Mixed Topics

There is no safe amount of alcohol consumption for the brain; even moderate drinking adversely affects brain structure and function, according a British study of more 25,000 adults.

“This is one of the largest studies of alcohol and brain health to date,” Anya Topiwala, DPhil, University of Oxford (England), told this news organization.

“There have been previous claims the relationship between alcohol and brain health are J-shaped (ie., small amounts are protective), but we formally tested this and did not find it to be the case. In fact, we found that any level of alcohol was associated with poorer brain health, compared to no alcohol,” Dr. Topiwala added.

The study, which has not yet been peer reviewed, was published online May 12 in MedRxiv.
 

Global impact on the brain

Using the UK Biobank, the researchers evaluated brain health on the basis of structural and functional brain MRI measures in 25,378 adults. Participants provided detailed information on their alcohol intake. The cohort included 691 never-drinkers, 617 former drinkers, and 24,069 current drinkers.

Median alcohol intake was 13.5 units (102 g) weekly. Almost half of the sample (48.2%) were drinking above current UK low-risk guidelines (14 units, 112 g weekly), but few were heavy drinkers (>50 units, 400 g weekly).

After adjusting for all known potential confounders and multiple comparisons, a higher volume of alcohol consumed per week was associated with lower gray matter in “almost all areas of the brain,” Dr. Topiwala said in an interview.

Alcohol consumption accounted for up to 0.8% of gray matter volume variance. “The size of the effect is small, albeit greater than any other modifiable risk factor. These brain changes have been previously linked to aging, poorer performance on memory changes, and dementia,” Dr. Topiwala said.

Widespread negative associations were also found between drinking alcohol and all the measures of white matter integrity that were assessed. There was a significant positive association between alcohol consumption and resting-state functional connectivity.

Higher blood pressure and body mass index “steepened” the negative associations between alcohol and brain health, and binge drinking had additive negative effects on brain structure beyond the absolute volume consumed.

There was no evidence that the risk for alcohol-related brain harm differs according to the type of alcohol consumed (wine, beer, or spirits).

A key limitation of the study is that the study population from the UK Biobank represents a sample that is healthier, better educated, and less deprived and is characterized by less ethnic diversity than the general population. “As with any observational study, we cannot infer causality from association,” the authors note.

What remains unclear, they say, is the duration of drinking needed to cause an effect on the brain. It may be that vulnerability is increased during periods of life in which dynamic brain changes occur, such as adolescence and older age.

They also note that some studies of alcohol-dependent individuals have suggested that at least some brain damage is reversible upon abstinence. Whether that is true for moderate drinkers is unknown.

On the basis of their findings, there is “no safe dose of alcohol for the brain,” Dr. Topiwala and colleagues conclude. They suggest that current low-risk drinking guidelines be revisited to take account of brain effects.
 

Experts weigh in

Several experts weighed in on the study in a statement from the nonprofit UK Science Media Center.

Paul Matthews, MD, head of the department of brain sciences, Imperial College London, noted that this “carefully performed preliminary report extends our earlier UK Dementia Research Institute study of a smaller group from same UK Biobank population also showing that even moderate drinking is associated with greater atrophy of the brain, as well as injury to the heart and liver.”

Dr. Matthews said the investigators’ conclusion that there is no safe threshold below which alcohol consumption has no toxic effects “echoes our own. We join with them in suggesting that current public health guidelines concerning alcohol consumption may need to be revisited.”

Rebecca Dewey, PhD, research fellow in neuroimaging, University of Nottingham (England), cautioned that “the degree to which very small changes in brain volume are harmful” is unknown.

“While there was no threshold under which alcohol consumption did not cause changes in the brain, there may a degree of brain volume difference that is irrelevant to brain health. We don’t know what these people’s brains looked like before they drank alcohol, so the brain may have learned to cope/compensate,” Dewey said.

Sadie Boniface, PhD, head of research at the Institute of Alcohol Studies and visiting researcher at King’s College London, said, “While we can’t yet say for sure whether there is ‘no safe level’ of alcohol regarding brain health at the moment, it has been known for decades that heavy drinking is bad for brain health.

“We also shouldn’t forget alcohol affects all parts of the body and there are multiple health risks. For example, it is already known there is ‘no safe level’ of alcohol consumption for the seven types of cancer caused by alcohol, as identified by the UK chief medical officers,” Dr. Boniface said.

The study was supported in part by the Wellcome Trust, Li Ka Shing Center for Health Information and Discovery, the National Institutes of Health, and the UK Medical Research Council. Dr. Topiwala, Dr. Boniface, Dr. Dewey, and Dr. Matthews have disclosed no relevant financial relationships.

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

There is no safe amount of alcohol consumption for the brain; even moderate drinking adversely affects brain structure and function, according a British study of more 25,000 adults.

“This is one of the largest studies of alcohol and brain health to date,” Anya Topiwala, DPhil, University of Oxford (England), told this news organization.

“There have been previous claims the relationship between alcohol and brain health are J-shaped (ie., small amounts are protective), but we formally tested this and did not find it to be the case. In fact, we found that any level of alcohol was associated with poorer brain health, compared to no alcohol,” Dr. Topiwala added.

The study, which has not yet been peer reviewed, was published online May 12 in MedRxiv.
 

Global impact on the brain

Using the UK Biobank, the researchers evaluated brain health on the basis of structural and functional brain MRI measures in 25,378 adults. Participants provided detailed information on their alcohol intake. The cohort included 691 never-drinkers, 617 former drinkers, and 24,069 current drinkers.

Median alcohol intake was 13.5 units (102 g) weekly. Almost half of the sample (48.2%) were drinking above current UK low-risk guidelines (14 units, 112 g weekly), but few were heavy drinkers (>50 units, 400 g weekly).

After adjusting for all known potential confounders and multiple comparisons, a higher volume of alcohol consumed per week was associated with lower gray matter in “almost all areas of the brain,” Dr. Topiwala said in an interview.

Alcohol consumption accounted for up to 0.8% of gray matter volume variance. “The size of the effect is small, albeit greater than any other modifiable risk factor. These brain changes have been previously linked to aging, poorer performance on memory changes, and dementia,” Dr. Topiwala said.

Widespread negative associations were also found between drinking alcohol and all the measures of white matter integrity that were assessed. There was a significant positive association between alcohol consumption and resting-state functional connectivity.

Higher blood pressure and body mass index “steepened” the negative associations between alcohol and brain health, and binge drinking had additive negative effects on brain structure beyond the absolute volume consumed.

There was no evidence that the risk for alcohol-related brain harm differs according to the type of alcohol consumed (wine, beer, or spirits).

A key limitation of the study is that the study population from the UK Biobank represents a sample that is healthier, better educated, and less deprived and is characterized by less ethnic diversity than the general population. “As with any observational study, we cannot infer causality from association,” the authors note.

What remains unclear, they say, is the duration of drinking needed to cause an effect on the brain. It may be that vulnerability is increased during periods of life in which dynamic brain changes occur, such as adolescence and older age.

They also note that some studies of alcohol-dependent individuals have suggested that at least some brain damage is reversible upon abstinence. Whether that is true for moderate drinkers is unknown.

On the basis of their findings, there is “no safe dose of alcohol for the brain,” Dr. Topiwala and colleagues conclude. They suggest that current low-risk drinking guidelines be revisited to take account of brain effects.
 

Experts weigh in

Several experts weighed in on the study in a statement from the nonprofit UK Science Media Center.

Paul Matthews, MD, head of the department of brain sciences, Imperial College London, noted that this “carefully performed preliminary report extends our earlier UK Dementia Research Institute study of a smaller group from same UK Biobank population also showing that even moderate drinking is associated with greater atrophy of the brain, as well as injury to the heart and liver.”

Dr. Matthews said the investigators’ conclusion that there is no safe threshold below which alcohol consumption has no toxic effects “echoes our own. We join with them in suggesting that current public health guidelines concerning alcohol consumption may need to be revisited.”

Rebecca Dewey, PhD, research fellow in neuroimaging, University of Nottingham (England), cautioned that “the degree to which very small changes in brain volume are harmful” is unknown.

“While there was no threshold under which alcohol consumption did not cause changes in the brain, there may a degree of brain volume difference that is irrelevant to brain health. We don’t know what these people’s brains looked like before they drank alcohol, so the brain may have learned to cope/compensate,” Dewey said.

Sadie Boniface, PhD, head of research at the Institute of Alcohol Studies and visiting researcher at King’s College London, said, “While we can’t yet say for sure whether there is ‘no safe level’ of alcohol regarding brain health at the moment, it has been known for decades that heavy drinking is bad for brain health.

“We also shouldn’t forget alcohol affects all parts of the body and there are multiple health risks. For example, it is already known there is ‘no safe level’ of alcohol consumption for the seven types of cancer caused by alcohol, as identified by the UK chief medical officers,” Dr. Boniface said.

The study was supported in part by the Wellcome Trust, Li Ka Shing Center for Health Information and Discovery, the National Institutes of Health, and the UK Medical Research Council. Dr. Topiwala, Dr. Boniface, Dr. Dewey, and Dr. Matthews have disclosed no relevant financial relationships.

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

There is no safe amount of alcohol consumption for the brain; even moderate drinking adversely affects brain structure and function, according a British study of more 25,000 adults.

“This is one of the largest studies of alcohol and brain health to date,” Anya Topiwala, DPhil, University of Oxford (England), told this news organization.

“There have been previous claims the relationship between alcohol and brain health are J-shaped (ie., small amounts are protective), but we formally tested this and did not find it to be the case. In fact, we found that any level of alcohol was associated with poorer brain health, compared to no alcohol,” Dr. Topiwala added.

The study, which has not yet been peer reviewed, was published online May 12 in MedRxiv.
 

Global impact on the brain

Using the UK Biobank, the researchers evaluated brain health on the basis of structural and functional brain MRI measures in 25,378 adults. Participants provided detailed information on their alcohol intake. The cohort included 691 never-drinkers, 617 former drinkers, and 24,069 current drinkers.

Median alcohol intake was 13.5 units (102 g) weekly. Almost half of the sample (48.2%) were drinking above current UK low-risk guidelines (14 units, 112 g weekly), but few were heavy drinkers (>50 units, 400 g weekly).

After adjusting for all known potential confounders and multiple comparisons, a higher volume of alcohol consumed per week was associated with lower gray matter in “almost all areas of the brain,” Dr. Topiwala said in an interview.

Alcohol consumption accounted for up to 0.8% of gray matter volume variance. “The size of the effect is small, albeit greater than any other modifiable risk factor. These brain changes have been previously linked to aging, poorer performance on memory changes, and dementia,” Dr. Topiwala said.

Widespread negative associations were also found between drinking alcohol and all the measures of white matter integrity that were assessed. There was a significant positive association between alcohol consumption and resting-state functional connectivity.

Higher blood pressure and body mass index “steepened” the negative associations between alcohol and brain health, and binge drinking had additive negative effects on brain structure beyond the absolute volume consumed.

There was no evidence that the risk for alcohol-related brain harm differs according to the type of alcohol consumed (wine, beer, or spirits).

A key limitation of the study is that the study population from the UK Biobank represents a sample that is healthier, better educated, and less deprived and is characterized by less ethnic diversity than the general population. “As with any observational study, we cannot infer causality from association,” the authors note.

What remains unclear, they say, is the duration of drinking needed to cause an effect on the brain. It may be that vulnerability is increased during periods of life in which dynamic brain changes occur, such as adolescence and older age.

They also note that some studies of alcohol-dependent individuals have suggested that at least some brain damage is reversible upon abstinence. Whether that is true for moderate drinkers is unknown.

On the basis of their findings, there is “no safe dose of alcohol for the brain,” Dr. Topiwala and colleagues conclude. They suggest that current low-risk drinking guidelines be revisited to take account of brain effects.
 

Experts weigh in

Several experts weighed in on the study in a statement from the nonprofit UK Science Media Center.

Paul Matthews, MD, head of the department of brain sciences, Imperial College London, noted that this “carefully performed preliminary report extends our earlier UK Dementia Research Institute study of a smaller group from same UK Biobank population also showing that even moderate drinking is associated with greater atrophy of the brain, as well as injury to the heart and liver.”

Dr. Matthews said the investigators’ conclusion that there is no safe threshold below which alcohol consumption has no toxic effects “echoes our own. We join with them in suggesting that current public health guidelines concerning alcohol consumption may need to be revisited.”

Rebecca Dewey, PhD, research fellow in neuroimaging, University of Nottingham (England), cautioned that “the degree to which very small changes in brain volume are harmful” is unknown.

“While there was no threshold under which alcohol consumption did not cause changes in the brain, there may a degree of brain volume difference that is irrelevant to brain health. We don’t know what these people’s brains looked like before they drank alcohol, so the brain may have learned to cope/compensate,” Dewey said.

Sadie Boniface, PhD, head of research at the Institute of Alcohol Studies and visiting researcher at King’s College London, said, “While we can’t yet say for sure whether there is ‘no safe level’ of alcohol regarding brain health at the moment, it has been known for decades that heavy drinking is bad for brain health.

“We also shouldn’t forget alcohol affects all parts of the body and there are multiple health risks. For example, it is already known there is ‘no safe level’ of alcohol consumption for the seven types of cancer caused by alcohol, as identified by the UK chief medical officers,” Dr. Boniface said.

The study was supported in part by the Wellcome Trust, Li Ka Shing Center for Health Information and Discovery, the National Institutes of Health, and the UK Medical Research Council. Dr. Topiwala, Dr. Boniface, Dr. Dewey, and Dr. Matthews have disclosed no relevant financial relationships.

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

The benefits of COVID-19 vaccination “enormously outweigh” the rare possible risk for heart-related complications, including myocarditis, the American Heart Association/American Stroke Association (ASA) says in new statement.

The message follows a Centers for Disease Control and Prevention report that the agency is monitoring the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for cases of myocarditis that have been associated with the mRNA vaccines against SARS-CoV-2 from Pfizer and Moderna.

The “relatively few” reported cases myocarditis in adolescents or young adults have involved males more often than females, more often followed the second dose rather than the first, and were usually seen in the 4 days after vaccination, the CDC’s COVID-19 Vaccine Safety Technical Work Group (VaST) found.

“Most cases appear to be mild, and follow-up of cases is ongoing,” the CDC says. “Within CDC safety monitoring systems, rates of myocarditis reports in the window following COVID-19 vaccination have not differed from expected baseline rates.”

In their statement, the AHA/ASA “strongly urge” all adults and children 12 years and older to receive a COVID-19 vaccine as soon as possible.

“The evidence continues to indicate that the COVID-19 vaccines are nearly 100% effective at preventing death and hospitalization due to COVID-19 infection,” the groups say.

Although the investigation of cases of myocarditis related to COVID-19 vaccination is ongoing, the AHA/ASA notes that myocarditis is typically the result of an actual viral infection, “and it is yet to be determined if these cases have any correlation to receiving a COVID-19 vaccine.”

