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Which biologic is best in Crohn’s? Jury’s still out
LAS VEGAS – Biologics have dramatically improved the treatment of Crohn’s disease (CD), an influential gastroenterologist told colleagues, but there is still no clear evidence suggesting which ones are best as first-line treatments.
When it comes to making a choice, insurer policies may play a role, said Gary R. Lichtenstein, MD, lead author of the American College of Gastroenterology’s 2018 treatment guidelines for CD. Otherwise, “you’re left with clinical factors, your own judgment, and some indirect data,” said Dr. Lichtenstein, professor of medicine at the University of Pennsylvania, Philadelphia, who spoke about the guidelines in a presentation at the Crohn’s & Colitis Congress – a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
Dr. Lichtenstein spoke about recommendations regarding treatment of CD in several areas. The following is a summary of some points he made:
Diagnosis: Some tests aren’t recommended
Classic signs and symptoms of CD include abdominal pain, diarrhea, fatigue, weight loss, failure to grow, anemia, and manifestations outside the intestines. Fecal calprotectin testing is recommended to differentiate inflammatory bowel disease from irritable bowel syndrome; genetic testing and serologic markers are not recommended for diagnosis.
Ileocolonoscopy is recommended for diagnosis and provides details about severity. Several factors suggest higher risk of progressive disease: Young age at diagnosis, initial extensive bowel involvement, perianal/severe rectal disease, and penetrating or stenosing phenotype at diagnosis.
Research is hinting that visceral adiposity may be a risk factor too, Dr. Lichtenstein said, adding that “the greater the number of poor prognostic factors, the worse the likelihood of needing a colectomy.”
Focus of treatment: Don’t just consider symptoms
For patients with moderate to severe disease, guidelines now suggest that physicians not just focus on symptoms but also consider endoscopic signs of response and healing. Guidelines also recommend paying attention to quality of life and levels of stress, anxiety, and depression.
Drug therapy: Biologics stand apart
Budesonide is appropriate for induction therapy in mild to moderate CD. There are many possible treatments for moderate to severe disease, including steroids for induction and thiopurines or methotrexate for maintenance
But biologics stand apart, Dr. Lichtenstein said, noting that “they have really been the mainstay of the treatment of our moderate to severe patients.”
Still, he cautioned that tumor necrosis factor (TNF) inhibitors are linked to a variety of adverse effects, including demyelination, heart failure, auto-immunity, infusion reactions, immunogenicity, infection, bone marrow suppression, and cancer. Specifically, the risk of lymphoma and melanoma may go up, although the absolute risk is low.
He added that a third of patients will not respond to TNF inhibitors, and about half of those who do respond may stop responding after a few years.
Among newer drugs, vedolizumab (Entyvio) is useful as an induction and maintenance drug in CD. “We recognize it has a slow onset of action,” Dr. Lichtenstein said. “Waiting is part of what one needs to do. Those who had prior anti-TNF failures are less likely to respond than those who have been anti-TNF naive.”
The drug has a favorable safety profile, he said.
Ustekinumab (Stelara) also has a favorable safety profile with very low infection risk, although Dr. Lichtenstein said he expects that the drug will be linked to a small increased risk of cancer. “Perhaps I’ll be wrong,” he said, “but time will tell.”
So which biologic is best? Direct head-to-head trials are lacking, Dr. Lichtenstein said. However, a 2018 systematic review and network meta-analysis analyzed clinical trial data and came to these conclusions: Infliximab (Remicade) and adalimumab (Humira) are best for induction of remission in biologic-naive patients; adalimumab and ustekinumab are best for induction of remission in TNF inhibitor–exposed patients; adalimumab and infliximab are best for maintenance of remission; and ustekinumab and infliximab are best in terms of lowest risk of adverse events or infection (Aliment Pharmacol Ther. 2018 Aug;48[4]:394-409).
Dr. Lichtenstein reports many disclosures with multiple drugmakers, including both grants/research support and consulting relationships with Celgene, Janssen Biotech, Salix, Shire, UCB and Warner Chilcott.
LAS VEGAS – Biologics have dramatically improved the treatment of Crohn’s disease (CD), an influential gastroenterologist told colleagues, but there is still no clear evidence suggesting which ones are best as first-line treatments.
When it comes to making a choice, insurer policies may play a role, said Gary R. Lichtenstein, MD, lead author of the American College of Gastroenterology’s 2018 treatment guidelines for CD. Otherwise, “you’re left with clinical factors, your own judgment, and some indirect data,” said Dr. Lichtenstein, professor of medicine at the University of Pennsylvania, Philadelphia, who spoke about the guidelines in a presentation at the Crohn’s & Colitis Congress – a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
Dr. Lichtenstein spoke about recommendations regarding treatment of CD in several areas. The following is a summary of some points he made:
Diagnosis: Some tests aren’t recommended
Classic signs and symptoms of CD include abdominal pain, diarrhea, fatigue, weight loss, failure to grow, anemia, and manifestations outside the intestines. Fecal calprotectin testing is recommended to differentiate inflammatory bowel disease from irritable bowel syndrome; genetic testing and serologic markers are not recommended for diagnosis.
Ileocolonoscopy is recommended for diagnosis and provides details about severity. Several factors suggest higher risk of progressive disease: Young age at diagnosis, initial extensive bowel involvement, perianal/severe rectal disease, and penetrating or stenosing phenotype at diagnosis.
Research is hinting that visceral adiposity may be a risk factor too, Dr. Lichtenstein said, adding that “the greater the number of poor prognostic factors, the worse the likelihood of needing a colectomy.”
Focus of treatment: Don’t just consider symptoms
For patients with moderate to severe disease, guidelines now suggest that physicians not just focus on symptoms but also consider endoscopic signs of response and healing. Guidelines also recommend paying attention to quality of life and levels of stress, anxiety, and depression.
Drug therapy: Biologics stand apart
Budesonide is appropriate for induction therapy in mild to moderate CD. There are many possible treatments for moderate to severe disease, including steroids for induction and thiopurines or methotrexate for maintenance
But biologics stand apart, Dr. Lichtenstein said, noting that “they have really been the mainstay of the treatment of our moderate to severe patients.”
Still, he cautioned that tumor necrosis factor (TNF) inhibitors are linked to a variety of adverse effects, including demyelination, heart failure, auto-immunity, infusion reactions, immunogenicity, infection, bone marrow suppression, and cancer. Specifically, the risk of lymphoma and melanoma may go up, although the absolute risk is low.
He added that a third of patients will not respond to TNF inhibitors, and about half of those who do respond may stop responding after a few years.
Among newer drugs, vedolizumab (Entyvio) is useful as an induction and maintenance drug in CD. “We recognize it has a slow onset of action,” Dr. Lichtenstein said. “Waiting is part of what one needs to do. Those who had prior anti-TNF failures are less likely to respond than those who have been anti-TNF naive.”
The drug has a favorable safety profile, he said.
Ustekinumab (Stelara) also has a favorable safety profile with very low infection risk, although Dr. Lichtenstein said he expects that the drug will be linked to a small increased risk of cancer. “Perhaps I’ll be wrong,” he said, “but time will tell.”
So which biologic is best? Direct head-to-head trials are lacking, Dr. Lichtenstein said. However, a 2018 systematic review and network meta-analysis analyzed clinical trial data and came to these conclusions: Infliximab (Remicade) and adalimumab (Humira) are best for induction of remission in biologic-naive patients; adalimumab and ustekinumab are best for induction of remission in TNF inhibitor–exposed patients; adalimumab and infliximab are best for maintenance of remission; and ustekinumab and infliximab are best in terms of lowest risk of adverse events or infection (Aliment Pharmacol Ther. 2018 Aug;48[4]:394-409).
Dr. Lichtenstein reports many disclosures with multiple drugmakers, including both grants/research support and consulting relationships with Celgene, Janssen Biotech, Salix, Shire, UCB and Warner Chilcott.
LAS VEGAS – Biologics have dramatically improved the treatment of Crohn’s disease (CD), an influential gastroenterologist told colleagues, but there is still no clear evidence suggesting which ones are best as first-line treatments.
When it comes to making a choice, insurer policies may play a role, said Gary R. Lichtenstein, MD, lead author of the American College of Gastroenterology’s 2018 treatment guidelines for CD. Otherwise, “you’re left with clinical factors, your own judgment, and some indirect data,” said Dr. Lichtenstein, professor of medicine at the University of Pennsylvania, Philadelphia, who spoke about the guidelines in a presentation at the Crohn’s & Colitis Congress – a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
Dr. Lichtenstein spoke about recommendations regarding treatment of CD in several areas. The following is a summary of some points he made:
Diagnosis: Some tests aren’t recommended
Classic signs and symptoms of CD include abdominal pain, diarrhea, fatigue, weight loss, failure to grow, anemia, and manifestations outside the intestines. Fecal calprotectin testing is recommended to differentiate inflammatory bowel disease from irritable bowel syndrome; genetic testing and serologic markers are not recommended for diagnosis.
Ileocolonoscopy is recommended for diagnosis and provides details about severity. Several factors suggest higher risk of progressive disease: Young age at diagnosis, initial extensive bowel involvement, perianal/severe rectal disease, and penetrating or stenosing phenotype at diagnosis.
Research is hinting that visceral adiposity may be a risk factor too, Dr. Lichtenstein said, adding that “the greater the number of poor prognostic factors, the worse the likelihood of needing a colectomy.”
Focus of treatment: Don’t just consider symptoms
For patients with moderate to severe disease, guidelines now suggest that physicians not just focus on symptoms but also consider endoscopic signs of response and healing. Guidelines also recommend paying attention to quality of life and levels of stress, anxiety, and depression.
Drug therapy: Biologics stand apart
Budesonide is appropriate for induction therapy in mild to moderate CD. There are many possible treatments for moderate to severe disease, including steroids for induction and thiopurines or methotrexate for maintenance
But biologics stand apart, Dr. Lichtenstein said, noting that “they have really been the mainstay of the treatment of our moderate to severe patients.”
Still, he cautioned that tumor necrosis factor (TNF) inhibitors are linked to a variety of adverse effects, including demyelination, heart failure, auto-immunity, infusion reactions, immunogenicity, infection, bone marrow suppression, and cancer. Specifically, the risk of lymphoma and melanoma may go up, although the absolute risk is low.
He added that a third of patients will not respond to TNF inhibitors, and about half of those who do respond may stop responding after a few years.
Among newer drugs, vedolizumab (Entyvio) is useful as an induction and maintenance drug in CD. “We recognize it has a slow onset of action,” Dr. Lichtenstein said. “Waiting is part of what one needs to do. Those who had prior anti-TNF failures are less likely to respond than those who have been anti-TNF naive.”
The drug has a favorable safety profile, he said.
Ustekinumab (Stelara) also has a favorable safety profile with very low infection risk, although Dr. Lichtenstein said he expects that the drug will be linked to a small increased risk of cancer. “Perhaps I’ll be wrong,” he said, “but time will tell.”
So which biologic is best? Direct head-to-head trials are lacking, Dr. Lichtenstein said. However, a 2018 systematic review and network meta-analysis analyzed clinical trial data and came to these conclusions: Infliximab (Remicade) and adalimumab (Humira) are best for induction of remission in biologic-naive patients; adalimumab and ustekinumab are best for induction of remission in TNF inhibitor–exposed patients; adalimumab and infliximab are best for maintenance of remission; and ustekinumab and infliximab are best in terms of lowest risk of adverse events or infection (Aliment Pharmacol Ther. 2018 Aug;48[4]:394-409).
Dr. Lichtenstein reports many disclosures with multiple drugmakers, including both grants/research support and consulting relationships with Celgene, Janssen Biotech, Salix, Shire, UCB and Warner Chilcott.
EXPERT ANALYSIS FROM CROHN’S & COLITIS CONGRESS
What’s the price of rude behavior in the hospital?
SAN DIEGO – Does rudeness from a colleague prevent physicians from noticing a diagnostic error and challenging it? A new study suggests it might not, at least in the context of hand-offs from dismissive and insulting fellow doctors.
Instead, a simulation found that experience seems to be the key factor in giving physicians the guts – or the awareness – to change course. Still, the findings hint that rudeness may still have a negative effect on one group – resident physicians.
