Upper GI Tract

WASHINGTON – Treatment with an oral formulation of budesonide was associated with significant improvements in dysphagia and esophageal eosinophil counts in adolescents and adults with eosinophilic esophagitis, in a study that is also the first to use a recently validated scoring instrument to evaluate medical therapy for this disorder in a randomized trial.

Results of the multicenter, double-blind, randomized study comparing treatment with an oral budesonide suspension to placebo for 12 weeks in almost 100 patients with eosinophilic esophagitis (EoE) were reported in two separate presentations at the annual Digestive Disease Week. One of the investigators, Dr. Evan Dellon of the Center for Gastrointestinal Biology and Disease, at the University of North Carolina, Chapel Hill, said that treatment with this “mucoadherent” formulation of the topical steroid was associated with significant improvements in dysphagia symptoms, as measured with the Dysphagia Symptom Questionnaire (DSQ), and a histologic response rate of 39%, vs. 3% among those on placebo.

“The study not only adds to the evidence that topical budesonide is effective for inducing histologic response in subjects with active EoE, but [also] shows for the first time that symptoms of dysphagia, as measured with a validated symptom instrument, improve concordantly with the histologic and endoscopic findings,” Dr. Dellon said in an interview after the meeting. “Moreover, this study shows that a topical steroid formulation designed specifically for EoE, rather than an asthma formulation that is adapted for esophageal use, will likely be a beneficial and potentially preferred clinical treatment option.”

Another study investigator, Dr. Ikuo Hirano, professor of medicine and director of the gastroenterology and hepatology fellowship program at Northwestern University, Chicago, reported that treatment was also associated with significant improvements in the EoE Endoscopic Reference Score, EREFS, which was designed to classify and grade the severity of five major endoscopic features of EoE: edema, rings, exudates, furrows, and stricture formation. This was the first study to use this validated endoscopic scoring instrument in a randomized controlled trial of a medical therapy in patients with EoE, he said at the meeting.

The study was conducted between 2012 and 2014 at 25 U.S. sites, in patients aged 11-40 years with EoE. Baseline demographic and endoscopic characteristics were similar in the two groups. Their mean age was 21-22 years (41% of those on placebo and 35% of those on budesonide were younger than age 18 years) and 69% were male; most patients had edema, all had dysphagia, and 39%-41% had heartburn. Patients were excluded if they had esophageal stricture on screening endoscopy that did not allow passage of a standard adult diagnostic endoscope.

Patients were randomized to treatment with budesonide suspension, at a dose of 2 mg twice a day (51 patients) or a placebo suspension (42 patients). The primary outcomes were a change in the DSQ score from baseline, and the proportion of patients with a histologic response, defined as at least 6 eosinophils per high-power field (eos/hpf) from all biopsies. The final analysis included 87 patients.

At baseline, the mean peak eosinophil counts were 156/hpf among those on budesonide and 130/hpf among those on placebo; after treatment, the mean peak counts dropped to 39/hpf among those on budesonide (a 65% reduction) and to 113/hpf among those on placebo (a 10% reduction), a statistically significant difference (P < .05), said Dr. Dellon, also with the department of medicine at UNC.

From a mean of about 29 in both groups at baseline, DSQ scores dropped by a mean of 14.3 among the treated patients, vs. 7.5 among those on placebo, which was a statistically significant difference (P = .0096). The other primary endpoint, the histologic response rate, was 39% among treated patients, vs. 3% among those on placebo, also a significant difference (P < .0001).

Adverse events were not different between the two groups, and growth velocity among those under age 18 years and cortisol levels were not different between the two groups, he added. There was one case of esophageal candidiasis in a patient on budesonide.

During his presentation, Dr. Hirano said that there were also significant improvements in EREFS scores from baseline in the proximal and distal esophagus among those treated with budesonide, but not among those on placebo. Based on EREFS scores, oral budesonide “resulted in significant improvement in endoscopic features of edema, exudate, rings, [and] furrows, compared to placebo,” but there was no significant change in strictures, another component of the EREFS, in either the treatment or placebo groups. However, patients with high-grade strictures were not enrolled in the study, he added.

After treatment, proximal, distal, and total EREFS scores correlated with peak eosinophil counts, a highly statistically significant finding.

Dr. Hirano said that the primary endpoints used in most EoE clinical trials to date have focused mostly on assessments of symptoms and histopathology, which have limitations. “Symptoms are difficult to quantify and often intermittent [and] they may improve as a result of changes in eating behavior and food avoidance,” he said. Patient-reported outcome instruments have been recently validated, “but have questionable utility in clinical practice” and histology “has shown limited correlation between degree of esophageal eosinophilia and symptom severity [and does not] assess for modeling, an important determinant of overall disease complications,” he added.

The utility of endoscopy in EoE includes the features that are present in vast majority of patients with EoE, and provides a gross assessment of overall disease activity, “both in terms of inflammatory and fibrostenotic features,” he said.

“Endoscopic outcomes are now emerging as clinically relevant endpoints of therapy of trials of eosinophilic esophagitis that supports and complements” symptom and histologic assessments, Dr. Hirano commented, adding that more studies are need to determine the “relative importance of these individual endoscopic features as well as the appropriate utilization of endoscopic parameters in disease management.”

The study was funded by Meritage Pharma, recently acquired by the Shire group of companies. All authors received research funds to conduct the study, and Dr. Hirano disclosed having worked as a consultant for Meritage. Dr. Dellon’s disclosures included receiving grant and research support from Meritage. Shire is developing the oral budesonide suspension formulation as a treatment for adolescents and adults with EoE.

[email protected]

WASHINGTON – Treatment with an oral formulation of budesonide was associated with significant improvements in dysphagia and esophageal eosinophil counts in adolescents and adults with eosinophilic esophagitis, in a study that is also the first to use a recently validated scoring instrument to evaluate medical therapy for this disorder in a randomized trial.

Results of the multicenter, double-blind, randomized study comparing treatment with an oral budesonide suspension to placebo for 12 weeks in almost 100 patients with eosinophilic esophagitis (EoE) were reported in two separate presentations at the annual Digestive Disease Week. One of the investigators, Dr. Evan Dellon of the Center for Gastrointestinal Biology and Disease, at the University of North Carolina, Chapel Hill, said that treatment with this “mucoadherent” formulation of the topical steroid was associated with significant improvements in dysphagia symptoms, as measured with the Dysphagia Symptom Questionnaire (DSQ), and a histologic response rate of 39%, vs. 3% among those on placebo.

“The study not only adds to the evidence that topical budesonide is effective for inducing histologic response in subjects with active EoE, but [also] shows for the first time that symptoms of dysphagia, as measured with a validated symptom instrument, improve concordantly with the histologic and endoscopic findings,” Dr. Dellon said in an interview after the meeting. “Moreover, this study shows that a topical steroid formulation designed specifically for EoE, rather than an asthma formulation that is adapted for esophageal use, will likely be a beneficial and potentially preferred clinical treatment option.”

Another study investigator, Dr. Ikuo Hirano, professor of medicine and director of the gastroenterology and hepatology fellowship program at Northwestern University, Chicago, reported that treatment was also associated with significant improvements in the EoE Endoscopic Reference Score, EREFS, which was designed to classify and grade the severity of five major endoscopic features of EoE: edema, rings, exudates, furrows, and stricture formation. This was the first study to use this validated endoscopic scoring instrument in a randomized controlled trial of a medical therapy in patients with EoE, he said at the meeting.

The study was conducted between 2012 and 2014 at 25 U.S. sites, in patients aged 11-40 years with EoE. Baseline demographic and endoscopic characteristics were similar in the two groups. Their mean age was 21-22 years (41% of those on placebo and 35% of those on budesonide were younger than age 18 years) and 69% were male; most patients had edema, all had dysphagia, and 39%-41% had heartburn. Patients were excluded if they had esophageal stricture on screening endoscopy that did not allow passage of a standard adult diagnostic endoscope.

Patients were randomized to treatment with budesonide suspension, at a dose of 2 mg twice a day (51 patients) or a placebo suspension (42 patients). The primary outcomes were a change in the DSQ score from baseline, and the proportion of patients with a histologic response, defined as at least 6 eosinophils per high-power field (eos/hpf) from all biopsies. The final analysis included 87 patients.

At baseline, the mean peak eosinophil counts were 156/hpf among those on budesonide and 130/hpf among those on placebo; after treatment, the mean peak counts dropped to 39/hpf among those on budesonide (a 65% reduction) and to 113/hpf among those on placebo (a 10% reduction), a statistically significant difference (P < .05), said Dr. Dellon, also with the department of medicine at UNC.

From a mean of about 29 in both groups at baseline, DSQ scores dropped by a mean of 14.3 among the treated patients, vs. 7.5 among those on placebo, which was a statistically significant difference (P = .0096). The other primary endpoint, the histologic response rate, was 39% among treated patients, vs. 3% among those on placebo, also a significant difference (P < .0001).

Adverse events were not different between the two groups, and growth velocity among those under age 18 years and cortisol levels were not different between the two groups, he added. There was one case of esophageal candidiasis in a patient on budesonide.

During his presentation, Dr. Hirano said that there were also significant improvements in EREFS scores from baseline in the proximal and distal esophagus among those treated with budesonide, but not among those on placebo. Based on EREFS scores, oral budesonide “resulted in significant improvement in endoscopic features of edema, exudate, rings, [and] furrows, compared to placebo,” but there was no significant change in strictures, another component of the EREFS, in either the treatment or placebo groups. However, patients with high-grade strictures were not enrolled in the study, he added.

After treatment, proximal, distal, and total EREFS scores correlated with peak eosinophil counts, a highly statistically significant finding.

Dr. Hirano said that the primary endpoints used in most EoE clinical trials to date have focused mostly on assessments of symptoms and histopathology, which have limitations. “Symptoms are difficult to quantify and often intermittent [and] they may improve as a result of changes in eating behavior and food avoidance,” he said. Patient-reported outcome instruments have been recently validated, “but have questionable utility in clinical practice” and histology “has shown limited correlation between degree of esophageal eosinophilia and symptom severity [and does not] assess for modeling, an important determinant of overall disease complications,” he added.

The utility of endoscopy in EoE includes the features that are present in vast majority of patients with EoE, and provides a gross assessment of overall disease activity, “both in terms of inflammatory and fibrostenotic features,” he said.

“Endoscopic outcomes are now emerging as clinically relevant endpoints of therapy of trials of eosinophilic esophagitis that supports and complements” symptom and histologic assessments, Dr. Hirano commented, adding that more studies are need to determine the “relative importance of these individual endoscopic features as well as the appropriate utilization of endoscopic parameters in disease management.”

The study was funded by Meritage Pharma, recently acquired by the Shire group of companies. All authors received research funds to conduct the study, and Dr. Hirano disclosed having worked as a consultant for Meritage. Dr. Dellon’s disclosures included receiving grant and research support from Meritage. Shire is developing the oral budesonide suspension formulation as a treatment for adolescents and adults with EoE.

