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Virtual Reality Brings Relief to Hospitalized Patients With Cancer
suggests a new randomized controlled trial.
While both interventions brought some pain relief, VR therapy yielded greater, longer-lasting comfort, reported lead author Hunter Groninger, MD, of MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.
“Investigators have explored immersive VR interventions in cancer populations for a variety of indications including anxiety, depression, fatigue, and procedure‐associated pain, particularly among patients with pediatric cancer and adult breast cancer,” the investigators wrote in Cancer. “Nevertheless, despite growing evidence supporting the efficacy of VR‐delivered interventions for analgesia, few data address its role to mitigate cancer‐related pain specifically.”
To address this knowledge gap, Dr. Groninger and colleagues enrolled 128 adult hospitalized patients with cancer of any kind, all of whom had moderate to severe pain (self-reported score at least 4 out of 10) within the past 24 hours.
Study Methods and Results
Patients were randomized to receive either 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy.
“[The VR therapy] provides noncompetitive experiences in which the user can move around and explore natural environments (e.g., beachscape, forest) from standing, seated, or fixed positions, including within a hospital bed or chair,” the investigators wrote. “We provided over‐the‐ear headphones to assure high sound quality for the experience in the virtual natural environment.”
The two-dimensional intervention, delivered via electronic tablet, featured a meditation with images of natural landscapes and instrumental background music.
“We chose this active control because it is readily available and reflects content similar to relaxation‐focused television channels that are increasingly common in hospital settings,” the investigators noted.
Compared with this more common approach, patients who received VR therapy had significantly greater immediate reduction in pain (mean change in pain score, –1.4 vs –0.7; P = .03). Twenty-four hours later, improvements in the VR group generally persisted, while pain level in the two-dimensional group returned almost to baseline (P = .004). In addition, patients in the VR group reported significantly greater improvements in general distress and pain bothersomeness.
“VR therapies may modulate the pain experience by reducing the level of attention paid to noxious stimuli, thereby suppressing transmission of painful sensations via pain processing pathways to the cerebral cortex, particularly with more active VR experiences compared to passive experiences,” the investigators wrote.
Downsides to Using VR
Although VR brought more benefit, participants in the VR group more often reported difficulty using the intervention compared with those who interacted with an electronic tablet.
Plus, one VR user described mild dizziness that resolved with pharmacologic intervention. Still, approximately 9 out of 10 participants in each group reported willingness to try the intervention again.
Future VR Research
“Virtual reality is a rapidly evolving technology with a wealth of potential patient‐facing applications,” the investigators wrote. “Future studies should explore repeated use, optimal dosing, and impact on VR therapy on opioid analgesic requirements as well as usability testing, VR content preferences and facilitators of analgesia, and barriers and facilitators to use in acute care settings.”
This study was supported by the American Cancer Society. The investigators disclosed no conflicts of interest.
suggests a new randomized controlled trial.
While both interventions brought some pain relief, VR therapy yielded greater, longer-lasting comfort, reported lead author Hunter Groninger, MD, of MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.
“Investigators have explored immersive VR interventions in cancer populations for a variety of indications including anxiety, depression, fatigue, and procedure‐associated pain, particularly among patients with pediatric cancer and adult breast cancer,” the investigators wrote in Cancer. “Nevertheless, despite growing evidence supporting the efficacy of VR‐delivered interventions for analgesia, few data address its role to mitigate cancer‐related pain specifically.”
To address this knowledge gap, Dr. Groninger and colleagues enrolled 128 adult hospitalized patients with cancer of any kind, all of whom had moderate to severe pain (self-reported score at least 4 out of 10) within the past 24 hours.
Study Methods and Results
Patients were randomized to receive either 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy.
“[The VR therapy] provides noncompetitive experiences in which the user can move around and explore natural environments (e.g., beachscape, forest) from standing, seated, or fixed positions, including within a hospital bed or chair,” the investigators wrote. “We provided over‐the‐ear headphones to assure high sound quality for the experience in the virtual natural environment.”
The two-dimensional intervention, delivered via electronic tablet, featured a meditation with images of natural landscapes and instrumental background music.
“We chose this active control because it is readily available and reflects content similar to relaxation‐focused television channels that are increasingly common in hospital settings,” the investigators noted.
Compared with this more common approach, patients who received VR therapy had significantly greater immediate reduction in pain (mean change in pain score, –1.4 vs –0.7; P = .03). Twenty-four hours later, improvements in the VR group generally persisted, while pain level in the two-dimensional group returned almost to baseline (P = .004). In addition, patients in the VR group reported significantly greater improvements in general distress and pain bothersomeness.
“VR therapies may modulate the pain experience by reducing the level of attention paid to noxious stimuli, thereby suppressing transmission of painful sensations via pain processing pathways to the cerebral cortex, particularly with more active VR experiences compared to passive experiences,” the investigators wrote.
Downsides to Using VR
Although VR brought more benefit, participants in the VR group more often reported difficulty using the intervention compared with those who interacted with an electronic tablet.
Plus, one VR user described mild dizziness that resolved with pharmacologic intervention. Still, approximately 9 out of 10 participants in each group reported willingness to try the intervention again.
Future VR Research
“Virtual reality is a rapidly evolving technology with a wealth of potential patient‐facing applications,” the investigators wrote. “Future studies should explore repeated use, optimal dosing, and impact on VR therapy on opioid analgesic requirements as well as usability testing, VR content preferences and facilitators of analgesia, and barriers and facilitators to use in acute care settings.”
This study was supported by the American Cancer Society. The investigators disclosed no conflicts of interest.
suggests a new randomized controlled trial.
While both interventions brought some pain relief, VR therapy yielded greater, longer-lasting comfort, reported lead author Hunter Groninger, MD, of MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.
“Investigators have explored immersive VR interventions in cancer populations for a variety of indications including anxiety, depression, fatigue, and procedure‐associated pain, particularly among patients with pediatric cancer and adult breast cancer,” the investigators wrote in Cancer. “Nevertheless, despite growing evidence supporting the efficacy of VR‐delivered interventions for analgesia, few data address its role to mitigate cancer‐related pain specifically.”
To address this knowledge gap, Dr. Groninger and colleagues enrolled 128 adult hospitalized patients with cancer of any kind, all of whom had moderate to severe pain (self-reported score at least 4 out of 10) within the past 24 hours.
Study Methods and Results
Patients were randomized to receive either 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy.
“[The VR therapy] provides noncompetitive experiences in which the user can move around and explore natural environments (e.g., beachscape, forest) from standing, seated, or fixed positions, including within a hospital bed or chair,” the investigators wrote. “We provided over‐the‐ear headphones to assure high sound quality for the experience in the virtual natural environment.”
The two-dimensional intervention, delivered via electronic tablet, featured a meditation with images of natural landscapes and instrumental background music.
“We chose this active control because it is readily available and reflects content similar to relaxation‐focused television channels that are increasingly common in hospital settings,” the investigators noted.
Compared with this more common approach, patients who received VR therapy had significantly greater immediate reduction in pain (mean change in pain score, –1.4 vs –0.7; P = .03). Twenty-four hours later, improvements in the VR group generally persisted, while pain level in the two-dimensional group returned almost to baseline (P = .004). In addition, patients in the VR group reported significantly greater improvements in general distress and pain bothersomeness.
“VR therapies may modulate the pain experience by reducing the level of attention paid to noxious stimuli, thereby suppressing transmission of painful sensations via pain processing pathways to the cerebral cortex, particularly with more active VR experiences compared to passive experiences,” the investigators wrote.
Downsides to Using VR
Although VR brought more benefit, participants in the VR group more often reported difficulty using the intervention compared with those who interacted with an electronic tablet.
Plus, one VR user described mild dizziness that resolved with pharmacologic intervention. Still, approximately 9 out of 10 participants in each group reported willingness to try the intervention again.
Future VR Research
“Virtual reality is a rapidly evolving technology with a wealth of potential patient‐facing applications,” the investigators wrote. “Future studies should explore repeated use, optimal dosing, and impact on VR therapy on opioid analgesic requirements as well as usability testing, VR content preferences and facilitators of analgesia, and barriers and facilitators to use in acute care settings.”
This study was supported by the American Cancer Society. The investigators disclosed no conflicts of interest.
FROM CANCER
Should Opioids Be Used for Chronic Cancer Pain?
from legal concerns to threats of violence, say the authors of new research.
These findings suggest that evidence-based, systematic guidance is needed to steer opioid usage in cancer survivorship, wrote lead author Hailey W. Bulls, PhD, of the University of Pittsburgh, and colleagues.
“Prescription opioids are considered the standard of care to treat moderate to severe cancer pain during active treatment, yet guidance in the posttreatment survivorship phase is much less clear,” the investigators wrote. “Existing clinical resources recognize that opioid prescribing in survivorship is complex and nuanced and that the relative benefits and risks in this population are not fully understood.”
Who Should Manage Chronic Cancer Pain?
Despite the knowledge gap, survivors are typically excluded from long-term opioid use studies, leaving providers in a largely data-free zone. Simultaneously, patients who had been receiving focused care during their cancer treatment find themselves with an ill-defined health care team.
“Without a clear transition of care, survivors may seek pain management services from a variety of specialties, including oncologists, palliative care clinicians, primary care clinicians, and pain management specialists,” the investigators wrote. “However, many clinicians may view pain management to be outside of their skill set and may not be well equipped to handle opioid continuation or deprescribing [or] to manage the potential consequences of long‐term opioid use like side effects, misuse, and/or opioid use disorder.”
What Factors Guide Opioid Prescribing Practices for Chronic Cancer Pain?
To learn more about prescribing practices in this setting, Dr. Bulls and colleagues conducted qualitative interviews with 20 providers representing four specialties: oncology (n = 5), palliative care (n = 8), primary care (n = 5), and pain management (n = 2). Eighteen of these participants were physicians and two were advanced practice providers. Average time in clinical practice was about 16 years.
These interviews yielded three themes.
First, no “medical home” exists for chronic pain management in cancer survivors.
“Although clinicians generally agreed that minimizing the role of opioids in chronic pain management in cancer survivors was desirable, they described a lack of common treatment protocols to guide pain management in survivorship,” the investigators wrote.
Second, the interviews revealed that prescribing strategies are partly driven by peer pressure, sometimes leading to tension between providers and feelings of self-doubt.
“I feel like there’s been this weird judgment thing that’s happened [to] the prescribers,” one primary care provider said during the interview. “Because, when I trained … pain was a vital sign, and we were supposed to treat pain, and now I feel like we’re all being judged for that.”
The third theme revolved around fear of consequences resulting from prescribing practices, including fears of violent repercussions.
“You may not know, but pain specialists have been shot in this country for [refusing to prescribe opioids],” one pain management specialist said during the interview. “There’s been a number of shootings of pain specialists who would not prescribe opioids. So, I mean, there’s real issues of violence.”
Meanwhile, a palliative care provider described legal pressure from the opposite direction:
“I think there’s a lot of fear of litigiousness … and loss of licenses. That sort of makes them pressure us into not prescribing opioids or sticking with a certain number per day that might not be therapeutic for a patient.”
Reflecting on these themes, the investigators identified “a fundamental uncertainty in survivorship pain management.”
What Strategies Might Improve Opioid Prescribing Practices for Chronic Cancer Pain?
After sharing their attitudes about prescribing opioids for chronic cancer pain, the clinicians were asked for suggestions to improve the situation.
They offered four main suggestions: create relevant guidelines, increase education and access to pain management options for clinicians, increase interdisciplinary communication across medical subspecialties, and promote multidisciplinary care in the survivorship setting.
Dr. Bulls and colleagues supported these strategies in their concluding remarks and called for more research.
This study was supported by the National Institute of Drug Abuse, the National Institutes of Health, the National Center for Advancing Translational Sciences, and the National Cancer Institute. The investigators disclosed relationships with Arcadia Health Solutions and Biomotivate.
from legal concerns to threats of violence, say the authors of new research.
These findings suggest that evidence-based, systematic guidance is needed to steer opioid usage in cancer survivorship, wrote lead author Hailey W. Bulls, PhD, of the University of Pittsburgh, and colleagues.
“Prescription opioids are considered the standard of care to treat moderate to severe cancer pain during active treatment, yet guidance in the posttreatment survivorship phase is much less clear,” the investigators wrote. “Existing clinical resources recognize that opioid prescribing in survivorship is complex and nuanced and that the relative benefits and risks in this population are not fully understood.”
Who Should Manage Chronic Cancer Pain?
Despite the knowledge gap, survivors are typically excluded from long-term opioid use studies, leaving providers in a largely data-free zone. Simultaneously, patients who had been receiving focused care during their cancer treatment find themselves with an ill-defined health care team.
“Without a clear transition of care, survivors may seek pain management services from a variety of specialties, including oncologists, palliative care clinicians, primary care clinicians, and pain management specialists,” the investigators wrote. “However, many clinicians may view pain management to be outside of their skill set and may not be well equipped to handle opioid continuation or deprescribing [or] to manage the potential consequences of long‐term opioid use like side effects, misuse, and/or opioid use disorder.”
What Factors Guide Opioid Prescribing Practices for Chronic Cancer Pain?
To learn more about prescribing practices in this setting, Dr. Bulls and colleagues conducted qualitative interviews with 20 providers representing four specialties: oncology (n = 5), palliative care (n = 8), primary care (n = 5), and pain management (n = 2). Eighteen of these participants were physicians and two were advanced practice providers. Average time in clinical practice was about 16 years.
