Background

Programmed death-ligand 1 (PD-L1) checkpoint inhibitors revolutionized the treatment of advanced non-small cell lung cancer (aNSCLC) by improving overall survival compared to chemotherapy. PD-L1 biomarker testing is paramount for informing treatment decisions in aNSCLC. Real-world data describing patterns of PD-L1 testing within the Veteran Health Administration (VHA) are limited. This retrospective study seeks to evaluate demographic and clinical factors associated with PD-L1 testing in VHA.

Methods

Veterans diagnosed with aNSCLC from 2019-2022 were identified using VHA’s Corporate Data Warehouse. Wilcoxon Rank Sum and Chi- Square tests measured association between receipt of PD-L1 testing and patient demographic and clinical characteristics at aNSCLC diagnosis. Logistic regression assessed predictors of PD-L1 testing, and subgroup analyses were performed for significant interactions.

Results

Our study included 4575 patients with aNSCLC; 57.0% received PD-L1 testing. The likelihood of PD-L1 testing increased among patients diagnosed with aNSCLC after 2019 vs during 2019 (OR≥1.118, p≤0.035) and in Black vs White patients (OR=1.227, p=0.011). However, the following had decreased likelihood of PD-L1 testing: patients with stage IIIB vs IV cancer (OR=0.683, p=0.004); non vs current/former smokers (OR=0.733, p=0.039); squamous (OR=0.863, p=0.030) or NOS (OR=0.695,p=0.013) vs. adenocarcinoma histology. Interactions were observed between patient residential region and residential rurality (p=0.003), and region and receipt of oncology community care consults (OCCC) (p=0.030). Patients in rural Midwest (OR=0.445,p=0.004) and rural South (OR=0.566, p=0.032) were less likely to receive PD-L1 testing than Metropolitan patients. Across patients with OCCC, Western US patients were more likely to receive PD-L1 testing (OR=1.554, p=0.001) than patients in other regions. However, within Midwestern patients, those without a OCCC were more likely to receive PD-L1 testing (OR=1.724, p< 0.001) than those with a OCCC. High comorbidity index (CCI≥3) is associated with an increased likelihood of PD-L1 testing in a univariable model (OR=1.286 vs. CCI=0,p=0.009), but not in the multivariable model (p=0.278).

Conclusions

We identified demographic and clinical factors, including regional differences in rurality and OCCC patterns, associated with PD-L1 testing. These factors can focus ongoing efforts to improve PD-L1 testing and efforts to be more in line with recommended care.

Background

Programmed death-ligand 1 (PD-L1) checkpoint inhibitors revolutionized the treatment of advanced non-small cell lung cancer (aNSCLC) by improving overall survival compared to chemotherapy. PD-L1 biomarker testing is paramount for informing treatment decisions in aNSCLC. Real-world data describing patterns of PD-L1 testing within the Veteran Health Administration (VHA) are limited. This retrospective study seeks to evaluate demographic and clinical factors associated with PD-L1 testing in VHA.

Methods

Veterans diagnosed with aNSCLC from 2019-2022 were identified using VHA’s Corporate Data Warehouse. Wilcoxon Rank Sum and Chi- Square tests measured association between receipt of PD-L1 testing and patient demographic and clinical characteristics at aNSCLC diagnosis. Logistic regression assessed predictors of PD-L1 testing, and subgroup analyses were performed for significant interactions.

Results

Our study included 4575 patients with aNSCLC; 57.0% received PD-L1 testing. The likelihood of PD-L1 testing increased among patients diagnosed with aNSCLC after 2019 vs during 2019 (OR≥1.118, p≤0.035) and in Black vs White patients (OR=1.227, p=0.011). However, the following had decreased likelihood of PD-L1 testing: patients with stage IIIB vs IV cancer (OR=0.683, p=0.004); non vs current/former smokers (OR=0.733, p=0.039); squamous (OR=0.863, p=0.030) or NOS (OR=0.695,p=0.013) vs. adenocarcinoma histology. Interactions were observed between patient residential region and residential rurality (p=0.003), and region and receipt of oncology community care consults (OCCC) (p=0.030). Patients in rural Midwest (OR=0.445,p=0.004) and rural South (OR=0.566, p=0.032) were less likely to receive PD-L1 testing than Metropolitan patients. Across patients with OCCC, Western US patients were more likely to receive PD-L1 testing (OR=1.554, p=0.001) than patients in other regions. However, within Midwestern patients, those without a OCCC were more likely to receive PD-L1 testing (OR=1.724, p< 0.001) than those with a OCCC. High comorbidity index (CCI≥3) is associated with an increased likelihood of PD-L1 testing in a univariable model (OR=1.286 vs. CCI=0,p=0.009), but not in the multivariable model (p=0.278).

Conclusions

We identified demographic and clinical factors, including regional differences in rurality and OCCC patterns, associated with PD-L1 testing. These factors can focus ongoing efforts to improve PD-L1 testing and efforts to be more in line with recommended care.

Background

Programmed death-ligand 1 (PD-L1) checkpoint inhibitors revolutionized the treatment of advanced non-small cell lung cancer (aNSCLC) by improving overall survival compared to chemotherapy. PD-L1 biomarker testing is paramount for informing treatment decisions in aNSCLC. Real-world data describing patterns of PD-L1 testing within the Veteran Health Administration (VHA) are limited. This retrospective study seeks to evaluate demographic and clinical factors associated with PD-L1 testing in VHA.

Methods

Veterans diagnosed with aNSCLC from 2019-2022 were identified using VHA’s Corporate Data Warehouse. Wilcoxon Rank Sum and Chi- Square tests measured association between receipt of PD-L1 testing and patient demographic and clinical characteristics at aNSCLC diagnosis. Logistic regression assessed predictors of PD-L1 testing, and subgroup analyses were performed for significant interactions.

