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More promising news for real-time histology during endoscopy
SAN DIEGO – In patients with ulcerative colitis, real-time histology via probe confocal laser endomicroscopy (pCLE) produces mucosal scores that reflect the findings of other approaches, a new study finds.
“The pCLE score is a paradigm which may be translated to modern high-definition endoscopes and new scoring systems,” said the study’s lead author Dr. Marietta Iacucci, clinical associate professor of medicine with the division of gastroenterology at the University of Calgary (Alta.). “We need to assess the inflammation in inflammatory bowel disease with more accurate scoring to determine subtle inflammation changes which relate to risk of flares and dysplastic changes.”
At issue: Endoscopic assessment of mucosal inflammation and healing. “This is the most important component of determining the severity of ulcerative colitis at clinical trial and in clinical practice,” Dr. Iacucci said. “Now, new endoscopy equipment, high-resolution imaging, electronic chromoendoscopy, and magnification with optical enhancement are changing the landscape and providing fine details of the mucosa, both in mucosal architecture and vascular architecture.”
The study examines real-time histology via pCLE, which “permits a slender probe to obtain real-time histology-like images after injection of fluorescein dye,” she said. “We aimed to determine whether there is an agreement between pCLE score and other new scoring systems such as the recently described iSCAN score, Mayo endoscopic subscore, and histologic scores.”
The researchers analyzed 90 patients (82 with ulcerative colitis and 8 controls, 54 male, median age 47 years, 19-79 years) assessed via iSCAN virtual chromoendoscopy and pCLE.
The pCLE scores were significantly correlated with several other measures such as Mayo endoscopy subscore (rs = 0.79; 95% confidence iinterval, 0.7-0.85; P less than .001) and the overall mucosal and vascular pattern iSCAN endoscopic score (rs = 0.83; 95% CI, 0.76-0.88; P = .0001).
The Harpaz histology score was also significantly correlated with pCLE (rs = 0.59; 95% CI, 0.44-0.71; P = .0001). In addition, pCLE features of leakage of fluorescein (rs = 0.75; 95% CI, 0.64-0.87; P less than .00001), vascular architecture (rs = 0.77; 95% CI, 0.67-0.84; P less than .0001) and blood flow (rs = 0.80; 95% CI, 0.71-0.86; P less than .00001) reflected the endoscopic iSCAN vascular pattern.
The sensitivity of pCLE to detect histologic inflammation was 92.6%.
In a discussion at the annual Digestive Disease Week, an attendee asked Dr. Iacucci if pCLE could replace endoscopy with biopsy. “I think it will add value when we have to decide if we need to continue biological therapy, which is very expensive,” she said.
She also noted that an analysis takes her only 5-10 minutes. “When we look at it from a cost-benefit perspective,” she said, “it’s another tool, especially when you need to make decisions.”
SAN DIEGO – In patients with ulcerative colitis, real-time histology via probe confocal laser endomicroscopy (pCLE) produces mucosal scores that reflect the findings of other approaches, a new study finds.
“The pCLE score is a paradigm which may be translated to modern high-definition endoscopes and new scoring systems,” said the study’s lead author Dr. Marietta Iacucci, clinical associate professor of medicine with the division of gastroenterology at the University of Calgary (Alta.). “We need to assess the inflammation in inflammatory bowel disease with more accurate scoring to determine subtle inflammation changes which relate to risk of flares and dysplastic changes.”
At issue: Endoscopic assessment of mucosal inflammation and healing. “This is the most important component of determining the severity of ulcerative colitis at clinical trial and in clinical practice,” Dr. Iacucci said. “Now, new endoscopy equipment, high-resolution imaging, electronic chromoendoscopy, and magnification with optical enhancement are changing the landscape and providing fine details of the mucosa, both in mucosal architecture and vascular architecture.”
The study examines real-time histology via pCLE, which “permits a slender probe to obtain real-time histology-like images after injection of fluorescein dye,” she said. “We aimed to determine whether there is an agreement between pCLE score and other new scoring systems such as the recently described iSCAN score, Mayo endoscopic subscore, and histologic scores.”
The researchers analyzed 90 patients (82 with ulcerative colitis and 8 controls, 54 male, median age 47 years, 19-79 years) assessed via iSCAN virtual chromoendoscopy and pCLE.
The pCLE scores were significantly correlated with several other measures such as Mayo endoscopy subscore (rs = 0.79; 95% confidence iinterval, 0.7-0.85; P less than .001) and the overall mucosal and vascular pattern iSCAN endoscopic score (rs = 0.83; 95% CI, 0.76-0.88; P = .0001).
The Harpaz histology score was also significantly correlated with pCLE (rs = 0.59; 95% CI, 0.44-0.71; P = .0001). In addition, pCLE features of leakage of fluorescein (rs = 0.75; 95% CI, 0.64-0.87; P less than .00001), vascular architecture (rs = 0.77; 95% CI, 0.67-0.84; P less than .0001) and blood flow (rs = 0.80; 95% CI, 0.71-0.86; P less than .00001) reflected the endoscopic iSCAN vascular pattern.
The sensitivity of pCLE to detect histologic inflammation was 92.6%.
In a discussion at the annual Digestive Disease Week, an attendee asked Dr. Iacucci if pCLE could replace endoscopy with biopsy. “I think it will add value when we have to decide if we need to continue biological therapy, which is very expensive,” she said.
She also noted that an analysis takes her only 5-10 minutes. “When we look at it from a cost-benefit perspective,” she said, “it’s another tool, especially when you need to make decisions.”
SAN DIEGO – In patients with ulcerative colitis, real-time histology via probe confocal laser endomicroscopy (pCLE) produces mucosal scores that reflect the findings of other approaches, a new study finds.
“The pCLE score is a paradigm which may be translated to modern high-definition endoscopes and new scoring systems,” said the study’s lead author Dr. Marietta Iacucci, clinical associate professor of medicine with the division of gastroenterology at the University of Calgary (Alta.). “We need to assess the inflammation in inflammatory bowel disease with more accurate scoring to determine subtle inflammation changes which relate to risk of flares and dysplastic changes.”
