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Support GI Research Through a Named Research Award
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 [email protected].
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.
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 [email protected].
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.
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 [email protected].
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.
Intestinal Methanogen Overgrowth Fosters More Constipation, Less Diarrhea
published in Clinical Gastroenterology and Hepatology.
, according to a systematic review and meta-analysis“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.
published in Clinical Gastroenterology and Hepatology.
, according to a systematic review and meta-analysis“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.
published in Clinical Gastroenterology and Hepatology.
, according to a systematic review and meta-analysis“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.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Common Medications Do Not Raise Microscopic Colitis Risk in Seniors
“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.
“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.
“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.
New Evidence Red Meat–Rich Diet Can Exacerbate IBD
Researchers from China observed that mice fed a red meat diet experienced more severe intestinal inflammation after colitis was experimentally induced compared to those on a control diet.
“These results highlight the necessity of dietary optimization, particularly the reduction of red meat consumption, as a preventive strategy against the development of IBD,” wrote Dan Tian, MD, PhD, with Capital Medical University, Beijing, China, and colleagues. The study was published online in Molecular Nutrition & Food Research.
Environmental Trigger
The exact causes of IBD remain unclear, but diet has long been considered a key environmental trigger. Western dietary patterns, which often feature high consumption of red and processed meats and low fiber, have been associated with higher IBD rates, especially ulcerative colitis.
Tian and colleagues tested the aggravating effects of three red meat diets on intestinal inflammation, gut microbiota composition, and susceptibility to colitis in mice.
They fed mice red meat diets prepared from pork, beef, and mutton for 2 weeks before inducing colitis using dextran sulfate sodium. They monitored the animals for changes in weight, colon length, tissue damage, and immune activity.
Histological analysis revealed that all three red meat diets aggravated colonic inflammation, with mutton producing the most pronounced effects.
RNA sequencing of colon tissue further showed that red meat intake activated pathways linked to inflammation. “Notably,” expression off proinflammatory cytokines, including interleukin (IL)-1 beta and IL-6, was significantly upregulated and expression of genes related to myeloid cell chemotaxis and activation was also increased, the researchers reported.
Flow cytometry confirmed that red meat diets promoted a surge in colonic myeloid immune cells, potentially driving inflammation. However, only minimal changes in T lymphocytes were observed, suggesting that red meat primarily drives innate immune rather than adaptive immune activation, they suggested.
While overall microbial diversity was not significantly altered, red meat-fed mice displayed marked dysbiosis.
Beneficial bacteria such as Streptococcus, Akkermansia, Faecalibacterium, and Lactococcus declined, while harmful groups including Clostridium and Mucispirillum increased. Each type of meat had distinct microbial effects, but all skewed the balance toward potentially harmful bacteria known to promote gut inflammation.
Overall, these results suggest that red meat diets exacerbate colitis by simultaneously promoting immune cell infiltration and disturbing microbial communities in the gut.
The fact that these effects occurred without significant change in weight, suggests that red meat consumption exerts proinflammatory effects through mechanisms other than weight gain.
“These results offer valuable insights into the relationship between dietary interventions and IBD, suggesting that a balanced diet, adequate nutrients, and moderated red meat consumption may help prevent the development of IBD,” the researchers concluded.
In support of their findings, a 2024 umbrella review that synthesized data from multiple cohort and observational studies, found strong associations between Western-style dietary patterns — including high processed/red meat, saturated fats, and additives — and both the incidence and progression of IBD.
The study had no commercial funding. The authors declared having no conflicts of interest.
A version of this article appeared on Medscape.com.
Researchers from China observed that mice fed a red meat diet experienced more severe intestinal inflammation after colitis was experimentally induced compared to those on a control diet.
“These results highlight the necessity of dietary optimization, particularly the reduction of red meat consumption, as a preventive strategy against the development of IBD,” wrote Dan Tian, MD, PhD, with Capital Medical University, Beijing, China, and colleagues. The study was published online in Molecular Nutrition & Food Research.
Environmental Trigger
The exact causes of IBD remain unclear, but diet has long been considered a key environmental trigger. Western dietary patterns, which often feature high consumption of red and processed meats and low fiber, have been associated with higher IBD rates, especially ulcerative colitis.
Tian and colleagues tested the aggravating effects of three red meat diets on intestinal inflammation, gut microbiota composition, and susceptibility to colitis in mice.
They fed mice red meat diets prepared from pork, beef, and mutton for 2 weeks before inducing colitis using dextran sulfate sodium. They monitored the animals for changes in weight, colon length, tissue damage, and immune activity.
Histological analysis revealed that all three red meat diets aggravated colonic inflammation, with mutton producing the most pronounced effects.
RNA sequencing of colon tissue further showed that red meat intake activated pathways linked to inflammation. “Notably,” expression off proinflammatory cytokines, including interleukin (IL)-1 beta and IL-6, was significantly upregulated and expression of genes related to myeloid cell chemotaxis and activation was also increased, the researchers reported.
Flow cytometry confirmed that red meat diets promoted a surge in colonic myeloid immune cells, potentially driving inflammation. However, only minimal changes in T lymphocytes were observed, suggesting that red meat primarily drives innate immune rather than adaptive immune activation, they suggested.
While overall microbial diversity was not significantly altered, red meat-fed mice displayed marked dysbiosis.
Beneficial bacteria such as Streptococcus, Akkermansia, Faecalibacterium, and Lactococcus declined, while harmful groups including Clostridium and Mucispirillum increased. Each type of meat had distinct microbial effects, but all skewed the balance toward potentially harmful bacteria known to promote gut inflammation.
Overall, these results suggest that red meat diets exacerbate colitis by simultaneously promoting immune cell infiltration and disturbing microbial communities in the gut.
The fact that these effects occurred without significant change in weight, suggests that red meat consumption exerts proinflammatory effects through mechanisms other than weight gain.
“These results offer valuable insights into the relationship between dietary interventions and IBD, suggesting that a balanced diet, adequate nutrients, and moderated red meat consumption may help prevent the development of IBD,” the researchers concluded.
In support of their findings, a 2024 umbrella review that synthesized data from multiple cohort and observational studies, found strong associations between Western-style dietary patterns — including high processed/red meat, saturated fats, and additives — and both the incidence and progression of IBD.
The study had no commercial funding. The authors declared having no conflicts of interest.
A version of this article appeared on Medscape.com.
Researchers from China observed that mice fed a red meat diet experienced more severe intestinal inflammation after colitis was experimentally induced compared to those on a control diet.
“These results highlight the necessity of dietary optimization, particularly the reduction of red meat consumption, as a preventive strategy against the development of IBD,” wrote Dan Tian, MD, PhD, with Capital Medical University, Beijing, China, and colleagues. The study was published online in Molecular Nutrition & Food Research.
Environmental Trigger
The exact causes of IBD remain unclear, but diet has long been considered a key environmental trigger. Western dietary patterns, which often feature high consumption of red and processed meats and low fiber, have been associated with higher IBD rates, especially ulcerative colitis.
Tian and colleagues tested the aggravating effects of three red meat diets on intestinal inflammation, gut microbiota composition, and susceptibility to colitis in mice.
They fed mice red meat diets prepared from pork, beef, and mutton for 2 weeks before inducing colitis using dextran sulfate sodium. They monitored the animals for changes in weight, colon length, tissue damage, and immune activity.
Histological analysis revealed that all three red meat diets aggravated colonic inflammation, with mutton producing the most pronounced effects.
RNA sequencing of colon tissue further showed that red meat intake activated pathways linked to inflammation. “Notably,” expression off proinflammatory cytokines, including interleukin (IL)-1 beta and IL-6, was significantly upregulated and expression of genes related to myeloid cell chemotaxis and activation was also increased, the researchers reported.
