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Updated systematic review of aspirin primary prevention shows benefits, risks
Using daily aspirin treatment for the primary prevention of cardiovascular events remains an individualized decision that needs to balance a person’s risks for ischemic events and bleeding, according to results from a new systematic review of 15 randomized, aspirin-prevention trials, including results from 3 major trials that researchers reported during 2018.
“The findings suggest that the decision to use aspirin for primary prevention should be tailored to the individual patients based on estimated atherosclerotic cardiovascular disease risk and perceived bleeding risk, as well as patient preferences regarding the types of event prevented versus potential bleeding caused,” Jawahar L. Mehta, MD, and his associates wrote in an article published on June 10 in the Journal of the American College of Cardiology.
The authors also concluded that if a person decides to use aspirin for primary prevention, then a low dose of 100 mg/day or less is recommended.
This new systematic review follows two reviews published earlier in 2019 that reached roughly similar conclusions after analyzing largely the same randomized trial data, including the same three major trials from 2018. One of these prior reviews included data from 13 trials and a total of 164,225 people (JAMA. 2019 Jan 22;321[3]:277-87). The second review had data from 11 trials with 157,248 people (Eur Heart J. 2019 Feb 14;40[7]:607-17). The newly published review used data collected by 15 trials from 165,502 people.
The three 2018 trials that triggered the updated data assessments were the ARRIVE trial, with 12,546 people randomized (Lancet. 2018 Sep 22;392[10152]:1036-46), the ASPREE trial, with 19,114 people randomized (New Engl J Med. 2018 Oct 18;379[16]:1509-18), and the ASCEND trial, with 15,480 people randomized (New Engl J Med. 2018 Oct 18;379[16]:1529-39).
As stated in the new report from Dr. Mehta, a professor of medicine at the University of Arkansas for Medical Sciences in Little Rock, and his associates, the recent trial results from 2018 added new data from more than 45,000 additional subjects, a development that warranted a reappraisal of the evidence for aspirin’s efficacy and safety for primary prevention in contemporary practice.
The major findings from the analysis by Dr. Mehta and his associates were that in adults without a history of cardiovascular disease, daily aspirin use reduced the incidence of MIs, with a number needed to treat (NNT) of 357; reduced ischemic stroke (NNT, 500), reduced transient ischemic attack (NNT, 370), and reduced the overall, combined rate of all major adverse cardiovascular events (NNT, 263). But on the safety side, daily aspirin led to an increased rate of major bleeding episodes, with a number needed to harm (NNH) of 222, increased intracranial bleeds (NNH, 1,000), and an increase in gastrointestinal bleeds (NNH, 385).
The analysis “demonstrates a potential reduction of net benefit with aspirin in the contemporary era,” the authors concluded. They also noted that the benefits from aspirin prevention were, as expected, “more pronounced” among people with a higher estimated risk from atherosclerotic cardiovascular disease.
The systematic review findings came against the backdrop of a recently released primary prevention guideline from the American College of Cardiology and American Heart Association (J Am Coll Card. 2019 Mar. doi: 10.1016/j.jacc.2019.03.010). The guideline said that aspirin prophylaxis for primary prevention “might be considered” for adults aged 40-70 years, but should not be used for people who are older than 70, and also should not be given to people with an increased risk for bleeding. In general, the experts who produced this guideline said that aspirin prophylaxis should be infrequent.
The new analysis also found no reduction in the incidence of cancer or cancer-related death linked with aspirin use for primary prevention. The systematic review published earlier in 2019 in JAMA also found no link between aspirin use and cancer incidence or mortality. The review from the European Heart Journal did not report on the link between aspirin use and cancer incidence or mortality.
Dr. Mehta has been a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Medimmune, and Pfizer, and has received grant support from AstraZeneca, Bayer, and Boehringer Ingelheim.
On Twitter @mitchelzoler
SOURCE: Abdelaziz HK et al. J Am Coll Cardiol. 2019 Jun 10. doi: 10.1016/j.jacc.2019.03.501.
The three trials published in 2018 that added important new data on primary prevention for cardiovascular disease with aspirin must ideally be interpreted within the context of the totality of evidence on this subject. This was achieved in the analysis reported by Dr. Mehta and his associates, as well as in other more recent publications.
Making a decision about using aspirin for primary prevention in individuals based on trial data is very challenging because it requires weighing a modest potential benefit that people gain from daily aspirin for preventing a first cardiovascular event against the modest risk of an adverse bleeding event. It does not suffice simply to compare the number of cardiovascular and bleeding events, because those two types of events do not have the same immediate or long-term consequences. Each patient must make a personal choice between the risks and benefits.
The greatest potential benefit from aspirin prophylaxis seems to be in people with increased cardiovascular risk but with no increased bleeding risk. In general, this means people aged 50-59 years old, and also possibly those aged 60-69 years old if their estimated 10-year cardiovascular disease risk is more than 10%. It may make more sense to first focus on other risk-reducing steps, such as smoking cessation, blood pressure control, and statin treatment. After that, prophylactic aspirin may be reasonable for people who retain a 10-year cardiovascular disease risk of more than 10% who are also not at increased bleeding risk. That seems to make it prudent to avoid aspirin for primary prevention once people reach the age of 70 years, although people who have been taking aspirin safely for a period of time before reaching 70 might reasonably consider continuing the prophylaxis for a period of time.
This and similar reviews continue to have major limitations. The duration of the trials they reviewed, a mean of 6.4 years, is insufficient to understand the full effect from aspirin prophylaxis. Also, none of the recent reviews used a patient-level meta-analysis, which could better help us understand aspirin’s action in key subgroups, such as women, patients with diabetes, and patients on treatments such as statins that reduce their cardiovascular risk.
Michael Pignone, MD, is professor and chair of medicine at the University of Texas Dell Medical School in Austin. He had no disclosures. He made these comments in an editorial that accompanied the report (J Am Coll Cardiol. 2019 Jun 10. doi: 10.1016/j.jacc.2019.03.502).
The three trials published in 2018 that added important new data on primary prevention for cardiovascular disease with aspirin must ideally be interpreted within the context of the totality of evidence on this subject. This was achieved in the analysis reported by Dr. Mehta and his associates, as well as in other more recent publications.
Making a decision about using aspirin for primary prevention in individuals based on trial data is very challenging because it requires weighing a modest potential benefit that people gain from daily aspirin for preventing a first cardiovascular event against the modest risk of an adverse bleeding event. It does not suffice simply to compare the number of cardiovascular and bleeding events, because those two types of events do not have the same immediate or long-term consequences. Each patient must make a personal choice between the risks and benefits.
The greatest potential benefit from aspirin prophylaxis seems to be in people with increased cardiovascular risk but with no increased bleeding risk. In general, this means people aged 50-59 years old, and also possibly those aged 60-69 years old if their estimated 10-year cardiovascular disease risk is more than 10%. It may make more sense to first focus on other risk-reducing steps, such as smoking cessation, blood pressure control, and statin treatment. After that, prophylactic aspirin may be reasonable for people who retain a 10-year cardiovascular disease risk of more than 10% who are also not at increased bleeding risk. That seems to make it prudent to avoid aspirin for primary prevention once people reach the age of 70 years, although people who have been taking aspirin safely for a period of time before reaching 70 might reasonably consider continuing the prophylaxis for a period of time.
This and similar reviews continue to have major limitations. The duration of the trials they reviewed, a mean of 6.4 years, is insufficient to understand the full effect from aspirin prophylaxis. Also, none of the recent reviews used a patient-level meta-analysis, which could better help us understand aspirin’s action in key subgroups, such as women, patients with diabetes, and patients on treatments such as statins that reduce their cardiovascular risk.
Michael Pignone, MD, is professor and chair of medicine at the University of Texas Dell Medical School in Austin. He had no disclosures. He made these comments in an editorial that accompanied the report (J Am Coll Cardiol. 2019 Jun 10. doi: 10.1016/j.jacc.2019.03.502).
The three trials published in 2018 that added important new data on primary prevention for cardiovascular disease with aspirin must ideally be interpreted within the context of the totality of evidence on this subject. This was achieved in the analysis reported by Dr. Mehta and his associates, as well as in other more recent publications.
Making a decision about using aspirin for primary prevention in individuals based on trial data is very challenging because it requires weighing a modest potential benefit that people gain from daily aspirin for preventing a first cardiovascular event against the modest risk of an adverse bleeding event. It does not suffice simply to compare the number of cardiovascular and bleeding events, because those two types of events do not have the same immediate or long-term consequences. Each patient must make a personal choice between the risks and benefits.
The greatest potential benefit from aspirin prophylaxis seems to be in people with increased cardiovascular risk but with no increased bleeding risk. In general, this means people aged 50-59 years old, and also possibly those aged 60-69 years old if their estimated 10-year cardiovascular disease risk is more than 10%. It may make more sense to first focus on other risk-reducing steps, such as smoking cessation, blood pressure control, and statin treatment. After that, prophylactic aspirin may be reasonable for people who retain a 10-year cardiovascular disease risk of more than 10% who are also not at increased bleeding risk. That seems to make it prudent to avoid aspirin for primary prevention once people reach the age of 70 years, although people who have been taking aspirin safely for a period of time before reaching 70 might reasonably consider continuing the prophylaxis for a period of time.
This and similar reviews continue to have major limitations. The duration of the trials they reviewed, a mean of 6.4 years, is insufficient to understand the full effect from aspirin prophylaxis. Also, none of the recent reviews used a patient-level meta-analysis, which could better help us understand aspirin’s action in key subgroups, such as women, patients with diabetes, and patients on treatments such as statins that reduce their cardiovascular risk.
Michael Pignone, MD, is professor and chair of medicine at the University of Texas Dell Medical School in Austin. He had no disclosures. He made these comments in an editorial that accompanied the report (J Am Coll Cardiol. 2019 Jun 10. doi: 10.1016/j.jacc.2019.03.502).
Using daily aspirin treatment for the primary prevention of cardiovascular events remains an individualized decision that needs to balance a person’s risks for ischemic events and bleeding, according to results from a new systematic review of 15 randomized, aspirin-prevention trials, including results from 3 major trials that researchers reported during 2018.
“The findings suggest that the decision to use aspirin for primary prevention should be tailored to the individual patients based on estimated atherosclerotic cardiovascular disease risk and perceived bleeding risk, as well as patient preferences regarding the types of event prevented versus potential bleeding caused,” Jawahar L. Mehta, MD, and his associates wrote in an article published on June 10 in the Journal of the American College of Cardiology.
The authors also concluded that if a person decides to use aspirin for primary prevention, then a low dose of 100 mg/day or less is recommended.
This new systematic review follows two reviews published earlier in 2019 that reached roughly similar conclusions after analyzing largely the same randomized trial data, including the same three major trials from 2018. One of these prior reviews included data from 13 trials and a total of 164,225 people (JAMA. 2019 Jan 22;321[3]:277-87). The second review had data from 11 trials with 157,248 people (Eur Heart J. 2019 Feb 14;40[7]:607-17). The newly published review used data collected by 15 trials from 165,502 people.
The three 2018 trials that triggered the updated data assessments were the ARRIVE trial, with 12,546 people randomized (Lancet. 2018 Sep 22;392[10152]:1036-46), the ASPREE trial, with 19,114 people randomized (New Engl J Med. 2018 Oct 18;379[16]:1509-18), and the ASCEND trial, with 15,480 people randomized (New Engl J Med. 2018 Oct 18;379[16]:1529-39).
As stated in the new report from Dr. Mehta, a professor of medicine at the University of Arkansas for Medical Sciences in Little Rock, and his associates, the recent trial results from 2018 added new data from more than 45,000 additional subjects, a development that warranted a reappraisal of the evidence for aspirin’s efficacy and safety for primary prevention in contemporary practice.
