Federal Practitioner

Dual checkpoint blockade allowed 70.6% of patients with microsatellite instability-high (MSI-H) resectable gastric or gastroesophageal junction adenocarcinoma (G/GEJAC) to avoid surgery in a small cohort of the INFINITY study.

MSI-H tumors account for roughly 10% of early G/GEJACs. They respond well to immunotherapy, with high rates of pathologic complete responses. The Italian INFINITY trial set out to test whether some patients with these tumors might not need gastrectomy.

The trial treated MSI-H patients with durvalumab 1500 mg once a month for 3 months along with 1 300-mg dose of the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blocker tremelimumab on day 1. The 18 patients in cohort 1 proceeded to surgery, with a 60% pathologic complete response rate. An additional 18 patients in cohort 2 were the subject of a presentation at the American Association for Cancer Research (AACR) Annual Meeting 2026. These patients were assessed for clinical complete response; if present, they went on to surveillance; if not, they had surgery.

To qualify for a clinical complete response and surveillance, patients were required to have negative findings on CT and PET scans; tumor-informed circulating tumor DNA (ctDNA); and upper endoscopy with ultrasound, including bite-on-bite biopsies and nodal sampling. Surveillance afterward included CT, endoscopy with biopsies, and ctDNA every 12 weeks for up to 2 years.

Among 17 evaluable patients, 1 withdrew consent during immunotherapy, 13 (76%) had a clinical complete response and started surveillance, and the other 4 went to surgery. One patient in the surveillance group had a local regrowth after 4 months, underwent salvage surgery, and remained disease-free. At a median follow-up of 27.1 months, there were no additional progression events.

Overall, 12 of the 17 patients (70.6%) were gastrectomy-free at 2 years without additional treatment. Progression-free survival was 94.1%, and all patients were alive.

“The results are very encouraging,” lead investigator Alberto Leone, MD, said while presenting the results at the AACR annual meeting.

“Nonoperative management could be a safe and effective strategy for patients achieving a clinical complete response after only 3 months of dual immunotherapy,” said Leone, who is a gastrointestinal medical oncologist at the Istituto Nazionale dei Tumori, Milan, Italy. “However, the optimal strategy needs to be established in larger randomized trials.”

Study discussant Yelena Janjagian, MD, gastrointestinal medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, said the findings were important, particularly given that 70.6% of patients avoided a potentially life-altering gastrectomy.

In addition to surgery, the study also calls into question the need for chemotherapy, long the backbone of management alongside surgery, she said. To replace it, however, “it appears that dual checkpoint blockade will be required for a chemotherapy-free approach to achieve organ preservation.”

“Anti-PD-1 alone is not sufficient; we need CTLA-4 to expand and reactivate tumor-specific immunity,” Janjagian continued.

Ultimately, she expects immunotherapy to shift management of MSI-H cancers away from surgery, although some patients will still likely need an operation.

In addition to being MSI-H, patients in the study were mismatch repair deficient and Epstein-Barr virus-negative with T2/T3 tumors; T4 tumors were excluded.

Tumor-agnostic plasma ctDNA was positive at baseline in 13 patients and cleared in 11 after treatment. Higher baseline plasma ctDNA trended toward a lower likelihood of reaching a clinical complete response. Specificity was 100%, so when positive, the test was “very highly informative,” Leone said.

Three patients had grade 3 adverse events (hyperthyroidism, increased gamma-glutamyl transferase, and colitis) that resolved with steroids. There were no grade 4 events, treatment discontinuation, or deaths.

The work was funded by the GONO Foundation and AstraZeneca, the maker of durvalumab and tremelimumab. Leone reported having no disclosures. Janjagian reported having extensive industry ties, including travel funding, consulting fees, and research support from AstraZeneca.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: [email protected] 

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

Dual checkpoint blockade allowed 70.6% of patients with microsatellite instability-high (MSI-H) resectable gastric or gastroesophageal junction adenocarcinoma (G/GEJAC) to avoid surgery in a small cohort of the INFINITY study.

MSI-H tumors account for roughly 10% of early G/GEJACs. They respond well to immunotherapy, with high rates of pathologic complete responses. The Italian INFINITY trial set out to test whether some patients with these tumors might not need gastrectomy.

The trial treated MSI-H patients with durvalumab 1500 mg once a month for 3 months along with 1 300-mg dose of the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blocker tremelimumab on day 1. The 18 patients in cohort 1 proceeded to surgery, with a 60% pathologic complete response rate. An additional 18 patients in cohort 2 were the subject of a presentation at the American Association for Cancer Research (AACR) Annual Meeting 2026. These patients were assessed for clinical complete response; if present, they went on to surveillance; if not, they had surgery.

To qualify for a clinical complete response and surveillance, patients were required to have negative findings on CT and PET scans; tumor-informed circulating tumor DNA (ctDNA); and upper endoscopy with ultrasound, including bite-on-bite biopsies and nodal sampling. Surveillance afterward included CT, endoscopy with biopsies, and ctDNA every 12 weeks for up to 2 years.

Among 17 evaluable patients, 1 withdrew consent during immunotherapy, 13 (76%) had a clinical complete response and started surveillance, and the other 4 went to surgery. One patient in the surveillance group had a local regrowth after 4 months, underwent salvage surgery, and remained disease-free. At a median follow-up of 27.1 months, there were no additional progression events.

Overall, 12 of the 17 patients (70.6%) were gastrectomy-free at 2 years without additional treatment. Progression-free survival was 94.1%, and all patients were alive.

“The results are very encouraging,” lead investigator Alberto Leone, MD, said while presenting the results at the AACR annual meeting.

“Nonoperative management could be a safe and effective strategy for patients achieving a clinical complete response after only 3 months of dual immunotherapy,” said Leone, who is a gastrointestinal medical oncologist at the Istituto Nazionale dei Tumori, Milan, Italy. “However, the optimal strategy needs to be established in larger randomized trials.”

Study discussant Yelena Janjagian, MD, gastrointestinal medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, said the findings were important, particularly given that 70.6% of patients avoided a potentially life-altering gastrectomy.

In addition to surgery, the study also calls into question the need for chemotherapy, long the backbone of management alongside surgery, she said. To replace it, however, “it appears that dual checkpoint blockade will be required for a chemotherapy-free approach to achieve organ preservation.”

“Anti-PD-1 alone is not sufficient; we need CTLA-4 to expand and reactivate tumor-specific immunity,” Janjagian continued.

Ultimately, she expects immunotherapy to shift management of MSI-H cancers away from surgery, although some patients will still likely need an operation.

In addition to being MSI-H, patients in the study were mismatch repair deficient and Epstein-Barr virus-negative with T2/T3 tumors; T4 tumors were excluded.

Tumor-agnostic plasma ctDNA was positive at baseline in 13 patients and cleared in 11 after treatment. Higher baseline plasma ctDNA trended toward a lower likelihood of reaching a clinical complete response. Specificity was 100%, so when positive, the test was “very highly informative,” Leone said.

Three patients had grade 3 adverse events (hyperthyroidism, increased gamma-glutamyl transferase, and colitis) that resolved with steroids. There were no grade 4 events, treatment discontinuation, or deaths.

The work was funded by the GONO Foundation and AstraZeneca, the maker of durvalumab and tremelimumab. Leone reported having no disclosures. Janjagian reported having extensive industry ties, including travel funding, consulting fees, and research support from AstraZeneca.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: [email protected] 

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

Dual checkpoint blockade allowed 70.6% of patients with microsatellite instability-high (MSI-H) resectable gastric or gastroesophageal junction adenocarcinoma (G/GEJAC) to avoid surgery in a small cohort of the INFINITY study.

MSI-H tumors account for roughly 10% of early G/GEJACs. They respond well to immunotherapy, with high rates of pathologic complete responses. The Italian INFINITY trial set out to test whether some patients with these tumors might not need gastrectomy.

The trial treated MSI-H patients with durvalumab 1500 mg once a month for 3 months along with 1 300-mg dose of the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blocker tremelimumab on day 1. The 18 patients in cohort 1 proceeded to surgery, with a 60% pathologic complete response rate. An additional 18 patients in cohort 2 were the subject of a presentation at the American Association for Cancer Research (AACR) Annual Meeting 2026. These patients were assessed for clinical complete response; if present, they went on to surveillance; if not, they had surgery.

To qualify for a clinical complete response and surveillance, patients were required to have negative findings on CT and PET scans; tumor-informed circulating tumor DNA (ctDNA); and upper endoscopy with ultrasound, including bite-on-bite biopsies and nodal sampling. Surveillance afterward included CT, endoscopy with biopsies, and ctDNA every 12 weeks for up to 2 years.

Among 17 evaluable patients, 1 withdrew consent during immunotherapy, 13 (76%) had a clinical complete response and started surveillance, and the other 4 went to surgery. One patient in the surveillance group had a local regrowth after 4 months, underwent salvage surgery, and remained disease-free. At a median follow-up of 27.1 months, there were no additional progression events.

Overall, 12 of the 17 patients (70.6%) were gastrectomy-free at 2 years without additional treatment. Progression-free survival was 94.1%, and all patients were alive.

“The results are very encouraging,” lead investigator Alberto Leone, MD, said while presenting the results at the AACR annual meeting.

“Nonoperative management could be a safe and effective strategy for patients achieving a clinical complete response after only 3 months of dual immunotherapy,” said Leone, who is a gastrointestinal medical oncologist at the Istituto Nazionale dei Tumori, Milan, Italy. “However, the optimal strategy needs to be established in larger randomized trials.”

Study discussant Yelena Janjagian, MD, gastrointestinal medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, said the findings were important, particularly given that 70.6% of patients avoided a potentially life-altering gastrectomy.

In addition to surgery, the study also calls into question the need for chemotherapy, long the backbone of management alongside surgery, she said. To replace it, however, “it appears that dual checkpoint blockade will be required for a chemotherapy-free approach to achieve organ preservation.”

“Anti-PD-1 alone is not sufficient; we need CTLA-4 to expand and reactivate tumor-specific immunity,” Janjagian continued.

Ultimately, she expects immunotherapy to shift management of MSI-H cancers away from surgery, although some patients will still likely need an operation.

In addition to being MSI-H, patients in the study were mismatch repair deficient and Epstein-Barr virus-negative with T2/T3 tumors; T4 tumors were excluded.

Tumor-agnostic plasma ctDNA was positive at baseline in 13 patients and cleared in 11 after treatment. Higher baseline plasma ctDNA trended toward a lower likelihood of reaching a clinical complete response. Specificity was 100%, so when positive, the test was “very highly informative,” Leone said.

Three patients had grade 3 adverse events (hyperthyroidism, increased gamma-glutamyl transferase, and colitis) that resolved with steroids. There were no grade 4 events, treatment discontinuation, or deaths.

The work was funded by the GONO Foundation and AstraZeneca, the maker of durvalumab and tremelimumab. Leone reported having no disclosures. Janjagian reported having extensive industry ties, including travel funding, consulting fees, and research support from AstraZeneca.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: [email protected] 

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

A personalized messenger RNA (mRNA) vaccine for pancreatic cancer continues to show promise for improving patient survival, according to 6-year follow-up results of a phase 1 clinical study.

Among the 8 out of 16 patients in the study who initially experienced an immune response to the vaccine, seven (87.5%) were still alive at follow-up, lead investigator Vinod P. Balachandran, MD, reported at the American Association for Cancer Research (AACR) Annual Meeting 2026.

Of the eight patients who did not respond, two (25%) were still alive, with a median survival time of 3.4 years. “This suggests that personalized vaccines can stimulate the immune system in some pancreatic cancer patients, and that these patients continue to do well for several years after vaccination,” said Balachandran, director of the Olayan Center for Cancer Vaccines at Memorial Sloan Kettering Cancer Center in New York City.

The findings suggest that this vaccine has the potential to improve outcomes in patients with pancreatic cancer, which is one of the deadliest cancers, he said.

The 5-year survival rate for pancreatic cancer is currently 13%, according to the American Cancer Society’s Cancer Statistics 2026 report.

Initial results of the trial evaluating the individualized neoantigen vaccine — autogene cevumeran, which is being developed by BioNTech and Genentech — were published in Nature in February 2025.

After pancreatic cancer surgery and chemo-immunotherapy, patients with pancreatic ductal adenocarcinoma (PDAC) received a vaccine personalized to each patient based on unique changes in their tumor DNA.

The eight patients with vaccine-induced T cells had prolonged recurrence-free survival (RFS; median not reached), whereas nonresponders had a median RFS of 13.4 months, the authors had reported in the Nature paper.

This correlation was not confounded by other factors, including those associated with the patient, tumor, treatment, and host immune fitness, Balachandran noted.

In the responders, the T-cell clones had “high magnitude and exceptional longevity,” with an average estimated lifespan of 7.7 years, he said.

A fundamental challenge in developing cancer vaccines has been generating durable functional T cells specific for tumor antigens, and these findings suggest that mRNA-lipoplex vaccines against somatic mutation-derived neoantigens like autogene cevumeran may help overcome this challenge in pancreatic cancer, he and his colleagues concluded in the Nature paper.

The latest findings presented at the AACR annual meeting further underscore the potential of this approach.

At the 6-year follow-up, median RFS was “still not reached” in the vaccine responders vs 1.1 year in the nonresponders, he noted.

“This translates to a difference in overall survival,” he said. “Seven of eight [responders to the vaccine] are still alive 4.5-6 years after surgery.”

And of the 2 of 8 nonresponders still alive, one appears to be mounting a subclinical vaccine-induced T-cell response, he added, noting that this “suggests that inducible vaccine immunity may also impact survival in PDAC.”

“The implication here, we believe, is that even if a cancer has very mutational by-products [like PDAC], these mutational by-products can empower potent and composite immunity,” he said. “This is important because it could potentially expand vaccine eligibility to many cancers.”

Currently, there are about 50 neoantigen vaccine trials in solid tumors ongoing worldwide, he noted.

Memorial Sloan Kettering reports that Genentech and BioNTech are now testing autogene cevumeran in a larger patient population at numerous sites worldwide.

Balachandran reported receiving research support from Genentech, Merck Sharp & Dohme, and AbbVie.

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge, and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at [email protected] or on X: @SW_MedReporter.

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

A personalized messenger RNA (mRNA) vaccine for pancreatic cancer continues to show promise for improving patient survival, according to 6-year follow-up results of a phase 1 clinical study.

Among the 8 out of 16 patients in the study who initially experienced an immune response to the vaccine, seven (87.5%) were still alive at follow-up, lead investigator Vinod P. Balachandran, MD, reported at the American Association for Cancer Research (AACR) Annual Meeting 2026.

Of the eight patients who did not respond, two (25%) were still alive, with a median survival time of 3.4 years. “This suggests that personalized vaccines can stimulate the immune system in some pancreatic cancer patients, and that these patients continue to do well for several years after vaccination,” said Balachandran, director of the Olayan Center for Cancer Vaccines at Memorial Sloan Kettering Cancer Center in New York City.

The findings suggest that this vaccine has the potential to improve outcomes in patients with pancreatic cancer, which is one of the deadliest cancers, he said.

The 5-year survival rate for pancreatic cancer is currently 13%, according to the American Cancer Society’s Cancer Statistics 2026 report.

Initial results of the trial evaluating the individualized neoantigen vaccine — autogene cevumeran, which is being developed by BioNTech and Genentech — were published in Nature in February 2025.

After pancreatic cancer surgery and chemo-immunotherapy, patients with pancreatic ductal adenocarcinoma (PDAC) received a vaccine personalized to each patient based on unique changes in their tumor DNA.

The eight patients with vaccine-induced T cells had prolonged recurrence-free survival (RFS; median not reached), whereas nonresponders had a median RFS of 13.4 months, the authors had reported in the Nature paper.

This correlation was not confounded by other factors, including those associated with the patient, tumor, treatment, and host immune fitness, Balachandran noted.

In the responders, the T-cell clones had “high magnitude and exceptional longevity,” with an average estimated lifespan of 7.7 years, he said.

A fundamental challenge in developing cancer vaccines has been generating durable functional T cells specific for tumor antigens, and these findings suggest that mRNA-lipoplex vaccines against somatic mutation-derived neoantigens like autogene cevumeran may help overcome this challenge in pancreatic cancer, he and his colleagues concluded in the Nature paper.

The latest findings presented at the AACR annual meeting further underscore the potential of this approach.

At the 6-year follow-up, median RFS was “still not reached” in the vaccine responders vs 1.1 year in the nonresponders, he noted.

“This translates to a difference in overall survival,” he said. “Seven of eight [responders to the vaccine] are still alive 4.5-6 years after surgery.”

And of the 2 of 8 nonresponders still alive, one appears to be mounting a subclinical vaccine-induced T-cell response, he added, noting that this “suggests that inducible vaccine immunity may also impact survival in PDAC.”

“The implication here, we believe, is that even if a cancer has very mutational by-products [like PDAC], these mutational by-products can empower potent and composite immunity,” he said. “This is important because it could potentially expand vaccine eligibility to many cancers.”

Currently, there are about 50 neoantigen vaccine trials in solid tumors ongoing worldwide, he noted.

Memorial Sloan Kettering reports that Genentech and BioNTech are now testing autogene cevumeran in a larger patient population at numerous sites worldwide.

Balachandran reported receiving research support from Genentech, Merck Sharp & Dohme, and AbbVie.

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge, and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at [email protected] or on X: @SW_MedReporter.

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

A personalized messenger RNA (mRNA) vaccine for pancreatic cancer continues to show promise for improving patient survival, according to 6-year follow-up results of a phase 1 clinical study.

