Federal Practitioner

The Food and Drug Administration has sent warning letters to three companies, including Amazon, for selling mole and skin tag removal products that have not been approved by the agency, according to a press release issued on Aug. 9.

In addition to Amazon.com, the other two companies are Ariella Naturals, and Justified Laboratories.

Currently, no over-the-counter products are FDA-approved for the at-home removal of moles and skin tags, and use of unapproved products could be dangerous to consumers, according to the statement. These products may be sold as ointments, gels, sticks, or liquids, and may contain high concentrations of salicylic acid or other harmful ingredients. Introducing unapproved products in to interstate commerce violates the Federal Food, Drug, and Cosmetic Act.

Two products sold on Amazon are the “Deisana Skin Tag Remover, Mole Remover and Repair Gel Set” and “Skincell Mole Skin Tag Corrector Serum,” according to the letter sent to Amazon.

The warning letters alert the three companies that they have 15 days from receipt to address any violations. However, warning letters are not a final FDA action, according to the statement.

“The agency’s rigorous surveillance works to identify threats to public health and stop these products from reaching our communities,” Donald D. Ashley, JD, director of the Office of Compliance in the FDA’s Center for Drug Evaluation and Research, said in the press release. “This includes where online retailers like Amazon are involved in the interstate sale of unapproved drug products. We will continue to work diligently to ensure that online retailers do not sell products that violate federal law,” he added.

The statement emphasized that moles should be evaluated by a health care professional, as attempts at self-diagnosis and at-home treatment could lead to a delayed cancer diagnosis, and potentially to cancer progression.

Products marketed to consumers for at-home removal of moles, skin tags, and other skin lesions could cause injuries, infections, and scarring, according to a related consumer update first posted by the FDA in June, which was updated after the warning letters were sent out.

Consumers and health care professionals are encouraged to report any adverse events related to mole removal or skin tag removal products to the agency’s MedWatch Adverse Event Reporting program.

The FDA also offers an online guide, BeSafeRx, with advice for consumers about potential risks of using online pharmacies and how to do so safely.

The Food and Drug Administration has sent warning letters to three companies, including Amazon, for selling mole and skin tag removal products that have not been approved by the agency, according to a press release issued on Aug. 9.

In addition to Amazon.com, the other two companies are Ariella Naturals, and Justified Laboratories.

Currently, no over-the-counter products are FDA-approved for the at-home removal of moles and skin tags, and use of unapproved products could be dangerous to consumers, according to the statement. These products may be sold as ointments, gels, sticks, or liquids, and may contain high concentrations of salicylic acid or other harmful ingredients. Introducing unapproved products in to interstate commerce violates the Federal Food, Drug, and Cosmetic Act.

Two products sold on Amazon are the “Deisana Skin Tag Remover, Mole Remover and Repair Gel Set” and “Skincell Mole Skin Tag Corrector Serum,” according to the letter sent to Amazon.

The warning letters alert the three companies that they have 15 days from receipt to address any violations. However, warning letters are not a final FDA action, according to the statement.

“The agency’s rigorous surveillance works to identify threats to public health and stop these products from reaching our communities,” Donald D. Ashley, JD, director of the Office of Compliance in the FDA’s Center for Drug Evaluation and Research, said in the press release. “This includes where online retailers like Amazon are involved in the interstate sale of unapproved drug products. We will continue to work diligently to ensure that online retailers do not sell products that violate federal law,” he added.

The statement emphasized that moles should be evaluated by a health care professional, as attempts at self-diagnosis and at-home treatment could lead to a delayed cancer diagnosis, and potentially to cancer progression.

Products marketed to consumers for at-home removal of moles, skin tags, and other skin lesions could cause injuries, infections, and scarring, according to a related consumer update first posted by the FDA in June, which was updated after the warning letters were sent out.

Consumers and health care professionals are encouraged to report any adverse events related to mole removal or skin tag removal products to the agency’s MedWatch Adverse Event Reporting program.

The FDA also offers an online guide, BeSafeRx, with advice for consumers about potential risks of using online pharmacies and how to do so safely.

The Food and Drug Administration has sent warning letters to three companies, including Amazon, for selling mole and skin tag removal products that have not been approved by the agency, according to a press release issued on Aug. 9.

In addition to Amazon.com, the other two companies are Ariella Naturals, and Justified Laboratories.

Currently, no over-the-counter products are FDA-approved for the at-home removal of moles and skin tags, and use of unapproved products could be dangerous to consumers, according to the statement. These products may be sold as ointments, gels, sticks, or liquids, and may contain high concentrations of salicylic acid or other harmful ingredients. Introducing unapproved products in to interstate commerce violates the Federal Food, Drug, and Cosmetic Act.

Two products sold on Amazon are the “Deisana Skin Tag Remover, Mole Remover and Repair Gel Set” and “Skincell Mole Skin Tag Corrector Serum,” according to the letter sent to Amazon.

The warning letters alert the three companies that they have 15 days from receipt to address any violations. However, warning letters are not a final FDA action, according to the statement.

“The agency’s rigorous surveillance works to identify threats to public health and stop these products from reaching our communities,” Donald D. Ashley, JD, director of the Office of Compliance in the FDA’s Center for Drug Evaluation and Research, said in the press release. “This includes where online retailers like Amazon are involved in the interstate sale of unapproved drug products. We will continue to work diligently to ensure that online retailers do not sell products that violate federal law,” he added.

The statement emphasized that moles should be evaluated by a health care professional, as attempts at self-diagnosis and at-home treatment could lead to a delayed cancer diagnosis, and potentially to cancer progression.

Products marketed to consumers for at-home removal of moles, skin tags, and other skin lesions could cause injuries, infections, and scarring, according to a related consumer update first posted by the FDA in June, which was updated after the warning letters were sent out.

Consumers and health care professionals are encouraged to report any adverse events related to mole removal or skin tag removal products to the agency’s MedWatch Adverse Event Reporting program.

The FDA also offers an online guide, BeSafeRx, with advice for consumers about potential risks of using online pharmacies and how to do so safely.

New York City veterinarian Erin Kulick used to be a weekend warrior. Only 2½ years ago, the 38-year-old new mother played ultimate Frisbee and flag football with friends. She went for regular 30-minute runs to burn off stress.

Now, Dr. Kulick is usually so exhausted, she can’t walk nonstop for 15 minutes. She recently tried to take her 4-year-old son, Cooper, to the American Museum of Natural History for his first visit, but ended up on a bench outside the museum, sobbing in the rain, because she couldn’t even get through the first hurdle of standing in line. “I just wanted to be there with my kid,” she said.

Dr. Kulick got sick with COVID-19 at the start of the pandemic in March 2020, 9 months before the first vaccine would be approved. Now she is among the estimated one in five infected Americans, or 19%, whose symptoms developed into long COVID.

Dr. Kulick also is now vaccinated and boosted. Had a vaccine been available sooner, could it have protected her from long COVID?

Evidence is starting to show it’s likely.

“The best way not to have long COVID is not to have COVID at all,” said Leora Horwitz, MD, a professor of population health and medicine at New York University. “To the extent that vaccination can prevent you from getting COVID at all, then it helps to reduce long COVID.”

And just as vaccines reduce the risk of severe disease, hospitalization, and death, they also seem to reduce the risk of long COVID if people do get breakthrough infections. People with more serious initial illness appear more likely to have prolonged symptoms, but those with milder disease can certainly get it, too.

“You’re more likely to have long COVID with more severe disease, and we have ample evidence that vaccination reduces the severity of disease,” Dr. Horwitz said. “We also now have quite a lot of evidence that vaccination does reduce your risk of long COVID – probably because it reduces your risk of severe disease.”

There is little consensus about how much vaccines can lower the risk of long-term COVID symptoms, but several studies suggest that number lies anywhere from 15% to more than 80%.

That might seem like a big variation, but infectious disease experts argue that trying to interpret the gap isn’t as important as noticing what’s consistent across all these studies: “Vaccines do offer some protection, but it’s incomplete,” said Ziyad Al-Aly, MD, chief of research and development at the Veterans Affairs St. Louis Health Care System. Dr. Al-Aly, who has led several large studies on long COVID, said focusing on the fact that vaccines do offer some protection is a much better public health message than looking at the different levels of risk.

“Vaccines do a miraculous job for what they were designed to do,” said Dr. Al-Aly. “Vaccines were designed to reduce the risk of hospitalization ... and for that, vaccines are still holding up, even with all the changes in the virus.”

Still, Elena Azzolini, MD, PhD, head of the Humanitas Research Hospital’s vaccination center in Milan, thinks some studies may have underestimated the level of long COVID protection from vaccines because of limits in the study methods, such as not including enough women, who are more affected by long COVID. Her recent study, which looked at 2,560 health care professionals working in nine Italian centers from March 2020 to April 2022, focused on the risk for healthy women and men in their 20s to their 70s.

In the paper, Dr. Azzolini and associates reported that two or three doses of vaccine reduced the risk of hospitalization from COVID-19 from 42% among those who are unvaccinated to 16%-17%. In other words, they found unvaccinated people in the study were nearly three times as likely to have serious symptoms for longer than 4 weeks.

But Dr. Azzolini and Dr. Al-Aly still say that, even for the vaccinated, as long as COVID is around, masks are necessary. That’s because current vaccines don’t do enough to reduce transmission, said Dr. Al-Aly. “The only way that can really help [stop] transmission is covering our nose and mouth with a mask.”
 

How vaccinations affect people who already have long COVID

Some long COVID patients have said they got better after they get boosted, while some say they’re getting worse, said Dr. Horwitz, who is also a lead investigator at the National Institutes of Health’s flagship RECOVER program, a 4-year research project to study long COVID across the United States. (The NIH is still recruiting volunteers for these studies, which are also open to people who have never had COVID.)

One study published in the British Medical Journal analyzed survey data of more than 28,000 people infected with COVID in the United Kingdom and found a 13% reduction in long-term symptoms after a first dose of the vaccine, although it was unclear from the data if the improvement was sustained.

A second dose was associated with another 8% improvement over a 2-month period. “It’s reassuring that we see an average modest improvement in symptoms, not an average worsening in symptoms,” said Daniel Ayoubkhani, principal statistician at the U.K. Office for National Statistics and lead author of the study. Of course, the experience will differ among different people.

“It doesn’t appear that vaccination is the silver bullet that’s going to eradicate long COVID,” he said, but evidence from multiple studies suggests vaccines may help people with long-term symptoms.

Akiko Iwasaki, PhD, an immunobiologist at Yale University, New Haven, Conn., told a White House summit in July that one of the best ways to prevent long COVID is to develop the next generation of vaccines that also prevent milder cases by blocking transmission in the first place.

Back in New York, Dr. Kulick is now triple vaccinated. She’s due for a fourth dose soon but admits she’s “terrified every time” that she’s going to get sicker.

In her Facebook support group for long COVID, she reads that most people with prolonged symptoms handle it well. She has also noticed some of her symptoms eased after her first two doses of vaccine.

Since being diagnosed, Dr. Kulick learned she has a genetic condition, Ehlers-Danlos syndrome, which affects connective tissues that support skin, joints, organs, and blood vessels, and which her doctors say may have made her more prone to long COVID. She’s also being screened for autoimmune diseases, but for now, the only relief she has found has come from long COVID physical therapy, changes to her diet, and integrative medicine.

Dr. Kulick is still trying to figure out how she can get better while keeping her long hours at her veterinary job – and her health benefits. She is thankful her husband is a devoted caregiver to their son and a professional jazz musician with a schedule that allows for some flexibility.

“But it’s really hard when every week feels like I’ve run a marathon,” she said. “I can barely make it through.”

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

New York City veterinarian Erin Kulick used to be a weekend warrior. Only 2½ years ago, the 38-year-old new mother played ultimate Frisbee and flag football with friends. She went for regular 30-minute runs to burn off stress.

Now, Dr. Kulick is usually so exhausted, she can’t walk nonstop for 15 minutes. She recently tried to take her 4-year-old son, Cooper, to the American Museum of Natural History for his first visit, but ended up on a bench outside the museum, sobbing in the rain, because she couldn’t even get through the first hurdle of standing in line. “I just wanted to be there with my kid,” she said.

Dr. Kulick got sick with COVID-19 at the start of the pandemic in March 2020, 9 months before the first vaccine would be approved. Now she is among the estimated one in five infected Americans, or 19%, whose symptoms developed into long COVID.

Dr. Kulick also is now vaccinated and boosted. Had a vaccine been available sooner, could it have protected her from long COVID?

Evidence is starting to show it’s likely.

“The best way not to have long COVID is not to have COVID at all,” said Leora Horwitz, MD, a professor of population health and medicine at New York University. “To the extent that vaccination can prevent you from getting COVID at all, then it helps to reduce long COVID.”

And just as vaccines reduce the risk of severe disease, hospitalization, and death, they also seem to reduce the risk of long COVID if people do get breakthrough infections. People with more serious initial illness appear more likely to have prolonged symptoms, but those with milder disease can certainly get it, too.

“You’re more likely to have long COVID with more severe disease, and we have ample evidence that vaccination reduces the severity of disease,” Dr. Horwitz said. “We also now have quite a lot of evidence that vaccination does reduce your risk of long COVID – probably because it reduces your risk of severe disease.”

There is little consensus about how much vaccines can lower the risk of long-term COVID symptoms, but several studies suggest that number lies anywhere from 15% to more than 80%.

That might seem like a big variation, but infectious disease experts argue that trying to interpret the gap isn’t as important as noticing what’s consistent across all these studies: “Vaccines do offer some protection, but it’s incomplete,” said Ziyad Al-Aly, MD, chief of research and development at the Veterans Affairs St. Louis Health Care System. Dr. Al-Aly, who has led several large studies on long COVID, said focusing on the fact that vaccines do offer some protection is a much better public health message than looking at the different levels of risk.

“Vaccines do a miraculous job for what they were designed to do,” said Dr. Al-Aly. “Vaccines were designed to reduce the risk of hospitalization ... and for that, vaccines are still holding up, even with all the changes in the virus.”