At issue: Endoscopic assessment of mucosal inflammation and healing. “This is the most important component of determining the severity of ulcerative colitis at clinical trial and in clinical practice,” Dr. Iacucci said. “Now, new endoscopy equipment, high-resolution imaging, electronic chromoendoscopy, and magnification with optical enhancement are changing the landscape and providing fine details of the mucosa, both in mucosal architecture and vascular architecture.”
The study examines real-time histology via pCLE, which “permits a slender probe to obtain real-time histology-like images after injection of fluorescein dye,” she said. “We aimed to determine whether there is an agreement between pCLE score and other new scoring systems such as the recently described iSCAN score, Mayo endoscopic subscore, and histologic scores.”
The researchers analyzed 90 patients (82 with ulcerative colitis and 8 controls, 54 male, median age 47 years, 19-79 years) assessed via iSCAN virtual chromoendoscopy and pCLE.
The pCLE scores were significantly correlated with several other measures such as Mayo endoscopy subscore (rs = 0.79; 95% confidence iinterval, 0.7-0.85; P less than .001) and the overall mucosal and vascular pattern iSCAN endoscopic score (rs = 0.83; 95% CI, 0.76-0.88; P = .0001).
The Harpaz histology score was also significantly correlated with pCLE (rs = 0.59; 95% CI, 0.44-0.71; P = .0001). In addition, pCLE features of leakage of fluorescein (rs = 0.75; 95% CI, 0.64-0.87; P less than .00001), vascular architecture (rs = 0.77; 95% CI, 0.67-0.84; P less than .0001) and blood flow (rs = 0.80; 95% CI, 0.71-0.86; P less than .00001) reflected the endoscopic iSCAN vascular pattern.
The sensitivity of pCLE to detect histologic inflammation was 92.6%.
In a discussion at the annual Digestive Disease Week, an attendee asked Dr. Iacucci if pCLE could replace endoscopy with biopsy. “I think it will add value when we have to decide if we need to continue biological therapy, which is very expensive,” she said.
She also noted that an analysis takes her only 5-10 minutes. “When we look at it from a cost-benefit perspective,” she said, “it’s another tool, especially when you need to make decisions.”
AT DDW® 2016
Key clinical point: Endoscopies hold potential for real-time histological analyses via pCLE and virtual electronic chromoendoscopy.
Major finding: pCLE scores were significantly correlated with several other measures such as Mayo endoscopy subscore (rs = 0.76; 95% CI, 0.65-0.84; P less than .001) and mucosal and vascular pattern iSCAN endoscopic score (rs = 0.83; 95% CI, 0.75-0.90; P = .0001). The sensitivity of pCLE to detect histologic inflammation was 92.6%.
Data source: 81 patients (73 with ulcerative and 8 controls, 48 male, median age 50, 20-79 years of age) were assessed with virtual chromoendoscopy and pCLE after IV fluorescein.
Disclosures: The study is funded by research grants from the University of Calgary and Pentax. Dr. Iacucci reported no relevant disclosures.
Women underrepresented as GI division chiefs
SAN DIEGO – Despite an increase in women entering the gastroenterology field, a new study finds that they are severely underrepresented in academia as fellowship program directors and division chiefs.
In addition, most female program directors have lower academic ranks than did their male counterparts.
“A lack of female leadership can detract future women from entering the field,” said study lead author Dr. Sonali Paul, a gastroenterologist and research fellow in medicine at Massachusetts General Hospital in Boston. “Further research is needed to understand these barriers, whether they’re due to personal choice or more systemic issues. Understanding the challenges women face in academic promotions will allow for policy changes.”
According to statistics quoted in the study, women made up more than a third of gastroenterology fellowship positions and 18% of the academic workforce in 2013. At the same time, more than half of medical graduates are women.
“The role of women in GI is important, especially given that studies have shown that women prefer female endoscopists,” Dr. Paul said. And women make up significant portions of the patient load in GI clinical practices, she said.
But it hasn’t been clear if the increase in fellowship positions has corresponded to a higher number of women in positions of academic leadership.
To better understand the situation, Dr. Paul and her associates analyzed the gender and academic rank of GI fellowship program directors and division chiefs in 2015. The researchers analyzed websites and social media to gather the data and also made direct contacts, Dr. Paul said.
At 165 academic GI programs, 85% of these positions were held by men. Of program directors, 81% were male; 89% of division chiefs were male.
Of the men who hold these positions, half were program directors and half were division chiefs. Among women, however, 67% were program directors and 33% were division chiefs.
There was also a disparity in terms of academic experience. Female division chiefs were less likely to be professors (46%), compared with male division chiefs (82%).
Why the disparity? One possible explanation is a “leaky pipeline,” Dr. Paul said. This refers to the fact that women leave academic medicine at higher rates than men do.
Family obligations are one explanation, she said, “but I don’t think that explains everything in the process. A lot of women have felt that promotion was of no benefit to them and that there was a lack of encouragement.”
Dr. Paul notes that the study has limitations. It’s cross sectional, and misclassification errors are possible.
During a discussion period, a questioner noted that it takes time for an academic physician to move up: “Shouldn’t we look at the fraction of graduates in 1996 who were female and now are professors? It’s unusual for someone at less than a professor rank to be division chief, as compared with program director.” Dr. Paul agreed that this would be a good avenue of research.
In addition, she said, “it will be important to examine if these gender disparities are unique to gastroenterology or if they extend into other specialties that are more female dominant, such as rheumatology or geriatrics.”
SAN DIEGO – Despite an increase in women entering the gastroenterology field, a new study finds that they are severely underrepresented in academia as fellowship program directors and division chiefs.
In addition, most female program directors have lower academic ranks than did their male counterparts.
“A lack of female leadership can detract future women from entering the field,” said study lead author Dr. Sonali Paul, a gastroenterologist and research fellow in medicine at Massachusetts General Hospital in Boston. “Further research is needed to understand these barriers, whether they’re due to personal choice or more systemic issues. Understanding the challenges women face in academic promotions will allow for policy changes.”