The major findings from the analysis by Dr. Mehta and his associates were that in adults without a history of cardiovascular disease, daily aspirin use reduced the incidence of MIs, with a number needed to treat (NNT) of 357; reduced ischemic stroke (NNT, 500), reduced transient ischemic attack (NNT, 370), and reduced the overall, combined rate of all major adverse cardiovascular events (NNT, 263). But on the safety side, daily aspirin led to an increased rate of major bleeding episodes, with a number needed to harm (NNH) of 222, increased intracranial bleeds (NNH, 1,000), and an increase in gastrointestinal bleeds (NNH, 385).
The analysis “demonstrates a potential reduction of net benefit with aspirin in the contemporary era,” the authors concluded. They also noted that the benefits from aspirin prevention were, as expected, “more pronounced” among people with a higher estimated risk from atherosclerotic cardiovascular disease.
The systematic review findings came against the backdrop of a recently released primary prevention guideline from the American College of Cardiology and American Heart Association (J Am Coll Card. 2019 Mar. doi: 10.1016/j.jacc.2019.03.010). The guideline said that aspirin prophylaxis for primary prevention “might be considered” for adults aged 40-70 years, but should not be used for people who are older than 70, and also should not be given to people with an increased risk for bleeding. In general, the experts who produced this guideline said that aspirin prophylaxis should be infrequent.
The new analysis also found no reduction in the incidence of cancer or cancer-related death linked with aspirin use for primary prevention. The systematic review published earlier in 2019 in JAMA also found no link between aspirin use and cancer incidence or mortality. The review from the European Heart Journal did not report on the link between aspirin use and cancer incidence or mortality.
Dr. Mehta has been a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Medimmune, and Pfizer, and has received grant support from AstraZeneca, Bayer, and Boehringer Ingelheim.
On Twitter @mitchelzoler
SOURCE: Abdelaziz HK et al. J Am Coll Cardiol. 2019 Jun 10. doi: 10.1016/j.jacc.2019.03.501.
Using daily aspirin treatment for the primary prevention of cardiovascular events remains an individualized decision that needs to balance a person’s risks for ischemic events and bleeding, according to results from a new systematic review of 15 randomized, aspirin-prevention trials, including results from 3 major trials that researchers reported during 2018.
“The findings suggest that the decision to use aspirin for primary prevention should be tailored to the individual patients based on estimated atherosclerotic cardiovascular disease risk and perceived bleeding risk, as well as patient preferences regarding the types of event prevented versus potential bleeding caused,” Jawahar L. Mehta, MD, and his associates wrote in an article published on June 10 in the Journal of the American College of Cardiology.
The authors also concluded that if a person decides to use aspirin for primary prevention, then a low dose of 100 mg/day or less is recommended.
This new systematic review follows two reviews published earlier in 2019 that reached roughly similar conclusions after analyzing largely the same randomized trial data, including the same three major trials from 2018. One of these prior reviews included data from 13 trials and a total of 164,225 people (JAMA. 2019 Jan 22;321[3]:277-87). The second review had data from 11 trials with 157,248 people (Eur Heart J. 2019 Feb 14;40[7]:607-17). The newly published review used data collected by 15 trials from 165,502 people.
The three 2018 trials that triggered the updated data assessments were the ARRIVE trial, with 12,546 people randomized (Lancet. 2018 Sep 22;392[10152]:1036-46), the ASPREE trial, with 19,114 people randomized (New Engl J Med. 2018 Oct 18;379[16]:1509-18), and the ASCEND trial, with 15,480 people randomized (New Engl J Med. 2018 Oct 18;379[16]:1529-39).
As stated in the new report from Dr. Mehta, a professor of medicine at the University of Arkansas for Medical Sciences in Little Rock, and his associates, the recent trial results from 2018 added new data from more than 45,000 additional subjects, a development that warranted a reappraisal of the evidence for aspirin’s efficacy and safety for primary prevention in contemporary practice.
The major findings from the analysis by Dr. Mehta and his associates were that in adults without a history of cardiovascular disease, daily aspirin use reduced the incidence of MIs, with a number needed to treat (NNT) of 357; reduced ischemic stroke (NNT, 500), reduced transient ischemic attack (NNT, 370), and reduced the overall, combined rate of all major adverse cardiovascular events (NNT, 263). But on the safety side, daily aspirin led to an increased rate of major bleeding episodes, with a number needed to harm (NNH) of 222, increased intracranial bleeds (NNH, 1,000), and an increase in gastrointestinal bleeds (NNH, 385).
The analysis “demonstrates a potential reduction of net benefit with aspirin in the contemporary era,” the authors concluded. They also noted that the benefits from aspirin prevention were, as expected, “more pronounced” among people with a higher estimated risk from atherosclerotic cardiovascular disease.
The systematic review findings came against the backdrop of a recently released primary prevention guideline from the American College of Cardiology and American Heart Association (J Am Coll Card. 2019 Mar. doi: 10.1016/j.jacc.2019.03.010). The guideline said that aspirin prophylaxis for primary prevention “might be considered” for adults aged 40-70 years, but should not be used for people who are older than 70, and also should not be given to people with an increased risk for bleeding. In general, the experts who produced this guideline said that aspirin prophylaxis should be infrequent.
The new analysis also found no reduction in the incidence of cancer or cancer-related death linked with aspirin use for primary prevention. The systematic review published earlier in 2019 in JAMA also found no link between aspirin use and cancer incidence or mortality. The review from the European Heart Journal did not report on the link between aspirin use and cancer incidence or mortality.
Dr. Mehta has been a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Medimmune, and Pfizer, and has received grant support from AstraZeneca, Bayer, and Boehringer Ingelheim.
On Twitter @mitchelzoler
SOURCE: Abdelaziz HK et al. J Am Coll Cardiol. 2019 Jun 10. doi: 10.1016/j.jacc.2019.03.501.
FROM JACC
Key clinical point: Cumulative trial results continue to show that aspirin primary prevention cuts CVD events while boosting major bleeds.
Major finding: Aspirin prophylaxis cut cardiovascular events with an NNT of 263, but increased major bleeds with an NNH of 222.
Study details: Systematic review of data from 165,502 people enrolled in 15 randomized trials.
Disclosures: Dr. Mehta has been a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Medimmune, and Pfizer, and has received grant support from AstraZeneca, Bayer, and Boehringer Ingelheim.
Source: Abdelaziz HK et al. J Am Coll Cardiol. 2019 Jun 10. doi: 10.1016/j.jacc.2019.03.501.
Novel molecular panel found to aid in eosinophilic gastritis diagnosis
SAN DIEGO – A new scoring system based on a set of 18 informative genes was sufficient to diagnose cases of eosinophilic gastritis, results from a molecular analysis showed.
The system, known as EG diagnostic panel 18 (EGDP18), “can provide clinicians with a better diagnostic classification of ambiguous cases of eosinophilic gastritis, indicating a strong correlation with disease severity,” lead study author Tetsuo Shoda, MD, PhD, said at the annual Digestive Disease Week®.“The EG molecular profile also strongly correlates with particular endoscopic and histological features, thus providing insight into pathogenesis for EG.”
In an effort to develop an EG diagnostic panel, to validate its utility for EG diagnosis and management, and to better understand disease pathogenesis, Dr. Shoda and his colleagues used RNA sequencing to generate genome-wide gene expression profiles from gastric biopsies. Next, they developed an EG diagnostic panel focusing on a set of 48 informative genes, and analyzed its performance in a discovery cohort (55 EG and 39 controls) and subsequently an independent validation cohort (67 EG and 27 controls). The EGDP score was calculated by summation of delta CT values of the most highly dysregulated 18 genes. For diagnosis, the researchers calculated the area under the receiver operating characteristic curve (AUC), and used Spearman correlation to analyze associations.
Dr. Shoda, a research fellow at Cincinnati Children’s Hospital Medical Center, reported that the EGDP18 score identified active EG patients in both cohorts (P less than .0001, AUC equal to or greater than 0.95). In the discovery cohort, a score of less than zero resulted in a sensitivity of 95.2%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 95.8%. In the validation cohort, a score of less than zero resulted in a sensitivity of 88.9%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 94.1%.
The researchers observed a significant inverse correlation between the EGDP18 score and gastric eosinophil counts cross-sectionally and longitudinally. The score also showed comparable levels and high correlation between the gastric antrum and body. In addition, when analyzed by EGDP18 score, 63% of ambiguous tissue eosinophils were found to be molecularly equivalent to active EG, “suggesting the capacity to offer an objective cutoff for EG diagnosis,” Dr. Shoda said.
The researchers reported having no financial disclosures.
SOURCE: Shoda T et al. DDW 2019, Abstract 165. doi: 10.1016/S0016-5085(19)36878-7.
SAN DIEGO – A new scoring system based on a set of 18 informative genes was sufficient to diagnose cases of eosinophilic gastritis, results from a molecular analysis showed.
The system, known as EG diagnostic panel 18 (EGDP18), “can provide clinicians with a better diagnostic classification of ambiguous cases of eosinophilic gastritis, indicating a strong correlation with disease severity,” lead study author Tetsuo Shoda, MD, PhD, said at the annual Digestive Disease Week®.“The EG molecular profile also strongly correlates with particular endoscopic and histological features, thus providing insight into pathogenesis for EG.”
In an effort to develop an EG diagnostic panel, to validate its utility for EG diagnosis and management, and to better understand disease pathogenesis, Dr. Shoda and his colleagues used RNA sequencing to generate genome-wide gene expression profiles from gastric biopsies. Next, they developed an EG diagnostic panel focusing on a set of 48 informative genes, and analyzed its performance in a discovery cohort (55 EG and 39 controls) and subsequently an independent validation cohort (67 EG and 27 controls). The EGDP score was calculated by summation of delta CT values of the most highly dysregulated 18 genes. For diagnosis, the researchers calculated the area under the receiver operating characteristic curve (AUC), and used Spearman correlation to analyze associations.
Dr. Shoda, a research fellow at Cincinnati Children’s Hospital Medical Center, reported that the EGDP18 score identified active EG patients in both cohorts (P less than .0001, AUC equal to or greater than 0.95). In the discovery cohort, a score of less than zero resulted in a sensitivity of 95.2%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 95.8%. In the validation cohort, a score of less than zero resulted in a sensitivity of 88.9%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 94.1%.
The researchers observed a significant inverse correlation between the EGDP18 score and gastric eosinophil counts cross-sectionally and longitudinally. The score also showed comparable levels and high correlation between the gastric antrum and body. In addition, when analyzed by EGDP18 score, 63% of ambiguous tissue eosinophils were found to be molecularly equivalent to active EG, “suggesting the capacity to offer an objective cutoff for EG diagnosis,” Dr. Shoda said.
The researchers reported having no financial disclosures.
SOURCE: Shoda T et al. DDW 2019, Abstract 165. doi: 10.1016/S0016-5085(19)36878-7.
SAN DIEGO – A new scoring system based on a set of 18 informative genes was sufficient to diagnose cases of eosinophilic gastritis, results from a molecular analysis showed.
The system, known as EG diagnostic panel 18 (EGDP18), “can provide clinicians with a better diagnostic classification of ambiguous cases of eosinophilic gastritis, indicating a strong correlation with disease severity,” lead study author Tetsuo Shoda, MD, PhD, said at the annual Digestive Disease Week®.“The EG molecular profile also strongly correlates with particular endoscopic and histological features, thus providing insight into pathogenesis for EG.”
In an effort to develop an EG diagnostic panel, to validate its utility for EG diagnosis and management, and to better understand disease pathogenesis, Dr. Shoda and his colleagues used RNA sequencing to generate genome-wide gene expression profiles from gastric biopsies. Next, they developed an EG diagnostic panel focusing on a set of 48 informative genes, and analyzed its performance in a discovery cohort (55 EG and 39 controls) and subsequently an independent validation cohort (67 EG and 27 controls). The EGDP score was calculated by summation of delta CT values of the most highly dysregulated 18 genes. For diagnosis, the researchers calculated the area under the receiver operating characteristic curve (AUC), and used Spearman correlation to analyze associations.