“It appears that we are building resilience somewhere in training,” said study lead author Michael Avesar, MD, a pediatric critical care medicine fellow at Children’s Hospital Los Angeles.
Dr. Avesar spoke in an interview following the presentation of the study findings at the Critical Care Congress sponsored by the Society of Critical Care Medicine.
The initial motivation of the study wasn’t to gain more understanding of rudeness in medicine. Instead, Dr. Avesar said, “We started off with trying to find ways to understand how physicians think during high-stakes decisions in stressful or time-limited situations. We wanted to see if people were able to challenge the momentum of diagnostic error. That’s when we learned more about the rudeness literature.”
Yes, it’s true: Researchers have devoted time to studying rudeness in medicine. After all, it’s quite common. A 2017 Israeli study in Pediatrics declared it’s “routinely experienced by medical teams.” That study, also based on simulations, determined that “rudeness has robust, deleterious effects on the performance of medical teams. Moreover, exposure to rudeness debilitated the very collaborative mechanisms recognized as essential for patient care and safety” (Pediatrics. 2017 Feb. doi: 10.1542/peds.2016-2305).
For the new study, Dr. Avesar and his colleagues ultimately decided to explore possible links between rudeness and diagnostic error. To explore the issue, they created a simulation of a hand-off of a pediatric patient from the operating team to the ICU.
In the simulation, the “physician” handing off the “patient” incorrectly noted a diagnosis of sepsis. In fact, the patient had cardiac tamponade.
The physician, played by an actor, was instructed to either act in a neutral fashion during the hand-off or be rude. But rudeness, it turns out, isn’t easy to define, even if we all think we know it when we see it.
“There’s a lot of debate as to what is ‘rude,’ ” Dr. Avesar said. The researchers settled on a level of rudeness that wasn’t “too mean” but was still inappropriate: It featured frequent interruptions during the hand-off, lack of eye contact, and abrupt departures. In some simulations, the actor insulted the colleagues of the recipient of the hand-off.
In other words, Dr. Avesar said, the actor was a jerk.
The researchers tested the “neutral” and “rude” hand-off scenarios in 41 simulations. The physicians who played the recipients of the hand-offs included 11 attendings, 14 fellows, and 16 residents.
Eighty-two percent of the attendings (9/11) challenged the diagnosis, as did 86% (12/14) of the fellows. Only 31% (5/16) of residents challenged the diagnosis; this difference from the other groups was statistically significant.
Half of the eight residents exposed to a “neutral” handoff challenged the correct diagnosis, while only 13% (1/8) of those who were treated rudely did. “While the P value was not significant, previous literature focused on residents supports this trend,” Dr. Avesar said.
It’s possible that certain residents gain the knowledge and experience to overcome rudeness over time, he said. That, he said, leads to an intriguing question: “Could we find out how resilience is learned and how to replicate it?”
Moving forward, he said, the team will try to figure out whether there’s a link between personality types and reactions to rudeness.
Eventually, he said, the team may test ways to reduce the effects of rudeness and boost critical thinking. “We see this as a long-term strategy to enhance medical education and patient safety,” he said.
No study funding is reported. Dr. Avesar reports no relevant disclosures.
SOURCE: Avesar M et al. Crit Care Med. 2019 Jan;47(1):682, Abstract 1412.
SAN DIEGO – Does rudeness from a colleague prevent physicians from noticing a diagnostic error and challenging it? A new study suggests it might not, at least in the context of hand-offs from dismissive and insulting fellow doctors.
Instead, a simulation found that experience seems to be the key factor in giving physicians the guts – or the awareness – to change course. Still, the findings hint that rudeness may still have a negative effect on one group – resident physicians.
“It appears that we are building resilience somewhere in training,” said study lead author Michael Avesar, MD, a pediatric critical care medicine fellow at Children’s Hospital Los Angeles.
Dr. Avesar spoke in an interview following the presentation of the study findings at the Critical Care Congress sponsored by the Society of Critical Care Medicine.
The initial motivation of the study wasn’t to gain more understanding of rudeness in medicine. Instead, Dr. Avesar said, “We started off with trying to find ways to understand how physicians think during high-stakes decisions in stressful or time-limited situations. We wanted to see if people were able to challenge the momentum of diagnostic error. That’s when we learned more about the rudeness literature.”
Yes, it’s true: Researchers have devoted time to studying rudeness in medicine. After all, it’s quite common. A 2017 Israeli study in Pediatrics declared it’s “routinely experienced by medical teams.” That study, also based on simulations, determined that “rudeness has robust, deleterious effects on the performance of medical teams. Moreover, exposure to rudeness debilitated the very collaborative mechanisms recognized as essential for patient care and safety” (Pediatrics. 2017 Feb. doi: 10.1542/peds.2016-2305).
For the new study, Dr. Avesar and his colleagues ultimately decided to explore possible links between rudeness and diagnostic error. To explore the issue, they created a simulation of a hand-off of a pediatric patient from the operating team to the ICU.
In the simulation, the “physician” handing off the “patient” incorrectly noted a diagnosis of sepsis. In fact, the patient had cardiac tamponade.
The physician, played by an actor, was instructed to either act in a neutral fashion during the hand-off or be rude. But rudeness, it turns out, isn’t easy to define, even if we all think we know it when we see it.
“There’s a lot of debate as to what is ‘rude,’ ” Dr. Avesar said. The researchers settled on a level of rudeness that wasn’t “too mean” but was still inappropriate: It featured frequent interruptions during the hand-off, lack of eye contact, and abrupt departures. In some simulations, the actor insulted the colleagues of the recipient of the hand-off.
In other words, Dr. Avesar said, the actor was a jerk.
The researchers tested the “neutral” and “rude” hand-off scenarios in 41 simulations. The physicians who played the recipients of the hand-offs included 11 attendings, 14 fellows, and 16 residents.
Eighty-two percent of the attendings (9/11) challenged the diagnosis, as did 86% (12/14) of the fellows. Only 31% (5/16) of residents challenged the diagnosis; this difference from the other groups was statistically significant.
Half of the eight residents exposed to a “neutral” handoff challenged the correct diagnosis, while only 13% (1/8) of those who were treated rudely did. “While the P value was not significant, previous literature focused on residents supports this trend,” Dr. Avesar said.
It’s possible that certain residents gain the knowledge and experience to overcome rudeness over time, he said. That, he said, leads to an intriguing question: “Could we find out how resilience is learned and how to replicate it?”
Moving forward, he said, the team will try to figure out whether there’s a link between personality types and reactions to rudeness.
Eventually, he said, the team may test ways to reduce the effects of rudeness and boost critical thinking. “We see this as a long-term strategy to enhance medical education and patient safety,” he said.
No study funding is reported. Dr. Avesar reports no relevant disclosures.
SOURCE: Avesar M et al. Crit Care Med. 2019 Jan;47(1):682, Abstract 1412.
SAN DIEGO – Does rudeness from a colleague prevent physicians from noticing a diagnostic error and challenging it? A new study suggests it might not, at least in the context of hand-offs from dismissive and insulting fellow doctors.
Instead, a simulation found that experience seems to be the key factor in giving physicians the guts – or the awareness – to change course. Still, the findings hint that rudeness may still have a negative effect on one group – resident physicians.
“It appears that we are building resilience somewhere in training,” said study lead author Michael Avesar, MD, a pediatric critical care medicine fellow at Children’s Hospital Los Angeles.
Dr. Avesar spoke in an interview following the presentation of the study findings at the Critical Care Congress sponsored by the Society of Critical Care Medicine.
The initial motivation of the study wasn’t to gain more understanding of rudeness in medicine. Instead, Dr. Avesar said, “We started off with trying to find ways to understand how physicians think during high-stakes decisions in stressful or time-limited situations. We wanted to see if people were able to challenge the momentum of diagnostic error. That’s when we learned more about the rudeness literature.”
Yes, it’s true: Researchers have devoted time to studying rudeness in medicine. After all, it’s quite common. A 2017 Israeli study in Pediatrics declared it’s “routinely experienced by medical teams.” That study, also based on simulations, determined that “rudeness has robust, deleterious effects on the performance of medical teams. Moreover, exposure to rudeness debilitated the very collaborative mechanisms recognized as essential for patient care and safety” (Pediatrics. 2017 Feb. doi: 10.1542/peds.2016-2305).
For the new study, Dr. Avesar and his colleagues ultimately decided to explore possible links between rudeness and diagnostic error. To explore the issue, they created a simulation of a hand-off of a pediatric patient from the operating team to the ICU.
In the simulation, the “physician” handing off the “patient” incorrectly noted a diagnosis of sepsis. In fact, the patient had cardiac tamponade.
The physician, played by an actor, was instructed to either act in a neutral fashion during the hand-off or be rude. But rudeness, it turns out, isn’t easy to define, even if we all think we know it when we see it.
“There’s a lot of debate as to what is ‘rude,’ ” Dr. Avesar said. The researchers settled on a level of rudeness that wasn’t “too mean” but was still inappropriate: It featured frequent interruptions during the hand-off, lack of eye contact, and abrupt departures. In some simulations, the actor insulted the colleagues of the recipient of the hand-off.
In other words, Dr. Avesar said, the actor was a jerk.
The researchers tested the “neutral” and “rude” hand-off scenarios in 41 simulations. The physicians who played the recipients of the hand-offs included 11 attendings, 14 fellows, and 16 residents.
Eighty-two percent of the attendings (9/11) challenged the diagnosis, as did 86% (12/14) of the fellows. Only 31% (5/16) of residents challenged the diagnosis; this difference from the other groups was statistically significant.
Half of the eight residents exposed to a “neutral” handoff challenged the correct diagnosis, while only 13% (1/8) of those who were treated rudely did. “While the P value was not significant, previous literature focused on residents supports this trend,” Dr. Avesar said.
It’s possible that certain residents gain the knowledge and experience to overcome rudeness over time, he said. That, he said, leads to an intriguing question: “Could we find out how resilience is learned and how to replicate it?”
Moving forward, he said, the team will try to figure out whether there’s a link between personality types and reactions to rudeness.
Eventually, he said, the team may test ways to reduce the effects of rudeness and boost critical thinking. “We see this as a long-term strategy to enhance medical education and patient safety,” he said.
No study funding is reported. Dr. Avesar reports no relevant disclosures.
SOURCE: Avesar M et al. Crit Care Med. 2019 Jan;47(1):682, Abstract 1412.
REPORTING FROM CCC48
Umbilical cord allograft may boost diabetic foot ulcer healing
Dehydrated human umbilical cord allograft may have benefit over alginate wound dressings as a treatment for chronic, nonhealing diabetic foot ulcers (DFU), findings from an industry-funded, randomized controlled study suggest.
The findings “provide additional evidence of the safety and efficacy of dehydrated placental tissues,” wrote William Tettelbach, MD, and his colleagues. Their report is in International Wound Journal.
The burden of diabetic foot disease in the United States is immense. A 2014 study estimated that treatment of DFUs alone cost public and private insurers as much as $13 billion per year (Diabetes Care. 2014;37(3):651-8).
MiMedx, which funded the new study, has developed a product called EpiCord to protect the DFU wound site. The product’s website describes it as a “unique, thick membrane derived from umbilical cord” that’s “minimally manipulated, dehydrated, [and] non-viable” (www.mimedx.com/epicord). The study authors noted that “immunogenicity of placental tissue lends credence to its use as an allograft material for difficult-to-heal wounds.”
For the new study, which was conducted from 2016 to 2018 and led by Dr. Tettelbach, an infectious disease specialist who is now an employee of MiMedx, the researchers enlisted 155 adult patients with stubborn DFUs at 11 centers in the United States.
All the ulcers had 30% or less wound area reduction after 14 days of standard care. The majority of patients (81%) were male; 63% were obese, 43% were smokers, and 17% had a prior amputation.
The patients were randomly assigned to receive a weekly application of EpiCord (n = 101) or treatment with an alginate wound dressing (n = 54) in addition to standard care. The percentage of patients whose wounds healed completely by 12 weeks later was higher in the study group than in those who were treated with alginate dressings (70% vs. 48%, respectively; P = .0089), per an intent-to-treat analysis.
The researchers also focused purely on patients who had received adequate debridement (107/155 ulcers, 69%). Of those ulcers, 64/67 (96%), in the study group healed completely at 12 weeks, compared with 26/40 (65%) of the alginate group (P less than .0001.)
