Recently, two studies were published addressing the potential association of childhood cancer and assisted reproductive technology. For more than a decade and a half, it has been acknowledged that ART is associated with increased concern both with structural birth defects, as well as imprinting disorders. As both of these issues have been linked to greater cancer risk in children, it is important to decipher the impact of ART on childhood cancer risk.

Published online April 1 in JAMA Pediatrics, the study, “Association of in vitro fertilization [IVF] with childhood cancer in the United States,”¹ by LG Spector et al. looked retrospectively at birth and cancer registries in 14 states with 8 years of data on 275,686 children were conceived via ART through 2013, who were compared with 2,266,847 children selected randomly.

The overall cancer rate per 1,000,000 person-years was low in both groups: 252 for the IVF group and 193 for the control group, for an overall hazard risk of 1.17. Of note, the rate of hepatic tumors was higher among the IVF group than the non-IVF group (18 vs. 5.7; hazard ratio, 2.46). There appeared to be no association with specific IVF treatments, whether children were conceived by donor egg vs. autologous egg; frozen embryos vs. fresh embryos; use of intracytoplasmic sperm injection (ICSI) vs. none; assisted hatching vs. none; and day-3 vs. day-5 transfer. The researchers concluded that the “increased rate of embryonal cancers, particularly hepatic tumors, that could not be attributed to IVF rather than to underlying infertility.”

This first and largest cohort study of association between IVF and the risk of childhood cancer ever published showed little evidence of excess risk of most cancers, including more common cancers such as leukemia.

The authors did note limitations in their study. Mothers who conceived via IVF were more likely to be white, non-Hispanic, more educated, and older. Could this patient population undergoing ART be at greater risk of producing offspring with cancer concerns? If that were the case – and not great risk of childhood cancer in ART, per se – one therefore would extrapolate that couples undergoing ART vs. alternative infertility treatment should not show a treatment-biased risk (i.e., ART vs. non-ART).

This was demonstrated recently in the study, “Risk of cancer in children and young adults conceived by assisted reproductive technology.”² This Dutch historical cohort study with prospective follow-up of a median 21 years evaluated 47,690 live-born children, of which 24,269 were ART conceived, 13,761 naturally conceived, and 9,660 conceived naturally or with fertility drugs but not by ART.

Overall, cancer risk was not increased in ART-conceived children, compared with naturally conceived subfertile women or even the general population. A nonsignificant increased risk was observed in children conceived by ICSI or cryopreservation.

On the basis of these two studies, there appears to be no significant increased risk of cancer in children conceived through fertility treatment, including ART.

Although these studies do not support the conclusion reached by a 2013 meta-analysis of 9 studies that specifically looked at ART and 16 other studies that looked at other types of medically assisted reproduction (such medically assisted reproduction as reproduction achieved through ovulation induction; controlled ovarian stimulation; ovulation triggering; intrauterine, intracervical, or intravaginal insemination) which reported a significant increased risk of overall cancers (1.33), including leukemia, CNS cancer, and neuroblastoma,³ they do agree more closely with two prospective studies conducted in the United Kingdom and Nordic countries.

In the U.K. study,⁴ there was no overall increased risk of cancer associated with ART, but two types of cancer were noted to be higher in the ART-conceived group – hepatoblastoma (3.27 risk) and rhabdomyosarcoma (2.62 risk) – but the absolute risk of these two types of cancer was small in this 17-year study of 106,013 children. This, of course, would be consistent with the JAMA Pediatrics study. In the Nordic study,⁵ similar to the Dutch Study, IVF was not associated with a significant increased risk of cancer (1.08). The Nordic study included 91,796 children born of ART-assisted pregnancies, compared with 358,419 children born after spontaneous conceptions.

The evidence so far shows that there appears to be no significant increased risk of cancer overall associated with fertility treatments, including IVF.
 

Dr. Miller is a clinical associate professor at the University of Illinois in Chicago and past president of the AAGL. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in metropolitan Chicago and the director of minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, Ill. He also is a member of Ob.Gyn. News editorial advisory board. Dr. Miller disclosed that he is president of the Advanced IVF Institute in Park Ridge and Naperville, Ill.

References

1. JAMA Pediatr. 2019 Apr 1. doi: 10.1001/jamapediatrics.2019.0392.

2. Hum Reprod. 2019 Apr 1;34(4):740-50.

3. Fertil Steril. 2013 Jul. doi: 10.1016/j.fertnstert.2013.03.017.

4. N Engl J Med. 2013 Nov 7;369(19):1819-27.

5. Hum Reprod. 2014 Sep;29(9):2050-7.

Recently, two studies were published addressing the potential association of childhood cancer and assisted reproductive technology. For more than a decade and a half, it has been acknowledged that ART is associated with increased concern both with structural birth defects, as well as imprinting disorders. As both of these issues have been linked to greater cancer risk in children, it is important to decipher the impact of ART on childhood cancer risk.

Published online April 1 in JAMA Pediatrics, the study, “Association of in vitro fertilization [IVF] with childhood cancer in the United States,”¹ by LG Spector et al. looked retrospectively at birth and cancer registries in 14 states with 8 years of data on 275,686 children were conceived via ART through 2013, who were compared with 2,266,847 children selected randomly.

The overall cancer rate per 1,000,000 person-years was low in both groups: 252 for the IVF group and 193 for the control group, for an overall hazard risk of 1.17. Of note, the rate of hepatic tumors was higher among the IVF group than the non-IVF group (18 vs. 5.7; hazard ratio, 2.46). There appeared to be no association with specific IVF treatments, whether children were conceived by donor egg vs. autologous egg; frozen embryos vs. fresh embryos; use of intracytoplasmic sperm injection (ICSI) vs. none; assisted hatching vs. none; and day-3 vs. day-5 transfer. The researchers concluded that the “increased rate of embryonal cancers, particularly hepatic tumors, that could not be attributed to IVF rather than to underlying infertility.”

This first and largest cohort study of association between IVF and the risk of childhood cancer ever published showed little evidence of excess risk of most cancers, including more common cancers such as leukemia.

The authors did note limitations in their study. Mothers who conceived via IVF were more likely to be white, non-Hispanic, more educated, and older. Could this patient population undergoing ART be at greater risk of producing offspring with cancer concerns? If that were the case – and not great risk of childhood cancer in ART, per se – one therefore would extrapolate that couples undergoing ART vs. alternative infertility treatment should not show a treatment-biased risk (i.e., ART vs. non-ART).

This was demonstrated recently in the study, “Risk of cancer in children and young adults conceived by assisted reproductive technology.”² This Dutch historical cohort study with prospective follow-up of a median 21 years evaluated 47,690 live-born children, of which 24,269 were ART conceived, 13,761 naturally conceived, and 9,660 conceived naturally or with fertility drugs but not by ART.

Overall, cancer risk was not increased in ART-conceived children, compared with naturally conceived subfertile women or even the general population. A nonsignificant increased risk was observed in children conceived by ICSI or cryopreservation.

On the basis of these two studies, there appears to be no significant increased risk of cancer in children conceived through fertility treatment, including ART.

Although these studies do not support the conclusion reached by a 2013 meta-analysis of 9 studies that specifically looked at ART and 16 other studies that looked at other types of medically assisted reproduction (such medically assisted reproduction as reproduction achieved through ovulation induction; controlled ovarian stimulation; ovulation triggering; intrauterine, intracervical, or intravaginal insemination) which reported a significant increased risk of overall cancers (1.33), including leukemia, CNS cancer, and neuroblastoma,³ they do agree more closely with two prospective studies conducted in the United Kingdom and Nordic countries.

In the U.K. study,⁴ there was no overall increased risk of cancer associated with ART, but two types of cancer were noted to be higher in the ART-conceived group – hepatoblastoma (3.27 risk) and rhabdomyosarcoma (2.62 risk) – but the absolute risk of these two types of cancer was small in this 17-year study of 106,013 children. This, of course, would be consistent with the JAMA Pediatrics study. In the Nordic study,⁵ similar to the Dutch Study, IVF was not associated with a significant increased risk of cancer (1.08). The Nordic study included 91,796 children born of ART-assisted pregnancies, compared with 358,419 children born after spontaneous conceptions.

The evidence so far shows that there appears to be no significant increased risk of cancer overall associated with fertility treatments, including IVF.
 

Dr. Miller is a clinical associate professor at the University of Illinois in Chicago and past president of the AAGL. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in metropolitan Chicago and the director of minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, Ill. He also is a member of Ob.Gyn. News editorial advisory board. Dr. Miller disclosed that he is president of the Advanced IVF Institute in Park Ridge and Naperville, Ill.

References

1. JAMA Pediatr. 2019 Apr 1. doi: 10.1001/jamapediatrics.2019.0392.

2. Hum Reprod. 2019 Apr 1;34(4):740-50.

3. Fertil Steril. 2013 Jul. doi: 10.1016/j.fertnstert.2013.03.017.

4. N Engl J Med. 2013 Nov 7;369(19):1819-27.

5. Hum Reprod. 2014 Sep;29(9):2050-7.

Recently, two studies were published addressing the potential association of childhood cancer and assisted reproductive technology. For more than a decade and a half, it has been acknowledged that ART is associated with increased concern both with structural birth defects, as well as imprinting disorders. As both of these issues have been linked to greater cancer risk in children, it is important to decipher the impact of ART on childhood cancer risk.

Published online April 1 in JAMA Pediatrics, the study, “Association of in vitro fertilization [IVF] with childhood cancer in the United States,”¹ by LG Spector et al. looked retrospectively at birth and cancer registries in 14 states with 8 years of data on 275,686 children were conceived via ART through 2013, who were compared with 2,266,847 children selected randomly.

The overall cancer rate per 1,000,000 person-years was low in both groups: 252 for the IVF group and 193 for the control group, for an overall hazard risk of 1.17. Of note, the rate of hepatic tumors was higher among the IVF group than the non-IVF group (18 vs. 5.7; hazard ratio, 2.46). There appeared to be no association with specific IVF treatments, whether children were conceived by donor egg vs. autologous egg; frozen embryos vs. fresh embryos; use of intracytoplasmic sperm injection (ICSI) vs. none; assisted hatching vs. none; and day-3 vs. day-5 transfer. The researchers concluded that the “increased rate of embryonal cancers, particularly hepatic tumors, that could not be attributed to IVF rather than to underlying infertility.”

This first and largest cohort study of association between IVF and the risk of childhood cancer ever published showed little evidence of excess risk of most cancers, including more common cancers such as leukemia.

The authors did note limitations in their study. Mothers who conceived via IVF were more likely to be white, non-Hispanic, more educated, and older. Could this patient population undergoing ART be at greater risk of producing offspring with cancer concerns? If that were the case – and not great risk of childhood cancer in ART, per se – one therefore would extrapolate that couples undergoing ART vs. alternative infertility treatment should not show a treatment-biased risk (i.e., ART vs. non-ART).

This was demonstrated recently in the study, “Risk of cancer in children and young adults conceived by assisted reproductive technology.”² This Dutch historical cohort study with prospective follow-up of a median 21 years evaluated 47,690 live-born children, of which 24,269 were ART conceived, 13,761 naturally conceived, and 9,660 conceived naturally or with fertility drugs but not by ART.

Overall, cancer risk was not increased in ART-conceived children, compared with naturally conceived subfertile women or even the general population. A nonsignificant increased risk was observed in children conceived by ICSI or cryopreservation.

On the basis of these two studies, there appears to be no significant increased risk of cancer in children conceived through fertility treatment, including ART.

Although these studies do not support the conclusion reached by a 2013 meta-analysis of 9 studies that specifically looked at ART and 16 other studies that looked at other types of medically assisted reproduction (such medically assisted reproduction as reproduction achieved through ovulation induction; controlled ovarian stimulation; ovulation triggering; intrauterine, intracervical, or intravaginal insemination) which reported a significant increased risk of overall cancers (1.33), including leukemia, CNS cancer, and neuroblastoma,³ they do agree more closely with two prospective studies conducted in the United Kingdom and Nordic countries.