Flow cytometry confirmed that red meat diets promoted a surge in colonic myeloid immune cells, potentially driving inflammation. However, only minimal changes in T lymphocytes were observed, suggesting that red meat primarily drives innate immune rather than adaptive immune activation, they suggested.
While overall microbial diversity was not significantly altered, red meat-fed mice displayed marked dysbiosis.
Beneficial bacteria such as Streptococcus, Akkermansia, Faecalibacterium, and Lactococcus declined, while harmful groups including Clostridium and Mucispirillum increased. Each type of meat had distinct microbial effects, but all skewed the balance toward potentially harmful bacteria known to promote gut inflammation.
Overall, these results suggest that red meat diets exacerbate colitis by simultaneously promoting immune cell infiltration and disturbing microbial communities in the gut.
The fact that these effects occurred without significant change in weight, suggests that red meat consumption exerts proinflammatory effects through mechanisms other than weight gain.
“These results offer valuable insights into the relationship between dietary interventions and IBD, suggesting that a balanced diet, adequate nutrients, and moderated red meat consumption may help prevent the development of IBD,” the researchers concluded.
In support of their findings, a 2024 umbrella review that synthesized data from multiple cohort and observational studies, found strong associations between Western-style dietary patterns — including high processed/red meat, saturated fats, and additives — and both the incidence and progression of IBD.
The study had no commercial funding. The authors declared having no conflicts of interest.
A version of this article appeared on Medscape.com.
HPV Vaccine Reduces Immune Disease Risk in Women
TOPLINE: Human Papillomavirus (HPV) vaccination is associated with reduced risks of rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes among females aged 9 to 45 years. The analysis of 208,638 vaccinated individuals shows particularly strong protective effects in those aged 9 to 26 years and recipients of 9-valent HPV vaccines.
METHODOLOGY:
Researchers analyzed data from the US Collaborative Network in TriNetX spanning January 1, 2018, to December 20, 2022, enrolling 208,638 females aged 9 to 45 years who received HPV vaccination and matching them with 208,638 unvaccinated individuals using propensity scores.
Analysis included Cox proportional hazard regression to estimate hazard ratios and 95% CIs for immune-mediated diseases, with subgroup analyses stratified by age, race, smoking, obesity, asthma, and HPV vaccine types.
Participants were monitored from 31 days up to 365 days following their respective index dates, with sensitivity analyses conducted to evaluate short-term outcomes and compare results with influenza virus vaccine recipients.
TAKEAWAY:
HPV vaccination demonstrated reduced risks for rheumatoid arthritis (hazard ratio [HR], 0.487; 95% confidence interval [CI], 0.311-0.762), systemic lupus erythematosus (HR, 0.287; 95% CI, 0.179-0.460), and dermatomyositis (HR, 0.299; 95% CI, 0.098-0.908).
Recipients showed lower risks for inflammatory bowel disease (HR, 0.876; 95% CI, 0.811-0.946), celiac disease (HR, 0.400; 95% CI, 0.304-0.526), and type 1 diabetes (HR, 0.242; 95% CI, 0.184-0.318).
Subgroup analyses revealed significant risk reductions among females aged 9 to 26 years and those receiving 9-valent HPV vaccines compared to unvaccinated populations.
White and Black/African American individuals demonstrated reduced risks for various immune-mediated diseases, while Asians showed lower risks only for inflammatory bowel disease and overall immune-mediated diseases.
SOURCE: The study was led by Qianru Zhang, MD, Beijing Tsinghua Changgung Hospital in Beijing, China, James Cheng-Chung Wei, and Shiow-Ing Wang who contributed equally as first authors. It was published online in QJM: An International Journal of Medicine.
LIMITATIONS: According to the authors, research relying on Electronic Health Records (EHR) faced several constraints, including the absence of serial data on HPV antibody titers in vaccinated individuals and limited data regarding vaccination dosing numbers. Additionally, the current functionality of TriNetX prevented performing interaction terms in the statistical model for comprehensive subgroup analysis stratified by age, race, and vaccine types.
DISCLOSURES: The study received support from Chung Shan Medical University Hospital (Grant No. CSH-2023-E-001-Y2), Kaohsiung Veterans General Hospital (KSVGH 113-117), National Science and Technology Council (NSTC 112-2314-B-075B-020), and KSVNSU112-008. The funders had no role in the study's design, conduct, data analysis, or manuscript approval.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
TOPLINE: Human Papillomavirus (HPV) vaccination is associated with reduced risks of rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes among females aged 9 to 45 years. The analysis of 208,638 vaccinated individuals shows particularly strong protective effects in those aged 9 to 26 years and recipients of 9-valent HPV vaccines.
METHODOLOGY:
Researchers analyzed data from the US Collaborative Network in TriNetX spanning January 1, 2018, to December 20, 2022, enrolling 208,638 females aged 9 to 45 years who received HPV vaccination and matching them with 208,638 unvaccinated individuals using propensity scores.
Analysis included Cox proportional hazard regression to estimate hazard ratios and 95% CIs for immune-mediated diseases, with subgroup analyses stratified by age, race, smoking, obesity, asthma, and HPV vaccine types.
Participants were monitored from 31 days up to 365 days following their respective index dates, with sensitivity analyses conducted to evaluate short-term outcomes and compare results with influenza virus vaccine recipients.
TAKEAWAY:
HPV vaccination demonstrated reduced risks for rheumatoid arthritis (hazard ratio [HR], 0.487; 95% confidence interval [CI], 0.311-0.762), systemic lupus erythematosus (HR, 0.287; 95% CI, 0.179-0.460), and dermatomyositis (HR, 0.299; 95% CI, 0.098-0.908).
Recipients showed lower risks for inflammatory bowel disease (HR, 0.876; 95% CI, 0.811-0.946), celiac disease (HR, 0.400; 95% CI, 0.304-0.526), and type 1 diabetes (HR, 0.242; 95% CI, 0.184-0.318).
Subgroup analyses revealed significant risk reductions among females aged 9 to 26 years and those receiving 9-valent HPV vaccines compared to unvaccinated populations.
White and Black/African American individuals demonstrated reduced risks for various immune-mediated diseases, while Asians showed lower risks only for inflammatory bowel disease and overall immune-mediated diseases.
SOURCE: The study was led by Qianru Zhang, MD, Beijing Tsinghua Changgung Hospital in Beijing, China, James Cheng-Chung Wei, and Shiow-Ing Wang who contributed equally as first authors. It was published online in QJM: An International Journal of Medicine.
LIMITATIONS: According to the authors, research relying on Electronic Health Records (EHR) faced several constraints, including the absence of serial data on HPV antibody titers in vaccinated individuals and limited data regarding vaccination dosing numbers. Additionally, the current functionality of TriNetX prevented performing interaction terms in the statistical model for comprehensive subgroup analysis stratified by age, race, and vaccine types.
DISCLOSURES: The study received support from Chung Shan Medical University Hospital (Grant No. CSH-2023-E-001-Y2), Kaohsiung Veterans General Hospital (KSVGH 113-117), National Science and Technology Council (NSTC 112-2314-B-075B-020), and KSVNSU112-008. The funders had no role in the study's design, conduct, data analysis, or manuscript approval.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
TOPLINE: Human Papillomavirus (HPV) vaccination is associated with reduced risks of rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes among females aged 9 to 45 years. The analysis of 208,638 vaccinated individuals shows particularly strong protective effects in those aged 9 to 26 years and recipients of 9-valent HPV vaccines.