According to statistics quoted in the study, women made up more than a third of gastroenterology fellowship positions and 18% of the academic workforce in 2013. At the same time, more than half of medical graduates are women.
“The role of women in GI is important, especially given that studies have shown that women prefer female endoscopists,” Dr. Paul said. And women make up significant portions of the patient load in GI clinical practices, she said.
But it hasn’t been clear if the increase in fellowship positions has corresponded to a higher number of women in positions of academic leadership.
To better understand the situation, Dr. Paul and her associates analyzed the gender and academic rank of GI fellowship program directors and division chiefs in 2015. The researchers analyzed websites and social media to gather the data and also made direct contacts, Dr. Paul said.
At 165 academic GI programs, 85% of these positions were held by men. Of program directors, 81% were male; 89% of division chiefs were male.
Of the men who hold these positions, half were program directors and half were division chiefs. Among women, however, 67% were program directors and 33% were division chiefs.
There was also a disparity in terms of academic experience. Female division chiefs were less likely to be professors (46%), compared with male division chiefs (82%).
Why the disparity? One possible explanation is a “leaky pipeline,” Dr. Paul said. This refers to the fact that women leave academic medicine at higher rates than men do.
Family obligations are one explanation, she said, “but I don’t think that explains everything in the process. A lot of women have felt that promotion was of no benefit to them and that there was a lack of encouragement.”
Dr. Paul notes that the study has limitations. It’s cross sectional, and misclassification errors are possible.
During a discussion period, a questioner noted that it takes time for an academic physician to move up: “Shouldn’t we look at the fraction of graduates in 1996 who were female and now are professors? It’s unusual for someone at less than a professor rank to be division chief, as compared with program director.” Dr. Paul agreed that this would be a good avenue of research.
In addition, she said, “it will be important to examine if these gender disparities are unique to gastroenterology or if they extend into other specialties that are more female dominant, such as rheumatology or geriatrics.”
SAN DIEGO – Despite an increase in women entering the gastroenterology field, a new study finds that they are severely underrepresented in academia as fellowship program directors and division chiefs.
In addition, most female program directors have lower academic ranks than did their male counterparts.
“A lack of female leadership can detract future women from entering the field,” said study lead author Dr. Sonali Paul, a gastroenterologist and research fellow in medicine at Massachusetts General Hospital in Boston. “Further research is needed to understand these barriers, whether they’re due to personal choice or more systemic issues. Understanding the challenges women face in academic promotions will allow for policy changes.”
According to statistics quoted in the study, women made up more than a third of gastroenterology fellowship positions and 18% of the academic workforce in 2013. At the same time, more than half of medical graduates are women.
“The role of women in GI is important, especially given that studies have shown that women prefer female endoscopists,” Dr. Paul said. And women make up significant portions of the patient load in GI clinical practices, she said.
But it hasn’t been clear if the increase in fellowship positions has corresponded to a higher number of women in positions of academic leadership.
To better understand the situation, Dr. Paul and her associates analyzed the gender and academic rank of GI fellowship program directors and division chiefs in 2015. The researchers analyzed websites and social media to gather the data and also made direct contacts, Dr. Paul said.
At 165 academic GI programs, 85% of these positions were held by men. Of program directors, 81% were male; 89% of division chiefs were male.
Of the men who hold these positions, half were program directors and half were division chiefs. Among women, however, 67% were program directors and 33% were division chiefs.
There was also a disparity in terms of academic experience. Female division chiefs were less likely to be professors (46%), compared with male division chiefs (82%).
Why the disparity? One possible explanation is a “leaky pipeline,” Dr. Paul said. This refers to the fact that women leave academic medicine at higher rates than men do.
Family obligations are one explanation, she said, “but I don’t think that explains everything in the process. A lot of women have felt that promotion was of no benefit to them and that there was a lack of encouragement.”
Dr. Paul notes that the study has limitations. It’s cross sectional, and misclassification errors are possible.
During a discussion period, a questioner noted that it takes time for an academic physician to move up: “Shouldn’t we look at the fraction of graduates in 1996 who were female and now are professors? It’s unusual for someone at less than a professor rank to be division chief, as compared with program director.” Dr. Paul agreed that this would be a good avenue of research.
In addition, she said, “it will be important to examine if these gender disparities are unique to gastroenterology or if they extend into other specialties that are more female dominant, such as rheumatology or geriatrics.”
AT DDW® 2016
Ozanimod linked to histologic healing of moderate, severe ulcerative colitis
SAN DIEGO – A new analysis of phase II research finds that the experimental drug ozanimod prompted histologic healing in ulcerative colitis patients at 8 and 32 weeks.
“Ozanimod both induces and maintains remissions in a proportion of patients with refractory ulcerative colitis,” said study coauthor Dr. Stephen B. Hanauer, professor of medicine and medical director of the Digestive Health Center at Northwestern University, Chicago. “It’s a safe and effective oral drug for ulcerative colitis and possibly Crohn’s disease.”
Ozanimod, an experimental drug developed by Celgene and its subsidiary Receptos, has been undergoing review as a treatment for both multiple sclerosis and ulcerative colitis.
“Ozanimod impacts lymphocyte trafficking by retaining lymphocytes in lymph nodes and prevents recirculation. The mechanism of action is impairing S1P [sphingosine-1-phosphate] that ‘traps’ lymphocytes in lymph nodes.” Dr. Hanauer said.
“Other mechanisms by which lymphocyte trafficking has been inhibited have been effective in treating multiple sclerosis and Crohn’s disease (natalizumab) and both ulcerative colitis and Crohn’s disease (vedolizumab),” he said. However, he said, natalizumab has been linked to a risk of progressive multifocal leukoencephalopathy, a rare and mostly fatal brain disease.
Vedolizumab, meanwhile, “is a biologic that requires IV infusions.” By contrast, he says, ozanimod is an oral drug.
In a recent issue of the New England Journal of Medicine, researchers published findings from a phase II randomized, double-blind, placebo-controlled trial of ozanimod in 197 patients with moderate to severe ulcerative colitis. Patients were assigned to high dose (n = 67), low dose (n = 65), or placebo (n = 65) (N Engl J Med. 2016 May;374:1754-62).