In the U.K. study,⁴ there was no overall increased risk of cancer associated with ART, but two types of cancer were noted to be higher in the ART-conceived group – hepatoblastoma (3.27 risk) and rhabdomyosarcoma (2.62 risk) – but the absolute risk of these two types of cancer was small in this 17-year study of 106,013 children. This, of course, would be consistent with the JAMA Pediatrics study. In the Nordic study,⁵ similar to the Dutch Study, IVF was not associated with a significant increased risk of cancer (1.08). The Nordic study included 91,796 children born of ART-assisted pregnancies, compared with 358,419 children born after spontaneous conceptions.

The evidence so far shows that there appears to be no significant increased risk of cancer overall associated with fertility treatments, including IVF.
 

Dr. Miller is a clinical associate professor at the University of Illinois in Chicago and past president of the AAGL. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in metropolitan Chicago and the director of minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, Ill. He also is a member of Ob.Gyn. News editorial advisory board. Dr. Miller disclosed that he is president of the Advanced IVF Institute in Park Ridge and Naperville, Ill.

References

1. JAMA Pediatr. 2019 Apr 1. doi: 10.1001/jamapediatrics.2019.0392.

2. Hum Reprod. 2019 Apr 1;34(4):740-50.

3. Fertil Steril. 2013 Jul. doi: 10.1016/j.fertnstert.2013.03.017.

4. N Engl J Med. 2013 Nov 7;369(19):1819-27.

5. Hum Reprod. 2014 Sep;29(9):2050-7.

The U.S. Food and Drug Administration has approved the first two-drug, fixed-dose, complete regimen for HIV-infected adults, according to an FDA press announcement.

Dovato (dolutegravir and lamivudine), a product of ViiV Healthcare, is intended to serve “as a complete regimen” for the treatment of HIV-1 infection in adults who have had no previous antiretroviral treatment and who have an infection with no known or suspected genetic substitutions associated with resistance to the individual components of Dovato.

“With this approval, patients who have never been treated have the option of taking a two-drug regimen in a single tablet while eliminating additional toxicity and potential drug interactions from a third drug,” said Debra Birnkrant, MD, director of the FDA’s Division of Antiviral Products.

The Dovato labeling includes a Boxed Warning that patients infected with both HIV and hepatitis B should add additional treatment for their HBV or consider a different drug regimen. The most common adverse reactions with Dovato were headache, diarrhea, nausea, insomnia, and fatigue. In addition, the FDA warned that, as there is a known risk for neural tube defects with dolutegravir, patients are advised to avoid use of Dovato at the time of conception through the first trimester of pregnancy.

mlesney@mdedge.com

The U.S. Food and Drug Administration has approved the first two-drug, fixed-dose, complete regimen for HIV-infected adults, according to an FDA press announcement.

Dovato (dolutegravir and lamivudine), a product of ViiV Healthcare, is intended to serve “as a complete regimen” for the treatment of HIV-1 infection in adults who have had no previous antiretroviral treatment and who have an infection with no known or suspected genetic substitutions associated with resistance to the individual components of Dovato.

“With this approval, patients who have never been treated have the option of taking a two-drug regimen in a single tablet while eliminating additional toxicity and potential drug interactions from a third drug,” said Debra Birnkrant, MD, director of the FDA’s Division of Antiviral Products.

The Dovato labeling includes a Boxed Warning that patients infected with both HIV and hepatitis B should add additional treatment for their HBV or consider a different drug regimen. The most common adverse reactions with Dovato were headache, diarrhea, nausea, insomnia, and fatigue. In addition, the FDA warned that, as there is a known risk for neural tube defects with dolutegravir, patients are advised to avoid use of Dovato at the time of conception through the first trimester of pregnancy.

mlesney@mdedge.com

The U.S. Food and Drug Administration has approved the first two-drug, fixed-dose, complete regimen for HIV-infected adults, according to an FDA press announcement.

Dovato (dolutegravir and lamivudine), a product of ViiV Healthcare, is intended to serve “as a complete regimen” for the treatment of HIV-1 infection in adults who have had no previous antiretroviral treatment and who have an infection with no known or suspected genetic substitutions associated with resistance to the individual components of Dovato.

“With this approval, patients who have never been treated have the option of taking a two-drug regimen in a single tablet while eliminating additional toxicity and potential drug interactions from a third drug,” said Debra Birnkrant, MD, director of the FDA’s Division of Antiviral Products.

The Dovato labeling includes a Boxed Warning that patients infected with both HIV and hepatitis B should add additional treatment for their HBV or consider a different drug regimen. The most common adverse reactions with Dovato were headache, diarrhea, nausea, insomnia, and fatigue. In addition, the FDA warned that, as there is a known risk for neural tube defects with dolutegravir, patients are advised to avoid use of Dovato at the time of conception through the first trimester of pregnancy.

mlesney@mdedge.com

Clinicians should offer biennial mammography to screen for breast cancer in asymptomatic average-risk women aged 50-74 years and should abandon clinical breast examinations (CBE) for screening in such women of any age, according to a new guideline from the American College of Physicians.

Catherine Yeulet/Thinkstock

Further, clinicians should discuss whether to screen with mammography in average-risk women aged 40-49 years and consider potential harms and benefits, as well as patient preferences. Providers should discontinue screening average-risk women at age 75 years and women with a life expectancy of 10 years or less, Amir Qaseem, MD, PhD, of the ACP and colleagues wrote on behalf of the ACP Clinical Guidelines Committee.

The ACP guidance also addresses the varying recommendations from other organizations on the age at which to start and stop screening and on screening intervals, noting that “areas of disagreement include screening in women aged 40 to 49 years, screening in women aged 75 years or older, and recommended screening intervals,” and stresses the importance of patient input.

“Women should be informed participants in personalized decisions about breast cancer screening,” the authors wrote, adding that those under age 50 years without a clear preference for screening should not be screened.

However, the evidence shows that most average-risk women with no symptoms will benefit from mammography every other year beginning at age 50 years, they said.

The statement, published online April 8 in the Annals of Internal Medicine, was derived from a review of seven existing English-language breast cancer screening guidelines and the evidence cited in those guidelines. It’s intended to be a resource for all clinicians.

It differs from the 2017 American College of Obstetricians and Gynecologists (ACOG) guidelines in that ACOG recommends CBE and does not address screening in those with a life expectancy of less than 10 years. It also differs from the 2016 U.S. Preventive Services Task Force (USPSTF) guidelines, which make no recommendation on CBE and also do not address screening in those with a life expectancy of less than 10 years.

Other guidelines, such as those from the American College of Radiology, American Cancer Society (ACS), the Canadian Task Force on Preventive Health Care, and the National Comprehensive Cancer Network, recommend CBE, and the World Health Organization guidelines recommend CBE in low resource settings.

“Although CBE continues to be used as part of the examination of symptomatic women, data are sparse on screening asymptomatic women using CBE alone or combined with mammography,” the ACP guideline authors wrote. “The ACS recommends against CBE in average-risk women of any age because of the lack of demonstrated benefit and the potential for false-positive results.”

The guidance, which does not apply to patients with prior abnormal screening results or those at higher breast cancer risk, also includes an evidence-driven “talking points with patients” section based on frequently asked questions.

An important goal of the ACP Clinical Guidelines Committee in developing the guidance is to reduce overdiagnosis and overtreatment, which affects about 20% of women diagnosed over a 10-year period.

The committee reviewed all national guidelines published in English between January 1, 2013, and November 15, 2017, in the National Guideline Clearinghouse or Guidelines International Network library, and it also selected other guidelines commonly used in clinical practice. The committee evaluated the quality of each by using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument.

Alex Krist, MD, the USPSTF vice-chairperson, offered support for the “shift toward shared decision making that is emerging” and added it’s “part of a larger movement toward empowering people with information not only about the potential benefits but also the potential harms of screening tests.”

“In its 2016 recommendation, the Task Force found that the value of mammography increases with age, with women ages 50-74 benefiting most from screening. For women in their 40s, the Task Force also found that mammography screening every two years can be effective,” he told this publication. “We recommend that the decision to start screening should be an individual one, taking into account a woman’s health history, preferences, and how she values the different potential benefits and harms.”

Dr. Krist further noted that the USPSTF, ACP, and many others “have all affirmed that mammography is an important tool to reduce breast cancer mortality and that the benefits of mammography increase with age.”

Likewise, Robert Smith, PhD, vice president of cancer screening for the ACS, noted that the ACP guidance generally aligns with ACS and USPSTF guidelines because all “support informed decision making starting at age 40, and screening every two years starting at age 50 (USPSTF) or 55 (ACS).”

“The fact that all guidelines are not totally in sync is not unexpected. ... The most important thing to recognize is that all of these guidelines stress that regular mammography plays an important role in breast cancer early detection, and women should be aware of its benefits and limitations, and also remain vigilant and report any breast changes,” he said.

The guidance authors reported having no conflicts of interest.

sworcester@mdedge.com

SOURCE: Qaseem A et al., Ann Intern Med. 2019. doi: 10.7326/M18-2147.

Clinicians should offer biennial mammography to screen for breast cancer in asymptomatic average-risk women aged 50-74 years and should abandon clinical breast examinations (CBE) for screening in such women of any age, according to a new guideline from the American College of Physicians.

Catherine Yeulet/Thinkstock

Further, clinicians should discuss whether to screen with mammography in average-risk women aged 40-49 years and consider potential harms and benefits, as well as patient preferences. Providers should discontinue screening average-risk women at age 75 years and women with a life expectancy of 10 years or less, Amir Qaseem, MD, PhD, of the ACP and colleagues wrote on behalf of the ACP Clinical Guidelines Committee.

The ACP guidance also addresses the varying recommendations from other organizations on the age at which to start and stop screening and on screening intervals, noting that “areas of disagreement include screening in women aged 40 to 49 years, screening in women aged 75 years or older, and recommended screening intervals,” and stresses the importance of patient input.

“Women should be informed participants in personalized decisions about breast cancer screening,” the authors wrote, adding that those under age 50 years without a clear preference for screening should not be screened.

However, the evidence shows that most average-risk women with no symptoms will benefit from mammography every other year beginning at age 50 years, they said.

The statement, published online April 8 in the Annals of Internal Medicine, was derived from a review of seven existing English-language breast cancer screening guidelines and the evidence cited in those guidelines. It’s intended to be a resource for all clinicians.

It differs from the 2017 American College of Obstetricians and Gynecologists (ACOG) guidelines in that ACOG recommends CBE and does not address screening in those with a life expectancy of less than 10 years. It also differs from the 2016 U.S. Preventive Services Task Force (USPSTF) guidelines, which make no recommendation on CBE and also do not address screening in those with a life expectancy of less than 10 years.

Other guidelines, such as those from the American College of Radiology, American Cancer Society (ACS), the Canadian Task Force on Preventive Health Care, and the National Comprehensive Cancer Network, recommend CBE, and the World Health Organization guidelines recommend CBE in low resource settings.

“Although CBE continues to be used as part of the examination of symptomatic women, data are sparse on screening asymptomatic women using CBE alone or combined with mammography,” the ACP guideline authors wrote. “The ACS recommends against CBE in average-risk women of any age because of the lack of demonstrated benefit and the potential for false-positive results.”

The guidance, which does not apply to patients with prior abnormal screening results or those at higher breast cancer risk, also includes an evidence-driven “talking points with patients” section based on frequently asked questions.

An important goal of the ACP Clinical Guidelines Committee in developing the guidance is to reduce overdiagnosis and overtreatment, which affects about 20% of women diagnosed over a 10-year period.

The committee reviewed all national guidelines published in English between January 1, 2013, and November 15, 2017, in the National Guideline Clearinghouse or Guidelines International Network library, and it also selected other guidelines commonly used in clinical practice. The committee evaluated the quality of each by using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument.

Alex Krist, MD, the USPSTF vice-chairperson, offered support for the “shift toward shared decision making that is emerging” and added it’s “part of a larger movement toward empowering people with information not only about the potential benefits but also the potential harms of screening tests.”

“In its 2016 recommendation, the Task Force found that the value of mammography increases with age, with women ages 50-74 benefiting most from screening. For women in their 40s, the Task Force also found that mammography screening every two years can be effective,” he told this publication. “We recommend that the decision to start screening should be an individual one, taking into account a woman’s health history, preferences, and how she values the different potential benefits and harms.”