Results

Our study included 4575 patients with aNSCLC; 57.0% received PD-L1 testing. The likelihood of PD-L1 testing increased among patients diagnosed with aNSCLC after 2019 vs during 2019 (OR≥1.118, p≤0.035) and in Black vs White patients (OR=1.227, p=0.011). However, the following had decreased likelihood of PD-L1 testing: patients with stage IIIB vs IV cancer (OR=0.683, p=0.004); non vs current/former smokers (OR=0.733, p=0.039); squamous (OR=0.863, p=0.030) or NOS (OR=0.695,p=0.013) vs. adenocarcinoma histology. Interactions were observed between patient residential region and residential rurality (p=0.003), and region and receipt of oncology community care consults (OCCC) (p=0.030). Patients in rural Midwest (OR=0.445,p=0.004) and rural South (OR=0.566, p=0.032) were less likely to receive PD-L1 testing than Metropolitan patients. Across patients with OCCC, Western US patients were more likely to receive PD-L1 testing (OR=1.554, p=0.001) than patients in other regions. However, within Midwestern patients, those without a OCCC were more likely to receive PD-L1 testing (OR=1.724, p< 0.001) than those with a OCCC. High comorbidity index (CCI≥3) is associated with an increased likelihood of PD-L1 testing in a univariable model (OR=1.286 vs. CCI=0,p=0.009), but not in the multivariable model (p=0.278).

Conclusions

We identified demographic and clinical factors, including regional differences in rurality and OCCC patterns, associated with PD-L1 testing. These factors can focus ongoing efforts to improve PD-L1 testing and efforts to be more in line with recommended care.

Background

Offering participation in clinical trials is a standard of care practice in oncology. It is also considered a quality indicator by various professional cancer societies, including the American Societies of Hematology (ASH) and Clinical Oncology (ASCO). In 2023, VA launched Clinical Cancer Research Services (CCRS) to ensure that all Veterans with cancer can participate in a clinical trial should they choose to do so. Research teams struggle to identify and engage potentially eligible patients. This is a complex process involving eligibility screening, outreach, and personalized support, which frequently involves a manual workflow with inefficiencies, delays, and missed opportunities for patients. To support CCRS’s mission, we used VA Enterprise Cloud (VAEC) to rapidly develop a clinical workflow support application for CCRS team members.

Methods

We used an internally developed framework to rapidly define program aims, provider workflows, opportunities to augment with data products, and lean principles applied to health information technology to design a clinical workflow supporting application. Data products leveraged VAEC’s Summit Data Platform (SDP), an open, multi-cloud platform for ingesting, curating, and managing multi-source VHA data into usable products. User interface was developed in a low code/no code power platform environment, which integrates with SDP and is also available in VAEC.

Results

An initial aim was identified as supporting engagement for the ‘Reaching Rural Cancer Survivors Who Smoke Using Text-based Cessation Interventions’ study. Augmented workflow was identified by meeting principal stakeholders and staff. Data product development involved retrieval of cancer diagnoses from the VA cancer registry system and smoking status from CDW HealthFactors. Rural residence was identified using 2023 Rural-Urban Continuum Codes. Application design, testing and refinement followed. Design to implementation was accomplished over the span of two months: from Aug 5, 2024 to Oct 3, 2024. Over the next seven months, the application identified 2,603 potentially eligible Veterans, and a single navigator using the tool was able to review 456 cases, send 189 study letters, and enroll 5 Veterans.

Conclusions

Clinical workflow support tools that leverage cloud infrastructure such as VAEC and Summit Data Platform can improve system efficiencies and increase access to clinical trials.

Background

Offering participation in clinical trials is a standard of care practice in oncology. It is also considered a quality indicator by various professional cancer societies, including the American Societies of Hematology (ASH) and Clinical Oncology (ASCO). In 2023, VA launched Clinical Cancer Research Services (CCRS) to ensure that all Veterans with cancer can participate in a clinical trial should they choose to do so. Research teams struggle to identify and engage potentially eligible patients. This is a complex process involving eligibility screening, outreach, and personalized support, which frequently involves a manual workflow with inefficiencies, delays, and missed opportunities for patients. To support CCRS’s mission, we used VA Enterprise Cloud (VAEC) to rapidly develop a clinical workflow support application for CCRS team members.

Methods

We used an internally developed framework to rapidly define program aims, provider workflows, opportunities to augment with data products, and lean principles applied to health information technology to design a clinical workflow supporting application. Data products leveraged VAEC’s Summit Data Platform (SDP), an open, multi-cloud platform for ingesting, curating, and managing multi-source VHA data into usable products. User interface was developed in a low code/no code power platform environment, which integrates with SDP and is also available in VAEC.

Results

An initial aim was identified as supporting engagement for the ‘Reaching Rural Cancer Survivors Who Smoke Using Text-based Cessation Interventions’ study. Augmented workflow was identified by meeting principal stakeholders and staff. Data product development involved retrieval of cancer diagnoses from the VA cancer registry system and smoking status from CDW HealthFactors. Rural residence was identified using 2023 Rural-Urban Continuum Codes. Application design, testing and refinement followed. Design to implementation was accomplished over the span of two months: from Aug 5, 2024 to Oct 3, 2024. Over the next seven months, the application identified 2,603 potentially eligible Veterans, and a single navigator using the tool was able to review 456 cases, send 189 study letters, and enroll 5 Veterans.

Conclusions

Clinical workflow support tools that leverage cloud infrastructure such as VAEC and Summit Data Platform can improve system efficiencies and increase access to clinical trials.