The researchers did not notice any adverse effects related to either dressing.
According to the study, the findings regarding EpiCord are comparable with a sister study of a similar product by the same company that was tested in diabetic lower-extremity ulcers. That study, of a product called EpiFix, was published in the same issue of the journal (Int Wound J. 2019 Feb;16[1]:19-29).
“A thicker and more durable allograft such as EpiCord may be a good choice for implantation into deeper wounds and in situations where suturing the allograft in place is desired,” the authors wrote of the EpiCord study.
MiMedx provided research funding to all of the authors.
SOURCE: Tettelbach W et al. Int Wound J. 2019;16(1):122-130. doi: 10.1111/iwj.12976.
Dehydrated human umbilical cord allograft may have benefit over alginate wound dressings as a treatment for chronic, nonhealing diabetic foot ulcers (DFU), findings from an industry-funded, randomized controlled study suggest.
The findings “provide additional evidence of the safety and efficacy of dehydrated placental tissues,” wrote William Tettelbach, MD, and his colleagues. Their report is in International Wound Journal.
The burden of diabetic foot disease in the United States is immense. A 2014 study estimated that treatment of DFUs alone cost public and private insurers as much as $13 billion per year (Diabetes Care. 2014;37(3):651-8).
MiMedx, which funded the new study, has developed a product called EpiCord to protect the DFU wound site. The product’s website describes it as a “unique, thick membrane derived from umbilical cord” that’s “minimally manipulated, dehydrated, [and] non-viable” (www.mimedx.com/epicord). The study authors noted that “immunogenicity of placental tissue lends credence to its use as an allograft material for difficult-to-heal wounds.”
For the new study, which was conducted from 2016 to 2018 and led by Dr. Tettelbach, an infectious disease specialist who is now an employee of MiMedx, the researchers enlisted 155 adult patients with stubborn DFUs at 11 centers in the United States.
All the ulcers had 30% or less wound area reduction after 14 days of standard care. The majority of patients (81%) were male; 63% were obese, 43% were smokers, and 17% had a prior amputation.
The patients were randomly assigned to receive a weekly application of EpiCord (n = 101) or treatment with an alginate wound dressing (n = 54) in addition to standard care. The percentage of patients whose wounds healed completely by 12 weeks later was higher in the study group than in those who were treated with alginate dressings (70% vs. 48%, respectively; P = .0089), per an intent-to-treat analysis.
The researchers also focused purely on patients who had received adequate debridement (107/155 ulcers, 69%). Of those ulcers, 64/67 (96%), in the study group healed completely at 12 weeks, compared with 26/40 (65%) of the alginate group (P less than .0001.)
The researchers did not notice any adverse effects related to either dressing.
According to the study, the findings regarding EpiCord are comparable with a sister study of a similar product by the same company that was tested in diabetic lower-extremity ulcers. That study, of a product called EpiFix, was published in the same issue of the journal (Int Wound J. 2019 Feb;16[1]:19-29).
“A thicker and more durable allograft such as EpiCord may be a good choice for implantation into deeper wounds and in situations where suturing the allograft in place is desired,” the authors wrote of the EpiCord study.
MiMedx provided research funding to all of the authors.
SOURCE: Tettelbach W et al. Int Wound J. 2019;16(1):122-130. doi: 10.1111/iwj.12976.
Dehydrated human umbilical cord allograft may have benefit over alginate wound dressings as a treatment for chronic, nonhealing diabetic foot ulcers (DFU), findings from an industry-funded, randomized controlled study suggest.
The findings “provide additional evidence of the safety and efficacy of dehydrated placental tissues,” wrote William Tettelbach, MD, and his colleagues. Their report is in International Wound Journal.
The burden of diabetic foot disease in the United States is immense. A 2014 study estimated that treatment of DFUs alone cost public and private insurers as much as $13 billion per year (Diabetes Care. 2014;37(3):651-8).
MiMedx, which funded the new study, has developed a product called EpiCord to protect the DFU wound site. The product’s website describes it as a “unique, thick membrane derived from umbilical cord” that’s “minimally manipulated, dehydrated, [and] non-viable” (www.mimedx.com/epicord). The study authors noted that “immunogenicity of placental tissue lends credence to its use as an allograft material for difficult-to-heal wounds.”
For the new study, which was conducted from 2016 to 2018 and led by Dr. Tettelbach, an infectious disease specialist who is now an employee of MiMedx, the researchers enlisted 155 adult patients with stubborn DFUs at 11 centers in the United States.
All the ulcers had 30% or less wound area reduction after 14 days of standard care. The majority of patients (81%) were male; 63% were obese, 43% were smokers, and 17% had a prior amputation.
The patients were randomly assigned to receive a weekly application of EpiCord (n = 101) or treatment with an alginate wound dressing (n = 54) in addition to standard care. The percentage of patients whose wounds healed completely by 12 weeks later was higher in the study group than in those who were treated with alginate dressings (70% vs. 48%, respectively; P = .0089), per an intent-to-treat analysis.
The researchers also focused purely on patients who had received adequate debridement (107/155 ulcers, 69%). Of those ulcers, 64/67 (96%), in the study group healed completely at 12 weeks, compared with 26/40 (65%) of the alginate group (P less than .0001.)
The researchers did not notice any adverse effects related to either dressing.
According to the study, the findings regarding EpiCord are comparable with a sister study of a similar product by the same company that was tested in diabetic lower-extremity ulcers. That study, of a product called EpiFix, was published in the same issue of the journal (Int Wound J. 2019 Feb;16[1]:19-29).
“A thicker and more durable allograft such as EpiCord may be a good choice for implantation into deeper wounds and in situations where suturing the allograft in place is desired,” the authors wrote of the EpiCord study.
MiMedx provided research funding to all of the authors.
SOURCE: Tettelbach W et al. Int Wound J. 2019;16(1):122-130. doi: 10.1111/iwj.12976.
FROM INTERNATIONAL WOUND JOURNAL
Consider therapeutic drug monitoring in stubborn IBD cases
LAS VEGAS – An estimated 10%-30% of patients with inflammatory bowel disease (IBD) don’t respond to biologics, leaving physicians with a big question: What now? Evidence suggests the best strategy is an approach grounded in therapeutic drug monitoring, appropriate disease monitoring, and other strategies, a gastroenterologist told colleagues.
“We can’t look at any one of these tools in isolation,” said Edward V. Loftus Jr., MD, professor of medicine at the Mayo Clinic in Rochester, Minn. He spoke about a reactive approach to stubborn cases of IBD at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
Dr. Loftus offered several tips and tidbits about managing IBD, especially when patients fail to appropriately respond to biologics.
- Many other conditions can cause symptoms that may appear to suggest lack of response to medication in IBD. These can include celiac disease, bacterial overgrowth, bile salt diarrhea, irritable bowel syndrome, hypersensitivity colitis, short bowel syndrome, and carbohydrate malabsorption. As a result, “before you make big changes in biologics or immunomodulators, make sure you’re actually confirming the presence of inflammation,” Dr. Loftus advised. Appropriate tests may be a colonoscopy/ileoscopy, CT or MR enterography, or a simple fecal calprotectin test; he also recommended that physicians exclude complications such as stricture, fistula, and abscess.
- The definition of lack of response in IBD has evolved over the years, Dr. Loftus said. The definition ideally refers to clinical response after an appropriate time period, such as 14 weeks of treatment (infliximab) or 8-12 weeks of treatment (injectable anti–tumor necrosis factor [TNF] drugs).
- Factors linked to primary nonresponse include disease duration of 2 years or more, smoking, and elevated C-reactive protein.
- Secondary lack of response – when drugs lose effectiveness over time even though they previously were effective – is common in IBD, with research suggesting it may affect about 20% of patients on infliximab or adalimumab.
- When patients fail to fully respond to a therapeutic level of an anti-TNF drug, research suggests it may be more effective to switch to another one rather than increase the dose, Dr. Loftus said.
- In cases of secondary lack of response in patients taking anti-TNF drugs, AGA guidelines suggest therapeutic drug monitoring may be appropriate, Dr. Loftus said. However, the AGA doesn’t make any recommendations regarding therapeutic drug monitoring in cases where IBD is dormant while patients are on anti-TNF drugs.
- Research suggests that a treat-to-target approach – designed to reach specific testing targets – may boost the effectiveness of therapeutic drug monitoring, Dr. Loftus said, and algorithm-based treatment might be even better.
“Therapeutic drug management in isolation will only get you so far,” he advised. “But don’t be confused. The drug level is not the target. The absence of inflammation is the target.”
Dr. Loftus reported recent relationships (research support and consultant) with multiple drugmakers, including AbbVie, Bristol-Myers Squibb, Pfizer, Gilead, Celgene, Eli Lilly, and several others.
LAS VEGAS – An estimated 10%-30% of patients with inflammatory bowel disease (IBD) don’t respond to biologics, leaving physicians with a big question: What now? Evidence suggests the best strategy is an approach grounded in therapeutic drug monitoring, appropriate disease monitoring, and other strategies, a gastroenterologist told colleagues.
“We can’t look at any one of these tools in isolation,” said Edward V. Loftus Jr., MD, professor of medicine at the Mayo Clinic in Rochester, Minn. He spoke about a reactive approach to stubborn cases of IBD at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
Dr. Loftus offered several tips and tidbits about managing IBD, especially when patients fail to appropriately respond to biologics.
- Many other conditions can cause symptoms that may appear to suggest lack of response to medication in IBD. These can include celiac disease, bacterial overgrowth, bile salt diarrhea, irritable bowel syndrome, hypersensitivity colitis, short bowel syndrome, and carbohydrate malabsorption. As a result, “before you make big changes in biologics or immunomodulators, make sure you’re actually confirming the presence of inflammation,” Dr. Loftus advised. Appropriate tests may be a colonoscopy/ileoscopy, CT or MR enterography, or a simple fecal calprotectin test; he also recommended that physicians exclude complications such as stricture, fistula, and abscess.
- The definition of lack of response in IBD has evolved over the years, Dr. Loftus said. The definition ideally refers to clinical response after an appropriate time period, such as 14 weeks of treatment (infliximab) or 8-12 weeks of treatment (injectable anti–tumor necrosis factor [TNF] drugs).
- Factors linked to primary nonresponse include disease duration of 2 years or more, smoking, and elevated C-reactive protein.
- Secondary lack of response – when drugs lose effectiveness over time even though they previously were effective – is common in IBD, with research suggesting it may affect about 20% of patients on infliximab or adalimumab.
- When patients fail to fully respond to a therapeutic level of an anti-TNF drug, research suggests it may be more effective to switch to another one rather than increase the dose, Dr. Loftus said.
- In cases of secondary lack of response in patients taking anti-TNF drugs, AGA guidelines suggest therapeutic drug monitoring may be appropriate, Dr. Loftus said. However, the AGA doesn’t make any recommendations regarding therapeutic drug monitoring in cases where IBD is dormant while patients are on anti-TNF drugs.
- Research suggests that a treat-to-target approach – designed to reach specific testing targets – may boost the effectiveness of therapeutic drug monitoring, Dr. Loftus said, and algorithm-based treatment might be even better.
“Therapeutic drug management in isolation will only get you so far,” he advised. “But don’t be confused. The drug level is not the target. The absence of inflammation is the target.”
Dr. Loftus reported recent relationships (research support and consultant) with multiple drugmakers, including AbbVie, Bristol-Myers Squibb, Pfizer, Gilead, Celgene, Eli Lilly, and several others.
LAS VEGAS – An estimated 10%-30% of patients with inflammatory bowel disease (IBD) don’t respond to biologics, leaving physicians with a big question: What now? Evidence suggests the best strategy is an approach grounded in therapeutic drug monitoring, appropriate disease monitoring, and other strategies, a gastroenterologist told colleagues.
“We can’t look at any one of these tools in isolation,” said Edward V. Loftus Jr., MD, professor of medicine at the Mayo Clinic in Rochester, Minn. He spoke about a reactive approach to stubborn cases of IBD at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
Dr. Loftus offered several tips and tidbits about managing IBD, especially when patients fail to appropriately respond to biologics.