“We’ve lost hundreds of children, and there have been thousands who have been hospitalized, thousands who developed an inflammatory syndrome, and one of the pieces of that can be myocarditis,” Richard Besser, MD, president and CEO of the Robert Wood Johnson Foundation (RWJF), said today on ABC’s Good Morning America.

Still, “from my perspective, the risk of COVID is so much greater than any theoretical risk from the vaccine,” said Dr. Besser, former acting director of the CDC.

The symptoms that can occur after COVID-19 vaccination include tiredness, headache, muscle pain, chills, fever, and nausea, reminds the AHA/ASA statement. Such symptoms would “typically appear within 24-48 hours and usually pass within 36-48 hours after receiving the vaccine.”

All health care providers should be aware of the “very rare” adverse events that could be related to a COVID-19 vaccine, including myocarditis, blood clots, low platelets, and symptoms of severe inflammation, it says.

“Health care professionals should strongly consider inquiring about the timing of any recent COVID vaccination among patients presenting with these conditions, as needed, in order to provide appropriate treatment quickly,” the statement advises.

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

The benefits of COVID-19 vaccination “enormously outweigh” the rare possible risk for heart-related complications, including myocarditis, the American Heart Association/American Stroke Association (ASA) says in new statement.

The message follows a Centers for Disease Control and Prevention report that the agency is monitoring the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for cases of myocarditis that have been associated with the mRNA vaccines against SARS-CoV-2 from Pfizer and Moderna.

The “relatively few” reported cases myocarditis in adolescents or young adults have involved males more often than females, more often followed the second dose rather than the first, and were usually seen in the 4 days after vaccination, the CDC’s COVID-19 Vaccine Safety Technical Work Group (VaST) found.

“Most cases appear to be mild, and follow-up of cases is ongoing,” the CDC says. “Within CDC safety monitoring systems, rates of myocarditis reports in the window following COVID-19 vaccination have not differed from expected baseline rates.”

In their statement, the AHA/ASA “strongly urge” all adults and children 12 years and older to receive a COVID-19 vaccine as soon as possible.

“The evidence continues to indicate that the COVID-19 vaccines are nearly 100% effective at preventing death and hospitalization due to COVID-19 infection,” the groups say.

Although the investigation of cases of myocarditis related to COVID-19 vaccination is ongoing, the AHA/ASA notes that myocarditis is typically the result of an actual viral infection, “and it is yet to be determined if these cases have any correlation to receiving a COVID-19 vaccine.”

“We’ve lost hundreds of children, and there have been thousands who have been hospitalized, thousands who developed an inflammatory syndrome, and one of the pieces of that can be myocarditis,” Richard Besser, MD, president and CEO of the Robert Wood Johnson Foundation (RWJF), said today on ABC’s Good Morning America.

Still, “from my perspective, the risk of COVID is so much greater than any theoretical risk from the vaccine,” said Dr. Besser, former acting director of the CDC.

The symptoms that can occur after COVID-19 vaccination include tiredness, headache, muscle pain, chills, fever, and nausea, reminds the AHA/ASA statement. Such symptoms would “typically appear within 24-48 hours and usually pass within 36-48 hours after receiving the vaccine.”

All health care providers should be aware of the “very rare” adverse events that could be related to a COVID-19 vaccine, including myocarditis, blood clots, low platelets, and symptoms of severe inflammation, it says.

“Health care professionals should strongly consider inquiring about the timing of any recent COVID vaccination among patients presenting with these conditions, as needed, in order to provide appropriate treatment quickly,” the statement advises.

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

The benefits of COVID-19 vaccination “enormously outweigh” the rare possible risk for heart-related complications, including myocarditis, the American Heart Association/American Stroke Association (ASA) says in new statement.

The message follows a Centers for Disease Control and Prevention report that the agency is monitoring the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for cases of myocarditis that have been associated with the mRNA vaccines against SARS-CoV-2 from Pfizer and Moderna.

The “relatively few” reported cases myocarditis in adolescents or young adults have involved males more often than females, more often followed the second dose rather than the first, and were usually seen in the 4 days after vaccination, the CDC’s COVID-19 Vaccine Safety Technical Work Group (VaST) found.

“Most cases appear to be mild, and follow-up of cases is ongoing,” the CDC says. “Within CDC safety monitoring systems, rates of myocarditis reports in the window following COVID-19 vaccination have not differed from expected baseline rates.”

In their statement, the AHA/ASA “strongly urge” all adults and children 12 years and older to receive a COVID-19 vaccine as soon as possible.

“The evidence continues to indicate that the COVID-19 vaccines are nearly 100% effective at preventing death and hospitalization due to COVID-19 infection,” the groups say.

Although the investigation of cases of myocarditis related to COVID-19 vaccination is ongoing, the AHA/ASA notes that myocarditis is typically the result of an actual viral infection, “and it is yet to be determined if these cases have any correlation to receiving a COVID-19 vaccine.”

“We’ve lost hundreds of children, and there have been thousands who have been hospitalized, thousands who developed an inflammatory syndrome, and one of the pieces of that can be myocarditis,” Richard Besser, MD, president and CEO of the Robert Wood Johnson Foundation (RWJF), said today on ABC’s Good Morning America.

Still, “from my perspective, the risk of COVID is so much greater than any theoretical risk from the vaccine,” said Dr. Besser, former acting director of the CDC.

The symptoms that can occur after COVID-19 vaccination include tiredness, headache, muscle pain, chills, fever, and nausea, reminds the AHA/ASA statement. Such symptoms would “typically appear within 24-48 hours and usually pass within 36-48 hours after receiving the vaccine.”

All health care providers should be aware of the “very rare” adverse events that could be related to a COVID-19 vaccine, including myocarditis, blood clots, low platelets, and symptoms of severe inflammation, it says.

“Health care professionals should strongly consider inquiring about the timing of any recent COVID vaccination among patients presenting with these conditions, as needed, in order to provide appropriate treatment quickly,” the statement advises.

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

To the Editor:

Bullous pemphigoid (BP) is an autoimmune blistering disease that typically affects the elderly, with an incidence of approximately 7 new cases per million.¹ The pathogenesis of BP involves autoantibodies to BP antigens 180 and 230 at the dermoepidermal junction. Bullous pemphigoid has been associated with the use of multiple medications; vaccines; and physical damage to the skin, including trauma, radiation, and surgery.²

Several classes of medications may cause BP; one study described an association of BP with loop diuretics,³ while others found higher incidences of BP in patients taking aldosterone antagonists and neuroleptics.⁴ We describe a case of drug-triggered BP to liraglutide, a glucagonlike peptide 1 (GLP-1) receptor agonist.

A 75-year-old man presented to dermatology for evaluation of a vesicular eruption on the head, neck, trunk, and arms of 6 months’ duration. The eruption developed 2 weeks after starting liraglutide 1.2 mg subcutaneously daily for diabetes mellitus. The patient had a medical history of type 2 diabetes mellitus, hypertension, stroke, and prostate cancer treated with prostatectomy, and he also was taking insulin. Liraglutide was discontinued shortly after the onset of the eruption.

Physical examination revealed annular plaques on the head, neck, trunk, and arms with central hypopigmentation and hyperpigmented borders (Figure 1). Two tense bullae were evident on the left flank (Figure 2). Histopathology revealed a subepidermal blister, mixed perivascular infiltrate with numerous eosinophils, and pigment incontinence (Figure 3). Direct immunofluorescence showed linear deposition of IgG and C3 along the basement membrane zone that was localized to the roof of the blister on salt-split analysis. No microorganisms were identified on periodic acid–Schiff, Grocott-Gomori methenamine-silver, acid-fast bacilli, and Fite stains. The patient initially was treated with clobetasol ointment 0.05%, leading to marginal improvement. He declined treatment with prednisone or dapsone, and he was started on doxycycline. Seven months after stopping liraglutide and starting doxycycline, the patient had no blisters, but residual pigmentary changes remained.

Two types of BP have been described in response to medications: drug-induced BP and drug-triggered BP. Drug-induced BP presents as an acute, self-limited eruption that typically resolves after withdrawal of the offending agent. It tends to involve a younger population and may present with mucosal involvement and target lesions on the palms and soles. Direct immunofluorescence shows linear IgG and C3 deposition at the basement membrane zone. Patients tend to respond quickly to systemic corticosteroids and have low recurrence rates. Drug-triggered BP is a chronic form of BP that is caused by a medication and is not resolved with removal of the offending agent.⁵ Therefore, drug-triggered BP is more difficult to detect, especially in patients taking multiple medications.

Our patient represents a case of drug-triggered BP to liraglutide. Liraglutide is a GLP-1 receptor agonist that is US Food and Drug Administration approved for the treatment of type 2 diabetes mellitus. Glucagonlike peptide 1 is an incretin hormone that is secreted by the intestine during digestion. It binds to the GLP-1 receptor leading to an increase in glucose-dependent insulin secretion and a decrease in glucagon secretion.⁶ Glucagonlike peptide 1 agonists also affect the immune system; liraglutide has been shown to modestly improve psoriasis, reduce the number of dermal gamma delta T cells, and decrease IL-17 expression.⁷ Glucagonlike peptide 1 agonists also produce anti-inflammatory effects on multiple organs including the liver, brain, vasculature, kidney, and skin.⁸

Dipeptidyl peptidase 4 (DPP-4) inhibitors that function to inhibit the degradation of GLP-1 and other peptides also have been reported to cause BP. In several patients, the DPP-4 inhibitors vildagliptin and sitagliptin caused drug-induced BP that resolved with discontinuation of the medication.⁹ Dipeptidyl peptidase 4 is expressed in various organ systems including the skin, and inhibition of DPP-4 enhances eosinophil mobilization in the blood and recruitment to the skin in animal models.¹⁰

Although the pathogenesis of BP involves autoantibodies to BP antigens 180 and 230, these antibodies are not sufficient to cause disease, as antibasement antibodies have been detected in patients without clinically evident BP. These patients, however, may be more susceptible to developing medication-induced BP. Several hypotheses regarding the pathogenesis of medication-induced BP have been proposed, including immune dysregulation, molecular mimicry, and cross-reactivity to a prior sensitizing agent.⁵ Liraglutide and the DPP-4 inhibitors affect the immune system, supporting the hypothesis of immune dysregulation; however, the exact mechanism of how immune modulating medications such as GLP-1 agonists and DPP-4 inhibitors cause BP remains unclear.

The effects of liraglutide and the DPP-4 inhibitors on the immune system may play a role in the pathogenesis of drug-triggered BP and drug-induced BP, respectively. Additional studies of the immunomodulatory effects of GLP-1 agonists and DPP-4 inhibitors may help elucidate the pathogenesis of drug-triggered or drug-induced BP.

To the Editor:

Bullous pemphigoid (BP) is an autoimmune blistering disease that typically affects the elderly, with an incidence of approximately 7 new cases per million.¹ The pathogenesis of BP involves autoantibodies to BP antigens 180 and 230 at the dermoepidermal junction. Bullous pemphigoid has been associated with the use of multiple medications; vaccines; and physical damage to the skin, including trauma, radiation, and surgery.²

Several classes of medications may cause BP; one study described an association of BP with loop diuretics,³ while others found higher incidences of BP in patients taking aldosterone antagonists and neuroleptics.⁴ We describe a case of drug-triggered BP to liraglutide, a glucagonlike peptide 1 (GLP-1) receptor agonist.

A 75-year-old man presented to dermatology for evaluation of a vesicular eruption on the head, neck, trunk, and arms of 6 months’ duration. The eruption developed 2 weeks after starting liraglutide 1.2 mg subcutaneously daily for diabetes mellitus. The patient had a medical history of type 2 diabetes mellitus, hypertension, stroke, and prostate cancer treated with prostatectomy, and he also was taking insulin. Liraglutide was discontinued shortly after the onset of the eruption.

Physical examination revealed annular plaques on the head, neck, trunk, and arms with central hypopigmentation and hyperpigmented borders (Figure 1). Two tense bullae were evident on the left flank (Figure 2). Histopathology revealed a subepidermal blister, mixed perivascular infiltrate with numerous eosinophils, and pigment incontinence (Figure 3). Direct immunofluorescence showed linear deposition of IgG and C3 along the basement membrane zone that was localized to the roof of the blister on salt-split analysis. No microorganisms were identified on periodic acid–Schiff, Grocott-Gomori methenamine-silver, acid-fast bacilli, and Fite stains. The patient initially was treated with clobetasol ointment 0.05%, leading to marginal improvement. He declined treatment with prednisone or dapsone, and he was started on doxycycline. Seven months after stopping liraglutide and starting doxycycline, the patient had no blisters, but residual pigmentary changes remained.

Two types of BP have been described in response to medications: drug-induced BP and drug-triggered BP. Drug-induced BP presents as an acute, self-limited eruption that typically resolves after withdrawal of the offending agent. It tends to involve a younger population and may present with mucosal involvement and target lesions on the palms and soles. Direct immunofluorescence shows linear IgG and C3 deposition at the basement membrane zone. Patients tend to respond quickly to systemic corticosteroids and have low recurrence rates. Drug-triggered BP is a chronic form of BP that is caused by a medication and is not resolved with removal of the offending agent.⁵ Therefore, drug-triggered BP is more difficult to detect, especially in patients taking multiple medications.

Our patient represents a case of drug-triggered BP to liraglutide. Liraglutide is a GLP-1 receptor agonist that is US Food and Drug Administration approved for the treatment of type 2 diabetes mellitus. Glucagonlike peptide 1 is an incretin hormone that is secreted by the intestine during digestion. It binds to the GLP-1 receptor leading to an increase in glucose-dependent insulin secretion and a decrease in glucagon secretion.⁶ Glucagonlike peptide 1 agonists also affect the immune system; liraglutide has been shown to modestly improve psoriasis, reduce the number of dermal gamma delta T cells, and decrease IL-17 expression.⁷ Glucagonlike peptide 1 agonists also produce anti-inflammatory effects on multiple organs including the liver, brain, vasculature, kidney, and skin.⁸

Dipeptidyl peptidase 4 (DPP-4) inhibitors that function to inhibit the degradation of GLP-1 and other peptides also have been reported to cause BP. In several patients, the DPP-4 inhibitors vildagliptin and sitagliptin caused drug-induced BP that resolved with discontinuation of the medication.⁹ Dipeptidyl peptidase 4 is expressed in various organ systems including the skin, and inhibition of DPP-4 enhances eosinophil mobilization in the blood and recruitment to the skin in animal models.¹⁰

Although the pathogenesis of BP involves autoantibodies to BP antigens 180 and 230, these antibodies are not sufficient to cause disease, as antibasement antibodies have been detected in patients without clinically evident BP. These patients, however, may be more susceptible to developing medication-induced BP. Several hypotheses regarding the pathogenesis of medication-induced BP have been proposed, including immune dysregulation, molecular mimicry, and cross-reactivity to a prior sensitizing agent.⁵ Liraglutide and the DPP-4 inhibitors affect the immune system, supporting the hypothesis of immune dysregulation; however, the exact mechanism of how immune modulating medications such as GLP-1 agonists and DPP-4 inhibitors cause BP remains unclear.