Background

Offering participation in clinical trials is a standard of care practice in oncology. It is also considered a quality indicator by various professional cancer societies, including the American Societies of Hematology (ASH) and Clinical Oncology (ASCO). In 2023, VA launched Clinical Cancer Research Services (CCRS) to ensure that all Veterans with cancer can participate in a clinical trial should they choose to do so. Research teams struggle to identify and engage potentially eligible patients. This is a complex process involving eligibility screening, outreach, and personalized support, which frequently involves a manual workflow with inefficiencies, delays, and missed opportunities for patients. To support CCRS’s mission, we used VA Enterprise Cloud (VAEC) to rapidly develop a clinical workflow support application for CCRS team members.

Methods

We used an internally developed framework to rapidly define program aims, provider workflows, opportunities to augment with data products, and lean principles applied to health information technology to design a clinical workflow supporting application. Data products leveraged VAEC’s Summit Data Platform (SDP), an open, multi-cloud platform for ingesting, curating, and managing multi-source VHA data into usable products. User interface was developed in a low code/no code power platform environment, which integrates with SDP and is also available in VAEC.

Results

An initial aim was identified as supporting engagement for the ‘Reaching Rural Cancer Survivors Who Smoke Using Text-based Cessation Interventions’ study. Augmented workflow was identified by meeting principal stakeholders and staff. Data product development involved retrieval of cancer diagnoses from the VA cancer registry system and smoking status from CDW HealthFactors. Rural residence was identified using 2023 Rural-Urban Continuum Codes. Application design, testing and refinement followed. Design to implementation was accomplished over the span of two months: from Aug 5, 2024 to Oct 3, 2024. Over the next seven months, the application identified 2,603 potentially eligible Veterans, and a single navigator using the tool was able to review 456 cases, send 189 study letters, and enroll 5 Veterans.

Conclusions

Clinical workflow support tools that leverage cloud infrastructure such as VAEC and Summit Data Platform can improve system efficiencies and increase access to clinical trials.

Did you know you can honor a family member, friend, or colleague whose life has been touched by GI research through a gift to the AGA Research Foundation? Your gift will honor a loved one or yourself and support the AGA Research Awards Program, while giving you a tax benefit.

Named award. An AGA pilot award can be renamed after you or a loved one, and targeted for a specific gastrointestinal research area. A new pilot research award can be established with a pledge of $40,000+ or through an estate gift. Gifts of cash or appreciated securities may be used to establish a named award. 

Your next step. A named award gift is a wonderful way to acknowledge a loved one’s vision for the future. To learn more about ways to recognize your honoree, contact us at foundation@gastro.org.

A lack of funding can prevent talented individuals from pursuing a research career, thereby denying them the opportunity to conduct work that will ultimately benefit patients with critical needs. A named award donation to the AGA Research Foundation will help support and fund investigators with a research grant in the field of gastroenterology and hepatology.

Did you know you can honor a family member, friend, or colleague whose life has been touched by GI research through a gift to the AGA Research Foundation? Your gift will honor a loved one or yourself and support the AGA Research Awards Program, while giving you a tax benefit.

Named award. An AGA pilot award can be renamed after you or a loved one, and targeted for a specific gastrointestinal research area. A new pilot research award can be established with a pledge of $40,000+ or through an estate gift. Gifts of cash or appreciated securities may be used to establish a named award. 

Your next step. A named award gift is a wonderful way to acknowledge a loved one’s vision for the future. To learn more about ways to recognize your honoree, contact us at foundation@gastro.org.

A lack of funding can prevent talented individuals from pursuing a research career, thereby denying them the opportunity to conduct work that will ultimately benefit patients with critical needs. A named award donation to the AGA Research Foundation will help support and fund investigators with a research grant in the field of gastroenterology and hepatology.

Did you know you can honor a family member, friend, or colleague whose life has been touched by GI research through a gift to the AGA Research Foundation? Your gift will honor a loved one or yourself and support the AGA Research Awards Program, while giving you a tax benefit.

Named award. An AGA pilot award can be renamed after you or a loved one, and targeted for a specific gastrointestinal research area. A new pilot research award can be established with a pledge of $40,000+ or through an estate gift. Gifts of cash or appreciated securities may be used to establish a named award. 

Your next step. A named award gift is a wonderful way to acknowledge a loved one’s vision for the future. To learn more about ways to recognize your honoree, contact us at foundation@gastro.org.

A lack of funding can prevent talented individuals from pursuing a research career, thereby denying them the opportunity to conduct work that will ultimately benefit patients with critical needs. A named award donation to the AGA Research Foundation will help support and fund investigators with a research grant in the field of gastroenterology and hepatology.

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.







 

TOPLINE: A large-scale case-control study using the Million Veteran Program (MVP) found The study found independent associations of both genetic predisposition and Agent Orange (AO) exposure for several lymphoid malignant neoplasm subtypes.

METHODOLOGY:

• A case-control study included 255,155 US veterans enrolled in the MVP with available genotype, Agent Orange exposure information, and lymphoid malignant neoplasm diagnosis from January 1, 1965, through June T1, 2024.

• Analysis focused on non-Hispanic White veterans (median age 67 years; 92.5% male) due to ancestry distribution requirements for genome-wide association studies data availability.

• Researchers excluded 628 samples across all lymphoid malignant neoplasm groups and 61,343 control samples due to unavailability of AO exposure information.

• Investigators analyzed risk for chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, marginal zone lymphoma, and multiple myeloma as primary outcomes.

TAKEAWAY:

• Agent Orange exposure was associated with increased risk for chronic lymphocytic leukemia (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.40-1.84), diffuse large B-cell lymphoma (OR, 1.26; 95% CI, 1.03-1.53), follicular lymphoma (OR, 1.71; 95% CI, 1.39-2.11), and multiple myeloma (OR, 1.58; 95% CI, 1.35-1.86).