Dr. Shoda, a research fellow at Cincinnati Children’s Hospital Medical Center, reported that the EGDP18 score identified active EG patients in both cohorts (P less than .0001, AUC equal to or greater than 0.95). In the discovery cohort, a score of less than zero resulted in a sensitivity of 95.2%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 95.8%. In the validation cohort, a score of less than zero resulted in a sensitivity of 88.9%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 94.1%.
The researchers observed a significant inverse correlation between the EGDP18 score and gastric eosinophil counts cross-sectionally and longitudinally. The score also showed comparable levels and high correlation between the gastric antrum and body. In addition, when analyzed by EGDP18 score, 63% of ambiguous tissue eosinophils were found to be molecularly equivalent to active EG, “suggesting the capacity to offer an objective cutoff for EG diagnosis,” Dr. Shoda said.
The researchers reported having no financial disclosures.
SOURCE: Shoda T et al. DDW 2019, Abstract 165. doi: 10.1016/S0016-5085(19)36878-7.
REPORTING FROM DDW 2019
Coffee, tea, and soda all up GERD risk
SAN DIEGO – .
In an interview following the oral presentation, Raaj S. Mehta, MD, said that patients in his primary care panel at Massachusetts General Hospital, Boston, where he’s a senior resident, frequently came to him with GERD. In addition to questions about diet, patients frequently wanted to know which beverages might provoke or exacerbate their GERD.
In trying to help his patients, Dr. Mehta said he realized that there wasn’t a prospective evidence base to answer their questions about beverages and GERD, so he and his colleagues used data from the Nurses’ Health Study II (NHS II), a prospective cohort study, to look at the association between various beverages and the incidence of GERD.
“What’s exciting is that we were able to find that coffee, tea, and soda – all three – increase your risk for gastroesophageal reflux disease,” Dr. Mehta said in a video interview. “At the highest quintile level, so looking at people who consume six or more cups per day, you’re looking at maybe a 25%-35% increase in risk of reflux disease.”
There was a dose-response relationship as well: “You do see a slight increase as you go from one cup, to two, to three, and so on, all the way up to six cups” of the offending beverages, said Dr. Mehta.
Overall, the risk for GERD rose from 1.17 to 1.34 with coffee consumption as servings per day increased from less than one to six or more (P for trend less than .0001). Tea consumption was associated with increased GERD risk ranging from 1.08 to 1.26 as consumption rose (P for trend .001). For soda, the increased risk went from 1.12 at less than one serving daily, to 1.41 at four to five servings daily, and then fell to 1.29 at six or more daily servings (P for trend less than .0001).
Whether the beverages were caffeinated or not, said Dr. Mehta, only made a “minimal difference” in GERD risk.
“In contrast, we didn’t see an association for beverages like water, juice, and milk,” he said – reassuring findings in light of fruit juice’s anecdotal status as a GERD culprit.
The NHS II collected data every 2 years from 48,308 female nurses aged 42-62 years at the beginning of the study. Every 4 years dietary information was collected, and on the opposite 4-year cycle, participants answered questions about GERD. Medication use, including the incident use of proton pump inhibitors, was collected every 2 years.
Patients with baseline GERD or use of PPIs or H2 receptor antagonists were excluded from participation.
The quantity and type of beverages were assessed by food frequency questionnaires; other demographic, dietary, and medication variables were also gathered and used to adjust the statistical analysis.
A substitution analysis answered the “what-if” question of the effect of substituting two glasses of plain water daily for either coffee, tea, or soda. Dr. Mehta and colleagues saw a modest reduction in risk for GERD with this strategy.
In addition to the prospective nature of the study (abstract 514, doi: 10.1016/S0016-5085(19)37044-1), the large sample size, high follow-up rates, and well validated dietary data were all strengths, said Dr. Mehta. However, the study’s population is relatively homogeneous, and residual confounding couldn’t be excluded. Also, GERD was defined by self-report, though participants were asked to respond to clear, validated criteria.
For Dr. Mehta, he’s glad to have a clear answer to a common clinic question. “I think that this is one additional thing that I can recommend as a primary care provider to my patients when they come into my office,” he said.
Dr. Mehta reported no conflicts of interest.
Encourage your patients to visit the AGA GI Patient Center for education by specialists for patients about GERD symptoms and treatments at https://www.gastro.org/practice-guidance/gi-patient-center/topic/gastroesophageal-reflux-disease-gerd.
SAN DIEGO – .
In an interview following the oral presentation, Raaj S. Mehta, MD, said that patients in his primary care panel at Massachusetts General Hospital, Boston, where he’s a senior resident, frequently came to him with GERD. In addition to questions about diet, patients frequently wanted to know which beverages might provoke or exacerbate their GERD.
In trying to help his patients, Dr. Mehta said he realized that there wasn’t a prospective evidence base to answer their questions about beverages and GERD, so he and his colleagues used data from the Nurses’ Health Study II (NHS II), a prospective cohort study, to look at the association between various beverages and the incidence of GERD.
“What’s exciting is that we were able to find that coffee, tea, and soda – all three – increase your risk for gastroesophageal reflux disease,” Dr. Mehta said in a video interview. “At the highest quintile level, so looking at people who consume six or more cups per day, you’re looking at maybe a 25%-35% increase in risk of reflux disease.”
There was a dose-response relationship as well: “You do see a slight increase as you go from one cup, to two, to three, and so on, all the way up to six cups” of the offending beverages, said Dr. Mehta.
Overall, the risk for GERD rose from 1.17 to 1.34 with coffee consumption as servings per day increased from less than one to six or more (P for trend less than .0001). Tea consumption was associated with increased GERD risk ranging from 1.08 to 1.26 as consumption rose (P for trend .001). For soda, the increased risk went from 1.12 at less than one serving daily, to 1.41 at four to five servings daily, and then fell to 1.29 at six or more daily servings (P for trend less than .0001).
Whether the beverages were caffeinated or not, said Dr. Mehta, only made a “minimal difference” in GERD risk.
“In contrast, we didn’t see an association for beverages like water, juice, and milk,” he said – reassuring findings in light of fruit juice’s anecdotal status as a GERD culprit.
The NHS II collected data every 2 years from 48,308 female nurses aged 42-62 years at the beginning of the study. Every 4 years dietary information was collected, and on the opposite 4-year cycle, participants answered questions about GERD. Medication use, including the incident use of proton pump inhibitors, was collected every 2 years.
Patients with baseline GERD or use of PPIs or H2 receptor antagonists were excluded from participation.
The quantity and type of beverages were assessed by food frequency questionnaires; other demographic, dietary, and medication variables were also gathered and used to adjust the statistical analysis.
A substitution analysis answered the “what-if” question of the effect of substituting two glasses of plain water daily for either coffee, tea, or soda. Dr. Mehta and colleagues saw a modest reduction in risk for GERD with this strategy.
In addition to the prospective nature of the study (abstract 514, doi: 10.1016/S0016-5085(19)37044-1), the large sample size, high follow-up rates, and well validated dietary data were all strengths, said Dr. Mehta. However, the study’s population is relatively homogeneous, and residual confounding couldn’t be excluded. Also, GERD was defined by self-report, though participants were asked to respond to clear, validated criteria.
For Dr. Mehta, he’s glad to have a clear answer to a common clinic question. “I think that this is one additional thing that I can recommend as a primary care provider to my patients when they come into my office,” he said.
Dr. Mehta reported no conflicts of interest.
Encourage your patients to visit the AGA GI Patient Center for education by specialists for patients about GERD symptoms and treatments at https://www.gastro.org/practice-guidance/gi-patient-center/topic/gastroesophageal-reflux-disease-gerd.
SAN DIEGO – .
In an interview following the oral presentation, Raaj S. Mehta, MD, said that patients in his primary care panel at Massachusetts General Hospital, Boston, where he’s a senior resident, frequently came to him with GERD. In addition to questions about diet, patients frequently wanted to know which beverages might provoke or exacerbate their GERD.
In trying to help his patients, Dr. Mehta said he realized that there wasn’t a prospective evidence base to answer their questions about beverages and GERD, so he and his colleagues used data from the Nurses’ Health Study II (NHS II), a prospective cohort study, to look at the association between various beverages and the incidence of GERD.
“What’s exciting is that we were able to find that coffee, tea, and soda – all three – increase your risk for gastroesophageal reflux disease,” Dr. Mehta said in a video interview. “At the highest quintile level, so looking at people who consume six or more cups per day, you’re looking at maybe a 25%-35% increase in risk of reflux disease.”
There was a dose-response relationship as well: “You do see a slight increase as you go from one cup, to two, to three, and so on, all the way up to six cups” of the offending beverages, said Dr. Mehta.
Overall, the risk for GERD rose from 1.17 to 1.34 with coffee consumption as servings per day increased from less than one to six or more (P for trend less than .0001). Tea consumption was associated with increased GERD risk ranging from 1.08 to 1.26 as consumption rose (P for trend .001). For soda, the increased risk went from 1.12 at less than one serving daily, to 1.41 at four to five servings daily, and then fell to 1.29 at six or more daily servings (P for trend less than .0001).
Whether the beverages were caffeinated or not, said Dr. Mehta, only made a “minimal difference” in GERD risk.
“In contrast, we didn’t see an association for beverages like water, juice, and milk,” he said – reassuring findings in light of fruit juice’s anecdotal status as a GERD culprit.
The NHS II collected data every 2 years from 48,308 female nurses aged 42-62 years at the beginning of the study. Every 4 years dietary information was collected, and on the opposite 4-year cycle, participants answered questions about GERD. Medication use, including the incident use of proton pump inhibitors, was collected every 2 years.
Patients with baseline GERD or use of PPIs or H2 receptor antagonists were excluded from participation.
The quantity and type of beverages were assessed by food frequency questionnaires; other demographic, dietary, and medication variables were also gathered and used to adjust the statistical analysis.
A substitution analysis answered the “what-if” question of the effect of substituting two glasses of plain water daily for either coffee, tea, or soda. Dr. Mehta and colleagues saw a modest reduction in risk for GERD with this strategy.
In addition to the prospective nature of the study (abstract 514, doi: 10.1016/S0016-5085(19)37044-1), the large sample size, high follow-up rates, and well validated dietary data were all strengths, said Dr. Mehta. However, the study’s population is relatively homogeneous, and residual confounding couldn’t be excluded. Also, GERD was defined by self-report, though participants were asked to respond to clear, validated criteria.
For Dr. Mehta, he’s glad to have a clear answer to a common clinic question. “I think that this is one additional thing that I can recommend as a primary care provider to my patients when they come into my office,” he said.
Dr. Mehta reported no conflicts of interest.
Encourage your patients to visit the AGA GI Patient Center for education by specialists for patients about GERD symptoms and treatments at https://www.gastro.org/practice-guidance/gi-patient-center/topic/gastroesophageal-reflux-disease-gerd.
REPORTING FROM DDW 2019
Meta-analysis finds no link between PPI use and risk of dementia
The finding runs counter to recent studies, including a large pharmacoepidemiological claims data analysis from Germany, that propose an association between proton pump inhibitor (PPI) use and the development of dementia (JAMA Neurol. 2016;73[4]:410-6). “The issue with these studies is that they’re based on retrospective claims data and pharmacoepidemiological studies and insurance databases that don’t really give you a good causality basis,” lead study author Saad Alrajhi, MD, said in an interview at the annual Digestive Disease Week.
In an effort to better characterize the association between PPI exposure and dementia, Dr. Alrajhi, a gastroenterology fellow at McGill University, Montreal, and colleagues conducted a meta-analysis of all fully published randomized clinical trials or observational studies comparing use of PPIs and occurrence of dementia. The researchers queried Embase, MEDLINE, and ISI Web of Knowledge for relevant studies that were published from 1995 through September 2018. Next, they assessed the quality of the studies by using the Cochrane risk assessment tool for RCTs or the Newcastle-Ottawa Scale for observational studies.