These interviews yielded three themes.
First, no “medical home” exists for chronic pain management in cancer survivors.
“Although clinicians generally agreed that minimizing the role of opioids in chronic pain management in cancer survivors was desirable, they described a lack of common treatment protocols to guide pain management in survivorship,” the investigators wrote.
Second, the interviews revealed that prescribing strategies are partly driven by peer pressure, sometimes leading to tension between providers and feelings of self-doubt.
“I feel like there’s been this weird judgment thing that’s happened [to] the prescribers,” one primary care provider said during the interview. “Because, when I trained … pain was a vital sign, and we were supposed to treat pain, and now I feel like we’re all being judged for that.”
The third theme revolved around fear of consequences resulting from prescribing practices, including fears of violent repercussions.
“You may not know, but pain specialists have been shot in this country for [refusing to prescribe opioids],” one pain management specialist said during the interview. “There’s been a number of shootings of pain specialists who would not prescribe opioids. So, I mean, there’s real issues of violence.”
Meanwhile, a palliative care provider described legal pressure from the opposite direction:
“I think there’s a lot of fear of litigiousness … and loss of licenses. That sort of makes them pressure us into not prescribing opioids or sticking with a certain number per day that might not be therapeutic for a patient.”
Reflecting on these themes, the investigators identified “a fundamental uncertainty in survivorship pain management.”
What Strategies Might Improve Opioid Prescribing Practices for Chronic Cancer Pain?
After sharing their attitudes about prescribing opioids for chronic cancer pain, the clinicians were asked for suggestions to improve the situation.
They offered four main suggestions: create relevant guidelines, increase education and access to pain management options for clinicians, increase interdisciplinary communication across medical subspecialties, and promote multidisciplinary care in the survivorship setting.
Dr. Bulls and colleagues supported these strategies in their concluding remarks and called for more research.
This study was supported by the National Institute of Drug Abuse, the National Institutes of Health, the National Center for Advancing Translational Sciences, and the National Cancer Institute. The investigators disclosed relationships with Arcadia Health Solutions and Biomotivate.
from legal concerns to threats of violence, say the authors of new research.
These findings suggest that evidence-based, systematic guidance is needed to steer opioid usage in cancer survivorship, wrote lead author Hailey W. Bulls, PhD, of the University of Pittsburgh, and colleagues.
“Prescription opioids are considered the standard of care to treat moderate to severe cancer pain during active treatment, yet guidance in the posttreatment survivorship phase is much less clear,” the investigators wrote. “Existing clinical resources recognize that opioid prescribing in survivorship is complex and nuanced and that the relative benefits and risks in this population are not fully understood.”
Who Should Manage Chronic Cancer Pain?
Despite the knowledge gap, survivors are typically excluded from long-term opioid use studies, leaving providers in a largely data-free zone. Simultaneously, patients who had been receiving focused care during their cancer treatment find themselves with an ill-defined health care team.
“Without a clear transition of care, survivors may seek pain management services from a variety of specialties, including oncologists, palliative care clinicians, primary care clinicians, and pain management specialists,” the investigators wrote. “However, many clinicians may view pain management to be outside of their skill set and may not be well equipped to handle opioid continuation or deprescribing [or] to manage the potential consequences of long‐term opioid use like side effects, misuse, and/or opioid use disorder.”
What Factors Guide Opioid Prescribing Practices for Chronic Cancer Pain?
To learn more about prescribing practices in this setting, Dr. Bulls and colleagues conducted qualitative interviews with 20 providers representing four specialties: oncology (n = 5), palliative care (n = 8), primary care (n = 5), and pain management (n = 2). Eighteen of these participants were physicians and two were advanced practice providers. Average time in clinical practice was about 16 years.
These interviews yielded three themes.
First, no “medical home” exists for chronic pain management in cancer survivors.
“Although clinicians generally agreed that minimizing the role of opioids in chronic pain management in cancer survivors was desirable, they described a lack of common treatment protocols to guide pain management in survivorship,” the investigators wrote.
Second, the interviews revealed that prescribing strategies are partly driven by peer pressure, sometimes leading to tension between providers and feelings of self-doubt.
“I feel like there’s been this weird judgment thing that’s happened [to] the prescribers,” one primary care provider said during the interview. “Because, when I trained … pain was a vital sign, and we were supposed to treat pain, and now I feel like we’re all being judged for that.”
The third theme revolved around fear of consequences resulting from prescribing practices, including fears of violent repercussions.
“You may not know, but pain specialists have been shot in this country for [refusing to prescribe opioids],” one pain management specialist said during the interview. “There’s been a number of shootings of pain specialists who would not prescribe opioids. So, I mean, there’s real issues of violence.”
Meanwhile, a palliative care provider described legal pressure from the opposite direction:
“I think there’s a lot of fear of litigiousness … and loss of licenses. That sort of makes them pressure us into not prescribing opioids or sticking with a certain number per day that might not be therapeutic for a patient.”
Reflecting on these themes, the investigators identified “a fundamental uncertainty in survivorship pain management.”
What Strategies Might Improve Opioid Prescribing Practices for Chronic Cancer Pain?
After sharing their attitudes about prescribing opioids for chronic cancer pain, the clinicians were asked for suggestions to improve the situation.
They offered four main suggestions: create relevant guidelines, increase education and access to pain management options for clinicians, increase interdisciplinary communication across medical subspecialties, and promote multidisciplinary care in the survivorship setting.
Dr. Bulls and colleagues supported these strategies in their concluding remarks and called for more research.
This study was supported by the National Institute of Drug Abuse, the National Institutes of Health, the National Center for Advancing Translational Sciences, and the National Cancer Institute. The investigators disclosed relationships with Arcadia Health Solutions and Biomotivate.
FROM CANCER
Computer-Aided Colonoscopy Falls Short in Real-World Practice
, according to investigators.
Although CADe did not increase burden of colonoscopy in the real-world, these real-world detection rates casts doubt on the generalizability of positive findings from randomized trials, reported lead author Harsh K. Patel, MD, of the University of Kansas Medical Center, Kansas City, Missouri, and colleagues.
CADe-assisted colonoscopy has gained increasing attention for its potential to improve ADR, particularly with the recent publication of a meta-analysis involving 20 randomized controlled trials (RCTs), Dr. Patel and colleagues wrote in Clinical Gastroenterology and Hepatology. “However, results of RCTs are not necessarily reproducible in clinical practice.”
RCTs evaluating this technology are susceptible to various issues with validity, they noted, such as psychological bias stemming from lack of blinding to the possibility that CADe could reduce operator attention, paradoxically “deskilling” endoscopists.
The present meta-analysis aimed to overcome these potential shortfalls by analyzing nonrandomized data from eight studies involving 9,782 patients.
“The lack of a highly controlled setting reduces the psychological pressure of the endoscopists to demonstrate a possible benefit of CADe (i.e., the operator bias) and allows endoscopists to use CADe according to their preferences and attitudes which we usually experience in a real-world clinical practice,” the investigators wrote. “On the other hand, noncontrolled factors may affect the outcome of the study, especially when considering that an equivalent distribution of prevalence of disease is required for a fair assessment of the effectiveness of the intervention.”
This approach revealed less favorable outcomes than those reported by RCTs.
CADe-assisted ADR was not significantly different from ADR for standard colonoscopy (44% vs 38%; risk ratio, 1.11; 95% CI, 0.97-1.28), nor was mean number of adenomas detected per colonoscopy (0.93 vs 0.79; mean difference, 0.14; 95% CI, -0.04-0.32).
“Our study provides a contrasting perspective to those results previously known from the randomized studies,” the investigators wrote.
While detection benefits were not identified, burden of CADe-assisted colonoscopy was not elevated either.
Mean nonneoplastic lesions per colonoscopy was similar between modalities (0.52 vs 0.47; mean difference, 0.14; 95% CI, -0.07-0.34), as was withdrawal time (14.3 vs 13.4 minutes; mean difference, 0.8 minutes; 95% CI, -0.18-1.90).
Dr. Patel and colleagues described “a high level of heterogeneity that was qualitatively and quantitatively distinct from the heterogeneity discovered in the prior meta-analysis of RCTs.” Unlike the RCT meta-analysis, which had no studies with an ADR outcome favoring the control arm, the present meta-analysis found that one third of the included studies favored the control arm.
“This qualitative difference generates a much higher degree of ambiguity, as it does not apply only to the magnitude of the effect of CADe, but it puts in question the actual existence of any CADe-related benefit,” they wrote. “An important point to make is that the analysis of adenoma and serrated lesions per colonoscopy supported the qualitative heterogeneity, favoring the control arm over the CADe arm, in the direction of the effect.”
Dr. Patel and colleagues suggested that the concurrent lack of benefit and lack of harm associated with CADe in the present meta-analysis is “interesting,” and may point to underutilization or a lack of effect of CADe.
“To address the uncertainties in the current literature, we recommend conducting additional randomized studies in a more pragmatic setting,” they concluded.
This meta-analysis was supported by the European Commission and AIRC. The investigators disclosed relationships with NEC, Satisfy, Odin, and others.
The advent of AI in colonoscopy through computer-aided detection (CADe) systems has been promising, with over 20 randomized controlled trials (RCTs) affirming its benefits. However, this enthusiasm has been tempered by several recent nonrandomized studies indicating no real-world advantage, as discussed in Patel et al.’s systematic review and meta-analysis in Clinical Gastroenterology and Hepatology.
In addition, a critical consideration with evaluating any AI/CADe system is they often undergo frequent updates, each promising improved accuracy, sensitivity, and specificity. This is an interesting dilemma and raises questions about the enduring relevance of studies conducted using outdated versions of CADe.
In my opinion, the jury is still out on the effectiveness of CADe for colonoscopy in a real-world setting. The definitive assessment of CADe’s real-world value necessitates larger, well-structured trials that mirror actual clinical environments and span extended periods of time, taking care to minimize biases that may have influenced the results of current published studies.
Nabil M. Mansour, MD, is assistant professor of medicine in the Section of Gastroenterology, Baylor College of Medicine, Houston. He has served as a consultant for Iterative Health.
The advent of AI in colonoscopy through computer-aided detection (CADe) systems has been promising, with over 20 randomized controlled trials (RCTs) affirming its benefits. However, this enthusiasm has been tempered by several recent nonrandomized studies indicating no real-world advantage, as discussed in Patel et al.’s systematic review and meta-analysis in Clinical Gastroenterology and Hepatology.
In addition, a critical consideration with evaluating any AI/CADe system is they often undergo frequent updates, each promising improved accuracy, sensitivity, and specificity. This is an interesting dilemma and raises questions about the enduring relevance of studies conducted using outdated versions of CADe.
In my opinion, the jury is still out on the effectiveness of CADe for colonoscopy in a real-world setting. The definitive assessment of CADe’s real-world value necessitates larger, well-structured trials that mirror actual clinical environments and span extended periods of time, taking care to minimize biases that may have influenced the results of current published studies.
Nabil M. Mansour, MD, is assistant professor of medicine in the Section of Gastroenterology, Baylor College of Medicine, Houston. He has served as a consultant for Iterative Health.
The advent of AI in colonoscopy through computer-aided detection (CADe) systems has been promising, with over 20 randomized controlled trials (RCTs) affirming its benefits. However, this enthusiasm has been tempered by several recent nonrandomized studies indicating no real-world advantage, as discussed in Patel et al.’s systematic review and meta-analysis in Clinical Gastroenterology and Hepatology.
In addition, a critical consideration with evaluating any AI/CADe system is they often undergo frequent updates, each promising improved accuracy, sensitivity, and specificity. This is an interesting dilemma and raises questions about the enduring relevance of studies conducted using outdated versions of CADe.
In my opinion, the jury is still out on the effectiveness of CADe for colonoscopy in a real-world setting. The definitive assessment of CADe’s real-world value necessitates larger, well-structured trials that mirror actual clinical environments and span extended periods of time, taking care to minimize biases that may have influenced the results of current published studies.
Nabil M. Mansour, MD, is assistant professor of medicine in the Section of Gastroenterology, Baylor College of Medicine, Houston. He has served as a consultant for Iterative Health.
, according to investigators.
Although CADe did not increase burden of colonoscopy in the real-world, these real-world detection rates casts doubt on the generalizability of positive findings from randomized trials, reported lead author Harsh K. Patel, MD, of the University of Kansas Medical Center, Kansas City, Missouri, and colleagues.
CADe-assisted colonoscopy has gained increasing attention for its potential to improve ADR, particularly with the recent publication of a meta-analysis involving 20 randomized controlled trials (RCTs), Dr. Patel and colleagues wrote in Clinical Gastroenterology and Hepatology. “However, results of RCTs are not necessarily reproducible in clinical practice.”
RCTs evaluating this technology are susceptible to various issues with validity, they noted, such as psychological bias stemming from lack of blinding to the possibility that CADe could reduce operator attention, paradoxically “deskilling” endoscopists.
The present meta-analysis aimed to overcome these potential shortfalls by analyzing nonrandomized data from eight studies involving 9,782 patients.
“The lack of a highly controlled setting reduces the psychological pressure of the endoscopists to demonstrate a possible benefit of CADe (i.e., the operator bias) and allows endoscopists to use CADe according to their preferences and attitudes which we usually experience in a real-world clinical practice,” the investigators wrote. “On the other hand, noncontrolled factors may affect the outcome of the study, especially when considering that an equivalent distribution of prevalence of disease is required for a fair assessment of the effectiveness of the intervention.”