Among the 8 out of 16 patients in the study who initially experienced an immune response to the vaccine, seven (87.5%) were still alive at follow-up, lead investigator Vinod P. Balachandran, MD, reported at the American Association for Cancer Research (AACR) Annual Meeting 2026.

Of the eight patients who did not respond, two (25%) were still alive, with a median survival time of 3.4 years. “This suggests that personalized vaccines can stimulate the immune system in some pancreatic cancer patients, and that these patients continue to do well for several years after vaccination,” said Balachandran, director of the Olayan Center for Cancer Vaccines at Memorial Sloan Kettering Cancer Center in New York City.

The findings suggest that this vaccine has the potential to improve outcomes in patients with pancreatic cancer, which is one of the deadliest cancers, he said.

The 5-year survival rate for pancreatic cancer is currently 13%, according to the American Cancer Society’s Cancer Statistics 2026 report.

Initial results of the trial evaluating the individualized neoantigen vaccine — autogene cevumeran, which is being developed by BioNTech and Genentech — were published in Nature in February 2025.

After pancreatic cancer surgery and chemo-immunotherapy, patients with pancreatic ductal adenocarcinoma (PDAC) received a vaccine personalized to each patient based on unique changes in their tumor DNA.

The eight patients with vaccine-induced T cells had prolonged recurrence-free survival (RFS; median not reached), whereas nonresponders had a median RFS of 13.4 months, the authors had reported in the Nature paper.

This correlation was not confounded by other factors, including those associated with the patient, tumor, treatment, and host immune fitness, Balachandran noted.

In the responders, the T-cell clones had “high magnitude and exceptional longevity,” with an average estimated lifespan of 7.7 years, he said.

A fundamental challenge in developing cancer vaccines has been generating durable functional T cells specific for tumor antigens, and these findings suggest that mRNA-lipoplex vaccines against somatic mutation-derived neoantigens like autogene cevumeran may help overcome this challenge in pancreatic cancer, he and his colleagues concluded in the Nature paper.

The latest findings presented at the AACR annual meeting further underscore the potential of this approach.

At the 6-year follow-up, median RFS was “still not reached” in the vaccine responders vs 1.1 year in the nonresponders, he noted.

“This translates to a difference in overall survival,” he said. “Seven of eight [responders to the vaccine] are still alive 4.5-6 years after surgery.”

And of the 2 of 8 nonresponders still alive, one appears to be mounting a subclinical vaccine-induced T-cell response, he added, noting that this “suggests that inducible vaccine immunity may also impact survival in PDAC.”

“The implication here, we believe, is that even if a cancer has very mutational by-products [like PDAC], these mutational by-products can empower potent and composite immunity,” he said. “This is important because it could potentially expand vaccine eligibility to many cancers.”

Currently, there are about 50 neoantigen vaccine trials in solid tumors ongoing worldwide, he noted.

Memorial Sloan Kettering reports that Genentech and BioNTech are now testing autogene cevumeran in a larger patient population at numerous sites worldwide.

Balachandran reported receiving research support from Genentech, Merck Sharp & Dohme, and AbbVie.

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge, and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at [email protected] or on X: @SW_MedReporter.

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

TOPLINE:

A large cohort study found that the use of GLP-1 receptor agonists (GLP-1 RAs) over 3 years was associated with a modestly increased risk for nonarteritic anterior ischemic optic neuropathy (NAION) compared with the use of SGLT2 inhibitors in veterans with type 2 diabetes (T2D).

METHODOLOGY:

• Pharmacovigilance reports and emerging, but inconsistent, population-based studies suggest that the use of GLP-1 RAs may be linked to ocular adverse events, including a possible increased risk for NAION; however, it remains unclear whether the association is specific to NAION as compared with other optic disorders.
• Researchers conducted a target trial emulation study using nationwide electronic health records from the US Department of Veterans Affairs to compare the 3-year risk for NAION among veterans with T2D who initiated GLP-1 RAs vs SGLT2 inhibitors.
• The study included 588,168 veterans with T2D, of whom 139,546 initiated GLP-1 RA therapy (mean age, 65.33 years; 90.2% male) and 448,622 initiated SGLT2 inhibitor therapy (mean age, 67.94 years; 95.3% male) between 2017 and 2024; groups were subsequently matched using propensity score-based inverse probability weighting.
• Cases of NAION were identified from medical records using standard diagnostic codes; cases diagnosed by an eye care specialist and repeat diagnoses were also evaluated.
• The 3-year cumulative incidence, cumulative incidence difference (CID), and cumulative incidence ratio of NAION were estimated.

TAKEAWAY:

• Over 3 years, individuals who started GLP-1 RAs had a small but statistically significant increase in the risk for NAION compared with those who started SGLT2 inhibitors — 39.07 vs 29.33 cases per 10,000 people (CID, 9.98 per 10,000 people; 95% CI, 3.48-14.03) — and a relative increase of about 35% (cumulative incidence ratio, 1.35; 95% CI, 1.11-1.51).
• The increased risk for NAION with the use of GLP-1 RAs was consistent across definitions: diagnosis by an eye care specialist (CID, 8.73; 95% CI, 2.46-12.89), repeat diagnoses (CID, 6.35; 95% CI, 2.40-9.65), and repeat diagnoses with a specialist (CID, 5.91; 95% CI, 2.00-8.88).
• Compared with the use of SGLT2 inhibitors, the use of GLP-1 RAs was not associated with an increased risk for other optic disorders such as diabetic retinopathy, macular degeneration, retinal vascular occlusion, or optic neuritis.
• The frequency of ophthalmology or optometry clinic visits during follow-up was found to be similar between the two groups, suggesting that the association with NAION was not due to differential surveillance.

IN PRACTICE

“GLP-1 RA use was associated with a modestly increased risk of NAION compared with [SGLT2 inhibitor] use. While the absolute risk remains low, the specificity of this finding may warrant heightened vigilance,” the authors of the study wrote.

SOURCE:

The study was led by Taeyoung Choi, MS, Clinical Epidemiology Center, Research and Development Service, VA St Louis Health Care System, St. Louis. It was published online on April 30, 2026, in JAMA Network Open.

LIMITATIONS:

The study cohort was older and predominantly male, limiting generalizability to other populations. Residual confounding, selection bias, and outcome misclassification could not be fully excluded.

DISCLOSURES:

The study was funded by the US Department of Veterans Affairs. Two authors reported being uncompensated consultants for Pfizer.

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

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

TOPLINE:

A large cohort study found that the use of GLP-1 receptor agonists (GLP-1 RAs) over 3 years was associated with a modestly increased risk for nonarteritic anterior ischemic optic neuropathy (NAION) compared with the use of SGLT2 inhibitors in veterans with type 2 diabetes (T2D).

METHODOLOGY:

• Pharmacovigilance reports and emerging, but inconsistent, population-based studies suggest that the use of GLP-1 RAs may be linked to ocular adverse events, including a possible increased risk for NAION; however, it remains unclear whether the association is specific to NAION as compared with other optic disorders.
• Researchers conducted a target trial emulation study using nationwide electronic health records from the US Department of Veterans Affairs to compare the 3-year risk for NAION among veterans with T2D who initiated GLP-1 RAs vs SGLT2 inhibitors.
• The study included 588,168 veterans with T2D, of whom 139,546 initiated GLP-1 RA therapy (mean age, 65.33 years; 90.2% male) and 448,622 initiated SGLT2 inhibitor therapy (mean age, 67.94 years; 95.3% male) between 2017 and 2024; groups were subsequently matched using propensity score-based inverse probability weighting.
• Cases of NAION were identified from medical records using standard diagnostic codes; cases diagnosed by an eye care specialist and repeat diagnoses were also evaluated.
• The 3-year cumulative incidence, cumulative incidence difference (CID), and cumulative incidence ratio of NAION were estimated.

TAKEAWAY:

• Over 3 years, individuals who started GLP-1 RAs had a small but statistically significant increase in the risk for NAION compared with those who started SGLT2 inhibitors — 39.07 vs 29.33 cases per 10,000 people (CID, 9.98 per 10,000 people; 95% CI, 3.48-14.03) — and a relative increase of about 35% (cumulative incidence ratio, 1.35; 95% CI, 1.11-1.51).
• The increased risk for NAION with the use of GLP-1 RAs was consistent across definitions: diagnosis by an eye care specialist (CID, 8.73; 95% CI, 2.46-12.89), repeat diagnoses (CID, 6.35; 95% CI, 2.40-9.65), and repeat diagnoses with a specialist (CID, 5.91; 95% CI, 2.00-8.88).
• Compared with the use of SGLT2 inhibitors, the use of GLP-1 RAs was not associated with an increased risk for other optic disorders such as diabetic retinopathy, macular degeneration, retinal vascular occlusion, or optic neuritis.
• The frequency of ophthalmology or optometry clinic visits during follow-up was found to be similar between the two groups, suggesting that the association with NAION was not due to differential surveillance.

IN PRACTICE

“GLP-1 RA use was associated with a modestly increased risk of NAION compared with [SGLT2 inhibitor] use. While the absolute risk remains low, the specificity of this finding may warrant heightened vigilance,” the authors of the study wrote.

SOURCE:

The study was led by Taeyoung Choi, MS, Clinical Epidemiology Center, Research and Development Service, VA St Louis Health Care System, St. Louis. It was published online on April 30, 2026, in JAMA Network Open.

LIMITATIONS:

The study cohort was older and predominantly male, limiting generalizability to other populations. Residual confounding, selection bias, and outcome misclassification could not be fully excluded.

DISCLOSURES:

The study was funded by the US Department of Veterans Affairs. Two authors reported being uncompensated consultants for Pfizer.

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

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

TOPLINE:

A large cohort study found that the use of GLP-1 receptor agonists (GLP-1 RAs) over 3 years was associated with a modestly increased risk for nonarteritic anterior ischemic optic neuropathy (NAION) compared with the use of SGLT2 inhibitors in veterans with type 2 diabetes (T2D).

METHODOLOGY:

• Pharmacovigilance reports and emerging, but inconsistent, population-based studies suggest that the use of GLP-1 RAs may be linked to ocular adverse events, including a possible increased risk for NAION; however, it remains unclear whether the association is specific to NAION as compared with other optic disorders.
• Researchers conducted a target trial emulation study using nationwide electronic health records from the US Department of Veterans Affairs to compare the 3-year risk for NAION among veterans with T2D who initiated GLP-1 RAs vs SGLT2 inhibitors.
• The study included 588,168 veterans with T2D, of whom 139,546 initiated GLP-1 RA therapy (mean age, 65.33 years; 90.2% male) and 448,622 initiated SGLT2 inhibitor therapy (mean age, 67.94 years; 95.3% male) between 2017 and 2024; groups were subsequently matched using propensity score-based inverse probability weighting.
• Cases of NAION were identified from medical records using standard diagnostic codes; cases diagnosed by an eye care specialist and repeat diagnoses were also evaluated.
• The 3-year cumulative incidence, cumulative incidence difference (CID), and cumulative incidence ratio of NAION were estimated.

TAKEAWAY:

• Over 3 years, individuals who started GLP-1 RAs had a small but statistically significant increase in the risk for NAION compared with those who started SGLT2 inhibitors — 39.07 vs 29.33 cases per 10,000 people (CID, 9.98 per 10,000 people; 95% CI, 3.48-14.03) — and a relative increase of about 35% (cumulative incidence ratio, 1.35; 95% CI, 1.11-1.51).
• The increased risk for NAION with the use of GLP-1 RAs was consistent across definitions: diagnosis by an eye care specialist (CID, 8.73; 95% CI, 2.46-12.89), repeat diagnoses (CID, 6.35; 95% CI, 2.40-9.65), and repeat diagnoses with a specialist (CID, 5.91; 95% CI, 2.00-8.88).
• Compared with the use of SGLT2 inhibitors, the use of GLP-1 RAs was not associated with an increased risk for other optic disorders such as diabetic retinopathy, macular degeneration, retinal vascular occlusion, or optic neuritis.
• The frequency of ophthalmology or optometry clinic visits during follow-up was found to be similar between the two groups, suggesting that the association with NAION was not due to differential surveillance.

IN PRACTICE

“GLP-1 RA use was associated with a modestly increased risk of NAION compared with [SGLT2 inhibitor] use. While the absolute risk remains low, the specificity of this finding may warrant heightened vigilance,” the authors of the study wrote.

SOURCE:

The study was led by Taeyoung Choi, MS, Clinical Epidemiology Center, Research and Development Service, VA St Louis Health Care System, St. Louis. It was published online on April 30, 2026, in JAMA Network Open.

LIMITATIONS:

The study cohort was older and predominantly male, limiting generalizability to other populations. Residual confounding, selection bias, and outcome misclassification could not be fully excluded.

DISCLOSURES:

The study was funded by the US Department of Veterans Affairs. Two authors reported being uncompensated consultants for Pfizer.

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

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

The US Department of Veterans Affairs (VA) recently announced plans to offer $7 million in new transportation services grants that could benefit 4.7 million veterans who live in rural areas. The grants would expand free transportation to medical appointments, something VA Secretary Doug Collins said is designed to “help break down the geographic barriers to health care some rural veterans face.”

Funding could be distributed later in 2026 to veteran service organizations, state agencies, and groups that transport veterans for health care. Eligible veterans would not need to do anything—the transportation is free for those living in qualifying areas.

Travel time and distance from health care facilities are significant barriers to receiving appropriate and timely care. The 2014 Veterans Access, Choice and Accountability Act (Choice) was intended to improve timely access to outpatient health care for veterans by allowing them to receive care from community facilities paid for by the VA. Under Choice, eligible veterans become eligible to receive community care if they have to drive > 40 miles to the nearest VA facility or wait > 30 days for care. 

Even with this provision, many of the 2.7 million rural veterans enrolled in Veterans Health Administration (VHA) remained far from care. For instance, the VA Office of Rural Health says the closest facility for veterans in Hollis, Alaska, is > 1000 miles away. 

Moreover, 56% of rural veterans enrolled in VHA care are aged > 65 years, and more likely to be diagnosed with diabetes, high blood pressure, and heart conditions than veterans living in more urban areas. Although studies comparing health outcomes between rural and urban veterans are sparse, research has long shown that lacking access to routine health care may worsen long-term outcomes.  

The VA has also announced other initiatives aimed at improving health care for veterans, among them the opening of 34 new facilities. Other projects:

• The Electronic Health Record (EHR) modernization project resumed April 11 with new deployments in Michigan. The VA says the new EHR system will result in more consistent medical records, fewer repeated tests, and better coordination between VA facilities and military health services.

• In March, the VA announced a $112 million grant opportunity to strengthen community‑based suicide prevention programs, focusing on outreach outside traditional VA settings.

• In February, the VA said it raised its spending cap for in‑home and community‑based services for veterans with complex medical needs, adding coverage for veterans with spinal cord injuries, Amyotrophic Lateral Sclerosis, and others.

• In January, the VA announced plans to invest $4.8 billion in fiscal year 2026 to modernize, repair, and improve health care facilities nationwide via infrastructure upgrades, major building repairs, and improvements to EHR systems.

The US Department of Veterans Affairs (VA) recently announced plans to offer $7 million in new transportation services grants that could benefit 4.7 million veterans who live in rural areas. The grants would expand free transportation to medical appointments, something VA Secretary Doug Collins said is designed to “help break down the geographic barriers to health care some rural veterans face.”

Funding could be distributed later in 2026 to veteran service organizations, state agencies, and groups that transport veterans for health care. Eligible veterans would not need to do anything—the transportation is free for those living in qualifying areas.

Travel time and distance from health care facilities are significant barriers to receiving appropriate and timely care. The 2014 Veterans Access, Choice and Accountability Act (Choice) was intended to improve timely access to outpatient health care for veterans by allowing them to receive care from community facilities paid for by the VA. Under Choice, eligible veterans become eligible to receive community care if they have to drive > 40 miles to the nearest VA facility or wait > 30 days for care. 

Even with this provision, many of the 2.7 million rural veterans enrolled in Veterans Health Administration (VHA) remained far from care. For instance, the VA Office of Rural Health says the closest facility for veterans in Hollis, Alaska, is > 1000 miles away. 

Moreover, 56% of rural veterans enrolled in VHA care are aged > 65 years, and more likely to be diagnosed with diabetes, high blood pressure, and heart conditions than veterans living in more urban areas. Although studies comparing health outcomes between rural and urban veterans are sparse, research has long shown that lacking access to routine health care may worsen long-term outcomes.  

The VA has also announced other initiatives aimed at improving health care for veterans, among them the opening of 34 new facilities. Other projects:

• The Electronic Health Record (EHR) modernization project resumed April 11 with new deployments in Michigan. The VA says the new EHR system will result in more consistent medical records, fewer repeated tests, and better coordination between VA facilities and military health services.

• In March, the VA announced a $112 million grant opportunity to strengthen community‑based suicide prevention programs, focusing on outreach outside traditional VA settings.

• In February, the VA said it raised its spending cap for in‑home and community‑based services for veterans with complex medical needs, adding coverage for veterans with spinal cord injuries, Amyotrophic Lateral Sclerosis, and others.

• In January, the VA announced plans to invest $4.8 billion in fiscal year 2026 to modernize, repair, and improve health care facilities nationwide via infrastructure upgrades, major building repairs, and improvements to EHR systems.

The US Department of Veterans Affairs (VA) recently announced plans to offer $7 million in new transportation services grants that could benefit 4.7 million veterans who live in rural areas. The grants would expand free transportation to medical appointments, something VA Secretary Doug Collins said is designed to “help break down the geographic barriers to health care some rural veterans face.”

Funding could be distributed later in 2026 to veteran service organizations, state agencies, and groups that transport veterans for health care. Eligible veterans would not need to do anything—the transportation is free for those living in qualifying areas.