• Polygenic risk scores showed significant associations with all subtypes: chronic lymphocytic leukemia (OR, 1.81; 95% CI, 1.70-1.93), diffuse large B-cell lymphoma (OR, 1.12; 95% CI, 1.02-1.21), follicular lymphoma (OR, 1.33; 95% CI, 1.21-1.47), marginal zone lymphoma (OR, 1.17; 95% CI, 1.04-1.32), and multiple myeloma (OR, 1.41; 95% CI, 1.31-1.52).

• No significant polygenic risk score and AO exposure interactions were observed in the development of any lymphoid malignant neoplasm subtypes.

• The researchers found independent associations of both genetic predisposition and Agent Orange exposure on several lymphoid malignant neoplasm subtypes.

IN PRACTICE:

"Our study addressed the public health concerns surrounding AO exposure and lymphoid malignant neoplasms, finding that both AO exposure and polygenic risk are independently associated with disease, suggesting potentially distinct and additive pathways that merit further investigation,” the authors wrote.

SOURCE: The study was led by Xueyi Teng, PhD, Department of Biological Chemistry, School of Medicine, University of California in Irvine, and Helen Ma, MD, Tibor Rubin Veterans Affairs Medical Center in Long Beach. It was published online in JAMA Network Open.

LIMITATIONS: According to the authors, while this represents the largest study of Agent Orange exposure and genetic risk in lymphoid malignant neoplasm development, the power to find interaction associations in specific subtypes might be limited. Self-reported AO exposure may have introduced survival bias, especially in aggressive subtypes, as patients with aggressive tumors might have died before joining the MVP. Additionally, approximately half of the patients were diagnosed with lymphoid malignant neoplasm before self-reporting AO exposure in the survey, potentially introducing recall bias.

DISCLOSURES: Xueyi Teng, PhD, reported receiving grants from the George E. Hewitt Foundation for Medical Research Postdoc Fellowship during the conduct of the study. The research was supported by grant MVPOOO and Veterans Affairs Career Development Award 1IK2CX002437-O1A1. No other disclosures were reported.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE: A large-scale case-control study using the Million Veteran Program (MVP) found The study found independent associations of both genetic predisposition and Agent Orange (AO) exposure for several lymphoid malignant neoplasm subtypes.

METHODOLOGY:

• A case-control study included 255,155 US veterans enrolled in the MVP with available genotype, Agent Orange exposure information, and lymphoid malignant neoplasm diagnosis from January 1, 1965, through June T1, 2024.

• Analysis focused on non-Hispanic White veterans (median age 67 years; 92.5% male) due to ancestry distribution requirements for genome-wide association studies data availability.

• Researchers excluded 628 samples across all lymphoid malignant neoplasm groups and 61,343 control samples due to unavailability of AO exposure information.

• Investigators analyzed risk for chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, marginal zone lymphoma, and multiple myeloma as primary outcomes.

TAKEAWAY:

• Agent Orange exposure was associated with increased risk for chronic lymphocytic leukemia (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.40-1.84), diffuse large B-cell lymphoma (OR, 1.26; 95% CI, 1.03-1.53), follicular lymphoma (OR, 1.71; 95% CI, 1.39-2.11), and multiple myeloma (OR, 1.58; 95% CI, 1.35-1.86).

• Polygenic risk scores showed significant associations with all subtypes: chronic lymphocytic leukemia (OR, 1.81; 95% CI, 1.70-1.93), diffuse large B-cell lymphoma (OR, 1.12; 95% CI, 1.02-1.21), follicular lymphoma (OR, 1.33; 95% CI, 1.21-1.47), marginal zone lymphoma (OR, 1.17; 95% CI, 1.04-1.32), and multiple myeloma (OR, 1.41; 95% CI, 1.31-1.52).

• No significant polygenic risk score and AO exposure interactions were observed in the development of any lymphoid malignant neoplasm subtypes.

• The researchers found independent associations of both genetic predisposition and Agent Orange exposure on several lymphoid malignant neoplasm subtypes.

IN PRACTICE:

"Our study addressed the public health concerns surrounding AO exposure and lymphoid malignant neoplasms, finding that both AO exposure and polygenic risk are independently associated with disease, suggesting potentially distinct and additive pathways that merit further investigation,” the authors wrote.

SOURCE: The study was led by Xueyi Teng, PhD, Department of Biological Chemistry, School of Medicine, University of California in Irvine, and Helen Ma, MD, Tibor Rubin Veterans Affairs Medical Center in Long Beach. It was published online in JAMA Network Open.

LIMITATIONS: According to the authors, while this represents the largest study of Agent Orange exposure and genetic risk in lymphoid malignant neoplasm development, the power to find interaction associations in specific subtypes might be limited. Self-reported AO exposure may have introduced survival bias, especially in aggressive subtypes, as patients with aggressive tumors might have died before joining the MVP. Additionally, approximately half of the patients were diagnosed with lymphoid malignant neoplasm before self-reporting AO exposure in the survey, potentially introducing recall bias.

DISCLOSURES: Xueyi Teng, PhD, reported receiving grants from the George E. Hewitt Foundation for Medical Research Postdoc Fellowship during the conduct of the study. The research was supported by grant MVPOOO and Veterans Affairs Career Development Award 1IK2CX002437-O1A1. No other disclosures were reported.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE: A large-scale case-control study using the Million Veteran Program (MVP) found The study found independent associations of both genetic predisposition and Agent Orange (AO) exposure for several lymphoid malignant neoplasm subtypes.