This approach revealed less favorable outcomes than those reported by RCTs.
CADe-assisted ADR was not significantly different from ADR for standard colonoscopy (44% vs 38%; risk ratio, 1.11; 95% CI, 0.97-1.28), nor was mean number of adenomas detected per colonoscopy (0.93 vs 0.79; mean difference, 0.14; 95% CI, -0.04-0.32).
“Our study provides a contrasting perspective to those results previously known from the randomized studies,” the investigators wrote.
While detection benefits were not identified, burden of CADe-assisted colonoscopy was not elevated either.
Mean nonneoplastic lesions per colonoscopy was similar between modalities (0.52 vs 0.47; mean difference, 0.14; 95% CI, -0.07-0.34), as was withdrawal time (14.3 vs 13.4 minutes; mean difference, 0.8 minutes; 95% CI, -0.18-1.90).
Dr. Patel and colleagues described “a high level of heterogeneity that was qualitatively and quantitatively distinct from the heterogeneity discovered in the prior meta-analysis of RCTs.” Unlike the RCT meta-analysis, which had no studies with an ADR outcome favoring the control arm, the present meta-analysis found that one third of the included studies favored the control arm.
“This qualitative difference generates a much higher degree of ambiguity, as it does not apply only to the magnitude of the effect of CADe, but it puts in question the actual existence of any CADe-related benefit,” they wrote. “An important point to make is that the analysis of adenoma and serrated lesions per colonoscopy supported the qualitative heterogeneity, favoring the control arm over the CADe arm, in the direction of the effect.”
Dr. Patel and colleagues suggested that the concurrent lack of benefit and lack of harm associated with CADe in the present meta-analysis is “interesting,” and may point to underutilization or a lack of effect of CADe.
“To address the uncertainties in the current literature, we recommend conducting additional randomized studies in a more pragmatic setting,” they concluded.
This meta-analysis was supported by the European Commission and AIRC. The investigators disclosed relationships with NEC, Satisfy, Odin, and others.
, according to investigators.
Although CADe did not increase burden of colonoscopy in the real-world, these real-world detection rates casts doubt on the generalizability of positive findings from randomized trials, reported lead author Harsh K. Patel, MD, of the University of Kansas Medical Center, Kansas City, Missouri, and colleagues.
CADe-assisted colonoscopy has gained increasing attention for its potential to improve ADR, particularly with the recent publication of a meta-analysis involving 20 randomized controlled trials (RCTs), Dr. Patel and colleagues wrote in Clinical Gastroenterology and Hepatology. “However, results of RCTs are not necessarily reproducible in clinical practice.”
RCTs evaluating this technology are susceptible to various issues with validity, they noted, such as psychological bias stemming from lack of blinding to the possibility that CADe could reduce operator attention, paradoxically “deskilling” endoscopists.
The present meta-analysis aimed to overcome these potential shortfalls by analyzing nonrandomized data from eight studies involving 9,782 patients.
“The lack of a highly controlled setting reduces the psychological pressure of the endoscopists to demonstrate a possible benefit of CADe (i.e., the operator bias) and allows endoscopists to use CADe according to their preferences and attitudes which we usually experience in a real-world clinical practice,” the investigators wrote. “On the other hand, noncontrolled factors may affect the outcome of the study, especially when considering that an equivalent distribution of prevalence of disease is required for a fair assessment of the effectiveness of the intervention.”
This approach revealed less favorable outcomes than those reported by RCTs.
CADe-assisted ADR was not significantly different from ADR for standard colonoscopy (44% vs 38%; risk ratio, 1.11; 95% CI, 0.97-1.28), nor was mean number of adenomas detected per colonoscopy (0.93 vs 0.79; mean difference, 0.14; 95% CI, -0.04-0.32).
“Our study provides a contrasting perspective to those results previously known from the randomized studies,” the investigators wrote.
While detection benefits were not identified, burden of CADe-assisted colonoscopy was not elevated either.
Mean nonneoplastic lesions per colonoscopy was similar between modalities (0.52 vs 0.47; mean difference, 0.14; 95% CI, -0.07-0.34), as was withdrawal time (14.3 vs 13.4 minutes; mean difference, 0.8 minutes; 95% CI, -0.18-1.90).
Dr. Patel and colleagues described “a high level of heterogeneity that was qualitatively and quantitatively distinct from the heterogeneity discovered in the prior meta-analysis of RCTs.” Unlike the RCT meta-analysis, which had no studies with an ADR outcome favoring the control arm, the present meta-analysis found that one third of the included studies favored the control arm.
“This qualitative difference generates a much higher degree of ambiguity, as it does not apply only to the magnitude of the effect of CADe, but it puts in question the actual existence of any CADe-related benefit,” they wrote. “An important point to make is that the analysis of adenoma and serrated lesions per colonoscopy supported the qualitative heterogeneity, favoring the control arm over the CADe arm, in the direction of the effect.”
Dr. Patel and colleagues suggested that the concurrent lack of benefit and lack of harm associated with CADe in the present meta-analysis is “interesting,” and may point to underutilization or a lack of effect of CADe.
“To address the uncertainties in the current literature, we recommend conducting additional randomized studies in a more pragmatic setting,” they concluded.
This meta-analysis was supported by the European Commission and AIRC. The investigators disclosed relationships with NEC, Satisfy, Odin, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Most Cancer Trial Centers Located Closer to White, Affluent Populations
This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.
“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”
Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.
“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.
To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.
These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).
The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.
“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.
The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.
In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.
“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”
A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.
This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.
“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”
Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.
“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.
To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.
These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).
The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.
“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.
The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.
In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.
“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”
A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.
This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.
“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”
Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.
“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.
To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.
These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).
The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.
“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.
The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.
In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.
“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”
A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.
FROM JAMA ONCOLOGY
IBS Placebo Responses Predicted By Patient Beliefs, Relationship with Provider
, according to investigators.
These findings may improve prediction of placebo responses in IBS, and may help avoid patient-provider “mismatch,” both of which can alter treatment outcomes and confound clinical trial findings, reported lead author Jeffrey M. Lackner, PsyD, chief of the division of behavioral medicine at the University of Buffalo, New York, and colleagues.
“A relatively large (40%) placebo response in IBS trials obscures potentially useful, mechanistic, and pharmacodynamically induced symptom changes among agents that do reach market,” the investigators wrote in Gastro Hep Advances. “This begs the question of what individual difference factors distinguish placebo responders.”
While previous studies have explored placebo patient predictors in IBS, most focused on study design and baseline personal characteristics such as age and sex, with none yielding prognostically reliable findings, according to Dr. Lackner and colleagues. Mid-treatment factors such as patient-provider dynamics have not been featured in published meta-analyses, they noted, despite their potential importance.
“This limitation partly reflects the demands of efficacy trials that prioritize pre- and posttreatment data over that collected during acute phase, when the putative mechanisms underpinning placebo effects play out,” the investigators wrote. “The expectation that one can benefit from a treatment, for example, is optimally assessed after its rationale is delivered but before a clinically thorough regimen is provided, meaning that it cannot be fruitfully assessed at baseline along with other personal characteristics when treatment rationale is not fully disclosed. The same applies to relational factors such as patient-physician interactions that define the context where treatment is delivered, and placebo response presumably incubates.”
To explore the above factors, Dr. Lackner and colleagues conducted a secondary analysis of 145 patients with Rome III-diagnosed IBS from the Irritable Bowel Syndrome Outcome Study.
During the study, patients were randomized to receive either 10 sessions of clinic-based cognitive behavioral therapy (CBT), 4 sessions of minimal-contact CBT, or 4 sessions of supportive counseling and education without any prescribed behavior changes. Responses were measured by the IBS version of the Clinical Global Improvement Scale, with evaluations conducted at the treatment midpoint and 2 weeks after treatment.
Candidate predictors at baseline included pain catastrophizing, somatization, emotion regulation, neuroticism, stress, and others, while clinical factors included treatment expectancy/credibility and patient-provider relationship.
Responses during treatment were significantly associated with lower somatization and stress level at baseline, as well as greater patient-provider agreement on treatment tasks (P less than .001).
Posttreatment responses were significantly associated with baseline gastroenterologist-rated IBS severity, anxiety, agreement that the patient and the provider shared goals from a provider perspective, and ability to reframe stressful events in a positive light (P less than .001). That ability to reconsider emotions was also associated with a faster placebo response (P = .011).
“The strength of placebo responsiveness is subject to the influence of patient factors that precede treatment delivery (rethinking or reinterpreting stressful situations in everyday life in a way that reduces their subsequent impact) and specific elements of provider-patient interactions that occur while treatment is delivered, particularly practitioners’ estimation that patients agree on their goals and tasks to achieve them,” Dr. Lackner and colleagues concluded. “We believe this line of research can help identify factors that drive placebo response and narrow the patient-provider ‘mismatch’ that undermines the quality, satisfaction, and efficiency of IBS care regardless of what treatment is delivered.”
The study was supported by the NIH. The investigators disclosed no conflicts of interest.
Irritable bowel syndrome (IBS) is associated with impaired functioning and work or school absenteeism. Current treatments are suboptimal and there is a need for improved management strategies. A challenge in designing trials can be placebo response. Placebo can also be a treatment modality with approximately 40% response in adults and children with IBS. The study by Lackner et al. provides predictors of the magnitude, and timing of placebo response. Accordingly, certain behaviors and strategies adopted by patients and clinicians in addition to pharmacotherapy can harness greater clinical improvements.
While patient factors such as stress levels, somatization, and anxiety played a role in predicting rapid and delayed placebo response, an interesting domain was “cognitive reappraisal,” the ability to alter the impact of stressful events by reframing unpleasantness toward them. This was associated with greater global improvement post treatment and differed between rapid and delayed responders. Cognitive reappraisal has shown changes in the limbic system such as activation of the prefrontal cortex like placebo analgesia. Thus, optimal introduction of treatments to patients may be important to maximize the cognitive appraisal abilities, enhance expectation effects, and improve treatment outcomes. Similarly, minimizing nocebo effects may be equally important to decrease side effects.
The agreement between patients and clinicians on treatment goals and tasks also predicted response. Thus, developing thorough treatment goals beforehand could be crucial to sustain treatment responses. For example, improved functioning may be a goal to agree upon rather than symptom reduction alone before commencement of treatment. Similarly, shared decision-making during treatment may have a tremendous influence on favorable outcomes.
Neha Santucci, MD, MBBS, is director of the Disorders of Gut-Brain Interaction Program at the Neurogastroenterology and Motility Center, Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, and associate professor of pediatrics, University of Cincinnati College of Medicine.
Irritable bowel syndrome (IBS) is associated with impaired functioning and work or school absenteeism. Current treatments are suboptimal and there is a need for improved management strategies. A challenge in designing trials can be placebo response. Placebo can also be a treatment modality with approximately 40% response in adults and children with IBS. The study by Lackner et al. provides predictors of the magnitude, and timing of placebo response. Accordingly, certain behaviors and strategies adopted by patients and clinicians in addition to pharmacotherapy can harness greater clinical improvements.
While patient factors such as stress levels, somatization, and anxiety played a role in predicting rapid and delayed placebo response, an interesting domain was “cognitive reappraisal,” the ability to alter the impact of stressful events by reframing unpleasantness toward them. This was associated with greater global improvement post treatment and differed between rapid and delayed responders. Cognitive reappraisal has shown changes in the limbic system such as activation of the prefrontal cortex like placebo analgesia. Thus, optimal introduction of treatments to patients may be important to maximize the cognitive appraisal abilities, enhance expectation effects, and improve treatment outcomes. Similarly, minimizing nocebo effects may be equally important to decrease side effects.
The agreement between patients and clinicians on treatment goals and tasks also predicted response. Thus, developing thorough treatment goals beforehand could be crucial to sustain treatment responses. For example, improved functioning may be a goal to agree upon rather than symptom reduction alone before commencement of treatment. Similarly, shared decision-making during treatment may have a tremendous influence on favorable outcomes.
Neha Santucci, MD, MBBS, is director of the Disorders of Gut-Brain Interaction Program at the Neurogastroenterology and Motility Center, Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, and associate professor of pediatrics, University of Cincinnati College of Medicine.
Irritable bowel syndrome (IBS) is associated with impaired functioning and work or school absenteeism. Current treatments are suboptimal and there is a need for improved management strategies. A challenge in designing trials can be placebo response. Placebo can also be a treatment modality with approximately 40% response in adults and children with IBS. The study by Lackner et al. provides predictors of the magnitude, and timing of placebo response. Accordingly, certain behaviors and strategies adopted by patients and clinicians in addition to pharmacotherapy can harness greater clinical improvements.
While patient factors such as stress levels, somatization, and anxiety played a role in predicting rapid and delayed placebo response, an interesting domain was “cognitive reappraisal,” the ability to alter the impact of stressful events by reframing unpleasantness toward them. This was associated with greater global improvement post treatment and differed between rapid and delayed responders. Cognitive reappraisal has shown changes in the limbic system such as activation of the prefrontal cortex like placebo analgesia. Thus, optimal introduction of treatments to patients may be important to maximize the cognitive appraisal abilities, enhance expectation effects, and improve treatment outcomes. Similarly, minimizing nocebo effects may be equally important to decrease side effects.