Travel time and distance from health care facilities are significant barriers to receiving appropriate and timely care. The 2014 Veterans Access, Choice and Accountability Act (Choice) was intended to improve timely access to outpatient health care for veterans by allowing them to receive care from community facilities paid for by the VA. Under Choice, eligible veterans become eligible to receive community care if they have to drive > 40 miles to the nearest VA facility or wait > 30 days for care. 

Even with this provision, many of the 2.7 million rural veterans enrolled in Veterans Health Administration (VHA) remained far from care. For instance, the VA Office of Rural Health says the closest facility for veterans in Hollis, Alaska, is > 1000 miles away. 

Moreover, 56% of rural veterans enrolled in VHA care are aged > 65 years, and more likely to be diagnosed with diabetes, high blood pressure, and heart conditions than veterans living in more urban areas. Although studies comparing health outcomes between rural and urban veterans are sparse, research has long shown that lacking access to routine health care may worsen long-term outcomes.  

The VA has also announced other initiatives aimed at improving health care for veterans, among them the opening of 34 new facilities. Other projects:

• The Electronic Health Record (EHR) modernization project resumed April 11 with new deployments in Michigan. The VA says the new EHR system will result in more consistent medical records, fewer repeated tests, and better coordination between VA facilities and military health services.

• In March, the VA announced a $112 million grant opportunity to strengthen community‑based suicide prevention programs, focusing on outreach outside traditional VA settings.

• In February, the VA said it raised its spending cap for in‑home and community‑based services for veterans with complex medical needs, adding coverage for veterans with spinal cord injuries, Amyotrophic Lateral Sclerosis, and others.

• In January, the VA announced plans to invest $4.8 billion in fiscal year 2026 to modernize, repair, and improve health care facilities nationwide via infrastructure upgrades, major building repairs, and improvements to EHR systems.

Cardiac rehabilitation (CR) remains dramatically underused among US veterans, as < 11% of eligible patients attend a single session and usage appears to be declining over time, a recently published retrospective cohort study reported. 

CR use is much lower among eligible patients across the US Department of Veterans Affairs (VA) compared with Medicare (10.4% vs. 28%, respectively), reported researchers at Veterans Affairs Connecticut Healthcare System and Yale School of Medicine, in JACC: Advances. 

The overall CR rate in the VA was lower than the 13.2% reported in a 2018 study. And while there was no significant difference in use between men and women, veterans from the poorest neighborhoods were less likely to take advantage of CR compared with veterans from the wealthiest neighborhoods (adjusted odds ratio, 0.82; P < .001).

“As providers, the time to act is now,” Merilyn Varghese, MD, MSc, said in an interview with Federal Practitioner. “We need to urgently get more of our veterans to cardiac rehab.”

As Varghese explained, “CR is a preventive intervention that has been shown to improve quality of life and reduce mortality and hospitalizations for patients with specific cardiac conditions.”

Patients may be eligible if they have experienced myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass surgery (CABG), heart transplant, valve surgery, stable angina, or stable heart failure. 

“CR combines multiple aspects of cardiac care such as exercise training, medication management, and behavioral assessments,” Varghese said. “For example, patients who have had a heart attack may have challenges in getting back to an exercise routine, managing new medications, and adjusting to life after such an event. CR can help bridge the gap between hospital to home.” In-person CR typically includes 3 sessions per week for 12 weeks.  

In 2024, a systematic review and meta-analysis reported that CR reduces all-cause mortality (relative risk, 0.74): “These results support the utilization of CR as a critical element in the management of further secondary prevention of CVDs (cardiovascular diseases).”

Examining VA Data

Researchers conducted the 2026 study “to better understand the current landscape of CR among veterans, particularly among women veterans who comprise a significant part of the veteran population but have previously been underrepresented in research,” Varghese said.

“Women veterans also share a different burden of cardiovascular risk factors, so understanding CR participation among both women and men veterans was of particular interest.”

The study tracked 82,496 VA-enrolled veterans eligible for CR from 2021-2023 (3.6% women). Average age of participants were 64.0 years among women and 71.5 years among men. Among women, 58.3% were White, and 31.8% were Black, and 2.24% were Asian. Among men, 71.9% were White, 18.8% were Black, and 2.3% were Asian. 

The rates of CR participation were low among both men (10.4%) and women (10.2%). Older people and Black patients were less likely to take part in CR than younger people and White patients, according to the study. Those who underwent CABG and PCI were more likely to participate in CR compared with those who had heart attacks only.

As for the gap in use between the wealthiest and poorest neighborhoods, Varghese said: “Area deprivation may compound some of the other barriers to CR access, including transportation difficulties, work responsibilities, and out-of-pocket costs.”

How can CR uptake be improved? “A key first step is understanding who can be referred, and second, to spend time discussing the importance of attending with veterans,” Varghese said. “Studies have shown that provider engagement and championing of CR are important positive facilitators that encourage CR participation.

“The VA has been at the forefront of innovation with the home-based CR program that offers veterans a way to attend CR remotely,” she added. “Expanding such novel methods of CR delivery is likely part of the solution to expand CR access.”

Outside Perspective: Make Referrals the Default

Justin Bachmann, MD, MPH, staff physician and research scientist at VA Tennessee Valley Healthcare System, told Federal Practitioner that CR is an American College of Cardiology/American Heart Association Class I recommended secondary prevention therapy following MI, PCI, and CABG “with strong evidence for reduced cardiovascular mortality and improved function and quality of life.”

Still, CR “has been persistently underused for decades as travel, cost, scheduling, and uneven geographic capacity create real logistical barriers,” said Bachmann, who serves as the medical director of a VA Office of Rural Health home-based CR program. 

Bachmann praised the study methodology and offered this advice to colleagues: “Embed CR referral in the post-MI, post-PCI, and post-CABG order sets so that referral is the default. Scale home-based CR well beyond the roughly 40 sites where it is currently available, and track facility-level referral and enrollment rates as quality measures.”

Preventive cardiology specialist Randal J. Thomas, MD, professor of Medicine at the Mayo Clinic in Rochester, Minn., echoed the importance of physician referral to Federal Practitioner.

“Patients can’t actually participate [directly] in most programs. They must have a physician referral,” he said. “The physician referral and the strength of referral is key. If a physician says, ‘You can go there if you want, but it’s not that important,’ the patients aren’t going to go.”

Outside Perspective: VA Deserves Blame

“The VA lags far behind most medical systems,” according to Quinn R. Pack, MD, associate professor of medicine at the University of Massachusetts Chan Medical School-Baystate. “Some of this is probably the patient population—more mental health problems, more smoking, more disease. But I’d squarely put most of this on the VA health system. They haven’t created the systems of care that make attending cardiac rehabilitation easy, reliable, and consistent.”

He noted that that automatic referral combined with a bedside visit by a liaison such as a representative of a CR program can double or triple enrollment.

“When physicians and nurses really encourage patients to go [to CR], these words are powerful,” Pack said. “When a patient enrolls in cardiac rehabilitation, we help them form new habits of exercise.”

No study fundings are reported. The Varghese discloses a relationship with the Veterans Health Administration. Other study authors had no disclosures. Bachmann disclosed a relationship with the VA. Pack and Thomas have no disclosures. 

Cardiac rehabilitation (CR) remains dramatically underused among US veterans, as < 11% of eligible patients attend a single session and usage appears to be declining over time, a recently published retrospective cohort study reported. 

CR use is much lower among eligible patients across the US Department of Veterans Affairs (VA) compared with Medicare (10.4% vs. 28%, respectively), reported researchers at Veterans Affairs Connecticut Healthcare System and Yale School of Medicine, in JACC: Advances. 

The overall CR rate in the VA was lower than the 13.2% reported in a 2018 study. And while there was no significant difference in use between men and women, veterans from the poorest neighborhoods were less likely to take advantage of CR compared with veterans from the wealthiest neighborhoods (adjusted odds ratio, 0.82; P < .001).

“As providers, the time to act is now,” Merilyn Varghese, MD, MSc, said in an interview with Federal Practitioner. “We need to urgently get more of our veterans to cardiac rehab.”

As Varghese explained, “CR is a preventive intervention that has been shown to improve quality of life and reduce mortality and hospitalizations for patients with specific cardiac conditions.”

Patients may be eligible if they have experienced myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass surgery (CABG), heart transplant, valve surgery, stable angina, or stable heart failure. 

“CR combines multiple aspects of cardiac care such as exercise training, medication management, and behavioral assessments,” Varghese said. “For example, patients who have had a heart attack may have challenges in getting back to an exercise routine, managing new medications, and adjusting to life after such an event. CR can help bridge the gap between hospital to home.” In-person CR typically includes 3 sessions per week for 12 weeks.  

In 2024, a systematic review and meta-analysis reported that CR reduces all-cause mortality (relative risk, 0.74): “These results support the utilization of CR as a critical element in the management of further secondary prevention of CVDs (cardiovascular diseases).”

Examining VA Data

Researchers conducted the 2026 study “to better understand the current landscape of CR among veterans, particularly among women veterans who comprise a significant part of the veteran population but have previously been underrepresented in research,” Varghese said.

“Women veterans also share a different burden of cardiovascular risk factors, so understanding CR participation among both women and men veterans was of particular interest.”

The study tracked 82,496 VA-enrolled veterans eligible for CR from 2021-2023 (3.6% women). Average age of participants were 64.0 years among women and 71.5 years among men. Among women, 58.3% were White, and 31.8% were Black, and 2.24% were Asian. Among men, 71.9% were White, 18.8% were Black, and 2.3% were Asian. 

The rates of CR participation were low among both men (10.4%) and women (10.2%). Older people and Black patients were less likely to take part in CR than younger people and White patients, according to the study. Those who underwent CABG and PCI were more likely to participate in CR compared with those who had heart attacks only.

As for the gap in use between the wealthiest and poorest neighborhoods, Varghese said: “Area deprivation may compound some of the other barriers to CR access, including transportation difficulties, work responsibilities, and out-of-pocket costs.”

How can CR uptake be improved? “A key first step is understanding who can be referred, and second, to spend time discussing the importance of attending with veterans,” Varghese said. “Studies have shown that provider engagement and championing of CR are important positive facilitators that encourage CR participation.

“The VA has been at the forefront of innovation with the home-based CR program that offers veterans a way to attend CR remotely,” she added. “Expanding such novel methods of CR delivery is likely part of the solution to expand CR access.”

Outside Perspective: Make Referrals the Default

Justin Bachmann, MD, MPH, staff physician and research scientist at VA Tennessee Valley Healthcare System, told Federal Practitioner that CR is an American College of Cardiology/American Heart Association Class I recommended secondary prevention therapy following MI, PCI, and CABG “with strong evidence for reduced cardiovascular mortality and improved function and quality of life.”

Still, CR “has been persistently underused for decades as travel, cost, scheduling, and uneven geographic capacity create real logistical barriers,” said Bachmann, who serves as the medical director of a VA Office of Rural Health home-based CR program. 

Bachmann praised the study methodology and offered this advice to colleagues: “Embed CR referral in the post-MI, post-PCI, and post-CABG order sets so that referral is the default. Scale home-based CR well beyond the roughly 40 sites where it is currently available, and track facility-level referral and enrollment rates as quality measures.”

Preventive cardiology specialist Randal J. Thomas, MD, professor of Medicine at the Mayo Clinic in Rochester, Minn., echoed the importance of physician referral to Federal Practitioner.

“Patients can’t actually participate [directly] in most programs. They must have a physician referral,” he said. “The physician referral and the strength of referral is key. If a physician says, ‘You can go there if you want, but it’s not that important,’ the patients aren’t going to go.”

Outside Perspective: VA Deserves Blame

“The VA lags far behind most medical systems,” according to Quinn R. Pack, MD, associate professor of medicine at the University of Massachusetts Chan Medical School-Baystate. “Some of this is probably the patient population—more mental health problems, more smoking, more disease. But I’d squarely put most of this on the VA health system. They haven’t created the systems of care that make attending cardiac rehabilitation easy, reliable, and consistent.”

He noted that that automatic referral combined with a bedside visit by a liaison such as a representative of a CR program can double or triple enrollment.

“When physicians and nurses really encourage patients to go [to CR], these words are powerful,” Pack said. “When a patient enrolls in cardiac rehabilitation, we help them form new habits of exercise.”

No study fundings are reported. The Varghese discloses a relationship with the Veterans Health Administration. Other study authors had no disclosures. Bachmann disclosed a relationship with the VA. Pack and Thomas have no disclosures. 

Cardiac rehabilitation (CR) remains dramatically underused among US veterans, as < 11% of eligible patients attend a single session and usage appears to be declining over time, a recently published retrospective cohort study reported. 

CR use is much lower among eligible patients across the US Department of Veterans Affairs (VA) compared with Medicare (10.4% vs. 28%, respectively), reported researchers at Veterans Affairs Connecticut Healthcare System and Yale School of Medicine, in JACC: Advances. 

The overall CR rate in the VA was lower than the 13.2% reported in a 2018 study. And while there was no significant difference in use between men and women, veterans from the poorest neighborhoods were less likely to take advantage of CR compared with veterans from the wealthiest neighborhoods (adjusted odds ratio, 0.82; P < .001).

“As providers, the time to act is now,” Merilyn Varghese, MD, MSc, said in an interview with Federal Practitioner. “We need to urgently get more of our veterans to cardiac rehab.”

As Varghese explained, “CR is a preventive intervention that has been shown to improve quality of life and reduce mortality and hospitalizations for patients with specific cardiac conditions.”

Patients may be eligible if they have experienced myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass surgery (CABG), heart transplant, valve surgery, stable angina, or stable heart failure. 

“CR combines multiple aspects of cardiac care such as exercise training, medication management, and behavioral assessments,” Varghese said. “For example, patients who have had a heart attack may have challenges in getting back to an exercise routine, managing new medications, and adjusting to life after such an event. CR can help bridge the gap between hospital to home.” In-person CR typically includes 3 sessions per week for 12 weeks.  

In 2024, a systematic review and meta-analysis reported that CR reduces all-cause mortality (relative risk, 0.74): “These results support the utilization of CR as a critical element in the management of further secondary prevention of CVDs (cardiovascular diseases).”

Examining VA Data

Researchers conducted the 2026 study “to better understand the current landscape of CR among veterans, particularly among women veterans who comprise a significant part of the veteran population but have previously been underrepresented in research,” Varghese said.

“Women veterans also share a different burden of cardiovascular risk factors, so understanding CR participation among both women and men veterans was of particular interest.”

The study tracked 82,496 VA-enrolled veterans eligible for CR from 2021-2023 (3.6% women). Average age of participants were 64.0 years among women and 71.5 years among men. Among women, 58.3% were White, and 31.8% were Black, and 2.24% were Asian. Among men, 71.9% were White, 18.8% were Black, and 2.3% were Asian. 

The rates of CR participation were low among both men (10.4%) and women (10.2%). Older people and Black patients were less likely to take part in CR than younger people and White patients, according to the study. Those who underwent CABG and PCI were more likely to participate in CR compared with those who had heart attacks only.

As for the gap in use between the wealthiest and poorest neighborhoods, Varghese said: “Area deprivation may compound some of the other barriers to CR access, including transportation difficulties, work responsibilities, and out-of-pocket costs.”

How can CR uptake be improved? “A key first step is understanding who can be referred, and second, to spend time discussing the importance of attending with veterans,” Varghese said. “Studies have shown that provider engagement and championing of CR are important positive facilitators that encourage CR participation.

“The VA has been at the forefront of innovation with the home-based CR program that offers veterans a way to attend CR remotely,” she added. “Expanding such novel methods of CR delivery is likely part of the solution to expand CR access.”

Outside Perspective: Make Referrals the Default

Justin Bachmann, MD, MPH, staff physician and research scientist at VA Tennessee Valley Healthcare System, told Federal Practitioner that CR is an American College of Cardiology/American Heart Association Class I recommended secondary prevention therapy following MI, PCI, and CABG “with strong evidence for reduced cardiovascular mortality and improved function and quality of life.”

Still, CR “has been persistently underused for decades as travel, cost, scheduling, and uneven geographic capacity create real logistical barriers,” said Bachmann, who serves as the medical director of a VA Office of Rural Health home-based CR program. 

Bachmann praised the study methodology and offered this advice to colleagues: “Embed CR referral in the post-MI, post-PCI, and post-CABG order sets so that referral is the default. Scale home-based CR well beyond the roughly 40 sites where it is currently available, and track facility-level referral and enrollment rates as quality measures.”

Preventive cardiology specialist Randal J. Thomas, MD, professor of Medicine at the Mayo Clinic in Rochester, Minn., echoed the importance of physician referral to Federal Practitioner.

“Patients can’t actually participate [directly] in most programs. They must have a physician referral,” he said. “The physician referral and the strength of referral is key. If a physician says, ‘You can go there if you want, but it’s not that important,’ the patients aren’t going to go.”

Outside Perspective: VA Deserves Blame

“The VA lags far behind most medical systems,” according to Quinn R. Pack, MD, associate professor of medicine at the University of Massachusetts Chan Medical School-Baystate. “Some of this is probably the patient population—more mental health problems, more smoking, more disease. But I’d squarely put most of this on the VA health system. They haven’t created the systems of care that make attending cardiac rehabilitation easy, reliable, and consistent.”

He noted that that automatic referral combined with a bedside visit by a liaison such as a representative of a CR program can double or triple enrollment.

“When physicians and nurses really encourage patients to go [to CR], these words are powerful,” Pack said. “When a patient enrolls in cardiac rehabilitation, we help them form new habits of exercise.”

No study fundings are reported. The Varghese discloses a relationship with the Veterans Health Administration. Other study authors had no disclosures. Bachmann disclosed a relationship with the VA. Pack and Thomas have no disclosures. 

