the difference was “small and of uncertain clinical importance,” the authors conclude.
 

Filling a research gap

Commenting on the findings, Alexandre T. Rotta, MD, professor of pediatrics and chief of the division of pediatric critical care medicine, Duke University Medical Center, Durham, N.C., said the study “addresses an important yet vastly understudied gap: long-term neurocognitive morbidity in children exposed to critical care.”

Dr. Rotta, who is also a coauthor of an accompanying editorial, noted that the fact that the “vast majority of children with an IQ significantly lower than their siblings were under the age of 4 years suggests that the developing immature brain may be particularly susceptible to the effects of critical illness and therapies required to treat it.”

The study “underscores the need to include assessments of long-term morbidity as part of any future trial evaluating interventions in pediatric critical care,” he added.

The study was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development for RESTORE-Cognition and by grants for the RESTORE trial from the National Heart, Lung, and Blood Institute and the National Institute of Nursing Research, National Institutes of Health. Dr. Watson and coauthors report no relevant financial relationships. Dr. Rotta has received personal fees from Vapotherm for lecturing and development of educational materials and from Breas US for participation in a scientific advisory board, as well as royalties from Elsevier for editorial work outside the submitted work. His coauthor reports no relevant financial relationships.

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

The debate on whether the popular class of antihypertensive drugs, angiotensin receptor blockers (ARBs), may be associated with an increased risk for cancer has been reopened with the publication of a new meta-analysis.

The analysis found an increasing risk for cancer, and specifically lung cancer, with increasing cumulative exposure to these drugs.

The findings are reported in a study published online in PLOS ONE.

The author of this new meta-analysis is Ilke Sipahi, MD, a cardiologist from Acibadem University Medical School, Istanbul, who previously raised this issue in an initial meta-analysis published in 2010.

“The new meta-analysis is important because it is the first study to investigate whether there is a dose response in the association between ARBs and cancer,” Dr. Sipahi told this news organization.

“I found a clear signal of increased risk of cancer as exposure to ARBs increased, and the association started to become significant when the maximum dose was taken for 3 years,” he added.

Dr. Sipahi explained that in the first meta-analysis published in Lancet Oncology, he and his colleagues reported an increased cancer risk with ARBs based on observations from high-exposure trials – those that included higher doses of ARBs with a long duration of follow-up.

Following this publication, an investigation by the U.S. Food and Drug Administration refuted the risk, and a collaboration of ARB trial investigators also performed an analysis published in the Journal of Hypertension (2011. doi: 10.1097/HJH.0b013e328344a7de), which again did not show an increased risk for cancer with use of ARBs.

Dr. Sipahi claims that those analyses by the FDA and the ARB Trialists Collaboration, which were all trial-level meta-analyses, diluted the “high exposure” data (including higher doses taken for longer periods of time) with a large amount of other data on much lower exposures (lower doses and/or shorter time periods).

“The overall risk would then inevitably become nonsignificant. These analyses also did not look at different exposure levels,” he says.

“For cancer, the degree of exposure is obviously very important. The risk associated with smoking 2 or 3 cigarettes a day for a year is very different from that of smoking 2 packs a day for 40 years. The same principle applies to taking a medication,” Dr. Sipahi asserts.

From these latest data, he estimates that 120 patients needed to be treated with the maximal daily dose of an ARB for 4.7 years for one excess cancer diagnosis, and 464 patients needed to be treated for one excess lung cancer.

“Given that at least 200 million individuals are being treated with an ARB globally, approximately 1.7 million excess cancers (and 430,000 lung cancers) in 4.6 years could be potentially caused by this class of drugs,” he suggests.

For the current analysis, Dr. Sipahi used trial-level data taken from the paper by the ARB Trialists Collaboration and investigated the effect of exposure to ARBs – including both the dose taken and the length of treatment – on risk for cancer. He performed metaregression analyses that he says has not been done before.

“I mathematically quantitated the degree of exposure in each trial. And when the degree of exposure was correlated with risk of cancer, there was a significant association.”

The new meta-analysis includes 15 randomized controlled trials. The two coprimary outcomes were the relationship between cumulative exposure to ARBs and risk for all cancers combined and the relationship between cumulative exposure and risk for lung cancer.

In the trials, 74,021 patients were randomly assigned to an ARB, resulting in a total cumulative exposure of 172,389 person-years of exposure to daily high dose (or equivalent), and 61,197 patients were randomly assigned to control.

Results showed a highly significant correlation between the degree of cumulative exposure to ARBs and risk for all cancers combined (slope = 0.07; 95% confidence interval, 0.03-0.11; P < .001) and also lung cancer (slope = 0.16; 95% CI, 0.05-0.27; P = .003).

In trials where the cumulative exposure was greater than 3 years of exposure to daily high dose, there was a statistically significant increase in risk for all cancers combined (risk ratio, 1.11; 95% CI, 1.03-1.19; P = .006).

There was also a statistically significant increase in risk for lung cancers in trials where the cumulative exposure was greater than 2.5 years (RR, 1.21; 95% CI, 1.02-1.44; P = .03).

In trials with lower cumulative exposure to ARBs, there was no increased risk either for all cancers combined or lung cancer.