Still, Elena Azzolini, MD, PhD, head of the Humanitas Research Hospital’s vaccination center in Milan, thinks some studies may have underestimated the level of long COVID protection from vaccines because of limits in the study methods, such as not including enough women, who are more affected by long COVID. Her recent study, which looked at 2,560 health care professionals working in nine Italian centers from March 2020 to April 2022, focused on the risk for healthy women and men in their 20s to their 70s.

In the paper, Dr. Azzolini and associates reported that two or three doses of vaccine reduced the risk of hospitalization from COVID-19 from 42% among those who are unvaccinated to 16%-17%. In other words, they found unvaccinated people in the study were nearly three times as likely to have serious symptoms for longer than 4 weeks.

But Dr. Azzolini and Dr. Al-Aly still say that, even for the vaccinated, as long as COVID is around, masks are necessary. That’s because current vaccines don’t do enough to reduce transmission, said Dr. Al-Aly. “The only way that can really help [stop] transmission is covering our nose and mouth with a mask.”
 

How vaccinations affect people who already have long COVID

Some long COVID patients have said they got better after they get boosted, while some say they’re getting worse, said Dr. Horwitz, who is also a lead investigator at the National Institutes of Health’s flagship RECOVER program, a 4-year research project to study long COVID across the United States. (The NIH is still recruiting volunteers for these studies, which are also open to people who have never had COVID.)

One study published in the British Medical Journal analyzed survey data of more than 28,000 people infected with COVID in the United Kingdom and found a 13% reduction in long-term symptoms after a first dose of the vaccine, although it was unclear from the data if the improvement was sustained.

A second dose was associated with another 8% improvement over a 2-month period. “It’s reassuring that we see an average modest improvement in symptoms, not an average worsening in symptoms,” said Daniel Ayoubkhani, principal statistician at the U.K. Office for National Statistics and lead author of the study. Of course, the experience will differ among different people.

“It doesn’t appear that vaccination is the silver bullet that’s going to eradicate long COVID,” he said, but evidence from multiple studies suggests vaccines may help people with long-term symptoms.

Akiko Iwasaki, PhD, an immunobiologist at Yale University, New Haven, Conn., told a White House summit in July that one of the best ways to prevent long COVID is to develop the next generation of vaccines that also prevent milder cases by blocking transmission in the first place.

Back in New York, Dr. Kulick is now triple vaccinated. She’s due for a fourth dose soon but admits she’s “terrified every time” that she’s going to get sicker.

In her Facebook support group for long COVID, she reads that most people with prolonged symptoms handle it well. She has also noticed some of her symptoms eased after her first two doses of vaccine.

Since being diagnosed, Dr. Kulick learned she has a genetic condition, Ehlers-Danlos syndrome, which affects connective tissues that support skin, joints, organs, and blood vessels, and which her doctors say may have made her more prone to long COVID. She’s also being screened for autoimmune diseases, but for now, the only relief she has found has come from long COVID physical therapy, changes to her diet, and integrative medicine.

Dr. Kulick is still trying to figure out how she can get better while keeping her long hours at her veterinary job – and her health benefits. She is thankful her husband is a devoted caregiver to their son and a professional jazz musician with a schedule that allows for some flexibility.

“But it’s really hard when every week feels like I’ve run a marathon,” she said. “I can barely make it through.”

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

New York City veterinarian Erin Kulick used to be a weekend warrior. Only 2½ years ago, the 38-year-old new mother played ultimate Frisbee and flag football with friends. She went for regular 30-minute runs to burn off stress.

Now, Dr. Kulick is usually so exhausted, she can’t walk nonstop for 15 minutes. She recently tried to take her 4-year-old son, Cooper, to the American Museum of Natural History for his first visit, but ended up on a bench outside the museum, sobbing in the rain, because she couldn’t even get through the first hurdle of standing in line. “I just wanted to be there with my kid,” she said.

Dr. Kulick got sick with COVID-19 at the start of the pandemic in March 2020, 9 months before the first vaccine would be approved. Now she is among the estimated one in five infected Americans, or 19%, whose symptoms developed into long COVID.

Dr. Kulick also is now vaccinated and boosted. Had a vaccine been available sooner, could it have protected her from long COVID?

Evidence is starting to show it’s likely.

“The best way not to have long COVID is not to have COVID at all,” said Leora Horwitz, MD, a professor of population health and medicine at New York University. “To the extent that vaccination can prevent you from getting COVID at all, then it helps to reduce long COVID.”

And just as vaccines reduce the risk of severe disease, hospitalization, and death, they also seem to reduce the risk of long COVID if people do get breakthrough infections. People with more serious initial illness appear more likely to have prolonged symptoms, but those with milder disease can certainly get it, too.

“You’re more likely to have long COVID with more severe disease, and we have ample evidence that vaccination reduces the severity of disease,” Dr. Horwitz said. “We also now have quite a lot of evidence that vaccination does reduce your risk of long COVID – probably because it reduces your risk of severe disease.”

There is little consensus about how much vaccines can lower the risk of long-term COVID symptoms, but several studies suggest that number lies anywhere from 15% to more than 80%.

That might seem like a big variation, but infectious disease experts argue that trying to interpret the gap isn’t as important as noticing what’s consistent across all these studies: “Vaccines do offer some protection, but it’s incomplete,” said Ziyad Al-Aly, MD, chief of research and development at the Veterans Affairs St. Louis Health Care System. Dr. Al-Aly, who has led several large studies on long COVID, said focusing on the fact that vaccines do offer some protection is a much better public health message than looking at the different levels of risk.

“Vaccines do a miraculous job for what they were designed to do,” said Dr. Al-Aly. “Vaccines were designed to reduce the risk of hospitalization ... and for that, vaccines are still holding up, even with all the changes in the virus.”

Still, Elena Azzolini, MD, PhD, head of the Humanitas Research Hospital’s vaccination center in Milan, thinks some studies may have underestimated the level of long COVID protection from vaccines because of limits in the study methods, such as not including enough women, who are more affected by long COVID. Her recent study, which looked at 2,560 health care professionals working in nine Italian centers from March 2020 to April 2022, focused on the risk for healthy women and men in their 20s to their 70s.

In the paper, Dr. Azzolini and associates reported that two or three doses of vaccine reduced the risk of hospitalization from COVID-19 from 42% among those who are unvaccinated to 16%-17%. In other words, they found unvaccinated people in the study were nearly three times as likely to have serious symptoms for longer than 4 weeks.

But Dr. Azzolini and Dr. Al-Aly still say that, even for the vaccinated, as long as COVID is around, masks are necessary. That’s because current vaccines don’t do enough to reduce transmission, said Dr. Al-Aly. “The only way that can really help [stop] transmission is covering our nose and mouth with a mask.”
 

How vaccinations affect people who already have long COVID

Some long COVID patients have said they got better after they get boosted, while some say they’re getting worse, said Dr. Horwitz, who is also a lead investigator at the National Institutes of Health’s flagship RECOVER program, a 4-year research project to study long COVID across the United States. (The NIH is still recruiting volunteers for these studies, which are also open to people who have never had COVID.)

One study published in the British Medical Journal analyzed survey data of more than 28,000 people infected with COVID in the United Kingdom and found a 13% reduction in long-term symptoms after a first dose of the vaccine, although it was unclear from the data if the improvement was sustained.

A second dose was associated with another 8% improvement over a 2-month period. “It’s reassuring that we see an average modest improvement in symptoms, not an average worsening in symptoms,” said Daniel Ayoubkhani, principal statistician at the U.K. Office for National Statistics and lead author of the study. Of course, the experience will differ among different people.

“It doesn’t appear that vaccination is the silver bullet that’s going to eradicate long COVID,” he said, but evidence from multiple studies suggests vaccines may help people with long-term symptoms.

Akiko Iwasaki, PhD, an immunobiologist at Yale University, New Haven, Conn., told a White House summit in July that one of the best ways to prevent long COVID is to develop the next generation of vaccines that also prevent milder cases by blocking transmission in the first place.

Back in New York, Dr. Kulick is now triple vaccinated. She’s due for a fourth dose soon but admits she’s “terrified every time” that she’s going to get sicker.

In her Facebook support group for long COVID, she reads that most people with prolonged symptoms handle it well. She has also noticed some of her symptoms eased after her first two doses of vaccine.

Since being diagnosed, Dr. Kulick learned she has a genetic condition, Ehlers-Danlos syndrome, which affects connective tissues that support skin, joints, organs, and blood vessels, and which her doctors say may have made her more prone to long COVID. She’s also being screened for autoimmune diseases, but for now, the only relief she has found has come from long COVID physical therapy, changes to her diet, and integrative medicine.

Dr. Kulick is still trying to figure out how she can get better while keeping her long hours at her veterinary job – and her health benefits. She is thankful her husband is a devoted caregiver to their son and a professional jazz musician with a schedule that allows for some flexibility.

“But it’s really hard when every week feels like I’ve run a marathon,” she said. “I can barely make it through.”

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

Time-restricted eating during the earlier part of the day (eTRE) may promote weight loss and reduce blood pressure, new findings suggest.

Previous studies have produced mixed results regarding the weight-loss potential for intermittent fasting, the practice of alternating eating with extended fasting, and the “time-restricted eating” format, where eating is restricted to a specific, often 10-hour, time window during the day.

In a new randomized clinical trial of 90 people with obesity in which that time window was 7 AM through 3 PM, so 8 hours long, researchers report that “eTRE was more effective for losing weight and lowering diastolic blood pressure than was eating over a period of 12 or more hours at 14 weeks. The eTRE intervention may therefore be an effective treatment for both obesity and hypertension.” The study, by Humaira Jamshed, PhD, of the department of nutrition sciences, University of Alabama at Birmingham, and colleagues, was published in JAMA Internal Medicine.

In an accompanying invited commentary, Shalender Bhasin, MBBS, points out that the study findings differ from those of a previous trial published in April of 139 adults conducted in China, which did not find a significant weight loss benefit with TRE versus ad lib eating.

“The scientific premise and the preclinical data of the effects of TRE are promising, but the inconsistency among studies renders it difficult to draw strong inferences from these well-conducted but relatively small trials,” notes Dr. Bhasin, of Harvard Medical School, Boston.
 

Need for larger and longer trials of TRE

Dr. Bhasin says – and the study authors also acknowledge – that much larger randomized clinical trials of longer duration are needed “to comprehensively evaluate the hypothesized benefits and risks of long-term TRE of calorically restricted diets in adults.”

Commenting on the study for the U.K. Science Media Centre, Simon Steenson, PhD, nutrition scientist, British Nutrition Foundation, said “one of the strengths of this new study is the trial design and the number of people who were recruited compared to many of the previous trials to date.”

However, Dr. Steenson also pointed to the prior Chinese research as evidence that the inconsistencies across studies highlight the need for larger and longer trials, with cardiovascular as well as weight-loss endpoints.

Still, Dr. Steenson said, “For individuals who may find that this pattern of eating fits better with their lifestyle and preferences, time-restricted feeding is one option for reducing overall calorie intake that might be a suitable approach for some. Ultimately, it is about finding the best approach to moderate calorie intake that works for each person, as successful and sustained weight loss is about ensuring the diet is feasible to follow in the long-term.”
 

Differences in weight loss, diastolic BP, but not all measures

The study population included 90 adults seen at the Weight Loss Medicine clinic at the University of Alabama at Birmingham between August 2018 and December 2019. Participants had a body mass index of 30-60 kg/m², and none had diabetes. 

They were randomized to eTRE with the 7 AM to PM eating window or a control schedule with eating across 12 hours or more, mimicking U.S. median mealtimes, at least 6 days a week. All participants received 30-minute weight-loss counseling sessions at baseline and at weeks 2, 6, and 10 and were advised to follow a diet of 500 kcal/day below their resting energy expenditure and exercise 75-150 minutes per week.

The eTRE group adhered with their schedule a mean of 6 days per week, lower than the 6.3 days among controls (P = .03), and adherence declined by about 0.4 days per week in the eTRE group over the 14 weeks (P = .001).  

At 14 weeks, both the eTRE group and controls had lost clinically meaningful amounts of weight, at –6.3 kg and –4.0 kg, respectively, but the –2.3 kg difference was significant (P = .002).

However, there was no difference in absolute fat loss (P = .09) or ratio of fat loss to weight loss (P = .43). There were also no significant differences in changes in other body composition parameters, including visceral fat and waist circumference.

Diastolic blood pressure was lowered by an additional 4 mmHg in the eTRE group, compared with controls at 14 weeks (P = .04), but there were no significant differences in systolic blood pressure, heart rate, glucose, A1c levels, insulin levels, measures of insulin resistance, or plasma lipids.

There were no differences between the two groups in self-reported physical activity, energy intake, or dietary macronutrient composition either. However, weight-loss modeling in 77 participants with at least two weight measurements indicated that the eTRE group reduced their intake by about 214 kcal/day, compared with controls (P = .04).

Those in the eTRE group also showed greater improvements in measures of mood disturbance, vigor-activity, fatigue-inertia, and depression-dejection. Other mood and sleep endpoints were similar between groups.

In a secondary analysis of just the 59 participants who completed the study, eTRE was also more effective at reducing body fat (P = .047) and trunk fat (P = .03).

About 41% of the eTRE completers planned to continue the practice after the study concluded.

The study was supported by grants from the National Center for Advancing Translational Sciences of the National Institutes of Health and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Jamshed has reported no relevant financial relationships. Dr. Bhasin has reported receiving grants to his institution for research on which Dr. Bhasin is the principal investigator from AbbVie and MIB, receiving personal fees from OPKO and Aditum and holding equity interest in FPT and XYOne. Dr. Steenson has declared funding in support of the British Nutrition Foundation that comes from a range of sources.

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

Time-restricted eating during the earlier part of the day (eTRE) may promote weight loss and reduce blood pressure, new findings suggest.

Previous studies have produced mixed results regarding the weight-loss potential for intermittent fasting, the practice of alternating eating with extended fasting, and the “time-restricted eating” format, where eating is restricted to a specific, often 10-hour, time window during the day.