CHICAGO — Exposure to toxic smoke from military burn pits may be putting millions of US veterans at risk for neurologic disorders, new research suggested, raising fresh questions about the long-term health consequences of a widely used wartime waste-disposal practice.

Investigators found that veterans who lived or worked near the open-air pits — used to burn everything from plastics to medical waste — were significantly more likely to develop conditions including headache and vertigo.

“It’s been estimated that over time, approximately 4 million veterans may have been exposed to the combustion of plastics, metals, medical waste, human waste, and other chemicals,” said study investigator Sarah Anthony, research assistant with the VA Headache Centers of Excellence and the Department of Neurology at Yale School of Medicine, New Haven, Connecticut.

The findings were presented on April 21 at the American Academy of Neurology (AAN) 2026 Annual Meeting.

Toxic Legacy

Open burn pits — large, open-air sites used to burn military waste — were widely used during US deployments in Iraq and Afghanistan after 9/11. The fires produced thick plumes of smoke containing a complex mix of hazardous pollutants, including fine particulate matter, volatile organic compounds, and carcinogenic chemicals, exposing service members who lived and worked nearby.

Amid growing concerns, the Department of Veterans Affairs (VA) established the Airborne Hazards and Open Burn Pit Registry in 2014 to study the long-term health effects of deployment-related airborne exposures, including burn pits, Anthony said.

Since its inception, multiple studies have linked burn pit exposure to respiratory conditions such as chronic bronchitis and chronic obstructive pulmonary disease, as well as cardiovascular issues such as hypertension. More recently, Anthony et al reported an association between burn pit exposure and incident headache.

To better understand whether those risks extend beyond previously reported conditions, the researchers set out to examine the relationship between burn pit exposure and a broader range of neurologic disorders.

Analyzing data from > 245,000 registry participants, researchers found that 66% had ≥ 1 neurologic diagnosis, largely driven by common conditions such as headache.

Those with the highest exposure — living near burn pits and performing related duties — had 36% higher odds of developing a neurologic disorder than less-exposed veterans (odds ratio [OR], 1.36).

The risk for any headache disorder was 57% higher (OR, 1.57) and the risk for vertigo was 25% higher (OR, 1.25) in those with the highest exposure levels than in their peers with lower burn pit exposure.

For every additional 6 months of exposure, the odds of developing any neurologic disorder, headache, or vertigo continued to rise, reinforcing concerns about long-term harm to the brain.

There were no statistically significant associations between burn pit exposure and several other neurologic diseases, including epilepsy and amyotrophic lateral sclerosis.

The researchers also found an inverse association between burn pit exposure and Parkinson’s disease, meaning exposed veterans appeared less likely to be diagnosed with the disorder. However, Anthony cautioned that this may reflect the relatively young age of the study population rather than a true protective effect.

Anthony emphasized that the findings are preliminary and may underestimate long-term risks as many neurologic diseases develop over decades. She also noted that burn pit exposure was based on self-reported registry data, which has the potential to introduce bias.

Additional work is needed to understand the neurologic sequela of deployment-related airborne hazards, including exposure to open burn pits “as this remains important for veteran health policy, long term surveillance, and clinical care,” she said.

Long-term monitoring is critical, particularly as exposed veterans age and further studies should consider leveraging data from the VA toxic exposure screening initiatives, which are now part of routine care, as mandated by the Promise to Address Comprehensive Toxics Act.

Predictable Associations, More Study Needed

These findings, said David D. Lo, MD, PhD, distinguished professor of biomedical sciences, University of California Riverside, School of Medicine, said this is “another study that aims to highlight an association between possible burn pit exposure and a variety of health effects.”

Given the well-established risks of inhaling smoke from burning mixed waste, the findings are not surprising, said Lo, who was not involved in the research.

He noted that the study has important limitations, particularly because exposure was based on self-reports, making it difficult to accurately measure how much smoke individual participants were actually exposed to.

“If these findings are suggestive, it is hoped that they spur very real direct funding for more detailed clinical studies on the mechanisms of how the burn pit exposure would actually be responsible for one or more of the clinical outcomes listed in this study, instead of just adding up more statistical correlations,” said Lo.

This study had no commercial funding. Disclosure information for study authors is available in the original study publication. Lo reported having no relevant disclosures.

A version of this article appeared on Medscape.com.

CHICAGO — Exposure to toxic smoke from military burn pits may be putting millions of US veterans at risk for neurologic disorders, new research suggested, raising fresh questions about the long-term health consequences of a widely used wartime waste-disposal practice.

Investigators found that veterans who lived or worked near the open-air pits — used to burn everything from plastics to medical waste — were significantly more likely to develop conditions including headache and vertigo.

“It’s been estimated that over time, approximately 4 million veterans may have been exposed to the combustion of plastics, metals, medical waste, human waste, and other chemicals,” said study investigator Sarah Anthony, research assistant with the VA Headache Centers of Excellence and the Department of Neurology at Yale School of Medicine, New Haven, Connecticut.

The findings were presented on April 21 at the American Academy of Neurology (AAN) 2026 Annual Meeting.

Toxic Legacy

Open burn pits — large, open-air sites used to burn military waste — were widely used during US deployments in Iraq and Afghanistan after 9/11. The fires produced thick plumes of smoke containing a complex mix of hazardous pollutants, including fine particulate matter, volatile organic compounds, and carcinogenic chemicals, exposing service members who lived and worked nearby.

Amid growing concerns, the Department of Veterans Affairs (VA) established the Airborne Hazards and Open Burn Pit Registry in 2014 to study the long-term health effects of deployment-related airborne exposures, including burn pits, Anthony said.

Since its inception, multiple studies have linked burn pit exposure to respiratory conditions such as chronic bronchitis and chronic obstructive pulmonary disease, as well as cardiovascular issues such as hypertension. More recently, Anthony et al reported an association between burn pit exposure and incident headache.

To better understand whether those risks extend beyond previously reported conditions, the researchers set out to examine the relationship between burn pit exposure and a broader range of neurologic disorders.

Analyzing data from > 245,000 registry participants, researchers found that 66% had ≥ 1 neurologic diagnosis, largely driven by common conditions such as headache.

Those with the highest exposure — living near burn pits and performing related duties — had 36% higher odds of developing a neurologic disorder than less-exposed veterans (odds ratio [OR], 1.36).

The risk for any headache disorder was 57% higher (OR, 1.57) and the risk for vertigo was 25% higher (OR, 1.25) in those with the highest exposure levels than in their peers with lower burn pit exposure.

For every additional 6 months of exposure, the odds of developing any neurologic disorder, headache, or vertigo continued to rise, reinforcing concerns about long-term harm to the brain.

There were no statistically significant associations between burn pit exposure and several other neurologic diseases, including epilepsy and amyotrophic lateral sclerosis.

The researchers also found an inverse association between burn pit exposure and Parkinson’s disease, meaning exposed veterans appeared less likely to be diagnosed with the disorder. However, Anthony cautioned that this may reflect the relatively young age of the study population rather than a true protective effect.

Anthony emphasized that the findings are preliminary and may underestimate long-term risks as many neurologic diseases develop over decades. She also noted that burn pit exposure was based on self-reported registry data, which has the potential to introduce bias.

Additional work is needed to understand the neurologic sequela of deployment-related airborne hazards, including exposure to open burn pits “as this remains important for veteran health policy, long term surveillance, and clinical care,” she said.

Long-term monitoring is critical, particularly as exposed veterans age and further studies should consider leveraging data from the VA toxic exposure screening initiatives, which are now part of routine care, as mandated by the Promise to Address Comprehensive Toxics Act.

Predictable Associations, More Study Needed

These findings, said David D. Lo, MD, PhD, distinguished professor of biomedical sciences, University of California Riverside, School of Medicine, said this is “another study that aims to highlight an association between possible burn pit exposure and a variety of health effects.”

Given the well-established risks of inhaling smoke from burning mixed waste, the findings are not surprising, said Lo, who was not involved in the research.

He noted that the study has important limitations, particularly because exposure was based on self-reports, making it difficult to accurately measure how much smoke individual participants were actually exposed to.

“If these findings are suggestive, it is hoped that they spur very real direct funding for more detailed clinical studies on the mechanisms of how the burn pit exposure would actually be responsible for one or more of the clinical outcomes listed in this study, instead of just adding up more statistical correlations,” said Lo.

This study had no commercial funding. Disclosure information for study authors is available in the original study publication. Lo reported having no relevant disclosures.

A version of this article appeared on Medscape.com.

CHICAGO — Exposure to toxic smoke from military burn pits may be putting millions of US veterans at risk for neurologic disorders, new research suggested, raising fresh questions about the long-term health consequences of a widely used wartime waste-disposal practice.

Investigators found that veterans who lived or worked near the open-air pits — used to burn everything from plastics to medical waste — were significantly more likely to develop conditions including headache and vertigo.

“It’s been estimated that over time, approximately 4 million veterans may have been exposed to the combustion of plastics, metals, medical waste, human waste, and other chemicals,” said study investigator Sarah Anthony, research assistant with the VA Headache Centers of Excellence and the Department of Neurology at Yale School of Medicine, New Haven, Connecticut.

The findings were presented on April 21 at the American Academy of Neurology (AAN) 2026 Annual Meeting.

Toxic Legacy

Open burn pits — large, open-air sites used to burn military waste — were widely used during US deployments in Iraq and Afghanistan after 9/11. The fires produced thick plumes of smoke containing a complex mix of hazardous pollutants, including fine particulate matter, volatile organic compounds, and carcinogenic chemicals, exposing service members who lived and worked nearby.

Amid growing concerns, the Department of Veterans Affairs (VA) established the Airborne Hazards and Open Burn Pit Registry in 2014 to study the long-term health effects of deployment-related airborne exposures, including burn pits, Anthony said.

Since its inception, multiple studies have linked burn pit exposure to respiratory conditions such as chronic bronchitis and chronic obstructive pulmonary disease, as well as cardiovascular issues such as hypertension. More recently, Anthony et al reported an association between burn pit exposure and incident headache.

To better understand whether those risks extend beyond previously reported conditions, the researchers set out to examine the relationship between burn pit exposure and a broader range of neurologic disorders.

Analyzing data from > 245,000 registry participants, researchers found that 66% had ≥ 1 neurologic diagnosis, largely driven by common conditions such as headache.

Those with the highest exposure — living near burn pits and performing related duties — had 36% higher odds of developing a neurologic disorder than less-exposed veterans (odds ratio [OR], 1.36).

The risk for any headache disorder was 57% higher (OR, 1.57) and the risk for vertigo was 25% higher (OR, 1.25) in those with the highest exposure levels than in their peers with lower burn pit exposure.

For every additional 6 months of exposure, the odds of developing any neurologic disorder, headache, or vertigo continued to rise, reinforcing concerns about long-term harm to the brain.

There were no statistically significant associations between burn pit exposure and several other neurologic diseases, including epilepsy and amyotrophic lateral sclerosis.

The researchers also found an inverse association between burn pit exposure and Parkinson’s disease, meaning exposed veterans appeared less likely to be diagnosed with the disorder. However, Anthony cautioned that this may reflect the relatively young age of the study population rather than a true protective effect.

Anthony emphasized that the findings are preliminary and may underestimate long-term risks as many neurologic diseases develop over decades. She also noted that burn pit exposure was based on self-reported registry data, which has the potential to introduce bias.

Additional work is needed to understand the neurologic sequela of deployment-related airborne hazards, including exposure to open burn pits “as this remains important for veteran health policy, long term surveillance, and clinical care,” she said.

Long-term monitoring is critical, particularly as exposed veterans age and further studies should consider leveraging data from the VA toxic exposure screening initiatives, which are now part of routine care, as mandated by the Promise to Address Comprehensive Toxics Act.

Predictable Associations, More Study Needed

These findings, said David D. Lo, MD, PhD, distinguished professor of biomedical sciences, University of California Riverside, School of Medicine, said this is “another study that aims to highlight an association between possible burn pit exposure and a variety of health effects.”

Given the well-established risks of inhaling smoke from burning mixed waste, the findings are not surprising, said Lo, who was not involved in the research.

He noted that the study has important limitations, particularly because exposure was based on self-reports, making it difficult to accurately measure how much smoke individual participants were actually exposed to.

“If these findings are suggestive, it is hoped that they spur very real direct funding for more detailed clinical studies on the mechanisms of how the burn pit exposure would actually be responsible for one or more of the clinical outcomes listed in this study, instead of just adding up more statistical correlations,” said Lo.

This study had no commercial funding. Disclosure information for study authors is available in the original study publication. Lo reported having no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Among US veterans with type 2 diabetes (T2D), adherence to 6 to 8 healthy lifestyle factors combined with GLP‑1 receptor agonist (RA) use was associated with a notably lower risk for major adverse cardiovascular events (MACE) than adherence to three or fewer lifestyle factors without GLP‑1 therapy.

METHODOLOGY:

• GLP-1 RAs help manage cardiovascular risk in patients with T2D; however, lifestyle change remains the foundation of diabetes care. The long-term combined effect of these drugs together with a healthy lifestyle on MACE is not fully understood.
• Researchers conducted a prospective cohort study of 98,261 US veterans with T2D between January 2011 and September 2023, with a follow-up duration of 632,543 person-years, to examine the combined impact of GLP-1 RA use and adherence to eight lifestyle habits on cardiovascular outcomes.
• The 8 low-risk lifestyle habits assessed were healthy eating, regular physical activity (≥ 7.5 metabolic equivalent hours/week), nonsmoking, restful sleep (7-9 hours/day), no or moderate alcohol intake (absence of frequent heavy drinking), good stress management, strong social connection and support, and no opioid use disorder.
• GLP‑1 RA use was ascertained from Veterans Health Administration pharmacy records. The primary outcome was MACE, defined as nonfatal stroke, nonfatal myocardial infarction, or cardiovascular death.

TAKEAWAY:

• Participants adhering to all 8 low-risk lifestyle habits had a 60% lower risk for MACE than those adhering to ≤ 1 (multivariable-adjusted hazard ratio [HR], 0.40; P < .0001).
• All 8 low-risk lifestyle factors were independently associated with a lower risk for MACE, with no opioid use disorder showing the strongest association (HR, 0.77; 95% CI, 0.66-0.89).
• Participants using GLP-1 RAs had a 16% lower risk for MACE than those not receiving GLP-1 therapy and receiving usual care (multivariable-adjusted HR, 0.84; 95% CI, 0.76-0.92).
• Participants using GLP-1 RAs who also adhered to 6 to 8 low-risk lifestyle factors had a 43% lower risk for MACE than those not receiving GLP-1 therapy who adhered to three or fewer lifestyle factors (HR, 0.57; 95% CI, 0.46-0.71).

IN PRACTICE:

"In a healthcare landscape, in which GLP-1 [RAs] remain costly and access is uneven, the additive benefit of lifestyle adherence highlighted by this study has important implications for health equity, resource allocation, and the long-term sustainability of diabetes care," experts noted in an accompanying editorial.

SOURCE:

The study was led by Xuan-Mai T. Nguyen, MD, Department of Medicine, UCLA David Geffen School of Medicine in Los Angeles. It was published online in The Lancet Diabetes & Endocrinology.

LIMITATIONS:

The analyses were based on Veterans Health Administration electronic health record data, and healthcare use outside this system was only incompletely captured. The estimation was based on observational data in which lifestyle factors were assessed at baseline. The cohort consisted of predominantly male veterans, which might limit generalizability to other populations.

DISCLOSURES:

The study used data from the Million Veteran Program (MVP) and was supported by Veterans Affairs MVP awards, along with additional support from other sources. One author reported receiving consulting fees, speaker honoraria, meeting/travel support; participation on advisory boards; and ownership of stock or stock options from certain companies in the healthcare and life sciences sectors. Another author reported receiving a research grant from a consulting/analysis firm.

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

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

TOPLINE:

Among US veterans with type 2 diabetes (T2D), adherence to 6 to 8 healthy lifestyle factors combined with GLP‑1 receptor agonist (RA) use was associated with a notably lower risk for major adverse cardiovascular events (MACE) than adherence to three or fewer lifestyle factors without GLP‑1 therapy.

METHODOLOGY:

• GLP-1 RAs help manage cardiovascular risk in patients with T2D; however, lifestyle change remains the foundation of diabetes care. The long-term combined effect of these drugs together with a healthy lifestyle on MACE is not fully understood.
• Researchers conducted a prospective cohort study of 98,261 US veterans with T2D between January 2011 and September 2023, with a follow-up duration of 632,543 person-years, to examine the combined impact of GLP-1 RA use and adherence to eight lifestyle habits on cardiovascular outcomes.
• The 8 low-risk lifestyle habits assessed were healthy eating, regular physical activity (≥ 7.5 metabolic equivalent hours/week), nonsmoking, restful sleep (7-9 hours/day), no or moderate alcohol intake (absence of frequent heavy drinking), good stress management, strong social connection and support, and no opioid use disorder.
• GLP‑1 RA use was ascertained from Veterans Health Administration pharmacy records. The primary outcome was MACE, defined as nonfatal stroke, nonfatal myocardial infarction, or cardiovascular death.

TAKEAWAY:

• Participants adhering to all 8 low-risk lifestyle habits had a 60% lower risk for MACE than those adhering to ≤ 1 (multivariable-adjusted hazard ratio [HR], 0.40; P < .0001).
• All 8 low-risk lifestyle factors were independently associated with a lower risk for MACE, with no opioid use disorder showing the strongest association (HR, 0.77; 95% CI, 0.66-0.89).
• Participants using GLP-1 RAs had a 16% lower risk for MACE than those not receiving GLP-1 therapy and receiving usual care (multivariable-adjusted HR, 0.84; 95% CI, 0.76-0.92).
• Participants using GLP-1 RAs who also adhered to 6 to 8 low-risk lifestyle factors had a 43% lower risk for MACE than those not receiving GLP-1 therapy who adhered to three or fewer lifestyle factors (HR, 0.57; 95% CI, 0.46-0.71).