The effects of liraglutide and the DPP-4 inhibitors on the immune system may play a role in the pathogenesis of drug-triggered BP and drug-induced BP, respectively. Additional studies of the immunomodulatory effects of GLP-1 agonists and DPP-4 inhibitors may help elucidate the pathogenesis of drug-triggered or drug-induced BP.

To the Editor:

Bullous pemphigoid (BP) is an autoimmune blistering disease that typically affects the elderly, with an incidence of approximately 7 new cases per million.¹ The pathogenesis of BP involves autoantibodies to BP antigens 180 and 230 at the dermoepidermal junction. Bullous pemphigoid has been associated with the use of multiple medications; vaccines; and physical damage to the skin, including trauma, radiation, and surgery.²

Several classes of medications may cause BP; one study described an association of BP with loop diuretics,³ while others found higher incidences of BP in patients taking aldosterone antagonists and neuroleptics.⁴ We describe a case of drug-triggered BP to liraglutide, a glucagonlike peptide 1 (GLP-1) receptor agonist.

A 75-year-old man presented to dermatology for evaluation of a vesicular eruption on the head, neck, trunk, and arms of 6 months’ duration. The eruption developed 2 weeks after starting liraglutide 1.2 mg subcutaneously daily for diabetes mellitus. The patient had a medical history of type 2 diabetes mellitus, hypertension, stroke, and prostate cancer treated with prostatectomy, and he also was taking insulin. Liraglutide was discontinued shortly after the onset of the eruption.

Physical examination revealed annular plaques on the head, neck, trunk, and arms with central hypopigmentation and hyperpigmented borders (Figure 1). Two tense bullae were evident on the left flank (Figure 2). Histopathology revealed a subepidermal blister, mixed perivascular infiltrate with numerous eosinophils, and pigment incontinence (Figure 3). Direct immunofluorescence showed linear deposition of IgG and C3 along the basement membrane zone that was localized to the roof of the blister on salt-split analysis. No microorganisms were identified on periodic acid–Schiff, Grocott-Gomori methenamine-silver, acid-fast bacilli, and Fite stains. The patient initially was treated with clobetasol ointment 0.05%, leading to marginal improvement. He declined treatment with prednisone or dapsone, and he was started on doxycycline. Seven months after stopping liraglutide and starting doxycycline, the patient had no blisters, but residual pigmentary changes remained.

Two types of BP have been described in response to medications: drug-induced BP and drug-triggered BP. Drug-induced BP presents as an acute, self-limited eruption that typically resolves after withdrawal of the offending agent. It tends to involve a younger population and may present with mucosal involvement and target lesions on the palms and soles. Direct immunofluorescence shows linear IgG and C3 deposition at the basement membrane zone. Patients tend to respond quickly to systemic corticosteroids and have low recurrence rates. Drug-triggered BP is a chronic form of BP that is caused by a medication and is not resolved with removal of the offending agent.⁵ Therefore, drug-triggered BP is more difficult to detect, especially in patients taking multiple medications.

Our patient represents a case of drug-triggered BP to liraglutide. Liraglutide is a GLP-1 receptor agonist that is US Food and Drug Administration approved for the treatment of type 2 diabetes mellitus. Glucagonlike peptide 1 is an incretin hormone that is secreted by the intestine during digestion. It binds to the GLP-1 receptor leading to an increase in glucose-dependent insulin secretion and a decrease in glucagon secretion.⁶ Glucagonlike peptide 1 agonists also affect the immune system; liraglutide has been shown to modestly improve psoriasis, reduce the number of dermal gamma delta T cells, and decrease IL-17 expression.⁷ Glucagonlike peptide 1 agonists also produce anti-inflammatory effects on multiple organs including the liver, brain, vasculature, kidney, and skin.⁸

Dipeptidyl peptidase 4 (DPP-4) inhibitors that function to inhibit the degradation of GLP-1 and other peptides also have been reported to cause BP. In several patients, the DPP-4 inhibitors vildagliptin and sitagliptin caused drug-induced BP that resolved with discontinuation of the medication.⁹ Dipeptidyl peptidase 4 is expressed in various organ systems including the skin, and inhibition of DPP-4 enhances eosinophil mobilization in the blood and recruitment to the skin in animal models.¹⁰

Although the pathogenesis of BP involves autoantibodies to BP antigens 180 and 230, these antibodies are not sufficient to cause disease, as antibasement antibodies have been detected in patients without clinically evident BP. These patients, however, may be more susceptible to developing medication-induced BP. Several hypotheses regarding the pathogenesis of medication-induced BP have been proposed, including immune dysregulation, molecular mimicry, and cross-reactivity to a prior sensitizing agent.⁵ Liraglutide and the DPP-4 inhibitors affect the immune system, supporting the hypothesis of immune dysregulation; however, the exact mechanism of how immune modulating medications such as GLP-1 agonists and DPP-4 inhibitors cause BP remains unclear.

The effects of liraglutide and the DPP-4 inhibitors on the immune system may play a role in the pathogenesis of drug-triggered BP and drug-induced BP, respectively. Additional studies of the immunomodulatory effects of GLP-1 agonists and DPP-4 inhibitors may help elucidate the pathogenesis of drug-triggered or drug-induced BP.

Physicians’ trust in health care system leaders has taken a steep drop during the COVID-19 pandemic, according to a survey conducted by NORC at the University of Chicago on behalf of the American Board of Internal Medicine Foundation.

Survey results, released May 21, indicate that 30% of physicians say their trust in the U.S. health care system and health care leadership has decreased during the pandemic. Only 18% reported an increase in trust.

Physicians, however, have great trust in their fellow clinicians.

In the survey of 600 physicians, 94% said they trust doctors within their practice; 85% trusted doctors outside of their practice; and 89% trusted nurses. That trust increased during the pandemic, with 41% saying their trust in fellow physicians rose and 37% saying their trust in nurses did.

In a separate survey, NORC asked patients about their trust in various aspects of health care. Among 2,069 respondents, a wide majority reported that they trust doctors (84%) and nurses (85%), but only 64% trusted the health care system as a whole. One in three consumers (32%) said their trust in the health care system decreased during the pandemic, compared with 11% who said their trust increased.

The ABIM Foundation released the research findings on May 21 as part of Building Trust, a national campaign that aims to boost trust among patients, clinicians, system leaders, researchers, and others.

Richard J. Baron, MD, president and chief executive officer of the ABIM Foundation, said in an interview, “Clearly there’s lower trust in health care organization leaders and executives, and that’s troubling.

“Science by itself is not enough,” he said. “Becoming trustworthy has to be a core project of everybody in health care.”

Deterioration in physicians’ trust during the pandemic comes in part from failed promises of adequate personal protective equipment and some physicians’ loss of income as a result of the crisis, Dr. Baron said.

He added that the vaccine rollout was very uneven and that policies as to which elective procedures could be performed were handled differently in different parts of the country.

He also noted that, early on, transparency was lacking as to how many COVID patients hospitals were treating, which may have contributed to the decrease in trust in the system.
 

Fear of being known as ‘the COVID hospital’

Hospitals were afraid of being known as “the COVID hospital” and losing patients who were afraid to come there, Dr. Baron said.

He said the COVID-19 epidemic exacerbated problems regarding trust, but that trust has been declining for some time. The Building Trust campaign will focus on solutions in breaches of trust as physicians move increasingly toward being employees of huge systems, according to Dr. Baron.

However, trust works both ways, Dr. Baron notes. Physicians can be champions for their health care system or “throw the system under the bus,” he said.

For example, if a patient complains about the appointment system, clinicians who trust their institutions may say the system usually works and that they will try to make sure the patient has a better experience next time. Clinicians without trust may say they agree that the health care system doesn’t know what it is doing, and patients may further lose confidence when physicians validate their complaint, and patients may then go elsewhere.
 

78% of patients trust primary care doctor

When asked whether they trust their primary care physician, 78% of patients said yes. However, trust in doctors was higher among people who were older (90%), White (82%), or had high income (89%). Among people reporting lower trust, 25% said their physician spends too little time with them, and 14% said their doctor does not know or listen to them.

The survey shows that government agencies have work to do to earn trust. Responses indicate that 43% of physicians said they have “complete trust” in government health care agencies, such as the U.S. Food and Drug Administration and the Centers for Disease Control and Prevention, which is substantially higher than other parts of the health care system. However, trust in agencies declined for 43% of physician respondents and increased for 21%.

Dhruv Khullar, MD, MPP, of the department of health policy and economics at Weill Cornell Medical College in New York, told this news organization the survey results match what he sees anecdotally in medicine – that physicians have been losing trust in the system but not in their colleagues.

He said the sample size of 600 is enough to be influential, though he said he would like to know the response rate, which was not calculated for this survey.

He added that, in large part, physicians’ lack of trust in their systems may come from generally being asked to see more patients and to meet more metrics during the same or shorter periods.

Physicians’ lack of trust in the system can have significant consequences, he said. It can lead to burnout, which has been linked with poorer quality of care and physician turnover, he noted.

COVID-19 led some physicians to wonder whether their system had their best interests at heart, insofar as access to adequate medicines and supplies as well as emotional support were inconsistent, Dr. Khullar said.

He said that to regain trust health care systems need to ask themselves questions in three areas. The first is whether their goals are focused on the best interest of the organization or the best interest of the patient.

“Next is competency,” Dr. Khullar said. “Maybe your motives are right, but are you able to deliver? Are you delivering a good product, whether clinical services or something else?”

The third area is transparency, he said. “Are you going to be honest and forthright in what we’re doing and where we’re going?”

Caroline Pearson, senior vice president of health care strategy for NORC, said the emailed survey was conducted between Dec. 29, 2020, and Feb. 5, 2021, with a health care survey partner that maintains a nationwide panel of physicians across specialties.

She said this report is fairly novel insofar as surveys are more typically conducted regarding patients’ trust of their doctors or of the health care system.

Ms. Pearson said because health care is delivered in teams, understanding the level of trust among the entities helps ensure that care will be delivered effectively and seamlessly with high quality.

“We want our patients to trust our doctors, but we really want doctors to trust each other and trust the hospitals and systems in which they’re working,” she said.

Dr. Baron, Ms. Pearson, and Dr. Khullar report no relevant financial relationships.

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

Physicians’ trust in health care system leaders has taken a steep drop during the COVID-19 pandemic, according to a survey conducted by NORC at the University of Chicago on behalf of the American Board of Internal Medicine Foundation.

Survey results, released May 21, indicate that 30% of physicians say their trust in the U.S. health care system and health care leadership has decreased during the pandemic. Only 18% reported an increase in trust.

Physicians, however, have great trust in their fellow clinicians.

In the survey of 600 physicians, 94% said they trust doctors within their practice; 85% trusted doctors outside of their practice; and 89% trusted nurses. That trust increased during the pandemic, with 41% saying their trust in fellow physicians rose and 37% saying their trust in nurses did.

In a separate survey, NORC asked patients about their trust in various aspects of health care. Among 2,069 respondents, a wide majority reported that they trust doctors (84%) and nurses (85%), but only 64% trusted the health care system as a whole. One in three consumers (32%) said their trust in the health care system decreased during the pandemic, compared with 11% who said their trust increased.

The ABIM Foundation released the research findings on May 21 as part of Building Trust, a national campaign that aims to boost trust among patients, clinicians, system leaders, researchers, and others.

Richard J. Baron, MD, president and chief executive officer of the ABIM Foundation, said in an interview, “Clearly there’s lower trust in health care organization leaders and executives, and that’s troubling.

“Science by itself is not enough,” he said. “Becoming trustworthy has to be a core project of everybody in health care.”

Deterioration in physicians’ trust during the pandemic comes in part from failed promises of adequate personal protective equipment and some physicians’ loss of income as a result of the crisis, Dr. Baron said.

He added that the vaccine rollout was very uneven and that policies as to which elective procedures could be performed were handled differently in different parts of the country.

He also noted that, early on, transparency was lacking as to how many COVID patients hospitals were treating, which may have contributed to the decrease in trust in the system.
 

Fear of being known as ‘the COVID hospital’

Hospitals were afraid of being known as “the COVID hospital” and losing patients who were afraid to come there, Dr. Baron said.

He said the COVID-19 epidemic exacerbated problems regarding trust, but that trust has been declining for some time. The Building Trust campaign will focus on solutions in breaches of trust as physicians move increasingly toward being employees of huge systems, according to Dr. Baron.

However, trust works both ways, Dr. Baron notes. Physicians can be champions for their health care system or “throw the system under the bus,” he said.

For example, if a patient complains about the appointment system, clinicians who trust their institutions may say the system usually works and that they will try to make sure the patient has a better experience next time. Clinicians without trust may say they agree that the health care system doesn’t know what it is doing, and patients may further lose confidence when physicians validate their complaint, and patients may then go elsewhere.
 

78% of patients trust primary care doctor

When asked whether they trust their primary care physician, 78% of patients said yes. However, trust in doctors was higher among people who were older (90%), White (82%), or had high income (89%). Among people reporting lower trust, 25% said their physician spends too little time with them, and 14% said their doctor does not know or listen to them.

The survey shows that government agencies have work to do to earn trust. Responses indicate that 43% of physicians said they have “complete trust” in government health care agencies, such as the U.S. Food and Drug Administration and the Centers for Disease Control and Prevention, which is substantially higher than other parts of the health care system. However, trust in agencies declined for 43% of physician respondents and increased for 21%.

Dhruv Khullar, MD, MPP, of the department of health policy and economics at Weill Cornell Medical College in New York, told this news organization the survey results match what he sees anecdotally in medicine – that physicians have been losing trust in the system but not in their colleagues.

He said the sample size of 600 is enough to be influential, though he said he would like to know the response rate, which was not calculated for this survey.

He added that, in large part, physicians’ lack of trust in their systems may come from generally being asked to see more patients and to meet more metrics during the same or shorter periods.

Physicians’ lack of trust in the system can have significant consequences, he said. It can lead to burnout, which has been linked with poorer quality of care and physician turnover, he noted.

COVID-19 led some physicians to wonder whether their system had their best interests at heart, insofar as access to adequate medicines and supplies as well as emotional support were inconsistent, Dr. Khullar said.

He said that to regain trust health care systems need to ask themselves questions in three areas. The first is whether their goals are focused on the best interest of the organization or the best interest of the patient.

“Next is competency,” Dr. Khullar said. “Maybe your motives are right, but are you able to deliver? Are you delivering a good product, whether clinical services or something else?”

The third area is transparency, he said. “Are you going to be honest and forthright in what we’re doing and where we’re going?”

Caroline Pearson, senior vice president of health care strategy for NORC, said the emailed survey was conducted between Dec. 29, 2020, and Feb. 5, 2021, with a health care survey partner that maintains a nationwide panel of physicians across specialties.

She said this report is fairly novel insofar as surveys are more typically conducted regarding patients’ trust of their doctors or of the health care system.

Ms. Pearson said because health care is delivered in teams, understanding the level of trust among the entities helps ensure that care will be delivered effectively and seamlessly with high quality.