METHODOLOGY:
Researchers analyzed data from the US Collaborative Network in TriNetX spanning January 1, 2018, to December 20, 2022, enrolling 208,638 females aged 9 to 45 years who received HPV vaccination and matching them with 208,638 unvaccinated individuals using propensity scores.
Analysis included Cox proportional hazard regression to estimate hazard ratios and 95% CIs for immune-mediated diseases, with subgroup analyses stratified by age, race, smoking, obesity, asthma, and HPV vaccine types.
Participants were monitored from 31 days up to 365 days following their respective index dates, with sensitivity analyses conducted to evaluate short-term outcomes and compare results with influenza virus vaccine recipients.
TAKEAWAY:
HPV vaccination demonstrated reduced risks for rheumatoid arthritis (hazard ratio [HR], 0.487; 95% confidence interval [CI], 0.311-0.762), systemic lupus erythematosus (HR, 0.287; 95% CI, 0.179-0.460), and dermatomyositis (HR, 0.299; 95% CI, 0.098-0.908).
Recipients showed lower risks for inflammatory bowel disease (HR, 0.876; 95% CI, 0.811-0.946), celiac disease (HR, 0.400; 95% CI, 0.304-0.526), and type 1 diabetes (HR, 0.242; 95% CI, 0.184-0.318).
Subgroup analyses revealed significant risk reductions among females aged 9 to 26 years and those receiving 9-valent HPV vaccines compared to unvaccinated populations.
White and Black/African American individuals demonstrated reduced risks for various immune-mediated diseases, while Asians showed lower risks only for inflammatory bowel disease and overall immune-mediated diseases.
SOURCE: The study was led by Qianru Zhang, MD, Beijing Tsinghua Changgung Hospital in Beijing, China, James Cheng-Chung Wei, and Shiow-Ing Wang who contributed equally as first authors. It was published online in QJM: An International Journal of Medicine.
LIMITATIONS: According to the authors, research relying on Electronic Health Records (EHR) faced several constraints, including the absence of serial data on HPV antibody titers in vaccinated individuals and limited data regarding vaccination dosing numbers. Additionally, the current functionality of TriNetX prevented performing interaction terms in the statistical model for comprehensive subgroup analysis stratified by age, race, and vaccine types.
DISCLOSURES: The study received support from Chung Shan Medical University Hospital (Grant No. CSH-2023-E-001-Y2), Kaohsiung Veterans General Hospital (KSVGH 113-117), National Science and Technology Council (NSTC 112-2314-B-075B-020), and KSVNSU112-008. The funders had no role in the study's design, conduct, data analysis, or manuscript approval.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
DoD Surveillance: Low to Moderate Effectiveness for Flu Vaccine
A mid-season analysis of the influenza vaccine by the US Department of Defensive (DoD) Global Respiratory Pathogen Surveillance Program (DoDGRPSP) has reported low to moderate vaccine effectiveness (VE).
The study included 295 Military Health System (MHS) beneficiaries (adults and children) who tested positive for influenza and 965 controls who tested negative. Vaccinated patients had received the 2024-2025 influenza vaccine at least 14 days prior to symptom onset. The study conducted VE analyses for influenza A (any subtype), influenza A(H1N1)pdm09, and influenza A(H3N2).
Overall, moderate effectiveness against influenza A(H1N1)pdm09 was reported in all beneficiaries and children aged 6 months to 17 years. In adults aged 18 to 64 years—and all beneficiaries—there was moderate effectiveness against influenza A(H3N2). VE estimates against influenza A (any subtype) for all beneficiaries, children, and adults were not significant; VE estimates were also not effective among children for influenza A(H3N2) and in adults for influenza A(H1N1)pdm09.
Adjusted VE estimates among all participants for influenza A (any subtypes), influenza A(H1N1)pdm09, and influenza A(H3N2) were 25%, 58%, and 42%, respectively. VE for influenza B was not calculated due to a low number of cases.
Flu vaccination rates for adults are usually in the 30% to 60% range despite the recommended target of 70%. Flu vaccination rates were rising by around 1% to 2% annually before 2020, but began dropping after the COVID-19 pandemic, especially in higher-risk groups. In adults aged ≥ 65 years, flu vaccination rates dropped from 52% in 2019-2020 to 43% in 2024-2025.
According to the Centers for Disease Control and Prevention (CDC), at the end of the 2023-2024 flu season, 9.2 million fewer doses were administered in pharmacies and doctors offices compared with the baseline before the COVID-19 pandemic. Since 2022, private manufacturers have distributed significantly fewer influenza vaccine doses.
Each March, the US Food and Drug Association (FDA) Vaccines and Related Biological Products Advisory Committee (VRBPAC) meets to analyze the current influenza season and forecast the next. The committee reviews and discusses data on influenza strain circulation and VE, which come from DoDGRPSP analyses. In February, US Department of Health and Human Services officials indefinitely postponed a public meeting of the CDC Advisory Committee on Immunization Practice (ACIP), at which members were also expected to discuss, among other things, VE and vaccine recommendations. The FDA canceled a March 13 VRBPAC meeting and provided no reason for the cancelation to members. That day, however, the FDA issued new recommendations for the influenza vaccine for the 2025-2026 season without the input of VRBPAC. Instead, experts from the FDA, CDC, and DoD made recommendations after reviewing surveillance data from the US and globally.
For the 2025-2026 influenza season, the FDA recommends the vaccines be trivalent and target 2 strains of influenza A and 1 strain of influenza B. The FDA anticipates there will be an “adequate and diverse supply” of approved trivalent seasonal influenza vaccines. Trivalent flu vaccines are formulated to protect against 3 influenza viruses: an A(H1N1) virus, an A(H3N2) virus, and a B/Victoria virus. All influenza vaccines for the 2025-2026 season are anticipated to be trivalent in the US.
A mid-season analysis of the influenza vaccine by the US Department of Defensive (DoD) Global Respiratory Pathogen Surveillance Program (DoDGRPSP) has reported low to moderate vaccine effectiveness (VE).
The study included 295 Military Health System (MHS) beneficiaries (adults and children) who tested positive for influenza and 965 controls who tested negative. Vaccinated patients had received the 2024-2025 influenza vaccine at least 14 days prior to symptom onset. The study conducted VE analyses for influenza A (any subtype), influenza A(H1N1)pdm09, and influenza A(H3N2).
Overall, moderate effectiveness against influenza A(H1N1)pdm09 was reported in all beneficiaries and children aged 6 months to 17 years. In adults aged 18 to 64 years—and all beneficiaries—there was moderate effectiveness against influenza A(H3N2). VE estimates against influenza A (any subtype) for all beneficiaries, children, and adults were not significant; VE estimates were also not effective among children for influenza A(H3N2) and in adults for influenza A(H1N1)pdm09.
Adjusted VE estimates among all participants for influenza A (any subtypes), influenza A(H1N1)pdm09, and influenza A(H3N2) were 25%, 58%, and 42%, respectively. VE for influenza B was not calculated due to a low number of cases.
Flu vaccination rates for adults are usually in the 30% to 60% range despite the recommended target of 70%. Flu vaccination rates were rising by around 1% to 2% annually before 2020, but began dropping after the COVID-19 pandemic, especially in higher-risk groups. In adults aged ≥ 65 years, flu vaccination rates dropped from 52% in 2019-2020 to 43% in 2024-2025.
According to the Centers for Disease Control and Prevention (CDC), at the end of the 2023-2024 flu season, 9.2 million fewer doses were administered in pharmacies and doctors offices compared with the baseline before the COVID-19 pandemic. Since 2022, private manufacturers have distributed significantly fewer influenza vaccine doses.