Dr. Krist further noted that the USPSTF, ACP, and many others “have all affirmed that mammography is an important tool to reduce breast cancer mortality and that the benefits of mammography increase with age.”

Likewise, Robert Smith, PhD, vice president of cancer screening for the ACS, noted that the ACP guidance generally aligns with ACS and USPSTF guidelines because all “support informed decision making starting at age 40, and screening every two years starting at age 50 (USPSTF) or 55 (ACS).”

“The fact that all guidelines are not totally in sync is not unexpected. ... The most important thing to recognize is that all of these guidelines stress that regular mammography plays an important role in breast cancer early detection, and women should be aware of its benefits and limitations, and also remain vigilant and report any breast changes,” he said.

The guidance authors reported having no conflicts of interest.

sworcester@mdedge.com

SOURCE: Qaseem A et al., Ann Intern Med. 2019. doi: 10.7326/M18-2147.

Clinicians should offer biennial mammography to screen for breast cancer in asymptomatic average-risk women aged 50-74 years and should abandon clinical breast examinations (CBE) for screening in such women of any age, according to a new guideline from the American College of Physicians.

Catherine Yeulet/Thinkstock

Further, clinicians should discuss whether to screen with mammography in average-risk women aged 40-49 years and consider potential harms and benefits, as well as patient preferences. Providers should discontinue screening average-risk women at age 75 years and women with a life expectancy of 10 years or less, Amir Qaseem, MD, PhD, of the ACP and colleagues wrote on behalf of the ACP Clinical Guidelines Committee.

The ACP guidance also addresses the varying recommendations from other organizations on the age at which to start and stop screening and on screening intervals, noting that “areas of disagreement include screening in women aged 40 to 49 years, screening in women aged 75 years or older, and recommended screening intervals,” and stresses the importance of patient input.

“Women should be informed participants in personalized decisions about breast cancer screening,” the authors wrote, adding that those under age 50 years without a clear preference for screening should not be screened.

However, the evidence shows that most average-risk women with no symptoms will benefit from mammography every other year beginning at age 50 years, they said.

The statement, published online April 8 in the Annals of Internal Medicine, was derived from a review of seven existing English-language breast cancer screening guidelines and the evidence cited in those guidelines. It’s intended to be a resource for all clinicians.

It differs from the 2017 American College of Obstetricians and Gynecologists (ACOG) guidelines in that ACOG recommends CBE and does not address screening in those with a life expectancy of less than 10 years. It also differs from the 2016 U.S. Preventive Services Task Force (USPSTF) guidelines, which make no recommendation on CBE and also do not address screening in those with a life expectancy of less than 10 years.

Other guidelines, such as those from the American College of Radiology, American Cancer Society (ACS), the Canadian Task Force on Preventive Health Care, and the National Comprehensive Cancer Network, recommend CBE, and the World Health Organization guidelines recommend CBE in low resource settings.

“Although CBE continues to be used as part of the examination of symptomatic women, data are sparse on screening asymptomatic women using CBE alone or combined with mammography,” the ACP guideline authors wrote. “The ACS recommends against CBE in average-risk women of any age because of the lack of demonstrated benefit and the potential for false-positive results.”

The guidance, which does not apply to patients with prior abnormal screening results or those at higher breast cancer risk, also includes an evidence-driven “talking points with patients” section based on frequently asked questions.

An important goal of the ACP Clinical Guidelines Committee in developing the guidance is to reduce overdiagnosis and overtreatment, which affects about 20% of women diagnosed over a 10-year period.

The committee reviewed all national guidelines published in English between January 1, 2013, and November 15, 2017, in the National Guideline Clearinghouse or Guidelines International Network library, and it also selected other guidelines commonly used in clinical practice. The committee evaluated the quality of each by using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument.

Alex Krist, MD, the USPSTF vice-chairperson, offered support for the “shift toward shared decision making that is emerging” and added it’s “part of a larger movement toward empowering people with information not only about the potential benefits but also the potential harms of screening tests.”

“In its 2016 recommendation, the Task Force found that the value of mammography increases with age, with women ages 50-74 benefiting most from screening. For women in their 40s, the Task Force also found that mammography screening every two years can be effective,” he told this publication. “We recommend that the decision to start screening should be an individual one, taking into account a woman’s health history, preferences, and how she values the different potential benefits and harms.”

Dr. Krist further noted that the USPSTF, ACP, and many others “have all affirmed that mammography is an important tool to reduce breast cancer mortality and that the benefits of mammography increase with age.”

Likewise, Robert Smith, PhD, vice president of cancer screening for the ACS, noted that the ACP guidance generally aligns with ACS and USPSTF guidelines because all “support informed decision making starting at age 40, and screening every two years starting at age 50 (USPSTF) or 55 (ACS).”

“The fact that all guidelines are not totally in sync is not unexpected. ... The most important thing to recognize is that all of these guidelines stress that regular mammography plays an important role in breast cancer early detection, and women should be aware of its benefits and limitations, and also remain vigilant and report any breast changes,” he said.

The guidance authors reported having no conflicts of interest.

sworcester@mdedge.com

SOURCE: Qaseem A et al., Ann Intern Med. 2019. doi: 10.7326/M18-2147.

A small study offers a tantalizing hint that the gout drug colchicine could help reduce inflammation-related complications of metabolic syndrome.

The 3-month trial did not meet its primary endpoint – change in insulin sensitivity as measured by a glucose tolerance test – but it did hit several secondary goals, all of which were related to the inflammation that accompanies prediabetes, Jack A. Yanovski, MD, and colleagues wrote in Diabetes, Obesity, and Metabolism.

“Colchicine is well-known to have anti-inflammatory properties, although its effect on obesity-associated inflammation has not previously been investigated,” said Dr. Yanovski of the National institutes of Health and his coauthors. “Classically, it has been posited that colchicine blocks inflammation by impeding leukocyte locomotion, diapedesis, and, ultimately, recruitment to sites of inflammation. ... Recently, it has been shown that colchicine also inhibits the formation of the NLRP3 [NOD-like receptor family pyrin domain-containing 3] inflammasome, an important component of the obesity-associated inflammatory cascade.”

The NLRP3 inflammasome has been shown to play an important part in promoting the inflammatory state of obesity, the authors noted. When a cell senses danger, NLRP3 uses microtubules to create an inflammasome that then produces interleukin-1 beta gene and interleukin-18. One of colchicine’s known actions is to inhibit microtubule formation, suggesting that it could put the brakes on this process.

The study comprised 40 patients who had metabolic syndrome, significant insulin resistance, and elevated inflammatory markers. Among the exclusionary criteria were having a significant medical illness, a history of gout, and recent or current use of colchicine.

The patients were randomized to colchicine 0.6 mg or placebo twice daily for 3 months. No dietary advice was given during the study period. Of the 40 randomized patients, 37 completed the 3-month study, though none left because of adverse events.

Although there were no significant between-group differences in levels of fasting insulin, colchicine did significantly decrease inflammatory markers, compared with placebo. C-reactive protein dropped by 2.8 mg/L in the active group but increased slightly in the placebo group. The erythrocyte sedimentation rate also decreased in the colchicine group, compared with placebo (difference, –5.9 mm/hr; P = .07). The active group experienced an improvement in fasting insulin as measured by the homeostasis model assessment–estimated insulin resistance index and in glucose effectiveness, which suggests metabolic improvement.

“Larger trials are needed to investigate whether colchicine has efficacy in improving insulin resistance and/or preventing the onset of diabetes mellitus in at-risk individuals with obesity-associated inflammation,” the authors concluded.

The study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by the National Institutes of Health. None of the authors reported any disclosures or conflicts of interest relating to this study.

msullivan@mdedge.com

SOURCE: Yanovski JA et al. Diabetes Obes Metab. 2019 Mar 14. doi: 10.1111/dom.13702.

A small study offers a tantalizing hint that the gout drug colchicine could help reduce inflammation-related complications of metabolic syndrome.

The 3-month trial did not meet its primary endpoint – change in insulin sensitivity as measured by a glucose tolerance test – but it did hit several secondary goals, all of which were related to the inflammation that accompanies prediabetes, Jack A. Yanovski, MD, and colleagues wrote in Diabetes, Obesity, and Metabolism.

“Colchicine is well-known to have anti-inflammatory properties, although its effect on obesity-associated inflammation has not previously been investigated,” said Dr. Yanovski of the National institutes of Health and his coauthors. “Classically, it has been posited that colchicine blocks inflammation by impeding leukocyte locomotion, diapedesis, and, ultimately, recruitment to sites of inflammation. ... Recently, it has been shown that colchicine also inhibits the formation of the NLRP3 [NOD-like receptor family pyrin domain-containing 3] inflammasome, an important component of the obesity-associated inflammatory cascade.”

The NLRP3 inflammasome has been shown to play an important part in promoting the inflammatory state of obesity, the authors noted. When a cell senses danger, NLRP3 uses microtubules to create an inflammasome that then produces interleukin-1 beta gene and interleukin-18. One of colchicine’s known actions is to inhibit microtubule formation, suggesting that it could put the brakes on this process.

The study comprised 40 patients who had metabolic syndrome, significant insulin resistance, and elevated inflammatory markers. Among the exclusionary criteria were having a significant medical illness, a history of gout, and recent or current use of colchicine.

The patients were randomized to colchicine 0.6 mg or placebo twice daily for 3 months. No dietary advice was given during the study period. Of the 40 randomized patients, 37 completed the 3-month study, though none left because of adverse events.

Although there were no significant between-group differences in levels of fasting insulin, colchicine did significantly decrease inflammatory markers, compared with placebo. C-reactive protein dropped by 2.8 mg/L in the active group but increased slightly in the placebo group. The erythrocyte sedimentation rate also decreased in the colchicine group, compared with placebo (difference, –5.9 mm/hr; P = .07). The active group experienced an improvement in fasting insulin as measured by the homeostasis model assessment–estimated insulin resistance index and in glucose effectiveness, which suggests metabolic improvement.

“Larger trials are needed to investigate whether colchicine has efficacy in improving insulin resistance and/or preventing the onset of diabetes mellitus in at-risk individuals with obesity-associated inflammation,” the authors concluded.

The study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by the National Institutes of Health. None of the authors reported any disclosures or conflicts of interest relating to this study.

msullivan@mdedge.com

SOURCE: Yanovski JA et al. Diabetes Obes Metab. 2019 Mar 14. doi: 10.1111/dom.13702.

A small study offers a tantalizing hint that the gout drug colchicine could help reduce inflammation-related complications of metabolic syndrome.

The 3-month trial did not meet its primary endpoint – change in insulin sensitivity as measured by a glucose tolerance test – but it did hit several secondary goals, all of which were related to the inflammation that accompanies prediabetes, Jack A. Yanovski, MD, and colleagues wrote in Diabetes, Obesity, and Metabolism.

“Colchicine is well-known to have anti-inflammatory properties, although its effect on obesity-associated inflammation has not previously been investigated,” said Dr. Yanovski of the National institutes of Health and his coauthors. “Classically, it has been posited that colchicine blocks inflammation by impeding leukocyte locomotion, diapedesis, and, ultimately, recruitment to sites of inflammation. ... Recently, it has been shown that colchicine also inhibits the formation of the NLRP3 [NOD-like receptor family pyrin domain-containing 3] inflammasome, an important component of the obesity-associated inflammatory cascade.”

The NLRP3 inflammasome has been shown to play an important part in promoting the inflammatory state of obesity, the authors noted. When a cell senses danger, NLRP3 uses microtubules to create an inflammasome that then produces interleukin-1 beta gene and interleukin-18. One of colchicine’s known actions is to inhibit microtubule formation, suggesting that it could put the brakes on this process.

The study comprised 40 patients who had metabolic syndrome, significant insulin resistance, and elevated inflammatory markers. Among the exclusionary criteria were having a significant medical illness, a history of gout, and recent or current use of colchicine.

