From the Journals

Adults with gastrointestinal (GI) diseases are significantly more likely to experience sleep disturbances than those without GI conditions, a new study involving more than 10,000 individuals has found.

“Emerging evidence suggests a bidirectional relationship between GI diseases and sleep disorders, whereby dysfunction in one domain may exacerbate the other,” wrote Shicheng Ye, PhD, of The Third Clinical Medical College of Guangzhou University of Chinese Medicine, and colleagues. However, previous studies on the association between GI and sleep problems have been small, and the role of depression as a mediator has not been well explored.

In the study, which was published online in BMC Gastroenterology, the researchers reviewed data from the US National Health and Nutrition Examination Survey between 2005 and 2014. The study population included 10,626 adults aged 20 years or older, with a mean age of 45.6 years, 50.8% of whom were women. Of these, 6444 were identified as having GI disease on the basis of a “yes” response to the question of whether they had a stomach or intestinal illness with vomiting or diarrhea within the past 30 days.

Researchers also examined responses to survey questions related to sleep duration, trouble sleeping, and diagnosis of a sleep disorder. Individuals with vs without GI diseases had a significantly higher prevalence of sleep trouble (37.99% vs 24.21%; P < .001) and a greater frequency of diagnosed sleep disorders (14.99% vs 8.08%; P < .001).

An analysis adjusted for demographic, lifestyle, and clinical factors found that individuals with vs without GI diseases were 70% more likely to have sleep trouble. Individuals with vs without GI diseases were also significantly more likely to have a diagnosed sleep disorder and a reduction in sleep duration (adjusted odds ratio, 1.8; adjusted beta, -0.15).

The association between GI diseases and sleep problems remained consistent across individuals of multiple subgroups, including those without hypertension, diabetes, or a history of smoking. It also remained significant among individuals with coronary heart disease and higher scores on the dietary index for gut microbiota. No significant interaction effects related to age, sex, or chronic disease appeared in any subgroup (P > .05).

An additional mediation analysis found that depression partly mediated the associations between GI diseases and sleep issues. Depression accounted for 21.29% of the total effect on sleep problems, 19.23% of the effect on sleep disorders, and 26.68% of the effect on sleep duration.

The mediating role of depression on the association between GI disease and sleep problems may not be exclusive, the researchers wrote. Other potential mechanisms may include systemic inflammation, visceral hypersensitivity, and metabolic dysfunction.

The findings were limited by several factors, including the possibly underpowered sample size for machine-learning models and the reliance on self-reports of GI diseases, sleep outcomes, and coronary heart disease, the researchers noted. Other limitations included the inability to adjust for confounding factors, including obstructive sleep apnea, chronic pain, and hypertension.

However, the results illustrate the need to address both psychological and GI factors in clinical practice to improve sleep health, the researchers wrote. More research is needed to identify causal pathways and develop targeted, multidimensional interventions for this interconnected trio of health problems.

 

Increasing Evidence for Gut-Brain Interaction

Both sleep disorders and disorders of GBI (DGBI) are highly prevalent worldwide, Jatin Roper, MD, gastroenterologist and associate professor of medicine at Duke University, Durham, North Carolina, told GI & Hepatology News.

“A growing body of evidence suggests that DGBI, including irritable bowel syndrome, are caused by imbalances in signaling between the brain and the intestine, which include the vagus nerve, hormonal signals, the gut microbiota, and immune system,” said Roper, who was not involved in the current study.

“Since many sleep disturbances are centrally mediated, it is plausible that sleep and gastrointestinal disorders could be mechanistically linked,” he said. Rigorous analysis of patient databases for a possible association between sleep and GI disorders, as was done in the current study, is an important step.

The current study findings were not unexpected, “particularly the finding that depression may mediate a link between sleep and GI disorders, because depression is well known to be associated to sleep disturbances and DGBI,” Roper said.

However, GI doctors often do not ask patients about problems with sleep, and pulmonary doctors or sleep specialists may not ask patients about GI symptoms, Roper noted. Similarly, patients may not bring up all their symptoms when seeing these specialists.

“The current study underscores the need for comprehensive, multisystem evaluations in specialty clinics for sleep and GI conditions and appropriate referrals to specialists, when necessary,” he said.

The research raised an important question of whether sleep and GI disorders are associated with each other because of other underlying medical conditions, which may be difficult to control for in cross-sectional studies, or whether sleep problems cause GI problems or vice versa, Roper said. Other uncertainties include whether the conditions are biologically linked, possibly through shared changes in the brain-gut axis.

Long-term observational studies would be useful to identify whether sleep disturbances precede DGBI or vice versa, Roper added.

The study received no outside funding. The researchers and Roper had no financial conflicts to disclose.

A version of this article first appeared on Medscape.com.

Adults with gastrointestinal (GI) diseases are significantly more likely to experience sleep disturbances than those without GI conditions, a new study involving more than 10,000 individuals has found.

“Emerging evidence suggests a bidirectional relationship between GI diseases and sleep disorders, whereby dysfunction in one domain may exacerbate the other,” wrote Shicheng Ye, PhD, of The Third Clinical Medical College of Guangzhou University of Chinese Medicine, and colleagues. However, previous studies on the association between GI and sleep problems have been small, and the role of depression as a mediator has not been well explored.

In the study, which was published online in BMC Gastroenterology, the researchers reviewed data from the US National Health and Nutrition Examination Survey between 2005 and 2014. The study population included 10,626 adults aged 20 years or older, with a mean age of 45.6 years, 50.8% of whom were women. Of these, 6444 were identified as having GI disease on the basis of a “yes” response to the question of whether they had a stomach or intestinal illness with vomiting or diarrhea within the past 30 days.

Researchers also examined responses to survey questions related to sleep duration, trouble sleeping, and diagnosis of a sleep disorder. Individuals with vs without GI diseases had a significantly higher prevalence of sleep trouble (37.99% vs 24.21%; P < .001) and a greater frequency of diagnosed sleep disorders (14.99% vs 8.08%; P < .001).

An analysis adjusted for demographic, lifestyle, and clinical factors found that individuals with vs without GI diseases were 70% more likely to have sleep trouble. Individuals with vs without GI diseases were also significantly more likely to have a diagnosed sleep disorder and a reduction in sleep duration (adjusted odds ratio, 1.8; adjusted beta, -0.15).

The association between GI diseases and sleep problems remained consistent across individuals of multiple subgroups, including those without hypertension, diabetes, or a history of smoking. It also remained significant among individuals with coronary heart disease and higher scores on the dietary index for gut microbiota. No significant interaction effects related to age, sex, or chronic disease appeared in any subgroup (P > .05).

An additional mediation analysis found that depression partly mediated the associations between GI diseases and sleep issues. Depression accounted for 21.29% of the total effect on sleep problems, 19.23% of the effect on sleep disorders, and 26.68% of the effect on sleep duration.

The mediating role of depression on the association between GI disease and sleep problems may not be exclusive, the researchers wrote. Other potential mechanisms may include systemic inflammation, visceral hypersensitivity, and metabolic dysfunction.

The findings were limited by several factors, including the possibly underpowered sample size for machine-learning models and the reliance on self-reports of GI diseases, sleep outcomes, and coronary heart disease, the researchers noted. Other limitations included the inability to adjust for confounding factors, including obstructive sleep apnea, chronic pain, and hypertension.

However, the results illustrate the need to address both psychological and GI factors in clinical practice to improve sleep health, the researchers wrote. More research is needed to identify causal pathways and develop targeted, multidimensional interventions for this interconnected trio of health problems.

 

Increasing Evidence for Gut-Brain Interaction

Both sleep disorders and disorders of GBI (DGBI) are highly prevalent worldwide, Jatin Roper, MD, gastroenterologist and associate professor of medicine at Duke University, Durham, North Carolina, told GI & Hepatology News.

“A growing body of evidence suggests that DGBI, including irritable bowel syndrome, are caused by imbalances in signaling between the brain and the intestine, which include the vagus nerve, hormonal signals, the gut microbiota, and immune system,” said Roper, who was not involved in the current study.

“Since many sleep disturbances are centrally mediated, it is plausible that sleep and gastrointestinal disorders could be mechanistically linked,” he said. Rigorous analysis of patient databases for a possible association between sleep and GI disorders, as was done in the current study, is an important step.

The current study findings were not unexpected, “particularly the finding that depression may mediate a link between sleep and GI disorders, because depression is well known to be associated to sleep disturbances and DGBI,” Roper said.

However, GI doctors often do not ask patients about problems with sleep, and pulmonary doctors or sleep specialists may not ask patients about GI symptoms, Roper noted. Similarly, patients may not bring up all their symptoms when seeing these specialists.

“The current study underscores the need for comprehensive, multisystem evaluations in specialty clinics for sleep and GI conditions and appropriate referrals to specialists, when necessary,” he said.

The research raised an important question of whether sleep and GI disorders are associated with each other because of other underlying medical conditions, which may be difficult to control for in cross-sectional studies, or whether sleep problems cause GI problems or vice versa, Roper said. Other uncertainties include whether the conditions are biologically linked, possibly through shared changes in the brain-gut axis.

Long-term observational studies would be useful to identify whether sleep disturbances precede DGBI or vice versa, Roper added.

The study received no outside funding. The researchers and Roper had no financial conflicts to disclose.

A version of this article first appeared on Medscape.com.

Adults with gastrointestinal (GI) diseases are significantly more likely to experience sleep disturbances than those without GI conditions, a new study involving more than 10,000 individuals has found.

“Emerging evidence suggests a bidirectional relationship between GI diseases and sleep disorders, whereby dysfunction in one domain may exacerbate the other,” wrote Shicheng Ye, PhD, of The Third Clinical Medical College of Guangzhou University of Chinese Medicine, and colleagues. However, previous studies on the association between GI and sleep problems have been small, and the role of depression as a mediator has not been well explored.

In the study, which was published online in BMC Gastroenterology, the researchers reviewed data from the US National Health and Nutrition Examination Survey between 2005 and 2014. The study population included 10,626 adults aged 20 years or older, with a mean age of 45.6 years, 50.8% of whom were women. Of these, 6444 were identified as having GI disease on the basis of a “yes” response to the question of whether they had a stomach or intestinal illness with vomiting or diarrhea within the past 30 days.

Researchers also examined responses to survey questions related to sleep duration, trouble sleeping, and diagnosis of a sleep disorder. Individuals with vs without GI diseases had a significantly higher prevalence of sleep trouble (37.99% vs 24.21%; P < .001) and a greater frequency of diagnosed sleep disorders (14.99% vs 8.08%; P < .001).

An analysis adjusted for demographic, lifestyle, and clinical factors found that individuals with vs without GI diseases were 70% more likely to have sleep trouble. Individuals with vs without GI diseases were also significantly more likely to have a diagnosed sleep disorder and a reduction in sleep duration (adjusted odds ratio, 1.8; adjusted beta, -0.15).

The association between GI diseases and sleep problems remained consistent across individuals of multiple subgroups, including those without hypertension, diabetes, or a history of smoking. It also remained significant among individuals with coronary heart disease and higher scores on the dietary index for gut microbiota. No significant interaction effects related to age, sex, or chronic disease appeared in any subgroup (P > .05).

An additional mediation analysis found that depression partly mediated the associations between GI diseases and sleep issues. Depression accounted for 21.29% of the total effect on sleep problems, 19.23% of the effect on sleep disorders, and 26.68% of the effect on sleep duration.

The mediating role of depression on the association between GI disease and sleep problems may not be exclusive, the researchers wrote. Other potential mechanisms may include systemic inflammation, visceral hypersensitivity, and metabolic dysfunction.

The findings were limited by several factors, including the possibly underpowered sample size for machine-learning models and the reliance on self-reports of GI diseases, sleep outcomes, and coronary heart disease, the researchers noted. Other limitations included the inability to adjust for confounding factors, including obstructive sleep apnea, chronic pain, and hypertension.

However, the results illustrate the need to address both psychological and GI factors in clinical practice to improve sleep health, the researchers wrote. More research is needed to identify causal pathways and develop targeted, multidimensional interventions for this interconnected trio of health problems.

 

Increasing Evidence for Gut-Brain Interaction

Both sleep disorders and disorders of GBI (DGBI) are highly prevalent worldwide, Jatin Roper, MD, gastroenterologist and associate professor of medicine at Duke University, Durham, North Carolina, told GI & Hepatology News.

“A growing body of evidence suggests that DGBI, including irritable bowel syndrome, are caused by imbalances in signaling between the brain and the intestine, which include the vagus nerve, hormonal signals, the gut microbiota, and immune system,” said Roper, who was not involved in the current study.

“Since many sleep disturbances are centrally mediated, it is plausible that sleep and gastrointestinal disorders could be mechanistically linked,” he said. Rigorous analysis of patient databases for a possible association between sleep and GI disorders, as was done in the current study, is an important step.

The current study findings were not unexpected, “particularly the finding that depression may mediate a link between sleep and GI disorders, because depression is well known to be associated to sleep disturbances and DGBI,” Roper said.

