Federal Practitioner

The annual issue of Cancer Data Trends, produced in collaboration with the Association of VA Hematology/Oncology (AVAHO), highlights the latest research in some of the top cancers impacting US veterans. 

In this issue:

1. Prostate Cancer: Exposures, Racial Differences, and Treatment Trends
2. Expanding Breast Cancer Care for Women Veterans: Genetic Testing and New Therapies
3. Multiple Myeloma: Herbicide Exposure, BMI, and Novel Quadruplet Regimens
4. Melanoma in Veterans: Higher Risk, Delayed Diagnosis, and Evolving Solutions
5. Colorectal Cancer Trends and Digital Interventions in Veterans
6. Advancing HCC Management: Updated Guidelines and VHA's Innovative Screening Trial
7. Mental Health Care in Veterans With Cancer

The annual issue of Cancer Data Trends, produced in collaboration with the Association of VA Hematology/Oncology (AVAHO), highlights the latest research in some of the top cancers impacting US veterans. 

In this issue:

1. Prostate Cancer: Exposures, Racial Differences, and Treatment Trends
2. Expanding Breast Cancer Care for Women Veterans: Genetic Testing and New Therapies
3. Multiple Myeloma: Herbicide Exposure, BMI, and Novel Quadruplet Regimens
4. Melanoma in Veterans: Higher Risk, Delayed Diagnosis, and Evolving Solutions
5. Colorectal Cancer Trends and Digital Interventions in Veterans
6. Advancing HCC Management: Updated Guidelines and VHA's Innovative Screening Trial
7. Mental Health Care in Veterans With Cancer

The annual issue of Cancer Data Trends, produced in collaboration with the Association of VA Hematology/Oncology (AVAHO), highlights the latest research in some of the top cancers impacting US veterans. 

In this issue:

1. Prostate Cancer: Exposures, Racial Differences, and Treatment Trends
2. Expanding Breast Cancer Care for Women Veterans: Genetic Testing and New Therapies
3. Multiple Myeloma: Herbicide Exposure, BMI, and Novel Quadruplet Regimens
4. Melanoma in Veterans: Higher Risk, Delayed Diagnosis, and Evolving Solutions
5. Colorectal Cancer Trends and Digital Interventions in Veterans
6. Advancing HCC Management: Updated Guidelines and VHA's Innovative Screening Trial
7. Mental Health Care in Veterans With Cancer

TOPLINE: Interviews with 23 male veterans (aged 35-49 years) at average-risk for colorectal cancer (CRC) and 8 primary care practitioners (PCPs) found broad acceptability of the Colon Age concept, with 96% of patients agreeing to calculation. PCPs describe its potential use to support screening discussions (fecal immunochemical test [FIT] vs colonoscopy) but emphasize workflow barriers, requesting electronic medical record integration and “time neutral” implementation.

METHODOLOGY:

• Researchers conducted semistructured qualitative interviews with 31 participants (23 male veteran patients aged 35-49 years and 8 PCPs) at the Richard L. Roudebush Veterans Affairs Medical Center between June and September 2022.

• Patients were eligible if they were at average risk for CRC, had no prior screening (colonoscopy or fecal immunochemical test [FIT]), no inflammatory bowel disease, and no significant family history of CRC.

• Interviews explored participants' experiences with CRC screening, understanding of the Colon Age tool, and perceived clinical use.

• Audio-recorded interviews were transcribed, deidentified, and analyzed using the constant comparison method with open and focused coding phases until saturation was reached. 

TAKEAWAY:

• Among 23 male veteran patients (mean age 47 years), 96% agreed to have their Colon Age calculated; 68% had a Colon Age below their biological age, 14% higher than their biological age, and 18% equal to their biological age.

• Patients accepted the Colon Age concept, finding it easy to understand and helpful for being informed about their health, though most were unaware of screening options beyond colonoscopy prior to the interview.

• The 8 PCPs (mean age 53 years, 50% female, mean 29 years in practice) interviewed found the tool acceptable and useful for screening conversations, improving uptake, and facilitating shared decision-making, particularly in gray zone cases where screening decisions are unclear.

• PCPs emphasized the need for the tool to be integrated into the electronic medical record system and expressed concerns about time commitment, consistency with practice guidelines, and the validation process, stating they would only use the tool if it were time neutral and evidence-based. 

IN PRACTICE: “Although the age at which to begin colorectal cancer screening in the US was lowered to 45 years in 2018, uptake of screening in persons aged 45 to 49 has been slow,” wrote the authors of the study.

SOURCE:The study was led by researchers at the VA Center for Health Information and Communication. It was published online on July 15 in BMC Primary Care.

LIMITATIONS: The study was conducted at a single VA medical center in the Midwest and all patient participants were male, which may limit generalizability to nonveteran patients, female patients, and non-VA clinicians. The Colon Age tool has limitations, as it was based on a risk prediction model with modest discrimination, and the linkage to screening recommendations was based on arbitrary Surveillance, Epidemiology and End Results thresholds chosen by the tool developers. Additionally, the qualitative nature of the study with a small sample size may not capture the full range of perspectives across diverse health care settings and patient populations.

DISCLOSURES: The primary author received support from Health Services Research and Development, Veterans Administration. Funding for this project was provided by Richard L. Roudebush VA Medical Center Indianapolis, Indiana Center for Health Information, and Communication COIN funds. The authors reported no relevant conflicts of interest.

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

TOPLINE: Interviews with 23 male veterans (aged 35-49 years) at average-risk for colorectal cancer (CRC) and 8 primary care practitioners (PCPs) found broad acceptability of the Colon Age concept, with 96% of patients agreeing to calculation. PCPs describe its potential use to support screening discussions (fecal immunochemical test [FIT] vs colonoscopy) but emphasize workflow barriers, requesting electronic medical record integration and “time neutral” implementation.

METHODOLOGY:

• Researchers conducted semistructured qualitative interviews with 31 participants (23 male veteran patients aged 35-49 years and 8 PCPs) at the Richard L. Roudebush Veterans Affairs Medical Center between June and September 2022.

• Patients were eligible if they were at average risk for CRC, had no prior screening (colonoscopy or fecal immunochemical test [FIT]), no inflammatory bowel disease, and no significant family history of CRC.

• Interviews explored participants' experiences with CRC screening, understanding of the Colon Age tool, and perceived clinical use.

• Audio-recorded interviews were transcribed, deidentified, and analyzed using the constant comparison method with open and focused coding phases until saturation was reached. 

TAKEAWAY:

• Among 23 male veteran patients (mean age 47 years), 96% agreed to have their Colon Age calculated; 68% had a Colon Age below their biological age, 14% higher than their biological age, and 18% equal to their biological age.

• Patients accepted the Colon Age concept, finding it easy to understand and helpful for being informed about their health, though most were unaware of screening options beyond colonoscopy prior to the interview.

• The 8 PCPs (mean age 53 years, 50% female, mean 29 years in practice) interviewed found the tool acceptable and useful for screening conversations, improving uptake, and facilitating shared decision-making, particularly in gray zone cases where screening decisions are unclear.

• PCPs emphasized the need for the tool to be integrated into the electronic medical record system and expressed concerns about time commitment, consistency with practice guidelines, and the validation process, stating they would only use the tool if it were time neutral and evidence-based. 

IN PRACTICE: “Although the age at which to begin colorectal cancer screening in the US was lowered to 45 years in 2018, uptake of screening in persons aged 45 to 49 has been slow,” wrote the authors of the study.

SOURCE:The study was led by researchers at the VA Center for Health Information and Communication. It was published online on July 15 in BMC Primary Care.

LIMITATIONS: The study was conducted at a single VA medical center in the Midwest and all patient participants were male, which may limit generalizability to nonveteran patients, female patients, and non-VA clinicians. The Colon Age tool has limitations, as it was based on a risk prediction model with modest discrimination, and the linkage to screening recommendations was based on arbitrary Surveillance, Epidemiology and End Results thresholds chosen by the tool developers. Additionally, the qualitative nature of the study with a small sample size may not capture the full range of perspectives across diverse health care settings and patient populations.

DISCLOSURES: The primary author received support from Health Services Research and Development, Veterans Administration. Funding for this project was provided by Richard L. Roudebush VA Medical Center Indianapolis, Indiana Center for Health Information, and Communication COIN funds. The authors reported no relevant conflicts of interest.

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

TOPLINE: Interviews with 23 male veterans (aged 35-49 years) at average-risk for colorectal cancer (CRC) and 8 primary care practitioners (PCPs) found broad acceptability of the Colon Age concept, with 96% of patients agreeing to calculation. PCPs describe its potential use to support screening discussions (fecal immunochemical test [FIT] vs colonoscopy) but emphasize workflow barriers, requesting electronic medical record integration and “time neutral” implementation.

METHODOLOGY:

• Researchers conducted semistructured qualitative interviews with 31 participants (23 male veteran patients aged 35-49 years and 8 PCPs) at the Richard L. Roudebush Veterans Affairs Medical Center between June and September 2022.

• Patients were eligible if they were at average risk for CRC, had no prior screening (colonoscopy or fecal immunochemical test [FIT]), no inflammatory bowel disease, and no significant family history of CRC.

• Interviews explored participants' experiences with CRC screening, understanding of the Colon Age tool, and perceived clinical use.

• Audio-recorded interviews were transcribed, deidentified, and analyzed using the constant comparison method with open and focused coding phases until saturation was reached. 

TAKEAWAY:

• Among 23 male veteran patients (mean age 47 years), 96% agreed to have their Colon Age calculated; 68% had a Colon Age below their biological age, 14% higher than their biological age, and 18% equal to their biological age.

• Patients accepted the Colon Age concept, finding it easy to understand and helpful for being informed about their health, though most were unaware of screening options beyond colonoscopy prior to the interview.

• The 8 PCPs (mean age 53 years, 50% female, mean 29 years in practice) interviewed found the tool acceptable and useful for screening conversations, improving uptake, and facilitating shared decision-making, particularly in gray zone cases where screening decisions are unclear.

• PCPs emphasized the need for the tool to be integrated into the electronic medical record system and expressed concerns about time commitment, consistency with practice guidelines, and the validation process, stating they would only use the tool if it were time neutral and evidence-based. 

IN PRACTICE: “Although the age at which to begin colorectal cancer screening in the US was lowered to 45 years in 2018, uptake of screening in persons aged 45 to 49 has been slow,” wrote the authors of the study.

SOURCE:The study was led by researchers at the VA Center for Health Information and Communication. It was published online on July 15 in BMC Primary Care.

LIMITATIONS: The study was conducted at a single VA medical center in the Midwest and all patient participants were male, which may limit generalizability to nonveteran patients, female patients, and non-VA clinicians. The Colon Age tool has limitations, as it was based on a risk prediction model with modest discrimination, and the linkage to screening recommendations was based on arbitrary Surveillance, Epidemiology and End Results thresholds chosen by the tool developers. Additionally, the qualitative nature of the study with a small sample size may not capture the full range of perspectives across diverse health care settings and patient populations.

DISCLOSURES: The primary author received support from Health Services Research and Development, Veterans Administration. Funding for this project was provided by Richard L. Roudebush VA Medical Center Indianapolis, Indiana Center for Health Information, and Communication COIN funds. The authors reported no relevant conflicts of interest.

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

Colorectal cancer (CRC) in the United States continues to move in two different directions — decreasing in older adults and rising in younger adults, especially in those aged 20-49 years, according to the latest statistics from the American Cancer Society (ACS).

The ACS report, published online earlier this month, revealed that CRC incidence rates declined by 2.5% annually in adults aged ≥ 65 years but increased by 3% annually in adults aged 20-49 between 2013 and 2022 — higher than earlier estimates of 1% to 2% annual increases.

The trends are “concerning” and a “stark reminder that we’re seeing a shifting epidemiology,” said Folasade (Fola) May, MD, PhD, MPhil, director of the gastroenterology quality improvement program at UCLA Health in Los Angeles, who wasn’t involved in the analysis.

The report highlights the need for better education and symptom awareness — including bleeding, iron deficiency symptoms, and changes in bowel habits — among patients and doctors, who may not routinely consider cancer in younger adults, May explained.

“Because so many of the young people diagnosed present with advanced stage disease, early workup is critical to saving lives,” she said.

Rapidly Changing Landscape

In the United States, CRC is the third-most commonly diagnosed cancer in both men and women. CRC is also the second-leading cause of cancer-related deaths and the leading cause in adults aged < 50 years.

“After decades of progress, the risk of dying from colorectal cancer is climbing in younger generations of men and women, confirming a real uptick in disease because of something we’re doing or some other exposure,” Rebecca Siegel, MPH, senior scientific director of surveillance research at ACS and lead author of the report, said in a statement.

For the latest CRC statistics report, ACS scientists analyzed population-based registries, including the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program, and mortality data from the CDC’s National Center for Health Statistics.

The report estimated that 158,850 new CRC cases will be diagnosed in the US in 2026, including 108,860 colon cancers and 49,990 rectal cancers; an estimated 55,230 people will die from the disease.

Overall, CRC incidence declined by 0.9% annually from 2013 to 2022, driven by decreases of 2.5% per year in adults aged ≥ 65 years. During the same period, however, incidence rates rose by about 3% per year in adults aged 20-49 years and by 0.4% per year in those aged 50-64 years. CRC mortality also continued to trend downward in adults aged ≥ 65 years by > 2% per year, but mortality increased by 1% per year in adults aged < 50 years since 2004 and in adults aged 50-64 years since 2019.

Nearly half of new CRC cases (45%) now occur in adults aged < 65 years, up from 27% in 1995, illustrating a major shift toward younger age groups, the authors said. Half of early-onset cases occur in people aged 45-49 years who are now eligible for screening, and 3 of 4 early-onset CRC cases are diagnosed at an advanced stage, including about 27% with distant metastases.

“This is partly because of less screening, but it also reflects diagnostic delays,” according to Siegel and coauthors, who noted data show screening uptake remains low in individuals aged 45-49 (37%) and 50-54 (55%) years. The incidence of early-onset CRC increased across all racial and ethnic groups in the US, from 2% annually in Black individuals to 4% annually in Hispanic individuals between 2013 and 2022.

Aside from early-onset trends, the analysis found that tumor location trends shifted as well. Rectal cancer incidence increased in all ages combined (by 1% per year from 2018 to 2022), reversing decades of decline and now accounting for nearly one third of all CRC, compared with 27% in the mid-2000s.

The report also indicated that racial and ethnic disparities persist. Alaska Native individuals had the highest CRC incidence (80.9 per 100,000) and mortality (31.5 per 100,000) in the US, more than twofold that of White patients (35.2 and 12.9 per 100,000, respectively). Asian American, Native Hawaiian, and other Pacific Islanders had the lowest incidence (28.5 per 100,000) and mortality rates (9.2 per 100,000).

Although cancer registries like SEER are not perfect, they are “the best data we have” and overall the SEER data “very reliably represent what is going on in the US population,” May said.

The latest findings also further underscore that CRC is “worsening among younger generations and highlight the immediate need for eligible adults to begin screening at the recommended age of 45,” William Dahut, MD, ACS chief scientific officer, said in the statement.

The study had no commercial funding. The authors and May reported no relevant financial relationships.

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

Colorectal cancer (CRC) in the United States continues to move in two different directions — decreasing in older adults and rising in younger adults, especially in those aged 20-49 years, according to the latest statistics from the American Cancer Society (ACS).

The ACS report, published online earlier this month, revealed that CRC incidence rates declined by 2.5% annually in adults aged ≥ 65 years but increased by 3% annually in adults aged 20-49 between 2013 and 2022 — higher than earlier estimates of 1% to 2% annual increases.

The trends are “concerning” and a “stark reminder that we’re seeing a shifting epidemiology,” said Folasade (Fola) May, MD, PhD, MPhil, director of the gastroenterology quality improvement program at UCLA Health in Los Angeles, who wasn’t involved in the analysis.

The report highlights the need for better education and symptom awareness — including bleeding, iron deficiency symptoms, and changes in bowel habits — among patients and doctors, who may not routinely consider cancer in younger adults, May explained.

“Because so many of the young people diagnosed present with advanced stage disease, early workup is critical to saving lives,” she said.

Rapidly Changing Landscape

In the United States, CRC is the third-most commonly diagnosed cancer in both men and women. CRC is also the second-leading cause of cancer-related deaths and the leading cause in adults aged < 50 years.

“After decades of progress, the risk of dying from colorectal cancer is climbing in younger generations of men and women, confirming a real uptick in disease because of something we’re doing or some other exposure,” Rebecca Siegel, MPH, senior scientific director of surveillance research at ACS and lead author of the report, said in a statement.

For the latest CRC statistics report, ACS scientists analyzed population-based registries, including the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program, and mortality data from the CDC’s National Center for Health Statistics.

The report estimated that 158,850 new CRC cases will be diagnosed in the US in 2026, including 108,860 colon cancers and 49,990 rectal cancers; an estimated 55,230 people will die from the disease.

Overall, CRC incidence declined by 0.9% annually from 2013 to 2022, driven by decreases of 2.5% per year in adults aged ≥ 65 years. During the same period, however, incidence rates rose by about 3% per year in adults aged 20-49 years and by 0.4% per year in those aged 50-64 years. CRC mortality also continued to trend downward in adults aged ≥ 65 years by > 2% per year, but mortality increased by 1% per year in adults aged < 50 years since 2004 and in adults aged 50-64 years since 2019.

Nearly half of new CRC cases (45%) now occur in adults aged < 65 years, up from 27% in 1995, illustrating a major shift toward younger age groups, the authors said. Half of early-onset cases occur in people aged 45-49 years who are now eligible for screening, and 3 of 4 early-onset CRC cases are diagnosed at an advanced stage, including about 27% with distant metastases.

“This is partly because of less screening, but it also reflects diagnostic delays,” according to Siegel and coauthors, who noted data show screening uptake remains low in individuals aged 45-49 (37%) and 50-54 (55%) years. The incidence of early-onset CRC increased across all racial and ethnic groups in the US, from 2% annually in Black individuals to 4% annually in Hispanic individuals between 2013 and 2022.

Aside from early-onset trends, the analysis found that tumor location trends shifted as well. Rectal cancer incidence increased in all ages combined (by 1% per year from 2018 to 2022), reversing decades of decline and now accounting for nearly one third of all CRC, compared with 27% in the mid-2000s.

The report also indicated that racial and ethnic disparities persist. Alaska Native individuals had the highest CRC incidence (80.9 per 100,000) and mortality (31.5 per 100,000) in the US, more than twofold that of White patients (35.2 and 12.9 per 100,000, respectively). Asian American, Native Hawaiian, and other Pacific Islanders had the lowest incidence (28.5 per 100,000) and mortality rates (9.2 per 100,000).

Although cancer registries like SEER are not perfect, they are “the best data we have” and overall the SEER data “very reliably represent what is going on in the US population,” May said.

The latest findings also further underscore that CRC is “worsening among younger generations and highlight the immediate need for eligible adults to begin screening at the recommended age of 45,” William Dahut, MD, ACS chief scientific officer, said in the statement.

The study had no commercial funding. The authors and May reported no relevant financial relationships.

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

Colorectal cancer (CRC) in the United States continues to move in two different directions — decreasing in older adults and rising in younger adults, especially in those aged 20-49 years, according to the latest statistics from the American Cancer Society (ACS).

The ACS report, published online earlier this month, revealed that CRC incidence rates declined by 2.5% annually in adults aged ≥ 65 years but increased by 3% annually in adults aged 20-49 between 2013 and 2022 — higher than earlier estimates of 1% to 2% annual increases.

The trends are “concerning” and a “stark reminder that we’re seeing a shifting epidemiology,” said Folasade (Fola) May, MD, PhD, MPhil, director of the gastroenterology quality improvement program at UCLA Health in Los Angeles, who wasn’t involved in the analysis.

The report highlights the need for better education and symptom awareness — including bleeding, iron deficiency symptoms, and changes in bowel habits — among patients and doctors, who may not routinely consider cancer in younger adults, May explained.

“Because so many of the young people diagnosed present with advanced stage disease, early workup is critical to saving lives,” she said.

Rapidly Changing Landscape

In the United States, CRC is the third-most commonly diagnosed cancer in both men and women. CRC is also the second-leading cause of cancer-related deaths and the leading cause in adults aged < 50 years.

“After decades of progress, the risk of dying from colorectal cancer is climbing in younger generations of men and women, confirming a real uptick in disease because of something we’re doing or some other exposure,” Rebecca Siegel, MPH, senior scientific director of surveillance research at ACS and lead author of the report, said in a statement.

For the latest CRC statistics report, ACS scientists analyzed population-based registries, including the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program, and mortality data from the CDC’s National Center for Health Statistics.

The report estimated that 158,850 new CRC cases will be diagnosed in the US in 2026, including 108,860 colon cancers and 49,990 rectal cancers; an estimated 55,230 people will die from the disease.

Overall, CRC incidence declined by 0.9% annually from 2013 to 2022, driven by decreases of 2.5% per year in adults aged ≥ 65 years. During the same period, however, incidence rates rose by about 3% per year in adults aged 20-49 years and by 0.4% per year in those aged 50-64 years. CRC mortality also continued to trend downward in adults aged ≥ 65 years by > 2% per year, but mortality increased by 1% per year in adults aged < 50 years since 2004 and in adults aged 50-64 years since 2019.

Nearly half of new CRC cases (45%) now occur in adults aged < 65 years, up from 27% in 1995, illustrating a major shift toward younger age groups, the authors said. Half of early-onset cases occur in people aged 45-49 years who are now eligible for screening, and 3 of 4 early-onset CRC cases are diagnosed at an advanced stage, including about 27% with distant metastases.