The patients were randomized to colchicine 0.6 mg or placebo twice daily for 3 months. No dietary advice was given during the study period. Of the 40 randomized patients, 37 completed the 3-month study, though none left because of adverse events.

Although there were no significant between-group differences in levels of fasting insulin, colchicine did significantly decrease inflammatory markers, compared with placebo. C-reactive protein dropped by 2.8 mg/L in the active group but increased slightly in the placebo group. The erythrocyte sedimentation rate also decreased in the colchicine group, compared with placebo (difference, –5.9 mm/hr; P = .07). The active group experienced an improvement in fasting insulin as measured by the homeostasis model assessment–estimated insulin resistance index and in glucose effectiveness, which suggests metabolic improvement.

“Larger trials are needed to investigate whether colchicine has efficacy in improving insulin resistance and/or preventing the onset of diabetes mellitus in at-risk individuals with obesity-associated inflammation,” the authors concluded.

The study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by the National Institutes of Health. None of the authors reported any disclosures or conflicts of interest relating to this study.

msullivan@mdedge.com

SOURCE: Yanovski JA et al. Diabetes Obes Metab. 2019 Mar 14. doi: 10.1111/dom.13702.

The Diagnosis: Juvenile Dermatomyositis 

Juvenile dermatomyositis (JDM) is a rare idiopathic inflammatory myopathy of childhood that is autoimmune in nature with an annual incidence ranging from 2.5 to 4.1 cases per million children. Its peak incidence is between 5 and 10 years of age, and it affects girls more than boys at a 2-fold to 5-fold greater rate.¹ Juvenile dermatomyositis is characterized by skeletal muscle weakness in the presence of distinctive rashes, including Gottron papules and heliotrope erythema. Muscle weakness typically is proximal and symmetrical, and eventually patients may have trouble rising from a seated position or lifting objects overhead. Other skin manifestations include nail fold capillary changes, calcinosis cutis, and less commonly ulcerations signifying vasculopathy of the skin.² A subset of patients will present with juvenile amyopathic dermatomyositis. These children have the characteristic skin changes without the muscle weakness or elevated muscle enzymes for more than 6 months; however, one-quarter may go on to develop mysositis.³ 

Diagnosis of JDM traditionally was based on the following 5 diagnostic criteria: characteristic skin rash, proximal muscle weakness, elevated muscle enzymes, myopathic changes on electromyogram, and typical muscle biopsy.¹ Current practice shows a broadening of diagnostic criteria using new techniques in the diagnosis of JDM. To make the diagnosis, the patient must have the characteristic skin manifestations with a minimum of 3 other criteria.⁴ A 2006 international consensus survey expanded the list of criteria to include typical findings on magnetic resonance imaging (MRI), nail fold capillaroscopy abnormalities, calcinosis, and
dysphonia.⁵  

To assess muscle disease, MRI is utilized because it is a reliable noninvasive tool to assess muscle inflammation. Muscle biopsy is only recommended if the diagnosis is unclear.⁵ The results of the MRI in our patient displayed symmetric mild fatty atrophy of the gluteus maximus muscle, as well as edema in the right rectus femoris and left vastus lateralis muscles, suggesting early findings of myositis. Muscle enzymes may not be diagnostic because  they are not always elevated at diagnosis. Our patient had a normal creatinine kinase level (92 U/L [reference range, <190 U/L]), and both aldolase and lactate dehydrogenase also were within reference range. Conversely, antinuclear antibodies frequently are positive in patients with JDM, such as in our patient at a 1:320 dilution, but are nonspecific and nondiagnostic. It is recommended to include nail fold capillaroscopy to evaluate periungual capillary changes because nailfold capillary density is a sensitive measure of both skin and muscle disease.⁵ Using dermoscopy, nail fold capillary dilation was observed in our patient. 

Other differential diagnoses can have somewhat similar clinical features to JDM. Infantile papular acrodermatitis, commonly referred to as Gianotti-Crosti syndrome, is a viral exanthem that affects children (median age, 2 years).⁶ The rash appears as monomorphous, flat-topped, pink to brown papules affecting the face, buttocks, and arms; it typically spontaneously resolves in 10 days.⁶ 

Juvenile-onset lupus is a chronic autoimmune disorder that can involve any organ system and typically affects children aged 11 to 12 years with a female preponderance. Skin manifestations are similar to adult-onset lupus and include malar rash, discoid rash, oral ulcerations, petechiae, palpable purpura, and digital telangiectasia and ulcers. ⁷ 

Juvenile scleroderma is rare connective-tissue disorder that also has multiple organ involvement. Cutaneous involvement can range from isolated morphealike plaques to diffuse sclerotic lesions with growth disturbances, contractures, and facial atrophy.⁸ 

Verrucae planae, commonly referred to as flat warts, are papules caused primarily by human papillomavirus types 3, 10, 28, and 41. Children and young adults commonly are affected, and warts can appear on the hands, as in our patient.⁶ 

Treatment of JDM depends on disease severity at initial presentation and requires a multidisciplinary approach. The mainstay of treatment is high-dose oral prednisone in combination with disease-modifying drugs such as methotrexate and cyclosporin A. Patients with more severe presentations (eg, ulcerative skin disease) or life-threatening organ involvement are treated with cyclophosphamide, usually in combination with high-dose glucocorticoids.⁹ 

Early detection with aggressive treatment is vital to reduce morbidity and mortality from organ damage and disease complications. Mortality rates have dropped to 3%¹⁰ in recent decades with the use of systemic glucocorticoids. Delayed treatment is associated with a prolonged disease course and poorer outcomes. Disease complications in children with JDM include osteoporosis, calcinosis, and intestinal perforation; however, with early treatment, children with JDM can expect full recovery and to live a normal life as compared to adults with dermatomyositis.¹⁰ 

Prior to our patient's diagnosis, the family was assigned to move to an overseas location through the US Military with no direct access to advanced medical care. Early detection and diagnosis of JDM through an astute clinical examination allowed the patient and her family to remain in the continental United States to continue receiving specialty care.   
 

The Diagnosis: Juvenile Dermatomyositis 

Juvenile dermatomyositis (JDM) is a rare idiopathic inflammatory myopathy of childhood that is autoimmune in nature with an annual incidence ranging from 2.5 to 4.1 cases per million children. Its peak incidence is between 5 and 10 years of age, and it affects girls more than boys at a 2-fold to 5-fold greater rate.¹ Juvenile dermatomyositis is characterized by skeletal muscle weakness in the presence of distinctive rashes, including Gottron papules and heliotrope erythema. Muscle weakness typically is proximal and symmetrical, and eventually patients may have trouble rising from a seated position or lifting objects overhead. Other skin manifestations include nail fold capillary changes, calcinosis cutis, and less commonly ulcerations signifying vasculopathy of the skin.² A subset of patients will present with juvenile amyopathic dermatomyositis. These children have the characteristic skin changes without the muscle weakness or elevated muscle enzymes for more than 6 months; however, one-quarter may go on to develop mysositis.³ 

Diagnosis of JDM traditionally was based on the following 5 diagnostic criteria: characteristic skin rash, proximal muscle weakness, elevated muscle enzymes, myopathic changes on electromyogram, and typical muscle biopsy.¹ Current practice shows a broadening of diagnostic criteria using new techniques in the diagnosis of JDM. To make the diagnosis, the patient must have the characteristic skin manifestations with a minimum of 3 other criteria.⁴ A 2006 international consensus survey expanded the list of criteria to include typical findings on magnetic resonance imaging (MRI), nail fold capillaroscopy abnormalities, calcinosis, and
dysphonia.⁵  

To assess muscle disease, MRI is utilized because it is a reliable noninvasive tool to assess muscle inflammation. Muscle biopsy is only recommended if the diagnosis is unclear.⁵ The results of the MRI in our patient displayed symmetric mild fatty atrophy of the gluteus maximus muscle, as well as edema in the right rectus femoris and left vastus lateralis muscles, suggesting early findings of myositis. Muscle enzymes may not be diagnostic because  they are not always elevated at diagnosis. Our patient had a normal creatinine kinase level (92 U/L [reference range, <190 U/L]), and both aldolase and lactate dehydrogenase also were within reference range. Conversely, antinuclear antibodies frequently are positive in patients with JDM, such as in our patient at a 1:320 dilution, but are nonspecific and nondiagnostic. It is recommended to include nail fold capillaroscopy to evaluate periungual capillary changes because nailfold capillary density is a sensitive measure of both skin and muscle disease.⁵ Using dermoscopy, nail fold capillary dilation was observed in our patient. 

Other differential diagnoses can have somewhat similar clinical features to JDM. Infantile papular acrodermatitis, commonly referred to as Gianotti-Crosti syndrome, is a viral exanthem that affects children (median age, 2 years).⁶ The rash appears as monomorphous, flat-topped, pink to brown papules affecting the face, buttocks, and arms; it typically spontaneously resolves in 10 days.⁶ 

Juvenile-onset lupus is a chronic autoimmune disorder that can involve any organ system and typically affects children aged 11 to 12 years with a female preponderance. Skin manifestations are similar to adult-onset lupus and include malar rash, discoid rash, oral ulcerations, petechiae, palpable purpura, and digital telangiectasia and ulcers. ⁷ 

Juvenile scleroderma is rare connective-tissue disorder that also has multiple organ involvement. Cutaneous involvement can range from isolated morphealike plaques to diffuse sclerotic lesions with growth disturbances, contractures, and facial atrophy.⁸ 

Verrucae planae, commonly referred to as flat warts, are papules caused primarily by human papillomavirus types 3, 10, 28, and 41. Children and young adults commonly are affected, and warts can appear on the hands, as in our patient.⁶ 

Treatment of JDM depends on disease severity at initial presentation and requires a multidisciplinary approach. The mainstay of treatment is high-dose oral prednisone in combination with disease-modifying drugs such as methotrexate and cyclosporin A. Patients with more severe presentations (eg, ulcerative skin disease) or life-threatening organ involvement are treated with cyclophosphamide, usually in combination with high-dose glucocorticoids.⁹ 

Early detection with aggressive treatment is vital to reduce morbidity and mortality from organ damage and disease complications. Mortality rates have dropped to 3%¹⁰ in recent decades with the use of systemic glucocorticoids. Delayed treatment is associated with a prolonged disease course and poorer outcomes. Disease complications in children with JDM include osteoporosis, calcinosis, and intestinal perforation; however, with early treatment, children with JDM can expect full recovery and to live a normal life as compared to adults with dermatomyositis.¹⁰ 

Prior to our patient's diagnosis, the family was assigned to move to an overseas location through the US Military with no direct access to advanced medical care. Early detection and diagnosis of JDM through an astute clinical examination allowed the patient and her family to remain in the continental United States to continue receiving specialty care.   
 

The Diagnosis: Juvenile Dermatomyositis 

Juvenile dermatomyositis (JDM) is a rare idiopathic inflammatory myopathy of childhood that is autoimmune in nature with an annual incidence ranging from 2.5 to 4.1 cases per million children. Its peak incidence is between 5 and 10 years of age, and it affects girls more than boys at a 2-fold to 5-fold greater rate.¹ Juvenile dermatomyositis is characterized by skeletal muscle weakness in the presence of distinctive rashes, including Gottron papules and heliotrope erythema. Muscle weakness typically is proximal and symmetrical, and eventually patients may have trouble rising from a seated position or lifting objects overhead. Other skin manifestations include nail fold capillary changes, calcinosis cutis, and less commonly ulcerations signifying vasculopathy of the skin.² A subset of patients will present with juvenile amyopathic dermatomyositis. These children have the characteristic skin changes without the muscle weakness or elevated muscle enzymes for more than 6 months; however, one-quarter may go on to develop mysositis.³ 

Diagnosis of JDM traditionally was based on the following 5 diagnostic criteria: characteristic skin rash, proximal muscle weakness, elevated muscle enzymes, myopathic changes on electromyogram, and typical muscle biopsy.¹ Current practice shows a broadening of diagnostic criteria using new techniques in the diagnosis of JDM. To make the diagnosis, the patient must have the characteristic skin manifestations with a minimum of 3 other criteria.⁴ A 2006 international consensus survey expanded the list of criteria to include typical findings on magnetic resonance imaging (MRI), nail fold capillaroscopy abnormalities, calcinosis, and
dysphonia.⁵  

To assess muscle disease, MRI is utilized because it is a reliable noninvasive tool to assess muscle inflammation. Muscle biopsy is only recommended if the diagnosis is unclear.⁵ The results of the MRI in our patient displayed symmetric mild fatty atrophy of the gluteus maximus muscle, as well as edema in the right rectus femoris and left vastus lateralis muscles, suggesting early findings of myositis. Muscle enzymes may not be diagnostic because  they are not always elevated at diagnosis. Our patient had a normal creatinine kinase level (92 U/L [reference range, <190 U/L]), and both aldolase and lactate dehydrogenase also were within reference range. Conversely, antinuclear antibodies frequently are positive in patients with JDM, such as in our patient at a 1:320 dilution, but are nonspecific and nondiagnostic. It is recommended to include nail fold capillaroscopy to evaluate periungual capillary changes because nailfold capillary density is a sensitive measure of both skin and muscle disease.⁵ Using dermoscopy, nail fold capillary dilation was observed in our patient. 

