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SGLT2 inhibitors, developed for T2D, now ‘belong to cardiologists and nephrologists’
It’s passé to think of the sodium-glucose cotransporter 2 (SGLT2) inhibitor drugs as agents that primarily treat hyperglycemia because their major clinical role has rapidly morphed into treating or preventing heart failure and chronic kidney disease.
This change suddenly thrust primary responsibility for prescribing these drug into the hands of cardiologists and nephrologists, though endocrinologists, diabetologists, and primary care physicians remain in the prescribing mix, experts agreed at the virtual annual scientific sessions of the American Diabetes Association.
“Glucose lowering plays little or no role in the cardiorenal protection from drugs in the sodium-glucose cotransporter 2 inhibitor class,” said David Z. Cherney, MD, a nephrologist and professor of medicine at the University of Toronto.
The SGLT2 inhibitor drugs “belong to cardiologists and nephrologists,” declared endocrinologist Yehuda Handelsman, MD, an endocrinologist and diabetes specialist who is medical director of The Metabolic Institute of America in Tarzana, Calif.
But therein lies a problem. “Cardiologists and nephrologists often say that they don’t want to start SGLT2 inhibitors because they do not want to interfere with the glucose reducing medications a patient takes,” Dr. Cherney added.
“Cardiologists are absolutely afraid to prescribe SGLT2 inhibitors,” claimed John J.V. McMurray MD, a professor of medical cardiology at the University of Glasgow. “Cardiologists need to talk with diabetologists about the importance of treating heart failure” in patients with type 2 diabetes (T2D), and diabetologists “need to help cardiologists understand how to use these and other effective glucose-lowering drugs that reduce cardiovascular disease risk,” said Dr. McMurray during the ADA sessions.
“I don’t think any medical specialty owns this drug class,” said Silvio E. Inzucchi, MD, professor of medicine at Yale University, New Haven, Conn., and director of the Yale Medicine Diabetes Center. “No permission is needed” from an endocrinologist for another specialist to prescribe an SGLT2 inhibitor to patients with T2D or to appropriate patients without diabetes, he maintained.
The need for greater involvement by cardiologists in prescribing SGLT2 inhibitors to patients with T2D was underscored in findings recently reported by Dr. Inzucchi and associates. They analyzed the physician encounters that patients with T2D had with cardiologists and endocrinologists during 2017 at two U.S. health systems: one centered around clinicians affiliated with Yale Medicine and Yale University, and a second with clinicians drawn from the staffs of the Saint Luke’s Health System, including Saint Luke’s Mid America Heart Institute in Kansas City, Mo.
During 2017, the two systems has outpatient encounters with 109,747 patients with T2D, who averaged 67 years of age and were roughly evenly split between women and men: 43% had prevalent cardiovascular disease, including 30% with coronary artery disease and 15% with heart failure. These patients had more than 110,000 physician visits, and the number of these consultations with a cardiologist was double the number with an endocrinologist, Dr. Inzucchi and associates recently reported (Cardiovasc Endocrinol Metab. 2020 Jun;9[2]:56-9).
Among the 30% of T2D patients with prevalent cardiovascular disease, the consultation rate with a cardiologist was four times greater than with an endocrinologist; among the 15% with heart failure, a visit with a cardiologist was nearly seven times more common that with an endocrinologist.
“Based on these data, cardiovascular specialists encouraging the use of these medications, or, if comfortable, actually prescribing these medications, would likely significantly hasten the adoption of evidence-based glucose-lowering therapies in those patients most apt to benefit from them,” concluded the study’s authors.
Dr. Cherney has been a consultant to or has received honoraria from AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, Merck, Mitsubishi Tanabe Pharma, and Sanofi. Dr. Handelsman has been a consultant to or speaker on behalf of Amarin, Amgen, Applied Therapeutic, AstraZeneca, Boehringer Ingelheim, Esperion, Gilead, Janssen, Merck, Merck-Pfizer, Novo Nordisk, Regeneron, and Sanofi. Dr. McMurray’s employer, the University of Glasgow, received payments from AstraZeneca for his involvement in trials involving dapagliflozin. Dr. Inzucchi has been a consultant to or helped run trials for Abbott, AstraZeneca, Boehringer Ingelheim, Merck, Novo Nordisk, Sanofi/Lexicon, and vTv Therapeutics.
It’s passé to think of the sodium-glucose cotransporter 2 (SGLT2) inhibitor drugs as agents that primarily treat hyperglycemia because their major clinical role has rapidly morphed into treating or preventing heart failure and chronic kidney disease.
This change suddenly thrust primary responsibility for prescribing these drug into the hands of cardiologists and nephrologists, though endocrinologists, diabetologists, and primary care physicians remain in the prescribing mix, experts agreed at the virtual annual scientific sessions of the American Diabetes Association.
“Glucose lowering plays little or no role in the cardiorenal protection from drugs in the sodium-glucose cotransporter 2 inhibitor class,” said David Z. Cherney, MD, a nephrologist and professor of medicine at the University of Toronto.
The SGLT2 inhibitor drugs “belong to cardiologists and nephrologists,” declared endocrinologist Yehuda Handelsman, MD, an endocrinologist and diabetes specialist who is medical director of The Metabolic Institute of America in Tarzana, Calif.
But therein lies a problem. “Cardiologists and nephrologists often say that they don’t want to start SGLT2 inhibitors because they do not want to interfere with the glucose reducing medications a patient takes,” Dr. Cherney added.
“Cardiologists are absolutely afraid to prescribe SGLT2 inhibitors,” claimed John J.V. McMurray MD, a professor of medical cardiology at the University of Glasgow. “Cardiologists need to talk with diabetologists about the importance of treating heart failure” in patients with type 2 diabetes (T2D), and diabetologists “need to help cardiologists understand how to use these and other effective glucose-lowering drugs that reduce cardiovascular disease risk,” said Dr. McMurray during the ADA sessions.
“I don’t think any medical specialty owns this drug class,” said Silvio E. Inzucchi, MD, professor of medicine at Yale University, New Haven, Conn., and director of the Yale Medicine Diabetes Center. “No permission is needed” from an endocrinologist for another specialist to prescribe an SGLT2 inhibitor to patients with T2D or to appropriate patients without diabetes, he maintained.
The need for greater involvement by cardiologists in prescribing SGLT2 inhibitors to patients with T2D was underscored in findings recently reported by Dr. Inzucchi and associates. They analyzed the physician encounters that patients with T2D had with cardiologists and endocrinologists during 2017 at two U.S. health systems: one centered around clinicians affiliated with Yale Medicine and Yale University, and a second with clinicians drawn from the staffs of the Saint Luke’s Health System, including Saint Luke’s Mid America Heart Institute in Kansas City, Mo.
During 2017, the two systems has outpatient encounters with 109,747 patients with T2D, who averaged 67 years of age and were roughly evenly split between women and men: 43% had prevalent cardiovascular disease, including 30% with coronary artery disease and 15% with heart failure. These patients had more than 110,000 physician visits, and the number of these consultations with a cardiologist was double the number with an endocrinologist, Dr. Inzucchi and associates recently reported (Cardiovasc Endocrinol Metab. 2020 Jun;9[2]:56-9).
Among the 30% of T2D patients with prevalent cardiovascular disease, the consultation rate with a cardiologist was four times greater than with an endocrinologist; among the 15% with heart failure, a visit with a cardiologist was nearly seven times more common that with an endocrinologist.
“Based on these data, cardiovascular specialists encouraging the use of these medications, or, if comfortable, actually prescribing these medications, would likely significantly hasten the adoption of evidence-based glucose-lowering therapies in those patients most apt to benefit from them,” concluded the study’s authors.
Dr. Cherney has been a consultant to or has received honoraria from AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, Merck, Mitsubishi Tanabe Pharma, and Sanofi. Dr. Handelsman has been a consultant to or speaker on behalf of Amarin, Amgen, Applied Therapeutic, AstraZeneca, Boehringer Ingelheim, Esperion, Gilead, Janssen, Merck, Merck-Pfizer, Novo Nordisk, Regeneron, and Sanofi. Dr. McMurray’s employer, the University of Glasgow, received payments from AstraZeneca for his involvement in trials involving dapagliflozin. Dr. Inzucchi has been a consultant to or helped run trials for Abbott, AstraZeneca, Boehringer Ingelheim, Merck, Novo Nordisk, Sanofi/Lexicon, and vTv Therapeutics.
It’s passé to think of the sodium-glucose cotransporter 2 (SGLT2) inhibitor drugs as agents that primarily treat hyperglycemia because their major clinical role has rapidly morphed into treating or preventing heart failure and chronic kidney disease.
This change suddenly thrust primary responsibility for prescribing these drug into the hands of cardiologists and nephrologists, though endocrinologists, diabetologists, and primary care physicians remain in the prescribing mix, experts agreed at the virtual annual scientific sessions of the American Diabetes Association.
“Glucose lowering plays little or no role in the cardiorenal protection from drugs in the sodium-glucose cotransporter 2 inhibitor class,” said David Z. Cherney, MD, a nephrologist and professor of medicine at the University of Toronto.
The SGLT2 inhibitor drugs “belong to cardiologists and nephrologists,” declared endocrinologist Yehuda Handelsman, MD, an endocrinologist and diabetes specialist who is medical director of The Metabolic Institute of America in Tarzana, Calif.
But therein lies a problem. “Cardiologists and nephrologists often say that they don’t want to start SGLT2 inhibitors because they do not want to interfere with the glucose reducing medications a patient takes,” Dr. Cherney added.
“Cardiologists are absolutely afraid to prescribe SGLT2 inhibitors,” claimed John J.V. McMurray MD, a professor of medical cardiology at the University of Glasgow. “Cardiologists need to talk with diabetologists about the importance of treating heart failure” in patients with type 2 diabetes (T2D), and diabetologists “need to help cardiologists understand how to use these and other effective glucose-lowering drugs that reduce cardiovascular disease risk,” said Dr. McMurray during the ADA sessions.
“I don’t think any medical specialty owns this drug class,” said Silvio E. Inzucchi, MD, professor of medicine at Yale University, New Haven, Conn., and director of the Yale Medicine Diabetes Center. “No permission is needed” from an endocrinologist for another specialist to prescribe an SGLT2 inhibitor to patients with T2D or to appropriate patients without diabetes, he maintained.
The need for greater involvement by cardiologists in prescribing SGLT2 inhibitors to patients with T2D was underscored in findings recently reported by Dr. Inzucchi and associates. They analyzed the physician encounters that patients with T2D had with cardiologists and endocrinologists during 2017 at two U.S. health systems: one centered around clinicians affiliated with Yale Medicine and Yale University, and a second with clinicians drawn from the staffs of the Saint Luke’s Health System, including Saint Luke’s Mid America Heart Institute in Kansas City, Mo.
During 2017, the two systems has outpatient encounters with 109,747 patients with T2D, who averaged 67 years of age and were roughly evenly split between women and men: 43% had prevalent cardiovascular disease, including 30% with coronary artery disease and 15% with heart failure. These patients had more than 110,000 physician visits, and the number of these consultations with a cardiologist was double the number with an endocrinologist, Dr. Inzucchi and associates recently reported (Cardiovasc Endocrinol Metab. 2020 Jun;9[2]:56-9).
Among the 30% of T2D patients with prevalent cardiovascular disease, the consultation rate with a cardiologist was four times greater than with an endocrinologist; among the 15% with heart failure, a visit with a cardiologist was nearly seven times more common that with an endocrinologist.
“Based on these data, cardiovascular specialists encouraging the use of these medications, or, if comfortable, actually prescribing these medications, would likely significantly hasten the adoption of evidence-based glucose-lowering therapies in those patients most apt to benefit from them,” concluded the study’s authors.
Dr. Cherney has been a consultant to or has received honoraria from AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, Merck, Mitsubishi Tanabe Pharma, and Sanofi. Dr. Handelsman has been a consultant to or speaker on behalf of Amarin, Amgen, Applied Therapeutic, AstraZeneca, Boehringer Ingelheim, Esperion, Gilead, Janssen, Merck, Merck-Pfizer, Novo Nordisk, Regeneron, and Sanofi. Dr. McMurray’s employer, the University of Glasgow, received payments from AstraZeneca for his involvement in trials involving dapagliflozin. Dr. Inzucchi has been a consultant to or helped run trials for Abbott, AstraZeneca, Boehringer Ingelheim, Merck, Novo Nordisk, Sanofi/Lexicon, and vTv Therapeutics.
FROM ADA 2020
Novel program cuts weight retention after gestational diabetes
An online, lifestyle-based weight loss initiative known as the Balance After Baby (BAB) program is effective at reducing weight retention a year after birth among women with recent gestational diabetes.
Specifically, results of the study were positive in women of most ethnicities, bar those of a small group of Hispanic origin.
Jacinda Nicklas, MD, from the University of Colorado at Denver, Aurora, presented findings of the BAB trial during the virtual annual scientific sessions of the American Diabetes Association. She was coprincipal investigator alongside Ellen Seely, MD, from Brigham and Women’s Hospital, Boston.
“Looking at the entire population of women on the BAB program, there was a trend in weight loss from 6 weeks postpartum to 12 months (P = .09), and significantly less postpartum weight retention at 12 months (P = .04),” Dr. Nicklas said.
“Through this effect on postpartum weight retention, the BAB program has potential to delay or prevent development of type 2 diabetes in women with recent gestational diabetes, while the web-based, remote nature of the program is scalable and very relevant in current times,” she added. “However, the lack of efficacy in Hispanic women means it needs to be modified to be successful in this ethnic group.”
Frank Qian, MD, who also presented during the same session, said the BAB program has potential as a viable way of preventing both future pregnancy complications and the progression to overt type 2 diabetes in this high-risk population.
“Large-scale epidemiologic studies show us that weight gain from pregnancy is a major risk factor for long-term cardiometabolic risk, particularly for women with a history of gestational diabetes,” he observed. “In turn, it is critical to implement lifestyle interventions that can help women get as close to the weight they were before pregnancy as possible and keep that weight off.”
Postpartum weight retention a modifiable risk factor for type 2 diabetes
Current evidence shows that a large proportion of women who develop gestational diabetes go on to develop type 2 diabetes within 10 years and that women with a history of gestational diabetes are more likely to retain or gain weight postpartum.
Dr. Nicklas also pointed out that obesity and weight gain are the strongest modifiable risk factors for type 2 diabetes.
“We know from the Diabetes Prevention Program [DPP] that an intensive lifestyle program in women who had had gestational diabetes led to a 53% reduction in type 2 diabetes,” Dr. Nicklas noted.
However, she added there were barriers to adhering to the intensive DPP program – which required 16 one-on-one meetings in the first 24 weeks – including travel, as some participants lived quite remotely, or family responsibilities. Consequently, Dr. Nicklas and colleagues developed the BAB pilot trial, which involved web-based delivery with remote coaching.
The trial involved women with a history of gestational diabetes who were, on average, 7 weeks postpartum. The key outcome was weight at 12 months, compared with both 6-week postpartum weight and prepregnancy weight.
Based on encouraging results in the pilot trial – in which the intervention group showed significant weight loss from 6-week postpartum weight and in 12-month weight retention – a larger, two-site trial was initiated, the BAB Intervention randomized, controlled trial.
Outcome measures were the same as for the pilot study. The 181 participants were aged 18-45 years, had recent gestational diabetes, and had a mean prepregnancy body mass index of approximately 29 kg/m2. Around half were college educated, and 28% were from lower income households. Overall, 48% were white, 22% Asian, 17% African American, and 13% were of other ethnicities, with just over a third being Hispanic.
The initial study visit was at 6 weeks postpartum. Women were randomized to the behavioral intervention website plus a lifestyle coach group or to a control group that consisted of a website plus knowledge links.
The intervention website required women to complete some DPP-derived and bonus modules, and also featured action plans, tracked weight and steps, and had a direct link to contact their lifestyle coach. Follow-up visits were held at 6 and 12 months and A1c, waist circumference, and height/weight were measured. A total of 86% eligible women completed the 6- and 12-month visits.
Why didn’t the BAB program work in Hispanic women?
“The overall result showed that weight change from 6 weeks postpartum to 12 months revealed a slight gain in the control group of 1.3 pounds and a loss in the intervention group of 1.8 pounds, resulting in a between-group difference of 3.1 pounds [P = .09],” reported Dr. Nicklas. Adjustment for gestational weight gain and breastfeeding had no substantial effect.
When 12-month weight retention versus prepregnancy weight was assessed, the former was halved in participants in the BAB program.