Dr. Sipahi reports that the cumulative exposure-risk relationship with ARBs was independent of background angiotensin-converting enzyme (ACE) inhibitor treatment or the type of control (placebo or nonplacebo control).

But he acknowledges that since this is a trial-level analysis, the effects of patient characteristics such as age and smoking status could not be examined because of lack of patient-level data.

Dr. Sipahi says he does not know the mechanism behind these findings, but he draws attention to the recent withdrawal of several thousand lots of ARB formulations because of the presence of potentially carcinogenic impurities that have been suggested to be a byproduct of ARB synthesis.

He also claims that unlike some other classes of antihypertensives, ARBs have not been shown to reduce the risk for MI, leading him to conclude that “other classes of antihypertensives with good safety and efficacy data (such as ACE-inhibitors, calcium-channel blockers or others) should become the preferred first-line agents in the treatment of hypertension.”

Dr. Sipahi wants the FDA to reinvestigate the issue of ARBs and cancer risk using individual patient data. “They already have the patient-level data from the trials. They should look at it more carefully and look at exposure levels and how they relate to cancer risk,” he said. “And the fact that there have been studies linking high ARB exposure levels to increased cancer risk should at least get a warning on the drug labels.”
 

A ‘clear increase’ in risk

Dr. Sipahi also points out that a link between ARBs and cancer has been found in another meta-analysis performed in 2013 by senior FDA analyst Thomas Marciniak, MD.

“Because he worked at the FDA, [Dr.] Marciniak had access to individual patent data. This is the best type of analysis and generally produces more accurate results than a trial-level meta-analysis,” Dr. Sipahi commented.

Dr. Marciniak’s analysis, which is available on the FDA website as part of another document, was not officially published elsewhere, and no further action has been taken on the issue.

Contacted by this news organization, Dr. Marciniak, who has now retired from the FDA, said he not only conducted a patient-level meta-analysis but also followed up adverse effects reported in the trials that could have been a symptom of cancer to establish further whether the patient was later diagnosed with cancer or not.

“I used every scrap of information sent in, including serious adverse event reports. I saw a clear increase in lung cancer risk with the ARBs,” Dr. Marciniak said. He did not, however, perform a dose-response relationship analysis.

Asked why his analysis and those from Dr. Sipahi reach different conclusions to those from the ARB Trialists Collaboration and the official FDA investigations, Dr. Marciniak said: “It may be that there were too many low-exposure trials that just washed out the difference. But trial data generally do not capture adverse events such as cancer, which takes a long time to develop, very well, and if you’re not really looking for it, you’re probably not going to find it.”

Dr. Marciniak said that Dr. Sipahi’s current findings are in line with his results. “Finding a dose response, to me, is extremely compelling, and I think the signal here is real,” he commented. “I think this new paper from Dr. Sipahi verifies what I found. I think the FDA should now release all individual patient data it has.”

Contacted for comment, an FDA spokesperson said, “Generally the FDA does not comment on specific studies but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”

They added: “The FDA has ongoing assessment, surveillance, compliance, and pharmaceutical quality efforts across every product area, and we will continue to work with drug manufacturers to ensure safe, effective, and high-quality drugs for the American public. When we identify new and previously unrecognized risks to safety and quality, we react swiftly to resolve the problem, as we have done in responding to the recent findings of nitrosamines in certain medicines.”
 

Analysis ‘should be taken seriously’

Commenting on this new study, Steve Nissen, MD, a key figure in analyzing such complex data and who has himself uncovered problems with high-profile drugs in the past, says the current analysis should be taken seriously. 

Dr. Nissen, who was Dr. Sipahi’s senior during his post-doc position at the Cleveland Clinic, wrote an editorial accompanying Dr. Sipahi’s first paper and calling for urgent regulatory review of the evidence.

He says the new findings add to previous evidence suggesting a possible risk for cancer with ARBs.

“[Dr.] Sipahi is a capable researcher, and this analysis needs to be taken seriously, but it needs to be verified. It is not possible to draw a strong conclusion on this analysis, as it is not based on individual patient data, but I don’t think it should be ignored,” Dr. Nissen stated.

“I will say again what I said 12 years ago – that the regulatory agencies need to carefully review all their data in a very detailed way. The FDA and EMA have access to the individual patient data and are both very capable of doing the required analyses.”
 

Limitations of trial-level analysis

Asked to evaluate the statistics in the current paper, Andrew Althouse, PhD, an assistant professor of medicine at the University of Pittsburgh, and a clinical trial statistician, explained that the best way to do a thorough analysis of the relationship between ARB exposure and risk for incident cancer would involve the use of patient-level data.

“As such data were not available to Dr. Sipahi, I believe he is doing as well as he can. But without full access to individual patient-level data from the respective trials, it is difficult to support any firm conclusions,” Dr. Althouse said in an interview.

He suggested that the meta-regression analyses used in the paper were unable to properly estimate the relationship between ARB exposure and risk for incident cancer. 

“Taken at face value, the current analysis suggests that [in] trials with longer follow-up duration (and therefore greater cumulative exposure to ARB for the treatment group), the risk of developing cancer for patients in the ARB group versus the non-ARB group was progressively higher. But this study doesn’t take into account the actual amount of follow-up time for individual patients or potential differences in the amount of follow-up time between the two groups in each trial,” he noted.