The agreement between patients and clinicians on treatment goals and tasks also predicted response. Thus, developing thorough treatment goals beforehand could be crucial to sustain treatment responses. For example, improved functioning may be a goal to agree upon rather than symptom reduction alone before commencement of treatment. Similarly, shared decision-making during treatment may have a tremendous influence on favorable outcomes.
Neha Santucci, MD, MBBS, is director of the Disorders of Gut-Brain Interaction Program at the Neurogastroenterology and Motility Center, Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, and associate professor of pediatrics, University of Cincinnati College of Medicine.
, according to investigators.
These findings may improve prediction of placebo responses in IBS, and may help avoid patient-provider “mismatch,” both of which can alter treatment outcomes and confound clinical trial findings, reported lead author Jeffrey M. Lackner, PsyD, chief of the division of behavioral medicine at the University of Buffalo, New York, and colleagues.
“A relatively large (40%) placebo response in IBS trials obscures potentially useful, mechanistic, and pharmacodynamically induced symptom changes among agents that do reach market,” the investigators wrote in Gastro Hep Advances. “This begs the question of what individual difference factors distinguish placebo responders.”
While previous studies have explored placebo patient predictors in IBS, most focused on study design and baseline personal characteristics such as age and sex, with none yielding prognostically reliable findings, according to Dr. Lackner and colleagues. Mid-treatment factors such as patient-provider dynamics have not been featured in published meta-analyses, they noted, despite their potential importance.
“This limitation partly reflects the demands of efficacy trials that prioritize pre- and posttreatment data over that collected during acute phase, when the putative mechanisms underpinning placebo effects play out,” the investigators wrote. “The expectation that one can benefit from a treatment, for example, is optimally assessed after its rationale is delivered but before a clinically thorough regimen is provided, meaning that it cannot be fruitfully assessed at baseline along with other personal characteristics when treatment rationale is not fully disclosed. The same applies to relational factors such as patient-physician interactions that define the context where treatment is delivered, and placebo response presumably incubates.”
To explore the above factors, Dr. Lackner and colleagues conducted a secondary analysis of 145 patients with Rome III-diagnosed IBS from the Irritable Bowel Syndrome Outcome Study.
During the study, patients were randomized to receive either 10 sessions of clinic-based cognitive behavioral therapy (CBT), 4 sessions of minimal-contact CBT, or 4 sessions of supportive counseling and education without any prescribed behavior changes. Responses were measured by the IBS version of the Clinical Global Improvement Scale, with evaluations conducted at the treatment midpoint and 2 weeks after treatment.
Candidate predictors at baseline included pain catastrophizing, somatization, emotion regulation, neuroticism, stress, and others, while clinical factors included treatment expectancy/credibility and patient-provider relationship.
Responses during treatment were significantly associated with lower somatization and stress level at baseline, as well as greater patient-provider agreement on treatment tasks (P less than .001).
Posttreatment responses were significantly associated with baseline gastroenterologist-rated IBS severity, anxiety, agreement that the patient and the provider shared goals from a provider perspective, and ability to reframe stressful events in a positive light (P less than .001). That ability to reconsider emotions was also associated with a faster placebo response (P = .011).
“The strength of placebo responsiveness is subject to the influence of patient factors that precede treatment delivery (rethinking or reinterpreting stressful situations in everyday life in a way that reduces their subsequent impact) and specific elements of provider-patient interactions that occur while treatment is delivered, particularly practitioners’ estimation that patients agree on their goals and tasks to achieve them,” Dr. Lackner and colleagues concluded. “We believe this line of research can help identify factors that drive placebo response and narrow the patient-provider ‘mismatch’ that undermines the quality, satisfaction, and efficiency of IBS care regardless of what treatment is delivered.”
The study was supported by the NIH. The investigators disclosed no conflicts of interest.
, according to investigators.
These findings may improve prediction of placebo responses in IBS, and may help avoid patient-provider “mismatch,” both of which can alter treatment outcomes and confound clinical trial findings, reported lead author Jeffrey M. Lackner, PsyD, chief of the division of behavioral medicine at the University of Buffalo, New York, and colleagues.
“A relatively large (40%) placebo response in IBS trials obscures potentially useful, mechanistic, and pharmacodynamically induced symptom changes among agents that do reach market,” the investigators wrote in Gastro Hep Advances. “This begs the question of what individual difference factors distinguish placebo responders.”
While previous studies have explored placebo patient predictors in IBS, most focused on study design and baseline personal characteristics such as age and sex, with none yielding prognostically reliable findings, according to Dr. Lackner and colleagues. Mid-treatment factors such as patient-provider dynamics have not been featured in published meta-analyses, they noted, despite their potential importance.
“This limitation partly reflects the demands of efficacy trials that prioritize pre- and posttreatment data over that collected during acute phase, when the putative mechanisms underpinning placebo effects play out,” the investigators wrote. “The expectation that one can benefit from a treatment, for example, is optimally assessed after its rationale is delivered but before a clinically thorough regimen is provided, meaning that it cannot be fruitfully assessed at baseline along with other personal characteristics when treatment rationale is not fully disclosed. The same applies to relational factors such as patient-physician interactions that define the context where treatment is delivered, and placebo response presumably incubates.”
To explore the above factors, Dr. Lackner and colleagues conducted a secondary analysis of 145 patients with Rome III-diagnosed IBS from the Irritable Bowel Syndrome Outcome Study.
During the study, patients were randomized to receive either 10 sessions of clinic-based cognitive behavioral therapy (CBT), 4 sessions of minimal-contact CBT, or 4 sessions of supportive counseling and education without any prescribed behavior changes. Responses were measured by the IBS version of the Clinical Global Improvement Scale, with evaluations conducted at the treatment midpoint and 2 weeks after treatment.
Candidate predictors at baseline included pain catastrophizing, somatization, emotion regulation, neuroticism, stress, and others, while clinical factors included treatment expectancy/credibility and patient-provider relationship.
Responses during treatment were significantly associated with lower somatization and stress level at baseline, as well as greater patient-provider agreement on treatment tasks (P less than .001).
Posttreatment responses were significantly associated with baseline gastroenterologist-rated IBS severity, anxiety, agreement that the patient and the provider shared goals from a provider perspective, and ability to reframe stressful events in a positive light (P less than .001). That ability to reconsider emotions was also associated with a faster placebo response (P = .011).
“The strength of placebo responsiveness is subject to the influence of patient factors that precede treatment delivery (rethinking or reinterpreting stressful situations in everyday life in a way that reduces their subsequent impact) and specific elements of provider-patient interactions that occur while treatment is delivered, particularly practitioners’ estimation that patients agree on their goals and tasks to achieve them,” Dr. Lackner and colleagues concluded. “We believe this line of research can help identify factors that drive placebo response and narrow the patient-provider ‘mismatch’ that undermines the quality, satisfaction, and efficiency of IBS care regardless of what treatment is delivered.”
The study was supported by the NIH. The investigators disclosed no conflicts of interest.
FROM GASTRO HEP ADVANCES
Global Rates of H. Pylori, Gastric Cancer, Dropping Together
, according to investigators.
These findings suggest that decreasing H. pylori prevalence does indeed reduce rates of gastric cancer, although large-scale clinical trials are needed to solidify confidence in this apparent relationship, reported lead author Yi Chun Chen, PhD, of National Taiwan University, Taipei, and colleagues.
“Eradication of H. pylori infection heals chronic active gastritis and peptic ulcer disease and reduces the risk of peptic ulcer bleeding in aspirin users and the risk of gastric cancer in infected individuals,” the investigators wrote in Gastroenterology. “However, whether reduction of the prevalence of H. pylori is associated with a reduction of the incidence of gastric cancer at the population level remains uncertain.”
According to several previous meta-analyses, the global rate of H. pylori infection has been in a downtrend, but Dr. Chen and colleagues pointed out several limitations of these publications, including scarcity of recent data, insufficiently representative data, inconsistent diagnostic methods, and lack of adjustment for socioeconomic status.
“We therefore conducted this comprehensive systematic review and meta-analysis, including healthy individuals recruited in hospital-based studies, to provide an updated global prevalence and the secular trend of H. pylori infection,” the investigators wrote, noting that they leveraged meta-regression analysis to “identify factors affecting heterogeneity of the prevalence,” and concurrently evaluated the corresponding global incidence of gastric cancer.
Their dataset, which included 1,748 articles from 111 countries, suggested that the global rate of H. pylori is indeed in a downtrend.
From a crude global prevalence of 52.6% prior to 1990, the rate of H. pylori decreased to 43.9% among adults in 2015-2022, but was “still as high as” 35.1% among children and adolescents in the same 2015-2022 period. Multivariate regression analysis showed that prevalence decreased significantly, by 15.9%, among adults, but not in children and adolescents.
“The significant reduction of H. pylori prevalence in adults can be explained by the improvement of socioeconomic status, cleaner water supply, better sanitation and hygiene status, and widening of indication for eradication therapy,” Dr. Chen and colleagues wrote. “The higher prevalence in adults than in children/adolescents is explained by the cohort effect because most H. pylori infection is acquired in childhood.”
Global incidence of gastric cancer among both male and female individuals declined approximately in parallel with decreasing prevalence of H. pylori. Rates of gastric cancer decreased most in high-incidence countries such as Brazil, Japan, and China.
“These studies collectively provide evidence for the causal association of H. pylori infection and gastric cancer and that elimination of this bacterium can prevent the development of gastric cancer,” the investigators wrote.
Still, more work is needed.
“Future prospective studies should be conducted to confirm whether public health interventions or mass screening and eradication of H. pylori infection to reduce its prevalence may reduce the incidence of gastric cancer at population level,” Dr. Chen and colleagues concluded. “Besides, it is also important to consider the potential adverse consequences of H. pylori eradication, such as emergence of antibiotic resistance. The benefit-to-harm ratio and cost-effectiveness should also be taken into account.”
The study was funded by the National Taiwan University Hospital, the Taiwan Ministry of Science and Technology, the Taiwan Ministry of Health and Welfare, and others. The investigators disclosed no conflicts of interest.
Chen et al.’s study establishes a connection between the global decline in H. pylori infection rates and the decrease in gastric cancer cases, analyzing data from 1,748 articles across 111 countries. It highlights a significant drop in adult H. pylori prevalence from 52.6% before 1990 to 43.9% between 2015 and 2022, crediting improvements in socioeconomic conditions, water quality, and sanitation, along with targeted eradication efforts. This emphasizes the critical role of public health measures in reducing H. pylori infections and, consequently, gastric cancer risks, showcasing the success of eradication campaigns and widespread screening.
Nevertheless, the research advises caution regarding the widespread elimination of H. pylori due to the risk of antibiotic resistance. It advocates for a measured evaluation of the pros and cons, as well as the cost-effectiveness of such interventions. The authors call for additional large-scale clinical trials to verify these results and improve public health tactics.
The findings indicate that precise public health actions can greatly influence disease prevention, underlining the necessity of well-informed policies backed by ongoing clinical research and trials. Such an informed approach is essential to confirm that the advantages of eradication surpass the potential dangers, particularly considering the growing concern over antibiotic resistance. This study lays the groundwork for effective gastric cancer prevention strategies and emphasizes the ongoing need for research to shape sound public health policies and actions.
Li-Ju Chen, PhD, is a postdoctoral researcher in the Division of Clinical Epidemiology and Aging Research at the German Cancer Research Center, Heidelberg, Germany. She declared no conflicts of interest in regard to this review.
Chen et al.’s study establishes a connection between the global decline in H. pylori infection rates and the decrease in gastric cancer cases, analyzing data from 1,748 articles across 111 countries. It highlights a significant drop in adult H. pylori prevalence from 52.6% before 1990 to 43.9% between 2015 and 2022, crediting improvements in socioeconomic conditions, water quality, and sanitation, along with targeted eradication efforts. This emphasizes the critical role of public health measures in reducing H. pylori infections and, consequently, gastric cancer risks, showcasing the success of eradication campaigns and widespread screening.
Nevertheless, the research advises caution regarding the widespread elimination of H. pylori due to the risk of antibiotic resistance. It advocates for a measured evaluation of the pros and cons, as well as the cost-effectiveness of such interventions. The authors call for additional large-scale clinical trials to verify these results and improve public health tactics.
The findings indicate that precise public health actions can greatly influence disease prevention, underlining the necessity of well-informed policies backed by ongoing clinical research and trials. Such an informed approach is essential to confirm that the advantages of eradication surpass the potential dangers, particularly considering the growing concern over antibiotic resistance. This study lays the groundwork for effective gastric cancer prevention strategies and emphasizes the ongoing need for research to shape sound public health policies and actions.
Li-Ju Chen, PhD, is a postdoctoral researcher in the Division of Clinical Epidemiology and Aging Research at the German Cancer Research Center, Heidelberg, Germany. She declared no conflicts of interest in regard to this review.
Chen et al.’s study establishes a connection between the global decline in H. pylori infection rates and the decrease in gastric cancer cases, analyzing data from 1,748 articles across 111 countries. It highlights a significant drop in adult H. pylori prevalence from 52.6% before 1990 to 43.9% between 2015 and 2022, crediting improvements in socioeconomic conditions, water quality, and sanitation, along with targeted eradication efforts. This emphasizes the critical role of public health measures in reducing H. pylori infections and, consequently, gastric cancer risks, showcasing the success of eradication campaigns and widespread screening.
Nevertheless, the research advises caution regarding the widespread elimination of H. pylori due to the risk of antibiotic resistance. It advocates for a measured evaluation of the pros and cons, as well as the cost-effectiveness of such interventions. The authors call for additional large-scale clinical trials to verify these results and improve public health tactics.