However, GI doctors often do not ask patients about problems with sleep, and pulmonary doctors or sleep specialists may not ask patients about GI symptoms, Roper noted. Similarly, patients may not bring up all their symptoms when seeing these specialists.

“The current study underscores the need for comprehensive, multisystem evaluations in specialty clinics for sleep and GI conditions and appropriate referrals to specialists, when necessary,” he said.

The research raised an important question of whether sleep and GI disorders are associated with each other because of other underlying medical conditions, which may be difficult to control for in cross-sectional studies, or whether sleep problems cause GI problems or vice versa, Roper said. Other uncertainties include whether the conditions are biologically linked, possibly through shared changes in the brain-gut axis.

Long-term observational studies would be useful to identify whether sleep disturbances precede DGBI or vice versa, Roper added.

The study received no outside funding. The researchers and Roper had no financial conflicts to disclose.

A version of this article first appeared on Medscape.com.

Patients with intestinal methanogen overgrowth (IMO) have a higher rate and severity of constipation but a lower rate and severity of diarrhea, according to a systematic review and meta-analysis published in Clinical Gastroenterology and Hepatology.

“The distinct phenotype of patients with IMO should be incorporated in patient-reported outcome measures and further correlated with mechanistic microbiome studies,” wrote investigators led by gastroenterologist Ali Rezaie, MD, MSc, medical director of the GI Motility Program at Cedars-Sinai Medical Center and director of biotechnology in the center’s Medically Associated Science and Technology (MAST) Program. Recognizing specific GI symptom profiles can improve diagnosis and treatment strategies, facilitating further clinical trials and targeted microbiome studies to optimize patient care. 

Excessive luminal loads of methanogenic archaea – archaea being bacteria-like prokaryotes and one of the main three domains of the tree of life – have been implicated in the pathophysiology of various diseases, including constipation. 

 

The Study

To elucidate the phenotypical presentation of IMO in patients, Rezaie’s group compared the prevalence and severity of gastrointestinal (GI) symptoms in individuals who had IMO with those who did not have IMO. IMO was based on excess levels of this gaseous GI byproduct in exhaled breath tests.

Searching electronic databases from inception to September 2023, the researchers identified 19 eligible studies from diverse geographical regions with 1293 IMO patients and 3208 controls. Eleven studies were performed in the United States; the other studies were conducted in France (n = 2), India (n = 2), New Zealand (n = 1), South Korea (n = 1), Italy (n = 1), and the United Kingdom (n = 1). Thirteen studies were of high quality, as defined by a Newcastle-Ottawa Assessment Scale score of 6. 

Patients with IMO were found to exhibit a range of GI symptoms, including bloating (78%), constipation (51%), diarrhea (33%), abdominal pain (65%), nausea (30%), and flatulence (56%).

In other findings:

• Patients with IMO had a significantly higher prevalence of constipation vs controls: 47% vs 38% (odds ratio [OR], 2.04, 95% confidence interval [CI], 1.48-2.83, P < .0001).
• They had a lower prevalence of diarrhea: 37% vs 52% (OR .58, 95% CI, .37-.90, P = .01); and nausea: 32% vs 45%; (OR, .75; 95% CI, .60-.94, P = .01).
• Patients with IMO had more severe constipation: standard mean deviation [SMD], .77 (95% CI, .11-1.43, P = .02) and a lower severity of diarrhea: SMD, –.71 (95% CI, –1.39 to –.03, P = .04). Significant heterogeneity of effect, however, was detected.
• Constipation was more prevalent in IMO diagnosed with the lactulose breath test and the glucose breath test and constipation was particularly prevalent in Europe and the United States.

Mechanism of Action

The findings on constipation and diarrhea corroborate methane’s slowing physiologic effects on motility, the authors noted. It has been consistently found to delay gut transit, both small bowel and colonic transit.

Mechanistically, methane reduces small intestinal peristaltic velocity while augmenting non-propagating contraction amplitude, suggesting that reduction of intestinal transit time is mediated through promotion of non-propulsive contractions.

“This study further consolidates methane’s causal role in constipation and paves the way to establish validated disease-specific patient-reported outcomes,” Rezaie and associates wrote, calling for longitudinal and mechanistic studies assessing the archaeome in order to advance understanding of IMO.

This study was funded in part by Nancy Stark and Stanley Lezman in support of the MAST Program’s Innovation Project at Cedars-Sinai.

Rezaie serves as a consultant/speaker for Bausch Health. Cedars-Sinai Medical Center has a licensing agreement with Gemelli Biotech, in which Rezaie and coauthor Pimentel have equity. They also hold equity in Good LIFE. Pimentel consults for and has received grant support from Bausch Health.

Patients with intestinal methanogen overgrowth (IMO) have a higher rate and severity of constipation but a lower rate and severity of diarrhea, according to a systematic review and meta-analysis published in Clinical Gastroenterology and Hepatology.

“The distinct phenotype of patients with IMO should be incorporated in patient-reported outcome measures and further correlated with mechanistic microbiome studies,” wrote investigators led by gastroenterologist Ali Rezaie, MD, MSc, medical director of the GI Motility Program at Cedars-Sinai Medical Center and director of biotechnology in the center’s Medically Associated Science and Technology (MAST) Program. Recognizing specific GI symptom profiles can improve diagnosis and treatment strategies, facilitating further clinical trials and targeted microbiome studies to optimize patient care. 

Excessive luminal loads of methanogenic archaea – archaea being bacteria-like prokaryotes and one of the main three domains of the tree of life – have been implicated in the pathophysiology of various diseases, including constipation. 

 

The Study

To elucidate the phenotypical presentation of IMO in patients, Rezaie’s group compared the prevalence and severity of gastrointestinal (GI) symptoms in individuals who had IMO with those who did not have IMO. IMO was based on excess levels of this gaseous GI byproduct in exhaled breath tests.

Searching electronic databases from inception to September 2023, the researchers identified 19 eligible studies from diverse geographical regions with 1293 IMO patients and 3208 controls. Eleven studies were performed in the United States; the other studies were conducted in France (n = 2), India (n = 2), New Zealand (n = 1), South Korea (n = 1), Italy (n = 1), and the United Kingdom (n = 1). Thirteen studies were of high quality, as defined by a Newcastle-Ottawa Assessment Scale score of 6. 

Patients with IMO were found to exhibit a range of GI symptoms, including bloating (78%), constipation (51%), diarrhea (33%), abdominal pain (65%), nausea (30%), and flatulence (56%).

In other findings:

• Patients with IMO had a significantly higher prevalence of constipation vs controls: 47% vs 38% (odds ratio [OR], 2.04, 95% confidence interval [CI], 1.48-2.83, P < .0001).
• They had a lower prevalence of diarrhea: 37% vs 52% (OR .58, 95% CI, .37-.90, P = .01); and nausea: 32% vs 45%; (OR, .75; 95% CI, .60-.94, P = .01).
• Patients with IMO had more severe constipation: standard mean deviation [SMD], .77 (95% CI, .11-1.43, P = .02) and a lower severity of diarrhea: SMD, –.71 (95% CI, –1.39 to –.03, P = .04). Significant heterogeneity of effect, however, was detected.
• Constipation was more prevalent in IMO diagnosed with the lactulose breath test and the glucose breath test and constipation was particularly prevalent in Europe and the United States.

Mechanism of Action

The findings on constipation and diarrhea corroborate methane’s slowing physiologic effects on motility, the authors noted. It has been consistently found to delay gut transit, both small bowel and colonic transit.

Mechanistically, methane reduces small intestinal peristaltic velocity while augmenting non-propagating contraction amplitude, suggesting that reduction of intestinal transit time is mediated through promotion of non-propulsive contractions.

“This study further consolidates methane’s causal role in constipation and paves the way to establish validated disease-specific patient-reported outcomes,” Rezaie and associates wrote, calling for longitudinal and mechanistic studies assessing the archaeome in order to advance understanding of IMO.

This study was funded in part by Nancy Stark and Stanley Lezman in support of the MAST Program’s Innovation Project at Cedars-Sinai.

Rezaie serves as a consultant/speaker for Bausch Health. Cedars-Sinai Medical Center has a licensing agreement with Gemelli Biotech, in which Rezaie and coauthor Pimentel have equity. They also hold equity in Good LIFE. Pimentel consults for and has received grant support from Bausch Health.

Patients with intestinal methanogen overgrowth (IMO) have a higher rate and severity of constipation but a lower rate and severity of diarrhea, according to a systematic review and meta-analysis published in Clinical Gastroenterology and Hepatology.

“The distinct phenotype of patients with IMO should be incorporated in patient-reported outcome measures and further correlated with mechanistic microbiome studies,” wrote investigators led by gastroenterologist Ali Rezaie, MD, MSc, medical director of the GI Motility Program at Cedars-Sinai Medical Center and director of biotechnology in the center’s Medically Associated Science and Technology (MAST) Program. Recognizing specific GI symptom profiles can improve diagnosis and treatment strategies, facilitating further clinical trials and targeted microbiome studies to optimize patient care. 

Excessive luminal loads of methanogenic archaea – archaea being bacteria-like prokaryotes and one of the main three domains of the tree of life – have been implicated in the pathophysiology of various diseases, including constipation. 

 

The Study

To elucidate the phenotypical presentation of IMO in patients, Rezaie’s group compared the prevalence and severity of gastrointestinal (GI) symptoms in individuals who had IMO with those who did not have IMO. IMO was based on excess levels of this gaseous GI byproduct in exhaled breath tests.

Searching electronic databases from inception to September 2023, the researchers identified 19 eligible studies from diverse geographical regions with 1293 IMO patients and 3208 controls. Eleven studies were performed in the United States; the other studies were conducted in France (n = 2), India (n = 2), New Zealand (n = 1), South Korea (n = 1), Italy (n = 1), and the United Kingdom (n = 1). Thirteen studies were of high quality, as defined by a Newcastle-Ottawa Assessment Scale score of 6. 

Patients with IMO were found to exhibit a range of GI symptoms, including bloating (78%), constipation (51%), diarrhea (33%), abdominal pain (65%), nausea (30%), and flatulence (56%).

In other findings:

• Patients with IMO had a significantly higher prevalence of constipation vs controls: 47% vs 38% (odds ratio [OR], 2.04, 95% confidence interval [CI], 1.48-2.83, P < .0001).
• They had a lower prevalence of diarrhea: 37% vs 52% (OR .58, 95% CI, .37-.90, P = .01); and nausea: 32% vs 45%; (OR, .75; 95% CI, .60-.94, P = .01).
• Patients with IMO had more severe constipation: standard mean deviation [SMD], .77 (95% CI, .11-1.43, P = .02) and a lower severity of diarrhea: SMD, –.71 (95% CI, –1.39 to –.03, P = .04). Significant heterogeneity of effect, however, was detected.
• Constipation was more prevalent in IMO diagnosed with the lactulose breath test and the glucose breath test and constipation was particularly prevalent in Europe and the United States.

Mechanism of Action

The findings on constipation and diarrhea corroborate methane’s slowing physiologic effects on motility, the authors noted. It has been consistently found to delay gut transit, both small bowel and colonic transit.

Mechanistically, methane reduces small intestinal peristaltic velocity while augmenting non-propagating contraction amplitude, suggesting that reduction of intestinal transit time is mediated through promotion of non-propulsive contractions.

“This study further consolidates methane’s causal role in constipation and paves the way to establish validated disease-specific patient-reported outcomes,” Rezaie and associates wrote, calling for longitudinal and mechanistic studies assessing the archaeome in order to advance understanding of IMO.

This study was funded in part by Nancy Stark and Stanley Lezman in support of the MAST Program’s Innovation Project at Cedars-Sinai.

Rezaie serves as a consultant/speaker for Bausch Health. Cedars-Sinai Medical Center has a licensing agreement with Gemelli Biotech, in which Rezaie and coauthor Pimentel have equity. They also hold equity in Good LIFE. Pimentel consults for and has received grant support from Bausch Health.

No evidence of a causal relationship between previously suspected pharmacologic triggers and increased risk of microscopic colitis (MC) emerged from a nationwide longitudinal study of older Swedish individuals in a national database.

“Sensitivity analyses suggest that previously reported associations and persistent association with SSRI [selective serotonin reuptake inhibitor] initiation may be due to surveillance bias,” wrote gastroenterologist Hamed Khalili, MD, MPH, of Massachusetts General Hospital, Boston, and colleagues in Annals of Internal Medicine, advising clinicians to carefully balance the benefits of these medication classes against the very low likelihood of a causal relationship with MC.

While two smaller studies had challenged the belief that these medications can cause MC, Khalili told GI & Hepatology News, “the quality of the data that supported or refuted this hypothesis were low. Nevertheless, most in the field consider MC to be largely related to medications so we thought it was important to systematically answer this question.”