“We want our patients to trust our doctors, but we really want doctors to trust each other and trust the hospitals and systems in which they’re working,” she said.

Dr. Baron, Ms. Pearson, and Dr. Khullar report no relevant financial relationships.

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

Physicians’ trust in health care system leaders has taken a steep drop during the COVID-19 pandemic, according to a survey conducted by NORC at the University of Chicago on behalf of the American Board of Internal Medicine Foundation.

Survey results, released May 21, indicate that 30% of physicians say their trust in the U.S. health care system and health care leadership has decreased during the pandemic. Only 18% reported an increase in trust.

Physicians, however, have great trust in their fellow clinicians.

In the survey of 600 physicians, 94% said they trust doctors within their practice; 85% trusted doctors outside of their practice; and 89% trusted nurses. That trust increased during the pandemic, with 41% saying their trust in fellow physicians rose and 37% saying their trust in nurses did.

In a separate survey, NORC asked patients about their trust in various aspects of health care. Among 2,069 respondents, a wide majority reported that they trust doctors (84%) and nurses (85%), but only 64% trusted the health care system as a whole. One in three consumers (32%) said their trust in the health care system decreased during the pandemic, compared with 11% who said their trust increased.

The ABIM Foundation released the research findings on May 21 as part of Building Trust, a national campaign that aims to boost trust among patients, clinicians, system leaders, researchers, and others.

Richard J. Baron, MD, president and chief executive officer of the ABIM Foundation, said in an interview, “Clearly there’s lower trust in health care organization leaders and executives, and that’s troubling.

“Science by itself is not enough,” he said. “Becoming trustworthy has to be a core project of everybody in health care.”

Deterioration in physicians’ trust during the pandemic comes in part from failed promises of adequate personal protective equipment and some physicians’ loss of income as a result of the crisis, Dr. Baron said.

He added that the vaccine rollout was very uneven and that policies as to which elective procedures could be performed were handled differently in different parts of the country.

He also noted that, early on, transparency was lacking as to how many COVID patients hospitals were treating, which may have contributed to the decrease in trust in the system.
 

Fear of being known as ‘the COVID hospital’

Hospitals were afraid of being known as “the COVID hospital” and losing patients who were afraid to come there, Dr. Baron said.

He said the COVID-19 epidemic exacerbated problems regarding trust, but that trust has been declining for some time. The Building Trust campaign will focus on solutions in breaches of trust as physicians move increasingly toward being employees of huge systems, according to Dr. Baron.

However, trust works both ways, Dr. Baron notes. Physicians can be champions for their health care system or “throw the system under the bus,” he said.

For example, if a patient complains about the appointment system, clinicians who trust their institutions may say the system usually works and that they will try to make sure the patient has a better experience next time. Clinicians without trust may say they agree that the health care system doesn’t know what it is doing, and patients may further lose confidence when physicians validate their complaint, and patients may then go elsewhere.
 

78% of patients trust primary care doctor

When asked whether they trust their primary care physician, 78% of patients said yes. However, trust in doctors was higher among people who were older (90%), White (82%), or had high income (89%). Among people reporting lower trust, 25% said their physician spends too little time with them, and 14% said their doctor does not know or listen to them.

The survey shows that government agencies have work to do to earn trust. Responses indicate that 43% of physicians said they have “complete trust” in government health care agencies, such as the U.S. Food and Drug Administration and the Centers for Disease Control and Prevention, which is substantially higher than other parts of the health care system. However, trust in agencies declined for 43% of physician respondents and increased for 21%.

Dhruv Khullar, MD, MPP, of the department of health policy and economics at Weill Cornell Medical College in New York, told this news organization the survey results match what he sees anecdotally in medicine – that physicians have been losing trust in the system but not in their colleagues.

He said the sample size of 600 is enough to be influential, though he said he would like to know the response rate, which was not calculated for this survey.

He added that, in large part, physicians’ lack of trust in their systems may come from generally being asked to see more patients and to meet more metrics during the same or shorter periods.

Physicians’ lack of trust in the system can have significant consequences, he said. It can lead to burnout, which has been linked with poorer quality of care and physician turnover, he noted.

COVID-19 led some physicians to wonder whether their system had their best interests at heart, insofar as access to adequate medicines and supplies as well as emotional support were inconsistent, Dr. Khullar said.

He said that to regain trust health care systems need to ask themselves questions in three areas. The first is whether their goals are focused on the best interest of the organization or the best interest of the patient.

“Next is competency,” Dr. Khullar said. “Maybe your motives are right, but are you able to deliver? Are you delivering a good product, whether clinical services or something else?”

The third area is transparency, he said. “Are you going to be honest and forthright in what we’re doing and where we’re going?”

Caroline Pearson, senior vice president of health care strategy for NORC, said the emailed survey was conducted between Dec. 29, 2020, and Feb. 5, 2021, with a health care survey partner that maintains a nationwide panel of physicians across specialties.

She said this report is fairly novel insofar as surveys are more typically conducted regarding patients’ trust of their doctors or of the health care system.

Ms. Pearson said because health care is delivered in teams, understanding the level of trust among the entities helps ensure that care will be delivered effectively and seamlessly with high quality.

“We want our patients to trust our doctors, but we really want doctors to trust each other and trust the hospitals and systems in which they’re working,” she said.

Dr. Baron, Ms. Pearson, and Dr. Khullar report no relevant financial relationships.

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

Mycophenolate mofetil, commonly used as a first-line corticosteroid-sparing agent for moderate to severe cases of the autoimmune blistering skin condition pemphigus vulgaris, has been found to be inferior to the biologic agent rituximab.

Mycophenolate mofetil is widely accepted as a first-in-line corticosteroid-sparing agent for pemphigus vulgaris, but few studies have compared the effectiveness of the two treatments for pemphigus vulgaris. The European Academy of Dermatology and Venereology recommends rituximab (Rituxan), a CD20 inhibitor, as first-line treatment for patients with new-onset cases of moderate to severe intensity or for patients who fail to achieve clinical remission with systemic corticosteroids with or without other immunosuppressive treatments.

In the current study, published online on May 19, 2021, in the New England Journal of Medicine, researchers led by Victoria P. Werth, MD, professor of dermatology at the University of Pennsylvania, Philadelphia, conducted a randomized, controlled trial of 135 patients (mean age, 48 years; 53% women) with moderate to severe pemphigus vulgaris with 67 receiving rituximab and 68 receiving mycophenolate mofetil (99% of patients in the rituximab group and 85% of patients in the mycophenolate mofetil group completed the trial).

Patients in the rituximab group received 1,000 mg of IV rituximab on days 1, 15, 168, and 182 of the study, plus twice-daily oral placebo. Intravenous methylprednisolone at 100 mg was administered before each rituximab infusion to reduce infusion-related reactions. Patients in the second group were given mycophenolate mofetil orally twice daily, starting at 1 g/day in divided doses and adjusted to 2 g/day in divided doses by week 2. They also received placebo infusions on days 1, 15, 168, and 182 of the study.

Patients in both groups received oral glucocorticoids throughout the course of the trial: an average of 3,545 mg for the rituximab treatment group and a cumulative dose of 5,140 mg for the group treated with mycophenolate mofetil, a statistically significant difference (P < .001). Outcomes based on 62 patients treated with rituximab and 63 on MMF, a modified intention-to-treat group.

By week 52, 25 patients (40%) who were treated with rituximab experienced complete sustained remission (the primary endpoint), compared with 6 patients (10%) in the mycophenolate mofetil group (95% confidence interval, 15-45, P < .001).

Only six patients in the rituximab group experienced a disease flare as compared with 44 patients in the mycophenolate mofetil group (adjusted rate ratio, 0.12; 95% CI, 0.05-0.29; P < .001). Serious adverse events occurred in 15 of 67 patients (22%) in the rituximab group and in 10 of 68 (15%) in the mycophenolate mofetil group with 3 patients in the rituximab group and 26 in the mycophenolate mofetil receiving rescue therapy.

Second to remission, the goal of treatment for pemphigus vulgaris is to reduce the use of glucocorticoids, Dr. Werth and colleagues wrote, adding: “The results of this trial showed that rituximab was superior to mycophenolate mofetil in producing sustained complete remission over 52 weeks among patients with moderate to severe pemphigus vulgaris. Rituximab had a greater glucocorticoid-sparing effect than mycophenolate mofetil, but more patients in this group had serious adverse events.”

Most adverse events in the rituximab group were limited to infusion-related reactions, but serious adverse events occurred in 15 patients (including pneumonia and upper respiratory tract infection, cellulitis and acute pyelonephritis, viral pneumonia, and skin infection). Ten patients in the mycophenolate mofetil group experienced serious adverse events (pneumonia and influenza, cellulitis and sepsis, herpes zoster, and pyelonephritis).

The current study had several limitations, primarily its small size. Plus, the authors noted a short follow-up period after glucocorticoids were stopped.

Mycophenolate mofetil, along with immunosuppressants, is approved in the United States as a treatment for organ rejection in patients who have received kidney, heart or liver transplants. But it is also used off label for pemphigus vulgaris and in rheumatology as a treatment for lupus, rheumatoid arthritis, vasculitis, inflammatory bowel disease (Crohn’s disease), inflammatory eye disease (uveitis) as well as kidney and skin disorders.

In the 2018 treatment guidelines for pemphigus by the European Dermatology Forum and the EADV, mycophenolate mofetil is recommended as a first-line corticosteroid sparing agent for pemphigus vulgaris.

Rituximab was approved in 2018 as the first biologic therapy for patients with pemphigus vulgaris and is currently recommended as a treatment for patients with pemphigus. But how well it works in comparison with the long-established mycophenolate mofetil hasn’t been extensively studied.

Other smaller studies show that mycophenolate mofetil has a treatment effect, but those studies were small. The Ritux 3 trial, published in The Lancet showed that rituximab plus glucocorticoids as opposed to glucocorticoids alone was beneficial in treating pemphigus.

“Rituximab has moved toward first-line therapy for moderate to severe pemphigus as recommended by an international panel of experts,” Dr. Werth said in an interview.

In her practice, Dr. Werth said that she has observed similar outcomes in clinical practice for patients prescribed oral mycophenolate mofetil. “Patients take a long time to get to remission and frequently end up staying on prednisone and long-term mycophenolate mofetil,” she said. She uses mycophenolate mofetil less often since rituximab has been shown to be effective for many patients, but mycophenolate mofetil “still has a place for patients who don’t want, or can’t tolerate, rituximab, or for cases in which rituximab doesn’t work.”

This study was supported by a grant from Hoffmann–La Roche. Dr. Werth disclosed having served as a consultant to Genentech on pemphigus, and that the University of Pennsylvania has received a grant/contract to perform a rituximab–mycophenolate mofetil trial for pemphigus vulgaris.

Mycophenolate mofetil, commonly used as a first-line corticosteroid-sparing agent for moderate to severe cases of the autoimmune blistering skin condition pemphigus vulgaris, has been found to be inferior to the biologic agent rituximab.

Mycophenolate mofetil is widely accepted as a first-in-line corticosteroid-sparing agent for pemphigus vulgaris, but few studies have compared the effectiveness of the two treatments for pemphigus vulgaris. The European Academy of Dermatology and Venereology recommends rituximab (Rituxan), a CD20 inhibitor, as first-line treatment for patients with new-onset cases of moderate to severe intensity or for patients who fail to achieve clinical remission with systemic corticosteroids with or without other immunosuppressive treatments.

In the current study, published online on May 19, 2021, in the New England Journal of Medicine, researchers led by Victoria P. Werth, MD, professor of dermatology at the University of Pennsylvania, Philadelphia, conducted a randomized, controlled trial of 135 patients (mean age, 48 years; 53% women) with moderate to severe pemphigus vulgaris with 67 receiving rituximab and 68 receiving mycophenolate mofetil (99% of patients in the rituximab group and 85% of patients in the mycophenolate mofetil group completed the trial).

Patients in the rituximab group received 1,000 mg of IV rituximab on days 1, 15, 168, and 182 of the study, plus twice-daily oral placebo. Intravenous methylprednisolone at 100 mg was administered before each rituximab infusion to reduce infusion-related reactions. Patients in the second group were given mycophenolate mofetil orally twice daily, starting at 1 g/day in divided doses and adjusted to 2 g/day in divided doses by week 2. They also received placebo infusions on days 1, 15, 168, and 182 of the study.

Patients in both groups received oral glucocorticoids throughout the course of the trial: an average of 3,545 mg for the rituximab treatment group and a cumulative dose of 5,140 mg for the group treated with mycophenolate mofetil, a statistically significant difference (P < .001). Outcomes based on 62 patients treated with rituximab and 63 on MMF, a modified intention-to-treat group.

By week 52, 25 patients (40%) who were treated with rituximab experienced complete sustained remission (the primary endpoint), compared with 6 patients (10%) in the mycophenolate mofetil group (95% confidence interval, 15-45, P < .001).

Only six patients in the rituximab group experienced a disease flare as compared with 44 patients in the mycophenolate mofetil group (adjusted rate ratio, 0.12; 95% CI, 0.05-0.29; P < .001). Serious adverse events occurred in 15 of 67 patients (22%) in the rituximab group and in 10 of 68 (15%) in the mycophenolate mofetil group with 3 patients in the rituximab group and 26 in the mycophenolate mofetil receiving rescue therapy.

Second to remission, the goal of treatment for pemphigus vulgaris is to reduce the use of glucocorticoids, Dr. Werth and colleagues wrote, adding: “The results of this trial showed that rituximab was superior to mycophenolate mofetil in producing sustained complete remission over 52 weeks among patients with moderate to severe pemphigus vulgaris. Rituximab had a greater glucocorticoid-sparing effect than mycophenolate mofetil, but more patients in this group had serious adverse events.”

Most adverse events in the rituximab group were limited to infusion-related reactions, but serious adverse events occurred in 15 patients (including pneumonia and upper respiratory tract infection, cellulitis and acute pyelonephritis, viral pneumonia, and skin infection). Ten patients in the mycophenolate mofetil group experienced serious adverse events (pneumonia and influenza, cellulitis and sepsis, herpes zoster, and pyelonephritis).

The current study had several limitations, primarily its small size. Plus, the authors noted a short follow-up period after glucocorticoids were stopped.

Mycophenolate mofetil, along with immunosuppressants, is approved in the United States as a treatment for organ rejection in patients who have received kidney, heart or liver transplants. But it is also used off label for pemphigus vulgaris and in rheumatology as a treatment for lupus, rheumatoid arthritis, vasculitis, inflammatory bowel disease (Crohn’s disease), inflammatory eye disease (uveitis) as well as kidney and skin disorders.

In the 2018 treatment guidelines for pemphigus by the European Dermatology Forum and the EADV, mycophenolate mofetil is recommended as a first-line corticosteroid sparing agent for pemphigus vulgaris.

Rituximab was approved in 2018 as the first biologic therapy for patients with pemphigus vulgaris and is currently recommended as a treatment for patients with pemphigus. But how well it works in comparison with the long-established mycophenolate mofetil hasn’t been extensively studied.