The control group gained a mean of 10.1 pounds, and those in the intervention group gained a mean of 5.3 pounds, equivalent to a difference of 4.8 pounds (P = .04).
A prespecified analysis was conducted of 120 non-Hispanic women. At 12 months, weight retention, compared with prepregnancy weight showed an increase of 9 pounds in the control group versus 1.8 pounds in the intervention group (P = .01).
By comparison, in the small group of Hispanic women only, weight retention at 12 months compared to prepregnancy weight showed a 12.7-pound increase and a 13.3-pound increase in the control and intervention groups respectively, reported Dr. Nicklas.
Addressing the key question of why the BAB program was ineffective in Hispanic women, Dr. Nicklas said, “The literature tells us that low income Hispanic women are twice as likely to experience postpartum weight retention compared to white non-Hispanic women. But we also know that low-income Hispanic women generally engage less with interventions, and there is a higher acceptance of overweight among this ethnic group.”
The researchers hope to follow the women from their trial to determine who progresses to type 2 diabetes.
“Hispanic women are a high-risk population for gestational diabetes and type 2 diabetes, and we plan to identify the best options to help Hispanic women with a history of gestational diabetes prevent type 2 diabetes,” Dr. Nicklas said in an interview.
Dr. Qian also remarked on the differences observed in the weight loss outcomes for non-Hispanic versus Hispanic women, noting that it highlights the importance of studying lifestyle interventions in diverse populations. “Environmental and cultural factors that may differ across different racial or ethnic groups could impact the effectiveness of such interventions.
Dr. Nicklas and Dr. Qian have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
An online, lifestyle-based weight loss initiative known as the Balance After Baby (BAB) program is effective at reducing weight retention a year after birth among women with recent gestational diabetes.
Specifically, results of the study were positive in women of most ethnicities, bar those of a small group of Hispanic origin.
Jacinda Nicklas, MD, from the University of Colorado at Denver, Aurora, presented findings of the BAB trial during the virtual annual scientific sessions of the American Diabetes Association. She was coprincipal investigator alongside Ellen Seely, MD, from Brigham and Women’s Hospital, Boston.
“Looking at the entire population of women on the BAB program, there was a trend in weight loss from 6 weeks postpartum to 12 months (P = .09), and significantly less postpartum weight retention at 12 months (P = .04),” Dr. Nicklas said.
“Through this effect on postpartum weight retention, the BAB program has potential to delay or prevent development of type 2 diabetes in women with recent gestational diabetes, while the web-based, remote nature of the program is scalable and very relevant in current times,” she added. “However, the lack of efficacy in Hispanic women means it needs to be modified to be successful in this ethnic group.”
Frank Qian, MD, who also presented during the same session, said the BAB program has potential as a viable way of preventing both future pregnancy complications and the progression to overt type 2 diabetes in this high-risk population.
“Large-scale epidemiologic studies show us that weight gain from pregnancy is a major risk factor for long-term cardiometabolic risk, particularly for women with a history of gestational diabetes,” he observed. “In turn, it is critical to implement lifestyle interventions that can help women get as close to the weight they were before pregnancy as possible and keep that weight off.”
Postpartum weight retention a modifiable risk factor for type 2 diabetes
Current evidence shows that a large proportion of women who develop gestational diabetes go on to develop type 2 diabetes within 10 years and that women with a history of gestational diabetes are more likely to retain or gain weight postpartum.
Dr. Nicklas also pointed out that obesity and weight gain are the strongest modifiable risk factors for type 2 diabetes.
“We know from the Diabetes Prevention Program [DPP] that an intensive lifestyle program in women who had had gestational diabetes led to a 53% reduction in type 2 diabetes,” Dr. Nicklas noted.
However, she added there were barriers to adhering to the intensive DPP program – which required 16 one-on-one meetings in the first 24 weeks – including travel, as some participants lived quite remotely, or family responsibilities. Consequently, Dr. Nicklas and colleagues developed the BAB pilot trial, which involved web-based delivery with remote coaching.
The trial involved women with a history of gestational diabetes who were, on average, 7 weeks postpartum. The key outcome was weight at 12 months, compared with both 6-week postpartum weight and prepregnancy weight.
Based on encouraging results in the pilot trial – in which the intervention group showed significant weight loss from 6-week postpartum weight and in 12-month weight retention – a larger, two-site trial was initiated, the BAB Intervention randomized, controlled trial.
Outcome measures were the same as for the pilot study. The 181 participants were aged 18-45 years, had recent gestational diabetes, and had a mean prepregnancy body mass index of approximately 29 kg/m2. Around half were college educated, and 28% were from lower income households. Overall, 48% were white, 22% Asian, 17% African American, and 13% were of other ethnicities, with just over a third being Hispanic.
The initial study visit was at 6 weeks postpartum. Women were randomized to the behavioral intervention website plus a lifestyle coach group or to a control group that consisted of a website plus knowledge links.
The intervention website required women to complete some DPP-derived and bonus modules, and also featured action plans, tracked weight and steps, and had a direct link to contact their lifestyle coach. Follow-up visits were held at 6 and 12 months and A1c, waist circumference, and height/weight were measured. A total of 86% eligible women completed the 6- and 12-month visits.
Why didn’t the BAB program work in Hispanic women?
“The overall result showed that weight change from 6 weeks postpartum to 12 months revealed a slight gain in the control group of 1.3 pounds and a loss in the intervention group of 1.8 pounds, resulting in a between-group difference of 3.1 pounds [P = .09],” reported Dr. Nicklas. Adjustment for gestational weight gain and breastfeeding had no substantial effect.
When 12-month weight retention versus prepregnancy weight was assessed, the former was halved in participants in the BAB program.
The control group gained a mean of 10.1 pounds, and those in the intervention group gained a mean of 5.3 pounds, equivalent to a difference of 4.8 pounds (P = .04).
A prespecified analysis was conducted of 120 non-Hispanic women. At 12 months, weight retention, compared with prepregnancy weight showed an increase of 9 pounds in the control group versus 1.8 pounds in the intervention group (P = .01).
By comparison, in the small group of Hispanic women only, weight retention at 12 months compared to prepregnancy weight showed a 12.7-pound increase and a 13.3-pound increase in the control and intervention groups respectively, reported Dr. Nicklas.
Addressing the key question of why the BAB program was ineffective in Hispanic women, Dr. Nicklas said, “The literature tells us that low income Hispanic women are twice as likely to experience postpartum weight retention compared to white non-Hispanic women. But we also know that low-income Hispanic women generally engage less with interventions, and there is a higher acceptance of overweight among this ethnic group.”
The researchers hope to follow the women from their trial to determine who progresses to type 2 diabetes.
“Hispanic women are a high-risk population for gestational diabetes and type 2 diabetes, and we plan to identify the best options to help Hispanic women with a history of gestational diabetes prevent type 2 diabetes,” Dr. Nicklas said in an interview.
Dr. Qian also remarked on the differences observed in the weight loss outcomes for non-Hispanic versus Hispanic women, noting that it highlights the importance of studying lifestyle interventions in diverse populations. “Environmental and cultural factors that may differ across different racial or ethnic groups could impact the effectiveness of such interventions.
Dr. Nicklas and Dr. Qian have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
An online, lifestyle-based weight loss initiative known as the Balance After Baby (BAB) program is effective at reducing weight retention a year after birth among women with recent gestational diabetes.
Specifically, results of the study were positive in women of most ethnicities, bar those of a small group of Hispanic origin.
Jacinda Nicklas, MD, from the University of Colorado at Denver, Aurora, presented findings of the BAB trial during the virtual annual scientific sessions of the American Diabetes Association. She was coprincipal investigator alongside Ellen Seely, MD, from Brigham and Women’s Hospital, Boston.
“Looking at the entire population of women on the BAB program, there was a trend in weight loss from 6 weeks postpartum to 12 months (P = .09), and significantly less postpartum weight retention at 12 months (P = .04),” Dr. Nicklas said.
“Through this effect on postpartum weight retention, the BAB program has potential to delay or prevent development of type 2 diabetes in women with recent gestational diabetes, while the web-based, remote nature of the program is scalable and very relevant in current times,” she added. “However, the lack of efficacy in Hispanic women means it needs to be modified to be successful in this ethnic group.”
Frank Qian, MD, who also presented during the same session, said the BAB program has potential as a viable way of preventing both future pregnancy complications and the progression to overt type 2 diabetes in this high-risk population.
“Large-scale epidemiologic studies show us that weight gain from pregnancy is a major risk factor for long-term cardiometabolic risk, particularly for women with a history of gestational diabetes,” he observed. “In turn, it is critical to implement lifestyle interventions that can help women get as close to the weight they were before pregnancy as possible and keep that weight off.”
Postpartum weight retention a modifiable risk factor for type 2 diabetes
Current evidence shows that a large proportion of women who develop gestational diabetes go on to develop type 2 diabetes within 10 years and that women with a history of gestational diabetes are more likely to retain or gain weight postpartum.
Dr. Nicklas also pointed out that obesity and weight gain are the strongest modifiable risk factors for type 2 diabetes.
“We know from the Diabetes Prevention Program [DPP] that an intensive lifestyle program in women who had had gestational diabetes led to a 53% reduction in type 2 diabetes,” Dr. Nicklas noted.
However, she added there were barriers to adhering to the intensive DPP program – which required 16 one-on-one meetings in the first 24 weeks – including travel, as some participants lived quite remotely, or family responsibilities. Consequently, Dr. Nicklas and colleagues developed the BAB pilot trial, which involved web-based delivery with remote coaching.
The trial involved women with a history of gestational diabetes who were, on average, 7 weeks postpartum. The key outcome was weight at 12 months, compared with both 6-week postpartum weight and prepregnancy weight.
Based on encouraging results in the pilot trial – in which the intervention group showed significant weight loss from 6-week postpartum weight and in 12-month weight retention – a larger, two-site trial was initiated, the BAB Intervention randomized, controlled trial.
Outcome measures were the same as for the pilot study. The 181 participants were aged 18-45 years, had recent gestational diabetes, and had a mean prepregnancy body mass index of approximately 29 kg/m2. Around half were college educated, and 28% were from lower income households. Overall, 48% were white, 22% Asian, 17% African American, and 13% were of other ethnicities, with just over a third being Hispanic.
The initial study visit was at 6 weeks postpartum. Women were randomized to the behavioral intervention website plus a lifestyle coach group or to a control group that consisted of a website plus knowledge links.
The intervention website required women to complete some DPP-derived and bonus modules, and also featured action plans, tracked weight and steps, and had a direct link to contact their lifestyle coach. Follow-up visits were held at 6 and 12 months and A1c, waist circumference, and height/weight were measured. A total of 86% eligible women completed the 6- and 12-month visits.
Why didn’t the BAB program work in Hispanic women?
“The overall result showed that weight change from 6 weeks postpartum to 12 months revealed a slight gain in the control group of 1.3 pounds and a loss in the intervention group of 1.8 pounds, resulting in a between-group difference of 3.1 pounds [P = .09],” reported Dr. Nicklas. Adjustment for gestational weight gain and breastfeeding had no substantial effect.
When 12-month weight retention versus prepregnancy weight was assessed, the former was halved in participants in the BAB program.
The control group gained a mean of 10.1 pounds, and those in the intervention group gained a mean of 5.3 pounds, equivalent to a difference of 4.8 pounds (P = .04).
A prespecified analysis was conducted of 120 non-Hispanic women. At 12 months, weight retention, compared with prepregnancy weight showed an increase of 9 pounds in the control group versus 1.8 pounds in the intervention group (P = .01).
By comparison, in the small group of Hispanic women only, weight retention at 12 months compared to prepregnancy weight showed a 12.7-pound increase and a 13.3-pound increase in the control and intervention groups respectively, reported Dr. Nicklas.
Addressing the key question of why the BAB program was ineffective in Hispanic women, Dr. Nicklas said, “The literature tells us that low income Hispanic women are twice as likely to experience postpartum weight retention compared to white non-Hispanic women. But we also know that low-income Hispanic women generally engage less with interventions, and there is a higher acceptance of overweight among this ethnic group.”
The researchers hope to follow the women from their trial to determine who progresses to type 2 diabetes.
“Hispanic women are a high-risk population for gestational diabetes and type 2 diabetes, and we plan to identify the best options to help Hispanic women with a history of gestational diabetes prevent type 2 diabetes,” Dr. Nicklas said in an interview.
Dr. Qian also remarked on the differences observed in the weight loss outcomes for non-Hispanic versus Hispanic women, noting that it highlights the importance of studying lifestyle interventions in diverse populations. “Environmental and cultural factors that may differ across different racial or ethnic groups could impact the effectiveness of such interventions.
Dr. Nicklas and Dr. Qian have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM ADA 2020
MRI reliably identifies significant prostate cancer
Prostate cancers that are missed on multiparametric (mp) MRI are small and “not life-threatening,” according to an analysis of data from the Prostate MR Imaging Study (PROMIS).
“Our work suggests that MRI scans of the prostate appear to deliver crucial information about a man’s risk of dying from prostate cancer, even before he has a biopsy,” said Joseph Norris, BM BS, from University College London.
“This may mean that we can finally move prostate cancer to a position in which we can use imaging as the primary tool to direct further investigations, treatment, and prediction of risk,” he told Medscape Medical News.
This is “a position that all other solid organ cancers have reached,” said Norris, who will present the findings at the upcoming virtual European Association of Urology 2020 Congress.
All 576 PROMIS participants underwent an mpMRI scan, a transrectal ultrasonography (TRUS)–guided biopsy, and a template prostate mapping (TPM) biopsy taken at 5-mm intervals across the entire prostate.
PROMIS researchers previously showed that mpMRI had a 93% sensitivity for clinically significant cancer, whereas TRUS biopsy had only a 48% sensitivity, as reported by Medscape Medical News. And they concluded that the use of mpMRI as a first-line diagnostic tool could prevent 27% of all biopsies, which can have serious adverse effects, such as pain, urinary problems, infection, bleeding, and erectile dysfunction.
However, in their study looking at the accuracy of mpMRI and TRUS biopsy, the researchers did not investigate the severity of the 7% of cancers that mpMRI missed. “What if those missed cancers are, in fact, aggressive? That’s what we set out to examine,” Norris explained.
So he and his colleagues conducted a post ad hoc analysis of the PROMIS participants in whom clinically significant cancer had been detected with TPM biopsy to see which of those cancers had been detected with mpMRI. The findings were published online in European Urology.
Cancers met the strict definition of clinically significant if they had a Gleason score of at least 4+3 for a tumor of any length, or a maximum cancer core length (MCCL) greater than 6 mm for a cancer of any grade. They met the less-strict definition if they had a Gleason score of at least 3+4 for a tumor of any length, or a MCCL greater than 4 mm for a cancer of any grade.
In PROMIS, TPM biopsy detected 230 cancers that met the strict definition of clinically significant and 331 that met the less-strict definition.
Overall Gleason scores were significantly lower for the 17 strict-definition cancers not detected with 1.5 T mpMRI than for those detected with mpMRI (P = .0007), as were maximum Gleason scores (P < .0001).
Median MCCL was 3 mm shorter for all 17 tumors missed with mpMRI than for those detected with mpMRI (5 vs 8 mm; P < .0001).
mpMRI detected all tumors identified on TPM biopsy that had an overall Gleason score greater than 3+4 (Gleason grades 3 to 5) or a maximum Gleason score greater than 4+3 (Gleason grades 4 and 5).
“This finding is important, given that in PROMIS, no men with an overall Gleason score of 4+3 had cancer missed by MRI, indicating that actually MRI may be able to identify all truly significant cancers,” said Norris.
Adding PSA Density Threshold
To further assess cancers missed on mpMRI, the researchers looked at prostate-specific antigen (PSA) density, calculated as total PSA level (ng/mL) divided by prostate volume (mL).
“We found that if we applied a threshold PSA density to men with normal-looking MRI scans, we could reduce the proportion of missed significant cancer to just 5%. This is exciting; it means we can make MRI an even more effective test for prostate cancer in a very simple way,” Norris reported.
“These data show that no highly aggressive prostate cancers were missed by MRI, either at the level of the whole prostate or at the individual needle level,” said Norris. This should lead to positive outcomes in the long term.
And since the PROMIS data were gathered, MRI technology has improved, he said. The “MRI scanners in PROMIS were 1.5 Tesla,” whereas today’s machines are 3.0 T, which could increase the detection of significant prostate cancer.
In fact, “our analysis here potentially overestimates the amount of undetected disease,” he noted.