“This is partly because of less screening, but it also reflects diagnostic delays,” according to Siegel and coauthors, who noted data show screening uptake remains low in individuals aged 45-49 (37%) and 50-54 (55%) years. The incidence of early-onset CRC increased across all racial and ethnic groups in the US, from 2% annually in Black individuals to 4% annually in Hispanic individuals between 2013 and 2022.

Aside from early-onset trends, the analysis found that tumor location trends shifted as well. Rectal cancer incidence increased in all ages combined (by 1% per year from 2018 to 2022), reversing decades of decline and now accounting for nearly one third of all CRC, compared with 27% in the mid-2000s.

The report also indicated that racial and ethnic disparities persist. Alaska Native individuals had the highest CRC incidence (80.9 per 100,000) and mortality (31.5 per 100,000) in the US, more than twofold that of White patients (35.2 and 12.9 per 100,000, respectively). Asian American, Native Hawaiian, and other Pacific Islanders had the lowest incidence (28.5 per 100,000) and mortality rates (9.2 per 100,000).

Although cancer registries like SEER are not perfect, they are “the best data we have” and overall the SEER data “very reliably represent what is going on in the US population,” May said.

The latest findings also further underscore that CRC is “worsening among younger generations and highlight the immediate need for eligible adults to begin screening at the recommended age of 45,” William Dahut, MD, ACS chief scientific officer, said in the statement.

The study had no commercial funding. The authors and May reported no relevant financial relationships.

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

Anxiety, depression, and suicide rates are elevated for veterans who are survivors of testicular cancer (TC) compared with veterans without cancer, a retrospective analysis finds.

Over 5 years, the cumulative incidence of anxiety and depression was 53.4% in veterans with TC vs 35.0% in matched controls (P < .001; hazard ratio [HR], 1.66), reported Aditya Bagrodia, MD, professor of urology and radiation oncology at the University of California San Diego, et al in Cancer Medicine. The cumulative incidence of suicidality was 5.0% and 0.1%, respectively (P < .001; HR, 22.99).

“More than half of men with testicular cancer contend with these diagnoses,” Bagrodia told Federal Practitioner. “There are risk factors, including chemotherapy, being single or divorced, or unemployed.”

Patients in these groups warrant aggressive screening and intervention, Bagrodia said. TC is the most common cancer in men in the military and the most common malignancy in men aged 18 to 45 years, Bagrodia said: “The vast majority of men who have testicular cancer are curable.”

Patients, however, face an intense burden. 

“One theme that comes up consistently from patients and caregivers is centered around mental health impact, brain fog, anxiety, depression, and difficulty concentrating,” Bagrodia said. “We wanted to dig into this a little bit further. The idea is to shed light on how common these diagnoses are on these young cancer survivors and intervene so we could positively impact their quality of life.”

The study analyzed 2022 patients with TC and 6375 matched controls enrolled at the US Department of Veterans Affairs (VA) from 1990 through 2016. In the cancer cohort, the mean age at diagnosis was 42.46 years, and ages ranged from 18 to 88 years; 89.7% of patients were White, 6.0% were Black, 2.4% were other race, 1.2% were Asian/Pacific Islander, and 0.7% were Native; 6.2% were Hispanic; and 19.9% were diagnosed between 1990 and 1999.

Factors linked to higher rates of anxiety/depression among patients with TC included divorce (HR 1.15, P = .044), unemployment (HR 1.68, P < .001), and receipt of chemotherapy (HR 1.20, P < .001).

The incidence of de novo anxiety/depression was 30.1% for patients with TC vs 16.7% for controls (P < .001), and the incidence of de novo suicidality was 2.4% for patients and 0.1% for controls.

“These are men who are going to beat their cancer and go on to live for decades and decades,” Bagrodia said. “We found that the impact of a diagnosis and chemotherapy can persist beyond the initial time frame.”

It’s not clear, however, why chemotherapy boosts the risk, Bagrodia said. Clinicians who treat patients with TC should let them know that anxiety, depression, and suicidality are common and treatable concerns.

“We've got some wonderful support services, therapy, and medications that can help out with those diagnoses,” Bagrodia said.

The study authors noted limitations such as the retrospective study design and limited consideration of factors that may affect mental health.

“Additionally, the baseline rates of anxiety, depression, and suicidality are high in the VA population, which may limit ability to apply results to the civilian population,” Bagrodia said.

Genitourinary oncologist Philippe Spiess, MD, of Moffitt Cancer Center in Tampa, praised the study in an interview, saying it provides stronger evidence than previous research. 

"It's not only about screening but surveillance, because you never know what kind of challenges they have in their lives,” Spiess told Federal Practitioner, emphasizing the need for clinicians to continue to monitor patients. “They're young, they're vulnerable. Don’t assume they're going to get help somewhere else. You need to be that source that facilitates it.”

No funding is reported. Bagrodia and other authors have no disclosures. Spiess has no disclosures. 

Anxiety, depression, and suicide rates are elevated for veterans who are survivors of testicular cancer (TC) compared with veterans without cancer, a retrospective analysis finds.

Over 5 years, the cumulative incidence of anxiety and depression was 53.4% in veterans with TC vs 35.0% in matched controls (P < .001; hazard ratio [HR], 1.66), reported Aditya Bagrodia, MD, professor of urology and radiation oncology at the University of California San Diego, et al in Cancer Medicine. The cumulative incidence of suicidality was 5.0% and 0.1%, respectively (P < .001; HR, 22.99).

“More than half of men with testicular cancer contend with these diagnoses,” Bagrodia told Federal Practitioner. “There are risk factors, including chemotherapy, being single or divorced, or unemployed.”

Patients in these groups warrant aggressive screening and intervention, Bagrodia said. TC is the most common cancer in men in the military and the most common malignancy in men aged 18 to 45 years, Bagrodia said: “The vast majority of men who have testicular cancer are curable.”

Patients, however, face an intense burden. 

“One theme that comes up consistently from patients and caregivers is centered around mental health impact, brain fog, anxiety, depression, and difficulty concentrating,” Bagrodia said. “We wanted to dig into this a little bit further. The idea is to shed light on how common these diagnoses are on these young cancer survivors and intervene so we could positively impact their quality of life.”

The study analyzed 2022 patients with TC and 6375 matched controls enrolled at the US Department of Veterans Affairs (VA) from 1990 through 2016. In the cancer cohort, the mean age at diagnosis was 42.46 years, and ages ranged from 18 to 88 years; 89.7% of patients were White, 6.0% were Black, 2.4% were other race, 1.2% were Asian/Pacific Islander, and 0.7% were Native; 6.2% were Hispanic; and 19.9% were diagnosed between 1990 and 1999.

Factors linked to higher rates of anxiety/depression among patients with TC included divorce (HR 1.15, P = .044), unemployment (HR 1.68, P < .001), and receipt of chemotherapy (HR 1.20, P < .001).

The incidence of de novo anxiety/depression was 30.1% for patients with TC vs 16.7% for controls (P < .001), and the incidence of de novo suicidality was 2.4% for patients and 0.1% for controls.

“These are men who are going to beat their cancer and go on to live for decades and decades,” Bagrodia said. “We found that the impact of a diagnosis and chemotherapy can persist beyond the initial time frame.”

It’s not clear, however, why chemotherapy boosts the risk, Bagrodia said. Clinicians who treat patients with TC should let them know that anxiety, depression, and suicidality are common and treatable concerns.

“We've got some wonderful support services, therapy, and medications that can help out with those diagnoses,” Bagrodia said.

The study authors noted limitations such as the retrospective study design and limited consideration of factors that may affect mental health.

“Additionally, the baseline rates of anxiety, depression, and suicidality are high in the VA population, which may limit ability to apply results to the civilian population,” Bagrodia said.

Genitourinary oncologist Philippe Spiess, MD, of Moffitt Cancer Center in Tampa, praised the study in an interview, saying it provides stronger evidence than previous research. 

"It's not only about screening but surveillance, because you never know what kind of challenges they have in their lives,” Spiess told Federal Practitioner, emphasizing the need for clinicians to continue to monitor patients. “They're young, they're vulnerable. Don’t assume they're going to get help somewhere else. You need to be that source that facilitates it.”

No funding is reported. Bagrodia and other authors have no disclosures. Spiess has no disclosures. 

Anxiety, depression, and suicide rates are elevated for veterans who are survivors of testicular cancer (TC) compared with veterans without cancer, a retrospective analysis finds.

Over 5 years, the cumulative incidence of anxiety and depression was 53.4% in veterans with TC vs 35.0% in matched controls (P < .001; hazard ratio [HR], 1.66), reported Aditya Bagrodia, MD, professor of urology and radiation oncology at the University of California San Diego, et al in Cancer Medicine. The cumulative incidence of suicidality was 5.0% and 0.1%, respectively (P < .001; HR, 22.99).

“More than half of men with testicular cancer contend with these diagnoses,” Bagrodia told Federal Practitioner. “There are risk factors, including chemotherapy, being single or divorced, or unemployed.”

Patients in these groups warrant aggressive screening and intervention, Bagrodia said. TC is the most common cancer in men in the military and the most common malignancy in men aged 18 to 45 years, Bagrodia said: “The vast majority of men who have testicular cancer are curable.”

Patients, however, face an intense burden. 

“One theme that comes up consistently from patients and caregivers is centered around mental health impact, brain fog, anxiety, depression, and difficulty concentrating,” Bagrodia said. “We wanted to dig into this a little bit further. The idea is to shed light on how common these diagnoses are on these young cancer survivors and intervene so we could positively impact their quality of life.”

The study analyzed 2022 patients with TC and 6375 matched controls enrolled at the US Department of Veterans Affairs (VA) from 1990 through 2016. In the cancer cohort, the mean age at diagnosis was 42.46 years, and ages ranged from 18 to 88 years; 89.7% of patients were White, 6.0% were Black, 2.4% were other race, 1.2% were Asian/Pacific Islander, and 0.7% were Native; 6.2% were Hispanic; and 19.9% were diagnosed between 1990 and 1999.

Factors linked to higher rates of anxiety/depression among patients with TC included divorce (HR 1.15, P = .044), unemployment (HR 1.68, P < .001), and receipt of chemotherapy (HR 1.20, P < .001).

The incidence of de novo anxiety/depression was 30.1% for patients with TC vs 16.7% for controls (P < .001), and the incidence of de novo suicidality was 2.4% for patients and 0.1% for controls.

“These are men who are going to beat their cancer and go on to live for decades and decades,” Bagrodia said. “We found that the impact of a diagnosis and chemotherapy can persist beyond the initial time frame.”

It’s not clear, however, why chemotherapy boosts the risk, Bagrodia said. Clinicians who treat patients with TC should let them know that anxiety, depression, and suicidality are common and treatable concerns.

“We've got some wonderful support services, therapy, and medications that can help out with those diagnoses,” Bagrodia said.

The study authors noted limitations such as the retrospective study design and limited consideration of factors that may affect mental health.

“Additionally, the baseline rates of anxiety, depression, and suicidality are high in the VA population, which may limit ability to apply results to the civilian population,” Bagrodia said.

Genitourinary oncologist Philippe Spiess, MD, of Moffitt Cancer Center in Tampa, praised the study in an interview, saying it provides stronger evidence than previous research. 

"It's not only about screening but surveillance, because you never know what kind of challenges they have in their lives,” Spiess told Federal Practitioner, emphasizing the need for clinicians to continue to monitor patients. “They're young, they're vulnerable. Don’t assume they're going to get help somewhere else. You need to be that source that facilitates it.”

No funding is reported. Bagrodia and other authors have no disclosures. Spiess has no disclosures. 

An international study of nearly 2 million people suggests that meat-free diets can help stave off several major cancers — but it also reached some unexpected conclusions.

In what researchers describe as the largest-ever meta-analysis of meatless diets and cancer risk, compared with meat-eaters, vegetarians showed reduced risks for five cancers, including breast, prostate, and pancreatic. That was independent of factors such as physical activity, body weight, smoking habits, alcohol intake, and medical history.

“This study is really good news for those that follow a vegetarian diet because they have a lower risk of five cancer sites, some of which are really prevalent in the population,” study lead author Yashvee Dunneram, PhD, of Newcastle University, Tyne, England, said at a press briefing on the findings.

The analysis, published in the British Journal of Cancer, looked at data from nine observational studies conducted in the UK, US, India, and Taiwan. In total, they included more than 1.8 million participants who completed detailed questionnaires on lifestyle and medical factors and were followed for a median of 16 years.

While most were omnivores, the population included over 63,000 vegetarians. And compared with their meat-eating counterparts, vegetarians had reduced risks for:

• Multiple myeloma, 31% lower (hazard ratio [HR], 0.69; 95% CI, 0.51-0.93);
• Kidney cancer, 28% lower (HR, 0.72; 95% CI, 0.57-0.92);
• Pancreatic cancer, 21% lower (HR, 0.79; 95% CI, 0.65-0.97);
• Prostate cancer, 12% lower (HR, 0.88; 95% CI, 0.79-0.97); and
• Breast cancer, 9% lower (HR, 0.91; 95% CI, 0.86-0.97).

On the other hand, vegetarians were no less likely to develop colorectal cancer than meat-eaters — which would seem to conflict with a large body of evidence linking high intake of red and processed meats to an increased risk for the disease and consumption of whole grains and fiber to a protective effect.

Dunneram said her team was, in fact, “quite surprised with this finding.”

But the researchers also stressed that the reported intake of processed meats in this global study was low, at a median of about 16 g/d. For comparison, the average intake in the UK general population is more than double that amount.

That point was echoed by Dagfinn Aune, PhD, a researcher at Imperial College London, London, England, who was not involved in the study.

“It’s possible that lumping all meat-eaters (regardless of how much or little meat they ate) together may have diluted any effects of vegetarian diets on cancer risk, particularly if meat intake was low in some studies,” Aune said in comments shared via Science Media Centre.

In another unexpected finding, vegetarians had nearly double the risk for esophageal squamous cell carcinoma compared with meat-eaters.

Senior author Aurora Perez-Cornago, PhD, a nutritional epidemiologist at the University of Oxford, Oxford, England, said she could only speculate on the reasons.

It’s possible, for example, that people who exclude meat from their diets are more likely to have certain nutritional deficiencies. Perez-Cornago noted that low intake of riboflavin (vitamin B2, largely found in meat) has been tied to esophageal cancer risk.

Perhaps most surprising of all, vegans — who eschew all animal products, including dairy foods — had a 40% greater risk for colorectal cancer than meat-eaters (HR, 1.40; 95% CI, 1.12-1.75).

Again, the reasons are unclear, but Dunneram said it could be related to a mineral lacking in some vegans’ diets: calcium. Research has tied higher intake of dairy products, and specifically calcium, to lower colorectal cancer risk.

However, the findings on vegan diets could also come down to numbers, the researchers pointed out: The analysis included 8849 vegans in total and found only 93 cases of colorectal cancer among vegans across seven studies from the US and UK.

Aune said that studies including a “much larger” number of vegans are needed. He also noted that based on prior cohort studies, vegans (and vegetarians) may have a lower overall cancer incidence than meat-eaters.

On balance, the study authors said, meat-free diets may help reduce cancer risk — but vegetarians and vegans might need to boost their intake of certain nutrients, from fortified foods or supplements.

The analysis did have several limitations, according to Anne McTiernan, MD, PhD, a professor at Fred Hutch Cancer Center in Seattle, who studies lifestyle factors and cancer risk.

Besides the relatively small number of vegans, the study lacked data on Black and Hispanic individuals, which limits its generalizability, McTiernan told Medscape Medical News.

And as with any observational research, confounders are an issue. People who follow meat-free diets tend to maintain a lower body weight over time, for example.

Still, McTiernan doubted that body weight fully accounts for the reduced cancer risks seen here as the researchers adjusted for BMI (with weight and height self-reported in some studies and measured in others).

As for the take-home message, McTiernan agreed that vegans, in particular, may want to be careful that they are getting enough of certain vitamins and minerals.

But overall, the findings support the types of plant-rich diets long endorsed by groups such as the World Cancer Research Fund/American Institute for Cancer Research, the experts said.

The analysis also hinted at benefits from cutting out red and processed meat alone.

Among nearly 43,000 pescatarians — people who eat fish but no meat or poultry — the risks for breast (HR, 0.93), colorectal (HR, 0.85), and kidney (HR, 0.73) cancers were reduced relative to meat-eaters. Meanwhile, men who reported eating poultry, but no red or processed meat, had a decreased risk for prostate cancer (HR, 0.93).

In sum, Aune said, “these findings provide further support for dietary recommendations that emphasize higher intakes of whole plant foods, such as whole grains, fruits, vegetables, nuts and legumes and less meat.” And, McTiernan noted, it’s never too late for people to change their dietary habits.

“Clinical trials have shown immediate benefits to vegetarian diets, like reductions in lipids and weight loss — things that can affect health across the board,” she said.

This study was funded by the World Cancer Research Fund, Cancer Research UK, the Medical Research Council and others. The authors declared having no competing interests.

Ernie Mundell is a freelance medical journalist based in Los Angeles. He has more than 30 years of experience, including editorial positions at Reuters Health and HealthDay.

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

An international study of nearly 2 million people suggests that meat-free diets can help stave off several major cancers — but it also reached some unexpected conclusions.

In what researchers describe as the largest-ever meta-analysis of meatless diets and cancer risk, compared with meat-eaters, vegetarians showed reduced risks for five cancers, including breast, prostate, and pancreatic. That was independent of factors such as physical activity, body weight, smoking habits, alcohol intake, and medical history.

“This study is really good news for those that follow a vegetarian diet because they have a lower risk of five cancer sites, some of which are really prevalent in the population,” study lead author Yashvee Dunneram, PhD, of Newcastle University, Tyne, England, said at a press briefing on the findings.

The analysis, published in the British Journal of Cancer, looked at data from nine observational studies conducted in the UK, US, India, and Taiwan. In total, they included more than 1.8 million participants who completed detailed questionnaires on lifestyle and medical factors and were followed for a median of 16 years.

While most were omnivores, the population included over 63,000 vegetarians. And compared with their meat-eating counterparts, vegetarians had reduced risks for:

• Multiple myeloma, 31% lower (hazard ratio [HR], 0.69; 95% CI, 0.51-0.93);
• Kidney cancer, 28% lower (HR, 0.72; 95% CI, 0.57-0.92);
• Pancreatic cancer, 21% lower (HR, 0.79; 95% CI, 0.65-0.97);
• Prostate cancer, 12% lower (HR, 0.88; 95% CI, 0.79-0.97); and
• Breast cancer, 9% lower (HR, 0.91; 95% CI, 0.86-0.97).

On the other hand, vegetarians were no less likely to develop colorectal cancer than meat-eaters — which would seem to conflict with a large body of evidence linking high intake of red and processed meats to an increased risk for the disease and consumption of whole grains and fiber to a protective effect.

Dunneram said her team was, in fact, “quite surprised with this finding.”

But the researchers also stressed that the reported intake of processed meats in this global study was low, at a median of about 16 g/d. For comparison, the average intake in the UK general population is more than double that amount.

That point was echoed by Dagfinn Aune, PhD, a researcher at Imperial College London, London, England, who was not involved in the study.

“It’s possible that lumping all meat-eaters (regardless of how much or little meat they ate) together may have diluted any effects of vegetarian diets on cancer risk, particularly if meat intake was low in some studies,” Aune said in comments shared via Science Media Centre.

In another unexpected finding, vegetarians had nearly double the risk for esophageal squamous cell carcinoma compared with meat-eaters.

Senior author Aurora Perez-Cornago, PhD, a nutritional epidemiologist at the University of Oxford, Oxford, England, said she could only speculate on the reasons.

It’s possible, for example, that people who exclude meat from their diets are more likely to have certain nutritional deficiencies. Perez-Cornago noted that low intake of riboflavin (vitamin B2, largely found in meat) has been tied to esophageal cancer risk.

Perhaps most surprising of all, vegans — who eschew all animal products, including dairy foods — had a 40% greater risk for colorectal cancer than meat-eaters (HR, 1.40; 95% CI, 1.12-1.75).

Again, the reasons are unclear, but Dunneram said it could be related to a mineral lacking in some vegans’ diets: calcium. Research has tied higher intake of dairy products, and specifically calcium, to lower colorectal cancer risk.

However, the findings on vegan diets could also come down to numbers, the researchers pointed out: The analysis included 8849 vegans in total and found only 93 cases of colorectal cancer among vegans across seven studies from the US and UK.

Aune said that studies including a “much larger” number of vegans are needed. He also noted that based on prior cohort studies, vegans (and vegetarians) may have a lower overall cancer incidence than meat-eaters.

On balance, the study authors said, meat-free diets may help reduce cancer risk — but vegetarians and vegans might need to boost their intake of certain nutrients, from fortified foods or supplements.

The analysis did have several limitations, according to Anne McTiernan, MD, PhD, a professor at Fred Hutch Cancer Center in Seattle, who studies lifestyle factors and cancer risk.

Besides the relatively small number of vegans, the study lacked data on Black and Hispanic individuals, which limits its generalizability, McTiernan told Medscape Medical News.

And as with any observational research, confounders are an issue. People who follow meat-free diets tend to maintain a lower body weight over time, for example.

Still, McTiernan doubted that body weight fully accounts for the reduced cancer risks seen here as the researchers adjusted for BMI (with weight and height self-reported in some studies and measured in others).

As for the take-home message, McTiernan agreed that vegans, in particular, may want to be careful that they are getting enough of certain vitamins and minerals.

But overall, the findings support the types of plant-rich diets long endorsed by groups such as the World Cancer Research Fund/American Institute for Cancer Research, the experts said.

The analysis also hinted at benefits from cutting out red and processed meat alone.

