Federal Practitioner

The US Department of Veterans Affairs (VA) has outlined > 300,000 exemptions to the federal hiring freeze to fill essential benefits and health positions. The exempted positions are primarily medical support staff. While the exemptions include pharmacists, physicians and nurses were not included. The day after taking office for the second time, President Trump signed an Executive Order implementing a “freeze on the hiring of Federal civilian employees, to be applied throughout the executive branch” but left many of the details to individual agencies.

Set to last 90 days, the hiring freeze forced Federal agencies to develop plans to reduce the size of their workforces through efficiencies and attrition, Trump said. These agencies would also not be able to hire contractors.

Three days later, however, the VA responded “Following successful implementation of President Trump’s federal hiring freeze, the Department of Veterans Affairs announced several exemptions to the policy. These exemptions clarify the department’s ability to continue filling essential positions that provide health care and other vital services to Veterans and VA beneficiaries.”

This allowed > 304,000 jobs to be exempt from the freeze. Almost 92% of the VA’s 450,000 employees work in health care and health administration and support services. Most of the exemptions involve support staff. No physicians, mental health professionals or nursing positions are on the list. However, it does include 12,622 pharmacists and 5,975 pharmacy technicians. 

The VA worked in accordance with the White House and Office of Personnel Management to develop the updated guidance, Acting Veterans Affairs Secretary Todd Hunter said. In a Jan. 21 memo, Hunter wrote: "Positions critical to delivering care to veterans in the Veteran[s] Health Administration ... are exempted under the category of public safety.”

According to Hunter's memo, no other vacancies that existed as of midday Monday will be filled. Candidates who received job offers before noon on Jan. 20 and have a start date on or before Feb. 8 will be onboarded, while those with a start date after Feb. 8—or one that is undetermined—will have their offers rescinded.

The first Trump Administration began the same way in 2017, initiating a freeze on Federal hiring and receiving a similar response from the VA. In 2017, the hiring of doctors and nurses continued while that freeze was in effect, but onboarding of new support and administrative staff was not. Then-Secretary of Veterans Affairs Dr. David J. Shulkin said, “VA is committed to serving veterans, but at the same time improving efficiency and reducing bureaucracy.” 

The current Executive Order states it “shall not adversely impact veterans’ benefits and does not apply to positions related to public safety” (or military personnel, immigration enforcement, and national security). It also says it does not adversely impact the provision of Social Security, Medicare, or Veterans’ benefits. 

“Under President Trump’s leadership, VA will always do what is necessary to provide America’s Veterans with the benefits and services they have earned. The targeted hiring-freeze exemptions announced today underscore that fact,” said VA Director of Media Affairs Morgan Ackley.  

Some in Congress feel the VA should be doing more, though, and are pushing for an exemption of all VA employees. On Friday, Senate Veterans’ Affairs Committee Ranking Member Richard Blumenthal (D-CT) released a statement on the exemptions. “The latest Administration hiring freeze announcement still falls short. While I’m encouraged the President responded to our concerns by exempting certain VA personnel, only a clear, unequivocal statement to exempt all VA employees from the hiring freeze will reassure me—and veterans—they will receive the care and benefits they need and deserve. The exemptions listed yesterday provide more questions than answers and fail to include key personnel, including Veterans Benefits Administration employees. The Trump Administration is going to try to confuse the issue with a lot of vague assurances. We need a clear commitment every VA employee is exempt—effective immediately. Moreover, the Trump Administration must address the offers it has already rescinded that are now exempt.”

Blumenthal and 24 Democratic Senators also signed a letter to that effect, stressing concerns about the negative impact the hiring freeze will have on the delivery of veterans’ health care and benefits nationwide “if not quickly reversed.” Blumenthal also pressed Doug Collins (R-GA), Trump’s nominee for VA Secretary, to push back against a hiring freeze at VA, if his nomination is confirmed: “This is going to be a first test of your leadership.”

“We’ll take a look at the current levels of employees that we have and where they’re properly located,” Collins said, adding that he was “still examining” the freeze’s impact on the VA. “We will work under the Executive Order [Trump] has given us.” 

Blumenthal argued that the new exemptions exclude a number of critical positions at VA. Among them include all positions at the Veterans Benefits Administration and National Cemetery Administration, which provide veterans’ claims processing, survivor benefits, GI Bill education benefits, and burial scheduling and operations; many nonclinical positions critical to VA hospital functioning, including patient advocates, food service workers, and chaplains; and positions relating to construction project management for new hospitals and clinics, new nursing homes, new cemetery construction, leases, and repairs to existing VA facilities.

The US Department of Veterans Affairs (VA) has outlined > 300,000 exemptions to the federal hiring freeze to fill essential benefits and health positions. The exempted positions are primarily medical support staff. While the exemptions include pharmacists, physicians and nurses were not included. The day after taking office for the second time, President Trump signed an Executive Order implementing a “freeze on the hiring of Federal civilian employees, to be applied throughout the executive branch” but left many of the details to individual agencies.

Set to last 90 days, the hiring freeze forced Federal agencies to develop plans to reduce the size of their workforces through efficiencies and attrition, Trump said. These agencies would also not be able to hire contractors.

Three days later, however, the VA responded “Following successful implementation of President Trump’s federal hiring freeze, the Department of Veterans Affairs announced several exemptions to the policy. These exemptions clarify the department’s ability to continue filling essential positions that provide health care and other vital services to Veterans and VA beneficiaries.”

This allowed > 304,000 jobs to be exempt from the freeze. Almost 92% of the VA’s 450,000 employees work in health care and health administration and support services. Most of the exemptions involve support staff. No physicians, mental health professionals or nursing positions are on the list. However, it does include 12,622 pharmacists and 5,975 pharmacy technicians. 

The VA worked in accordance with the White House and Office of Personnel Management to develop the updated guidance, Acting Veterans Affairs Secretary Todd Hunter said. In a Jan. 21 memo, Hunter wrote: "Positions critical to delivering care to veterans in the Veteran[s] Health Administration ... are exempted under the category of public safety.”

According to Hunter's memo, no other vacancies that existed as of midday Monday will be filled. Candidates who received job offers before noon on Jan. 20 and have a start date on or before Feb. 8 will be onboarded, while those with a start date after Feb. 8—or one that is undetermined—will have their offers rescinded.

The first Trump Administration began the same way in 2017, initiating a freeze on Federal hiring and receiving a similar response from the VA. In 2017, the hiring of doctors and nurses continued while that freeze was in effect, but onboarding of new support and administrative staff was not. Then-Secretary of Veterans Affairs Dr. David J. Shulkin said, “VA is committed to serving veterans, but at the same time improving efficiency and reducing bureaucracy.” 

The current Executive Order states it “shall not adversely impact veterans’ benefits and does not apply to positions related to public safety” (or military personnel, immigration enforcement, and national security). It also says it does not adversely impact the provision of Social Security, Medicare, or Veterans’ benefits. 

“Under President Trump’s leadership, VA will always do what is necessary to provide America’s Veterans with the benefits and services they have earned. The targeted hiring-freeze exemptions announced today underscore that fact,” said VA Director of Media Affairs Morgan Ackley.  

Some in Congress feel the VA should be doing more, though, and are pushing for an exemption of all VA employees. On Friday, Senate Veterans’ Affairs Committee Ranking Member Richard Blumenthal (D-CT) released a statement on the exemptions. “The latest Administration hiring freeze announcement still falls short. While I’m encouraged the President responded to our concerns by exempting certain VA personnel, only a clear, unequivocal statement to exempt all VA employees from the hiring freeze will reassure me—and veterans—they will receive the care and benefits they need and deserve. The exemptions listed yesterday provide more questions than answers and fail to include key personnel, including Veterans Benefits Administration employees. The Trump Administration is going to try to confuse the issue with a lot of vague assurances. We need a clear commitment every VA employee is exempt—effective immediately. Moreover, the Trump Administration must address the offers it has already rescinded that are now exempt.”

Blumenthal and 24 Democratic Senators also signed a letter to that effect, stressing concerns about the negative impact the hiring freeze will have on the delivery of veterans’ health care and benefits nationwide “if not quickly reversed.” Blumenthal also pressed Doug Collins (R-GA), Trump’s nominee for VA Secretary, to push back against a hiring freeze at VA, if his nomination is confirmed: “This is going to be a first test of your leadership.”

“We’ll take a look at the current levels of employees that we have and where they’re properly located,” Collins said, adding that he was “still examining” the freeze’s impact on the VA. “We will work under the Executive Order [Trump] has given us.” 

Blumenthal argued that the new exemptions exclude a number of critical positions at VA. Among them include all positions at the Veterans Benefits Administration and National Cemetery Administration, which provide veterans’ claims processing, survivor benefits, GI Bill education benefits, and burial scheduling and operations; many nonclinical positions critical to VA hospital functioning, including patient advocates, food service workers, and chaplains; and positions relating to construction project management for new hospitals and clinics, new nursing homes, new cemetery construction, leases, and repairs to existing VA facilities.

The US Department of Veterans Affairs (VA) has outlined > 300,000 exemptions to the federal hiring freeze to fill essential benefits and health positions. The exempted positions are primarily medical support staff. While the exemptions include pharmacists, physicians and nurses were not included. The day after taking office for the second time, President Trump signed an Executive Order implementing a “freeze on the hiring of Federal civilian employees, to be applied throughout the executive branch” but left many of the details to individual agencies.

Set to last 90 days, the hiring freeze forced Federal agencies to develop plans to reduce the size of their workforces through efficiencies and attrition, Trump said. These agencies would also not be able to hire contractors.

Three days later, however, the VA responded “Following successful implementation of President Trump’s federal hiring freeze, the Department of Veterans Affairs announced several exemptions to the policy. These exemptions clarify the department’s ability to continue filling essential positions that provide health care and other vital services to Veterans and VA beneficiaries.”

This allowed > 304,000 jobs to be exempt from the freeze. Almost 92% of the VA’s 450,000 employees work in health care and health administration and support services. Most of the exemptions involve support staff. No physicians, mental health professionals or nursing positions are on the list. However, it does include 12,622 pharmacists and 5,975 pharmacy technicians. 

The VA worked in accordance with the White House and Office of Personnel Management to develop the updated guidance, Acting Veterans Affairs Secretary Todd Hunter said. In a Jan. 21 memo, Hunter wrote: "Positions critical to delivering care to veterans in the Veteran[s] Health Administration ... are exempted under the category of public safety.”

According to Hunter's memo, no other vacancies that existed as of midday Monday will be filled. Candidates who received job offers before noon on Jan. 20 and have a start date on or before Feb. 8 will be onboarded, while those with a start date after Feb. 8—or one that is undetermined—will have their offers rescinded.