Prostate cancer that is not clinically significant is often monitored with active surveillance, so “invisible” cancers missed on mpMRI could actually be looked at in a positive light, he explained.
Variation in technique, interpretation
But the quality of care when it comes to the diagnosis of prostate cancer is not equal everywhere, said Gerald Andriole, MD, from the Washington School of Medicine in St. Louis, Missouri.
“When you get an MRI in a center that doesn’t do a lot of prostate cancer testing, you may not have the best software and you may have a radiologist who is not that experienced,” he told Medscape Medical News. Specialized cancer centers of excellence tend to do a great job finding prostate cancer, “but other centers have high significant-miss rates or high overcall rates.”
“The elephant in the room remains the considerable variation in technique and interobserver interpretation of prostate mpMRI,” write Steven Monda, MD, and Marc Dall’Era, MD, both from UC Davis Health in Sacramento, California, in an editorial that accompanies the new PROMIS analysis.
“These problems must be addressed and remedied in each institution before relying on results from PROMIS to drive changes in clinical practice,” they add.
Norris, Andriole, Monda, and Dall’Era have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Prostate cancers that are missed on multiparametric (mp) MRI are small and “not life-threatening,” according to an analysis of data from the Prostate MR Imaging Study (PROMIS).
“Our work suggests that MRI scans of the prostate appear to deliver crucial information about a man’s risk of dying from prostate cancer, even before he has a biopsy,” said Joseph Norris, BM BS, from University College London.
“This may mean that we can finally move prostate cancer to a position in which we can use imaging as the primary tool to direct further investigations, treatment, and prediction of risk,” he told Medscape Medical News.
This is “a position that all other solid organ cancers have reached,” said Norris, who will present the findings at the upcoming virtual European Association of Urology 2020 Congress.
All 576 PROMIS participants underwent an mpMRI scan, a transrectal ultrasonography (TRUS)–guided biopsy, and a template prostate mapping (TPM) biopsy taken at 5-mm intervals across the entire prostate.
PROMIS researchers previously showed that mpMRI had a 93% sensitivity for clinically significant cancer, whereas TRUS biopsy had only a 48% sensitivity, as reported by Medscape Medical News. And they concluded that the use of mpMRI as a first-line diagnostic tool could prevent 27% of all biopsies, which can have serious adverse effects, such as pain, urinary problems, infection, bleeding, and erectile dysfunction.
However, in their study looking at the accuracy of mpMRI and TRUS biopsy, the researchers did not investigate the severity of the 7% of cancers that mpMRI missed. “What if those missed cancers are, in fact, aggressive? That’s what we set out to examine,” Norris explained.
So he and his colleagues conducted a post ad hoc analysis of the PROMIS participants in whom clinically significant cancer had been detected with TPM biopsy to see which of those cancers had been detected with mpMRI. The findings were published online in European Urology.
Cancers met the strict definition of clinically significant if they had a Gleason score of at least 4+3 for a tumor of any length, or a maximum cancer core length (MCCL) greater than 6 mm for a cancer of any grade. They met the less-strict definition if they had a Gleason score of at least 3+4 for a tumor of any length, or a MCCL greater than 4 mm for a cancer of any grade.
In PROMIS, TPM biopsy detected 230 cancers that met the strict definition of clinically significant and 331 that met the less-strict definition.
Overall Gleason scores were significantly lower for the 17 strict-definition cancers not detected with 1.5 T mpMRI than for those detected with mpMRI (P = .0007), as were maximum Gleason scores (P < .0001).
Median MCCL was 3 mm shorter for all 17 tumors missed with mpMRI than for those detected with mpMRI (5 vs 8 mm; P < .0001).
mpMRI detected all tumors identified on TPM biopsy that had an overall Gleason score greater than 3+4 (Gleason grades 3 to 5) or a maximum Gleason score greater than 4+3 (Gleason grades 4 and 5).
“This finding is important, given that in PROMIS, no men with an overall Gleason score of 4+3 had cancer missed by MRI, indicating that actually MRI may be able to identify all truly significant cancers,” said Norris.
Adding PSA Density Threshold
To further assess cancers missed on mpMRI, the researchers looked at prostate-specific antigen (PSA) density, calculated as total PSA level (ng/mL) divided by prostate volume (mL).
“We found that if we applied a threshold PSA density to men with normal-looking MRI scans, we could reduce the proportion of missed significant cancer to just 5%. This is exciting; it means we can make MRI an even more effective test for prostate cancer in a very simple way,” Norris reported.
“These data show that no highly aggressive prostate cancers were missed by MRI, either at the level of the whole prostate or at the individual needle level,” said Norris. This should lead to positive outcomes in the long term.
And since the PROMIS data were gathered, MRI technology has improved, he said. The “MRI scanners in PROMIS were 1.5 Tesla,” whereas today’s machines are 3.0 T, which could increase the detection of significant prostate cancer.
In fact, “our analysis here potentially overestimates the amount of undetected disease,” he noted.
Prostate cancer that is not clinically significant is often monitored with active surveillance, so “invisible” cancers missed on mpMRI could actually be looked at in a positive light, he explained.
Variation in technique, interpretation
But the quality of care when it comes to the diagnosis of prostate cancer is not equal everywhere, said Gerald Andriole, MD, from the Washington School of Medicine in St. Louis, Missouri.
“When you get an MRI in a center that doesn’t do a lot of prostate cancer testing, you may not have the best software and you may have a radiologist who is not that experienced,” he told Medscape Medical News. Specialized cancer centers of excellence tend to do a great job finding prostate cancer, “but other centers have high significant-miss rates or high overcall rates.”
“The elephant in the room remains the considerable variation in technique and interobserver interpretation of prostate mpMRI,” write Steven Monda, MD, and Marc Dall’Era, MD, both from UC Davis Health in Sacramento, California, in an editorial that accompanies the new PROMIS analysis.
“These problems must be addressed and remedied in each institution before relying on results from PROMIS to drive changes in clinical practice,” they add.
Norris, Andriole, Monda, and Dall’Era have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Prostate cancers that are missed on multiparametric (mp) MRI are small and “not life-threatening,” according to an analysis of data from the Prostate MR Imaging Study (PROMIS).
“Our work suggests that MRI scans of the prostate appear to deliver crucial information about a man’s risk of dying from prostate cancer, even before he has a biopsy,” said Joseph Norris, BM BS, from University College London.
“This may mean that we can finally move prostate cancer to a position in which we can use imaging as the primary tool to direct further investigations, treatment, and prediction of risk,” he told Medscape Medical News.
This is “a position that all other solid organ cancers have reached,” said Norris, who will present the findings at the upcoming virtual European Association of Urology 2020 Congress.
All 576 PROMIS participants underwent an mpMRI scan, a transrectal ultrasonography (TRUS)–guided biopsy, and a template prostate mapping (TPM) biopsy taken at 5-mm intervals across the entire prostate.
PROMIS researchers previously showed that mpMRI had a 93% sensitivity for clinically significant cancer, whereas TRUS biopsy had only a 48% sensitivity, as reported by Medscape Medical News. And they concluded that the use of mpMRI as a first-line diagnostic tool could prevent 27% of all biopsies, which can have serious adverse effects, such as pain, urinary problems, infection, bleeding, and erectile dysfunction.
However, in their study looking at the accuracy of mpMRI and TRUS biopsy, the researchers did not investigate the severity of the 7% of cancers that mpMRI missed. “What if those missed cancers are, in fact, aggressive? That’s what we set out to examine,” Norris explained.
So he and his colleagues conducted a post ad hoc analysis of the PROMIS participants in whom clinically significant cancer had been detected with TPM biopsy to see which of those cancers had been detected with mpMRI. The findings were published online in European Urology.
Cancers met the strict definition of clinically significant if they had a Gleason score of at least 4+3 for a tumor of any length, or a maximum cancer core length (MCCL) greater than 6 mm for a cancer of any grade. They met the less-strict definition if they had a Gleason score of at least 3+4 for a tumor of any length, or a MCCL greater than 4 mm for a cancer of any grade.
In PROMIS, TPM biopsy detected 230 cancers that met the strict definition of clinically significant and 331 that met the less-strict definition.
Overall Gleason scores were significantly lower for the 17 strict-definition cancers not detected with 1.5 T mpMRI than for those detected with mpMRI (P = .0007), as were maximum Gleason scores (P < .0001).
Median MCCL was 3 mm shorter for all 17 tumors missed with mpMRI than for those detected with mpMRI (5 vs 8 mm; P < .0001).
mpMRI detected all tumors identified on TPM biopsy that had an overall Gleason score greater than 3+4 (Gleason grades 3 to 5) or a maximum Gleason score greater than 4+3 (Gleason grades 4 and 5).
“This finding is important, given that in PROMIS, no men with an overall Gleason score of 4+3 had cancer missed by MRI, indicating that actually MRI may be able to identify all truly significant cancers,” said Norris.
Adding PSA Density Threshold
To further assess cancers missed on mpMRI, the researchers looked at prostate-specific antigen (PSA) density, calculated as total PSA level (ng/mL) divided by prostate volume (mL).
“We found that if we applied a threshold PSA density to men with normal-looking MRI scans, we could reduce the proportion of missed significant cancer to just 5%. This is exciting; it means we can make MRI an even more effective test for prostate cancer in a very simple way,” Norris reported.
“These data show that no highly aggressive prostate cancers were missed by MRI, either at the level of the whole prostate or at the individual needle level,” said Norris. This should lead to positive outcomes in the long term.
And since the PROMIS data were gathered, MRI technology has improved, he said. The “MRI scanners in PROMIS were 1.5 Tesla,” whereas today’s machines are 3.0 T, which could increase the detection of significant prostate cancer.
In fact, “our analysis here potentially overestimates the amount of undetected disease,” he noted.
Prostate cancer that is not clinically significant is often monitored with active surveillance, so “invisible” cancers missed on mpMRI could actually be looked at in a positive light, he explained.
Variation in technique, interpretation
But the quality of care when it comes to the diagnosis of prostate cancer is not equal everywhere, said Gerald Andriole, MD, from the Washington School of Medicine in St. Louis, Missouri.
“When you get an MRI in a center that doesn’t do a lot of prostate cancer testing, you may not have the best software and you may have a radiologist who is not that experienced,” he told Medscape Medical News. Specialized cancer centers of excellence tend to do a great job finding prostate cancer, “but other centers have high significant-miss rates or high overcall rates.”
“The elephant in the room remains the considerable variation in technique and interobserver interpretation of prostate mpMRI,” write Steven Monda, MD, and Marc Dall’Era, MD, both from UC Davis Health in Sacramento, California, in an editorial that accompanies the new PROMIS analysis.
“These problems must be addressed and remedied in each institution before relying on results from PROMIS to drive changes in clinical practice,” they add.
Norris, Andriole, Monda, and Dall’Era have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Psychiatry trainees subjected to high levels of physical, sexual, verbal abuse from patients
More than 80% of psychiatric trainees have experienced some kind of verbal, physical, or sexual assault from patients, and approximately one-third have been physically attacked multiple times, new survey results show.
Such incidents, said study investigator Victor Pereira-Sanchez, MD, from the department of child and adolescent psychiatry at New York University take a toll on the trainees’ well-being and may ultimately affect the quality of patient care.
“The extent of violence against psychiatric trainees is alarming and calls for the implementation of effective training, prevention, and intervention measures,” Dr. Pereira-Sanchez said in an interview.
The findings were presented at the European Psychiatric Association (EPA) 2020 Congress, which was virtual this year because of the COVID-19 pandemic.
Widespread problem
Violence against health care professionals is widespread among clinicians in EDs with psychiatry trainees “more exposed and vulnerable,” Dr. Pereira-Sanchez said during his presentation.
In 2017, the European Federation of Psychiatric Trainees established a group of researchers to describe “the extent and consequences of violence against psychiatric trainees in Europe and beyond,” he said. The group developed a 15-item questionnaire asking young clinicians about experiences of physical, sexual, and verbal assault at work. The survey was posted online by partner institutions via social media.
A total of 827 psychiatric trainees, the majority of whom were from France and the United Kingdom, completed the survey. Respondents had an average age of 31 years, and 68% were women. On average, respondents had completed 51.3% of their psychiatric training.
with 92.0% reporting verbal assaults, 44.1% physical assaults, and 9.3% sexual assaults. In addition, 14.2% had been assaulted once, 51.9% had been assaulted two to five times, and 33.9% had been assaulted more than five times during their training. Results also showed that assaults were more likely to occur on an inpatient ward (63.4%) or the ED (56.9%), although 37.2% occurred in an outpatient setting and 4.2% in community settings. The majority of respondents (69.0%) did not report their assaults, and 67.3% did not call police or security personnel.
The most common emotions experienced by trainees following an assault were fear, rage, and anxiety. Guilt, sadness, feeling unsupported, and self-doubt were also reported.
Dr. Pereira-Sanchez noted the low rate of reported assaults is likely because trainees view it as “part of the job to get insulted, it’s part of the job to suffer minor physical violence.”
Individuals who did report assaults tended to be those who had been assaulted more than five times and those who felt more anxiety, rage, and fear.
“Basically, those who experience more emotional consequences and physical consequences tend to report more,” he said.
In addition, trainees tended to report assaults if they worked in an institution that provided protocols and training in prevention and management of patient aggression.
However, he added, most respondents reported they were not aware of their center’s protocols with respect to assaults and were not trained in the management or prevention of patient violence.
Management tools key
Commenting on the study in an interview, Renee Binder, MD, professor of psychiatry at University of California, San Francisco, said the findings show that, “when patients are out of control, they may act inappropriately, including verbal, physical, and sexual assaults.”
Consequently, “clinicians should be prepared and have management tools,” said Dr. Binder, who was not involved in the research.
She noted that derogatory statements and racial slurs were included among the verbal assaults, which is particularly common in inpatient units and EDs where “patients may be acutely psychotic or manic and out of control,” she said.
However, Dr. Binder pointed out that the investigators did not separate mild and more severe forms of physical and sexual assault.
“If the authors had more finely separated out the types of physical and sexual assaults, they probably would have found that mild types of assaults are much more common than more severe assaults,” she said.
Dr. Pereira-Sanchez’s fellowship program is funded by Fundacion Alicia Koplowitz. He and Dr. Binder have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
More than 80% of psychiatric trainees have experienced some kind of verbal, physical, or sexual assault from patients, and approximately one-third have been physically attacked multiple times, new survey results show.
Such incidents, said study investigator Victor Pereira-Sanchez, MD, from the department of child and adolescent psychiatry at New York University take a toll on the trainees’ well-being and may ultimately affect the quality of patient care.
“The extent of violence against psychiatric trainees is alarming and calls for the implementation of effective training, prevention, and intervention measures,” Dr. Pereira-Sanchez said in an interview.
The findings were presented at the European Psychiatric Association (EPA) 2020 Congress, which was virtual this year because of the COVID-19 pandemic.
Widespread problem
Violence against health care professionals is widespread among clinicians in EDs with psychiatry trainees “more exposed and vulnerable,” Dr. Pereira-Sanchez said during his presentation.
In 2017, the European Federation of Psychiatric Trainees established a group of researchers to describe “the extent and consequences of violence against psychiatric trainees in Europe and beyond,” he said. The group developed a 15-item questionnaire asking young clinicians about experiences of physical, sexual, and verbal assault at work. The survey was posted online by partner institutions via social media.
A total of 827 psychiatric trainees, the majority of whom were from France and the United Kingdom, completed the survey. Respondents had an average age of 31 years, and 68% were women. On average, respondents had completed 51.3% of their psychiatric training.
with 92.0% reporting verbal assaults, 44.1% physical assaults, and 9.3% sexual assaults. In addition, 14.2% had been assaulted once, 51.9% had been assaulted two to five times, and 33.9% had been assaulted more than five times during their training. Results also showed that assaults were more likely to occur on an inpatient ward (63.4%) or the ED (56.9%), although 37.2% occurred in an outpatient setting and 4.2% in community settings. The majority of respondents (69.0%) did not report their assaults, and 67.3% did not call police or security personnel.
The most common emotions experienced by trainees following an assault were fear, rage, and anxiety. Guilt, sadness, feeling unsupported, and self-doubt were also reported.
Dr. Pereira-Sanchez noted the low rate of reported assaults is likely because trainees view it as “part of the job to get insulted, it’s part of the job to suffer minor physical violence.”
Individuals who did report assaults tended to be those who had been assaulted more than five times and those who felt more anxiety, rage, and fear.
“Basically, those who experience more emotional consequences and physical consequences tend to report more,” he said.
In addition, trainees tended to report assaults if they worked in an institution that provided protocols and training in prevention and management of patient aggression.