The findings indicate that precise public health actions can greatly influence disease prevention, underlining the necessity of well-informed policies backed by ongoing clinical research and trials. Such an informed approach is essential to confirm that the advantages of eradication surpass the potential dangers, particularly considering the growing concern over antibiotic resistance. This study lays the groundwork for effective gastric cancer prevention strategies and emphasizes the ongoing need for research to shape sound public health policies and actions.
Li-Ju Chen, PhD, is a postdoctoral researcher in the Division of Clinical Epidemiology and Aging Research at the German Cancer Research Center, Heidelberg, Germany. She declared no conflicts of interest in regard to this review.
, according to investigators.
These findings suggest that decreasing H. pylori prevalence does indeed reduce rates of gastric cancer, although large-scale clinical trials are needed to solidify confidence in this apparent relationship, reported lead author Yi Chun Chen, PhD, of National Taiwan University, Taipei, and colleagues.
“Eradication of H. pylori infection heals chronic active gastritis and peptic ulcer disease and reduces the risk of peptic ulcer bleeding in aspirin users and the risk of gastric cancer in infected individuals,” the investigators wrote in Gastroenterology. “However, whether reduction of the prevalence of H. pylori is associated with a reduction of the incidence of gastric cancer at the population level remains uncertain.”
According to several previous meta-analyses, the global rate of H. pylori infection has been in a downtrend, but Dr. Chen and colleagues pointed out several limitations of these publications, including scarcity of recent data, insufficiently representative data, inconsistent diagnostic methods, and lack of adjustment for socioeconomic status.
“We therefore conducted this comprehensive systematic review and meta-analysis, including healthy individuals recruited in hospital-based studies, to provide an updated global prevalence and the secular trend of H. pylori infection,” the investigators wrote, noting that they leveraged meta-regression analysis to “identify factors affecting heterogeneity of the prevalence,” and concurrently evaluated the corresponding global incidence of gastric cancer.
Their dataset, which included 1,748 articles from 111 countries, suggested that the global rate of H. pylori is indeed in a downtrend.
From a crude global prevalence of 52.6% prior to 1990, the rate of H. pylori decreased to 43.9% among adults in 2015-2022, but was “still as high as” 35.1% among children and adolescents in the same 2015-2022 period. Multivariate regression analysis showed that prevalence decreased significantly, by 15.9%, among adults, but not in children and adolescents.
“The significant reduction of H. pylori prevalence in adults can be explained by the improvement of socioeconomic status, cleaner water supply, better sanitation and hygiene status, and widening of indication for eradication therapy,” Dr. Chen and colleagues wrote. “The higher prevalence in adults than in children/adolescents is explained by the cohort effect because most H. pylori infection is acquired in childhood.”
Global incidence of gastric cancer among both male and female individuals declined approximately in parallel with decreasing prevalence of H. pylori. Rates of gastric cancer decreased most in high-incidence countries such as Brazil, Japan, and China.
“These studies collectively provide evidence for the causal association of H. pylori infection and gastric cancer and that elimination of this bacterium can prevent the development of gastric cancer,” the investigators wrote.
Still, more work is needed.
“Future prospective studies should be conducted to confirm whether public health interventions or mass screening and eradication of H. pylori infection to reduce its prevalence may reduce the incidence of gastric cancer at population level,” Dr. Chen and colleagues concluded. “Besides, it is also important to consider the potential adverse consequences of H. pylori eradication, such as emergence of antibiotic resistance. The benefit-to-harm ratio and cost-effectiveness should also be taken into account.”
The study was funded by the National Taiwan University Hospital, the Taiwan Ministry of Science and Technology, the Taiwan Ministry of Health and Welfare, and others. The investigators disclosed no conflicts of interest.
, according to investigators.
These findings suggest that decreasing H. pylori prevalence does indeed reduce rates of gastric cancer, although large-scale clinical trials are needed to solidify confidence in this apparent relationship, reported lead author Yi Chun Chen, PhD, of National Taiwan University, Taipei, and colleagues.
“Eradication of H. pylori infection heals chronic active gastritis and peptic ulcer disease and reduces the risk of peptic ulcer bleeding in aspirin users and the risk of gastric cancer in infected individuals,” the investigators wrote in Gastroenterology. “However, whether reduction of the prevalence of H. pylori is associated with a reduction of the incidence of gastric cancer at the population level remains uncertain.”
According to several previous meta-analyses, the global rate of H. pylori infection has been in a downtrend, but Dr. Chen and colleagues pointed out several limitations of these publications, including scarcity of recent data, insufficiently representative data, inconsistent diagnostic methods, and lack of adjustment for socioeconomic status.
“We therefore conducted this comprehensive systematic review and meta-analysis, including healthy individuals recruited in hospital-based studies, to provide an updated global prevalence and the secular trend of H. pylori infection,” the investigators wrote, noting that they leveraged meta-regression analysis to “identify factors affecting heterogeneity of the prevalence,” and concurrently evaluated the corresponding global incidence of gastric cancer.
Their dataset, which included 1,748 articles from 111 countries, suggested that the global rate of H. pylori is indeed in a downtrend.
From a crude global prevalence of 52.6% prior to 1990, the rate of H. pylori decreased to 43.9% among adults in 2015-2022, but was “still as high as” 35.1% among children and adolescents in the same 2015-2022 period. Multivariate regression analysis showed that prevalence decreased significantly, by 15.9%, among adults, but not in children and adolescents.
“The significant reduction of H. pylori prevalence in adults can be explained by the improvement of socioeconomic status, cleaner water supply, better sanitation and hygiene status, and widening of indication for eradication therapy,” Dr. Chen and colleagues wrote. “The higher prevalence in adults than in children/adolescents is explained by the cohort effect because most H. pylori infection is acquired in childhood.”
Global incidence of gastric cancer among both male and female individuals declined approximately in parallel with decreasing prevalence of H. pylori. Rates of gastric cancer decreased most in high-incidence countries such as Brazil, Japan, and China.
“These studies collectively provide evidence for the causal association of H. pylori infection and gastric cancer and that elimination of this bacterium can prevent the development of gastric cancer,” the investigators wrote.
Still, more work is needed.
“Future prospective studies should be conducted to confirm whether public health interventions or mass screening and eradication of H. pylori infection to reduce its prevalence may reduce the incidence of gastric cancer at population level,” Dr. Chen and colleagues concluded. “Besides, it is also important to consider the potential adverse consequences of H. pylori eradication, such as emergence of antibiotic resistance. The benefit-to-harm ratio and cost-effectiveness should also be taken into account.”
The study was funded by the National Taiwan University Hospital, the Taiwan Ministry of Science and Technology, the Taiwan Ministry of Health and Welfare, and others. The investigators disclosed no conflicts of interest.
FROM GASTROENTEROLOGY
Study Characterizes Pathologic B-Cell Maturation in Crohn’s Disease
, according to investigators.
These findings begin to address a knowledge gap in Crohn’s disease that has been more thoroughly explored in ulcerative colitis, reported lead author Sonja Kappel-Latif, MD, PhD, of Medical University of Vienna, Vienna, Austria, and colleagues.
“Recent studies have investigated the role of B-cell responses in ulcerative colitis, which exclusively affects the colon, whereas data in CD, which mainly affects the terminal ileum, are insufficient,” the investigators wrote in wrote in Cellular and Molecular Gastroenterology and Hepatology. “Granuloma formation within the thickened, inflamed mesentery of patients with CD, however, is associated with significantly worse outcome, and microstructural analysis has suggested increased numbers of B cells in CD mesentery.”
Previous studies have shown that abnormal B-cell development in patients with CD leads to development of IgG targeting commensal — instead of pathogenic — gut bacteria. Yet B-cell receptor sequencing in CD has only been conducted on peripheral blood, despite awareness that anticommensal IgG antibodies can be transported across mucosal barriers in patients with ulcerative colitis, sustaining intestinal inflammation.
To better characterize local B-cell responses in CD, the investigators evaluated paired samples of draining mesenteric lymph nodes (MLNs) from both healthy and adjacently affected intestinal tissue, yielding a range of findings.
First, the investigators noted that CD19+ B cells and CD45+ leukocytes were expanded in affected MLNs, while T cells were reduced. A closer look showed that IgD-CD27- B cells were more abundant among CD19+CD45+ B cells in affected MLNs. Within this CD45+CD19+CD27+IgD- B-cell fraction, CD38- memory B cells were reduced.
The above findings suggest “ongoing antigenic stimulation within affected MLNs,” the investigators wrote.
Further comparison of paired samples showed that germinal centers (within which B cells mature) were significantly larger in affected MLNs, and contained dark and light zones. In contrast, healthy MLNs had smaller, more immature germinal centers.
Due to T-cell dependence during B-cell isotype switching within these germinal centers, the investigators next conducted immunohistochemistry staining for Bcl6, a “master regulator” of T-follicular helper cells expressed in class-switching B cells, and Ki67, which indicates cell proliferation. These analyses shows that both markers were “highly positive” within the germinal centers of affected MLNs.
Next, Dr. Kappel-Latif and colleagues conducted B-cell receptor (BCR) sequencing to characterize differences in class switching. Compared with healthy MLNs, affected MLNs showed decreased use of IGHA and IGHE alongside a significant uptick in IGHG1/2.
Further analyses showed that somatic hypermutation (SHM) frequency was significantly higher in IGHM and IGHA B cells, which was driven by mutations in complementary determining regions (CDRs) and framework regions of IGHA B cells, and mutations in the CDRs of IGHM B cells.
BCR diversity increased in the IGHG1/2 B cells, but remained unchanged in the IGHM or IGHA B cells.
“Overall, our results indicate ongoing class switching within draining MLNs of affected intestinal segments, with a shift toward IGHG1/2 BCRs,” the investigators concluded. “The lack of high SHM rates within IGHG1/2 BCRs, the difference between IGHA and IGHG1/2 BCRs in single MLNs, and increased diversity in IGHG1/2 BCRs suggests that many antigens do not result in long-lasting immunologic stimulation, and IGHA and IGHG1/2 responses may target different pathogens/commensals.”
The study was supported by the Austrian Science Fund and the Major of Vienna. The investigators disclosed no conflicts of interest.
The pathophysiology of inflammatory bowel disease (IBD) is complex and involves multiple mechanisms. Among these mechanisms, dysfunction and overactivation of the intestinal immune system are widely implicated. Dysfunctions in both the innate and adaptive immune systems have been demonstrated. However, mucosal immunology research related to IBD has long been particularly focused on T lymphocytes due to the failure of the rituximab clinical trial (anti-CD20) in ulcerative colitis (UC). Recent data have indicated modifications in the landscape of B lymphocyte subpopulations within the inflamed mucosa of patients with UC or ileal Crohn’s disease (CD).
Similarly, to what was previously shown in the inflamed colonic and ileal mucosa of IBD patients, isotype usage showed a skewing from IgA to IgG1. Further analysis of the B cell receptor (BCR) showed a very diverse repertoire of B cells, reflecting a large panel of antigenic stimulation. As we know, IBD are complex diseases that may not be explained by a single or a limited set of antigenic drivers.
Whether these changes in the B-cell compartment are a triggering event of inflammation or a bystander, reflecting the increased intestinal permeability and exposure to microbiota antigens during inflammation, remains to be explored and further studied.
Mathieu Uzzan, MD, PhD, is based in the gastroenterology department, Hopital Henri Mondor, APHP, Créteil, France. He has no relevant disclosures.
The pathophysiology of inflammatory bowel disease (IBD) is complex and involves multiple mechanisms. Among these mechanisms, dysfunction and overactivation of the intestinal immune system are widely implicated. Dysfunctions in both the innate and adaptive immune systems have been demonstrated. However, mucosal immunology research related to IBD has long been particularly focused on T lymphocytes due to the failure of the rituximab clinical trial (anti-CD20) in ulcerative colitis (UC). Recent data have indicated modifications in the landscape of B lymphocyte subpopulations within the inflamed mucosa of patients with UC or ileal Crohn’s disease (CD).
Similarly, to what was previously shown in the inflamed colonic and ileal mucosa of IBD patients, isotype usage showed a skewing from IgA to IgG1. Further analysis of the B cell receptor (BCR) showed a very diverse repertoire of B cells, reflecting a large panel of antigenic stimulation. As we know, IBD are complex diseases that may not be explained by a single or a limited set of antigenic drivers.
Whether these changes in the B-cell compartment are a triggering event of inflammation or a bystander, reflecting the increased intestinal permeability and exposure to microbiota antigens during inflammation, remains to be explored and further studied.
Mathieu Uzzan, MD, PhD, is based in the gastroenterology department, Hopital Henri Mondor, APHP, Créteil, France. He has no relevant disclosures.
The pathophysiology of inflammatory bowel disease (IBD) is complex and involves multiple mechanisms. Among these mechanisms, dysfunction and overactivation of the intestinal immune system are widely implicated. Dysfunctions in both the innate and adaptive immune systems have been demonstrated. However, mucosal immunology research related to IBD has long been particularly focused on T lymphocytes due to the failure of the rituximab clinical trial (anti-CD20) in ulcerative colitis (UC). Recent data have indicated modifications in the landscape of B lymphocyte subpopulations within the inflamed mucosa of patients with UC or ileal Crohn’s disease (CD).