Each March, the US Food and Drug Association (FDA) Vaccines and Related Biological Products Advisory Committee (VRBPAC) meets to analyze the current influenza season and forecast the next. The committee reviews and discusses data on influenza strain circulation and VE, which come from DoDGRPSP analyses. In February, US Department of Health and Human Services officials indefinitely postponed a public meeting of the CDC Advisory Committee on Immunization Practice (ACIP), at which members were also expected to discuss, among other things, VE and vaccine recommendations. The FDA canceled a March 13 VRBPAC meeting and provided no reason for the cancelation to members. That day, however, the FDA issued new recommendations for the influenza vaccine for the 2025-2026 season without the input of VRBPAC. Instead, experts from the FDA, CDC, and DoD made recommendations after reviewing surveillance data from the US and globally.
For the 2025-2026 influenza season, the FDA recommends the vaccines be trivalent and target 2 strains of influenza A and 1 strain of influenza B. The FDA anticipates there will be an “adequate and diverse supply” of approved trivalent seasonal influenza vaccines. Trivalent flu vaccines are formulated to protect against 3 influenza viruses: an A(H1N1) virus, an A(H3N2) virus, and a B/Victoria virus. All influenza vaccines for the 2025-2026 season are anticipated to be trivalent in the US.
A mid-season analysis of the influenza vaccine by the US Department of Defensive (DoD) Global Respiratory Pathogen Surveillance Program (DoDGRPSP) has reported low to moderate vaccine effectiveness (VE).
The study included 295 Military Health System (MHS) beneficiaries (adults and children) who tested positive for influenza and 965 controls who tested negative. Vaccinated patients had received the 2024-2025 influenza vaccine at least 14 days prior to symptom onset. The study conducted VE analyses for influenza A (any subtype), influenza A(H1N1)pdm09, and influenza A(H3N2).
Overall, moderate effectiveness against influenza A(H1N1)pdm09 was reported in all beneficiaries and children aged 6 months to 17 years. In adults aged 18 to 64 years—and all beneficiaries—there was moderate effectiveness against influenza A(H3N2). VE estimates against influenza A (any subtype) for all beneficiaries, children, and adults were not significant; VE estimates were also not effective among children for influenza A(H3N2) and in adults for influenza A(H1N1)pdm09.
Adjusted VE estimates among all participants for influenza A (any subtypes), influenza A(H1N1)pdm09, and influenza A(H3N2) were 25%, 58%, and 42%, respectively. VE for influenza B was not calculated due to a low number of cases.
Flu vaccination rates for adults are usually in the 30% to 60% range despite the recommended target of 70%. Flu vaccination rates were rising by around 1% to 2% annually before 2020, but began dropping after the COVID-19 pandemic, especially in higher-risk groups. In adults aged ≥ 65 years, flu vaccination rates dropped from 52% in 2019-2020 to 43% in 2024-2025.
According to the Centers for Disease Control and Prevention (CDC), at the end of the 2023-2024 flu season, 9.2 million fewer doses were administered in pharmacies and doctors offices compared with the baseline before the COVID-19 pandemic. Since 2022, private manufacturers have distributed significantly fewer influenza vaccine doses.
Each March, the US Food and Drug Association (FDA) Vaccines and Related Biological Products Advisory Committee (VRBPAC) meets to analyze the current influenza season and forecast the next. The committee reviews and discusses data on influenza strain circulation and VE, which come from DoDGRPSP analyses. In February, US Department of Health and Human Services officials indefinitely postponed a public meeting of the CDC Advisory Committee on Immunization Practice (ACIP), at which members were also expected to discuss, among other things, VE and vaccine recommendations. The FDA canceled a March 13 VRBPAC meeting and provided no reason for the cancelation to members. That day, however, the FDA issued new recommendations for the influenza vaccine for the 2025-2026 season without the input of VRBPAC. Instead, experts from the FDA, CDC, and DoD made recommendations after reviewing surveillance data from the US and globally.
For the 2025-2026 influenza season, the FDA recommends the vaccines be trivalent and target 2 strains of influenza A and 1 strain of influenza B. The FDA anticipates there will be an “adequate and diverse supply” of approved trivalent seasonal influenza vaccines. Trivalent flu vaccines are formulated to protect against 3 influenza viruses: an A(H1N1) virus, an A(H3N2) virus, and a B/Victoria virus. All influenza vaccines for the 2025-2026 season are anticipated to be trivalent in the US.
ACES Act to Study Cancer in Aviators Is Now Law
A bipartisan bill establishing research directives aimed at revealing cancer risks among military aviators and aircrews recently became law.
Spearheaded by Sen. Mark Kelly (D-AZ) and Sen. Tom Cotton (R-AR), as well as Rep. August Pfluger (R-TX-11) and Rep. Jimmy Panetta (D-CA-19), all of whom are veterans, the Aviator Cancer Examination Study (ACES) Act was signed into law on August 14. The ACES Act will address cancer rates among Army, Navy, Air Force, and Marine Corps aircrew members by directing the Secretary of the US Department of Veterans Affairs to study cancer incidence and mortality rates among these populations.
Military aviators and aircrews face a 15% to 24% higher rate of cancer compared with the general US population, including a 75% higher rate of melanoma, 31% higher rate of thyroid cancer, 20% higher rate of prostate cancer, and 11% higher rate of female breast cancer, with potential links to non-Hodgkin lymphoma and testicular cancer. These individuals are also diagnosed earlier in life, at the median age of 55 years compared with 67 years. However, further investigation is still needed to understand why.
“By better understanding the correlation between aviator service and cancer, we can better assist our military and provide more adequate care for our veterans,” Kelly said.
Some reasons for the higher rates of cancer in aviators seem clear, such as the association between dioxin exposure and cancer. In a study of cancer incidence and mortality in Air Force veterans of the Vietnam War, incidence of melanoma and prostate cancer was increased among White veterans who sprayed herbicides during Operation Ranch Hand. The risk of cancer at any site, prostate cancer, and melanoma was increased in the highest dioxin exposure category among veterans who spent ≤ 2 years in Southeast Asia.
However, some links between these veterans and increased cancer rates are less clear. In a review of 28 studies (including 18 studies in military settings), slight evidence was found for associations between jet fuel exposure and various outcomes including cancer. Cosmic ionizing radiation (CIR) exposure is another possible cause. Several epidemiological studies have documented elevated incidence and mortality for several cancers in flight crews, but a link between them and CIR exposure has not been established.
Certain occupations have been associated with increased risk of testicular germ cell tumors, including aircraft maintenance, military pilots, fighter pilots, and aircrews. Those associations led to hypotheses that job-related chemical exposures (eg, per- and polyfluoroalkyl substances, solvents, paints, hydrocarbons in degreasing/lubricating agents, lubricating oils) may increase risk. A study of young active-duty Air Force servicemen found that pilots and men with aircraft maintenance jobs had elevated tenosynovial giant cell tumor risk, but indicates that further research is needed to “elucidate specific occupational exposures underlying these associations.”
“As a former Navy pilot, there are certain risks that we know and accept come with our service, but we know far less about the health risks that are affecting many aviators and aircrews years later,” Kelly said in a statement. “Veteran aviators and aircrews deserve answers about the correlation between their job and cancer risks so we can reduce those risks for future pilots. Getting this across the finish line has been a bipartisan effort from the start, and I’m proud to see this bill become law so we can deliver real answers and accountability for those who served.”
“The ACES Act is now the law of the land,” Cotton added. “We owe it to past, present, and future aviators in the armed forces to study the prevalence of cancer among this group of veterans.”
The ACES Act complements Kelly’s bipartisan Counting Veterans’ Cancer Act, which requires Veterans Health Administration facilities to share cancer data with state cancer registries, thereby guaranteeing their inclusion in the national registries. Key provisions of the Counting Veterans’ Cancer Act were included in the first government funding package of fiscal year 2024.