The first Trump Administration began the same way in 2017, initiating a freeze on Federal hiring and receiving a similar response from the VA. In 2017, the hiring of doctors and nurses continued while that freeze was in effect, but onboarding of new support and administrative staff was not. Then-Secretary of Veterans Affairs Dr. David J. Shulkin said, “VA is committed to serving veterans, but at the same time improving efficiency and reducing bureaucracy.” 

The current Executive Order states it “shall not adversely impact veterans’ benefits and does not apply to positions related to public safety” (or military personnel, immigration enforcement, and national security). It also says it does not adversely impact the provision of Social Security, Medicare, or Veterans’ benefits. 

“Under President Trump’s leadership, VA will always do what is necessary to provide America’s Veterans with the benefits and services they have earned. The targeted hiring-freeze exemptions announced today underscore that fact,” said VA Director of Media Affairs Morgan Ackley.  

Some in Congress feel the VA should be doing more, though, and are pushing for an exemption of all VA employees. On Friday, Senate Veterans’ Affairs Committee Ranking Member Richard Blumenthal (D-CT) released a statement on the exemptions. “The latest Administration hiring freeze announcement still falls short. While I’m encouraged the President responded to our concerns by exempting certain VA personnel, only a clear, unequivocal statement to exempt all VA employees from the hiring freeze will reassure me—and veterans—they will receive the care and benefits they need and deserve. The exemptions listed yesterday provide more questions than answers and fail to include key personnel, including Veterans Benefits Administration employees. The Trump Administration is going to try to confuse the issue with a lot of vague assurances. We need a clear commitment every VA employee is exempt—effective immediately. Moreover, the Trump Administration must address the offers it has already rescinded that are now exempt.”

Blumenthal and 24 Democratic Senators also signed a letter to that effect, stressing concerns about the negative impact the hiring freeze will have on the delivery of veterans’ health care and benefits nationwide “if not quickly reversed.” Blumenthal also pressed Doug Collins (R-GA), Trump’s nominee for VA Secretary, to push back against a hiring freeze at VA, if his nomination is confirmed: “This is going to be a first test of your leadership.”

“We’ll take a look at the current levels of employees that we have and where they’re properly located,” Collins said, adding that he was “still examining” the freeze’s impact on the VA. “We will work under the Executive Order [Trump] has given us.” 

Blumenthal argued that the new exemptions exclude a number of critical positions at VA. Among them include all positions at the Veterans Benefits Administration and National Cemetery Administration, which provide veterans’ claims processing, survivor benefits, GI Bill education benefits, and burial scheduling and operations; many nonclinical positions critical to VA hospital functioning, including patient advocates, food service workers, and chaplains; and positions relating to construction project management for new hospitals and clinics, new nursing homes, new cemetery construction, leases, and repairs to existing VA facilities.

A study of more than 2 million veterans with diabetes builds on evidence of broad-ranging benefits and risks of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in the clinical setting, providing an “atlas” mapping extensive outcomes and some new insights to potentially explore in more rigorous clinical trials.

“This is the largest study on GLP-1 receptor agonists,” first author Ziyad Al-Aly, MD, chief of research and development at the US Department of Veterans Affairs (VA) St. Louis Healthcare System, in St. Louis, told this news organization regarding the research, published this week, in Nature Medicine.

“The [study] reflects the real experiences of people using GLP-1 RAs [in the VA] clinical setting,” he said.

“Altogether, our discovery approach confirms previous studies and clinical trials and also uncovers previously unreported benefits and risks of GLP-1 RAs,” the authors wrote.

For the comprehensive study, Al-Aly and his colleagues evaluated data from the US Department of Veterans Affairs on more than 2 million veterans treated for diabetes between October 2017 and December 2023, assessing GLP-1 RA treatment in comparison with other diabetes therapies regarding a striking 175 clinical outcomes.

Of the patients, 215,970 initiated treatment with GLP-1 RAs; 159,465 started sulfonylureas, 117,989 dipeptidyl peptidase 4 inhibitors, and 258,614 were initiated on sodium-glucose cotransporter-2 inhibitors.

The study also included a composite group of the latter three drug groups (n = 536,068), and a control group of 1,203,097 of patients receiving usual care, who were compared with usual care with the addition of GLP-1 RAs.

After inverse probability weighting, the groups were well-balanced in terms of their baseline characteristics. While the majority in the VA cohort overall were White men, the study adjusted for gender, age, race, comorbidities, and an extensive array of covariates.

With an average follow-up of 3.68 years, after the multivariate adjustment, GLP-1 RAs showed “effectiveness and risks that extended beyond those currently recognized,” in comparison with each of the treatment groups and with the main control group of usual care, the authors reported.

For the largest comparison with the main control group of usual care alone, the addition of GLP-1 RAs was associated with a decreased risk in 24% of the outcomes evaluated, and an increased risk in 10.86% of outcomes, with no significant difference for the remaining 65.14% of outcomes.

Of the various benefits, key improvements included a reduced risk for several substance use disorders including alcohol (hazard ratio [HR], 0.89) and opioid (HR, 0.87) use, suicidal ideation, attempt or intentional self-harm (HR, 0.90), seizures (HR, 0.90), neurocognitive disorders including Alzheimer disease (HR, 0.88) and dementia (HR, 0.92), coagulation and clotting disorders (HR, 0.92), and cardiac arrest (HR, 0.78).

Further benefits vs usual care alone included a reduced risk for infectious illnesses (HR, 0.88), acute kidney injury (HR, 0.88), and chronic kidney disease (CKD) (HR, 0.97; P <.05 for all the outcomes).

In terms of risks associated with GLP-1 RAs, in addition to the well-known risks for nausea and vomiting, additional increased risks vs usual care included gastrointestinal disorders such as noninfectious gastroenteritis (HR, 1.12), hypotension (HR, 1.06), arthritis (HR, 1.11), tendinitis and synovitis (HR, 1.10), interstitial nephritis (HR, 1.06), nephrolithiasis (HR, 1.15), and the known risk for drug-induced acute pancreatitis (HR, 2.46).

 

Neuropsychiatric Effects

Among the various benefits in the study, Al-Aly said some of the most intriguing are those involving the brain.

“I am struck by the consistent effects on many neuropsychiatric disorders — this aligns with data showing the presence of GLP-1 receptors in the brain and evidence showing that GLP-1s permeates through the blood brain barrier and acts on the brain to reduce inflammation and oxidative stress, improve neuroplasticity, etc.,” he said.

“Clearly, there is a neurotropic effect. There is also the possibility of an effect on the immune system/fighting infection — with reduced risks of infections, sepsis, etc.”

The reductions in suicidal ideation are encouraging after earlier reports of suicidal thoughts and self-injury among young users of GLP-1 RAs prompted concerns, including a 2023 review of the drug use by the European Medicines Agency that ultimately found no causal association, the authors added. The US Food and Drug Administration also found no association with GLP-1s and suicide risk.

The reductions in addictive behaviors are also encouraging and are consistent with the role of GLP-1 receptors in the brain in terms of impulse control and reward signaling that can relate to addictive behaviors, Al-Aly explained.

The reduced risks for dementia and Alzheimer disease are likewise consistent with preclinical studies in animal models of Alzheimer disease, as well as clinical studies showing a reduced risk for dementia in patients with type 2 diabetes, the authors noted.

The observed reduced risk for seizures further “adds to an emerging body of knowledge, both mechanistic and early clinical data, indicative of the anticonvulsant properties of GLP-1 RA use,” they added.

“GLP-1 RAs should be further evaluated in future studies as potential adjuvant therapeutics for epilepsy and its associated comorbidities,” the authors suggested.

 

Kidneys

While the findings support evidence of protective effects of GLP-1 RAs on the kidneys and a reduction in CKD risk, notable risks observed, also involving the kidneys, include nephrolithiasis or kidney stones.

Al-Aly noted the mechanisms with kidney stone formation are very different from CKD, and he speculated that the risk for the former could in fact stem from potentially low hydration with GLP-1 RA use.

“When patients are on GLP-1 RAs, they definitely eat a lot less to lose weight, but they also hydrate themselves less,” he explained in a press briefing. “They drink less water because they feel full very quickly after eating, and I’m just theorizing, but perhaps chronic dehydration [is behind] the increased risk of kidney stones.”

 

Modest Effects?

While, overall, the benefits of GLP-1 RA drugs showed modest benefits ranging between a 10% and 20% reduction for most outcomes, Al-Aly said those effects are still important.

“The modest effect does not negate the potential value of these drugs, especially for conditions where few effective treatment options exist, for example, dementia,” he said in the press statement.

“This may also imply that these drugs are most beneficial when used in conjunction with other interventions, such as lifestyle changes or other medications.”

 

Potential Confounders A Concern

Commenting on the study, David M. Nathan, MD, founder of the MGH Diabetes Center and a professor of medicine at Harvard Medical School, in Boston, Massachusetts, noted that, while the study is hypothesis-generating, the key limitation is its observational nature.

“The authors did a perfectly respectable job of doing all you can do to adjust for [confounders], but with these kinds of studies, as much as you try to statistically account for differences in the populations before they were put on the drug, you can never truly adjust for all the potential confounders that may influence the results,” he told this news organization.

In addition, the 3.8-year follow-up time of the study, as the authors acknowledge, is especially short considering that GLP-1 RAs are generally recommended to be taken indefinitely.

“You have to take these drugs presumably for a lifetime and we have no idea what the longer-term benefits and risks are,” Nathan said.

Nathan, who was among the first investigators to evaluate GLP-1 RAs about 30 years ago, underscored that “I do think that these drugs are generally really spectacular; they’ve taken over the world and they are probably the single greatest pharmaceutical story of the 21st century.”

“But much more rigorous randomized trials would be needed to prove study results that haven’t already been established in previous clinical trials,” he said.

“The types of [randomized] trials that are necessary are very expensive and require a huge amount of work, but at the end of the day, they provide proof as to what does and doesn’t work, and what the true risks are,” he added. “Whether the GLP-RAs will cure all ills and bring about world peace needs to be proved.”

In further comments provided through the Science Media Center, Stephen O’Rahilly, FRS, a professor of clinical biochemistry and medicine and director of the Wellcome-MRC Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, England, echoed Nathan’s concern that “studies such as these have to be interpreted very cautiously as the people studied have not been randomly allocated to GLP-1 RA treatment, so any difference between those taking and not taking the class of drug could potentially be attributable to factors other than the drug.”

He noted, however, that “the study provides useful reassurance about the safety of this class of drugs. The expected benefits on heart disease, stroke and other cardiovascular and most kidney diseases are clearly seen.”

Al-Aly reported being an uncompensated consultant for Pfizer. Nathan, who has previously conducted clinical trials on GLP-1 RAs, currently has no relationships to report. O’Rahilly reported receiving remuneration from several pharmaceutical companies for scientific advice relating to the development of drugs for metabolic diseases, but none involving GLP-1 RAs in the past 3 years.