However, he added, most respondents reported they were not aware of their center’s protocols with respect to assaults and were not trained in the management or prevention of patient violence.
Management tools key
Commenting on the study in an interview, Renee Binder, MD, professor of psychiatry at University of California, San Francisco, said the findings show that, “when patients are out of control, they may act inappropriately, including verbal, physical, and sexual assaults.”
Consequently, “clinicians should be prepared and have management tools,” said Dr. Binder, who was not involved in the research.
She noted that derogatory statements and racial slurs were included among the verbal assaults, which is particularly common in inpatient units and EDs where “patients may be acutely psychotic or manic and out of control,” she said.
However, Dr. Binder pointed out that the investigators did not separate mild and more severe forms of physical and sexual assault.
“If the authors had more finely separated out the types of physical and sexual assaults, they probably would have found that mild types of assaults are much more common than more severe assaults,” she said.
Dr. Pereira-Sanchez’s fellowship program is funded by Fundacion Alicia Koplowitz. He and Dr. Binder have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
More than 80% of psychiatric trainees have experienced some kind of verbal, physical, or sexual assault from patients, and approximately one-third have been physically attacked multiple times, new survey results show.
Such incidents, said study investigator Victor Pereira-Sanchez, MD, from the department of child and adolescent psychiatry at New York University take a toll on the trainees’ well-being and may ultimately affect the quality of patient care.
“The extent of violence against psychiatric trainees is alarming and calls for the implementation of effective training, prevention, and intervention measures,” Dr. Pereira-Sanchez said in an interview.
The findings were presented at the European Psychiatric Association (EPA) 2020 Congress, which was virtual this year because of the COVID-19 pandemic.
Widespread problem
Violence against health care professionals is widespread among clinicians in EDs with psychiatry trainees “more exposed and vulnerable,” Dr. Pereira-Sanchez said during his presentation.
In 2017, the European Federation of Psychiatric Trainees established a group of researchers to describe “the extent and consequences of violence against psychiatric trainees in Europe and beyond,” he said. The group developed a 15-item questionnaire asking young clinicians about experiences of physical, sexual, and verbal assault at work. The survey was posted online by partner institutions via social media.
A total of 827 psychiatric trainees, the majority of whom were from France and the United Kingdom, completed the survey. Respondents had an average age of 31 years, and 68% were women. On average, respondents had completed 51.3% of their psychiatric training.
with 92.0% reporting verbal assaults, 44.1% physical assaults, and 9.3% sexual assaults. In addition, 14.2% had been assaulted once, 51.9% had been assaulted two to five times, and 33.9% had been assaulted more than five times during their training. Results also showed that assaults were more likely to occur on an inpatient ward (63.4%) or the ED (56.9%), although 37.2% occurred in an outpatient setting and 4.2% in community settings. The majority of respondents (69.0%) did not report their assaults, and 67.3% did not call police or security personnel.
The most common emotions experienced by trainees following an assault were fear, rage, and anxiety. Guilt, sadness, feeling unsupported, and self-doubt were also reported.
Dr. Pereira-Sanchez noted the low rate of reported assaults is likely because trainees view it as “part of the job to get insulted, it’s part of the job to suffer minor physical violence.”
Individuals who did report assaults tended to be those who had been assaulted more than five times and those who felt more anxiety, rage, and fear.
“Basically, those who experience more emotional consequences and physical consequences tend to report more,” he said.
In addition, trainees tended to report assaults if they worked in an institution that provided protocols and training in prevention and management of patient aggression.
However, he added, most respondents reported they were not aware of their center’s protocols with respect to assaults and were not trained in the management or prevention of patient violence.
Management tools key
Commenting on the study in an interview, Renee Binder, MD, professor of psychiatry at University of California, San Francisco, said the findings show that, “when patients are out of control, they may act inappropriately, including verbal, physical, and sexual assaults.”
Consequently, “clinicians should be prepared and have management tools,” said Dr. Binder, who was not involved in the research.
She noted that derogatory statements and racial slurs were included among the verbal assaults, which is particularly common in inpatient units and EDs where “patients may be acutely psychotic or manic and out of control,” she said.
However, Dr. Binder pointed out that the investigators did not separate mild and more severe forms of physical and sexual assault.
“If the authors had more finely separated out the types of physical and sexual assaults, they probably would have found that mild types of assaults are much more common than more severe assaults,” she said.
Dr. Pereira-Sanchez’s fellowship program is funded by Fundacion Alicia Koplowitz. He and Dr. Binder have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Be wary of ‘for eczema’ claims on labels of popular moisturizers
Be wary of “for eczema” advertising claims contained on the labels of popular skin moisturizers.
Results from a study presented during the virtual annual meeting of the Society for Pediatric Dermatology found that .
“Prescription medications are important for managing eczema flares, but a lot of the work in treating eczema is preventative, done by consistently moisturizing the skin at home with drug store products,” co-first study author Catherine L. Ludwig, said in an interview. “Allergic contact dermatitis occurs more commonly in people with eczema. A previous study was done in characterizing the allergenic potential of drug store moisturizers and found that 88% of moisturizers contain at least one common allergen. Many moisturizers are marketed specifically to eczema, but the allergen content of these products are unknown.”
For the current study, Ms. Ludwig, a medical student at the University of Illinois at Chicago and co-first author Alyssa M. Thompson, a medical student at the University of Arizona, Tucson, and their colleagues compiled a list of the top 30 moisturizers “for eczema” sold by Amazon, Target, and Walmart. For each moisturizer they recorded common ingredients and marketing claims related to benefits for atopic dermatitis, including eczema relief, sensitive/gentle skin, hypoallergenic, anti-itch, anti-inflammatory, clinically proven, oatmeal, dermatologist recommended/approved, organic, fragrance-free, for baby, or National Eczema Association approved. To establish allergenic potential, the researchers used MATLAB to compare ingredient lists to compounds listed as common allergens in the American Contact Dermatitis Society’s Contact Allergen Management Program database (ACDS CAMP). Next, they used the Mann-Whitney U test to evaluate differences in allergen count between products with and without specific marketing claims.
Ms. Ludwig and her associates found that 28 of 30 products analyzed (93%) contained at least one allergen, with an overall average allergen count of 3.60. The three most prevalent allergens were cetyl alcohol (70%), phenoxyethanol (50%), and aloe (33%). “Anti-inflammatory” moisturizers had the greatest average number of allergens (4.00), followed by “anti-itch” (3.71) and “oatmeal” (3.71). Only products claiming to be “hypoallergenic” had significantly lower allergenic ingredient count (an average of 2.45) than those without the claim (P = .011).
“It was validating to see that eczema moisturizer products marketed as ‘hypoallergenic’ truly do have fewer allergenic ingredients than moisturizers without the claim,” Ms. Ludwig said. “However, it was surprising to see that even products marketed to eczema patients, who have a higher prevalence of allergic contact dermatitis, contain an average of 3.6 common allergens. As dermatology providers, we can relay to patients and parents that relying solely on ‘for eczema’ claims is not advisable. Clinicians should acquaint themselves with the top allergens (cetyl alcohol, phenoxyethanol, and aloe) and keep these ingredients, as well as affordability and patient preferences, in mind when making product recommendations.”
The study’s senior author, Vivian Y. Shi, MD, is a stock shareholder of Learn Health and has served as an advisory board member and/or investigator, and/or received research funding from AbbVie, Burt’s Bees, GpSkin, LEO Pharma, Eli Lilly, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Skin Actives Scientific, and SUN Pharma, and the Foundation for Atopic Dermatitis, Global Parents for Eczema Research, and the National Eczema Association. The other study authors reported having no financial disclosures.
Be wary of “for eczema” advertising claims contained on the labels of popular skin moisturizers.
Results from a study presented during the virtual annual meeting of the Society for Pediatric Dermatology found that .
“Prescription medications are important for managing eczema flares, but a lot of the work in treating eczema is preventative, done by consistently moisturizing the skin at home with drug store products,” co-first study author Catherine L. Ludwig, said in an interview. “Allergic contact dermatitis occurs more commonly in people with eczema. A previous study was done in characterizing the allergenic potential of drug store moisturizers and found that 88% of moisturizers contain at least one common allergen. Many moisturizers are marketed specifically to eczema, but the allergen content of these products are unknown.”
For the current study, Ms. Ludwig, a medical student at the University of Illinois at Chicago and co-first author Alyssa M. Thompson, a medical student at the University of Arizona, Tucson, and their colleagues compiled a list of the top 30 moisturizers “for eczema” sold by Amazon, Target, and Walmart. For each moisturizer they recorded common ingredients and marketing claims related to benefits for atopic dermatitis, including eczema relief, sensitive/gentle skin, hypoallergenic, anti-itch, anti-inflammatory, clinically proven, oatmeal, dermatologist recommended/approved, organic, fragrance-free, for baby, or National Eczema Association approved. To establish allergenic potential, the researchers used MATLAB to compare ingredient lists to compounds listed as common allergens in the American Contact Dermatitis Society’s Contact Allergen Management Program database (ACDS CAMP). Next, they used the Mann-Whitney U test to evaluate differences in allergen count between products with and without specific marketing claims.
Ms. Ludwig and her associates found that 28 of 30 products analyzed (93%) contained at least one allergen, with an overall average allergen count of 3.60. The three most prevalent allergens were cetyl alcohol (70%), phenoxyethanol (50%), and aloe (33%). “Anti-inflammatory” moisturizers had the greatest average number of allergens (4.00), followed by “anti-itch” (3.71) and “oatmeal” (3.71). Only products claiming to be “hypoallergenic” had significantly lower allergenic ingredient count (an average of 2.45) than those without the claim (P = .011).
“It was validating to see that eczema moisturizer products marketed as ‘hypoallergenic’ truly do have fewer allergenic ingredients than moisturizers without the claim,” Ms. Ludwig said. “However, it was surprising to see that even products marketed to eczema patients, who have a higher prevalence of allergic contact dermatitis, contain an average of 3.6 common allergens. As dermatology providers, we can relay to patients and parents that relying solely on ‘for eczema’ claims is not advisable. Clinicians should acquaint themselves with the top allergens (cetyl alcohol, phenoxyethanol, and aloe) and keep these ingredients, as well as affordability and patient preferences, in mind when making product recommendations.”
The study’s senior author, Vivian Y. Shi, MD, is a stock shareholder of Learn Health and has served as an advisory board member and/or investigator, and/or received research funding from AbbVie, Burt’s Bees, GpSkin, LEO Pharma, Eli Lilly, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Skin Actives Scientific, and SUN Pharma, and the Foundation for Atopic Dermatitis, Global Parents for Eczema Research, and the National Eczema Association. The other study authors reported having no financial disclosures.
Be wary of “for eczema” advertising claims contained on the labels of popular skin moisturizers.
Results from a study presented during the virtual annual meeting of the Society for Pediatric Dermatology found that .
“Prescription medications are important for managing eczema flares, but a lot of the work in treating eczema is preventative, done by consistently moisturizing the skin at home with drug store products,” co-first study author Catherine L. Ludwig, said in an interview. “Allergic contact dermatitis occurs more commonly in people with eczema. A previous study was done in characterizing the allergenic potential of drug store moisturizers and found that 88% of moisturizers contain at least one common allergen. Many moisturizers are marketed specifically to eczema, but the allergen content of these products are unknown.”
For the current study, Ms. Ludwig, a medical student at the University of Illinois at Chicago and co-first author Alyssa M. Thompson, a medical student at the University of Arizona, Tucson, and their colleagues compiled a list of the top 30 moisturizers “for eczema” sold by Amazon, Target, and Walmart. For each moisturizer they recorded common ingredients and marketing claims related to benefits for atopic dermatitis, including eczema relief, sensitive/gentle skin, hypoallergenic, anti-itch, anti-inflammatory, clinically proven, oatmeal, dermatologist recommended/approved, organic, fragrance-free, for baby, or National Eczema Association approved. To establish allergenic potential, the researchers used MATLAB to compare ingredient lists to compounds listed as common allergens in the American Contact Dermatitis Society’s Contact Allergen Management Program database (ACDS CAMP). Next, they used the Mann-Whitney U test to evaluate differences in allergen count between products with and without specific marketing claims.
Ms. Ludwig and her associates found that 28 of 30 products analyzed (93%) contained at least one allergen, with an overall average allergen count of 3.60. The three most prevalent allergens were cetyl alcohol (70%), phenoxyethanol (50%), and aloe (33%). “Anti-inflammatory” moisturizers had the greatest average number of allergens (4.00), followed by “anti-itch” (3.71) and “oatmeal” (3.71). Only products claiming to be “hypoallergenic” had significantly lower allergenic ingredient count (an average of 2.45) than those without the claim (P = .011).
“It was validating to see that eczema moisturizer products marketed as ‘hypoallergenic’ truly do have fewer allergenic ingredients than moisturizers without the claim,” Ms. Ludwig said. “However, it was surprising to see that even products marketed to eczema patients, who have a higher prevalence of allergic contact dermatitis, contain an average of 3.6 common allergens. As dermatology providers, we can relay to patients and parents that relying solely on ‘for eczema’ claims is not advisable. Clinicians should acquaint themselves with the top allergens (cetyl alcohol, phenoxyethanol, and aloe) and keep these ingredients, as well as affordability and patient preferences, in mind when making product recommendations.”
The study’s senior author, Vivian Y. Shi, MD, is a stock shareholder of Learn Health and has served as an advisory board member and/or investigator, and/or received research funding from AbbVie, Burt’s Bees, GpSkin, LEO Pharma, Eli Lilly, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Skin Actives Scientific, and SUN Pharma, and the Foundation for Atopic Dermatitis, Global Parents for Eczema Research, and the National Eczema Association. The other study authors reported having no financial disclosures.
FROM SPD 2020
Analysis of early onset cancers suggests need for genetic testing
according to a presentation at the AACR virtual meeting II.
Investigators analyzed blood samples from 1,201 patients who were aged 18-39 years when diagnosed with a solid tumor malignancy.
In this group, there were 877 patients with early onset cancers, defined as cancers for which 39 years of age is greater than 1 standard deviation below the mean age of diagnosis for the cancer type.
The remaining 324 patients had young adult cancers, defined as cancers for which 39 years of age is less than 1 standard deviation below the mean age of diagnosis.
The most common early onset cancers were breast, colorectal, kidney, pancreas, and ovarian cancer.
The most common young adult cancers were sarcoma, brain cancer, and testicular cancer, as expected, said investigator Zsofia K. Stadler, MD, of Memorial Sloan Kettering Cancer Center in New York.
Dr. Stadler and colleagues performed next-generation sequencing of the patient samples using a panel of up to 88 genes previously implicated in cancer predisposition. This revealed a significantly higher prevalence of germline mutations in patients with early onset cancers than in those with young adult cancers – 21% and 13%, respectively (P = .002).
In patients with only high- and moderate-risk cancer susceptibility genes, the prevalence was 15% in the early onset group and 10% in the young adult group (P = .01). “Among the early onset cancer group, pancreas, breast, and kidney cancer patients harbored the highest rates of germline mutations,” Dr. Stadler said, noting that the spectrum of mutated genes differed in early onset and young adult cancer patients.
“In early onset patients, the most commonly mutated genes were BRCA1 and BRCA2 [4.9%], Lynch syndrome genes [2.2%], ATM [1.6%], and CHECK2 [1.7%],” Dr. Stadler said. “On the other hand, in young adults, TP53 mutations [2.2%], and SDHA and SDHB mutations dominated [1.9%], with the majority of mutations occurring in sarcoma patients.”
These findings suggest the prevalence of inherited cancer susceptibility syndromes in young adults with cancer is not uniform.
“We found a very high prevalence of germline mutations in young patients with cancer types that typically present at later ages,” Dr. Stadler said, referring to the early onset patients.
Conversely, the young adult cancer patients had a prevalence and spectrum of mutations more similar to what is seen in pediatric cancer populations, she noted.
The findings are surprising, according to AACR past president Elaine R. Mardis, PhD, of The Ohio State University in Columbus.
Dr. Mardis said the results show that, in young adults with early onset cancers, “the germline prevalence of these mutations is significantly higher than we had previously thought.”
“Although representing only about 4% of all cancers, young adults with cancer ... face unique challenges,” Dr. Stadler said. “Identifying whether a young patient’s cancer occurred in the setting of an inherited cancer predisposition syndrome is especially important in this patient population.”
Such knowledge “can significantly impact the risk of second primary cancers and the need for increased surveillance measures or even risk-reducing surgeries,” Dr. Stadler explained. She added that it can also have implications for identifying at-risk family members, such as younger siblings or children who should pursue genetic testing and appropriate prevention measures.