At 8 weeks, clinical remission (Mayo Clinic score less than or equal to 2, with no subscore over 1) occurred in 16% of patients who received 1-mg doses (P = .048) and 14% of those who received the 0.5-mg doses (P = .14); the remission rate was 6% for placebo.
The new analysis examined histologic improvement from baseline to 8 and 32 weeks. (Those who reached clinical response continued through 32 weeks.) Improvement was greater in the high-dose group than in the placebo group at week 8 (Geboes score [–4.37 vs. –2.20; P = .0345]) and week 32 (Geboes score [–5.50 vs. –2.24; P = .0033]); low-dose improvement was greater than placebo but didn’t reach statistical significance.
Histologic remission (Geboes score less than 2) occurred in 15/67 (22.4%) for high dose (P = .0705, compared with placebo), 9/65 (13.8%) for low dose (P = .6294, compared with placebo) and 7/65 (10.8%) for placebo at week 8. At week 32, remission was 21/67 (31.3%) for high dose (P = 0.0006, compared with placebo), 15/65 (23.1%) for low dose (P = .0164, compared with placebo) and 5/65 (7.7%) for placebo.
Adverse events were “minor, without significant cardiotoxicity or risk of infections,” Dr. Hanauer said. The events affected 26/67 (38.8%) patients on the high dose, 26/65 (40.0%) on the low dose, and 26/65 (40.0%) on placebo; worsening of ulcerative colitis and anemia were most common, especially in the placebo group.
The cost of the drug is unclear, Dr. Hanauer said.
The patients are now in open-label follow-up, he said.
The study is industry funded by Receptos. Dr. Hanauer is on the ozanimod steering committee and consults for Celgene and its subsidiary research division, Receptos.
SAN DIEGO – A new analysis of phase II research finds that the experimental drug ozanimod prompted histologic healing in ulcerative colitis patients at 8 and 32 weeks.
“Ozanimod both induces and maintains remissions in a proportion of patients with refractory ulcerative colitis,” said study coauthor Dr. Stephen B. Hanauer, professor of medicine and medical director of the Digestive Health Center at Northwestern University, Chicago. “It’s a safe and effective oral drug for ulcerative colitis and possibly Crohn’s disease.”
Ozanimod, an experimental drug developed by Celgene and its subsidiary Receptos, has been undergoing review as a treatment for both multiple sclerosis and ulcerative colitis.
“Ozanimod impacts lymphocyte trafficking by retaining lymphocytes in lymph nodes and prevents recirculation. The mechanism of action is impairing S1P [sphingosine-1-phosphate] that ‘traps’ lymphocytes in lymph nodes.” Dr. Hanauer said.
“Other mechanisms by which lymphocyte trafficking has been inhibited have been effective in treating multiple sclerosis and Crohn’s disease (natalizumab) and both ulcerative colitis and Crohn’s disease (vedolizumab),” he said. However, he said, natalizumab has been linked to a risk of progressive multifocal leukoencephalopathy, a rare and mostly fatal brain disease.
Vedolizumab, meanwhile, “is a biologic that requires IV infusions.” By contrast, he says, ozanimod is an oral drug.
In a recent issue of the New England Journal of Medicine, researchers published findings from a phase II randomized, double-blind, placebo-controlled trial of ozanimod in 197 patients with moderate to severe ulcerative colitis. Patients were assigned to high dose (n = 67), low dose (n = 65), or placebo (n = 65) (N Engl J Med. 2016 May;374:1754-62).
At 8 weeks, clinical remission (Mayo Clinic score less than or equal to 2, with no subscore over 1) occurred in 16% of patients who received 1-mg doses (P = .048) and 14% of those who received the 0.5-mg doses (P = .14); the remission rate was 6% for placebo.
The new analysis examined histologic improvement from baseline to 8 and 32 weeks. (Those who reached clinical response continued through 32 weeks.) Improvement was greater in the high-dose group than in the placebo group at week 8 (Geboes score [–4.37 vs. –2.20; P = .0345]) and week 32 (Geboes score [–5.50 vs. –2.24; P = .0033]); low-dose improvement was greater than placebo but didn’t reach statistical significance.
Histologic remission (Geboes score less than 2) occurred in 15/67 (22.4%) for high dose (P = .0705, compared with placebo), 9/65 (13.8%) for low dose (P = .6294, compared with placebo) and 7/65 (10.8%) for placebo at week 8. At week 32, remission was 21/67 (31.3%) for high dose (P = 0.0006, compared with placebo), 15/65 (23.1%) for low dose (P = .0164, compared with placebo) and 5/65 (7.7%) for placebo.
Adverse events were “minor, without significant cardiotoxicity or risk of infections,” Dr. Hanauer said. The events affected 26/67 (38.8%) patients on the high dose, 26/65 (40.0%) on the low dose, and 26/65 (40.0%) on placebo; worsening of ulcerative colitis and anemia were most common, especially in the placebo group.
The cost of the drug is unclear, Dr. Hanauer said.
The patients are now in open-label follow-up, he said.
The study is industry funded by Receptos. Dr. Hanauer is on the ozanimod steering committee and consults for Celgene and its subsidiary research division, Receptos.
SAN DIEGO – A new analysis of phase II research finds that the experimental drug ozanimod prompted histologic healing in ulcerative colitis patients at 8 and 32 weeks.
“Ozanimod both induces and maintains remissions in a proportion of patients with refractory ulcerative colitis,” said study coauthor Dr. Stephen B. Hanauer, professor of medicine and medical director of the Digestive Health Center at Northwestern University, Chicago. “It’s a safe and effective oral drug for ulcerative colitis and possibly Crohn’s disease.”
Ozanimod, an experimental drug developed by Celgene and its subsidiary Receptos, has been undergoing review as a treatment for both multiple sclerosis and ulcerative colitis.
“Ozanimod impacts lymphocyte trafficking by retaining lymphocytes in lymph nodes and prevents recirculation. The mechanism of action is impairing S1P [sphingosine-1-phosphate] that ‘traps’ lymphocytes in lymph nodes.” Dr. Hanauer said.