IN PRACTICE:

"In a healthcare landscape, in which GLP-1 [RAs] remain costly and access is uneven, the additive benefit of lifestyle adherence highlighted by this study has important implications for health equity, resource allocation, and the long-term sustainability of diabetes care," experts noted in an accompanying editorial.

SOURCE:

The study was led by Xuan-Mai T. Nguyen, MD, Department of Medicine, UCLA David Geffen School of Medicine in Los Angeles. It was published online in The Lancet Diabetes & Endocrinology.

LIMITATIONS:

The analyses were based on Veterans Health Administration electronic health record data, and healthcare use outside this system was only incompletely captured. The estimation was based on observational data in which lifestyle factors were assessed at baseline. The cohort consisted of predominantly male veterans, which might limit generalizability to other populations.

DISCLOSURES:

The study used data from the Million Veteran Program (MVP) and was supported by Veterans Affairs MVP awards, along with additional support from other sources. One author reported receiving consulting fees, speaker honoraria, meeting/travel support; participation on advisory boards; and ownership of stock or stock options from certain companies in the healthcare and life sciences sectors. Another author reported receiving a research grant from a consulting/analysis firm.

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

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

TOPLINE:

Among US veterans with type 2 diabetes (T2D), adherence to 6 to 8 healthy lifestyle factors combined with GLP‑1 receptor agonist (RA) use was associated with a notably lower risk for major adverse cardiovascular events (MACE) than adherence to three or fewer lifestyle factors without GLP‑1 therapy.

METHODOLOGY:

• GLP-1 RAs help manage cardiovascular risk in patients with T2D; however, lifestyle change remains the foundation of diabetes care. The long-term combined effect of these drugs together with a healthy lifestyle on MACE is not fully understood.
• Researchers conducted a prospective cohort study of 98,261 US veterans with T2D between January 2011 and September 2023, with a follow-up duration of 632,543 person-years, to examine the combined impact of GLP-1 RA use and adherence to eight lifestyle habits on cardiovascular outcomes.
• The 8 low-risk lifestyle habits assessed were healthy eating, regular physical activity (≥ 7.5 metabolic equivalent hours/week), nonsmoking, restful sleep (7-9 hours/day), no or moderate alcohol intake (absence of frequent heavy drinking), good stress management, strong social connection and support, and no opioid use disorder.
• GLP‑1 RA use was ascertained from Veterans Health Administration pharmacy records. The primary outcome was MACE, defined as nonfatal stroke, nonfatal myocardial infarction, or cardiovascular death.

TAKEAWAY:

• Participants adhering to all 8 low-risk lifestyle habits had a 60% lower risk for MACE than those adhering to ≤ 1 (multivariable-adjusted hazard ratio [HR], 0.40; P < .0001).
• All 8 low-risk lifestyle factors were independently associated with a lower risk for MACE, with no opioid use disorder showing the strongest association (HR, 0.77; 95% CI, 0.66-0.89).
• Participants using GLP-1 RAs had a 16% lower risk for MACE than those not receiving GLP-1 therapy and receiving usual care (multivariable-adjusted HR, 0.84; 95% CI, 0.76-0.92).
• Participants using GLP-1 RAs who also adhered to 6 to 8 low-risk lifestyle factors had a 43% lower risk for MACE than those not receiving GLP-1 therapy who adhered to three or fewer lifestyle factors (HR, 0.57; 95% CI, 0.46-0.71).

IN PRACTICE:

"In a healthcare landscape, in which GLP-1 [RAs] remain costly and access is uneven, the additive benefit of lifestyle adherence highlighted by this study has important implications for health equity, resource allocation, and the long-term sustainability of diabetes care," experts noted in an accompanying editorial.

SOURCE:

The study was led by Xuan-Mai T. Nguyen, MD, Department of Medicine, UCLA David Geffen School of Medicine in Los Angeles. It was published online in The Lancet Diabetes & Endocrinology.

LIMITATIONS:

The analyses were based on Veterans Health Administration electronic health record data, and healthcare use outside this system was only incompletely captured. The estimation was based on observational data in which lifestyle factors were assessed at baseline. The cohort consisted of predominantly male veterans, which might limit generalizability to other populations.

DISCLOSURES:

The study used data from the Million Veteran Program (MVP) and was supported by Veterans Affairs MVP awards, along with additional support from other sources. One author reported receiving consulting fees, speaker honoraria, meeting/travel support; participation on advisory boards; and ownership of stock or stock options from certain companies in the healthcare and life sciences sectors. Another author reported receiving a research grant from a consulting/analysis firm.

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

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

Women with epithelial ovarian cancer treated in the US Department of Defense (DoD) universal health care system demonstrate better 5-year survival compared with similar patients from the national population. The survival advantage persists across multiple age groups and disease stages, with particularly notable improvements in patients aged 35-49 years and those with stage III disease.

METHODOLOGY:

• Researchers compared 1504 patients with invasive stage I-IV epithelial ovarian carcinoma from the Automated Center Tumor Registry (ACTUR) for the DoD with 6016 matched patients from the 18-region Surveillance, Epidemiology, and End Results (SEER) program between 1987 and 2013.
• Patients from ACTUR were matched in a 1:4 ratio with SEER patients stratified for age, race, year of diagnosis, and histology, including serous carcinoma, clear cell carcinoma, mucinous carcinoma, and endometrioid carcinoma with adenocarcinoma subtypes.
• Five-year overall survival was evaluated using the Kaplan-Meier method and compared using log-rank test, with median follow-up time of 46 months in ACTUR and 44 months in SEER.
• Adjusted hazard ratio (AHR) and 95% CI for all-cause mortality were estimated from multivariable Cox proportional regression modeling controlling for age, race, year of diagnosis, region of diagnosis, stage, histology, and grade.

TAKEAWAY:

• Overall survival differs between registries: 5-year survival of 53.2% in ACTUR vs 47.7% in matched SEER cohort (log-rank P = .001).
• In the primary adjusted model, ACTUR is associated with a lower risk for all-cause mortality vs SEER (AHR, 0.83; 95% CI, 0.76-0.91; P < .0001).
• Subset results retain lower adjusted risk for death for ACTUR vs SEER among ages 35-49 years (AHR, 0.66; 95% CI, 0.52-0.83; P = .0005), ages ≥ 65 years (AHR, 0.82; 95% CI, 0.70-0.96; P = .016), and stage III cancer (AHR, 0.79; 95% CI, 0.69-0.91; P = .0015).
• Histology-stratified findings show lower adjusted risk for death in ACTUR vs SEER for clear cell carcinoma (AHR, 0.63; 95% CI, 0.43-0.93; P =.02) and for endometrioid and other adenocarcinomas (AHR, 0.68; 95% CI, 0.56-0.81; P < .0001).

IN PRACTICE:

"This study is envisioned to be a stepping stone to further investigations of survival and other cancer health outcomes starting with patients diagnosed between 2014 and 2024 with epithelial carcinoma of the ovary, fallopian tube, or primary peritoneum in the DoD Healthcare System versus the national population or other Healthcare Systems,” wrote the authors of the study. “Dedicated funding and support in the [Military Health System] are needed to invest in infrastructure, technology, security, education, and research.”

SOURCE:

The study was led by Kathleen M. Darcy, PhD, and Christopher M. Tarney, MD, from the Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery & Obstetrics, Uniformed Services University, Walter Reed National Military Medical Center in Bethesda, Maryland. It was published online in Military Medicine.

LIMITATIONS:

The retrospective cohort study design limits causal inference. Although groups were balanced by age, race, year, and region of diagnosis, other demographic factors and socioeconomic variables such as patient comorbidities, educational attainment, household income, and health insurance status were not available and may have affected results. The databases fundamentally differ in how data are acquired, with ACTUR following hospital-based Facility Oncology Registry Data Standards and SEER being a national population-based registry, potentially affecting data quality, consistency, and reliability of survival outcome comparisons. The inclusion of patients diagnosed only through 2013 represents a limitation as it does not allow for contemporary evaluation of survival outcomes, particularly given advances over the past decade including maximal cytoreductive effort to no residual disease, increased adoption of neoadjuvant chemotherapy, and introduction of targeted maintenance agents. The study could not incorporate details regarding residual disease status or control for specifics regarding surgical and medical management, including primary vs interval debulking surgery or the type and timing of agents utilized in first-line, maintenance, and recurrent disease settings. Data regarding circulating biomarkers including CA125, molecular subtypes or alterations, and stratification by homologous recombination deficiency vs proficiency status were not available. Epithelial carcinomas of the fallopian tube and primary peritoneum were excluded from this study, which now are commonly incorporated with ovarian carcinomas. Results may not be generalizable to other populations given the unique characteristics of the Military Health System beneficiary population.

DISCLOSURES:

This research received funding from the Uniformed Services University from the Defense Health Program to the Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., including award HU0001-18-2-0032 to the Murtha Cancer Center Research Program and awards HU0001-19-2-0031 and HU0001-24-2-0047 to the Gynecologic Cancer Center of Excellence Program. All coauthors disclosed no 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.

Women with epithelial ovarian cancer treated in the US Department of Defense (DoD) universal health care system demonstrate better 5-year survival compared with similar patients from the national population. The survival advantage persists across multiple age groups and disease stages, with particularly notable improvements in patients aged 35-49 years and those with stage III disease.

METHODOLOGY:

• Researchers compared 1504 patients with invasive stage I-IV epithelial ovarian carcinoma from the Automated Center Tumor Registry (ACTUR) for the DoD with 6016 matched patients from the 18-region Surveillance, Epidemiology, and End Results (SEER) program between 1987 and 2013.
• Patients from ACTUR were matched in a 1:4 ratio with SEER patients stratified for age, race, year of diagnosis, and histology, including serous carcinoma, clear cell carcinoma, mucinous carcinoma, and endometrioid carcinoma with adenocarcinoma subtypes.
• Five-year overall survival was evaluated using the Kaplan-Meier method and compared using log-rank test, with median follow-up time of 46 months in ACTUR and 44 months in SEER.
• Adjusted hazard ratio (AHR) and 95% CI for all-cause mortality were estimated from multivariable Cox proportional regression modeling controlling for age, race, year of diagnosis, region of diagnosis, stage, histology, and grade.

TAKEAWAY:

• Overall survival differs between registries: 5-year survival of 53.2% in ACTUR vs 47.7% in matched SEER cohort (log-rank P = .001).
• In the primary adjusted model, ACTUR is associated with a lower risk for all-cause mortality vs SEER (AHR, 0.83; 95% CI, 0.76-0.91; P < .0001).
• Subset results retain lower adjusted risk for death for ACTUR vs SEER among ages 35-49 years (AHR, 0.66; 95% CI, 0.52-0.83; P = .0005), ages ≥ 65 years (AHR, 0.82; 95% CI, 0.70-0.96; P = .016), and stage III cancer (AHR, 0.79; 95% CI, 0.69-0.91; P = .0015).
• Histology-stratified findings show lower adjusted risk for death in ACTUR vs SEER for clear cell carcinoma (AHR, 0.63; 95% CI, 0.43-0.93; P =.02) and for endometrioid and other adenocarcinomas (AHR, 0.68; 95% CI, 0.56-0.81; P < .0001).

IN PRACTICE:

"This study is envisioned to be a stepping stone to further investigations of survival and other cancer health outcomes starting with patients diagnosed between 2014 and 2024 with epithelial carcinoma of the ovary, fallopian tube, or primary peritoneum in the DoD Healthcare System versus the national population or other Healthcare Systems,” wrote the authors of the study. “Dedicated funding and support in the [Military Health System] are needed to invest in infrastructure, technology, security, education, and research.”

SOURCE:

The study was led by Kathleen M. Darcy, PhD, and Christopher M. Tarney, MD, from the Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery & Obstetrics, Uniformed Services University, Walter Reed National Military Medical Center in Bethesda, Maryland. It was published online in Military Medicine.

LIMITATIONS:

The retrospective cohort study design limits causal inference. Although groups were balanced by age, race, year, and region of diagnosis, other demographic factors and socioeconomic variables such as patient comorbidities, educational attainment, household income, and health insurance status were not available and may have affected results. The databases fundamentally differ in how data are acquired, with ACTUR following hospital-based Facility Oncology Registry Data Standards and SEER being a national population-based registry, potentially affecting data quality, consistency, and reliability of survival outcome comparisons. The inclusion of patients diagnosed only through 2013 represents a limitation as it does not allow for contemporary evaluation of survival outcomes, particularly given advances over the past decade including maximal cytoreductive effort to no residual disease, increased adoption of neoadjuvant chemotherapy, and introduction of targeted maintenance agents. The study could not incorporate details regarding residual disease status or control for specifics regarding surgical and medical management, including primary vs interval debulking surgery or the type and timing of agents utilized in first-line, maintenance, and recurrent disease settings. Data regarding circulating biomarkers including CA125, molecular subtypes or alterations, and stratification by homologous recombination deficiency vs proficiency status were not available. Epithelial carcinomas of the fallopian tube and primary peritoneum were excluded from this study, which now are commonly incorporated with ovarian carcinomas. Results may not be generalizable to other populations given the unique characteristics of the Military Health System beneficiary population.

DISCLOSURES:

This research received funding from the Uniformed Services University from the Defense Health Program to the Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., including award HU0001-18-2-0032 to the Murtha Cancer Center Research Program and awards HU0001-19-2-0031 and HU0001-24-2-0047 to the Gynecologic Cancer Center of Excellence Program. All coauthors disclosed no 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.

Women with epithelial ovarian cancer treated in the US Department of Defense (DoD) universal health care system demonstrate better 5-year survival compared with similar patients from the national population. The survival advantage persists across multiple age groups and disease stages, with particularly notable improvements in patients aged 35-49 years and those with stage III disease.

METHODOLOGY:

• Researchers compared 1504 patients with invasive stage I-IV epithelial ovarian carcinoma from the Automated Center Tumor Registry (ACTUR) for the DoD with 6016 matched patients from the 18-region Surveillance, Epidemiology, and End Results (SEER) program between 1987 and 2013.
• Patients from ACTUR were matched in a 1:4 ratio with SEER patients stratified for age, race, year of diagnosis, and histology, including serous carcinoma, clear cell carcinoma, mucinous carcinoma, and endometrioid carcinoma with adenocarcinoma subtypes.
• Five-year overall survival was evaluated using the Kaplan-Meier method and compared using log-rank test, with median follow-up time of 46 months in ACTUR and 44 months in SEER.
• Adjusted hazard ratio (AHR) and 95% CI for all-cause mortality were estimated from multivariable Cox proportional regression modeling controlling for age, race, year of diagnosis, region of diagnosis, stage, histology, and grade.

TAKEAWAY:

• Overall survival differs between registries: 5-year survival of 53.2% in ACTUR vs 47.7% in matched SEER cohort (log-rank P = .001).
• In the primary adjusted model, ACTUR is associated with a lower risk for all-cause mortality vs SEER (AHR, 0.83; 95% CI, 0.76-0.91; P < .0001).
• Subset results retain lower adjusted risk for death for ACTUR vs SEER among ages 35-49 years (AHR, 0.66; 95% CI, 0.52-0.83; P = .0005), ages ≥ 65 years (AHR, 0.82; 95% CI, 0.70-0.96; P = .016), and stage III cancer (AHR, 0.79; 95% CI, 0.69-0.91; P = .0015).
• Histology-stratified findings show lower adjusted risk for death in ACTUR vs SEER for clear cell carcinoma (AHR, 0.63; 95% CI, 0.43-0.93; P =.02) and for endometrioid and other adenocarcinomas (AHR, 0.68; 95% CI, 0.56-0.81; P < .0001).

IN PRACTICE:

"This study is envisioned to be a stepping stone to further investigations of survival and other cancer health outcomes starting with patients diagnosed between 2014 and 2024 with epithelial carcinoma of the ovary, fallopian tube, or primary peritoneum in the DoD Healthcare System versus the national population or other Healthcare Systems,” wrote the authors of the study. “Dedicated funding and support in the [Military Health System] are needed to invest in infrastructure, technology, security, education, and research.”

SOURCE:

The study was led by Kathleen M. Darcy, PhD, and Christopher M. Tarney, MD, from the Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery & Obstetrics, Uniformed Services University, Walter Reed National Military Medical Center in Bethesda, Maryland. It was published online in Military Medicine.

LIMITATIONS:

The retrospective cohort study design limits causal inference. Although groups were balanced by age, race, year, and region of diagnosis, other demographic factors and socioeconomic variables such as patient comorbidities, educational attainment, household income, and health insurance status were not available and may have affected results. The databases fundamentally differ in how data are acquired, with ACTUR following hospital-based Facility Oncology Registry Data Standards and SEER being a national population-based registry, potentially affecting data quality, consistency, and reliability of survival outcome comparisons. The inclusion of patients diagnosed only through 2013 represents a limitation as it does not allow for contemporary evaluation of survival outcomes, particularly given advances over the past decade including maximal cytoreductive effort to no residual disease, increased adoption of neoadjuvant chemotherapy, and introduction of targeted maintenance agents. The study could not incorporate details regarding residual disease status or control for specifics regarding surgical and medical management, including primary vs interval debulking surgery or the type and timing of agents utilized in first-line, maintenance, and recurrent disease settings. Data regarding circulating biomarkers including CA125, molecular subtypes or alterations, and stratification by homologous recombination deficiency vs proficiency status were not available. Epithelial carcinomas of the fallopian tube and primary peritoneum were excluded from this study, which now are commonly incorporated with ovarian carcinomas. Results may not be generalizable to other populations given the unique characteristics of the Military Health System beneficiary population.