Other differential diagnoses can have somewhat similar clinical features to JDM. Infantile papular acrodermatitis, commonly referred to as Gianotti-Crosti syndrome, is a viral exanthem that affects children (median age, 2 years).⁶ The rash appears as monomorphous, flat-topped, pink to brown papules affecting the face, buttocks, and arms; it typically spontaneously resolves in 10 days.⁶ 

Juvenile-onset lupus is a chronic autoimmune disorder that can involve any organ system and typically affects children aged 11 to 12 years with a female preponderance. Skin manifestations are similar to adult-onset lupus and include malar rash, discoid rash, oral ulcerations, petechiae, palpable purpura, and digital telangiectasia and ulcers. ⁷ 

Juvenile scleroderma is rare connective-tissue disorder that also has multiple organ involvement. Cutaneous involvement can range from isolated morphealike plaques to diffuse sclerotic lesions with growth disturbances, contractures, and facial atrophy.⁸ 

Verrucae planae, commonly referred to as flat warts, are papules caused primarily by human papillomavirus types 3, 10, 28, and 41. Children and young adults commonly are affected, and warts can appear on the hands, as in our patient.⁶ 

Treatment of JDM depends on disease severity at initial presentation and requires a multidisciplinary approach. The mainstay of treatment is high-dose oral prednisone in combination with disease-modifying drugs such as methotrexate and cyclosporin A. Patients with more severe presentations (eg, ulcerative skin disease) or life-threatening organ involvement are treated with cyclophosphamide, usually in combination with high-dose glucocorticoids.⁹ 

Early detection with aggressive treatment is vital to reduce morbidity and mortality from organ damage and disease complications. Mortality rates have dropped to 3%¹⁰ in recent decades with the use of systemic glucocorticoids. Delayed treatment is associated with a prolonged disease course and poorer outcomes. Disease complications in children with JDM include osteoporosis, calcinosis, and intestinal perforation; however, with early treatment, children with JDM can expect full recovery and to live a normal life as compared to adults with dermatomyositis.¹⁰ 

Prior to our patient's diagnosis, the family was assigned to move to an overseas location through the US Military with no direct access to advanced medical care. Early detection and diagnosis of JDM through an astute clinical examination allowed the patient and her family to remain in the continental United States to continue receiving specialty care.   
 

WASHINGTON – Hidradenitis suppurativa (HS) management should be individualized in patients, with consideration of their comorbidities, and therapies should be layered and rotated to improve efficacy, Ginette Okoye, MD, said at the annual meeting of the American Academy of Dermatology.

Jeff Craven/MDedge News

Pregnant women with HS can benefit from treatment with metformin, but dermatologists should consult with the patient’s obstetrician-gynecologist as the medication is classified as pregnancy category B. In addition, metformin should not be given to patients with a glomerular filtration rate (GFR) less than 45 mL/min, and long-term use is associated with low vitamin B₁₂ levels, she said.

“I often layer this with the antibiotic therapy, so my patient may be on clindamycin, rifampin, and metformin,” said Dr. Okoye. “If they are, you can give them a much lower dose of metformin since rifampin increases the plasma concentration of metformin.”

Patients with HS may also respond well to finasteride at doses between 1 mg and 5 mg once daily, an off-label use for this medication. Finasteride, which targets type 2 5-alpha-reductase, reduces the levels of dihydrotestosterone within hair follicles, which can improve HS symptoms, she said. However, she discusses potential side effects of finasteride use with patients, which include reduced libido, abnormal ejaculation, breast tenderness, prostate cancer, and depression. She also referred to postmarketing data suggesting that finasteride can lead to post-finasteride syndrome, characterized by symptoms that include depression and anhedonia, even long after stopping treatment, she said.

“I still think that it’s worth a try,” Dr. Okoye commented. “Many of our HS patients already are dealing with depression because of their disease. ... In 3 months, we talk about their symptoms, [and] make sure that they’re feeling okay before continuing.”

While finasteride is not appropriate for women of childbearing potential (pregnancy category X), it can be an option for women with HS who are of childbearing age but are not at risk for becoming pregnant, Dr. Okoye added, which can be determined by discussing a patient’s family planning goals. For example, she said, “if you have a woman of childbearing age but she’s in a same-sex relationship and has no intention of having children, then maybe finasteride is an option for her.”

The mineralocorticoid- and aldosterone-receptor antagonist spironolactone, used off label for acne treatment, also has antiandrogenic properties and is an option for patients with HS “at the higher end of the dosing spectrum” with 100-200 mg daily. However, Dr. Okoye referred to a recently published single-center retrospective study that showed a low daily dose of 75 mg was effective for HS (J Am Acad Dermatol. 2019 Jan;80[1]:114-9).

While spironolactone increases the risk of hyperkalemia, in patients with no preexisting renal disease under 50 years of age, monitoring is not necessary because there is little to no risk of clinical hyperkalemia in these patients, she said. Combining spironolactone or finasteride with OCs may increase antiandrogenic activity, she noted.

The data on effectiveness of hormonal contraceptives are mixed with regard to treatment of HS, with some studies showing benefit or worsening of the disease with OC use. “I think one of the reasons the data is so ‘dirty’ is because OCs range widely in terms of their ingredients and in terms of how androgenic their progesterones are,” Dr. Okoye commented.

OCs increase the risk of venous thromboembolism (VTE), but Dr. Okoye noted the risk is less than a patient would experience during pregnancy. “When you talk to dermatologists, there are two camps: some dermatologists who are very comfortable prescribing OCs, and dermatologists who prefer not to, given the risk of VTEs,” she said. However, risk should also be applied to patient population and location, she noted.

“If you are in an area [where] you serve a patient population that has fewer options for access to care, and if you don’t prescribe the OCs, those patients have to wait several months before getting on therapy, said Dr. Okoye. “Maybe that’s a case where you might want to start the OC [with] one or two refills while they find an OB, but it’s really up to you and your risk aversion.”

Dietary factors may also contribute to HS, but more studies are needed to analyze how sugar and carbohydrates contribute to the condition. Instead of taking for granted that a patient will understand what reducing dietary carbohydrate and sugar intake means, Dr. Okoye said, “I like to get very specific; ask them what they’re drinking on a daily basis.”

With regard to weight loss, there is little to link significant weight loss and symptom improvement. However, weight loss could help with comorbid conditions in patients with HS, like metabolic syndrome, and subsequent skin reduction may reduce friction of intertriginous areas, she pointed out.

Dr. Okoye reports receiving grants and/or research funding from Eli Lilly.

WASHINGTON – Hidradenitis suppurativa (HS) management should be individualized in patients, with consideration of their comorbidities, and therapies should be layered and rotated to improve efficacy, Ginette Okoye, MD, said at the annual meeting of the American Academy of Dermatology.

Jeff Craven/MDedge News

Pregnant women with HS can benefit from treatment with metformin, but dermatologists should consult with the patient’s obstetrician-gynecologist as the medication is classified as pregnancy category B. In addition, metformin should not be given to patients with a glomerular filtration rate (GFR) less than 45 mL/min, and long-term use is associated with low vitamin B₁₂ levels, she said.

“I often layer this with the antibiotic therapy, so my patient may be on clindamycin, rifampin, and metformin,” said Dr. Okoye. “If they are, you can give them a much lower dose of metformin since rifampin increases the plasma concentration of metformin.”

Patients with HS may also respond well to finasteride at doses between 1 mg and 5 mg once daily, an off-label use for this medication. Finasteride, which targets type 2 5-alpha-reductase, reduces the levels of dihydrotestosterone within hair follicles, which can improve HS symptoms, she said. However, she discusses potential side effects of finasteride use with patients, which include reduced libido, abnormal ejaculation, breast tenderness, prostate cancer, and depression. She also referred to postmarketing data suggesting that finasteride can lead to post-finasteride syndrome, characterized by symptoms that include depression and anhedonia, even long after stopping treatment, she said.

“I still think that it’s worth a try,” Dr. Okoye commented. “Many of our HS patients already are dealing with depression because of their disease. ... In 3 months, we talk about their symptoms, [and] make sure that they’re feeling okay before continuing.”

While finasteride is not appropriate for women of childbearing potential (pregnancy category X), it can be an option for women with HS who are of childbearing age but are not at risk for becoming pregnant, Dr. Okoye added, which can be determined by discussing a patient’s family planning goals. For example, she said, “if you have a woman of childbearing age but she’s in a same-sex relationship and has no intention of having children, then maybe finasteride is an option for her.”

The mineralocorticoid- and aldosterone-receptor antagonist spironolactone, used off label for acne treatment, also has antiandrogenic properties and is an option for patients with HS “at the higher end of the dosing spectrum” with 100-200 mg daily. However, Dr. Okoye referred to a recently published single-center retrospective study that showed a low daily dose of 75 mg was effective for HS (J Am Acad Dermatol. 2019 Jan;80[1]:114-9).

While spironolactone increases the risk of hyperkalemia, in patients with no preexisting renal disease under 50 years of age, monitoring is not necessary because there is little to no risk of clinical hyperkalemia in these patients, she said. Combining spironolactone or finasteride with OCs may increase antiandrogenic activity, she noted.

The data on effectiveness of hormonal contraceptives are mixed with regard to treatment of HS, with some studies showing benefit or worsening of the disease with OC use. “I think one of the reasons the data is so ‘dirty’ is because OCs range widely in terms of their ingredients and in terms of how androgenic their progesterones are,” Dr. Okoye commented.

OCs increase the risk of venous thromboembolism (VTE), but Dr. Okoye noted the risk is less than a patient would experience during pregnancy. “When you talk to dermatologists, there are two camps: some dermatologists who are very comfortable prescribing OCs, and dermatologists who prefer not to, given the risk of VTEs,” she said. However, risk should also be applied to patient population and location, she noted.

“If you are in an area [where] you serve a patient population that has fewer options for access to care, and if you don’t prescribe the OCs, those patients have to wait several months before getting on therapy, said Dr. Okoye. “Maybe that’s a case where you might want to start the OC [with] one or two refills while they find an OB, but it’s really up to you and your risk aversion.”

Dietary factors may also contribute to HS, but more studies are needed to analyze how sugar and carbohydrates contribute to the condition. Instead of taking for granted that a patient will understand what reducing dietary carbohydrate and sugar intake means, Dr. Okoye said, “I like to get very specific; ask them what they’re drinking on a daily basis.”

With regard to weight loss, there is little to link significant weight loss and symptom improvement. However, weight loss could help with comorbid conditions in patients with HS, like metabolic syndrome, and subsequent skin reduction may reduce friction of intertriginous areas, she pointed out.

Dr. Okoye reports receiving grants and/or research funding from Eli Lilly.

WASHINGTON – Hidradenitis suppurativa (HS) management should be individualized in patients, with consideration of their comorbidities, and therapies should be layered and rotated to improve efficacy, Ginette Okoye, MD, said at the annual meeting of the American Academy of Dermatology.