“Other mechanisms by which lymphocyte trafficking has been inhibited have been effective in treating multiple sclerosis and Crohn’s disease (natalizumab) and both ulcerative colitis and Crohn’s disease (vedolizumab),” he said. However, he said, natalizumab has been linked to a risk of progressive multifocal leukoencephalopathy, a rare and mostly fatal brain disease.
Vedolizumab, meanwhile, “is a biologic that requires IV infusions.” By contrast, he says, ozanimod is an oral drug.
In a recent issue of the New England Journal of Medicine, researchers published findings from a phase II randomized, double-blind, placebo-controlled trial of ozanimod in 197 patients with moderate to severe ulcerative colitis. Patients were assigned to high dose (n = 67), low dose (n = 65), or placebo (n = 65) (N Engl J Med. 2016 May;374:1754-62).
At 8 weeks, clinical remission (Mayo Clinic score less than or equal to 2, with no subscore over 1) occurred in 16% of patients who received 1-mg doses (P = .048) and 14% of those who received the 0.5-mg doses (P = .14); the remission rate was 6% for placebo.
The new analysis examined histologic improvement from baseline to 8 and 32 weeks. (Those who reached clinical response continued through 32 weeks.) Improvement was greater in the high-dose group than in the placebo group at week 8 (Geboes score [–4.37 vs. –2.20; P = .0345]) and week 32 (Geboes score [–5.50 vs. –2.24; P = .0033]); low-dose improvement was greater than placebo but didn’t reach statistical significance.
Histologic remission (Geboes score less than 2) occurred in 15/67 (22.4%) for high dose (P = .0705, compared with placebo), 9/65 (13.8%) for low dose (P = .6294, compared with placebo) and 7/65 (10.8%) for placebo at week 8. At week 32, remission was 21/67 (31.3%) for high dose (P = 0.0006, compared with placebo), 15/65 (23.1%) for low dose (P = .0164, compared with placebo) and 5/65 (7.7%) for placebo.
Adverse events were “minor, without significant cardiotoxicity or risk of infections,” Dr. Hanauer said. The events affected 26/67 (38.8%) patients on the high dose, 26/65 (40.0%) on the low dose, and 26/65 (40.0%) on placebo; worsening of ulcerative colitis and anemia were most common, especially in the placebo group.
The cost of the drug is unclear, Dr. Hanauer said.
The patients are now in open-label follow-up, he said.
The study is industry funded by Receptos. Dr. Hanauer is on the ozanimod steering committee and consults for Celgene and its subsidiary research division, Receptos.
AT DDW® 2016
Key clinical point: In addition to clinical remission, response, and endoscopic mucosal healing, ozanimod appears to offer benefits on the histologic front.
Major finding: Histologic improvement was greater in patients who took higher dose of ozanimod (1 mg) than placebo at week 8 (Geboes score [–4.37 vs. –2.20; P = .0345]) and 32 (Geboes score [–5.50 vs. –2.24; P = .0033]). The lower dose (0.5 mg) showed improvement, but it was not statistically significant.
Data source: Randomized, double-blind, placebo-controlled phase II trial of 197 patients (high dose, 67; low dose, 65; placebo, 65).
Disclosures: The study was industry funded by Receptos. Dr. Hanauer is on the ozanimod steering committee and consults for Celgene and its subsidiary research division, Receptos.
Long-term benefits seen in sacral nerve stimulation for constipation in kids
SAN DIEGO – Children with refractory constipation may benefit from sacral nerve stimulation, although complications are common, according to a study that found benefits over more than 2 years, as well as evidence that parents like the treatment.
Sacral nerve stimulation is an accepted treatment for refractory constipation in adults, but long-term research in kids has been lacking.
The current study showed that sacral nerve stimulation (SNS) “can be used successfully for some children with intractable constipation, and the improvement seen with SNS treatment can be durable,” said study lead author Dr. Peter Lu, a pediatric gastroenterology fellow with Nationwide Children’s Hospital in Columbus, Ohio. “However, much more research is needed before more widespread adoption of SNS for treatment of this population.”
An estimated 12% of children suffer from constipation, and about 10% of those will still have symptoms despite laxative use, said Dr. Lu, who presented the findings at the annual Digestive Disease Week.
“We regularly see children in our GI clinic who have severe constipation leading to frequent episodes of overflow fecal incontinence, often throughout the day at school,” Dr. Lu said. “As you might imagine, this is incredibly embarrassing and isolating.”
According to Dr. Lu, treatments include anal sphincter botulinum injection, antegrade continence enema (ACE), colonic resection, and SNS.
Adult research has shown that SNS is effective in the treatment of constipation and fetal incontinence, Dr. Lu said, but research in children is limited and only looked at effects over a period of 4-12 months. “The durability of symptom improvement has not been really shown,” he said.
Dr. Lu and associates tracked 25 children (52% male; mean age, 14.0 years) with refractory constipation: 17 had functional constipation, 6 had an anorectal malformation, 1 had Hirschsprung’s disease, and 1 had a tethered cord. Comorbid conditions included fecal incontinence (18, 72%) and urinary symptoms (16, 64%). Thirteen (52%) used ACEs at baseline.
At the most recent follow-up, the number using laxatives fell from 16/64% to 11/44% (P = .16).
Of 13 subjects using ACEs, 8 (62%) had undergone closure of their appendicostomy or cecostomy and the other 5 (38%) had reduced ACE frequency by follow-up. ACE use fell from 12/48% to 5/20% (P = .03).
Scores on the PedsQL GI Symptom Scale and Fecal Incontinence Severity Index and on most Fecal Incontinence Quality of Life Scale domains had improved at follow-up.
At a mean of 2.4 years for constipation scores and 1.8 years for symptom scores, 16 parents completed questionnaires. Median Glasgow Children’s Benefit Inventory (GCBI) scores were +42.7 (interquartile range, 23.4-77.1), and 15 (94%) reported GCBI scores greater than 0. Fourteen (88%) said they’d allow their children to undergo SNS again if they could make the choice once more.