In a new randomized clinical trial of 90 people with obesity in which that time window was 7 AM through 3 PM, so 8 hours long, researchers report that “eTRE was more effective for losing weight and lowering diastolic blood pressure than was eating over a period of 12 or more hours at 14 weeks. The eTRE intervention may therefore be an effective treatment for both obesity and hypertension.” The study, by Humaira Jamshed, PhD, of the department of nutrition sciences, University of Alabama at Birmingham, and colleagues, was published in JAMA Internal Medicine.

In an accompanying invited commentary, Shalender Bhasin, MBBS, points out that the study findings differ from those of a previous trial published in April of 139 adults conducted in China, which did not find a significant weight loss benefit with TRE versus ad lib eating.

“The scientific premise and the preclinical data of the effects of TRE are promising, but the inconsistency among studies renders it difficult to draw strong inferences from these well-conducted but relatively small trials,” notes Dr. Bhasin, of Harvard Medical School, Boston.
 

Need for larger and longer trials of TRE

Dr. Bhasin says – and the study authors also acknowledge – that much larger randomized clinical trials of longer duration are needed “to comprehensively evaluate the hypothesized benefits and risks of long-term TRE of calorically restricted diets in adults.”

Commenting on the study for the U.K. Science Media Centre, Simon Steenson, PhD, nutrition scientist, British Nutrition Foundation, said “one of the strengths of this new study is the trial design and the number of people who were recruited compared to many of the previous trials to date.”

However, Dr. Steenson also pointed to the prior Chinese research as evidence that the inconsistencies across studies highlight the need for larger and longer trials, with cardiovascular as well as weight-loss endpoints.

Still, Dr. Steenson said, “For individuals who may find that this pattern of eating fits better with their lifestyle and preferences, time-restricted feeding is one option for reducing overall calorie intake that might be a suitable approach for some. Ultimately, it is about finding the best approach to moderate calorie intake that works for each person, as successful and sustained weight loss is about ensuring the diet is feasible to follow in the long-term.”
 

Differences in weight loss, diastolic BP, but not all measures

The study population included 90 adults seen at the Weight Loss Medicine clinic at the University of Alabama at Birmingham between August 2018 and December 2019. Participants had a body mass index of 30-60 kg/m², and none had diabetes. 

They were randomized to eTRE with the 7 AM to PM eating window or a control schedule with eating across 12 hours or more, mimicking U.S. median mealtimes, at least 6 days a week. All participants received 30-minute weight-loss counseling sessions at baseline and at weeks 2, 6, and 10 and were advised to follow a diet of 500 kcal/day below their resting energy expenditure and exercise 75-150 minutes per week.

The eTRE group adhered with their schedule a mean of 6 days per week, lower than the 6.3 days among controls (P = .03), and adherence declined by about 0.4 days per week in the eTRE group over the 14 weeks (P = .001).  

At 14 weeks, both the eTRE group and controls had lost clinically meaningful amounts of weight, at –6.3 kg and –4.0 kg, respectively, but the –2.3 kg difference was significant (P = .002).

However, there was no difference in absolute fat loss (P = .09) or ratio of fat loss to weight loss (P = .43). There were also no significant differences in changes in other body composition parameters, including visceral fat and waist circumference.

Diastolic blood pressure was lowered by an additional 4 mmHg in the eTRE group, compared with controls at 14 weeks (P = .04), but there were no significant differences in systolic blood pressure, heart rate, glucose, A1c levels, insulin levels, measures of insulin resistance, or plasma lipids.

There were no differences between the two groups in self-reported physical activity, energy intake, or dietary macronutrient composition either. However, weight-loss modeling in 77 participants with at least two weight measurements indicated that the eTRE group reduced their intake by about 214 kcal/day, compared with controls (P = .04).

Those in the eTRE group also showed greater improvements in measures of mood disturbance, vigor-activity, fatigue-inertia, and depression-dejection. Other mood and sleep endpoints were similar between groups.

In a secondary analysis of just the 59 participants who completed the study, eTRE was also more effective at reducing body fat (P = .047) and trunk fat (P = .03).

About 41% of the eTRE completers planned to continue the practice after the study concluded.

The study was supported by grants from the National Center for Advancing Translational Sciences of the National Institutes of Health and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Jamshed has reported no relevant financial relationships. Dr. Bhasin has reported receiving grants to his institution for research on which Dr. Bhasin is the principal investigator from AbbVie and MIB, receiving personal fees from OPKO and Aditum and holding equity interest in FPT and XYOne. Dr. Steenson has declared funding in support of the British Nutrition Foundation that comes from a range of sources.

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

Time-restricted eating during the earlier part of the day (eTRE) may promote weight loss and reduce blood pressure, new findings suggest.

Previous studies have produced mixed results regarding the weight-loss potential for intermittent fasting, the practice of alternating eating with extended fasting, and the “time-restricted eating” format, where eating is restricted to a specific, often 10-hour, time window during the day.

In a new randomized clinical trial of 90 people with obesity in which that time window was 7 AM through 3 PM, so 8 hours long, researchers report that “eTRE was more effective for losing weight and lowering diastolic blood pressure than was eating over a period of 12 or more hours at 14 weeks. The eTRE intervention may therefore be an effective treatment for both obesity and hypertension.” The study, by Humaira Jamshed, PhD, of the department of nutrition sciences, University of Alabama at Birmingham, and colleagues, was published in JAMA Internal Medicine.

In an accompanying invited commentary, Shalender Bhasin, MBBS, points out that the study findings differ from those of a previous trial published in April of 139 adults conducted in China, which did not find a significant weight loss benefit with TRE versus ad lib eating.

“The scientific premise and the preclinical data of the effects of TRE are promising, but the inconsistency among studies renders it difficult to draw strong inferences from these well-conducted but relatively small trials,” notes Dr. Bhasin, of Harvard Medical School, Boston.
 

Need for larger and longer trials of TRE

Dr. Bhasin says – and the study authors also acknowledge – that much larger randomized clinical trials of longer duration are needed “to comprehensively evaluate the hypothesized benefits and risks of long-term TRE of calorically restricted diets in adults.”

Commenting on the study for the U.K. Science Media Centre, Simon Steenson, PhD, nutrition scientist, British Nutrition Foundation, said “one of the strengths of this new study is the trial design and the number of people who were recruited compared to many of the previous trials to date.”

However, Dr. Steenson also pointed to the prior Chinese research as evidence that the inconsistencies across studies highlight the need for larger and longer trials, with cardiovascular as well as weight-loss endpoints.

Still, Dr. Steenson said, “For individuals who may find that this pattern of eating fits better with their lifestyle and preferences, time-restricted feeding is one option for reducing overall calorie intake that might be a suitable approach for some. Ultimately, it is about finding the best approach to moderate calorie intake that works for each person, as successful and sustained weight loss is about ensuring the diet is feasible to follow in the long-term.”
 

Differences in weight loss, diastolic BP, but not all measures

The study population included 90 adults seen at the Weight Loss Medicine clinic at the University of Alabama at Birmingham between August 2018 and December 2019. Participants had a body mass index of 30-60 kg/m², and none had diabetes. 

They were randomized to eTRE with the 7 AM to PM eating window or a control schedule with eating across 12 hours or more, mimicking U.S. median mealtimes, at least 6 days a week. All participants received 30-minute weight-loss counseling sessions at baseline and at weeks 2, 6, and 10 and were advised to follow a diet of 500 kcal/day below their resting energy expenditure and exercise 75-150 minutes per week.

The eTRE group adhered with their schedule a mean of 6 days per week, lower than the 6.3 days among controls (P = .03), and adherence declined by about 0.4 days per week in the eTRE group over the 14 weeks (P = .001).  

At 14 weeks, both the eTRE group and controls had lost clinically meaningful amounts of weight, at –6.3 kg and –4.0 kg, respectively, but the –2.3 kg difference was significant (P = .002).

However, there was no difference in absolute fat loss (P = .09) or ratio of fat loss to weight loss (P = .43). There were also no significant differences in changes in other body composition parameters, including visceral fat and waist circumference.

Diastolic blood pressure was lowered by an additional 4 mmHg in the eTRE group, compared with controls at 14 weeks (P = .04), but there were no significant differences in systolic blood pressure, heart rate, glucose, A1c levels, insulin levels, measures of insulin resistance, or plasma lipids.

There were no differences between the two groups in self-reported physical activity, energy intake, or dietary macronutrient composition either. However, weight-loss modeling in 77 participants with at least two weight measurements indicated that the eTRE group reduced their intake by about 214 kcal/day, compared with controls (P = .04).

Those in the eTRE group also showed greater improvements in measures of mood disturbance, vigor-activity, fatigue-inertia, and depression-dejection. Other mood and sleep endpoints were similar between groups.

In a secondary analysis of just the 59 participants who completed the study, eTRE was also more effective at reducing body fat (P = .047) and trunk fat (P = .03).

About 41% of the eTRE completers planned to continue the practice after the study concluded.

The study was supported by grants from the National Center for Advancing Translational Sciences of the National Institutes of Health and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Jamshed has reported no relevant financial relationships. Dr. Bhasin has reported receiving grants to his institution for research on which Dr. Bhasin is the principal investigator from AbbVie and MIB, receiving personal fees from OPKO and Aditum and holding equity interest in FPT and XYOne. Dr. Steenson has declared funding in support of the British Nutrition Foundation that comes from a range of sources.

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

Many women with symptoms of menopause are turning to cannabis for help, researchers have found, despite a lack of evidence that the drug works for these issues. 

In a survey of perimenopausal and menopausal women who said they’ve used cannabis, nearly 80% said they use medical marijuana to alleviate symptoms such as sleep disturbances, hot flashes, and mood swings. 

“Increasingly, we see greater numbers of individuals exploiting the use of cannabis and cannabinoids for lots of conditions. We realized there was no long-term data on how women were treating themselves for conditions like menopause,” said Staci Gruber, PhD, director of the Marijuana Investigations for Neuroscientific Discovery (MIND) program at McLean Hospital, an affiliate of Harvard Medical School, Boston, who led the study.

Dr. Gruber and her colleagues surveyed 131 perimenopausal and 127 postmenopausal women about their use of cannabis, identifying them through targeted advertising and social media platforms such as Twitter, Facebook, and Reddit.

The survey, published in Menopause, found 83.5% reported habitual cannabis use and 86% said they were current users. Around half of the women reported mixed medical/recreational use; 30.8% reported recreational use only and 17.7% said they only used medical forms of the drug.

The three most common modes of cannabis use were smoking a joint, bowl, or bong (84.3%); using edibles (78.3%);, and vaping oils (52.6%).

The researchers found that women in perimenopause reported markedly worse symptoms than did those in menopause, and these women tended to use a wider variety of cannabis products.

Dr. Gruber said clinicians should be asking their menopausal patients if they use cannabis to alleviate their symptoms. 

Stephanie Faubion, MD, MBA, a women’s health expert at Mayo Clinic in Rochester, Minn., and Jacksonville, Fla., said the looming question is whether cannabis in fact works in these patients. 

“What we need is to figure out whether it works for women, and that hasn’t been studied yet,” she said. 

Dr. Faubion, medical director for the North American Menopause Society, said the society is now conducting a review of worldwide data on nonhormonal treatments for symptoms of menopause. The report, which will examine the most current research on the effects of cannabis, hypnosis, diet, exercise, acupuncture, yoga, and meditation, will be released in 2023, she said.

Dr. Gruber said she hopes her group’s research will open the doors to more detailed explorations of how strains of cannabis and their levels of cannabidiol, a chemical compound in cannabis plants, and tetrahydrocannabinol, the main psychoactive component in cannabis, affect the symptoms women experience from menopause. Clinical trials for products aimed at specific symptoms also will be important, she added.

“We have a paucity of data from primary care clinicians,” Dr. Gruber said. “We, as researchers and clinicians, should be providing women with the research to make informed choices.”

The study was supported by private donations to the MIND program at McLean Hospital. No funding sources were involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Dr. Gruber reported grants from the National Institute on Drug Abuse, Foria/Praxis Ventures, and Charlotte’s Web. She reported personal fees from the Coalition for Cannabis Policy, Education and Regulation; Beth Israel Deaconess; Fenway Health; Greenwich Biosciences Cannabis Education Working Group; and National Academy of Neuropsychology outside the submitted work. Dr. Faubion reported no relevant financial relationships.

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

Many women with symptoms of menopause are turning to cannabis for help, researchers have found, despite a lack of evidence that the drug works for these issues. 

In a survey of perimenopausal and menopausal women who said they’ve used cannabis, nearly 80% said they use medical marijuana to alleviate symptoms such as sleep disturbances, hot flashes, and mood swings. 

“Increasingly, we see greater numbers of individuals exploiting the use of cannabis and cannabinoids for lots of conditions. We realized there was no long-term data on how women were treating themselves for conditions like menopause,” said Staci Gruber, PhD, director of the Marijuana Investigations for Neuroscientific Discovery (MIND) program at McLean Hospital, an affiliate of Harvard Medical School, Boston, who led the study.

Dr. Gruber and her colleagues surveyed 131 perimenopausal and 127 postmenopausal women about their use of cannabis, identifying them through targeted advertising and social media platforms such as Twitter, Facebook, and Reddit.

The survey, published in Menopause, found 83.5% reported habitual cannabis use and 86% said they were current users. Around half of the women reported mixed medical/recreational use; 30.8% reported recreational use only and 17.7% said they only used medical forms of the drug.

The three most common modes of cannabis use were smoking a joint, bowl, or bong (84.3%); using edibles (78.3%);, and vaping oils (52.6%).

The researchers found that women in perimenopause reported markedly worse symptoms than did those in menopause, and these women tended to use a wider variety of cannabis products.

Dr. Gruber said clinicians should be asking their menopausal patients if they use cannabis to alleviate their symptoms. 

Stephanie Faubion, MD, MBA, a women’s health expert at Mayo Clinic in Rochester, Minn., and Jacksonville, Fla., said the looming question is whether cannabis in fact works in these patients. 

“What we need is to figure out whether it works for women, and that hasn’t been studied yet,” she said. 

Dr. Faubion, medical director for the North American Menopause Society, said the society is now conducting a review of worldwide data on nonhormonal treatments for symptoms of menopause. The report, which will examine the most current research on the effects of cannabis, hypnosis, diet, exercise, acupuncture, yoga, and meditation, will be released in 2023, she said.