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

A study of more than 2 million veterans with diabetes builds on evidence of broad-ranging benefits and risks of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in the clinical setting, providing an “atlas” mapping extensive outcomes and some new insights to potentially explore in more rigorous clinical trials.

“This is the largest study on GLP-1 receptor agonists,” first author Ziyad Al-Aly, MD, chief of research and development at the US Department of Veterans Affairs (VA) St. Louis Healthcare System, in St. Louis, told this news organization regarding the research, published this week, in Nature Medicine.

“The [study] reflects the real experiences of people using GLP-1 RAs [in the VA] clinical setting,” he said.

“Altogether, our discovery approach confirms previous studies and clinical trials and also uncovers previously unreported benefits and risks of GLP-1 RAs,” the authors wrote.

For the comprehensive study, Al-Aly and his colleagues evaluated data from the US Department of Veterans Affairs on more than 2 million veterans treated for diabetes between October 2017 and December 2023, assessing GLP-1 RA treatment in comparison with other diabetes therapies regarding a striking 175 clinical outcomes.

Of the patients, 215,970 initiated treatment with GLP-1 RAs; 159,465 started sulfonylureas, 117,989 dipeptidyl peptidase 4 inhibitors, and 258,614 were initiated on sodium-glucose cotransporter-2 inhibitors.

The study also included a composite group of the latter three drug groups (n = 536,068), and a control group of 1,203,097 of patients receiving usual care, who were compared with usual care with the addition of GLP-1 RAs.

After inverse probability weighting, the groups were well-balanced in terms of their baseline characteristics. While the majority in the VA cohort overall were White men, the study adjusted for gender, age, race, comorbidities, and an extensive array of covariates.

With an average follow-up of 3.68 years, after the multivariate adjustment, GLP-1 RAs showed “effectiveness and risks that extended beyond those currently recognized,” in comparison with each of the treatment groups and with the main control group of usual care, the authors reported.

For the largest comparison with the main control group of usual care alone, the addition of GLP-1 RAs was associated with a decreased risk in 24% of the outcomes evaluated, and an increased risk in 10.86% of outcomes, with no significant difference for the remaining 65.14% of outcomes.

Of the various benefits, key improvements included a reduced risk for several substance use disorders including alcohol (hazard ratio [HR], 0.89) and opioid (HR, 0.87) use, suicidal ideation, attempt or intentional self-harm (HR, 0.90), seizures (HR, 0.90), neurocognitive disorders including Alzheimer disease (HR, 0.88) and dementia (HR, 0.92), coagulation and clotting disorders (HR, 0.92), and cardiac arrest (HR, 0.78).

Further benefits vs usual care alone included a reduced risk for infectious illnesses (HR, 0.88), acute kidney injury (HR, 0.88), and chronic kidney disease (CKD) (HR, 0.97; P <.05 for all the outcomes).

In terms of risks associated with GLP-1 RAs, in addition to the well-known risks for nausea and vomiting, additional increased risks vs usual care included gastrointestinal disorders such as noninfectious gastroenteritis (HR, 1.12), hypotension (HR, 1.06), arthritis (HR, 1.11), tendinitis and synovitis (HR, 1.10), interstitial nephritis (HR, 1.06), nephrolithiasis (HR, 1.15), and the known risk for drug-induced acute pancreatitis (HR, 2.46).

 

Neuropsychiatric Effects

Among the various benefits in the study, Al-Aly said some of the most intriguing are those involving the brain.

“I am struck by the consistent effects on many neuropsychiatric disorders — this aligns with data showing the presence of GLP-1 receptors in the brain and evidence showing that GLP-1s permeates through the blood brain barrier and acts on the brain to reduce inflammation and oxidative stress, improve neuroplasticity, etc.,” he said.

“Clearly, there is a neurotropic effect. There is also the possibility of an effect on the immune system/fighting infection — with reduced risks of infections, sepsis, etc.”

The reductions in suicidal ideation are encouraging after earlier reports of suicidal thoughts and self-injury among young users of GLP-1 RAs prompted concerns, including a 2023 review of the drug use by the European Medicines Agency that ultimately found no causal association, the authors added. The US Food and Drug Administration also found no association with GLP-1s and suicide risk.

The reductions in addictive behaviors are also encouraging and are consistent with the role of GLP-1 receptors in the brain in terms of impulse control and reward signaling that can relate to addictive behaviors, Al-Aly explained.

The reduced risks for dementia and Alzheimer disease are likewise consistent with preclinical studies in animal models of Alzheimer disease, as well as clinical studies showing a reduced risk for dementia in patients with type 2 diabetes, the authors noted.

The observed reduced risk for seizures further “adds to an emerging body of knowledge, both mechanistic and early clinical data, indicative of the anticonvulsant properties of GLP-1 RA use,” they added.

“GLP-1 RAs should be further evaluated in future studies as potential adjuvant therapeutics for epilepsy and its associated comorbidities,” the authors suggested.

 

Kidneys

While the findings support evidence of protective effects of GLP-1 RAs on the kidneys and a reduction in CKD risk, notable risks observed, also involving the kidneys, include nephrolithiasis or kidney stones.

Al-Aly noted the mechanisms with kidney stone formation are very different from CKD, and he speculated that the risk for the former could in fact stem from potentially low hydration with GLP-1 RA use.

“When patients are on GLP-1 RAs, they definitely eat a lot less to lose weight, but they also hydrate themselves less,” he explained in a press briefing. “They drink less water because they feel full very quickly after eating, and I’m just theorizing, but perhaps chronic dehydration [is behind] the increased risk of kidney stones.”

 

Modest Effects?

While, overall, the benefits of GLP-1 RA drugs showed modest benefits ranging between a 10% and 20% reduction for most outcomes, Al-Aly said those effects are still important.

“The modest effect does not negate the potential value of these drugs, especially for conditions where few effective treatment options exist, for example, dementia,” he said in the press statement.

“This may also imply that these drugs are most beneficial when used in conjunction with other interventions, such as lifestyle changes or other medications.”

 

Potential Confounders A Concern

Commenting on the study, David M. Nathan, MD, founder of the MGH Diabetes Center and a professor of medicine at Harvard Medical School, in Boston, Massachusetts, noted that, while the study is hypothesis-generating, the key limitation is its observational nature.

“The authors did a perfectly respectable job of doing all you can do to adjust for [confounders], but with these kinds of studies, as much as you try to statistically account for differences in the populations before they were put on the drug, you can never truly adjust for all the potential confounders that may influence the results,” he told this news organization.

In addition, the 3.8-year follow-up time of the study, as the authors acknowledge, is especially short considering that GLP-1 RAs are generally recommended to be taken indefinitely.

“You have to take these drugs presumably for a lifetime and we have no idea what the longer-term benefits and risks are,” Nathan said.

Nathan, who was among the first investigators to evaluate GLP-1 RAs about 30 years ago, underscored that “I do think that these drugs are generally really spectacular; they’ve taken over the world and they are probably the single greatest pharmaceutical story of the 21st century.”

“But much more rigorous randomized trials would be needed to prove study results that haven’t already been established in previous clinical trials,” he said.

“The types of [randomized] trials that are necessary are very expensive and require a huge amount of work, but at the end of the day, they provide proof as to what does and doesn’t work, and what the true risks are,” he added. “Whether the GLP-RAs will cure all ills and bring about world peace needs to be proved.”

In further comments provided through the Science Media Center, Stephen O’Rahilly, FRS, a professor of clinical biochemistry and medicine and director of the Wellcome-MRC Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, England, echoed Nathan’s concern that “studies such as these have to be interpreted very cautiously as the people studied have not been randomly allocated to GLP-1 RA treatment, so any difference between those taking and not taking the class of drug could potentially be attributable to factors other than the drug.”

He noted, however, that “the study provides useful reassurance about the safety of this class of drugs. The expected benefits on heart disease, stroke and other cardiovascular and most kidney diseases are clearly seen.”

Al-Aly reported being an uncompensated consultant for Pfizer. Nathan, who has previously conducted clinical trials on GLP-1 RAs, currently has no relationships to report. O’Rahilly reported receiving remuneration from several pharmaceutical companies for scientific advice relating to the development of drugs for metabolic diseases, but none involving GLP-1 RAs in the past 3 years.

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

A study of more than 2 million veterans with diabetes builds on evidence of broad-ranging benefits and risks of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in the clinical setting, providing an “atlas” mapping extensive outcomes and some new insights to potentially explore in more rigorous clinical trials.

“This is the largest study on GLP-1 receptor agonists,” first author Ziyad Al-Aly, MD, chief of research and development at the US Department of Veterans Affairs (VA) St. Louis Healthcare System, in St. Louis, told this news organization regarding the research, published this week, in Nature Medicine.

“The [study] reflects the real experiences of people using GLP-1 RAs [in the VA] clinical setting,” he said.

“Altogether, our discovery approach confirms previous studies and clinical trials and also uncovers previously unreported benefits and risks of GLP-1 RAs,” the authors wrote.

For the comprehensive study, Al-Aly and his colleagues evaluated data from the US Department of Veterans Affairs on more than 2 million veterans treated for diabetes between October 2017 and December 2023, assessing GLP-1 RA treatment in comparison with other diabetes therapies regarding a striking 175 clinical outcomes.

Of the patients, 215,970 initiated treatment with GLP-1 RAs; 159,465 started sulfonylureas, 117,989 dipeptidyl peptidase 4 inhibitors, and 258,614 were initiated on sodium-glucose cotransporter-2 inhibitors.

The study also included a composite group of the latter three drug groups (n = 536,068), and a control group of 1,203,097 of patients receiving usual care, who were compared with usual care with the addition of GLP-1 RAs.

After inverse probability weighting, the groups were well-balanced in terms of their baseline characteristics. While the majority in the VA cohort overall were White men, the study adjusted for gender, age, race, comorbidities, and an extensive array of covariates.

With an average follow-up of 3.68 years, after the multivariate adjustment, GLP-1 RAs showed “effectiveness and risks that extended beyond those currently recognized,” in comparison with each of the treatment groups and with the main control group of usual care, the authors reported.

For the largest comparison with the main control group of usual care alone, the addition of GLP-1 RAs was associated with a decreased risk in 24% of the outcomes evaluated, and an increased risk in 10.86% of outcomes, with no significant difference for the remaining 65.14% of outcomes.

Of the various benefits, key improvements included a reduced risk for several substance use disorders including alcohol (hazard ratio [HR], 0.89) and opioid (HR, 0.87) use, suicidal ideation, attempt or intentional self-harm (HR, 0.90), seizures (HR, 0.90), neurocognitive disorders including Alzheimer disease (HR, 0.88) and dementia (HR, 0.92), coagulation and clotting disorders (HR, 0.92), and cardiac arrest (HR, 0.78).