While most medications thought to trigger MC were found not to be causally linked, he added, “we did observe a marginal association with SSRIs but could not rule out the possibility that the association is related to residual bias.”

The authors noted that the incidence of MC in older persons is rising rapidly and is thought to account for more than 30% of chronic diarrhea cases in this group.

Despite weak evidence in the literature, the treatment guidelines of several societies, including the American Gastroenterological Association, recommend discontinuing potential pharmacologic triggers as first-line prevention or as an adjunct therapy, particularly in recurrent or refractory MC. But this approach may be ineffective in patients with established disease and could lead to inappropriate discontinuation of medication such as antihypertensives, the authors argued.

As to proposed mechanisms of action, said Khalili, “for PPIs [proton-pump inhibitors,] people thought it was related to changes in the gut microbiome. For NSAIDs [nonsteroidal anti-inflammatory drugs], people thought it could be related to changes in the gut barrier function. But overall, not a single mechanism would have explained all the prior associations that were observed.”

While medications such as PPIs and SSRIs can cause diarrhea in a small subset of users, Khalili added, “most patients generally catch these side effects very quickly and realize that stopping these medications will improve their diarrhea. This is very different than most patients we as gastroenterologists see with a new diagnosis of MC. Many of them may have been on these medications for a long time. We believe that stopping medications in these patients is unnecessary.” 

 

Study Details

The investigators looked at eligible residents in Sweden age 65 years or older in the years 2006 to 2017 (n = 191,482 to 2,634,777). Participants had no history of inflammatory bowel disease and different cohorts were examined for various common medications from calcium channel blockers to statins.

With a primary outcome of biopsy-verified MC, dates of diagnosis were obtained from Sweden’s national histopathology cohort ESPRESSO (Epidemiology Strengthened by Histopathology Reports in Sweden). Among the findings:

• The 12- and 24-month cumulative incidences of MC were less than 0.05% under all treatment strategies.
• Estimated 12-month risk differences were close to null under angiotensin-converting enzyme vs calcium-channel blocker (CCB) initiation, angiotensin-receptor blocker vs CCB initiation, NSAID initiation vs noninitiation, PPI inhibitor initiation vs noninitiation, and statin initiation vs noninitiation.
• The estimated 12-month risk difference was 0.04% (95% CI, 0.03%-0.05%) for SSRIs vs mirtazapine.
• Results were similar for 24-month risk differences. Several medications such as SSRIs were also associated with increased risk for undergoing colonoscopy with a normal colorectal mucosa biopsy result.

“We think it’s unlikely that stopping these medications will improve symptoms of MC,” Khalili said. 

Commenting on the paper but not involved in it, Jordan E. Axelrad, MD, MPH, codirector of the Inflammatory Bowel Disease Center at NYU Langone Health in New York City, said, “This study strengthens the argument that MC is an immune-mediated disease, not primarily driven by drug exposures. But future studies in diverse cohorts are required to validate these findings.” He said the study nevertheless provides reassurance that previously reported associations may have been overstated or confounded by factors such as reverse causation and increased healthcare utilization preceding the MC diagnosis.

In the meantime, Axelrad added, the findings “may reduce the inclination to promptly discontinue medications historically associated with MC in newly diagnosed cases. Also, these data help shift the clinical focus away from medication cessation alone and toward a needed and broader MC management strategy. US-based validation would likely highlight these changes in our patients.”

Despite concerns about the study’s unmeasured confounding because of differential healthcare utilization or surveillance, the modest association observed between SSRI and MC is supported by literature linking catecholamine and serotonin to gut innate immunity and microbiota, Khalili’s group wrote. “However, this finding may also be confounded by other factors including persisting surveillance and protopathic bias, especially since an association was also seen for risk for receipt of a colonoscopy with normal mucosa.”

Khalili believes the Swedish results are applicable even to the more diverse US population. He noted that lack of primary care data limited measurement of and adjustment for symptoms and medical diagnoses that increase risk. But according to Axelrad, MC is more prevalent in White, older patients, who are well-represented in Swedish cohorts but to a lesser extent in US populations. “Additionally, environmental factors and medication use patterns differ between Sweden and the US, particularly in regard to over-the-counter medication access.”

The findings have implications for future research in pharmacoepidemiologic studies of gastrointestinal-related outcomes. Since many routinely prescribed medications such as SSRIs were associated with an apparent increased risk for colonoscopies with normal colorectal biopsy results, future studies that examine gastrointestinal-specific adverse events should carefully consider potential surveillance bias.

In the meantime, Khalili stressed, it’s important to highlight that while some of these medications cause diarrhea in a small subset of patients, stopping medications in these patients is unnecessary.

This study was supported by the National Institutes of Health (NIH) and the Swedish Research Council. Khalili disclosed grants from the Crohn’s & Coiltis Foundation, the NIH and the Helmsley CharitableTrust, as well as stock ownership in Cylinder Health. One coauthor is employed by Massachusetts General Hospital. Axelrad had no relevant competing interests.







 

No evidence of a causal relationship between previously suspected pharmacologic triggers and increased risk of microscopic colitis (MC) emerged from a nationwide longitudinal study of older Swedish individuals in a national database.

“Sensitivity analyses suggest that previously reported associations and persistent association with SSRI [selective serotonin reuptake inhibitor] initiation may be due to surveillance bias,” wrote gastroenterologist Hamed Khalili, MD, MPH, of Massachusetts General Hospital, Boston, and colleagues in Annals of Internal Medicine, advising clinicians to carefully balance the benefits of these medication classes against the very low likelihood of a causal relationship with MC.

While two smaller studies had challenged the belief that these medications can cause MC, Khalili told GI & Hepatology News, “the quality of the data that supported or refuted this hypothesis were low. Nevertheless, most in the field consider MC to be largely related to medications so we thought it was important to systematically answer this question.”

While most medications thought to trigger MC were found not to be causally linked, he added, “we did observe a marginal association with SSRIs but could not rule out the possibility that the association is related to residual bias.”

The authors noted that the incidence of MC in older persons is rising rapidly and is thought to account for more than 30% of chronic diarrhea cases in this group.

Despite weak evidence in the literature, the treatment guidelines of several societies, including the American Gastroenterological Association, recommend discontinuing potential pharmacologic triggers as first-line prevention or as an adjunct therapy, particularly in recurrent or refractory MC. But this approach may be ineffective in patients with established disease and could lead to inappropriate discontinuation of medication such as antihypertensives, the authors argued.

As to proposed mechanisms of action, said Khalili, “for PPIs [proton-pump inhibitors,] people thought it was related to changes in the gut microbiome. For NSAIDs [nonsteroidal anti-inflammatory drugs], people thought it could be related to changes in the gut barrier function. But overall, not a single mechanism would have explained all the prior associations that were observed.”

While medications such as PPIs and SSRIs can cause diarrhea in a small subset of users, Khalili added, “most patients generally catch these side effects very quickly and realize that stopping these medications will improve their diarrhea. This is very different than most patients we as gastroenterologists see with a new diagnosis of MC. Many of them may have been on these medications for a long time. We believe that stopping medications in these patients is unnecessary.” 

 

Study Details

The investigators looked at eligible residents in Sweden age 65 years or older in the years 2006 to 2017 (n = 191,482 to 2,634,777). Participants had no history of inflammatory bowel disease and different cohorts were examined for various common medications from calcium channel blockers to statins.

With a primary outcome of biopsy-verified MC, dates of diagnosis were obtained from Sweden’s national histopathology cohort ESPRESSO (Epidemiology Strengthened by Histopathology Reports in Sweden). Among the findings:

• The 12- and 24-month cumulative incidences of MC were less than 0.05% under all treatment strategies.
• Estimated 12-month risk differences were close to null under angiotensin-converting enzyme vs calcium-channel blocker (CCB) initiation, angiotensin-receptor blocker vs CCB initiation, NSAID initiation vs noninitiation, PPI inhibitor initiation vs noninitiation, and statin initiation vs noninitiation.
• The estimated 12-month risk difference was 0.04% (95% CI, 0.03%-0.05%) for SSRIs vs mirtazapine.
• Results were similar for 24-month risk differences. Several medications such as SSRIs were also associated with increased risk for undergoing colonoscopy with a normal colorectal mucosa biopsy result.

“We think it’s unlikely that stopping these medications will improve symptoms of MC,” Khalili said. 

Commenting on the paper but not involved in it, Jordan E. Axelrad, MD, MPH, codirector of the Inflammatory Bowel Disease Center at NYU Langone Health in New York City, said, “This study strengthens the argument that MC is an immune-mediated disease, not primarily driven by drug exposures. But future studies in diverse cohorts are required to validate these findings.” He said the study nevertheless provides reassurance that previously reported associations may have been overstated or confounded by factors such as reverse causation and increased healthcare utilization preceding the MC diagnosis.

In the meantime, Axelrad added, the findings “may reduce the inclination to promptly discontinue medications historically associated with MC in newly diagnosed cases. Also, these data help shift the clinical focus away from medication cessation alone and toward a needed and broader MC management strategy. US-based validation would likely highlight these changes in our patients.”

Despite concerns about the study’s unmeasured confounding because of differential healthcare utilization or surveillance, the modest association observed between SSRI and MC is supported by literature linking catecholamine and serotonin to gut innate immunity and microbiota, Khalili’s group wrote. “However, this finding may also be confounded by other factors including persisting surveillance and protopathic bias, especially since an association was also seen for risk for receipt of a colonoscopy with normal mucosa.”

Khalili believes the Swedish results are applicable even to the more diverse US population. He noted that lack of primary care data limited measurement of and adjustment for symptoms and medical diagnoses that increase risk. But according to Axelrad, MC is more prevalent in White, older patients, who are well-represented in Swedish cohorts but to a lesser extent in US populations. “Additionally, environmental factors and medication use patterns differ between Sweden and the US, particularly in regard to over-the-counter medication access.”

The findings have implications for future research in pharmacoepidemiologic studies of gastrointestinal-related outcomes. Since many routinely prescribed medications such as SSRIs were associated with an apparent increased risk for colonoscopies with normal colorectal biopsy results, future studies that examine gastrointestinal-specific adverse events should carefully consider potential surveillance bias.

In the meantime, Khalili stressed, it’s important to highlight that while some of these medications cause diarrhea in a small subset of patients, stopping medications in these patients is unnecessary.

This study was supported by the National Institutes of Health (NIH) and the Swedish Research Council. Khalili disclosed grants from the Crohn’s & Coiltis Foundation, the NIH and the Helmsley CharitableTrust, as well as stock ownership in Cylinder Health. One coauthor is employed by Massachusetts General Hospital. Axelrad had no relevant competing interests.







 

No evidence of a causal relationship between previously suspected pharmacologic triggers and increased risk of microscopic colitis (MC) emerged from a nationwide longitudinal study of older Swedish individuals in a national database.

“Sensitivity analyses suggest that previously reported associations and persistent association with SSRI [selective serotonin reuptake inhibitor] initiation may be due to surveillance bias,” wrote gastroenterologist Hamed Khalili, MD, MPH, of Massachusetts General Hospital, Boston, and colleagues in Annals of Internal Medicine, advising clinicians to carefully balance the benefits of these medication classes against the very low likelihood of a causal relationship with MC.

While two smaller studies had challenged the belief that these medications can cause MC, Khalili told GI & Hepatology News, “the quality of the data that supported or refuted this hypothesis were low. Nevertheless, most in the field consider MC to be largely related to medications so we thought it was important to systematically answer this question.”

While most medications thought to trigger MC were found not to be causally linked, he added, “we did observe a marginal association with SSRIs but could not rule out the possibility that the association is related to residual bias.”

The authors noted that the incidence of MC in older persons is rising rapidly and is thought to account for more than 30% of chronic diarrhea cases in this group.

Despite weak evidence in the literature, the treatment guidelines of several societies, including the American Gastroenterological Association, recommend discontinuing potential pharmacologic triggers as first-line prevention or as an adjunct therapy, particularly in recurrent or refractory MC. But this approach may be ineffective in patients with established disease and could lead to inappropriate discontinuation of medication such as antihypertensives, the authors argued.

As to proposed mechanisms of action, said Khalili, “for PPIs [proton-pump inhibitors,] people thought it was related to changes in the gut microbiome. For NSAIDs [nonsteroidal anti-inflammatory drugs], people thought it could be related to changes in the gut barrier function. But overall, not a single mechanism would have explained all the prior associations that were observed.”

While medications such as PPIs and SSRIs can cause diarrhea in a small subset of users, Khalili added, “most patients generally catch these side effects very quickly and realize that stopping these medications will improve their diarrhea. This is very different than most patients we as gastroenterologists see with a new diagnosis of MC. Many of them may have been on these medications for a long time. We believe that stopping medications in these patients is unnecessary.” 

 

Study Details

The investigators looked at eligible residents in Sweden age 65 years or older in the years 2006 to 2017 (n = 191,482 to 2,634,777). Participants had no history of inflammatory bowel disease and different cohorts were examined for various common medications from calcium channel blockers to statins.