Jeff Craven/MDedge News

Pregnant women with HS can benefit from treatment with metformin, but dermatologists should consult with the patient’s obstetrician-gynecologist as the medication is classified as pregnancy category B. In addition, metformin should not be given to patients with a glomerular filtration rate (GFR) less than 45 mL/min, and long-term use is associated with low vitamin B₁₂ levels, she said.

“I often layer this with the antibiotic therapy, so my patient may be on clindamycin, rifampin, and metformin,” said Dr. Okoye. “If they are, you can give them a much lower dose of metformin since rifampin increases the plasma concentration of metformin.”

Patients with HS may also respond well to finasteride at doses between 1 mg and 5 mg once daily, an off-label use for this medication. Finasteride, which targets type 2 5-alpha-reductase, reduces the levels of dihydrotestosterone within hair follicles, which can improve HS symptoms, she said. However, she discusses potential side effects of finasteride use with patients, which include reduced libido, abnormal ejaculation, breast tenderness, prostate cancer, and depression. She also referred to postmarketing data suggesting that finasteride can lead to post-finasteride syndrome, characterized by symptoms that include depression and anhedonia, even long after stopping treatment, she said.

“I still think that it’s worth a try,” Dr. Okoye commented. “Many of our HS patients already are dealing with depression because of their disease. ... In 3 months, we talk about their symptoms, [and] make sure that they’re feeling okay before continuing.”

While finasteride is not appropriate for women of childbearing potential (pregnancy category X), it can be an option for women with HS who are of childbearing age but are not at risk for becoming pregnant, Dr. Okoye added, which can be determined by discussing a patient’s family planning goals. For example, she said, “if you have a woman of childbearing age but she’s in a same-sex relationship and has no intention of having children, then maybe finasteride is an option for her.”

The mineralocorticoid- and aldosterone-receptor antagonist spironolactone, used off label for acne treatment, also has antiandrogenic properties and is an option for patients with HS “at the higher end of the dosing spectrum” with 100-200 mg daily. However, Dr. Okoye referred to a recently published single-center retrospective study that showed a low daily dose of 75 mg was effective for HS (J Am Acad Dermatol. 2019 Jan;80[1]:114-9).

While spironolactone increases the risk of hyperkalemia, in patients with no preexisting renal disease under 50 years of age, monitoring is not necessary because there is little to no risk of clinical hyperkalemia in these patients, she said. Combining spironolactone or finasteride with OCs may increase antiandrogenic activity, she noted.

The data on effectiveness of hormonal contraceptives are mixed with regard to treatment of HS, with some studies showing benefit or worsening of the disease with OC use. “I think one of the reasons the data is so ‘dirty’ is because OCs range widely in terms of their ingredients and in terms of how androgenic their progesterones are,” Dr. Okoye commented.

OCs increase the risk of venous thromboembolism (VTE), but Dr. Okoye noted the risk is less than a patient would experience during pregnancy. “When you talk to dermatologists, there are two camps: some dermatologists who are very comfortable prescribing OCs, and dermatologists who prefer not to, given the risk of VTEs,” she said. However, risk should also be applied to patient population and location, she noted.

“If you are in an area [where] you serve a patient population that has fewer options for access to care, and if you don’t prescribe the OCs, those patients have to wait several months before getting on therapy, said Dr. Okoye. “Maybe that’s a case where you might want to start the OC [with] one or two refills while they find an OB, but it’s really up to you and your risk aversion.”

Dietary factors may also contribute to HS, but more studies are needed to analyze how sugar and carbohydrates contribute to the condition. Instead of taking for granted that a patient will understand what reducing dietary carbohydrate and sugar intake means, Dr. Okoye said, “I like to get very specific; ask them what they’re drinking on a daily basis.”

With regard to weight loss, there is little to link significant weight loss and symptom improvement. However, weight loss could help with comorbid conditions in patients with HS, like metabolic syndrome, and subsequent skin reduction may reduce friction of intertriginous areas, she pointed out.

Dr. Okoye reports receiving grants and/or research funding from Eli Lilly.

Altered mental status (AMS) is a common presentation to the emergency department (ED) for older patients and is often due to underlying drug-associated adverse effects (AEs), medical or psychiatric illness, or neurologic disease. EDs often have protocols for diagnosing and managing AMS to assess the underlying etiology. A formal assessment with a full history and physical examination is paramount to diagnosing the cause of AMS.

Oral metronidazole is a commonly used antibiotic for anaerobic bacterial infections and Clostridium difficile-associated diarrhea and colitis.¹Metronidazole produces cytotoxic intermediates that cause DNA strand breakage and destabilization, resulting in bactericidal activity in host cells.²Common AEs include gastrointestinal symptoms such as nausea, vomiting, and diarrhea; less common AEs can involve the nervous system and include seizures, peripheral neuropathy, dizziness, ataxia, and encephalopathy.^3,4A pattern of magnetic resonance image (MRI) abnormalities typically located at the cerebellar dentate nucleus midbrain, dorsal pons, medulla, and splenium of the corpus callosum have been associated with metronidazole usage.⁵

Hyperbaric oxygen therapy (HBOT) is a treatment modality used as the primary therapy for decompression sickness, arterial gas embolism, and carbon monoxide poisoning. HBOT is used as adjuvant therapy for osteonecrosis caused by radiation or bisphosphonate use.^6,7 HBOT increases the partial pressure of oxygen in plasma and increases the amount of oxygen delivered to tissues throughout the body.⁸Hyperoxia, defined as an elevated partial pressure of oxygen leading to excess oxygenation to tissues and organs, increases production of reactive oxygen and nitrogen species, which are signaling factors in a variety of pathways that stimulate angiogenesis.⁸ AEs of HBOT include barotrauma-related injuries and oxygen toxicity, such as respiratory distress or central nervous system (CNS) symptoms.⁹ Severe CNS AEs occur in 1% to 2% of patients undergoing therapy and manifest as generalized tonic-clonic seizures, typically in patients with preexisting neurologic disorders, brain injury, or lowered seizure threshold.^7,8,10 There have been no documented incidences of HBOT inducing acute encephalopathy.

Case Presentation

A 63-year-old male smoker with no history of alcohol use presented to the ED with an acute onset of lightheadedness, confusion, and poor coordination following his second HBOT for radiation-induced osteonecrosis of the mandible. The patient reported chronic, slowly progressive pain and numbness of the feet that began 4 years earlier. He noted marked worsening of pain and difficulty standing and walking 3 to 4 months prior to presentation.

Ten years prior, the patient was diagnosed with cancer of the right tonsil. A tonsillectomy with wide margins was performed, followed by 35 rounds of radiation treatment and 2 rounds of chemotherapy with cisplatin.

In May 2017, the patient presented with a lump in the right cheek that was diagnosed as osteonecrosis of the mandible. An oral surgeon prescribed metronidazole 500 mg qid and amoxicillin 500 mg tid. The patient was adherent until presentation in November 2017. Following lack of improvement of the osteonecrosis from antibiotic therapy, oral surgery was planned, and the patient was referred for HBOT with a planned 20 HBOT preoperative treatments and 10 postoperative treatments.

Following his first 2-hour HBOT treatment on November 13, 2017, the patient complained of light-headedness, confusion, and incoordination. While driving on a familiar route to his home, he collided with a tree that was 6 feet from the curb. The patient attempted to drive another vehicle later that day, resulting in a second motor vehicle accident. There was no significant injury reported in either accident.

His partner described the patient’s episode of disorientation lasting 6 to 8 hours, during which he “looked drunk” and was unable to sit in a chair without falling. The following morning, the patient had improved mental status but had not returned to baseline. His second HBOT treatment took place that day, and again, the patient acutely experienced light-headedness and confusion following completion. Therapy was suspended, and the patient was referred to the ED for further evaluation. Mild facial asymmetry without weakness, decreased sensation from toes to knees bilaterally, and absent Achilles reflexes bilaterally were found on neurologic examination. He exhibited past-pointing on finger-to-nose testing bilaterally. He was able to ambulate independently, but he could not perform tandem gait.

An MRI of the brain showed abnormal T2 hyperintensity found bilaterally at the dentate nuclei and inferior colliculi. The splenium of the corpus callosum also showed mild involvement with hyperintense lesions. Laboratory tests of the patient’s complete blood count; comprehensive metabolic panel; vitamins B₁, B₆, B₁₂; and folic acid levels had no notable abnormalities and were within normal limits.

Metronidazole and HBOT therapy were discontinued, and all of the patient’s symptoms resolved within 2 weeks. A repeat examination and MRI performed 1 month later showed resolution of all the patient’s clinical findings and MRI abnormalities. HBOT was resumed without the recurrence of previously described symptoms.

Discussion

This patient’s encephalopathic symptoms correlate temporally with the onset of HBOT. There is no medical literature suggesting a relationship between HBOT and encephalopathic symptoms with MRI abnormalities, and in fact, some studies suggest HBOT as a treatment for hypoxic-ischemic encephalopathy in neonates.¹¹ This led us to believe that the HBOT may have exacerbated some underlying condition, evidenced by the specific MRI findings of T2 fluid-attenuated inversion recovery (FLAIR) hyperintensities in the dentate nuclei and inferior colliculi (Figures 1 and 2). 

Differential diagnoses for T2 hyperintense lesions in the dentate nuclei include metronidazole toxicity, acute Wernicke encephalopathy (WE), and methyl bromide intoxication. Diseases that would have presented in infancy with similar MRI findings (Canavan disease, maple-syrup urine disease, and glutaric aciduria type 1) were not considered plausible.^12-14 

Despite his denial of alcohol use, the patient was at risk for malnutrition secondary to his mandibular lesion and difficulty eating. Clinically, he presented with episodes of confusion and ataxia, consistent with 2 of the classic triad of symptoms of WE (no ocular abnormalities noted on exam). Typical MRI findings in WE include signal intensity alterations (including T2 hyperintensities) in the medial thalami, mammillary bodies, collicular bodies, and periaqueductal and periventricular regions.^14,15 Atypical MRI findings in WE include symmetric signal intensity changes in the cerebellum, dentate nuclei, caudate nuclei, red nuclei, cranial nerve nuclei, and splenium.¹⁴ Of note, atypical MRI findings were more common in patients without alcohol use disorders and WE, and typical MRI findings were more common in patients with alcohol use disorders.¹⁴ However, this patient’s report of no alcohol use and the serum thiamine level being within normal limits (173 nmol/L; range 78-185 nmol/L) made acute WE less likely than metronidonazale-induced encephalopathy (MIE).

The most common neurologic AE of metronidazole is distal symmetric sensory polyneuropathy, which also can have motor or autonomic features.^16,17 While our patient had a history of peripheral neuropathy, he noted marked worsening of foot pain 3 months after initiating metronidazole therapy. A potential mechanism involves metronidazole or its cytotoxic intermediates binding neuronal ribonucleic acids, thus inhibiting protein synthesis and resulting in degenerative neuronal changes and reversible axonal swelling (as opposed to the DNA interference attributed to the drug’s mechanism of bactericidal action).¹⁸ Neuropathies may result from prolonged high-dose metronidazole therapy (cumulative dose > 42 g),³ but they also have been seen in short-term use of high dosages.¹⁷

CNS AEs are much rarer and are thought to be associated with metronidazole’s ability to cross the blood-brain barrier. These patients present as a toxic encephalopathy with cerebellar dysfunction (dysarthria, ataxia) as the most common presentation, followed by AMS and seizures.⁴ Our patient presented with acute confusion and ataxia. Animal studies suggest that γ-aminobutyric acid (GABA) receptor modulation in the cerebellar and vestibular systems may contribute to this neurotoxicity, but no definitive mechanism of injury has been found.¹⁹

On MRI, MIE most commonly presents with hyperintense lesions in the bilateral cerebellar dentate nucleus on T2-weighted and FLAIR images.^5,20 The midbrain, dorsal pons, medulla, and corpus callosum also can show increased signal intensity.⁵ This AE does not seem to be dose- or duration-dependent, and most cases report complete or partial resolution of symptoms following discontinuation of the drug, though this is not absolute.^4,13,21 The patient’s MRI findings were highly consistent with MIE (Figure 2).