METHODOLOGY:

• A case-control study included 255,155 US veterans enrolled in the MVP with available genotype, Agent Orange exposure information, and lymphoid malignant neoplasm diagnosis from January 1, 1965, through June T1, 2024.

• Analysis focused on non-Hispanic White veterans (median age 67 years; 92.5% male) due to ancestry distribution requirements for genome-wide association studies data availability.

• Researchers excluded 628 samples across all lymphoid malignant neoplasm groups and 61,343 control samples due to unavailability of AO exposure information.

• Investigators analyzed risk for chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, marginal zone lymphoma, and multiple myeloma as primary outcomes.

TAKEAWAY:

• Agent Orange exposure was associated with increased risk for chronic lymphocytic leukemia (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.40-1.84), diffuse large B-cell lymphoma (OR, 1.26; 95% CI, 1.03-1.53), follicular lymphoma (OR, 1.71; 95% CI, 1.39-2.11), and multiple myeloma (OR, 1.58; 95% CI, 1.35-1.86).

• Polygenic risk scores showed significant associations with all subtypes: chronic lymphocytic leukemia (OR, 1.81; 95% CI, 1.70-1.93), diffuse large B-cell lymphoma (OR, 1.12; 95% CI, 1.02-1.21), follicular lymphoma (OR, 1.33; 95% CI, 1.21-1.47), marginal zone lymphoma (OR, 1.17; 95% CI, 1.04-1.32), and multiple myeloma (OR, 1.41; 95% CI, 1.31-1.52).

• No significant polygenic risk score and AO exposure interactions were observed in the development of any lymphoid malignant neoplasm subtypes.

• The researchers found independent associations of both genetic predisposition and Agent Orange exposure on several lymphoid malignant neoplasm subtypes.

IN PRACTICE:

"Our study addressed the public health concerns surrounding AO exposure and lymphoid malignant neoplasms, finding that both AO exposure and polygenic risk are independently associated with disease, suggesting potentially distinct and additive pathways that merit further investigation,” the authors wrote.

SOURCE: The study was led by Xueyi Teng, PhD, Department of Biological Chemistry, School of Medicine, University of California in Irvine, and Helen Ma, MD, Tibor Rubin Veterans Affairs Medical Center in Long Beach. It was published online in JAMA Network Open.

LIMITATIONS: According to the authors, while this represents the largest study of Agent Orange exposure and genetic risk in lymphoid malignant neoplasm development, the power to find interaction associations in specific subtypes might be limited. Self-reported AO exposure may have introduced survival bias, especially in aggressive subtypes, as patients with aggressive tumors might have died before joining the MVP. Additionally, approximately half of the patients were diagnosed with lymphoid malignant neoplasm before self-reporting AO exposure in the survey, potentially introducing recall bias.

DISCLOSURES: Xueyi Teng, PhD, reported receiving grants from the George E. Hewitt Foundation for Medical Research Postdoc Fellowship during the conduct of the study. The research was supported by grant MVPOOO and Veterans Affairs Career Development Award 1IK2CX002437-O1A1. No other disclosures were reported.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

Despite more treatments and heightened awareness, Americans with irritable bowel syndrome (IBS) report worsening impacts on work, home, and social life compared with a decade ago. 

A new survey from AGA, in partnership with The Harris Poll, revealed that IBS symptoms interfere with people’s lives an average of 19 days each month — about 11 days affecting work or school and 8 days curtailing personal activities. 

Missed work or school has climbed to 3.6 days per month from 2.1 days in 2015 — the last time the AGA released the “IBS in America” survey. And more patients report spending less time with family and friends because of their symptoms (58% now, up from 48% in 2015). 

The latest survey was conducted in fall 2024 among more than 2000 patients with IBS and 600 healthcare providers, including gastroenterologists, primary care physicians, and advanced practitioners.

 

Stark Realities of Life With IBS

Fewer patients in 2024 described their IBS symptoms as very or extremely bothersome (43%, compared to 62% in 2015), yet three quarters said it’s tough to manage their symptoms and most can’t accurately predict whether they will experience symptoms on a given day.

All this affects patients’ willingness or ability to make plans. More than three quarters (77%) said they avoid situations where bathroom access is limited, and nearly that many (72%) said their symptoms cause them to stay home more often.

About 7 in 10 patients said their IBS symptoms make them feel like they’re not “normal” or that their symptoms prevent them from reaching their full potential.

“The findings of this survey underscore the persistent challenges and impact IBS has on patients’ lives,” said Andrea Shin, MD, gastroenterologist with UCLA Health, Los Angeles, and AGA patient education advisor. 

“Despite progress in the medical community’s approach to diagnosing and managing IBS, patients continue to suffer significant disruptions to their personal and professional lives,” Shin noted. 

 

How Is IBS Treated?

Treatment options for IBS have evolved over the last decade or so and now include several FDA-approved agents, such as plecanatide (Trulance) and tenapanor (Ibsrela) for IBS with constipation (IBS-C) and rifaximin (Xifaxan) and eluxadoline (Viberzi) for IBS with diarrhea (IBS-D).

According to patients who have tried them, prescription medications are among the most helpful treatments (18% for IBS-C and 19% for IBS-D).

Yet, clinicians tend to prioritize fiber, nonprescription laxatives, and exercise for IBS-C, and diet changes, antidiarrheals, and probiotics for IBS-D, over prescription medications, the survey found. 

Nonetheless, about 78% of patients reported being satisfied with what they take for their symptoms, with about one quarter very satisfied.

Compared to 10 years ago, more physicians in the latest survey said effective relief of abdominal pain (49% vs 39%) or diarrhea/constipation (47% vs 33%) and the availability of treatment options (49% vs 34%) are what is most lacking in IBS treatment today, despite advancements in the IBS treatment landscape.