- Many other conditions can cause symptoms that may appear to suggest lack of response to medication in IBD. These can include celiac disease, bacterial overgrowth, bile salt diarrhea, irritable bowel syndrome, hypersensitivity colitis, short bowel syndrome, and carbohydrate malabsorption. As a result, “before you make big changes in biologics or immunomodulators, make sure you’re actually confirming the presence of inflammation,” Dr. Loftus advised. Appropriate tests may be a colonoscopy/ileoscopy, CT or MR enterography, or a simple fecal calprotectin test; he also recommended that physicians exclude complications such as stricture, fistula, and abscess.
- The definition of lack of response in IBD has evolved over the years, Dr. Loftus said. The definition ideally refers to clinical response after an appropriate time period, such as 14 weeks of treatment (infliximab) or 8-12 weeks of treatment (injectable anti–tumor necrosis factor [TNF] drugs).
- Factors linked to primary nonresponse include disease duration of 2 years or more, smoking, and elevated C-reactive protein.
- Secondary lack of response – when drugs lose effectiveness over time even though they previously were effective – is common in IBD, with research suggesting it may affect about 20% of patients on infliximab or adalimumab.
- When patients fail to fully respond to a therapeutic level of an anti-TNF drug, research suggests it may be more effective to switch to another one rather than increase the dose, Dr. Loftus said.
- In cases of secondary lack of response in patients taking anti-TNF drugs, AGA guidelines suggest therapeutic drug monitoring may be appropriate, Dr. Loftus said. However, the AGA doesn’t make any recommendations regarding therapeutic drug monitoring in cases where IBD is dormant while patients are on anti-TNF drugs.
- Research suggests that a treat-to-target approach – designed to reach specific testing targets – may boost the effectiveness of therapeutic drug monitoring, Dr. Loftus said, and algorithm-based treatment might be even better.
“Therapeutic drug management in isolation will only get you so far,” he advised. “But don’t be confused. The drug level is not the target. The absence of inflammation is the target.”
Dr. Loftus reported recent relationships (research support and consultant) with multiple drugmakers, including AbbVie, Bristol-Myers Squibb, Pfizer, Gilead, Celgene, Eli Lilly, and several others.
EXPERT ANALYSIS FROM THE CROHN’S & COLITIS CONGRESS
Antidepressants may be best add-on to antipsychotics in schizophrenia
Antidepressants could be the best adjunctive treatment for adult outpatients with schizophrenia who are taking a second-generation antipsychotic and need a change in medication, results of an observational study suggest. Patients who added antidepressants to their treatment had a lower risk of psychiatric hospitalization and emergency room visits than did those who tried an alternative antipsychotic, and those who took mood stabilizers and benzodiazepines were significantly more likely to die over 365 days.
Specifically, “the possibility that adjunctive use of gabapentin is associated with increased risk of death raises a serious concern,” wrote T. Scott Stroup, MD, MPH, of the department of psychiatry at Columbia University, New York, and his associates in JAMA Psychiatry.
Often, Dr. Stroup and his associates noted, second-generation antipsychotics often are insufficient to alleviate symptoms and leave patients with functional limitations. said Dr. Stroup, who is also affiliated with the New York State Psychiatric Institute, and his associates.
Using a Medicaid database, the researchers retrospectively tracked 81,921 outpatients with schizophrenia (aged 18-64 years; mean age, 41 years; 46% women) who were treated with a single antipsychotic from 2001-2010. Each patient added an antidepressant (31,117), a benzodiazepine (11,941), a mood stabilizer (12,849), or another second-generation antipsychotic (26,014).
The researchers examined treatment outcomes over a yearlong period after patients began their new treatment and compared the various groups to the reference group (those who began taking an additional antipsychotic medication).
Compared with the reference group, patients who took an antidepressant had a lower risk of psychiatric hospitalization (hazard ratio, 0.84; 95% confidence interval, 0.80-0.88), while the benzodiazepine group had a higher risk (HR, 1.08; 95% CI, 1.02-1.15), and the mood stabilizer group saw no major difference (HR, 0.98; 95% CI, 0.94-1.03). Similar results were found for the risk of psychiatric emergency department visits, compared with the reference group: The HR with the addition of an antidepressant was 0.92 (95% CI, 0.88-0.96), 1.12 with a benzodiazepine (95% CI, 1.07-1.19), and 0.99 with a mood stabilizer (95% CI, 0.94-1.04).
In regard to mortality, the researchers found that mood stabilizers and benzodiazepines stood apart on the risk front with HRs of 1.31 (95% CI, 1.04-1.66) and 1.22 (95% CI, 0.98-1.52), respectively. Among mood stabilizer use, Gabapentin accounted for 1,755 initiations (13.7%) and was associated with 45 deaths (28.0%), the researchers reported. “No other mood stabilizer appeared to be associated with a higher rate of death than the others.”
Dr. Stroup and his associates cited several limitations. One is that the results might not be generalizable because the investigators looked only at patients who were enrolled in the Medicaid program. Nevertheless, “improved pharmacologic treatment of schizophrenia and consequent reduced need for hospitalization and ED visits associated with more antidepressant and less benzodiazepine use would represent a significant benefit for individuals and for public health,” they wrote.
The study authors reported various relationships with drugmakers, including Auspex, Intra-Cellular Therapies, Eli Lilly, Bristol-Myers Squibb, and Merck. The study was funded by a Patient-Centered Outcomes Research Institute award.
SOURCE: Stroup TS et al. JAMA Psychiatry. 2019 Feb 20. doi: 10.1001/jamapsychiatry.2018.4489.
Much of the research into adjunctive therapy in schizophrenia is of poor quality, and other hurdles make it difficult to understand the best treatment approach. The new study links the addition of an antidepressant to a substantial lowering of psychiatric hospitalization risk, compared with initiating another antipsychotic, wrote Donald C. Goff, MD. Previous randomized controlled trials (RCTs) have suggested that adding on antidepressants can moderately reduce symptoms – mainly negative ones – in schizophrenia. The study findings are preliminary and suggest that an RCT is in order.
Dr. Goff disclosed grants from Avanir.
These statements are based on an accompanying editorial by Dr. Goff of New York University (JAMA Psychiatry. 2019 Feb 20. doi: 10.1001/jamapsychiatry.2018.4318).
Much of the research into adjunctive therapy in schizophrenia is of poor quality, and other hurdles make it difficult to understand the best treatment approach. The new study links the addition of an antidepressant to a substantial lowering of psychiatric hospitalization risk, compared with initiating another antipsychotic, wrote Donald C. Goff, MD. Previous randomized controlled trials (RCTs) have suggested that adding on antidepressants can moderately reduce symptoms – mainly negative ones – in schizophrenia. The study findings are preliminary and suggest that an RCT is in order.
Dr. Goff disclosed grants from Avanir.
These statements are based on an accompanying editorial by Dr. Goff of New York University (JAMA Psychiatry. 2019 Feb 20. doi: 10.1001/jamapsychiatry.2018.4318).
Much of the research into adjunctive therapy in schizophrenia is of poor quality, and other hurdles make it difficult to understand the best treatment approach. The new study links the addition of an antidepressant to a substantial lowering of psychiatric hospitalization risk, compared with initiating another antipsychotic, wrote Donald C. Goff, MD. Previous randomized controlled trials (RCTs) have suggested that adding on antidepressants can moderately reduce symptoms – mainly negative ones – in schizophrenia. The study findings are preliminary and suggest that an RCT is in order.
Dr. Goff disclosed grants from Avanir.
These statements are based on an accompanying editorial by Dr. Goff of New York University (JAMA Psychiatry. 2019 Feb 20. doi: 10.1001/jamapsychiatry.2018.4318).
Antidepressants could be the best adjunctive treatment for adult outpatients with schizophrenia who are taking a second-generation antipsychotic and need a change in medication, results of an observational study suggest. Patients who added antidepressants to their treatment had a lower risk of psychiatric hospitalization and emergency room visits than did those who tried an alternative antipsychotic, and those who took mood stabilizers and benzodiazepines were significantly more likely to die over 365 days.
Specifically, “the possibility that adjunctive use of gabapentin is associated with increased risk of death raises a serious concern,” wrote T. Scott Stroup, MD, MPH, of the department of psychiatry at Columbia University, New York, and his associates in JAMA Psychiatry.
Often, Dr. Stroup and his associates noted, second-generation antipsychotics often are insufficient to alleviate symptoms and leave patients with functional limitations. said Dr. Stroup, who is also affiliated with the New York State Psychiatric Institute, and his associates.
Using a Medicaid database, the researchers retrospectively tracked 81,921 outpatients with schizophrenia (aged 18-64 years; mean age, 41 years; 46% women) who were treated with a single antipsychotic from 2001-2010. Each patient added an antidepressant (31,117), a benzodiazepine (11,941), a mood stabilizer (12,849), or another second-generation antipsychotic (26,014).
The researchers examined treatment outcomes over a yearlong period after patients began their new treatment and compared the various groups to the reference group (those who began taking an additional antipsychotic medication).
Compared with the reference group, patients who took an antidepressant had a lower risk of psychiatric hospitalization (hazard ratio, 0.84; 95% confidence interval, 0.80-0.88), while the benzodiazepine group had a higher risk (HR, 1.08; 95% CI, 1.02-1.15), and the mood stabilizer group saw no major difference (HR, 0.98; 95% CI, 0.94-1.03). Similar results were found for the risk of psychiatric emergency department visits, compared with the reference group: The HR with the addition of an antidepressant was 0.92 (95% CI, 0.88-0.96), 1.12 with a benzodiazepine (95% CI, 1.07-1.19), and 0.99 with a mood stabilizer (95% CI, 0.94-1.04).
In regard to mortality, the researchers found that mood stabilizers and benzodiazepines stood apart on the risk front with HRs of 1.31 (95% CI, 1.04-1.66) and 1.22 (95% CI, 0.98-1.52), respectively. Among mood stabilizer use, Gabapentin accounted for 1,755 initiations (13.7%) and was associated with 45 deaths (28.0%), the researchers reported. “No other mood stabilizer appeared to be associated with a higher rate of death than the others.”
Dr. Stroup and his associates cited several limitations. One is that the results might not be generalizable because the investigators looked only at patients who were enrolled in the Medicaid program. Nevertheless, “improved pharmacologic treatment of schizophrenia and consequent reduced need for hospitalization and ED visits associated with more antidepressant and less benzodiazepine use would represent a significant benefit for individuals and for public health,” they wrote.
The study authors reported various relationships with drugmakers, including Auspex, Intra-Cellular Therapies, Eli Lilly, Bristol-Myers Squibb, and Merck. The study was funded by a Patient-Centered Outcomes Research Institute award.
SOURCE: Stroup TS et al. JAMA Psychiatry. 2019 Feb 20. doi: 10.1001/jamapsychiatry.2018.4489.
Antidepressants could be the best adjunctive treatment for adult outpatients with schizophrenia who are taking a second-generation antipsychotic and need a change in medication, results of an observational study suggest. Patients who added antidepressants to their treatment had a lower risk of psychiatric hospitalization and emergency room visits than did those who tried an alternative antipsychotic, and those who took mood stabilizers and benzodiazepines were significantly more likely to die over 365 days.
Specifically, “the possibility that adjunctive use of gabapentin is associated with increased risk of death raises a serious concern,” wrote T. Scott Stroup, MD, MPH, of the department of psychiatry at Columbia University, New York, and his associates in JAMA Psychiatry.
Often, Dr. Stroup and his associates noted, second-generation antipsychotics often are insufficient to alleviate symptoms and leave patients with functional limitations. said Dr. Stroup, who is also affiliated with the New York State Psychiatric Institute, and his associates.
Using a Medicaid database, the researchers retrospectively tracked 81,921 outpatients with schizophrenia (aged 18-64 years; mean age, 41 years; 46% women) who were treated with a single antipsychotic from 2001-2010. Each patient added an antidepressant (31,117), a benzodiazepine (11,941), a mood stabilizer (12,849), or another second-generation antipsychotic (26,014).
The researchers examined treatment outcomes over a yearlong period after patients began their new treatment and compared the various groups to the reference group (those who began taking an additional antipsychotic medication).