[email protected]

WASHINGTON – Treatment with an oral formulation of budesonide was associated with significant improvements in dysphagia and esophageal eosinophil counts in adolescents and adults with eosinophilic esophagitis, in a study that is also the first to use a recently validated scoring instrument to evaluate medical therapy for this disorder in a randomized trial.

Results of the multicenter, double-blind, randomized study comparing treatment with an oral budesonide suspension to placebo for 12 weeks in almost 100 patients with eosinophilic esophagitis (EoE) were reported in two separate presentations at the annual Digestive Disease Week. One of the investigators, Dr. Evan Dellon of the Center for Gastrointestinal Biology and Disease, at the University of North Carolina, Chapel Hill, said that treatment with this “mucoadherent” formulation of the topical steroid was associated with significant improvements in dysphagia symptoms, as measured with the Dysphagia Symptom Questionnaire (DSQ), and a histologic response rate of 39%, vs. 3% among those on placebo.

“The study not only adds to the evidence that topical budesonide is effective for inducing histologic response in subjects with active EoE, but [also] shows for the first time that symptoms of dysphagia, as measured with a validated symptom instrument, improve concordantly with the histologic and endoscopic findings,” Dr. Dellon said in an interview after the meeting. “Moreover, this study shows that a topical steroid formulation designed specifically for EoE, rather than an asthma formulation that is adapted for esophageal use, will likely be a beneficial and potentially preferred clinical treatment option.”

Another study investigator, Dr. Ikuo Hirano, professor of medicine and director of the gastroenterology and hepatology fellowship program at Northwestern University, Chicago, reported that treatment was also associated with significant improvements in the EoE Endoscopic Reference Score, EREFS, which was designed to classify and grade the severity of five major endoscopic features of EoE: edema, rings, exudates, furrows, and stricture formation. This was the first study to use this validated endoscopic scoring instrument in a randomized controlled trial of a medical therapy in patients with EoE, he said at the meeting.

The study was conducted between 2012 and 2014 at 25 U.S. sites, in patients aged 11-40 years with EoE. Baseline demographic and endoscopic characteristics were similar in the two groups. Their mean age was 21-22 years (41% of those on placebo and 35% of those on budesonide were younger than age 18 years) and 69% were male; most patients had edema, all had dysphagia, and 39%-41% had heartburn. Patients were excluded if they had esophageal stricture on screening endoscopy that did not allow passage of a standard adult diagnostic endoscope.

Patients were randomized to treatment with budesonide suspension, at a dose of 2 mg twice a day (51 patients) or a placebo suspension (42 patients). The primary outcomes were a change in the DSQ score from baseline, and the proportion of patients with a histologic response, defined as at least 6 eosinophils per high-power field (eos/hpf) from all biopsies. The final analysis included 87 patients.

At baseline, the mean peak eosinophil counts were 156/hpf among those on budesonide and 130/hpf among those on placebo; after treatment, the mean peak counts dropped to 39/hpf among those on budesonide (a 65% reduction) and to 113/hpf among those on placebo (a 10% reduction), a statistically significant difference (P < .05), said Dr. Dellon, also with the department of medicine at UNC.

From a mean of about 29 in both groups at baseline, DSQ scores dropped by a mean of 14.3 among the treated patients, vs. 7.5 among those on placebo, which was a statistically significant difference (P = .0096). The other primary endpoint, the histologic response rate, was 39% among treated patients, vs. 3% among those on placebo, also a significant difference (P < .0001).

Adverse events were not different between the two groups, and growth velocity among those under age 18 years and cortisol levels were not different between the two groups, he added. There was one case of esophageal candidiasis in a patient on budesonide.

During his presentation, Dr. Hirano said that there were also significant improvements in EREFS scores from baseline in the proximal and distal esophagus among those treated with budesonide, but not among those on placebo. Based on EREFS scores, oral budesonide “resulted in significant improvement in endoscopic features of edema, exudate, rings, [and] furrows, compared to placebo,” but there was no significant change in strictures, another component of the EREFS, in either the treatment or placebo groups. However, patients with high-grade strictures were not enrolled in the study, he added.

After treatment, proximal, distal, and total EREFS scores correlated with peak eosinophil counts, a highly statistically significant finding.

Dr. Hirano said that the primary endpoints used in most EoE clinical trials to date have focused mostly on assessments of symptoms and histopathology, which have limitations. “Symptoms are difficult to quantify and often intermittent [and] they may improve as a result of changes in eating behavior and food avoidance,” he said. Patient-reported outcome instruments have been recently validated, “but have questionable utility in clinical practice” and histology “has shown limited correlation between degree of esophageal eosinophilia and symptom severity [and does not] assess for modeling, an important determinant of overall disease complications,” he added.

The utility of endoscopy in EoE includes the features that are present in vast majority of patients with EoE, and provides a gross assessment of overall disease activity, “both in terms of inflammatory and fibrostenotic features,” he said.

“Endoscopic outcomes are now emerging as clinically relevant endpoints of therapy of trials of eosinophilic esophagitis that supports and complements” symptom and histologic assessments, Dr. Hirano commented, adding that more studies are need to determine the “relative importance of these individual endoscopic features as well as the appropriate utilization of endoscopic parameters in disease management.”

The study was funded by Meritage Pharma, recently acquired by the Shire group of companies. All authors received research funds to conduct the study, and Dr. Hirano disclosed having worked as a consultant for Meritage. Dr. Dellon’s disclosures included receiving grant and research support from Meritage. Shire is developing the oral budesonide suspension formulation as a treatment for adolescents and adults with EoE.

[email protected]

WASHINGTON – Early resumption of antiplatelet agents or anticoagulants after a major gastrointestinal bleeding event is clearly associated with an increased risk of rebleeding, but a decreased risk of death, results from an observational study show.

Furthermore, anticoagulant treatment “is associated with a higher risk of rebleeding and death compared with antiplatelet treatment after a previous GI event,” Dr. Angel Lanas said to an overflow crowd at the annual Digestive Disease Week.

Patrice Wendling/Frontline Medical News

In a separate case-control study, Dr. Lanas and his associates recently reported that the risk of GI bleeding was twofold higher for anticoagulants than for low-dose aspirin in patients hospitalized for GI bleeding (Clin. Gastroenterol. Hepatol. 2015 May;13:906-12.e2. [doi:10.1016/j.cgh.2014.11.007])

The current study examined adverse events in a cohort of 160 patients who developed a major gastrointestinal bleed (GIB) while using anticoagulants and/or antiplatelet therapy between March 2008 and July 2013. Long-term interruption or short-term resumption of these treatments has important clinical implications and differences in the intrinsic risks between antiplatelet or anticoagulant users after drug resumption are not well established, said Dr. Lanas of the University of Zaragoza, Spain.

Drug use information was prospectively collected during the GIB event, with data during the follow-up period obtained from two different Spanish databases.

Treatment during the index bleeding event was continued without interruption in 11 patients and interrupted in 149 patients (93%). Among those whose therapy was interrupted, 21 (14%) never resumed therapy and 128 (86%) resumed therapy (118 patients within 15 days and 10 patients after 15 days). The 86% treatment resumption rate is much higher than the 40%-66% rates reported in previous studies, indicating that Spanish physicians restarted treatment quite early, Dr. Lanas observed.

Patrice Wendling/Frontline Medical News

The mean age at baseline was 76.6 years, 61.3% of patients were men, and half had a Charlson index score > 4. Median follow-up was 21.5 months (range 1-63 months).

Ischemic events did not differ between patients who did or did not restart anticoagulants or antiplatelets (16.4% vs. 14.3%; P value = .806). However, rebleeding occurred in 32% of patients who resumed therapy versus none who did not (P = .002), but deaths were higher in those who did not restart therapy (38.1% vs. 12.5%; P = .003), Dr. Lanas said.

These differences remain significant in Kaplan-Meier survival curves for death (P = .021) and rebleeding (P = .004).

A comparison of early therapy resumption (≤ 15 days) vs. delayed (mean delay 62 days) or no resumption revealed similar results. Early resumption was associated with a higher rate of rebleeding (32.2% vs. 9.7%; P = .012), but a lower rate of death (11% vs. 35.5%; P = .001), with no difference in ischemic events (17% vs. 13%; P = .586), Dr. Lanas said.

Again, the differences remain significant in Kaplan-Meier survival curves for death (P = .011) and rebleeding (P = .013).

When the investigators looked at rebleeding according to drug use, patients receiving anticoagulants vs. antiplatelets had significantly higher rates of rebleeding (34.7% vs. 20.5%; P = .043), death (22.2% vs. 10.2%; P = .038), and any event (68.1% vs. 52.3%; P = .043).

After adjustment for gender, age, Charlson index, diabetes, and arterial hypertension, the risk of rebleeding was more than threefold higher for dual antiplatelet and anticoagulant users than for antiplatelet-alone users (odds ratio, 3.45; P = .025) and was twofold higher for anticoagulant vs. antiplatelet users (OR, 2.07; P = .045), Dr. Lanas said.

Finally, an analysis of the cause of bleeding suggests the cause of rebleeding may be different from the original event and that there is a shift toward the lower GI tract, he added.

The index bleeding event was caused largely by an upper GI peptic ulcer in 48% of all 160 patients, with 43.7% of events due to lower GI diverticulosis, vascular lesions, ischemic, or other lesions. In contrast, peptic ulcers accounted for only 7% of rebleeding events, while lower GI events accounted for 72%. Proton pump inhibition use was evenly distributed in upper and lower GI bleeding, although effective endoscopic treatment may have influenced upper GI bleeds, Dr. Lanas said.

“The importance of this is that we may have very good therapy tools for the upper GI, but still we have problems controlling the bleeding from the lower GI,” he added.

During a discussion of the study, an audience member asked how many days clinicians should wait to restart anticoagulants or antiplatelets.

“In those patients with peptic ulcer bleeding, it’s better to just give the antiplatelet therapy soon after the bleeding event or just to not interrupt the aspirin because the morality at 30 days was higher in those who were interrupted,” Dr. Lanas advised. “...I think for the cutoff point to show differences for patients with a worse outcome versus those with a better outcome, you shouldn’t restart anticoagulant therapy before day 15 after the bleeding event.”

Dr. Lanas received consulting fees, speaking and teaching fees, other financial support, and grant and research support from Bayer.

[email protected]

On Twitter @pwendl

WASHINGTON – Early resumption of antiplatelet agents or anticoagulants after a major gastrointestinal bleeding event is clearly associated with an increased risk of rebleeding, but a decreased risk of death, results from an observational study show.

Furthermore, anticoagulant treatment “is associated with a higher risk of rebleeding and death compared with antiplatelet treatment after a previous GI event,” Dr. Angel Lanas said to an overflow crowd at the annual Digestive Disease Week.

Patrice Wendling/Frontline Medical News

In a separate case-control study, Dr. Lanas and his associates recently reported that the risk of GI bleeding was twofold higher for anticoagulants than for low-dose aspirin in patients hospitalized for GI bleeding (Clin. Gastroenterol. Hepatol. 2015 May;13:906-12.e2. [doi:10.1016/j.cgh.2014.11.007])

The current study examined adverse events in a cohort of 160 patients who developed a major gastrointestinal bleed (GIB) while using anticoagulants and/or antiplatelet therapy between March 2008 and July 2013. Long-term interruption or short-term resumption of these treatments has important clinical implications and differences in the intrinsic risks between antiplatelet or anticoagulant users after drug resumption are not well established, said Dr. Lanas of the University of Zaragoza, Spain.