Among nearly 43,000 pescatarians — people who eat fish but no meat or poultry — the risks for breast (HR, 0.93), colorectal (HR, 0.85), and kidney (HR, 0.73) cancers were reduced relative to meat-eaters. Meanwhile, men who reported eating poultry, but no red or processed meat, had a decreased risk for prostate cancer (HR, 0.93).

In sum, Aune said, “these findings provide further support for dietary recommendations that emphasize higher intakes of whole plant foods, such as whole grains, fruits, vegetables, nuts and legumes and less meat.” And, McTiernan noted, it’s never too late for people to change their dietary habits.

“Clinical trials have shown immediate benefits to vegetarian diets, like reductions in lipids and weight loss — things that can affect health across the board,” she said.

This study was funded by the World Cancer Research Fund, Cancer Research UK, the Medical Research Council and others. The authors declared having no competing interests.

Ernie Mundell is a freelance medical journalist based in Los Angeles. He has more than 30 years of experience, including editorial positions at Reuters Health and HealthDay.

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

An international study of nearly 2 million people suggests that meat-free diets can help stave off several major cancers — but it also reached some unexpected conclusions.

In what researchers describe as the largest-ever meta-analysis of meatless diets and cancer risk, compared with meat-eaters, vegetarians showed reduced risks for five cancers, including breast, prostate, and pancreatic. That was independent of factors such as physical activity, body weight, smoking habits, alcohol intake, and medical history.

“This study is really good news for those that follow a vegetarian diet because they have a lower risk of five cancer sites, some of which are really prevalent in the population,” study lead author Yashvee Dunneram, PhD, of Newcastle University, Tyne, England, said at a press briefing on the findings.

The analysis, published in the British Journal of Cancer, looked at data from nine observational studies conducted in the UK, US, India, and Taiwan. In total, they included more than 1.8 million participants who completed detailed questionnaires on lifestyle and medical factors and were followed for a median of 16 years.

While most were omnivores, the population included over 63,000 vegetarians. And compared with their meat-eating counterparts, vegetarians had reduced risks for:

• Multiple myeloma, 31% lower (hazard ratio [HR], 0.69; 95% CI, 0.51-0.93);
• Kidney cancer, 28% lower (HR, 0.72; 95% CI, 0.57-0.92);
• Pancreatic cancer, 21% lower (HR, 0.79; 95% CI, 0.65-0.97);
• Prostate cancer, 12% lower (HR, 0.88; 95% CI, 0.79-0.97); and
• Breast cancer, 9% lower (HR, 0.91; 95% CI, 0.86-0.97).

On the other hand, vegetarians were no less likely to develop colorectal cancer than meat-eaters — which would seem to conflict with a large body of evidence linking high intake of red and processed meats to an increased risk for the disease and consumption of whole grains and fiber to a protective effect.

Dunneram said her team was, in fact, “quite surprised with this finding.”

But the researchers also stressed that the reported intake of processed meats in this global study was low, at a median of about 16 g/d. For comparison, the average intake in the UK general population is more than double that amount.

That point was echoed by Dagfinn Aune, PhD, a researcher at Imperial College London, London, England, who was not involved in the study.

“It’s possible that lumping all meat-eaters (regardless of how much or little meat they ate) together may have diluted any effects of vegetarian diets on cancer risk, particularly if meat intake was low in some studies,” Aune said in comments shared via Science Media Centre.

In another unexpected finding, vegetarians had nearly double the risk for esophageal squamous cell carcinoma compared with meat-eaters.

Senior author Aurora Perez-Cornago, PhD, a nutritional epidemiologist at the University of Oxford, Oxford, England, said she could only speculate on the reasons.

It’s possible, for example, that people who exclude meat from their diets are more likely to have certain nutritional deficiencies. Perez-Cornago noted that low intake of riboflavin (vitamin B2, largely found in meat) has been tied to esophageal cancer risk.

Perhaps most surprising of all, vegans — who eschew all animal products, including dairy foods — had a 40% greater risk for colorectal cancer than meat-eaters (HR, 1.40; 95% CI, 1.12-1.75).

Again, the reasons are unclear, but Dunneram said it could be related to a mineral lacking in some vegans’ diets: calcium. Research has tied higher intake of dairy products, and specifically calcium, to lower colorectal cancer risk.

However, the findings on vegan diets could also come down to numbers, the researchers pointed out: The analysis included 8849 vegans in total and found only 93 cases of colorectal cancer among vegans across seven studies from the US and UK.

Aune said that studies including a “much larger” number of vegans are needed. He also noted that based on prior cohort studies, vegans (and vegetarians) may have a lower overall cancer incidence than meat-eaters.

On balance, the study authors said, meat-free diets may help reduce cancer risk — but vegetarians and vegans might need to boost their intake of certain nutrients, from fortified foods or supplements.

The analysis did have several limitations, according to Anne McTiernan, MD, PhD, a professor at Fred Hutch Cancer Center in Seattle, who studies lifestyle factors and cancer risk.

Besides the relatively small number of vegans, the study lacked data on Black and Hispanic individuals, which limits its generalizability, McTiernan told Medscape Medical News.

And as with any observational research, confounders are an issue. People who follow meat-free diets tend to maintain a lower body weight over time, for example.

Still, McTiernan doubted that body weight fully accounts for the reduced cancer risks seen here as the researchers adjusted for BMI (with weight and height self-reported in some studies and measured in others).

As for the take-home message, McTiernan agreed that vegans, in particular, may want to be careful that they are getting enough of certain vitamins and minerals.

But overall, the findings support the types of plant-rich diets long endorsed by groups such as the World Cancer Research Fund/American Institute for Cancer Research, the experts said.

The analysis also hinted at benefits from cutting out red and processed meat alone.

Among nearly 43,000 pescatarians — people who eat fish but no meat or poultry — the risks for breast (HR, 0.93), colorectal (HR, 0.85), and kidney (HR, 0.73) cancers were reduced relative to meat-eaters. Meanwhile, men who reported eating poultry, but no red or processed meat, had a decreased risk for prostate cancer (HR, 0.93).

In sum, Aune said, “these findings provide further support for dietary recommendations that emphasize higher intakes of whole plant foods, such as whole grains, fruits, vegetables, nuts and legumes and less meat.” And, McTiernan noted, it’s never too late for people to change their dietary habits.

“Clinical trials have shown immediate benefits to vegetarian diets, like reductions in lipids and weight loss — things that can affect health across the board,” she said.

This study was funded by the World Cancer Research Fund, Cancer Research UK, the Medical Research Council and others. The authors declared having no competing interests.

Ernie Mundell is a freelance medical journalist based in Los Angeles. He has more than 30 years of experience, including editorial positions at Reuters Health and HealthDay.

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

A trio of new studies, published simultaneously in February in Nature Medicine, add to growing evidence that manipulating the gut microbiome may enhance responses to immunotherapy in selected patients with cancer.

In these small, early-phase studies involving patients with metastatic renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), and melanoma receiving immune checkpoint inhibitor (ICI) therapy, fecal microbiota transplantation (FMT) was associated with objective response rates that compared favorably with historical or prespecified benchmarks.

The idea that microbiome modulation via FMT “can augment immunotherapy efficacy is probably a good one and these studies certainly support that hypothesis,” said Diwakar Davar, MD, assistant professor of medicine and an oncologist/hematologist at the University of Pittsburgh, Pennsylvania, who wasn’t part of the new work.While “an intriguing approach and certainly worthy of further evaluation,” Davar cautioned that the latest studies are not robust enough to answer the question conclusively.

Although ICIs have improved outcomes for patients with melanoma, NSCLC, and RCC, many patients still do not respond or eventually develop resistance. A growing body of evidence suggests that the gut microbiome can influence the effectiveness of ICI therapy. However, much of this evidence comes from preclinical studies showing that modulating the microbiome via FMT can alter responses to immunotherapy, along with small proof-of-concept human studies — predominantly in melanoma — suggesting this approach may help overcome primary or acquired resistance to anti-PD-1 therapy.

The new studies aimed to build on this foundation by exploring whether FMT could improve ICI responses and clinical outcomes in patients with NSCLC, melanoma, and RCC.

In the phase 2, open-label FMT-LUMINate trial, researchers tested a healthy-donor FMT delivered as oral capsules before patients began immunotherapy. FMT capsules were produced using 80-100 g of feces per dose from screened healthy donors, and patients consumed 30-40 capsules while under supervision. The study included 20 patients with NSCLC and high PD-L1 tumor expression receiving FMT before standard first-line pembrolizumab monotherapy and 20 patients with cutaneous melanoma receiving FMT before ipilimumab plus nivolumab.

In the NSCLC cohort, 16 patients (80%) achieved an objective response. The 80% objective response rate exceeded the prespecified efficacy threshold of 64% and was higher than previously described historical data, which ranged from 39% to 46%, the study team noted.

In the melanoma cohort, FMT before nivolumab and ipilimumab yielded an objective response rate of 75%, also exceeding the historical expected response rates of 50% to 58% among patients receiving this ICI combination.

In patients with NSCLC, no grade 3 or higher adverse events were reported. However, grade 3 or higher adverse events were reported in 13 (65%) patients in the melanoma group, suggesting a potentially accelerated onset of immune-related adverse events. Researchers also observed a higher-than-expected frequency of myocarditis in melanoma patients (15%). These toxicities clustered among patients who had FMT donors enriched in Prevotella spp, highlighting the importance of donor selection for future trials, the researchers explained.

The team plans to assess the potential of FMT to overcome primary resistance to ICI as part of the phase 2 CanBiome2 randomized trial, which aims to enroll 128 patients.

The RCC Data

The other two studies focused on FMT in patients with metastatic RCC. In the phase 1 PERFORM study, 20 treatment-naive patients with metastatic RCC added encapsulated healthy-donor FMT to standard ICI-based regimens — most commonly ipilimumab plus nivolumab, with some patients receiving pembrolizumab plus axitinib or pembrolizumab plus lenvatinib.

The primary endpoint was safety defined by the incidence and severity of immune-related adverse events. The safety endpoint was met; 50% of patients (10 of 20) experienced grade 3 immune-related adverse events, and there were no serious FMT-related toxicities and no grade 4 or 5 events.

Among 18 evaluable patients, nine (50%) achieved an objective response, including two who had complete responses (11%). Notably, most treatment responders did not develop any grade 3 or higher immune-related adverse events, the researchers reported.

Finally, in the phase 2a TACITO trial, 45 patients with treatment-naive metastatic RCC were randomly allocated to receive donor FMT or placebo FMT. Patients received three administrations over 6 months — first via colonoscopy then as capsulized doses, alongside pembrolizumab plus axitinib.

The primary endpoint of 12-month progression-free survival narrowly missed statistical significance — 70% vs 41% (P = .053) — but suggested a benefit in the donor FMT group.

“We need more than 1 year to appreciate statistical significance in terms of progression-free survival,” study investigator Gianluca Ianiro, MD, PhD, with Catholic University of the Sacred Heart, Rome, told Medscape Medical News.

As for secondary endpoints, median progression-free survival was significantly longer with donor FMT (24.0 vs 9.0 months; hazard ratio, 0.50; P = .035) and the objective response rate was higher with donor FMT (52% vs 32%).

Why Might FMT Boost ICI Response?

Conceptually, FMT is intended to reshape the gut ecosystem in ways that favor antitumor immunity, and possibly reduce immune dysregulation.

Across these new studies, the mechanistic story is moving beyond the idea that more diversity is good and toward a model that suggests a benefit to removing or suppressing taxa associated with resistance or inflammatory toxicity.

For example, in the TACITO trial, microbiome analysis confirmed that acquisition or loss of specific bacterial strains was associated with 12-month progression-free survival.

Additionally, results of the FMT-LUMINate trial hinted that the therapeutic benefit of FMT may be driven by eliminating harmful bacteria present at baseline, most notably Enterocloster, Clostridium and Streptococcus spp.

“This bacterial depletion was associated with a favorable immunometabolic milieu,” the FMT-LUMINate researchers wrote. Additionally, the results suggest that “failure to eliminate baseline deleterious taxa may sustain an immunosuppressive metabolic and systemic immune milieu that compromises ICI responses.”

Is FMT Ready for Prime Time?

Ianiro told Medscape Medical News he “definitely” thinks microbiome modulation could eventually become part of standard immunotherapy regimens.

Although the “signal” of benefit is clearly there, Davar cautioned that it’s too early to justify routine, off-trial use of FMT specifically to improve ICI response.

“These remain small, proof-of-concept studies. They are not adequately powered trials of fecal transplants and multiple different covariates haven’t been considered,” Davar said.

The study researchers noted that issues around donor selection and availability, dosing schedules, product standardization, and safety risk stratification need to be resolved.

For example, TACITO’s real-world experience shows logistics can matter. Delays occurred due to capsule unavailability and other scheduling barriers, which led to late dosing and missed or shifted treatments in some patients.

That’s a reminder that scaling FMT for oncology would require robust manufacturing, distribution, and time-sensitive coordination with ICI start dates.

More broadly, “whether FMT is the most suitable method of essentially changing the gut microbiome remains unclear,” explained Davar, who suggested that engineered microbiome therapeutics or tailored therapies may be a preferable, more scalable and tailored long-term solution.

Overall, does this new research provide impetus to develop stool banks? “Probably not,” Davar said.

But is it a call for interested parties to think about clinical trials and experimental products that could influence the gut microbiome? “Those are all probably good ideas,” he said.

The PERFORM, TACITO and FMT-LUMINate trials had no commercial funding. Saman Maleki Vareki, PhD, of the PERFORM trial, is a cofounder of LND Therapeutics Inc and has submitted a US patent application related to FMT donor screening. Ianiro has received personal fees for acting as a speaker for Biocodex and Illumina and for acting as a consultant/advisor for Ferring Therapeutics. Arielle Elkrief, MD, of the FMT-LUMINate trial, has received honoraria from AstraZeneca, Merck, Bristol Myers Squibb, and EMD Serono; consulting fees from EverImmune, NECBio, and Sanofi-Pasteur; and is an inventor on a patent regarding the microbiome and immunotherapy response. Davar had no relevant disclosures.

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

A trio of new studies, published simultaneously in February in Nature Medicine, add to growing evidence that manipulating the gut microbiome may enhance responses to immunotherapy in selected patients with cancer.

In these small, early-phase studies involving patients with metastatic renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), and melanoma receiving immune checkpoint inhibitor (ICI) therapy, fecal microbiota transplantation (FMT) was associated with objective response rates that compared favorably with historical or prespecified benchmarks.

The idea that microbiome modulation via FMT “can augment immunotherapy efficacy is probably a good one and these studies certainly support that hypothesis,” said Diwakar Davar, MD, assistant professor of medicine and an oncologist/hematologist at the University of Pittsburgh, Pennsylvania, who wasn’t part of the new work.While “an intriguing approach and certainly worthy of further evaluation,” Davar cautioned that the latest studies are not robust enough to answer the question conclusively.

Although ICIs have improved outcomes for patients with melanoma, NSCLC, and RCC, many patients still do not respond or eventually develop resistance. A growing body of evidence suggests that the gut microbiome can influence the effectiveness of ICI therapy. However, much of this evidence comes from preclinical studies showing that modulating the microbiome via FMT can alter responses to immunotherapy, along with small proof-of-concept human studies — predominantly in melanoma — suggesting this approach may help overcome primary or acquired resistance to anti-PD-1 therapy.

The new studies aimed to build on this foundation by exploring whether FMT could improve ICI responses and clinical outcomes in patients with NSCLC, melanoma, and RCC.

In the phase 2, open-label FMT-LUMINate trial, researchers tested a healthy-donor FMT delivered as oral capsules before patients began immunotherapy. FMT capsules were produced using 80-100 g of feces per dose from screened healthy donors, and patients consumed 30-40 capsules while under supervision. The study included 20 patients with NSCLC and high PD-L1 tumor expression receiving FMT before standard first-line pembrolizumab monotherapy and 20 patients with cutaneous melanoma receiving FMT before ipilimumab plus nivolumab.

In the NSCLC cohort, 16 patients (80%) achieved an objective response. The 80% objective response rate exceeded the prespecified efficacy threshold of 64% and was higher than previously described historical data, which ranged from 39% to 46%, the study team noted.

In the melanoma cohort, FMT before nivolumab and ipilimumab yielded an objective response rate of 75%, also exceeding the historical expected response rates of 50% to 58% among patients receiving this ICI combination.

In patients with NSCLC, no grade 3 or higher adverse events were reported. However, grade 3 or higher adverse events were reported in 13 (65%) patients in the melanoma group, suggesting a potentially accelerated onset of immune-related adverse events. Researchers also observed a higher-than-expected frequency of myocarditis in melanoma patients (15%). These toxicities clustered among patients who had FMT donors enriched in Prevotella spp, highlighting the importance of donor selection for future trials, the researchers explained.

The team plans to assess the potential of FMT to overcome primary resistance to ICI as part of the phase 2 CanBiome2 randomized trial, which aims to enroll 128 patients.

The RCC Data

The other two studies focused on FMT in patients with metastatic RCC. In the phase 1 PERFORM study, 20 treatment-naive patients with metastatic RCC added encapsulated healthy-donor FMT to standard ICI-based regimens — most commonly ipilimumab plus nivolumab, with some patients receiving pembrolizumab plus axitinib or pembrolizumab plus lenvatinib.

The primary endpoint was safety defined by the incidence and severity of immune-related adverse events. The safety endpoint was met; 50% of patients (10 of 20) experienced grade 3 immune-related adverse events, and there were no serious FMT-related toxicities and no grade 4 or 5 events.

Among 18 evaluable patients, nine (50%) achieved an objective response, including two who had complete responses (11%). Notably, most treatment responders did not develop any grade 3 or higher immune-related adverse events, the researchers reported.

Finally, in the phase 2a TACITO trial, 45 patients with treatment-naive metastatic RCC were randomly allocated to receive donor FMT or placebo FMT. Patients received three administrations over 6 months — first via colonoscopy then as capsulized doses, alongside pembrolizumab plus axitinib.

The primary endpoint of 12-month progression-free survival narrowly missed statistical significance — 70% vs 41% (P = .053) — but suggested a benefit in the donor FMT group.

“We need more than 1 year to appreciate statistical significance in terms of progression-free survival,” study investigator Gianluca Ianiro, MD, PhD, with Catholic University of the Sacred Heart, Rome, told Medscape Medical News.

As for secondary endpoints, median progression-free survival was significantly longer with donor FMT (24.0 vs 9.0 months; hazard ratio, 0.50; P = .035) and the objective response rate was higher with donor FMT (52% vs 32%).

Why Might FMT Boost ICI Response?

Conceptually, FMT is intended to reshape the gut ecosystem in ways that favor antitumor immunity, and possibly reduce immune dysregulation.

Across these new studies, the mechanistic story is moving beyond the idea that more diversity is good and toward a model that suggests a benefit to removing or suppressing taxa associated with resistance or inflammatory toxicity.

For example, in the TACITO trial, microbiome analysis confirmed that acquisition or loss of specific bacterial strains was associated with 12-month progression-free survival.

Additionally, results of the FMT-LUMINate trial hinted that the therapeutic benefit of FMT may be driven by eliminating harmful bacteria present at baseline, most notably Enterocloster, Clostridium and Streptococcus spp.

“This bacterial depletion was associated with a favorable immunometabolic milieu,” the FMT-LUMINate researchers wrote. Additionally, the results suggest that “failure to eliminate baseline deleterious taxa may sustain an immunosuppressive metabolic and systemic immune milieu that compromises ICI responses.”

Is FMT Ready for Prime Time?

Ianiro told Medscape Medical News he “definitely” thinks microbiome modulation could eventually become part of standard immunotherapy regimens.

Although the “signal” of benefit is clearly there, Davar cautioned that it’s too early to justify routine, off-trial use of FMT specifically to improve ICI response.

“These remain small, proof-of-concept studies. They are not adequately powered trials of fecal transplants and multiple different covariates haven’t been considered,” Davar said.

The study researchers noted that issues around donor selection and availability, dosing schedules, product standardization, and safety risk stratification need to be resolved.

For example, TACITO’s real-world experience shows logistics can matter. Delays occurred due to capsule unavailability and other scheduling barriers, which led to late dosing and missed or shifted treatments in some patients.

That’s a reminder that scaling FMT for oncology would require robust manufacturing, distribution, and time-sensitive coordination with ICI start dates.

More broadly, “whether FMT is the most suitable method of essentially changing the gut microbiome remains unclear,” explained Davar, who suggested that engineered microbiome therapeutics or tailored therapies may be a preferable, more scalable and tailored long-term solution.

Overall, does this new research provide impetus to develop stool banks? “Probably not,” Davar said.

But is it a call for interested parties to think about clinical trials and experimental products that could influence the gut microbiome? “Those are all probably good ideas,” he said.

The PERFORM, TACITO and FMT-LUMINate trials had no commercial funding. Saman Maleki Vareki, PhD, of the PERFORM trial, is a cofounder of LND Therapeutics Inc and has submitted a US patent application related to FMT donor screening. Ianiro has received personal fees for acting as a speaker for Biocodex and Illumina and for acting as a consultant/advisor for Ferring Therapeutics. Arielle Elkrief, MD, of the FMT-LUMINate trial, has received honoraria from AstraZeneca, Merck, Bristol Myers Squibb, and EMD Serono; consulting fees from EverImmune, NECBio, and Sanofi-Pasteur; and is an inventor on a patent regarding the microbiome and immunotherapy response. Davar had no relevant disclosures.

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

A trio of new studies, published simultaneously in February in Nature Medicine, add to growing evidence that manipulating the gut microbiome may enhance responses to immunotherapy in selected patients with cancer.

In these small, early-phase studies involving patients with metastatic renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), and melanoma receiving immune checkpoint inhibitor (ICI) therapy, fecal microbiota transplantation (FMT) was associated with objective response rates that compared favorably with historical or prespecified benchmarks.