Dr. Althouse says this raises the possibility of “competing risks” or the idea that if ARBs reduce cardiovascular disease and cardiovascular death, then there would be more patients remaining in that arm who could go on to develop cancer. “So a crude count of the number of cancer cases may look as though patients receiving ARBs are ‘more likely’ to develop cancer, but this is a mirage.”

He added: “When there are some patients dying during the study, the only way to tell whether the intervention actually increased the risk of other health-related complications is to have an analysis that properly accounts for each patient’s time-at-risk of the outcome. Unfortunately, properly analyzing this requires the use of patient-level data.”
 

Cardiologists skeptical?

Cardiology experts asked for thoughts on the new meta-analysis were also cautious to read too much into the findings.

Franz Messerli, MD, professor of medicine at the University of Bern, Switzerland, commented: “Perhaps one would simply ignore this rambling, cherrypicking-based condemnation of ARBs if it were not for the powerful negative connotation of the word cancer. Thus, the meta-analysis of Dr. Sipahi purporting that ARBs could be increasing the development of cancers in a cumulative way is of concern to both physicians and patients.”

But, raising a similar point to Dr. Althouse about competing risks, Dr. Messerli said: “We have to consider that as one gets older, the cardiovascular disease state and cancer state will compete with each other for the outcome of death. The better that therapies protect against cardiovascular death, the more they will increase life expectancy and thus the risk of cancer.”

He also added that “in head-to-head comparisons with ACE inhibitors, ARBs showed similar efficacy in terms of death, CV mortality, MI, stroke, and end-stage kidney disease, so can we agree that the attempt of Dr. Sipahi to disparage ARBs as a class is much ado about nothing?”

Dr. Nissen, however, said he views the idea of competing risk as “a bit of a stretch” in this case. “Although ARBs are effective antihypertensive drugs, I would say there is very little evidence that they would prolong survival versus other antihypertensives.”

Dr. Sipahi also claims that this argument is not relevant to the current analysis. “ARBs did not increase survival in any of the high-exposure trials that showed an excess in cancers. Therefore, competing outcomes, or ‘survival bias’ to be more specific, is not a possibility here,” he says.

George Bakris, MD, professor of medicine at the University of Chicago Medicine, noted that while the current study shows a slight increase in cancer incidence, especially lung cancer, among those taking ARBs for more than 3 years, it “totally ignores the overwhelming cardiovascular risk reduction seen in the trials.”

“Moreover,” he adds, “the author notes that the findings were independent of ACE-inhibitors, but he can’t rule out smoking and age as factors, two major risk factors for cancer and lung cancer, specifically. Thus, as typical of these types of analyses, the associations are probably true/true unrelated or, at best, partially related.”

Dr. Bakris referred to the potentially carcinogenic nitrosamine and azido compounds found in several ARB formulations that have resulted in recalls.

“At any stage of drug synthesis throughout each product’s lifetime, these impurities may evolve if an amine reacts with a nitrosating agent coexisting under appropriate conditions,” he said. “Drug regulatory authorities worldwide have established stringent guidelines on nitrosamine contamination for all drug products. The studies noted in the author’s analysis were done well before these guidelines were implemented. Hence, many of the issues raised by the authors using trials from 10-20 years ago are not of significant concern.”

Still, the cardiology experts all agreed on one thing – that patients should continue to take ARBs as prescribed.  

Noting that worldwide authorities are now addressing the issue of possible carcinogen contamination, Dr. Bakris stressed that patients “should not panic and should not stop their meds.”

Dr. Nissen added: “What we don’t want is for patents who are taking ARBs to stop taking these medications – hypertension is a deadly disorder, and these drugs have proven cardiovascular benefits.”

Dr. Sipahi received no specific funding for this work. He reports receiving lecture honoraria from Novartis, Boehringer Ingelheim, Sanofi, Sandoz, Bristol-Myers Squibb, Bayer, Pfizer, Ranbaxy, Servier, and ARIS and served on advisory boards for Novartis, Sanofi, Servier, Bristol-Myers Squibb, Pfizer, Bayer and I.E. Ulagay. The other commenters do not report any relevant disclosures.

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

The debate on whether the popular class of antihypertensive drugs, angiotensin receptor blockers (ARBs), may be associated with an increased risk for cancer has been reopened with the publication of a new meta-analysis.

The analysis found an increasing risk for cancer, and specifically lung cancer, with increasing cumulative exposure to these drugs.

The findings are reported in a study published online in PLOS ONE.

The author of this new meta-analysis is Ilke Sipahi, MD, a cardiologist from Acibadem University Medical School, Istanbul, who previously raised this issue in an initial meta-analysis published in 2010.

“The new meta-analysis is important because it is the first study to investigate whether there is a dose response in the association between ARBs and cancer,” Dr. Sipahi told this news organization.

“I found a clear signal of increased risk of cancer as exposure to ARBs increased, and the association started to become significant when the maximum dose was taken for 3 years,” he added.