Drug use information was prospectively collected during the GIB event, with data during the follow-up period obtained from two different Spanish databases.

Treatment during the index bleeding event was continued without interruption in 11 patients and interrupted in 149 patients (93%). Among those whose therapy was interrupted, 21 (14%) never resumed therapy and 128 (86%) resumed therapy (118 patients within 15 days and 10 patients after 15 days). The 86% treatment resumption rate is much higher than the 40%-66% rates reported in previous studies, indicating that Spanish physicians restarted treatment quite early, Dr. Lanas observed.

Patrice Wendling/Frontline Medical News

The mean age at baseline was 76.6 years, 61.3% of patients were men, and half had a Charlson index score > 4. Median follow-up was 21.5 months (range 1-63 months).

Ischemic events did not differ between patients who did or did not restart anticoagulants or antiplatelets (16.4% vs. 14.3%; P value = .806). However, rebleeding occurred in 32% of patients who resumed therapy versus none who did not (P = .002), but deaths were higher in those who did not restart therapy (38.1% vs. 12.5%; P = .003), Dr. Lanas said.

These differences remain significant in Kaplan-Meier survival curves for death (P = .021) and rebleeding (P = .004).

A comparison of early therapy resumption (≤ 15 days) vs. delayed (mean delay 62 days) or no resumption revealed similar results. Early resumption was associated with a higher rate of rebleeding (32.2% vs. 9.7%; P = .012), but a lower rate of death (11% vs. 35.5%; P = .001), with no difference in ischemic events (17% vs. 13%; P = .586), Dr. Lanas said.

Again, the differences remain significant in Kaplan-Meier survival curves for death (P = .011) and rebleeding (P = .013).

When the investigators looked at rebleeding according to drug use, patients receiving anticoagulants vs. antiplatelets had significantly higher rates of rebleeding (34.7% vs. 20.5%; P = .043), death (22.2% vs. 10.2%; P = .038), and any event (68.1% vs. 52.3%; P = .043).

After adjustment for gender, age, Charlson index, diabetes, and arterial hypertension, the risk of rebleeding was more than threefold higher for dual antiplatelet and anticoagulant users than for antiplatelet-alone users (odds ratio, 3.45; P = .025) and was twofold higher for anticoagulant vs. antiplatelet users (OR, 2.07; P = .045), Dr. Lanas said.

Finally, an analysis of the cause of bleeding suggests the cause of rebleeding may be different from the original event and that there is a shift toward the lower GI tract, he added.

The index bleeding event was caused largely by an upper GI peptic ulcer in 48% of all 160 patients, with 43.7% of events due to lower GI diverticulosis, vascular lesions, ischemic, or other lesions. In contrast, peptic ulcers accounted for only 7% of rebleeding events, while lower GI events accounted for 72%. Proton pump inhibition use was evenly distributed in upper and lower GI bleeding, although effective endoscopic treatment may have influenced upper GI bleeds, Dr. Lanas said.

“The importance of this is that we may have very good therapy tools for the upper GI, but still we have problems controlling the bleeding from the lower GI,” he added.

During a discussion of the study, an audience member asked how many days clinicians should wait to restart anticoagulants or antiplatelets.

“In those patients with peptic ulcer bleeding, it’s better to just give the antiplatelet therapy soon after the bleeding event or just to not interrupt the aspirin because the morality at 30 days was higher in those who were interrupted,” Dr. Lanas advised. “...I think for the cutoff point to show differences for patients with a worse outcome versus those with a better outcome, you shouldn’t restart anticoagulant therapy before day 15 after the bleeding event.”

Dr. Lanas received consulting fees, speaking and teaching fees, other financial support, and grant and research support from Bayer.

[email protected]

On Twitter @pwendl

WASHINGTON – Early resumption of antiplatelet agents or anticoagulants after a major gastrointestinal bleeding event is clearly associated with an increased risk of rebleeding, but a decreased risk of death, results from an observational study show.

Furthermore, anticoagulant treatment “is associated with a higher risk of rebleeding and death compared with antiplatelet treatment after a previous GI event,” Dr. Angel Lanas said to an overflow crowd at the annual Digestive Disease Week.

Patrice Wendling/Frontline Medical News

In a separate case-control study, Dr. Lanas and his associates recently reported that the risk of GI bleeding was twofold higher for anticoagulants than for low-dose aspirin in patients hospitalized for GI bleeding (Clin. Gastroenterol. Hepatol. 2015 May;13:906-12.e2. [doi:10.1016/j.cgh.2014.11.007])

The current study examined adverse events in a cohort of 160 patients who developed a major gastrointestinal bleed (GIB) while using anticoagulants and/or antiplatelet therapy between March 2008 and July 2013. Long-term interruption or short-term resumption of these treatments has important clinical implications and differences in the intrinsic risks between antiplatelet or anticoagulant users after drug resumption are not well established, said Dr. Lanas of the University of Zaragoza, Spain.

Drug use information was prospectively collected during the GIB event, with data during the follow-up period obtained from two different Spanish databases.

Treatment during the index bleeding event was continued without interruption in 11 patients and interrupted in 149 patients (93%). Among those whose therapy was interrupted, 21 (14%) never resumed therapy and 128 (86%) resumed therapy (118 patients within 15 days and 10 patients after 15 days). The 86% treatment resumption rate is much higher than the 40%-66% rates reported in previous studies, indicating that Spanish physicians restarted treatment quite early, Dr. Lanas observed.

Patrice Wendling/Frontline Medical News

The mean age at baseline was 76.6 years, 61.3% of patients were men, and half had a Charlson index score > 4. Median follow-up was 21.5 months (range 1-63 months).

Ischemic events did not differ between patients who did or did not restart anticoagulants or antiplatelets (16.4% vs. 14.3%; P value = .806). However, rebleeding occurred in 32% of patients who resumed therapy versus none who did not (P = .002), but deaths were higher in those who did not restart therapy (38.1% vs. 12.5%; P = .003), Dr. Lanas said.

These differences remain significant in Kaplan-Meier survival curves for death (P = .021) and rebleeding (P = .004).

A comparison of early therapy resumption (≤ 15 days) vs. delayed (mean delay 62 days) or no resumption revealed similar results. Early resumption was associated with a higher rate of rebleeding (32.2% vs. 9.7%; P = .012), but a lower rate of death (11% vs. 35.5%; P = .001), with no difference in ischemic events (17% vs. 13%; P = .586), Dr. Lanas said.

Again, the differences remain significant in Kaplan-Meier survival curves for death (P = .011) and rebleeding (P = .013).

When the investigators looked at rebleeding according to drug use, patients receiving anticoagulants vs. antiplatelets had significantly higher rates of rebleeding (34.7% vs. 20.5%; P = .043), death (22.2% vs. 10.2%; P = .038), and any event (68.1% vs. 52.3%; P = .043).

After adjustment for gender, age, Charlson index, diabetes, and arterial hypertension, the risk of rebleeding was more than threefold higher for dual antiplatelet and anticoagulant users than for antiplatelet-alone users (odds ratio, 3.45; P = .025) and was twofold higher for anticoagulant vs. antiplatelet users (OR, 2.07; P = .045), Dr. Lanas said.

Finally, an analysis of the cause of bleeding suggests the cause of rebleeding may be different from the original event and that there is a shift toward the lower GI tract, he added.

The index bleeding event was caused largely by an upper GI peptic ulcer in 48% of all 160 patients, with 43.7% of events due to lower GI diverticulosis, vascular lesions, ischemic, or other lesions. In contrast, peptic ulcers accounted for only 7% of rebleeding events, while lower GI events accounted for 72%. Proton pump inhibition use was evenly distributed in upper and lower GI bleeding, although effective endoscopic treatment may have influenced upper GI bleeds, Dr. Lanas said.

“The importance of this is that we may have very good therapy tools for the upper GI, but still we have problems controlling the bleeding from the lower GI,” he added.

During a discussion of the study, an audience member asked how many days clinicians should wait to restart anticoagulants or antiplatelets.

“In those patients with peptic ulcer bleeding, it’s better to just give the antiplatelet therapy soon after the bleeding event or just to not interrupt the aspirin because the morality at 30 days was higher in those who were interrupted,” Dr. Lanas advised. “...I think for the cutoff point to show differences for patients with a worse outcome versus those with a better outcome, you shouldn’t restart anticoagulant therapy before day 15 after the bleeding event.”

Dr. Lanas received consulting fees, speaking and teaching fees, other financial support, and grant and research support from Bayer.

[email protected]

On Twitter @pwendl

Menopausal hormone therapy is associated with an increased risk of major gastrointestinal bleeding, particularly in the lower gastrointestinal tract, that is associated with duration of use, a study has found.

Analysis of data from 73,863 women enrolled in the Nurses’ Health Study II in 1989 showed that current users of menopausal hormone therapy had a 46% increase in the risk of a major gastrointestinal bleed and a more than twofold increase in the risk of a lower GI bleed or ischemic colitis, compared with never users, said Dr. Prashant Singh of Massachusetts General Hospital, Boston.

Past users showed a much smaller increase risk of bleeding, while increasing duration of hormone therapy was significantly associated with increasing risk of major and low gastrointestinal bleeding.

“Although our findings show that menopausal hormone therapy may increase the risk of major GI bleeding, especially in the lower GI tract, it is important for these patients to know that this therapy is still an effective treatment; however, both clinician and patient should be more cautious in using this therapy in some cases, such as with patients who have a history of ischemic colitis,” Dr. Singh said at the annual Digestive Disease Week.

Dr. Singh does not have any relevant financial or other relationship with any manufacturer or provider of commercial products or services that he discussed during the presentation.

Menopausal hormone therapy is associated with an increased risk of major gastrointestinal bleeding, particularly in the lower gastrointestinal tract, that is associated with duration of use, a study has found.

Analysis of data from 73,863 women enrolled in the Nurses’ Health Study II in 1989 showed that current users of menopausal hormone therapy had a 46% increase in the risk of a major gastrointestinal bleed and a more than twofold increase in the risk of a lower GI bleed or ischemic colitis, compared with never users, said Dr. Prashant Singh of Massachusetts General Hospital, Boston.

Past users showed a much smaller increase risk of bleeding, while increasing duration of hormone therapy was significantly associated with increasing risk of major and low gastrointestinal bleeding.

“Although our findings show that menopausal hormone therapy may increase the risk of major GI bleeding, especially in the lower GI tract, it is important for these patients to know that this therapy is still an effective treatment; however, both clinician and patient should be more cautious in using this therapy in some cases, such as with patients who have a history of ischemic colitis,” Dr. Singh said at the annual Digestive Disease Week.

Dr. Singh does not have any relevant financial or other relationship with any manufacturer or provider of commercial products or services that he discussed during the presentation.