The idea that microbiome modulation via FMT “can augment immunotherapy efficacy is probably a good one and these studies certainly support that hypothesis,” said Diwakar Davar, MD, assistant professor of medicine and an oncologist/hematologist at the University of Pittsburgh, Pennsylvania, who wasn’t part of the new work.While “an intriguing approach and certainly worthy of further evaluation,” Davar cautioned that the latest studies are not robust enough to answer the question conclusively.

Although ICIs have improved outcomes for patients with melanoma, NSCLC, and RCC, many patients still do not respond or eventually develop resistance. A growing body of evidence suggests that the gut microbiome can influence the effectiveness of ICI therapy. However, much of this evidence comes from preclinical studies showing that modulating the microbiome via FMT can alter responses to immunotherapy, along with small proof-of-concept human studies — predominantly in melanoma — suggesting this approach may help overcome primary or acquired resistance to anti-PD-1 therapy.

The new studies aimed to build on this foundation by exploring whether FMT could improve ICI responses and clinical outcomes in patients with NSCLC, melanoma, and RCC.

In the phase 2, open-label FMT-LUMINate trial, researchers tested a healthy-donor FMT delivered as oral capsules before patients began immunotherapy. FMT capsules were produced using 80-100 g of feces per dose from screened healthy donors, and patients consumed 30-40 capsules while under supervision. The study included 20 patients with NSCLC and high PD-L1 tumor expression receiving FMT before standard first-line pembrolizumab monotherapy and 20 patients with cutaneous melanoma receiving FMT before ipilimumab plus nivolumab.

In the NSCLC cohort, 16 patients (80%) achieved an objective response. The 80% objective response rate exceeded the prespecified efficacy threshold of 64% and was higher than previously described historical data, which ranged from 39% to 46%, the study team noted.

In the melanoma cohort, FMT before nivolumab and ipilimumab yielded an objective response rate of 75%, also exceeding the historical expected response rates of 50% to 58% among patients receiving this ICI combination.

In patients with NSCLC, no grade 3 or higher adverse events were reported. However, grade 3 or higher adverse events were reported in 13 (65%) patients in the melanoma group, suggesting a potentially accelerated onset of immune-related adverse events. Researchers also observed a higher-than-expected frequency of myocarditis in melanoma patients (15%). These toxicities clustered among patients who had FMT donors enriched in Prevotella spp, highlighting the importance of donor selection for future trials, the researchers explained.

The team plans to assess the potential of FMT to overcome primary resistance to ICI as part of the phase 2 CanBiome2 randomized trial, which aims to enroll 128 patients.

The RCC Data

The other two studies focused on FMT in patients with metastatic RCC. In the phase 1 PERFORM study, 20 treatment-naive patients with metastatic RCC added encapsulated healthy-donor FMT to standard ICI-based regimens — most commonly ipilimumab plus nivolumab, with some patients receiving pembrolizumab plus axitinib or pembrolizumab plus lenvatinib.

The primary endpoint was safety defined by the incidence and severity of immune-related adverse events. The safety endpoint was met; 50% of patients (10 of 20) experienced grade 3 immune-related adverse events, and there were no serious FMT-related toxicities and no grade 4 or 5 events.

Among 18 evaluable patients, nine (50%) achieved an objective response, including two who had complete responses (11%). Notably, most treatment responders did not develop any grade 3 or higher immune-related adverse events, the researchers reported.

Finally, in the phase 2a TACITO trial, 45 patients with treatment-naive metastatic RCC were randomly allocated to receive donor FMT or placebo FMT. Patients received three administrations over 6 months — first via colonoscopy then as capsulized doses, alongside pembrolizumab plus axitinib.

The primary endpoint of 12-month progression-free survival narrowly missed statistical significance — 70% vs 41% (P = .053) — but suggested a benefit in the donor FMT group.

“We need more than 1 year to appreciate statistical significance in terms of progression-free survival,” study investigator Gianluca Ianiro, MD, PhD, with Catholic University of the Sacred Heart, Rome, told Medscape Medical News.

As for secondary endpoints, median progression-free survival was significantly longer with donor FMT (24.0 vs 9.0 months; hazard ratio, 0.50; P = .035) and the objective response rate was higher with donor FMT (52% vs 32%).

Why Might FMT Boost ICI Response?

Conceptually, FMT is intended to reshape the gut ecosystem in ways that favor antitumor immunity, and possibly reduce immune dysregulation.

Across these new studies, the mechanistic story is moving beyond the idea that more diversity is good and toward a model that suggests a benefit to removing or suppressing taxa associated with resistance or inflammatory toxicity.

For example, in the TACITO trial, microbiome analysis confirmed that acquisition or loss of specific bacterial strains was associated with 12-month progression-free survival.

Additionally, results of the FMT-LUMINate trial hinted that the therapeutic benefit of FMT may be driven by eliminating harmful bacteria present at baseline, most notably Enterocloster, Clostridium and Streptococcus spp.

“This bacterial depletion was associated with a favorable immunometabolic milieu,” the FMT-LUMINate researchers wrote. Additionally, the results suggest that “failure to eliminate baseline deleterious taxa may sustain an immunosuppressive metabolic and systemic immune milieu that compromises ICI responses.”

Is FMT Ready for Prime Time?

Ianiro told Medscape Medical News he “definitely” thinks microbiome modulation could eventually become part of standard immunotherapy regimens.

Although the “signal” of benefit is clearly there, Davar cautioned that it’s too early to justify routine, off-trial use of FMT specifically to improve ICI response.

“These remain small, proof-of-concept studies. They are not adequately powered trials of fecal transplants and multiple different covariates haven’t been considered,” Davar said.

The study researchers noted that issues around donor selection and availability, dosing schedules, product standardization, and safety risk stratification need to be resolved.

For example, TACITO’s real-world experience shows logistics can matter. Delays occurred due to capsule unavailability and other scheduling barriers, which led to late dosing and missed or shifted treatments in some patients.

That’s a reminder that scaling FMT for oncology would require robust manufacturing, distribution, and time-sensitive coordination with ICI start dates.

More broadly, “whether FMT is the most suitable method of essentially changing the gut microbiome remains unclear,” explained Davar, who suggested that engineered microbiome therapeutics or tailored therapies may be a preferable, more scalable and tailored long-term solution.

Overall, does this new research provide impetus to develop stool banks? “Probably not,” Davar said.

But is it a call for interested parties to think about clinical trials and experimental products that could influence the gut microbiome? “Those are all probably good ideas,” he said.

The PERFORM, TACITO and FMT-LUMINate trials had no commercial funding. Saman Maleki Vareki, PhD, of the PERFORM trial, is a cofounder of LND Therapeutics Inc and has submitted a US patent application related to FMT donor screening. Ianiro has received personal fees for acting as a speaker for Biocodex and Illumina and for acting as a consultant/advisor for Ferring Therapeutics. Arielle Elkrief, MD, of the FMT-LUMINate trial, has received honoraria from AstraZeneca, Merck, Bristol Myers Squibb, and EMD Serono; consulting fees from EverImmune, NECBio, and Sanofi-Pasteur; and is an inventor on a patent regarding the microbiome and immunotherapy response. Davar had no relevant disclosures.

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

The Public Health and Welfare Act of 1988 prohibited the use of federal funds to “provide individuals with hypodermic needles or syringes so that such individuals may use illegal drugs.”¹ Although the Act included the caveat that the US Surgeon General may determine that “a demonstration needle exchange program would be effective in reducing drug abuse,” and thus federal funds could be used, the legislation prohibited federal, state, and local agencies from funding syringe services programs (SSPs). SSPs use various harm reduction tools to improve public safety and reduce the potential harmful consequences of risky behaviors, similar to how using a seat belt while driving reduces the risk of injury or death.² SSPs are rooted in evidence-based practices, and several studies, according to the Centers for Disease Control and Prevention, have found that people who use drugs (PWUDs) who use community-based SSPs are 5 times more likely to enter treatment than those who do not use these programs. Additionally, these programs have shown an estimated 50% reduction in HIV and hepatitis C infections.³

Amid a 2015 HIV outbreak in Indiana among individuals sharing needles for injection drug use, Congress passed an omnibus spending bill that partially lifted the federal funding restriction. Federal funds now may be used for operational costs that support SSPs but may not be used to purchase syringes themselves.⁴

Following the 2015 legislation, federal agencies began implementing SSPs. The Veterans Health Administration (VHA) established SSPs at 3 medical centers in 2017.⁵ Veterans who participated in the programs were able to access supplies (eg, syringes, fentanyl test strips, wound care kits, and condoms) through donations to US Department of Veterans Affairs (VA) medical centers (VAMCs). The success of these programs laid the foundation for the VHA to implement SSPs nationally. VHA SSPs provided access to naloxone (an opioid overdose reversal medication), fentanyl test strips, condoms, sterile syringe distribution, testing for blood-borne viruses, HIV pre-exposure prophylaxis, as well as educational materials and resources, and low-barrier access to drug treatment (eg, medications for opioid use disorder [OUD]).

In 2020, the Biden Administration outlined 7 drug policy priorities, which included enhancing evidence-based harm reduction efforts. ⁶ This policy also discussed mandates for federal agencies to remove barriers to federal funding for purchasing syringes and other harm reduction supplies. The VHA responded to the policy by publishing guidance that recommended VAMCs develop and/or ensure veterans have access to harm reduction services in the community, where state law is not legally more stringent.⁷

In 2025 the Trump administration Statement of Drug Policy Priorities encouraged local jurisdictions to increase the availability of drug test strips and naloxone.⁸ These significant policy shifts moved SSPs from being housed mostly in local public health departments and community-based organizations to also being available at health care facilities. ⁹ VAMCs have unique opportunities to provide universal health care that includes both prevention services and other medical management to PWUD.

One study assessed staff perceptions of PWUD at a VAMC in preparation for a training program about harm reduction. The results indicated an overall positive staff perception of PWUD, although only the Drug and Drug Problems Perceptions Questionnaire (DDPPQ) was administered, which assessed comfort of working with this population and not explicitly the use of harm reduction.¹⁰ Another study interviewed clinical pharmacists, primary care clinicians, social workers, and directors of addiction and mental health services to determine barriers and facilitators (ie, potential opportunities to promote change) to implementing harm reduction at the VHA. The study identified barriers to be a lack of knowledge, time, and comfort, while suggesting opportunities for improvement were engagement of champions, communication and educational strategies, and adaptation of existing infrastructure.¹¹

While these findings are insightful for the VHA to disseminate a harm reduction program, there remains a gap in assessing staff willingness to provide harm reduction services. Evidence on harm reduction services among veterans is limited and more research is needed to better understand the role of these services and acceptance among enrolled veterans and VHA staff. Specifically, more research is needed on health care practitioners’ (HCPs) perceptions of harm reduction use.

Mental health care practitioners frequently treat patients with substance use disorders (SUDs), making them an ideal initial cohort to assess willingness to provide harm reduction to this population. By analyzing mental HCPs’ perceptions, additional interventions could be identified, implemented, and evaluated to improve their willingness to provide harm reduction tools.

This project focused on mental health clinicians with prescribing privileges: physicians (allopathic and osteopathic physicians), nurse practitioners, physician assistants, and clinical pharmacist practitioners. Mental health prescribers were selected because they are uniquely positioned at the intersection of prevention and treatment in drug use. Furthermore, mental health prescribers at the VAMCs included in this study are usually the primary point of entry to SUD clinics. This mixed-methods study used an anonymous online survey and voluntary postsurvey discussions with mental health care prescribers to elaborate on their beliefs and attitudes, providing deeper insight into their responses regarding harm reduction.

Methods

This project was conducted by the Veterans Integrated Services Network (VISN) 5 academic detailing team. VISN 5 serves veterans from economically and demographically diverse areas in Maryland; Washington, DC; West Virginia; and portions of Virginia, Pennsylvania, Ohio, and Kentucky. VAMCs in Baltimore, Maryland, and Washington, DC, serve a largely urban population while the 4 West Virginia facilities in Martinsburg, Huntington, Beckley, and Clarksburg, serve a largely rural population. West Virginia has been the epicenter of the opioid crisis and consistently has the highest drug overdose deaths per capita in the United States.¹² Among cities, Baltimore, Maryland, has the highest number of drug overdose deaths per capita with 174.1 per 100,000 people.^12,13

At the time of this project, the 6 VISN 5 VAMCs had established overdose education and naloxone distribution (OEND) programs. Although OEND programs have existed since 2013, VISN 5 SSPs and harm reduction services that provided fentanyl test strips were only available at the Martinsburg, Beckley, and Huntington VAMCs. All 6 VAMCs had substance use treatment programs with a variety of inpatient and outpatient mental health services. The Washington, DC and Baltimore VAMCs had opioid treatment programs that provided methadone maintenance.

The VISN 5 academic detailing team consists of 7 clinical pharmacists. These academic detailers plan annual systematic interventions to provide medical knowledge translation services on health-related campaigns. Academic detailers are trained in change management and motivational interviewing. They uniquely facilitate conversations with HCPs on various topics or campaigns, aiming for quality improvement and behavioral change through positive relationships and sharing resources.¹⁴ Academic detailing conversations and relationships with HCPs involve assessing and understanding HCP behaviors, including barriers and readiness to change to align with the goal of improving patient outcomes. Academic detailing has improved practice behaviors around providing OEND in VHA.¹⁵

To prepare for a harm reduction campaign, the academic detailers sought to gain insight from target VISN 5 mental health prescribers. Figure 1 outlines the project timeline, which started with emails inviting mental health prescribers to complete an anonymous online survey. Academic detailers from each site emailed mental health prescribers who completed the survey to determine interest in expanding on survey findings. Mental health prescribers who completed the survey could participate in a postsurvey discussion.

Surveys

Between January 29, 2024, and February 22, 2024, the academic detailers emailed facility mental health prescribers (N = 156) a link to an anonymous 15-question survey. The email informed recipients of the survey’s purpose: to gain a better understanding of prescriber perceptions of veterans with SUD and harm reduction programs and their willingness to provide harm reduction tools, to better determine interventions that could be implemented.

The survey collected prescriber demographic data and their perceptions of PWUD and harm reduction tools and education. Survey questions were extrapolated from validated surveys (eg, DDPPQ) and survey-based implicit association test.^16,17 The survey used multiple choice and 5-point Likert scale questions. Mental health prescribers were asked about their role at the VHA, years in practice, medical center affiliation, type of SUDs treated (eg, opioid, stimulant, alcohol, cannabis, or other), and whether they had previously met with academic detailers about harm reduction.

Respondents read statements about patients with or without SUD and provided Likert scale responses describing their regard, level of comfort, and preferences. The survey included Likert scale questions about respondents’ comfort in providing harm reduction education and supplies. Respondents also noted whether they believed harm reduction reduced substance use, harm reduction tools encourage people with SUD to continue using drugs, and whether HCPs can impact clinical change.

Postsurvey interviews with predetermined questions were conducted in-person or via video conference with ≥ 1 prescriber at each VAMC by an academic detailer. The postsurvey discussion offered an opportunity for respondents to further elaborate and describe previous experiences and current beliefs that may affect their attitudes toward people with SUD and their views on harm reduction. Participants received no compensation for survey completion or interviews.

Analysis

The Washington VAMC Institutional Review Board reviewed and approved this project as quality improvement with potential publication. No inferential statistics were calculated. Survey participant demographics were reported using frequencies and proportions reported for categorical variables. Notes from follow-up interviews were analyzed using the Prosci Awareness, Desire, Knowledge, Ability, and Reinforcement (ADKAR) Model for Change Management.¹⁸ This framework is used by academic detailers to determine a prescriber’s stage of change, which helps select the appropriate resources to move the clinician along a change framework. Completed postsurvey interview sheets, including notes written by the academic detailer, were analyzed by the project lead (NJ) who reviewed each interview sheet and analysis with the academic detailer who led the discussion.

Results

Sixty-six respondents completed the online survey (42% response rate), and 7 mental health prescribers participated in a postsurvey discussion. Thirty-one participants (47%) were physicians and 17 (26%) were in practice for > 20 years. Response rates reflected the size of mental health staff at each VAMC at the time of the survey: 17 respondents (26%) worked at each of the Martinsburg and Baltimore VAMCs, with fewer at the other VAMCs (Table 1). Alcohol use disorder was the most commonly reported SUD treated (n = 62; 33%), followed by cannabis use disorder (n = 40; 21%), OUD (n = 38; 20%), and stimulant use disorder (n = 37; 20%).

Respondents felt comfortable and confident educating patients on ways to reduce harm related to substance use (91%; mean [SD], 4.24 [0.84]). Most prescribers surveyed (97%; mean [SD], 1.59 [0.68]) disagreed or strongly disagreed that harm reduction encourages patients with SUD to continue using drugs, and all prescribers surveyed disagreed that there is nothing they can do to encourage harm reduction. Survey results were mixed for personal comfort in working with people with SUD vs people without SUD (Figure 2). Respondents were most willing to provide naloxone (95%; mean [SD], 4.71 [0.78]), compared to fentanyl test strips (61%; mean [SD], 3.61 [1.41]) or syringes (39%; mean [SD], 3.18 [1.39]). Respondents were neutral or least willing to provide syringes (Figure 3).

Seven postsurvey interviews were completed between academic detailers and mental health clinicians across the 6 VAMCs. Respondents included 1 physician assistant, 1 nurse practitioner, 1 pharmacist, and 4 physicians. Notes were analyzed using the ADKAR Change Competency Model to organize clinician stages of change (Table 2).

Barriers identified by interviewees included lack of mobile services, lack of confidence and awareness of the availability of harm reduction at their respective medical center, lack of time to discuss harm reduction, negative sentiments toward providing SUD-related harm reduction, discomfort with harm reduction products, and lack of knowledge and time to learn about harm reduction services. Opportunities identified to drive change in practice included additional time allotted during patient appointments, educational discussions and presentations to increase knowledge of and comfort with harm reduction tools, a clear clinical patient care workflow and process for harm reduction services, and reinforcement strategies to recognize success.

Discussion

This project investigated mental health prescribers’ perceptions of harm reduction at VAMCs in West Virginia, Maryland, and Washington, DC. While previous studies have demonstrated the efficacy of harm reduction tools, there is a lack of research on HCPs willingness to use these resources. This study suggests that while most respondents feel confident in and see the value of offering harm reduction resources to patients, a disparity exists between which resources HCPs are more likely to use and factors that would further enhance their ability to integrate harm reduction into practice. The follow-up interviews provided additional insight into the survey results.

Most respondents met the awareness and desire stage and moved to the knowledge, ability, or reinforcement ADKAR stage. It would be reasonable to extrapolate that most of the respondents felt comfortable with and were very likely to offer certain harm reduction tools. In the ADKAR interview analysis, the most common factors needed to drive change included having more time during patient appointments, additional education, clear processes for harm reduction services, and reinforcement strategies to sustain change. Respondents noted that harm reduction discussions took extra time in their already limited appointments with patients, which may have limited time for discussions surrounding all other mental health concerns. These discussions often necessitate in-depth conversations to accurately understand the patients’ needs. Given HCP time constraints, they may view harm reduction as lower in urgency and priority relative to other concerns. While most respondents were in the reinforcement phase, it is important to note the ADKAR model is fluid, and therefore an HCP could move forward or backward. This movement can be noted in the postsurvey interviews where, for example, prescriber 6 was determined to be in the reinforcement stage since they had already discussed harm reduction with patients. However, prescriber 6 also noted a barrier of unfamiliarity with local laws, which could shift them to the ADKAR knowledge stage.

Respondents noted that education through didactic sessions could lead to better incorporation of harm reduction into patient care. While harm reduction has evidence supporting its effectiveness, the respondents noted willingness to discuss harm reduction when treatment fails or the patient refuses treatment or referrals. Respondents expressed mixed opinions on use of harm reduction tools among patients with SUDs as some prescribers viewed harm reduction as part of a treatment plan and others viewed a return to drug use as a failure of treatment. Furthermore, respondents expressed hesitancy surrounding certain harm reduction tools, such as fentanyl test strips or syringes, and perceived these supplies as intended for medical use rather than harm reduction. HCPs may feel uncomfortable offering these supplies for drug use, despite their use for reducing risk.

Most responses were received from VAMCs with large mental health substance use programs. Respondents at larger, urban facilities (Washington, DC, and Baltimore, Maryland) expressed more hesitancy around using harm reduction tools despite having more harm reduction resources available compared to smaller or rural sites. These results align with previous studies that found no difference in prescribers providing medications for OUD in rural and urban VAMCs, showing urban sites, despite more resources, are not more willing to provide harm reduction or other addiction services.¹⁹ This evidence might indicate that urban sites may not use available resources (eg, methadone clinics) or that rural sites can provide just as robust medications for OUD care as urban sites.

Follow-up interview analysis indicated that HCPs lack knowledge of certain harm reduction tools. One-on-one peer discussions, like academic detailing, can facilitate discussions around a prescriber’s role in harm reduction, address gaps in knowledge by sharing what is available at the facilities for harm reduction, and suggest conversation points to help prescribers start harm reduction discussions with patients unwilling to begin treatment. Additionally, academic detailing can connect prescribers to available resources in the community to provide pragmatic approaches and suggestions. A clear and consistent treatment process may reduce barriers by reassuring prescribers they have support and by providing consistent directions so that prescribers do not waste time.

Reinforcement is important for sustaining change. VAMCs could consider positive feedback and other evidence-based reinforcement strategies (eg, social recognition, continuing education) to communicate that these changes are noticed and appreciated.²⁰ Late adopters may also be influenced by seeing positive feedback and results for peers. Systematic changes can be the catalyst for and sustain individual change.