Compared with the reference group, patients who took an antidepressant had a lower risk of psychiatric hospitalization (hazard ratio, 0.84; 95% confidence interval, 0.80-0.88), while the benzodiazepine group had a higher risk (HR, 1.08; 95% CI, 1.02-1.15), and the mood stabilizer group saw no major difference (HR, 0.98; 95% CI, 0.94-1.03). Similar results were found for the risk of psychiatric emergency department visits, compared with the reference group: The HR with the addition of an antidepressant was 0.92 (95% CI, 0.88-0.96), 1.12 with a benzodiazepine (95% CI, 1.07-1.19), and 0.99 with a mood stabilizer (95% CI, 0.94-1.04).
In regard to mortality, the researchers found that mood stabilizers and benzodiazepines stood apart on the risk front with HRs of 1.31 (95% CI, 1.04-1.66) and 1.22 (95% CI, 0.98-1.52), respectively. Among mood stabilizer use, Gabapentin accounted for 1,755 initiations (13.7%) and was associated with 45 deaths (28.0%), the researchers reported. “No other mood stabilizer appeared to be associated with a higher rate of death than the others.”
Dr. Stroup and his associates cited several limitations. One is that the results might not be generalizable because the investigators looked only at patients who were enrolled in the Medicaid program. Nevertheless, “improved pharmacologic treatment of schizophrenia and consequent reduced need for hospitalization and ED visits associated with more antidepressant and less benzodiazepine use would represent a significant benefit for individuals and for public health,” they wrote.
The study authors reported various relationships with drugmakers, including Auspex, Intra-Cellular Therapies, Eli Lilly, Bristol-Myers Squibb, and Merck. The study was funded by a Patient-Centered Outcomes Research Institute award.
SOURCE: Stroup TS et al. JAMA Psychiatry. 2019 Feb 20. doi: 10.1001/jamapsychiatry.2018.4489.
FROM JAMA PSYCHIATRY
Death data spur black-box warning for gout drug Uloric
, the Food and Drug Administration declared on Feb. 21. The agency is now mandating a black-box warning.
“Health care professionals should reserve Uloric for use only in patients who have failed or do not tolerate allopurinol,” the FDA announced. “Counsel patients about the cardiovascular risk with Uloric,” the agency suggested, and advise them to seek medical attention at once if they have cardiac symptoms such as chest pain, shortness of breath, rapid or irregular heartbeat, or dizziness.
The FDA’s move comes a decade after it approved febuxostat as a gout treatment. As the FDA noted in its announcement, “the number of medicines to treat gout is limited, and there is an unmet need for treatments for this disease.”
Research has suggested that both febuxostat and allopurinol have similar efficacy. Some experts have recommended febuxostat as an alternative for patients who shouldn’t take allopurinol (Semin Arthritis Rheum. 2013 Dec;43[3]:367-75).
However, research has raised concerns about febuxostat’s cardiac risk. In its Feb. 21 statement, the FDA pointed to the findings of a 2010-2017 postmarket clinical trial of 6,190 patients with gout who were treated with febuxostat or allopurinol (N Engl J Med. 2018;378:1200-10).
“In patients treated with Uloric, 15 deaths from heart-related causes were observed for every 1,000 patients treated for a year compared to 11 deaths from heart-related causes per 1,000 patients treated with allopurinol for a year,” the FDA said. “In addition, there were 26 deaths from any cause per 1,000 patients treated for a year with Uloric compared to 22 deaths per 1,000 patients treated for a year with allopurinol.”
, the Food and Drug Administration declared on Feb. 21. The agency is now mandating a black-box warning.
“Health care professionals should reserve Uloric for use only in patients who have failed or do not tolerate allopurinol,” the FDA announced. “Counsel patients about the cardiovascular risk with Uloric,” the agency suggested, and advise them to seek medical attention at once if they have cardiac symptoms such as chest pain, shortness of breath, rapid or irregular heartbeat, or dizziness.
The FDA’s move comes a decade after it approved febuxostat as a gout treatment. As the FDA noted in its announcement, “the number of medicines to treat gout is limited, and there is an unmet need for treatments for this disease.”
Research has suggested that both febuxostat and allopurinol have similar efficacy. Some experts have recommended febuxostat as an alternative for patients who shouldn’t take allopurinol (Semin Arthritis Rheum. 2013 Dec;43[3]:367-75).
However, research has raised concerns about febuxostat’s cardiac risk. In its Feb. 21 statement, the FDA pointed to the findings of a 2010-2017 postmarket clinical trial of 6,190 patients with gout who were treated with febuxostat or allopurinol (N Engl J Med. 2018;378:1200-10).
“In patients treated with Uloric, 15 deaths from heart-related causes were observed for every 1,000 patients treated for a year compared to 11 deaths from heart-related causes per 1,000 patients treated with allopurinol for a year,” the FDA said. “In addition, there were 26 deaths from any cause per 1,000 patients treated for a year with Uloric compared to 22 deaths per 1,000 patients treated for a year with allopurinol.”
, the Food and Drug Administration declared on Feb. 21. The agency is now mandating a black-box warning.
“Health care professionals should reserve Uloric for use only in patients who have failed or do not tolerate allopurinol,” the FDA announced. “Counsel patients about the cardiovascular risk with Uloric,” the agency suggested, and advise them to seek medical attention at once if they have cardiac symptoms such as chest pain, shortness of breath, rapid or irregular heartbeat, or dizziness.
The FDA’s move comes a decade after it approved febuxostat as a gout treatment. As the FDA noted in its announcement, “the number of medicines to treat gout is limited, and there is an unmet need for treatments for this disease.”
Research has suggested that both febuxostat and allopurinol have similar efficacy. Some experts have recommended febuxostat as an alternative for patients who shouldn’t take allopurinol (Semin Arthritis Rheum. 2013 Dec;43[3]:367-75).
However, research has raised concerns about febuxostat’s cardiac risk. In its Feb. 21 statement, the FDA pointed to the findings of a 2010-2017 postmarket clinical trial of 6,190 patients with gout who were treated with febuxostat or allopurinol (N Engl J Med. 2018;378:1200-10).
“In patients treated with Uloric, 15 deaths from heart-related causes were observed for every 1,000 patients treated for a year compared to 11 deaths from heart-related causes per 1,000 patients treated with allopurinol for a year,” the FDA said. “In addition, there were 26 deaths from any cause per 1,000 patients treated for a year with Uloric compared to 22 deaths per 1,000 patients treated for a year with allopurinol.”
Experts: Consider enteral therapy in CD, with caveats
LAS VEGAS – Temporarily switching to an enteral diet – without solid food – has the potential to reverse Crohn’s disease (CD), especially in children, a panel of experts told gastroenterologists here.
They acknowledged the controversial treatment requires strict adherence and can be impossible for some patients to tolerate. But it can be successful too, said gastroenterologist Lindsey G. Albenberg, DO, of Children’s Hospital of Philadelphia, where enteral nutrition therapy (ENT) is commonly used in patients with CD.
“Parents are obviously thrilled that there’s no exposure to immunosuppressive medications,” she said in a discussion about ENT at the Crohn’s & Colitis Congress - a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “Typically, we provide 80%-90% of calorie needs through a polymeric formula by mouth. If we see clinical response at 4-6 weeks or even earlier, then we will pursue a course of about 8-12 weeks.”
Research into the best role for ENT therapy in CD is limited. A 2018 Cochrane Library review found there’s “very low quality evidence” suggesting that ENT is better than steroids to induce remission in children. It also found there’s “very low quality evidence” that steroids are better than ENT in adults with CD (Cochrane Database Syst Rev. 2018 Apr 1. doi: 10.1002/14651858.CD000542.pub3).
According to clinician-scientist James D. Lewis, MD, MSCE, of the University of Pennsylvania, Philadelphia, ENT “has gotten a bad name in some ways because of a meta-analysis showing it was inferior to corticosteroids to induce remission.” In fact, he said, studies “didn’t look at mucosal healing and pooled together adults and children.”
In children, he said, the treatment seems to clearly be effective. The picture is less promising in adults. “Presumably that’s because those of you who are parents probably have more control over your young children than your own behavior,” he said, referring to management of food intake.
In adults, “there’s no reason to think it wouldn’t work,” he said. “But trying to convince adults to give up food is really challenging.”
Children who try ENT are often required to use a nasogastric feeding tube, an approach that adults tend to avoid. In kids, “it’s a question of knowing your patient,” said gastroenterologist David Suskind, MD, of Seattle Children’s Hospital. “If the patient says, ‘There’s no way you’ll put a nasal gastric tube in, and no way I will drink it [the ENT supplement],’ this may not be the best therapy. If they’re interested, we push forward. We get much better efficacy because the patients will do what we’re asking.”
Several panelists recommended that patients use polymeric formulations instead of elemental formulations because they’re more palatable. It can be a struggle, however, to stick with the treatment.
Kelly Issokson, MS, RD, CNSC, a dietitian with Cedars-Sinai Medical Center in Los Angeles, tried an ENT therapy for 30 days in order to understand what patients experience and said it was “very challenging.”
“When you sit down to a meal, you anticipate it, you start to salivate. With shakes, it was a lot more clinical,” she said. “The other thing I struggled with was texture and having it be so sweet. I’d freeze [the shakes] into ice cube trays and popsicles. That helped break the monotony. It changes the flavor and cuts the sweetness.”
Ms. Issokson urges her patients to stick with ENT for the entire period of therapy. “Studies show when patients introduce real foods the efficacy of inducing remission goes down. We recommend 100% calories and proteins coming from the formula,” she said. That means “no coffee, no broth, no tea, no nothing but the formula. Most of our patients are able to do that exclusively.”
Toward the end of therapy, around week 8 or 11, some patients tell her they crave food like soup. “I say OK, have a tiny bit,” she said, “but remember, this is only temporary. We’re almost at the end. Try to be 100% exclusive.”
Dr. Albenberg and Dr. Suskind report no disclosures. Ms. Issokson reports consulting fees (speaking and teaching) from AGA, Crohn’s & Colitis Foundation, Academy of Nutrition and Dietetics, and United Ostomy Association. Dr. Lewis reports many relationships – including consulting fees, ownership interest, and grant/research support – with Eli Lilly, Bristol‐Myers Squibb, Gilead, and others.
Correction, 2/22/19: An earlier version of this article misidentified the person in the first photo above.
LAS VEGAS – Temporarily switching to an enteral diet – without solid food – has the potential to reverse Crohn’s disease (CD), especially in children, a panel of experts told gastroenterologists here.
They acknowledged the controversial treatment requires strict adherence and can be impossible for some patients to tolerate. But it can be successful too, said gastroenterologist Lindsey G. Albenberg, DO, of Children’s Hospital of Philadelphia, where enteral nutrition therapy (ENT) is commonly used in patients with CD.
“Parents are obviously thrilled that there’s no exposure to immunosuppressive medications,” she said in a discussion about ENT at the Crohn’s & Colitis Congress - a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “Typically, we provide 80%-90% of calorie needs through a polymeric formula by mouth. If we see clinical response at 4-6 weeks or even earlier, then we will pursue a course of about 8-12 weeks.”
Research into the best role for ENT therapy in CD is limited. A 2018 Cochrane Library review found there’s “very low quality evidence” suggesting that ENT is better than steroids to induce remission in children. It also found there’s “very low quality evidence” that steroids are better than ENT in adults with CD (Cochrane Database Syst Rev. 2018 Apr 1. doi: 10.1002/14651858.CD000542.pub3).
According to clinician-scientist James D. Lewis, MD, MSCE, of the University of Pennsylvania, Philadelphia, ENT “has gotten a bad name in some ways because of a meta-analysis showing it was inferior to corticosteroids to induce remission.” In fact, he said, studies “didn’t look at mucosal healing and pooled together adults and children.”
In children, he said, the treatment seems to clearly be effective. The picture is less promising in adults. “Presumably that’s because those of you who are parents probably have more control over your young children than your own behavior,” he said, referring to management of food intake.
In adults, “there’s no reason to think it wouldn’t work,” he said. “But trying to convince adults to give up food is really challenging.”
Children who try ENT are often required to use a nasogastric feeding tube, an approach that adults tend to avoid. In kids, “it’s a question of knowing your patient,” said gastroenterologist David Suskind, MD, of Seattle Children’s Hospital. “If the patient says, ‘There’s no way you’ll put a nasal gastric tube in, and no way I will drink it [the ENT supplement],’ this may not be the best therapy. If they’re interested, we push forward. We get much better efficacy because the patients will do what we’re asking.”