Other smaller studies show that mycophenolate mofetil has a treatment effect, but those studies were small. The Ritux 3 trial, published in The Lancet showed that rituximab plus glucocorticoids as opposed to glucocorticoids alone was beneficial in treating pemphigus.

“Rituximab has moved toward first-line therapy for moderate to severe pemphigus as recommended by an international panel of experts,” Dr. Werth said in an interview.

In her practice, Dr. Werth said that she has observed similar outcomes in clinical practice for patients prescribed oral mycophenolate mofetil. “Patients take a long time to get to remission and frequently end up staying on prednisone and long-term mycophenolate mofetil,” she said. She uses mycophenolate mofetil less often since rituximab has been shown to be effective for many patients, but mycophenolate mofetil “still has a place for patients who don’t want, or can’t tolerate, rituximab, or for cases in which rituximab doesn’t work.”

This study was supported by a grant from Hoffmann–La Roche. Dr. Werth disclosed having served as a consultant to Genentech on pemphigus, and that the University of Pennsylvania has received a grant/contract to perform a rituximab–mycophenolate mofetil trial for pemphigus vulgaris.

Mycophenolate mofetil, commonly used as a first-line corticosteroid-sparing agent for moderate to severe cases of the autoimmune blistering skin condition pemphigus vulgaris, has been found to be inferior to the biologic agent rituximab.

Mycophenolate mofetil is widely accepted as a first-in-line corticosteroid-sparing agent for pemphigus vulgaris, but few studies have compared the effectiveness of the two treatments for pemphigus vulgaris. The European Academy of Dermatology and Venereology recommends rituximab (Rituxan), a CD20 inhibitor, as first-line treatment for patients with new-onset cases of moderate to severe intensity or for patients who fail to achieve clinical remission with systemic corticosteroids with or without other immunosuppressive treatments.

In the current study, published online on May 19, 2021, in the New England Journal of Medicine, researchers led by Victoria P. Werth, MD, professor of dermatology at the University of Pennsylvania, Philadelphia, conducted a randomized, controlled trial of 135 patients (mean age, 48 years; 53% women) with moderate to severe pemphigus vulgaris with 67 receiving rituximab and 68 receiving mycophenolate mofetil (99% of patients in the rituximab group and 85% of patients in the mycophenolate mofetil group completed the trial).

Patients in the rituximab group received 1,000 mg of IV rituximab on days 1, 15, 168, and 182 of the study, plus twice-daily oral placebo. Intravenous methylprednisolone at 100 mg was administered before each rituximab infusion to reduce infusion-related reactions. Patients in the second group were given mycophenolate mofetil orally twice daily, starting at 1 g/day in divided doses and adjusted to 2 g/day in divided doses by week 2. They also received placebo infusions on days 1, 15, 168, and 182 of the study.

Patients in both groups received oral glucocorticoids throughout the course of the trial: an average of 3,545 mg for the rituximab treatment group and a cumulative dose of 5,140 mg for the group treated with mycophenolate mofetil, a statistically significant difference (P < .001). Outcomes based on 62 patients treated with rituximab and 63 on MMF, a modified intention-to-treat group.

By week 52, 25 patients (40%) who were treated with rituximab experienced complete sustained remission (the primary endpoint), compared with 6 patients (10%) in the mycophenolate mofetil group (95% confidence interval, 15-45, P < .001).

Only six patients in the rituximab group experienced a disease flare as compared with 44 patients in the mycophenolate mofetil group (adjusted rate ratio, 0.12; 95% CI, 0.05-0.29; P < .001). Serious adverse events occurred in 15 of 67 patients (22%) in the rituximab group and in 10 of 68 (15%) in the mycophenolate mofetil group with 3 patients in the rituximab group and 26 in the mycophenolate mofetil receiving rescue therapy.

Second to remission, the goal of treatment for pemphigus vulgaris is to reduce the use of glucocorticoids, Dr. Werth and colleagues wrote, adding: “The results of this trial showed that rituximab was superior to mycophenolate mofetil in producing sustained complete remission over 52 weeks among patients with moderate to severe pemphigus vulgaris. Rituximab had a greater glucocorticoid-sparing effect than mycophenolate mofetil, but more patients in this group had serious adverse events.”

Most adverse events in the rituximab group were limited to infusion-related reactions, but serious adverse events occurred in 15 patients (including pneumonia and upper respiratory tract infection, cellulitis and acute pyelonephritis, viral pneumonia, and skin infection). Ten patients in the mycophenolate mofetil group experienced serious adverse events (pneumonia and influenza, cellulitis and sepsis, herpes zoster, and pyelonephritis).

The current study had several limitations, primarily its small size. Plus, the authors noted a short follow-up period after glucocorticoids were stopped.

Mycophenolate mofetil, along with immunosuppressants, is approved in the United States as a treatment for organ rejection in patients who have received kidney, heart or liver transplants. But it is also used off label for pemphigus vulgaris and in rheumatology as a treatment for lupus, rheumatoid arthritis, vasculitis, inflammatory bowel disease (Crohn’s disease), inflammatory eye disease (uveitis) as well as kidney and skin disorders.

In the 2018 treatment guidelines for pemphigus by the European Dermatology Forum and the EADV, mycophenolate mofetil is recommended as a first-line corticosteroid sparing agent for pemphigus vulgaris.

Rituximab was approved in 2018 as the first biologic therapy for patients with pemphigus vulgaris and is currently recommended as a treatment for patients with pemphigus. But how well it works in comparison with the long-established mycophenolate mofetil hasn’t been extensively studied.

Other smaller studies show that mycophenolate mofetil has a treatment effect, but those studies were small. The Ritux 3 trial, published in The Lancet showed that rituximab plus glucocorticoids as opposed to glucocorticoids alone was beneficial in treating pemphigus.

“Rituximab has moved toward first-line therapy for moderate to severe pemphigus as recommended by an international panel of experts,” Dr. Werth said in an interview.

In her practice, Dr. Werth said that she has observed similar outcomes in clinical practice for patients prescribed oral mycophenolate mofetil. “Patients take a long time to get to remission and frequently end up staying on prednisone and long-term mycophenolate mofetil,” she said. She uses mycophenolate mofetil less often since rituximab has been shown to be effective for many patients, but mycophenolate mofetil “still has a place for patients who don’t want, or can’t tolerate, rituximab, or for cases in which rituximab doesn’t work.”

This study was supported by a grant from Hoffmann–La Roche. Dr. Werth disclosed having served as a consultant to Genentech on pemphigus, and that the University of Pennsylvania has received a grant/contract to perform a rituximab–mycophenolate mofetil trial for pemphigus vulgaris.

Internal medicine primarily affords us the skill to cope with disorders of chronicity that rarely disappear. For every pneumococcal pneumonia we eradicate, we have multiple patients with HIV who will be treated indefinitely. Diabetes, once a lethal disease, is now a chronic condition for most patients, and even with treatment the trajectory is usually one of progression.

One gratifying exception in my professional lifetime has been the introduction of gastric surgeries that reduce morbidity and seem to extend the life span of those who successfully undergo these procedures. The Roux-en-Y gastric bypass and sleeve gastrectomy have kept thousands of patients in better health for many years, giving them a second chance. For a subset, however, this second chance comes with a stumbling block of substance use – most notably alcohol – that exceeds their preoperative use.
 

Increased alcohol use after surgery

A group affiliated with the Department of Veterans Affairs (VA) recently reviewed the large central database to identify changes in alcohol consumption among patients who had undergone successful bariatric surgery. The VA regularly administers the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), a survey validated as a reliable estimate of individual alcohol consumption. It is inserted into the VA electronic health record where it can be readily retrieved. By matching these survey results with individuals who underwent bariatric surgery at the VA and survived at least 8 years post op, the authors were able to follow trends in alcohol consumption, beginning 2 years before surgery through 8 years after.

Using the same database, the authors identified a larger number of nonoperative control patients with slightly less obesity but otherwise matched for several elements of comorbidity, such as hypertension, certain psychiatric disorders, and personal habits, including alcohol consumption.

Alcohol use was categorized as none, minor social use, and “unhealthy” use. Among those with no or minor social use preoperatively, 4% converted to unhealthy use at 3 years and about 5% at 8 years, significantly more than in the nonoperative control group. Those who had gastric bypass had somewhat more conversion than did those who had sleeve gastrectomy, though not significantly so.

Patients with an alcohol concern preoperatively took an interesting course. Consumption declined from 2 years pre op to the year of surgery, suggesting that curtailing its use may have been a surgical precondition. Postoperatively, they returned to unhealthy drinking levels. Those who underwent the sleeve gastrectomy consumed about the same amount of alcohol as did their matched nonoperative controls, but those who underwent bypass increased their baseline unhealthy use beyond that of the controls.

Because total abstinence is often the recommendation for treating alcoholism, the research group assessed how adherent the excessive drinkers were to abstinence. In anticipation of surgery, the rates of abstinence increased until the year of surgery, but by 3 years post op, consumption was often up to unhealthy levels, though no more than that of control participants with preexisting drinking problems.
 

Smoking and illicit drug use

Although increased alcohol consumption has generated the most studies, some attention has been given to smoking and illicit drug use, which may also increase over time.

One small study looked at composite tobacco, alcohol, and drug use pre- and postoperatively over 2 years, using population data. The authors found a parallel pattern of users voluntarily reducing their substance use in anticipation of surgery but relapsing as the procedure made them more functional and perhaps more independent. Of the substances people resumed, alcohol by far involved the largest increase in use from the preoperative baseline.

These studies, as important as they are, reveal what happened more effectively than they disclose why it happened. The latter requires some clinical experience. Curtailing cigarettes and alcohol use preoperatively may have been done to stay in the good graces of the surgeon. Many patients may have seen this as their path to a second chance that they intended to maintain.

The incentive to proceed to surgical weight loss, which incurs a measure of risk and forces changes in long ingrained eating habits, involves avoiding future morbidity and promoting longevity. Thus, the postoperative behaviors that threaten the long-term goal need to become a component of ongoing follow-up.

The acquisition of adverse behaviors not present preoperatively seems more difficult to sort out, and obligates those of us following these patients to ask about changes in alcohol use and provide resources for them should they need intervention.

Dr. Plotzker is a retired endocrinologist with 40 years of experience treating patients in both private practice and hospital settings.

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

Internal medicine primarily affords us the skill to cope with disorders of chronicity that rarely disappear. For every pneumococcal pneumonia we eradicate, we have multiple patients with HIV who will be treated indefinitely. Diabetes, once a lethal disease, is now a chronic condition for most patients, and even with treatment the trajectory is usually one of progression.

One gratifying exception in my professional lifetime has been the introduction of gastric surgeries that reduce morbidity and seem to extend the life span of those who successfully undergo these procedures. The Roux-en-Y gastric bypass and sleeve gastrectomy have kept thousands of patients in better health for many years, giving them a second chance. For a subset, however, this second chance comes with a stumbling block of substance use – most notably alcohol – that exceeds their preoperative use.
 

Increased alcohol use after surgery

A group affiliated with the Department of Veterans Affairs (VA) recently reviewed the large central database to identify changes in alcohol consumption among patients who had undergone successful bariatric surgery. The VA regularly administers the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), a survey validated as a reliable estimate of individual alcohol consumption. It is inserted into the VA electronic health record where it can be readily retrieved. By matching these survey results with individuals who underwent bariatric surgery at the VA and survived at least 8 years post op, the authors were able to follow trends in alcohol consumption, beginning 2 years before surgery through 8 years after.

Using the same database, the authors identified a larger number of nonoperative control patients with slightly less obesity but otherwise matched for several elements of comorbidity, such as hypertension, certain psychiatric disorders, and personal habits, including alcohol consumption.

Alcohol use was categorized as none, minor social use, and “unhealthy” use. Among those with no or minor social use preoperatively, 4% converted to unhealthy use at 3 years and about 5% at 8 years, significantly more than in the nonoperative control group. Those who had gastric bypass had somewhat more conversion than did those who had sleeve gastrectomy, though not significantly so.

Patients with an alcohol concern preoperatively took an interesting course. Consumption declined from 2 years pre op to the year of surgery, suggesting that curtailing its use may have been a surgical precondition. Postoperatively, they returned to unhealthy drinking levels. Those who underwent the sleeve gastrectomy consumed about the same amount of alcohol as did their matched nonoperative controls, but those who underwent bypass increased their baseline unhealthy use beyond that of the controls.

Because total abstinence is often the recommendation for treating alcoholism, the research group assessed how adherent the excessive drinkers were to abstinence. In anticipation of surgery, the rates of abstinence increased until the year of surgery, but by 3 years post op, consumption was often up to unhealthy levels, though no more than that of control participants with preexisting drinking problems.
 

Smoking and illicit drug use

Although increased alcohol consumption has generated the most studies, some attention has been given to smoking and illicit drug use, which may also increase over time.

One small study looked at composite tobacco, alcohol, and drug use pre- and postoperatively over 2 years, using population data. The authors found a parallel pattern of users voluntarily reducing their substance use in anticipation of surgery but relapsing as the procedure made them more functional and perhaps more independent. Of the substances people resumed, alcohol by far involved the largest increase in use from the preoperative baseline.

These studies, as important as they are, reveal what happened more effectively than they disclose why it happened. The latter requires some clinical experience. Curtailing cigarettes and alcohol use preoperatively may have been done to stay in the good graces of the surgeon. Many patients may have seen this as their path to a second chance that they intended to maintain.

The incentive to proceed to surgical weight loss, which incurs a measure of risk and forces changes in long ingrained eating habits, involves avoiding future morbidity and promoting longevity. Thus, the postoperative behaviors that threaten the long-term goal need to become a component of ongoing follow-up.

The acquisition of adverse behaviors not present preoperatively seems more difficult to sort out, and obligates those of us following these patients to ask about changes in alcohol use and provide resources for them should they need intervention.

Dr. Plotzker is a retired endocrinologist with 40 years of experience treating patients in both private practice and hospital settings.

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

Internal medicine primarily affords us the skill to cope with disorders of chronicity that rarely disappear. For every pneumococcal pneumonia we eradicate, we have multiple patients with HIV who will be treated indefinitely. Diabetes, once a lethal disease, is now a chronic condition for most patients, and even with treatment the trajectory is usually one of progression.

One gratifying exception in my professional lifetime has been the introduction of gastric surgeries that reduce morbidity and seem to extend the life span of those who successfully undergo these procedures. The Roux-en-Y gastric bypass and sleeve gastrectomy have kept thousands of patients in better health for many years, giving them a second chance. For a subset, however, this second chance comes with a stumbling block of substance use – most notably alcohol – that exceeds their preoperative use.
 

Increased alcohol use after surgery

A group affiliated with the Department of Veterans Affairs (VA) recently reviewed the large central database to identify changes in alcohol consumption among patients who had undergone successful bariatric surgery. The VA regularly administers the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), a survey validated as a reliable estimate of individual alcohol consumption. It is inserted into the VA electronic health record where it can be readily retrieved. By matching these survey results with individuals who underwent bariatric surgery at the VA and survived at least 8 years post op, the authors were able to follow trends in alcohol consumption, beginning 2 years before surgery through 8 years after.