Dr. Gruber said she hopes her group’s research will open the doors to more detailed explorations of how strains of cannabis and their levels of cannabidiol, a chemical compound in cannabis plants, and tetrahydrocannabinol, the main psychoactive component in cannabis, affect the symptoms women experience from menopause. Clinical trials for products aimed at specific symptoms also will be important, she added.

“We have a paucity of data from primary care clinicians,” Dr. Gruber said. “We, as researchers and clinicians, should be providing women with the research to make informed choices.”

The study was supported by private donations to the MIND program at McLean Hospital. No funding sources were involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Dr. Gruber reported grants from the National Institute on Drug Abuse, Foria/Praxis Ventures, and Charlotte’s Web. She reported personal fees from the Coalition for Cannabis Policy, Education and Regulation; Beth Israel Deaconess; Fenway Health; Greenwich Biosciences Cannabis Education Working Group; and National Academy of Neuropsychology outside the submitted work. Dr. Faubion reported no relevant financial relationships.

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

Many women with symptoms of menopause are turning to cannabis for help, researchers have found, despite a lack of evidence that the drug works for these issues. 

In a survey of perimenopausal and menopausal women who said they’ve used cannabis, nearly 80% said they use medical marijuana to alleviate symptoms such as sleep disturbances, hot flashes, and mood swings. 

“Increasingly, we see greater numbers of individuals exploiting the use of cannabis and cannabinoids for lots of conditions. We realized there was no long-term data on how women were treating themselves for conditions like menopause,” said Staci Gruber, PhD, director of the Marijuana Investigations for Neuroscientific Discovery (MIND) program at McLean Hospital, an affiliate of Harvard Medical School, Boston, who led the study.

Dr. Gruber and her colleagues surveyed 131 perimenopausal and 127 postmenopausal women about their use of cannabis, identifying them through targeted advertising and social media platforms such as Twitter, Facebook, and Reddit.

The survey, published in Menopause, found 83.5% reported habitual cannabis use and 86% said they were current users. Around half of the women reported mixed medical/recreational use; 30.8% reported recreational use only and 17.7% said they only used medical forms of the drug.

The three most common modes of cannabis use were smoking a joint, bowl, or bong (84.3%); using edibles (78.3%);, and vaping oils (52.6%).

The researchers found that women in perimenopause reported markedly worse symptoms than did those in menopause, and these women tended to use a wider variety of cannabis products.

Dr. Gruber said clinicians should be asking their menopausal patients if they use cannabis to alleviate their symptoms. 

Stephanie Faubion, MD, MBA, a women’s health expert at Mayo Clinic in Rochester, Minn., and Jacksonville, Fla., said the looming question is whether cannabis in fact works in these patients. 

“What we need is to figure out whether it works for women, and that hasn’t been studied yet,” she said. 

Dr. Faubion, medical director for the North American Menopause Society, said the society is now conducting a review of worldwide data on nonhormonal treatments for symptoms of menopause. The report, which will examine the most current research on the effects of cannabis, hypnosis, diet, exercise, acupuncture, yoga, and meditation, will be released in 2023, she said.

Dr. Gruber said she hopes her group’s research will open the doors to more detailed explorations of how strains of cannabis and their levels of cannabidiol, a chemical compound in cannabis plants, and tetrahydrocannabinol, the main psychoactive component in cannabis, affect the symptoms women experience from menopause. Clinical trials for products aimed at specific symptoms also will be important, she added.

“We have a paucity of data from primary care clinicians,” Dr. Gruber said. “We, as researchers and clinicians, should be providing women with the research to make informed choices.”

The study was supported by private donations to the MIND program at McLean Hospital. No funding sources were involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Dr. Gruber reported grants from the National Institute on Drug Abuse, Foria/Praxis Ventures, and Charlotte’s Web. She reported personal fees from the Coalition for Cannabis Policy, Education and Regulation; Beth Israel Deaconess; Fenway Health; Greenwich Biosciences Cannabis Education Working Group; and National Academy of Neuropsychology outside the submitted work. Dr. Faubion reported no relevant financial relationships.

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

Radiation therapy, along with surgery and systemic therapy, is a primary therapeutic modality for cancer management. At least half of cancer patients receive radiation as part of their treatment regimen.¹ Multiple studies demonstrate that radiotherapy is underutilized worldwide.² One reason for underutilization of radiotherapy globally is poor access to this treatment modality. Factors that contribute to poor access include long wait times for consultation, delays in treatment initiation, distance to a treatment facility, and poor coordination of care.

Taskforce Findings

The presence of onsite radiation oncology and its impact on utilization of radiotherapy is poorly studied. The Veterans Health Administration (VHA) Palliative Radiotherapy Taskforce recently conducted a survey to determine the barriers to referral and timeliness of treatment for palliative radiotherapy within the VHA.³ Key findings of this study comparing centers with onsite radiation departments with centers without onsite radiation departments include:

a. Radiation consults are more likely to be completed within 1 week of consult request at centers with onsite radiation therapy (68% vs 31%, respectively; P = .01).

b. Centers with onsite radiation therapy more frequently deliver emergent treatment within 24 hours for patients with spinal cord compression, an emergency condition in which prompt radiation can prevent or minimize long-term neurologic disability (94% vs 70%, respectively; P = .01).

c. Referring practitioners with onsite radiation departments are less likely to report difficulty contacting a radiation oncologist as a barrier to referral for palliative radiotherapy (0% vs 20%, respectively; P = .006).

d. Referring practitioners with onsite radiotherapy report patient travel as a barrier to referral for palliative radiotherapy less frequently (28% vs 71%, respectively; P < .001).

e. Practitioners with onsite radiation oncology departments are more likely to have multidisciplinary tumor boards (31% vs 3%, respectively; P = .01) and are more likely to be influenced by radiation oncology recommendations at tumor boards (69% vs 44%, respectively; P = .02).

Based on the findings of this study, the VHA Palliative Radiotherapy Taskforce has prepared this consensus statement regarding the importance of onsite radiation oncology departments at VHA medical centers. More information regarding our 5 key findings and their implications for patient care are as follows:

Timeliness of Radiation Oncology Consultation

Delays in radiation oncology consultation, which can also delay treatment initiation, are associated with poor satisfaction among both patients and referring clinicians.⁴ Wait times have been identified as a barrier to utilization of radiotherapy by both patients and clinicians.^5,6 Furthermore, delays in initiation of definitive therapy have been associated with worse outcomes, including worse overall survival.^7,8 Our survey study demonstrates that consults for palliative radiotherapy are occurring in a more timely manner at centers with onsite radiation departments. Radiation oncology consults are more frequently completed within 1 week at centers with onsite radiation oncology departments compared with centers without onsite radiation oncology departments (68% vs 31%, P = .01). This trend would likely be seen for nonpalliative, definitive cases as well. The presence of radiation oncology departments onsite at VHA medical centers is an important component of timely care for veterans to optimize outcomes of cancer treatment.

Timely Delivery of Radiotherapy for Oncologic Emergencies

There are a few scenarios in which emergent radiation treatment, within 24 hours, is indicated. These include malignant spinal cord compression, uncal herniation from brain metastasis, superior vena cava syndrome, and tumor hemorrhage.⁹ Studies on management of metastatic spinal cord compression demonstrate that delays in treatment are associated with reduced ambulation¹⁰ as well as loss of sphincter function and incontinence.¹¹

Our study demonstrates that VHA medical centers with onsite radiotherapy more frequently deliver radiotherapy within 24 hours for patients with metastatic spinal cord compression. This timely delivery of treatment is critical to optimizing functional status and quality of life in patients requiring treatment for oncologic emergencies. Revisiting treatment pathways for such situations at regular intervals is crucial given that residents and staff may rotate and be unfamiliar with emergency protocols.

Communication With Radiation Oncologists

Several studies have demonstrated that the inability to contact a radiation oncologist and poor communication result in decreased referrals for palliative radiotherapy.^12,13 Our study demonstrates that onsite radiation oncology is associated with improved ability to contact a radiation oncologist. About 20% of clinicians at facilities without onsite radiation oncology reported difficulty contacting a radiation oncologist, compared with 0% at facilities with onsite radiation departments (P = .006).

It is possible that increased radiation oncology presence at VHA medical centers, through attenuation of barriers related to contacting a radiation oncologist and improved communication, would lead to increased use of radiotherapy. Increased communication between referring clinicians and radiation oncologists also can help with education of those clinicians making the referral. Since knowledge gaps have been identified in multiple studies as a barrier to referral for radiotherapy, such communication and increased education on the role of radiotherapy could increase use.^12-14

Patient Travel

Patient ability to travel was the most commonly reported barrier (81%) to referral for palliative radiotherapy in our study. Travel time and transportation difficulties have been established in multiple studies as barriers to radiotherapy for both definitive and palliative management.^15-18 Travel for radiotherapy was much less frequently reported as a barrier among respondents with onsite radiation oncology departments compared with those without onsite radiation departments (28% vs 71%, respectively; P < .001).

It is therefore possible that expansion of VHA radiation oncology services, allowing for provision of onsite radiotherapy at more VHA facilities, would reduce travel burden. Increasing travel accommodations for patients and provision of patient lodging on hospital campuses, which is already offered at some VHA medical centers (ie, Fisher House Foundation), could also help attenuate this barrier.

Multidisciplinary Tumor Boards

Our study demonstrates that centers with onsite radiation departments more frequently hold multidisciplinary tumor boards compared with centers without radiation departments (31% vs 3%, respectively; P = .01). Multidisciplinary tumor boards allow subspecialties to meet regularly to communicate about patient care and can help mitigate barriers related to communication and education of the referring health care practitioners.

As cases are discussed in multidisciplinary tumor boards, health care practitioners have the opportunity to make recommendations and provide education on potential benefits and/or downsides of treatments offered by their respective specialties. Several studies have demonstrated that cases discussed at multidisciplinary tumor boards are more likely to be referred for radiation therapy.^19-21 Furthermore, multidisciplinary tumor boards have been associated with improved treatment outcomes.²²

Conclusions

In this consensus statement the VHA Palliative Radiotherapy Taskforce recommends the optimization of use of radiotherapy within the VHA. Radiation oncology services should be maintained where present in the VHA, with consideration for expansion of services to additional facilities. Telehealth should be used to expedite consults and treatment. Hypofractionation should be used, when appropriate, to ease travel burden. Options for transportation services and onsite housing, or hospitalization, should be understood by practitioners and offered to patients to mitigate barriers related to travel.

Radiation therapy, along with surgery and systemic therapy, is a primary therapeutic modality for cancer management. At least half of cancer patients receive radiation as part of their treatment regimen.¹ Multiple studies demonstrate that radiotherapy is underutilized worldwide.² One reason for underutilization of radiotherapy globally is poor access to this treatment modality. Factors that contribute to poor access include long wait times for consultation, delays in treatment initiation, distance to a treatment facility, and poor coordination of care.

Taskforce Findings

The presence of onsite radiation oncology and its impact on utilization of radiotherapy is poorly studied. The Veterans Health Administration (VHA) Palliative Radiotherapy Taskforce recently conducted a survey to determine the barriers to referral and timeliness of treatment for palliative radiotherapy within the VHA.³ Key findings of this study comparing centers with onsite radiation departments with centers without onsite radiation departments include:

a. Radiation consults are more likely to be completed within 1 week of consult request at centers with onsite radiation therapy (68% vs 31%, respectively; P = .01).

b. Centers with onsite radiation therapy more frequently deliver emergent treatment within 24 hours for patients with spinal cord compression, an emergency condition in which prompt radiation can prevent or minimize long-term neurologic disability (94% vs 70%, respectively; P = .01).

c. Referring practitioners with onsite radiation departments are less likely to report difficulty contacting a radiation oncologist as a barrier to referral for palliative radiotherapy (0% vs 20%, respectively; P = .006).

d. Referring practitioners with onsite radiotherapy report patient travel as a barrier to referral for palliative radiotherapy less frequently (28% vs 71%, respectively; P < .001).

e. Practitioners with onsite radiation oncology departments are more likely to have multidisciplinary tumor boards (31% vs 3%, respectively; P = .01) and are more likely to be influenced by radiation oncology recommendations at tumor boards (69% vs 44%, respectively; P = .02).

Based on the findings of this study, the VHA Palliative Radiotherapy Taskforce has prepared this consensus statement regarding the importance of onsite radiation oncology departments at VHA medical centers. More information regarding our 5 key findings and their implications for patient care are as follows:

Timeliness of Radiation Oncology Consultation

Delays in radiation oncology consultation, which can also delay treatment initiation, are associated with poor satisfaction among both patients and referring clinicians.⁴ Wait times have been identified as a barrier to utilization of radiotherapy by both patients and clinicians.^5,6 Furthermore, delays in initiation of definitive therapy have been associated with worse outcomes, including worse overall survival.^7,8 Our survey study demonstrates that consults for palliative radiotherapy are occurring in a more timely manner at centers with onsite radiation departments. Radiation oncology consults are more frequently completed within 1 week at centers with onsite radiation oncology departments compared with centers without onsite radiation oncology departments (68% vs 31%, P = .01). This trend would likely be seen for nonpalliative, definitive cases as well. The presence of radiation oncology departments onsite at VHA medical centers is an important component of timely care for veterans to optimize outcomes of cancer treatment.

Timely Delivery of Radiotherapy for Oncologic Emergencies

There are a few scenarios in which emergent radiation treatment, within 24 hours, is indicated. These include malignant spinal cord compression, uncal herniation from brain metastasis, superior vena cava syndrome, and tumor hemorrhage.⁹ Studies on management of metastatic spinal cord compression demonstrate that delays in treatment are associated with reduced ambulation¹⁰ as well as loss of sphincter function and incontinence.¹¹

Our study demonstrates that VHA medical centers with onsite radiotherapy more frequently deliver radiotherapy within 24 hours for patients with metastatic spinal cord compression. This timely delivery of treatment is critical to optimizing functional status and quality of life in patients requiring treatment for oncologic emergencies. Revisiting treatment pathways for such situations at regular intervals is crucial given that residents and staff may rotate and be unfamiliar with emergency protocols.