Further benefits vs usual care alone included a reduced risk for infectious illnesses (HR, 0.88), acute kidney injury (HR, 0.88), and chronic kidney disease (CKD) (HR, 0.97; P <.05 for all the outcomes).

In terms of risks associated with GLP-1 RAs, in addition to the well-known risks for nausea and vomiting, additional increased risks vs usual care included gastrointestinal disorders such as noninfectious gastroenteritis (HR, 1.12), hypotension (HR, 1.06), arthritis (HR, 1.11), tendinitis and synovitis (HR, 1.10), interstitial nephritis (HR, 1.06), nephrolithiasis (HR, 1.15), and the known risk for drug-induced acute pancreatitis (HR, 2.46).

 

Neuropsychiatric Effects

Among the various benefits in the study, Al-Aly said some of the most intriguing are those involving the brain.

“I am struck by the consistent effects on many neuropsychiatric disorders — this aligns with data showing the presence of GLP-1 receptors in the brain and evidence showing that GLP-1s permeates through the blood brain barrier and acts on the brain to reduce inflammation and oxidative stress, improve neuroplasticity, etc.,” he said.

“Clearly, there is a neurotropic effect. There is also the possibility of an effect on the immune system/fighting infection — with reduced risks of infections, sepsis, etc.”

The reductions in suicidal ideation are encouraging after earlier reports of suicidal thoughts and self-injury among young users of GLP-1 RAs prompted concerns, including a 2023 review of the drug use by the European Medicines Agency that ultimately found no causal association, the authors added. The US Food and Drug Administration also found no association with GLP-1s and suicide risk.

The reductions in addictive behaviors are also encouraging and are consistent with the role of GLP-1 receptors in the brain in terms of impulse control and reward signaling that can relate to addictive behaviors, Al-Aly explained.

The reduced risks for dementia and Alzheimer disease are likewise consistent with preclinical studies in animal models of Alzheimer disease, as well as clinical studies showing a reduced risk for dementia in patients with type 2 diabetes, the authors noted.

The observed reduced risk for seizures further “adds to an emerging body of knowledge, both mechanistic and early clinical data, indicative of the anticonvulsant properties of GLP-1 RA use,” they added.

“GLP-1 RAs should be further evaluated in future studies as potential adjuvant therapeutics for epilepsy and its associated comorbidities,” the authors suggested.

 

Kidneys

While the findings support evidence of protective effects of GLP-1 RAs on the kidneys and a reduction in CKD risk, notable risks observed, also involving the kidneys, include nephrolithiasis or kidney stones.

Al-Aly noted the mechanisms with kidney stone formation are very different from CKD, and he speculated that the risk for the former could in fact stem from potentially low hydration with GLP-1 RA use.

“When patients are on GLP-1 RAs, they definitely eat a lot less to lose weight, but they also hydrate themselves less,” he explained in a press briefing. “They drink less water because they feel full very quickly after eating, and I’m just theorizing, but perhaps chronic dehydration [is behind] the increased risk of kidney stones.”

 

Modest Effects?

While, overall, the benefits of GLP-1 RA drugs showed modest benefits ranging between a 10% and 20% reduction for most outcomes, Al-Aly said those effects are still important.

“The modest effect does not negate the potential value of these drugs, especially for conditions where few effective treatment options exist, for example, dementia,” he said in the press statement.

“This may also imply that these drugs are most beneficial when used in conjunction with other interventions, such as lifestyle changes or other medications.”

 

Potential Confounders A Concern

Commenting on the study, David M. Nathan, MD, founder of the MGH Diabetes Center and a professor of medicine at Harvard Medical School, in Boston, Massachusetts, noted that, while the study is hypothesis-generating, the key limitation is its observational nature.

“The authors did a perfectly respectable job of doing all you can do to adjust for [confounders], but with these kinds of studies, as much as you try to statistically account for differences in the populations before they were put on the drug, you can never truly adjust for all the potential confounders that may influence the results,” he told this news organization.

In addition, the 3.8-year follow-up time of the study, as the authors acknowledge, is especially short considering that GLP-1 RAs are generally recommended to be taken indefinitely.

“You have to take these drugs presumably for a lifetime and we have no idea what the longer-term benefits and risks are,” Nathan said.

Nathan, who was among the first investigators to evaluate GLP-1 RAs about 30 years ago, underscored that “I do think that these drugs are generally really spectacular; they’ve taken over the world and they are probably the single greatest pharmaceutical story of the 21st century.”

“But much more rigorous randomized trials would be needed to prove study results that haven’t already been established in previous clinical trials,” he said.

“The types of [randomized] trials that are necessary are very expensive and require a huge amount of work, but at the end of the day, they provide proof as to what does and doesn’t work, and what the true risks are,” he added. “Whether the GLP-RAs will cure all ills and bring about world peace needs to be proved.”

In further comments provided through the Science Media Center, Stephen O’Rahilly, FRS, a professor of clinical biochemistry and medicine and director of the Wellcome-MRC Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, England, echoed Nathan’s concern that “studies such as these have to be interpreted very cautiously as the people studied have not been randomly allocated to GLP-1 RA treatment, so any difference between those taking and not taking the class of drug could potentially be attributable to factors other than the drug.”

He noted, however, that “the study provides useful reassurance about the safety of this class of drugs. The expected benefits on heart disease, stroke and other cardiovascular and most kidney diseases are clearly seen.”

Al-Aly reported being an uncompensated consultant for Pfizer. Nathan, who has previously conducted clinical trials on GLP-1 RAs, currently has no relationships to report. O’Rahilly reported receiving remuneration from several pharmaceutical companies for scientific advice relating to the development of drugs for metabolic diseases, but none involving GLP-1 RAs in the past 3 years.

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

TOPLINE:

Dysbiosis of the oral microbiome is associated with various upper gastrointestinal (UGI) disorders and precancerous lesions, with specific microbial signatures varying by disease and oral site, research shows.

METHODOLOGY:

• Emerging evidence suggests that the oral microbiota may contribute to the development of gastrointestinal malignancies, leading to efforts to identify biomarkers for early detection and progress of disease.
• In this population-based cross-sectional study, researchers studied the association between the microbiome of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions.
• Participants included 388 adults who underwent upper endoscopy with biopsies for histopathologic analysis.
• UGI symptoms were evaluated using a validated tool, and 16S ribosomal RNA sequencing was used to characterize microbial diversity and composition of 380 saliva, 200 subgingival, and 267 buccal mucosa samples.

TAKEAWAY:

• Saliva dysbiosis was associated with several UGI disorders, including gastroesophageal reflux symptoms alone, symptomatic esophagitis, combined esophagitis and Barrett’s esophagus (BE), Helicobacter pylori–positive histology, chemical reactive gastritis, atrophic H pylori gastritis, and intestinal metaplasia.
• In contrast, dysbiosis in subgingival and buccal mucosa was more specifically associated with BE and atrophic H pylori gastritis.
• Among several identified genera, Prevotella and Fusobacterium in saliva were associated with gastric atrophy and intestinal metaplasia, and in subgingival samples, there was a notable link between Fretibacterium in BE and Fusobacterium in gastric atrophy and intestinal metaplasia.

IN PRACTICE:

“Our study for the first time suggests that microbiota in the subgingival and buccal regions may serve as more specific biomarkers for detecting precancerous lesions in asymptomatic patients, particularly for Barrett’s esophagus,” the authors wrote. “Saliva might be more appropriate for monitoring any UGI disorders at the population level.”

SOURCE:

The study, with first author Fatemeh Sadeghi, PhD, with Karolinska Institutet, Stockholm, Sweden, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The study used bacterial DNA, which cannot distinguish metabolically active bacteria. Data on diet and probiotic use were not collected. The cross-sectional design precludes conclusions about causality.

DISCLOSURES:

The authors declared no conflicts of interest. The study was funded by the Swedish Cancer Society and the Swedish Research Council.

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

TOPLINE:

Dysbiosis of the oral microbiome is associated with various upper gastrointestinal (UGI) disorders and precancerous lesions, with specific microbial signatures varying by disease and oral site, research shows.

METHODOLOGY:

• Emerging evidence suggests that the oral microbiota may contribute to the development of gastrointestinal malignancies, leading to efforts to identify biomarkers for early detection and progress of disease.
• In this population-based cross-sectional study, researchers studied the association between the microbiome of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions.
• Participants included 388 adults who underwent upper endoscopy with biopsies for histopathologic analysis.
• UGI symptoms were evaluated using a validated tool, and 16S ribosomal RNA sequencing was used to characterize microbial diversity and composition of 380 saliva, 200 subgingival, and 267 buccal mucosa samples.

TAKEAWAY:

• Saliva dysbiosis was associated with several UGI disorders, including gastroesophageal reflux symptoms alone, symptomatic esophagitis, combined esophagitis and Barrett’s esophagus (BE), Helicobacter pylori–positive histology, chemical reactive gastritis, atrophic H pylori gastritis, and intestinal metaplasia.
• In contrast, dysbiosis in subgingival and buccal mucosa was more specifically associated with BE and atrophic H pylori gastritis.
• Among several identified genera, Prevotella and Fusobacterium in saliva were associated with gastric atrophy and intestinal metaplasia, and in subgingival samples, there was a notable link between Fretibacterium in BE and Fusobacterium in gastric atrophy and intestinal metaplasia.

IN PRACTICE:

“Our study for the first time suggests that microbiota in the subgingival and buccal regions may serve as more specific biomarkers for detecting precancerous lesions in asymptomatic patients, particularly for Barrett’s esophagus,” the authors wrote. “Saliva might be more appropriate for monitoring any UGI disorders at the population level.”

SOURCE:

The study, with first author Fatemeh Sadeghi, PhD, with Karolinska Institutet, Stockholm, Sweden, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The study used bacterial DNA, which cannot distinguish metabolically active bacteria. Data on diet and probiotic use were not collected. The cross-sectional design precludes conclusions about causality.

DISCLOSURES:

The authors declared no conflicts of interest. The study was funded by the Swedish Cancer Society and the Swedish Research Council.

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

TOPLINE:

Dysbiosis of the oral microbiome is associated with various upper gastrointestinal (UGI) disorders and precancerous lesions, with specific microbial signatures varying by disease and oral site, research shows.

METHODOLOGY:

• Emerging evidence suggests that the oral microbiota may contribute to the development of gastrointestinal malignancies, leading to efforts to identify biomarkers for early detection and progress of disease.
• In this population-based cross-sectional study, researchers studied the association between the microbiome of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions.
• Participants included 388 adults who underwent upper endoscopy with biopsies for histopathologic analysis.
• UGI symptoms were evaluated using a validated tool, and 16S ribosomal RNA sequencing was used to characterize microbial diversity and composition of 380 saliva, 200 subgingival, and 267 buccal mucosa samples.