Menopausal hormone therapy is associated with an increased risk of major gastrointestinal bleeding, particularly in the lower gastrointestinal tract, that is associated with duration of use, a study has found.

Analysis of data from 73,863 women enrolled in the Nurses’ Health Study II in 1989 showed that current users of menopausal hormone therapy had a 46% increase in the risk of a major gastrointestinal bleed and a more than twofold increase in the risk of a lower GI bleed or ischemic colitis, compared with never users, said Dr. Prashant Singh of Massachusetts General Hospital, Boston.

Past users showed a much smaller increase risk of bleeding, while increasing duration of hormone therapy was significantly associated with increasing risk of major and low gastrointestinal bleeding.

“Although our findings show that menopausal hormone therapy may increase the risk of major GI bleeding, especially in the lower GI tract, it is important for these patients to know that this therapy is still an effective treatment; however, both clinician and patient should be more cautious in using this therapy in some cases, such as with patients who have a history of ischemic colitis,” Dr. Singh said at the annual Digestive Disease Week.

Dr. Singh does not have any relevant financial or other relationship with any manufacturer or provider of commercial products or services that he discussed during the presentation.

SEATTLE – Hospitals that perform at least one nongastric conduit esophageal reconstruction per year have half the esophagectomy mortality of hospitals that do not, according to a review by the Mayo Clinic in Rochester, Minn., of 11,211 esophagectomies in the Nationwide Inpatient Sample database from 2000 to 2011.

“There is tremendous variation in outcome after esophagectomy, and some advocate for regionalization to high-volume hospitals,” the investigators said. The findings suggest that case complexity could be one of the things that help define which hospitals do it best, they added.

The study seems to confirm that hospital case volume makes a difference in surgical outcomes, said Dr. Nabil Rizk, a thoracic surgeon at Memorial Sloan-Kettering Cancer Center in New York.

Dr. Rizk, a discussant on the paper at the American Association for Thoracic Surgery annual meeting, explained how the study fits into regionalization trends, but also shared his concerns about the work in an interview at the meeting.

[email protected]

SEATTLE – Hospitals that perform at least one nongastric conduit esophageal reconstruction per year have half the esophagectomy mortality of hospitals that do not, according to a review by the Mayo Clinic in Rochester, Minn., of 11,211 esophagectomies in the Nationwide Inpatient Sample database from 2000 to 2011.

“There is tremendous variation in outcome after esophagectomy, and some advocate for regionalization to high-volume hospitals,” the investigators said. The findings suggest that case complexity could be one of the things that help define which hospitals do it best, they added.

The study seems to confirm that hospital case volume makes a difference in surgical outcomes, said Dr. Nabil Rizk, a thoracic surgeon at Memorial Sloan-Kettering Cancer Center in New York.

Dr. Rizk, a discussant on the paper at the American Association for Thoracic Surgery annual meeting, explained how the study fits into regionalization trends, but also shared his concerns about the work in an interview at the meeting.

[email protected]

SEATTLE – Hospitals that perform at least one nongastric conduit esophageal reconstruction per year have half the esophagectomy mortality of hospitals that do not, according to a review by the Mayo Clinic in Rochester, Minn., of 11,211 esophagectomies in the Nationwide Inpatient Sample database from 2000 to 2011.

“There is tremendous variation in outcome after esophagectomy, and some advocate for regionalization to high-volume hospitals,” the investigators said. The findings suggest that case complexity could be one of the things that help define which hospitals do it best, they added.

The study seems to confirm that hospital case volume makes a difference in surgical outcomes, said Dr. Nabil Rizk, a thoracic surgeon at Memorial Sloan-Kettering Cancer Center in New York.

Dr. Rizk, a discussant on the paper at the American Association for Thoracic Surgery annual meeting, explained how the study fits into regionalization trends, but also shared his concerns about the work in an interview at the meeting.

[email protected]

pH-impedance testing best predicted response to reflux treatment when patients were off proton pump inhibitors, and abnormal acid exposure time was the single most useful testing parameter, a prospective study has found.

“Impedance-based reflux parameters complement but do not replace acid-based parameters in predicting symptom outcome from both medical and surgical antireflux therapy,” wrote Dr. Amit Patel and his associates at the Washington School of Medicine, St. Louis. The study appears in the May issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2014.08.02).

“Because abnormal acid reflux time and symptom-reflux correlation parameters are detected more often when testing is performed off therapy, pH-impedance testing off antisecretory therapy maximizes prediction of symptomatic outcome from GERD [gastroesophageal reflux disease] therapy,” the researchers wrote.

Clinicians continue to debate the role of pH-impedance testing in management of GERD, whether testing should be performed on or off antisecretory therapy, and which testing parameters are most useful for predicting treatment response, the investigators noted. Therefore, they followed 187 adults with persistent GERD symptoms who underwent pH-impedance testing at their center during a 5-year period. Average age of patients was 54 years, almost 71% were female, and none had histopathologic evidence of esophageal motor disorders. Almost half had been off proton pump inhibitors for 7 days when tested, and 68% were managed medically as opposed to surgically.

Global symptom assessment (GSS) and dominant symptom intensity (DSI) scores both improved significantly during an average of 40 months of follow-up, the researchers said. After the researchers controlled for demographics, symptoms at presentation, use of proton pump inhibitors (PPI), and parameters that predicted treatment response in the univariate analyses, only abnormal acid exposure time (AET) predicted linear improvement in DSI scores (P =.027), while abnormal AET (P =.002) and symptom association probability (P =.026) predicted significant improvements in linear and dichotomous GSS, they reported. Abnormal AET and being off PPIs during testing also more than doubled the odds of at least a 50% improvement in GSS.

In contrast, dichotomous reflux exposure time did not predict response in any of the analyses, said the investigators. “Established thresholds for the total number of reflux events did not predict linear or dichotomous global symptom severity improvement,” they added. “Our data therefore suggest that performing pH-impedance testing off PPI therapy increases the yield of abnormal AET and symptom-reflux association with reflux events, facilitating predicting value for symptom improvement with both medical and surgical antireflux therapy.”

The researchers could not corroborate patients’ compliance with antisecretory therapy, assess the reasons physicians chose medical or surgical management, or evaluate the impact of the placebo effect or other factors unrelated to reflux, they said.

The study was partly funded by the National Institute for Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, and the Washington University Department of Medicine Mentors in Medicine and Clinical Science Training and Research programs. The authors declared no relevant conflicts of interest.

pH-impedance testing best predicted response to reflux treatment when patients were off proton pump inhibitors, and abnormal acid exposure time was the single most useful testing parameter, a prospective study has found.

“Impedance-based reflux parameters complement but do not replace acid-based parameters in predicting symptom outcome from both medical and surgical antireflux therapy,” wrote Dr. Amit Patel and his associates at the Washington School of Medicine, St. Louis. The study appears in the May issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2014.08.02).

“Because abnormal acid reflux time and symptom-reflux correlation parameters are detected more often when testing is performed off therapy, pH-impedance testing off antisecretory therapy maximizes prediction of symptomatic outcome from GERD [gastroesophageal reflux disease] therapy,” the researchers wrote.

Clinicians continue to debate the role of pH-impedance testing in management of GERD, whether testing should be performed on or off antisecretory therapy, and which testing parameters are most useful for predicting treatment response, the investigators noted. Therefore, they followed 187 adults with persistent GERD symptoms who underwent pH-impedance testing at their center during a 5-year period. Average age of patients was 54 years, almost 71% were female, and none had histopathologic evidence of esophageal motor disorders. Almost half had been off proton pump inhibitors for 7 days when tested, and 68% were managed medically as opposed to surgically.

Global symptom assessment (GSS) and dominant symptom intensity (DSI) scores both improved significantly during an average of 40 months of follow-up, the researchers said. After the researchers controlled for demographics, symptoms at presentation, use of proton pump inhibitors (PPI), and parameters that predicted treatment response in the univariate analyses, only abnormal acid exposure time (AET) predicted linear improvement in DSI scores (P =.027), while abnormal AET (P =.002) and symptom association probability (P =.026) predicted significant improvements in linear and dichotomous GSS, they reported. Abnormal AET and being off PPIs during testing also more than doubled the odds of at least a 50% improvement in GSS.

In contrast, dichotomous reflux exposure time did not predict response in any of the analyses, said the investigators. “Established thresholds for the total number of reflux events did not predict linear or dichotomous global symptom severity improvement,” they added. “Our data therefore suggest that performing pH-impedance testing off PPI therapy increases the yield of abnormal AET and symptom-reflux association with reflux events, facilitating predicting value for symptom improvement with both medical and surgical antireflux therapy.”

The researchers could not corroborate patients’ compliance with antisecretory therapy, assess the reasons physicians chose medical or surgical management, or evaluate the impact of the placebo effect or other factors unrelated to reflux, they said.

The study was partly funded by the National Institute for Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, and the Washington University Department of Medicine Mentors in Medicine and Clinical Science Training and Research programs. The authors declared no relevant conflicts of interest.

pH-impedance testing best predicted response to reflux treatment when patients were off proton pump inhibitors, and abnormal acid exposure time was the single most useful testing parameter, a prospective study has found.

“Impedance-based reflux parameters complement but do not replace acid-based parameters in predicting symptom outcome from both medical and surgical antireflux therapy,” wrote Dr. Amit Patel and his associates at the Washington School of Medicine, St. Louis. The study appears in the May issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2014.08.02).

“Because abnormal acid reflux time and symptom-reflux correlation parameters are detected more often when testing is performed off therapy, pH-impedance testing off antisecretory therapy maximizes prediction of symptomatic outcome from GERD [gastroesophageal reflux disease] therapy,” the researchers wrote.

Clinicians continue to debate the role of pH-impedance testing in management of GERD, whether testing should be performed on or off antisecretory therapy, and which testing parameters are most useful for predicting treatment response, the investigators noted. Therefore, they followed 187 adults with persistent GERD symptoms who underwent pH-impedance testing at their center during a 5-year period. Average age of patients was 54 years, almost 71% were female, and none had histopathologic evidence of esophageal motor disorders. Almost half had been off proton pump inhibitors for 7 days when tested, and 68% were managed medically as opposed to surgically.

Global symptom assessment (GSS) and dominant symptom intensity (DSI) scores both improved significantly during an average of 40 months of follow-up, the researchers said. After the researchers controlled for demographics, symptoms at presentation, use of proton pump inhibitors (PPI), and parameters that predicted treatment response in the univariate analyses, only abnormal acid exposure time (AET) predicted linear improvement in DSI scores (P =.027), while abnormal AET (P =.002) and symptom association probability (P =.026) predicted significant improvements in linear and dichotomous GSS, they reported. Abnormal AET and being off PPIs during testing also more than doubled the odds of at least a 50% improvement in GSS.

In contrast, dichotomous reflux exposure time did not predict response in any of the analyses, said the investigators. “Established thresholds for the total number of reflux events did not predict linear or dichotomous global symptom severity improvement,” they added. “Our data therefore suggest that performing pH-impedance testing off PPI therapy increases the yield of abnormal AET and symptom-reflux association with reflux events, facilitating predicting value for symptom improvement with both medical and surgical antireflux therapy.”