Shifting perceptions and adopting change may be challenging, especially for SUD, which can be highly stigmatized. Promotion of successful change should be multifaceted and include both system and individual approaches. VHA systemic changes that could contribute to positive change include provision of time and access to SUD treatment training, a clear and sustainable treatment process, and reinforcement by recognizing success. In addition, facility leadership could provide support through dedicated time and resources during the workday for SUD treatment and harm reduction training. Support could empower HCPs and convey leadership support for harm reduction. This dedicated time could be used for didactic lecture sessions or individual meetings with academic detailers who can tailor discussions to the prescriber’s practice.

Strengths and Limitations

This survey included prescribers from a range of mental health care practice settings (eg, inpatient, outpatient clinic, rural, urban) and varied years of experience. This variety resulted in diverse perspectives and knowledge bases. Postsurvey interviews allowed academic detailers to gain deeper insight into answers in the survey, which can guide future interventions. Postsurvey interviews and application of the ADKAR model provided additional viewpoints on harm reduction.

A limitation of this project is the absence of an assessment of respondents’ harm reduction knowledge accuracy. Although respondents reported confidence in discussing harm reduction with patients, the survey did not assess whether their knowledge was accurate. Additionally, the survey did not ask about the availability of syringes and test strips at the prescribers’ VAMC, which could explain discrepancies in responses between naloxone and other forms of harm reduction (drug test strips and syringes were not available to all HCPs in the VISN). This lack of availability may have skewed responses. West Virginia SSPs, for example, were closed following legislative changes, which may contribute to stigma.²¹

Not all respondents were asked to do a follow-up interview, which limited the perspectives included in this study. Each site had ≥ 1 follow-up interview to limit the academic detailer’s workload. The initial survey included the phrase clean syringe, which can be stigmatizing and insinuate that PWUD are not clean. The preferred term would have been sterile syringe.²²

Conclusions

This survey of mental health prescribers found that most respondents are comfortable treating patients with SUD and confident in educating patients on harm reduction. Additionally, most respondents were more willing to provide naloxone vs fentanyl test strips or sterile syringes. A lack of time and awareness was the most frequently cited barrier to harm reduction services. As the VHA continues to expand access to harm reduction programs, which have proven to increase treatment rates and reduce disease, it will be imperative for HCPs, including mental health prescribers, to recognize the benefit of these programs for veterans with SUD. Future interventions should be designed and evaluated in collaboration with all HCPs and patients. This project determined ways to promote change for prescribers, but it will be important for further research to continue those conversations and incorporate patient perspectives.

The Public Health and Welfare Act of 1988 prohibited the use of federal funds to “provide individuals with hypodermic needles or syringes so that such individuals may use illegal drugs.”¹ Although the Act included the caveat that the US Surgeon General may determine that “a demonstration needle exchange program would be effective in reducing drug abuse,” and thus federal funds could be used, the legislation prohibited federal, state, and local agencies from funding syringe services programs (SSPs). SSPs use various harm reduction tools to improve public safety and reduce the potential harmful consequences of risky behaviors, similar to how using a seat belt while driving reduces the risk of injury or death.² SSPs are rooted in evidence-based practices, and several studies, according to the Centers for Disease Control and Prevention, have found that people who use drugs (PWUDs) who use community-based SSPs are 5 times more likely to enter treatment than those who do not use these programs. Additionally, these programs have shown an estimated 50% reduction in HIV and hepatitis C infections.³

Amid a 2015 HIV outbreak in Indiana among individuals sharing needles for injection drug use, Congress passed an omnibus spending bill that partially lifted the federal funding restriction. Federal funds now may be used for operational costs that support SSPs but may not be used to purchase syringes themselves.⁴

Following the 2015 legislation, federal agencies began implementing SSPs. The Veterans Health Administration (VHA) established SSPs at 3 medical centers in 2017.⁵ Veterans who participated in the programs were able to access supplies (eg, syringes, fentanyl test strips, wound care kits, and condoms) through donations to US Department of Veterans Affairs (VA) medical centers (VAMCs). The success of these programs laid the foundation for the VHA to implement SSPs nationally. VHA SSPs provided access to naloxone (an opioid overdose reversal medication), fentanyl test strips, condoms, sterile syringe distribution, testing for blood-borne viruses, HIV pre-exposure prophylaxis, as well as educational materials and resources, and low-barrier access to drug treatment (eg, medications for opioid use disorder [OUD]).

In 2020, the Biden Administration outlined 7 drug policy priorities, which included enhancing evidence-based harm reduction efforts. ⁶ This policy also discussed mandates for federal agencies to remove barriers to federal funding for purchasing syringes and other harm reduction supplies. The VHA responded to the policy by publishing guidance that recommended VAMCs develop and/or ensure veterans have access to harm reduction services in the community, where state law is not legally more stringent.⁷

In 2025 the Trump administration Statement of Drug Policy Priorities encouraged local jurisdictions to increase the availability of drug test strips and naloxone.⁸ These significant policy shifts moved SSPs from being housed mostly in local public health departments and community-based organizations to also being available at health care facilities. ⁹ VAMCs have unique opportunities to provide universal health care that includes both prevention services and other medical management to PWUD.

One study assessed staff perceptions of PWUD at a VAMC in preparation for a training program about harm reduction. The results indicated an overall positive staff perception of PWUD, although only the Drug and Drug Problems Perceptions Questionnaire (DDPPQ) was administered, which assessed comfort of working with this population and not explicitly the use of harm reduction.¹⁰ Another study interviewed clinical pharmacists, primary care clinicians, social workers, and directors of addiction and mental health services to determine barriers and facilitators (ie, potential opportunities to promote change) to implementing harm reduction at the VHA. The study identified barriers to be a lack of knowledge, time, and comfort, while suggesting opportunities for improvement were engagement of champions, communication and educational strategies, and adaptation of existing infrastructure.¹¹

While these findings are insightful for the VHA to disseminate a harm reduction program, there remains a gap in assessing staff willingness to provide harm reduction services. Evidence on harm reduction services among veterans is limited and more research is needed to better understand the role of these services and acceptance among enrolled veterans and VHA staff. Specifically, more research is needed on health care practitioners’ (HCPs) perceptions of harm reduction use.

Mental health care practitioners frequently treat patients with substance use disorders (SUDs), making them an ideal initial cohort to assess willingness to provide harm reduction to this population. By analyzing mental HCPs’ perceptions, additional interventions could be identified, implemented, and evaluated to improve their willingness to provide harm reduction tools.

This project focused on mental health clinicians with prescribing privileges: physicians (allopathic and osteopathic physicians), nurse practitioners, physician assistants, and clinical pharmacist practitioners. Mental health prescribers were selected because they are uniquely positioned at the intersection of prevention and treatment in drug use. Furthermore, mental health prescribers at the VAMCs included in this study are usually the primary point of entry to SUD clinics. This mixed-methods study used an anonymous online survey and voluntary postsurvey discussions with mental health care prescribers to elaborate on their beliefs and attitudes, providing deeper insight into their responses regarding harm reduction.

Methods

This project was conducted by the Veterans Integrated Services Network (VISN) 5 academic detailing team. VISN 5 serves veterans from economically and demographically diverse areas in Maryland; Washington, DC; West Virginia; and portions of Virginia, Pennsylvania, Ohio, and Kentucky. VAMCs in Baltimore, Maryland, and Washington, DC, serve a largely urban population while the 4 West Virginia facilities in Martinsburg, Huntington, Beckley, and Clarksburg, serve a largely rural population. West Virginia has been the epicenter of the opioid crisis and consistently has the highest drug overdose deaths per capita in the United States.¹² Among cities, Baltimore, Maryland, has the highest number of drug overdose deaths per capita with 174.1 per 100,000 people.^12,13

At the time of this project, the 6 VISN 5 VAMCs had established overdose education and naloxone distribution (OEND) programs. Although OEND programs have existed since 2013, VISN 5 SSPs and harm reduction services that provided fentanyl test strips were only available at the Martinsburg, Beckley, and Huntington VAMCs. All 6 VAMCs had substance use treatment programs with a variety of inpatient and outpatient mental health services. The Washington, DC and Baltimore VAMCs had opioid treatment programs that provided methadone maintenance.

The VISN 5 academic detailing team consists of 7 clinical pharmacists. These academic detailers plan annual systematic interventions to provide medical knowledge translation services on health-related campaigns. Academic detailers are trained in change management and motivational interviewing. They uniquely facilitate conversations with HCPs on various topics or campaigns, aiming for quality improvement and behavioral change through positive relationships and sharing resources.¹⁴ Academic detailing conversations and relationships with HCPs involve assessing and understanding HCP behaviors, including barriers and readiness to change to align with the goal of improving patient outcomes. Academic detailing has improved practice behaviors around providing OEND in VHA.¹⁵

To prepare for a harm reduction campaign, the academic detailers sought to gain insight from target VISN 5 mental health prescribers. Figure 1 outlines the project timeline, which started with emails inviting mental health prescribers to complete an anonymous online survey. Academic detailers from each site emailed mental health prescribers who completed the survey to determine interest in expanding on survey findings. Mental health prescribers who completed the survey could participate in a postsurvey discussion.

Surveys

Between January 29, 2024, and February 22, 2024, the academic detailers emailed facility mental health prescribers (N = 156) a link to an anonymous 15-question survey. The email informed recipients of the survey’s purpose: to gain a better understanding of prescriber perceptions of veterans with SUD and harm reduction programs and their willingness to provide harm reduction tools, to better determine interventions that could be implemented.

The survey collected prescriber demographic data and their perceptions of PWUD and harm reduction tools and education. Survey questions were extrapolated from validated surveys (eg, DDPPQ) and survey-based implicit association test.^16,17 The survey used multiple choice and 5-point Likert scale questions. Mental health prescribers were asked about their role at the VHA, years in practice, medical center affiliation, type of SUDs treated (eg, opioid, stimulant, alcohol, cannabis, or other), and whether they had previously met with academic detailers about harm reduction.

Respondents read statements about patients with or without SUD and provided Likert scale responses describing their regard, level of comfort, and preferences. The survey included Likert scale questions about respondents’ comfort in providing harm reduction education and supplies. Respondents also noted whether they believed harm reduction reduced substance use, harm reduction tools encourage people with SUD to continue using drugs, and whether HCPs can impact clinical change.

Postsurvey interviews with predetermined questions were conducted in-person or via video conference with ≥ 1 prescriber at each VAMC by an academic detailer. The postsurvey discussion offered an opportunity for respondents to further elaborate and describe previous experiences and current beliefs that may affect their attitudes toward people with SUD and their views on harm reduction. Participants received no compensation for survey completion or interviews.

Analysis

The Washington VAMC Institutional Review Board reviewed and approved this project as quality improvement with potential publication. No inferential statistics were calculated. Survey participant demographics were reported using frequencies and proportions reported for categorical variables. Notes from follow-up interviews were analyzed using the Prosci Awareness, Desire, Knowledge, Ability, and Reinforcement (ADKAR) Model for Change Management.¹⁸ This framework is used by academic detailers to determine a prescriber’s stage of change, which helps select the appropriate resources to move the clinician along a change framework. Completed postsurvey interview sheets, including notes written by the academic detailer, were analyzed by the project lead (NJ) who reviewed each interview sheet and analysis with the academic detailer who led the discussion.

Results

Sixty-six respondents completed the online survey (42% response rate), and 7 mental health prescribers participated in a postsurvey discussion. Thirty-one participants (47%) were physicians and 17 (26%) were in practice for > 20 years. Response rates reflected the size of mental health staff at each VAMC at the time of the survey: 17 respondents (26%) worked at each of the Martinsburg and Baltimore VAMCs, with fewer at the other VAMCs (Table 1). Alcohol use disorder was the most commonly reported SUD treated (n = 62; 33%), followed by cannabis use disorder (n = 40; 21%), OUD (n = 38; 20%), and stimulant use disorder (n = 37; 20%).

Respondents felt comfortable and confident educating patients on ways to reduce harm related to substance use (91%; mean [SD], 4.24 [0.84]). Most prescribers surveyed (97%; mean [SD], 1.59 [0.68]) disagreed or strongly disagreed that harm reduction encourages patients with SUD to continue using drugs, and all prescribers surveyed disagreed that there is nothing they can do to encourage harm reduction. Survey results were mixed for personal comfort in working with people with SUD vs people without SUD (Figure 2). Respondents were most willing to provide naloxone (95%; mean [SD], 4.71 [0.78]), compared to fentanyl test strips (61%; mean [SD], 3.61 [1.41]) or syringes (39%; mean [SD], 3.18 [1.39]). Respondents were neutral or least willing to provide syringes (Figure 3).

Seven postsurvey interviews were completed between academic detailers and mental health clinicians across the 6 VAMCs. Respondents included 1 physician assistant, 1 nurse practitioner, 1 pharmacist, and 4 physicians. Notes were analyzed using the ADKAR Change Competency Model to organize clinician stages of change (Table 2).

Barriers identified by interviewees included lack of mobile services, lack of confidence and awareness of the availability of harm reduction at their respective medical center, lack of time to discuss harm reduction, negative sentiments toward providing SUD-related harm reduction, discomfort with harm reduction products, and lack of knowledge and time to learn about harm reduction services. Opportunities identified to drive change in practice included additional time allotted during patient appointments, educational discussions and presentations to increase knowledge of and comfort with harm reduction tools, a clear clinical patient care workflow and process for harm reduction services, and reinforcement strategies to recognize success.

Discussion

This project investigated mental health prescribers’ perceptions of harm reduction at VAMCs in West Virginia, Maryland, and Washington, DC. While previous studies have demonstrated the efficacy of harm reduction tools, there is a lack of research on HCPs willingness to use these resources. This study suggests that while most respondents feel confident in and see the value of offering harm reduction resources to patients, a disparity exists between which resources HCPs are more likely to use and factors that would further enhance their ability to integrate harm reduction into practice. The follow-up interviews provided additional insight into the survey results.

Most respondents met the awareness and desire stage and moved to the knowledge, ability, or reinforcement ADKAR stage. It would be reasonable to extrapolate that most of the respondents felt comfortable with and were very likely to offer certain harm reduction tools. In the ADKAR interview analysis, the most common factors needed to drive change included having more time during patient appointments, additional education, clear processes for harm reduction services, and reinforcement strategies to sustain change. Respondents noted that harm reduction discussions took extra time in their already limited appointments with patients, which may have limited time for discussions surrounding all other mental health concerns. These discussions often necessitate in-depth conversations to accurately understand the patients’ needs. Given HCP time constraints, they may view harm reduction as lower in urgency and priority relative to other concerns. While most respondents were in the reinforcement phase, it is important to note the ADKAR model is fluid, and therefore an HCP could move forward or backward. This movement can be noted in the postsurvey interviews where, for example, prescriber 6 was determined to be in the reinforcement stage since they had already discussed harm reduction with patients. However, prescriber 6 also noted a barrier of unfamiliarity with local laws, which could shift them to the ADKAR knowledge stage.

Respondents noted that education through didactic sessions could lead to better incorporation of harm reduction into patient care. While harm reduction has evidence supporting its effectiveness, the respondents noted willingness to discuss harm reduction when treatment fails or the patient refuses treatment or referrals. Respondents expressed mixed opinions on use of harm reduction tools among patients with SUDs as some prescribers viewed harm reduction as part of a treatment plan and others viewed a return to drug use as a failure of treatment. Furthermore, respondents expressed hesitancy surrounding certain harm reduction tools, such as fentanyl test strips or syringes, and perceived these supplies as intended for medical use rather than harm reduction. HCPs may feel uncomfortable offering these supplies for drug use, despite their use for reducing risk.

Most responses were received from VAMCs with large mental health substance use programs. Respondents at larger, urban facilities (Washington, DC, and Baltimore, Maryland) expressed more hesitancy around using harm reduction tools despite having more harm reduction resources available compared to smaller or rural sites. These results align with previous studies that found no difference in prescribers providing medications for OUD in rural and urban VAMCs, showing urban sites, despite more resources, are not more willing to provide harm reduction or other addiction services.¹⁹ This evidence might indicate that urban sites may not use available resources (eg, methadone clinics) or that rural sites can provide just as robust medications for OUD care as urban sites.

Follow-up interview analysis indicated that HCPs lack knowledge of certain harm reduction tools. One-on-one peer discussions, like academic detailing, can facilitate discussions around a prescriber’s role in harm reduction, address gaps in knowledge by sharing what is available at the facilities for harm reduction, and suggest conversation points to help prescribers start harm reduction discussions with patients unwilling to begin treatment. Additionally, academic detailing can connect prescribers to available resources in the community to provide pragmatic approaches and suggestions. A clear and consistent treatment process may reduce barriers by reassuring prescribers they have support and by providing consistent directions so that prescribers do not waste time.

Reinforcement is important for sustaining change. VAMCs could consider positive feedback and other evidence-based reinforcement strategies (eg, social recognition, continuing education) to communicate that these changes are noticed and appreciated.²⁰ Late adopters may also be influenced by seeing positive feedback and results for peers. Systematic changes can be the catalyst for and sustain individual change.

Shifting perceptions and adopting change may be challenging, especially for SUD, which can be highly stigmatized. Promotion of successful change should be multifaceted and include both system and individual approaches. VHA systemic changes that could contribute to positive change include provision of time and access to SUD treatment training, a clear and sustainable treatment process, and reinforcement by recognizing success. In addition, facility leadership could provide support through dedicated time and resources during the workday for SUD treatment and harm reduction training. Support could empower HCPs and convey leadership support for harm reduction. This dedicated time could be used for didactic lecture sessions or individual meetings with academic detailers who can tailor discussions to the prescriber’s practice.

Strengths and Limitations

This survey included prescribers from a range of mental health care practice settings (eg, inpatient, outpatient clinic, rural, urban) and varied years of experience. This variety resulted in diverse perspectives and knowledge bases. Postsurvey interviews allowed academic detailers to gain deeper insight into answers in the survey, which can guide future interventions. Postsurvey interviews and application of the ADKAR model provided additional viewpoints on harm reduction.

A limitation of this project is the absence of an assessment of respondents’ harm reduction knowledge accuracy. Although respondents reported confidence in discussing harm reduction with patients, the survey did not assess whether their knowledge was accurate. Additionally, the survey did not ask about the availability of syringes and test strips at the prescribers’ VAMC, which could explain discrepancies in responses between naloxone and other forms of harm reduction (drug test strips and syringes were not available to all HCPs in the VISN). This lack of availability may have skewed responses. West Virginia SSPs, for example, were closed following legislative changes, which may contribute to stigma.²¹

Not all respondents were asked to do a follow-up interview, which limited the perspectives included in this study. Each site had ≥ 1 follow-up interview to limit the academic detailer’s workload. The initial survey included the phrase clean syringe, which can be stigmatizing and insinuate that PWUD are not clean. The preferred term would have been sterile syringe.²²

Conclusions

This survey of mental health prescribers found that most respondents are comfortable treating patients with SUD and confident in educating patients on harm reduction. Additionally, most respondents were more willing to provide naloxone vs fentanyl test strips or sterile syringes. A lack of time and awareness was the most frequently cited barrier to harm reduction services. As the VHA continues to expand access to harm reduction programs, which have proven to increase treatment rates and reduce disease, it will be imperative for HCPs, including mental health prescribers, to recognize the benefit of these programs for veterans with SUD. Future interventions should be designed and evaluated in collaboration with all HCPs and patients. This project determined ways to promote change for prescribers, but it will be important for further research to continue those conversations and incorporate patient perspectives.

The Public Health and Welfare Act of 1988 prohibited the use of federal funds to “provide individuals with hypodermic needles or syringes so that such individuals may use illegal drugs.”¹ Although the Act included the caveat that the US Surgeon General may determine that “a demonstration needle exchange program would be effective in reducing drug abuse,” and thus federal funds could be used, the legislation prohibited federal, state, and local agencies from funding syringe services programs (SSPs). SSPs use various harm reduction tools to improve public safety and reduce the potential harmful consequences of risky behaviors, similar to how using a seat belt while driving reduces the risk of injury or death.² SSPs are rooted in evidence-based practices, and several studies, according to the Centers for Disease Control and Prevention, have found that people who use drugs (PWUDs) who use community-based SSPs are 5 times more likely to enter treatment than those who do not use these programs. Additionally, these programs have shown an estimated 50% reduction in HIV and hepatitis C infections.³

Amid a 2015 HIV outbreak in Indiana among individuals sharing needles for injection drug use, Congress passed an omnibus spending bill that partially lifted the federal funding restriction. Federal funds now may be used for operational costs that support SSPs but may not be used to purchase syringes themselves.⁴

Following the 2015 legislation, federal agencies began implementing SSPs. The Veterans Health Administration (VHA) established SSPs at 3 medical centers in 2017.⁵ Veterans who participated in the programs were able to access supplies (eg, syringes, fentanyl test strips, wound care kits, and condoms) through donations to US Department of Veterans Affairs (VA) medical centers (VAMCs). The success of these programs laid the foundation for the VHA to implement SSPs nationally. VHA SSPs provided access to naloxone (an opioid overdose reversal medication), fentanyl test strips, condoms, sterile syringe distribution, testing for blood-borne viruses, HIV pre-exposure prophylaxis, as well as educational materials and resources, and low-barrier access to drug treatment (eg, medications for opioid use disorder [OUD]).

In 2020, the Biden Administration outlined 7 drug policy priorities, which included enhancing evidence-based harm reduction efforts. ⁶ This policy also discussed mandates for federal agencies to remove barriers to federal funding for purchasing syringes and other harm reduction supplies. The VHA responded to the policy by publishing guidance that recommended VAMCs develop and/or ensure veterans have access to harm reduction services in the community, where state law is not legally more stringent.⁷

In 2025 the Trump administration Statement of Drug Policy Priorities encouraged local jurisdictions to increase the availability of drug test strips and naloxone.⁸ These significant policy shifts moved SSPs from being housed mostly in local public health departments and community-based organizations to also being available at health care facilities. ⁹ VAMCs have unique opportunities to provide universal health care that includes both prevention services and other medical management to PWUD.