DISCLOSURES:

This research received funding from the Uniformed Services University from the Defense Health Program to the Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., including award HU0001-18-2-0032 to the Murtha Cancer Center Research Program and awards HU0001-19-2-0031 and HU0001-24-2-0047 to the Gynecologic Cancer Center of Excellence Program. All coauthors disclosed no 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.

Wildfire smoke exposure may be associated with increased risks for multiple types of cancer, suggests an analysis of prospective cohort data from over 90,000 individuals.

To determine how this widespread pollution might be affecting cancer risk, senior author Shuguang Leng, MBBS, PhD, and colleagues analyzed data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. That prospective national study enrolled approximately 154,000 participants between 1993 and 2001 and tracked cancer incidence through 2018. Of these, 91,460 participants had wildfire smoke exposure data and were included in the analysis.

During the 2006-2018 exposure period, the investigators identified incident cases of 242 ovarian, 800 colorectal, 896 bladder, 1696 hematopoietic, 1739 breast, and 1758 lung cancers, as well as 1127 melanoma cases. The median 36-month moving average for wildfire smoke PM_2.5 (fine particulate matter) across the cohort was 0.37 µg/m³.

Wildfire smoke exposure was significantly associated with increased risks for lung, colorectal, breast, bladder, and hematopoietic cancer, according to the results of the study presented by Leng at American Association for Cancer Research (AACR) Annual Meeting 2026.

Each 1 µg/m³ increase in the 36-month moving average of wildfire smoke PM_2.5 was associated with a 63% higher risk for hematopoietic cancer (HR, 1.63; 95% CI, 1.02-2.60), a nearly twofold higher risk for lung cancer (hazard ratio [HR], 1.92; 95% CI, 1.18-3.15), more than twofold higher risks for breast cancer (HR, 2.09; 95% CI, 1.34-3.26) and colorectal cancer (HR, 2.31; 95% CI, 1.11-4.81), and a more than threefold higher risk for bladder cancer (HR, 3.49; 95% CI, 1.66-7.34). No significant associations were observed for ovarian cancer or melanoma.

The investigators quantified wildfire smoke exposure at each participant’s residence on a monthly basis using three measures: near-ground wildfire smoke PM_2.5, wildfire smoke black carbon, and satellite-derived wildfire smoke plume-day counts, with measurements available from 2006 until first cancer diagnosis or last contact.

Given evidence that 3 years of air pollution exposure can influence the development of epidermal growth factor receptor-positive lung adenocarcinoma, the team modeled exposure as a time-varying variable using 36-month moving averages preceding each month. HRs were estimated using Cox proportional hazards models stratified by study center, with restricted cubic splines applied to evaluate dose-response relationships. Models were adjusted for age, sex, race and ethnicity, education, smoking history, BMI, and trial arm.

All five cancer types linked with wildfire smoke exposure showed linear dose-response relationships, Leng noted, “which means the higher the exposure, the higher the cancer risk.”

Results based on wildfire smoke plume-day counts were generally consistent with those for PM_2.5, while associations for black carbon exposure were observed only for breast and bladder cancers.

With wildfires on the rise, these findings suggest that the resulting smoke may become a “major driver for cancer burden in the US in the coming decades,” said Leng, of the University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico.

“Wildfire smoke has become a major source of air pollution in the United States,” he continued. Large fires in the US are three times more common than they were 50 years ago, and the “tons of toxicants and particles” released by these fires “can travel hundreds of miles to affect communities far away.”

The investigators also conducted histology-specific analyses, finding that adenocarcinoma showed the strongest association with wildfire smoke among lung cancer subtypes. Among colorectal cancers, proximal tumors appeared more sensitive to wildfire smoke exposure, while among bladder cancers, the association was strongest for muscle-invasive disease.

Wildfire Smoke Exposure Expected to Rise

Under even the most conservative climate projections, wildfire smoke exposure in the US is expected to rise over the next 20-30 years, Leng said.

Annual average wildfire smoke PM_2.5 levels, currently estimated at around 0.5 µg/m³, could rise to 1 µg/m³. Based on the study’s dose-response data, this would correspond to substantially greater cancer risk.

There will be “a much larger area” of the US exposed “at a much higher dose,” Leng predicted.

Mitigating the Risks of Wildfire Smoke

This is a “strong hypothesis-generating study,” Jun Wu, PhD, professor of environmental and occupational health at the UC Irvine Program in Public Health, Irvine, California, told Medscape Medical News.

“This is one of the first large, prospective US cohort studies to examine wildfire smoke specifically in relation to cancer risk, especially cancer sites beyond the lung,” Wu said. “A major strength is that the PLCO platform has around 91,000 participants with longitudinal follow-up and detailed covariate data, including smoking history, which is often a weak point in previous air pollution-cancer studies.”

According to Wu, who was not involved in the analysis but recently published data linking wildfire smoke exposure to preterm birth, the reported risks for colorectal, breast, bladder, and hematopoietic cancers represent novel contributions to the literature. However, she cautioned against viewing the specific HRs as a precise estimates of risk due to wide confidence intervals.

The findings should encourage individuals, public health officials, and clinicians to mitigate the risks of wildfire smoke, Wu said.

Specifically, she suggested that public health assessments expand beyond acute outcomes like emergency department visits to include long-term endpoints such as cancer, while community clean-air shelters need to be made more widely available.

She advised clinicians to incorporate wildfire exposure into routine patient histories and to provide vulnerable patients — such as those with asthma, chronic obstructive pulmonary disease, heart failure, or pregnancy — with smoke-season action plans.

Risk mitigation begins with awareness, according to Wu, who advised individuals check their local air quality index on AirNow.gov or PurpleAir.

On smoky days, she suggested prioritizing indoor air quality by keeping windows closed and running air purifiers. If going outside on such days is necessary, she suggested an N95 or KN95 mask, as these offer “meaningful protection,” while cloth and surgical masks do not.

These preventive steps may have once been out of the ordinary, Wu said, but the risk for wildfire smoke exposure is becoming a part of everyday life.

“The common thread is a shift in framing,” Wu said. “Wildfire smoke has traditionally been treated as an acute event, but the emerging evidence points to a chronic environmental exposure. Both our clinical and public health systems have room to grow into that reality.”

The analysis was funded by the National Institutes of Health. The investigators and Wu reported having no conflicts of interest.

This article was previously published on Medscape.

Wildfire smoke exposure may be associated with increased risks for multiple types of cancer, suggests an analysis of prospective cohort data from over 90,000 individuals.

To determine how this widespread pollution might be affecting cancer risk, senior author Shuguang Leng, MBBS, PhD, and colleagues analyzed data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. That prospective national study enrolled approximately 154,000 participants between 1993 and 2001 and tracked cancer incidence through 2018. Of these, 91,460 participants had wildfire smoke exposure data and were included in the analysis.

During the 2006-2018 exposure period, the investigators identified incident cases of 242 ovarian, 800 colorectal, 896 bladder, 1696 hematopoietic, 1739 breast, and 1758 lung cancers, as well as 1127 melanoma cases. The median 36-month moving average for wildfire smoke PM_2.5 (fine particulate matter) across the cohort was 0.37 µg/m³.

Wildfire smoke exposure was significantly associated with increased risks for lung, colorectal, breast, bladder, and hematopoietic cancer, according to the results of the study presented by Leng at American Association for Cancer Research (AACR) Annual Meeting 2026.

Each 1 µg/m³ increase in the 36-month moving average of wildfire smoke PM_2.5 was associated with a 63% higher risk for hematopoietic cancer (HR, 1.63; 95% CI, 1.02-2.60), a nearly twofold higher risk for lung cancer (hazard ratio [HR], 1.92; 95% CI, 1.18-3.15), more than twofold higher risks for breast cancer (HR, 2.09; 95% CI, 1.34-3.26) and colorectal cancer (HR, 2.31; 95% CI, 1.11-4.81), and a more than threefold higher risk for bladder cancer (HR, 3.49; 95% CI, 1.66-7.34). No significant associations were observed for ovarian cancer or melanoma.

The investigators quantified wildfire smoke exposure at each participant’s residence on a monthly basis using three measures: near-ground wildfire smoke PM_2.5, wildfire smoke black carbon, and satellite-derived wildfire smoke plume-day counts, with measurements available from 2006 until first cancer diagnosis or last contact.

Given evidence that 3 years of air pollution exposure can influence the development of epidermal growth factor receptor-positive lung adenocarcinoma, the team modeled exposure as a time-varying variable using 36-month moving averages preceding each month. HRs were estimated using Cox proportional hazards models stratified by study center, with restricted cubic splines applied to evaluate dose-response relationships. Models were adjusted for age, sex, race and ethnicity, education, smoking history, BMI, and trial arm.

All five cancer types linked with wildfire smoke exposure showed linear dose-response relationships, Leng noted, “which means the higher the exposure, the higher the cancer risk.”

Results based on wildfire smoke plume-day counts were generally consistent with those for PM_2.5, while associations for black carbon exposure were observed only for breast and bladder cancers.

With wildfires on the rise, these findings suggest that the resulting smoke may become a “major driver for cancer burden in the US in the coming decades,” said Leng, of the University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico.

“Wildfire smoke has become a major source of air pollution in the United States,” he continued. Large fires in the US are three times more common than they were 50 years ago, and the “tons of toxicants and particles” released by these fires “can travel hundreds of miles to affect communities far away.”

The investigators also conducted histology-specific analyses, finding that adenocarcinoma showed the strongest association with wildfire smoke among lung cancer subtypes. Among colorectal cancers, proximal tumors appeared more sensitive to wildfire smoke exposure, while among bladder cancers, the association was strongest for muscle-invasive disease.

Wildfire Smoke Exposure Expected to Rise

Under even the most conservative climate projections, wildfire smoke exposure in the US is expected to rise over the next 20-30 years, Leng said.

Annual average wildfire smoke PM_2.5 levels, currently estimated at around 0.5 µg/m³, could rise to 1 µg/m³. Based on the study’s dose-response data, this would correspond to substantially greater cancer risk.

There will be “a much larger area” of the US exposed “at a much higher dose,” Leng predicted.

Mitigating the Risks of Wildfire Smoke

This is a “strong hypothesis-generating study,” Jun Wu, PhD, professor of environmental and occupational health at the UC Irvine Program in Public Health, Irvine, California, told Medscape Medical News.

“This is one of the first large, prospective US cohort studies to examine wildfire smoke specifically in relation to cancer risk, especially cancer sites beyond the lung,” Wu said. “A major strength is that the PLCO platform has around 91,000 participants with longitudinal follow-up and detailed covariate data, including smoking history, which is often a weak point in previous air pollution-cancer studies.”

According to Wu, who was not involved in the analysis but recently published data linking wildfire smoke exposure to preterm birth, the reported risks for colorectal, breast, bladder, and hematopoietic cancers represent novel contributions to the literature. However, she cautioned against viewing the specific HRs as a precise estimates of risk due to wide confidence intervals.

The findings should encourage individuals, public health officials, and clinicians to mitigate the risks of wildfire smoke, Wu said.

Specifically, she suggested that public health assessments expand beyond acute outcomes like emergency department visits to include long-term endpoints such as cancer, while community clean-air shelters need to be made more widely available.

She advised clinicians to incorporate wildfire exposure into routine patient histories and to provide vulnerable patients — such as those with asthma, chronic obstructive pulmonary disease, heart failure, or pregnancy — with smoke-season action plans.

Risk mitigation begins with awareness, according to Wu, who advised individuals check their local air quality index on AirNow.gov or PurpleAir.

On smoky days, she suggested prioritizing indoor air quality by keeping windows closed and running air purifiers. If going outside on such days is necessary, she suggested an N95 or KN95 mask, as these offer “meaningful protection,” while cloth and surgical masks do not.

These preventive steps may have once been out of the ordinary, Wu said, but the risk for wildfire smoke exposure is becoming a part of everyday life.

“The common thread is a shift in framing,” Wu said. “Wildfire smoke has traditionally been treated as an acute event, but the emerging evidence points to a chronic environmental exposure. Both our clinical and public health systems have room to grow into that reality.”

The analysis was funded by the National Institutes of Health. The investigators and Wu reported having no conflicts of interest.

This article was previously published on Medscape.

Wildfire smoke exposure may be associated with increased risks for multiple types of cancer, suggests an analysis of prospective cohort data from over 90,000 individuals.

To determine how this widespread pollution might be affecting cancer risk, senior author Shuguang Leng, MBBS, PhD, and colleagues analyzed data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. That prospective national study enrolled approximately 154,000 participants between 1993 and 2001 and tracked cancer incidence through 2018. Of these, 91,460 participants had wildfire smoke exposure data and were included in the analysis.

During the 2006-2018 exposure period, the investigators identified incident cases of 242 ovarian, 800 colorectal, 896 bladder, 1696 hematopoietic, 1739 breast, and 1758 lung cancers, as well as 1127 melanoma cases. The median 36-month moving average for wildfire smoke PM_2.5 (fine particulate matter) across the cohort was 0.37 µg/m³.

Wildfire smoke exposure was significantly associated with increased risks for lung, colorectal, breast, bladder, and hematopoietic cancer, according to the results of the study presented by Leng at American Association for Cancer Research (AACR) Annual Meeting 2026.

Each 1 µg/m³ increase in the 36-month moving average of wildfire smoke PM_2.5 was associated with a 63% higher risk for hematopoietic cancer (HR, 1.63; 95% CI, 1.02-2.60), a nearly twofold higher risk for lung cancer (hazard ratio [HR], 1.92; 95% CI, 1.18-3.15), more than twofold higher risks for breast cancer (HR, 2.09; 95% CI, 1.34-3.26) and colorectal cancer (HR, 2.31; 95% CI, 1.11-4.81), and a more than threefold higher risk for bladder cancer (HR, 3.49; 95% CI, 1.66-7.34). No significant associations were observed for ovarian cancer or melanoma.

The investigators quantified wildfire smoke exposure at each participant’s residence on a monthly basis using three measures: near-ground wildfire smoke PM_2.5, wildfire smoke black carbon, and satellite-derived wildfire smoke plume-day counts, with measurements available from 2006 until first cancer diagnosis or last contact.

Given evidence that 3 years of air pollution exposure can influence the development of epidermal growth factor receptor-positive lung adenocarcinoma, the team modeled exposure as a time-varying variable using 36-month moving averages preceding each month. HRs were estimated using Cox proportional hazards models stratified by study center, with restricted cubic splines applied to evaluate dose-response relationships. Models were adjusted for age, sex, race and ethnicity, education, smoking history, BMI, and trial arm.

All five cancer types linked with wildfire smoke exposure showed linear dose-response relationships, Leng noted, “which means the higher the exposure, the higher the cancer risk.”

Results based on wildfire smoke plume-day counts were generally consistent with those for PM_2.5, while associations for black carbon exposure were observed only for breast and bladder cancers.

With wildfires on the rise, these findings suggest that the resulting smoke may become a “major driver for cancer burden in the US in the coming decades,” said Leng, of the University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico.

“Wildfire smoke has become a major source of air pollution in the United States,” he continued. Large fires in the US are three times more common than they were 50 years ago, and the “tons of toxicants and particles” released by these fires “can travel hundreds of miles to affect communities far away.”

The investigators also conducted histology-specific analyses, finding that adenocarcinoma showed the strongest association with wildfire smoke among lung cancer subtypes. Among colorectal cancers, proximal tumors appeared more sensitive to wildfire smoke exposure, while among bladder cancers, the association was strongest for muscle-invasive disease.

Wildfire Smoke Exposure Expected to Rise

Under even the most conservative climate projections, wildfire smoke exposure in the US is expected to rise over the next 20-30 years, Leng said.

Annual average wildfire smoke PM_2.5 levels, currently estimated at around 0.5 µg/m³, could rise to 1 µg/m³. Based on the study’s dose-response data, this would correspond to substantially greater cancer risk.

There will be “a much larger area” of the US exposed “at a much higher dose,” Leng predicted.

Mitigating the Risks of Wildfire Smoke

This is a “strong hypothesis-generating study,” Jun Wu, PhD, professor of environmental and occupational health at the UC Irvine Program in Public Health, Irvine, California, told Medscape Medical News.

“This is one of the first large, prospective US cohort studies to examine wildfire smoke specifically in relation to cancer risk, especially cancer sites beyond the lung,” Wu said. “A major strength is that the PLCO platform has around 91,000 participants with longitudinal follow-up and detailed covariate data, including smoking history, which is often a weak point in previous air pollution-cancer studies.”

According to Wu, who was not involved in the analysis but recently published data linking wildfire smoke exposure to preterm birth, the reported risks for colorectal, breast, bladder, and hematopoietic cancers represent novel contributions to the literature. However, she cautioned against viewing the specific HRs as a precise estimates of risk due to wide confidence intervals.

The findings should encourage individuals, public health officials, and clinicians to mitigate the risks of wildfire smoke, Wu said.

Specifically, she suggested that public health assessments expand beyond acute outcomes like emergency department visits to include long-term endpoints such as cancer, while community clean-air shelters need to be made more widely available.

She advised clinicians to incorporate wildfire exposure into routine patient histories and to provide vulnerable patients — such as those with asthma, chronic obstructive pulmonary disease, heart failure, or pregnancy — with smoke-season action plans.

Risk mitigation begins with awareness, according to Wu, who advised individuals check their local air quality index on AirNow.gov or PurpleAir.