The researchers could not corroborate patients’ compliance with antisecretory therapy, assess the reasons physicians chose medical or surgical management, or evaluate the impact of the placebo effect or other factors unrelated to reflux, they said.

The study was partly funded by the National Institute for Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, and the Washington University Department of Medicine Mentors in Medicine and Clinical Science Training and Research programs. The authors declared no relevant conflicts of interest.

High levels of psychological stress more than doubled the odds of peptic ulcers, and the link remained statistically significant even after controlling for factors such as Helicobacter pylori infection and cigarette smoking, according to a prospective study published in the March issue of Clinical Gastroenterology and Hepatology.

The findings contradict the widely accepted view that stress does not cause peptic ulcers, said Dr. Susan Levenstein of Aventino Medical Group in Rome and her associates. “Clinicians treating ulcer patients should investigate potential psychological stress among other risk factors,” they said.

Courtesy Wikimedia Commons/Ed Uthman/Creative Commons

Source: American Gastroenterological Association

Although “a vast literature links peptic ulcer to stress,” past studies suffered so many methodologic weaknesses that groups such as the U.S. National Institute of Diabetes and Digestive and Kidney Diseases rejected the evidence outright, Dr. Levenstein and her associates noted. Many studies were cross-sectional, for example, or did not control for confounders such as helicobacteriosis, they said.

To further study the effects of stress on ulcer risk, the researchers analyzed historical data from 76 patients who lacked a history of gastric and duodenal ulcers in 1982, but by 1994 had developed “distinct breach[es] in the mucosa” that were confirmed by endoscopy or contrast radiology. The researchers did not count erosions that lacked appreciable depth as ulcers, they noted (Clin. Gastroenterol. Hepatol. 2014 Aug. 8 [doi:10.1016/j.cgh.2014.07.052]).

Study subjects answered 12 questions about their stress levels, such as, “Do your hands easily shake?” “Do you often suffer from fits of dizziness?” “Do you constantly have thoughts that trouble and worry you?” and “Do you usually feel misunderstood by other people?” They answered these questions at baseline in 1982-1983, again in 1987-1988, and again in 1993-1994.

Respondents who scored in the top tertile for psychological stress had an ulcer incidence of 3.5%, compared with 1.6% for those in the lowest tertile (odds ratio, 2.2; 95% confidence interval, 1.2-3.9; P < .01), reported the investigators. And controlling for smoking, helicobacteriosis, use of nonsteroidal anti-inflammatory drugs, and low socioeconomic status only partially weakened the relationship between stress and ulcers, they said. After accounting for those risk factors, every one-point increase on the stress questionnaire still upped the odds of peptic ulcer by 12% (odds ratio, 1.12; 95% confidence interval, 1.01-1.23)they reported.

Helicobacteri pylori infection was the strongest independent predictor of ulcers (OR, 3.3; 95% CI, 2.02-5.69), while cigarette smoking came in a close second (OR, 2.91; 95% CI, 1.38-6.16), said the researchers. Notably, stress and helicobacteriosis did not seem to synergistically increase the chances of ulcers, they reported. “Stress affected H. pylori–related ulcers at least as much as those related to neither H. pylori nor nonsteroidal anti-inflammatory drugs,” they said.

Several factors might explain the stress-ulcer link, such as increased acid load, activation of the hypothalamic-pituitary-adrenal axis, shifts in blood flow, and cytokine activation that might impair gastrointestinal mucosal defenses, said the investigators. Although the baseline data in their study were more than 2 decades old, that meant that patients likely had not been treated to eradicate H. pylori and were less likely to have taken proton pump inhibitors than the current population that has over-the-counter access to PPIs, they added. They also noted that past studies found a particularly strong link between stress and bleeding or perforated ulcers, which have not declined as much as other types of ulcers. “These results support a multicausal model of peptic ulcer etiology, with intertwined biological and psychosocial components,” they concluded.

The Kirby Family Foundation funded the statistical analysis. The researchers reported no conflicts of interest.

High levels of psychological stress more than doubled the odds of peptic ulcers, and the link remained statistically significant even after controlling for factors such as Helicobacter pylori infection and cigarette smoking, according to a prospective study published in the March issue of Clinical Gastroenterology and Hepatology.

The findings contradict the widely accepted view that stress does not cause peptic ulcers, said Dr. Susan Levenstein of Aventino Medical Group in Rome and her associates. “Clinicians treating ulcer patients should investigate potential psychological stress among other risk factors,” they said.

Courtesy Wikimedia Commons/Ed Uthman/Creative Commons

Source: American Gastroenterological Association

Although “a vast literature links peptic ulcer to stress,” past studies suffered so many methodologic weaknesses that groups such as the U.S. National Institute of Diabetes and Digestive and Kidney Diseases rejected the evidence outright, Dr. Levenstein and her associates noted. Many studies were cross-sectional, for example, or did not control for confounders such as helicobacteriosis, they said.

To further study the effects of stress on ulcer risk, the researchers analyzed historical data from 76 patients who lacked a history of gastric and duodenal ulcers in 1982, but by 1994 had developed “distinct breach[es] in the mucosa” that were confirmed by endoscopy or contrast radiology. The researchers did not count erosions that lacked appreciable depth as ulcers, they noted (Clin. Gastroenterol. Hepatol. 2014 Aug. 8 [doi:10.1016/j.cgh.2014.07.052]).

Study subjects answered 12 questions about their stress levels, such as, “Do your hands easily shake?” “Do you often suffer from fits of dizziness?” “Do you constantly have thoughts that trouble and worry you?” and “Do you usually feel misunderstood by other people?” They answered these questions at baseline in 1982-1983, again in 1987-1988, and again in 1993-1994.

Respondents who scored in the top tertile for psychological stress had an ulcer incidence of 3.5%, compared with 1.6% for those in the lowest tertile (odds ratio, 2.2; 95% confidence interval, 1.2-3.9; P < .01), reported the investigators. And controlling for smoking, helicobacteriosis, use of nonsteroidal anti-inflammatory drugs, and low socioeconomic status only partially weakened the relationship between stress and ulcers, they said. After accounting for those risk factors, every one-point increase on the stress questionnaire still upped the odds of peptic ulcer by 12% (odds ratio, 1.12; 95% confidence interval, 1.01-1.23)they reported.

Helicobacteri pylori infection was the strongest independent predictor of ulcers (OR, 3.3; 95% CI, 2.02-5.69), while cigarette smoking came in a close second (OR, 2.91; 95% CI, 1.38-6.16), said the researchers. Notably, stress and helicobacteriosis did not seem to synergistically increase the chances of ulcers, they reported. “Stress affected H. pylori–related ulcers at least as much as those related to neither H. pylori nor nonsteroidal anti-inflammatory drugs,” they said.

Several factors might explain the stress-ulcer link, such as increased acid load, activation of the hypothalamic-pituitary-adrenal axis, shifts in blood flow, and cytokine activation that might impair gastrointestinal mucosal defenses, said the investigators. Although the baseline data in their study were more than 2 decades old, that meant that patients likely had not been treated to eradicate H. pylori and were less likely to have taken proton pump inhibitors than the current population that has over-the-counter access to PPIs, they added. They also noted that past studies found a particularly strong link between stress and bleeding or perforated ulcers, which have not declined as much as other types of ulcers. “These results support a multicausal model of peptic ulcer etiology, with intertwined biological and psychosocial components,” they concluded.

The Kirby Family Foundation funded the statistical analysis. The researchers reported no conflicts of interest.

High levels of psychological stress more than doubled the odds of peptic ulcers, and the link remained statistically significant even after controlling for factors such as Helicobacter pylori infection and cigarette smoking, according to a prospective study published in the March issue of Clinical Gastroenterology and Hepatology.

The findings contradict the widely accepted view that stress does not cause peptic ulcers, said Dr. Susan Levenstein of Aventino Medical Group in Rome and her associates. “Clinicians treating ulcer patients should investigate potential psychological stress among other risk factors,” they said.

Courtesy Wikimedia Commons/Ed Uthman/Creative Commons

Source: American Gastroenterological Association

Although “a vast literature links peptic ulcer to stress,” past studies suffered so many methodologic weaknesses that groups such as the U.S. National Institute of Diabetes and Digestive and Kidney Diseases rejected the evidence outright, Dr. Levenstein and her associates noted. Many studies were cross-sectional, for example, or did not control for confounders such as helicobacteriosis, they said.

To further study the effects of stress on ulcer risk, the researchers analyzed historical data from 76 patients who lacked a history of gastric and duodenal ulcers in 1982, but by 1994 had developed “distinct breach[es] in the mucosa” that were confirmed by endoscopy or contrast radiology. The researchers did not count erosions that lacked appreciable depth as ulcers, they noted (Clin. Gastroenterol. Hepatol. 2014 Aug. 8 [doi:10.1016/j.cgh.2014.07.052]).

Study subjects answered 12 questions about their stress levels, such as, “Do your hands easily shake?” “Do you often suffer from fits of dizziness?” “Do you constantly have thoughts that trouble and worry you?” and “Do you usually feel misunderstood by other people?” They answered these questions at baseline in 1982-1983, again in 1987-1988, and again in 1993-1994.

Respondents who scored in the top tertile for psychological stress had an ulcer incidence of 3.5%, compared with 1.6% for those in the lowest tertile (odds ratio, 2.2; 95% confidence interval, 1.2-3.9; P < .01), reported the investigators. And controlling for smoking, helicobacteriosis, use of nonsteroidal anti-inflammatory drugs, and low socioeconomic status only partially weakened the relationship between stress and ulcers, they said. After accounting for those risk factors, every one-point increase on the stress questionnaire still upped the odds of peptic ulcer by 12% (odds ratio, 1.12; 95% confidence interval, 1.01-1.23)they reported.

Helicobacteri pylori infection was the strongest independent predictor of ulcers (OR, 3.3; 95% CI, 2.02-5.69), while cigarette smoking came in a close second (OR, 2.91; 95% CI, 1.38-6.16), said the researchers. Notably, stress and helicobacteriosis did not seem to synergistically increase the chances of ulcers, they reported. “Stress affected H. pylori–related ulcers at least as much as those related to neither H. pylori nor nonsteroidal anti-inflammatory drugs,” they said.

Several factors might explain the stress-ulcer link, such as increased acid load, activation of the hypothalamic-pituitary-adrenal axis, shifts in blood flow, and cytokine activation that might impair gastrointestinal mucosal defenses, said the investigators. Although the baseline data in their study were more than 2 decades old, that meant that patients likely had not been treated to eradicate H. pylori and were less likely to have taken proton pump inhibitors than the current population that has over-the-counter access to PPIs, they added. They also noted that past studies found a particularly strong link between stress and bleeding or perforated ulcers, which have not declined as much as other types of ulcers. “These results support a multicausal model of peptic ulcer etiology, with intertwined biological and psychosocial components,” they concluded.

The Kirby Family Foundation funded the statistical analysis. The researchers reported no conflicts of interest.