“IBS is a condition that continues to challenge patients to find a treatment that consistently works for them,” said Jeffrey Roberts, founder of the IBS Patient Support Group community and World IBS Day.

“The AGA IBS in America Survey sheds light on patients who are still not being offered a variety of treatments that could provide them with a better quality of life. This continues to result in disruptions to their career, schooling, and life with their families and friends,” Roberts added.

A version of this article appeared on Medscape.com.

Despite more treatments and heightened awareness, Americans with irritable bowel syndrome (IBS) report worsening impacts on work, home, and social life compared with a decade ago. 

A new survey from AGA, in partnership with The Harris Poll, revealed that IBS symptoms interfere with people’s lives an average of 19 days each month — about 11 days affecting work or school and 8 days curtailing personal activities. 

Missed work or school has climbed to 3.6 days per month from 2.1 days in 2015 — the last time the AGA released the “IBS in America” survey. And more patients report spending less time with family and friends because of their symptoms (58% now, up from 48% in 2015). 

The latest survey was conducted in fall 2024 among more than 2000 patients with IBS and 600 healthcare providers, including gastroenterologists, primary care physicians, and advanced practitioners.

 

Stark Realities of Life With IBS

Fewer patients in 2024 described their IBS symptoms as very or extremely bothersome (43%, compared to 62% in 2015), yet three quarters said it’s tough to manage their symptoms and most can’t accurately predict whether they will experience symptoms on a given day.

All this affects patients’ willingness or ability to make plans. More than three quarters (77%) said they avoid situations where bathroom access is limited, and nearly that many (72%) said their symptoms cause them to stay home more often.

About 7 in 10 patients said their IBS symptoms make them feel like they’re not “normal” or that their symptoms prevent them from reaching their full potential.

“The findings of this survey underscore the persistent challenges and impact IBS has on patients’ lives,” said Andrea Shin, MD, gastroenterologist with UCLA Health, Los Angeles, and AGA patient education advisor. 

“Despite progress in the medical community’s approach to diagnosing and managing IBS, patients continue to suffer significant disruptions to their personal and professional lives,” Shin noted. 

 

How Is IBS Treated?

Treatment options for IBS have evolved over the last decade or so and now include several FDA-approved agents, such as plecanatide (Trulance) and tenapanor (Ibsrela) for IBS with constipation (IBS-C) and rifaximin (Xifaxan) and eluxadoline (Viberzi) for IBS with diarrhea (IBS-D).

According to patients who have tried them, prescription medications are among the most helpful treatments (18% for IBS-C and 19% for IBS-D).

Yet, clinicians tend to prioritize fiber, nonprescription laxatives, and exercise for IBS-C, and diet changes, antidiarrheals, and probiotics for IBS-D, over prescription medications, the survey found. 

Nonetheless, about 78% of patients reported being satisfied with what they take for their symptoms, with about one quarter very satisfied.

Compared to 10 years ago, more physicians in the latest survey said effective relief of abdominal pain (49% vs 39%) or diarrhea/constipation (47% vs 33%) and the availability of treatment options (49% vs 34%) are what is most lacking in IBS treatment today, despite advancements in the IBS treatment landscape.

“IBS is a condition that continues to challenge patients to find a treatment that consistently works for them,” said Jeffrey Roberts, founder of the IBS Patient Support Group community and World IBS Day.

“The AGA IBS in America Survey sheds light on patients who are still not being offered a variety of treatments that could provide them with a better quality of life. This continues to result in disruptions to their career, schooling, and life with their families and friends,” Roberts added.

A version of this article appeared on Medscape.com.

Despite more treatments and heightened awareness, Americans with irritable bowel syndrome (IBS) report worsening impacts on work, home, and social life compared with a decade ago. 

A new survey from AGA, in partnership with The Harris Poll, revealed that IBS symptoms interfere with people’s lives an average of 19 days each month — about 11 days affecting work or school and 8 days curtailing personal activities. 

Missed work or school has climbed to 3.6 days per month from 2.1 days in 2015 — the last time the AGA released the “IBS in America” survey. And more patients report spending less time with family and friends because of their symptoms (58% now, up from 48% in 2015). 

The latest survey was conducted in fall 2024 among more than 2000 patients with IBS and 600 healthcare providers, including gastroenterologists, primary care physicians, and advanced practitioners.

 

Stark Realities of Life With IBS

Fewer patients in 2024 described their IBS symptoms as very or extremely bothersome (43%, compared to 62% in 2015), yet three quarters said it’s tough to manage their symptoms and most can’t accurately predict whether they will experience symptoms on a given day.

All this affects patients’ willingness or ability to make plans. More than three quarters (77%) said they avoid situations where bathroom access is limited, and nearly that many (72%) said their symptoms cause them to stay home more often.

About 7 in 10 patients said their IBS symptoms make them feel like they’re not “normal” or that their symptoms prevent them from reaching their full potential.

“The findings of this survey underscore the persistent challenges and impact IBS has on patients’ lives,” said Andrea Shin, MD, gastroenterologist with UCLA Health, Los Angeles, and AGA patient education advisor. 

“Despite progress in the medical community’s approach to diagnosing and managing IBS, patients continue to suffer significant disruptions to their personal and professional lives,” Shin noted. 

 

How Is IBS Treated?

Treatment options for IBS have evolved over the last decade or so and now include several FDA-approved agents, such as plecanatide (Trulance) and tenapanor (Ibsrela) for IBS with constipation (IBS-C) and rifaximin (Xifaxan) and eluxadoline (Viberzi) for IBS with diarrhea (IBS-D).