Several panelists recommended that patients use polymeric formulations instead of elemental formulations because they’re more palatable. It can be a struggle, however, to stick with the treatment.
Kelly Issokson, MS, RD, CNSC, a dietitian with Cedars-Sinai Medical Center in Los Angeles, tried an ENT therapy for 30 days in order to understand what patients experience and said it was “very challenging.”
“When you sit down to a meal, you anticipate it, you start to salivate. With shakes, it was a lot more clinical,” she said. “The other thing I struggled with was texture and having it be so sweet. I’d freeze [the shakes] into ice cube trays and popsicles. That helped break the monotony. It changes the flavor and cuts the sweetness.”
Ms. Issokson urges her patients to stick with ENT for the entire period of therapy. “Studies show when patients introduce real foods the efficacy of inducing remission goes down. We recommend 100% calories and proteins coming from the formula,” she said. That means “no coffee, no broth, no tea, no nothing but the formula. Most of our patients are able to do that exclusively.”
Toward the end of therapy, around week 8 or 11, some patients tell her they crave food like soup. “I say OK, have a tiny bit,” she said, “but remember, this is only temporary. We’re almost at the end. Try to be 100% exclusive.”
Dr. Albenberg and Dr. Suskind report no disclosures. Ms. Issokson reports consulting fees (speaking and teaching) from AGA, Crohn’s & Colitis Foundation, Academy of Nutrition and Dietetics, and United Ostomy Association. Dr. Lewis reports many relationships – including consulting fees, ownership interest, and grant/research support – with Eli Lilly, Bristol‐Myers Squibb, Gilead, and others.
Correction, 2/22/19: An earlier version of this article misidentified the person in the first photo above.
LAS VEGAS – Temporarily switching to an enteral diet – without solid food – has the potential to reverse Crohn’s disease (CD), especially in children, a panel of experts told gastroenterologists here.
They acknowledged the controversial treatment requires strict adherence and can be impossible for some patients to tolerate. But it can be successful too, said gastroenterologist Lindsey G. Albenberg, DO, of Children’s Hospital of Philadelphia, where enteral nutrition therapy (ENT) is commonly used in patients with CD.
“Parents are obviously thrilled that there’s no exposure to immunosuppressive medications,” she said in a discussion about ENT at the Crohn’s & Colitis Congress - a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “Typically, we provide 80%-90% of calorie needs through a polymeric formula by mouth. If we see clinical response at 4-6 weeks or even earlier, then we will pursue a course of about 8-12 weeks.”
Research into the best role for ENT therapy in CD is limited. A 2018 Cochrane Library review found there’s “very low quality evidence” suggesting that ENT is better than steroids to induce remission in children. It also found there’s “very low quality evidence” that steroids are better than ENT in adults with CD (Cochrane Database Syst Rev. 2018 Apr 1. doi: 10.1002/14651858.CD000542.pub3).
According to clinician-scientist James D. Lewis, MD, MSCE, of the University of Pennsylvania, Philadelphia, ENT “has gotten a bad name in some ways because of a meta-analysis showing it was inferior to corticosteroids to induce remission.” In fact, he said, studies “didn’t look at mucosal healing and pooled together adults and children.”
In children, he said, the treatment seems to clearly be effective. The picture is less promising in adults. “Presumably that’s because those of you who are parents probably have more control over your young children than your own behavior,” he said, referring to management of food intake.
In adults, “there’s no reason to think it wouldn’t work,” he said. “But trying to convince adults to give up food is really challenging.”
Children who try ENT are often required to use a nasogastric feeding tube, an approach that adults tend to avoid. In kids, “it’s a question of knowing your patient,” said gastroenterologist David Suskind, MD, of Seattle Children’s Hospital. “If the patient says, ‘There’s no way you’ll put a nasal gastric tube in, and no way I will drink it [the ENT supplement],’ this may not be the best therapy. If they’re interested, we push forward. We get much better efficacy because the patients will do what we’re asking.”
Several panelists recommended that patients use polymeric formulations instead of elemental formulations because they’re more palatable. It can be a struggle, however, to stick with the treatment.
Kelly Issokson, MS, RD, CNSC, a dietitian with Cedars-Sinai Medical Center in Los Angeles, tried an ENT therapy for 30 days in order to understand what patients experience and said it was “very challenging.”
“When you sit down to a meal, you anticipate it, you start to salivate. With shakes, it was a lot more clinical,” she said. “The other thing I struggled with was texture and having it be so sweet. I’d freeze [the shakes] into ice cube trays and popsicles. That helped break the monotony. It changes the flavor and cuts the sweetness.”
Ms. Issokson urges her patients to stick with ENT for the entire period of therapy. “Studies show when patients introduce real foods the efficacy of inducing remission goes down. We recommend 100% calories and proteins coming from the formula,” she said. That means “no coffee, no broth, no tea, no nothing but the formula. Most of our patients are able to do that exclusively.”
Toward the end of therapy, around week 8 or 11, some patients tell her they crave food like soup. “I say OK, have a tiny bit,” she said, “but remember, this is only temporary. We’re almost at the end. Try to be 100% exclusive.”
Dr. Albenberg and Dr. Suskind report no disclosures. Ms. Issokson reports consulting fees (speaking and teaching) from AGA, Crohn’s & Colitis Foundation, Academy of Nutrition and Dietetics, and United Ostomy Association. Dr. Lewis reports many relationships – including consulting fees, ownership interest, and grant/research support – with Eli Lilly, Bristol‐Myers Squibb, Gilead, and others.
Correction, 2/22/19: An earlier version of this article misidentified the person in the first photo above.
EXPERT ANALYSIS FROM THE CROHN’S & COLITIS CONGRESS
Cochrane/IBD review roundup: Limited evidence keeps verdicts at bay
LAS VEGAS – Cochrane Library reviews of studies into inflammatory bowel disease (IBD) from 2018 revealed limited evidence – so far – to support enteral nutrition therapy (EN) and cannabis in Crohn’s disease (CD) and fecal transplantation in IBD.
But Morris Gordon, MBChB, MMed, PhD, a Cochrane Library researcher who provided a roundup for colleagues, said there’s tremendous opportunity to build upon existing research in these areas.
Dr. Gordon, a pediatrician with a special gastric interest at the University of Central Lancashire in Preston, England, spoke at the Crohn’s & Colitis Congress - a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
In his presentation, Dr. Gordon discussed several Cochrane Library reviews published in 2018 in these topic areas:
Enteral therapy
EN was a hot topic at the Crohn’s & Colitics Congress, which devoted a large panel discussion to the benefits of its use in inducing remission in CD, especially in children.
However, an updated 2018 Cochrane Library systematic review found that “very low quality evidence suggests that corticosteroid therapy may be more effective than EN for induction of clinical remission in adults with active CD. Very low quality evidence also suggests that EN may be more effective than steroids for induction of remission in children with active CD” (Cochrane Database Syst Rev. 2018 Apr 1. doi: 10.1002/14651858.CD000542.pub3).
The review recommended that “EN should be considered in pediatric CD patients or in adult patients who can comply with nasogastric tube feeding or perceive the formulations to be palatable, or when steroid side effects are not tolerated or better avoided.”
Another 2018 Cochrane Library Review concluded that “no firm conclusions regarding the efficacy and safety of enteral nutrition in quiescent CD can be drawn” (Cochrane Database Syst Rev. 2018 Aug 11. doi: 10.1002/14651858.CD005984.pub3).
Dr. Gordon noted that IBD guidelines support EN to induce CD remission in children, and he called for “high quality research” to provide more evidence to support this recommendation.
Cannabis
In regard to cannabis, Dr. Gordon referred to a 2018 Cochrane review that examined three studies that investigated its use in CD and determined “the effects of cannabis and cannabis oil on Crohn’s disease are uncertain” (Cochrane Database Syst Rev. 2018 Nov 8. doi: 10.1002/14651858.CD012853.pub2).
He said future studies should focus on the effect of cannabis on quality of life and pain reduction. “That’s where the research needs to go,” he said.
Another 2018 Cochrane review examined two small studies exploring the use of cannabis in ulcerative colitis and reported similar findings, declaring that “the effects of cannabis and cannabidiol on UC are uncertain” (Cochrane Database Syst Rev. 2018 Nov 8. doi: 10.1002/14651858.CD012954.pub2).
Fecal transplantation
The Cochrane Library also examined research into fecal transplantation for IBD. A 2018 review reported that “fecal microbiota transplantation may increase the proportion of participants achieving clinical remission in UC. However, the number of identified studies was small and the quality of evidence was low. There is uncertainty about the rate of serious adverse events. As a result, no solid conclusions can be drawn at this time” (Cochrane Database Syst Rev. 2018 Nov 13. doi: 10.1002/14651858.CD012774.pub2).
Still, Dr. Gordon said, fecal transplantation is “really promising.”
Another 2018 Cochrane review of IBD research – this one focusing on natalizumab (Tysabri) as a tool for induction of remission of CD – was more conclusive. It examined five trials and found that “high quality data suggest that natalizumab is effective for induction of clinical remission and response in some patients with moderately to severely active CD”(Cochrane Database Syst Rev. 2018 Aug 1. doi: 10.1002/14651858.CD006097.pub3).
However, the review noted that none of the studies was high powered enough to detect rare serious adverse effects such as progressive multifocal leukoencephalopathy (PML). “Due to the association with PML, and the availability of alternative agents that are not associated with PML, natalizumab is not likely to be used in patients who fail currently available medical therapy,” the reviewers wrote. “Further studies of natalizumab are not likely to be done.”
Dr. Gordon reports unrestricted travel grants over the past 3 years from Ferring, Synergy, Tillotts, and BioGaia. He holds a National Institute for Health Research Cochrane IBD Program Grant.
LAS VEGAS – Cochrane Library reviews of studies into inflammatory bowel disease (IBD) from 2018 revealed limited evidence – so far – to support enteral nutrition therapy (EN) and cannabis in Crohn’s disease (CD) and fecal transplantation in IBD.
But Morris Gordon, MBChB, MMed, PhD, a Cochrane Library researcher who provided a roundup for colleagues, said there’s tremendous opportunity to build upon existing research in these areas.
Dr. Gordon, a pediatrician with a special gastric interest at the University of Central Lancashire in Preston, England, spoke at the Crohn’s & Colitis Congress - a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
In his presentation, Dr. Gordon discussed several Cochrane Library reviews published in 2018 in these topic areas:
Enteral therapy
EN was a hot topic at the Crohn’s & Colitics Congress, which devoted a large panel discussion to the benefits of its use in inducing remission in CD, especially in children.
However, an updated 2018 Cochrane Library systematic review found that “very low quality evidence suggests that corticosteroid therapy may be more effective than EN for induction of clinical remission in adults with active CD. Very low quality evidence also suggests that EN may be more effective than steroids for induction of remission in children with active CD” (Cochrane Database Syst Rev. 2018 Apr 1. doi: 10.1002/14651858.CD000542.pub3).
The review recommended that “EN should be considered in pediatric CD patients or in adult patients who can comply with nasogastric tube feeding or perceive the formulations to be palatable, or when steroid side effects are not tolerated or better avoided.”
Another 2018 Cochrane Library Review concluded that “no firm conclusions regarding the efficacy and safety of enteral nutrition in quiescent CD can be drawn” (Cochrane Database Syst Rev. 2018 Aug 11. doi: 10.1002/14651858.CD005984.pub3).
Dr. Gordon noted that IBD guidelines support EN to induce CD remission in children, and he called for “high quality research” to provide more evidence to support this recommendation.
Cannabis
In regard to cannabis, Dr. Gordon referred to a 2018 Cochrane review that examined three studies that investigated its use in CD and determined “the effects of cannabis and cannabis oil on Crohn’s disease are uncertain” (Cochrane Database Syst Rev. 2018 Nov 8. doi: 10.1002/14651858.CD012853.pub2).
He said future studies should focus on the effect of cannabis on quality of life and pain reduction. “That’s where the research needs to go,” he said.
Another 2018 Cochrane review examined two small studies exploring the use of cannabis in ulcerative colitis and reported similar findings, declaring that “the effects of cannabis and cannabidiol on UC are uncertain” (Cochrane Database Syst Rev. 2018 Nov 8. doi: 10.1002/14651858.CD012954.pub2).