TAKEAWAY:

• Saliva dysbiosis was associated with several UGI disorders, including gastroesophageal reflux symptoms alone, symptomatic esophagitis, combined esophagitis and Barrett’s esophagus (BE), Helicobacter pylori–positive histology, chemical reactive gastritis, atrophic H pylori gastritis, and intestinal metaplasia.
• In contrast, dysbiosis in subgingival and buccal mucosa was more specifically associated with BE and atrophic H pylori gastritis.
• Among several identified genera, Prevotella and Fusobacterium in saliva were associated with gastric atrophy and intestinal metaplasia, and in subgingival samples, there was a notable link between Fretibacterium in BE and Fusobacterium in gastric atrophy and intestinal metaplasia.

IN PRACTICE:

“Our study for the first time suggests that microbiota in the subgingival and buccal regions may serve as more specific biomarkers for detecting precancerous lesions in asymptomatic patients, particularly for Barrett’s esophagus,” the authors wrote. “Saliva might be more appropriate for monitoring any UGI disorders at the population level.”

SOURCE:

The study, with first author Fatemeh Sadeghi, PhD, with Karolinska Institutet, Stockholm, Sweden, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The study used bacterial DNA, which cannot distinguish metabolically active bacteria. Data on diet and probiotic use were not collected. The cross-sectional design precludes conclusions about causality.

DISCLOSURES:

The authors declared no conflicts of interest. The study was funded by the Swedish Cancer Society and the Swedish Research Council.

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

TOPLINE: More than 28% of US Department of Veterans Affairs (VA) patients with colorectal cancer were diagnosed through emergency presentations, which were associated with a higher mortality risk. Emergency presentations increased during COVID-19 from prepandemic rates.

METHODOLOGY:

•       A retrospective cohort study analyzed 9096 incident colorectal cancer cancer cases diagnosed in the Veterans Health Administration from 2017 to 2021.
•       Researchers applied a validated algorithm to identify emergency presentations, defined as cancer diagnoses within 30 days following emergency care episodes or unplanned hospital admissions.
•       Analysis utilized multivariable logistic regression and Cox proportional hazards models to examine associations between emergency presentations and cancer stage, treatment, and mortality.

TAKEAWAY:

•      Patients with emergency presentations were more likely to have advanced stage disease (odds ratio [OR], 1.70; 95% CI, 1.53-1.88) compared to those without emergency presentations.
•      Emergency presentations were associated with lower likelihood of receiving cancer treatment (OR, 0.65; 95% CI, 0.56-0.75) and higher mortality risk (hazard ratio [HR], 1.70; 95% CI, 1.56-1.84).
•      The proportion of emergency presentations increased from 26.4% in 2017-2019 to 31.4% during the COVID-19 pandemic years 2020-2021 (P < .0001).

IN PRACTICE: " Our findings from one of the largest studies within a US population to examine emergency presentations among patients with colorectal cancer show that emergency presentations are common and an important negative predictor of cancer outcomes…Our study findings highlight the need for continued research and implementation efforts focused on measurement and mitigation of emergency presentations among patients with colorectal cancer.”

SOURCE: The study was led by the Center for Innovations in Quality, Effectiveness and Safety at Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston. It was published online on December 11 in Digestive Diseases and Sciences.

LIMITATIONS: The study's findings are limited by the predominantly male veteran population with lower socioeconomic status, which may affect generalizability. The equal access health care model used by the VA and its and strong screening programs may result in emergency presentation rates that differ from the private sector.

TOPLINE: More than 28% of US Department of Veterans Affairs (VA) patients with colorectal cancer were diagnosed through emergency presentations, which were associated with a higher mortality risk. Emergency presentations increased during COVID-19 from prepandemic rates.

METHODOLOGY:

•       A retrospective cohort study analyzed 9096 incident colorectal cancer cancer cases diagnosed in the Veterans Health Administration from 2017 to 2021.
•       Researchers applied a validated algorithm to identify emergency presentations, defined as cancer diagnoses within 30 days following emergency care episodes or unplanned hospital admissions.
•       Analysis utilized multivariable logistic regression and Cox proportional hazards models to examine associations between emergency presentations and cancer stage, treatment, and mortality.

TAKEAWAY:

•      Patients with emergency presentations were more likely to have advanced stage disease (odds ratio [OR], 1.70; 95% CI, 1.53-1.88) compared to those without emergency presentations.
•      Emergency presentations were associated with lower likelihood of receiving cancer treatment (OR, 0.65; 95% CI, 0.56-0.75) and higher mortality risk (hazard ratio [HR], 1.70; 95% CI, 1.56-1.84).
•      The proportion of emergency presentations increased from 26.4% in 2017-2019 to 31.4% during the COVID-19 pandemic years 2020-2021 (P < .0001).

IN PRACTICE: " Our findings from one of the largest studies within a US population to examine emergency presentations among patients with colorectal cancer show that emergency presentations are common and an important negative predictor of cancer outcomes…Our study findings highlight the need for continued research and implementation efforts focused on measurement and mitigation of emergency presentations among patients with colorectal cancer.”

SOURCE: The study was led by the Center for Innovations in Quality, Effectiveness and Safety at Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston. It was published online on December 11 in Digestive Diseases and Sciences.

LIMITATIONS: The study's findings are limited by the predominantly male veteran population with lower socioeconomic status, which may affect generalizability. The equal access health care model used by the VA and its and strong screening programs may result in emergency presentation rates that differ from the private sector.

TOPLINE: More than 28% of US Department of Veterans Affairs (VA) patients with colorectal cancer were diagnosed through emergency presentations, which were associated with a higher mortality risk. Emergency presentations increased during COVID-19 from prepandemic rates.

METHODOLOGY:

•       A retrospective cohort study analyzed 9096 incident colorectal cancer cancer cases diagnosed in the Veterans Health Administration from 2017 to 2021.
•       Researchers applied a validated algorithm to identify emergency presentations, defined as cancer diagnoses within 30 days following emergency care episodes or unplanned hospital admissions.
•       Analysis utilized multivariable logistic regression and Cox proportional hazards models to examine associations between emergency presentations and cancer stage, treatment, and mortality.

TAKEAWAY:

•      Patients with emergency presentations were more likely to have advanced stage disease (odds ratio [OR], 1.70; 95% CI, 1.53-1.88) compared to those without emergency presentations.
•      Emergency presentations were associated with lower likelihood of receiving cancer treatment (OR, 0.65; 95% CI, 0.56-0.75) and higher mortality risk (hazard ratio [HR], 1.70; 95% CI, 1.56-1.84).
•      The proportion of emergency presentations increased from 26.4% in 2017-2019 to 31.4% during the COVID-19 pandemic years 2020-2021 (P < .0001).

IN PRACTICE: " Our findings from one of the largest studies within a US population to examine emergency presentations among patients with colorectal cancer show that emergency presentations are common and an important negative predictor of cancer outcomes…Our study findings highlight the need for continued research and implementation efforts focused on measurement and mitigation of emergency presentations among patients with colorectal cancer.”

SOURCE: The study was led by the Center for Innovations in Quality, Effectiveness and Safety at Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston. It was published online on December 11 in Digestive Diseases and Sciences.

LIMITATIONS: The study's findings are limited by the predominantly male veteran population with lower socioeconomic status, which may affect generalizability. The equal access health care model used by the VA and its and strong screening programs may result in emergency presentation rates that differ from the private sector.

The US Food and Drug Administration (FDA) has approved sotorasib (Lumakras, Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for the treatment of certain adult patients with metastatic colorectal cancer (mCRC).

Specifically, the combination therapy is indicated for those with KRAS G12C-mutated mCRC, as determined using an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, according to the FDA notice. The FDA also approved the therascreen KRAS RGQ PCR Kit (QIAGEN GmbH) as a companion diagnostic device for identifying eligible patients.

Approval of sotorasib with panitumumab was based on findings from the randomized, open-label, controlled CodeBreaK 300 trial showing improved overall response rates (ORR) and progression-free survival (PFS) with sotorasib and panitumumab vs investigator’s choice of trifluridine/tipiracil or regorafenib, which are current standard-of-care options.

Median PFS was 5.6 months in 53 patients randomized to receive 960 mg of oral sotorasib once daily plus 6 mg/kg of intravenous (IV) panitumumab every 2 weeks, and 2 months in 54 patients randomized to receive standard-of-care therapy (hazard ratio, 0.48). The ORR was 26% vs 0% in the arms, respectively, and the duration of response in the sotorasib/panitumumab arm was 4.4 months. No significant difference in PFS was observed between the standard-of-care arm and a third arm with 53 patients who received 240 mg of oral sotorasib daily plus 6 mg/kg of IV panitumumab every 2 weeks.

Overall survival (OS) did not differ significantly between the treatment arms in the final analysis, but the study was not statistically powered for OS.

Adverse reactions occurring in at least 20% of patients receiving sotorasib/panitumumab were rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain. Common grade 3-4 laboratory abnormalities, which occurred in two or more patients, included decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium.

The recommended dose of sotorasib is 960 mg given orally once daily and administered before the first panitumumab infusion. The recommended panitumumab dose is 6 mg/kg as an IV infusion every 14 days until disease progression, unacceptable toxicity, or until sotorasib is withheld or discontinued, according to the full prescribing information.

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

The US Food and Drug Administration (FDA) has approved sotorasib (Lumakras, Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for the treatment of certain adult patients with metastatic colorectal cancer (mCRC).

Specifically, the combination therapy is indicated for those with KRAS G12C-mutated mCRC, as determined using an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, according to the FDA notice. The FDA also approved the therascreen KRAS RGQ PCR Kit (QIAGEN GmbH) as a companion diagnostic device for identifying eligible patients.

Approval of sotorasib with panitumumab was based on findings from the randomized, open-label, controlled CodeBreaK 300 trial showing improved overall response rates (ORR) and progression-free survival (PFS) with sotorasib and panitumumab vs investigator’s choice of trifluridine/tipiracil or regorafenib, which are current standard-of-care options.

Median PFS was 5.6 months in 53 patients randomized to receive 960 mg of oral sotorasib once daily plus 6 mg/kg of intravenous (IV) panitumumab every 2 weeks, and 2 months in 54 patients randomized to receive standard-of-care therapy (hazard ratio, 0.48). The ORR was 26% vs 0% in the arms, respectively, and the duration of response in the sotorasib/panitumumab arm was 4.4 months. No significant difference in PFS was observed between the standard-of-care arm and a third arm with 53 patients who received 240 mg of oral sotorasib daily plus 6 mg/kg of IV panitumumab every 2 weeks.