Communication With Radiation Oncologists

Several studies have demonstrated that the inability to contact a radiation oncologist and poor communication result in decreased referrals for palliative radiotherapy.^12,13 Our study demonstrates that onsite radiation oncology is associated with improved ability to contact a radiation oncologist. About 20% of clinicians at facilities without onsite radiation oncology reported difficulty contacting a radiation oncologist, compared with 0% at facilities with onsite radiation departments (P = .006).

It is possible that increased radiation oncology presence at VHA medical centers, through attenuation of barriers related to contacting a radiation oncologist and improved communication, would lead to increased use of radiotherapy. Increased communication between referring clinicians and radiation oncologists also can help with education of those clinicians making the referral. Since knowledge gaps have been identified in multiple studies as a barrier to referral for radiotherapy, such communication and increased education on the role of radiotherapy could increase use.^12-14

Patient Travel

Patient ability to travel was the most commonly reported barrier (81%) to referral for palliative radiotherapy in our study. Travel time and transportation difficulties have been established in multiple studies as barriers to radiotherapy for both definitive and palliative management.^15-18 Travel for radiotherapy was much less frequently reported as a barrier among respondents with onsite radiation oncology departments compared with those without onsite radiation departments (28% vs 71%, respectively; P < .001).

It is therefore possible that expansion of VHA radiation oncology services, allowing for provision of onsite radiotherapy at more VHA facilities, would reduce travel burden. Increasing travel accommodations for patients and provision of patient lodging on hospital campuses, which is already offered at some VHA medical centers (ie, Fisher House Foundation), could also help attenuate this barrier.

Multidisciplinary Tumor Boards

Our study demonstrates that centers with onsite radiation departments more frequently hold multidisciplinary tumor boards compared with centers without radiation departments (31% vs 3%, respectively; P = .01). Multidisciplinary tumor boards allow subspecialties to meet regularly to communicate about patient care and can help mitigate barriers related to communication and education of the referring health care practitioners.

As cases are discussed in multidisciplinary tumor boards, health care practitioners have the opportunity to make recommendations and provide education on potential benefits and/or downsides of treatments offered by their respective specialties. Several studies have demonstrated that cases discussed at multidisciplinary tumor boards are more likely to be referred for radiation therapy.^19-21 Furthermore, multidisciplinary tumor boards have been associated with improved treatment outcomes.²²

Conclusions

In this consensus statement the VHA Palliative Radiotherapy Taskforce recommends the optimization of use of radiotherapy within the VHA. Radiation oncology services should be maintained where present in the VHA, with consideration for expansion of services to additional facilities. Telehealth should be used to expedite consults and treatment. Hypofractionation should be used, when appropriate, to ease travel burden. Options for transportation services and onsite housing, or hospitalization, should be understood by practitioners and offered to patients to mitigate barriers related to travel.

Radiation therapy, along with surgery and systemic therapy, is a primary therapeutic modality for cancer management. At least half of cancer patients receive radiation as part of their treatment regimen.¹ Multiple studies demonstrate that radiotherapy is underutilized worldwide.² One reason for underutilization of radiotherapy globally is poor access to this treatment modality. Factors that contribute to poor access include long wait times for consultation, delays in treatment initiation, distance to a treatment facility, and poor coordination of care.

Taskforce Findings

The presence of onsite radiation oncology and its impact on utilization of radiotherapy is poorly studied. The Veterans Health Administration (VHA) Palliative Radiotherapy Taskforce recently conducted a survey to determine the barriers to referral and timeliness of treatment for palliative radiotherapy within the VHA.³ Key findings of this study comparing centers with onsite radiation departments with centers without onsite radiation departments include:

a. Radiation consults are more likely to be completed within 1 week of consult request at centers with onsite radiation therapy (68% vs 31%, respectively; P = .01).

b. Centers with onsite radiation therapy more frequently deliver emergent treatment within 24 hours for patients with spinal cord compression, an emergency condition in which prompt radiation can prevent or minimize long-term neurologic disability (94% vs 70%, respectively; P = .01).

c. Referring practitioners with onsite radiation departments are less likely to report difficulty contacting a radiation oncologist as a barrier to referral for palliative radiotherapy (0% vs 20%, respectively; P = .006).

d. Referring practitioners with onsite radiotherapy report patient travel as a barrier to referral for palliative radiotherapy less frequently (28% vs 71%, respectively; P < .001).

e. Practitioners with onsite radiation oncology departments are more likely to have multidisciplinary tumor boards (31% vs 3%, respectively; P = .01) and are more likely to be influenced by radiation oncology recommendations at tumor boards (69% vs 44%, respectively; P = .02).

Based on the findings of this study, the VHA Palliative Radiotherapy Taskforce has prepared this consensus statement regarding the importance of onsite radiation oncology departments at VHA medical centers. More information regarding our 5 key findings and their implications for patient care are as follows:

Timeliness of Radiation Oncology Consultation

Delays in radiation oncology consultation, which can also delay treatment initiation, are associated with poor satisfaction among both patients and referring clinicians.⁴ Wait times have been identified as a barrier to utilization of radiotherapy by both patients and clinicians.^5,6 Furthermore, delays in initiation of definitive therapy have been associated with worse outcomes, including worse overall survival.^7,8 Our survey study demonstrates that consults for palliative radiotherapy are occurring in a more timely manner at centers with onsite radiation departments. Radiation oncology consults are more frequently completed within 1 week at centers with onsite radiation oncology departments compared with centers without onsite radiation oncology departments (68% vs 31%, P = .01). This trend would likely be seen for nonpalliative, definitive cases as well. The presence of radiation oncology departments onsite at VHA medical centers is an important component of timely care for veterans to optimize outcomes of cancer treatment.

Timely Delivery of Radiotherapy for Oncologic Emergencies

There are a few scenarios in which emergent radiation treatment, within 24 hours, is indicated. These include malignant spinal cord compression, uncal herniation from brain metastasis, superior vena cava syndrome, and tumor hemorrhage.⁹ Studies on management of metastatic spinal cord compression demonstrate that delays in treatment are associated with reduced ambulation¹⁰ as well as loss of sphincter function and incontinence.¹¹

Our study demonstrates that VHA medical centers with onsite radiotherapy more frequently deliver radiotherapy within 24 hours for patients with metastatic spinal cord compression. This timely delivery of treatment is critical to optimizing functional status and quality of life in patients requiring treatment for oncologic emergencies. Revisiting treatment pathways for such situations at regular intervals is crucial given that residents and staff may rotate and be unfamiliar with emergency protocols.

Communication With Radiation Oncologists

Several studies have demonstrated that the inability to contact a radiation oncologist and poor communication result in decreased referrals for palliative radiotherapy.^12,13 Our study demonstrates that onsite radiation oncology is associated with improved ability to contact a radiation oncologist. About 20% of clinicians at facilities without onsite radiation oncology reported difficulty contacting a radiation oncologist, compared with 0% at facilities with onsite radiation departments (P = .006).

It is possible that increased radiation oncology presence at VHA medical centers, through attenuation of barriers related to contacting a radiation oncologist and improved communication, would lead to increased use of radiotherapy. Increased communication between referring clinicians and radiation oncologists also can help with education of those clinicians making the referral. Since knowledge gaps have been identified in multiple studies as a barrier to referral for radiotherapy, such communication and increased education on the role of radiotherapy could increase use.^12-14

Patient Travel

Patient ability to travel was the most commonly reported barrier (81%) to referral for palliative radiotherapy in our study. Travel time and transportation difficulties have been established in multiple studies as barriers to radiotherapy for both definitive and palliative management.^15-18 Travel for radiotherapy was much less frequently reported as a barrier among respondents with onsite radiation oncology departments compared with those without onsite radiation departments (28% vs 71%, respectively; P < .001).

It is therefore possible that expansion of VHA radiation oncology services, allowing for provision of onsite radiotherapy at more VHA facilities, would reduce travel burden. Increasing travel accommodations for patients and provision of patient lodging on hospital campuses, which is already offered at some VHA medical centers (ie, Fisher House Foundation), could also help attenuate this barrier.

Multidisciplinary Tumor Boards

Our study demonstrates that centers with onsite radiation departments more frequently hold multidisciplinary tumor boards compared with centers without radiation departments (31% vs 3%, respectively; P = .01). Multidisciplinary tumor boards allow subspecialties to meet regularly to communicate about patient care and can help mitigate barriers related to communication and education of the referring health care practitioners.

As cases are discussed in multidisciplinary tumor boards, health care practitioners have the opportunity to make recommendations and provide education on potential benefits and/or downsides of treatments offered by their respective specialties. Several studies have demonstrated that cases discussed at multidisciplinary tumor boards are more likely to be referred for radiation therapy.^19-21 Furthermore, multidisciplinary tumor boards have been associated with improved treatment outcomes.²²

Conclusions

In this consensus statement the VHA Palliative Radiotherapy Taskforce recommends the optimization of use of radiotherapy within the VHA. Radiation oncology services should be maintained where present in the VHA, with consideration for expansion of services to additional facilities. Telehealth should be used to expedite consults and treatment. Hypofractionation should be used, when appropriate, to ease travel burden. Options for transportation services and onsite housing, or hospitalization, should be understood by practitioners and offered to patients to mitigate barriers related to travel.

Multiple myeloma (MM) accounts for 1% to 2% of all cancers and slightly more than 17% of hematologic malignancies in the United States.¹ MM is characterized by the neoplastic proliferation of immunoglobulin (Ig)-producing plasma cells with ≥ 10% clonal plasma cells in the bone marrow or biopsy-proven bony or soft tissue plasmacytoma, plus presence of related organ or tissue impairment or presence of a biomarker associated with near-inevitable progression to end-organ damage.²

Background

Up to 97% of patients with MM will have a monoclonal (M) protein produced and secreted by the malignant plasma cells, which can be detected by protein electrophoresis of the serum and an aliquot of urine from a 24-hour collection combined with immunofixation of the serum and urine. The M protein in MM usually consists of IgG 50% of the time and light chains 16% of the time. Patients who lack detectable M protein are considered to have nonsecretory myeloma. MM presents with end-organ damage, which includes hypercalcemia, renal dysfunction, anemia, or lytic bone lesions. Patients with MM frequently present with renal insufficiency due to cast nephropathy or light chain deposition disease.³

MM is thought to evolve from monoclonal gammopathy of uncertain significance (MGUS), an asymptomatic premalignant stage of clonal plasma cell proliferation with a risk of progression to active myeloma at 1% per year.^4,5 Epidemiologic data suggest that people who develop MM have a genetic predisposition, but risk factors may develop or be acquired, such as age, immunosuppression, and environmental exposures. To better assess what causes transformation from MGUS to MM, it is important to identify agents that may cause this second hit.⁶

In November 1961, President John F. Kennedy authorized the start of Operation Ranch Hand, the US Air Force’s herbicide program during the Vietnam War. Twenty million gallons of various chemicals were sprayed in Vietnam, eastern Laos, and parts of Cambodia to defoliate rural land, depriving guerillas of their support base. Agent Orange (AO) was one of these chemicals; it is a mixed herbicide with traces of dioxin, a compound that has been associated with major health problems among exposed individuals.⁷ Several studies have evaluated exposure to AO and its potential harmful repercussions. Studies have assessed the link between AO and MGUS as well as AO to various leukemias, such as chronic lymphocytic leukemia.^8,9 Other studies have shown the relationship between AO exposure and worse outcomes in persons with MM.¹⁰ To date, only a single abstract from a US Department of Veterans Affairs (VA) medical center has investigated the relationships between AO exposure and MGUS, MM, and the rate of transformation. The VA study of patients seen from 2005 to 2015 in Detroit, Michigan, found that AO exposure led to an increase in cumulative incidence rate of MGUS/MM, suggesting possible changes in disease biology and genetics.¹¹

In this study, we aimed to determine the incidence of transformation of MGUS to MM in patients with and without exposure to AO. We then analyzed survival as a function of AO exposure, transformation, and clinical and sociodemographic variables. We also explored the impact of psychosocial variables and hematopoietic stem cell transplantation (HSCT), a standard of treatment for MM.

Methods

This retrospective cohort study assembled electronic health record (EHR) data from the Veterans Health Administration Corporate Data Warehouse (CDW). The VA Central Texas Veterans Healthcare System Institutional Review Board granted a waiver of consent for this record review. Eligible patients were Vietnam-era veterans who were in the military during the time that AO was used (1961-1971). Veterans were included if they were being cared for and received a diagnosis for MGUS or MM between October 1, 2009, and September 30, 2015 (all prevalent cases fiscal years 2010-2015). Cases were excluded if there was illogical death data or if age, race, ethnicity, body mass index (BMI), or prior-year diagnostic data were missing.

Measures

Patients were followed through April 2020. Presence of MGUS was defined by the International Classification of Diseases, Ninth Revision (ICD-9) diagnosis code 273.1. MM was identified by ICD-9 diagnosis codes 203.00, 203.01, and 203.02. The study index date was the earliest date of diagnosis of MGUS or MM in fiscal years 2010-2015. It was suspected that some patients with MM may have had a history of MGUS prior to this period. Therefore, for patients with MM, historical diagnosis of MGUS was extracted going back through the earliest data in the CDW (October 1999). Patients diagnosed with both MGUS and MM were considered transformation patients.