Dr. Sipahi explained that in the first meta-analysis published in Lancet Oncology, he and his colleagues reported an increased cancer risk with ARBs based on observations from high-exposure trials – those that included higher doses of ARBs with a long duration of follow-up.

Following this publication, an investigation by the U.S. Food and Drug Administration refuted the risk, and a collaboration of ARB trial investigators also performed an analysis published in the Journal of Hypertension (2011. doi: 10.1097/HJH.0b013e328344a7de), which again did not show an increased risk for cancer with use of ARBs.

Dr. Sipahi claims that those analyses by the FDA and the ARB Trialists Collaboration, which were all trial-level meta-analyses, diluted the “high exposure” data (including higher doses taken for longer periods of time) with a large amount of other data on much lower exposures (lower doses and/or shorter time periods).

“The overall risk would then inevitably become nonsignificant. These analyses also did not look at different exposure levels,” he says.

“For cancer, the degree of exposure is obviously very important. The risk associated with smoking 2 or 3 cigarettes a day for a year is very different from that of smoking 2 packs a day for 40 years. The same principle applies to taking a medication,” Dr. Sipahi asserts.

From these latest data, he estimates that 120 patients needed to be treated with the maximal daily dose of an ARB for 4.7 years for one excess cancer diagnosis, and 464 patients needed to be treated for one excess lung cancer.

“Given that at least 200 million individuals are being treated with an ARB globally, approximately 1.7 million excess cancers (and 430,000 lung cancers) in 4.6 years could be potentially caused by this class of drugs,” he suggests.

For the current analysis, Dr. Sipahi used trial-level data taken from the paper by the ARB Trialists Collaboration and investigated the effect of exposure to ARBs – including both the dose taken and the length of treatment – on risk for cancer. He performed metaregression analyses that he says has not been done before.

“I mathematically quantitated the degree of exposure in each trial. And when the degree of exposure was correlated with risk of cancer, there was a significant association.”

The new meta-analysis includes 15 randomized controlled trials. The two coprimary outcomes were the relationship between cumulative exposure to ARBs and risk for all cancers combined and the relationship between cumulative exposure and risk for lung cancer.

In the trials, 74,021 patients were randomly assigned to an ARB, resulting in a total cumulative exposure of 172,389 person-years of exposure to daily high dose (or equivalent), and 61,197 patients were randomly assigned to control.

Results showed a highly significant correlation between the degree of cumulative exposure to ARBs and risk for all cancers combined (slope = 0.07; 95% confidence interval, 0.03-0.11; P < .001) and also lung cancer (slope = 0.16; 95% CI, 0.05-0.27; P = .003).

In trials where the cumulative exposure was greater than 3 years of exposure to daily high dose, there was a statistically significant increase in risk for all cancers combined (risk ratio, 1.11; 95% CI, 1.03-1.19; P = .006).

There was also a statistically significant increase in risk for lung cancers in trials where the cumulative exposure was greater than 2.5 years (RR, 1.21; 95% CI, 1.02-1.44; P = .03).

In trials with lower cumulative exposure to ARBs, there was no increased risk either for all cancers combined or lung cancer.

Dr. Sipahi reports that the cumulative exposure-risk relationship with ARBs was independent of background angiotensin-converting enzyme (ACE) inhibitor treatment or the type of control (placebo or nonplacebo control).

But he acknowledges that since this is a trial-level analysis, the effects of patient characteristics such as age and smoking status could not be examined because of lack of patient-level data.

Dr. Sipahi says he does not know the mechanism behind these findings, but he draws attention to the recent withdrawal of several thousand lots of ARB formulations because of the presence of potentially carcinogenic impurities that have been suggested to be a byproduct of ARB synthesis.

He also claims that unlike some other classes of antihypertensives, ARBs have not been shown to reduce the risk for MI, leading him to conclude that “other classes of antihypertensives with good safety and efficacy data (such as ACE-inhibitors, calcium-channel blockers or others) should become the preferred first-line agents in the treatment of hypertension.”

Dr. Sipahi wants the FDA to reinvestigate the issue of ARBs and cancer risk using individual patient data. “They already have the patient-level data from the trials. They should look at it more carefully and look at exposure levels and how they relate to cancer risk,” he said. “And the fact that there have been studies linking high ARB exposure levels to increased cancer risk should at least get a warning on the drug labels.”
 

A ‘clear increase’ in risk

Dr. Sipahi also points out that a link between ARBs and cancer has been found in another meta-analysis performed in 2013 by senior FDA analyst Thomas Marciniak, MD.

“Because he worked at the FDA, [Dr.] Marciniak had access to individual patent data. This is the best type of analysis and generally produces more accurate results than a trial-level meta-analysis,” Dr. Sipahi commented.

Dr. Marciniak’s analysis, which is available on the FDA website as part of another document, was not officially published elsewhere, and no further action has been taken on the issue.

Contacted by this news organization, Dr. Marciniak, who has now retired from the FDA, said he not only conducted a patient-level meta-analysis but also followed up adverse effects reported in the trials that could have been a symptom of cancer to establish further whether the patient was later diagnosed with cancer or not.

“I used every scrap of information sent in, including serious adverse event reports. I saw a clear increase in lung cancer risk with the ARBs,” Dr. Marciniak said. He did not, however, perform a dose-response relationship analysis.