One study assessed staff perceptions of PWUD at a VAMC in preparation for a training program about harm reduction. The results indicated an overall positive staff perception of PWUD, although only the Drug and Drug Problems Perceptions Questionnaire (DDPPQ) was administered, which assessed comfort of working with this population and not explicitly the use of harm reduction.¹⁰ Another study interviewed clinical pharmacists, primary care clinicians, social workers, and directors of addiction and mental health services to determine barriers and facilitators (ie, potential opportunities to promote change) to implementing harm reduction at the VHA. The study identified barriers to be a lack of knowledge, time, and comfort, while suggesting opportunities for improvement were engagement of champions, communication and educational strategies, and adaptation of existing infrastructure.¹¹

While these findings are insightful for the VHA to disseminate a harm reduction program, there remains a gap in assessing staff willingness to provide harm reduction services. Evidence on harm reduction services among veterans is limited and more research is needed to better understand the role of these services and acceptance among enrolled veterans and VHA staff. Specifically, more research is needed on health care practitioners’ (HCPs) perceptions of harm reduction use.

Mental health care practitioners frequently treat patients with substance use disorders (SUDs), making them an ideal initial cohort to assess willingness to provide harm reduction to this population. By analyzing mental HCPs’ perceptions, additional interventions could be identified, implemented, and evaluated to improve their willingness to provide harm reduction tools.

This project focused on mental health clinicians with prescribing privileges: physicians (allopathic and osteopathic physicians), nurse practitioners, physician assistants, and clinical pharmacist practitioners. Mental health prescribers were selected because they are uniquely positioned at the intersection of prevention and treatment in drug use. Furthermore, mental health prescribers at the VAMCs included in this study are usually the primary point of entry to SUD clinics. This mixed-methods study used an anonymous online survey and voluntary postsurvey discussions with mental health care prescribers to elaborate on their beliefs and attitudes, providing deeper insight into their responses regarding harm reduction.

Methods

This project was conducted by the Veterans Integrated Services Network (VISN) 5 academic detailing team. VISN 5 serves veterans from economically and demographically diverse areas in Maryland; Washington, DC; West Virginia; and portions of Virginia, Pennsylvania, Ohio, and Kentucky. VAMCs in Baltimore, Maryland, and Washington, DC, serve a largely urban population while the 4 West Virginia facilities in Martinsburg, Huntington, Beckley, and Clarksburg, serve a largely rural population. West Virginia has been the epicenter of the opioid crisis and consistently has the highest drug overdose deaths per capita in the United States.¹² Among cities, Baltimore, Maryland, has the highest number of drug overdose deaths per capita with 174.1 per 100,000 people.^12,13

At the time of this project, the 6 VISN 5 VAMCs had established overdose education and naloxone distribution (OEND) programs. Although OEND programs have existed since 2013, VISN 5 SSPs and harm reduction services that provided fentanyl test strips were only available at the Martinsburg, Beckley, and Huntington VAMCs. All 6 VAMCs had substance use treatment programs with a variety of inpatient and outpatient mental health services. The Washington, DC and Baltimore VAMCs had opioid treatment programs that provided methadone maintenance.

The VISN 5 academic detailing team consists of 7 clinical pharmacists. These academic detailers plan annual systematic interventions to provide medical knowledge translation services on health-related campaigns. Academic detailers are trained in change management and motivational interviewing. They uniquely facilitate conversations with HCPs on various topics or campaigns, aiming for quality improvement and behavioral change through positive relationships and sharing resources.¹⁴ Academic detailing conversations and relationships with HCPs involve assessing and understanding HCP behaviors, including barriers and readiness to change to align with the goal of improving patient outcomes. Academic detailing has improved practice behaviors around providing OEND in VHA.¹⁵

To prepare for a harm reduction campaign, the academic detailers sought to gain insight from target VISN 5 mental health prescribers. Figure 1 outlines the project timeline, which started with emails inviting mental health prescribers to complete an anonymous online survey. Academic detailers from each site emailed mental health prescribers who completed the survey to determine interest in expanding on survey findings. Mental health prescribers who completed the survey could participate in a postsurvey discussion.

Surveys

Between January 29, 2024, and February 22, 2024, the academic detailers emailed facility mental health prescribers (N = 156) a link to an anonymous 15-question survey. The email informed recipients of the survey’s purpose: to gain a better understanding of prescriber perceptions of veterans with SUD and harm reduction programs and their willingness to provide harm reduction tools, to better determine interventions that could be implemented.

The survey collected prescriber demographic data and their perceptions of PWUD and harm reduction tools and education. Survey questions were extrapolated from validated surveys (eg, DDPPQ) and survey-based implicit association test.^16,17 The survey used multiple choice and 5-point Likert scale questions. Mental health prescribers were asked about their role at the VHA, years in practice, medical center affiliation, type of SUDs treated (eg, opioid, stimulant, alcohol, cannabis, or other), and whether they had previously met with academic detailers about harm reduction.

Respondents read statements about patients with or without SUD and provided Likert scale responses describing their regard, level of comfort, and preferences. The survey included Likert scale questions about respondents’ comfort in providing harm reduction education and supplies. Respondents also noted whether they believed harm reduction reduced substance use, harm reduction tools encourage people with SUD to continue using drugs, and whether HCPs can impact clinical change.

Postsurvey interviews with predetermined questions were conducted in-person or via video conference with ≥ 1 prescriber at each VAMC by an academic detailer. The postsurvey discussion offered an opportunity for respondents to further elaborate and describe previous experiences and current beliefs that may affect their attitudes toward people with SUD and their views on harm reduction. Participants received no compensation for survey completion or interviews.

Analysis

The Washington VAMC Institutional Review Board reviewed and approved this project as quality improvement with potential publication. No inferential statistics were calculated. Survey participant demographics were reported using frequencies and proportions reported for categorical variables. Notes from follow-up interviews were analyzed using the Prosci Awareness, Desire, Knowledge, Ability, and Reinforcement (ADKAR) Model for Change Management.¹⁸ This framework is used by academic detailers to determine a prescriber’s stage of change, which helps select the appropriate resources to move the clinician along a change framework. Completed postsurvey interview sheets, including notes written by the academic detailer, were analyzed by the project lead (NJ) who reviewed each interview sheet and analysis with the academic detailer who led the discussion.

Results

Sixty-six respondents completed the online survey (42% response rate), and 7 mental health prescribers participated in a postsurvey discussion. Thirty-one participants (47%) were physicians and 17 (26%) were in practice for > 20 years. Response rates reflected the size of mental health staff at each VAMC at the time of the survey: 17 respondents (26%) worked at each of the Martinsburg and Baltimore VAMCs, with fewer at the other VAMCs (Table 1). Alcohol use disorder was the most commonly reported SUD treated (n = 62; 33%), followed by cannabis use disorder (n = 40; 21%), OUD (n = 38; 20%), and stimulant use disorder (n = 37; 20%).

Respondents felt comfortable and confident educating patients on ways to reduce harm related to substance use (91%; mean [SD], 4.24 [0.84]). Most prescribers surveyed (97%; mean [SD], 1.59 [0.68]) disagreed or strongly disagreed that harm reduction encourages patients with SUD to continue using drugs, and all prescribers surveyed disagreed that there is nothing they can do to encourage harm reduction. Survey results were mixed for personal comfort in working with people with SUD vs people without SUD (Figure 2). Respondents were most willing to provide naloxone (95%; mean [SD], 4.71 [0.78]), compared to fentanyl test strips (61%; mean [SD], 3.61 [1.41]) or syringes (39%; mean [SD], 3.18 [1.39]). Respondents were neutral or least willing to provide syringes (Figure 3).

Seven postsurvey interviews were completed between academic detailers and mental health clinicians across the 6 VAMCs. Respondents included 1 physician assistant, 1 nurse practitioner, 1 pharmacist, and 4 physicians. Notes were analyzed using the ADKAR Change Competency Model to organize clinician stages of change (Table 2).

Barriers identified by interviewees included lack of mobile services, lack of confidence and awareness of the availability of harm reduction at their respective medical center, lack of time to discuss harm reduction, negative sentiments toward providing SUD-related harm reduction, discomfort with harm reduction products, and lack of knowledge and time to learn about harm reduction services. Opportunities identified to drive change in practice included additional time allotted during patient appointments, educational discussions and presentations to increase knowledge of and comfort with harm reduction tools, a clear clinical patient care workflow and process for harm reduction services, and reinforcement strategies to recognize success.

Discussion

This project investigated mental health prescribers’ perceptions of harm reduction at VAMCs in West Virginia, Maryland, and Washington, DC. While previous studies have demonstrated the efficacy of harm reduction tools, there is a lack of research on HCPs willingness to use these resources. This study suggests that while most respondents feel confident in and see the value of offering harm reduction resources to patients, a disparity exists between which resources HCPs are more likely to use and factors that would further enhance their ability to integrate harm reduction into practice. The follow-up interviews provided additional insight into the survey results.

Most respondents met the awareness and desire stage and moved to the knowledge, ability, or reinforcement ADKAR stage. It would be reasonable to extrapolate that most of the respondents felt comfortable with and were very likely to offer certain harm reduction tools. In the ADKAR interview analysis, the most common factors needed to drive change included having more time during patient appointments, additional education, clear processes for harm reduction services, and reinforcement strategies to sustain change. Respondents noted that harm reduction discussions took extra time in their already limited appointments with patients, which may have limited time for discussions surrounding all other mental health concerns. These discussions often necessitate in-depth conversations to accurately understand the patients’ needs. Given HCP time constraints, they may view harm reduction as lower in urgency and priority relative to other concerns. While most respondents were in the reinforcement phase, it is important to note the ADKAR model is fluid, and therefore an HCP could move forward or backward. This movement can be noted in the postsurvey interviews where, for example, prescriber 6 was determined to be in the reinforcement stage since they had already discussed harm reduction with patients. However, prescriber 6 also noted a barrier of unfamiliarity with local laws, which could shift them to the ADKAR knowledge stage.

Respondents noted that education through didactic sessions could lead to better incorporation of harm reduction into patient care. While harm reduction has evidence supporting its effectiveness, the respondents noted willingness to discuss harm reduction when treatment fails or the patient refuses treatment or referrals. Respondents expressed mixed opinions on use of harm reduction tools among patients with SUDs as some prescribers viewed harm reduction as part of a treatment plan and others viewed a return to drug use as a failure of treatment. Furthermore, respondents expressed hesitancy surrounding certain harm reduction tools, such as fentanyl test strips or syringes, and perceived these supplies as intended for medical use rather than harm reduction. HCPs may feel uncomfortable offering these supplies for drug use, despite their use for reducing risk.

Most responses were received from VAMCs with large mental health substance use programs. Respondents at larger, urban facilities (Washington, DC, and Baltimore, Maryland) expressed more hesitancy around using harm reduction tools despite having more harm reduction resources available compared to smaller or rural sites. These results align with previous studies that found no difference in prescribers providing medications for OUD in rural and urban VAMCs, showing urban sites, despite more resources, are not more willing to provide harm reduction or other addiction services.¹⁹ This evidence might indicate that urban sites may not use available resources (eg, methadone clinics) or that rural sites can provide just as robust medications for OUD care as urban sites.

Follow-up interview analysis indicated that HCPs lack knowledge of certain harm reduction tools. One-on-one peer discussions, like academic detailing, can facilitate discussions around a prescriber’s role in harm reduction, address gaps in knowledge by sharing what is available at the facilities for harm reduction, and suggest conversation points to help prescribers start harm reduction discussions with patients unwilling to begin treatment. Additionally, academic detailing can connect prescribers to available resources in the community to provide pragmatic approaches and suggestions. A clear and consistent treatment process may reduce barriers by reassuring prescribers they have support and by providing consistent directions so that prescribers do not waste time.

Reinforcement is important for sustaining change. VAMCs could consider positive feedback and other evidence-based reinforcement strategies (eg, social recognition, continuing education) to communicate that these changes are noticed and appreciated.²⁰ Late adopters may also be influenced by seeing positive feedback and results for peers. Systematic changes can be the catalyst for and sustain individual change.

Shifting perceptions and adopting change may be challenging, especially for SUD, which can be highly stigmatized. Promotion of successful change should be multifaceted and include both system and individual approaches. VHA systemic changes that could contribute to positive change include provision of time and access to SUD treatment training, a clear and sustainable treatment process, and reinforcement by recognizing success. In addition, facility leadership could provide support through dedicated time and resources during the workday for SUD treatment and harm reduction training. Support could empower HCPs and convey leadership support for harm reduction. This dedicated time could be used for didactic lecture sessions or individual meetings with academic detailers who can tailor discussions to the prescriber’s practice.

Strengths and Limitations

This survey included prescribers from a range of mental health care practice settings (eg, inpatient, outpatient clinic, rural, urban) and varied years of experience. This variety resulted in diverse perspectives and knowledge bases. Postsurvey interviews allowed academic detailers to gain deeper insight into answers in the survey, which can guide future interventions. Postsurvey interviews and application of the ADKAR model provided additional viewpoints on harm reduction.

A limitation of this project is the absence of an assessment of respondents’ harm reduction knowledge accuracy. Although respondents reported confidence in discussing harm reduction with patients, the survey did not assess whether their knowledge was accurate. Additionally, the survey did not ask about the availability of syringes and test strips at the prescribers’ VAMC, which could explain discrepancies in responses between naloxone and other forms of harm reduction (drug test strips and syringes were not available to all HCPs in the VISN). This lack of availability may have skewed responses. West Virginia SSPs, for example, were closed following legislative changes, which may contribute to stigma.²¹

Not all respondents were asked to do a follow-up interview, which limited the perspectives included in this study. Each site had ≥ 1 follow-up interview to limit the academic detailer’s workload. The initial survey included the phrase clean syringe, which can be stigmatizing and insinuate that PWUD are not clean. The preferred term would have been sterile syringe.²²

Conclusions

This survey of mental health prescribers found that most respondents are comfortable treating patients with SUD and confident in educating patients on harm reduction. Additionally, most respondents were more willing to provide naloxone vs fentanyl test strips or sterile syringes. A lack of time and awareness was the most frequently cited barrier to harm reduction services. As the VHA continues to expand access to harm reduction programs, which have proven to increase treatment rates and reduce disease, it will be imperative for HCPs, including mental health prescribers, to recognize the benefit of these programs for veterans with SUD. Future interventions should be designed and evaluated in collaboration with all HCPs and patients. This project determined ways to promote change for prescribers, but it will be important for further research to continue those conversations and incorporate patient perspectives.

Growing recognition of the limitations of long-term opioid therapy for chronic noncancer pain has highlighted the importance of nonpharmacologic approaches to pain treatment.^1,2 These treatments are varied and may include psychological and behavioral therapies (eg, cognitive behavioral therapy for chronic pain), exercise and movement therapies (eg, yoga), and manual therapies (eg, chiropractic). Body surface cold therapy, while predominantly used to reduce postoperative pain and inflammation,^3,4 pain subsequent to acute musculoskeletal injury,⁵ and pain related to muscle soreness,⁶ is a nonpharmacologic treatment that has shown pain-reducing benefits for chronic low back pain and knee osteoarthritis, as has its counterpart, superficial heat therapy.^7-9 Heat therapy has also been shown to improve strength, flexibility, and activities of daily living in patients with chronic low back pain.^10,11 Cold and heat therapies are commonly used complementarily. Cold therapies aim to reduce blood flow and inflammation and are often used immediately following trauma to an affected area, whereas heat therapies increase blood flow and metabolic activity and are commonly used to promote healing.⁵

Heat and cold therapies (also known as thermal therapies) benefit resource-limited health care systems, as most devices require a single expenditure and can be self-administered by patients at home as part of their pain self-management plan. In addition, these pain self-management tools may attenuate the need for more expensive specialty pain care and ongoing analgesic pharmacotherapy. Despite their potential, few studies have characterized the benefits of thermal therapies for patients with heterogeneous chronic pain syndromes.

The purpose of this retrospective cohort study was to examine the potential clinical and health system benefits of patient-administered thermal therapy. Our primary hypothesis was that patients with chronic musculoskeletal pain who received a thermal therapy self-management device would have fewer days of opioid prescriptions compared with a sample of matched control patients. Secondarily, we hypothesized that patients who received a thermal therapy device would have lower utilization of specialty pain care, fewer potentially hazardous opioid prescriptions (eg, high-dose opioid therapy and concurrent opioid and benzodiazepine prescriptions), fewer prescriptions for nonopioid analgesic medications, and decreased pain intensity when compared with matched controls.

Methods

This retrospective cohort study compared pain pharmacotherapy, pain treatment utilization, and pain intensity outcomes between patients who received a thermal therapy device and matched patients who did not. The study was approved by the US Department of Veterans Affairs (VA) Portland Health Care System Institutional Review Board and was granted a waiver of informed consent to access patient electronic health records (EHRs).

Pain Care

The VA uses ThermaZone thermal therapy devices (Innovative Medical Equipment) for chronic pain treatment. The device uses thermoelectric technology to provide point-of-contact cooling and heating therapy through site-specific pads (eg, ankle, knee, hip, back, elbow, shoulder). Patients place pads on sites where they experience pain, and temperature regulated water circulates through the device and to the pad, providing consistent, localized thermal therapy. The pads range in temperature from 1 °C to 52 °C, and temperatures are self-monitored and controlled by the patient.

Standard pain care in this study followed the VA stepped model of pain care, which builds on a foundation of patient education for pain self-management approaches (eg, exercise, mindfulness, relaxation, social support).¹² According to the VA stepped model of pain care, all patients with chronic pain should engage in these foundational self-management approaches. However, some patients require more intensive care. The VA stepped-up treatment engages primary and specialty care services—such as physical therapy, pharmacy, complementary and integrative health approaches, mental health, and substance use services—and, when indicated, may escalate treatment to interdisciplinary pain teams or tertiary pain centers. In this retrospective cohort study, treatment patients received a thermal therapy device and standard of care, whereas control patients received standard care only.

Sample Selection

Eligible patients were aged ≥ 18 years, had a musculoskeletal pain diagnosis documented in the EHR in the year prior to thermal therapy device receipt (or during the same period for a treatment patient’s matched control), and were enrolled in VA health care during the study period. Patients who died during the study period were excluded. Treatment patients received a thermal therapy device from the VA between January 1, 2017, and December 31, 2018, when complete data on thermal therapy devices were available. For control patients, the VA Corporate Data Warehouse (CDW) was used to identify VA patients with characteristics similar to those of treated patients.

We modeled the probability that a patient would receive a thermal therapy device using logistic regression. Predictor variables were measured in the year prior to device receipt and included variables associated with pain treatment utilization and analgesic pharmacotherapy receipt, as recommended by Brookhart et al.¹³ These included age, sex, race, ethnicity, VA service-connected disability status, comorbidities, receipt of medications for opioid use disorder, pain diagnoses, mental health diagnoses, and substance use disorder diagnoses.^14-19

The resulting propensity scores (eg, predicted probabilities) were used to match treatment patients 1:1 with control patients using a nearest-neighbor matching algorithm.²⁰ This procedure matches a control patient with the closest propensity score to that of the corresponding treatment patient. An exact match on VA facility was required (eg, treatment patients and matched controls received care at the same VA facility). Standardized differences were used to assess covariate balance between the matched groups, and kernel density plots of propensity scores tested for sufficient overlap.²¹ Control patients were selected from a pool of 1,150,149 patients.

Study Variables

The index date was the date the thermal therapy device was released to treatment patients or the same date for the matched controls. Data were extracted from the CDW over a 24-month period: 12 months prior to the index date through 12 months afterwards. Collecting data in the 12 months prior to treatment initiation allowed us to adjust for covariates and provided greater precision, as recommended for observational study designs.²²

Treatment conditions were defined dichotomously as receipt vs nonreceipt of a thermal therapy device. The primary outcome was the number of days of opioid use in the 12 months following the index date. Additional outcomes included days of high-dose opioid therapy (≥ 50 mg morphine equivalent [MME] daily), concurrent opioid and benzodiazepine prescriptions, and nonopioid analgesic pharmacotherapy (eg, nonsteroidal anti-inflammatory drugs, acetaminophen, muscle relaxants). All prescription data were based on medication fills obtained from VA pharmacy records. Additional outcomes included the number of visits to physical therapy, occupational therapy, physical medicine and rehabilitation, and interdisciplinary pain clinics, including interventional pain medicine.

Pain intensity ratings were collected as part of routine VA care using a numeric scale from 0 (no pain) to 10 (worst possible pain). Pain intensity trajectories were computed using all available EHR-derived pain intensity score data for each patient in the 12 months prior to and following the index date.

Covariates were extracted from the EHR and evaluated in the year prior to the index date, unless otherwise noted. They included age at the index date; self-reported sex, and race and ethnicity; service-connected disability status (disability awarded as a result of military service-related trauma or injury); Charlson Comorbidity Index; and diagnoses of opioid use disorder, alcohol use disorder, other substance use disorder, mood disorder, posttraumatic stress disorder, other anxiety disorder, psychotic disorder, neuropathic pain, and headache pain.²³ All diagnoses were coded as yes if identified in the EHR as a focus of treatment during any clinical encounter in the year prior to the index date or no if not identified as a focus of treatment.

The number of days patients had been living with pain was calculated and defined as the number of days from the first pain diagnosis available in a patient’s EHR to the index date. Finally, the number of pain-related surgeries (eg, surgeries with ≥ 1 pain diagnoses associated with the clinical encounter) and average pain intensity were computed for the pre- and postindex date evaluation periods and included as model covariates.