Other measures included age at index date, sex, race, ethnicity, VA priority status (a value 1 to 8 summarizing why the veteran qualified for VA care, such as military service-connected disability or very low income), and AO exposure authenticated per VA enrollment files and disability records. Service years were separated into 1961 to 1968 and 1969 to 1971 to match a change in the formulation of AO associated with decreased carcinogenic effect. Comorbidity data from the year prior to first MGUS/MM diagnosis in the observation period were extracted. Lifestyle factors associated with development of MGUS/MM were determined using the following codes: obesity per BMI calculation or diagnosis (ICD-9, 278.0), tobacco use per diagnosis (ICD-9, 305.1, V15.82), and survival from MGUS/MM diagnosis index date to date of death from any cause. Comorbidity was assessed using ICD-9 diagnosis codes to calculate the Charlson Comorbidity Index (CCI), which includes cardiovascular diseases, diabetes mellitus, liver and kidney diseases, cancers, and metastatic solid tumors. Cancers were omitted from our adapted CCI to avoid collinearity in the multivariable models. The theoretical maximum CCI score in this study was 25.^12,13 Additional conditions known to be associated with variation in outcomes among veterans using the VA were indicated, including major depressive disorder, posttraumatic stress disorder (PTSD), alcohol use disorder (AUD), substance use disorder (SUD), and common chronic disease (hypertension, lipid disorders).¹⁴

Statistical Analysis

Sample characteristics were represented by frequencies and percentages for categorical variables and means and SDs (or medians and ranges where appropriate) for continuous variables. A χ² test (or Fisher exact test when cell counts were low) assessed associations in bivariate comparisons. A 2-sample t test (or Wilcoxon rank sum test as appropriate) assessed differences in continuous variables between 2 groups. Kaplan-Meier curves depicted the unadjusted relationship of AO exposure to survival. Cox proportional hazards survival models examined an unadjusted model containing only the AO exposure indicator as a predictor and adjusted models were used for demographic and clinical factors for MGUS and patients with MM separately.

Predictors were age in decades, sex, Hispanic ethnicity, race, nicotine dependence, obesity, overweight, AUD, SUD, major depressive disorder, PTSD, and the adapted CCI. When modeling patients with MM, MGUS was added to the model to identify the transformation group. The interaction of AO with transformation was also analyzed for patients with MM. Results were reported as hazard ratios (HR) with their 95% CI.

Results

We identified 18,215 veterans diagnosed with either MGUS or MM during fiscal years 2010-2015 with 16,366 meeting inclusion criteria. Patients were excluded for missing data on exposure (n = 334), age (n = 12), race (n = 1058), ethnicity (n = 164), diagnosis (n = 47), treatment (n = 56), and BMI (n = 178). All were Vietnam War era veterans; 14 also served in other eras.

The cohort was 98.5% male (Table 1). Twenty-nine percent were Black veterans, 65% were White veterans, and 4% of individuals reported Hispanic ethnicity. Patients had a mean (SD) age of 66.7 (5.9) years (range, 52-96). Most patients were married (58%) or divorced/separated (27%). All were VA priority 1 to 5 (no 6, 7, or 8); 50% were priority 1 with 50% to 100% service-connected disability. Another 29% were eligible for VA care by reason of low income, 17% had 10% to 40% service-connected disability, and 4% were otherwise disabled.

Disscussion

Elucidating the pathophysiology and risk of transformation from MGUS to MM is an ongoing endeavor, even 35 years after the end of US involvement in the Vietnam War. Our study sought to understand a relationship between AO exposure, risk of MGUS transforming to MM, and associated mortality in US Vietnam War veterans. The rate of transformation (MGUS progressing to active MM) is well cited at 1% per year.¹⁵ Here, we found 12% of our cohort had undergone this transformation over 10 years.

Vietnam War era veterans who were exposed to AO during the Operation Ranch Hand period had 2.4 times greater risk of developing MGUS compared with veterans not exposed to AO.⁸ Our study was not designed to look at this association of AO exposure and MGUS/MM as this was a retrospective review to assess the difference in outcomes based on AO exposure. We found that AO exposure is associated with a decrease in mortality in contrast to a prior study showing worse survival with individuals with AO exposure.¹⁰ Another single center study found no association between AO exposure and overall survival, but it did identify an increased risk of progression from MGUS to MM.¹¹ Our study did not show increased risk of transformation but did show positive effect on survival.

Black individuals have twice the risk of developing MM compared with White individuals and are diagnosed at a younger age (66 vs 70 years, respectively).¹⁶ Interestingly, Black race was a protective factor in our study. Given the length of time (35 years) elapsed since the Vietnam War ended, it is likely that most vulnerable Black veterans did not survive until our observation period.

HSCT, as expected, was a protective factor for veterans undergoing this treatment modality, but it is unclear why such a small number (8%) underwent HSCT as this is a standard of care in the management of MM. Obesity was also found to be a protective factor in a prior study, which was also seen in our study cohort.⁸

Limitations

This study was limited by its retrospective review of survivors among the Vietnam-era cohort several decades after the exposure of concern. Clinician notes and full historical data, such as date of onset for any disorder, were unavailable. These data also relied on the practitioners caring for the veterans to make the correct diagnosis with the associated code so that the data could be captured. Neither AO exposure nor diagnoses codes were verified against other sources of data; however, validation studies over the years have supported the accuracy of the diagnosis codes recorded in the VA EHR.

Conclusions

Because AO exposure is a nonmodifiable risk factor, focus should be placed on modifiable risk factors (eg, nicotine dependence, alcohol and substance use disorders, underlying comorbid conditions) as these were associated with worse outcomes. Future studies will look at the correlation of AO exposure, cytogenetics, and clinical outcomes in these veterans to learn how best to identify their disease course and optimize their care in the latter part of their life.

Acknowledgments

This research was supported by the Central Texas Veterans Health Care System and Baylor Scott and White Health, both in Temple and Veterans Affairs Central Western Massachusetts Healthcare System, Leeds.

Multiple myeloma (MM) accounts for 1% to 2% of all cancers and slightly more than 17% of hematologic malignancies in the United States.¹ MM is characterized by the neoplastic proliferation of immunoglobulin (Ig)-producing plasma cells with ≥ 10% clonal plasma cells in the bone marrow or biopsy-proven bony or soft tissue plasmacytoma, plus presence of related organ or tissue impairment or presence of a biomarker associated with near-inevitable progression to end-organ damage.²

Background

Up to 97% of patients with MM will have a monoclonal (M) protein produced and secreted by the malignant plasma cells, which can be detected by protein electrophoresis of the serum and an aliquot of urine from a 24-hour collection combined with immunofixation of the serum and urine. The M protein in MM usually consists of IgG 50% of the time and light chains 16% of the time. Patients who lack detectable M protein are considered to have nonsecretory myeloma. MM presents with end-organ damage, which includes hypercalcemia, renal dysfunction, anemia, or lytic bone lesions. Patients with MM frequently present with renal insufficiency due to cast nephropathy or light chain deposition disease.³

MM is thought to evolve from monoclonal gammopathy of uncertain significance (MGUS), an asymptomatic premalignant stage of clonal plasma cell proliferation with a risk of progression to active myeloma at 1% per year.^4,5 Epidemiologic data suggest that people who develop MM have a genetic predisposition, but risk factors may develop or be acquired, such as age, immunosuppression, and environmental exposures. To better assess what causes transformation from MGUS to MM, it is important to identify agents that may cause this second hit.⁶

In November 1961, President John F. Kennedy authorized the start of Operation Ranch Hand, the US Air Force’s herbicide program during the Vietnam War. Twenty million gallons of various chemicals were sprayed in Vietnam, eastern Laos, and parts of Cambodia to defoliate rural land, depriving guerillas of their support base. Agent Orange (AO) was one of these chemicals; it is a mixed herbicide with traces of dioxin, a compound that has been associated with major health problems among exposed individuals.⁷ Several studies have evaluated exposure to AO and its potential harmful repercussions. Studies have assessed the link between AO and MGUS as well as AO to various leukemias, such as chronic lymphocytic leukemia.^8,9 Other studies have shown the relationship between AO exposure and worse outcomes in persons with MM.¹⁰ To date, only a single abstract from a US Department of Veterans Affairs (VA) medical center has investigated the relationships between AO exposure and MGUS, MM, and the rate of transformation. The VA study of patients seen from 2005 to 2015 in Detroit, Michigan, found that AO exposure led to an increase in cumulative incidence rate of MGUS/MM, suggesting possible changes in disease biology and genetics.¹¹

In this study, we aimed to determine the incidence of transformation of MGUS to MM in patients with and without exposure to AO. We then analyzed survival as a function of AO exposure, transformation, and clinical and sociodemographic variables. We also explored the impact of psychosocial variables and hematopoietic stem cell transplantation (HSCT), a standard of treatment for MM.

Methods

This retrospective cohort study assembled electronic health record (EHR) data from the Veterans Health Administration Corporate Data Warehouse (CDW). The VA Central Texas Veterans Healthcare System Institutional Review Board granted a waiver of consent for this record review. Eligible patients were Vietnam-era veterans who were in the military during the time that AO was used (1961-1971). Veterans were included if they were being cared for and received a diagnosis for MGUS or MM between October 1, 2009, and September 30, 2015 (all prevalent cases fiscal years 2010-2015). Cases were excluded if there was illogical death data or if age, race, ethnicity, body mass index (BMI), or prior-year diagnostic data were missing.

Measures

Patients were followed through April 2020. Presence of MGUS was defined by the International Classification of Diseases, Ninth Revision (ICD-9) diagnosis code 273.1. MM was identified by ICD-9 diagnosis codes 203.00, 203.01, and 203.02. The study index date was the earliest date of diagnosis of MGUS or MM in fiscal years 2010-2015. It was suspected that some patients with MM may have had a history of MGUS prior to this period. Therefore, for patients with MM, historical diagnosis of MGUS was extracted going back through the earliest data in the CDW (October 1999). Patients diagnosed with both MGUS and MM were considered transformation patients.

Other measures included age at index date, sex, race, ethnicity, VA priority status (a value 1 to 8 summarizing why the veteran qualified for VA care, such as military service-connected disability or very low income), and AO exposure authenticated per VA enrollment files and disability records. Service years were separated into 1961 to 1968 and 1969 to 1971 to match a change in the formulation of AO associated with decreased carcinogenic effect. Comorbidity data from the year prior to first MGUS/MM diagnosis in the observation period were extracted. Lifestyle factors associated with development of MGUS/MM were determined using the following codes: obesity per BMI calculation or diagnosis (ICD-9, 278.0), tobacco use per diagnosis (ICD-9, 305.1, V15.82), and survival from MGUS/MM diagnosis index date to date of death from any cause. Comorbidity was assessed using ICD-9 diagnosis codes to calculate the Charlson Comorbidity Index (CCI), which includes cardiovascular diseases, diabetes mellitus, liver and kidney diseases, cancers, and metastatic solid tumors. Cancers were omitted from our adapted CCI to avoid collinearity in the multivariable models. The theoretical maximum CCI score in this study was 25.^12,13 Additional conditions known to be associated with variation in outcomes among veterans using the VA were indicated, including major depressive disorder, posttraumatic stress disorder (PTSD), alcohol use disorder (AUD), substance use disorder (SUD), and common chronic disease (hypertension, lipid disorders).¹⁴

Statistical Analysis

Sample characteristics were represented by frequencies and percentages for categorical variables and means and SDs (or medians and ranges where appropriate) for continuous variables. A χ² test (or Fisher exact test when cell counts were low) assessed associations in bivariate comparisons. A 2-sample t test (or Wilcoxon rank sum test as appropriate) assessed differences in continuous variables between 2 groups. Kaplan-Meier curves depicted the unadjusted relationship of AO exposure to survival. Cox proportional hazards survival models examined an unadjusted model containing only the AO exposure indicator as a predictor and adjusted models were used for demographic and clinical factors for MGUS and patients with MM separately.

Predictors were age in decades, sex, Hispanic ethnicity, race, nicotine dependence, obesity, overweight, AUD, SUD, major depressive disorder, PTSD, and the adapted CCI. When modeling patients with MM, MGUS was added to the model to identify the transformation group. The interaction of AO with transformation was also analyzed for patients with MM. Results were reported as hazard ratios (HR) with their 95% CI.

Results

We identified 18,215 veterans diagnosed with either MGUS or MM during fiscal years 2010-2015 with 16,366 meeting inclusion criteria. Patients were excluded for missing data on exposure (n = 334), age (n = 12), race (n = 1058), ethnicity (n = 164), diagnosis (n = 47), treatment (n = 56), and BMI (n = 178). All were Vietnam War era veterans; 14 also served in other eras.

The cohort was 98.5% male (Table 1). Twenty-nine percent were Black veterans, 65% were White veterans, and 4% of individuals reported Hispanic ethnicity. Patients had a mean (SD) age of 66.7 (5.9) years (range, 52-96). Most patients were married (58%) or divorced/separated (27%). All were VA priority 1 to 5 (no 6, 7, or 8); 50% were priority 1 with 50% to 100% service-connected disability. Another 29% were eligible for VA care by reason of low income, 17% had 10% to 40% service-connected disability, and 4% were otherwise disabled.

Disscussion

Elucidating the pathophysiology and risk of transformation from MGUS to MM is an ongoing endeavor, even 35 years after the end of US involvement in the Vietnam War. Our study sought to understand a relationship between AO exposure, risk of MGUS transforming to MM, and associated mortality in US Vietnam War veterans. The rate of transformation (MGUS progressing to active MM) is well cited at 1% per year.¹⁵ Here, we found 12% of our cohort had undergone this transformation over 10 years.

Vietnam War era veterans who were exposed to AO during the Operation Ranch Hand period had 2.4 times greater risk of developing MGUS compared with veterans not exposed to AO.⁸ Our study was not designed to look at this association of AO exposure and MGUS/MM as this was a retrospective review to assess the difference in outcomes based on AO exposure. We found that AO exposure is associated with a decrease in mortality in contrast to a prior study showing worse survival with individuals with AO exposure.¹⁰ Another single center study found no association between AO exposure and overall survival, but it did identify an increased risk of progression from MGUS to MM.¹¹ Our study did not show increased risk of transformation but did show positive effect on survival.

Black individuals have twice the risk of developing MM compared with White individuals and are diagnosed at a younger age (66 vs 70 years, respectively).¹⁶ Interestingly, Black race was a protective factor in our study. Given the length of time (35 years) elapsed since the Vietnam War ended, it is likely that most vulnerable Black veterans did not survive until our observation period.

HSCT, as expected, was a protective factor for veterans undergoing this treatment modality, but it is unclear why such a small number (8%) underwent HSCT as this is a standard of care in the management of MM. Obesity was also found to be a protective factor in a prior study, which was also seen in our study cohort.⁸

Limitations

This study was limited by its retrospective review of survivors among the Vietnam-era cohort several decades after the exposure of concern. Clinician notes and full historical data, such as date of onset for any disorder, were unavailable. These data also relied on the practitioners caring for the veterans to make the correct diagnosis with the associated code so that the data could be captured. Neither AO exposure nor diagnoses codes were verified against other sources of data; however, validation studies over the years have supported the accuracy of the diagnosis codes recorded in the VA EHR.