Using the same database, the authors identified a larger number of nonoperative control patients with slightly less obesity but otherwise matched for several elements of comorbidity, such as hypertension, certain psychiatric disorders, and personal habits, including alcohol consumption.

Alcohol use was categorized as none, minor social use, and “unhealthy” use. Among those with no or minor social use preoperatively, 4% converted to unhealthy use at 3 years and about 5% at 8 years, significantly more than in the nonoperative control group. Those who had gastric bypass had somewhat more conversion than did those who had sleeve gastrectomy, though not significantly so.

Patients with an alcohol concern preoperatively took an interesting course. Consumption declined from 2 years pre op to the year of surgery, suggesting that curtailing its use may have been a surgical precondition. Postoperatively, they returned to unhealthy drinking levels. Those who underwent the sleeve gastrectomy consumed about the same amount of alcohol as did their matched nonoperative controls, but those who underwent bypass increased their baseline unhealthy use beyond that of the controls.

Because total abstinence is often the recommendation for treating alcoholism, the research group assessed how adherent the excessive drinkers were to abstinence. In anticipation of surgery, the rates of abstinence increased until the year of surgery, but by 3 years post op, consumption was often up to unhealthy levels, though no more than that of control participants with preexisting drinking problems.
 

Smoking and illicit drug use

Although increased alcohol consumption has generated the most studies, some attention has been given to smoking and illicit drug use, which may also increase over time.

One small study looked at composite tobacco, alcohol, and drug use pre- and postoperatively over 2 years, using population data. The authors found a parallel pattern of users voluntarily reducing their substance use in anticipation of surgery but relapsing as the procedure made them more functional and perhaps more independent. Of the substances people resumed, alcohol by far involved the largest increase in use from the preoperative baseline.

These studies, as important as they are, reveal what happened more effectively than they disclose why it happened. The latter requires some clinical experience. Curtailing cigarettes and alcohol use preoperatively may have been done to stay in the good graces of the surgeon. Many patients may have seen this as their path to a second chance that they intended to maintain.

The incentive to proceed to surgical weight loss, which incurs a measure of risk and forces changes in long ingrained eating habits, involves avoiding future morbidity and promoting longevity. Thus, the postoperative behaviors that threaten the long-term goal need to become a component of ongoing follow-up.

The acquisition of adverse behaviors not present preoperatively seems more difficult to sort out, and obligates those of us following these patients to ask about changes in alcohol use and provide resources for them should they need intervention.

Dr. Plotzker is a retired endocrinologist with 40 years of experience treating patients in both private practice and hospital settings.

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

Individuals at increased risk for dementia because of family history can reduce that risk by adopting healthy lifestyle behaviors, data from more than 300,000 adults aged 50-73 years suggest.

Having a parent or sibling with dementia can increase a person’s risk of developing dementia themselves by nearly 75%, compared with someone with no first-degree family history of dementia, according to Angelique Brellenthin, PhD, of Iowa State University, Ames, and colleagues.

In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting sponsored by the American Heart Association, the researchers reviewed information for 302,239 men and women who were enrolled in the U.K. Biobank, a population-based study of more than 500,000 individuals in the United Kingdom, between 2006 and 2010.

The study participants had no evidence of dementia at baseline, and completed questionnaires about family history and lifestyle. The questions included details about six healthy lifestyle behaviors: eating a healthy diet, engaging in at least 150 minutes of moderate to vigorous physical activity per week, sleeping 6-9 hours each night, drinking alcohol in moderation, not smoking, and maintaining a body mass index below the obese level (less than 30 kg/m²).

The researchers identified 1,698 participants (0.6%) who developed dementia over an average follow-up period of 8 years. Those with a family history (first-degree relative) of dementia had a 70% increased risk of dementia, compared with those who had no such family history.

Overall, individuals who engaged in all six healthy behaviors reduced their risk of dementia by about half, compared with those who engaged in two or fewer healthy behaviors. Engaging in three healthy behaviors reduced the risk of dementia by 30%, compared with engaging in two or fewer healthy behaviors, and this association held after controlling not only for family history of dementia, but also for other dementia risk factors such as age, sex, race, and education level, as well as high blood pressure, high cholesterol, and the presence of type 2 diabetes.

Similarly, among participants with a family history of dementia, those who engaged in three healthy lifestyle behaviors showed a 25%-35% reduction in dementia risk, compared with those who engaged in two or fewer healthy behaviors.

The study findings were limited by several factors including the inability to prove that lifestyle can cause or prevent dementia, only to show an association, the researchers noted. Also, the findings were limited by the reliance on self-reports, rather than genetic data, to confirm familial dementia.

However, the findings were strengthened by the large sample size, and the results suggest that a healthy lifestyle can impact cognitive health, and support the value of encouraging healthy behaviors in general, and especially among individuals with a family history of dementia, they said.
 

Small changes may promote prevention

The study is important now because, as the population ages, many individuals have a family member who has had dementia, said lead author Dr. Brellenthin, in an interview. “It’s important to understand how lifestyle behaviors affect the risk of dementia when it runs in families,” she said.

Dr. Brellenthin said she was surprised by some of the findings. “It was surprising to see that the risk of dementia was reduced with just three healthy behaviors [but was further reduced as you added more behaviors] compared to two or fewer behaviors. However, it was not surprising to see that these same lifestyle behaviors that tend to be good for the heart and body are also good for the brain.”

The evidence that following just three healthy behaviors can reduce the risk of dementia by 25%-35% for individuals with a familial history of dementia has clinical implications, Dr. Brellenthin said. “Many people are already following some of these behaviors like not smoking, so it might be possible to focus on adding just one more behavior, like getting enough sleep, and going from there.”

Commenting on the study, AHA President Mitchell S. V. Elkind, MD, said that the study “tells us that, yes, family history is important [in determining the risk of dementia], and much of that may be driven by genetic factors, but some of that impact can be mitigated or decreased by engaging in those important behaviors that we know are good to maintain brain health.

“The tricky thing, of course, is getting people to engage in these behaviors. That’s where a lot of work in the future will be: changing people’s behavior to become more healthy, and figuring out exactly which behaviors may be the easiest to engage in and be most likely to have public health impact,” added Dr. Elkind, professor of neurology and epidemiology at Columbia University and attending neurologist at New York–Presbyterian/Columbia University Irving Medical Center, New York.

The study received no outside funding, but the was research was conducted using the U.K. Biobank resources. The researchers had no financial conflicts to disclose.

Individuals at increased risk for dementia because of family history can reduce that risk by adopting healthy lifestyle behaviors, data from more than 300,000 adults aged 50-73 years suggest.

Having a parent or sibling with dementia can increase a person’s risk of developing dementia themselves by nearly 75%, compared with someone with no first-degree family history of dementia, according to Angelique Brellenthin, PhD, of Iowa State University, Ames, and colleagues.

In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting sponsored by the American Heart Association, the researchers reviewed information for 302,239 men and women who were enrolled in the U.K. Biobank, a population-based study of more than 500,000 individuals in the United Kingdom, between 2006 and 2010.

The study participants had no evidence of dementia at baseline, and completed questionnaires about family history and lifestyle. The questions included details about six healthy lifestyle behaviors: eating a healthy diet, engaging in at least 150 minutes of moderate to vigorous physical activity per week, sleeping 6-9 hours each night, drinking alcohol in moderation, not smoking, and maintaining a body mass index below the obese level (less than 30 kg/m²).

The researchers identified 1,698 participants (0.6%) who developed dementia over an average follow-up period of 8 years. Those with a family history (first-degree relative) of dementia had a 70% increased risk of dementia, compared with those who had no such family history.

Overall, individuals who engaged in all six healthy behaviors reduced their risk of dementia by about half, compared with those who engaged in two or fewer healthy behaviors. Engaging in three healthy behaviors reduced the risk of dementia by 30%, compared with engaging in two or fewer healthy behaviors, and this association held after controlling not only for family history of dementia, but also for other dementia risk factors such as age, sex, race, and education level, as well as high blood pressure, high cholesterol, and the presence of type 2 diabetes.

Similarly, among participants with a family history of dementia, those who engaged in three healthy lifestyle behaviors showed a 25%-35% reduction in dementia risk, compared with those who engaged in two or fewer healthy behaviors.

The study findings were limited by several factors including the inability to prove that lifestyle can cause or prevent dementia, only to show an association, the researchers noted. Also, the findings were limited by the reliance on self-reports, rather than genetic data, to confirm familial dementia.

However, the findings were strengthened by the large sample size, and the results suggest that a healthy lifestyle can impact cognitive health, and support the value of encouraging healthy behaviors in general, and especially among individuals with a family history of dementia, they said.
 

Small changes may promote prevention

The study is important now because, as the population ages, many individuals have a family member who has had dementia, said lead author Dr. Brellenthin, in an interview. “It’s important to understand how lifestyle behaviors affect the risk of dementia when it runs in families,” she said.

Dr. Brellenthin said she was surprised by some of the findings. “It was surprising to see that the risk of dementia was reduced with just three healthy behaviors [but was further reduced as you added more behaviors] compared to two or fewer behaviors. However, it was not surprising to see that these same lifestyle behaviors that tend to be good for the heart and body are also good for the brain.”

The evidence that following just three healthy behaviors can reduce the risk of dementia by 25%-35% for individuals with a familial history of dementia has clinical implications, Dr. Brellenthin said. “Many people are already following some of these behaviors like not smoking, so it might be possible to focus on adding just one more behavior, like getting enough sleep, and going from there.”

Commenting on the study, AHA President Mitchell S. V. Elkind, MD, said that the study “tells us that, yes, family history is important [in determining the risk of dementia], and much of that may be driven by genetic factors, but some of that impact can be mitigated or decreased by engaging in those important behaviors that we know are good to maintain brain health.

“The tricky thing, of course, is getting people to engage in these behaviors. That’s where a lot of work in the future will be: changing people’s behavior to become more healthy, and figuring out exactly which behaviors may be the easiest to engage in and be most likely to have public health impact,” added Dr. Elkind, professor of neurology and epidemiology at Columbia University and attending neurologist at New York–Presbyterian/Columbia University Irving Medical Center, New York.

The study received no outside funding, but the was research was conducted using the U.K. Biobank resources. The researchers had no financial conflicts to disclose.

Individuals at increased risk for dementia because of family history can reduce that risk by adopting healthy lifestyle behaviors, data from more than 300,000 adults aged 50-73 years suggest.

Having a parent or sibling with dementia can increase a person’s risk of developing dementia themselves by nearly 75%, compared with someone with no first-degree family history of dementia, according to Angelique Brellenthin, PhD, of Iowa State University, Ames, and colleagues.

In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting sponsored by the American Heart Association, the researchers reviewed information for 302,239 men and women who were enrolled in the U.K. Biobank, a population-based study of more than 500,000 individuals in the United Kingdom, between 2006 and 2010.

The study participants had no evidence of dementia at baseline, and completed questionnaires about family history and lifestyle. The questions included details about six healthy lifestyle behaviors: eating a healthy diet, engaging in at least 150 minutes of moderate to vigorous physical activity per week, sleeping 6-9 hours each night, drinking alcohol in moderation, not smoking, and maintaining a body mass index below the obese level (less than 30 kg/m²).

The researchers identified 1,698 participants (0.6%) who developed dementia over an average follow-up period of 8 years. Those with a family history (first-degree relative) of dementia had a 70% increased risk of dementia, compared with those who had no such family history.

Overall, individuals who engaged in all six healthy behaviors reduced their risk of dementia by about half, compared with those who engaged in two or fewer healthy behaviors. Engaging in three healthy behaviors reduced the risk of dementia by 30%, compared with engaging in two or fewer healthy behaviors, and this association held after controlling not only for family history of dementia, but also for other dementia risk factors such as age, sex, race, and education level, as well as high blood pressure, high cholesterol, and the presence of type 2 diabetes.

Similarly, among participants with a family history of dementia, those who engaged in three healthy lifestyle behaviors showed a 25%-35% reduction in dementia risk, compared with those who engaged in two or fewer healthy behaviors.

The study findings were limited by several factors including the inability to prove that lifestyle can cause or prevent dementia, only to show an association, the researchers noted. Also, the findings were limited by the reliance on self-reports, rather than genetic data, to confirm familial dementia.

However, the findings were strengthened by the large sample size, and the results suggest that a healthy lifestyle can impact cognitive health, and support the value of encouraging healthy behaviors in general, and especially among individuals with a family history of dementia, they said.
 

Small changes may promote prevention

The study is important now because, as the population ages, many individuals have a family member who has had dementia, said lead author Dr. Brellenthin, in an interview. “It’s important to understand how lifestyle behaviors affect the risk of dementia when it runs in families,” she said.

Dr. Brellenthin said she was surprised by some of the findings. “It was surprising to see that the risk of dementia was reduced with just three healthy behaviors [but was further reduced as you added more behaviors] compared to two or fewer behaviors. However, it was not surprising to see that these same lifestyle behaviors that tend to be good for the heart and body are also good for the brain.”

The evidence that following just three healthy behaviors can reduce the risk of dementia by 25%-35% for individuals with a familial history of dementia has clinical implications, Dr. Brellenthin said. “Many people are already following some of these behaviors like not smoking, so it might be possible to focus on adding just one more behavior, like getting enough sleep, and going from there.”

Commenting on the study, AHA President Mitchell S. V. Elkind, MD, said that the study “tells us that, yes, family history is important [in determining the risk of dementia], and much of that may be driven by genetic factors, but some of that impact can be mitigated or decreased by engaging in those important behaviors that we know are good to maintain brain health.

“The tricky thing, of course, is getting people to engage in these behaviors. That’s where a lot of work in the future will be: changing people’s behavior to become more healthy, and figuring out exactly which behaviors may be the easiest to engage in and be most likely to have public health impact,” added Dr. Elkind, professor of neurology and epidemiology at Columbia University and attending neurologist at New York–Presbyterian/Columbia University Irving Medical Center, New York.

The study received no outside funding, but the was research was conducted using the U.K. Biobank resources. The researchers had no financial conflicts to disclose.

Click here for the wrap-up issue of the SHM Converge Daily News newsletter.

Click here for the wrap-up issue of the SHM Converge Daily News newsletter.

Click here for the wrap-up issue of the SHM Converge Daily News newsletter.

The delivery of photobiomodulation therapy (PBMT) was found to limit the severity of acute radiodermatitis in patients undergoing treatment for head and neck cancer, according to results from the first randomized study of its kind.

“The use of light therapy-based applications for cancer therapy-related adverse events has steadily increased in the past 40 years,” lead study author Jolien Robijns, MSc, PhD, told this news organization during the annual conference of the American Society for Laser Medicine and Surgery. “The most well-known and studied indication of photobiomodulation therapy in supportive cancer care is oral mucositis,” she said, referring to a recent systematic review, which found that based on the available evidence, PBMT is an effective therapy for the prevention of oral mucositis, using well-defined PBM parameters in specific patient populations. “Various internationally well-recognized health organizations in oncology recommend PBMT to prevent and manage oral mucositis,” she added.