On smoky days, she suggested prioritizing indoor air quality by keeping windows closed and running air purifiers. If going outside on such days is necessary, she suggested an N95 or KN95 mask, as these offer “meaningful protection,” while cloth and surgical masks do not.

These preventive steps may have once been out of the ordinary, Wu said, but the risk for wildfire smoke exposure is becoming a part of everyday life.

“The common thread is a shift in framing,” Wu said. “Wildfire smoke has traditionally been treated as an acute event, but the emerging evidence points to a chronic environmental exposure. Both our clinical and public health systems have room to grow into that reality.”

The analysis was funded by the National Institutes of Health. The investigators and Wu reported having no conflicts of interest.

This article was previously published on Medscape.

Veterans are at higher risk for suicide compared with civilian populations.¹ Firearms are the most frequent cause of death in veteran deaths by suicide, likely because about 51% of veterans own ≥ 1 firearms and firearms are the most lethal and readily available mechanism.^1-3 Unsecure firearm storage practices (eg, storing firearms unlocked, in an unsecure location, or loaded with ammunition) are associated with increased suicide risk.⁴ Conversely, secure firearm storage (ie, storing firearms locked and unloaded) is associated with lower suicide risk.⁵

A 2019 study of veterans who own firearms found that only 22.2% store all their firearms unloaded and locked, while 32.7% store ≥ 1 firearm unlocked and loaded, and 45.2% store firearms both unlocked and loaded or locked and unloaded. Only 6.3% of veterans strongly agreed that having a firearm at home increased suicide risk among household members; however, 77.2% indicated they would ensure a household member could not access firearms if they were concerned about their suicidal ideation.⁶

Another study found that 9.2% of veterans receive lethal means safety counseling from their US Department of Veterans Affairs (VA)-affiliated or non-VA health care professional.⁷ These data highlight a need to educate veterans about the increased risk for suicide associated with storing an unsecured firearm in the household and to connect this understanding to their values of service and protection of others, while simultaneously preparing them and their family members for a potential mental health crisis.

Consistent with the government’s public health approach to suicide prevention, prevention efforts should also enlist the participation of individuals outside health care.⁸ For example, prior research has found that family members are considered highly credible, and engaging them could expand the reach of lethal means safety conversations. A qualitative analysis of 29 veterans found that 17 (57%) said they preferred having a concerned significant other (CSO) (eg, spouse, adult friend, or relative) involved in their suicide prevention care, while 21 (72%) said they would prefer having a CSO assisting in the secure storage of firearms.^9,10 Some veterans may be more amenable to a conversation about firearm access and suicide risk concerns initiated by a CSO rather than by a clinician, indicating the potential benefits of educating and involving CSOs in suicide prevention.¹¹ Involving CSOs in secure firearm storage planning may also strengthen the veteran’s sense of social support, a key protective factor against suicidal ideation.¹²

CSO involvement in secure firearm storage can provide the following benefits: (1) helping the veteran create a secure storage plan, including developing approaches to secure storage; (2) understanding warning signs of suicide; (3) helping the veteran limit access to firearms during a suicidal crisis; (4) helping the veteran remember the secure storage plan; (5) helping the veteran connect with mental health services; and (6) enhancing social support. In most instances, CSOs are physically close to the veteran (eg, live in the same household) and have a greater practical ability to support and affect change with respect to changes in firearm storage practices.

This article describes the development of an intervention that incorporates CSO involvement in firearms safety efforts for veterans with guidance from VA mental health care practitioners (HCPs). The goal is to provide HCPs and other key stakeholders with a detailed description of the intervention and to suggest potential strategies for how to involve CSOs in suicide prevention.

This article follows the Guideline for Reporting Evidence-based Practice Educational interventions and Teaching checklist, which was developed to facilitate standardized reporting and replication for education interventions.¹³ Applicable portions of the checklist are outlined, with others (ie, incentives, planned/unplanned changes, attendance, and other outcomes) to be addressed in future research.

FFAST INTERVENTION

Training (FFAST) intervention promotes voluntary secure firearm storage, engages CSOs in veteran mental health care, and provides psychoeducation and skills to support crisis management. The intervention was developed for all veterans who do not securely store firearms.

Theory

The intervention incorporates motivational interviewing techniques, as ambivalence about changing firearm storage behaviors is common, particularly when veterans own firearms for safety or protection.^6,14 Motivational interviewing is a collaborative approach that addresses a client’s ambivalence to change by eliciting and exploring the client’s own arguments related to change.¹⁴ An important aspect of developing this intervention was to ensure it would be culturally relevant to veteran firearm owners and their CSOs.¹⁵ Further, involvement of the CSO is intentional and meant to boost social support, a known buffering factor against suicide risk.¹²

Objectives

This intervention’s primary objective was for veteran participants to identify secure firearm storage practices and develop a plan for implementing them, including when a veteran or other household member experiences a mental health crisis. For CSOs, the primary objective is to learn how to help the veteran connect with mental health resources if needed and support secure firearm storage as necessary. The overall goal is to learn how to identify warning signs for suicide and how to respond to a mental health crisis through a collaborative process, including securing firearms in a crisis situation.

Materials, Educational Strategies, and Instructors

Training for delivering the intervention was provided via direct consultation with the developer of the intervention and manual. The manual contains pertinent background information to provide context for the intervention’s significance and rationale, including the role of firearms in suicides and current lethal means safety initiatives. It also describes the purpose and objective of each intervention component in detail in addition to providing a script for interventionists to follow to complete each objective.

Training materials for veterans and CSOs include a single Firearms Secure Storage Planning worksheet completed during the intervention, with which the interventionist guides participants through the creation of a secure firearm storage plan (Table). Educational strategies include psychoeducation and Socratic questioning (eg, questioning focused on guiding participants toward the intervention goals) delivered verbally by the interventionist.

The intervention is delivered in person or virtually during a single 90-minute session with a veteran and CSO. Veterans and CSOs work with the interventionist to complete collaborative activities during the session and have self-directive learning activities or homework.

The intervention has 4 primary components: (1) CSO involvement; (2) psychoeducation; (3) secure firearm storage; and (4) how to respond to a mental health crisis. Each CSO should have an established relationship with the veteran, be willing and able to be present during the intervention, and remain an encouraging support person for the veteran. The interventionist emphasizes that it is part of the VA mission for staff to care about the veteran, and that initiating such contact with a CSO is meant to prioritize veteran safety and the safety of their family. Psychoeducation on mental health symptoms, suicide warning signs, veteran suicide rates and lethal means, and the benefits of secure firearm storage, is incorporated in the intervention.

The secure firearm storage component consists of 7 subcomponents: (1) general lethal means secure storage; (2) warning signs; (3) dyad communication; (4) lethal means safety when symptoms emerge; (5) coping strategies; (6) social support; and (7) emergency contacts. A lethal means safety worksheet rooted in the Stanley and Brown suicide safety plan model and implemented in VA health care settings is used to facilitate discussions of secure storage (Appendix).¹⁶

CSOs typically have little or no suicidal crisis response training, yet they likely have more interaction with the veteran on a daily basis than HCPs, putting them in a vital position to identify a crisis early and connect the veteran with the proper care. The crisis component prepares the CSO and veteran to navigate a crisis scenario so they can practice their newly developed safety plan and increase their comfort in discussing mental health and suicidal crisis.

FICTIONAL CASE STUDY

Cole, aged 59 years, is a Persian Gulf War veteran and retired police officer. His medical history includes hypothyroidism, hypertension, type 2 diabetes mellitus, chronic posttraumatic stress disorder, major depressive disorder, and insomnia.

Cole's wife of > 30 years, Sheila, joined him for the FFAST intervention. They report having 4 firearms in the home, 3 of which are loaded but stored in a lockbox and 1 that Cole reports is kept on his person for protection. Cole reports passive suicidal ideation, but no plans or intent. When discussing warning signs that a mental health crisis is building, Cole describes feeling anxious, having a change in his speech patterns, and isolating himself. Sheila agrees, but also mentions that Cole is easily angered and becomes nonverbal. Cole and Sheila express difficulty communicating and appear to have a breakthrough moment when Cole says he does not like when Sheila repeats herself, as he feels like she is “poking” at him. Sheila shares concerns for his safety and that she only repeats herself because he refuses to talk.

Cole agrees to verbalize that he is safe but needs time to process his thoughts. Sheila agrees to give him space with a plan to revisit the conversation within an agreed upon timeline. When discussing an updated secure storage plan for their firearms when a mental health crisis is building, Cole commits to allowing Sheila to store the firearm currently on his person in their gun safe, with the ammunition stored separately, and to giving her the gun safe key. They agree to implement this practice until the mental health crisis has passed.

To mitigate a potential crisis, the interventionist discusses possible internal coping strategies for Cole, including writing, reading, walking the dog, listening to music, and baking. People and social settings that could provide distraction involve going to the gym, talking to his friend Carl or his daughter Kelly, and attending the men’s ministry at church. The intervention concludes by discussing professionals or agencies that Cole and Sheila could contact during a crisis. After the intervention, Cole and Sheila are asked to rate their likelihood of using the plan they established during the conversation on a scale of 0 to 10, with 0 being highly unlikely and 10 being extremely likely. Cole responds with 9 and Sheila responds with 10.

DISCUSSION

Lethal means safety remains a critical component of veteran suicide prevention. However, lethal means safety discussions are often implemented after suicide risk has been identified, which may be too late. Thus, having these conversations early and before a crisis may be imperative. Veterans have expressed a desire to have CSOs involved in their suicide prevention treatment, and CSOs can play a key role in recognizing risk factors during everyday life. The FFAST intervention addresses many of these gaps.

Having discussions in advance of a crisis allows veterans to consider an effective secure firearm storage plan outside of the context of a crisis. Including a CSO galvanizes another person to understand a veteran’s needs and assist with secure firearm storage, identify warning signs, and support them during a crisis. These discussions occur in a context where there is less pressure than during a crisis. Features that were more appealing to veterans and their CSOs were also incorporated, such as having the dyad build a plan that is conceptually similar to other public safety initiatives (eg, a fire safety plan, tornado plan, or hurricane plan). Previous research demonstrates that veterans appreciated the nonjudgmental approach and some preferred that clinicians approach the discussion of secure firearm storage within the context of general home and family safety.¹⁷ Additionally, this intervention can build on veterans’ prior military training in preparedness.

Other potential benefits associated with the FFAST intervention include creating an opportunity to strengthen communication between the veteran and CSO. While FFAST is intended to be used with all types of CSOs, this work is consistent with preliminary data from a couples-based suicide prevention study that indicated veterans and their partners reported increases in relationship functioning and marginal decreases in suicidal ideation.¹⁸ It is possible that communication strategies gained from the current intervention could improve veterans’ relationships with their CSOs, which are associated with a greater sense of social support and reduced suicide risk.¹²

The intervention is a brief, single session that may be appealing to veterans and CSOs with full schedules. Evidence suggests that even brief, single-session interventions have a significant impact on beliefs about secure firearm storage, knowledge of lethal means safety, and confidence in having secure firearm storage conversations.¹⁹ However, clinicians should be cautious when extrapolating from the findings of the current case example, which was a one-time intervention with no follow-up.

Future Directions

Pilot testing of the proposed intervention is underway, and future research will include feedback from veterans and CSOs, as well as feasibility and acceptability data collected during the pilot process. The pilot study uses a successive cohort design with an initial 2 sets of 5 veteran and CSO dyads, and subsequent funding has expanded the pilot study to include an additional 30 dyads. Qualitative interviews will be conducted separately with each veteran and CSO, and additional constructs such as feasibility, acceptability, barriers and facilitators to implementation, and changes in secure storage will be examined. This future research may provide a deeper understanding of the broader acceptability, feasibility, and satisfaction associated with a suicide prevention intervention focused on securing firearms and involving veterans and their CSOs. These data could be used to inform future implementation trials and inform the development of an implementation strategy. In the interim, the nature of the manual is summarized in the context of the urgency of suicide prevention in this at-risk population.

Conclusions

FFAST is a novel approach to veteran firearm suicide prevention. By involving CSOs and emphasizing mental health crisis preparedness between them and veterans, the dyad can work in association with HCPs to establish and exercise secure firearm storage practices as part of an at-home safety plan. Implementation of FFAST may be beneficial for all veterans, not only those who have been identified as being at high suicide risk.

Veterans are at higher risk for suicide compared with civilian populations.¹ Firearms are the most frequent cause of death in veteran deaths by suicide, likely because about 51% of veterans own ≥ 1 firearms and firearms are the most lethal and readily available mechanism.^1-3 Unsecure firearm storage practices (eg, storing firearms unlocked, in an unsecure location, or loaded with ammunition) are associated with increased suicide risk.⁴ Conversely, secure firearm storage (ie, storing firearms locked and unloaded) is associated with lower suicide risk.⁵

A 2019 study of veterans who own firearms found that only 22.2% store all their firearms unloaded and locked, while 32.7% store ≥ 1 firearm unlocked and loaded, and 45.2% store firearms both unlocked and loaded or locked and unloaded. Only 6.3% of veterans strongly agreed that having a firearm at home increased suicide risk among household members; however, 77.2% indicated they would ensure a household member could not access firearms if they were concerned about their suicidal ideation.⁶

Another study found that 9.2% of veterans receive lethal means safety counseling from their US Department of Veterans Affairs (VA)-affiliated or non-VA health care professional.⁷ These data highlight a need to educate veterans about the increased risk for suicide associated with storing an unsecured firearm in the household and to connect this understanding to their values of service and protection of others, while simultaneously preparing them and their family members for a potential mental health crisis.

Consistent with the government’s public health approach to suicide prevention, prevention efforts should also enlist the participation of individuals outside health care.⁸ For example, prior research has found that family members are considered highly credible, and engaging them could expand the reach of lethal means safety conversations. A qualitative analysis of 29 veterans found that 17 (57%) said they preferred having a concerned significant other (CSO) (eg, spouse, adult friend, or relative) involved in their suicide prevention care, while 21 (72%) said they would prefer having a CSO assisting in the secure storage of firearms.^9,10 Some veterans may be more amenable to a conversation about firearm access and suicide risk concerns initiated by a CSO rather than by a clinician, indicating the potential benefits of educating and involving CSOs in suicide prevention.¹¹ Involving CSOs in secure firearm storage planning may also strengthen the veteran’s sense of social support, a key protective factor against suicidal ideation.¹²

CSO involvement in secure firearm storage can provide the following benefits: (1) helping the veteran create a secure storage plan, including developing approaches to secure storage; (2) understanding warning signs of suicide; (3) helping the veteran limit access to firearms during a suicidal crisis; (4) helping the veteran remember the secure storage plan; (5) helping the veteran connect with mental health services; and (6) enhancing social support. In most instances, CSOs are physically close to the veteran (eg, live in the same household) and have a greater practical ability to support and affect change with respect to changes in firearm storage practices.

This article describes the development of an intervention that incorporates CSO involvement in firearms safety efforts for veterans with guidance from VA mental health care practitioners (HCPs). The goal is to provide HCPs and other key stakeholders with a detailed description of the intervention and to suggest potential strategies for how to involve CSOs in suicide prevention.

This article follows the Guideline for Reporting Evidence-based Practice Educational interventions and Teaching checklist, which was developed to facilitate standardized reporting and replication for education interventions.¹³ Applicable portions of the checklist are outlined, with others (ie, incentives, planned/unplanned changes, attendance, and other outcomes) to be addressed in future research.

FFAST INTERVENTION

Training (FFAST) intervention promotes voluntary secure firearm storage, engages CSOs in veteran mental health care, and provides psychoeducation and skills to support crisis management. The intervention was developed for all veterans who do not securely store firearms.

Theory

The intervention incorporates motivational interviewing techniques, as ambivalence about changing firearm storage behaviors is common, particularly when veterans own firearms for safety or protection.^6,14 Motivational interviewing is a collaborative approach that addresses a client’s ambivalence to change by eliciting and exploring the client’s own arguments related to change.¹⁴ An important aspect of developing this intervention was to ensure it would be culturally relevant to veteran firearm owners and their CSOs.¹⁵ Further, involvement of the CSO is intentional and meant to boost social support, a known buffering factor against suicide risk.¹²

Objectives

This intervention’s primary objective was for veteran participants to identify secure firearm storage practices and develop a plan for implementing them, including when a veteran or other household member experiences a mental health crisis. For CSOs, the primary objective is to learn how to help the veteran connect with mental health resources if needed and support secure firearm storage as necessary. The overall goal is to learn how to identify warning signs for suicide and how to respond to a mental health crisis through a collaborative process, including securing firearms in a crisis situation.

Materials, Educational Strategies, and Instructors

Training for delivering the intervention was provided via direct consultation with the developer of the intervention and manual. The manual contains pertinent background information to provide context for the intervention’s significance and rationale, including the role of firearms in suicides and current lethal means safety initiatives. It also describes the purpose and objective of each intervention component in detail in addition to providing a script for interventionists to follow to complete each objective.

Training materials for veterans and CSOs include a single Firearms Secure Storage Planning worksheet completed during the intervention, with which the interventionist guides participants through the creation of a secure firearm storage plan (Table). Educational strategies include psychoeducation and Socratic questioning (eg, questioning focused on guiding participants toward the intervention goals) delivered verbally by the interventionist.

The intervention is delivered in person or virtually during a single 90-minute session with a veteran and CSO. Veterans and CSOs work with the interventionist to complete collaborative activities during the session and have self-directive learning activities or homework.