Similarly, to what was previously shown in the inflamed colonic and ileal mucosa of IBD patients, isotype usage showed a skewing from IgA to IgG1. Further analysis of the B cell receptor (BCR) showed a very diverse repertoire of B cells, reflecting a large panel of antigenic stimulation. As we know, IBD are complex diseases that may not be explained by a single or a limited set of antigenic drivers.
Whether these changes in the B-cell compartment are a triggering event of inflammation or a bystander, reflecting the increased intestinal permeability and exposure to microbiota antigens during inflammation, remains to be explored and further studied.
Mathieu Uzzan, MD, PhD, is based in the gastroenterology department, Hopital Henri Mondor, APHP, Créteil, France. He has no relevant disclosures.
, according to investigators.
These findings begin to address a knowledge gap in Crohn’s disease that has been more thoroughly explored in ulcerative colitis, reported lead author Sonja Kappel-Latif, MD, PhD, of Medical University of Vienna, Vienna, Austria, and colleagues.
“Recent studies have investigated the role of B-cell responses in ulcerative colitis, which exclusively affects the colon, whereas data in CD, which mainly affects the terminal ileum, are insufficient,” the investigators wrote in wrote in Cellular and Molecular Gastroenterology and Hepatology. “Granuloma formation within the thickened, inflamed mesentery of patients with CD, however, is associated with significantly worse outcome, and microstructural analysis has suggested increased numbers of B cells in CD mesentery.”
Previous studies have shown that abnormal B-cell development in patients with CD leads to development of IgG targeting commensal — instead of pathogenic — gut bacteria. Yet B-cell receptor sequencing in CD has only been conducted on peripheral blood, despite awareness that anticommensal IgG antibodies can be transported across mucosal barriers in patients with ulcerative colitis, sustaining intestinal inflammation.
To better characterize local B-cell responses in CD, the investigators evaluated paired samples of draining mesenteric lymph nodes (MLNs) from both healthy and adjacently affected intestinal tissue, yielding a range of findings.
First, the investigators noted that CD19+ B cells and CD45+ leukocytes were expanded in affected MLNs, while T cells were reduced. A closer look showed that IgD-CD27- B cells were more abundant among CD19+CD45+ B cells in affected MLNs. Within this CD45+CD19+CD27+IgD- B-cell fraction, CD38- memory B cells were reduced.
The above findings suggest “ongoing antigenic stimulation within affected MLNs,” the investigators wrote.
Further comparison of paired samples showed that germinal centers (within which B cells mature) were significantly larger in affected MLNs, and contained dark and light zones. In contrast, healthy MLNs had smaller, more immature germinal centers.
Due to T-cell dependence during B-cell isotype switching within these germinal centers, the investigators next conducted immunohistochemistry staining for Bcl6, a “master regulator” of T-follicular helper cells expressed in class-switching B cells, and Ki67, which indicates cell proliferation. These analyses shows that both markers were “highly positive” within the germinal centers of affected MLNs.
Next, Dr. Kappel-Latif and colleagues conducted B-cell receptor (BCR) sequencing to characterize differences in class switching. Compared with healthy MLNs, affected MLNs showed decreased use of IGHA and IGHE alongside a significant uptick in IGHG1/2.
Further analyses showed that somatic hypermutation (SHM) frequency was significantly higher in IGHM and IGHA B cells, which was driven by mutations in complementary determining regions (CDRs) and framework regions of IGHA B cells, and mutations in the CDRs of IGHM B cells.
BCR diversity increased in the IGHG1/2 B cells, but remained unchanged in the IGHM or IGHA B cells.
“Overall, our results indicate ongoing class switching within draining MLNs of affected intestinal segments, with a shift toward IGHG1/2 BCRs,” the investigators concluded. “The lack of high SHM rates within IGHG1/2 BCRs, the difference between IGHA and IGHG1/2 BCRs in single MLNs, and increased diversity in IGHG1/2 BCRs suggests that many antigens do not result in long-lasting immunologic stimulation, and IGHA and IGHG1/2 responses may target different pathogens/commensals.”
The study was supported by the Austrian Science Fund and the Major of Vienna. The investigators disclosed no conflicts of interest.
, according to investigators.
These findings begin to address a knowledge gap in Crohn’s disease that has been more thoroughly explored in ulcerative colitis, reported lead author Sonja Kappel-Latif, MD, PhD, of Medical University of Vienna, Vienna, Austria, and colleagues.
“Recent studies have investigated the role of B-cell responses in ulcerative colitis, which exclusively affects the colon, whereas data in CD, which mainly affects the terminal ileum, are insufficient,” the investigators wrote in wrote in Cellular and Molecular Gastroenterology and Hepatology. “Granuloma formation within the thickened, inflamed mesentery of patients with CD, however, is associated with significantly worse outcome, and microstructural analysis has suggested increased numbers of B cells in CD mesentery.”
Previous studies have shown that abnormal B-cell development in patients with CD leads to development of IgG targeting commensal — instead of pathogenic — gut bacteria. Yet B-cell receptor sequencing in CD has only been conducted on peripheral blood, despite awareness that anticommensal IgG antibodies can be transported across mucosal barriers in patients with ulcerative colitis, sustaining intestinal inflammation.
To better characterize local B-cell responses in CD, the investigators evaluated paired samples of draining mesenteric lymph nodes (MLNs) from both healthy and adjacently affected intestinal tissue, yielding a range of findings.
First, the investigators noted that CD19+ B cells and CD45+ leukocytes were expanded in affected MLNs, while T cells were reduced. A closer look showed that IgD-CD27- B cells were more abundant among CD19+CD45+ B cells in affected MLNs. Within this CD45+CD19+CD27+IgD- B-cell fraction, CD38- memory B cells were reduced.
The above findings suggest “ongoing antigenic stimulation within affected MLNs,” the investigators wrote.
Further comparison of paired samples showed that germinal centers (within which B cells mature) were significantly larger in affected MLNs, and contained dark and light zones. In contrast, healthy MLNs had smaller, more immature germinal centers.
Due to T-cell dependence during B-cell isotype switching within these germinal centers, the investigators next conducted immunohistochemistry staining for Bcl6, a “master regulator” of T-follicular helper cells expressed in class-switching B cells, and Ki67, which indicates cell proliferation. These analyses shows that both markers were “highly positive” within the germinal centers of affected MLNs.
Next, Dr. Kappel-Latif and colleagues conducted B-cell receptor (BCR) sequencing to characterize differences in class switching. Compared with healthy MLNs, affected MLNs showed decreased use of IGHA and IGHE alongside a significant uptick in IGHG1/2.
Further analyses showed that somatic hypermutation (SHM) frequency was significantly higher in IGHM and IGHA B cells, which was driven by mutations in complementary determining regions (CDRs) and framework regions of IGHA B cells, and mutations in the CDRs of IGHM B cells.
BCR diversity increased in the IGHG1/2 B cells, but remained unchanged in the IGHM or IGHA B cells.
“Overall, our results indicate ongoing class switching within draining MLNs of affected intestinal segments, with a shift toward IGHG1/2 BCRs,” the investigators concluded. “The lack of high SHM rates within IGHG1/2 BCRs, the difference between IGHA and IGHG1/2 BCRs in single MLNs, and increased diversity in IGHG1/2 BCRs suggests that many antigens do not result in long-lasting immunologic stimulation, and IGHA and IGHG1/2 responses may target different pathogens/commensals.”
The study was supported by the Austrian Science Fund and the Major of Vienna. The investigators disclosed no conflicts of interest.
FROM CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
Global Meta-Analysis: 1 in 12 Adults May Have Fecal Incontinence
FI is more common among individuals 60 years and older, yet a considerable portion of younger people — almost 5% — may also suffer from FI, reported Isabelle Mack, PhD, of University Medical Hospital, Tübingen, Germany, and colleagues.
“Clinicians’ understanding of the prevalence and risk factors for FI have evolved with time,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Initially, FI was regarded as a symptom that predominantly affected older people, especially nursing home residents. Its prevalence among community-dwelling adults was underrecognized, possibly because persons with FI were hesitant to even disclose that they were symptomatic. Now, we recognize that FI is common in the community.”
The only previous meta-analysis of FI, published in 2006, included both community and noncommunity studies, and reported an FI prevalence of 4.3%. Two subsequent reviews put the median prevalence at 7.7%, yet neither offered geographic insights.
To address this knowledge gap, Dr. Mack and colleagues conducted a meta-analysis of 80 studies involving 548,316 community-dwelling teenagers and adults. The median response rate across the studies was 66%.
Evaluating these data revealed a pooled global prevalence of FI was 8.0%, with a lower rate of 5.4% when FI was confined to Rome criteria.
“Placed in perspective, the 8.0% prevalence of FI is lower than or similar to the global prevalence of IBS, as assessed by a meta-regression (11.2%) and by a systematic review (8.8%) using pre–Rome IV criteria, and it is twofold greater than the IBS prevalence assessed with Rome IV criteria,” the investigators wrote.
Among individuals aged 60 years and older, the FI prevalence was 9.3%, compared with 4.9% for younger people (odds ratio [OR], 1.75; 95% CI, 1.39-2.20).
“These differences are at least partly explained by age-associated declines in anorectal function (e.g., lower anal resting pressure and rectal distensibility, denervation of the external anal sphincter),” the investigators wrote.
FI was also significantly more common among women than men (9.1% vs 7.4%; OR, 1.17; 95% CI, 1.06-1.28).
“Although these differences in FI prevalence between men and women seem relatively small, most patients with FI who seek medical attention are women (unpublished data),” the investigators wrote. “We suspect that men less commonly seek medical attention for FI because they may be secretly resigned to having FI, because FI may have less of an emotional impact on men, and because health literacy with regard to FI is lower for men.”
Geographically, prevalence of FI was highest in Australia and Oceania, followed by North America, Asia, and Europe. Data were insufficient to estimates rates in the Middle East and Africa.
Dr. Mack and colleagues concluded by noting how bothersome FI is for so many individuals worldwide, which should warrant closer attention from the medical community.
“Because nearly one in four community-dwelling women with FI report that the symptom has a moderate or severe impact on one or more domains of quality of life, more resources should be devoted to research in this area,” they wrote. “Future epidemiologic studies of FI should also assess the severity of FI, risk factors for FI, and the impact of FI on quality of life. In addition, because some patients are reluctant to acknowledge or discuss FI during an in-person interview, written or internet-based surveys may be preferable.”
This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The investigators disclosed no conflicts of interest.
Fecal incontinence (FI) is the GI disease that remains invisible to many except its sufferers. Even in the seemingly safe confines of a physician’s office, many patients won’t admit to providers that they suffer from this socially isolating condition. This systematic review and meta-analysis by Mack et al. — like other prevalence studies before it — serves as a useful reminder just how common this hidden disease remains. While FI is common in institutionalized persons, this study importantly found that 1 in 12 community-dwelling individuals worldwide suffer from FI as well.
What should the practicing clinician take away from this study? Simply put, when it comes to FI, you need to ask: how often, how much, how urgent (or passive), and what type (solid or liquid). This disease is far too common to remain in the shadows, yet most GI fellows do not receive sufficient training on a condition that is so widespread.
Kyle Staller, MD, MPH, is director, GI Motility Laboratory at Massachusetts General Hospital and Harvard Medical School, both in Boston. He has served as a consultant for Anji, Ardelyx, GI Supply, Mahana, and Restalsis, and received research support from Ardelyx.
Fecal incontinence (FI) is the GI disease that remains invisible to many except its sufferers. Even in the seemingly safe confines of a physician’s office, many patients won’t admit to providers that they suffer from this socially isolating condition. This systematic review and meta-analysis by Mack et al. — like other prevalence studies before it — serves as a useful reminder just how common this hidden disease remains. While FI is common in institutionalized persons, this study importantly found that 1 in 12 community-dwelling individuals worldwide suffer from FI as well.
What should the practicing clinician take away from this study? Simply put, when it comes to FI, you need to ask: how often, how much, how urgent (or passive), and what type (solid or liquid). This disease is far too common to remain in the shadows, yet most GI fellows do not receive sufficient training on a condition that is so widespread.
Kyle Staller, MD, MPH, is director, GI Motility Laboratory at Massachusetts General Hospital and Harvard Medical School, both in Boston. He has served as a consultant for Anji, Ardelyx, GI Supply, Mahana, and Restalsis, and received research support from Ardelyx.
Fecal incontinence (FI) is the GI disease that remains invisible to many except its sufferers. Even in the seemingly safe confines of a physician’s office, many patients won’t admit to providers that they suffer from this socially isolating condition. This systematic review and meta-analysis by Mack et al. — like other prevalence studies before it — serves as a useful reminder just how common this hidden disease remains. While FI is common in institutionalized persons, this study importantly found that 1 in 12 community-dwelling individuals worldwide suffer from FI as well.
What should the practicing clinician take away from this study? Simply put, when it comes to FI, you need to ask: how often, how much, how urgent (or passive), and what type (solid or liquid). This disease is far too common to remain in the shadows, yet most GI fellows do not receive sufficient training on a condition that is so widespread.
Kyle Staller, MD, MPH, is director, GI Motility Laboratory at Massachusetts General Hospital and Harvard Medical School, both in Boston. He has served as a consultant for Anji, Ardelyx, GI Supply, Mahana, and Restalsis, and received research support from Ardelyx.
FI is more common among individuals 60 years and older, yet a considerable portion of younger people — almost 5% — may also suffer from FI, reported Isabelle Mack, PhD, of University Medical Hospital, Tübingen, Germany, and colleagues.