Based on the wound-healing and anti-inflammatory properties of PBMT, several studies have investigated its use for the prevention and management of acute radiodermatitis (ARD) since the 1990s, said Dr. Robijns, a postdoctoral researcher at Limburg Clinical Research Center in Hasselt, Belgium. Under the supervision of Jeroen Mebis, MD, PhD, at the Limburg Oncologic Laser Institute, she and her colleagues have been conducting clinical research on PBMT and ARD since 2014, with successful results. In 2020 they published a narrative review, which showed that based on nine clinical trials, PBMT could effectively reduce the incidence of severe ARD, decrease accompanying pain, and improve patients’ quality of life.

For the current study, known as the DERMISHEAD trial and published online March 9, 2021, in Radiotherapy and Oncology, investigators at Limburg Oncology Center at Jessa Hospital in Hasselt, and Hasselt University, recruited head and neck cancer patients who underwent bilateral radiotherapy with or without chemotherapy, for a total dose of 30-35 x 2 Gy . All patients received standard skin care combined with two PBMT or sham sessions twice per week during the complete course of RT, which resulted in 14 total sessions.

As described in the Radiotherapy and Oncology study, the commercially available device used for PBMT “consists of two laser diodes with different wavelengths (808-905 nm), peak powers (1.1-25 W), and emission modes (continuous and pulsed). Both diodes work simultaneously and synchronously with coincident propagation axes (average radiant power 3.3 W). The energy density (fluence) was set at 4 J/cm² based on earlier recommendations and on our clinical experience.” A blinded study nurse used Radiation Therapy Oncology Group criteria to evaluate the skin reactions.

After 303 patients were initially assessed for eligibility, 46 patients were enrolled in DERMISHEAD (18 in the placebo group and 28 in the PBMT group). At the end of radiotherapy, 77.8% of patients in the placebo group had a grade 2 or 3 skin reaction, compared with 28.6% of patients in the PBMT group (P = .001).

“The DERMISHEAD trial proved that PBMT significantly reduces the severity of ARD,” Dr. Robijns said. “Thereby, it improves the patients’ quality of life during their radiotherapy course. The trial supports the further implementation of PBM in the supportive care of cancer patients undergoing radiotherapy.”

The results are similar to those in the TRANSDERMIS trial, in which Dr. Robijns and her colleagues used PMBT to treat breast cancer patients.

“However, an interesting difference is that the percentage decrease in severe ARD was higher in the DERMISHEAD trial than in the TRANSDERMIS trial: 49% vs. 23%, respectively,” she noted. “This difference can be rationalized because in total, more control head and neck cancer patients developed grade 3 ARD than did control breast cancer patients (17% vs. 5%). A possible explanation of this finding can be related to the difference in treatment regimens and radiotherapy parameters between the two trials.”

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was asked to comment on the study, said that acute radiation dermatitis “can be very painful and distressing to patients, and over time, the skin changes can create long-term problems. Prevention of acute and chronic radiation dermatitis is worthwhile, particularly for patients at risk.”

This study, she added, “shows a benefit of photobiomodulation therapy as a potential preventative treatment. Notably, patients did not always follow up appropriately for the therapy, and the authors said that it is yet another thing that patients need to keep track of, in addition to their cancer therapy visits. Thus, optimally, it would be useful to have a biomarker of which patients would most benefit from treatments that prevent/potentiate radiation dermatitis.”

Dr. Robijns acknowledged certain limitations of the trial, including its small sample size and the scarcity of clinical trials on PBM and acute radiation dermatitis. “More studies are needed,” she said. “Future studies should focus on randomized controlled study designs with well-described and complete PBMT parameters in a larger and more diverse patient population. This would enable the implementation of PBM in the field of ARD and supportive cancer care, which would enhance wound care management and improve the patient’s quality of life.”

This work won a “best of clinical applications” abstract award from the ASLMS.

The research is part of the Limburg Clinical Research Center UHasselt-ZOL-Jessa, financially supported by the foundation Limburg Sterk Merk, province of Limburg, Flemish Government, Hasselt University, Ziekenhuis Oost-Limburg, and Jessa Hospital. The research is also funded by Kom op tegen Kanker (Stand up to Cancer), the Flemish Cancer Society, Limburgs Kankerfonds, and ASA Srl. Dr. Robijns reported having no financial disclosures.

[email protected]

The delivery of photobiomodulation therapy (PBMT) was found to limit the severity of acute radiodermatitis in patients undergoing treatment for head and neck cancer, according to results from the first randomized study of its kind.

“The use of light therapy-based applications for cancer therapy-related adverse events has steadily increased in the past 40 years,” lead study author Jolien Robijns, MSc, PhD, told this news organization during the annual conference of the American Society for Laser Medicine and Surgery. “The most well-known and studied indication of photobiomodulation therapy in supportive cancer care is oral mucositis,” she said, referring to a recent systematic review, which found that based on the available evidence, PBMT is an effective therapy for the prevention of oral mucositis, using well-defined PBM parameters in specific patient populations. “Various internationally well-recognized health organizations in oncology recommend PBMT to prevent and manage oral mucositis,” she added.

Based on the wound-healing and anti-inflammatory properties of PBMT, several studies have investigated its use for the prevention and management of acute radiodermatitis (ARD) since the 1990s, said Dr. Robijns, a postdoctoral researcher at Limburg Clinical Research Center in Hasselt, Belgium. Under the supervision of Jeroen Mebis, MD, PhD, at the Limburg Oncologic Laser Institute, she and her colleagues have been conducting clinical research on PBMT and ARD since 2014, with successful results. In 2020 they published a narrative review, which showed that based on nine clinical trials, PBMT could effectively reduce the incidence of severe ARD, decrease accompanying pain, and improve patients’ quality of life.

For the current study, known as the DERMISHEAD trial and published online March 9, 2021, in Radiotherapy and Oncology, investigators at Limburg Oncology Center at Jessa Hospital in Hasselt, and Hasselt University, recruited head and neck cancer patients who underwent bilateral radiotherapy with or without chemotherapy, for a total dose of 30-35 x 2 Gy . All patients received standard skin care combined with two PBMT or sham sessions twice per week during the complete course of RT, which resulted in 14 total sessions.

As described in the Radiotherapy and Oncology study, the commercially available device used for PBMT “consists of two laser diodes with different wavelengths (808-905 nm), peak powers (1.1-25 W), and emission modes (continuous and pulsed). Both diodes work simultaneously and synchronously with coincident propagation axes (average radiant power 3.3 W). The energy density (fluence) was set at 4 J/cm² based on earlier recommendations and on our clinical experience.” A blinded study nurse used Radiation Therapy Oncology Group criteria to evaluate the skin reactions.

After 303 patients were initially assessed for eligibility, 46 patients were enrolled in DERMISHEAD (18 in the placebo group and 28 in the PBMT group). At the end of radiotherapy, 77.8% of patients in the placebo group had a grade 2 or 3 skin reaction, compared with 28.6% of patients in the PBMT group (P = .001).

“The DERMISHEAD trial proved that PBMT significantly reduces the severity of ARD,” Dr. Robijns said. “Thereby, it improves the patients’ quality of life during their radiotherapy course. The trial supports the further implementation of PBM in the supportive care of cancer patients undergoing radiotherapy.”

The results are similar to those in the TRANSDERMIS trial, in which Dr. Robijns and her colleagues used PMBT to treat breast cancer patients.

“However, an interesting difference is that the percentage decrease in severe ARD was higher in the DERMISHEAD trial than in the TRANSDERMIS trial: 49% vs. 23%, respectively,” she noted. “This difference can be rationalized because in total, more control head and neck cancer patients developed grade 3 ARD than did control breast cancer patients (17% vs. 5%). A possible explanation of this finding can be related to the difference in treatment regimens and radiotherapy parameters between the two trials.”

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was asked to comment on the study, said that acute radiation dermatitis “can be very painful and distressing to patients, and over time, the skin changes can create long-term problems. Prevention of acute and chronic radiation dermatitis is worthwhile, particularly for patients at risk.”

This study, she added, “shows a benefit of photobiomodulation therapy as a potential preventative treatment. Notably, patients did not always follow up appropriately for the therapy, and the authors said that it is yet another thing that patients need to keep track of, in addition to their cancer therapy visits. Thus, optimally, it would be useful to have a biomarker of which patients would most benefit from treatments that prevent/potentiate radiation dermatitis.”

Dr. Robijns acknowledged certain limitations of the trial, including its small sample size and the scarcity of clinical trials on PBM and acute radiation dermatitis. “More studies are needed,” she said. “Future studies should focus on randomized controlled study designs with well-described and complete PBMT parameters in a larger and more diverse patient population. This would enable the implementation of PBM in the field of ARD and supportive cancer care, which would enhance wound care management and improve the patient’s quality of life.”

This work won a “best of clinical applications” abstract award from the ASLMS.

The research is part of the Limburg Clinical Research Center UHasselt-ZOL-Jessa, financially supported by the foundation Limburg Sterk Merk, province of Limburg, Flemish Government, Hasselt University, Ziekenhuis Oost-Limburg, and Jessa Hospital. The research is also funded by Kom op tegen Kanker (Stand up to Cancer), the Flemish Cancer Society, Limburgs Kankerfonds, and ASA Srl. Dr. Robijns reported having no financial disclosures.

[email protected]

The delivery of photobiomodulation therapy (PBMT) was found to limit the severity of acute radiodermatitis in patients undergoing treatment for head and neck cancer, according to results from the first randomized study of its kind.

“The use of light therapy-based applications for cancer therapy-related adverse events has steadily increased in the past 40 years,” lead study author Jolien Robijns, MSc, PhD, told this news organization during the annual conference of the American Society for Laser Medicine and Surgery. “The most well-known and studied indication of photobiomodulation therapy in supportive cancer care is oral mucositis,” she said, referring to a recent systematic review, which found that based on the available evidence, PBMT is an effective therapy for the prevention of oral mucositis, using well-defined PBM parameters in specific patient populations. “Various internationally well-recognized health organizations in oncology recommend PBMT to prevent and manage oral mucositis,” she added.

Based on the wound-healing and anti-inflammatory properties of PBMT, several studies have investigated its use for the prevention and management of acute radiodermatitis (ARD) since the 1990s, said Dr. Robijns, a postdoctoral researcher at Limburg Clinical Research Center in Hasselt, Belgium. Under the supervision of Jeroen Mebis, MD, PhD, at the Limburg Oncologic Laser Institute, she and her colleagues have been conducting clinical research on PBMT and ARD since 2014, with successful results. In 2020 they published a narrative review, which showed that based on nine clinical trials, PBMT could effectively reduce the incidence of severe ARD, decrease accompanying pain, and improve patients’ quality of life.

For the current study, known as the DERMISHEAD trial and published online March 9, 2021, in Radiotherapy and Oncology, investigators at Limburg Oncology Center at Jessa Hospital in Hasselt, and Hasselt University, recruited head and neck cancer patients who underwent bilateral radiotherapy with or without chemotherapy, for a total dose of 30-35 x 2 Gy . All patients received standard skin care combined with two PBMT or sham sessions twice per week during the complete course of RT, which resulted in 14 total sessions.

As described in the Radiotherapy and Oncology study, the commercially available device used for PBMT “consists of two laser diodes with different wavelengths (808-905 nm), peak powers (1.1-25 W), and emission modes (continuous and pulsed). Both diodes work simultaneously and synchronously with coincident propagation axes (average radiant power 3.3 W). The energy density (fluence) was set at 4 J/cm² based on earlier recommendations and on our clinical experience.” A blinded study nurse used Radiation Therapy Oncology Group criteria to evaluate the skin reactions.

After 303 patients were initially assessed for eligibility, 46 patients were enrolled in DERMISHEAD (18 in the placebo group and 28 in the PBMT group). At the end of radiotherapy, 77.8% of patients in the placebo group had a grade 2 or 3 skin reaction, compared with 28.6% of patients in the PBMT group (P = .001).

“The DERMISHEAD trial proved that PBMT significantly reduces the severity of ARD,” Dr. Robijns said. “Thereby, it improves the patients’ quality of life during their radiotherapy course. The trial supports the further implementation of PBM in the supportive care of cancer patients undergoing radiotherapy.”

The results are similar to those in the TRANSDERMIS trial, in which Dr. Robijns and her colleagues used PMBT to treat breast cancer patients.

“However, an interesting difference is that the percentage decrease in severe ARD was higher in the DERMISHEAD trial than in the TRANSDERMIS trial: 49% vs. 23%, respectively,” she noted. “This difference can be rationalized because in total, more control head and neck cancer patients developed grade 3 ARD than did control breast cancer patients (17% vs. 5%). A possible explanation of this finding can be related to the difference in treatment regimens and radiotherapy parameters between the two trials.”

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was asked to comment on the study, said that acute radiation dermatitis “can be very painful and distressing to patients, and over time, the skin changes can create long-term problems. Prevention of acute and chronic radiation dermatitis is worthwhile, particularly for patients at risk.”

This study, she added, “shows a benefit of photobiomodulation therapy as a potential preventative treatment. Notably, patients did not always follow up appropriately for the therapy, and the authors said that it is yet another thing that patients need to keep track of, in addition to their cancer therapy visits. Thus, optimally, it would be useful to have a biomarker of which patients would most benefit from treatments that prevent/potentiate radiation dermatitis.”

Dr. Robijns acknowledged certain limitations of the trial, including its small sample size and the scarcity of clinical trials on PBM and acute radiation dermatitis. “More studies are needed,” she said. “Future studies should focus on randomized controlled study designs with well-described and complete PBMT parameters in a larger and more diverse patient population. This would enable the implementation of PBM in the field of ARD and supportive cancer care, which would enhance wound care management and improve the patient’s quality of life.”

This work won a “best of clinical applications” abstract award from the ASLMS.

The research is part of the Limburg Clinical Research Center UHasselt-ZOL-Jessa, financially supported by the foundation Limburg Sterk Merk, province of Limburg, Flemish Government, Hasselt University, Ziekenhuis Oost-Limburg, and Jessa Hospital. The research is also funded by Kom op tegen Kanker (Stand up to Cancer), the Flemish Cancer Society, Limburgs Kankerfonds, and ASA Srl. Dr. Robijns reported having no financial disclosures.

[email protected]

Three-year survival rates were similarly high among postmenopausal women with high-risk early luminal breast cancer who were treated with either the neoadjuvant combination of letrozole and palbociclib (Ibrance) or standard neoadjuvant chemotherapy in the phase 2 NeoPAL study.

Progression-free survival (PFS) was a respective 86.7% and 87.2%, with a hazard ratio (HR) of 1.01 (P = .98) comparing the endocrine therapy and cyclin-dependent kinase (CDK) 4/6 inhibitor combination versus FEC/taxane chemotherapy.

There were also no differences between the two treatment arms in terms of invasive disease-free survival (iDFS, HR = 0.83, P = .71) or breast cancer–specific survival (BCSS), although the latter was an exploratory endpoint alongside overall survival (OS).