A bipartisan bill establishing research directives aimed at revealing cancer risks among military aviators and aircrews recently became law.
Spearheaded by Sen. Mark Kelly (D-AZ) and Sen. Tom Cotton (R-AR), as well as Rep. August Pfluger (R-TX-11) and Rep. Jimmy Panetta (D-CA-19), all of whom are veterans, the Aviator Cancer Examination Study (ACES) Act was signed into law on August 14. The ACES Act will address cancer rates among Army, Navy, Air Force, and Marine Corps aircrew members by directing the Secretary of the US Department of Veterans Affairs to study cancer incidence and mortality rates among these populations.
Military aviators and aircrews face a 15% to 24% higher rate of cancer compared with the general US population, including a 75% higher rate of melanoma, 31% higher rate of thyroid cancer, 20% higher rate of prostate cancer, and 11% higher rate of female breast cancer, with potential links to non-Hodgkin lymphoma and testicular cancer. These individuals are also diagnosed earlier in life, at the median age of 55 years compared with 67 years. However, further investigation is still needed to understand why.
“By better understanding the correlation between aviator service and cancer, we can better assist our military and provide more adequate care for our veterans,” Kelly said.
Some reasons for the higher rates of cancer in aviators seem clear, such as the association between dioxin exposure and cancer. In a study of cancer incidence and mortality in Air Force veterans of the Vietnam War, incidence of melanoma and prostate cancer was increased among White veterans who sprayed herbicides during Operation Ranch Hand. The risk of cancer at any site, prostate cancer, and melanoma was increased in the highest dioxin exposure category among veterans who spent ≤ 2 years in Southeast Asia.
However, some links between these veterans and increased cancer rates are less clear. In a review of 28 studies (including 18 studies in military settings), slight evidence was found for associations between jet fuel exposure and various outcomes including cancer. Cosmic ionizing radiation (CIR) exposure is another possible cause. Several epidemiological studies have documented elevated incidence and mortality for several cancers in flight crews, but a link between them and CIR exposure has not been established.
Certain occupations have been associated with increased risk of testicular germ cell tumors, including aircraft maintenance, military pilots, fighter pilots, and aircrews. Those associations led to hypotheses that job-related chemical exposures (eg, per- and polyfluoroalkyl substances, solvents, paints, hydrocarbons in degreasing/lubricating agents, lubricating oils) may increase risk. A study of young active-duty Air Force servicemen found that pilots and men with aircraft maintenance jobs had elevated tenosynovial giant cell tumor risk, but indicates that further research is needed to “elucidate specific occupational exposures underlying these associations.”
“As a former Navy pilot, there are certain risks that we know and accept come with our service, but we know far less about the health risks that are affecting many aviators and aircrews years later,” Kelly said in a statement. “Veteran aviators and aircrews deserve answers about the correlation between their job and cancer risks so we can reduce those risks for future pilots. Getting this across the finish line has been a bipartisan effort from the start, and I’m proud to see this bill become law so we can deliver real answers and accountability for those who served.”
“The ACES Act is now the law of the land,” Cotton added. “We owe it to past, present, and future aviators in the armed forces to study the prevalence of cancer among this group of veterans.”
The ACES Act complements Kelly’s bipartisan Counting Veterans’ Cancer Act, which requires Veterans Health Administration facilities to share cancer data with state cancer registries, thereby guaranteeing their inclusion in the national registries. Key provisions of the Counting Veterans’ Cancer Act were included in the first government funding package of fiscal year 2024.
A bipartisan bill establishing research directives aimed at revealing cancer risks among military aviators and aircrews recently became law.
Spearheaded by Sen. Mark Kelly (D-AZ) and Sen. Tom Cotton (R-AR), as well as Rep. August Pfluger (R-TX-11) and Rep. Jimmy Panetta (D-CA-19), all of whom are veterans, the Aviator Cancer Examination Study (ACES) Act was signed into law on August 14. The ACES Act will address cancer rates among Army, Navy, Air Force, and Marine Corps aircrew members by directing the Secretary of the US Department of Veterans Affairs to study cancer incidence and mortality rates among these populations.
Military aviators and aircrews face a 15% to 24% higher rate of cancer compared with the general US population, including a 75% higher rate of melanoma, 31% higher rate of thyroid cancer, 20% higher rate of prostate cancer, and 11% higher rate of female breast cancer, with potential links to non-Hodgkin lymphoma and testicular cancer. These individuals are also diagnosed earlier in life, at the median age of 55 years compared with 67 years. However, further investigation is still needed to understand why.
“By better understanding the correlation between aviator service and cancer, we can better assist our military and provide more adequate care for our veterans,” Kelly said.
Some reasons for the higher rates of cancer in aviators seem clear, such as the association between dioxin exposure and cancer. In a study of cancer incidence and mortality in Air Force veterans of the Vietnam War, incidence of melanoma and prostate cancer was increased among White veterans who sprayed herbicides during Operation Ranch Hand. The risk of cancer at any site, prostate cancer, and melanoma was increased in the highest dioxin exposure category among veterans who spent ≤ 2 years in Southeast Asia.
However, some links between these veterans and increased cancer rates are less clear. In a review of 28 studies (including 18 studies in military settings), slight evidence was found for associations between jet fuel exposure and various outcomes including cancer. Cosmic ionizing radiation (CIR) exposure is another possible cause. Several epidemiological studies have documented elevated incidence and mortality for several cancers in flight crews, but a link between them and CIR exposure has not been established.
Certain occupations have been associated with increased risk of testicular germ cell tumors, including aircraft maintenance, military pilots, fighter pilots, and aircrews. Those associations led to hypotheses that job-related chemical exposures (eg, per- and polyfluoroalkyl substances, solvents, paints, hydrocarbons in degreasing/lubricating agents, lubricating oils) may increase risk. A study of young active-duty Air Force servicemen found that pilots and men with aircraft maintenance jobs had elevated tenosynovial giant cell tumor risk, but indicates that further research is needed to “elucidate specific occupational exposures underlying these associations.”
“As a former Navy pilot, there are certain risks that we know and accept come with our service, but we know far less about the health risks that are affecting many aviators and aircrews years later,” Kelly said in a statement. “Veteran aviators and aircrews deserve answers about the correlation between their job and cancer risks so we can reduce those risks for future pilots. Getting this across the finish line has been a bipartisan effort from the start, and I’m proud to see this bill become law so we can deliver real answers and accountability for those who served.”
“The ACES Act is now the law of the land,” Cotton added. “We owe it to past, present, and future aviators in the armed forces to study the prevalence of cancer among this group of veterans.”
The ACES Act complements Kelly’s bipartisan Counting Veterans’ Cancer Act, which requires Veterans Health Administration facilities to share cancer data with state cancer registries, thereby guaranteeing their inclusion in the national registries. Key provisions of the Counting Veterans’ Cancer Act were included in the first government funding package of fiscal year 2024.
Agent Orange Exposure and Genetic Factors Independently Raise Risk for Multiple Lymphoma Types
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.
Housing Program Expansion Opens Doors to More Veterans
TOPLINE:Expanding United States Department of Housing and Urban Development-Veterans Affairs Supportive Housing (HUD-VASH) eligibility to veterans with other-than-honorable (OTH) discharge significantly increased their program enrollments without impacting services for those with honorable discharge. Emergency department visits increased for honorable discharge veterans while hospitalizations rose for both groups.
METHODOLOGY:
- A quality improvement study following SQUIRE 2.0 reporting guidelines analyzed data from 129,873 veterans enrolled in HUD-VASH between June 1, 2019, and September 30, 2021.