“Almost all reported benefit from SNS,” Dr. Lu said, “and all would still recommend SNS to other families with children who have similar symptoms.”
However, six patients (24%) had complications requiring surgery; four of those needed SNS replacement.
There are remaining questions. For one, “the mechanism of SNS treatment remains unclear,” Dr. Lu said. “We suspect that SNS leads to improvement by modulating anorectal function, and there has also been evidence that SNS can affect colonic motility. We are currently studying this further and hope to have a better understanding of how the treatment works soon.”
Dr. Lu and colleagues are also studying why patients have complications, with an eye toward identifying risk factors.
In a question and answer session, Dr. Lu acknowledged that many patients were lost to follow-up; some moved away. “Part of it was that we didn’t have the time to really track them down,” he said. “That’s something we definitely have to look at.” However, he noted that the 16 parents who did respond accounted for 5 of the 6 children who encountered complications.
Dr. Lu said he doesn’t recommend widespread use of SNS in children. “We need to have a better understanding of which patients will benefit from SNS and which patients will not,” Dr. Lu said.
No funding was reported. Dr. Lu had no relevant financial disclosures.
SAN DIEGO – Children with refractory constipation may benefit from sacral nerve stimulation, although complications are common, according to a study that found benefits over more than 2 years, as well as evidence that parents like the treatment.
Sacral nerve stimulation is an accepted treatment for refractory constipation in adults, but long-term research in kids has been lacking.
The current study showed that sacral nerve stimulation (SNS) “can be used successfully for some children with intractable constipation, and the improvement seen with SNS treatment can be durable,” said study lead author Dr. Peter Lu, a pediatric gastroenterology fellow with Nationwide Children’s Hospital in Columbus, Ohio. “However, much more research is needed before more widespread adoption of SNS for treatment of this population.”
An estimated 12% of children suffer from constipation, and about 10% of those will still have symptoms despite laxative use, said Dr. Lu, who presented the findings at the annual Digestive Disease Week.
“We regularly see children in our GI clinic who have severe constipation leading to frequent episodes of overflow fecal incontinence, often throughout the day at school,” Dr. Lu said. “As you might imagine, this is incredibly embarrassing and isolating.”
According to Dr. Lu, treatments include anal sphincter botulinum injection, antegrade continence enema (ACE), colonic resection, and SNS.
Adult research has shown that SNS is effective in the treatment of constipation and fetal incontinence, Dr. Lu said, but research in children is limited and only looked at effects over a period of 4-12 months. “The durability of symptom improvement has not been really shown,” he said.
Dr. Lu and associates tracked 25 children (52% male; mean age, 14.0 years) with refractory constipation: 17 had functional constipation, 6 had an anorectal malformation, 1 had Hirschsprung’s disease, and 1 had a tethered cord. Comorbid conditions included fecal incontinence (18, 72%) and urinary symptoms (16, 64%). Thirteen (52%) used ACEs at baseline.
At the most recent follow-up, the number using laxatives fell from 16/64% to 11/44% (P = .16).
Of 13 subjects using ACEs, 8 (62%) had undergone closure of their appendicostomy or cecostomy and the other 5 (38%) had reduced ACE frequency by follow-up. ACE use fell from 12/48% to 5/20% (P = .03).
Scores on the PedsQL GI Symptom Scale and Fecal Incontinence Severity Index and on most Fecal Incontinence Quality of Life Scale domains had improved at follow-up.
At a mean of 2.4 years for constipation scores and 1.8 years for symptom scores, 16 parents completed questionnaires. Median Glasgow Children’s Benefit Inventory (GCBI) scores were +42.7 (interquartile range, 23.4-77.1), and 15 (94%) reported GCBI scores greater than 0. Fourteen (88%) said they’d allow their children to undergo SNS again if they could make the choice once more.
“Almost all reported benefit from SNS,” Dr. Lu said, “and all would still recommend SNS to other families with children who have similar symptoms.”
However, six patients (24%) had complications requiring surgery; four of those needed SNS replacement.
There are remaining questions. For one, “the mechanism of SNS treatment remains unclear,” Dr. Lu said. “We suspect that SNS leads to improvement by modulating anorectal function, and there has also been evidence that SNS can affect colonic motility. We are currently studying this further and hope to have a better understanding of how the treatment works soon.”
Dr. Lu and colleagues are also studying why patients have complications, with an eye toward identifying risk factors.
In a question and answer session, Dr. Lu acknowledged that many patients were lost to follow-up; some moved away. “Part of it was that we didn’t have the time to really track them down,” he said. “That’s something we definitely have to look at.” However, he noted that the 16 parents who did respond accounted for 5 of the 6 children who encountered complications.
Dr. Lu said he doesn’t recommend widespread use of SNS in children. “We need to have a better understanding of which patients will benefit from SNS and which patients will not,” Dr. Lu said.
No funding was reported. Dr. Lu had no relevant financial disclosures.
SAN DIEGO – Children with refractory constipation may benefit from sacral nerve stimulation, although complications are common, according to a study that found benefits over more than 2 years, as well as evidence that parents like the treatment.
Sacral nerve stimulation is an accepted treatment for refractory constipation in adults, but long-term research in kids has been lacking.
The current study showed that sacral nerve stimulation (SNS) “can be used successfully for some children with intractable constipation, and the improvement seen with SNS treatment can be durable,” said study lead author Dr. Peter Lu, a pediatric gastroenterology fellow with Nationwide Children’s Hospital in Columbus, Ohio. “However, much more research is needed before more widespread adoption of SNS for treatment of this population.”
An estimated 12% of children suffer from constipation, and about 10% of those will still have symptoms despite laxative use, said Dr. Lu, who presented the findings at the annual Digestive Disease Week.
“We regularly see children in our GI clinic who have severe constipation leading to frequent episodes of overflow fecal incontinence, often throughout the day at school,” Dr. Lu said. “As you might imagine, this is incredibly embarrassing and isolating.”
According to Dr. Lu, treatments include anal sphincter botulinum injection, antegrade continence enema (ACE), colonic resection, and SNS.