Asked why his analysis and those from Dr. Sipahi reach different conclusions to those from the ARB Trialists Collaboration and the official FDA investigations, Dr. Marciniak said: “It may be that there were too many low-exposure trials that just washed out the difference. But trial data generally do not capture adverse events such as cancer, which takes a long time to develop, very well, and if you’re not really looking for it, you’re probably not going to find it.”

Dr. Marciniak said that Dr. Sipahi’s current findings are in line with his results. “Finding a dose response, to me, is extremely compelling, and I think the signal here is real,” he commented. “I think this new paper from Dr. Sipahi verifies what I found. I think the FDA should now release all individual patient data it has.”

Contacted for comment, an FDA spokesperson said, “Generally the FDA does not comment on specific studies but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”

They added: “The FDA has ongoing assessment, surveillance, compliance, and pharmaceutical quality efforts across every product area, and we will continue to work with drug manufacturers to ensure safe, effective, and high-quality drugs for the American public. When we identify new and previously unrecognized risks to safety and quality, we react swiftly to resolve the problem, as we have done in responding to the recent findings of nitrosamines in certain medicines.”
 

Analysis ‘should be taken seriously’

Commenting on this new study, Steve Nissen, MD, a key figure in analyzing such complex data and who has himself uncovered problems with high-profile drugs in the past, says the current analysis should be taken seriously. 

Dr. Nissen, who was Dr. Sipahi’s senior during his post-doc position at the Cleveland Clinic, wrote an editorial accompanying Dr. Sipahi’s first paper and calling for urgent regulatory review of the evidence.

He says the new findings add to previous evidence suggesting a possible risk for cancer with ARBs.

“[Dr.] Sipahi is a capable researcher, and this analysis needs to be taken seriously, but it needs to be verified. It is not possible to draw a strong conclusion on this analysis, as it is not based on individual patient data, but I don’t think it should be ignored,” Dr. Nissen stated.

“I will say again what I said 12 years ago – that the regulatory agencies need to carefully review all their data in a very detailed way. The FDA and EMA have access to the individual patient data and are both very capable of doing the required analyses.”
 

Limitations of trial-level analysis

Asked to evaluate the statistics in the current paper, Andrew Althouse, PhD, an assistant professor of medicine at the University of Pittsburgh, and a clinical trial statistician, explained that the best way to do a thorough analysis of the relationship between ARB exposure and risk for incident cancer would involve the use of patient-level data.

“As such data were not available to Dr. Sipahi, I believe he is doing as well as he can. But without full access to individual patient-level data from the respective trials, it is difficult to support any firm conclusions,” Dr. Althouse said in an interview.

He suggested that the meta-regression analyses used in the paper were unable to properly estimate the relationship between ARB exposure and risk for incident cancer. 

“Taken at face value, the current analysis suggests that [in] trials with longer follow-up duration (and therefore greater cumulative exposure to ARB for the treatment group), the risk of developing cancer for patients in the ARB group versus the non-ARB group was progressively higher. But this study doesn’t take into account the actual amount of follow-up time for individual patients or potential differences in the amount of follow-up time between the two groups in each trial,” he noted.

Dr. Althouse says this raises the possibility of “competing risks” or the idea that if ARBs reduce cardiovascular disease and cardiovascular death, then there would be more patients remaining in that arm who could go on to develop cancer. “So a crude count of the number of cancer cases may look as though patients receiving ARBs are ‘more likely’ to develop cancer, but this is a mirage.”

He added: “When there are some patients dying during the study, the only way to tell whether the intervention actually increased the risk of other health-related complications is to have an analysis that properly accounts for each patient’s time-at-risk of the outcome. Unfortunately, properly analyzing this requires the use of patient-level data.”
 

Cardiologists skeptical?

Cardiology experts asked for thoughts on the new meta-analysis were also cautious to read too much into the findings.

Franz Messerli, MD, professor of medicine at the University of Bern, Switzerland, commented: “Perhaps one would simply ignore this rambling, cherrypicking-based condemnation of ARBs if it were not for the powerful negative connotation of the word cancer. Thus, the meta-analysis of Dr. Sipahi purporting that ARBs could be increasing the development of cancers in a cumulative way is of concern to both physicians and patients.”

But, raising a similar point to Dr. Althouse about competing risks, Dr. Messerli said: “We have to consider that as one gets older, the cardiovascular disease state and cancer state will compete with each other for the outcome of death. The better that therapies protect against cardiovascular death, the more they will increase life expectancy and thus the risk of cancer.”

He also added that “in head-to-head comparisons with ACE inhibitors, ARBs showed similar efficacy in terms of death, CV mortality, MI, stroke, and end-stage kidney disease, so can we agree that the attempt of Dr. Sipahi to disparage ARBs as a class is much ado about nothing?”

Dr. Nissen, however, said he views the idea of competing risk as “a bit of a stretch” in this case. “Although ARBs are effective antihypertensive drugs, I would say there is very little evidence that they would prolong survival versus other antihypertensives.”