- Analysis included 127,876 veterans (98.5%) with honorable/general discharge and 1997 veterans (1.5%) with OTH discharge, with a mean age of 53.7 years.
- Researchers utilized an interrupted time series design to compare program enrollments and healthcare utilization before (June 2019-December 2020) and after (January 2021-September 2021) policy implementation.
- Data linkage between the Homeless Operations and Management Evaluation System database and VA Corporate Data Warehouse enabled tracking of emergency department visits, hospitalizations, and primary care visits.
TAKEAWAY:
- Monthly HUD-VASH enrollments showed a significant increase for OTH veterans after the policy change (difference in slopes, 1.90; 95% confidence interval [CI], 1.28-2.52), while honorable/general veterans experienced a non-significant increase (difference in slopes, 9.23; 95% CI, −20.35-38.79).
- Emergency department visits demonstrated a significant increase for honorable/general veterans (change in slope, 0.24; 95% CI, 0.12-0.35) but not for OTH veterans (change in slope, 0.08;
95% CI, −0.12-0.28). - Hospitalizations significantly increased for both OTH veterans (change in slope, 0.098; 95% CI, 0.009-0.170) and honorable/general veterans (change in slope, 0.078; 95% CI, 0.004-0.060).
- Primary care visits showed no significant changes for either group after the policy implementation (OTH: change in slope, −0.12; 95% CI, −0.65-0.42; honorable/general: change in slope, 0.20;
95% CI, −0.13-0.53).
IN PRACTICE:“Expanding HUD-VASH eligibility increased access to housing and social support for OTH veterans without disrupting services for those with honorable discharges,” the authors reported. “Efforts should focus on improving access to connecting OTH veterans with clinical services outside of HUD-VASH.”
SOURCE:The study was led by Thomas F. Nubong, MD, Center of Innovation for Long-Term Services and Supports, Providence Veterans Affairs Medical Center in Providence. It was published online on August 5 in JAMA Network Open.
LIMITATIONS: According to the authors, the study period overlapped with the COVID-19 pandemic, potentially affecting results. Additionally, staff training on the policy change varied across US Department of Veterans Affairs (VA) sites, introducing implementation inconsistencies. The single-group interrupted time series design, while effective for tracking temporal trends, limited formal comparisons between discharge groups.
DISCLOSURES: The analyses were conducted under the VA Homeless Programs Office with operational funding support. Jack Tsai, PhD, and Eric Jutkowitz, PhD, reported being principal investigators of a VA Merit study on the Impact of COVID-19 for the HUD-VASH program. James L. Rudolph, MD, reported receiving grants from Icosavax outside the submitted work and being a United States government employee.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
TOPLINE:Expanding United States Department of Housing and Urban Development-Veterans Affairs Supportive Housing (HUD-VASH) eligibility to veterans with other-than-honorable (OTH) discharge significantly increased their program enrollments without impacting services for those with honorable discharge. Emergency department visits increased for honorable discharge veterans while hospitalizations rose for both groups.
METHODOLOGY:
- A quality improvement study following SQUIRE 2.0 reporting guidelines analyzed data from 129,873 veterans enrolled in HUD-VASH between June 1, 2019, and September 30, 2021.
- Analysis included 127,876 veterans (98.5%) with honorable/general discharge and 1997 veterans (1.5%) with OTH discharge, with a mean age of 53.7 years.
- Researchers utilized an interrupted time series design to compare program enrollments and healthcare utilization before (June 2019-December 2020) and after (January 2021-September 2021) policy implementation.
- Data linkage between the Homeless Operations and Management Evaluation System database and VA Corporate Data Warehouse enabled tracking of emergency department visits, hospitalizations, and primary care visits.
TAKEAWAY:
- Monthly HUD-VASH enrollments showed a significant increase for OTH veterans after the policy change (difference in slopes, 1.90; 95% confidence interval [CI], 1.28-2.52), while honorable/general veterans experienced a non-significant increase (difference in slopes, 9.23; 95% CI, −20.35-38.79).
- Emergency department visits demonstrated a significant increase for honorable/general veterans (change in slope, 0.24; 95% CI, 0.12-0.35) but not for OTH veterans (change in slope, 0.08;
95% CI, −0.12-0.28). - Hospitalizations significantly increased for both OTH veterans (change in slope, 0.098; 95% CI, 0.009-0.170) and honorable/general veterans (change in slope, 0.078; 95% CI, 0.004-0.060).
- Primary care visits showed no significant changes for either group after the policy implementation (OTH: change in slope, −0.12; 95% CI, −0.65-0.42; honorable/general: change in slope, 0.20;
95% CI, −0.13-0.53).
IN PRACTICE:“Expanding HUD-VASH eligibility increased access to housing and social support for OTH veterans without disrupting services for those with honorable discharges,” the authors reported. “Efforts should focus on improving access to connecting OTH veterans with clinical services outside of HUD-VASH.”
SOURCE:The study was led by Thomas F. Nubong, MD, Center of Innovation for Long-Term Services and Supports, Providence Veterans Affairs Medical Center in Providence. It was published online on August 5 in JAMA Network Open.
LIMITATIONS: According to the authors, the study period overlapped with the COVID-19 pandemic, potentially affecting results. Additionally, staff training on the policy change varied across US Department of Veterans Affairs (VA) sites, introducing implementation inconsistencies. The single-group interrupted time series design, while effective for tracking temporal trends, limited formal comparisons between discharge groups.
DISCLOSURES: The analyses were conducted under the VA Homeless Programs Office with operational funding support. Jack Tsai, PhD, and Eric Jutkowitz, PhD, reported being principal investigators of a VA Merit study on the Impact of COVID-19 for the HUD-VASH program. James L. Rudolph, MD, reported receiving grants from Icosavax outside the submitted work and being a United States government employee.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
TOPLINE:Expanding United States Department of Housing and Urban Development-Veterans Affairs Supportive Housing (HUD-VASH) eligibility to veterans with other-than-honorable (OTH) discharge significantly increased their program enrollments without impacting services for those with honorable discharge. Emergency department visits increased for honorable discharge veterans while hospitalizations rose for both groups.
METHODOLOGY:
- A quality improvement study following SQUIRE 2.0 reporting guidelines analyzed data from 129,873 veterans enrolled in HUD-VASH between June 1, 2019, and September 30, 2021.
- Analysis included 127,876 veterans (98.5%) with honorable/general discharge and 1997 veterans (1.5%) with OTH discharge, with a mean age of 53.7 years.
- Researchers utilized an interrupted time series design to compare program enrollments and healthcare utilization before (June 2019-December 2020) and after (January 2021-September 2021) policy implementation.
- Data linkage between the Homeless Operations and Management Evaluation System database and VA Corporate Data Warehouse enabled tracking of emergency department visits, hospitalizations, and primary care visits.
TAKEAWAY:
- Monthly HUD-VASH enrollments showed a significant increase for OTH veterans after the policy change (difference in slopes, 1.90; 95% confidence interval [CI], 1.28-2.52), while honorable/general veterans experienced a non-significant increase (difference in slopes, 9.23; 95% CI, −20.35-38.79).
- Emergency department visits demonstrated a significant increase for honorable/general veterans (change in slope, 0.24; 95% CI, 0.12-0.35) but not for OTH veterans (change in slope, 0.08;
95% CI, −0.12-0.28). - Hospitalizations significantly increased for both OTH veterans (change in slope, 0.098; 95% CI, 0.009-0.170) and honorable/general veterans (change in slope, 0.078; 95% CI, 0.004-0.060).
- Primary care visits showed no significant changes for either group after the policy implementation (OTH: change in slope, −0.12; 95% CI, −0.65-0.42; honorable/general: change in slope, 0.20;
95% CI, −0.13-0.53).