“Clinicians’ understanding of the prevalence and risk factors for FI have evolved with time,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Initially, FI was regarded as a symptom that predominantly affected older people, especially nursing home residents. Its prevalence among community-dwelling adults was underrecognized, possibly because persons with FI were hesitant to even disclose that they were symptomatic. Now, we recognize that FI is common in the community.”
The only previous meta-analysis of FI, published in 2006, included both community and noncommunity studies, and reported an FI prevalence of 4.3%. Two subsequent reviews put the median prevalence at 7.7%, yet neither offered geographic insights.
To address this knowledge gap, Dr. Mack and colleagues conducted a meta-analysis of 80 studies involving 548,316 community-dwelling teenagers and adults. The median response rate across the studies was 66%.
Evaluating these data revealed a pooled global prevalence of FI was 8.0%, with a lower rate of 5.4% when FI was confined to Rome criteria.
“Placed in perspective, the 8.0% prevalence of FI is lower than or similar to the global prevalence of IBS, as assessed by a meta-regression (11.2%) and by a systematic review (8.8%) using pre–Rome IV criteria, and it is twofold greater than the IBS prevalence assessed with Rome IV criteria,” the investigators wrote.
Among individuals aged 60 years and older, the FI prevalence was 9.3%, compared with 4.9% for younger people (odds ratio [OR], 1.75; 95% CI, 1.39-2.20).
“These differences are at least partly explained by age-associated declines in anorectal function (e.g., lower anal resting pressure and rectal distensibility, denervation of the external anal sphincter),” the investigators wrote.
FI was also significantly more common among women than men (9.1% vs 7.4%; OR, 1.17; 95% CI, 1.06-1.28).
“Although these differences in FI prevalence between men and women seem relatively small, most patients with FI who seek medical attention are women (unpublished data),” the investigators wrote. “We suspect that men less commonly seek medical attention for FI because they may be secretly resigned to having FI, because FI may have less of an emotional impact on men, and because health literacy with regard to FI is lower for men.”
Geographically, prevalence of FI was highest in Australia and Oceania, followed by North America, Asia, and Europe. Data were insufficient to estimates rates in the Middle East and Africa.
Dr. Mack and colleagues concluded by noting how bothersome FI is for so many individuals worldwide, which should warrant closer attention from the medical community.
“Because nearly one in four community-dwelling women with FI report that the symptom has a moderate or severe impact on one or more domains of quality of life, more resources should be devoted to research in this area,” they wrote. “Future epidemiologic studies of FI should also assess the severity of FI, risk factors for FI, and the impact of FI on quality of life. In addition, because some patients are reluctant to acknowledge or discuss FI during an in-person interview, written or internet-based surveys may be preferable.”
This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The investigators disclosed no conflicts of interest.
FI is more common among individuals 60 years and older, yet a considerable portion of younger people — almost 5% — may also suffer from FI, reported Isabelle Mack, PhD, of University Medical Hospital, Tübingen, Germany, and colleagues.
“Clinicians’ understanding of the prevalence and risk factors for FI have evolved with time,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Initially, FI was regarded as a symptom that predominantly affected older people, especially nursing home residents. Its prevalence among community-dwelling adults was underrecognized, possibly because persons with FI were hesitant to even disclose that they were symptomatic. Now, we recognize that FI is common in the community.”
The only previous meta-analysis of FI, published in 2006, included both community and noncommunity studies, and reported an FI prevalence of 4.3%. Two subsequent reviews put the median prevalence at 7.7%, yet neither offered geographic insights.
To address this knowledge gap, Dr. Mack and colleagues conducted a meta-analysis of 80 studies involving 548,316 community-dwelling teenagers and adults. The median response rate across the studies was 66%.
Evaluating these data revealed a pooled global prevalence of FI was 8.0%, with a lower rate of 5.4% when FI was confined to Rome criteria.
“Placed in perspective, the 8.0% prevalence of FI is lower than or similar to the global prevalence of IBS, as assessed by a meta-regression (11.2%) and by a systematic review (8.8%) using pre–Rome IV criteria, and it is twofold greater than the IBS prevalence assessed with Rome IV criteria,” the investigators wrote.
Among individuals aged 60 years and older, the FI prevalence was 9.3%, compared with 4.9% for younger people (odds ratio [OR], 1.75; 95% CI, 1.39-2.20).
“These differences are at least partly explained by age-associated declines in anorectal function (e.g., lower anal resting pressure and rectal distensibility, denervation of the external anal sphincter),” the investigators wrote.
FI was also significantly more common among women than men (9.1% vs 7.4%; OR, 1.17; 95% CI, 1.06-1.28).
“Although these differences in FI prevalence between men and women seem relatively small, most patients with FI who seek medical attention are women (unpublished data),” the investigators wrote. “We suspect that men less commonly seek medical attention for FI because they may be secretly resigned to having FI, because FI may have less of an emotional impact on men, and because health literacy with regard to FI is lower for men.”
Geographically, prevalence of FI was highest in Australia and Oceania, followed by North America, Asia, and Europe. Data were insufficient to estimates rates in the Middle East and Africa.
Dr. Mack and colleagues concluded by noting how bothersome FI is for so many individuals worldwide, which should warrant closer attention from the medical community.
“Because nearly one in four community-dwelling women with FI report that the symptom has a moderate or severe impact on one or more domains of quality of life, more resources should be devoted to research in this area,” they wrote. “Future epidemiologic studies of FI should also assess the severity of FI, risk factors for FI, and the impact of FI on quality of life. In addition, because some patients are reluctant to acknowledge or discuss FI during an in-person interview, written or internet-based surveys may be preferable.”
This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The investigators disclosed no conflicts of interest.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
AGA Guides Usage of GLP-1 Receptor Agonists Before Endoscopy
The American Gastroenterological Association (AGA) has issued a rapid clinical practice update on the use of glucagon-like peptide 1 (GLP-1) receptor agonists prior to endoscopy.
The update was partly prompted by consensus-based perioperative guidance issued by the American Society of Anesthesiologists in June 2023, which advises withholding GLP-1 receptor agonists before endoscopy. This recommendation has caused some anesthesia providers to cancel or postpone endoscopic procedures, or even elect general endotracheal intubation over standard sedation.
“Many facilities and medical centers are now struggling to revise preprocedural protocols for patients taking this class of medications despite the lack of high-level evidence regarding how to proceed,” the panelists wrote in Clinical Gastroenterology and Hepatology. “Important questions include whether these preprocedural changes are necessary, if they truly mitigate periprocedural aspiration, or if the delays instituted by following this guidance might further compound the major problem currently faced nationwide: that of large numbers of patients awaiting endoscopic procedures because of delays from the COVID-19 pandemic, reduction in the recommended age threshold to start colorectal cancer screening in 2018, and workforce challenges.”
The rapid clinical practice update, commissioned and approved by the AGA, includes background on the relationship between GLP-1 receptor agonists and endoscopic procedures, followed by clinical strategies for patients taking these medications.
Lead panelist Jana G. Al Hashash, MD, MSc, AGAF, of Mayo Clinic, Jacksonville, Florida, and colleagues began by noting that GLP-1 receptor agonists have been associated with increased gastric residue in patients with diabetes, and among nondiabetic patients, increased gastric retention of solids but not liquids. Delayed gastric emptying and increased residual gastric contents may be more common among patients on GLP-1 agonists who have vomiting, nausea, dyspepsia, or abdominal bloating, they added.
The above findings “imply an increased risk of aspiration in patients receiving GLP-1 receptor agonist medications who present for procedures that require sedation,” the panelists wrote, but more data is needed to support this hypothesis.
Yet the implications for endoscopic risk are still unclear.
Residual liquid in the stomach, at least, is “less of an issue,” according to the update, since “it is easily removed during an esophagogastroduodenoscopy, and this is the first maneuver performed by endoscopists on entering the stomach.”
While residual solids in the stomach could theoretically increase risk of aspiration, other patients with gastroparesis, such as those taking opioids, are not routinely given “special dietary precautions or medication adjustments” prior to endoscopy, Dr. Al Hashash and colleagues wrote. Even patients with severe gastroparesis who are undergoing gastric peroral endoscopic myotomy (which depends upon an empty stomach), are only required to stop ingesting solid foods the day before the procedure, they noted.
“It is appropriate that the ASA’s perioperative suggestions for patients on GLP-1 [receptor agonists] are labeled ‘consensus-based guidance on perioperative management,’ because there is clearly insufficient published evidence for a robust systematic review and guideline,” they wrote. “As such, the ASA’s suggestions are expert opinions, which may inform but should not replace clinical judgment.”
, for whom withholding these medications “might provide more risk than benefit.”
Withholding GLP-1 receptor agonists may be safe and reasonable for patients taking them solely for weight loss, but “this should not be considered mandatory or evidence-based,” as it remains unclear whether withholding one dose is enough to restore normal gastric motility.
“Generally, in patients on GLP-1 receptor agonists who have followed standard perioperative procedures (typically an 8-hour solid-food fast and a 2-hour liquid fast) and who do not have symptoms of nausea, vomiting, dyspepsia, or abdominal distention, we advise proceeding with upper and/or lower endoscopy,” the panelists concluded.
The rapid clinical practice update was commissioned and approved by the AGA. The update panelists disclosed relationships with Apollo Endosurgery, Medtronic, Boston Scientific, and others.
The American Gastroenterological Association (AGA) has issued a rapid clinical practice update on the use of glucagon-like peptide 1 (GLP-1) receptor agonists prior to endoscopy.
The update was partly prompted by consensus-based perioperative guidance issued by the American Society of Anesthesiologists in June 2023, which advises withholding GLP-1 receptor agonists before endoscopy. This recommendation has caused some anesthesia providers to cancel or postpone endoscopic procedures, or even elect general endotracheal intubation over standard sedation.
“Many facilities and medical centers are now struggling to revise preprocedural protocols for patients taking this class of medications despite the lack of high-level evidence regarding how to proceed,” the panelists wrote in Clinical Gastroenterology and Hepatology. “Important questions include whether these preprocedural changes are necessary, if they truly mitigate periprocedural aspiration, or if the delays instituted by following this guidance might further compound the major problem currently faced nationwide: that of large numbers of patients awaiting endoscopic procedures because of delays from the COVID-19 pandemic, reduction in the recommended age threshold to start colorectal cancer screening in 2018, and workforce challenges.”
The rapid clinical practice update, commissioned and approved by the AGA, includes background on the relationship between GLP-1 receptor agonists and endoscopic procedures, followed by clinical strategies for patients taking these medications.
Lead panelist Jana G. Al Hashash, MD, MSc, AGAF, of Mayo Clinic, Jacksonville, Florida, and colleagues began by noting that GLP-1 receptor agonists have been associated with increased gastric residue in patients with diabetes, and among nondiabetic patients, increased gastric retention of solids but not liquids. Delayed gastric emptying and increased residual gastric contents may be more common among patients on GLP-1 agonists who have vomiting, nausea, dyspepsia, or abdominal bloating, they added.
The above findings “imply an increased risk of aspiration in patients receiving GLP-1 receptor agonist medications who present for procedures that require sedation,” the panelists wrote, but more data is needed to support this hypothesis.
Yet the implications for endoscopic risk are still unclear.
Residual liquid in the stomach, at least, is “less of an issue,” according to the update, since “it is easily removed during an esophagogastroduodenoscopy, and this is the first maneuver performed by endoscopists on entering the stomach.”
While residual solids in the stomach could theoretically increase risk of aspiration, other patients with gastroparesis, such as those taking opioids, are not routinely given “special dietary precautions or medication adjustments” prior to endoscopy, Dr. Al Hashash and colleagues wrote. Even patients with severe gastroparesis who are undergoing gastric peroral endoscopic myotomy (which depends upon an empty stomach), are only required to stop ingesting solid foods the day before the procedure, they noted.
“It is appropriate that the ASA’s perioperative suggestions for patients on GLP-1 [receptor agonists] are labeled ‘consensus-based guidance on perioperative management,’ because there is clearly insufficient published evidence for a robust systematic review and guideline,” they wrote. “As such, the ASA’s suggestions are expert opinions, which may inform but should not replace clinical judgment.”
, for whom withholding these medications “might provide more risk than benefit.”
Withholding GLP-1 receptor agonists may be safe and reasonable for patients taking them solely for weight loss, but “this should not be considered mandatory or evidence-based,” as it remains unclear whether withholding one dose is enough to restore normal gastric motility.
“Generally, in patients on GLP-1 receptor agonists who have followed standard perioperative procedures (typically an 8-hour solid-food fast and a 2-hour liquid fast) and who do not have symptoms of nausea, vomiting, dyspepsia, or abdominal distention, we advise proceeding with upper and/or lower endoscopy,” the panelists concluded.
The rapid clinical practice update was commissioned and approved by the AGA. The update panelists disclosed relationships with Apollo Endosurgery, Medtronic, Boston Scientific, and others.
The American Gastroenterological Association (AGA) has issued a rapid clinical practice update on the use of glucagon-like peptide 1 (GLP-1) receptor agonists prior to endoscopy.
The update was partly prompted by consensus-based perioperative guidance issued by the American Society of Anesthesiologists in June 2023, which advises withholding GLP-1 receptor agonists before endoscopy. This recommendation has caused some anesthesia providers to cancel or postpone endoscopic procedures, or even elect general endotracheal intubation over standard sedation.