With a primary outcome of biopsy-verified MC, dates of diagnosis were obtained from Sweden’s national histopathology cohort ESPRESSO (Epidemiology Strengthened by Histopathology Reports in Sweden). Among the findings:

• The 12- and 24-month cumulative incidences of MC were less than 0.05% under all treatment strategies.
• Estimated 12-month risk differences were close to null under angiotensin-converting enzyme vs calcium-channel blocker (CCB) initiation, angiotensin-receptor blocker vs CCB initiation, NSAID initiation vs noninitiation, PPI inhibitor initiation vs noninitiation, and statin initiation vs noninitiation.
• The estimated 12-month risk difference was 0.04% (95% CI, 0.03%-0.05%) for SSRIs vs mirtazapine.
• Results were similar for 24-month risk differences. Several medications such as SSRIs were also associated with increased risk for undergoing colonoscopy with a normal colorectal mucosa biopsy result.

“We think it’s unlikely that stopping these medications will improve symptoms of MC,” Khalili said. 

Commenting on the paper but not involved in it, Jordan E. Axelrad, MD, MPH, codirector of the Inflammatory Bowel Disease Center at NYU Langone Health in New York City, said, “This study strengthens the argument that MC is an immune-mediated disease, not primarily driven by drug exposures. But future studies in diverse cohorts are required to validate these findings.” He said the study nevertheless provides reassurance that previously reported associations may have been overstated or confounded by factors such as reverse causation and increased healthcare utilization preceding the MC diagnosis.

In the meantime, Axelrad added, the findings “may reduce the inclination to promptly discontinue medications historically associated with MC in newly diagnosed cases. Also, these data help shift the clinical focus away from medication cessation alone and toward a needed and broader MC management strategy. US-based validation would likely highlight these changes in our patients.”

Despite concerns about the study’s unmeasured confounding because of differential healthcare utilization or surveillance, the modest association observed between SSRI and MC is supported by literature linking catecholamine and serotonin to gut innate immunity and microbiota, Khalili’s group wrote. “However, this finding may also be confounded by other factors including persisting surveillance and protopathic bias, especially since an association was also seen for risk for receipt of a colonoscopy with normal mucosa.”

Khalili believes the Swedish results are applicable even to the more diverse US population. He noted that lack of primary care data limited measurement of and adjustment for symptoms and medical diagnoses that increase risk. But according to Axelrad, MC is more prevalent in White, older patients, who are well-represented in Swedish cohorts but to a lesser extent in US populations. “Additionally, environmental factors and medication use patterns differ between Sweden and the US, particularly in regard to over-the-counter medication access.”

The findings have implications for future research in pharmacoepidemiologic studies of gastrointestinal-related outcomes. Since many routinely prescribed medications such as SSRIs were associated with an apparent increased risk for colonoscopies with normal colorectal biopsy results, future studies that examine gastrointestinal-specific adverse events should carefully consider potential surveillance bias.

In the meantime, Khalili stressed, it’s important to highlight that while some of these medications cause diarrhea in a small subset of patients, stopping medications in these patients is unnecessary.

This study was supported by the National Institutes of Health (NIH) and the Swedish Research Council. Khalili disclosed grants from the Crohn’s & Coiltis Foundation, the NIH and the Helmsley CharitableTrust, as well as stock ownership in Cylinder Health. One coauthor is employed by Massachusetts General Hospital. Axelrad had no relevant competing interests.







 

A new study casts doubt on international guidelines advising up to a week of prophylactic antibiotics in patients with cirrhosis and upper gastrointestinal (GI) bleeding.

Pooled data from 14 randomized controlled trials (RCTs) found a high probability that no or shorter durations of antibiotic prophylaxis are not worse than longer durations in preventing death from any cause in these patients.

The findings suggest that recommendations for routine antibiotic prophylaxis in patients with cirrhosis and upper GI bleeding “should be reassessed,” the authors said.

They acknowledged, however, that the studies were of low-to-moderate quality and higher quality randomized clinical trial data are needed.

The study, with first author Connor Prosty, MD, of McGill University, in Montreal, Quebec, Canada, was published online in JAMA Internal Medicine.

 

Questionable Benefit?

Antibiotic prophylaxis became standard decades ago, when up to 60% of variceal bleeds were complicated by infections, which were thought to increase the risk for rebleeding and death. 

Yet, the evidence to support the recommendation remains limited, and a recent RCT called into question the necessity of prophylaxis. The study showed no statistically significant difference in mortality or infection among patients with Child-Pugh class A cirrhosis randomized to receive no prophylaxis compared to third-generation cephalosporin.

While generally perceived as safe, antibiotics have potential adverse effects and can select for resistant superinfections, Prosty and colleagues pointed out.

They also noted that shorter courses of antibiotics have been proven to be as good, if not better, than longer courses across numerous other infectious indications. Recommendations for primary and secondary antibiotic prophylaxis for spontaneous bacterial peritonitis are being reassessed due to a weak evidence base, lack of mortality benefit, and potential for harm.

To revisit antibiotic prophylaxis for upper GI bleeding in patients with cirrhosis, Prosty and colleagues did a systematic review and meta-analysis of 14 RCTs involving 1322 patients.

Two of the trials compared longer (5-7 days) with shorter (2-3 days) antibiotics, and 12 compared any antibiotic prophylaxis (1-10 days) to none.

The primary outcome was all-cause mortality, with a prespecified noninferiority margin of 5% on the risk difference (RD) scale. Secondary outcomes included early rebleeding and bacterial infections.

Overall, shorter antibiotic durations (including none) had a 97.3% probability of noninferiority to longer durations for all-cause mortality (RD, 0.9%; 95% credible interval [CrI], -2.6% to 4.9%).

Shorter durations had a 73.8% probability of noninferiority for early rebleeding (RD, 2.9%; 95% CrI, -4.2% to 10.0%) but were associated with more study-defined bacterial infections (RD, 15.2%; 95% CrI, 5.0%-25.9%). However, the authors cited methodological concerns about the definitions of these infections in the included studies.

The probabilities of noninferiority of shorter durations for mortality, early rebleeding, and bacterial infections were higher in studies published after 2004.

 

Change Practice Now?

“Our findings re-open the discussion surrounding the long-standing and firmly held belief that antibiotic prophylaxis has a mortality benefit in patients with cirrhosis presenting with upper gastrointestinal bleeds,” Prosty and colleagues wrote.

They cautioned, however, that the study quality was “low to moderate, bacterial infections were heterogeneously defined, and no studies reported adverse events. Higher-quality RCTs are needed to determine the benefit and optimal duration of antibiotic prophylaxis in the modern era of advanced interventions.”

The authors of a commentary published with the study noted that management of upper GI bleeding in cirrhosis patients has “greatly improved” since the 1990s, when some of the trials included in the analysis were conducted.

Hepatologists Catherine Mezzacappa, MD, MPH, and Guadalupe Garcia-Tsao, MD, both at the Yale School of Medicine, New Haven, Connecticut, agree that it “may be time to revisit whether prophylactic antibiotics continue to provide benefit in patients with cirrhosis and upper GI bleeding, and if so, in which patients.”

They caution, however, that the current level of evidence is “inadequate to answer whether it is time to stop this practice, which has become the standard of care.

New trials for shorter duration and no antibiotic prophylaxis “should be designed in specific patient populations to compare sequelae of antibiotic prophylaxis, including subsequent infections and all-cause mortality,” Mezzacappa and Garcia-Tsao concluded.

The study received no specific funding. The authors and commentary writers had no relevant disclosures.

 

A version of this article appeared on Medscape.com.

A new study casts doubt on international guidelines advising up to a week of prophylactic antibiotics in patients with cirrhosis and upper gastrointestinal (GI) bleeding.

Pooled data from 14 randomized controlled trials (RCTs) found a high probability that no or shorter durations of antibiotic prophylaxis are not worse than longer durations in preventing death from any cause in these patients.

The findings suggest that recommendations for routine antibiotic prophylaxis in patients with cirrhosis and upper GI bleeding “should be reassessed,” the authors said.

They acknowledged, however, that the studies were of low-to-moderate quality and higher quality randomized clinical trial data are needed.

The study, with first author Connor Prosty, MD, of McGill University, in Montreal, Quebec, Canada, was published online in JAMA Internal Medicine.

 

Questionable Benefit?

Antibiotic prophylaxis became standard decades ago, when up to 60% of variceal bleeds were complicated by infections, which were thought to increase the risk for rebleeding and death. 

Yet, the evidence to support the recommendation remains limited, and a recent RCT called into question the necessity of prophylaxis. The study showed no statistically significant difference in mortality or infection among patients with Child-Pugh class A cirrhosis randomized to receive no prophylaxis compared to third-generation cephalosporin.

While generally perceived as safe, antibiotics have potential adverse effects and can select for resistant superinfections, Prosty and colleagues pointed out.

They also noted that shorter courses of antibiotics have been proven to be as good, if not better, than longer courses across numerous other infectious indications. Recommendations for primary and secondary antibiotic prophylaxis for spontaneous bacterial peritonitis are being reassessed due to a weak evidence base, lack of mortality benefit, and potential for harm.

To revisit antibiotic prophylaxis for upper GI bleeding in patients with cirrhosis, Prosty and colleagues did a systematic review and meta-analysis of 14 RCTs involving 1322 patients.

Two of the trials compared longer (5-7 days) with shorter (2-3 days) antibiotics, and 12 compared any antibiotic prophylaxis (1-10 days) to none.

The primary outcome was all-cause mortality, with a prespecified noninferiority margin of 5% on the risk difference (RD) scale. Secondary outcomes included early rebleeding and bacterial infections.

Overall, shorter antibiotic durations (including none) had a 97.3% probability of noninferiority to longer durations for all-cause mortality (RD, 0.9%; 95% credible interval [CrI], -2.6% to 4.9%).

Shorter durations had a 73.8% probability of noninferiority for early rebleeding (RD, 2.9%; 95% CrI, -4.2% to 10.0%) but were associated with more study-defined bacterial infections (RD, 15.2%; 95% CrI, 5.0%-25.9%). However, the authors cited methodological concerns about the definitions of these infections in the included studies.

The probabilities of noninferiority of shorter durations for mortality, early rebleeding, and bacterial infections were higher in studies published after 2004.

 

Change Practice Now?

“Our findings re-open the discussion surrounding the long-standing and firmly held belief that antibiotic prophylaxis has a mortality benefit in patients with cirrhosis presenting with upper gastrointestinal bleeds,” Prosty and colleagues wrote.

They cautioned, however, that the study quality was “low to moderate, bacterial infections were heterogeneously defined, and no studies reported adverse events. Higher-quality RCTs are needed to determine the benefit and optimal duration of antibiotic prophylaxis in the modern era of advanced interventions.”

The authors of a commentary published with the study noted that management of upper GI bleeding in cirrhosis patients has “greatly improved” since the 1990s, when some of the trials included in the analysis were conducted.

Hepatologists Catherine Mezzacappa, MD, MPH, and Guadalupe Garcia-Tsao, MD, both at the Yale School of Medicine, New Haven, Connecticut, agree that it “may be time to revisit whether prophylactic antibiotics continue to provide benefit in patients with cirrhosis and upper GI bleeding, and if so, in which patients.”

They caution, however, that the current level of evidence is “inadequate to answer whether it is time to stop this practice, which has become the standard of care.

New trials for shorter duration and no antibiotic prophylaxis “should be designed in specific patient populations to compare sequelae of antibiotic prophylaxis, including subsequent infections and all-cause mortality,” Mezzacappa and Garcia-Tsao concluded.

The study received no specific funding. The authors and commentary writers had no relevant disclosures.

 

A version of this article appeared on Medscape.com.

A new study casts doubt on international guidelines advising up to a week of prophylactic antibiotics in patients with cirrhosis and upper gastrointestinal (GI) bleeding.

Pooled data from 14 randomized controlled trials (RCTs) found a high probability that no or shorter durations of antibiotic prophylaxis are not worse than longer durations in preventing death from any cause in these patients.

The findings suggest that recommendations for routine antibiotic prophylaxis in patients with cirrhosis and upper GI bleeding “should be reassessed,” the authors said.

They acknowledged, however, that the studies were of low-to-moderate quality and higher quality randomized clinical trial data are needed.

The study, with first author Connor Prosty, MD, of McGill University, in Montreal, Quebec, Canada, was published online in JAMA Internal Medicine.

 

Questionable Benefit?

Antibiotic prophylaxis became standard decades ago, when up to 60% of variceal bleeds were complicated by infections, which were thought to increase the risk for rebleeding and death. 

Yet, the evidence to support the recommendation remains limited, and a recent RCT called into question the necessity of prophylaxis. The study showed no statistically significant difference in mortality or infection among patients with Child-Pugh class A cirrhosis randomized to receive no prophylaxis compared to third-generation cephalosporin.

While generally perceived as safe, antibiotics have potential adverse effects and can select for resistant superinfections, Prosty and colleagues pointed out.