According to patients who have tried them, prescription medications are among the most helpful treatments (18% for IBS-C and 19% for IBS-D).

Yet, clinicians tend to prioritize fiber, nonprescription laxatives, and exercise for IBS-C, and diet changes, antidiarrheals, and probiotics for IBS-D, over prescription medications, the survey found. 

Nonetheless, about 78% of patients reported being satisfied with what they take for their symptoms, with about one quarter very satisfied.

Compared to 10 years ago, more physicians in the latest survey said effective relief of abdominal pain (49% vs 39%) or diarrhea/constipation (47% vs 33%) and the availability of treatment options (49% vs 34%) are what is most lacking in IBS treatment today, despite advancements in the IBS treatment landscape.

“IBS is a condition that continues to challenge patients to find a treatment that consistently works for them,” said Jeffrey Roberts, founder of the IBS Patient Support Group community and World IBS Day.

“The AGA IBS in America Survey sheds light on patients who are still not being offered a variety of treatments that could provide them with a better quality of life. This continues to result in disruptions to their career, schooling, and life with their families and friends,” Roberts added.

A version of this article appeared on Medscape.com.

The FDA has granted accelerated approval to Novo Nordisk’s Wegovy for the treatment of metabolic-associated steatohepatitis (MASH) in adults with moderate-to-advanced fibrosis but without cirrhosis.

The once-weekly 2.4 mg semaglutide subcutaneous injection is given in conjunction with a reduced calorie diet and increased physical activity.

Among people living with overweight or obesity globally, 1 in 3 also have MASH.

The accelerated approval was based on part-one results from the ongoing two-part, phase-3 ESSENCE trial, in which Wegovy demonstrated a significant improvement in liver fibrosis with no worsening of steatohepatitis, as well as resolution of steatohepatitis with no worsening of liver fibrosis, compared with placebo at week 72. Those results were published online in April in The New England Journal of Medicine.

For the trial, 800 participants were randomly assigned to either Wegovy (534 participants) or placebo (266 participants) in addition to lifestyle changes. The mean age was 56 years and the mean BMI was 34. Most patients were white individuals (67.5%) and women (57.1%), and 55.9% of the patients had type 2 diabetes; 250 patients (31.3%) had stage II fibrosis and 550 (68.8%) had stage III fibrosis. Participants were on stable doses of lipid-lowering, glucose-management, and weight-loss medications.

At week 72, the first primary endpoint showed 63% of the 534 people treated with Wegovy achieved resolution of steatohepatitis and no worsening of liver fibrosis compared with 34% of 266 individuals treated with placebo — a statistically significant difference.

The second primary endpoint showed 37% of people treated with Wegovy achieved improvement in liver fibrosis and no worsening of steatohepatitis compared with 22% of those treated with placebo, also a significant difference.

A confirmatory secondary endpoint at week 72 showed 33% of patients treated with Wegovy achieved both resolution of steatohepatitis and improvement in liver fibrosis compared with 16% of those treated with placebo — a statistically significant difference in response rate of 17%.

In addition, 83.5% of the patients in the semaglutide group maintained the target dose of 2.4 mg until week 72.

Wegovy is also indicated, along with diet and physical activity, to reduce the risk for major cardiovascular events in adults with known heart disease and with either obesity or overweight. It is also indicated for adults and children aged 12 years or older with obesity, and some adults with overweight who also have weight-related medical problems, to help them lose excess body weight and keep the weight off.

 

What’s Next for Wegovy?

In February 2025, Novo Nordisk filed for regulatory approval in the EU, followed by regulatory submission in Japan in May 2025. Also in May, the FDA accepted a filing application for oral semaglutide 25 mg.

Furthermore, “There’s an expected readout of part 2 of ESSENCE in 2029, which aims to demonstrate treatment with Wegovy lowers the risk of liver-related clinical events, compared to placebo, in patients with MASH and F2 or F3 fibrosis at week 240,” a Novo Nordisk spokesperson told GI & Hepatology News.

Although the company has the technology to produce semaglutide as a pill or tablet, she said, “the US launch of oral semaglutide for obesity will be contingent on portfolio prioritization and manufacturing capacity.” The company has not yet submitted the 50 mg oral semaglutide to regulatory authorities.

“The oral form requires more active pharmaceutical ingredient (API),” she noted. “Given that we have a fixed amount of API, the injectable form enables us to treat more patients. We are currently expanding our oral and injectable production capacities globally with the aim of serving as many patients as possible. It requires time to build, install, validate, and ramp-up these production processes.”

 

A version of this article appeared on Medscape.com.

The FDA has granted accelerated approval to Novo Nordisk’s Wegovy for the treatment of metabolic-associated steatohepatitis (MASH) in adults with moderate-to-advanced fibrosis but without cirrhosis.

The once-weekly 2.4 mg semaglutide subcutaneous injection is given in conjunction with a reduced calorie diet and increased physical activity.

Among people living with overweight or obesity globally, 1 in 3 also have MASH.

The accelerated approval was based on part-one results from the ongoing two-part, phase-3 ESSENCE trial, in which Wegovy demonstrated a significant improvement in liver fibrosis with no worsening of steatohepatitis, as well as resolution of steatohepatitis with no worsening of liver fibrosis, compared with placebo at week 72. Those results were published online in April in The New England Journal of Medicine.

For the trial, 800 participants were randomly assigned to either Wegovy (534 participants) or placebo (266 participants) in addition to lifestyle changes. The mean age was 56 years and the mean BMI was 34. Most patients were white individuals (67.5%) and women (57.1%), and 55.9% of the patients had type 2 diabetes; 250 patients (31.3%) had stage II fibrosis and 550 (68.8%) had stage III fibrosis. Participants were on stable doses of lipid-lowering, glucose-management, and weight-loss medications.