As the primary outcome, the researchers compared dementia incidence after PPI exposure (experimental group) versus no PPI exposure (control group). Development of Alzheimer’s dementia was a secondary outcome. Sensitivity analyses consisted of excluding one study at a time, and assessing results among studies of highest qualities. Subgroup analyses included stratifying patients by age. To report odds ratios, Dr. Alrajhi and colleagues used fixed or random effects models based on the absence or presence of heterogeneity.
Of 549 studies assessed, 5 met the criteria for inclusion in the final analysis: 3 case-control studies and 2 cohort studies, with a total of 472,933 patients. All of the studies scored 8 or 9 on the Newcastle-Ottawa scale, indicating high quality. Significant heterogeneity was noted for all analyses. The researchers found that the incidence of dementia was not significantly increased among patients in the PPI-exposed group (odd ratio, 1.08 (95% confidence interval, 0.97-1.20; P = .18). Sensitivity analyses confirmed the robustness of the results. Subgroup analysis showed no between-group differences among studies that included a minimum age above 65 years (three studies) or less than age 65 (two studies). PPI exposure was not associated with the development of Alzheimer’s dementia (two studies) (OR, 1.32 (95% CI, 0.80-2.17; P = .27).
“In the absence of randomized trial evidence, a PPI prescribing approach based on appropriate utilization of guideline-based prescription should be done without the extra fear of the association of dementia,” Dr. Alrajhi said.
The researchers reported having no financial disclosures.
The finding runs counter to recent studies, including a large pharmacoepidemiological claims data analysis from Germany, that propose an association between proton pump inhibitor (PPI) use and the development of dementia (JAMA Neurol. 2016;73[4]:410-6). “The issue with these studies is that they’re based on retrospective claims data and pharmacoepidemiological studies and insurance databases that don’t really give you a good causality basis,” lead study author Saad Alrajhi, MD, said in an interview at the annual Digestive Disease Week.
In an effort to better characterize the association between PPI exposure and dementia, Dr. Alrajhi, a gastroenterology fellow at McGill University, Montreal, and colleagues conducted a meta-analysis of all fully published randomized clinical trials or observational studies comparing use of PPIs and occurrence of dementia. The researchers queried Embase, MEDLINE, and ISI Web of Knowledge for relevant studies that were published from 1995 through September 2018. Next, they assessed the quality of the studies by using the Cochrane risk assessment tool for RCTs or the Newcastle-Ottawa Scale for observational studies.
As the primary outcome, the researchers compared dementia incidence after PPI exposure (experimental group) versus no PPI exposure (control group). Development of Alzheimer’s dementia was a secondary outcome. Sensitivity analyses consisted of excluding one study at a time, and assessing results among studies of highest qualities. Subgroup analyses included stratifying patients by age. To report odds ratios, Dr. Alrajhi and colleagues used fixed or random effects models based on the absence or presence of heterogeneity.
Of 549 studies assessed, 5 met the criteria for inclusion in the final analysis: 3 case-control studies and 2 cohort studies, with a total of 472,933 patients. All of the studies scored 8 or 9 on the Newcastle-Ottawa scale, indicating high quality. Significant heterogeneity was noted for all analyses. The researchers found that the incidence of dementia was not significantly increased among patients in the PPI-exposed group (odd ratio, 1.08 (95% confidence interval, 0.97-1.20; P = .18). Sensitivity analyses confirmed the robustness of the results. Subgroup analysis showed no between-group differences among studies that included a minimum age above 65 years (three studies) or less than age 65 (two studies). PPI exposure was not associated with the development of Alzheimer’s dementia (two studies) (OR, 1.32 (95% CI, 0.80-2.17; P = .27).
“In the absence of randomized trial evidence, a PPI prescribing approach based on appropriate utilization of guideline-based prescription should be done without the extra fear of the association of dementia,” Dr. Alrajhi said.
The researchers reported having no financial disclosures.
The finding runs counter to recent studies, including a large pharmacoepidemiological claims data analysis from Germany, that propose an association between proton pump inhibitor (PPI) use and the development of dementia (JAMA Neurol. 2016;73[4]:410-6). “The issue with these studies is that they’re based on retrospective claims data and pharmacoepidemiological studies and insurance databases that don’t really give you a good causality basis,” lead study author Saad Alrajhi, MD, said in an interview at the annual Digestive Disease Week.
In an effort to better characterize the association between PPI exposure and dementia, Dr. Alrajhi, a gastroenterology fellow at McGill University, Montreal, and colleagues conducted a meta-analysis of all fully published randomized clinical trials or observational studies comparing use of PPIs and occurrence of dementia. The researchers queried Embase, MEDLINE, and ISI Web of Knowledge for relevant studies that were published from 1995 through September 2018. Next, they assessed the quality of the studies by using the Cochrane risk assessment tool for RCTs or the Newcastle-Ottawa Scale for observational studies.
As the primary outcome, the researchers compared dementia incidence after PPI exposure (experimental group) versus no PPI exposure (control group). Development of Alzheimer’s dementia was a secondary outcome. Sensitivity analyses consisted of excluding one study at a time, and assessing results among studies of highest qualities. Subgroup analyses included stratifying patients by age. To report odds ratios, Dr. Alrajhi and colleagues used fixed or random effects models based on the absence or presence of heterogeneity.
Of 549 studies assessed, 5 met the criteria for inclusion in the final analysis: 3 case-control studies and 2 cohort studies, with a total of 472,933 patients. All of the studies scored 8 or 9 on the Newcastle-Ottawa scale, indicating high quality. Significant heterogeneity was noted for all analyses. The researchers found that the incidence of dementia was not significantly increased among patients in the PPI-exposed group (odd ratio, 1.08 (95% confidence interval, 0.97-1.20; P = .18). Sensitivity analyses confirmed the robustness of the results. Subgroup analysis showed no between-group differences among studies that included a minimum age above 65 years (three studies) or less than age 65 (two studies). PPI exposure was not associated with the development of Alzheimer’s dementia (two studies) (OR, 1.32 (95% CI, 0.80-2.17; P = .27).
“In the absence of randomized trial evidence, a PPI prescribing approach based on appropriate utilization of guideline-based prescription should be done without the extra fear of the association of dementia,” Dr. Alrajhi said.
The researchers reported having no financial disclosures.
REPORTING FROM DDW 2019
Treatment-resistant GERD reported by more than half of patients
SAN DIEGO – Gastroesophageal reflux disease refractory to proton pump inhibitors may affect nearly half of those treated, according to the findings of a population-based sample of more than 70,000 Americans.
As part of the National Institutes of Health GI Patient Reported Outcomes Measurement Information System (NIH GI-PROMIS) questionnaire, respondents could download a free app called “My GI Health,” which led them through a series of questions about GI diseases. Sean Delshad, MD, MBA, of Cedars-Sinai Medical Center Los Angeles, and his colleagues examined data on symptom responses about GERD and heartburn.
Their somewhat surprising findings were that 44% of respondents had ever had GERD and that 70% of those respondents had symptoms in the past week. GERD seemed to be more common in women than in men, and in non-Hispanic whites more than other demographic groups. The rate of proton pump inhibitor–refractory GERD was reported at 54%.
Dr. Delshad discussed the implications of the study results for treatment and research in a video interview at the annual Digestive Disease Week.
SAN DIEGO – Gastroesophageal reflux disease refractory to proton pump inhibitors may affect nearly half of those treated, according to the findings of a population-based sample of more than 70,000 Americans.
As part of the National Institutes of Health GI Patient Reported Outcomes Measurement Information System (NIH GI-PROMIS) questionnaire, respondents could download a free app called “My GI Health,” which led them through a series of questions about GI diseases. Sean Delshad, MD, MBA, of Cedars-Sinai Medical Center Los Angeles, and his colleagues examined data on symptom responses about GERD and heartburn.
Their somewhat surprising findings were that 44% of respondents had ever had GERD and that 70% of those respondents had symptoms in the past week. GERD seemed to be more common in women than in men, and in non-Hispanic whites more than other demographic groups. The rate of proton pump inhibitor–refractory GERD was reported at 54%.
Dr. Delshad discussed the implications of the study results for treatment and research in a video interview at the annual Digestive Disease Week.
SAN DIEGO – Gastroesophageal reflux disease refractory to proton pump inhibitors may affect nearly half of those treated, according to the findings of a population-based sample of more than 70,000 Americans.
As part of the National Institutes of Health GI Patient Reported Outcomes Measurement Information System (NIH GI-PROMIS) questionnaire, respondents could download a free app called “My GI Health,” which led them through a series of questions about GI diseases. Sean Delshad, MD, MBA, of Cedars-Sinai Medical Center Los Angeles, and his colleagues examined data on symptom responses about GERD and heartburn.
Their somewhat surprising findings were that 44% of respondents had ever had GERD and that 70% of those respondents had symptoms in the past week. GERD seemed to be more common in women than in men, and in non-Hispanic whites more than other demographic groups. The rate of proton pump inhibitor–refractory GERD was reported at 54%.
Dr. Delshad discussed the implications of the study results for treatment and research in a video interview at the annual Digestive Disease Week.
REPORTING FROM DDW 2019
Immunostaining boosts pathologists’ accuracy in Barrett’s esophagus
SAN DIEGO – Years of experience and an academic medical center affiliation predicted the accuracy of pathologists reviewing biopsies from patients with Barrett’s esophagus, according to the results of a multinational study.
Those with 5 or more years of experience were less likely to make major diagnostic errors in reviewing Barrett’s esophagus biopsies (odds ratio [OR], 0.48, 95% confidence interval, 0.31-0.74). Pathologists who worked in nonacademic settings were more likely to make a major diagnostic error (OR, 1.76; 95% CI, 1.15-2.69) when reviewing hematoxylin and eosin-stained slides alone, but the addition of p53 immunostaining greatly improved accuracy.
Current guidelines recommend expert evaluation of Barrett’s esophagus biopsies that show dysplasia, but exact determination of expert review status had been lacking, according to Marnix Jansen, MD, a pathologist at University College London.
“The guidelines say that biopsies with dysplasia need to be reviewed by an expert pathologist, but don’t define what makes an expert pathologist,” Dr. Jansen said in an interview at the annual Digestive Disease Week.
“We wanted to advance the field by for the first time creating objective and quantitative standards” to delineate the characteristics of an expert pathologist in reviewing Barrett’s esophagus tissue samples, said Dr. Jansen. The study’s first author is Myrtle J. van der Wel, MD, of Amsterdam University Medical Center, the Netherlands.
More than 6,000 individual case diagnoses were used in the study, which included pathologists from more than 20 countries. Before the pathologists began reviewing the case set, they answered a questionnaire about training, practice context, years of experience, case volume, and other demographic characteristics.
“We then sent those biopsies around the world to ... 55 pathologists in the U.S., in Europe, Japan, Australia, even some in South America – so really around the whole globe,” explained Dr. Jansen. Biopsies were assessed by each pathologist before and after p53 immunostaining.
“Once we had the final dataset – which is massive, because we had 6,000 case diagnoses within our dataset – we could then regress those variables back onto the consensus data,” providing a first-ever look at “clear predictors of what the pathologist looks like that will score on a par with where the experts are,” said Dr. Jansen.
The results? “You need at least 5 years of experience. On top of that, if you are a pathologist working in a [nonacademic center], you are at a slightly increased risk of making major diagnostic errors,” said Dr. Jansen. However, the analysis convincingly showed that the addition of p53 immunostaining neutralized the risk for these pathologists – a strength of having such a large dataset, he said.
The study also affirmed the safety of digital pathology for expert review, said Dr. Jansen: “One of the reassuring points of our study was that we found that the best concordance was for nondysplastic Barrett’s, and high-grade dysplasia, which really replicates known glass slide characteristics. So we can really say that digital pathology is safe for this application – which is very relevant for pathologists that are taking in cases from outside for expert review.”
Concordance rates for nondysplastic Barrett’s esophagus and high-grade dysplasia were over 70%; for low-grade dysplasia, rates were intermediate at 42%.