Dr. Sipahi also claims that this argument is not relevant to the current analysis. “ARBs did not increase survival in any of the high-exposure trials that showed an excess in cancers. Therefore, competing outcomes, or ‘survival bias’ to be more specific, is not a possibility here,” he says.

George Bakris, MD, professor of medicine at the University of Chicago Medicine, noted that while the current study shows a slight increase in cancer incidence, especially lung cancer, among those taking ARBs for more than 3 years, it “totally ignores the overwhelming cardiovascular risk reduction seen in the trials.”

“Moreover,” he adds, “the author notes that the findings were independent of ACE-inhibitors, but he can’t rule out smoking and age as factors, two major risk factors for cancer and lung cancer, specifically. Thus, as typical of these types of analyses, the associations are probably true/true unrelated or, at best, partially related.”

Dr. Bakris referred to the potentially carcinogenic nitrosamine and azido compounds found in several ARB formulations that have resulted in recalls.

“At any stage of drug synthesis throughout each product’s lifetime, these impurities may evolve if an amine reacts with a nitrosating agent coexisting under appropriate conditions,” he said. “Drug regulatory authorities worldwide have established stringent guidelines on nitrosamine contamination for all drug products. The studies noted in the author’s analysis were done well before these guidelines were implemented. Hence, many of the issues raised by the authors using trials from 10-20 years ago are not of significant concern.”

Still, the cardiology experts all agreed on one thing – that patients should continue to take ARBs as prescribed.  

Noting that worldwide authorities are now addressing the issue of possible carcinogen contamination, Dr. Bakris stressed that patients “should not panic and should not stop their meds.”

Dr. Nissen added: “What we don’t want is for patents who are taking ARBs to stop taking these medications – hypertension is a deadly disorder, and these drugs have proven cardiovascular benefits.”

Dr. Sipahi received no specific funding for this work. He reports receiving lecture honoraria from Novartis, Boehringer Ingelheim, Sanofi, Sandoz, Bristol-Myers Squibb, Bayer, Pfizer, Ranbaxy, Servier, and ARIS and served on advisory boards for Novartis, Sanofi, Servier, Bristol-Myers Squibb, Pfizer, Bayer and I.E. Ulagay. The other commenters do not report any relevant disclosures.

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

The debate on whether the popular class of antihypertensive drugs, angiotensin receptor blockers (ARBs), may be associated with an increased risk for cancer has been reopened with the publication of a new meta-analysis.

The analysis found an increasing risk for cancer, and specifically lung cancer, with increasing cumulative exposure to these drugs.

The findings are reported in a study published online in PLOS ONE.

The author of this new meta-analysis is Ilke Sipahi, MD, a cardiologist from Acibadem University Medical School, Istanbul, who previously raised this issue in an initial meta-analysis published in 2010.

“The new meta-analysis is important because it is the first study to investigate whether there is a dose response in the association between ARBs and cancer,” Dr. Sipahi told this news organization.

“I found a clear signal of increased risk of cancer as exposure to ARBs increased, and the association started to become significant when the maximum dose was taken for 3 years,” he added.

Dr. Sipahi explained that in the first meta-analysis published in Lancet Oncology, he and his colleagues reported an increased cancer risk with ARBs based on observations from high-exposure trials – those that included higher doses of ARBs with a long duration of follow-up.

Following this publication, an investigation by the U.S. Food and Drug Administration refuted the risk, and a collaboration of ARB trial investigators also performed an analysis published in the Journal of Hypertension (2011. doi: 10.1097/HJH.0b013e328344a7de), which again did not show an increased risk for cancer with use of ARBs.

Dr. Sipahi claims that those analyses by the FDA and the ARB Trialists Collaboration, which were all trial-level meta-analyses, diluted the “high exposure” data (including higher doses taken for longer periods of time) with a large amount of other data on much lower exposures (lower doses and/or shorter time periods).

“The overall risk would then inevitably become nonsignificant. These analyses also did not look at different exposure levels,” he says.

“For cancer, the degree of exposure is obviously very important. The risk associated with smoking 2 or 3 cigarettes a day for a year is very different from that of smoking 2 packs a day for 40 years. The same principle applies to taking a medication,” Dr. Sipahi asserts.

From these latest data, he estimates that 120 patients needed to be treated with the maximal daily dose of an ARB for 4.7 years for one excess cancer diagnosis, and 464 patients needed to be treated for one excess lung cancer.

“Given that at least 200 million individuals are being treated with an ARB globally, approximately 1.7 million excess cancers (and 430,000 lung cancers) in 4.6 years could be potentially caused by this class of drugs,” he suggests.

For the current analysis, Dr. Sipahi used trial-level data taken from the paper by the ARB Trialists Collaboration and investigated the effect of exposure to ARBs – including both the dose taken and the length of treatment – on risk for cancer. He performed metaregression analyses that he says has not been done before.

“I mathematically quantitated the degree of exposure in each trial. And when the degree of exposure was correlated with risk of cancer, there was a significant association.”

The new meta-analysis includes 15 randomized controlled trials. The two coprimary outcomes were the relationship between cumulative exposure to ARBs and risk for all cancers combined and the relationship between cumulative exposure and risk for lung cancer.