Statistical Analyses

For the 4 pharmacotherapy and 4 nonpharmacologic treatment usage outcomes, we tested the fit of linear models and several models with count distributions using the Bayesian information criterion.²⁴ Count distributions included Poisson, zero-inflated Poisson, negative binomial, and zero-inflated negative binomial. With 1 exception (days of high-dose opioid use), a negative binomial distribution best fit the data. For days of high-dose opioid use, a Gaussian distribution best fit the data.

Eight separate mixed-effects regression analyses compared changes in each outcome from the 12-month preindex period through the 12-month postindex period between treatment and control patients by testing the Time × Treatment interaction. This approach statistically accounts for observed pretreatment differences in outcome variables. Statistics for the main effects of time and treatment are also presented. To reduce bias, models controlled for covariates specified previously.

For pain intensity, we used random-effects growth modeling to quantify both fixed and random effects of pain intensity at the index date (eg, the model intercept), which estimates pain at the time of treatment initiation, and change in pain during the 12 months following the index date (eg, the model slope), which characterizes the trajectory of pain intensity ratings.²⁵ The model included piecewise components of pain score trajectories in the 12 months prior to the index date and in the 12 months following the index date. Several types of change for the 12-month postindex observation period were explored—including quadratic and cubic curvilinear change. A linear model for change in pain over time provided the best fit based on the Bayesian information criterion and parsimony of model parameters.²⁶ We report estimates of change in pain over time in monthly intervals for ease of interpretation. However, models used all individual pain scores rather than computing monthly averages when > 1 pain score was available within a month, as recommended in previous research.²⁷ This approach makes optimal use of all available data. Both random effects (intercept and slope) were regressed onto the set of covariates described previously.

This study used data available in the EHR over the 24-month observation period. We characterize the density (eg, frequency) of all outcome variables by treatment condition in the Appendix. Because the hypotheses were directional, the authors used a 2-sided α = 0.10 and applied a Bonferroni correction for the 9 statistical tests performed, resulting in an adjusted α of 0.01. Treatment utilization and pharmacotherapy outcome analyses were performed in Stata, version 16.1. Random-effects growth modeling of pain score trajectories was performed using Mplus, version 8.8.

Results

There were 2182 patients in the treatment group and 2182 matched controls. The mean (SD) age was 54 (15) years; 81% were male, and about two-thirds (68%) identified as White and non-Hispanic. Mental health comorbidities were common, with > 40% of the sample having diagnoses of a mood disorder and/or posttraumatic stress disorder. Nearly all patients (90%) had VA service-connected disability ratings. Among patients with chronic musculoskeletal pain, 8% had comorbid neuropathic pain and 14% had headache. The mean (SD) duration of chronic pain across both patient groups was 3416 (2016) days, or about 9.4 years (Table 1).

Pharmacotherapy

High-dose opioid use (> 50 MME daily dose), days of opioid use, and concurrent opioid and benzodiazepine use decreased for all patients from the pre- to posttreatment period (Table 2). However, high-dose opioid use (Time × Treatment interaction, 3.24; 99% CI, 0.34 to 6.14) (Figure 1A) and concurrent opioid and benzodiazepine use (Time × Treatment interaction, 0.76; 99% CI, 0.67 to 0.86) (Figure 1B) had a larger decrease for the treatment vs matched control group. Treatment and matched control patients had comparable reductions in days of opioid use (Time × Treatment interaction, 0.98; 99% CI, 0.91 to 1.05) (Figure 1C). Neither group showed changes in nonopioid analgesic pharmacotherapy over time (main effect of time, incidence rate ratio [IRR], 1.03; 99% CI, 0.99 to 1.07; Time × Treatment interaction, 0.95; 99% CI, 0.90 to 1.01) (Figure 1D).

Nonpharmacologic Pain Treatment

The number of physical therapy and pain clinic visits declined for treatment patients and increased slightly for matched control patients (Figure 2A and 2B). For occupational therapy visits, neither group showed changes over time (main effect of time IRR, 1.03; 99% CI, 0.83 to 1.22; Time × Treatment interaction, 1.20; 99% CI, 0.93 to 1.46) (Figure 2C). For physical medicine and rehabilitation visits, both groups decreased use over time (main effect of time IRR, 0.78; 99% CI, 0.66 to 0.90), but this decrease did not differ between treatment and control patients (Time × Treatment interaction, 1.16; 99% CI, 0.94 to 1.37) (Figure 2D).

Pain Intensity

Pain intensity decreased for both groups by an estimated 0.02 points per month (99% CI, -0.04 to -0.01; P < .01), or 0.24 points over the 12-month postindex follow-up period (Figure 3). There were no statistically significant differences between treatment and control patients in pain intensity changes over the follow-up period (B = -0.02; 99% CI, -0.06 to 0.02; P = .15).

Discussion

Patients with musculoskeletal pain who received a thermal therapy device showed a larger decline in use of some specialty pain treatments, including physical therapy and specialty pain clinic services, when compared with matched control patients. One possible explanation is that patients who used the device may have had their pain adequately managed and thus required less specialty pain care. However, the absence of clinically significant changes in pain intensity over time suggests that pain intensity alone did not account for the observed changes in pain treatment use. We were unable to measure constructs of pain interference or functioning, which may be better predictors of functional restoration, as these data are not routinely collected within the VA and documented in the EHR. Future studies could clarify these findings by including measures of pain interference and functioning.

Although the overall declines in physical therapy and specialty pain clinic use associated with thermal therapy were modest (< 1 visit per patient), the impact of these reductions can be profound. In resource-limited health care settings, even small reductions in high-cost care utilization could be of great value in that health systems could offset costs associated with treating chronic pain without compromising quality of care or key clinical outcomes, such as pain intensity. This study, however, did not include a cost analysis. Future studies should incorporate formal cost analyses to quantify cost offsets that may result from decreased specialty pain treatment use.

Patients who received thermal therapy devices did not show clinically meaningful reductions in pain intensity over time, defined as reductions in pain intensity of 1.7 to 2.0 on a 0 to 10 scale.^28,29 This finding is consistent with prior research that demonstrates relatively stable pain intensity self-ratings longitudinally by patients with chronic pain diagnoses, when assessed in the context of usual clinical care.³⁰ This finding, however, is inconsistent with prior literature that demonstrates pain-reducing benefits of thermal therapy for low back pain and knee osteoarthritis.^7-9

In this study, pain intensity ratings were derived from the EHR during routine outpatient clinical encounters and not at the time thermal therapy was self-administered, as has been done in prior clinical trials.^7-9 Pain location was not specified at the time of pain ratings, and it is possible that patients may have been endorsing pain in areas of the body that had not been treated by thermal therapy. Patient-level variability in pain intensity ratings (eg, within-patient range over time) was not examined, although prior research indicates substantial variability.³⁰ While average pain intensity ratings in the current study did not change, an examination of patient variability warrants further study, as a narrowing of pain intensity ratings can be perceived, by patients, as demonstrable improvement and has been associated with improved physical and psychological outcomes.³¹ Furthermore, pain intensity does not characterize physical or emotional functioning that can be captured with more comprehensive validated measures, some of which are recommended outcomes in pain clinical trials.³²

Our findings point to reductions in all forms of opioid use across both treatment and control patients. Data from the VA and in the US more generally point to downward trends in opioid prescribing during the study period.³³ This decline is likely due to increased use of risk mitigation approaches, such as routine urine drug screens and review of prescription drug monitoring databases.³⁴ These state-level databases track prescribing of controlled substances, including opioids and benzodiazepines, within a state. Implementation of these practices has been associated with declines in higher risk opioid prescribing.³⁴ Findings from this study further point to associations of reduced higher risk opioid use among patients who received thermal therapy devices. In the full sample of patients, reductions in days of opioid use, high-dose opioid use, and co-use of opioids and benzodiazepines were observed across all patients, with greater reductions observed in high-dose opioid use and concurrent opioid and benzodiazepine use among patients who received a thermal therapy device. Experimental studies indicate that the endogenous opioid system is implicated in pain relief and activated by thermal therapies. ³⁵ Differential reductions in higher-risk opioid use among patients who received thermal therapy devices in our study may be associated with endogenous opioid activation, though this was not specifically measured. It is also unclear whether thermal therapy was provided by clinicians in the context of opioid tapering or other risk mitigation efforts, or patients reduced higher risk opioid use of their own volition. Prior research has identified both patient- and clinician-initiated opioid tapering and discontinuation.³⁶ While a thorough explication of opioid dose reduction was beyond the scope of this study, future qualitative work could help explain potential benefits of thermal therapy in the context of analgesic pharmacotherapy use, including opioid medications.

Limitations

The extent to which patients used the thermal therapy device could not be measured; therefore, device receipt was used as a proxy for use. However, it was not possible to determine whether the frequency and duration of device use was associated with study outcomes. Treatment and control groups demonstrated some differences in outcome variables at the index date. Potential known biases were addressed using propensity score matching procedures and statistical procedures that controlled for patient demographic and clinical characteristics, as well as pretreatment values of all outcome variables. Nevertheless, as an observational study, this analysis cannot account for all known and unknown confounders, and a randomized controlled trial is needed to make claims of causality. The study population consisted of US veterans and included a low proportion of women. As a result, the findings may not be generalizable to other patient populations. Finally, prescription dispensing data, used as a proxy for pharmacotherapy use, do not necessarily reflect actual medication use.

Conclusions

This study is among the first to examine associations between thermal therapy and specialty pain treatment and analgesic pharmacotherapy use among US veterans. Although the retrospective cohort study design does not allow causal inferences regarding the efficacy of thermal therapy for veterans with chronic musculoskeletal pain, confidence in the findings is strengthened by methodological and statistical control of known confounders. Future trials employing experimental designs are needed to further clarify the clinical and health systems benefits of thermal therapy for musculoskeletal pain syndromes.

Growing recognition of the limitations of long-term opioid therapy for chronic noncancer pain has highlighted the importance of nonpharmacologic approaches to pain treatment.^1,2 These treatments are varied and may include psychological and behavioral therapies (eg, cognitive behavioral therapy for chronic pain), exercise and movement therapies (eg, yoga), and manual therapies (eg, chiropractic). Body surface cold therapy, while predominantly used to reduce postoperative pain and inflammation,^3,4 pain subsequent to acute musculoskeletal injury,⁵ and pain related to muscle soreness,⁶ is a nonpharmacologic treatment that has shown pain-reducing benefits for chronic low back pain and knee osteoarthritis, as has its counterpart, superficial heat therapy.^7-9 Heat therapy has also been shown to improve strength, flexibility, and activities of daily living in patients with chronic low back pain.^10,11 Cold and heat therapies are commonly used complementarily. Cold therapies aim to reduce blood flow and inflammation and are often used immediately following trauma to an affected area, whereas heat therapies increase blood flow and metabolic activity and are commonly used to promote healing.⁵

Heat and cold therapies (also known as thermal therapies) benefit resource-limited health care systems, as most devices require a single expenditure and can be self-administered by patients at home as part of their pain self-management plan. In addition, these pain self-management tools may attenuate the need for more expensive specialty pain care and ongoing analgesic pharmacotherapy. Despite their potential, few studies have characterized the benefits of thermal therapies for patients with heterogeneous chronic pain syndromes.

The purpose of this retrospective cohort study was to examine the potential clinical and health system benefits of patient-administered thermal therapy. Our primary hypothesis was that patients with chronic musculoskeletal pain who received a thermal therapy self-management device would have fewer days of opioid prescriptions compared with a sample of matched control patients. Secondarily, we hypothesized that patients who received a thermal therapy device would have lower utilization of specialty pain care, fewer potentially hazardous opioid prescriptions (eg, high-dose opioid therapy and concurrent opioid and benzodiazepine prescriptions), fewer prescriptions for nonopioid analgesic medications, and decreased pain intensity when compared with matched controls.

Methods

This retrospective cohort study compared pain pharmacotherapy, pain treatment utilization, and pain intensity outcomes between patients who received a thermal therapy device and matched patients who did not. The study was approved by the US Department of Veterans Affairs (VA) Portland Health Care System Institutional Review Board and was granted a waiver of informed consent to access patient electronic health records (EHRs).

Pain Care

The VA uses ThermaZone thermal therapy devices (Innovative Medical Equipment) for chronic pain treatment. The device uses thermoelectric technology to provide point-of-contact cooling and heating therapy through site-specific pads (eg, ankle, knee, hip, back, elbow, shoulder). Patients place pads on sites where they experience pain, and temperature regulated water circulates through the device and to the pad, providing consistent, localized thermal therapy. The pads range in temperature from 1 °C to 52 °C, and temperatures are self-monitored and controlled by the patient.

Standard pain care in this study followed the VA stepped model of pain care, which builds on a foundation of patient education for pain self-management approaches (eg, exercise, mindfulness, relaxation, social support).¹² According to the VA stepped model of pain care, all patients with chronic pain should engage in these foundational self-management approaches. However, some patients require more intensive care. The VA stepped-up treatment engages primary and specialty care services—such as physical therapy, pharmacy, complementary and integrative health approaches, mental health, and substance use services—and, when indicated, may escalate treatment to interdisciplinary pain teams or tertiary pain centers. In this retrospective cohort study, treatment patients received a thermal therapy device and standard of care, whereas control patients received standard care only.

Sample Selection

Eligible patients were aged ≥ 18 years, had a musculoskeletal pain diagnosis documented in the EHR in the year prior to thermal therapy device receipt (or during the same period for a treatment patient’s matched control), and were enrolled in VA health care during the study period. Patients who died during the study period were excluded. Treatment patients received a thermal therapy device from the VA between January 1, 2017, and December 31, 2018, when complete data on thermal therapy devices were available. For control patients, the VA Corporate Data Warehouse (CDW) was used to identify VA patients with characteristics similar to those of treated patients.

We modeled the probability that a patient would receive a thermal therapy device using logistic regression. Predictor variables were measured in the year prior to device receipt and included variables associated with pain treatment utilization and analgesic pharmacotherapy receipt, as recommended by Brookhart et al.¹³ These included age, sex, race, ethnicity, VA service-connected disability status, comorbidities, receipt of medications for opioid use disorder, pain diagnoses, mental health diagnoses, and substance use disorder diagnoses.^14-19

The resulting propensity scores (eg, predicted probabilities) were used to match treatment patients 1:1 with control patients using a nearest-neighbor matching algorithm.²⁰ This procedure matches a control patient with the closest propensity score to that of the corresponding treatment patient. An exact match on VA facility was required (eg, treatment patients and matched controls received care at the same VA facility). Standardized differences were used to assess covariate balance between the matched groups, and kernel density plots of propensity scores tested for sufficient overlap.²¹ Control patients were selected from a pool of 1,150,149 patients.

Study Variables

The index date was the date the thermal therapy device was released to treatment patients or the same date for the matched controls. Data were extracted from the CDW over a 24-month period: 12 months prior to the index date through 12 months afterwards. Collecting data in the 12 months prior to treatment initiation allowed us to adjust for covariates and provided greater precision, as recommended for observational study designs.²²

Treatment conditions were defined dichotomously as receipt vs nonreceipt of a thermal therapy device. The primary outcome was the number of days of opioid use in the 12 months following the index date. Additional outcomes included days of high-dose opioid therapy (≥ 50 mg morphine equivalent [MME] daily), concurrent opioid and benzodiazepine prescriptions, and nonopioid analgesic pharmacotherapy (eg, nonsteroidal anti-inflammatory drugs, acetaminophen, muscle relaxants). All prescription data were based on medication fills obtained from VA pharmacy records. Additional outcomes included the number of visits to physical therapy, occupational therapy, physical medicine and rehabilitation, and interdisciplinary pain clinics, including interventional pain medicine.

Pain intensity ratings were collected as part of routine VA care using a numeric scale from 0 (no pain) to 10 (worst possible pain). Pain intensity trajectories were computed using all available EHR-derived pain intensity score data for each patient in the 12 months prior to and following the index date.

Covariates were extracted from the EHR and evaluated in the year prior to the index date, unless otherwise noted. They included age at the index date; self-reported sex, and race and ethnicity; service-connected disability status (disability awarded as a result of military service-related trauma or injury); Charlson Comorbidity Index; and diagnoses of opioid use disorder, alcohol use disorder, other substance use disorder, mood disorder, posttraumatic stress disorder, other anxiety disorder, psychotic disorder, neuropathic pain, and headache pain.²³ All diagnoses were coded as yes if identified in the EHR as a focus of treatment during any clinical encounter in the year prior to the index date or no if not identified as a focus of treatment.

The number of days patients had been living with pain was calculated and defined as the number of days from the first pain diagnosis available in a patient’s EHR to the index date. Finally, the number of pain-related surgeries (eg, surgeries with ≥ 1 pain diagnoses associated with the clinical encounter) and average pain intensity were computed for the pre- and postindex date evaluation periods and included as model covariates.

Statistical Analyses

For the 4 pharmacotherapy and 4 nonpharmacologic treatment usage outcomes, we tested the fit of linear models and several models with count distributions using the Bayesian information criterion.²⁴ Count distributions included Poisson, zero-inflated Poisson, negative binomial, and zero-inflated negative binomial. With 1 exception (days of high-dose opioid use), a negative binomial distribution best fit the data. For days of high-dose opioid use, a Gaussian distribution best fit the data.

Eight separate mixed-effects regression analyses compared changes in each outcome from the 12-month preindex period through the 12-month postindex period between treatment and control patients by testing the Time × Treatment interaction. This approach statistically accounts for observed pretreatment differences in outcome variables. Statistics for the main effects of time and treatment are also presented. To reduce bias, models controlled for covariates specified previously.

For pain intensity, we used random-effects growth modeling to quantify both fixed and random effects of pain intensity at the index date (eg, the model intercept), which estimates pain at the time of treatment initiation, and change in pain during the 12 months following the index date (eg, the model slope), which characterizes the trajectory of pain intensity ratings.²⁵ The model included piecewise components of pain score trajectories in the 12 months prior to the index date and in the 12 months following the index date. Several types of change for the 12-month postindex observation period were explored—including quadratic and cubic curvilinear change. A linear model for change in pain over time provided the best fit based on the Bayesian information criterion and parsimony of model parameters.²⁶ We report estimates of change in pain over time in monthly intervals for ease of interpretation. However, models used all individual pain scores rather than computing monthly averages when > 1 pain score was available within a month, as recommended in previous research.²⁷ This approach makes optimal use of all available data. Both random effects (intercept and slope) were regressed onto the set of covariates described previously.

This study used data available in the EHR over the 24-month observation period. We characterize the density (eg, frequency) of all outcome variables by treatment condition in the Appendix. Because the hypotheses were directional, the authors used a 2-sided α = 0.10 and applied a Bonferroni correction for the 9 statistical tests performed, resulting in an adjusted α of 0.01. Treatment utilization and pharmacotherapy outcome analyses were performed in Stata, version 16.1. Random-effects growth modeling of pain score trajectories was performed using Mplus, version 8.8.

Results

There were 2182 patients in the treatment group and 2182 matched controls. The mean (SD) age was 54 (15) years; 81% were male, and about two-thirds (68%) identified as White and non-Hispanic. Mental health comorbidities were common, with > 40% of the sample having diagnoses of a mood disorder and/or posttraumatic stress disorder. Nearly all patients (90%) had VA service-connected disability ratings. Among patients with chronic musculoskeletal pain, 8% had comorbid neuropathic pain and 14% had headache. The mean (SD) duration of chronic pain across both patient groups was 3416 (2016) days, or about 9.4 years (Table 1).

Pharmacotherapy

High-dose opioid use (> 50 MME daily dose), days of opioid use, and concurrent opioid and benzodiazepine use decreased for all patients from the pre- to posttreatment period (Table 2). However, high-dose opioid use (Time × Treatment interaction, 3.24; 99% CI, 0.34 to 6.14) (Figure 1A) and concurrent opioid and benzodiazepine use (Time × Treatment interaction, 0.76; 99% CI, 0.67 to 0.86) (Figure 1B) had a larger decrease for the treatment vs matched control group. Treatment and matched control patients had comparable reductions in days of opioid use (Time × Treatment interaction, 0.98; 99% CI, 0.91 to 1.05) (Figure 1C). Neither group showed changes in nonopioid analgesic pharmacotherapy over time (main effect of time, incidence rate ratio [IRR], 1.03; 99% CI, 0.99 to 1.07; Time × Treatment interaction, 0.95; 99% CI, 0.90 to 1.01) (Figure 1D).

Nonpharmacologic Pain Treatment

The number of physical therapy and pain clinic visits declined for treatment patients and increased slightly for matched control patients (Figure 2A and 2B). For occupational therapy visits, neither group showed changes over time (main effect of time IRR, 1.03; 99% CI, 0.83 to 1.22; Time × Treatment interaction, 1.20; 99% CI, 0.93 to 1.46) (Figure 2C). For physical medicine and rehabilitation visits, both groups decreased use over time (main effect of time IRR, 0.78; 99% CI, 0.66 to 0.90), but this decrease did not differ between treatment and control patients (Time × Treatment interaction, 1.16; 99% CI, 0.94 to 1.37) (Figure 2D).

Pain Intensity

Pain intensity decreased for both groups by an estimated 0.02 points per month (99% CI, -0.04 to -0.01; P < .01), or 0.24 points over the 12-month postindex follow-up period (Figure 3). There were no statistically significant differences between treatment and control patients in pain intensity changes over the follow-up period (B = -0.02; 99% CI, -0.06 to 0.02; P = .15).