Adult research has shown that SNS is effective in the treatment of constipation and fetal incontinence, Dr. Lu said, but research in children is limited and only looked at effects over a period of 4-12 months. “The durability of symptom improvement has not been really shown,” he said.
Dr. Lu and associates tracked 25 children (52% male; mean age, 14.0 years) with refractory constipation: 17 had functional constipation, 6 had an anorectal malformation, 1 had Hirschsprung’s disease, and 1 had a tethered cord. Comorbid conditions included fecal incontinence (18, 72%) and urinary symptoms (16, 64%). Thirteen (52%) used ACEs at baseline.
At the most recent follow-up, the number using laxatives fell from 16/64% to 11/44% (P = .16).
Of 13 subjects using ACEs, 8 (62%) had undergone closure of their appendicostomy or cecostomy and the other 5 (38%) had reduced ACE frequency by follow-up. ACE use fell from 12/48% to 5/20% (P = .03).
Scores on the PedsQL GI Symptom Scale and Fecal Incontinence Severity Index and on most Fecal Incontinence Quality of Life Scale domains had improved at follow-up.
At a mean of 2.4 years for constipation scores and 1.8 years for symptom scores, 16 parents completed questionnaires. Median Glasgow Children’s Benefit Inventory (GCBI) scores were +42.7 (interquartile range, 23.4-77.1), and 15 (94%) reported GCBI scores greater than 0. Fourteen (88%) said they’d allow their children to undergo SNS again if they could make the choice once more.
“Almost all reported benefit from SNS,” Dr. Lu said, “and all would still recommend SNS to other families with children who have similar symptoms.”
However, six patients (24%) had complications requiring surgery; four of those needed SNS replacement.
There are remaining questions. For one, “the mechanism of SNS treatment remains unclear,” Dr. Lu said. “We suspect that SNS leads to improvement by modulating anorectal function, and there has also been evidence that SNS can affect colonic motility. We are currently studying this further and hope to have a better understanding of how the treatment works soon.”
Dr. Lu and colleagues are also studying why patients have complications, with an eye toward identifying risk factors.
In a question and answer session, Dr. Lu acknowledged that many patients were lost to follow-up; some moved away. “Part of it was that we didn’t have the time to really track them down,” he said. “That’s something we definitely have to look at.” However, he noted that the 16 parents who did respond accounted for 5 of the 6 children who encountered complications.
Dr. Lu said he doesn’t recommend widespread use of SNS in children. “We need to have a better understanding of which patients will benefit from SNS and which patients will not,” Dr. Lu said.
No funding was reported. Dr. Lu had no relevant financial disclosures.
AT DDW 2016
Key clinical point: Children with refractory constipation may benefit from sacral nerve stimulation although complications are common.
Major finding: The use of laxatives fell from 64% to 44% by follow-up (P =.16), as did ACE use, which went from 48% to 20% (P = .03). All parents who weren’t lost to follow-up said they’d recommend the treatment.
Data source: A prospective cohort of 25 children (52% male; mean age, 14 years; all under 21) with refractory constipation who were treated for more than 2 years.
Disclosures: No funding was reported. Dr. Lu had no relevant financial disclosures.
SSRIs don’t boost risk in patients with bleeding peptic ulcers
SAN DIEGO – Taking selective serotonin reuptake inhibitors (SSRIs) was not associated with an increased risk of endoscopy-refractory bleeding, rebleeding, or in-hospital mortality among 14,343 consecutive patients admitted with bleeding peptic ulcer in Denmark.
The study suggests that patients with bleeding peptic ulcers can “continue SSRI treatment if the treatment is well indicated,” and that these patients can otherwise receive treatment similar to that of other patients with peptic ulcer bleeding, Dr. Stig B. Laursen reported at the annual Digestive Disease Week.
Observational research has linked use of SSRI antidepressants to an approximately 1.5-fold increase in upper GI bleeding in peptic ulcer bleeding cases, said Dr. Laursen of Odense (Denmark) University Hospital. Studies, mostly in vitro ones, indicate SSRIs decrease the function of thrombocytes and fibrin formation via lowered levels of serotonin. Therefore, it has been suggested that temporarily discontinuing SSRIs may benefit patients with bleeding peptic ulcers.
However, sudden cessation of SSRIs can be associated with withdrawal symptoms, which have been reported in up to one-third of such patients.
Dr. Laursen and his associates prospectively analyzed data for 14,343 consecutive patients admitted with bleeding peptic ulcers in Denmark from 2006 to 2014. They investigated associations between SSRI use and several outcomes, adjusted for confounding factors including age, sex, comorbidity, anemia, medication use, circulatory failure at hospital admission, location of ulcer, stigmata of bleeding, and weekend admission.
After adjustment for confounding risk factors, SSRIs were not associated with increased risk of endoscopy-refractory bleeding (odds ratio [OR] 95% confidence interval [CI]: 1.01 [0.78-1.30]), rebleeding (OR [95% CI]: 0.94 [0.81-1.10]), or in-hospital mortality (hazard ratio [95% CI]: 0.84 [0.68-1.05]).
“Patients taking SSRIs have the same outcomes following peptic ulcer bleeding as non-SSRI users. This suggests that there is no clinically significant impairment of hemostatic function,” Dr. Laursen said. “Therefore, it seems safe to continue SSRI treatment in patients developing peptic ulcer bleeding and thereby avoid development of withdrawal symptoms.”
Dr. Laursen noted that the study has several limitations. It’s not a randomized controlled trial, he said, and there’s no information about the types of SSRIs that the patients were taking. Also, there’s a lack of information about possible discontinuation of SSRIs during hospitalization. However, he said, “that doesn’t seem to be a major confounder.”
During the question-and-answer session following his presentation, Dr. Laursen said the increased risk of poor outcome is quite low, but “there may be a small risk that we haven’t found yet. But if it’s small, maybe it doesn’t have an impact in day-to-day practice.”
The research is hospital-funded. Dr. Laursen had no financial disclosures to report.