An improved version of a neurostimulator device for treating gastroparesis has been approved by the Food and Drug Administration, according to the manufacturer.

In a Jan. 23 press release, Medtronic said that the FDA had approved a new version of the Enterra neurostimulator device, which has been available since 2000. It was approved as a treatment for chronic, intractable (drug refractory) nausea and vomiting associated with gastroparesis related to diabetes or of idiopathic etiology in patients aged 18-70 years, under a Humanitarian Device Exemption.

The programmable device – a battery-powered neurostimulator implanted under the skin in the lower abdominal region – “uses mild electrical pulses to stimulate the antrum portion of the stomach muscle wall,” which “may reduce the symptoms of nausea and the number of vomiting episodes related to gastroparesis,” according to the Medtronic website. The improvements of the new version – the Enterra II system – include new programming software and an indicator that alerts the clinician and patient when the device needs to be replaced; the battery lasts from 5 to 10 years. In addition, it does not have a magnetic activation switch, so it is more compatible with electromagnetic interference, according to the website.

A humanitarian use device “is a device that is intended to benefit patients by treating or diagnosing a disease or condition that affects or is manifested in fewer than 4,000 individuals in the United States per year,” according to the FDA. For approval, the company submits a humanitarian device exemption application, which does not require submission of effectiveness data, but “must contain sufficient information for the FDA to determine that the device does not pose an unreasonable or significant risk of illness or injury, and that the probable benefit to health outweighs the risk of injury or illness from its use, taking into account the probable risks and benefits of currently available devices or alternative forms of treatment.”

The Medtronic release points out that use of the gastric electrical stimulation therapy at a medical center requires approval from the center’s Institutional Review Board.

[email protected]

An improved version of a neurostimulator device for treating gastroparesis has been approved by the Food and Drug Administration, according to the manufacturer.

In a Jan. 23 press release, Medtronic said that the FDA had approved a new version of the Enterra neurostimulator device, which has been available since 2000. It was approved as a treatment for chronic, intractable (drug refractory) nausea and vomiting associated with gastroparesis related to diabetes or of idiopathic etiology in patients aged 18-70 years, under a Humanitarian Device Exemption.

The programmable device – a battery-powered neurostimulator implanted under the skin in the lower abdominal region – “uses mild electrical pulses to stimulate the antrum portion of the stomach muscle wall,” which “may reduce the symptoms of nausea and the number of vomiting episodes related to gastroparesis,” according to the Medtronic website. The improvements of the new version – the Enterra II system – include new programming software and an indicator that alerts the clinician and patient when the device needs to be replaced; the battery lasts from 5 to 10 years. In addition, it does not have a magnetic activation switch, so it is more compatible with electromagnetic interference, according to the website.

A humanitarian use device “is a device that is intended to benefit patients by treating or diagnosing a disease or condition that affects or is manifested in fewer than 4,000 individuals in the United States per year,” according to the FDA. For approval, the company submits a humanitarian device exemption application, which does not require submission of effectiveness data, but “must contain sufficient information for the FDA to determine that the device does not pose an unreasonable or significant risk of illness or injury, and that the probable benefit to health outweighs the risk of injury or illness from its use, taking into account the probable risks and benefits of currently available devices or alternative forms of treatment.”

The Medtronic release points out that use of the gastric electrical stimulation therapy at a medical center requires approval from the center’s Institutional Review Board.

[email protected]

An improved version of a neurostimulator device for treating gastroparesis has been approved by the Food and Drug Administration, according to the manufacturer.

In a Jan. 23 press release, Medtronic said that the FDA had approved a new version of the Enterra neurostimulator device, which has been available since 2000. It was approved as a treatment for chronic, intractable (drug refractory) nausea and vomiting associated with gastroparesis related to diabetes or of idiopathic etiology in patients aged 18-70 years, under a Humanitarian Device Exemption.

The programmable device – a battery-powered neurostimulator implanted under the skin in the lower abdominal region – “uses mild electrical pulses to stimulate the antrum portion of the stomach muscle wall,” which “may reduce the symptoms of nausea and the number of vomiting episodes related to gastroparesis,” according to the Medtronic website. The improvements of the new version – the Enterra II system – include new programming software and an indicator that alerts the clinician and patient when the device needs to be replaced; the battery lasts from 5 to 10 years. In addition, it does not have a magnetic activation switch, so it is more compatible with electromagnetic interference, according to the website.

A humanitarian use device “is a device that is intended to benefit patients by treating or diagnosing a disease or condition that affects or is manifested in fewer than 4,000 individuals in the United States per year,” according to the FDA. For approval, the company submits a humanitarian device exemption application, which does not require submission of effectiveness data, but “must contain sufficient information for the FDA to determine that the device does not pose an unreasonable or significant risk of illness or injury, and that the probable benefit to health outweighs the risk of injury or illness from its use, taking into account the probable risks and benefits of currently available devices or alternative forms of treatment.”

The Medtronic release points out that use of the gastric electrical stimulation therapy at a medical center requires approval from the center’s Institutional Review Board.

[email protected]

Transoral esophagogastric fundoplication can be an effective treatment for patients seeking to alleviate symptoms associated with gastroesophageal reflux disease, particularly in individuals with persistent regurgitation despite prior treatment with proton pump inhibitor therapy, according to the results of a new study published in the February issue of Gastroenterology (doi:10.1053/j.gastro.2014.10.009).

“Gastroesophageal reflux disease (GERD) remains one of the most common conditions for which Americans take daily medication, and PPI use has more than doubled in the last decade,” wrote lead authors Dr. John G. Hunter of Oregon Health & Science University in Portland, and Dr. Peter J. Kahrilas of Northwestern University in Chicago, and their associates. “Despite this, up to 40% of proton pump inhibitor (PPI)–dependent GERD patients have troublesome symptoms of GERD, despite PPI therapy.”

In the Randomized EsophyX vs Sham, Placebo-Controlled Transoral Fundoplication (RESPECT) trial, investigators screened 696 patients who were experiencing “troublesome regurgitation” despite daily PPI treatment. These subjects were evaluated via three validated GERD-specific symptom scales, and were either on or off PPI use at the time of trial commencement. Post trial, patients were blinded to therapy and were reassessed at intervals of 2, 12, and 26 weeks. All patients underwent 48-hour esophageal pH monitoring and esophagogastroduodenoscopy at 66 months after the trial ended.

© nebari/Thinkstock

Regurgitation severity was based on the Montreal definition, which was used to measure efficacy of treatments given as part of the study. The Montreal definition of reflux is described by the authors as “either mucosal damage or troublesome symptoms attributable to reflux.” Those with “least troublesome” regurgitation while on PPIs “underwent barium swallow, esophagogastroduodenoscopy, 48-hour esophageal pH monitoring (off PPIs), and high-resolution esophageal manometry analyses.”

Eighty-seven subjects with GERD and hiatal hernias of at least 2 centimeters were randomly assigned to groups that underwent transoral fundoplication (TF) followed by placebo treatment after 6 months, while 42 subjects, who made up the control group, underwent a “sham surgery” and began regimens of once- or twice-daily omeprazole medication for 6 months.

Results showed that 67% of patients who received TF treatment experienced elimination of adverse regurgitation vs. 45% of those treated with PPI (P = .023). Control of esophageal pH also improved noticeably in patients who received TF treatment versus those who did not (9.3% vs. 6.3% on average, respectively, P < .001), but not in patients who received the “sham surgery” (8.6% preop vs. 8.9% postop on average). Fewer patients who received TF treatment recorded having “no response” after 3 months compared with those in the control group (11% vs. 36%, respectively, P = .004).

“Transoral fundoplication may fill the ‘therapeutic gap’ that exists between PPI and laparoscopic fundoplication,” wrote the authors. “Considering the virtual absence of dysphagia and bloating after TF, which may be problematic with LINX [LINX Reflux Management System], it would appear that TF is an option for patients with troublesome regurgitation, as well as for patients with troublesome GERD symptoms who wish not to take PPI over a protracted period of time.”

Several coauthors disclosed ties with the study sponsor EndoGastric Solutions of Redmond, Wash., as well as individual potential conflicts of interest.

[email protected]

Transoral esophagogastric fundoplication can be an effective treatment for patients seeking to alleviate symptoms associated with gastroesophageal reflux disease, particularly in individuals with persistent regurgitation despite prior treatment with proton pump inhibitor therapy, according to the results of a new study published in the February issue of Gastroenterology (doi:10.1053/j.gastro.2014.10.009).

“Gastroesophageal reflux disease (GERD) remains one of the most common conditions for which Americans take daily medication, and PPI use has more than doubled in the last decade,” wrote lead authors Dr. John G. Hunter of Oregon Health & Science University in Portland, and Dr. Peter J. Kahrilas of Northwestern University in Chicago, and their associates. “Despite this, up to 40% of proton pump inhibitor (PPI)–dependent GERD patients have troublesome symptoms of GERD, despite PPI therapy.”

In the Randomized EsophyX vs Sham, Placebo-Controlled Transoral Fundoplication (RESPECT) trial, investigators screened 696 patients who were experiencing “troublesome regurgitation” despite daily PPI treatment. These subjects were evaluated via three validated GERD-specific symptom scales, and were either on or off PPI use at the time of trial commencement. Post trial, patients were blinded to therapy and were reassessed at intervals of 2, 12, and 26 weeks. All patients underwent 48-hour esophageal pH monitoring and esophagogastroduodenoscopy at 66 months after the trial ended.

© nebari/Thinkstock

Regurgitation severity was based on the Montreal definition, which was used to measure efficacy of treatments given as part of the study. The Montreal definition of reflux is described by the authors as “either mucosal damage or troublesome symptoms attributable to reflux.” Those with “least troublesome” regurgitation while on PPIs “underwent barium swallow, esophagogastroduodenoscopy, 48-hour esophageal pH monitoring (off PPIs), and high-resolution esophageal manometry analyses.”

Eighty-seven subjects with GERD and hiatal hernias of at least 2 centimeters were randomly assigned to groups that underwent transoral fundoplication (TF) followed by placebo treatment after 6 months, while 42 subjects, who made up the control group, underwent a “sham surgery” and began regimens of once- or twice-daily omeprazole medication for 6 months.

Results showed that 67% of patients who received TF treatment experienced elimination of adverse regurgitation vs. 45% of those treated with PPI (P = .023). Control of esophageal pH also improved noticeably in patients who received TF treatment versus those who did not (9.3% vs. 6.3% on average, respectively, P < .001), but not in patients who received the “sham surgery” (8.6% preop vs. 8.9% postop on average). Fewer patients who received TF treatment recorded having “no response” after 3 months compared with those in the control group (11% vs. 36%, respectively, P = .004).

“Transoral fundoplication may fill the ‘therapeutic gap’ that exists between PPI and laparoscopic fundoplication,” wrote the authors. “Considering the virtual absence of dysphagia and bloating after TF, which may be problematic with LINX [LINX Reflux Management System], it would appear that TF is an option for patients with troublesome regurgitation, as well as for patients with troublesome GERD symptoms who wish not to take PPI over a protracted period of time.”