Overall survival (OS) did not differ significantly between the treatment arms in the final analysis, but the study was not statistically powered for OS.

Adverse reactions occurring in at least 20% of patients receiving sotorasib/panitumumab were rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain. Common grade 3-4 laboratory abnormalities, which occurred in two or more patients, included decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium.

The recommended dose of sotorasib is 960 mg given orally once daily and administered before the first panitumumab infusion. The recommended panitumumab dose is 6 mg/kg as an IV infusion every 14 days until disease progression, unacceptable toxicity, or until sotorasib is withheld or discontinued, according to the full prescribing information.

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

The US Food and Drug Administration (FDA) has approved sotorasib (Lumakras, Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for the treatment of certain adult patients with metastatic colorectal cancer (mCRC).

Specifically, the combination therapy is indicated for those with KRAS G12C-mutated mCRC, as determined using an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, according to the FDA notice. The FDA also approved the therascreen KRAS RGQ PCR Kit (QIAGEN GmbH) as a companion diagnostic device for identifying eligible patients.

Approval of sotorasib with panitumumab was based on findings from the randomized, open-label, controlled CodeBreaK 300 trial showing improved overall response rates (ORR) and progression-free survival (PFS) with sotorasib and panitumumab vs investigator’s choice of trifluridine/tipiracil or regorafenib, which are current standard-of-care options.

Median PFS was 5.6 months in 53 patients randomized to receive 960 mg of oral sotorasib once daily plus 6 mg/kg of intravenous (IV) panitumumab every 2 weeks, and 2 months in 54 patients randomized to receive standard-of-care therapy (hazard ratio, 0.48). The ORR was 26% vs 0% in the arms, respectively, and the duration of response in the sotorasib/panitumumab arm was 4.4 months. No significant difference in PFS was observed between the standard-of-care arm and a third arm with 53 patients who received 240 mg of oral sotorasib daily plus 6 mg/kg of IV panitumumab every 2 weeks.

Overall survival (OS) did not differ significantly between the treatment arms in the final analysis, but the study was not statistically powered for OS.

Adverse reactions occurring in at least 20% of patients receiving sotorasib/panitumumab were rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain. Common grade 3-4 laboratory abnormalities, which occurred in two or more patients, included decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium.

The recommended dose of sotorasib is 960 mg given orally once daily and administered before the first panitumumab infusion. The recommended panitumumab dose is 6 mg/kg as an IV infusion every 14 days until disease progression, unacceptable toxicity, or until sotorasib is withheld or discontinued, according to the full prescribing information.

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

Exposure to Agent Orange and depleted urology are associated with increased risk of bladder cancer, according to a recent Urology meta-analysis. About 3200 US veterans are diagnosed with bladder cancer each year, which is the fourth most diagnosed cancer among veterans. “Identifying veterans exposed to these risk factors is crucial for implementing screening protocols and connecting them with preventive healthcare measures when possible,” the authors said. 

A meta-analysis using narrative synthesis to incorporate diverse studies examined the impact of exposure to Agent Orange, depleted uranium exposure, contaminated drinking water, and other environmental contaminants. The researchers found 7 studies of Agent Orange exposure that in total showed a statistically significant increase in bladder cancer risk (hazard ratio [HR], 1.17; 95% confidence interval [CI], 1.01-1.36; P < .001) among 2,705,283 veterans. Six studies revealed that depleted uranium exposure caused a statistically significant association with bladder cancer as well (HR, 2.13; 95% CI, 1.31-3.48; P = .002) among 28,899 patients. Exposure to contaminated drinking water exposure in 4 studies also suggested an increased bladder cancer risk (HR, 1.25; 95% CI, 0.97-1.61; P = .08) among 370,408 veterans. 

The authors identified other factors that also contributed to increased bladder cancer risk, including smoking, occupational exposures to substances like asbestos and diesel fumes, and exposure to ionizing radiation from nuclear tests. “These findings emphasize the urgent need for enhanced clinical management strategies and preventive measures for veterans exposed to these carcinogenic agents,” the authors asserted. 

The authors report no relevant conflicts of interest.

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

Exposure to Agent Orange and depleted urology are associated with increased risk of bladder cancer, according to a recent Urology meta-analysis. About 3200 US veterans are diagnosed with bladder cancer each year, which is the fourth most diagnosed cancer among veterans. “Identifying veterans exposed to these risk factors is crucial for implementing screening protocols and connecting them with preventive healthcare measures when possible,” the authors said. 

A meta-analysis using narrative synthesis to incorporate diverse studies examined the impact of exposure to Agent Orange, depleted uranium exposure, contaminated drinking water, and other environmental contaminants. The researchers found 7 studies of Agent Orange exposure that in total showed a statistically significant increase in bladder cancer risk (hazard ratio [HR], 1.17; 95% confidence interval [CI], 1.01-1.36; P < .001) among 2,705,283 veterans. Six studies revealed that depleted uranium exposure caused a statistically significant association with bladder cancer as well (HR, 2.13; 95% CI, 1.31-3.48; P = .002) among 28,899 patients. Exposure to contaminated drinking water exposure in 4 studies also suggested an increased bladder cancer risk (HR, 1.25; 95% CI, 0.97-1.61; P = .08) among 370,408 veterans. 

The authors identified other factors that also contributed to increased bladder cancer risk, including smoking, occupational exposures to substances like asbestos and diesel fumes, and exposure to ionizing radiation from nuclear tests. “These findings emphasize the urgent need for enhanced clinical management strategies and preventive measures for veterans exposed to these carcinogenic agents,” the authors asserted. 

The authors report no relevant conflicts of interest.

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

Exposure to Agent Orange and depleted urology are associated with increased risk of bladder cancer, according to a recent Urology meta-analysis. About 3200 US veterans are diagnosed with bladder cancer each year, which is the fourth most diagnosed cancer among veterans. “Identifying veterans exposed to these risk factors is crucial for implementing screening protocols and connecting them with preventive healthcare measures when possible,” the authors said. 

A meta-analysis using narrative synthesis to incorporate diverse studies examined the impact of exposure to Agent Orange, depleted uranium exposure, contaminated drinking water, and other environmental contaminants. The researchers found 7 studies of Agent Orange exposure that in total showed a statistically significant increase in bladder cancer risk (hazard ratio [HR], 1.17; 95% confidence interval [CI], 1.01-1.36; P < .001) among 2,705,283 veterans. Six studies revealed that depleted uranium exposure caused a statistically significant association with bladder cancer as well (HR, 2.13; 95% CI, 1.31-3.48; P = .002) among 28,899 patients. Exposure to contaminated drinking water exposure in 4 studies also suggested an increased bladder cancer risk (HR, 1.25; 95% CI, 0.97-1.61; P = .08) among 370,408 veterans. 

The authors identified other factors that also contributed to increased bladder cancer risk, including smoking, occupational exposures to substances like asbestos and diesel fumes, and exposure to ionizing radiation from nuclear tests. “These findings emphasize the urgent need for enhanced clinical management strategies and preventive measures for veterans exposed to these carcinogenic agents,” the authors asserted. 

The authors report no relevant conflicts of interest.

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

In his parting words as US Surgeon General, Vivek Murthy, MD, MBA, urges togetherness as it works through current and future issues, as opposed to continuing down the path of divisiveness.

“Today, we are faced with a profound choice: do we continue with the status quo, marked by pain, disconnection, and division? Or do we choose a different path—one of joy, health, and fulfillment where we turn toward each other instead of away from each other, where we choose love over fear; where we recognize community as the irreplaceable foundation for our well-being?” Murthy writes in his Jan. 7 valedictory essay. “As I finish my tenure as Surgeon General, this is my parting prescription, my final wish for all of us: choose community.”

Murthy based his essay on personal and professional experiences from his tenures as the 19th and 21st US Surgeon General. He outlines his individual perspective on the root causes of widespread pain and unhappiness he has seen across America and offers a prescription for how we can “cultivate health and fulfillment.”

The core pillars of community—relationships, service, and purpose—are powerful drivers of fulfillment, Murthy writes, because “community is a powerful source of life satisfaction and life expectancy.” In his essay, he describes how these elements affect our health.

Relationships can be a powerful source of joy and support. They can act as buffers to stress and break down the barriers of loneliness and improve your overall health. According to Murthy, one-third of adults and one-half of young people experience loneliness; and social disconnectedness increases the risk of heart disease, dementia, depression, anxiety, and premature death.

Service comprises the actions we take that benefit others. Research shows that sustained service efforts can reduce the risk of hypertension, stroke, early death, depression, and cognitive decline.

And purpose is the feeling of having an overarching life aim to guide our decisions and actions. Simply, it is the “why” we do something, and according to Murthy, a high sense of individual purpose may reduce the risk of early death as well as stroke, lung disease, and dementia.

Building community isn’t always easy, Murthy wrote. It requires “rethinking and, in some cases, rejecting the conventional wisdom that tells us what defines success and a good life.” At the conclusion of his essay, Murthy notes how choices we make now must be made with an eye toward the future.

“The choice we make to build community has the power to change lives and transform society,” he writes. “Let us never forget that good people with hearts full of love can change the world.”

In his parting words as US Surgeon General, Vivek Murthy, MD, MBA, urges togetherness as it works through current and future issues, as opposed to continuing down the path of divisiveness.

“Today, we are faced with a profound choice: do we continue with the status quo, marked by pain, disconnection, and division? Or do we choose a different path—one of joy, health, and fulfillment where we turn toward each other instead of away from each other, where we choose love over fear; where we recognize community as the irreplaceable foundation for our well-being?” Murthy writes in his Jan. 7 valedictory essay. “As I finish my tenure as Surgeon General, this is my parting prescription, my final wish for all of us: choose community.”

Murthy based his essay on personal and professional experiences from his tenures as the 19th and 21st US Surgeon General. He outlines his individual perspective on the root causes of widespread pain and unhappiness he has seen across America and offers a prescription for how we can “cultivate health and fulfillment.”

The core pillars of community—relationships, service, and purpose—are powerful drivers of fulfillment, Murthy writes, because “community is a powerful source of life satisfaction and life expectancy.” In his essay, he describes how these elements affect our health.

Relationships can be a powerful source of joy and support. They can act as buffers to stress and break down the barriers of loneliness and improve your overall health. According to Murthy, one-third of adults and one-half of young people experience loneliness; and social disconnectedness increases the risk of heart disease, dementia, depression, anxiety, and premature death.

Service comprises the actions we take that benefit others. Research shows that sustained service efforts can reduce the risk of hypertension, stroke, early death, depression, and cognitive decline.

And purpose is the feeling of having an overarching life aim to guide our decisions and actions. Simply, it is the “why” we do something, and according to Murthy, a high sense of individual purpose may reduce the risk of early death as well as stroke, lung disease, and dementia.