In the trials, 74,021 patients were randomly assigned to an ARB, resulting in a total cumulative exposure of 172,389 person-years of exposure to daily high dose (or equivalent), and 61,197 patients were randomly assigned to control.

Results showed a highly significant correlation between the degree of cumulative exposure to ARBs and risk for all cancers combined (slope = 0.07; 95% confidence interval, 0.03-0.11; P < .001) and also lung cancer (slope = 0.16; 95% CI, 0.05-0.27; P = .003).

In trials where the cumulative exposure was greater than 3 years of exposure to daily high dose, there was a statistically significant increase in risk for all cancers combined (risk ratio, 1.11; 95% CI, 1.03-1.19; P = .006).

There was also a statistically significant increase in risk for lung cancers in trials where the cumulative exposure was greater than 2.5 years (RR, 1.21; 95% CI, 1.02-1.44; P = .03).

In trials with lower cumulative exposure to ARBs, there was no increased risk either for all cancers combined or lung cancer.

Dr. Sipahi reports that the cumulative exposure-risk relationship with ARBs was independent of background angiotensin-converting enzyme (ACE) inhibitor treatment or the type of control (placebo or nonplacebo control).

But he acknowledges that since this is a trial-level analysis, the effects of patient characteristics such as age and smoking status could not be examined because of lack of patient-level data.

Dr. Sipahi says he does not know the mechanism behind these findings, but he draws attention to the recent withdrawal of several thousand lots of ARB formulations because of the presence of potentially carcinogenic impurities that have been suggested to be a byproduct of ARB synthesis.

He also claims that unlike some other classes of antihypertensives, ARBs have not been shown to reduce the risk for MI, leading him to conclude that “other classes of antihypertensives with good safety and efficacy data (such as ACE-inhibitors, calcium-channel blockers or others) should become the preferred first-line agents in the treatment of hypertension.”

Dr. Sipahi wants the FDA to reinvestigate the issue of ARBs and cancer risk using individual patient data. “They already have the patient-level data from the trials. They should look at it more carefully and look at exposure levels and how they relate to cancer risk,” he said. “And the fact that there have been studies linking high ARB exposure levels to increased cancer risk should at least get a warning on the drug labels.”
 

A ‘clear increase’ in risk

Dr. Sipahi also points out that a link between ARBs and cancer has been found in another meta-analysis performed in 2013 by senior FDA analyst Thomas Marciniak, MD.

“Because he worked at the FDA, [Dr.] Marciniak had access to individual patent data. This is the best type of analysis and generally produces more accurate results than a trial-level meta-analysis,” Dr. Sipahi commented.

Dr. Marciniak’s analysis, which is available on the FDA website as part of another document, was not officially published elsewhere, and no further action has been taken on the issue.

Contacted by this news organization, Dr. Marciniak, who has now retired from the FDA, said he not only conducted a patient-level meta-analysis but also followed up adverse effects reported in the trials that could have been a symptom of cancer to establish further whether the patient was later diagnosed with cancer or not.

“I used every scrap of information sent in, including serious adverse event reports. I saw a clear increase in lung cancer risk with the ARBs,” Dr. Marciniak said. He did not, however, perform a dose-response relationship analysis.

Asked why his analysis and those from Dr. Sipahi reach different conclusions to those from the ARB Trialists Collaboration and the official FDA investigations, Dr. Marciniak said: “It may be that there were too many low-exposure trials that just washed out the difference. But trial data generally do not capture adverse events such as cancer, which takes a long time to develop, very well, and if you’re not really looking for it, you’re probably not going to find it.”

Dr. Marciniak said that Dr. Sipahi’s current findings are in line with his results. “Finding a dose response, to me, is extremely compelling, and I think the signal here is real,” he commented. “I think this new paper from Dr. Sipahi verifies what I found. I think the FDA should now release all individual patient data it has.”

Contacted for comment, an FDA spokesperson said, “Generally the FDA does not comment on specific studies but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”

They added: “The FDA has ongoing assessment, surveillance, compliance, and pharmaceutical quality efforts across every product area, and we will continue to work with drug manufacturers to ensure safe, effective, and high-quality drugs for the American public. When we identify new and previously unrecognized risks to safety and quality, we react swiftly to resolve the problem, as we have done in responding to the recent findings of nitrosamines in certain medicines.”
 

Analysis ‘should be taken seriously’

Commenting on this new study, Steve Nissen, MD, a key figure in analyzing such complex data and who has himself uncovered problems with high-profile drugs in the past, says the current analysis should be taken seriously. 

Dr. Nissen, who was Dr. Sipahi’s senior during his post-doc position at the Cleveland Clinic, wrote an editorial accompanying Dr. Sipahi’s first paper and calling for urgent regulatory review of the evidence.

He says the new findings add to previous evidence suggesting a possible risk for cancer with ARBs.

“[Dr.] Sipahi is a capable researcher, and this analysis needs to be taken seriously, but it needs to be verified. It is not possible to draw a strong conclusion on this analysis, as it is not based on individual patient data, but I don’t think it should be ignored,” Dr. Nissen stated.

“I will say again what I said 12 years ago – that the regulatory agencies need to carefully review all their data in a very detailed way. The FDA and EMA have access to the individual patient data and are both very capable of doing the required analyses.”
 