The intervention has 4 primary components: (1) CSO involvement; (2) psychoeducation; (3) secure firearm storage; and (4) how to respond to a mental health crisis. Each CSO should have an established relationship with the veteran, be willing and able to be present during the intervention, and remain an encouraging support person for the veteran. The interventionist emphasizes that it is part of the VA mission for staff to care about the veteran, and that initiating such contact with a CSO is meant to prioritize veteran safety and the safety of their family. Psychoeducation on mental health symptoms, suicide warning signs, veteran suicide rates and lethal means, and the benefits of secure firearm storage, is incorporated in the intervention.

The secure firearm storage component consists of 7 subcomponents: (1) general lethal means secure storage; (2) warning signs; (3) dyad communication; (4) lethal means safety when symptoms emerge; (5) coping strategies; (6) social support; and (7) emergency contacts. A lethal means safety worksheet rooted in the Stanley and Brown suicide safety plan model and implemented in VA health care settings is used to facilitate discussions of secure storage (Appendix).¹⁶

CSOs typically have little or no suicidal crisis response training, yet they likely have more interaction with the veteran on a daily basis than HCPs, putting them in a vital position to identify a crisis early and connect the veteran with the proper care. The crisis component prepares the CSO and veteran to navigate a crisis scenario so they can practice their newly developed safety plan and increase their comfort in discussing mental health and suicidal crisis.

FICTIONAL CASE STUDY

Cole, aged 59 years, is a Persian Gulf War veteran and retired police officer. His medical history includes hypothyroidism, hypertension, type 2 diabetes mellitus, chronic posttraumatic stress disorder, major depressive disorder, and insomnia.

Cole's wife of > 30 years, Sheila, joined him for the FFAST intervention. They report having 4 firearms in the home, 3 of which are loaded but stored in a lockbox and 1 that Cole reports is kept on his person for protection. Cole reports passive suicidal ideation, but no plans or intent. When discussing warning signs that a mental health crisis is building, Cole describes feeling anxious, having a change in his speech patterns, and isolating himself. Sheila agrees, but also mentions that Cole is easily angered and becomes nonverbal. Cole and Sheila express difficulty communicating and appear to have a breakthrough moment when Cole says he does not like when Sheila repeats herself, as he feels like she is “poking” at him. Sheila shares concerns for his safety and that she only repeats herself because he refuses to talk.

Cole agrees to verbalize that he is safe but needs time to process his thoughts. Sheila agrees to give him space with a plan to revisit the conversation within an agreed upon timeline. When discussing an updated secure storage plan for their firearms when a mental health crisis is building, Cole commits to allowing Sheila to store the firearm currently on his person in their gun safe, with the ammunition stored separately, and to giving her the gun safe key. They agree to implement this practice until the mental health crisis has passed.

To mitigate a potential crisis, the interventionist discusses possible internal coping strategies for Cole, including writing, reading, walking the dog, listening to music, and baking. People and social settings that could provide distraction involve going to the gym, talking to his friend Carl or his daughter Kelly, and attending the men’s ministry at church. The intervention concludes by discussing professionals or agencies that Cole and Sheila could contact during a crisis. After the intervention, Cole and Sheila are asked to rate their likelihood of using the plan they established during the conversation on a scale of 0 to 10, with 0 being highly unlikely and 10 being extremely likely. Cole responds with 9 and Sheila responds with 10.

DISCUSSION

Lethal means safety remains a critical component of veteran suicide prevention. However, lethal means safety discussions are often implemented after suicide risk has been identified, which may be too late. Thus, having these conversations early and before a crisis may be imperative. Veterans have expressed a desire to have CSOs involved in their suicide prevention treatment, and CSOs can play a key role in recognizing risk factors during everyday life. The FFAST intervention addresses many of these gaps.

Having discussions in advance of a crisis allows veterans to consider an effective secure firearm storage plan outside of the context of a crisis. Including a CSO galvanizes another person to understand a veteran’s needs and assist with secure firearm storage, identify warning signs, and support them during a crisis. These discussions occur in a context where there is less pressure than during a crisis. Features that were more appealing to veterans and their CSOs were also incorporated, such as having the dyad build a plan that is conceptually similar to other public safety initiatives (eg, a fire safety plan, tornado plan, or hurricane plan). Previous research demonstrates that veterans appreciated the nonjudgmental approach and some preferred that clinicians approach the discussion of secure firearm storage within the context of general home and family safety.¹⁷ Additionally, this intervention can build on veterans’ prior military training in preparedness.

Other potential benefits associated with the FFAST intervention include creating an opportunity to strengthen communication between the veteran and CSO. While FFAST is intended to be used with all types of CSOs, this work is consistent with preliminary data from a couples-based suicide prevention study that indicated veterans and their partners reported increases in relationship functioning and marginal decreases in suicidal ideation.¹⁸ It is possible that communication strategies gained from the current intervention could improve veterans’ relationships with their CSOs, which are associated with a greater sense of social support and reduced suicide risk.¹²

The intervention is a brief, single session that may be appealing to veterans and CSOs with full schedules. Evidence suggests that even brief, single-session interventions have a significant impact on beliefs about secure firearm storage, knowledge of lethal means safety, and confidence in having secure firearm storage conversations.¹⁹ However, clinicians should be cautious when extrapolating from the findings of the current case example, which was a one-time intervention with no follow-up.

Future Directions

Pilot testing of the proposed intervention is underway, and future research will include feedback from veterans and CSOs, as well as feasibility and acceptability data collected during the pilot process. The pilot study uses a successive cohort design with an initial 2 sets of 5 veteran and CSO dyads, and subsequent funding has expanded the pilot study to include an additional 30 dyads. Qualitative interviews will be conducted separately with each veteran and CSO, and additional constructs such as feasibility, acceptability, barriers and facilitators to implementation, and changes in secure storage will be examined. This future research may provide a deeper understanding of the broader acceptability, feasibility, and satisfaction associated with a suicide prevention intervention focused on securing firearms and involving veterans and their CSOs. These data could be used to inform future implementation trials and inform the development of an implementation strategy. In the interim, the nature of the manual is summarized in the context of the urgency of suicide prevention in this at-risk population.

Conclusions

FFAST is a novel approach to veteran firearm suicide prevention. By involving CSOs and emphasizing mental health crisis preparedness between them and veterans, the dyad can work in association with HCPs to establish and exercise secure firearm storage practices as part of an at-home safety plan. Implementation of FFAST may be beneficial for all veterans, not only those who have been identified as being at high suicide risk.

Veterans are at higher risk for suicide compared with civilian populations.¹ Firearms are the most frequent cause of death in veteran deaths by suicide, likely because about 51% of veterans own ≥ 1 firearms and firearms are the most lethal and readily available mechanism.^1-3 Unsecure firearm storage practices (eg, storing firearms unlocked, in an unsecure location, or loaded with ammunition) are associated with increased suicide risk.⁴ Conversely, secure firearm storage (ie, storing firearms locked and unloaded) is associated with lower suicide risk.⁵

A 2019 study of veterans who own firearms found that only 22.2% store all their firearms unloaded and locked, while 32.7% store ≥ 1 firearm unlocked and loaded, and 45.2% store firearms both unlocked and loaded or locked and unloaded. Only 6.3% of veterans strongly agreed that having a firearm at home increased suicide risk among household members; however, 77.2% indicated they would ensure a household member could not access firearms if they were concerned about their suicidal ideation.⁶

Another study found that 9.2% of veterans receive lethal means safety counseling from their US Department of Veterans Affairs (VA)-affiliated or non-VA health care professional.⁷ These data highlight a need to educate veterans about the increased risk for suicide associated with storing an unsecured firearm in the household and to connect this understanding to their values of service and protection of others, while simultaneously preparing them and their family members for a potential mental health crisis.

Consistent with the government’s public health approach to suicide prevention, prevention efforts should also enlist the participation of individuals outside health care.⁸ For example, prior research has found that family members are considered highly credible, and engaging them could expand the reach of lethal means safety conversations. A qualitative analysis of 29 veterans found that 17 (57%) said they preferred having a concerned significant other (CSO) (eg, spouse, adult friend, or relative) involved in their suicide prevention care, while 21 (72%) said they would prefer having a CSO assisting in the secure storage of firearms.^9,10 Some veterans may be more amenable to a conversation about firearm access and suicide risk concerns initiated by a CSO rather than by a clinician, indicating the potential benefits of educating and involving CSOs in suicide prevention.¹¹ Involving CSOs in secure firearm storage planning may also strengthen the veteran’s sense of social support, a key protective factor against suicidal ideation.¹²

CSO involvement in secure firearm storage can provide the following benefits: (1) helping the veteran create a secure storage plan, including developing approaches to secure storage; (2) understanding warning signs of suicide; (3) helping the veteran limit access to firearms during a suicidal crisis; (4) helping the veteran remember the secure storage plan; (5) helping the veteran connect with mental health services; and (6) enhancing social support. In most instances, CSOs are physically close to the veteran (eg, live in the same household) and have a greater practical ability to support and affect change with respect to changes in firearm storage practices.

This article describes the development of an intervention that incorporates CSO involvement in firearms safety efforts for veterans with guidance from VA mental health care practitioners (HCPs). The goal is to provide HCPs and other key stakeholders with a detailed description of the intervention and to suggest potential strategies for how to involve CSOs in suicide prevention.

This article follows the Guideline for Reporting Evidence-based Practice Educational interventions and Teaching checklist, which was developed to facilitate standardized reporting and replication for education interventions.¹³ Applicable portions of the checklist are outlined, with others (ie, incentives, planned/unplanned changes, attendance, and other outcomes) to be addressed in future research.

FFAST INTERVENTION

Training (FFAST) intervention promotes voluntary secure firearm storage, engages CSOs in veteran mental health care, and provides psychoeducation and skills to support crisis management. The intervention was developed for all veterans who do not securely store firearms.

Theory

The intervention incorporates motivational interviewing techniques, as ambivalence about changing firearm storage behaviors is common, particularly when veterans own firearms for safety or protection.^6,14 Motivational interviewing is a collaborative approach that addresses a client’s ambivalence to change by eliciting and exploring the client’s own arguments related to change.¹⁴ An important aspect of developing this intervention was to ensure it would be culturally relevant to veteran firearm owners and their CSOs.¹⁵ Further, involvement of the CSO is intentional and meant to boost social support, a known buffering factor against suicide risk.¹²

Objectives

This intervention’s primary objective was for veteran participants to identify secure firearm storage practices and develop a plan for implementing them, including when a veteran or other household member experiences a mental health crisis. For CSOs, the primary objective is to learn how to help the veteran connect with mental health resources if needed and support secure firearm storage as necessary. The overall goal is to learn how to identify warning signs for suicide and how to respond to a mental health crisis through a collaborative process, including securing firearms in a crisis situation.

Materials, Educational Strategies, and Instructors

Training for delivering the intervention was provided via direct consultation with the developer of the intervention and manual. The manual contains pertinent background information to provide context for the intervention’s significance and rationale, including the role of firearms in suicides and current lethal means safety initiatives. It also describes the purpose and objective of each intervention component in detail in addition to providing a script for interventionists to follow to complete each objective.

Training materials for veterans and CSOs include a single Firearms Secure Storage Planning worksheet completed during the intervention, with which the interventionist guides participants through the creation of a secure firearm storage plan (Table). Educational strategies include psychoeducation and Socratic questioning (eg, questioning focused on guiding participants toward the intervention goals) delivered verbally by the interventionist.

The intervention is delivered in person or virtually during a single 90-minute session with a veteran and CSO. Veterans and CSOs work with the interventionist to complete collaborative activities during the session and have self-directive learning activities or homework.

The intervention has 4 primary components: (1) CSO involvement; (2) psychoeducation; (3) secure firearm storage; and (4) how to respond to a mental health crisis. Each CSO should have an established relationship with the veteran, be willing and able to be present during the intervention, and remain an encouraging support person for the veteran. The interventionist emphasizes that it is part of the VA mission for staff to care about the veteran, and that initiating such contact with a CSO is meant to prioritize veteran safety and the safety of their family. Psychoeducation on mental health symptoms, suicide warning signs, veteran suicide rates and lethal means, and the benefits of secure firearm storage, is incorporated in the intervention.

The secure firearm storage component consists of 7 subcomponents: (1) general lethal means secure storage; (2) warning signs; (3) dyad communication; (4) lethal means safety when symptoms emerge; (5) coping strategies; (6) social support; and (7) emergency contacts. A lethal means safety worksheet rooted in the Stanley and Brown suicide safety plan model and implemented in VA health care settings is used to facilitate discussions of secure storage (Appendix).¹⁶

CSOs typically have little or no suicidal crisis response training, yet they likely have more interaction with the veteran on a daily basis than HCPs, putting them in a vital position to identify a crisis early and connect the veteran with the proper care. The crisis component prepares the CSO and veteran to navigate a crisis scenario so they can practice their newly developed safety plan and increase their comfort in discussing mental health and suicidal crisis.

FICTIONAL CASE STUDY

Cole, aged 59 years, is a Persian Gulf War veteran and retired police officer. His medical history includes hypothyroidism, hypertension, type 2 diabetes mellitus, chronic posttraumatic stress disorder, major depressive disorder, and insomnia.

Cole's wife of > 30 years, Sheila, joined him for the FFAST intervention. They report having 4 firearms in the home, 3 of which are loaded but stored in a lockbox and 1 that Cole reports is kept on his person for protection. Cole reports passive suicidal ideation, but no plans or intent. When discussing warning signs that a mental health crisis is building, Cole describes feeling anxious, having a change in his speech patterns, and isolating himself. Sheila agrees, but also mentions that Cole is easily angered and becomes nonverbal. Cole and Sheila express difficulty communicating and appear to have a breakthrough moment when Cole says he does not like when Sheila repeats herself, as he feels like she is “poking” at him. Sheila shares concerns for his safety and that she only repeats herself because he refuses to talk.

Cole agrees to verbalize that he is safe but needs time to process his thoughts. Sheila agrees to give him space with a plan to revisit the conversation within an agreed upon timeline. When discussing an updated secure storage plan for their firearms when a mental health crisis is building, Cole commits to allowing Sheila to store the firearm currently on his person in their gun safe, with the ammunition stored separately, and to giving her the gun safe key. They agree to implement this practice until the mental health crisis has passed.

To mitigate a potential crisis, the interventionist discusses possible internal coping strategies for Cole, including writing, reading, walking the dog, listening to music, and baking. People and social settings that could provide distraction involve going to the gym, talking to his friend Carl or his daughter Kelly, and attending the men’s ministry at church. The intervention concludes by discussing professionals or agencies that Cole and Sheila could contact during a crisis. After the intervention, Cole and Sheila are asked to rate their likelihood of using the plan they established during the conversation on a scale of 0 to 10, with 0 being highly unlikely and 10 being extremely likely. Cole responds with 9 and Sheila responds with 10.

DISCUSSION

Lethal means safety remains a critical component of veteran suicide prevention. However, lethal means safety discussions are often implemented after suicide risk has been identified, which may be too late. Thus, having these conversations early and before a crisis may be imperative. Veterans have expressed a desire to have CSOs involved in their suicide prevention treatment, and CSOs can play a key role in recognizing risk factors during everyday life. The FFAST intervention addresses many of these gaps.

Having discussions in advance of a crisis allows veterans to consider an effective secure firearm storage plan outside of the context of a crisis. Including a CSO galvanizes another person to understand a veteran’s needs and assist with secure firearm storage, identify warning signs, and support them during a crisis. These discussions occur in a context where there is less pressure than during a crisis. Features that were more appealing to veterans and their CSOs were also incorporated, such as having the dyad build a plan that is conceptually similar to other public safety initiatives (eg, a fire safety plan, tornado plan, or hurricane plan). Previous research demonstrates that veterans appreciated the nonjudgmental approach and some preferred that clinicians approach the discussion of secure firearm storage within the context of general home and family safety.¹⁷ Additionally, this intervention can build on veterans’ prior military training in preparedness.

Other potential benefits associated with the FFAST intervention include creating an opportunity to strengthen communication between the veteran and CSO. While FFAST is intended to be used with all types of CSOs, this work is consistent with preliminary data from a couples-based suicide prevention study that indicated veterans and their partners reported increases in relationship functioning and marginal decreases in suicidal ideation.¹⁸ It is possible that communication strategies gained from the current intervention could improve veterans’ relationships with their CSOs, which are associated with a greater sense of social support and reduced suicide risk.¹²

The intervention is a brief, single session that may be appealing to veterans and CSOs with full schedules. Evidence suggests that even brief, single-session interventions have a significant impact on beliefs about secure firearm storage, knowledge of lethal means safety, and confidence in having secure firearm storage conversations.¹⁹ However, clinicians should be cautious when extrapolating from the findings of the current case example, which was a one-time intervention with no follow-up.

Future Directions

Pilot testing of the proposed intervention is underway, and future research will include feedback from veterans and CSOs, as well as feasibility and acceptability data collected during the pilot process. The pilot study uses a successive cohort design with an initial 2 sets of 5 veteran and CSO dyads, and subsequent funding has expanded the pilot study to include an additional 30 dyads. Qualitative interviews will be conducted separately with each veteran and CSO, and additional constructs such as feasibility, acceptability, barriers and facilitators to implementation, and changes in secure storage will be examined. This future research may provide a deeper understanding of the broader acceptability, feasibility, and satisfaction associated with a suicide prevention intervention focused on securing firearms and involving veterans and their CSOs. These data could be used to inform future implementation trials and inform the development of an implementation strategy. In the interim, the nature of the manual is summarized in the context of the urgency of suicide prevention in this at-risk population.

Conclusions

FFAST is a novel approach to veteran firearm suicide prevention. By involving CSOs and emphasizing mental health crisis preparedness between them and veterans, the dyad can work in association with HCPs to establish and exercise secure firearm storage practices as part of an at-home safety plan. Implementation of FFAST may be beneficial for all veterans, not only those who have been identified as being at high suicide risk.