Building community isn’t always easy, Murthy wrote. It requires “rethinking and, in some cases, rejecting the conventional wisdom that tells us what defines success and a good life.” At the conclusion of his essay, Murthy notes how choices we make now must be made with an eye toward the future.

“The choice we make to build community has the power to change lives and transform society,” he writes. “Let us never forget that good people with hearts full of love can change the world.”

In his parting words as US Surgeon General, Vivek Murthy, MD, MBA, urges togetherness as it works through current and future issues, as opposed to continuing down the path of divisiveness.

“Today, we are faced with a profound choice: do we continue with the status quo, marked by pain, disconnection, and division? Or do we choose a different path—one of joy, health, and fulfillment where we turn toward each other instead of away from each other, where we choose love over fear; where we recognize community as the irreplaceable foundation for our well-being?” Murthy writes in his Jan. 7 valedictory essay. “As I finish my tenure as Surgeon General, this is my parting prescription, my final wish for all of us: choose community.”

Murthy based his essay on personal and professional experiences from his tenures as the 19th and 21st US Surgeon General. He outlines his individual perspective on the root causes of widespread pain and unhappiness he has seen across America and offers a prescription for how we can “cultivate health and fulfillment.”

The core pillars of community—relationships, service, and purpose—are powerful drivers of fulfillment, Murthy writes, because “community is a powerful source of life satisfaction and life expectancy.” In his essay, he describes how these elements affect our health.

Relationships can be a powerful source of joy and support. They can act as buffers to stress and break down the barriers of loneliness and improve your overall health. According to Murthy, one-third of adults and one-half of young people experience loneliness; and social disconnectedness increases the risk of heart disease, dementia, depression, anxiety, and premature death.

Service comprises the actions we take that benefit others. Research shows that sustained service efforts can reduce the risk of hypertension, stroke, early death, depression, and cognitive decline.

And purpose is the feeling of having an overarching life aim to guide our decisions and actions. Simply, it is the “why” we do something, and according to Murthy, a high sense of individual purpose may reduce the risk of early death as well as stroke, lung disease, and dementia.

Building community isn’t always easy, Murthy wrote. It requires “rethinking and, in some cases, rejecting the conventional wisdom that tells us what defines success and a good life.” At the conclusion of his essay, Murthy notes how choices we make now must be made with an eye toward the future.

“The choice we make to build community has the power to change lives and transform society,” he writes. “Let us never forget that good people with hearts full of love can change the world.”

The number of sexual assaults in the US military dropped for the first time in a decade, according an annual report from the Pentagon, while benefits claims for assault survivors are on the rise. 

     Records show that 29,000 active-duty members reported being sexually assaulted in 2023, or 7000 fewer than in 2021. A confidential survey also found the number of service members who experienced some type of unwanted sexual contact dropped nearly 20%, leaving the Pentagon “cautiously optimistic“ its investments in preventing sexual assault and building a healthy climate are having an impact.

     Despite these investments, issues persist. An Army anesthesiologist recently pleaded guilty to 41 charges of sexual misconduct involving 21 victims at Madigan Army Medical Center at Joint Base Lewis-McChord in Washington. The alleged incidents occurred between 2019 and 2022 and involved the doctor unnecessarily focusing on the genital area of patients during what he described as routine examinations. Maj. Michael Stockin faces nearly 14 years in prison, should the judge accept the plea agreement Stockin and his attorneys made with government prosecutors.

     Additionally, a report from the Watson Institute of International and Public Affairs at Brown University indicated that 24% of active-duty women and 1.9% of active-duty men experienced sexual assault from 2001 to 2021.During post-9/11 wars, “the prioritization of force readiness above all else allowed the problem of sexual assault to fester, papering over internal violence and gender inequalities within military institutions,” the report said. There was also a slight uptick in reports of military sexual assaults in 2020, when troops were largely on lockdown as a result of the COVID-19 pandemic.

     Efforts to address sexual assault in the military have increased in the past 10 years to the tune of 10 Department of Defense Inspector General engagements, 60 Government Accountability Office recommendations, > 200 government panel and task force recommendations, > 150 Congressional provisions, and > 50 Secretary of Defense initiatives. Additionally, the 2022 National Defense Authorization gave authority in sexual assault cases to independent prosecutors rather than commanders. Other reforms have included incorporating trauma-informed practices in the claims process.

     Meanwhile, the US Department of Veterans Affairs (VA) has also been attempting to convince more sexual assault survivors to file claims for benefits. Assistant Deputy Under Secretary for Field Operations Kenesha Britton said in December that the VA has held 3500 events in the past 14 months focused on benefits for victims of military sexual assault and harassment. It appears to be working, as the VA received 57,400 claims for military sexual trauma in fiscal year 2024 (an 18% increase from 2023), and approved > 63% of them, compared to 40% more than a decade ago. Prior to Oct. 1, VA staffers processed > 11,000 cases in a single day twice. Since that date, they have processed that amount on 9 separate occasions.

     “We recognize the remarkable courage it takes for survivors of military sexual trauma to seek the benefits and support they’ve earned,” Britton said. “Our mission is driven by a commitment to ensure survivors are met with care, dignity and sensitivity throughout the claims process.”

     The increase in trust is a byproduct of the outreach campaigns, VA Under Secretary for Benefits Josh Jacobs said: “[M]ore veterans are coming in to apply for benefits and I think that has to do with building trust because we are actively trying to reach veterans telling them we want to connect them with their earned benefits.”

The number of sexual assaults in the US military dropped for the first time in a decade, according an annual report from the Pentagon, while benefits claims for assault survivors are on the rise. 

     Records show that 29,000 active-duty members reported being sexually assaulted in 2023, or 7000 fewer than in 2021. A confidential survey also found the number of service members who experienced some type of unwanted sexual contact dropped nearly 20%, leaving the Pentagon “cautiously optimistic“ its investments in preventing sexual assault and building a healthy climate are having an impact.

     Despite these investments, issues persist. An Army anesthesiologist recently pleaded guilty to 41 charges of sexual misconduct involving 21 victims at Madigan Army Medical Center at Joint Base Lewis-McChord in Washington. The alleged incidents occurred between 2019 and 2022 and involved the doctor unnecessarily focusing on the genital area of patients during what he described as routine examinations. Maj. Michael Stockin faces nearly 14 years in prison, should the judge accept the plea agreement Stockin and his attorneys made with government prosecutors.

     Additionally, a report from the Watson Institute of International and Public Affairs at Brown University indicated that 24% of active-duty women and 1.9% of active-duty men experienced sexual assault from 2001 to 2021.During post-9/11 wars, “the prioritization of force readiness above all else allowed the problem of sexual assault to fester, papering over internal violence and gender inequalities within military institutions,” the report said. There was also a slight uptick in reports of military sexual assaults in 2020, when troops were largely on lockdown as a result of the COVID-19 pandemic.

     Efforts to address sexual assault in the military have increased in the past 10 years to the tune of 10 Department of Defense Inspector General engagements, 60 Government Accountability Office recommendations, > 200 government panel and task force recommendations, > 150 Congressional provisions, and > 50 Secretary of Defense initiatives. Additionally, the 2022 National Defense Authorization gave authority in sexual assault cases to independent prosecutors rather than commanders. Other reforms have included incorporating trauma-informed practices in the claims process.

     Meanwhile, the US Department of Veterans Affairs (VA) has also been attempting to convince more sexual assault survivors to file claims for benefits. Assistant Deputy Under Secretary for Field Operations Kenesha Britton said in December that the VA has held 3500 events in the past 14 months focused on benefits for victims of military sexual assault and harassment. It appears to be working, as the VA received 57,400 claims for military sexual trauma in fiscal year 2024 (an 18% increase from 2023), and approved > 63% of them, compared to 40% more than a decade ago. Prior to Oct. 1, VA staffers processed > 11,000 cases in a single day twice. Since that date, they have processed that amount on 9 separate occasions.

     “We recognize the remarkable courage it takes for survivors of military sexual trauma to seek the benefits and support they’ve earned,” Britton said. “Our mission is driven by a commitment to ensure survivors are met with care, dignity and sensitivity throughout the claims process.”

     The increase in trust is a byproduct of the outreach campaigns, VA Under Secretary for Benefits Josh Jacobs said: “[M]ore veterans are coming in to apply for benefits and I think that has to do with building trust because we are actively trying to reach veterans telling them we want to connect them with their earned benefits.”

The number of sexual assaults in the US military dropped for the first time in a decade, according an annual report from the Pentagon, while benefits claims for assault survivors are on the rise. 

     Records show that 29,000 active-duty members reported being sexually assaulted in 2023, or 7000 fewer than in 2021. A confidential survey also found the number of service members who experienced some type of unwanted sexual contact dropped nearly 20%, leaving the Pentagon “cautiously optimistic“ its investments in preventing sexual assault and building a healthy climate are having an impact.

     Despite these investments, issues persist. An Army anesthesiologist recently pleaded guilty to 41 charges of sexual misconduct involving 21 victims at Madigan Army Medical Center at Joint Base Lewis-McChord in Washington. The alleged incidents occurred between 2019 and 2022 and involved the doctor unnecessarily focusing on the genital area of patients during what he described as routine examinations. Maj. Michael Stockin faces nearly 14 years in prison, should the judge accept the plea agreement Stockin and his attorneys made with government prosecutors.

     Additionally, a report from the Watson Institute of International and Public Affairs at Brown University indicated that 24% of active-duty women and 1.9% of active-duty men experienced sexual assault from 2001 to 2021.During post-9/11 wars, “the prioritization of force readiness above all else allowed the problem of sexual assault to fester, papering over internal violence and gender inequalities within military institutions,” the report said. There was also a slight uptick in reports of military sexual assaults in 2020, when troops were largely on lockdown as a result of the COVID-19 pandemic.

     Efforts to address sexual assault in the military have increased in the past 10 years to the tune of 10 Department of Defense Inspector General engagements, 60 Government Accountability Office recommendations, > 200 government panel and task force recommendations, > 150 Congressional provisions, and > 50 Secretary of Defense initiatives. Additionally, the 2022 National Defense Authorization gave authority in sexual assault cases to independent prosecutors rather than commanders. Other reforms have included incorporating trauma-informed practices in the claims process.

     Meanwhile, the US Department of Veterans Affairs (VA) has also been attempting to convince more sexual assault survivors to file claims for benefits. Assistant Deputy Under Secretary for Field Operations Kenesha Britton said in December that the VA has held 3500 events in the past 14 months focused on benefits for victims of military sexual assault and harassment. It appears to be working, as the VA received 57,400 claims for military sexual trauma in fiscal year 2024 (an 18% increase from 2023), and approved > 63% of them, compared to 40% more than a decade ago. Prior to Oct. 1, VA staffers processed > 11,000 cases in a single day twice. Since that date, they have processed that amount on 9 separate occasions.