Fecal transplantation
The Cochrane Library also examined research into fecal transplantation for IBD. A 2018 review reported that “fecal microbiota transplantation may increase the proportion of participants achieving clinical remission in UC. However, the number of identified studies was small and the quality of evidence was low. There is uncertainty about the rate of serious adverse events. As a result, no solid conclusions can be drawn at this time” (Cochrane Database Syst Rev. 2018 Nov 13. doi: 10.1002/14651858.CD012774.pub2).
Still, Dr. Gordon said, fecal transplantation is “really promising.”
Another 2018 Cochrane review of IBD research – this one focusing on natalizumab (Tysabri) as a tool for induction of remission of CD – was more conclusive. It examined five trials and found that “high quality data suggest that natalizumab is effective for induction of clinical remission and response in some patients with moderately to severely active CD”(Cochrane Database Syst Rev. 2018 Aug 1. doi: 10.1002/14651858.CD006097.pub3).
However, the review noted that none of the studies was high powered enough to detect rare serious adverse effects such as progressive multifocal leukoencephalopathy (PML). “Due to the association with PML, and the availability of alternative agents that are not associated with PML, natalizumab is not likely to be used in patients who fail currently available medical therapy,” the reviewers wrote. “Further studies of natalizumab are not likely to be done.”
Dr. Gordon reports unrestricted travel grants over the past 3 years from Ferring, Synergy, Tillotts, and BioGaia. He holds a National Institute for Health Research Cochrane IBD Program Grant.
LAS VEGAS – Cochrane Library reviews of studies into inflammatory bowel disease (IBD) from 2018 revealed limited evidence – so far – to support enteral nutrition therapy (EN) and cannabis in Crohn’s disease (CD) and fecal transplantation in IBD.
But Morris Gordon, MBChB, MMed, PhD, a Cochrane Library researcher who provided a roundup for colleagues, said there’s tremendous opportunity to build upon existing research in these areas.
Dr. Gordon, a pediatrician with a special gastric interest at the University of Central Lancashire in Preston, England, spoke at the Crohn’s & Colitis Congress - a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
In his presentation, Dr. Gordon discussed several Cochrane Library reviews published in 2018 in these topic areas:
Enteral therapy
EN was a hot topic at the Crohn’s & Colitics Congress, which devoted a large panel discussion to the benefits of its use in inducing remission in CD, especially in children.
However, an updated 2018 Cochrane Library systematic review found that “very low quality evidence suggests that corticosteroid therapy may be more effective than EN for induction of clinical remission in adults with active CD. Very low quality evidence also suggests that EN may be more effective than steroids for induction of remission in children with active CD” (Cochrane Database Syst Rev. 2018 Apr 1. doi: 10.1002/14651858.CD000542.pub3).
The review recommended that “EN should be considered in pediatric CD patients or in adult patients who can comply with nasogastric tube feeding or perceive the formulations to be palatable, or when steroid side effects are not tolerated or better avoided.”
Another 2018 Cochrane Library Review concluded that “no firm conclusions regarding the efficacy and safety of enteral nutrition in quiescent CD can be drawn” (Cochrane Database Syst Rev. 2018 Aug 11. doi: 10.1002/14651858.CD005984.pub3).
Dr. Gordon noted that IBD guidelines support EN to induce CD remission in children, and he called for “high quality research” to provide more evidence to support this recommendation.
Cannabis
In regard to cannabis, Dr. Gordon referred to a 2018 Cochrane review that examined three studies that investigated its use in CD and determined “the effects of cannabis and cannabis oil on Crohn’s disease are uncertain” (Cochrane Database Syst Rev. 2018 Nov 8. doi: 10.1002/14651858.CD012853.pub2).
He said future studies should focus on the effect of cannabis on quality of life and pain reduction. “That’s where the research needs to go,” he said.
Another 2018 Cochrane review examined two small studies exploring the use of cannabis in ulcerative colitis and reported similar findings, declaring that “the effects of cannabis and cannabidiol on UC are uncertain” (Cochrane Database Syst Rev. 2018 Nov 8. doi: 10.1002/14651858.CD012954.pub2).
Fecal transplantation
The Cochrane Library also examined research into fecal transplantation for IBD. A 2018 review reported that “fecal microbiota transplantation may increase the proportion of participants achieving clinical remission in UC. However, the number of identified studies was small and the quality of evidence was low. There is uncertainty about the rate of serious adverse events. As a result, no solid conclusions can be drawn at this time” (Cochrane Database Syst Rev. 2018 Nov 13. doi: 10.1002/14651858.CD012774.pub2).
Still, Dr. Gordon said, fecal transplantation is “really promising.”
Another 2018 Cochrane review of IBD research – this one focusing on natalizumab (Tysabri) as a tool for induction of remission of CD – was more conclusive. It examined five trials and found that “high quality data suggest that natalizumab is effective for induction of clinical remission and response in some patients with moderately to severely active CD”(Cochrane Database Syst Rev. 2018 Aug 1. doi: 10.1002/14651858.CD006097.pub3).
However, the review noted that none of the studies was high powered enough to detect rare serious adverse effects such as progressive multifocal leukoencephalopathy (PML). “Due to the association with PML, and the availability of alternative agents that are not associated with PML, natalizumab is not likely to be used in patients who fail currently available medical therapy,” the reviewers wrote. “Further studies of natalizumab are not likely to be done.”
Dr. Gordon reports unrestricted travel grants over the past 3 years from Ferring, Synergy, Tillotts, and BioGaia. He holds a National Institute for Health Research Cochrane IBD Program Grant.
EXPERT ANALYSIS FROM THE CROHN’S & COLITIS CONGRESS
Disruptive behavior on the job linked to depression, burnout
SAN DIEGO – Hospitals pay a price for bad behavior by staff in the workplace, results of a large multicenter study suggest.
A work culture in which disruptive behavior is tolerated can have consequences. Research on this topic has linked disruptive behavior by staff in the health care setting to increased frequency of medical errors and lower quality of care (Am J Med Qual. 2011 Sep-Oct;26(5):372-9; J Caring Sci. 2016 Sep 1;5(3):241-9). This new study, based on a workplace culture survey of 7,923 health care workers and 325 work settings at 16 hospitals in a large West Coast health care system, found , researchers found. The paper was presented by study lead Allison Hadley, MD, of Duke Children’s Hospital, Durham, N.C., at the Critical Care Congress sponsored by the Society of Critical Care Medicine.
The investigators developed a novel survey scale for evaluating disruptive behaviors in the health care setting. The objective was to look at the associations between disruptive behavior, teamwork, safety culture, burnout, and depression. Disruptive behaviors included turning backs or hanging up the phone before a conversation is over, bullying or trying to publicly humiliate other staff, making inappropriate comments (with sexual, racial, religious, or ethnic slurs), and physical aggression (such as throwing, hitting, and pushing).
San Francisco internist Alan H. Rosenstein, MD, who studies disruptive behavior in medicine, said in an interview that the findings confirm anecdotal experience of medical staff. “One of the downsides of disruptive behavior is very unsatisfied and unhappy people,” he said
The investigators used a t-test analysis to study the strength of the association between disruptive behavior and work culture in health care work settings. They found a statistically significant association between less disruptive behavior and lower levels of burnout and depression among staff (t = 6.4 and t = 4.1, respectively, P less than .001) and higher levels of teamwork, safety culture, and work-life balance (t = 10.2, t = 9.5 and t = 5.8, respectively, P less than .001). Settings in which disruptive behaviors were more common were more likely to have poor teamwork culture (P less than .001) and safety climate (P less than .001), and higher rates of depression (P less than .001). Settings in which disruptive behaviors were more common were more likely to have poor teamwork culture (P less than .001) and safety climate (P less than .001), and higher rates of depression (P less than .001).
Bullying was reported at about 40% of workplaces with low teamwork levels, compared with nearly 20% in those with high teamwork levels.
Physical aggression was reported in nearly 20% of those workplaces with low teamwork levels, compared with 5% in workplaces with high teamwork levels (P less than .001).
Researchers also found that disruptive behaviors were least common during day shifts and more common among health care workers who care for both adults and children than among those who care for only adults. “Teamwork, safety culture, and work-life balance were highest in those [hospital] units with the least disruptive behaviors,” said Dr. Hadley.
Overall, the highest positive correlation was found between higher levels of teamwork and lower levels of disruptive behavior, Dr. Hadley said. If a hospital department is trying to address one issue to improve disruptive behavior, she’d suggest it “focus on teamwork first. I hope that would have the greatest impact.”
Dr. Rosenstein, who has conducted several studies on disruptive behavior, said the key to improving the workplace is to “build a culture based on the mission of providing patient care. It’s not to save a dollar, to make a dollar. The mission is patient care.”
What’s next? Dr. Hadley said her team is continuing to work on developing a scale to measure disruptive behavior in the workplace.
No study funding was reported. Dr. Hadley and Dr. Rosenstein reported no relevant disclosures.
SOURCE: Hadley A et al. CCC48, Abstract 114.
SAN DIEGO – Hospitals pay a price for bad behavior by staff in the workplace, results of a large multicenter study suggest.
A work culture in which disruptive behavior is tolerated can have consequences. Research on this topic has linked disruptive behavior by staff in the health care setting to increased frequency of medical errors and lower quality of care (Am J Med Qual. 2011 Sep-Oct;26(5):372-9; J Caring Sci. 2016 Sep 1;5(3):241-9). This new study, based on a workplace culture survey of 7,923 health care workers and 325 work settings at 16 hospitals in a large West Coast health care system, found , researchers found. The paper was presented by study lead Allison Hadley, MD, of Duke Children’s Hospital, Durham, N.C., at the Critical Care Congress sponsored by the Society of Critical Care Medicine.
The investigators developed a novel survey scale for evaluating disruptive behaviors in the health care setting. The objective was to look at the associations between disruptive behavior, teamwork, safety culture, burnout, and depression. Disruptive behaviors included turning backs or hanging up the phone before a conversation is over, bullying or trying to publicly humiliate other staff, making inappropriate comments (with sexual, racial, religious, or ethnic slurs), and physical aggression (such as throwing, hitting, and pushing).
San Francisco internist Alan H. Rosenstein, MD, who studies disruptive behavior in medicine, said in an interview that the findings confirm anecdotal experience of medical staff. “One of the downsides of disruptive behavior is very unsatisfied and unhappy people,” he said
The investigators used a t-test analysis to study the strength of the association between disruptive behavior and work culture in health care work settings. They found a statistically significant association between less disruptive behavior and lower levels of burnout and depression among staff (t = 6.4 and t = 4.1, respectively, P less than .001) and higher levels of teamwork, safety culture, and work-life balance (t = 10.2, t = 9.5 and t = 5.8, respectively, P less than .001). Settings in which disruptive behaviors were more common were more likely to have poor teamwork culture (P less than .001) and safety climate (P less than .001), and higher rates of depression (P less than .001). Settings in which disruptive behaviors were more common were more likely to have poor teamwork culture (P less than .001) and safety climate (P less than .001), and higher rates of depression (P less than .001).
Bullying was reported at about 40% of workplaces with low teamwork levels, compared with nearly 20% in those with high teamwork levels.
Physical aggression was reported in nearly 20% of those workplaces with low teamwork levels, compared with 5% in workplaces with high teamwork levels (P less than .001).
Researchers also found that disruptive behaviors were least common during day shifts and more common among health care workers who care for both adults and children than among those who care for only adults. “Teamwork, safety culture, and work-life balance were highest in those [hospital] units with the least disruptive behaviors,” said Dr. Hadley.
Overall, the highest positive correlation was found between higher levels of teamwork and lower levels of disruptive behavior, Dr. Hadley said. If a hospital department is trying to address one issue to improve disruptive behavior, she’d suggest it “focus on teamwork first. I hope that would have the greatest impact.”
Dr. Rosenstein, who has conducted several studies on disruptive behavior, said the key to improving the workplace is to “build a culture based on the mission of providing patient care. It’s not to save a dollar, to make a dollar. The mission is patient care.”
What’s next? Dr. Hadley said her team is continuing to work on developing a scale to measure disruptive behavior in the workplace.
No study funding was reported. Dr. Hadley and Dr. Rosenstein reported no relevant disclosures.
SOURCE: Hadley A et al. CCC48, Abstract 114.
SAN DIEGO – Hospitals pay a price for bad behavior by staff in the workplace, results of a large multicenter study suggest.