Going forward, the study can inform the next iteration of guidelines for pathologist review of Barrett’s dysplasia, said Dr. Jansen. Rather than just recommending expert review, the guidelines can include a quantitative assessment of what’s needed. “You need to have to have at least 5 years of experience, and if you work in a [community hospital], to use a p53, and that is collectively what amounts to expertise in Barrett’s pathology.”
A follow-up study with a similar design is planned within the United Kingdom, the Netherlands, and the United States. This study, which Dr. Jansen said would enroll hundreds of pathologists, will include an intervention arm that administers a tutorial with the aim of improving concordance scoring.
Dr. Jansen reported no relevant conflicts of interest.
SAN DIEGO – Years of experience and an academic medical center affiliation predicted the accuracy of pathologists reviewing biopsies from patients with Barrett’s esophagus, according to the results of a multinational study.
Those with 5 or more years of experience were less likely to make major diagnostic errors in reviewing Barrett’s esophagus biopsies (odds ratio [OR], 0.48, 95% confidence interval, 0.31-0.74). Pathologists who worked in nonacademic settings were more likely to make a major diagnostic error (OR, 1.76; 95% CI, 1.15-2.69) when reviewing hematoxylin and eosin-stained slides alone, but the addition of p53 immunostaining greatly improved accuracy.
Current guidelines recommend expert evaluation of Barrett’s esophagus biopsies that show dysplasia, but exact determination of expert review status had been lacking, according to Marnix Jansen, MD, a pathologist at University College London.
“The guidelines say that biopsies with dysplasia need to be reviewed by an expert pathologist, but don’t define what makes an expert pathologist,” Dr. Jansen said in an interview at the annual Digestive Disease Week.
“We wanted to advance the field by for the first time creating objective and quantitative standards” to delineate the characteristics of an expert pathologist in reviewing Barrett’s esophagus tissue samples, said Dr. Jansen. The study’s first author is Myrtle J. van der Wel, MD, of Amsterdam University Medical Center, the Netherlands.
More than 6,000 individual case diagnoses were used in the study, which included pathologists from more than 20 countries. Before the pathologists began reviewing the case set, they answered a questionnaire about training, practice context, years of experience, case volume, and other demographic characteristics.
“We then sent those biopsies around the world to ... 55 pathologists in the U.S., in Europe, Japan, Australia, even some in South America – so really around the whole globe,” explained Dr. Jansen. Biopsies were assessed by each pathologist before and after p53 immunostaining.
“Once we had the final dataset – which is massive, because we had 6,000 case diagnoses within our dataset – we could then regress those variables back onto the consensus data,” providing a first-ever look at “clear predictors of what the pathologist looks like that will score on a par with where the experts are,” said Dr. Jansen.
The results? “You need at least 5 years of experience. On top of that, if you are a pathologist working in a [nonacademic center], you are at a slightly increased risk of making major diagnostic errors,” said Dr. Jansen. However, the analysis convincingly showed that the addition of p53 immunostaining neutralized the risk for these pathologists – a strength of having such a large dataset, he said.
The study also affirmed the safety of digital pathology for expert review, said Dr. Jansen: “One of the reassuring points of our study was that we found that the best concordance was for nondysplastic Barrett’s, and high-grade dysplasia, which really replicates known glass slide characteristics. So we can really say that digital pathology is safe for this application – which is very relevant for pathologists that are taking in cases from outside for expert review.”
Concordance rates for nondysplastic Barrett’s esophagus and high-grade dysplasia were over 70%; for low-grade dysplasia, rates were intermediate at 42%.
Going forward, the study can inform the next iteration of guidelines for pathologist review of Barrett’s dysplasia, said Dr. Jansen. Rather than just recommending expert review, the guidelines can include a quantitative assessment of what’s needed. “You need to have to have at least 5 years of experience, and if you work in a [community hospital], to use a p53, and that is collectively what amounts to expertise in Barrett’s pathology.”
A follow-up study with a similar design is planned within the United Kingdom, the Netherlands, and the United States. This study, which Dr. Jansen said would enroll hundreds of pathologists, will include an intervention arm that administers a tutorial with the aim of improving concordance scoring.
Dr. Jansen reported no relevant conflicts of interest.
SAN DIEGO – Years of experience and an academic medical center affiliation predicted the accuracy of pathologists reviewing biopsies from patients with Barrett’s esophagus, according to the results of a multinational study.
Those with 5 or more years of experience were less likely to make major diagnostic errors in reviewing Barrett’s esophagus biopsies (odds ratio [OR], 0.48, 95% confidence interval, 0.31-0.74). Pathologists who worked in nonacademic settings were more likely to make a major diagnostic error (OR, 1.76; 95% CI, 1.15-2.69) when reviewing hematoxylin and eosin-stained slides alone, but the addition of p53 immunostaining greatly improved accuracy.
Current guidelines recommend expert evaluation of Barrett’s esophagus biopsies that show dysplasia, but exact determination of expert review status had been lacking, according to Marnix Jansen, MD, a pathologist at University College London.
“The guidelines say that biopsies with dysplasia need to be reviewed by an expert pathologist, but don’t define what makes an expert pathologist,” Dr. Jansen said in an interview at the annual Digestive Disease Week.
“We wanted to advance the field by for the first time creating objective and quantitative standards” to delineate the characteristics of an expert pathologist in reviewing Barrett’s esophagus tissue samples, said Dr. Jansen. The study’s first author is Myrtle J. van der Wel, MD, of Amsterdam University Medical Center, the Netherlands.
More than 6,000 individual case diagnoses were used in the study, which included pathologists from more than 20 countries. Before the pathologists began reviewing the case set, they answered a questionnaire about training, practice context, years of experience, case volume, and other demographic characteristics.
“We then sent those biopsies around the world to ... 55 pathologists in the U.S., in Europe, Japan, Australia, even some in South America – so really around the whole globe,” explained Dr. Jansen. Biopsies were assessed by each pathologist before and after p53 immunostaining.
“Once we had the final dataset – which is massive, because we had 6,000 case diagnoses within our dataset – we could then regress those variables back onto the consensus data,” providing a first-ever look at “clear predictors of what the pathologist looks like that will score on a par with where the experts are,” said Dr. Jansen.
The results? “You need at least 5 years of experience. On top of that, if you are a pathologist working in a [nonacademic center], you are at a slightly increased risk of making major diagnostic errors,” said Dr. Jansen. However, the analysis convincingly showed that the addition of p53 immunostaining neutralized the risk for these pathologists – a strength of having such a large dataset, he said.
The study also affirmed the safety of digital pathology for expert review, said Dr. Jansen: “One of the reassuring points of our study was that we found that the best concordance was for nondysplastic Barrett’s, and high-grade dysplasia, which really replicates known glass slide characteristics. So we can really say that digital pathology is safe for this application – which is very relevant for pathologists that are taking in cases from outside for expert review.”
Concordance rates for nondysplastic Barrett’s esophagus and high-grade dysplasia were over 70%; for low-grade dysplasia, rates were intermediate at 42%.
Going forward, the study can inform the next iteration of guidelines for pathologist review of Barrett’s dysplasia, said Dr. Jansen. Rather than just recommending expert review, the guidelines can include a quantitative assessment of what’s needed. “You need to have to have at least 5 years of experience, and if you work in a [community hospital], to use a p53, and that is collectively what amounts to expertise in Barrett’s pathology.”
A follow-up study with a similar design is planned within the United Kingdom, the Netherlands, and the United States. This study, which Dr. Jansen said would enroll hundreds of pathologists, will include an intervention arm that administers a tutorial with the aim of improving concordance scoring.
Dr. Jansen reported no relevant conflicts of interest.
REPORTING FROM DDW 2019
Button batteries that pass to the stomach may warrant rapid endoscopic removal
SAN DIEGO – A button battery lodged in a child’s esophagus is an acknowledged emergency, but there is less evidence about retrieval of button batteries that have passed to the stomach. Observation alone has been recommended when an x-ray determines that the button battery has passed to the stomach within 2 hours of ingestion, when the battery is less than 20 mm, and the child is aged at least 5 years.
At the annual Digestive Disease Week, Racha Khalaf, MD, and Thomas Walker, MD, both of Children’s Hospital Colorado, Aurora, presented data that call this approach into question. Their retrospective cohort study of 4 years’ worth of records from four pediatric centers in the United States identified 68 cases in which a pediatric gastroenterologist had endoscopically removed the button battery. In 60% of those cases, the battery had already caused mucosal damage varying from minor to deep necrosis and perforation.
Further, the degree of injury was not correlated with symptoms, strengthening the recommendation for retrieving the button battery from the stomach.
In our exclusive video interview, Dr. Khalaf and Dr. Walker discussed the impact of their findings for guidelines for pediatric gastroenterologists and Poison Control Center advice to parents about ingestion of button batteries.
Their study was partly supported by a Cystic Fibrosis Foundational Grant Award and by National Institutes of Health Training Grants.
SAN DIEGO – A button battery lodged in a child’s esophagus is an acknowledged emergency, but there is less evidence about retrieval of button batteries that have passed to the stomach. Observation alone has been recommended when an x-ray determines that the button battery has passed to the stomach within 2 hours of ingestion, when the battery is less than 20 mm, and the child is aged at least 5 years.
At the annual Digestive Disease Week, Racha Khalaf, MD, and Thomas Walker, MD, both of Children’s Hospital Colorado, Aurora, presented data that call this approach into question. Their retrospective cohort study of 4 years’ worth of records from four pediatric centers in the United States identified 68 cases in which a pediatric gastroenterologist had endoscopically removed the button battery. In 60% of those cases, the battery had already caused mucosal damage varying from minor to deep necrosis and perforation.
Further, the degree of injury was not correlated with symptoms, strengthening the recommendation for retrieving the button battery from the stomach.
In our exclusive video interview, Dr. Khalaf and Dr. Walker discussed the impact of their findings for guidelines for pediatric gastroenterologists and Poison Control Center advice to parents about ingestion of button batteries.
Their study was partly supported by a Cystic Fibrosis Foundational Grant Award and by National Institutes of Health Training Grants.
SAN DIEGO – A button battery lodged in a child’s esophagus is an acknowledged emergency, but there is less evidence about retrieval of button batteries that have passed to the stomach. Observation alone has been recommended when an x-ray determines that the button battery has passed to the stomach within 2 hours of ingestion, when the battery is less than 20 mm, and the child is aged at least 5 years.
At the annual Digestive Disease Week, Racha Khalaf, MD, and Thomas Walker, MD, both of Children’s Hospital Colorado, Aurora, presented data that call this approach into question. Their retrospective cohort study of 4 years’ worth of records from four pediatric centers in the United States identified 68 cases in which a pediatric gastroenterologist had endoscopically removed the button battery. In 60% of those cases, the battery had already caused mucosal damage varying from minor to deep necrosis and perforation.
Further, the degree of injury was not correlated with symptoms, strengthening the recommendation for retrieving the button battery from the stomach.
In our exclusive video interview, Dr. Khalaf and Dr. Walker discussed the impact of their findings for guidelines for pediatric gastroenterologists and Poison Control Center advice to parents about ingestion of button batteries.
Their study was partly supported by a Cystic Fibrosis Foundational Grant Award and by National Institutes of Health Training Grants.
REPORTING FROM DDW 2019
Report card may foretell achalasia surgery outcomes
BALTIMORE – The Eckardt score has been established as a tool to evaluate outcomes of surgery for achalasia, but researchers have developed a report card that uses multiple variables that may provide a more accurate picture of surgical outcomes, according to results of study reported at the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons.
“The use of an accurate score to assess outcomes after achalasia surgery shows outstanding results,” said Ealaf Shemmeri, MD, of Swedish Medical Center in Seattle. “Using patient-reported symptoms, objective measures, and rates of reinterventions organized into a report card provides a more comprehensive and informative view.”