At week 72, the first primary endpoint showed 63% of the 534 people treated with Wegovy achieved resolution of steatohepatitis and no worsening of liver fibrosis compared with 34% of 266 individuals treated with placebo — a statistically significant difference.

The second primary endpoint showed 37% of people treated with Wegovy achieved improvement in liver fibrosis and no worsening of steatohepatitis compared with 22% of those treated with placebo, also a significant difference.

A confirmatory secondary endpoint at week 72 showed 33% of patients treated with Wegovy achieved both resolution of steatohepatitis and improvement in liver fibrosis compared with 16% of those treated with placebo — a statistically significant difference in response rate of 17%.

In addition, 83.5% of the patients in the semaglutide group maintained the target dose of 2.4 mg until week 72.

Wegovy is also indicated, along with diet and physical activity, to reduce the risk for major cardiovascular events in adults with known heart disease and with either obesity or overweight. It is also indicated for adults and children aged 12 years or older with obesity, and some adults with overweight who also have weight-related medical problems, to help them lose excess body weight and keep the weight off.

 

What’s Next for Wegovy?

In February 2025, Novo Nordisk filed for regulatory approval in the EU, followed by regulatory submission in Japan in May 2025. Also in May, the FDA accepted a filing application for oral semaglutide 25 mg.

Furthermore, “There’s an expected readout of part 2 of ESSENCE in 2029, which aims to demonstrate treatment with Wegovy lowers the risk of liver-related clinical events, compared to placebo, in patients with MASH and F2 or F3 fibrosis at week 240,” a Novo Nordisk spokesperson told GI & Hepatology News.

Although the company has the technology to produce semaglutide as a pill or tablet, she said, “the US launch of oral semaglutide for obesity will be contingent on portfolio prioritization and manufacturing capacity.” The company has not yet submitted the 50 mg oral semaglutide to regulatory authorities.

“The oral form requires more active pharmaceutical ingredient (API),” she noted. “Given that we have a fixed amount of API, the injectable form enables us to treat more patients. We are currently expanding our oral and injectable production capacities globally with the aim of serving as many patients as possible. It requires time to build, install, validate, and ramp-up these production processes.”

 

A version of this article appeared on Medscape.com.

The FDA has granted accelerated approval to Novo Nordisk’s Wegovy for the treatment of metabolic-associated steatohepatitis (MASH) in adults with moderate-to-advanced fibrosis but without cirrhosis.

The once-weekly 2.4 mg semaglutide subcutaneous injection is given in conjunction with a reduced calorie diet and increased physical activity.

Among people living with overweight or obesity globally, 1 in 3 also have MASH.

The accelerated approval was based on part-one results from the ongoing two-part, phase-3 ESSENCE trial, in which Wegovy demonstrated a significant improvement in liver fibrosis with no worsening of steatohepatitis, as well as resolution of steatohepatitis with no worsening of liver fibrosis, compared with placebo at week 72. Those results were published online in April in The New England Journal of Medicine.

For the trial, 800 participants were randomly assigned to either Wegovy (534 participants) or placebo (266 participants) in addition to lifestyle changes. The mean age was 56 years and the mean BMI was 34. Most patients were white individuals (67.5%) and women (57.1%), and 55.9% of the patients had type 2 diabetes; 250 patients (31.3%) had stage II fibrosis and 550 (68.8%) had stage III fibrosis. Participants were on stable doses of lipid-lowering, glucose-management, and weight-loss medications.

At week 72, the first primary endpoint showed 63% of the 534 people treated with Wegovy achieved resolution of steatohepatitis and no worsening of liver fibrosis compared with 34% of 266 individuals treated with placebo — a statistically significant difference.

The second primary endpoint showed 37% of people treated with Wegovy achieved improvement in liver fibrosis and no worsening of steatohepatitis compared with 22% of those treated with placebo, also a significant difference.

A confirmatory secondary endpoint at week 72 showed 33% of patients treated with Wegovy achieved both resolution of steatohepatitis and improvement in liver fibrosis compared with 16% of those treated with placebo — a statistically significant difference in response rate of 17%.

In addition, 83.5% of the patients in the semaglutide group maintained the target dose of 2.4 mg until week 72.

Wegovy is also indicated, along with diet and physical activity, to reduce the risk for major cardiovascular events in adults with known heart disease and with either obesity or overweight. It is also indicated for adults and children aged 12 years or older with obesity, and some adults with overweight who also have weight-related medical problems, to help them lose excess body weight and keep the weight off.

 

What’s Next for Wegovy?

In February 2025, Novo Nordisk filed for regulatory approval in the EU, followed by regulatory submission in Japan in May 2025. Also in May, the FDA accepted a filing application for oral semaglutide 25 mg.

Furthermore, “There’s an expected readout of part 2 of ESSENCE in 2029, which aims to demonstrate treatment with Wegovy lowers the risk of liver-related clinical events, compared to placebo, in patients with MASH and F2 or F3 fibrosis at week 240,” a Novo Nordisk spokesperson told GI & Hepatology News.

Although the company has the technology to produce semaglutide as a pill or tablet, she said, “the US launch of oral semaglutide for obesity will be contingent on portfolio prioritization and manufacturing capacity.” The company has not yet submitted the 50 mg oral semaglutide to regulatory authorities.

“The oral form requires more active pharmaceutical ingredient (API),” she noted. “Given that we have a fixed amount of API, the injectable form enables us to treat more patients. We are currently expanding our oral and injectable production capacities globally with the aim of serving as many patients as possible. It requires time to build, install, validate, and ramp-up these production processes.”

 

A version of this article appeared on Medscape.com.