They also noted that shorter courses of antibiotics have been proven to be as good, if not better, than longer courses across numerous other infectious indications. Recommendations for primary and secondary antibiotic prophylaxis for spontaneous bacterial peritonitis are being reassessed due to a weak evidence base, lack of mortality benefit, and potential for harm.

To revisit antibiotic prophylaxis for upper GI bleeding in patients with cirrhosis, Prosty and colleagues did a systematic review and meta-analysis of 14 RCTs involving 1322 patients.

Two of the trials compared longer (5-7 days) with shorter (2-3 days) antibiotics, and 12 compared any antibiotic prophylaxis (1-10 days) to none.

The primary outcome was all-cause mortality, with a prespecified noninferiority margin of 5% on the risk difference (RD) scale. Secondary outcomes included early rebleeding and bacterial infections.

Overall, shorter antibiotic durations (including none) had a 97.3% probability of noninferiority to longer durations for all-cause mortality (RD, 0.9%; 95% credible interval [CrI], -2.6% to 4.9%).

Shorter durations had a 73.8% probability of noninferiority for early rebleeding (RD, 2.9%; 95% CrI, -4.2% to 10.0%) but were associated with more study-defined bacterial infections (RD, 15.2%; 95% CrI, 5.0%-25.9%). However, the authors cited methodological concerns about the definitions of these infections in the included studies.

The probabilities of noninferiority of shorter durations for mortality, early rebleeding, and bacterial infections were higher in studies published after 2004.

 

Change Practice Now?

“Our findings re-open the discussion surrounding the long-standing and firmly held belief that antibiotic prophylaxis has a mortality benefit in patients with cirrhosis presenting with upper gastrointestinal bleeds,” Prosty and colleagues wrote.

They cautioned, however, that the study quality was “low to moderate, bacterial infections were heterogeneously defined, and no studies reported adverse events. Higher-quality RCTs are needed to determine the benefit and optimal duration of antibiotic prophylaxis in the modern era of advanced interventions.”

The authors of a commentary published with the study noted that management of upper GI bleeding in cirrhosis patients has “greatly improved” since the 1990s, when some of the trials included in the analysis were conducted.

Hepatologists Catherine Mezzacappa, MD, MPH, and Guadalupe Garcia-Tsao, MD, both at the Yale School of Medicine, New Haven, Connecticut, agree that it “may be time to revisit whether prophylactic antibiotics continue to provide benefit in patients with cirrhosis and upper GI bleeding, and if so, in which patients.”

They caution, however, that the current level of evidence is “inadequate to answer whether it is time to stop this practice, which has become the standard of care.

New trials for shorter duration and no antibiotic prophylaxis “should be designed in specific patient populations to compare sequelae of antibiotic prophylaxis, including subsequent infections and all-cause mortality,” Mezzacappa and Garcia-Tsao concluded.

The study received no specific funding. The authors and commentary writers had no relevant disclosures.

 

A version of this article appeared on Medscape.com.

An increase of patients presenting with the complex combination of hypermobile Ehlers-Danlos syndrome (hEDS) with co-existing gastrointestinal (GI) symptoms, postural orthostatic tachycardia syndrome (POTS), and/or mast cell activation syndrome (MCAS), has prompted the issuance of clinical practice guidance from AGA to help clinicians comprehend such cases.

“Recognizing and treating GI symptoms in patients with hEDS or hypermobility spectrum disorders and comorbid POTS or MCAS present major challenges for clinicians, who often feel under equipped to address their needs,” AGA reported in the update, published in Clinical Gastroenterology and Hepatology.

Importantly, “the poor understanding of these overlapping syndromes can lead to nonstandardized approaches to diagnostic evaluation and management,” the authors noted.

“Gastroenterology providers should be aware of the features of [these syndromes] to recognize the full complexity of patients presenting with multisystemic symptoms.”

Hypermobility spectrum disorders, which include hEDS, are typically genetic, and patients experience pain along with joint hypermobility, or extreme flexibility of joints beyond the normal range of motion.

With research showing that most of those patients — up to 98% — also experience GI symptoms, gastroenterologists may be encountering them more commonly than realized, Lucinda A. Harris, MD, AGAF, of the Mayo Clinic School of Medicine, in Scottsdale, Arizona, explained to GI & Hepatology News.

“As our knowledge in gastroenterology has progressed, we realize that hypermobility itself predisposes individuals to disorders of brain-gut interaction,” she said. “We may only be seeing the tip of the iceberg when it comes to diagnosing patients with hypermobility.”

Additionally, “many of these patients have POTS, which has also been increasingly diagnosed,” Harris added. “The strong overlap of these conditions prompted us to present this data.”

With a lack of evidence-based understanding of the overlapping syndromes, AGA’s guidance does not carry formal ratings but is drawn from a review of the published literature and expert opinion.

In addition to the key recommendation of being aware of the observed combination of syndromes, their recommendations include:

• Regarding testing: Testing for POTS/MCAS should be targeted to patients presenting with clinical manifestations of the disorders, but universal testing for POTS/MCAS in all patients with hEDS or hypermobility spectrum disorders is not currently supported by the evidence, the guidance advises.
• Gastroenterologists seeing patients with disorders of gut-brain interaction should inquire about joint hypermobility and strongly consider incorporating the Beighton score for assessing joint hypermobility into their practice as a screening tool; if the screen is positive, gastroenterologists may consider applying 2017 diagnostic criteria to diagnose hEDS or offer appropriate referral to a specialist where resources are available, the AGA recommends.
• Medical management: Management of GI symptoms in hEDS or hypermobility spectrum disorders and POTS/MCAS should focus on treating the most prominent GI symptoms and abnormal GI function test results.
• In addition to general disorders of gut-brain interactions and GI motility disorder treatment, management should also include treating any symptoms attributable to POTS and/or MCAS.

Treatment of POTS may include increasing fluid and salt intake, exercise training, and use of compression garments. Special pharmacological treatments for volume expansion, heart rate control, and vasoconstriction with integrated care from multiple specialties (eg, cardiology, neurology) should be considered in patients who do not respond to conservative lifestyle measures.

In patients presenting to gastroenterology providers, testing for mast cell disorders including MCAS should be considered in patients with hEDS or hypermobility spectrum disorders and disorders of gut-brain interaction with episodic symptoms that suggest a more generalized mast cell disorder involving two or more physiological systems. However, current data does not support the use of these tests for routine evaluation of GI symptoms in all patients with hEDS or hypermobility spectrum disorders without clinical or laboratory evidence of a primary or secondary mast cell disorder, the authors noted.

Harris explained that patients presenting with gut-brain disorders are often mistakenly classified as having irritable bowel syndrome or dyspepsia, whereas these conditions may be affecting the GI disorders they have.

“For example, a patient with Ehlers-Danlos syndrome might have problems with constipation, which is impacted by pelvic floor dysfunction,” she said. “Due to their hypermobility, they may experience more pelvic floor descent than usual.”

“If we do not recognize this, the patient risks developing rectal prolapse or not effectively addressing their constipation.”

Regarding patient characteristics, Harris said that those with hEDS and POTS appear to more likely be women and tend to present in younger patients, aged 18-50 years. Of note, there is no genetic test for hEDS.

“The take-home point for clinicians should be to consider POTS and Ehlers-Danlos syndrome when encountering young female patients with symptoms of palpitations, hypermobility, and orthostatic intolerance,” she said.

“Recognizing hypermobility is crucial, not only for GI symptoms but also to prevent joint dislocations, tendon ruptures, and other connective tissue issues.”

Clinicians are further urged to “offer informed counseling, and guide patients away from unreliable sources or fragmented care to foster therapeutic relationships and evidence-based care,” the authors added.

 

Deciphering Gut-Brain Disorder Challenges

Commenting to GI & Hepatology News, Clair Francomano, MD, a professor of medical and molecular genetics at the Indiana University School of Medicine, in Indianapolis, said the new guidance sheds important light on the syndromes.

“I’m delighted to see this guidance offered through the AGA as it will encourage gastroenterologists to think of EDS, POTS and MCAS when they are evaluating patients with disorders of gut-brain interaction,” Francomano said.

“This should allow patients to receive more accurate and timely diagnoses and appropriate management.”

Francomano noted that the Ehlers-Danlos Society, which provides information for clinicians and patients alike on the syndromes, and where she serves on the medical scientific board, has also been active in raising awareness.

“While co-occurrence of POTS and MCAS with EDS has in fact been recognized for many years, I do think awareness is increasing, in large part due to the advocacy and educational efforts of the Ehlers-Danlos Society,” she said.

The take-home message? “When clinicians see disorders of the gut-brain axis, POTS or MCAS, they should be thinking, ‘Could this be related to joint hypermobility or Ehlers-Danlos syndrome?’” Francomano said.

Harris reported serving as a consultant for AbbVie, Ardelyx, Salix, and Gemelli Biotech and reported receiving research support from Takeda and Anyx. Francomano did not report any relevant disclosures.

A version of this article appeared on Medscape.com.

An increase of patients presenting with the complex combination of hypermobile Ehlers-Danlos syndrome (hEDS) with co-existing gastrointestinal (GI) symptoms, postural orthostatic tachycardia syndrome (POTS), and/or mast cell activation syndrome (MCAS), has prompted the issuance of clinical practice guidance from AGA to help clinicians comprehend such cases.

“Recognizing and treating GI symptoms in patients with hEDS or hypermobility spectrum disorders and comorbid POTS or MCAS present major challenges for clinicians, who often feel under equipped to address their needs,” AGA reported in the update, published in Clinical Gastroenterology and Hepatology.

Importantly, “the poor understanding of these overlapping syndromes can lead to nonstandardized approaches to diagnostic evaluation and management,” the authors noted.

“Gastroenterology providers should be aware of the features of [these syndromes] to recognize the full complexity of patients presenting with multisystemic symptoms.”

Hypermobility spectrum disorders, which include hEDS, are typically genetic, and patients experience pain along with joint hypermobility, or extreme flexibility of joints beyond the normal range of motion.

With research showing that most of those patients — up to 98% — also experience GI symptoms, gastroenterologists may be encountering them more commonly than realized, Lucinda A. Harris, MD, AGAF, of the Mayo Clinic School of Medicine, in Scottsdale, Arizona, explained to GI & Hepatology News.

“As our knowledge in gastroenterology has progressed, we realize that hypermobility itself predisposes individuals to disorders of brain-gut interaction,” she said. “We may only be seeing the tip of the iceberg when it comes to diagnosing patients with hypermobility.”

Additionally, “many of these patients have POTS, which has also been increasingly diagnosed,” Harris added. “The strong overlap of these conditions prompted us to present this data.”

With a lack of evidence-based understanding of the overlapping syndromes, AGA’s guidance does not carry formal ratings but is drawn from a review of the published literature and expert opinion.

In addition to the key recommendation of being aware of the observed combination of syndromes, their recommendations include:

• Regarding testing: Testing for POTS/MCAS should be targeted to patients presenting with clinical manifestations of the disorders, but universal testing for POTS/MCAS in all patients with hEDS or hypermobility spectrum disorders is not currently supported by the evidence, the guidance advises.
• Gastroenterologists seeing patients with disorders of gut-brain interaction should inquire about joint hypermobility and strongly consider incorporating the Beighton score for assessing joint hypermobility into their practice as a screening tool; if the screen is positive, gastroenterologists may consider applying 2017 diagnostic criteria to diagnose hEDS or offer appropriate referral to a specialist where resources are available, the AGA recommends.
• Medical management: Management of GI symptoms in hEDS or hypermobility spectrum disorders and POTS/MCAS should focus on treating the most prominent GI symptoms and abnormal GI function test results.
• In addition to general disorders of gut-brain interactions and GI motility disorder treatment, management should also include treating any symptoms attributable to POTS and/or MCAS.

Treatment of POTS may include increasing fluid and salt intake, exercise training, and use of compression garments. Special pharmacological treatments for volume expansion, heart rate control, and vasoconstriction with integrated care from multiple specialties (eg, cardiology, neurology) should be considered in patients who do not respond to conservative lifestyle measures.

In patients presenting to gastroenterology providers, testing for mast cell disorders including MCAS should be considered in patients with hEDS or hypermobility spectrum disorders and disorders of gut-brain interaction with episodic symptoms that suggest a more generalized mast cell disorder involving two or more physiological systems. However, current data does not support the use of these tests for routine evaluation of GI symptoms in all patients with hEDS or hypermobility spectrum disorders without clinical or laboratory evidence of a primary or secondary mast cell disorder, the authors noted.

Harris explained that patients presenting with gut-brain disorders are often mistakenly classified as having irritable bowel syndrome or dyspepsia, whereas these conditions may be affecting the GI disorders they have.

“For example, a patient with Ehlers-Danlos syndrome might have problems with constipation, which is impacted by pelvic floor dysfunction,” she said. “Due to their hypermobility, they may experience more pelvic floor descent than usual.”