The Eckardt score evaluates four symptoms to evaluate outcomes of surgery to treat achalasia: weight loss, retrosternal pain, regurgitation, and dysphagia. “However, it does not address the other changes that can occur after myotomy, including the quality of swallowing and the onset of reflux disease,” she said. “Thus, there is a need for a more comprehensive assessment of quality after achalasia treatment.”
So the Swedish investigators set out to devise a report card that provides “a comprehensive and informative assessment” of surgical myotomy outcomes, she said. This involved a retrospective, single-center chart review of 185 patients who had surgical myotomy for primary achalasia from 2005 to 2017.
To determine patient-reported outcomes, the report card defines success as an Eckardt score below 3, Dakkak dysphagia score above 40, and GERD-HRQL (health-related quality of life) score below 10. The objective measures consisted of DeMeester (pH) score below 14.72, no column at 5 minutes on timed barium swallow, normalized integrated relaxation pressure less than 15 on manometry, and absence of esophagitis on endoscopy. For the third pillar of the report card, no reintervention was recorded as a success, Dr. Shemmeri said.
Regarding the etiology of achalasia in the study population, 42 had type 1, 109 had type 2, and 34 had type 3. A total of 71 patients had per oral endoscopic myotomy and 114 had Heller myotomy, 92 with Dor fundoplication and 20 with Toupet. Major perioperative complications included four per oral endoscopic myotomy patients who developed a leak requiring intervention. Six patients required return to the operating room for persistent dysphagia, Dr. Shemmeri said.
After the procedures, 93% of study patients reported an Eckardt score less than 3. However, only 45% have a Dakkak dysphagia score greater than 40 and 71% had a GERD-HRQL score less than 10, Dr. Shemmeri said. The objective measures told a similar story: Integrated relaxation pressure normalized in 80%, barium clearance was achieved in 61%, normal esophageal mucosa was recorded in 71%, “but pH testing was normal only 50% of the time,” Dr. Shemmeri said.
“The final success of not needing intervention is 79%,” she said. At this point in the study, 139 patients were available for follow-up. Among the 29 who needed reintervention, 19 had dilation below 20 mm Hg, 3 underwent pneumatic dilation, and 2 had botulinum toxin. Two patients required a redo myotomy, two had antireflux surgery, and one had an esophagectomy.
“When you only focus on a singular outcome, you can miss the whole story that occurs after myotomy,” Dr. Shemmeri said. “Providing a comprehensive tool gives you the ability to identify areas for improvement in your achalasia practice. Its simplicity allows it to be applied in various settings.” In the academic setting, it can be a tool for evaluating technologies and approaches for postmyotomy management. In hospitals and surgeons’ practices, it can aid in quality improvement, comparative outcomes research, and in evaluating operative approaches to myotomy.
The outcomes highlight the high prevalence of GERD, thus stressing the importance of pH testing after myotomy, Dr. Shemmeri said. Her study team recommends pH testing at 6-month follow-up because patients may not always self-report the extent of esophagitis present. Coauthor Brian Louie, MD, also of Swedish Medical Center, added during the discussion that ongoing follow-up of achalasia patients is necessary to address issues patients encounter with their swallowing over time.
Dr. Shemmeri had no relevant financial relationships to disclose. Dr. Louie reported relationships with Boston Scientific, ERBE, and Olympus.
SOURCE: Shemmeri E et al. SAGES 2019, Presentation S085.
BALTIMORE – The Eckardt score has been established as a tool to evaluate outcomes of surgery for achalasia, but researchers have developed a report card that uses multiple variables that may provide a more accurate picture of surgical outcomes, according to results of study reported at the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons.
“The use of an accurate score to assess outcomes after achalasia surgery shows outstanding results,” said Ealaf Shemmeri, MD, of Swedish Medical Center in Seattle. “Using patient-reported symptoms, objective measures, and rates of reinterventions organized into a report card provides a more comprehensive and informative view.”
The Eckardt score evaluates four symptoms to evaluate outcomes of surgery to treat achalasia: weight loss, retrosternal pain, regurgitation, and dysphagia. “However, it does not address the other changes that can occur after myotomy, including the quality of swallowing and the onset of reflux disease,” she said. “Thus, there is a need for a more comprehensive assessment of quality after achalasia treatment.”
So the Swedish investigators set out to devise a report card that provides “a comprehensive and informative assessment” of surgical myotomy outcomes, she said. This involved a retrospective, single-center chart review of 185 patients who had surgical myotomy for primary achalasia from 2005 to 2017.
To determine patient-reported outcomes, the report card defines success as an Eckardt score below 3, Dakkak dysphagia score above 40, and GERD-HRQL (health-related quality of life) score below 10. The objective measures consisted of DeMeester (pH) score below 14.72, no column at 5 minutes on timed barium swallow, normalized integrated relaxation pressure less than 15 on manometry, and absence of esophagitis on endoscopy. For the third pillar of the report card, no reintervention was recorded as a success, Dr. Shemmeri said.
Regarding the etiology of achalasia in the study population, 42 had type 1, 109 had type 2, and 34 had type 3. A total of 71 patients had per oral endoscopic myotomy and 114 had Heller myotomy, 92 with Dor fundoplication and 20 with Toupet. Major perioperative complications included four per oral endoscopic myotomy patients who developed a leak requiring intervention. Six patients required return to the operating room for persistent dysphagia, Dr. Shemmeri said.
After the procedures, 93% of study patients reported an Eckardt score less than 3. However, only 45% have a Dakkak dysphagia score greater than 40 and 71% had a GERD-HRQL score less than 10, Dr. Shemmeri said. The objective measures told a similar story: Integrated relaxation pressure normalized in 80%, barium clearance was achieved in 61%, normal esophageal mucosa was recorded in 71%, “but pH testing was normal only 50% of the time,” Dr. Shemmeri said.
“The final success of not needing intervention is 79%,” she said. At this point in the study, 139 patients were available for follow-up. Among the 29 who needed reintervention, 19 had dilation below 20 mm Hg, 3 underwent pneumatic dilation, and 2 had botulinum toxin. Two patients required a redo myotomy, two had antireflux surgery, and one had an esophagectomy.
“When you only focus on a singular outcome, you can miss the whole story that occurs after myotomy,” Dr. Shemmeri said. “Providing a comprehensive tool gives you the ability to identify areas for improvement in your achalasia practice. Its simplicity allows it to be applied in various settings.” In the academic setting, it can be a tool for evaluating technologies and approaches for postmyotomy management. In hospitals and surgeons’ practices, it can aid in quality improvement, comparative outcomes research, and in evaluating operative approaches to myotomy.
The outcomes highlight the high prevalence of GERD, thus stressing the importance of pH testing after myotomy, Dr. Shemmeri said. Her study team recommends pH testing at 6-month follow-up because patients may not always self-report the extent of esophagitis present. Coauthor Brian Louie, MD, also of Swedish Medical Center, added during the discussion that ongoing follow-up of achalasia patients is necessary to address issues patients encounter with their swallowing over time.
Dr. Shemmeri had no relevant financial relationships to disclose. Dr. Louie reported relationships with Boston Scientific, ERBE, and Olympus.
SOURCE: Shemmeri E et al. SAGES 2019, Presentation S085.
BALTIMORE – The Eckardt score has been established as a tool to evaluate outcomes of surgery for achalasia, but researchers have developed a report card that uses multiple variables that may provide a more accurate picture of surgical outcomes, according to results of study reported at the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons.
“The use of an accurate score to assess outcomes after achalasia surgery shows outstanding results,” said Ealaf Shemmeri, MD, of Swedish Medical Center in Seattle. “Using patient-reported symptoms, objective measures, and rates of reinterventions organized into a report card provides a more comprehensive and informative view.”
The Eckardt score evaluates four symptoms to evaluate outcomes of surgery to treat achalasia: weight loss, retrosternal pain, regurgitation, and dysphagia. “However, it does not address the other changes that can occur after myotomy, including the quality of swallowing and the onset of reflux disease,” she said. “Thus, there is a need for a more comprehensive assessment of quality after achalasia treatment.”
So the Swedish investigators set out to devise a report card that provides “a comprehensive and informative assessment” of surgical myotomy outcomes, she said. This involved a retrospective, single-center chart review of 185 patients who had surgical myotomy for primary achalasia from 2005 to 2017.
To determine patient-reported outcomes, the report card defines success as an Eckardt score below 3, Dakkak dysphagia score above 40, and GERD-HRQL (health-related quality of life) score below 10. The objective measures consisted of DeMeester (pH) score below 14.72, no column at 5 minutes on timed barium swallow, normalized integrated relaxation pressure less than 15 on manometry, and absence of esophagitis on endoscopy. For the third pillar of the report card, no reintervention was recorded as a success, Dr. Shemmeri said.
Regarding the etiology of achalasia in the study population, 42 had type 1, 109 had type 2, and 34 had type 3. A total of 71 patients had per oral endoscopic myotomy and 114 had Heller myotomy, 92 with Dor fundoplication and 20 with Toupet. Major perioperative complications included four per oral endoscopic myotomy patients who developed a leak requiring intervention. Six patients required return to the operating room for persistent dysphagia, Dr. Shemmeri said.
After the procedures, 93% of study patients reported an Eckardt score less than 3. However, only 45% have a Dakkak dysphagia score greater than 40 and 71% had a GERD-HRQL score less than 10, Dr. Shemmeri said. The objective measures told a similar story: Integrated relaxation pressure normalized in 80%, barium clearance was achieved in 61%, normal esophageal mucosa was recorded in 71%, “but pH testing was normal only 50% of the time,” Dr. Shemmeri said.
“The final success of not needing intervention is 79%,” she said. At this point in the study, 139 patients were available for follow-up. Among the 29 who needed reintervention, 19 had dilation below 20 mm Hg, 3 underwent pneumatic dilation, and 2 had botulinum toxin. Two patients required a redo myotomy, two had antireflux surgery, and one had an esophagectomy.
“When you only focus on a singular outcome, you can miss the whole story that occurs after myotomy,” Dr. Shemmeri said. “Providing a comprehensive tool gives you the ability to identify areas for improvement in your achalasia practice. Its simplicity allows it to be applied in various settings.” In the academic setting, it can be a tool for evaluating technologies and approaches for postmyotomy management. In hospitals and surgeons’ practices, it can aid in quality improvement, comparative outcomes research, and in evaluating operative approaches to myotomy.
The outcomes highlight the high prevalence of GERD, thus stressing the importance of pH testing after myotomy, Dr. Shemmeri said. Her study team recommends pH testing at 6-month follow-up because patients may not always self-report the extent of esophagitis present. Coauthor Brian Louie, MD, also of Swedish Medical Center, added during the discussion that ongoing follow-up of achalasia patients is necessary to address issues patients encounter with their swallowing over time.
Dr. Shemmeri had no relevant financial relationships to disclose. Dr. Louie reported relationships with Boston Scientific, ERBE, and Olympus.
SOURCE: Shemmeri E et al. SAGES 2019, Presentation S085.
REPORTING FROM SAGES 2019
Look for functional esophageal disorders if GERD patients fail PPIs
In a small, first-in-kind study, functional heartburn or reflux hypersensitivity affected fully 75% of patients whose gastroesophageal reflux disease symptoms had not improved with once-daily proton pump inhibitor therapy.
At the same time, proton pump inhibitor (PPI) responders and nonresponders had similar impedance and pH parameters, reported Jason Abdallah, MD, of Case Western Reserve University, Cleveland, and his associates. The findings show “the important role of esophageal hypersensitivity in this patient population.” For these patients, the investigators suggested adding a neuromodulator and possibly psychotherapy, such as cognitive-behavioral therapy, hypnotherapy, relaxation techniques, mindfulness, and biofeedback.
Symptoms in up to 45% of patients with gastroesophageal reflux disease (GERD) persist despite once-daily PPI therapy, Dr. Abdallah and his associates wrote in Clinical Gastroenterology and Hepatology. For the study, they compared reflux characteristics and patterns between 13 patients whose GERD symptoms had fully resolved on standard once-daily PPIs and 16 patients who reported at least twice-weekly heartburn, regurgitation, or both for at least 3 months, despite treatment. Patients in both groups continued PPIs and underwent upper endoscopy and combined esophageal impedance–pH monitoring.