“The lack of difference is impressive,” said Hope S. Rugo, MD, FASCO, who commented independently on the study’s findings after their presentation at the European Society for Medical Oncology: Breast Cancer virtual meeting.

“Overall survival in patients who received chemotherapy appears to be better, but the very small numbers here make interpretation of this difference impossible,” observed Dr. Rugo, professor of medicine at the University of California San Francisco’s Helen Diller Family Comprehensive Cancer Center.

“Unfortunately, this study is underpowered for definitive conclusions,” acknowledged study investigator Suzette Delaloge, MD, associate professor of medical oncology at Institut Gustave Roussy in Villejuif, France.

However, “it shows that the nonchemotherapy, preoperative letrozole/palbociclib approach deserves further exploration and could be an option for a chemotherapy-free regimen in some specific cases.”
 

Primary data already reported

The NeoPAL study was an open-label, randomized study conducted in 27 centers throughout France that compared the preoperative use of letrozole plus palbociclib to neoadjuvant chemotherapy in 106 postmenopausal patients with either luminal A or B node-positive disease.

Patients were considered for inclusion in the trial if they had been newly diagnosed with estrogen receptor (ER)-positive, HER2-negative stage I-III breast cancer and were not candidates for breast conservation. Genetic testing was used to confirm that only those with luminal B, or luminal A and who were node positive were recruited.

Neoadjuvant treatment consisted of either letrozole (2.5 mg/day) and palbociclib (125 mg daily for 3 weeks out of 4 weeks) for 19 weeks or three 21-day cycles of 5-fluorouracil (500 mg/m²), epirubicin (100 mg/m²), and cyclophosphamide (500 mg/m²), followed by three 21-day cycles of docetaxel (100 mg/m²).

The primary endpoint was the pathological complete response (pCR), defined as a residual cancer burden (RCB) of 0 to 1. Results, which have already been reported, showed equivalent, but perhaps disappointingly low, pathological responses in both the letrozole/palbociclib and chemotherapy arms (3.8% and 5.9%, respectively).

There were, however, identical clinical responses (at around 75%) and “encouraging biomarker responses in the Prosigna-defined high risk luminal breast cancer population,” Dr. Delaloge said.

The NeoPAL findings were on par with those of the CORALLEEN study, Dr. Delaloge suggested. That trial, as Dr. Rugo has also pointed out, was conducted in 106 patients with luminal B early breast cancer and used a combination of letrozole and the CDK 4/6 inhibitor ribociclib (Kisquali).
 

Future studies needed

NeoPAL “is a small study with relatively short follow-up even for hormone receptor-positive, high-risk disease,” Dr. Rugo observed. However, she qualified “this short follow-up can be very meaningful in high-risk disease.” as shown by other CDK 4/6 inhibitor trials.

Dr. Rugo also noted: “Short-term biologic endpoints are clearly more informative following and during neoadjuvant endocrine therapy than pCR and this trial, as well as the data from previous studies, indicates that this is the case.”

Further, Dr. Rugo said: “Antiproliferative response is enhanced with CDK 4/6 inhibitors, but this doesn’t seem to translate into a difference in pCR. The lack of impact on longer term, outcome to date, provides support for ongoing trials.”

Two such trials are already underway. The 200-patient CARABELA trial started recruitment in March last year and is comparing endocrine therapy with letrozole plus the CDK 4/6 inhibitor abemaciclib (Verzenio) to standard chemotherapy in patients with hormone receptor–positive, high-risk Ki67 disease.

Then there is the ADAPTcycle trial, a large open-label, phase 3 trial that is randomizing patients based on Ki67 and recurrence score after a short preoperative induction with endocrine therapy to postoperative chemotherapy or to 2 years of endocrine therapy plus ribociclib, with both arms receiving a standard course of 5 years of endocrine therapy.

“These two studies have provided interesting information that will help us design studies in the future,” said Dr. Rugo.

Not only that, but they will also help “investigate the subgroups of patients that benefit the most from CDK 4/6 inhibitors and better study neoadjuvant endocrine therapy which is an important option for patients that can be evaluated in terms of its efficacy by short term measures of antiproliferative response.”

NeoPAL was sponsored by UNICANCER with funding from Pfizer and NanoString Technologies. Dr. Delaloge disclosed receiving research grants or funding via her institution from Pfizer, AstraZeneca, Roche, Merck, Sanofi, Lilly, Novartis, BMS, Orion, Daiichi, Puma, and Pierre Fabre. Dr. Rugo reported receipt of grants via her institution to perform clinical trials from Pfizer and multiple other companies. She disclosed receiving honoraria from PUMA, Samsung, and Mylan.

Three-year survival rates were similarly high among postmenopausal women with high-risk early luminal breast cancer who were treated with either the neoadjuvant combination of letrozole and palbociclib (Ibrance) or standard neoadjuvant chemotherapy in the phase 2 NeoPAL study.

Progression-free survival (PFS) was a respective 86.7% and 87.2%, with a hazard ratio (HR) of 1.01 (P = .98) comparing the endocrine therapy and cyclin-dependent kinase (CDK) 4/6 inhibitor combination versus FEC/taxane chemotherapy.

There were also no differences between the two treatment arms in terms of invasive disease-free survival (iDFS, HR = 0.83, P = .71) or breast cancer–specific survival (BCSS), although the latter was an exploratory endpoint alongside overall survival (OS).

“The lack of difference is impressive,” said Hope S. Rugo, MD, FASCO, who commented independently on the study’s findings after their presentation at the European Society for Medical Oncology: Breast Cancer virtual meeting.

“Overall survival in patients who received chemotherapy appears to be better, but the very small numbers here make interpretation of this difference impossible,” observed Dr. Rugo, professor of medicine at the University of California San Francisco’s Helen Diller Family Comprehensive Cancer Center.

“Unfortunately, this study is underpowered for definitive conclusions,” acknowledged study investigator Suzette Delaloge, MD, associate professor of medical oncology at Institut Gustave Roussy in Villejuif, France.

However, “it shows that the nonchemotherapy, preoperative letrozole/palbociclib approach deserves further exploration and could be an option for a chemotherapy-free regimen in some specific cases.”
 

Primary data already reported

The NeoPAL study was an open-label, randomized study conducted in 27 centers throughout France that compared the preoperative use of letrozole plus palbociclib to neoadjuvant chemotherapy in 106 postmenopausal patients with either luminal A or B node-positive disease.

Patients were considered for inclusion in the trial if they had been newly diagnosed with estrogen receptor (ER)-positive, HER2-negative stage I-III breast cancer and were not candidates for breast conservation. Genetic testing was used to confirm that only those with luminal B, or luminal A and who were node positive were recruited.

Neoadjuvant treatment consisted of either letrozole (2.5 mg/day) and palbociclib (125 mg daily for 3 weeks out of 4 weeks) for 19 weeks or three 21-day cycles of 5-fluorouracil (500 mg/m²), epirubicin (100 mg/m²), and cyclophosphamide (500 mg/m²), followed by three 21-day cycles of docetaxel (100 mg/m²).

The primary endpoint was the pathological complete response (pCR), defined as a residual cancer burden (RCB) of 0 to 1. Results, which have already been reported, showed equivalent, but perhaps disappointingly low, pathological responses in both the letrozole/palbociclib and chemotherapy arms (3.8% and 5.9%, respectively).

There were, however, identical clinical responses (at around 75%) and “encouraging biomarker responses in the Prosigna-defined high risk luminal breast cancer population,” Dr. Delaloge said.

The NeoPAL findings were on par with those of the CORALLEEN study, Dr. Delaloge suggested. That trial, as Dr. Rugo has also pointed out, was conducted in 106 patients with luminal B early breast cancer and used a combination of letrozole and the CDK 4/6 inhibitor ribociclib (Kisquali).
 

Future studies needed

NeoPAL “is a small study with relatively short follow-up even for hormone receptor-positive, high-risk disease,” Dr. Rugo observed. However, she qualified “this short follow-up can be very meaningful in high-risk disease.” as shown by other CDK 4/6 inhibitor trials.

Dr. Rugo also noted: “Short-term biologic endpoints are clearly more informative following and during neoadjuvant endocrine therapy than pCR and this trial, as well as the data from previous studies, indicates that this is the case.”

Further, Dr. Rugo said: “Antiproliferative response is enhanced with CDK 4/6 inhibitors, but this doesn’t seem to translate into a difference in pCR. The lack of impact on longer term, outcome to date, provides support for ongoing trials.”

Two such trials are already underway. The 200-patient CARABELA trial started recruitment in March last year and is comparing endocrine therapy with letrozole plus the CDK 4/6 inhibitor abemaciclib (Verzenio) to standard chemotherapy in patients with hormone receptor–positive, high-risk Ki67 disease.

Then there is the ADAPTcycle trial, a large open-label, phase 3 trial that is randomizing patients based on Ki67 and recurrence score after a short preoperative induction with endocrine therapy to postoperative chemotherapy or to 2 years of endocrine therapy plus ribociclib, with both arms receiving a standard course of 5 years of endocrine therapy.

“These two studies have provided interesting information that will help us design studies in the future,” said Dr. Rugo.

Not only that, but they will also help “investigate the subgroups of patients that benefit the most from CDK 4/6 inhibitors and better study neoadjuvant endocrine therapy which is an important option for patients that can be evaluated in terms of its efficacy by short term measures of antiproliferative response.”

NeoPAL was sponsored by UNICANCER with funding from Pfizer and NanoString Technologies. Dr. Delaloge disclosed receiving research grants or funding via her institution from Pfizer, AstraZeneca, Roche, Merck, Sanofi, Lilly, Novartis, BMS, Orion, Daiichi, Puma, and Pierre Fabre. Dr. Rugo reported receipt of grants via her institution to perform clinical trials from Pfizer and multiple other companies. She disclosed receiving honoraria from PUMA, Samsung, and Mylan.

Three-year survival rates were similarly high among postmenopausal women with high-risk early luminal breast cancer who were treated with either the neoadjuvant combination of letrozole and palbociclib (Ibrance) or standard neoadjuvant chemotherapy in the phase 2 NeoPAL study.

Progression-free survival (PFS) was a respective 86.7% and 87.2%, with a hazard ratio (HR) of 1.01 (P = .98) comparing the endocrine therapy and cyclin-dependent kinase (CDK) 4/6 inhibitor combination versus FEC/taxane chemotherapy.

There were also no differences between the two treatment arms in terms of invasive disease-free survival (iDFS, HR = 0.83, P = .71) or breast cancer–specific survival (BCSS), although the latter was an exploratory endpoint alongside overall survival (OS).

“The lack of difference is impressive,” said Hope S. Rugo, MD, FASCO, who commented independently on the study’s findings after their presentation at the European Society for Medical Oncology: Breast Cancer virtual meeting.

“Overall survival in patients who received chemotherapy appears to be better, but the very small numbers here make interpretation of this difference impossible,” observed Dr. Rugo, professor of medicine at the University of California San Francisco’s Helen Diller Family Comprehensive Cancer Center.

“Unfortunately, this study is underpowered for definitive conclusions,” acknowledged study investigator Suzette Delaloge, MD, associate professor of medical oncology at Institut Gustave Roussy in Villejuif, France.

However, “it shows that the nonchemotherapy, preoperative letrozole/palbociclib approach deserves further exploration and could be an option for a chemotherapy-free regimen in some specific cases.”
 

Primary data already reported

The NeoPAL study was an open-label, randomized study conducted in 27 centers throughout France that compared the preoperative use of letrozole plus palbociclib to neoadjuvant chemotherapy in 106 postmenopausal patients with either luminal A or B node-positive disease.

Patients were considered for inclusion in the trial if they had been newly diagnosed with estrogen receptor (ER)-positive, HER2-negative stage I-III breast cancer and were not candidates for breast conservation. Genetic testing was used to confirm that only those with luminal B, or luminal A and who were node positive were recruited.

Neoadjuvant treatment consisted of either letrozole (2.5 mg/day) and palbociclib (125 mg daily for 3 weeks out of 4 weeks) for 19 weeks or three 21-day cycles of 5-fluorouracil (500 mg/m²), epirubicin (100 mg/m²), and cyclophosphamide (500 mg/m²), followed by three 21-day cycles of docetaxel (100 mg/m²).

The primary endpoint was the pathological complete response (pCR), defined as a residual cancer burden (RCB) of 0 to 1. Results, which have already been reported, showed equivalent, but perhaps disappointingly low, pathological responses in both the letrozole/palbociclib and chemotherapy arms (3.8% and 5.9%, respectively).

There were, however, identical clinical responses (at around 75%) and “encouraging biomarker responses in the Prosigna-defined high risk luminal breast cancer population,” Dr. Delaloge said.

The NeoPAL findings were on par with those of the CORALLEEN study, Dr. Delaloge suggested. That trial, as Dr. Rugo has also pointed out, was conducted in 106 patients with luminal B early breast cancer and used a combination of letrozole and the CDK 4/6 inhibitor ribociclib (Kisquali).
 

Future studies needed

NeoPAL “is a small study with relatively short follow-up even for hormone receptor-positive, high-risk disease,” Dr. Rugo observed. However, she qualified “this short follow-up can be very meaningful in high-risk disease.” as shown by other CDK 4/6 inhibitor trials.

Dr. Rugo also noted: “Short-term biologic endpoints are clearly more informative following and during neoadjuvant endocrine therapy than pCR and this trial, as well as the data from previous studies, indicates that this is the case.”

Further, Dr. Rugo said: “Antiproliferative response is enhanced with CDK 4/6 inhibitors, but this doesn’t seem to translate into a difference in pCR. The lack of impact on longer term, outcome to date, provides support for ongoing trials.”

Two such trials are already underway. The 200-patient CARABELA trial started recruitment in March last year and is comparing endocrine therapy with letrozole plus the CDK 4/6 inhibitor abemaciclib (Verzenio) to standard chemotherapy in patients with hormone receptor–positive, high-risk Ki67 disease.

Then there is the ADAPTcycle trial, a large open-label, phase 3 trial that is randomizing patients based on Ki67 and recurrence score after a short preoperative induction with endocrine therapy to postoperative chemotherapy or to 2 years of endocrine therapy plus ribociclib, with both arms receiving a standard course of 5 years of endocrine therapy.

“These two studies have provided interesting information that will help us design studies in the future,” said Dr. Rugo.

Not only that, but they will also help “investigate the subgroups of patients that benefit the most from CDK 4/6 inhibitors and better study neoadjuvant endocrine therapy which is an important option for patients that can be evaluated in terms of its efficacy by short term measures of antiproliferative response.”

NeoPAL was sponsored by UNICANCER with funding from Pfizer and NanoString Technologies. Dr. Delaloge disclosed receiving research grants or funding via her institution from Pfizer, AstraZeneca, Roche, Merck, Sanofi, Lilly, Novartis, BMS, Orion, Daiichi, Puma, and Pierre Fabre. Dr. Rugo reported receipt of grants via her institution to perform clinical trials from Pfizer and multiple other companies. She disclosed receiving honoraria from PUMA, Samsung, and Mylan.