IN PRACTICE:“Expanding HUD-VASH eligibility increased access to housing and social support for OTH veterans without disrupting services for those with honorable discharges,” the authors reported. “Efforts should focus on improving access to connecting OTH veterans with clinical services outside of HUD-VASH.”
SOURCE:The study was led by Thomas F. Nubong, MD, Center of Innovation for Long-Term Services and Supports, Providence Veterans Affairs Medical Center in Providence. It was published online on August 5 in JAMA Network Open.
LIMITATIONS: According to the authors, the study period overlapped with the COVID-19 pandemic, potentially affecting results. Additionally, staff training on the policy change varied across US Department of Veterans Affairs (VA) sites, introducing implementation inconsistencies. The single-group interrupted time series design, while effective for tracking temporal trends, limited formal comparisons between discharge groups.
DISCLOSURES: The analyses were conducted under the VA Homeless Programs Office with operational funding support. Jack Tsai, PhD, and Eric Jutkowitz, PhD, reported being principal investigators of a VA Merit study on the Impact of COVID-19 for the HUD-VASH program. James L. Rudolph, MD, reported receiving grants from Icosavax outside the submitted work and being a United States government employee.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
Critical Access for Veterans Bill Would Undermine VA Care
The Critical Access for Veterans Care Act, S.1868, introduced in May by Senators Kevin Cramer (R-ND) and Tim Sheehy (R-MT), would fundamentally reshape how veterans living in rural communities access private health care. The legislation establishes a new paradigm impacting veterans enrolled in US Department of Veterans Affairs (VA) health care who reside within 35 miles of any Centers for Medicare & Medicaid Services-designated Critical Access Hospital (CAH) or affiliated clinic. The bill would allow veterans unprecedented autonomy to self-refer directly to these facilities.
However, despite its seemingly straightforward title, the bill will not expedite care delivery, reduce travel burdens, or enhance network critical care capacity for veterans living in rural areas. Instead, the bill would further privatize veteran health care delivery by permitting veterans within this geographic radius to independently pursue care at CAHs and clinics without prior authorization. The legislation would establish a parallel referral system that erodes the Veterans Community Care Program (VCCP) eligibility determinations that were meticulously developed under the VA MISSION Act of 2018.
Some lawmakers have repeatedly pushed to eliminate VA's authorization role in the past 6 years, seeking to grant unrestricted private sector access to various veteran populations, particularly those requiring mental health services. Sponsors of the current bill are explicitly pursuing this same objective, characterizing VA authorization as an “unnecessary roadblock” that should be removed. However, this characterization misrepresents the actual function and value of the authorization process.
Over the past 6 years, provisions in the VA MISSION Act and other laws for predetermining veteran eligibility for private care have provided veterans with broad access while maintaining oversight and accountability. Enrolled veterans may receive comprehensive emergency medical and psychiatric care at any health care facility, including CAHs. They are guaranteed unrestricted walk-in urgent care access anywhere in the country. Veterans can also obtain outpatient and inpatient services through VCCP clinicians when they meet the following established access criteria: VA facilities exceed 30-minute travel times for primary and mental health services or 60 minutes for specialty care, or when appointment wait times surpass 20 days for primary/mental health care or 28 days for specialty services. Nearly half of covered veterans used this option in FY2023.
This bill does more than upend the established paradigm of VCCP eligibility requirements: it also eliminates the critical function of utilization review and accountability. Its passage would establish a dangerous precedent. By eliminating drive time and wait time eligibility standards and simultaneously removing VA’s ability to manage use, the bill generates powerful political momentum to extend identical provisions to all enrolled veterans. Furthermore, this legislation could specifically precipitate the downsizing or closure of VA community-based outpatient clinics (CBOCs) in areas served by CAHs. North Dakota, for example, operates 5 CBOCs that could be affected. Veterans who live in rural areas within the standard 30- to 60-minute drive time of a CBOC and can secure appointments within the established 20- to 28-day timeframes would no longer be subject to the same eligibility criteria that govern all covered veterans.
The Veterans Healthcare Policy Institute (VHPI) has serious reservations about legislation that eliminates VA's indispensable authorization and referral functions for supplemental private care. Founded in 2016, the VHPI is a nonprofit, nonpartisan organization dedicated to analyzing health care, disability compensation, and benefits for US veterans and their families. It provides fact-based research to educate the public and improve care quality both within and outside the VA.
New initiatives threaten to drastically reduce veterans' health and disability benefits through staff cuts and service reductions that will limit access to earned benefits and life-sustaining health care. Attacks against the VA also threaten to erode the training that produces new cohorts of health professionals, dramatically exacerbating the nation’s already dire shortages of physicians, nurses, psychologists and social workers.
VHPI’s coverage of Veterans Health Administration downsizing within rural health care provides important context. Starting with a comprehensive 15-page white paper published in 2024, VHPI has consistently highlighted how veterans living in rural communities face the same health care access challenges as all rural Americans—living in regions with severe shortages of health care facilities, professionals, and support staff. Lawmakers who assume veterans living in rural areas will experience shorter wait times and drive distances through private sector care fundamentally misunderstand these systemic issues
VHPI is committed to rigorously scrutinize policies that may compromise high quality care for veterans, especially those living in rural areas. The organization recently examined the flawed assumptions underlying these misguided policies. On August 12, VHPI released an in-depth analysis of private sector clinicians’ capacity to care for veterans in across all 50 states titled “Veterans’ Health Care Choice—Myth or Reality? A State- by- State Reality Check of the False Promise of VA Privatization.” This analysis revealed that, in most states, and in all rural states, the private sector system was struggling to meet even the basic needs of non-veterans. As one long time VA expert stated, to imagine that the system could absorb an influx of millions of veterans – particularly when new cuts to Medicaid and other healthcare funding are implemented, is “delusional.”
Russell Lemle and Suzanne Gordon are senior policy analysts at the Veterans Healthcare Policy Institute. Suzanne Gordon is author of Wounds of War.
The Critical Access for Veterans Care Act, S.1868, introduced in May by Senators Kevin Cramer (R-ND) and Tim Sheehy (R-MT), would fundamentally reshape how veterans living in rural communities access private health care. The legislation establishes a new paradigm impacting veterans enrolled in US Department of Veterans Affairs (VA) health care who reside within 35 miles of any Centers for Medicare & Medicaid Services-designated Critical Access Hospital (CAH) or affiliated clinic. The bill would allow veterans unprecedented autonomy to self-refer directly to these facilities.
However, despite its seemingly straightforward title, the bill will not expedite care delivery, reduce travel burdens, or enhance network critical care capacity for veterans living in rural areas. Instead, the bill would further privatize veteran health care delivery by permitting veterans within this geographic radius to independently pursue care at CAHs and clinics without prior authorization. The legislation would establish a parallel referral system that erodes the Veterans Community Care Program (VCCP) eligibility determinations that were meticulously developed under the VA MISSION Act of 2018.
Some lawmakers have repeatedly pushed to eliminate VA's authorization role in the past 6 years, seeking to grant unrestricted private sector access to various veteran populations, particularly those requiring mental health services. Sponsors of the current bill are explicitly pursuing this same objective, characterizing VA authorization as an “unnecessary roadblock” that should be removed. However, this characterization misrepresents the actual function and value of the authorization process.
Over the past 6 years, provisions in the VA MISSION Act and other laws for predetermining veteran eligibility for private care have provided veterans with broad access while maintaining oversight and accountability. Enrolled veterans may receive comprehensive emergency medical and psychiatric care at any health care facility, including CAHs. They are guaranteed unrestricted walk-in urgent care access anywhere in the country. Veterans can also obtain outpatient and inpatient services through VCCP clinicians when they meet the following established access criteria: VA facilities exceed 30-minute travel times for primary and mental health services or 60 minutes for specialty care, or when appointment wait times surpass 20 days for primary/mental health care or 28 days for specialty services. Nearly half of covered veterans used this option in FY2023.