The average age of patients in this study was 54.5 years, with a standard deviation of 14.5 years. Demographic and clinical characteristics were similar between groups, and patients in both groups were receiving omeprazole, esomeprazole, or pantoprazole. Four (31%) PPI responders had abnormal pH test results, as did four (25%) nonresponders. Responders and nonresponders had similar numbers of reflux events; proportions of events that were acidic, weakly acidic, or alkaline; and mean total time with pH less than 4.0.
Additionally, most patients in both groups had normal endoscopic findings. One PPI responder had Los Angeles grade A erosive esophagitis, and two PPI responders had short-segment Barrett’s esophagus. Three PPI responders and two PPI nonresponders had nonobstructive Schatzki rings, and one PPI nonresponder had an esophageal stricture. Finally, five PPI responders (38%) and three nonresponders (19%) had hiatal hernias (P = .41).
In patients with GERD, “PPI failure” does not reflect a unique pattern of reflux events, acid exposure, or nonacidic reflux parameters, Dr. Abdallah and his associates concluded. The fact that most PPI nonresponders had a concurrent functional esophageal disorder – either reflux hypersensitivity or functional heartburn – “support[s] the hypothesis that PPI failure is primarily driven by esophageal hypersensitivity.”
This was a small study – recruitment “was hampered by the invasive nature of some of the procedures,” they wrote. “In addition, it is our experience that many patients who have responded to PPI [therapy] are reluctant to undergo invasive testing as part of a study protocol. Therefore, we believe that these types of prospective, invasive studies are rather difficult to perform but, at the same time, provide essential insight into the understanding of refractory GERD.”
No external funding sources were acknowledged. The senior author reported ties to Ironwood Pharmaceuticals, Mederi Therapeutics, Ethicon, AstraZeneca, and Takeda. The other researchers reported no conflicts of interest.
SOURCE: Abdallah J et al. Clin Gastroenterol Hepatol. 2018 Jun 15. doi: 10.1016/j.cgh.2018.09.006.
In a small, first-in-kind study, functional heartburn or reflux hypersensitivity affected fully 75% of patients whose gastroesophageal reflux disease symptoms had not improved with once-daily proton pump inhibitor therapy.
At the same time, proton pump inhibitor (PPI) responders and nonresponders had similar impedance and pH parameters, reported Jason Abdallah, MD, of Case Western Reserve University, Cleveland, and his associates. The findings show “the important role of esophageal hypersensitivity in this patient population.” For these patients, the investigators suggested adding a neuromodulator and possibly psychotherapy, such as cognitive-behavioral therapy, hypnotherapy, relaxation techniques, mindfulness, and biofeedback.
Symptoms in up to 45% of patients with gastroesophageal reflux disease (GERD) persist despite once-daily PPI therapy, Dr. Abdallah and his associates wrote in Clinical Gastroenterology and Hepatology. For the study, they compared reflux characteristics and patterns between 13 patients whose GERD symptoms had fully resolved on standard once-daily PPIs and 16 patients who reported at least twice-weekly heartburn, regurgitation, or both for at least 3 months, despite treatment. Patients in both groups continued PPIs and underwent upper endoscopy and combined esophageal impedance–pH monitoring.
The average age of patients in this study was 54.5 years, with a standard deviation of 14.5 years. Demographic and clinical characteristics were similar between groups, and patients in both groups were receiving omeprazole, esomeprazole, or pantoprazole. Four (31%) PPI responders had abnormal pH test results, as did four (25%) nonresponders. Responders and nonresponders had similar numbers of reflux events; proportions of events that were acidic, weakly acidic, or alkaline; and mean total time with pH less than 4.0.
Additionally, most patients in both groups had normal endoscopic findings. One PPI responder had Los Angeles grade A erosive esophagitis, and two PPI responders had short-segment Barrett’s esophagus. Three PPI responders and two PPI nonresponders had nonobstructive Schatzki rings, and one PPI nonresponder had an esophageal stricture. Finally, five PPI responders (38%) and three nonresponders (19%) had hiatal hernias (P = .41).
In patients with GERD, “PPI failure” does not reflect a unique pattern of reflux events, acid exposure, or nonacidic reflux parameters, Dr. Abdallah and his associates concluded. The fact that most PPI nonresponders had a concurrent functional esophageal disorder – either reflux hypersensitivity or functional heartburn – “support[s] the hypothesis that PPI failure is primarily driven by esophageal hypersensitivity.”
This was a small study – recruitment “was hampered by the invasive nature of some of the procedures,” they wrote. “In addition, it is our experience that many patients who have responded to PPI [therapy] are reluctant to undergo invasive testing as part of a study protocol. Therefore, we believe that these types of prospective, invasive studies are rather difficult to perform but, at the same time, provide essential insight into the understanding of refractory GERD.”
No external funding sources were acknowledged. The senior author reported ties to Ironwood Pharmaceuticals, Mederi Therapeutics, Ethicon, AstraZeneca, and Takeda. The other researchers reported no conflicts of interest.
SOURCE: Abdallah J et al. Clin Gastroenterol Hepatol. 2018 Jun 15. doi: 10.1016/j.cgh.2018.09.006.
In a small, first-in-kind study, functional heartburn or reflux hypersensitivity affected fully 75% of patients whose gastroesophageal reflux disease symptoms had not improved with once-daily proton pump inhibitor therapy.
At the same time, proton pump inhibitor (PPI) responders and nonresponders had similar impedance and pH parameters, reported Jason Abdallah, MD, of Case Western Reserve University, Cleveland, and his associates. The findings show “the important role of esophageal hypersensitivity in this patient population.” For these patients, the investigators suggested adding a neuromodulator and possibly psychotherapy, such as cognitive-behavioral therapy, hypnotherapy, relaxation techniques, mindfulness, and biofeedback.
Symptoms in up to 45% of patients with gastroesophageal reflux disease (GERD) persist despite once-daily PPI therapy, Dr. Abdallah and his associates wrote in Clinical Gastroenterology and Hepatology. For the study, they compared reflux characteristics and patterns between 13 patients whose GERD symptoms had fully resolved on standard once-daily PPIs and 16 patients who reported at least twice-weekly heartburn, regurgitation, or both for at least 3 months, despite treatment. Patients in both groups continued PPIs and underwent upper endoscopy and combined esophageal impedance–pH monitoring.
The average age of patients in this study was 54.5 years, with a standard deviation of 14.5 years. Demographic and clinical characteristics were similar between groups, and patients in both groups were receiving omeprazole, esomeprazole, or pantoprazole. Four (31%) PPI responders had abnormal pH test results, as did four (25%) nonresponders. Responders and nonresponders had similar numbers of reflux events; proportions of events that were acidic, weakly acidic, or alkaline; and mean total time with pH less than 4.0.
Additionally, most patients in both groups had normal endoscopic findings. One PPI responder had Los Angeles grade A erosive esophagitis, and two PPI responders had short-segment Barrett’s esophagus. Three PPI responders and two PPI nonresponders had nonobstructive Schatzki rings, and one PPI nonresponder had an esophageal stricture. Finally, five PPI responders (38%) and three nonresponders (19%) had hiatal hernias (P = .41).
In patients with GERD, “PPI failure” does not reflect a unique pattern of reflux events, acid exposure, or nonacidic reflux parameters, Dr. Abdallah and his associates concluded. The fact that most PPI nonresponders had a concurrent functional esophageal disorder – either reflux hypersensitivity or functional heartburn – “support[s] the hypothesis that PPI failure is primarily driven by esophageal hypersensitivity.”
This was a small study – recruitment “was hampered by the invasive nature of some of the procedures,” they wrote. “In addition, it is our experience that many patients who have responded to PPI [therapy] are reluctant to undergo invasive testing as part of a study protocol. Therefore, we believe that these types of prospective, invasive studies are rather difficult to perform but, at the same time, provide essential insight into the understanding of refractory GERD.”
No external funding sources were acknowledged. The senior author reported ties to Ironwood Pharmaceuticals, Mederi Therapeutics, Ethicon, AstraZeneca, and Takeda. The other researchers reported no conflicts of interest.
SOURCE: Abdallah J et al. Clin Gastroenterol Hepatol. 2018 Jun 15. doi: 10.1016/j.cgh.2018.09.006.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Mucosal impedance contour rapidly distinguished GERD, non-GERD, and eosinophilic esophagitis
.
Source: American Gastroenterological Association
Each group showed a significantly different (P less than .01) pattern of mucosal impedance (MI), or disruption of mucosal integrity, along the esophageal axis, wrote Dhyanesh A. Patel, MD, of Vanderbilt University Medical Center in Nashville, Tenn., and his associates. Patients without GERD had higher MI values along all esophageal segments, while GERD was characterized by below-normal values in the distal esophagus only, and eosinophilic esophagitis led to low values throughout the esophagus.
The findings were validated in a separate patient cohort, and the only reported adverse event was an episode of mild chest pain. “This contour heatmap could easily be employed to establish a diagnosis during endoscopy, independent of biopsy or pH monitoring,” the investigators wrote in Gastroenterology. They cautioned that the balloon catheter cannot be safely used in patients with severe fibrostenotic disease.
Current definitive diagnostics for GERD leave much to be desired. Transnasal probes are imprecise and uncomfortable, and they can be insensitive if discomfort causes patients to vary normal activity or skip meals. Wireless ambulatory pH monitoring is more tolerable but unreliable and measures only acidity of refluxed material at a single point along the esophagus. These tests also “fail to account for day-to-day variability of reflux, as they only provide a 24- to 48-hour snapshot of a disease process that is chronic in nature,” the researchers wrote. Eosinophilic esophagitis is becoming more common and usually requires proximal and distal biopsies for diagnosis.
Mucosal impedance contour pattern testing is based on the fact that both GERD and eosinophilic esophagitis involve increased distance between esophageal epithelial cells. The amount of intercellular dilatation correlates inversely with MI values. In proof-of-concept studies, individuals with GERD, non-GERD, eosinophilic esophagitis, and achalasia had distinct MI patterns. However, these studies tested a single-channel catheter system that took only point measurements and was subject to interoperator variability. To improve on this concept, Dr. Patel and his associates mounted radial and axial sensors on a balloon catheter to measure MI at 180-degree intervals along a 10-cm esophageal segment.
They tested the new device prospectively in 69 patients undergoing esophagogastroduodenoscopy with or without pH monitoring (which was used as the standard). In all, 24 patients had GERD, 21 had eosinophilic esophagitis, and 24 had normal findings. By using the intercept and slope of the balloon MI measurements, the researchers detected GERD with an area under the receiver operating characteristic curve (AUC) of 0.67, eosinophilic esophagitis with an AUC of 0.84, and non-GERD with an AUC of 0.83.
These findings held up in a separate validation cohort of 36 patients (28 with GERD and eight with eosinophilic esophagitis) from three tertiary care centers. The probability of eosinophilic esophagitis was highest in patients with low distal MI values (that is, a low intercept) and a low slope (showing that MI values remained low proximally). A low distal MI intercept with a steeper positive slope suggested GERD, while a higher distal MI intercept with a steep slope signified non-GERD.
The system “potentially obviates the need for 24- to 48-hour ambulatory wireless pH monitoring or esophageal biopsies for histopathology,” the researchers concluded. “This can help reduce diagnostic and treatment latency and might allow for monitoring disease activity over time.”
The National Institutes of Health funded the external validation analysis. Diversatek Healthcare, which patented the device together with Vanderbilt University, gave research funding to four coinvestigators, including the senior author. Dr. Patel and the other five coinvestigators reported having no conflicts of interest.
SOURCE: Patel DA et al. Gastroenterology. 2019 Jan 31. doi: 10.1053/j.gastro.2019.01.253.