Conclusion

This patient’s highly specific MRI findings, neurologic examination consistent with confusion, ataxia, length-dependent sensory neuropathy, and 360-g cumulative dose of metronidazole over the previous 6 months suggest he experienced MIE. The mechanism of how HBOT precipitated the patient’s altered mental status, incoordination, and worsening of peripheral neuropathy is unknown. Although encephalopathy with MRI abnormalities as described is not a reported AE of HBOT, it may be unrecognized. It is possible that without HBOT the patient would have remained asymptomatic apart from his peripheral neuropathy.

We propose HBOT may exacerbate or increase the risk of a patient developing MIE. Our patient was able to safely resume HBOT after metronidazole was discontinued, suggesting that the combination was the causation for the development of encephalopathy. We do not believe any similar cases have been reported.

Altered mental status (AMS) is a common presentation to the emergency department (ED) for older patients and is often due to underlying drug-associated adverse effects (AEs), medical or psychiatric illness, or neurologic disease. EDs often have protocols for diagnosing and managing AMS to assess the underlying etiology. A formal assessment with a full history and physical examination is paramount to diagnosing the cause of AMS.

Oral metronidazole is a commonly used antibiotic for anaerobic bacterial infections and Clostridium difficile-associated diarrhea and colitis.¹Metronidazole produces cytotoxic intermediates that cause DNA strand breakage and destabilization, resulting in bactericidal activity in host cells.²Common AEs include gastrointestinal symptoms such as nausea, vomiting, and diarrhea; less common AEs can involve the nervous system and include seizures, peripheral neuropathy, dizziness, ataxia, and encephalopathy.^3,4A pattern of magnetic resonance image (MRI) abnormalities typically located at the cerebellar dentate nucleus midbrain, dorsal pons, medulla, and splenium of the corpus callosum have been associated with metronidazole usage.⁵

Hyperbaric oxygen therapy (HBOT) is a treatment modality used as the primary therapy for decompression sickness, arterial gas embolism, and carbon monoxide poisoning. HBOT is used as adjuvant therapy for osteonecrosis caused by radiation or bisphosphonate use.^6,7 HBOT increases the partial pressure of oxygen in plasma and increases the amount of oxygen delivered to tissues throughout the body.⁸Hyperoxia, defined as an elevated partial pressure of oxygen leading to excess oxygenation to tissues and organs, increases production of reactive oxygen and nitrogen species, which are signaling factors in a variety of pathways that stimulate angiogenesis.⁸ AEs of HBOT include barotrauma-related injuries and oxygen toxicity, such as respiratory distress or central nervous system (CNS) symptoms.⁹ Severe CNS AEs occur in 1% to 2% of patients undergoing therapy and manifest as generalized tonic-clonic seizures, typically in patients with preexisting neurologic disorders, brain injury, or lowered seizure threshold.^7,8,10 There have been no documented incidences of HBOT inducing acute encephalopathy.

Case Presentation

A 63-year-old male smoker with no history of alcohol use presented to the ED with an acute onset of lightheadedness, confusion, and poor coordination following his second HBOT for radiation-induced osteonecrosis of the mandible. The patient reported chronic, slowly progressive pain and numbness of the feet that began 4 years earlier. He noted marked worsening of pain and difficulty standing and walking 3 to 4 months prior to presentation.

Ten years prior, the patient was diagnosed with cancer of the right tonsil. A tonsillectomy with wide margins was performed, followed by 35 rounds of radiation treatment and 2 rounds of chemotherapy with cisplatin.

In May 2017, the patient presented with a lump in the right cheek that was diagnosed as osteonecrosis of the mandible. An oral surgeon prescribed metronidazole 500 mg qid and amoxicillin 500 mg tid. The patient was adherent until presentation in November 2017. Following lack of improvement of the osteonecrosis from antibiotic therapy, oral surgery was planned, and the patient was referred for HBOT with a planned 20 HBOT preoperative treatments and 10 postoperative treatments.

Following his first 2-hour HBOT treatment on November 13, 2017, the patient complained of light-headedness, confusion, and incoordination. While driving on a familiar route to his home, he collided with a tree that was 6 feet from the curb. The patient attempted to drive another vehicle later that day, resulting in a second motor vehicle accident. There was no significant injury reported in either accident.

His partner described the patient’s episode of disorientation lasting 6 to 8 hours, during which he “looked drunk” and was unable to sit in a chair without falling. The following morning, the patient had improved mental status but had not returned to baseline. His second HBOT treatment took place that day, and again, the patient acutely experienced light-headedness and confusion following completion. Therapy was suspended, and the patient was referred to the ED for further evaluation. Mild facial asymmetry without weakness, decreased sensation from toes to knees bilaterally, and absent Achilles reflexes bilaterally were found on neurologic examination. He exhibited past-pointing on finger-to-nose testing bilaterally. He was able to ambulate independently, but he could not perform tandem gait.

An MRI of the brain showed abnormal T2 hyperintensity found bilaterally at the dentate nuclei and inferior colliculi. The splenium of the corpus callosum also showed mild involvement with hyperintense lesions. Laboratory tests of the patient’s complete blood count; comprehensive metabolic panel; vitamins B₁, B₆, B₁₂; and folic acid levels had no notable abnormalities and were within normal limits.

Metronidazole and HBOT therapy were discontinued, and all of the patient’s symptoms resolved within 2 weeks. A repeat examination and MRI performed 1 month later showed resolution of all the patient’s clinical findings and MRI abnormalities. HBOT was resumed without the recurrence of previously described symptoms.

Discussion

This patient’s encephalopathic symptoms correlate temporally with the onset of HBOT. There is no medical literature suggesting a relationship between HBOT and encephalopathic symptoms with MRI abnormalities, and in fact, some studies suggest HBOT as a treatment for hypoxic-ischemic encephalopathy in neonates.¹¹ This led us to believe that the HBOT may have exacerbated some underlying condition, evidenced by the specific MRI findings of T2 fluid-attenuated inversion recovery (FLAIR) hyperintensities in the dentate nuclei and inferior colliculi (Figures 1 and 2). 

Differential diagnoses for T2 hyperintense lesions in the dentate nuclei include metronidazole toxicity, acute Wernicke encephalopathy (WE), and methyl bromide intoxication. Diseases that would have presented in infancy with similar MRI findings (Canavan disease, maple-syrup urine disease, and glutaric aciduria type 1) were not considered plausible.^12-14 

Despite his denial of alcohol use, the patient was at risk for malnutrition secondary to his mandibular lesion and difficulty eating. Clinically, he presented with episodes of confusion and ataxia, consistent with 2 of the classic triad of symptoms of WE (no ocular abnormalities noted on exam). Typical MRI findings in WE include signal intensity alterations (including T2 hyperintensities) in the medial thalami, mammillary bodies, collicular bodies, and periaqueductal and periventricular regions.^14,15 Atypical MRI findings in WE include symmetric signal intensity changes in the cerebellum, dentate nuclei, caudate nuclei, red nuclei, cranial nerve nuclei, and splenium.¹⁴ Of note, atypical MRI findings were more common in patients without alcohol use disorders and WE, and typical MRI findings were more common in patients with alcohol use disorders.¹⁴ However, this patient’s report of no alcohol use and the serum thiamine level being within normal limits (173 nmol/L; range 78-185 nmol/L) made acute WE less likely than metronidonazale-induced encephalopathy (MIE).

The most common neurologic AE of metronidazole is distal symmetric sensory polyneuropathy, which also can have motor or autonomic features.^16,17 While our patient had a history of peripheral neuropathy, he noted marked worsening of foot pain 3 months after initiating metronidazole therapy. A potential mechanism involves metronidazole or its cytotoxic intermediates binding neuronal ribonucleic acids, thus inhibiting protein synthesis and resulting in degenerative neuronal changes and reversible axonal swelling (as opposed to the DNA interference attributed to the drug’s mechanism of bactericidal action).¹⁸ Neuropathies may result from prolonged high-dose metronidazole therapy (cumulative dose > 42 g),³ but they also have been seen in short-term use of high dosages.¹⁷

CNS AEs are much rarer and are thought to be associated with metronidazole’s ability to cross the blood-brain barrier. These patients present as a toxic encephalopathy with cerebellar dysfunction (dysarthria, ataxia) as the most common presentation, followed by AMS and seizures.⁴ Our patient presented with acute confusion and ataxia. Animal studies suggest that γ-aminobutyric acid (GABA) receptor modulation in the cerebellar and vestibular systems may contribute to this neurotoxicity, but no definitive mechanism of injury has been found.¹⁹

On MRI, MIE most commonly presents with hyperintense lesions in the bilateral cerebellar dentate nucleus on T2-weighted and FLAIR images.^5,20 The midbrain, dorsal pons, medulla, and corpus callosum also can show increased signal intensity.⁵ This AE does not seem to be dose- or duration-dependent, and most cases report complete or partial resolution of symptoms following discontinuation of the drug, though this is not absolute.^4,13,21 The patient’s MRI findings were highly consistent with MIE (Figure 2).

Conclusion

This patient’s highly specific MRI findings, neurologic examination consistent with confusion, ataxia, length-dependent sensory neuropathy, and 360-g cumulative dose of metronidazole over the previous 6 months suggest he experienced MIE. The mechanism of how HBOT precipitated the patient’s altered mental status, incoordination, and worsening of peripheral neuropathy is unknown. Although encephalopathy with MRI abnormalities as described is not a reported AE of HBOT, it may be unrecognized. It is possible that without HBOT the patient would have remained asymptomatic apart from his peripheral neuropathy.

We propose HBOT may exacerbate or increase the risk of a patient developing MIE. Our patient was able to safely resume HBOT after metronidazole was discontinued, suggesting that the combination was the causation for the development of encephalopathy. We do not believe any similar cases have been reported.

Altered mental status (AMS) is a common presentation to the emergency department (ED) for older patients and is often due to underlying drug-associated adverse effects (AEs), medical or psychiatric illness, or neurologic disease. EDs often have protocols for diagnosing and managing AMS to assess the underlying etiology. A formal assessment with a full history and physical examination is paramount to diagnosing the cause of AMS.

Oral metronidazole is a commonly used antibiotic for anaerobic bacterial infections and Clostridium difficile-associated diarrhea and colitis.¹Metronidazole produces cytotoxic intermediates that cause DNA strand breakage and destabilization, resulting in bactericidal activity in host cells.²Common AEs include gastrointestinal symptoms such as nausea, vomiting, and diarrhea; less common AEs can involve the nervous system and include seizures, peripheral neuropathy, dizziness, ataxia, and encephalopathy.^3,4A pattern of magnetic resonance image (MRI) abnormalities typically located at the cerebellar dentate nucleus midbrain, dorsal pons, medulla, and splenium of the corpus callosum have been associated with metronidazole usage.⁵

Hyperbaric oxygen therapy (HBOT) is a treatment modality used as the primary therapy for decompression sickness, arterial gas embolism, and carbon monoxide poisoning. HBOT is used as adjuvant therapy for osteonecrosis caused by radiation or bisphosphonate use.^6,7 HBOT increases the partial pressure of oxygen in plasma and increases the amount of oxygen delivered to tissues throughout the body.⁸Hyperoxia, defined as an elevated partial pressure of oxygen leading to excess oxygenation to tissues and organs, increases production of reactive oxygen and nitrogen species, which are signaling factors in a variety of pathways that stimulate angiogenesis.⁸ AEs of HBOT include barotrauma-related injuries and oxygen toxicity, such as respiratory distress or central nervous system (CNS) symptoms.⁹ Severe CNS AEs occur in 1% to 2% of patients undergoing therapy and manifest as generalized tonic-clonic seizures, typically in patients with preexisting neurologic disorders, brain injury, or lowered seizure threshold.^7,8,10 There have been no documented incidences of HBOT inducing acute encephalopathy.

Case Presentation

A 63-year-old male smoker with no history of alcohol use presented to the ED with an acute onset of lightheadedness, confusion, and poor coordination following his second HBOT for radiation-induced osteonecrosis of the mandible. The patient reported chronic, slowly progressive pain and numbness of the feet that began 4 years earlier. He noted marked worsening of pain and difficulty standing and walking 3 to 4 months prior to presentation.