Several coauthors disclosed ties with the study sponsor EndoGastric Solutions of Redmond, Wash., as well as individual potential conflicts of interest.

[email protected]

Transoral esophagogastric fundoplication can be an effective treatment for patients seeking to alleviate symptoms associated with gastroesophageal reflux disease, particularly in individuals with persistent regurgitation despite prior treatment with proton pump inhibitor therapy, according to the results of a new study published in the February issue of Gastroenterology (doi:10.1053/j.gastro.2014.10.009).

“Gastroesophageal reflux disease (GERD) remains one of the most common conditions for which Americans take daily medication, and PPI use has more than doubled in the last decade,” wrote lead authors Dr. John G. Hunter of Oregon Health & Science University in Portland, and Dr. Peter J. Kahrilas of Northwestern University in Chicago, and their associates. “Despite this, up to 40% of proton pump inhibitor (PPI)–dependent GERD patients have troublesome symptoms of GERD, despite PPI therapy.”

In the Randomized EsophyX vs Sham, Placebo-Controlled Transoral Fundoplication (RESPECT) trial, investigators screened 696 patients who were experiencing “troublesome regurgitation” despite daily PPI treatment. These subjects were evaluated via three validated GERD-specific symptom scales, and were either on or off PPI use at the time of trial commencement. Post trial, patients were blinded to therapy and were reassessed at intervals of 2, 12, and 26 weeks. All patients underwent 48-hour esophageal pH monitoring and esophagogastroduodenoscopy at 66 months after the trial ended.

© nebari/Thinkstock

Regurgitation severity was based on the Montreal definition, which was used to measure efficacy of treatments given as part of the study. The Montreal definition of reflux is described by the authors as “either mucosal damage or troublesome symptoms attributable to reflux.” Those with “least troublesome” regurgitation while on PPIs “underwent barium swallow, esophagogastroduodenoscopy, 48-hour esophageal pH monitoring (off PPIs), and high-resolution esophageal manometry analyses.”

Eighty-seven subjects with GERD and hiatal hernias of at least 2 centimeters were randomly assigned to groups that underwent transoral fundoplication (TF) followed by placebo treatment after 6 months, while 42 subjects, who made up the control group, underwent a “sham surgery” and began regimens of once- or twice-daily omeprazole medication for 6 months.

Results showed that 67% of patients who received TF treatment experienced elimination of adverse regurgitation vs. 45% of those treated with PPI (P = .023). Control of esophageal pH also improved noticeably in patients who received TF treatment versus those who did not (9.3% vs. 6.3% on average, respectively, P < .001), but not in patients who received the “sham surgery” (8.6% preop vs. 8.9% postop on average). Fewer patients who received TF treatment recorded having “no response” after 3 months compared with those in the control group (11% vs. 36%, respectively, P = .004).

“Transoral fundoplication may fill the ‘therapeutic gap’ that exists between PPI and laparoscopic fundoplication,” wrote the authors. “Considering the virtual absence of dysphagia and bloating after TF, which may be problematic with LINX [LINX Reflux Management System], it would appear that TF is an option for patients with troublesome regurgitation, as well as for patients with troublesome GERD symptoms who wish not to take PPI over a protracted period of time.”

Several coauthors disclosed ties with the study sponsor EndoGastric Solutions of Redmond, Wash., as well as individual potential conflicts of interest.

[email protected]

Topical steroid therapy improved some indicators of mucosal integrity in patients with eosinophilic esophagitis, but proton pump inhibitor therapy did not, according to two studies reported in the November issue of Clinical Gastroenterology and Hepatology.

The first study found that topical fluticasone therapy at a dose of 880 mcg twice daily for 2 months helped correct esophageal spongiosis, or dilated intercellular space, in patients with eosinophilic esophagitis (EoE). Spongiosis scores for treated patients were significantly lower than for untreated patients (0.4 vs. 1.3; P = .016), said Dr. David Katzka at the Mayo Clinic in Rochester, Minn. and his associates (Clin. Gastroenterol. Hepatol. 2014 [doi:10.1016/j.cgh.2014.02.039]).

In the study, histologic analyses also showed that improved spongiosis scores in treated patients correlated with increased density of two tight junction proteins, filaggrin (P = .001) and zonula occludens-3 (P = .016), said the investigators. These proteins might help regulate antigenic penetration of the esophageal mucosa and also could permit migration of white blood cells, they said. “Loss of tight junction regulators and dilation of intercellular spaces appear to be involved in the pathophysiology of EoE and could be targets for treatment,” the researchers concluded. But they also noted that their study did not examine the same patients before and after steroid therapy and did not look at desmosomes, intercellular junctions that past research has suggested might be affected in EoE.

For the second study, Dr. Bram van Rhijn and his associates at the Academic Medical Center in the Netherlands compared endoscopies of 16 patients with dysphagia and suspected (unconfirmed) EoE with 11 controls, both at baseline and after 8 weeks of high-dose esomeprazole treatment. Esophageal mucosal integrity was “severely impaired” in patients with confirmed EoE and in those with proton pump inhibitor–responsive eosinophilia (PPRE), the researchers said (Clin. Gasteroenterol. Hepatol. 2014 [doi:10.1016/j.cgh.2014.02.037]).

In both forms of disease, molecules as large as 40,000 daltons were able to pass through the compromised esophageal mucosa, Dr. Bram van Rhijn and his associates reported. “This size is similar to the size of most plant and animal food allergens to which EoE patients are sensitized,” they added. Esophageal permeability might increase the rate of immune exposure to allergens, thereby mediating EoE and PPRE, they said.

On mucosal functional tests, both EoE and PPRE were associated with reduced transepithelial electrical resistance and lower electrical tissue impedance, most notably in patients with EoE (P less than .001 for both, compared with controls), the investigators reported. Proton pump inhibitor treatment partially reversed these changes in patients with PPRE but showed no effect for patients with EoE, they said. This finding suggests that acid reflux might play a role in PPRE, but not in EOE, they concluded.

Dr. Katzka and his associates disclosed no funding sources and reported having no conflicts of interest. Dr. Rhijn and his associates were supported by the Netherlands Organization for Scientific Research. Two of Dr. Rhijn’s coauthors reported financial relationships with AstraZeneca, Endostim, Medical Measurement Systems, Shire, and GlaxoSmithKline.

Topical steroid therapy improved some indicators of mucosal integrity in patients with eosinophilic esophagitis, but proton pump inhibitor therapy did not, according to two studies reported in the November issue of Clinical Gastroenterology and Hepatology.

The first study found that topical fluticasone therapy at a dose of 880 mcg twice daily for 2 months helped correct esophageal spongiosis, or dilated intercellular space, in patients with eosinophilic esophagitis (EoE). Spongiosis scores for treated patients were significantly lower than for untreated patients (0.4 vs. 1.3; P = .016), said Dr. David Katzka at the Mayo Clinic in Rochester, Minn. and his associates (Clin. Gastroenterol. Hepatol. 2014 [doi:10.1016/j.cgh.2014.02.039]).

In the study, histologic analyses also showed that improved spongiosis scores in treated patients correlated with increased density of two tight junction proteins, filaggrin (P = .001) and zonula occludens-3 (P = .016), said the investigators. These proteins might help regulate antigenic penetration of the esophageal mucosa and also could permit migration of white blood cells, they said. “Loss of tight junction regulators and dilation of intercellular spaces appear to be involved in the pathophysiology of EoE and could be targets for treatment,” the researchers concluded. But they also noted that their study did not examine the same patients before and after steroid therapy and did not look at desmosomes, intercellular junctions that past research has suggested might be affected in EoE.

For the second study, Dr. Bram van Rhijn and his associates at the Academic Medical Center in the Netherlands compared endoscopies of 16 patients with dysphagia and suspected (unconfirmed) EoE with 11 controls, both at baseline and after 8 weeks of high-dose esomeprazole treatment. Esophageal mucosal integrity was “severely impaired” in patients with confirmed EoE and in those with proton pump inhibitor–responsive eosinophilia (PPRE), the researchers said (Clin. Gasteroenterol. Hepatol. 2014 [doi:10.1016/j.cgh.2014.02.037]).

In both forms of disease, molecules as large as 40,000 daltons were able to pass through the compromised esophageal mucosa, Dr. Bram van Rhijn and his associates reported. “This size is similar to the size of most plant and animal food allergens to which EoE patients are sensitized,” they added. Esophageal permeability might increase the rate of immune exposure to allergens, thereby mediating EoE and PPRE, they said.

On mucosal functional tests, both EoE and PPRE were associated with reduced transepithelial electrical resistance and lower electrical tissue impedance, most notably in patients with EoE (P less than .001 for both, compared with controls), the investigators reported. Proton pump inhibitor treatment partially reversed these changes in patients with PPRE but showed no effect for patients with EoE, they said. This finding suggests that acid reflux might play a role in PPRE, but not in EOE, they concluded.

Dr. Katzka and his associates disclosed no funding sources and reported having no conflicts of interest. Dr. Rhijn and his associates were supported by the Netherlands Organization for Scientific Research. Two of Dr. Rhijn’s coauthors reported financial relationships with AstraZeneca, Endostim, Medical Measurement Systems, Shire, and GlaxoSmithKline.

Topical steroid therapy improved some indicators of mucosal integrity in patients with eosinophilic esophagitis, but proton pump inhibitor therapy did not, according to two studies reported in the November issue of Clinical Gastroenterology and Hepatology.

The first study found that topical fluticasone therapy at a dose of 880 mcg twice daily for 2 months helped correct esophageal spongiosis, or dilated intercellular space, in patients with eosinophilic esophagitis (EoE). Spongiosis scores for treated patients were significantly lower than for untreated patients (0.4 vs. 1.3; P = .016), said Dr. David Katzka at the Mayo Clinic in Rochester, Minn. and his associates (Clin. Gastroenterol. Hepatol. 2014 [doi:10.1016/j.cgh.2014.02.039]).

In the study, histologic analyses also showed that improved spongiosis scores in treated patients correlated with increased density of two tight junction proteins, filaggrin (P = .001) and zonula occludens-3 (P = .016), said the investigators. These proteins might help regulate antigenic penetration of the esophageal mucosa and also could permit migration of white blood cells, they said. “Loss of tight junction regulators and dilation of intercellular spaces appear to be involved in the pathophysiology of EoE and could be targets for treatment,” the researchers concluded. But they also noted that their study did not examine the same patients before and after steroid therapy and did not look at desmosomes, intercellular junctions that past research has suggested might be affected in EoE.

For the second study, Dr. Bram van Rhijn and his associates at the Academic Medical Center in the Netherlands compared endoscopies of 16 patients with dysphagia and suspected (unconfirmed) EoE with 11 controls, both at baseline and after 8 weeks of high-dose esomeprazole treatment. Esophageal mucosal integrity was “severely impaired” in patients with confirmed EoE and in those with proton pump inhibitor–responsive eosinophilia (PPRE), the researchers said (Clin. Gasteroenterol. Hepatol. 2014 [doi:10.1016/j.cgh.2014.02.037]).