Evaluating esophageal disorders such as GERD or eosinophilic esophagitis can be time consuming for patients in clinical practice and requires multiple visits to complete testing and obtain results. Other than visualizing complications of reflux such as erosive esophagitis or Barrett’s esophagus, there has been no immediate option to diagnose GERD in standard practice during routine endoscopy. Furthermore, the decision to pursue long-term medication or surgery for GERD relies on a brief pH assessment to be truly representative of a patient’s everyday symptoms. Follow-up of eosinophilic esophagitis requires repeated upper endoscopies with biopsies after every incremental change in medication or diet, which unsurprisingly, can reduce compliance with ongoing management for what is often a readily treatable condition.
Both GERD and eosinophilic esophagitis can be characterized by changes in esophageal mucosal impedance. Rather than directly measuring the pH or eosinophil counts, Dr. Patel and associates prospectively validated the diagnostic test performance of an add-on endoscopic mucosal impedance device that might enable the gastroenterologist to rule out GERD or rule in eosinophilic esophagitis during the index endoscopy with reasonable accuracy (AUC above 0.8 to rule out GERD or rule in eosinophilic esophagitis) while adding 2-3 minutes of procedure time. One patient was admitted for chest pain after use of the device but was discharged without complication, and the authors caution against use in severe fibrostenotic disease.
While work to refine a clinical prediction model with this technology is ongoing, the promise of diagnosing and following common esophageal conditions of GERD and eosinophilic esophagitis during endoscopy would have clear value in expediting care and enhancing compliance with treatment.
Eric D. Shah, MD, MBA, is assistant professor of medicine, director of gastrointestinal motility, esophageal, and swallowing disorders center, Geisel School of Medicine, Dartmouth College, Hanover, N.H. He has no disclosures.
Evaluating esophageal disorders such as GERD or eosinophilic esophagitis can be time consuming for patients in clinical practice and requires multiple visits to complete testing and obtain results. Other than visualizing complications of reflux such as erosive esophagitis or Barrett’s esophagus, there has been no immediate option to diagnose GERD in standard practice during routine endoscopy. Furthermore, the decision to pursue long-term medication or surgery for GERD relies on a brief pH assessment to be truly representative of a patient’s everyday symptoms. Follow-up of eosinophilic esophagitis requires repeated upper endoscopies with biopsies after every incremental change in medication or diet, which unsurprisingly, can reduce compliance with ongoing management for what is often a readily treatable condition.
Both GERD and eosinophilic esophagitis can be characterized by changes in esophageal mucosal impedance. Rather than directly measuring the pH or eosinophil counts, Dr. Patel and associates prospectively validated the diagnostic test performance of an add-on endoscopic mucosal impedance device that might enable the gastroenterologist to rule out GERD or rule in eosinophilic esophagitis during the index endoscopy with reasonable accuracy (AUC above 0.8 to rule out GERD or rule in eosinophilic esophagitis) while adding 2-3 minutes of procedure time. One patient was admitted for chest pain after use of the device but was discharged without complication, and the authors caution against use in severe fibrostenotic disease.
While work to refine a clinical prediction model with this technology is ongoing, the promise of diagnosing and following common esophageal conditions of GERD and eosinophilic esophagitis during endoscopy would have clear value in expediting care and enhancing compliance with treatment.
Eric D. Shah, MD, MBA, is assistant professor of medicine, director of gastrointestinal motility, esophageal, and swallowing disorders center, Geisel School of Medicine, Dartmouth College, Hanover, N.H. He has no disclosures.
Evaluating esophageal disorders such as GERD or eosinophilic esophagitis can be time consuming for patients in clinical practice and requires multiple visits to complete testing and obtain results. Other than visualizing complications of reflux such as erosive esophagitis or Barrett’s esophagus, there has been no immediate option to diagnose GERD in standard practice during routine endoscopy. Furthermore, the decision to pursue long-term medication or surgery for GERD relies on a brief pH assessment to be truly representative of a patient’s everyday symptoms. Follow-up of eosinophilic esophagitis requires repeated upper endoscopies with biopsies after every incremental change in medication or diet, which unsurprisingly, can reduce compliance with ongoing management for what is often a readily treatable condition.
Both GERD and eosinophilic esophagitis can be characterized by changes in esophageal mucosal impedance. Rather than directly measuring the pH or eosinophil counts, Dr. Patel and associates prospectively validated the diagnostic test performance of an add-on endoscopic mucosal impedance device that might enable the gastroenterologist to rule out GERD or rule in eosinophilic esophagitis during the index endoscopy with reasonable accuracy (AUC above 0.8 to rule out GERD or rule in eosinophilic esophagitis) while adding 2-3 minutes of procedure time. One patient was admitted for chest pain after use of the device but was discharged without complication, and the authors caution against use in severe fibrostenotic disease.
While work to refine a clinical prediction model with this technology is ongoing, the promise of diagnosing and following common esophageal conditions of GERD and eosinophilic esophagitis during endoscopy would have clear value in expediting care and enhancing compliance with treatment.
Eric D. Shah, MD, MBA, is assistant professor of medicine, director of gastrointestinal motility, esophageal, and swallowing disorders center, Geisel School of Medicine, Dartmouth College, Hanover, N.H. He has no disclosures.
.
Source: American Gastroenterological Association
Each group showed a significantly different (P less than .01) pattern of mucosal impedance (MI), or disruption of mucosal integrity, along the esophageal axis, wrote Dhyanesh A. Patel, MD, of Vanderbilt University Medical Center in Nashville, Tenn., and his associates. Patients without GERD had higher MI values along all esophageal segments, while GERD was characterized by below-normal values in the distal esophagus only, and eosinophilic esophagitis led to low values throughout the esophagus.
The findings were validated in a separate patient cohort, and the only reported adverse event was an episode of mild chest pain. “This contour heatmap could easily be employed to establish a diagnosis during endoscopy, independent of biopsy or pH monitoring,” the investigators wrote in Gastroenterology. They cautioned that the balloon catheter cannot be safely used in patients with severe fibrostenotic disease.
Current definitive diagnostics for GERD leave much to be desired. Transnasal probes are imprecise and uncomfortable, and they can be insensitive if discomfort causes patients to vary normal activity or skip meals. Wireless ambulatory pH monitoring is more tolerable but unreliable and measures only acidity of refluxed material at a single point along the esophagus. These tests also “fail to account for day-to-day variability of reflux, as they only provide a 24- to 48-hour snapshot of a disease process that is chronic in nature,” the researchers wrote. Eosinophilic esophagitis is becoming more common and usually requires proximal and distal biopsies for diagnosis.
Mucosal impedance contour pattern testing is based on the fact that both GERD and eosinophilic esophagitis involve increased distance between esophageal epithelial cells. The amount of intercellular dilatation correlates inversely with MI values. In proof-of-concept studies, individuals with GERD, non-GERD, eosinophilic esophagitis, and achalasia had distinct MI patterns. However, these studies tested a single-channel catheter system that took only point measurements and was subject to interoperator variability. To improve on this concept, Dr. Patel and his associates mounted radial and axial sensors on a balloon catheter to measure MI at 180-degree intervals along a 10-cm esophageal segment.
They tested the new device prospectively in 69 patients undergoing esophagogastroduodenoscopy with or without pH monitoring (which was used as the standard). In all, 24 patients had GERD, 21 had eosinophilic esophagitis, and 24 had normal findings. By using the intercept and slope of the balloon MI measurements, the researchers detected GERD with an area under the receiver operating characteristic curve (AUC) of 0.67, eosinophilic esophagitis with an AUC of 0.84, and non-GERD with an AUC of 0.83.
These findings held up in a separate validation cohort of 36 patients (28 with GERD and eight with eosinophilic esophagitis) from three tertiary care centers. The probability of eosinophilic esophagitis was highest in patients with low distal MI values (that is, a low intercept) and a low slope (showing that MI values remained low proximally). A low distal MI intercept with a steeper positive slope suggested GERD, while a higher distal MI intercept with a steep slope signified non-GERD.
The system “potentially obviates the need for 24- to 48-hour ambulatory wireless pH monitoring or esophageal biopsies for histopathology,” the researchers concluded. “This can help reduce diagnostic and treatment latency and might allow for monitoring disease activity over time.”
The National Institutes of Health funded the external validation analysis. Diversatek Healthcare, which patented the device together with Vanderbilt University, gave research funding to four coinvestigators, including the senior author. Dr. Patel and the other five coinvestigators reported having no conflicts of interest.
SOURCE: Patel DA et al. Gastroenterology. 2019 Jan 31. doi: 10.1053/j.gastro.2019.01.253.
.
Source: American Gastroenterological Association
Each group showed a significantly different (P less than .01) pattern of mucosal impedance (MI), or disruption of mucosal integrity, along the esophageal axis, wrote Dhyanesh A. Patel, MD, of Vanderbilt University Medical Center in Nashville, Tenn., and his associates. Patients without GERD had higher MI values along all esophageal segments, while GERD was characterized by below-normal values in the distal esophagus only, and eosinophilic esophagitis led to low values throughout the esophagus.
The findings were validated in a separate patient cohort, and the only reported adverse event was an episode of mild chest pain. “This contour heatmap could easily be employed to establish a diagnosis during endoscopy, independent of biopsy or pH monitoring,” the investigators wrote in Gastroenterology. They cautioned that the balloon catheter cannot be safely used in patients with severe fibrostenotic disease.
Current definitive diagnostics for GERD leave much to be desired. Transnasal probes are imprecise and uncomfortable, and they can be insensitive if discomfort causes patients to vary normal activity or skip meals. Wireless ambulatory pH monitoring is more tolerable but unreliable and measures only acidity of refluxed material at a single point along the esophagus. These tests also “fail to account for day-to-day variability of reflux, as they only provide a 24- to 48-hour snapshot of a disease process that is chronic in nature,” the researchers wrote. Eosinophilic esophagitis is becoming more common and usually requires proximal and distal biopsies for diagnosis.
Mucosal impedance contour pattern testing is based on the fact that both GERD and eosinophilic esophagitis involve increased distance between esophageal epithelial cells. The amount of intercellular dilatation correlates inversely with MI values. In proof-of-concept studies, individuals with GERD, non-GERD, eosinophilic esophagitis, and achalasia had distinct MI patterns. However, these studies tested a single-channel catheter system that took only point measurements and was subject to interoperator variability. To improve on this concept, Dr. Patel and his associates mounted radial and axial sensors on a balloon catheter to measure MI at 180-degree intervals along a 10-cm esophageal segment.
They tested the new device prospectively in 69 patients undergoing esophagogastroduodenoscopy with or without pH monitoring (which was used as the standard). In all, 24 patients had GERD, 21 had eosinophilic esophagitis, and 24 had normal findings. By using the intercept and slope of the balloon MI measurements, the researchers detected GERD with an area under the receiver operating characteristic curve (AUC) of 0.67, eosinophilic esophagitis with an AUC of 0.84, and non-GERD with an AUC of 0.83.
These findings held up in a separate validation cohort of 36 patients (28 with GERD and eight with eosinophilic esophagitis) from three tertiary care centers. The probability of eosinophilic esophagitis was highest in patients with low distal MI values (that is, a low intercept) and a low slope (showing that MI values remained low proximally). A low distal MI intercept with a steeper positive slope suggested GERD, while a higher distal MI intercept with a steep slope signified non-GERD.
The system “potentially obviates the need for 24- to 48-hour ambulatory wireless pH monitoring or esophageal biopsies for histopathology,” the researchers concluded. “This can help reduce diagnostic and treatment latency and might allow for monitoring disease activity over time.”
The National Institutes of Health funded the external validation analysis. Diversatek Healthcare, which patented the device together with Vanderbilt University, gave research funding to four coinvestigators, including the senior author. Dr. Patel and the other five coinvestigators reported having no conflicts of interest.
SOURCE: Patel DA et al. Gastroenterology. 2019 Jan 31. doi: 10.1053/j.gastro.2019.01.253.
FROM GASTROENTEROLOGY