“Our results suggest that, among patients with early onset cancer, the increased prevalence of germline mutations supports a role for genetic testing, irrespective of tumor type,” Dr. Stadler said.
This study was partially funded by the Precision, Interception and Prevention Program, the Robert and Katie Niehaus Center for Inherited Cancer Genomics, the Marie-Josee and Henry R. Kravis Center for Molecular Oncology, and a National Cancer Institute Cancer Center Core Grant. Dr. Stadler reported that an immediate family member serves as a consultant in ophthalmology for Allergan, Adverum Biotechnologies, Alimera Sciences, BioMarin, Fortress Biotech, Genentech/Roche, Novartis, Optos, Regeneron, Regenxbio, and Spark Therapeutics. Dr. Mardis disclosed relationships with Qiagen NV, Pact Pharma LLC, Moderna Inc., and Interpreta LLC.
SOURCE: Stadler Z et al. AACR 2020, Abstract 1122.
according to a presentation at the AACR virtual meeting II.
Investigators analyzed blood samples from 1,201 patients who were aged 18-39 years when diagnosed with a solid tumor malignancy.
In this group, there were 877 patients with early onset cancers, defined as cancers for which 39 years of age is greater than 1 standard deviation below the mean age of diagnosis for the cancer type.
The remaining 324 patients had young adult cancers, defined as cancers for which 39 years of age is less than 1 standard deviation below the mean age of diagnosis.
The most common early onset cancers were breast, colorectal, kidney, pancreas, and ovarian cancer.
The most common young adult cancers were sarcoma, brain cancer, and testicular cancer, as expected, said investigator Zsofia K. Stadler, MD, of Memorial Sloan Kettering Cancer Center in New York.
Dr. Stadler and colleagues performed next-generation sequencing of the patient samples using a panel of up to 88 genes previously implicated in cancer predisposition. This revealed a significantly higher prevalence of germline mutations in patients with early onset cancers than in those with young adult cancers – 21% and 13%, respectively (P = .002).
In patients with only high- and moderate-risk cancer susceptibility genes, the prevalence was 15% in the early onset group and 10% in the young adult group (P = .01). “Among the early onset cancer group, pancreas, breast, and kidney cancer patients harbored the highest rates of germline mutations,” Dr. Stadler said, noting that the spectrum of mutated genes differed in early onset and young adult cancer patients.
“In early onset patients, the most commonly mutated genes were BRCA1 and BRCA2 [4.9%], Lynch syndrome genes [2.2%], ATM [1.6%], and CHECK2 [1.7%],” Dr. Stadler said. “On the other hand, in young adults, TP53 mutations [2.2%], and SDHA and SDHB mutations dominated [1.9%], with the majority of mutations occurring in sarcoma patients.”
These findings suggest the prevalence of inherited cancer susceptibility syndromes in young adults with cancer is not uniform.
“We found a very high prevalence of germline mutations in young patients with cancer types that typically present at later ages,” Dr. Stadler said, referring to the early onset patients.
Conversely, the young adult cancer patients had a prevalence and spectrum of mutations more similar to what is seen in pediatric cancer populations, she noted.
The findings are surprising, according to AACR past president Elaine R. Mardis, PhD, of The Ohio State University in Columbus.
Dr. Mardis said the results show that, in young adults with early onset cancers, “the germline prevalence of these mutations is significantly higher than we had previously thought.”
“Although representing only about 4% of all cancers, young adults with cancer ... face unique challenges,” Dr. Stadler said. “Identifying whether a young patient’s cancer occurred in the setting of an inherited cancer predisposition syndrome is especially important in this patient population.”
Such knowledge “can significantly impact the risk of second primary cancers and the need for increased surveillance measures or even risk-reducing surgeries,” Dr. Stadler explained. She added that it can also have implications for identifying at-risk family members, such as younger siblings or children who should pursue genetic testing and appropriate prevention measures.
“Our results suggest that, among patients with early onset cancer, the increased prevalence of germline mutations supports a role for genetic testing, irrespective of tumor type,” Dr. Stadler said.
This study was partially funded by the Precision, Interception and Prevention Program, the Robert and Katie Niehaus Center for Inherited Cancer Genomics, the Marie-Josee and Henry R. Kravis Center for Molecular Oncology, and a National Cancer Institute Cancer Center Core Grant. Dr. Stadler reported that an immediate family member serves as a consultant in ophthalmology for Allergan, Adverum Biotechnologies, Alimera Sciences, BioMarin, Fortress Biotech, Genentech/Roche, Novartis, Optos, Regeneron, Regenxbio, and Spark Therapeutics. Dr. Mardis disclosed relationships with Qiagen NV, Pact Pharma LLC, Moderna Inc., and Interpreta LLC.
SOURCE: Stadler Z et al. AACR 2020, Abstract 1122.
according to a presentation at the AACR virtual meeting II.
Investigators analyzed blood samples from 1,201 patients who were aged 18-39 years when diagnosed with a solid tumor malignancy.
In this group, there were 877 patients with early onset cancers, defined as cancers for which 39 years of age is greater than 1 standard deviation below the mean age of diagnosis for the cancer type.
The remaining 324 patients had young adult cancers, defined as cancers for which 39 years of age is less than 1 standard deviation below the mean age of diagnosis.
The most common early onset cancers were breast, colorectal, kidney, pancreas, and ovarian cancer.
The most common young adult cancers were sarcoma, brain cancer, and testicular cancer, as expected, said investigator Zsofia K. Stadler, MD, of Memorial Sloan Kettering Cancer Center in New York.
Dr. Stadler and colleagues performed next-generation sequencing of the patient samples using a panel of up to 88 genes previously implicated in cancer predisposition. This revealed a significantly higher prevalence of germline mutations in patients with early onset cancers than in those with young adult cancers – 21% and 13%, respectively (P = .002).
In patients with only high- and moderate-risk cancer susceptibility genes, the prevalence was 15% in the early onset group and 10% in the young adult group (P = .01). “Among the early onset cancer group, pancreas, breast, and kidney cancer patients harbored the highest rates of germline mutations,” Dr. Stadler said, noting that the spectrum of mutated genes differed in early onset and young adult cancer patients.
“In early onset patients, the most commonly mutated genes were BRCA1 and BRCA2 [4.9%], Lynch syndrome genes [2.2%], ATM [1.6%], and CHECK2 [1.7%],” Dr. Stadler said. “On the other hand, in young adults, TP53 mutations [2.2%], and SDHA and SDHB mutations dominated [1.9%], with the majority of mutations occurring in sarcoma patients.”
These findings suggest the prevalence of inherited cancer susceptibility syndromes in young adults with cancer is not uniform.
“We found a very high prevalence of germline mutations in young patients with cancer types that typically present at later ages,” Dr. Stadler said, referring to the early onset patients.
Conversely, the young adult cancer patients had a prevalence and spectrum of mutations more similar to what is seen in pediatric cancer populations, she noted.
The findings are surprising, according to AACR past president Elaine R. Mardis, PhD, of The Ohio State University in Columbus.
Dr. Mardis said the results show that, in young adults with early onset cancers, “the germline prevalence of these mutations is significantly higher than we had previously thought.”
“Although representing only about 4% of all cancers, young adults with cancer ... face unique challenges,” Dr. Stadler said. “Identifying whether a young patient’s cancer occurred in the setting of an inherited cancer predisposition syndrome is especially important in this patient population.”
Such knowledge “can significantly impact the risk of second primary cancers and the need for increased surveillance measures or even risk-reducing surgeries,” Dr. Stadler explained. She added that it can also have implications for identifying at-risk family members, such as younger siblings or children who should pursue genetic testing and appropriate prevention measures.
“Our results suggest that, among patients with early onset cancer, the increased prevalence of germline mutations supports a role for genetic testing, irrespective of tumor type,” Dr. Stadler said.
This study was partially funded by the Precision, Interception and Prevention Program, the Robert and Katie Niehaus Center for Inherited Cancer Genomics, the Marie-Josee and Henry R. Kravis Center for Molecular Oncology, and a National Cancer Institute Cancer Center Core Grant. Dr. Stadler reported that an immediate family member serves as a consultant in ophthalmology for Allergan, Adverum Biotechnologies, Alimera Sciences, BioMarin, Fortress Biotech, Genentech/Roche, Novartis, Optos, Regeneron, Regenxbio, and Spark Therapeutics. Dr. Mardis disclosed relationships with Qiagen NV, Pact Pharma LLC, Moderna Inc., and Interpreta LLC.
SOURCE: Stadler Z et al. AACR 2020, Abstract 1122.
FROM AACR 2020
Acetaminophen beats fentanyl in STEMI
Swapping out intravenous fentanyl in favor of IV acetaminophen in patients with ST-elevation MI (STEMI) provides comparable pain relief but with desirably higher blood levels of ticagrelor both immediately after primary percutaneous intervention and 1 hour post procedure.
That’s according to results of the Dutch ON-TIME 3 trial, presented by Anne H. Tavenier, MD, at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.
“Our trial results have implications for the prehospital treatment of STEMI patients,” said Dr. Tavenier, a cardiologist at the Isala Clinic in Zwolle, the Netherlands.
The explanation for the success of this novel STEMI pain management strategy? The synthetic opioid fentanyl impairs gastrointestinal absorption of oral P2Y12 receptor antagonists such as ticagrelor. Opiates do so as well, whereas acetaminophen does not, she explained.
The potent platelet inhibition provided by oral P2Y12 inhibitors is crucial to successful primary PCI for STEMI. But these platelet inhibitory effects are inherently slowed in STEMI patients owing to hemodynamic changes and delayed GI absorption. And even though both American College of Cardiology/American Heart Association and European Society of Cardiology guidelines recommend the use of opioids for pain control in STEMI patients, the fact is that these medications further delay the absorption of oral P2Y12 inhibitors. And this delay is further exacerbated by the nausea and vomiting which are common side effects of IV fentanyl, she continued.
The impetus for the ON-TIME 3 trial was straightforward, the cardiologist said: “For years, STEMI patients have been treated with morphine or morphinelike drugs like fentanyl because of pain or sympathetic stress. To date, trials investigating alternative analgesics to opioids have been scarce.”
ON-TIME 3 was a multicenter, open-label, phase 4 clinical trial in which 195 STEMI patients with a self-reported pain score of at least 4 on a 0-10 scale received crushed ticagrelor in the ambulance along with either 1,000 mg of IV acetaminophen or fentanyl at 1-2 mcg/kg.
Ticagrelor blood levels were significantly higher in the IV acetaminophen group when measured just prior to primary PCI (151 ng/mL versus 60 ng/mL in the IV fentanyl group; immediately after PCI (326 versus 115 ng/mL), and 1 hour post PCI (488 versus 372 ng/mL).
However, there was no significant between-group difference in levels of platelet reactivity units measured immediately after primary PCI, Dr. Tavenier added.
Discussant Christoph K. Naber, MD, PhD, confessed that prior to ON-TIME 3 he was unaware that administering opioids to STEMI patients results in delayed absorption of oral P2Y12 inhibitors. Upon delving into the literature, however, he found that this is indeed a well-documented problem.
“The open question I have about this very elegant trial is whether the increased P2Y12 levels will translate into a measurable difference in clinical outcomes,” said Dr. Naber, an interventional cardiologist at the Wilhemshaven (Germany) Clinic.
The answer to that question would require a larger, longer-term trial. And he’s disinclined to wait around for that to happen.
“I think when we look at the risk balance, the risk of switching from an opioid to acetaminophen, if it works for the patient, is rather low. So this might be something to introduce in my practice,” the cardiologist said.
Dr. Tavenier and Dr. Naber reported having no financial conflicts of interest.
SOURCE: Tavenier AH. EuroPCR 2020.
Swapping out intravenous fentanyl in favor of IV acetaminophen in patients with ST-elevation MI (STEMI) provides comparable pain relief but with desirably higher blood levels of ticagrelor both immediately after primary percutaneous intervention and 1 hour post procedure.
That’s according to results of the Dutch ON-TIME 3 trial, presented by Anne H. Tavenier, MD, at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.
“Our trial results have implications for the prehospital treatment of STEMI patients,” said Dr. Tavenier, a cardiologist at the Isala Clinic in Zwolle, the Netherlands.
The explanation for the success of this novel STEMI pain management strategy? The synthetic opioid fentanyl impairs gastrointestinal absorption of oral P2Y12 receptor antagonists such as ticagrelor. Opiates do so as well, whereas acetaminophen does not, she explained.
The potent platelet inhibition provided by oral P2Y12 inhibitors is crucial to successful primary PCI for STEMI. But these platelet inhibitory effects are inherently slowed in STEMI patients owing to hemodynamic changes and delayed GI absorption. And even though both American College of Cardiology/American Heart Association and European Society of Cardiology guidelines recommend the use of opioids for pain control in STEMI patients, the fact is that these medications further delay the absorption of oral P2Y12 inhibitors. And this delay is further exacerbated by the nausea and vomiting which are common side effects of IV fentanyl, she continued.
The impetus for the ON-TIME 3 trial was straightforward, the cardiologist said: “For years, STEMI patients have been treated with morphine or morphinelike drugs like fentanyl because of pain or sympathetic stress. To date, trials investigating alternative analgesics to opioids have been scarce.”
ON-TIME 3 was a multicenter, open-label, phase 4 clinical trial in which 195 STEMI patients with a self-reported pain score of at least 4 on a 0-10 scale received crushed ticagrelor in the ambulance along with either 1,000 mg of IV acetaminophen or fentanyl at 1-2 mcg/kg.
Ticagrelor blood levels were significantly higher in the IV acetaminophen group when measured just prior to primary PCI (151 ng/mL versus 60 ng/mL in the IV fentanyl group; immediately after PCI (326 versus 115 ng/mL), and 1 hour post PCI (488 versus 372 ng/mL).
However, there was no significant between-group difference in levels of platelet reactivity units measured immediately after primary PCI, Dr. Tavenier added.
Discussant Christoph K. Naber, MD, PhD, confessed that prior to ON-TIME 3 he was unaware that administering opioids to STEMI patients results in delayed absorption of oral P2Y12 inhibitors. Upon delving into the literature, however, he found that this is indeed a well-documented problem.
“The open question I have about this very elegant trial is whether the increased P2Y12 levels will translate into a measurable difference in clinical outcomes,” said Dr. Naber, an interventional cardiologist at the Wilhemshaven (Germany) Clinic.
The answer to that question would require a larger, longer-term trial. And he’s disinclined to wait around for that to happen.
“I think when we look at the risk balance, the risk of switching from an opioid to acetaminophen, if it works for the patient, is rather low. So this might be something to introduce in my practice,” the cardiologist said.
Dr. Tavenier and Dr. Naber reported having no financial conflicts of interest.
SOURCE: Tavenier AH. EuroPCR 2020.
Swapping out intravenous fentanyl in favor of IV acetaminophen in patients with ST-elevation MI (STEMI) provides comparable pain relief but with desirably higher blood levels of ticagrelor both immediately after primary percutaneous intervention and 1 hour post procedure.
That’s according to results of the Dutch ON-TIME 3 trial, presented by Anne H. Tavenier, MD, at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.
“Our trial results have implications for the prehospital treatment of STEMI patients,” said Dr. Tavenier, a cardiologist at the Isala Clinic in Zwolle, the Netherlands.
The explanation for the success of this novel STEMI pain management strategy? The synthetic opioid fentanyl impairs gastrointestinal absorption of oral P2Y12 receptor antagonists such as ticagrelor. Opiates do so as well, whereas acetaminophen does not, she explained.
The potent platelet inhibition provided by oral P2Y12 inhibitors is crucial to successful primary PCI for STEMI. But these platelet inhibitory effects are inherently slowed in STEMI patients owing to hemodynamic changes and delayed GI absorption. And even though both American College of Cardiology/American Heart Association and European Society of Cardiology guidelines recommend the use of opioids for pain control in STEMI patients, the fact is that these medications further delay the absorption of oral P2Y12 inhibitors. And this delay is further exacerbated by the nausea and vomiting which are common side effects of IV fentanyl, she continued.
The impetus for the ON-TIME 3 trial was straightforward, the cardiologist said: “For years, STEMI patients have been treated with morphine or morphinelike drugs like fentanyl because of pain or sympathetic stress. To date, trials investigating alternative analgesics to opioids have been scarce.”