In both forms of disease, molecules as large as 40,000 daltons were able to pass through the compromised esophageal mucosa, Dr. Bram van Rhijn and his associates reported. “This size is similar to the size of most plant and animal food allergens to which EoE patients are sensitized,” they added. Esophageal permeability might increase the rate of immune exposure to allergens, thereby mediating EoE and PPRE, they said.

On mucosal functional tests, both EoE and PPRE were associated with reduced transepithelial electrical resistance and lower electrical tissue impedance, most notably in patients with EoE (P less than .001 for both, compared with controls), the investigators reported. Proton pump inhibitor treatment partially reversed these changes in patients with PPRE but showed no effect for patients with EoE, they said. This finding suggests that acid reflux might play a role in PPRE, but not in EOE, they concluded.

Dr. Katzka and his associates disclosed no funding sources and reported having no conflicts of interest. Dr. Rhijn and his associates were supported by the Netherlands Organization for Scientific Research. Two of Dr. Rhijn’s coauthors reported financial relationships with AstraZeneca, Endostim, Medical Measurement Systems, Shire, and GlaxoSmithKline.

Combining nonsteroidal anti-inflammatory drugs with selective serotonin reuptake inhibitors increased the risk of upper gastrointestinal bleeding by up to 190% beyond the baseline risk found for NSAID monotherapy, researchers reported in the October issue of Gastroenterology.

Patients also faced excess risks of upper GI bleeding when they took corticosteroids, aldosterone antagonists, or anticoagulants together with low-dose aspirin or nonselective NSAIDs, although the effect was not seen for COX-2 inhibitors, said Dr. Gwen Masclee at Erasmus Medical Center in Rotterdam, the Netherlands and her associates.

© khuntapol / ThinkStockPhotos.com

Source: American Gastroenterological Association

The findings should help clinicians tailor treatments to minimize chances of upper gastrointestinal bleeding, particularly for elderly patients who often take multiple drugs, the investigators said (Gastroenterology 2014 [doi:10.1053/j.gastro.2014.06.007]).

The researchers analyzed 114,835 cases of upper gastrointestinal bleeding, including all gastroduodenal ulcers and hemorrhages extracted from seven electronic health record databases from the Netherlands, Italy, and Denmark. Three databases included primary care data, and four were administrative claims data, the investigators said. Cases served as their own controls, they noted.

Monotherapy with prescription nonselective NSAIDs increased the chances of an upper gastrointestinal bleed by 4.3 times, compared with not using any of the drugs studied (95% confidence interval, 4.1-4.4), the researchers said. Notably, bleeding risk from taking either nonselective NSAIDs or corticosteroids was the same, they said, adding that previous studies have yielded inconsistent findings on the topic. The incidence ratios for monotherapy with low-dose aspirin and COX-2 inhibitors were slightly lower at 3.1 (95% CI, 2.9-3.2) and 2.9 (95% CI, 2.7-3.2), respectively, they added.

Combining nonselective NSAIDs, COX-2 inhibitors, or low-dose aspirin with SSRIs led to excess risks of upper gastrointestinal bleeding of 1.6 (95% CI, 0.5-2.6), 1.9 (95% CI, 0.2-3.4), and 0.49 (–0.05-1.03), respectively, the researchers reported. "From a biological point of view, this interaction seems plausible because SSRIs decrease the serotonin level, resulting in impaired thrombocyte aggregation and an increased risk of bleeding in general," they said.

Corticosteroids combined with nonselective NSAIDs led to the greatest increases in bleeding risk, with an incidence ratio of 12.8 (95% CI, 11.1-14.7), compared with nonuse of any drug studied, and an excess risk of 5.5 (3.7-7.3), compared with NSAID use alone, said the researchers. Adding aldosterone antagonists to nonselective NSAIDs led to an excess risk of 4.46, compared with using nonselective NSAIDs alone, they reported (95% CI, 1.79-7.13).

Because the study did not capture over-the-counter NSAID prescriptions, it could have underestimated use of these drugs, the investigators said. Also, changes in health or NSAID use during the study could have created residual confounding, although sensitivity analyses did not reveal problems, they reported. They added that misclassification of some data could have led them to underestimate risks. "Finally, we did not take any carryover effect or dose of drug exposure into account, which potentially limits the generalizability concerning causality of the associations," they concluded.

Five authors reported employment or other financial support from Erasmus University Medical Center, AstraZeneca, Janssen, PHARMO Institute, and the European Medicines Agency. The other authors reported no relevant conflicts of interests.

Combining nonsteroidal anti-inflammatory drugs with selective serotonin reuptake inhibitors increased the risk of upper gastrointestinal bleeding by up to 190% beyond the baseline risk found for NSAID monotherapy, researchers reported in the October issue of Gastroenterology.

Patients also faced excess risks of upper GI bleeding when they took corticosteroids, aldosterone antagonists, or anticoagulants together with low-dose aspirin or nonselective NSAIDs, although the effect was not seen for COX-2 inhibitors, said Dr. Gwen Masclee at Erasmus Medical Center in Rotterdam, the Netherlands and her associates.

© khuntapol / ThinkStockPhotos.com

Source: American Gastroenterological Association

The findings should help clinicians tailor treatments to minimize chances of upper gastrointestinal bleeding, particularly for elderly patients who often take multiple drugs, the investigators said (Gastroenterology 2014 [doi:10.1053/j.gastro.2014.06.007]).

The researchers analyzed 114,835 cases of upper gastrointestinal bleeding, including all gastroduodenal ulcers and hemorrhages extracted from seven electronic health record databases from the Netherlands, Italy, and Denmark. Three databases included primary care data, and four were administrative claims data, the investigators said. Cases served as their own controls, they noted.

Monotherapy with prescription nonselective NSAIDs increased the chances of an upper gastrointestinal bleed by 4.3 times, compared with not using any of the drugs studied (95% confidence interval, 4.1-4.4), the researchers said. Notably, bleeding risk from taking either nonselective NSAIDs or corticosteroids was the same, they said, adding that previous studies have yielded inconsistent findings on the topic. The incidence ratios for monotherapy with low-dose aspirin and COX-2 inhibitors were slightly lower at 3.1 (95% CI, 2.9-3.2) and 2.9 (95% CI, 2.7-3.2), respectively, they added.

Combining nonselective NSAIDs, COX-2 inhibitors, or low-dose aspirin with SSRIs led to excess risks of upper gastrointestinal bleeding of 1.6 (95% CI, 0.5-2.6), 1.9 (95% CI, 0.2-3.4), and 0.49 (–0.05-1.03), respectively, the researchers reported. "From a biological point of view, this interaction seems plausible because SSRIs decrease the serotonin level, resulting in impaired thrombocyte aggregation and an increased risk of bleeding in general," they said.

Corticosteroids combined with nonselective NSAIDs led to the greatest increases in bleeding risk, with an incidence ratio of 12.8 (95% CI, 11.1-14.7), compared with nonuse of any drug studied, and an excess risk of 5.5 (3.7-7.3), compared with NSAID use alone, said the researchers. Adding aldosterone antagonists to nonselective NSAIDs led to an excess risk of 4.46, compared with using nonselective NSAIDs alone, they reported (95% CI, 1.79-7.13).

Because the study did not capture over-the-counter NSAID prescriptions, it could have underestimated use of these drugs, the investigators said. Also, changes in health or NSAID use during the study could have created residual confounding, although sensitivity analyses did not reveal problems, they reported. They added that misclassification of some data could have led them to underestimate risks. "Finally, we did not take any carryover effect or dose of drug exposure into account, which potentially limits the generalizability concerning causality of the associations," they concluded.

Five authors reported employment or other financial support from Erasmus University Medical Center, AstraZeneca, Janssen, PHARMO Institute, and the European Medicines Agency. The other authors reported no relevant conflicts of interests.

Combining nonsteroidal anti-inflammatory drugs with selective serotonin reuptake inhibitors increased the risk of upper gastrointestinal bleeding by up to 190% beyond the baseline risk found for NSAID monotherapy, researchers reported in the October issue of Gastroenterology.

Patients also faced excess risks of upper GI bleeding when they took corticosteroids, aldosterone antagonists, or anticoagulants together with low-dose aspirin or nonselective NSAIDs, although the effect was not seen for COX-2 inhibitors, said Dr. Gwen Masclee at Erasmus Medical Center in Rotterdam, the Netherlands and her associates.

© khuntapol / ThinkStockPhotos.com

Source: American Gastroenterological Association

The findings should help clinicians tailor treatments to minimize chances of upper gastrointestinal bleeding, particularly for elderly patients who often take multiple drugs, the investigators said (Gastroenterology 2014 [doi:10.1053/j.gastro.2014.06.007]).

The researchers analyzed 114,835 cases of upper gastrointestinal bleeding, including all gastroduodenal ulcers and hemorrhages extracted from seven electronic health record databases from the Netherlands, Italy, and Denmark. Three databases included primary care data, and four were administrative claims data, the investigators said. Cases served as their own controls, they noted.

Monotherapy with prescription nonselective NSAIDs increased the chances of an upper gastrointestinal bleed by 4.3 times, compared with not using any of the drugs studied (95% confidence interval, 4.1-4.4), the researchers said. Notably, bleeding risk from taking either nonselective NSAIDs or corticosteroids was the same, they said, adding that previous studies have yielded inconsistent findings on the topic. The incidence ratios for monotherapy with low-dose aspirin and COX-2 inhibitors were slightly lower at 3.1 (95% CI, 2.9-3.2) and 2.9 (95% CI, 2.7-3.2), respectively, they added.

Combining nonselective NSAIDs, COX-2 inhibitors, or low-dose aspirin with SSRIs led to excess risks of upper gastrointestinal bleeding of 1.6 (95% CI, 0.5-2.6), 1.9 (95% CI, 0.2-3.4), and 0.49 (–0.05-1.03), respectively, the researchers reported. "From a biological point of view, this interaction seems plausible because SSRIs decrease the serotonin level, resulting in impaired thrombocyte aggregation and an increased risk of bleeding in general," they said.

Corticosteroids combined with nonselective NSAIDs led to the greatest increases in bleeding risk, with an incidence ratio of 12.8 (95% CI, 11.1-14.7), compared with nonuse of any drug studied, and an excess risk of 5.5 (3.7-7.3), compared with NSAID use alone, said the researchers. Adding aldosterone antagonists to nonselective NSAIDs led to an excess risk of 4.46, compared with using nonselective NSAIDs alone, they reported (95% CI, 1.79-7.13).

Because the study did not capture over-the-counter NSAID prescriptions, it could have underestimated use of these drugs, the investigators said. Also, changes in health or NSAID use during the study could have created residual confounding, although sensitivity analyses did not reveal problems, they reported. They added that misclassification of some data could have led them to underestimate risks. "Finally, we did not take any carryover effect or dose of drug exposure into account, which potentially limits the generalizability concerning causality of the associations," they concluded.

Five authors reported employment or other financial support from Erasmus University Medical Center, AstraZeneca, Janssen, PHARMO Institute, and the European Medicines Agency. The other authors reported no relevant conflicts of interests.