     “We recognize the remarkable courage it takes for survivors of military sexual trauma to seek the benefits and support they’ve earned,” Britton said. “Our mission is driven by a commitment to ensure survivors are met with care, dignity and sensitivity throughout the claims process.”

     The increase in trust is a byproduct of the outreach campaigns, VA Under Secretary for Benefits Josh Jacobs said: “[M]ore veterans are coming in to apply for benefits and I think that has to do with building trust because we are actively trying to reach veterans telling them we want to connect them with their earned benefits.”

A major prospective study of more than half a million UK women conducted over almost 17 years has confirmed an association between dietary calcium intake and decreased risk of colorectal cancer. 

Cancer Research UK (CRUK), which funded the study, said that it demonstrated the benefits of a healthy, balanced diet for lowering cancer risk.

Colorectal cancer is the third most common cancer worldwide. Incidence rates vary markedly, with higher rates observed in high-income countries. The risk increases for individuals who migrate from low- to high-incidence areas, suggesting that lifestyle and environmental factors contribute to its development.

While alcohol and processed meats are established carcinogens, and red meat is classified as probably carcinogenic, there is a lack of consensus regarding the relationships between other dietary factors and colorectal cancer risk. This uncertainty may be due, at least in part, to relatively few studies giving comprehensive results on all food types, as well as dietary measurement errors, and/or small sample sizes.

 

Study Tracked 97 Dietary Factors

To address these gaps, the research team, led by the University of Oxford in England, tracked the intake of 97 dietary factors in 542,778 women from 2001 for an average of 16.6 years. During this period 12,251 participants developed colorectal cancer. The women completed detailed dietary questionnaires at baseline, with 7% participating in at least one subsequent 24-hour online dietary assessment.

Women diagnosed with colorectal cancer were generally older, taller, more likely to have a family history of bowel cancer, and have more adverse health behaviors, compared with participants overall.

 

Calcium Intake Showed the Strongest Protective Association

Relative risks (RR) for colorectal cancer were calculated for intakes of all 97 dietary factors, with significant associations found for 17 of them. Calcium intake showed the strongest protective effect, with each additional 300 mg per day – equivalent to a large glass of milk – associated with a 17% reduced RR. 

Six dairy-related factors associated with calcium – dairy milk, yogurt, riboflavin, magnesium, phosphorus, and potassium intakes – also demonstrated inverse associations with colorectal cancer risk. Weaker protective effects were noted for breakfast cereal, fruit, wholegrains, carbohydrates, fibre, total sugars, folate, and vitamin C. However, the team commented that these inverse associations might reflect residual confounding from other lifestyle or other dietary factors.

Calcium’s protective role was independent of dairy milk intake. The study, published in Nature Communications, concluded that, while “dairy products help protect against colorectal cancer,” that protection is “driven largely or wholly by calcium.”

 

Alcohol and Processed Meat Confirmed as Risk Factors

As expected, alcohol showed the reverse association, with each additional 20 g daily – equivalent to one large glass of wine – associated with a 15% RR increase. Weaker associations were seen for the combined category of red and processed meat, with each additional 30 g per day associated with an 8% increased RR for colorectal cancer. This association was minimally affected by diet and lifestyle factors.

Commenting to the Science Media Centre (SMC), Tom Sanders, professor emeritus of nutrition and dietetics at King’s College London, England, said: “One theory is that the calcium may bind to free bile acids in the gut, preventing the harmful effects of free bile acids on gut mucosa.” However, the lactose content in milk also has effects on large bowel microflora, which may in turn affect risk.

Also commenting to the SMC, David Nunan, senior research fellow at the University of Oxford’s Centre for Evidence Based Medicine, who was not involved in the study, cautioned that the findings were subject to the bias inherent in observational studies. “These biases often inflate the estimated associations compared to controlled experiments,” he said. Nunan advised caution in interpreting the findings, as more robust research, such as randomized controlled trials, would be needed to establish causation.

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

A major prospective study of more than half a million UK women conducted over almost 17 years has confirmed an association between dietary calcium intake and decreased risk of colorectal cancer. 

Cancer Research UK (CRUK), which funded the study, said that it demonstrated the benefits of a healthy, balanced diet for lowering cancer risk.

Colorectal cancer is the third most common cancer worldwide. Incidence rates vary markedly, with higher rates observed in high-income countries. The risk increases for individuals who migrate from low- to high-incidence areas, suggesting that lifestyle and environmental factors contribute to its development.

While alcohol and processed meats are established carcinogens, and red meat is classified as probably carcinogenic, there is a lack of consensus regarding the relationships between other dietary factors and colorectal cancer risk. This uncertainty may be due, at least in part, to relatively few studies giving comprehensive results on all food types, as well as dietary measurement errors, and/or small sample sizes.

 

Study Tracked 97 Dietary Factors

To address these gaps, the research team, led by the University of Oxford in England, tracked the intake of 97 dietary factors in 542,778 women from 2001 for an average of 16.6 years. During this period 12,251 participants developed colorectal cancer. The women completed detailed dietary questionnaires at baseline, with 7% participating in at least one subsequent 24-hour online dietary assessment.

Women diagnosed with colorectal cancer were generally older, taller, more likely to have a family history of bowel cancer, and have more adverse health behaviors, compared with participants overall.

 

Calcium Intake Showed the Strongest Protective Association

Relative risks (RR) for colorectal cancer were calculated for intakes of all 97 dietary factors, with significant associations found for 17 of them. Calcium intake showed the strongest protective effect, with each additional 300 mg per day – equivalent to a large glass of milk – associated with a 17% reduced RR. 

Six dairy-related factors associated with calcium – dairy milk, yogurt, riboflavin, magnesium, phosphorus, and potassium intakes – also demonstrated inverse associations with colorectal cancer risk. Weaker protective effects were noted for breakfast cereal, fruit, wholegrains, carbohydrates, fibre, total sugars, folate, and vitamin C. However, the team commented that these inverse associations might reflect residual confounding from other lifestyle or other dietary factors.

Calcium’s protective role was independent of dairy milk intake. The study, published in Nature Communications, concluded that, while “dairy products help protect against colorectal cancer,” that protection is “driven largely or wholly by calcium.”

 

Alcohol and Processed Meat Confirmed as Risk Factors

As expected, alcohol showed the reverse association, with each additional 20 g daily – equivalent to one large glass of wine – associated with a 15% RR increase. Weaker associations were seen for the combined category of red and processed meat, with each additional 30 g per day associated with an 8% increased RR for colorectal cancer. This association was minimally affected by diet and lifestyle factors.

Commenting to the Science Media Centre (SMC), Tom Sanders, professor emeritus of nutrition and dietetics at King’s College London, England, said: “One theory is that the calcium may bind to free bile acids in the gut, preventing the harmful effects of free bile acids on gut mucosa.” However, the lactose content in milk also has effects on large bowel microflora, which may in turn affect risk.

Also commenting to the SMC, David Nunan, senior research fellow at the University of Oxford’s Centre for Evidence Based Medicine, who was not involved in the study, cautioned that the findings were subject to the bias inherent in observational studies. “These biases often inflate the estimated associations compared to controlled experiments,” he said. Nunan advised caution in interpreting the findings, as more robust research, such as randomized controlled trials, would be needed to establish causation.

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

A major prospective study of more than half a million UK women conducted over almost 17 years has confirmed an association between dietary calcium intake and decreased risk of colorectal cancer. 

Cancer Research UK (CRUK), which funded the study, said that it demonstrated the benefits of a healthy, balanced diet for lowering cancer risk.

Colorectal cancer is the third most common cancer worldwide. Incidence rates vary markedly, with higher rates observed in high-income countries. The risk increases for individuals who migrate from low- to high-incidence areas, suggesting that lifestyle and environmental factors contribute to its development.

While alcohol and processed meats are established carcinogens, and red meat is classified as probably carcinogenic, there is a lack of consensus regarding the relationships between other dietary factors and colorectal cancer risk. This uncertainty may be due, at least in part, to relatively few studies giving comprehensive results on all food types, as well as dietary measurement errors, and/or small sample sizes.

 

Study Tracked 97 Dietary Factors

To address these gaps, the research team, led by the University of Oxford in England, tracked the intake of 97 dietary factors in 542,778 women from 2001 for an average of 16.6 years. During this period 12,251 participants developed colorectal cancer. The women completed detailed dietary questionnaires at baseline, with 7% participating in at least one subsequent 24-hour online dietary assessment.

Women diagnosed with colorectal cancer were generally older, taller, more likely to have a family history of bowel cancer, and have more adverse health behaviors, compared with participants overall.

 

Calcium Intake Showed the Strongest Protective Association

Relative risks (RR) for colorectal cancer were calculated for intakes of all 97 dietary factors, with significant associations found for 17 of them. Calcium intake showed the strongest protective effect, with each additional 300 mg per day – equivalent to a large glass of milk – associated with a 17% reduced RR. 

Six dairy-related factors associated with calcium – dairy milk, yogurt, riboflavin, magnesium, phosphorus, and potassium intakes – also demonstrated inverse associations with colorectal cancer risk. Weaker protective effects were noted for breakfast cereal, fruit, wholegrains, carbohydrates, fibre, total sugars, folate, and vitamin C. However, the team commented that these inverse associations might reflect residual confounding from other lifestyle or other dietary factors.

Calcium’s protective role was independent of dairy milk intake. The study, published in Nature Communications, concluded that, while “dairy products help protect against colorectal cancer,” that protection is “driven largely or wholly by calcium.”

 

Alcohol and Processed Meat Confirmed as Risk Factors

As expected, alcohol showed the reverse association, with each additional 20 g daily – equivalent to one large glass of wine – associated with a 15% RR increase. Weaker associations were seen for the combined category of red and processed meat, with each additional 30 g per day associated with an 8% increased RR for colorectal cancer. This association was minimally affected by diet and lifestyle factors.

Commenting to the Science Media Centre (SMC), Tom Sanders, professor emeritus of nutrition and dietetics at King’s College London, England, said: “One theory is that the calcium may bind to free bile acids in the gut, preventing the harmful effects of free bile acids on gut mucosa.” However, the lactose content in milk also has effects on large bowel microflora, which may in turn affect risk.

Also commenting to the SMC, David Nunan, senior research fellow at the University of Oxford’s Centre for Evidence Based Medicine, who was not involved in the study, cautioned that the findings were subject to the bias inherent in observational studies. “These biases often inflate the estimated associations compared to controlled experiments,” he said. Nunan advised caution in interpreting the findings, as more robust research, such as randomized controlled trials, would be needed to establish causation.

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