Conclusions

Because AO exposure is a nonmodifiable risk factor, focus should be placed on modifiable risk factors (eg, nicotine dependence, alcohol and substance use disorders, underlying comorbid conditions) as these were associated with worse outcomes. Future studies will look at the correlation of AO exposure, cytogenetics, and clinical outcomes in these veterans to learn how best to identify their disease course and optimize their care in the latter part of their life.

Acknowledgments

This research was supported by the Central Texas Veterans Health Care System and Baylor Scott and White Health, both in Temple and Veterans Affairs Central Western Massachusetts Healthcare System, Leeds.

Multiple myeloma (MM) accounts for 1% to 2% of all cancers and slightly more than 17% of hematologic malignancies in the United States.¹ MM is characterized by the neoplastic proliferation of immunoglobulin (Ig)-producing plasma cells with ≥ 10% clonal plasma cells in the bone marrow or biopsy-proven bony or soft tissue plasmacytoma, plus presence of related organ or tissue impairment or presence of a biomarker associated with near-inevitable progression to end-organ damage.²

Background

Up to 97% of patients with MM will have a monoclonal (M) protein produced and secreted by the malignant plasma cells, which can be detected by protein electrophoresis of the serum and an aliquot of urine from a 24-hour collection combined with immunofixation of the serum and urine. The M protein in MM usually consists of IgG 50% of the time and light chains 16% of the time. Patients who lack detectable M protein are considered to have nonsecretory myeloma. MM presents with end-organ damage, which includes hypercalcemia, renal dysfunction, anemia, or lytic bone lesions. Patients with MM frequently present with renal insufficiency due to cast nephropathy or light chain deposition disease.³

MM is thought to evolve from monoclonal gammopathy of uncertain significance (MGUS), an asymptomatic premalignant stage of clonal plasma cell proliferation with a risk of progression to active myeloma at 1% per year.^4,5 Epidemiologic data suggest that people who develop MM have a genetic predisposition, but risk factors may develop or be acquired, such as age, immunosuppression, and environmental exposures. To better assess what causes transformation from MGUS to MM, it is important to identify agents that may cause this second hit.⁶

In November 1961, President John F. Kennedy authorized the start of Operation Ranch Hand, the US Air Force’s herbicide program during the Vietnam War. Twenty million gallons of various chemicals were sprayed in Vietnam, eastern Laos, and parts of Cambodia to defoliate rural land, depriving guerillas of their support base. Agent Orange (AO) was one of these chemicals; it is a mixed herbicide with traces of dioxin, a compound that has been associated with major health problems among exposed individuals.⁷ Several studies have evaluated exposure to AO and its potential harmful repercussions. Studies have assessed the link between AO and MGUS as well as AO to various leukemias, such as chronic lymphocytic leukemia.^8,9 Other studies have shown the relationship between AO exposure and worse outcomes in persons with MM.¹⁰ To date, only a single abstract from a US Department of Veterans Affairs (VA) medical center has investigated the relationships between AO exposure and MGUS, MM, and the rate of transformation. The VA study of patients seen from 2005 to 2015 in Detroit, Michigan, found that AO exposure led to an increase in cumulative incidence rate of MGUS/MM, suggesting possible changes in disease biology and genetics.¹¹

In this study, we aimed to determine the incidence of transformation of MGUS to MM in patients with and without exposure to AO. We then analyzed survival as a function of AO exposure, transformation, and clinical and sociodemographic variables. We also explored the impact of psychosocial variables and hematopoietic stem cell transplantation (HSCT), a standard of treatment for MM.

Methods

This retrospective cohort study assembled electronic health record (EHR) data from the Veterans Health Administration Corporate Data Warehouse (CDW). The VA Central Texas Veterans Healthcare System Institutional Review Board granted a waiver of consent for this record review. Eligible patients were Vietnam-era veterans who were in the military during the time that AO was used (1961-1971). Veterans were included if they were being cared for and received a diagnosis for MGUS or MM between October 1, 2009, and September 30, 2015 (all prevalent cases fiscal years 2010-2015). Cases were excluded if there was illogical death data or if age, race, ethnicity, body mass index (BMI), or prior-year diagnostic data were missing.

Measures

Patients were followed through April 2020. Presence of MGUS was defined by the International Classification of Diseases, Ninth Revision (ICD-9) diagnosis code 273.1. MM was identified by ICD-9 diagnosis codes 203.00, 203.01, and 203.02. The study index date was the earliest date of diagnosis of MGUS or MM in fiscal years 2010-2015. It was suspected that some patients with MM may have had a history of MGUS prior to this period. Therefore, for patients with MM, historical diagnosis of MGUS was extracted going back through the earliest data in the CDW (October 1999). Patients diagnosed with both MGUS and MM were considered transformation patients.

Other measures included age at index date, sex, race, ethnicity, VA priority status (a value 1 to 8 summarizing why the veteran qualified for VA care, such as military service-connected disability or very low income), and AO exposure authenticated per VA enrollment files and disability records. Service years were separated into 1961 to 1968 and 1969 to 1971 to match a change in the formulation of AO associated with decreased carcinogenic effect. Comorbidity data from the year prior to first MGUS/MM diagnosis in the observation period were extracted. Lifestyle factors associated with development of MGUS/MM were determined using the following codes: obesity per BMI calculation or diagnosis (ICD-9, 278.0), tobacco use per diagnosis (ICD-9, 305.1, V15.82), and survival from MGUS/MM diagnosis index date to date of death from any cause. Comorbidity was assessed using ICD-9 diagnosis codes to calculate the Charlson Comorbidity Index (CCI), which includes cardiovascular diseases, diabetes mellitus, liver and kidney diseases, cancers, and metastatic solid tumors. Cancers were omitted from our adapted CCI to avoid collinearity in the multivariable models. The theoretical maximum CCI score in this study was 25.^12,13 Additional conditions known to be associated with variation in outcomes among veterans using the VA were indicated, including major depressive disorder, posttraumatic stress disorder (PTSD), alcohol use disorder (AUD), substance use disorder (SUD), and common chronic disease (hypertension, lipid disorders).¹⁴

Statistical Analysis

Sample characteristics were represented by frequencies and percentages for categorical variables and means and SDs (or medians and ranges where appropriate) for continuous variables. A χ² test (or Fisher exact test when cell counts were low) assessed associations in bivariate comparisons. A 2-sample t test (or Wilcoxon rank sum test as appropriate) assessed differences in continuous variables between 2 groups. Kaplan-Meier curves depicted the unadjusted relationship of AO exposure to survival. Cox proportional hazards survival models examined an unadjusted model containing only the AO exposure indicator as a predictor and adjusted models were used for demographic and clinical factors for MGUS and patients with MM separately.

Predictors were age in decades, sex, Hispanic ethnicity, race, nicotine dependence, obesity, overweight, AUD, SUD, major depressive disorder, PTSD, and the adapted CCI. When modeling patients with MM, MGUS was added to the model to identify the transformation group. The interaction of AO with transformation was also analyzed for patients with MM. Results were reported as hazard ratios (HR) with their 95% CI.

Results

We identified 18,215 veterans diagnosed with either MGUS or MM during fiscal years 2010-2015 with 16,366 meeting inclusion criteria. Patients were excluded for missing data on exposure (n = 334), age (n = 12), race (n = 1058), ethnicity (n = 164), diagnosis (n = 47), treatment (n = 56), and BMI (n = 178). All were Vietnam War era veterans; 14 also served in other eras.

The cohort was 98.5% male (Table 1). Twenty-nine percent were Black veterans, 65% were White veterans, and 4% of individuals reported Hispanic ethnicity. Patients had a mean (SD) age of 66.7 (5.9) years (range, 52-96). Most patients were married (58%) or divorced/separated (27%). All were VA priority 1 to 5 (no 6, 7, or 8); 50% were priority 1 with 50% to 100% service-connected disability. Another 29% were eligible for VA care by reason of low income, 17% had 10% to 40% service-connected disability, and 4% were otherwise disabled.

Disscussion

Elucidating the pathophysiology and risk of transformation from MGUS to MM is an ongoing endeavor, even 35 years after the end of US involvement in the Vietnam War. Our study sought to understand a relationship between AO exposure, risk of MGUS transforming to MM, and associated mortality in US Vietnam War veterans. The rate of transformation (MGUS progressing to active MM) is well cited at 1% per year.¹⁵ Here, we found 12% of our cohort had undergone this transformation over 10 years.

Vietnam War era veterans who were exposed to AO during the Operation Ranch Hand period had 2.4 times greater risk of developing MGUS compared with veterans not exposed to AO.⁸ Our study was not designed to look at this association of AO exposure and MGUS/MM as this was a retrospective review to assess the difference in outcomes based on AO exposure. We found that AO exposure is associated with a decrease in mortality in contrast to a prior study showing worse survival with individuals with AO exposure.¹⁰ Another single center study found no association between AO exposure and overall survival, but it did identify an increased risk of progression from MGUS to MM.¹¹ Our study did not show increased risk of transformation but did show positive effect on survival.

Black individuals have twice the risk of developing MM compared with White individuals and are diagnosed at a younger age (66 vs 70 years, respectively).¹⁶ Interestingly, Black race was a protective factor in our study. Given the length of time (35 years) elapsed since the Vietnam War ended, it is likely that most vulnerable Black veterans did not survive until our observation period.

HSCT, as expected, was a protective factor for veterans undergoing this treatment modality, but it is unclear why such a small number (8%) underwent HSCT as this is a standard of care in the management of MM. Obesity was also found to be a protective factor in a prior study, which was also seen in our study cohort.⁸

Limitations

This study was limited by its retrospective review of survivors among the Vietnam-era cohort several decades after the exposure of concern. Clinician notes and full historical data, such as date of onset for any disorder, were unavailable. These data also relied on the practitioners caring for the veterans to make the correct diagnosis with the associated code so that the data could be captured. Neither AO exposure nor diagnoses codes were verified against other sources of data; however, validation studies over the years have supported the accuracy of the diagnosis codes recorded in the VA EHR.

Conclusions

Because AO exposure is a nonmodifiable risk factor, focus should be placed on modifiable risk factors (eg, nicotine dependence, alcohol and substance use disorders, underlying comorbid conditions) as these were associated with worse outcomes. Future studies will look at the correlation of AO exposure, cytogenetics, and clinical outcomes in these veterans to learn how best to identify their disease course and optimize their care in the latter part of their life.

Acknowledgments

This research was supported by the Central Texas Veterans Health Care System and Baylor Scott and White Health, both in Temple and Veterans Affairs Central Western Massachusetts Healthcare System, Leeds.

The negative impact of the unnecessary prescribing of antibiotic is well known. Consequences include exposing patients to antibiotic adverse effects, risk of overgrowth of pathogenetic organisms such as clostridial species, unnecessary cost of drugs, and development of selection of antibiotic-resistant organisms in the populace at large. Acute viral respiratory infections are among the leading causes of inappropriate antibiotic usage.¹ In a study of 1000 adults with respiratory tract infections in an outpatient setting, 77% of patients were prescribed antibiotics, and the treatment was inappropriate in 64% of those who received prescriptions.² Patient expectations and clinician perceptions of these expectations play a role. One study showed that 54% of clinicians felt their patients expected to receive antibiotics for a visit due to an acute respiratory infection (ARI), such as a cough or cold; 26% of patients did in fact have this expectation.³

The US Department of Veterans Affairs (VA) Central Ohio Health Care System is a large ambulatory care facility, with 4 associated community-based outpatient clinics, serving more than 43,000 central Ohio veterans and completing more than 500,000 medical appointments annually. An antimicrobial stewardship program has been in place since 2013. In May 2018, the clinical pharmacist assigned to the program alerted medical leadership that, of 67 patients seen in primary care for ARIs between April 16, 2018, and May 15, 2018, 42 (63%) had been prescribed an antibiotic. Based on this finding, clinical leadership designed a process improvement program aimed at reducing inappropriate antibiotic usage for the treatment of uncomplicated ARls likely due to viral pathogens. Key components were clinician and patient education and the substitution of a symptomatic treatment kit in place of an antibiotic prescription.

Methods

Facility clinical leadership, assisted by Volunteer Services, developed a Viral Illness Support Pack to be dispensed by primary care practitioners (PCPs) to patients presenting with symptoms of viral ARIs. The contents of this support pack are shown in the Figure. Patients were provided with tissues, throat lozenges, lip balm, acetaminophen, hand sanitizer, a surgical mask, patient instructions, and the Antibiotics Aren’t Always the Answer pamphlet.⁴ The contents of the viral support pack were purchased through Volunteer Services using donated funds. In total, 460 packs were distributed to the primary care patient aligned care teams (PACTs), including the community-based outpatient clinics.

Clinicians and care teams received academic detailing prior to distribution of the viral support packs, stressing the importance of avoiding antibiotics to treat viral illnesses. Viral illness support packs were available for distribution from December 1, 2018, through March 31, 2019. The frequency of antibiotic dispensing to patients coded for ARI during this period was compared with that of the same time period in the previous year. All charts were reviewed for coding accuracy. Patients with illnesses requiring antibiotic treatment, such as pneumonia, exacerbations of chronic obstructive pulmonary disease and chronic bronchitis, and streptococcal pharyngitis, were excluded from the study. Statistical significance was determined using the unpaired t test.

Results

From December 1, 2018, to March 31, 2019, 357 viral support packs were distributed to patients (Table). For the historical control period from December 1, 2017, through March 31, 2018, 508 patients were treated for ARIs. Of these, 295 (58%) received clinically inappropriate antibiotics. In contrast, of the 627 patients treated for ARIs during the study period from December 1, 2018, through March 31, 2019, 310 (49%) received clinically inappropriate antibiotics. The 9% decrease during the period when viral support packs were distributed, compared with the prior year, was statistically significant (P = .02).

Discussion

The decrease in antibiotic prescriptions for ARIs was statistically significant. The success of this project can be attributed to 3 factors: clinician education, patient education, and the option for PCPs to provide symptomatic treatment for these patients rather than prescribe an antibiotic.