A work culture in which disruptive behavior is tolerated can have consequences. Research on this topic has linked disruptive behavior by staff in the health care setting to increased frequency of medical errors and lower quality of care (Am J Med Qual. 2011 Sep-Oct;26(5):372-9; J Caring Sci. 2016 Sep 1;5(3):241-9). This new study, based on a workplace culture survey of 7,923 health care workers and 325 work settings at 16 hospitals in a large West Coast health care system, found , researchers found. The paper was presented by study lead Allison Hadley, MD, of Duke Children’s Hospital, Durham, N.C., at the Critical Care Congress sponsored by the Society of Critical Care Medicine.
The investigators developed a novel survey scale for evaluating disruptive behaviors in the health care setting. The objective was to look at the associations between disruptive behavior, teamwork, safety culture, burnout, and depression. Disruptive behaviors included turning backs or hanging up the phone before a conversation is over, bullying or trying to publicly humiliate other staff, making inappropriate comments (with sexual, racial, religious, or ethnic slurs), and physical aggression (such as throwing, hitting, and pushing).
San Francisco internist Alan H. Rosenstein, MD, who studies disruptive behavior in medicine, said in an interview that the findings confirm anecdotal experience of medical staff. “One of the downsides of disruptive behavior is very unsatisfied and unhappy people,” he said
The investigators used a t-test analysis to study the strength of the association between disruptive behavior and work culture in health care work settings. They found a statistically significant association between less disruptive behavior and lower levels of burnout and depression among staff (t = 6.4 and t = 4.1, respectively, P less than .001) and higher levels of teamwork, safety culture, and work-life balance (t = 10.2, t = 9.5 and t = 5.8, respectively, P less than .001). Settings in which disruptive behaviors were more common were more likely to have poor teamwork culture (P less than .001) and safety climate (P less than .001), and higher rates of depression (P less than .001). Settings in which disruptive behaviors were more common were more likely to have poor teamwork culture (P less than .001) and safety climate (P less than .001), and higher rates of depression (P less than .001).
Bullying was reported at about 40% of workplaces with low teamwork levels, compared with nearly 20% in those with high teamwork levels.
Physical aggression was reported in nearly 20% of those workplaces with low teamwork levels, compared with 5% in workplaces with high teamwork levels (P less than .001).
Researchers also found that disruptive behaviors were least common during day shifts and more common among health care workers who care for both adults and children than among those who care for only adults. “Teamwork, safety culture, and work-life balance were highest in those [hospital] units with the least disruptive behaviors,” said Dr. Hadley.
Overall, the highest positive correlation was found between higher levels of teamwork and lower levels of disruptive behavior, Dr. Hadley said. If a hospital department is trying to address one issue to improve disruptive behavior, she’d suggest it “focus on teamwork first. I hope that would have the greatest impact.”
Dr. Rosenstein, who has conducted several studies on disruptive behavior, said the key to improving the workplace is to “build a culture based on the mission of providing patient care. It’s not to save a dollar, to make a dollar. The mission is patient care.”
What’s next? Dr. Hadley said her team is continuing to work on developing a scale to measure disruptive behavior in the workplace.
No study funding was reported. Dr. Hadley and Dr. Rosenstein reported no relevant disclosures.
SOURCE: Hadley A et al. CCC48, Abstract 114.
REPORTING FROM CCC48
Delays of 1-2+ years in IBD diagnosis are common, patients say
LAS VEGAS – Delays in diagnosis of inflammatory bowel disease (IBD) appear to be very common and often extensive, a new survey of U.S. patients suggests. Nearly two-thirds said their diagnosis was delayed past symptom onset for more than a year, and almost half reported a delay of more than 2 years.
On average, patients who experienced diagnosis delays said they’d seen an average of 3.5 physicians. “Most patients reported that they received an uncertain or wrong diagnosis by their primary care physician or gastroenterologist,” said study coauthor Ryan C. Ungaro, MD, of Icahn School of Medicine at Mount Sinai, New York, in an interview prior to the presentation of the study findings at the Crohn’s & Colitis Congress - a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
“Working at a tertiary care IBD center, we noticed that many patients tell us it took them a long time to get diagnosed with Crohn’s disease [CD] or ulcerative colitis [UC],” said Dr. Ungaro. “There are some studies on delay in diagnosis in Europe but none in the U.S. We hypothesized that diagnostic delay is a major issue for IBD patients in the U.S.”
The study authors offered a survey to 2,341 patients with IBD; 1,121 responded to the questions. Of those, 68% reported their diagnosis was delayed, with 64% reporting a delay of over 1 year and 48% reporting a delay over 2 years.
Compared with those with UC, patients with CD were more likely to report more than 1-year delays (70% vs. 48%; P less than .0001) and more than 2-year delays (52% vs. 37%; P = .0008).
Patients who reported delays said they saw an average of 3.5 physicians before getting an IBD diagnosis. The patients most commonly blamed their incorrect diagnosis on primary care providers (58%) and gastroenterologists (28%).
“Most likely, CD may be misdiagnosed because the common presenting symptoms – abdominal pain, diarrhea – are also seen in other common gastrointestinal conditions such as irritable bowel syndrome,” Dr. Ungaro said. “In contrast, most patients with UC present with rectal bleeding which is a ‘red flag’ symptom that is more likely to get worked up.”
In some cases, patients blamed themselves, reporting “that they personally did not feel their symptoms warranted work-up or were too embarrassed by their symptoms to tell anyone,” Dr. Ungaro said. “The other theme that was noted was access – delay or difficulty seeing a gastroenterologist.”
Going forward, “diagnostic delay may be improved through patient education regarding awareness of alarm symptoms for IBD,” said gastroenterologist and study lead author Zane Gallinger, MD, FRCPC, of the University of Toronto at Mount Sinai Hospital, in an interview. According to him, these symptoms include diarrhea, abdominal pain, weight loss, family history of CD, perianal abscess, and fistula and fever.
At the primary care level, Dr. Gallinger said that noninvasive tests such as fecal calprotectin can help identify patients with inflammatory conditions and that “more rapid access to gastroenterologists for earlier diagnosis of IBD can improve patient outcomes.”
The Crohn’s and Colitis Foundation funded the study. Dr. Gallinger reported relationships with Takeda and AbbVie.
SOURCE: Gallinger Z et al. Crohn’s & Colitis Congress, Abstract P030.
LAS VEGAS – Delays in diagnosis of inflammatory bowel disease (IBD) appear to be very common and often extensive, a new survey of U.S. patients suggests. Nearly two-thirds said their diagnosis was delayed past symptom onset for more than a year, and almost half reported a delay of more than 2 years.
On average, patients who experienced diagnosis delays said they’d seen an average of 3.5 physicians. “Most patients reported that they received an uncertain or wrong diagnosis by their primary care physician or gastroenterologist,” said study coauthor Ryan C. Ungaro, MD, of Icahn School of Medicine at Mount Sinai, New York, in an interview prior to the presentation of the study findings at the Crohn’s & Colitis Congress - a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
“Working at a tertiary care IBD center, we noticed that many patients tell us it took them a long time to get diagnosed with Crohn’s disease [CD] or ulcerative colitis [UC],” said Dr. Ungaro. “There are some studies on delay in diagnosis in Europe but none in the U.S. We hypothesized that diagnostic delay is a major issue for IBD patients in the U.S.”
The study authors offered a survey to 2,341 patients with IBD; 1,121 responded to the questions. Of those, 68% reported their diagnosis was delayed, with 64% reporting a delay of over 1 year and 48% reporting a delay over 2 years.
Compared with those with UC, patients with CD were more likely to report more than 1-year delays (70% vs. 48%; P less than .0001) and more than 2-year delays (52% vs. 37%; P = .0008).
Patients who reported delays said they saw an average of 3.5 physicians before getting an IBD diagnosis. The patients most commonly blamed their incorrect diagnosis on primary care providers (58%) and gastroenterologists (28%).
“Most likely, CD may be misdiagnosed because the common presenting symptoms – abdominal pain, diarrhea – are also seen in other common gastrointestinal conditions such as irritable bowel syndrome,” Dr. Ungaro said. “In contrast, most patients with UC present with rectal bleeding which is a ‘red flag’ symptom that is more likely to get worked up.”
In some cases, patients blamed themselves, reporting “that they personally did not feel their symptoms warranted work-up or were too embarrassed by their symptoms to tell anyone,” Dr. Ungaro said. “The other theme that was noted was access – delay or difficulty seeing a gastroenterologist.”
Going forward, “diagnostic delay may be improved through patient education regarding awareness of alarm symptoms for IBD,” said gastroenterologist and study lead author Zane Gallinger, MD, FRCPC, of the University of Toronto at Mount Sinai Hospital, in an interview. According to him, these symptoms include diarrhea, abdominal pain, weight loss, family history of CD, perianal abscess, and fistula and fever.
At the primary care level, Dr. Gallinger said that noninvasive tests such as fecal calprotectin can help identify patients with inflammatory conditions and that “more rapid access to gastroenterologists for earlier diagnosis of IBD can improve patient outcomes.”
The Crohn’s and Colitis Foundation funded the study. Dr. Gallinger reported relationships with Takeda and AbbVie.
SOURCE: Gallinger Z et al. Crohn’s & Colitis Congress, Abstract P030.
LAS VEGAS – Delays in diagnosis of inflammatory bowel disease (IBD) appear to be very common and often extensive, a new survey of U.S. patients suggests. Nearly two-thirds said their diagnosis was delayed past symptom onset for more than a year, and almost half reported a delay of more than 2 years.
On average, patients who experienced diagnosis delays said they’d seen an average of 3.5 physicians. “Most patients reported that they received an uncertain or wrong diagnosis by their primary care physician or gastroenterologist,” said study coauthor Ryan C. Ungaro, MD, of Icahn School of Medicine at Mount Sinai, New York, in an interview prior to the presentation of the study findings at the Crohn’s & Colitis Congress - a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
“Working at a tertiary care IBD center, we noticed that many patients tell us it took them a long time to get diagnosed with Crohn’s disease [CD] or ulcerative colitis [UC],” said Dr. Ungaro. “There are some studies on delay in diagnosis in Europe but none in the U.S. We hypothesized that diagnostic delay is a major issue for IBD patients in the U.S.”
The study authors offered a survey to 2,341 patients with IBD; 1,121 responded to the questions. Of those, 68% reported their diagnosis was delayed, with 64% reporting a delay of over 1 year and 48% reporting a delay over 2 years.
Compared with those with UC, patients with CD were more likely to report more than 1-year delays (70% vs. 48%; P less than .0001) and more than 2-year delays (52% vs. 37%; P = .0008).
Patients who reported delays said they saw an average of 3.5 physicians before getting an IBD diagnosis. The patients most commonly blamed their incorrect diagnosis on primary care providers (58%) and gastroenterologists (28%).
“Most likely, CD may be misdiagnosed because the common presenting symptoms – abdominal pain, diarrhea – are also seen in other common gastrointestinal conditions such as irritable bowel syndrome,” Dr. Ungaro said. “In contrast, most patients with UC present with rectal bleeding which is a ‘red flag’ symptom that is more likely to get worked up.”
In some cases, patients blamed themselves, reporting “that they personally did not feel their symptoms warranted work-up or were too embarrassed by their symptoms to tell anyone,” Dr. Ungaro said. “The other theme that was noted was access – delay or difficulty seeing a gastroenterologist.”
Going forward, “diagnostic delay may be improved through patient education regarding awareness of alarm symptoms for IBD,” said gastroenterologist and study lead author Zane Gallinger, MD, FRCPC, of the University of Toronto at Mount Sinai Hospital, in an interview. According to him, these symptoms include diarrhea, abdominal pain, weight loss, family history of CD, perianal abscess, and fistula and fever.
At the primary care level, Dr. Gallinger said that noninvasive tests such as fecal calprotectin can help identify patients with inflammatory conditions and that “more rapid access to gastroenterologists for earlier diagnosis of IBD can improve patient outcomes.”
The Crohn’s and Colitis Foundation funded the study. Dr. Gallinger reported relationships with Takeda and AbbVie.
SOURCE: Gallinger Z et al. Crohn’s & Colitis Congress, Abstract P030.
REPORTING FROM THE CROHN’S & COLITIS CONGRESS