Limitations of trial-level analysis

Asked to evaluate the statistics in the current paper, Andrew Althouse, PhD, an assistant professor of medicine at the University of Pittsburgh, and a clinical trial statistician, explained that the best way to do a thorough analysis of the relationship between ARB exposure and risk for incident cancer would involve the use of patient-level data.

“As such data were not available to Dr. Sipahi, I believe he is doing as well as he can. But without full access to individual patient-level data from the respective trials, it is difficult to support any firm conclusions,” Dr. Althouse said in an interview.

He suggested that the meta-regression analyses used in the paper were unable to properly estimate the relationship between ARB exposure and risk for incident cancer. 

“Taken at face value, the current analysis suggests that [in] trials with longer follow-up duration (and therefore greater cumulative exposure to ARB for the treatment group), the risk of developing cancer for patients in the ARB group versus the non-ARB group was progressively higher. But this study doesn’t take into account the actual amount of follow-up time for individual patients or potential differences in the amount of follow-up time between the two groups in each trial,” he noted.

Dr. Althouse says this raises the possibility of “competing risks” or the idea that if ARBs reduce cardiovascular disease and cardiovascular death, then there would be more patients remaining in that arm who could go on to develop cancer. “So a crude count of the number of cancer cases may look as though patients receiving ARBs are ‘more likely’ to develop cancer, but this is a mirage.”

He added: “When there are some patients dying during the study, the only way to tell whether the intervention actually increased the risk of other health-related complications is to have an analysis that properly accounts for each patient’s time-at-risk of the outcome. Unfortunately, properly analyzing this requires the use of patient-level data.”
 

Cardiologists skeptical?

Cardiology experts asked for thoughts on the new meta-analysis were also cautious to read too much into the findings.

Franz Messerli, MD, professor of medicine at the University of Bern, Switzerland, commented: “Perhaps one would simply ignore this rambling, cherrypicking-based condemnation of ARBs if it were not for the powerful negative connotation of the word cancer. Thus, the meta-analysis of Dr. Sipahi purporting that ARBs could be increasing the development of cancers in a cumulative way is of concern to both physicians and patients.”

But, raising a similar point to Dr. Althouse about competing risks, Dr. Messerli said: “We have to consider that as one gets older, the cardiovascular disease state and cancer state will compete with each other for the outcome of death. The better that therapies protect against cardiovascular death, the more they will increase life expectancy and thus the risk of cancer.”

He also added that “in head-to-head comparisons with ACE inhibitors, ARBs showed similar efficacy in terms of death, CV mortality, MI, stroke, and end-stage kidney disease, so can we agree that the attempt of Dr. Sipahi to disparage ARBs as a class is much ado about nothing?”

Dr. Nissen, however, said he views the idea of competing risk as “a bit of a stretch” in this case. “Although ARBs are effective antihypertensive drugs, I would say there is very little evidence that they would prolong survival versus other antihypertensives.”

Dr. Sipahi also claims that this argument is not relevant to the current analysis. “ARBs did not increase survival in any of the high-exposure trials that showed an excess in cancers. Therefore, competing outcomes, or ‘survival bias’ to be more specific, is not a possibility here,” he says.

George Bakris, MD, professor of medicine at the University of Chicago Medicine, noted that while the current study shows a slight increase in cancer incidence, especially lung cancer, among those taking ARBs for more than 3 years, it “totally ignores the overwhelming cardiovascular risk reduction seen in the trials.”

“Moreover,” he adds, “the author notes that the findings were independent of ACE-inhibitors, but he can’t rule out smoking and age as factors, two major risk factors for cancer and lung cancer, specifically. Thus, as typical of these types of analyses, the associations are probably true/true unrelated or, at best, partially related.”

Dr. Bakris referred to the potentially carcinogenic nitrosamine and azido compounds found in several ARB formulations that have resulted in recalls.

“At any stage of drug synthesis throughout each product’s lifetime, these impurities may evolve if an amine reacts with a nitrosating agent coexisting under appropriate conditions,” he said. “Drug regulatory authorities worldwide have established stringent guidelines on nitrosamine contamination for all drug products. The studies noted in the author’s analysis were done well before these guidelines were implemented. Hence, many of the issues raised by the authors using trials from 10-20 years ago are not of significant concern.”

Still, the cardiology experts all agreed on one thing – that patients should continue to take ARBs as prescribed.  

Noting that worldwide authorities are now addressing the issue of possible carcinogen contamination, Dr. Bakris stressed that patients “should not panic and should not stop their meds.”

Dr. Nissen added: “What we don’t want is for patents who are taking ARBs to stop taking these medications – hypertension is a deadly disorder, and these drugs have proven cardiovascular benefits.”

Dr. Sipahi received no specific funding for this work. He reports receiving lecture honoraria from Novartis, Boehringer Ingelheim, Sanofi, Sandoz, Bristol-Myers Squibb, Bayer, Pfizer, Ranbaxy, Servier, and ARIS and served on advisory boards for Novartis, Sanofi, Servier, Bristol-Myers Squibb, Pfizer, Bayer and I.E. Ulagay. The other commenters do not report any relevant disclosures.

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