This bill does more than upend the established paradigm of VCCP eligibility requirements: it also eliminates the critical function of utilization review and accountability. Its passage would establish a dangerous precedent. By eliminating drive time and wait time eligibility standards and simultaneously removing VA’s ability to manage use, the bill generates powerful political momentum to extend identical provisions to all enrolled veterans. Furthermore, this legislation could specifically precipitate the downsizing or closure of VA community-based outpatient clinics (CBOCs) in areas served by CAHs. North Dakota, for example, operates 5 CBOCs that could be affected. Veterans who live in rural areas within the standard 30- to 60-minute drive time of a CBOC and can secure appointments within the established 20- to 28-day timeframes would no longer be subject to the same eligibility criteria that govern all covered veterans.
The Veterans Healthcare Policy Institute (VHPI) has serious reservations about legislation that eliminates VA's indispensable authorization and referral functions for supplemental private care. Founded in 2016, the VHPI is a nonprofit, nonpartisan organization dedicated to analyzing health care, disability compensation, and benefits for US veterans and their families. It provides fact-based research to educate the public and improve care quality both within and outside the VA.
New initiatives threaten to drastically reduce veterans' health and disability benefits through staff cuts and service reductions that will limit access to earned benefits and life-sustaining health care. Attacks against the VA also threaten to erode the training that produces new cohorts of health professionals, dramatically exacerbating the nation’s already dire shortages of physicians, nurses, psychologists and social workers.
VHPI’s coverage of Veterans Health Administration downsizing within rural health care provides important context. Starting with a comprehensive 15-page white paper published in 2024, VHPI has consistently highlighted how veterans living in rural communities face the same health care access challenges as all rural Americans—living in regions with severe shortages of health care facilities, professionals, and support staff. Lawmakers who assume veterans living in rural areas will experience shorter wait times and drive distances through private sector care fundamentally misunderstand these systemic issues
VHPI is committed to rigorously scrutinize policies that may compromise high quality care for veterans, especially those living in rural areas. The organization recently examined the flawed assumptions underlying these misguided policies. On August 12, VHPI released an in-depth analysis of private sector clinicians’ capacity to care for veterans in across all 50 states titled “Veterans’ Health Care Choice—Myth or Reality? A State- by- State Reality Check of the False Promise of VA Privatization.” This analysis revealed that, in most states, and in all rural states, the private sector system was struggling to meet even the basic needs of non-veterans. As one long time VA expert stated, to imagine that the system could absorb an influx of millions of veterans – particularly when new cuts to Medicaid and other healthcare funding are implemented, is “delusional.”
Russell Lemle and Suzanne Gordon are senior policy analysts at the Veterans Healthcare Policy Institute. Suzanne Gordon is author of Wounds of War.
The Critical Access for Veterans Care Act, S.1868, introduced in May by Senators Kevin Cramer (R-ND) and Tim Sheehy (R-MT), would fundamentally reshape how veterans living in rural communities access private health care. The legislation establishes a new paradigm impacting veterans enrolled in US Department of Veterans Affairs (VA) health care who reside within 35 miles of any Centers for Medicare & Medicaid Services-designated Critical Access Hospital (CAH) or affiliated clinic. The bill would allow veterans unprecedented autonomy to self-refer directly to these facilities.
However, despite its seemingly straightforward title, the bill will not expedite care delivery, reduce travel burdens, or enhance network critical care capacity for veterans living in rural areas. Instead, the bill would further privatize veteran health care delivery by permitting veterans within this geographic radius to independently pursue care at CAHs and clinics without prior authorization. The legislation would establish a parallel referral system that erodes the Veterans Community Care Program (VCCP) eligibility determinations that were meticulously developed under the VA MISSION Act of 2018.
Some lawmakers have repeatedly pushed to eliminate VA's authorization role in the past 6 years, seeking to grant unrestricted private sector access to various veteran populations, particularly those requiring mental health services. Sponsors of the current bill are explicitly pursuing this same objective, characterizing VA authorization as an “unnecessary roadblock” that should be removed. However, this characterization misrepresents the actual function and value of the authorization process.
Over the past 6 years, provisions in the VA MISSION Act and other laws for predetermining veteran eligibility for private care have provided veterans with broad access while maintaining oversight and accountability. Enrolled veterans may receive comprehensive emergency medical and psychiatric care at any health care facility, including CAHs. They are guaranteed unrestricted walk-in urgent care access anywhere in the country. Veterans can also obtain outpatient and inpatient services through VCCP clinicians when they meet the following established access criteria: VA facilities exceed 30-minute travel times for primary and mental health services or 60 minutes for specialty care, or when appointment wait times surpass 20 days for primary/mental health care or 28 days for specialty services. Nearly half of covered veterans used this option in FY2023.
This bill does more than upend the established paradigm of VCCP eligibility requirements: it also eliminates the critical function of utilization review and accountability. Its passage would establish a dangerous precedent. By eliminating drive time and wait time eligibility standards and simultaneously removing VA’s ability to manage use, the bill generates powerful political momentum to extend identical provisions to all enrolled veterans. Furthermore, this legislation could specifically precipitate the downsizing or closure of VA community-based outpatient clinics (CBOCs) in areas served by CAHs. North Dakota, for example, operates 5 CBOCs that could be affected. Veterans who live in rural areas within the standard 30- to 60-minute drive time of a CBOC and can secure appointments within the established 20- to 28-day timeframes would no longer be subject to the same eligibility criteria that govern all covered veterans.
The Veterans Healthcare Policy Institute (VHPI) has serious reservations about legislation that eliminates VA's indispensable authorization and referral functions for supplemental private care. Founded in 2016, the VHPI is a nonprofit, nonpartisan organization dedicated to analyzing health care, disability compensation, and benefits for US veterans and their families. It provides fact-based research to educate the public and improve care quality both within and outside the VA.
New initiatives threaten to drastically reduce veterans' health and disability benefits through staff cuts and service reductions that will limit access to earned benefits and life-sustaining health care. Attacks against the VA also threaten to erode the training that produces new cohorts of health professionals, dramatically exacerbating the nation’s already dire shortages of physicians, nurses, psychologists and social workers.
VHPI’s coverage of Veterans Health Administration downsizing within rural health care provides important context. Starting with a comprehensive 15-page white paper published in 2024, VHPI has consistently highlighted how veterans living in rural communities face the same health care access challenges as all rural Americans—living in regions with severe shortages of health care facilities, professionals, and support staff. Lawmakers who assume veterans living in rural areas will experience shorter wait times and drive distances through private sector care fundamentally misunderstand these systemic issues
VHPI is committed to rigorously scrutinize policies that may compromise high quality care for veterans, especially those living in rural areas. The organization recently examined the flawed assumptions underlying these misguided policies. On August 12, VHPI released an in-depth analysis of private sector clinicians’ capacity to care for veterans in across all 50 states titled “Veterans’ Health Care Choice—Myth or Reality? A State- by- State Reality Check of the False Promise of VA Privatization.” This analysis revealed that, in most states, and in all rural states, the private sector system was struggling to meet even the basic needs of non-veterans. As one long time VA expert stated, to imagine that the system could absorb an influx of millions of veterans – particularly when new cuts to Medicaid and other healthcare funding are implemented, is “delusional.”
Russell Lemle and Suzanne Gordon are senior policy analysts at the Veterans Healthcare Policy Institute. Suzanne Gordon is author of Wounds of War.