ON-TIME 3 was a multicenter, open-label, phase 4 clinical trial in which 195 STEMI patients with a self-reported pain score of at least 4 on a 0-10 scale received crushed ticagrelor in the ambulance along with either 1,000 mg of IV acetaminophen or fentanyl at 1-2 mcg/kg.
Ticagrelor blood levels were significantly higher in the IV acetaminophen group when measured just prior to primary PCI (151 ng/mL versus 60 ng/mL in the IV fentanyl group; immediately after PCI (326 versus 115 ng/mL), and 1 hour post PCI (488 versus 372 ng/mL).
However, there was no significant between-group difference in levels of platelet reactivity units measured immediately after primary PCI, Dr. Tavenier added.
Discussant Christoph K. Naber, MD, PhD, confessed that prior to ON-TIME 3 he was unaware that administering opioids to STEMI patients results in delayed absorption of oral P2Y12 inhibitors. Upon delving into the literature, however, he found that this is indeed a well-documented problem.
“The open question I have about this very elegant trial is whether the increased P2Y12 levels will translate into a measurable difference in clinical outcomes,” said Dr. Naber, an interventional cardiologist at the Wilhemshaven (Germany) Clinic.
The answer to that question would require a larger, longer-term trial. And he’s disinclined to wait around for that to happen.
“I think when we look at the risk balance, the risk of switching from an opioid to acetaminophen, if it works for the patient, is rather low. So this might be something to introduce in my practice,” the cardiologist said.
Dr. Tavenier and Dr. Naber reported having no financial conflicts of interest.
SOURCE: Tavenier AH. EuroPCR 2020.
REPORTING FROM EUROPCR 2020
PASDAS beats DAS28 in measuring psoriatic arthritis treat-to-target success
Measuring success with a treat-to-target strategy in psoriatic arthritis patients proved to be more comprehensive with the Psoriatic Arthritis Disease Activity Score (PASDAS) than it was with the Disease Activity Score in 28 joints (DAS28), according to findings from a prospective cohort study.
Fewer patients had a low disease activity score according to DAS28, and a higher percentage of patients deemed adequately treated according to DAS28 were found to have residual disease activity, compared with the number of patients so categorized according to PASDAS, researcher Michelle Mulder reported in her presentation of the study at the virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).
“PASDAS implementation in a tightly monitored PsA [psoriatic arthritis] cohort suggests relevant residual disease burden, even though DAS28 was measured at every visit previously,” said Ms. Mulder, an MD/PhD student at Sint Maartenskliniek in Nijmegen, The Netherlands.
The presentation was convincing to Philip Helliwell, MD, PhD, who is a professor of clinical rheumatology at Leeds (England) University, and was also one of the developers of PASDAS. “We know it can be used in clinical practice with a certain amount of organization and clinical staff to help you,” he said during another presentation at GRAPPA.
Treat to target is a widely accepted therapeutic strategy. It’s particularly common in rheumatoid arthritis, but increasing evidence suggests that it improves patient outcomes in psoriatic arthritis. DAS28 is frequently used in treat-to-target approaches in rheumatoid arthritis, and often gets applied to psoriatic arthritis since rheumatologists are already comfortable with it, according to Ms. Mulder. “However, DAS28 has shown some limitations when used in psoriatic arthritis. For example, its joint count is limited to only 28 joints, and it does not take all PsA domains into account,” she said.
DAS28 was previously used at Sint Maartenskliniek in combination with psoriatic arthritis–specific assessment recommendations, but the institution opted in 2019 to switch to PASDAS, which was developed by GRAPPA and the European League Against Rheumatism. “To better adhere to international PsA guidelines, we chose to implement PASDAS in our cohort with the assumption that it might improve patient care,” Ms. Mulder said.
With DAS28, clinicians measured the C-reactive protein (CRP) and Patient Global Visual Analog Scale (VAS) domains and were advised to examine 28 joints for tender and swollen joint count domains. Under the PASDAS guidance, clinicians examined 68 joints for tenderness, 66 joints for swelling, CRP, Patient Global VAS, Physician Global VAS, Leeds Enthesitis Index, dactylitis, and the 12-item Short Form Physical Composite Scale. They also examined the skin, nails, and axial disease.
To examine the effects of the switch from DAS28 to PASDAS, the researchers compared outcomes in 855 patients before and after the change during March to December 2019. The mean age of patients was 55 years, and 46% were female. The mean disease duration was 10 years, and the mean PASDAS score was 3.1. A total of 96% of participants were negative for anti-cyclic citrullinated peptide. Overall, 30% had arthritis, 9% had axial disease, 3% had dactylitis, 21% had enthesitis, 51% had skin disease, and 42% had nail disease.
About three-quarters (77.4%) of patients reached the threshold of low disease activity (LDA) according to the DAS28 measure, while 53.1% did so using the PASDAS. High disease activity occurred in 7.8% of patients according to DAS28, compared with 2.7% as measured by PASDAS. Patients who reached only the DAS28 LDA target but not the PASDAS target, compared with patients who reached the LDA target in both measures, had significantly worse counts for swelling in 66 joints (0.7 vs. 0.2; P < .001) and tenderness in 68 joints (2.1 vs. 0.7; P < .001), as well as worse scores for enthesitis (0.5 vs. 0.1; P < .001), dactylitis (4% vs. 1%; P = .005), patient global VAS (44.0 vs. 14.4; P < .001), Health Assessment Questionnaire (0.8 vs. 0.4; P < .001) and Patient Acceptable Symptom State (unacceptable score in 17% vs. 3%; P < .001).
Ms. Mulder acknowledged that PASDAS imposes a significant burden on clinicians, and noted that Sint Maartenskliniek created patient infrastructure to handle the load. “It’s very important that you set up your clinic in a specific way. When the patient comes in, we draw blood immediately and we ask them to fill in the questionnaires, and then they go to a specialized nurse who measures all the different components of the PASDAS. It took a lot of time to train the specialized nurses and to implement the PASDAS score in our electronic health records. After we did those things, it was quite easy because we have this whole setup. It takes time and it is difficult, but it is definitely possible to do it,” Ms. Mulder said during a live Q&A following her prerecorded presentation.
The study received no funding. Ms. Mulder had no relevant financial disclosures. Dr. Helliwell has financial ties to AbbVie, Amgen, Celgen, Galapagos, Janssen, Novartis, Pfizer, and UCB.
SOURCE: Mulder M et al. GRAPPA 2020 Virtual Annual Meeting.
Measuring success with a treat-to-target strategy in psoriatic arthritis patients proved to be more comprehensive with the Psoriatic Arthritis Disease Activity Score (PASDAS) than it was with the Disease Activity Score in 28 joints (DAS28), according to findings from a prospective cohort study.
Fewer patients had a low disease activity score according to DAS28, and a higher percentage of patients deemed adequately treated according to DAS28 were found to have residual disease activity, compared with the number of patients so categorized according to PASDAS, researcher Michelle Mulder reported in her presentation of the study at the virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).
“PASDAS implementation in a tightly monitored PsA [psoriatic arthritis] cohort suggests relevant residual disease burden, even though DAS28 was measured at every visit previously,” said Ms. Mulder, an MD/PhD student at Sint Maartenskliniek in Nijmegen, The Netherlands.
The presentation was convincing to Philip Helliwell, MD, PhD, who is a professor of clinical rheumatology at Leeds (England) University, and was also one of the developers of PASDAS. “We know it can be used in clinical practice with a certain amount of organization and clinical staff to help you,” he said during another presentation at GRAPPA.
Treat to target is a widely accepted therapeutic strategy. It’s particularly common in rheumatoid arthritis, but increasing evidence suggests that it improves patient outcomes in psoriatic arthritis. DAS28 is frequently used in treat-to-target approaches in rheumatoid arthritis, and often gets applied to psoriatic arthritis since rheumatologists are already comfortable with it, according to Ms. Mulder. “However, DAS28 has shown some limitations when used in psoriatic arthritis. For example, its joint count is limited to only 28 joints, and it does not take all PsA domains into account,” she said.
DAS28 was previously used at Sint Maartenskliniek in combination with psoriatic arthritis–specific assessment recommendations, but the institution opted in 2019 to switch to PASDAS, which was developed by GRAPPA and the European League Against Rheumatism. “To better adhere to international PsA guidelines, we chose to implement PASDAS in our cohort with the assumption that it might improve patient care,” Ms. Mulder said.
With DAS28, clinicians measured the C-reactive protein (CRP) and Patient Global Visual Analog Scale (VAS) domains and were advised to examine 28 joints for tender and swollen joint count domains. Under the PASDAS guidance, clinicians examined 68 joints for tenderness, 66 joints for swelling, CRP, Patient Global VAS, Physician Global VAS, Leeds Enthesitis Index, dactylitis, and the 12-item Short Form Physical Composite Scale. They also examined the skin, nails, and axial disease.
To examine the effects of the switch from DAS28 to PASDAS, the researchers compared outcomes in 855 patients before and after the change during March to December 2019. The mean age of patients was 55 years, and 46% were female. The mean disease duration was 10 years, and the mean PASDAS score was 3.1. A total of 96% of participants were negative for anti-cyclic citrullinated peptide. Overall, 30% had arthritis, 9% had axial disease, 3% had dactylitis, 21% had enthesitis, 51% had skin disease, and 42% had nail disease.
About three-quarters (77.4%) of patients reached the threshold of low disease activity (LDA) according to the DAS28 measure, while 53.1% did so using the PASDAS. High disease activity occurred in 7.8% of patients according to DAS28, compared with 2.7% as measured by PASDAS. Patients who reached only the DAS28 LDA target but not the PASDAS target, compared with patients who reached the LDA target in both measures, had significantly worse counts for swelling in 66 joints (0.7 vs. 0.2; P < .001) and tenderness in 68 joints (2.1 vs. 0.7; P < .001), as well as worse scores for enthesitis (0.5 vs. 0.1; P < .001), dactylitis (4% vs. 1%; P = .005), patient global VAS (44.0 vs. 14.4; P < .001), Health Assessment Questionnaire (0.8 vs. 0.4; P < .001) and Patient Acceptable Symptom State (unacceptable score in 17% vs. 3%; P < .001).
Ms. Mulder acknowledged that PASDAS imposes a significant burden on clinicians, and noted that Sint Maartenskliniek created patient infrastructure to handle the load. “It’s very important that you set up your clinic in a specific way. When the patient comes in, we draw blood immediately and we ask them to fill in the questionnaires, and then they go to a specialized nurse who measures all the different components of the PASDAS. It took a lot of time to train the specialized nurses and to implement the PASDAS score in our electronic health records. After we did those things, it was quite easy because we have this whole setup. It takes time and it is difficult, but it is definitely possible to do it,” Ms. Mulder said during a live Q&A following her prerecorded presentation.
The study received no funding. Ms. Mulder had no relevant financial disclosures. Dr. Helliwell has financial ties to AbbVie, Amgen, Celgen, Galapagos, Janssen, Novartis, Pfizer, and UCB.
SOURCE: Mulder M et al. GRAPPA 2020 Virtual Annual Meeting.
Measuring success with a treat-to-target strategy in psoriatic arthritis patients proved to be more comprehensive with the Psoriatic Arthritis Disease Activity Score (PASDAS) than it was with the Disease Activity Score in 28 joints (DAS28), according to findings from a prospective cohort study.
Fewer patients had a low disease activity score according to DAS28, and a higher percentage of patients deemed adequately treated according to DAS28 were found to have residual disease activity, compared with the number of patients so categorized according to PASDAS, researcher Michelle Mulder reported in her presentation of the study at the virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).
“PASDAS implementation in a tightly monitored PsA [psoriatic arthritis] cohort suggests relevant residual disease burden, even though DAS28 was measured at every visit previously,” said Ms. Mulder, an MD/PhD student at Sint Maartenskliniek in Nijmegen, The Netherlands.
The presentation was convincing to Philip Helliwell, MD, PhD, who is a professor of clinical rheumatology at Leeds (England) University, and was also one of the developers of PASDAS. “We know it can be used in clinical practice with a certain amount of organization and clinical staff to help you,” he said during another presentation at GRAPPA.
Treat to target is a widely accepted therapeutic strategy. It’s particularly common in rheumatoid arthritis, but increasing evidence suggests that it improves patient outcomes in psoriatic arthritis. DAS28 is frequently used in treat-to-target approaches in rheumatoid arthritis, and often gets applied to psoriatic arthritis since rheumatologists are already comfortable with it, according to Ms. Mulder. “However, DAS28 has shown some limitations when used in psoriatic arthritis. For example, its joint count is limited to only 28 joints, and it does not take all PsA domains into account,” she said.
DAS28 was previously used at Sint Maartenskliniek in combination with psoriatic arthritis–specific assessment recommendations, but the institution opted in 2019 to switch to PASDAS, which was developed by GRAPPA and the European League Against Rheumatism. “To better adhere to international PsA guidelines, we chose to implement PASDAS in our cohort with the assumption that it might improve patient care,” Ms. Mulder said.
With DAS28, clinicians measured the C-reactive protein (CRP) and Patient Global Visual Analog Scale (VAS) domains and were advised to examine 28 joints for tender and swollen joint count domains. Under the PASDAS guidance, clinicians examined 68 joints for tenderness, 66 joints for swelling, CRP, Patient Global VAS, Physician Global VAS, Leeds Enthesitis Index, dactylitis, and the 12-item Short Form Physical Composite Scale. They also examined the skin, nails, and axial disease.
To examine the effects of the switch from DAS28 to PASDAS, the researchers compared outcomes in 855 patients before and after the change during March to December 2019. The mean age of patients was 55 years, and 46% were female. The mean disease duration was 10 years, and the mean PASDAS score was 3.1. A total of 96% of participants were negative for anti-cyclic citrullinated peptide. Overall, 30% had arthritis, 9% had axial disease, 3% had dactylitis, 21% had enthesitis, 51% had skin disease, and 42% had nail disease.
About three-quarters (77.4%) of patients reached the threshold of low disease activity (LDA) according to the DAS28 measure, while 53.1% did so using the PASDAS. High disease activity occurred in 7.8% of patients according to DAS28, compared with 2.7% as measured by PASDAS. Patients who reached only the DAS28 LDA target but not the PASDAS target, compared with patients who reached the LDA target in both measures, had significantly worse counts for swelling in 66 joints (0.7 vs. 0.2; P < .001) and tenderness in 68 joints (2.1 vs. 0.7; P < .001), as well as worse scores for enthesitis (0.5 vs. 0.1; P < .001), dactylitis (4% vs. 1%; P = .005), patient global VAS (44.0 vs. 14.4; P < .001), Health Assessment Questionnaire (0.8 vs. 0.4; P < .001) and Patient Acceptable Symptom State (unacceptable score in 17% vs. 3%; P < .001).
Ms. Mulder acknowledged that PASDAS imposes a significant burden on clinicians, and noted that Sint Maartenskliniek created patient infrastructure to handle the load. “It’s very important that you set up your clinic in a specific way. When the patient comes in, we draw blood immediately and we ask them to fill in the questionnaires, and then they go to a specialized nurse who measures all the different components of the PASDAS. It took a lot of time to train the specialized nurses and to implement the PASDAS score in our electronic health records. After we did those things, it was quite easy because we have this whole setup. It takes time and it is difficult, but it is definitely possible to do it,” Ms. Mulder said during a live Q&A following her prerecorded presentation.
The study received no funding. Ms. Mulder had no relevant financial disclosures. Dr. Helliwell has financial ties to AbbVie, Amgen, Celgen, Galapagos, Janssen, Novartis, Pfizer, and UCB.
SOURCE: Mulder M et al. GRAPPA 2020 Virtual Annual Meeting.
FROM GRAPPA 2020 VIRTUAL ANNUAL MEETING
Caution urged for antidepressant use in bipolar depression
Although patients with bipolar disorder commonly experience depressive symptoms, clinicians should be very cautious about treating them with antidepressants, especially as monotherapy, experts asserted in a recent debate on the topic as part of the European Psychiatric Association (EPA) 2020 Congress.
At the Congress, which was virtual this year because of the COVID-19 pandemic, psychiatric experts said that clinicians should also screen patients for mixed symptoms that are better treated with mood stabilizers. These same experts also raised concerns over long-term antidepressant use, recommending continued use only in patients who relapse after stopping antidepressants.
Isabella Pacchiarotti, MD, PhD, Centro de Investigación Biomédica en Red de Salud Mental, Barcelona, Spain, argued against the use of antidepressants in treating bipolar disorder; Guy Goodwin, PhD, however, took the “pro” stance.
Goodwin, a professor of psychiatry at the University of Oxford in the UK, admitted that there is a “paucity of data” on the role of antidepressants in bipolar disorder.