“If we do not recognize this, the patient risks developing rectal prolapse or not effectively addressing their constipation.”

Regarding patient characteristics, Harris said that those with hEDS and POTS appear to more likely be women and tend to present in younger patients, aged 18-50 years. Of note, there is no genetic test for hEDS.

“The take-home point for clinicians should be to consider POTS and Ehlers-Danlos syndrome when encountering young female patients with symptoms of palpitations, hypermobility, and orthostatic intolerance,” she said.

“Recognizing hypermobility is crucial, not only for GI symptoms but also to prevent joint dislocations, tendon ruptures, and other connective tissue issues.”

Clinicians are further urged to “offer informed counseling, and guide patients away from unreliable sources or fragmented care to foster therapeutic relationships and evidence-based care,” the authors added.

 

Deciphering Gut-Brain Disorder Challenges

Commenting to GI & Hepatology News, Clair Francomano, MD, a professor of medical and molecular genetics at the Indiana University School of Medicine, in Indianapolis, said the new guidance sheds important light on the syndromes.

“I’m delighted to see this guidance offered through the AGA as it will encourage gastroenterologists to think of EDS, POTS and MCAS when they are evaluating patients with disorders of gut-brain interaction,” Francomano said.

“This should allow patients to receive more accurate and timely diagnoses and appropriate management.”

Francomano noted that the Ehlers-Danlos Society, which provides information for clinicians and patients alike on the syndromes, and where she serves on the medical scientific board, has also been active in raising awareness.

“While co-occurrence of POTS and MCAS with EDS has in fact been recognized for many years, I do think awareness is increasing, in large part due to the advocacy and educational efforts of the Ehlers-Danlos Society,” she said.

The take-home message? “When clinicians see disorders of the gut-brain axis, POTS or MCAS, they should be thinking, ‘Could this be related to joint hypermobility or Ehlers-Danlos syndrome?’” Francomano said.

Harris reported serving as a consultant for AbbVie, Ardelyx, Salix, and Gemelli Biotech and reported receiving research support from Takeda and Anyx. Francomano did not report any relevant disclosures.

A version of this article appeared on Medscape.com.

An increase of patients presenting with the complex combination of hypermobile Ehlers-Danlos syndrome (hEDS) with co-existing gastrointestinal (GI) symptoms, postural orthostatic tachycardia syndrome (POTS), and/or mast cell activation syndrome (MCAS), has prompted the issuance of clinical practice guidance from AGA to help clinicians comprehend such cases.

“Recognizing and treating GI symptoms in patients with hEDS or hypermobility spectrum disorders and comorbid POTS or MCAS present major challenges for clinicians, who often feel under equipped to address their needs,” AGA reported in the update, published in Clinical Gastroenterology and Hepatology.

Importantly, “the poor understanding of these overlapping syndromes can lead to nonstandardized approaches to diagnostic evaluation and management,” the authors noted.

“Gastroenterology providers should be aware of the features of [these syndromes] to recognize the full complexity of patients presenting with multisystemic symptoms.”

Hypermobility spectrum disorders, which include hEDS, are typically genetic, and patients experience pain along with joint hypermobility, or extreme flexibility of joints beyond the normal range of motion.

With research showing that most of those patients — up to 98% — also experience GI symptoms, gastroenterologists may be encountering them more commonly than realized, Lucinda A. Harris, MD, AGAF, of the Mayo Clinic School of Medicine, in Scottsdale, Arizona, explained to GI & Hepatology News.

“As our knowledge in gastroenterology has progressed, we realize that hypermobility itself predisposes individuals to disorders of brain-gut interaction,” she said. “We may only be seeing the tip of the iceberg when it comes to diagnosing patients with hypermobility.”

Additionally, “many of these patients have POTS, which has also been increasingly diagnosed,” Harris added. “The strong overlap of these conditions prompted us to present this data.”

With a lack of evidence-based understanding of the overlapping syndromes, AGA’s guidance does not carry formal ratings but is drawn from a review of the published literature and expert opinion.

In addition to the key recommendation of being aware of the observed combination of syndromes, their recommendations include:

• Regarding testing: Testing for POTS/MCAS should be targeted to patients presenting with clinical manifestations of the disorders, but universal testing for POTS/MCAS in all patients with hEDS or hypermobility spectrum disorders is not currently supported by the evidence, the guidance advises.
• Gastroenterologists seeing patients with disorders of gut-brain interaction should inquire about joint hypermobility and strongly consider incorporating the Beighton score for assessing joint hypermobility into their practice as a screening tool; if the screen is positive, gastroenterologists may consider applying 2017 diagnostic criteria to diagnose hEDS or offer appropriate referral to a specialist where resources are available, the AGA recommends.
• Medical management: Management of GI symptoms in hEDS or hypermobility spectrum disorders and POTS/MCAS should focus on treating the most prominent GI symptoms and abnormal GI function test results.
• In addition to general disorders of gut-brain interactions and GI motility disorder treatment, management should also include treating any symptoms attributable to POTS and/or MCAS.

Treatment of POTS may include increasing fluid and salt intake, exercise training, and use of compression garments. Special pharmacological treatments for volume expansion, heart rate control, and vasoconstriction with integrated care from multiple specialties (eg, cardiology, neurology) should be considered in patients who do not respond to conservative lifestyle measures.

In patients presenting to gastroenterology providers, testing for mast cell disorders including MCAS should be considered in patients with hEDS or hypermobility spectrum disorders and disorders of gut-brain interaction with episodic symptoms that suggest a more generalized mast cell disorder involving two or more physiological systems. However, current data does not support the use of these tests for routine evaluation of GI symptoms in all patients with hEDS or hypermobility spectrum disorders without clinical or laboratory evidence of a primary or secondary mast cell disorder, the authors noted.

Harris explained that patients presenting with gut-brain disorders are often mistakenly classified as having irritable bowel syndrome or dyspepsia, whereas these conditions may be affecting the GI disorders they have.

“For example, a patient with Ehlers-Danlos syndrome might have problems with constipation, which is impacted by pelvic floor dysfunction,” she said. “Due to their hypermobility, they may experience more pelvic floor descent than usual.”

“If we do not recognize this, the patient risks developing rectal prolapse or not effectively addressing their constipation.”

Regarding patient characteristics, Harris said that those with hEDS and POTS appear to more likely be women and tend to present in younger patients, aged 18-50 years. Of note, there is no genetic test for hEDS.

“The take-home point for clinicians should be to consider POTS and Ehlers-Danlos syndrome when encountering young female patients with symptoms of palpitations, hypermobility, and orthostatic intolerance,” she said.

“Recognizing hypermobility is crucial, not only for GI symptoms but also to prevent joint dislocations, tendon ruptures, and other connective tissue issues.”

Clinicians are further urged to “offer informed counseling, and guide patients away from unreliable sources or fragmented care to foster therapeutic relationships and evidence-based care,” the authors added.

 

Deciphering Gut-Brain Disorder Challenges

Commenting to GI & Hepatology News, Clair Francomano, MD, a professor of medical and molecular genetics at the Indiana University School of Medicine, in Indianapolis, said the new guidance sheds important light on the syndromes.

“I’m delighted to see this guidance offered through the AGA as it will encourage gastroenterologists to think of EDS, POTS and MCAS when they are evaluating patients with disorders of gut-brain interaction,” Francomano said.

“This should allow patients to receive more accurate and timely diagnoses and appropriate management.”

Francomano noted that the Ehlers-Danlos Society, which provides information for clinicians and patients alike on the syndromes, and where she serves on the medical scientific board, has also been active in raising awareness.

“While co-occurrence of POTS and MCAS with EDS has in fact been recognized for many years, I do think awareness is increasing, in large part due to the advocacy and educational efforts of the Ehlers-Danlos Society,” she said.

The take-home message? “When clinicians see disorders of the gut-brain axis, POTS or MCAS, they should be thinking, ‘Could this be related to joint hypermobility or Ehlers-Danlos syndrome?’” Francomano said.

Harris reported serving as a consultant for AbbVie, Ardelyx, Salix, and Gemelli Biotech and reported receiving research support from Takeda and Anyx. Francomano did not report any relevant disclosures.

A version of this article appeared on Medscape.com.

Out-of-pocket costs for bowel preparation are deterring people, especially vulnerable and underserved groups, from colonoscopy for colorectal cancer (CRC) screening, a large insurance-claims analysis in Gastroenterology reported.

Moreover, this cost-sharing contravenes the preventive-care provisions for bowel preparation mandated by the Affordable Care Act (ACA).

Led by Gastroenterologist Eric D. Shah, MD, MBA, a clinical associate professor at the University of Michigan in Ann Arbor, Michigan, the study found a significant proportion of prescribed bowel preparation claims — 53% for commercial plans and 83% for Medicare — still involve patient cost-sharing, indicating noncompliance with ACA guidelines. Although expense-sharing was less prevalent among Medicaid claims (just 27%), it was not eliminated, suggesting room for improvement in coverage enforcement across the board.

“Colon cancer is unique in that it can be prevented with colonoscopy, but where are the patients? Bowel prep is a major reason that patients defer screening,” Shah told GI & Hepatology News. He said his group was quite surprised that the majority in the study cohort were paying something out of pocket when these costs should have been covered. “Primary care doctors may not think to ask about bowel prep costs when they order screening colonoscopies.”

The findings emerged from an analysis of 2,593,079 prescription drug claims: 52.9% from commercial plans, 35% from Medicare Part D plans, and 8.3% from Medicaid plans.

“These patient costs of $30 or $50 are a real not a theoretical deterrent,” said Whitney Jones, MD, a gastroenterologist, adjunct clinical professor at the University of Louisville in Louisville, Kentucky, and founder of the nonprofit Colon Cancer Prevention Project. Jones was not involved in the analysis. “Some insurers require prior patient authorization for the low-dose preps, but gastroenterologists are doing so many colonoscopies they don’t always have time to get a PA [prior authorization] on everyone.” 

With the increasing use of blood and stool-based CRC testing, he added, “when you get a positive result, it’s really important to have the procedure quickly.” And appropriate bowel preparation is a small, cost-effective portion of the total costs of colonoscopy, a procedure that ultimately saves insurers significant money in treatment costs.

The authors noted that while CRC is the second-leading cause of cancer-related deaths in the US, screening rates remain low, with only 59% of adults aged 45 years or older up to date with screening. Screening rates are particularly low among racial and ethnic minority groups as compared with White individuals, a disparity that highlights the need to address existing barriers and enhance screening efforts.

In the current study, shared costs by bowel preparation volume also varied. Low-volume formulations had consistently higher out-of-pocket costs: a median of $60 for low-volume vs $10 for high-volume in commercial plans. In Medicare, 75% of high-volume claims had shared costs compared with 90% for their low-volume counterparts. The cost-sharing difference was slightly narrower with Medicaid: 27% of high-volume claims vs 30% of low-volume claims.

This is concerning, as low-volume options, which are preferred by patients for their better tolerability, can enhance uptake and adherence and improve colonoscopy outcomes. Shah advises physicians to consider prescribing low-volume preparations. “Let patients know about the potential out-of-pocket cost and about copay cards and assistance programs and use high-volume preps as an alternative rather than a go-to,” he said.

As to costs across insurance types, among commercial plans, the median nonzero out-of-pocket cost was $10 for high-volume and $60 for low-volume product claims. For Medicare, the median nonzero out-of-pocket cost was $8 for high-volume and $55.99 for low-volume products.

Under the ACA, CRC screening is classified as a recommended preventive service, requiring health plans to cover it without cost-sharing. Although the Centers for Medicare & Medicaid Services previously tried to enforce this mandate in 2015 and 2016, stating that colonoscopy preparation medications should be covered at no cost, many health plans are still not compliant.

At the nonfederal level, Jones noted, Kentucky, which has a significant high-risk population, recently became the first state to pass legislation requiring health benefit plans to cover all guideline-recommended CRC exams and lab tests.

For its part, AGA has also called on payers to eliminate all cost-sharing barriers across the CRC screening continuum.

Of note, the study authors said, the higher compliance with the ACA mandate in commercial and Medicaid plans than in Medicare highlights disparities that may disproportionately affect vulnerable older adults. While nearly half of commercial patients and nearly three quarters of Medicaid patients incurred zero out-of-pocket costs, fewer than 17% of Medicare beneficiaries, or 1 in 6, did so.

Although these costs may be low relative to the colonoscopy, they nevertheless can deter uptake of preventive screenings, potentially leading to higher CRC incidence and mortality. “While some patients may be willing to pay modest out-of-pocket costs, any required payment, however small, can serve as a barrier to preventative care, particularly in underserved populations,” they wrote. “These financial barriers will continue to contribute to widening disparities and hinder progress toward equitable screening outcomes.”

In the meantime, said Shah, “Physicians should advocate now to their representatives in Congress that bowel prep costs should already be covered as part of the ACA.”

This study was funded by Sebela Pharmaceuticals, maker of SUFLAVE preparation. The authors had no conflicts of interest to declare. Jones is a speaker and consultant for Grail LLC.