The importance of antibiotic stewardship has been emphasized to all PCPs at the VA Central Ohio Health Care System. Antibiotic stewardship has been the subject of grand rounds. Prior to distribution of the viral support pack, the chief of specialty medicine, the project’s champion, spoke to all PCPs. Adequate numbers of viral support packs were distributed to all primary care teams.

In addition to direct clinician-to-patient education at the time of the patients’ visits, educational materials were included in the viral support pack. The Antibiotics Aren’t Always the Answer pamphlet is available from the Centers for Disease Control and Prevention. It covers the importance of antibiotic awareness, discusses what antibiotics do and do not treat, how to stay healthy, and causes of antibiotic resistance. The pamphlet contains the clear message that antibiotics are not only ineffective against viral illness, but also can cause significant undesirable outcomes.

The pamphlet Viral Illness Support Pack Traffic Light Card (eAppendix available online at doi:10.12788/fp.0302) provides important clinical information to the patients about their illness. Patients are instructed to contact their primary care team if they are worse after 3 days of illness; symptoms are not improving after 10 days; or they experience blood in respiratory secretions, chills or generalized aching, and localized pain that is one-sided or significantly worsening. Patients are clearly informed to seek further care if not improving with symptomatic treatment.

The ability to provide patients with symptomatic relief, including throat lozenges, lip balm, and acetaminophen, was felt to be important in the success of the project. Furthermore, this eliminated an extra step of the patient needing to visit the pharmacy.

Limitations

Limitations of the study included starting distribution of the support packs somewhat after the onset of the viral illness season, failure to reach all prescribers for academic detailing at the start of the program, and several instances of temporary unavailability of the support packs in some areas.

Conclusions

Patients with ARIs are often significantly symptomatic and frequently believe that they require an antibiotic for treatment. Clinicians may adjust their behavior in response to their patients’ expectations, stated or unstated. The results of this project demonstrate that the combination of patient education and the ready availability of a nonantibiotic symptomatic treatment option can significantly decrease the unnecessary prescribing of antibiotics for viral illnesses.

Acknowledgments

The authors are grateful to Ms. Traci Washington for assistance in sourcing materials; to Karen Corr, PhD, and Anthony Restuccio, MD, for advice on methods; to Mr. Daniel Pignatelli for assistance with data interpretation; and to Mr. Keith Skidmore, Ms. Crystal Conley, and Ms. Megan Harris for assistance with assembling the Viral Illness Support Packs.

The negative impact of the unnecessary prescribing of antibiotic is well known. Consequences include exposing patients to antibiotic adverse effects, risk of overgrowth of pathogenetic organisms such as clostridial species, unnecessary cost of drugs, and development of selection of antibiotic-resistant organisms in the populace at large. Acute viral respiratory infections are among the leading causes of inappropriate antibiotic usage.¹ In a study of 1000 adults with respiratory tract infections in an outpatient setting, 77% of patients were prescribed antibiotics, and the treatment was inappropriate in 64% of those who received prescriptions.² Patient expectations and clinician perceptions of these expectations play a role. One study showed that 54% of clinicians felt their patients expected to receive antibiotics for a visit due to an acute respiratory infection (ARI), such as a cough or cold; 26% of patients did in fact have this expectation.³

The US Department of Veterans Affairs (VA) Central Ohio Health Care System is a large ambulatory care facility, with 4 associated community-based outpatient clinics, serving more than 43,000 central Ohio veterans and completing more than 500,000 medical appointments annually. An antimicrobial stewardship program has been in place since 2013. In May 2018, the clinical pharmacist assigned to the program alerted medical leadership that, of 67 patients seen in primary care for ARIs between April 16, 2018, and May 15, 2018, 42 (63%) had been prescribed an antibiotic. Based on this finding, clinical leadership designed a process improvement program aimed at reducing inappropriate antibiotic usage for the treatment of uncomplicated ARls likely due to viral pathogens. Key components were clinician and patient education and the substitution of a symptomatic treatment kit in place of an antibiotic prescription.

Methods

Facility clinical leadership, assisted by Volunteer Services, developed a Viral Illness Support Pack to be dispensed by primary care practitioners (PCPs) to patients presenting with symptoms of viral ARIs. The contents of this support pack are shown in the Figure. Patients were provided with tissues, throat lozenges, lip balm, acetaminophen, hand sanitizer, a surgical mask, patient instructions, and the Antibiotics Aren’t Always the Answer pamphlet.⁴ The contents of the viral support pack were purchased through Volunteer Services using donated funds. In total, 460 packs were distributed to the primary care patient aligned care teams (PACTs), including the community-based outpatient clinics.

Clinicians and care teams received academic detailing prior to distribution of the viral support packs, stressing the importance of avoiding antibiotics to treat viral illnesses. Viral illness support packs were available for distribution from December 1, 2018, through March 31, 2019. The frequency of antibiotic dispensing to patients coded for ARI during this period was compared with that of the same time period in the previous year. All charts were reviewed for coding accuracy. Patients with illnesses requiring antibiotic treatment, such as pneumonia, exacerbations of chronic obstructive pulmonary disease and chronic bronchitis, and streptococcal pharyngitis, were excluded from the study. Statistical significance was determined using the unpaired t test.

Results

From December 1, 2018, to March 31, 2019, 357 viral support packs were distributed to patients (Table). For the historical control period from December 1, 2017, through March 31, 2018, 508 patients were treated for ARIs. Of these, 295 (58%) received clinically inappropriate antibiotics. In contrast, of the 627 patients treated for ARIs during the study period from December 1, 2018, through March 31, 2019, 310 (49%) received clinically inappropriate antibiotics. The 9% decrease during the period when viral support packs were distributed, compared with the prior year, was statistically significant (P = .02).

Discussion

The decrease in antibiotic prescriptions for ARIs was statistically significant. The success of this project can be attributed to 3 factors: clinician education, patient education, and the option for PCPs to provide symptomatic treatment for these patients rather than prescribe an antibiotic.

The importance of antibiotic stewardship has been emphasized to all PCPs at the VA Central Ohio Health Care System. Antibiotic stewardship has been the subject of grand rounds. Prior to distribution of the viral support pack, the chief of specialty medicine, the project’s champion, spoke to all PCPs. Adequate numbers of viral support packs were distributed to all primary care teams.

In addition to direct clinician-to-patient education at the time of the patients’ visits, educational materials were included in the viral support pack. The Antibiotics Aren’t Always the Answer pamphlet is available from the Centers for Disease Control and Prevention. It covers the importance of antibiotic awareness, discusses what antibiotics do and do not treat, how to stay healthy, and causes of antibiotic resistance. The pamphlet contains the clear message that antibiotics are not only ineffective against viral illness, but also can cause significant undesirable outcomes.

The pamphlet Viral Illness Support Pack Traffic Light Card (eAppendix available online at doi:10.12788/fp.0302) provides important clinical information to the patients about their illness. Patients are instructed to contact their primary care team if they are worse after 3 days of illness; symptoms are not improving after 10 days; or they experience blood in respiratory secretions, chills or generalized aching, and localized pain that is one-sided or significantly worsening. Patients are clearly informed to seek further care if not improving with symptomatic treatment.

The ability to provide patients with symptomatic relief, including throat lozenges, lip balm, and acetaminophen, was felt to be important in the success of the project. Furthermore, this eliminated an extra step of the patient needing to visit the pharmacy.

Limitations

Limitations of the study included starting distribution of the support packs somewhat after the onset of the viral illness season, failure to reach all prescribers for academic detailing at the start of the program, and several instances of temporary unavailability of the support packs in some areas.

Conclusions

Patients with ARIs are often significantly symptomatic and frequently believe that they require an antibiotic for treatment. Clinicians may adjust their behavior in response to their patients’ expectations, stated or unstated. The results of this project demonstrate that the combination of patient education and the ready availability of a nonantibiotic symptomatic treatment option can significantly decrease the unnecessary prescribing of antibiotics for viral illnesses.

Acknowledgments

The authors are grateful to Ms. Traci Washington for assistance in sourcing materials; to Karen Corr, PhD, and Anthony Restuccio, MD, for advice on methods; to Mr. Daniel Pignatelli for assistance with data interpretation; and to Mr. Keith Skidmore, Ms. Crystal Conley, and Ms. Megan Harris for assistance with assembling the Viral Illness Support Packs.

The negative impact of the unnecessary prescribing of antibiotic is well known. Consequences include exposing patients to antibiotic adverse effects, risk of overgrowth of pathogenetic organisms such as clostridial species, unnecessary cost of drugs, and development of selection of antibiotic-resistant organisms in the populace at large. Acute viral respiratory infections are among the leading causes of inappropriate antibiotic usage.¹ In a study of 1000 adults with respiratory tract infections in an outpatient setting, 77% of patients were prescribed antibiotics, and the treatment was inappropriate in 64% of those who received prescriptions.² Patient expectations and clinician perceptions of these expectations play a role. One study showed that 54% of clinicians felt their patients expected to receive antibiotics for a visit due to an acute respiratory infection (ARI), such as a cough or cold; 26% of patients did in fact have this expectation.³

The US Department of Veterans Affairs (VA) Central Ohio Health Care System is a large ambulatory care facility, with 4 associated community-based outpatient clinics, serving more than 43,000 central Ohio veterans and completing more than 500,000 medical appointments annually. An antimicrobial stewardship program has been in place since 2013. In May 2018, the clinical pharmacist assigned to the program alerted medical leadership that, of 67 patients seen in primary care for ARIs between April 16, 2018, and May 15, 2018, 42 (63%) had been prescribed an antibiotic. Based on this finding, clinical leadership designed a process improvement program aimed at reducing inappropriate antibiotic usage for the treatment of uncomplicated ARls likely due to viral pathogens. Key components were clinician and patient education and the substitution of a symptomatic treatment kit in place of an antibiotic prescription.

Methods

Facility clinical leadership, assisted by Volunteer Services, developed a Viral Illness Support Pack to be dispensed by primary care practitioners (PCPs) to patients presenting with symptoms of viral ARIs. The contents of this support pack are shown in the Figure. Patients were provided with tissues, throat lozenges, lip balm, acetaminophen, hand sanitizer, a surgical mask, patient instructions, and the Antibiotics Aren’t Always the Answer pamphlet.⁴ The contents of the viral support pack were purchased through Volunteer Services using donated funds. In total, 460 packs were distributed to the primary care patient aligned care teams (PACTs), including the community-based outpatient clinics.

Clinicians and care teams received academic detailing prior to distribution of the viral support packs, stressing the importance of avoiding antibiotics to treat viral illnesses. Viral illness support packs were available for distribution from December 1, 2018, through March 31, 2019. The frequency of antibiotic dispensing to patients coded for ARI during this period was compared with that of the same time period in the previous year. All charts were reviewed for coding accuracy. Patients with illnesses requiring antibiotic treatment, such as pneumonia, exacerbations of chronic obstructive pulmonary disease and chronic bronchitis, and streptococcal pharyngitis, were excluded from the study. Statistical significance was determined using the unpaired t test.

Results

From December 1, 2018, to March 31, 2019, 357 viral support packs were distributed to patients (Table). For the historical control period from December 1, 2017, through March 31, 2018, 508 patients were treated for ARIs. Of these, 295 (58%) received clinically inappropriate antibiotics. In contrast, of the 627 patients treated for ARIs during the study period from December 1, 2018, through March 31, 2019, 310 (49%) received clinically inappropriate antibiotics. The 9% decrease during the period when viral support packs were distributed, compared with the prior year, was statistically significant (P = .02).

Discussion

The decrease in antibiotic prescriptions for ARIs was statistically significant. The success of this project can be attributed to 3 factors: clinician education, patient education, and the option for PCPs to provide symptomatic treatment for these patients rather than prescribe an antibiotic.

The importance of antibiotic stewardship has been emphasized to all PCPs at the VA Central Ohio Health Care System. Antibiotic stewardship has been the subject of grand rounds. Prior to distribution of the viral support pack, the chief of specialty medicine, the project’s champion, spoke to all PCPs. Adequate numbers of viral support packs were distributed to all primary care teams.

In addition to direct clinician-to-patient education at the time of the patients’ visits, educational materials were included in the viral support pack. The Antibiotics Aren’t Always the Answer pamphlet is available from the Centers for Disease Control and Prevention. It covers the importance of antibiotic awareness, discusses what antibiotics do and do not treat, how to stay healthy, and causes of antibiotic resistance. The pamphlet contains the clear message that antibiotics are not only ineffective against viral illness, but also can cause significant undesirable outcomes.

The pamphlet Viral Illness Support Pack Traffic Light Card (eAppendix available online at doi:10.12788/fp.0302) provides important clinical information to the patients about their illness. Patients are instructed to contact their primary care team if they are worse after 3 days of illness; symptoms are not improving after 10 days; or they experience blood in respiratory secretions, chills or generalized aching, and localized pain that is one-sided or significantly worsening. Patients are clearly informed to seek further care if not improving with symptomatic treatment.

The ability to provide patients with symptomatic relief, including throat lozenges, lip balm, and acetaminophen, was felt to be important in the success of the project. Furthermore, this eliminated an extra step of the patient needing to visit the pharmacy.

Limitations

Limitations of the study included starting distribution of the support packs somewhat after the onset of the viral illness season, failure to reach all prescribers for academic detailing at the start of the program, and several instances of temporary unavailability of the support packs in some areas.

Conclusions

Patients with ARIs are often significantly symptomatic and frequently believe that they require an antibiotic for treatment. Clinicians may adjust their behavior in response to their patients’ expectations, stated or unstated. The results of this project demonstrate that the combination of patient education and the ready availability of a nonantibiotic symptomatic treatment option can significantly decrease the unnecessary prescribing of antibiotics for viral illnesses.

Acknowledgments

The authors are grateful to Ms. Traci Washington for assistance in sourcing materials; to Karen Corr, PhD, and Anthony Restuccio, MD, for advice on methods; to Mr. Daniel Pignatelli for assistance with data interpretation; and to Mr. Keith Skidmore, Ms. Crystal Conley, and Ms. Megan Harris for assistance with assembling the Viral Illness Support Packs.