Nevertheless, there are “circumstances that one really has to treat with antidepressants simply because other things have been tried and have not worked,” he told conference attendees.
Challenging, Controversial Topic
The debate was chaired by Eduard Vieta, MD, PhD, chair of the Department of Psychiatry and Psychology at the University of Barcelona Hospital Clinic, Spain.
Vieta said the question over whether antidepressants should be used in the depressive phase of bipolar illness is “perhaps the most challenging ... especially in the area of bipolar disorder.”
At the beginning of the presentation, Vieta asked the audience for their opinion in order to have a “baseline” for the debate: among 164 respondents, 73% were in favor of using antidepressants in bipolar depression.
“Clearly there is a majority, so Isabella [Dr Pacchiarotti] is going to have a hard time improving these numbers,” Vieta noted.
Up first, Pacchiarotti began by noting that this topic remains “an area of big controversy.” However, the real question “should not be the pros and cons of antidepressants but more when and how to use them.»
Of the three phases of bipolar disorder, acute depression «poses the greatest difficulties,» she added.
This is because of the relative paucity of studies in the area, the often heated debates on the specific role of antidepressants, the discrepancy in conclusions between meta-analyses, and the currently approved therapeutic options being associated with “not very high response rates,” Pacchiarotti said.
The diagnostic criteria for unipolar and bipolar depression are “basically the same,” she noted. However, it’s important to be able to distinguish between the two conditions, as up to one fifth of patients with unipolar depression suffer from undiagnosed bipolar disorder, she explained.
Moreover, several studies have identified key symptoms in bipolar depression, such as hyperphagia and hypersomnia, increased anxiety, and psychotic and psychomotor symptoms.
As previously reported by Medscape Medical News, a task force report was released in 2013 by the International Society for Bipolar Disorder (ISBD) on antidepressant use in bipolar disorders. Pacchiarotti and Goodwin were among the report’s authors, which concluded that available evidence on this issue is methodologically weak.
This is largely because of a lack of placebo-controlled studies in this patient population (bipolar depression, alongside suicidal ideation, is often an exclusion criteria in clinical antidepressant trials).
Many guidelines consequently do not consider antidepressants to be a first-line option as monotherapy in bipolar depression, although some name the drugs as second- or third-line options.
In 2013, the ISBD recommended that antidepressant monotherapy should be “avoided” in bipolar I disorder; and in bipolar I and II depression, the treatment should be accompanied by at least two concomitant core manic symptoms.
“What Has Changed?”
Antidepressants should be used “only if there is a history of a positive response,” whereas maintenance therapy should be considered if a patient relapses into a depressive episode after stopping the drugs, the report notes.
Pacchiarotti noted that since the recommendations were published nothing has changed, noting that antidepressant efficacy in bipolar depression “remains unproven.”
The issue is not whether antidepressants are effective in bipolar depression but rather are there subpopulations where these medications are helpful or harmful, she added.
The key to understanding the heterogeneity of responses to antidepressants, she said, is the concept of a bipolar spectrum and a dimensional approach to distinguishing between bipolar disorder and unipolar depression.
In addition, the definition of a mixed episode in the DSM-IV-TR differs from that of an episode with mixed characteristics in the DSM-5, which Pacchiarotti said offers a better understanding of the phenomenon while seemingly disposing with the idea of mixed depression.
Based on previous research, there is some suggestion that a depressive state exists between major depressive disorder and bipolar I disorder with mixed features, and hypomania state between bipolar II and I disorder, also with mixed features.
Pacchiarotti said the role of antidepressants in the treatment of bipolar depression remains “controversial” and there is a need for both short- and long-term studies of their use in both bipolar I and bipolar II disorder with real-world inclusion criteria.
The concept of a bipolar spectrum needs to be considered a more “dimensional approach” to depression, with mixed features seen as a “transversal” contraindication for antidepressant use, she concluded.
In Favor — With Caveats
Taking the opposite position and arguing in favor of antidepressant use, albeit cautiously, Goodwin said previous work has shown that stable patients with bipolar disorder experience depression of variable severity about 50% of the time.
The truth is that patients do not have a depressive episode for extended periods but instead have depressive symptoms, he said. “So how we manage and treat depression really matters.”
In an analysis, Goodwin and his colleagues estimated that the cost of bipolar disorder is approximately £12,600 ($16,000) per patient per year, of which only 30.6% is attributable to healthcare costs and 68.1% to indirect costs. This means the impact on the patient is also felt by society.
He agreed with Pacchiarotti’s assertion of a bipolar spectrum and the need for a dimensional approach.
“All the patients along the spectrum have the symptoms of depression and they differ in the extent to which they show symptoms of mania, which will include irritability,” he added.
Goodwin argued that there is no evidence to suggest that the depression experienced at one end of the scale is any different from that at the other. However, safety issues around antidepressant use “really relate to the additional symptoms you see with increasing evidence of bipolarity.”
In addition, the whole discussion is confounded by comorbidity, “with symptoms that sometimes coalesce into our concept of borderline personality disorder” or attention deficit hyperactivity disorder, he said.
Goodwin said there is “very little doubt” that antidepressants have an effect vs placebo. “The argument is over whether the effect is large and whether we should regard it as clinically significant.”
He noted that previous studies have shown a range of effect sizes with antidepressants, but the “massive” confidence intervals mean that “one is free to believe pretty much what one likes.”
The only antidepressant medication that is statistically significantly different from placebo is fluoxetine combined with olanzapine. However, that conclusion is based on “little data,” said Goodwin.
In terms of long-term management, there is “extremely little” randomized data for maintenance treatment with antidepressants in bipolar disorder. “So this does not support” long-term use, he added.
Still, although choice of antidepressant remains a guess, there is “just about support” for using them, Goodwin noted.
He urged clinicians not to dismiss antidepressant use, but to use them only where there is a clinical need and for as little time as possible. Patients with bipolar disorder should continue to take antidepressants if they relapse after they come off these medications.
However, all of that sits “in contrast” to how they’re currently used in clinical practice, Goodwin said.
Caution Urged
After the debate, the audience was asked to vote again. This time, The remaining 12% voted against the practice.
Summarizing the discussion, Vieta said that “we should be cautious” when using antidepressants in bipolar depression. However, “we should be able to use them when necessary,” he added.
Although their use as monotherapy is not best practice, especially in bipolar I disorder, there may be a subset of bipolar II patients in whom monotherapy “might still be acceptable; but I don’t think it’s a good idea,” Vieta said.
He added that clinicians should very carefully screen for mixed symptoms, which call for the prescription of other drugs, such as olanzapine and fluoxetine.
“The other important message is that we have to be even more cautious in the long term with the use of antidepressants, and we should be able to use them when there is a comorbidity” that calls for their use, Vieta concluded.
Pacchiarotti reported having received speaker fees and educational grants from Adamed, AstraZeneca, Janssen-Cilag, and Lundbeck. Goodwin reported having received honoraria from Angellini, Medscape, Pfizer, Servier, Shire, and Sun; having shares in P1vital Products; past employment as medical director of P1vital Products; and advisory board membership for Compass Pathways, Minerva, MSD, Novartis, Lundbeck, Sage, Servier, and Shire. Vieta has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Although patients with bipolar disorder commonly experience depressive symptoms, clinicians should be very cautious about treating them with antidepressants, especially as monotherapy, experts asserted in a recent debate on the topic as part of the European Psychiatric Association (EPA) 2020 Congress.
At the Congress, which was virtual this year because of the COVID-19 pandemic, psychiatric experts said that clinicians should also screen patients for mixed symptoms that are better treated with mood stabilizers. These same experts also raised concerns over long-term antidepressant use, recommending continued use only in patients who relapse after stopping antidepressants.
Isabella Pacchiarotti, MD, PhD, Centro de Investigación Biomédica en Red de Salud Mental, Barcelona, Spain, argued against the use of antidepressants in treating bipolar disorder; Guy Goodwin, PhD, however, took the “pro” stance.
Goodwin, a professor of psychiatry at the University of Oxford in the UK, admitted that there is a “paucity of data” on the role of antidepressants in bipolar disorder.
Nevertheless, there are “circumstances that one really has to treat with antidepressants simply because other things have been tried and have not worked,” he told conference attendees.
Challenging, Controversial Topic
The debate was chaired by Eduard Vieta, MD, PhD, chair of the Department of Psychiatry and Psychology at the University of Barcelona Hospital Clinic, Spain.
Vieta said the question over whether antidepressants should be used in the depressive phase of bipolar illness is “perhaps the most challenging ... especially in the area of bipolar disorder.”
At the beginning of the presentation, Vieta asked the audience for their opinion in order to have a “baseline” for the debate: among 164 respondents, 73% were in favor of using antidepressants in bipolar depression.
“Clearly there is a majority, so Isabella [Dr Pacchiarotti] is going to have a hard time improving these numbers,” Vieta noted.
Up first, Pacchiarotti began by noting that this topic remains “an area of big controversy.” However, the real question “should not be the pros and cons of antidepressants but more when and how to use them.»
Of the three phases of bipolar disorder, acute depression «poses the greatest difficulties,» she added.
This is because of the relative paucity of studies in the area, the often heated debates on the specific role of antidepressants, the discrepancy in conclusions between meta-analyses, and the currently approved therapeutic options being associated with “not very high response rates,” Pacchiarotti said.
The diagnostic criteria for unipolar and bipolar depression are “basically the same,” she noted. However, it’s important to be able to distinguish between the two conditions, as up to one fifth of patients with unipolar depression suffer from undiagnosed bipolar disorder, she explained.
Moreover, several studies have identified key symptoms in bipolar depression, such as hyperphagia and hypersomnia, increased anxiety, and psychotic and psychomotor symptoms.
As previously reported by Medscape Medical News, a task force report was released in 2013 by the International Society for Bipolar Disorder (ISBD) on antidepressant use in bipolar disorders. Pacchiarotti and Goodwin were among the report’s authors, which concluded that available evidence on this issue is methodologically weak.
This is largely because of a lack of placebo-controlled studies in this patient population (bipolar depression, alongside suicidal ideation, is often an exclusion criteria in clinical antidepressant trials).
Many guidelines consequently do not consider antidepressants to be a first-line option as monotherapy in bipolar depression, although some name the drugs as second- or third-line options.
In 2013, the ISBD recommended that antidepressant monotherapy should be “avoided” in bipolar I disorder; and in bipolar I and II depression, the treatment should be accompanied by at least two concomitant core manic symptoms.
“What Has Changed?”
Antidepressants should be used “only if there is a history of a positive response,” whereas maintenance therapy should be considered if a patient relapses into a depressive episode after stopping the drugs, the report notes.
Pacchiarotti noted that since the recommendations were published nothing has changed, noting that antidepressant efficacy in bipolar depression “remains unproven.”
The issue is not whether antidepressants are effective in bipolar depression but rather are there subpopulations where these medications are helpful or harmful, she added.
The key to understanding the heterogeneity of responses to antidepressants, she said, is the concept of a bipolar spectrum and a dimensional approach to distinguishing between bipolar disorder and unipolar depression.
In addition, the definition of a mixed episode in the DSM-IV-TR differs from that of an episode with mixed characteristics in the DSM-5, which Pacchiarotti said offers a better understanding of the phenomenon while seemingly disposing with the idea of mixed depression.
Based on previous research, there is some suggestion that a depressive state exists between major depressive disorder and bipolar I disorder with mixed features, and hypomania state between bipolar II and I disorder, also with mixed features.
Pacchiarotti said the role of antidepressants in the treatment of bipolar depression remains “controversial” and there is a need for both short- and long-term studies of their use in both bipolar I and bipolar II disorder with real-world inclusion criteria.
The concept of a bipolar spectrum needs to be considered a more “dimensional approach” to depression, with mixed features seen as a “transversal” contraindication for antidepressant use, she concluded.
In Favor — With Caveats
Taking the opposite position and arguing in favor of antidepressant use, albeit cautiously, Goodwin said previous work has shown that stable patients with bipolar disorder experience depression of variable severity about 50% of the time.
The truth is that patients do not have a depressive episode for extended periods but instead have depressive symptoms, he said. “So how we manage and treat depression really matters.”
In an analysis, Goodwin and his colleagues estimated that the cost of bipolar disorder is approximately £12,600 ($16,000) per patient per year, of which only 30.6% is attributable to healthcare costs and 68.1% to indirect costs. This means the impact on the patient is also felt by society.
He agreed with Pacchiarotti’s assertion of a bipolar spectrum and the need for a dimensional approach.
“All the patients along the spectrum have the symptoms of depression and they differ in the extent to which they show symptoms of mania, which will include irritability,” he added.
Goodwin argued that there is no evidence to suggest that the depression experienced at one end of the scale is any different from that at the other. However, safety issues around antidepressant use “really relate to the additional symptoms you see with increasing evidence of bipolarity.”
In addition, the whole discussion is confounded by comorbidity, “with symptoms that sometimes coalesce into our concept of borderline personality disorder” or attention deficit hyperactivity disorder, he said.
Goodwin said there is “very little doubt” that antidepressants have an effect vs placebo. “The argument is over whether the effect is large and whether we should regard it as clinically significant.”
He noted that previous studies have shown a range of effect sizes with antidepressants, but the “massive” confidence intervals mean that “one is free to believe pretty much what one likes.”
The only antidepressant medication that is statistically significantly different from placebo is fluoxetine combined with olanzapine. However, that conclusion is based on “little data,” said Goodwin.
In terms of long-term management, there is “extremely little” randomized data for maintenance treatment with antidepressants in bipolar disorder. “So this does not support” long-term use, he added.
Still, although choice of antidepressant remains a guess, there is “just about support” for using them, Goodwin noted.
He urged clinicians not to dismiss antidepressant use, but to use them only where there is a clinical need and for as little time as possible. Patients with bipolar disorder should continue to take antidepressants if they relapse after they come off these medications.
However, all of that sits “in contrast” to how they’re currently used in clinical practice, Goodwin said.
Caution Urged
After the debate, the audience was asked to vote again. This time, The remaining 12% voted against the practice.
Summarizing the discussion, Vieta said that “we should be cautious” when using antidepressants in bipolar depression. However, “we should be able to use them when necessary,” he added.
Although their use as monotherapy is not best practice, especially in bipolar I disorder, there may be a subset of bipolar II patients in whom monotherapy “might still be acceptable; but I don’t think it’s a good idea,” Vieta said.
He added that clinicians should very carefully screen for mixed symptoms, which call for the prescription of other drugs, such as olanzapine and fluoxetine.
“The other important message is that we have to be even more cautious in the long term with the use of antidepressants, and we should be able to use them when there is a comorbidity” that calls for their use, Vieta concluded.
Pacchiarotti reported having received speaker fees and educational grants from Adamed, AstraZeneca, Janssen-Cilag, and Lundbeck. Goodwin reported having received honoraria from Angellini, Medscape, Pfizer, Servier, Shire, and Sun; having shares in P1vital Products; past employment as medical director of P1vital Products; and advisory board membership for Compass Pathways, Minerva, MSD, Novartis, Lundbeck, Sage, Servier, and Shire. Vieta has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Although patients with bipolar disorder commonly experience depressive symptoms, clinicians should be very cautious about treating them with antidepressants, especially as monotherapy, experts asserted in a recent debate on the topic as part of the European Psychiatric Association (EPA) 2020 Congress.
At the Congress, which was virtual this year because of the COVID-19 pandemic, psychiatric experts said that clinicians should also screen patients for mixed symptoms that are better treated with mood stabilizers. These same experts also raised concerns over long-term antidepressant use, recommending continued use only in patients who relapse after stopping antidepressants.
Isabella Pacchiarotti, MD, PhD, Centro de Investigación Biomédica en Red de Salud Mental, Barcelona, Spain, argued against the use of antidepressants in treating bipolar disorder; Guy Goodwin, PhD, however, took the “pro” stance.
Goodwin, a professor of psychiatry at the University of Oxford in the UK, admitted that there is a “paucity of data” on the role of antidepressants in bipolar disorder.
Nevertheless, there are “circumstances that one really has to treat with antidepressants simply because other things have been tried and have not worked,” he told conference attendees.
Challenging, Controversial Topic
The debate was chaired by Eduard Vieta, MD, PhD, chair of the Department of Psychiatry and Psychology at the University of Barcelona Hospital Clinic, Spain.
Vieta said the question over whether antidepressants should be used in the depressive phase of bipolar illness is “perhaps the most challenging ... especially in the area of bipolar disorder.”