A version of this article appeared on Medscape.com.

Out-of-pocket costs for bowel preparation are deterring people, especially vulnerable and underserved groups, from colonoscopy for colorectal cancer (CRC) screening, a large insurance-claims analysis in Gastroenterology reported.

Moreover, this cost-sharing contravenes the preventive-care provisions for bowel preparation mandated by the Affordable Care Act (ACA).

Led by Gastroenterologist Eric D. Shah, MD, MBA, a clinical associate professor at the University of Michigan in Ann Arbor, Michigan, the study found a significant proportion of prescribed bowel preparation claims — 53% for commercial plans and 83% for Medicare — still involve patient cost-sharing, indicating noncompliance with ACA guidelines. Although expense-sharing was less prevalent among Medicaid claims (just 27%), it was not eliminated, suggesting room for improvement in coverage enforcement across the board.

“Colon cancer is unique in that it can be prevented with colonoscopy, but where are the patients? Bowel prep is a major reason that patients defer screening,” Shah told GI & Hepatology News. He said his group was quite surprised that the majority in the study cohort were paying something out of pocket when these costs should have been covered. “Primary care doctors may not think to ask about bowel prep costs when they order screening colonoscopies.”

The findings emerged from an analysis of 2,593,079 prescription drug claims: 52.9% from commercial plans, 35% from Medicare Part D plans, and 8.3% from Medicaid plans.

“These patient costs of $30 or $50 are a real not a theoretical deterrent,” said Whitney Jones, MD, a gastroenterologist, adjunct clinical professor at the University of Louisville in Louisville, Kentucky, and founder of the nonprofit Colon Cancer Prevention Project. Jones was not involved in the analysis. “Some insurers require prior patient authorization for the low-dose preps, but gastroenterologists are doing so many colonoscopies they don’t always have time to get a PA [prior authorization] on everyone.” 

With the increasing use of blood and stool-based CRC testing, he added, “when you get a positive result, it’s really important to have the procedure quickly.” And appropriate bowel preparation is a small, cost-effective portion of the total costs of colonoscopy, a procedure that ultimately saves insurers significant money in treatment costs.

The authors noted that while CRC is the second-leading cause of cancer-related deaths in the US, screening rates remain low, with only 59% of adults aged 45 years or older up to date with screening. Screening rates are particularly low among racial and ethnic minority groups as compared with White individuals, a disparity that highlights the need to address existing barriers and enhance screening efforts.

In the current study, shared costs by bowel preparation volume also varied. Low-volume formulations had consistently higher out-of-pocket costs: a median of $60 for low-volume vs $10 for high-volume in commercial plans. In Medicare, 75% of high-volume claims had shared costs compared with 90% for their low-volume counterparts. The cost-sharing difference was slightly narrower with Medicaid: 27% of high-volume claims vs 30% of low-volume claims.

This is concerning, as low-volume options, which are preferred by patients for their better tolerability, can enhance uptake and adherence and improve colonoscopy outcomes. Shah advises physicians to consider prescribing low-volume preparations. “Let patients know about the potential out-of-pocket cost and about copay cards and assistance programs and use high-volume preps as an alternative rather than a go-to,” he said.

As to costs across insurance types, among commercial plans, the median nonzero out-of-pocket cost was $10 for high-volume and $60 for low-volume product claims. For Medicare, the median nonzero out-of-pocket cost was $8 for high-volume and $55.99 for low-volume products.

Under the ACA, CRC screening is classified as a recommended preventive service, requiring health plans to cover it without cost-sharing. Although the Centers for Medicare & Medicaid Services previously tried to enforce this mandate in 2015 and 2016, stating that colonoscopy preparation medications should be covered at no cost, many health plans are still not compliant.

At the nonfederal level, Jones noted, Kentucky, which has a significant high-risk population, recently became the first state to pass legislation requiring health benefit plans to cover all guideline-recommended CRC exams and lab tests.

For its part, AGA has also called on payers to eliminate all cost-sharing barriers across the CRC screening continuum.

Of note, the study authors said, the higher compliance with the ACA mandate in commercial and Medicaid plans than in Medicare highlights disparities that may disproportionately affect vulnerable older adults. While nearly half of commercial patients and nearly three quarters of Medicaid patients incurred zero out-of-pocket costs, fewer than 17% of Medicare beneficiaries, or 1 in 6, did so.

Although these costs may be low relative to the colonoscopy, they nevertheless can deter uptake of preventive screenings, potentially leading to higher CRC incidence and mortality. “While some patients may be willing to pay modest out-of-pocket costs, any required payment, however small, can serve as a barrier to preventative care, particularly in underserved populations,” they wrote. “These financial barriers will continue to contribute to widening disparities and hinder progress toward equitable screening outcomes.”

In the meantime, said Shah, “Physicians should advocate now to their representatives in Congress that bowel prep costs should already be covered as part of the ACA.”

This study was funded by Sebela Pharmaceuticals, maker of SUFLAVE preparation. The authors had no conflicts of interest to declare. Jones is a speaker and consultant for Grail LLC.

A version of this article appeared on Medscape.com.

Out-of-pocket costs for bowel preparation are deterring people, especially vulnerable and underserved groups, from colonoscopy for colorectal cancer (CRC) screening, a large insurance-claims analysis in Gastroenterology reported.

Moreover, this cost-sharing contravenes the preventive-care provisions for bowel preparation mandated by the Affordable Care Act (ACA).

Led by Gastroenterologist Eric D. Shah, MD, MBA, a clinical associate professor at the University of Michigan in Ann Arbor, Michigan, the study found a significant proportion of prescribed bowel preparation claims — 53% for commercial plans and 83% for Medicare — still involve patient cost-sharing, indicating noncompliance with ACA guidelines. Although expense-sharing was less prevalent among Medicaid claims (just 27%), it was not eliminated, suggesting room for improvement in coverage enforcement across the board.

“Colon cancer is unique in that it can be prevented with colonoscopy, but where are the patients? Bowel prep is a major reason that patients defer screening,” Shah told GI & Hepatology News. He said his group was quite surprised that the majority in the study cohort were paying something out of pocket when these costs should have been covered. “Primary care doctors may not think to ask about bowel prep costs when they order screening colonoscopies.”

The findings emerged from an analysis of 2,593,079 prescription drug claims: 52.9% from commercial plans, 35% from Medicare Part D plans, and 8.3% from Medicaid plans.

“These patient costs of $30 or $50 are a real not a theoretical deterrent,” said Whitney Jones, MD, a gastroenterologist, adjunct clinical professor at the University of Louisville in Louisville, Kentucky, and founder of the nonprofit Colon Cancer Prevention Project. Jones was not involved in the analysis. “Some insurers require prior patient authorization for the low-dose preps, but gastroenterologists are doing so many colonoscopies they don’t always have time to get a PA [prior authorization] on everyone.” 

With the increasing use of blood and stool-based CRC testing, he added, “when you get a positive result, it’s really important to have the procedure quickly.” And appropriate bowel preparation is a small, cost-effective portion of the total costs of colonoscopy, a procedure that ultimately saves insurers significant money in treatment costs.

The authors noted that while CRC is the second-leading cause of cancer-related deaths in the US, screening rates remain low, with only 59% of adults aged 45 years or older up to date with screening. Screening rates are particularly low among racial and ethnic minority groups as compared with White individuals, a disparity that highlights the need to address existing barriers and enhance screening efforts.

In the current study, shared costs by bowel preparation volume also varied. Low-volume formulations had consistently higher out-of-pocket costs: a median of $60 for low-volume vs $10 for high-volume in commercial plans. In Medicare, 75% of high-volume claims had shared costs compared with 90% for their low-volume counterparts. The cost-sharing difference was slightly narrower with Medicaid: 27% of high-volume claims vs 30% of low-volume claims.

This is concerning, as low-volume options, which are preferred by patients for their better tolerability, can enhance uptake and adherence and improve colonoscopy outcomes. Shah advises physicians to consider prescribing low-volume preparations. “Let patients know about the potential out-of-pocket cost and about copay cards and assistance programs and use high-volume preps as an alternative rather than a go-to,” he said.

As to costs across insurance types, among commercial plans, the median nonzero out-of-pocket cost was $10 for high-volume and $60 for low-volume product claims. For Medicare, the median nonzero out-of-pocket cost was $8 for high-volume and $55.99 for low-volume products.

Under the ACA, CRC screening is classified as a recommended preventive service, requiring health plans to cover it without cost-sharing. Although the Centers for Medicare & Medicaid Services previously tried to enforce this mandate in 2015 and 2016, stating that colonoscopy preparation medications should be covered at no cost, many health plans are still not compliant.

At the nonfederal level, Jones noted, Kentucky, which has a significant high-risk population, recently became the first state to pass legislation requiring health benefit plans to cover all guideline-recommended CRC exams and lab tests.

For its part, AGA has also called on payers to eliminate all cost-sharing barriers across the CRC screening continuum.

Of note, the study authors said, the higher compliance with the ACA mandate in commercial and Medicaid plans than in Medicare highlights disparities that may disproportionately affect vulnerable older adults. While nearly half of commercial patients and nearly three quarters of Medicaid patients incurred zero out-of-pocket costs, fewer than 17% of Medicare beneficiaries, or 1 in 6, did so.

Although these costs may be low relative to the colonoscopy, they nevertheless can deter uptake of preventive screenings, potentially leading to higher CRC incidence and mortality. “While some patients may be willing to pay modest out-of-pocket costs, any required payment, however small, can serve as a barrier to preventative care, particularly in underserved populations,” they wrote. “These financial barriers will continue to contribute to widening disparities and hinder progress toward equitable screening outcomes.”

In the meantime, said Shah, “Physicians should advocate now to their representatives in Congress that bowel prep costs should already be covered as part of the ACA.”

This study was funded by Sebela Pharmaceuticals, maker of SUFLAVE preparation. The authors had no conflicts of interest to declare. Jones is a speaker and consultant for Grail LLC.

A version of this article appeared on Medscape.com.

Diets high in packaged breads, cookies, and other highly processed grain products may raise the risk for inflammatory bowel disease (IBD), while minimally processed grain products may offer some protection, a large study has found.

The sweeping analysis of 124,590 adults from 21 countries found that those eating at least 19 g of ultraprocessed grains a day were about twice as likely to be diagnosed with IBD as peers eating less than 9 g daily.

“Our study adds robust evidence from a large, diverse global cohort that frequent consumption of ultraprocessed grains is associated with an increased risk of developing inflammatory bowel disease,” Neeraj Narula, MD, MPH, gastroenterologist and associate professor of medicine, McMaster University, Hamilton, Ontario, Canada, told GI & Hepatology News.

The study also “further clarifies that not all grains carry risk — minimally processed grains like fresh bread and rice were associated with lower risk even. These results build on and specify previous findings linking ultraprocessed foods more broadly to IBD,” Narula said.

The study was published in The American Journal of Gastroenterology.

 

Diet Matters to IBD Risk

According to the latest US data (2021-2023), ultraprocessed foods made up 62% of daily calories for young people and 53% for adults in 2021-2023.

The Prospective Urban Rural Epidemiology (PURE) study has followed participants aged 35-70 years for a median of nearly 13 years. At enrollment, volunteers completed country-specific food-frequency questionnaires, enabling researchers to quantify usual intake of more than 130 food items and track new cases of IBD reported at biennial follow-ups.

The researchers classified packaged breads, sweet breakfast cereals, crackers, pastries and ready-to-heat pizza or pasta as ultraprocessed grains because they are refined and typically contain additives such as emulsifiers and preservatives. Fresh bakery bread and plain rice were analyzed separately as minimally processed grain references.

During a median of 12.9 years, 605 participants developed IBD; 497 developed ulcerative colitis (UC) and 108 developed Crohn’s disease. 

Increased intake of ultraprocessed grains was associated with a higher risk for IBD, with hazard ratios (HR) of 2.08 for intake of ≥ 50 g/d and 1.37 for 19-50 g/d compared to intake of < 19 g/d. The increased risk was largely driven by a significantly increased risk for UC (HR, 2.46) and not Crohn’s disease (HR, 0.98).

Among the different ultraprocessed grain products, packaged bread stood out: Consuming ≥ 30 g/d of packaged bread (a little more than one slice) was associated with a greater than twofold increased risk for IBD (HR, 2.11) compared to no intake of packaged bread.

In contrast, greater consumption of fresh bread was associated with a reduced risk of developing IBD (HR, 0.61 for ≥ 65 g/d and 0.45 for 16-65 g/d compared to < 16 g/d).

Increased intake of rice was also associated with a lower risk of developing IBD (HR, 0.63 for ≥ 1 serving/d and 0.99 for < 1 serving/d).

When the researchers widened the lens to all ultraprocessed foods — from sodas to salty snacks — the risk for IBD climbed further.