“Many facilities and medical centers are now struggling to revise preprocedural protocols for patients taking this class of medications despite the lack of high-level evidence regarding how to proceed,” the panelists wrote in Clinical Gastroenterology and Hepatology. “Important questions include whether these preprocedural changes are necessary, if they truly mitigate periprocedural aspiration, or if the delays instituted by following this guidance might further compound the major problem currently faced nationwide: that of large numbers of patients awaiting endoscopic procedures because of delays from the COVID-19 pandemic, reduction in the recommended age threshold to start colorectal cancer screening in 2018, and workforce challenges.”
The rapid clinical practice update, commissioned and approved by the AGA, includes background on the relationship between GLP-1 receptor agonists and endoscopic procedures, followed by clinical strategies for patients taking these medications.
Lead panelist Jana G. Al Hashash, MD, MSc, AGAF, of Mayo Clinic, Jacksonville, Florida, and colleagues began by noting that GLP-1 receptor agonists have been associated with increased gastric residue in patients with diabetes, and among nondiabetic patients, increased gastric retention of solids but not liquids. Delayed gastric emptying and increased residual gastric contents may be more common among patients on GLP-1 agonists who have vomiting, nausea, dyspepsia, or abdominal bloating, they added.
The above findings “imply an increased risk of aspiration in patients receiving GLP-1 receptor agonist medications who present for procedures that require sedation,” the panelists wrote, but more data is needed to support this hypothesis.
Yet the implications for endoscopic risk are still unclear.
Residual liquid in the stomach, at least, is “less of an issue,” according to the update, since “it is easily removed during an esophagogastroduodenoscopy, and this is the first maneuver performed by endoscopists on entering the stomach.”
While residual solids in the stomach could theoretically increase risk of aspiration, other patients with gastroparesis, such as those taking opioids, are not routinely given “special dietary precautions or medication adjustments” prior to endoscopy, Dr. Al Hashash and colleagues wrote. Even patients with severe gastroparesis who are undergoing gastric peroral endoscopic myotomy (which depends upon an empty stomach), are only required to stop ingesting solid foods the day before the procedure, they noted.
“It is appropriate that the ASA’s perioperative suggestions for patients on GLP-1 [receptor agonists] are labeled ‘consensus-based guidance on perioperative management,’ because there is clearly insufficient published evidence for a robust systematic review and guideline,” they wrote. “As such, the ASA’s suggestions are expert opinions, which may inform but should not replace clinical judgment.”
, for whom withholding these medications “might provide more risk than benefit.”
Withholding GLP-1 receptor agonists may be safe and reasonable for patients taking them solely for weight loss, but “this should not be considered mandatory or evidence-based,” as it remains unclear whether withholding one dose is enough to restore normal gastric motility.
“Generally, in patients on GLP-1 receptor agonists who have followed standard perioperative procedures (typically an 8-hour solid-food fast and a 2-hour liquid fast) and who do not have symptoms of nausea, vomiting, dyspepsia, or abdominal distention, we advise proceeding with upper and/or lower endoscopy,” the panelists concluded.
The rapid clinical practice update was commissioned and approved by the AGA. The update panelists disclosed relationships with Apollo Endosurgery, Medtronic, Boston Scientific, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
AGA Offers Practical Advice on IBD Diets
.
The new guidance, authored by Jana G. Al Hashash, MD, MSc, AGAF, of Mayo Clinic, Jacksonville, Florida, and colleagues, includes 12 best practices that address dietary options, enteral and parenteral nutrition, patient monitoring, and the need for multidisciplinary care.
“There is growing recognition of the role of diet in the care of patients with IBD, as both an etiopathogenic risk factor and, more recently, as a disease-modifying modality,” the update panelists wrote in Gastroenterology.
Historically, they noted, patients with IBD had been advised to avoid many different foods including fiber, but this strategy may result in unintended consequences.
“[T]hese approaches frequently led patients with IBD to avoid what are traditionally considered healthy foods, even after achieving clinical remission,” Dr. Al Hashash and colleagues wrote.
With an increasing body of data available for dietary interventions in both Crohn’s disease and ulcerative colitis, they wrote the present clinical practice update to offer some needed clarity.
A Starting Point
First, the panelists advise that, unless contraindicated, all patients with IBD follow a Mediterranean diet while minimizing salt, sugar, and ultraprocessed foods.
Patients with symptomatic intestinal strictures may struggle to digest raw fruits and vegetables due to their fibrous nature, they added, so these patients should first soften these foods through cooking, steaming, or “careful chewing” before consumption.
“No diet has consistently been found to decrease the rate of flares in adults with IBD,” the update panelists noted. “A diet low in red and processed meat may reduce ulcerative colitis flares, but has not been found to reduce relapse in Crohn’s disease.”
Beyond these dietary suggestions for adults, the update advises breastfeeding for newborns and a Mediterranean diet for children, as both may reduce risk of developing IBD.
Enteral Nutrition
The update suggests that exclusive enteral nutrition is a reasonable option to induce clinical remission and endoscopic response, or as a steroid-sparing bridge, in Crohn’s disease, although this may be more effective in children than adults.
Malnourished patients may also benefit from exclusive enteral nutrition prior to elective surgery for Crohn’s disease, Dr. Al Hashash and colleagues added, as this strategy can “optimize nutritional status and reduce postoperative complications.”
A Crohn’s disease exclusion diet, which involves partial enteral nutrition therapy, may be considered in mild or moderate cases, according to the update.
“Data on the use of enteral nutrition in the treatment of active ulcerative colitis are limited,” the panelists wrote, although early data suggest it is safe and well tolerated, and can improve prealbumin levels.
Parenteral Nutrition
The update recommends short-term parenteral nutrition for patients with phlegmonous inflammation and/or an intra-abdominal abscess, as this can act as a bridge to surgical intervention.
Patients with prolonged ileus, short bowel syndrome, or high-output gastrointestinal fistula may also be candidates for parenteral nutrition, as well as those who have tried and failed both oral and enteral nutrition.
Lastly, the update encourages transition from long-term parenteral nutrition to oral intake and customized hydration management “whenever possible.”
Monitoring and Multidisciplinary Care
Dr. Al Hashash and colleagues concluded by advising that all patients with complicated IBD be comanaged by a gastroenterologist and a registered dietitian, both of whom should remain watchful for signs of malnutrition.
Using serum protein as a surrogate marker of malnutrition is no longer recommended and there are different criteria that should be utilized to identify malnutrition. Routine iron and vitamin D testing are warranted, as well as B12 testing for patients with extensive ileal disease or a history of ileal surgery.
This clinical practice update was commissioned and approved by the AGA. The update panelists disclosed relationships with Merck, Celgene, Janssen, and others.
.
The new guidance, authored by Jana G. Al Hashash, MD, MSc, AGAF, of Mayo Clinic, Jacksonville, Florida, and colleagues, includes 12 best practices that address dietary options, enteral and parenteral nutrition, patient monitoring, and the need for multidisciplinary care.
“There is growing recognition of the role of diet in the care of patients with IBD, as both an etiopathogenic risk factor and, more recently, as a disease-modifying modality,” the update panelists wrote in Gastroenterology.
Historically, they noted, patients with IBD had been advised to avoid many different foods including fiber, but this strategy may result in unintended consequences.
“[T]hese approaches frequently led patients with IBD to avoid what are traditionally considered healthy foods, even after achieving clinical remission,” Dr. Al Hashash and colleagues wrote.
With an increasing body of data available for dietary interventions in both Crohn’s disease and ulcerative colitis, they wrote the present clinical practice update to offer some needed clarity.
A Starting Point
First, the panelists advise that, unless contraindicated, all patients with IBD follow a Mediterranean diet while minimizing salt, sugar, and ultraprocessed foods.
Patients with symptomatic intestinal strictures may struggle to digest raw fruits and vegetables due to their fibrous nature, they added, so these patients should first soften these foods through cooking, steaming, or “careful chewing” before consumption.
“No diet has consistently been found to decrease the rate of flares in adults with IBD,” the update panelists noted. “A diet low in red and processed meat may reduce ulcerative colitis flares, but has not been found to reduce relapse in Crohn’s disease.”
Beyond these dietary suggestions for adults, the update advises breastfeeding for newborns and a Mediterranean diet for children, as both may reduce risk of developing IBD.
Enteral Nutrition
The update suggests that exclusive enteral nutrition is a reasonable option to induce clinical remission and endoscopic response, or as a steroid-sparing bridge, in Crohn’s disease, although this may be more effective in children than adults.
Malnourished patients may also benefit from exclusive enteral nutrition prior to elective surgery for Crohn’s disease, Dr. Al Hashash and colleagues added, as this strategy can “optimize nutritional status and reduce postoperative complications.”
A Crohn’s disease exclusion diet, which involves partial enteral nutrition therapy, may be considered in mild or moderate cases, according to the update.
“Data on the use of enteral nutrition in the treatment of active ulcerative colitis are limited,” the panelists wrote, although early data suggest it is safe and well tolerated, and can improve prealbumin levels.
Parenteral Nutrition
The update recommends short-term parenteral nutrition for patients with phlegmonous inflammation and/or an intra-abdominal abscess, as this can act as a bridge to surgical intervention.
Patients with prolonged ileus, short bowel syndrome, or high-output gastrointestinal fistula may also be candidates for parenteral nutrition, as well as those who have tried and failed both oral and enteral nutrition.
Lastly, the update encourages transition from long-term parenteral nutrition to oral intake and customized hydration management “whenever possible.”
Monitoring and Multidisciplinary Care
Dr. Al Hashash and colleagues concluded by advising that all patients with complicated IBD be comanaged by a gastroenterologist and a registered dietitian, both of whom should remain watchful for signs of malnutrition.
Using serum protein as a surrogate marker of malnutrition is no longer recommended and there are different criteria that should be utilized to identify malnutrition. Routine iron and vitamin D testing are warranted, as well as B12 testing for patients with extensive ileal disease or a history of ileal surgery.
This clinical practice update was commissioned and approved by the AGA. The update panelists disclosed relationships with Merck, Celgene, Janssen, and others.
.
The new guidance, authored by Jana G. Al Hashash, MD, MSc, AGAF, of Mayo Clinic, Jacksonville, Florida, and colleagues, includes 12 best practices that address dietary options, enteral and parenteral nutrition, patient monitoring, and the need for multidisciplinary care.
“There is growing recognition of the role of diet in the care of patients with IBD, as both an etiopathogenic risk factor and, more recently, as a disease-modifying modality,” the update panelists wrote in Gastroenterology.
Historically, they noted, patients with IBD had been advised to avoid many different foods including fiber, but this strategy may result in unintended consequences.
“[T]hese approaches frequently led patients with IBD to avoid what are traditionally considered healthy foods, even after achieving clinical remission,” Dr. Al Hashash and colleagues wrote.
With an increasing body of data available for dietary interventions in both Crohn’s disease and ulcerative colitis, they wrote the present clinical practice update to offer some needed clarity.
A Starting Point
First, the panelists advise that, unless contraindicated, all patients with IBD follow a Mediterranean diet while minimizing salt, sugar, and ultraprocessed foods.
Patients with symptomatic intestinal strictures may struggle to digest raw fruits and vegetables due to their fibrous nature, they added, so these patients should first soften these foods through cooking, steaming, or “careful chewing” before consumption.
“No diet has consistently been found to decrease the rate of flares in adults with IBD,” the update panelists noted. “A diet low in red and processed meat may reduce ulcerative colitis flares, but has not been found to reduce relapse in Crohn’s disease.”
Beyond these dietary suggestions for adults, the update advises breastfeeding for newborns and a Mediterranean diet for children, as both may reduce risk of developing IBD.
Enteral Nutrition
The update suggests that exclusive enteral nutrition is a reasonable option to induce clinical remission and endoscopic response, or as a steroid-sparing bridge, in Crohn’s disease, although this may be more effective in children than adults.
Malnourished patients may also benefit from exclusive enteral nutrition prior to elective surgery for Crohn’s disease, Dr. Al Hashash and colleagues added, as this strategy can “optimize nutritional status and reduce postoperative complications.”
A Crohn’s disease exclusion diet, which involves partial enteral nutrition therapy, may be considered in mild or moderate cases, according to the update.
“Data on the use of enteral nutrition in the treatment of active ulcerative colitis are limited,” the panelists wrote, although early data suggest it is safe and well tolerated, and can improve prealbumin levels.
Parenteral Nutrition
The update recommends short-term parenteral nutrition for patients with phlegmonous inflammation and/or an intra-abdominal abscess, as this can act as a bridge to surgical intervention.
Patients with prolonged ileus, short bowel syndrome, or high-output gastrointestinal fistula may also be candidates for parenteral nutrition, as well as those who have tried and failed both oral and enteral nutrition.
Lastly, the update encourages transition from long-term parenteral nutrition to oral intake and customized hydration management “whenever possible.”
Monitoring and Multidisciplinary Care
Dr. Al Hashash and colleagues concluded by advising that all patients with complicated IBD be comanaged by a gastroenterologist and a registered dietitian, both of whom should remain watchful for signs of malnutrition.
Using serum protein as a surrogate marker of malnutrition is no longer recommended and there are different criteria that should be utilized to identify malnutrition. Routine iron and vitamin D testing are warranted, as well as B12 testing for patients with extensive ileal disease or a history of ileal surgery.
This clinical practice update was commissioned and approved by the AGA. The update panelists disclosed relationships with Merck, Celgene, Janssen, and others.
FROM GASTROENTEROLOGY