At the beginning of the presentation, Vieta asked the audience for their opinion in order to have a “baseline” for the debate: among 164 respondents, 73% were in favor of using antidepressants in bipolar depression.
“Clearly there is a majority, so Isabella [Dr Pacchiarotti] is going to have a hard time improving these numbers,” Vieta noted.
Up first, Pacchiarotti began by noting that this topic remains “an area of big controversy.” However, the real question “should not be the pros and cons of antidepressants but more when and how to use them.»
Of the three phases of bipolar disorder, acute depression «poses the greatest difficulties,» she added.
This is because of the relative paucity of studies in the area, the often heated debates on the specific role of antidepressants, the discrepancy in conclusions between meta-analyses, and the currently approved therapeutic options being associated with “not very high response rates,” Pacchiarotti said.
The diagnostic criteria for unipolar and bipolar depression are “basically the same,” she noted. However, it’s important to be able to distinguish between the two conditions, as up to one fifth of patients with unipolar depression suffer from undiagnosed bipolar disorder, she explained.
Moreover, several studies have identified key symptoms in bipolar depression, such as hyperphagia and hypersomnia, increased anxiety, and psychotic and psychomotor symptoms.
As previously reported by Medscape Medical News, a task force report was released in 2013 by the International Society for Bipolar Disorder (ISBD) on antidepressant use in bipolar disorders. Pacchiarotti and Goodwin were among the report’s authors, which concluded that available evidence on this issue is methodologically weak.
This is largely because of a lack of placebo-controlled studies in this patient population (bipolar depression, alongside suicidal ideation, is often an exclusion criteria in clinical antidepressant trials).
Many guidelines consequently do not consider antidepressants to be a first-line option as monotherapy in bipolar depression, although some name the drugs as second- or third-line options.
In 2013, the ISBD recommended that antidepressant monotherapy should be “avoided” in bipolar I disorder; and in bipolar I and II depression, the treatment should be accompanied by at least two concomitant core manic symptoms.
“What Has Changed?”
Antidepressants should be used “only if there is a history of a positive response,” whereas maintenance therapy should be considered if a patient relapses into a depressive episode after stopping the drugs, the report notes.
Pacchiarotti noted that since the recommendations were published nothing has changed, noting that antidepressant efficacy in bipolar depression “remains unproven.”
The issue is not whether antidepressants are effective in bipolar depression but rather are there subpopulations where these medications are helpful or harmful, she added.
The key to understanding the heterogeneity of responses to antidepressants, she said, is the concept of a bipolar spectrum and a dimensional approach to distinguishing between bipolar disorder and unipolar depression.
In addition, the definition of a mixed episode in the DSM-IV-TR differs from that of an episode with mixed characteristics in the DSM-5, which Pacchiarotti said offers a better understanding of the phenomenon while seemingly disposing with the idea of mixed depression.
Based on previous research, there is some suggestion that a depressive state exists between major depressive disorder and bipolar I disorder with mixed features, and hypomania state between bipolar II and I disorder, also with mixed features.
Pacchiarotti said the role of antidepressants in the treatment of bipolar depression remains “controversial” and there is a need for both short- and long-term studies of their use in both bipolar I and bipolar II disorder with real-world inclusion criteria.
The concept of a bipolar spectrum needs to be considered a more “dimensional approach” to depression, with mixed features seen as a “transversal” contraindication for antidepressant use, she concluded.
In Favor — With Caveats
Taking the opposite position and arguing in favor of antidepressant use, albeit cautiously, Goodwin said previous work has shown that stable patients with bipolar disorder experience depression of variable severity about 50% of the time.
The truth is that patients do not have a depressive episode for extended periods but instead have depressive symptoms, he said. “So how we manage and treat depression really matters.”
In an analysis, Goodwin and his colleagues estimated that the cost of bipolar disorder is approximately £12,600 ($16,000) per patient per year, of which only 30.6% is attributable to healthcare costs and 68.1% to indirect costs. This means the impact on the patient is also felt by society.
He agreed with Pacchiarotti’s assertion of a bipolar spectrum and the need for a dimensional approach.
“All the patients along the spectrum have the symptoms of depression and they differ in the extent to which they show symptoms of mania, which will include irritability,” he added.
Goodwin argued that there is no evidence to suggest that the depression experienced at one end of the scale is any different from that at the other. However, safety issues around antidepressant use “really relate to the additional symptoms you see with increasing evidence of bipolarity.”
In addition, the whole discussion is confounded by comorbidity, “with symptoms that sometimes coalesce into our concept of borderline personality disorder” or attention deficit hyperactivity disorder, he said.
Goodwin said there is “very little doubt” that antidepressants have an effect vs placebo. “The argument is over whether the effect is large and whether we should regard it as clinically significant.”
He noted that previous studies have shown a range of effect sizes with antidepressants, but the “massive” confidence intervals mean that “one is free to believe pretty much what one likes.”
The only antidepressant medication that is statistically significantly different from placebo is fluoxetine combined with olanzapine. However, that conclusion is based on “little data,” said Goodwin.
In terms of long-term management, there is “extremely little” randomized data for maintenance treatment with antidepressants in bipolar disorder. “So this does not support” long-term use, he added.
Still, although choice of antidepressant remains a guess, there is “just about support” for using them, Goodwin noted.
He urged clinicians not to dismiss antidepressant use, but to use them only where there is a clinical need and for as little time as possible. Patients with bipolar disorder should continue to take antidepressants if they relapse after they come off these medications.
However, all of that sits “in contrast” to how they’re currently used in clinical practice, Goodwin said.
Caution Urged
After the debate, the audience was asked to vote again. This time, The remaining 12% voted against the practice.
Summarizing the discussion, Vieta said that “we should be cautious” when using antidepressants in bipolar depression. However, “we should be able to use them when necessary,” he added.
Although their use as monotherapy is not best practice, especially in bipolar I disorder, there may be a subset of bipolar II patients in whom monotherapy “might still be acceptable; but I don’t think it’s a good idea,” Vieta said.
He added that clinicians should very carefully screen for mixed symptoms, which call for the prescription of other drugs, such as olanzapine and fluoxetine.
“The other important message is that we have to be even more cautious in the long term with the use of antidepressants, and we should be able to use them when there is a comorbidity” that calls for their use, Vieta concluded.
Pacchiarotti reported having received speaker fees and educational grants from Adamed, AstraZeneca, Janssen-Cilag, and Lundbeck. Goodwin reported having received honoraria from Angellini, Medscape, Pfizer, Servier, Shire, and Sun; having shares in P1vital Products; past employment as medical director of P1vital Products; and advisory board membership for Compass Pathways, Minerva, MSD, Novartis, Lundbeck, Sage, Servier, and Shire. Vieta has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Topical PDE-4 inhibitor for psoriasis effective in phase 2b trial
Once-daily – including challenging lesions in tough-to-treat intertriginous areas – in a phase 2b, randomized, double-blind, vehicle-controlled clinical trial, Mark G. Lebwohl, MD, reported at the virtual annual meeting of the American Academy of Dermatology.
The clinical improvement occurred rapidly. And topical roflumilast’s side effect profile was essentially the same as in vehicle-treated controls, which suggests a potential major advantage for the novel drug in future clinical practice. After all, topical treatment is the mainstay of psoriasis therapy, but the current topical agents – high-potency corticosteroids, vitamin D derivatives, and retinoids – have long-term tolerability, efficacy, or side effect issues, especially in treating sensitive skin areas, including the face and intertriginous areas.
“Roflumilast cream could really be a game changer,” predicted Dr. Lebwohl, professor and chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.
Phosphodiesterase-4 (PDE-4) activity is elevated in psoriatic skin. Indeed, inhibition of PDE-4 via oral apremilast (Otezla) is an established strategy for improving psoriasis through down-regulation of inflammatory cytokines including tumor necrosis factor–alpha, interleukins-17 and -23, and interferon-gamma. Notably, however, roflumilast is orders of magnitude more potent than any other PDE-4 inhibitor. An oral version marketed as Daliresp has been available for treatment of chronic obstructive pulmonary disease for nearly a decade.
The 12-week, multicenter, phase 2b study included 331 patients with chronic plaque psoriasis who were randomized to once-daily 0.3% roflumilast cream, 0.15% roflumilast cream, or vehicle. Three-quarters of participants had a baseline Investigator Global Assessment (IGA) score of 3, indicative of moderate disease.
The primary endpoint was achievement of an IGA score of 0 or 1 (clear or almost clear) at week 6. The observed improvement was dose related, although both doses of roflumilast were significantly more effective than vehicle. However, peak improvement occurred at week 8, not week 6, with subsequent plateauing of response through week 12. A week 8 IGA of 0 or 1 plus at least a 2-grade improvement from baseline occurred in 32% of the high-dose roflumilast group, 25% of those on the 0.15% formulation, and 10% of controls.
“The effect in improvement was very rapid, with a statistically significant improvement compared to vehicle for both concentrations as early as week 2,” Dr. Lebwohl said.
A key secondary endpoint focused on treatment response in intertriginous areas, since “those are the areas where we really don’t want to use steroids because of major irritation problems,” the dermatologist explained. At week 12, treatment success as defined by an intertriginous IGA score of 0 or 1 plus at least a 2-point improvement from baseline was seen in 86% of the 0.3% roflumilast cream group, 50% on low-dose therapy, and 29% of controls.
About 65% of subjects on high-dose roflumilast cream reported at least a 4-point reduction in the Worst Itch–Numerical Rating Scale by week 8, as did 58% of those on the low-dose version and 42% of controls. Another secondary endpoint – patient-reported burden of disease as captured in a Psoriasis Symptoms Diary – showed a significant divergence between both doses of roflumilast and vehicle as early as week 2.
“Adverse events were negligible,” Dr. Lebwohl said. “In fact, there was only one discontinuation in the 0.3% arm, compared to none with 0.15% and two with vehicle.”
The phase 3 program is now recruiting participants.
The phase 2b study was funded by Arcutis Biotherapeutics. Dr. Lebwohl reported receiving research funding from and serving as a consultant to that company and numerous others.
Once-daily – including challenging lesions in tough-to-treat intertriginous areas – in a phase 2b, randomized, double-blind, vehicle-controlled clinical trial, Mark G. Lebwohl, MD, reported at the virtual annual meeting of the American Academy of Dermatology.
The clinical improvement occurred rapidly. And topical roflumilast’s side effect profile was essentially the same as in vehicle-treated controls, which suggests a potential major advantage for the novel drug in future clinical practice. After all, topical treatment is the mainstay of psoriasis therapy, but the current topical agents – high-potency corticosteroids, vitamin D derivatives, and retinoids – have long-term tolerability, efficacy, or side effect issues, especially in treating sensitive skin areas, including the face and intertriginous areas.
“Roflumilast cream could really be a game changer,” predicted Dr. Lebwohl, professor and chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.
Phosphodiesterase-4 (PDE-4) activity is elevated in psoriatic skin. Indeed, inhibition of PDE-4 via oral apremilast (Otezla) is an established strategy for improving psoriasis through down-regulation of inflammatory cytokines including tumor necrosis factor–alpha, interleukins-17 and -23, and interferon-gamma. Notably, however, roflumilast is orders of magnitude more potent than any other PDE-4 inhibitor. An oral version marketed as Daliresp has been available for treatment of chronic obstructive pulmonary disease for nearly a decade.
The 12-week, multicenter, phase 2b study included 331 patients with chronic plaque psoriasis who were randomized to once-daily 0.3% roflumilast cream, 0.15% roflumilast cream, or vehicle. Three-quarters of participants had a baseline Investigator Global Assessment (IGA) score of 3, indicative of moderate disease.
The primary endpoint was achievement of an IGA score of 0 or 1 (clear or almost clear) at week 6. The observed improvement was dose related, although both doses of roflumilast were significantly more effective than vehicle. However, peak improvement occurred at week 8, not week 6, with subsequent plateauing of response through week 12. A week 8 IGA of 0 or 1 plus at least a 2-grade improvement from baseline occurred in 32% of the high-dose roflumilast group, 25% of those on the 0.15% formulation, and 10% of controls.
“The effect in improvement was very rapid, with a statistically significant improvement compared to vehicle for both concentrations as early as week 2,” Dr. Lebwohl said.
A key secondary endpoint focused on treatment response in intertriginous areas, since “those are the areas where we really don’t want to use steroids because of major irritation problems,” the dermatologist explained. At week 12, treatment success as defined by an intertriginous IGA score of 0 or 1 plus at least a 2-point improvement from baseline was seen in 86% of the 0.3% roflumilast cream group, 50% on low-dose therapy, and 29% of controls.
About 65% of subjects on high-dose roflumilast cream reported at least a 4-point reduction in the Worst Itch–Numerical Rating Scale by week 8, as did 58% of those on the low-dose version and 42% of controls. Another secondary endpoint – patient-reported burden of disease as captured in a Psoriasis Symptoms Diary – showed a significant divergence between both doses of roflumilast and vehicle as early as week 2.
“Adverse events were negligible,” Dr. Lebwohl said. “In fact, there was only one discontinuation in the 0.3% arm, compared to none with 0.15% and two with vehicle.”
The phase 3 program is now recruiting participants.
The phase 2b study was funded by Arcutis Biotherapeutics. Dr. Lebwohl reported receiving research funding from and serving as a consultant to that company and numerous others.
Once-daily – including challenging lesions in tough-to-treat intertriginous areas – in a phase 2b, randomized, double-blind, vehicle-controlled clinical trial, Mark G. Lebwohl, MD, reported at the virtual annual meeting of the American Academy of Dermatology.
The clinical improvement occurred rapidly. And topical roflumilast’s side effect profile was essentially the same as in vehicle-treated controls, which suggests a potential major advantage for the novel drug in future clinical practice. After all, topical treatment is the mainstay of psoriasis therapy, but the current topical agents – high-potency corticosteroids, vitamin D derivatives, and retinoids – have long-term tolerability, efficacy, or side effect issues, especially in treating sensitive skin areas, including the face and intertriginous areas.
“Roflumilast cream could really be a game changer,” predicted Dr. Lebwohl, professor and chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.
Phosphodiesterase-4 (PDE-4) activity is elevated in psoriatic skin. Indeed, inhibition of PDE-4 via oral apremilast (Otezla) is an established strategy for improving psoriasis through down-regulation of inflammatory cytokines including tumor necrosis factor–alpha, interleukins-17 and -23, and interferon-gamma. Notably, however, roflumilast is orders of magnitude more potent than any other PDE-4 inhibitor. An oral version marketed as Daliresp has been available for treatment of chronic obstructive pulmonary disease for nearly a decade.
The 12-week, multicenter, phase 2b study included 331 patients with chronic plaque psoriasis who were randomized to once-daily 0.3% roflumilast cream, 0.15% roflumilast cream, or vehicle. Three-quarters of participants had a baseline Investigator Global Assessment (IGA) score of 3, indicative of moderate disease.
The primary endpoint was achievement of an IGA score of 0 or 1 (clear or almost clear) at week 6. The observed improvement was dose related, although both doses of roflumilast were significantly more effective than vehicle. However, peak improvement occurred at week 8, not week 6, with subsequent plateauing of response through week 12. A week 8 IGA of 0 or 1 plus at least a 2-grade improvement from baseline occurred in 32% of the high-dose roflumilast group, 25% of those on the 0.15% formulation, and 10% of controls.
“The effect in improvement was very rapid, with a statistically significant improvement compared to vehicle for both concentrations as early as week 2,” Dr. Lebwohl said.
A key secondary endpoint focused on treatment response in intertriginous areas, since “those are the areas where we really don’t want to use steroids because of major irritation problems,” the dermatologist explained. At week 12, treatment success as defined by an intertriginous IGA score of 0 or 1 plus at least a 2-point improvement from baseline was seen in 86% of the 0.3% roflumilast cream group, 50% on low-dose therapy, and 29% of controls.
About 65% of subjects on high-dose roflumilast cream reported at least a 4-point reduction in the Worst Itch–Numerical Rating Scale by week 8, as did 58% of those on the low-dose version and 42% of controls. Another secondary endpoint – patient-reported burden of disease as captured in a Psoriasis Symptoms Diary – showed a significant divergence between both doses of roflumilast and vehicle as early as week 2.
“Adverse events were negligible,” Dr. Lebwohl said. “In fact, there was only one discontinuation in the 0.3% arm, compared to none with 0.15% and two with vehicle.”
The phase 3 program is now recruiting participants.
The phase 2b study was funded by Arcutis Biotherapeutics. Dr. Lebwohl reported receiving research funding from and serving as a consultant to that company and numerous others.
FROM AAD 20