Discussion

Patients with musculoskeletal pain who received a thermal therapy device showed a larger decline in use of some specialty pain treatments, including physical therapy and specialty pain clinic services, when compared with matched control patients. One possible explanation is that patients who used the device may have had their pain adequately managed and thus required less specialty pain care. However, the absence of clinically significant changes in pain intensity over time suggests that pain intensity alone did not account for the observed changes in pain treatment use. We were unable to measure constructs of pain interference or functioning, which may be better predictors of functional restoration, as these data are not routinely collected within the VA and documented in the EHR. Future studies could clarify these findings by including measures of pain interference and functioning.

Although the overall declines in physical therapy and specialty pain clinic use associated with thermal therapy were modest (< 1 visit per patient), the impact of these reductions can be profound. In resource-limited health care settings, even small reductions in high-cost care utilization could be of great value in that health systems could offset costs associated with treating chronic pain without compromising quality of care or key clinical outcomes, such as pain intensity. This study, however, did not include a cost analysis. Future studies should incorporate formal cost analyses to quantify cost offsets that may result from decreased specialty pain treatment use.

Patients who received thermal therapy devices did not show clinically meaningful reductions in pain intensity over time, defined as reductions in pain intensity of 1.7 to 2.0 on a 0 to 10 scale.^28,29 This finding is consistent with prior research that demonstrates relatively stable pain intensity self-ratings longitudinally by patients with chronic pain diagnoses, when assessed in the context of usual clinical care.³⁰ This finding, however, is inconsistent with prior literature that demonstrates pain-reducing benefits of thermal therapy for low back pain and knee osteoarthritis.^7-9

In this study, pain intensity ratings were derived from the EHR during routine outpatient clinical encounters and not at the time thermal therapy was self-administered, as has been done in prior clinical trials.^7-9 Pain location was not specified at the time of pain ratings, and it is possible that patients may have been endorsing pain in areas of the body that had not been treated by thermal therapy. Patient-level variability in pain intensity ratings (eg, within-patient range over time) was not examined, although prior research indicates substantial variability.³⁰ While average pain intensity ratings in the current study did not change, an examination of patient variability warrants further study, as a narrowing of pain intensity ratings can be perceived, by patients, as demonstrable improvement and has been associated with improved physical and psychological outcomes.³¹ Furthermore, pain intensity does not characterize physical or emotional functioning that can be captured with more comprehensive validated measures, some of which are recommended outcomes in pain clinical trials.³²

Our findings point to reductions in all forms of opioid use across both treatment and control patients. Data from the VA and in the US more generally point to downward trends in opioid prescribing during the study period.³³ This decline is likely due to increased use of risk mitigation approaches, such as routine urine drug screens and review of prescription drug monitoring databases.³⁴ These state-level databases track prescribing of controlled substances, including opioids and benzodiazepines, within a state. Implementation of these practices has been associated with declines in higher risk opioid prescribing.³⁴ Findings from this study further point to associations of reduced higher risk opioid use among patients who received thermal therapy devices. In the full sample of patients, reductions in days of opioid use, high-dose opioid use, and co-use of opioids and benzodiazepines were observed across all patients, with greater reductions observed in high-dose opioid use and concurrent opioid and benzodiazepine use among patients who received a thermal therapy device. Experimental studies indicate that the endogenous opioid system is implicated in pain relief and activated by thermal therapies. ³⁵ Differential reductions in higher-risk opioid use among patients who received thermal therapy devices in our study may be associated with endogenous opioid activation, though this was not specifically measured. It is also unclear whether thermal therapy was provided by clinicians in the context of opioid tapering or other risk mitigation efforts, or patients reduced higher risk opioid use of their own volition. Prior research has identified both patient- and clinician-initiated opioid tapering and discontinuation.³⁶ While a thorough explication of opioid dose reduction was beyond the scope of this study, future qualitative work could help explain potential benefits of thermal therapy in the context of analgesic pharmacotherapy use, including opioid medications.

Limitations

The extent to which patients used the thermal therapy device could not be measured; therefore, device receipt was used as a proxy for use. However, it was not possible to determine whether the frequency and duration of device use was associated with study outcomes. Treatment and control groups demonstrated some differences in outcome variables at the index date. Potential known biases were addressed using propensity score matching procedures and statistical procedures that controlled for patient demographic and clinical characteristics, as well as pretreatment values of all outcome variables. Nevertheless, as an observational study, this analysis cannot account for all known and unknown confounders, and a randomized controlled trial is needed to make claims of causality. The study population consisted of US veterans and included a low proportion of women. As a result, the findings may not be generalizable to other patient populations. Finally, prescription dispensing data, used as a proxy for pharmacotherapy use, do not necessarily reflect actual medication use.

Conclusions

This study is among the first to examine associations between thermal therapy and specialty pain treatment and analgesic pharmacotherapy use among US veterans. Although the retrospective cohort study design does not allow causal inferences regarding the efficacy of thermal therapy for veterans with chronic musculoskeletal pain, confidence in the findings is strengthened by methodological and statistical control of known confounders. Future trials employing experimental designs are needed to further clarify the clinical and health systems benefits of thermal therapy for musculoskeletal pain syndromes.

Growing recognition of the limitations of long-term opioid therapy for chronic noncancer pain has highlighted the importance of nonpharmacologic approaches to pain treatment.^1,2 These treatments are varied and may include psychological and behavioral therapies (eg, cognitive behavioral therapy for chronic pain), exercise and movement therapies (eg, yoga), and manual therapies (eg, chiropractic). Body surface cold therapy, while predominantly used to reduce postoperative pain and inflammation,^3,4 pain subsequent to acute musculoskeletal injury,⁵ and pain related to muscle soreness,⁶ is a nonpharmacologic treatment that has shown pain-reducing benefits for chronic low back pain and knee osteoarthritis, as has its counterpart, superficial heat therapy.^7-9 Heat therapy has also been shown to improve strength, flexibility, and activities of daily living in patients with chronic low back pain.^10,11 Cold and heat therapies are commonly used complementarily. Cold therapies aim to reduce blood flow and inflammation and are often used immediately following trauma to an affected area, whereas heat therapies increase blood flow and metabolic activity and are commonly used to promote healing.⁵

Heat and cold therapies (also known as thermal therapies) benefit resource-limited health care systems, as most devices require a single expenditure and can be self-administered by patients at home as part of their pain self-management plan. In addition, these pain self-management tools may attenuate the need for more expensive specialty pain care and ongoing analgesic pharmacotherapy. Despite their potential, few studies have characterized the benefits of thermal therapies for patients with heterogeneous chronic pain syndromes.

The purpose of this retrospective cohort study was to examine the potential clinical and health system benefits of patient-administered thermal therapy. Our primary hypothesis was that patients with chronic musculoskeletal pain who received a thermal therapy self-management device would have fewer days of opioid prescriptions compared with a sample of matched control patients. Secondarily, we hypothesized that patients who received a thermal therapy device would have lower utilization of specialty pain care, fewer potentially hazardous opioid prescriptions (eg, high-dose opioid therapy and concurrent opioid and benzodiazepine prescriptions), fewer prescriptions for nonopioid analgesic medications, and decreased pain intensity when compared with matched controls.

Methods

This retrospective cohort study compared pain pharmacotherapy, pain treatment utilization, and pain intensity outcomes between patients who received a thermal therapy device and matched patients who did not. The study was approved by the US Department of Veterans Affairs (VA) Portland Health Care System Institutional Review Board and was granted a waiver of informed consent to access patient electronic health records (EHRs).

Pain Care

The VA uses ThermaZone thermal therapy devices (Innovative Medical Equipment) for chronic pain treatment. The device uses thermoelectric technology to provide point-of-contact cooling and heating therapy through site-specific pads (eg, ankle, knee, hip, back, elbow, shoulder). Patients place pads on sites where they experience pain, and temperature regulated water circulates through the device and to the pad, providing consistent, localized thermal therapy. The pads range in temperature from 1 °C to 52 °C, and temperatures are self-monitored and controlled by the patient.

Standard pain care in this study followed the VA stepped model of pain care, which builds on a foundation of patient education for pain self-management approaches (eg, exercise, mindfulness, relaxation, social support).¹² According to the VA stepped model of pain care, all patients with chronic pain should engage in these foundational self-management approaches. However, some patients require more intensive care. The VA stepped-up treatment engages primary and specialty care services—such as physical therapy, pharmacy, complementary and integrative health approaches, mental health, and substance use services—and, when indicated, may escalate treatment to interdisciplinary pain teams or tertiary pain centers. In this retrospective cohort study, treatment patients received a thermal therapy device and standard of care, whereas control patients received standard care only.

Sample Selection

Eligible patients were aged ≥ 18 years, had a musculoskeletal pain diagnosis documented in the EHR in the year prior to thermal therapy device receipt (or during the same period for a treatment patient’s matched control), and were enrolled in VA health care during the study period. Patients who died during the study period were excluded. Treatment patients received a thermal therapy device from the VA between January 1, 2017, and December 31, 2018, when complete data on thermal therapy devices were available. For control patients, the VA Corporate Data Warehouse (CDW) was used to identify VA patients with characteristics similar to those of treated patients.

We modeled the probability that a patient would receive a thermal therapy device using logistic regression. Predictor variables were measured in the year prior to device receipt and included variables associated with pain treatment utilization and analgesic pharmacotherapy receipt, as recommended by Brookhart et al.¹³ These included age, sex, race, ethnicity, VA service-connected disability status, comorbidities, receipt of medications for opioid use disorder, pain diagnoses, mental health diagnoses, and substance use disorder diagnoses.^14-19

The resulting propensity scores (eg, predicted probabilities) were used to match treatment patients 1:1 with control patients using a nearest-neighbor matching algorithm.²⁰ This procedure matches a control patient with the closest propensity score to that of the corresponding treatment patient. An exact match on VA facility was required (eg, treatment patients and matched controls received care at the same VA facility). Standardized differences were used to assess covariate balance between the matched groups, and kernel density plots of propensity scores tested for sufficient overlap.²¹ Control patients were selected from a pool of 1,150,149 patients.

Study Variables

The index date was the date the thermal therapy device was released to treatment patients or the same date for the matched controls. Data were extracted from the CDW over a 24-month period: 12 months prior to the index date through 12 months afterwards. Collecting data in the 12 months prior to treatment initiation allowed us to adjust for covariates and provided greater precision, as recommended for observational study designs.²²

Treatment conditions were defined dichotomously as receipt vs nonreceipt of a thermal therapy device. The primary outcome was the number of days of opioid use in the 12 months following the index date. Additional outcomes included days of high-dose opioid therapy (≥ 50 mg morphine equivalent [MME] daily), concurrent opioid and benzodiazepine prescriptions, and nonopioid analgesic pharmacotherapy (eg, nonsteroidal anti-inflammatory drugs, acetaminophen, muscle relaxants). All prescription data were based on medication fills obtained from VA pharmacy records. Additional outcomes included the number of visits to physical therapy, occupational therapy, physical medicine and rehabilitation, and interdisciplinary pain clinics, including interventional pain medicine.

Pain intensity ratings were collected as part of routine VA care using a numeric scale from 0 (no pain) to 10 (worst possible pain). Pain intensity trajectories were computed using all available EHR-derived pain intensity score data for each patient in the 12 months prior to and following the index date.

Covariates were extracted from the EHR and evaluated in the year prior to the index date, unless otherwise noted. They included age at the index date; self-reported sex, and race and ethnicity; service-connected disability status (disability awarded as a result of military service-related trauma or injury); Charlson Comorbidity Index; and diagnoses of opioid use disorder, alcohol use disorder, other substance use disorder, mood disorder, posttraumatic stress disorder, other anxiety disorder, psychotic disorder, neuropathic pain, and headache pain.²³ All diagnoses were coded as yes if identified in the EHR as a focus of treatment during any clinical encounter in the year prior to the index date or no if not identified as a focus of treatment.

The number of days patients had been living with pain was calculated and defined as the number of days from the first pain diagnosis available in a patient’s EHR to the index date. Finally, the number of pain-related surgeries (eg, surgeries with ≥ 1 pain diagnoses associated with the clinical encounter) and average pain intensity were computed for the pre- and postindex date evaluation periods and included as model covariates.

Statistical Analyses

For the 4 pharmacotherapy and 4 nonpharmacologic treatment usage outcomes, we tested the fit of linear models and several models with count distributions using the Bayesian information criterion.²⁴ Count distributions included Poisson, zero-inflated Poisson, negative binomial, and zero-inflated negative binomial. With 1 exception (days of high-dose opioid use), a negative binomial distribution best fit the data. For days of high-dose opioid use, a Gaussian distribution best fit the data.

Eight separate mixed-effects regression analyses compared changes in each outcome from the 12-month preindex period through the 12-month postindex period between treatment and control patients by testing the Time × Treatment interaction. This approach statistically accounts for observed pretreatment differences in outcome variables. Statistics for the main effects of time and treatment are also presented. To reduce bias, models controlled for covariates specified previously.

For pain intensity, we used random-effects growth modeling to quantify both fixed and random effects of pain intensity at the index date (eg, the model intercept), which estimates pain at the time of treatment initiation, and change in pain during the 12 months following the index date (eg, the model slope), which characterizes the trajectory of pain intensity ratings.²⁵ The model included piecewise components of pain score trajectories in the 12 months prior to the index date and in the 12 months following the index date. Several types of change for the 12-month postindex observation period were explored—including quadratic and cubic curvilinear change. A linear model for change in pain over time provided the best fit based on the Bayesian information criterion and parsimony of model parameters.²⁶ We report estimates of change in pain over time in monthly intervals for ease of interpretation. However, models used all individual pain scores rather than computing monthly averages when > 1 pain score was available within a month, as recommended in previous research.²⁷ This approach makes optimal use of all available data. Both random effects (intercept and slope) were regressed onto the set of covariates described previously.

This study used data available in the EHR over the 24-month observation period. We characterize the density (eg, frequency) of all outcome variables by treatment condition in the Appendix. Because the hypotheses were directional, the authors used a 2-sided α = 0.10 and applied a Bonferroni correction for the 9 statistical tests performed, resulting in an adjusted α of 0.01. Treatment utilization and pharmacotherapy outcome analyses were performed in Stata, version 16.1. Random-effects growth modeling of pain score trajectories was performed using Mplus, version 8.8.

Results

There were 2182 patients in the treatment group and 2182 matched controls. The mean (SD) age was 54 (15) years; 81% were male, and about two-thirds (68%) identified as White and non-Hispanic. Mental health comorbidities were common, with > 40% of the sample having diagnoses of a mood disorder and/or posttraumatic stress disorder. Nearly all patients (90%) had VA service-connected disability ratings. Among patients with chronic musculoskeletal pain, 8% had comorbid neuropathic pain and 14% had headache. The mean (SD) duration of chronic pain across both patient groups was 3416 (2016) days, or about 9.4 years (Table 1).

Pharmacotherapy

High-dose opioid use (> 50 MME daily dose), days of opioid use, and concurrent opioid and benzodiazepine use decreased for all patients from the pre- to posttreatment period (Table 2). However, high-dose opioid use (Time × Treatment interaction, 3.24; 99% CI, 0.34 to 6.14) (Figure 1A) and concurrent opioid and benzodiazepine use (Time × Treatment interaction, 0.76; 99% CI, 0.67 to 0.86) (Figure 1B) had a larger decrease for the treatment vs matched control group. Treatment and matched control patients had comparable reductions in days of opioid use (Time × Treatment interaction, 0.98; 99% CI, 0.91 to 1.05) (Figure 1C). Neither group showed changes in nonopioid analgesic pharmacotherapy over time (main effect of time, incidence rate ratio [IRR], 1.03; 99% CI, 0.99 to 1.07; Time × Treatment interaction, 0.95; 99% CI, 0.90 to 1.01) (Figure 1D).

Nonpharmacologic Pain Treatment

The number of physical therapy and pain clinic visits declined for treatment patients and increased slightly for matched control patients (Figure 2A and 2B). For occupational therapy visits, neither group showed changes over time (main effect of time IRR, 1.03; 99% CI, 0.83 to 1.22; Time × Treatment interaction, 1.20; 99% CI, 0.93 to 1.46) (Figure 2C). For physical medicine and rehabilitation visits, both groups decreased use over time (main effect of time IRR, 0.78; 99% CI, 0.66 to 0.90), but this decrease did not differ between treatment and control patients (Time × Treatment interaction, 1.16; 99% CI, 0.94 to 1.37) (Figure 2D).

Pain Intensity

Pain intensity decreased for both groups by an estimated 0.02 points per month (99% CI, -0.04 to -0.01; P < .01), or 0.24 points over the 12-month postindex follow-up period (Figure 3). There were no statistically significant differences between treatment and control patients in pain intensity changes over the follow-up period (B = -0.02; 99% CI, -0.06 to 0.02; P = .15).

Discussion

Patients with musculoskeletal pain who received a thermal therapy device showed a larger decline in use of some specialty pain treatments, including physical therapy and specialty pain clinic services, when compared with matched control patients. One possible explanation is that patients who used the device may have had their pain adequately managed and thus required less specialty pain care. However, the absence of clinically significant changes in pain intensity over time suggests that pain intensity alone did not account for the observed changes in pain treatment use. We were unable to measure constructs of pain interference or functioning, which may be better predictors of functional restoration, as these data are not routinely collected within the VA and documented in the EHR. Future studies could clarify these findings by including measures of pain interference and functioning.

Although the overall declines in physical therapy and specialty pain clinic use associated with thermal therapy were modest (< 1 visit per patient), the impact of these reductions can be profound. In resource-limited health care settings, even small reductions in high-cost care utilization could be of great value in that health systems could offset costs associated with treating chronic pain without compromising quality of care or key clinical outcomes, such as pain intensity. This study, however, did not include a cost analysis. Future studies should incorporate formal cost analyses to quantify cost offsets that may result from decreased specialty pain treatment use.

Patients who received thermal therapy devices did not show clinically meaningful reductions in pain intensity over time, defined as reductions in pain intensity of 1.7 to 2.0 on a 0 to 10 scale.^28,29 This finding is consistent with prior research that demonstrates relatively stable pain intensity self-ratings longitudinally by patients with chronic pain diagnoses, when assessed in the context of usual clinical care.³⁰ This finding, however, is inconsistent with prior literature that demonstrates pain-reducing benefits of thermal therapy for low back pain and knee osteoarthritis.^7-9

In this study, pain intensity ratings were derived from the EHR during routine outpatient clinical encounters and not at the time thermal therapy was self-administered, as has been done in prior clinical trials.^7-9 Pain location was not specified at the time of pain ratings, and it is possible that patients may have been endorsing pain in areas of the body that had not been treated by thermal therapy. Patient-level variability in pain intensity ratings (eg, within-patient range over time) was not examined, although prior research indicates substantial variability.³⁰ While average pain intensity ratings in the current study did not change, an examination of patient variability warrants further study, as a narrowing of pain intensity ratings can be perceived, by patients, as demonstrable improvement and has been associated with improved physical and psychological outcomes.³¹ Furthermore, pain intensity does not characterize physical or emotional functioning that can be captured with more comprehensive validated measures, some of which are recommended outcomes in pain clinical trials.³²

Our findings point to reductions in all forms of opioid use across both treatment and control patients. Data from the VA and in the US more generally point to downward trends in opioid prescribing during the study period.³³ This decline is likely due to increased use of risk mitigation approaches, such as routine urine drug screens and review of prescription drug monitoring databases.³⁴ These state-level databases track prescribing of controlled substances, including opioids and benzodiazepines, within a state. Implementation of these practices has been associated with declines in higher risk opioid prescribing.³⁴ Findings from this study further point to associations of reduced higher risk opioid use among patients who received thermal therapy devices. In the full sample of patients, reductions in days of opioid use, high-dose opioid use, and co-use of opioids and benzodiazepines were observed across all patients, with greater reductions observed in high-dose opioid use and concurrent opioid and benzodiazepine use among patients who received a thermal therapy device. Experimental studies indicate that the endogenous opioid system is implicated in pain relief and activated by thermal therapies. ³⁵ Differential reductions in higher-risk opioid use among patients who received thermal therapy devices in our study may be associated with endogenous opioid activation, though this was not specifically measured. It is also unclear whether thermal therapy was provided by clinicians in the context of opioid tapering or other risk mitigation efforts, or patients reduced higher risk opioid use of their own volition. Prior research has identified both patient- and clinician-initiated opioid tapering and discontinuation.³⁶ While a thorough explication of opioid dose reduction was beyond the scope of this study, future qualitative work could help explain potential benefits of thermal therapy in the context of analgesic pharmacotherapy use, including opioid medications.

Limitations

The extent to which patients used the thermal therapy device could not be measured; therefore, device receipt was used as a proxy for use. However, it was not possible to determine whether the frequency and duration of device use was associated with study outcomes. Treatment and control groups demonstrated some differences in outcome variables at the index date. Potential known biases were addressed using propensity score matching procedures and statistical procedures that controlled for patient demographic and clinical characteristics, as well as pretreatment values of all outcome variables. Nevertheless, as an observational study, this analysis cannot account for all known and unknown confounders, and a randomized controlled trial is needed to make claims of causality. The study population consisted of US veterans and included a low proportion of women. As a result, the findings may not be generalizable to other patient populations. Finally, prescription dispensing data, used as a proxy for pharmacotherapy use, do not necessarily reflect actual medication use.

Conclusions

This study is among the first to examine associations between thermal therapy and specialty pain treatment and analgesic pharmacotherapy use among US veterans. Although the retrospective cohort study design does not allow causal inferences regarding the efficacy of thermal therapy for veterans with chronic musculoskeletal pain, confidence in the findings is strengthened by methodological and statistical control of known confounders. Future trials employing experimental designs are needed to further clarify the clinical and health systems benefits of thermal therapy for musculoskeletal pain syndromes.