Participants eating at least five servings a day had nearly a fourfold greater odds of IBD than those eating fewer than one serving (HR, 3.95) — a finding consistent with other data from the PURE study cohort.

 

What to Tell Patients?

The authors acknowledged in their paper that it’s difficult — if not impossible — to completely avoid ultraprocessed food in the Western diet.

They said their findings support “public health strategies to promote consumption of whole and minimally processed foods while reducing the consumption of highly processed alternatives.”

“I tell my patients that emerging literature shows an association between ultraprocessed food intake and IBD risk, but it’s not yet clear whether simply cutting out those foods will improve disease activity once IBD is established,” Narula told GI & Hepatology News.

“However, I still encourage patients to reduce ultraprocessed foods and to follow a Mediterranean-style diet — focusing on minimally processed grains, fruits, vegetables, healthy fats, and lean proteins — to support overall gut and general health,” Narula said.

Reached for comment, Ashwin Ananthakrishnan, MD, MPH, AGAF, associate professor of medicine, Massachusetts General Hospital, Boston, who wasn’t part of the study, said it “adds incrementally to the growing data on how ultraprocessed foods may affect the risk of IBD.”

“They (and others) have previously shown a link between general ultraprocessed food consumption and risk of IBD. Others have shown that some of this is mediated through refined grains. This study more specifically studies that question and demonstrates an association,” said Ananthkrishnan.

“This should not be used, however, to counsel patients. It does not study the impact of grain intake on patients with IBD. It may help inform population level preventive strategies (or in high-risk individuals) but requires more confirmation since there is significant heterogeneity between the various countries in this cohort. Countries that have high refined grain intake are also enriched in several other IBD risk factors (including genetics),” Ananthkrishnan told GI & Hepatology News.

The PURE study is an investigator-initiated study funded by the Population Health Research Institute, Hamilton Health Sciences Research Institute, Canadian Institutes of Health Research, and Heart and Stroke Foundation of Ontario. It received support from Canadian Institutes of Health Research’s Strategy for Patient Oriented Research, Ontario SPOR Support Unit, and Ontario Ministry of Health and Long-Term Care and unrestricted grants from several pharmaceutical companies. Narula declared receiving honoraria from Janssen, Abbvie, Takeda, Pfizer, Sandoz, Novartis, Iterative Health, Innomar Strategies, Fresinius Kabi, Amgen, Organon, Eli Lilly, and Ferring. Ananthkrishnan declared having no relevant disclosures.

A version of this article appeared on Medscape.com.

Diets high in packaged breads, cookies, and other highly processed grain products may raise the risk for inflammatory bowel disease (IBD), while minimally processed grain products may offer some protection, a large study has found.

The sweeping analysis of 124,590 adults from 21 countries found that those eating at least 19 g of ultraprocessed grains a day were about twice as likely to be diagnosed with IBD as peers eating less than 9 g daily.

“Our study adds robust evidence from a large, diverse global cohort that frequent consumption of ultraprocessed grains is associated with an increased risk of developing inflammatory bowel disease,” Neeraj Narula, MD, MPH, gastroenterologist and associate professor of medicine, McMaster University, Hamilton, Ontario, Canada, told GI & Hepatology News.

The study also “further clarifies that not all grains carry risk — minimally processed grains like fresh bread and rice were associated with lower risk even. These results build on and specify previous findings linking ultraprocessed foods more broadly to IBD,” Narula said.

The study was published in The American Journal of Gastroenterology.

 

Diet Matters to IBD Risk

According to the latest US data (2021-2023), ultraprocessed foods made up 62% of daily calories for young people and 53% for adults in 2021-2023.

The Prospective Urban Rural Epidemiology (PURE) study has followed participants aged 35-70 years for a median of nearly 13 years. At enrollment, volunteers completed country-specific food-frequency questionnaires, enabling researchers to quantify usual intake of more than 130 food items and track new cases of IBD reported at biennial follow-ups.

The researchers classified packaged breads, sweet breakfast cereals, crackers, pastries and ready-to-heat pizza or pasta as ultraprocessed grains because they are refined and typically contain additives such as emulsifiers and preservatives. Fresh bakery bread and plain rice were analyzed separately as minimally processed grain references.

During a median of 12.9 years, 605 participants developed IBD; 497 developed ulcerative colitis (UC) and 108 developed Crohn’s disease. 

Increased intake of ultraprocessed grains was associated with a higher risk for IBD, with hazard ratios (HR) of 2.08 for intake of ≥ 50 g/d and 1.37 for 19-50 g/d compared to intake of < 19 g/d. The increased risk was largely driven by a significantly increased risk for UC (HR, 2.46) and not Crohn’s disease (HR, 0.98).

Among the different ultraprocessed grain products, packaged bread stood out: Consuming ≥ 30 g/d of packaged bread (a little more than one slice) was associated with a greater than twofold increased risk for IBD (HR, 2.11) compared to no intake of packaged bread.

In contrast, greater consumption of fresh bread was associated with a reduced risk of developing IBD (HR, 0.61 for ≥ 65 g/d and 0.45 for 16-65 g/d compared to < 16 g/d).

Increased intake of rice was also associated with a lower risk of developing IBD (HR, 0.63 for ≥ 1 serving/d and 0.99 for < 1 serving/d).

When the researchers widened the lens to all ultraprocessed foods — from sodas to salty snacks — the risk for IBD climbed further.

Participants eating at least five servings a day had nearly a fourfold greater odds of IBD than those eating fewer than one serving (HR, 3.95) — a finding consistent with other data from the PURE study cohort.

 

What to Tell Patients?

The authors acknowledged in their paper that it’s difficult — if not impossible — to completely avoid ultraprocessed food in the Western diet.

They said their findings support “public health strategies to promote consumption of whole and minimally processed foods while reducing the consumption of highly processed alternatives.”

“I tell my patients that emerging literature shows an association between ultraprocessed food intake and IBD risk, but it’s not yet clear whether simply cutting out those foods will improve disease activity once IBD is established,” Narula told GI & Hepatology News.

“However, I still encourage patients to reduce ultraprocessed foods and to follow a Mediterranean-style diet — focusing on minimally processed grains, fruits, vegetables, healthy fats, and lean proteins — to support overall gut and general health,” Narula said.

Reached for comment, Ashwin Ananthakrishnan, MD, MPH, AGAF, associate professor of medicine, Massachusetts General Hospital, Boston, who wasn’t part of the study, said it “adds incrementally to the growing data on how ultraprocessed foods may affect the risk of IBD.”

“They (and others) have previously shown a link between general ultraprocessed food consumption and risk of IBD. Others have shown that some of this is mediated through refined grains. This study more specifically studies that question and demonstrates an association,” said Ananthkrishnan.

“This should not be used, however, to counsel patients. It does not study the impact of grain intake on patients with IBD. It may help inform population level preventive strategies (or in high-risk individuals) but requires more confirmation since there is significant heterogeneity between the various countries in this cohort. Countries that have high refined grain intake are also enriched in several other IBD risk factors (including genetics),” Ananthkrishnan told GI & Hepatology News.

The PURE study is an investigator-initiated study funded by the Population Health Research Institute, Hamilton Health Sciences Research Institute, Canadian Institutes of Health Research, and Heart and Stroke Foundation of Ontario. It received support from Canadian Institutes of Health Research’s Strategy for Patient Oriented Research, Ontario SPOR Support Unit, and Ontario Ministry of Health and Long-Term Care and unrestricted grants from several pharmaceutical companies. Narula declared receiving honoraria from Janssen, Abbvie, Takeda, Pfizer, Sandoz, Novartis, Iterative Health, Innomar Strategies, Fresinius Kabi, Amgen, Organon, Eli Lilly, and Ferring. Ananthkrishnan declared having no relevant disclosures.

A version of this article appeared on Medscape.com.

Diets high in packaged breads, cookies, and other highly processed grain products may raise the risk for inflammatory bowel disease (IBD), while minimally processed grain products may offer some protection, a large study has found.

The sweeping analysis of 124,590 adults from 21 countries found that those eating at least 19 g of ultraprocessed grains a day were about twice as likely to be diagnosed with IBD as peers eating less than 9 g daily.

“Our study adds robust evidence from a large, diverse global cohort that frequent consumption of ultraprocessed grains is associated with an increased risk of developing inflammatory bowel disease,” Neeraj Narula, MD, MPH, gastroenterologist and associate professor of medicine, McMaster University, Hamilton, Ontario, Canada, told GI & Hepatology News.

The study also “further clarifies that not all grains carry risk — minimally processed grains like fresh bread and rice were associated with lower risk even. These results build on and specify previous findings linking ultraprocessed foods more broadly to IBD,” Narula said.

The study was published in The American Journal of Gastroenterology.

 

Diet Matters to IBD Risk

According to the latest US data (2021-2023), ultraprocessed foods made up 62% of daily calories for young people and 53% for adults in 2021-2023.

The Prospective Urban Rural Epidemiology (PURE) study has followed participants aged 35-70 years for a median of nearly 13 years. At enrollment, volunteers completed country-specific food-frequency questionnaires, enabling researchers to quantify usual intake of more than 130 food items and track new cases of IBD reported at biennial follow-ups.

The researchers classified packaged breads, sweet breakfast cereals, crackers, pastries and ready-to-heat pizza or pasta as ultraprocessed grains because they are refined and typically contain additives such as emulsifiers and preservatives. Fresh bakery bread and plain rice were analyzed separately as minimally processed grain references.

During a median of 12.9 years, 605 participants developed IBD; 497 developed ulcerative colitis (UC) and 108 developed Crohn’s disease. 

Increased intake of ultraprocessed grains was associated with a higher risk for IBD, with hazard ratios (HR) of 2.08 for intake of ≥ 50 g/d and 1.37 for 19-50 g/d compared to intake of < 19 g/d. The increased risk was largely driven by a significantly increased risk for UC (HR, 2.46) and not Crohn’s disease (HR, 0.98).

Among the different ultraprocessed grain products, packaged bread stood out: Consuming ≥ 30 g/d of packaged bread (a little more than one slice) was associated with a greater than twofold increased risk for IBD (HR, 2.11) compared to no intake of packaged bread.

In contrast, greater consumption of fresh bread was associated with a reduced risk of developing IBD (HR, 0.61 for ≥ 65 g/d and 0.45 for 16-65 g/d compared to < 16 g/d).

Increased intake of rice was also associated with a lower risk of developing IBD (HR, 0.63 for ≥ 1 serving/d and 0.99 for < 1 serving/d).

When the researchers widened the lens to all ultraprocessed foods — from sodas to salty snacks — the risk for IBD climbed further.

Participants eating at least five servings a day had nearly a fourfold greater odds of IBD than those eating fewer than one serving (HR, 3.95) — a finding consistent with other data from the PURE study cohort.

 

What to Tell Patients?

The authors acknowledged in their paper that it’s difficult — if not impossible — to completely avoid ultraprocessed food in the Western diet.

They said their findings support “public health strategies to promote consumption of whole and minimally processed foods while reducing the consumption of highly processed alternatives.”

“I tell my patients that emerging literature shows an association between ultraprocessed food intake and IBD risk, but it’s not yet clear whether simply cutting out those foods will improve disease activity once IBD is established,” Narula told GI & Hepatology News.

“However, I still encourage patients to reduce ultraprocessed foods and to follow a Mediterranean-style diet — focusing on minimally processed grains, fruits, vegetables, healthy fats, and lean proteins — to support overall gut and general health,” Narula said.

Reached for comment, Ashwin Ananthakrishnan, MD, MPH, AGAF, associate professor of medicine, Massachusetts General Hospital, Boston, who wasn’t part of the study, said it “adds incrementally to the growing data on how ultraprocessed foods may affect the risk of IBD.”

“They (and others) have previously shown a link between general ultraprocessed food consumption and risk of IBD. Others have shown that some of this is mediated through refined grains. This study more specifically studies that question and demonstrates an association,” said Ananthkrishnan.

“This should not be used, however, to counsel patients. It does not study the impact of grain intake on patients with IBD. It may help inform population level preventive strategies (or in high-risk individuals) but requires more confirmation since there is significant heterogeneity between the various countries in this cohort. Countries that have high refined grain intake are also enriched in several other IBD risk factors (including genetics),” Ananthkrishnan told GI & Hepatology News.

The PURE study is an investigator-initiated study funded by the Population Health Research Institute, Hamilton Health Sciences Research Institute, Canadian Institutes of Health Research, and Heart and Stroke Foundation of Ontario. It received support from Canadian Institutes of Health Research’s Strategy for Patient Oriented Research, Ontario SPOR Support Unit, and Ontario Ministry of Health and Long-Term Care and unrestricted grants from several pharmaceutical companies. Narula declared receiving honoraria from Janssen, Abbvie, Takeda, Pfizer, Sandoz, Novartis, Iterative Health, Innomar Strategies, Fresinius Kabi, Amgen, Organon, Eli Lilly, and Ferring. Ananthkrishnan declared having no relevant disclosures.

A version of this article appeared on Medscape.com.