SAN DIEGO – Taking selective serotonin reuptake inhibitors (SSRIs) was not associated with an increased risk of endoscopy-refractory bleeding, rebleeding, or in-hospital mortality among 14,343 consecutive patients admitted with bleeding peptic ulcer in Denmark.
The study suggests that patients with bleeding peptic ulcers can “continue SSRI treatment if the treatment is well indicated,” and that these patients can otherwise receive treatment similar to that of other patients with peptic ulcer bleeding, Dr. Stig B. Laursen reported at the annual Digestive Disease Week.
Observational research has linked use of SSRI antidepressants to an approximately 1.5-fold increase in upper GI bleeding in peptic ulcer bleeding cases, said Dr. Laursen of Odense (Denmark) University Hospital. Studies, mostly in vitro ones, indicate SSRIs decrease the function of thrombocytes and fibrin formation via lowered levels of serotonin. Therefore, it has been suggested that temporarily discontinuing SSRIs may benefit patients with bleeding peptic ulcers.
However, sudden cessation of SSRIs can be associated with withdrawal symptoms, which have been reported in up to one-third of such patients.
Dr. Laursen and his associates prospectively analyzed data for 14,343 consecutive patients admitted with bleeding peptic ulcers in Denmark from 2006 to 2014. They investigated associations between SSRI use and several outcomes, adjusted for confounding factors including age, sex, comorbidity, anemia, medication use, circulatory failure at hospital admission, location of ulcer, stigmata of bleeding, and weekend admission.
After adjustment for confounding risk factors, SSRIs were not associated with increased risk of endoscopy-refractory bleeding (odds ratio [OR] 95% confidence interval [CI]: 1.01 [0.78-1.30]), rebleeding (OR [95% CI]: 0.94 [0.81-1.10]), or in-hospital mortality (hazard ratio [95% CI]: 0.84 [0.68-1.05]).
“Patients taking SSRIs have the same outcomes following peptic ulcer bleeding as non-SSRI users. This suggests that there is no clinically significant impairment of hemostatic function,” Dr. Laursen said. “Therefore, it seems safe to continue SSRI treatment in patients developing peptic ulcer bleeding and thereby avoid development of withdrawal symptoms.”
Dr. Laursen noted that the study has several limitations. It’s not a randomized controlled trial, he said, and there’s no information about the types of SSRIs that the patients were taking. Also, there’s a lack of information about possible discontinuation of SSRIs during hospitalization. However, he said, “that doesn’t seem to be a major confounder.”
During the question-and-answer session following his presentation, Dr. Laursen said the increased risk of poor outcome is quite low, but “there may be a small risk that we haven’t found yet. But if it’s small, maybe it doesn’t have an impact in day-to-day practice.”
The research is hospital-funded. Dr. Laursen had no financial disclosures to report.
SAN DIEGO – Taking selective serotonin reuptake inhibitors (SSRIs) was not associated with an increased risk of endoscopy-refractory bleeding, rebleeding, or in-hospital mortality among 14,343 consecutive patients admitted with bleeding peptic ulcer in Denmark.
The study suggests that patients with bleeding peptic ulcers can “continue SSRI treatment if the treatment is well indicated,” and that these patients can otherwise receive treatment similar to that of other patients with peptic ulcer bleeding, Dr. Stig B. Laursen reported at the annual Digestive Disease Week.
Observational research has linked use of SSRI antidepressants to an approximately 1.5-fold increase in upper GI bleeding in peptic ulcer bleeding cases, said Dr. Laursen of Odense (Denmark) University Hospital. Studies, mostly in vitro ones, indicate SSRIs decrease the function of thrombocytes and fibrin formation via lowered levels of serotonin. Therefore, it has been suggested that temporarily discontinuing SSRIs may benefit patients with bleeding peptic ulcers.
However, sudden cessation of SSRIs can be associated with withdrawal symptoms, which have been reported in up to one-third of such patients.
Dr. Laursen and his associates prospectively analyzed data for 14,343 consecutive patients admitted with bleeding peptic ulcers in Denmark from 2006 to 2014. They investigated associations between SSRI use and several outcomes, adjusted for confounding factors including age, sex, comorbidity, anemia, medication use, circulatory failure at hospital admission, location of ulcer, stigmata of bleeding, and weekend admission.
After adjustment for confounding risk factors, SSRIs were not associated with increased risk of endoscopy-refractory bleeding (odds ratio [OR] 95% confidence interval [CI]: 1.01 [0.78-1.30]), rebleeding (OR [95% CI]: 0.94 [0.81-1.10]), or in-hospital mortality (hazard ratio [95% CI]: 0.84 [0.68-1.05]).
“Patients taking SSRIs have the same outcomes following peptic ulcer bleeding as non-SSRI users. This suggests that there is no clinically significant impairment of hemostatic function,” Dr. Laursen said. “Therefore, it seems safe to continue SSRI treatment in patients developing peptic ulcer bleeding and thereby avoid development of withdrawal symptoms.”
Dr. Laursen noted that the study has several limitations. It’s not a randomized controlled trial, he said, and there’s no information about the types of SSRIs that the patients were taking. Also, there’s a lack of information about possible discontinuation of SSRIs during hospitalization. However, he said, “that doesn’t seem to be a major confounder.”
During the question-and-answer session following his presentation, Dr. Laursen said the increased risk of poor outcome is quite low, but “there may be a small risk that we haven’t found yet. But if it’s small, maybe it doesn’t have an impact in day-to-day practice.”
The research is hospital-funded. Dr. Laursen had no financial disclosures to report.
AT DDW 2016
Key clinical point: Patients with bleeding peptic ulcers who are on SSRIs may be able to avoid cessation and withdrawal symptoms because outcomes aren’t affected despite worsened bleeding.
Major finding: After adjustment for confounding factors, SSRIs didn’t significantly worsen endoscopy-refractory bleeding (OR 1.01), rebleeding (OR 0.94) or in-hospital mortality (HR 0.84).
Data source: Analysis of 14,343 consecutive patients with bleeding peptic ulcers in Denmark from 2006 to 2014.
Disclosures: The research is hospital funded. Dr. Laursen had no financial disclosures to report.