Ten years prior, the patient was diagnosed with cancer of the right tonsil. A tonsillectomy with wide margins was performed, followed by 35 rounds of radiation treatment and 2 rounds of chemotherapy with cisplatin.

In May 2017, the patient presented with a lump in the right cheek that was diagnosed as osteonecrosis of the mandible. An oral surgeon prescribed metronidazole 500 mg qid and amoxicillin 500 mg tid. The patient was adherent until presentation in November 2017. Following lack of improvement of the osteonecrosis from antibiotic therapy, oral surgery was planned, and the patient was referred for HBOT with a planned 20 HBOT preoperative treatments and 10 postoperative treatments.

Following his first 2-hour HBOT treatment on November 13, 2017, the patient complained of light-headedness, confusion, and incoordination. While driving on a familiar route to his home, he collided with a tree that was 6 feet from the curb. The patient attempted to drive another vehicle later that day, resulting in a second motor vehicle accident. There was no significant injury reported in either accident.

His partner described the patient’s episode of disorientation lasting 6 to 8 hours, during which he “looked drunk” and was unable to sit in a chair without falling. The following morning, the patient had improved mental status but had not returned to baseline. His second HBOT treatment took place that day, and again, the patient acutely experienced light-headedness and confusion following completion. Therapy was suspended, and the patient was referred to the ED for further evaluation. Mild facial asymmetry without weakness, decreased sensation from toes to knees bilaterally, and absent Achilles reflexes bilaterally were found on neurologic examination. He exhibited past-pointing on finger-to-nose testing bilaterally. He was able to ambulate independently, but he could not perform tandem gait.

An MRI of the brain showed abnormal T2 hyperintensity found bilaterally at the dentate nuclei and inferior colliculi. The splenium of the corpus callosum also showed mild involvement with hyperintense lesions. Laboratory tests of the patient’s complete blood count; comprehensive metabolic panel; vitamins B₁, B₆, B₁₂; and folic acid levels had no notable abnormalities and were within normal limits.

Metronidazole and HBOT therapy were discontinued, and all of the patient’s symptoms resolved within 2 weeks. A repeat examination and MRI performed 1 month later showed resolution of all the patient’s clinical findings and MRI abnormalities. HBOT was resumed without the recurrence of previously described symptoms.

Discussion

This patient’s encephalopathic symptoms correlate temporally with the onset of HBOT. There is no medical literature suggesting a relationship between HBOT and encephalopathic symptoms with MRI abnormalities, and in fact, some studies suggest HBOT as a treatment for hypoxic-ischemic encephalopathy in neonates.¹¹ This led us to believe that the HBOT may have exacerbated some underlying condition, evidenced by the specific MRI findings of T2 fluid-attenuated inversion recovery (FLAIR) hyperintensities in the dentate nuclei and inferior colliculi (Figures 1 and 2). 

Differential diagnoses for T2 hyperintense lesions in the dentate nuclei include metronidazole toxicity, acute Wernicke encephalopathy (WE), and methyl bromide intoxication. Diseases that would have presented in infancy with similar MRI findings (Canavan disease, maple-syrup urine disease, and glutaric aciduria type 1) were not considered plausible.^12-14 

Despite his denial of alcohol use, the patient was at risk for malnutrition secondary to his mandibular lesion and difficulty eating. Clinically, he presented with episodes of confusion and ataxia, consistent with 2 of the classic triad of symptoms of WE (no ocular abnormalities noted on exam). Typical MRI findings in WE include signal intensity alterations (including T2 hyperintensities) in the medial thalami, mammillary bodies, collicular bodies, and periaqueductal and periventricular regions.^14,15 Atypical MRI findings in WE include symmetric signal intensity changes in the cerebellum, dentate nuclei, caudate nuclei, red nuclei, cranial nerve nuclei, and splenium.¹⁴ Of note, atypical MRI findings were more common in patients without alcohol use disorders and WE, and typical MRI findings were more common in patients with alcohol use disorders.¹⁴ However, this patient’s report of no alcohol use and the serum thiamine level being within normal limits (173 nmol/L; range 78-185 nmol/L) made acute WE less likely than metronidonazale-induced encephalopathy (MIE).

The most common neurologic AE of metronidazole is distal symmetric sensory polyneuropathy, which also can have motor or autonomic features.^16,17 While our patient had a history of peripheral neuropathy, he noted marked worsening of foot pain 3 months after initiating metronidazole therapy. A potential mechanism involves metronidazole or its cytotoxic intermediates binding neuronal ribonucleic acids, thus inhibiting protein synthesis and resulting in degenerative neuronal changes and reversible axonal swelling (as opposed to the DNA interference attributed to the drug’s mechanism of bactericidal action).¹⁸ Neuropathies may result from prolonged high-dose metronidazole therapy (cumulative dose > 42 g),³ but they also have been seen in short-term use of high dosages.¹⁷

CNS AEs are much rarer and are thought to be associated with metronidazole’s ability to cross the blood-brain barrier. These patients present as a toxic encephalopathy with cerebellar dysfunction (dysarthria, ataxia) as the most common presentation, followed by AMS and seizures.⁴ Our patient presented with acute confusion and ataxia. Animal studies suggest that γ-aminobutyric acid (GABA) receptor modulation in the cerebellar and vestibular systems may contribute to this neurotoxicity, but no definitive mechanism of injury has been found.¹⁹

On MRI, MIE most commonly presents with hyperintense lesions in the bilateral cerebellar dentate nucleus on T2-weighted and FLAIR images.^5,20 The midbrain, dorsal pons, medulla, and corpus callosum also can show increased signal intensity.⁵ This AE does not seem to be dose- or duration-dependent, and most cases report complete or partial resolution of symptoms following discontinuation of the drug, though this is not absolute.^4,13,21 The patient’s MRI findings were highly consistent with MIE (Figure 2).

Conclusion

This patient’s highly specific MRI findings, neurologic examination consistent with confusion, ataxia, length-dependent sensory neuropathy, and 360-g cumulative dose of metronidazole over the previous 6 months suggest he experienced MIE. The mechanism of how HBOT precipitated the patient’s altered mental status, incoordination, and worsening of peripheral neuropathy is unknown. Although encephalopathy with MRI abnormalities as described is not a reported AE of HBOT, it may be unrecognized. It is possible that without HBOT the patient would have remained asymptomatic apart from his peripheral neuropathy.

We propose HBOT may exacerbate or increase the risk of a patient developing MIE. Our patient was able to safely resume HBOT after metronidazole was discontinued, suggesting that the combination was the causation for the development of encephalopathy. We do not believe any similar cases have been reported.

While private or other public health care organizations can refuse to care for patients who have displayed disruptive behavior (DB), the VA Response to Disruptive Behavior of Patients law (38 CFR §17.107) prohibits the Veterans Health Administration (VHA) of the Department of Veterans Affairs (VA) from refusing care to veterans who display DB.¹ The VHA defines DB as any behavior that is intimidating, threatening, or dangerous or that has, or could, jeopardize the health or safety of patients, VHA staff, or others.²

VA Response to DB Law

The VA Response to Disruptive Behavior of Patients requires the VHA to provide alternative care options that minimize risk while ensuring services; for example, providing care at a different location and/or time when additional staff are available to assist and monitor the patient. This can provide a unique opportunity to capture data on DB and the results of alternative forms of caring for this population. DB may represent a symptom of a health problem. Further, patients who are refused care because of DB may pose a threat to the community if their medical conditions are not treated or managed properly.

The reason public health care organizations refuse care to persons who display DB is clear: DBs hinder business operations, are financially taxing, and put health care workers at risk.^3-10 “In 2009, the VHA spent close to $5.5 million on workers’ compensation and medical expenditures for 425 incidents–or about $130,000 per DB incident (Hodgson M, Drummond D, Van Male L. Unpublished data, 2010).” In another study, 106 of 762 nurses in 1 hospital system reported an assault by a patient, and 30 required medical attention, which resulted in a total cost of $94,156.⁸ From 2002 to 2013, incidents of serious workplace violence requiring days off for an injured worker to recover on average were 4 times more common in health care than in other industries.^6-11 Incidents of patient violence and aggression toward staff transcend specialization; however, hospital nurses and staff from the emergency, rehabilitation and gerontology departments, psychiatric unit, and home-based services are more susceptible and vulnerable to DB incidents than are other types of employees.^8,10-19

Data reported by health care staff suggest that patients rather than staff members or visitors initiate > 70% of serious physical attacks against health care workers.^9,13,20-23 A 2015 study of VHA health care providers (HCPs) found that > 60% had experienced some form of DB, verbal abuse being the most prevalent, followed by sexual abuse and physical abuse.²⁰ Of 72,000 VHA staff responding to a nationwide survey, 13% experienced, on average, ≥ 1 assault by a veteran (eg, something was thrown at them; they were pushed, kicked, slapped; or were threatened or injured by a weapon).^8,21Although 13% may seem small, the incidents may have lasting financial and emotional distress. Risk factors associated with DB include medication nonadherence, history of drug and alcohol use, disappointment with care, history of violence, and untreated mental health concerns.^19,24,25 Also, unmarried and young patients are more likely to display violence against health care workers.²⁶

To meet its legal obligations and deliver empathetic care, the VHA documents and analyzes data on all patients who exhibit DB. A local DB Committee (DBC) reviews the data, whether it occurs in an inpatient or outpatient setting, such as community-based outpatient clinics. Once a DB incident is reported, the DBC begins an evidence-based risk evaluation, including the option of contacting the persons who displayed or experienced the DB. Goals are to (1) prevent future DB incidents; (2) detect vulnerabilities in the environment; and (3) collaborate with HCPs and patients to provide optimal care while improving the patient/provider interactions.

Effects of Disruptive Behavior

DB has negative consequences for both patients and health care workers and results in poor evaluations of care from both groups.^27-32 Aside from interfering with safe medical care, DB also impacts care for other patients by delaying access to care and increasing appointment wait times due to employee absenteeism and staff shortages.^3,4,20,32,33 For HCPs, patient violence is associated with unwillingness to provide care, briefer treatment periods, and decreases in occupational satisfaction, performance, and commitment.^10,28,31 Coping with DB can compromise the HCP’s ability to stay focused and engaged in providing health care, increasing errors.^9,15,31

Harmful health effects experienced by HCPs who have been victims of DB include fear, mood disorders, anxiety, all symptoms of psychological distress and posttraumatic stress disorder (PTSD).^{10,22,30,34-36} In a study of the impact on productivity of PTSD triggered by job-related DB, PTSD symptoms were associated with withdrawal from or minimizing encounters with patients, job turnover, and troubles with thinking.^35,36 Nurses with PTSD symptoms who stayed on the job had difficulty staying cognitively focused and managing “higher level work demands that required attention to detail or communication skills.”³⁶ Due to the detrimental impact of DB, it is reasonable to expect a decrease in the quality of care rendered to patients by impacted employees. The quality of care for all patients of HCPs who have experienced a DB is poorer than that of patients of HCPs who have not experienced a DB.²⁹

Reporting Disruptive Behavior

The literature suggests that consistent and effective DB reporting is pivotal to improving the outcome and quality of care for those displaying DB.^37-39 To provide high-quality health services to veterans who display DB, the VHA must promote the management and reporting of DB. Without knowledge of the full spectrum of DB events at VHA facilities, efforts to prevent or manage DB and ensure safety may have limited impact.^7,37 Reports can be used for clinical decision making to optimize staff training in delivery of quality care while assuring staff safety. More than 80% of DB incidents occur during interactions with patients, thus this is a clinical issue that can affect the outcome of patient care.^8,21

Documented DB reports are used to analyze the degree, frequency, and nature of incidents, which might reveal risk factors and develop preventive efforts and training for specific hazards.^8,39 Some have argued that implementing a standardized DB reporting system is a crucial first step toward minimizing hazards and improving health care.^38,40,41

When DB incidents were recorded through a hospital electronic reporting system and discussed in meetings, staff reported: (1) increased awareness of DB; (2) improved ability to manage DB incidents; and (3) amplified reporting of incidents.^38,41,42 These findings support similar results from studies of an intervention implemented at VA Community Living Centers (CLCs) from 2013 to 2017: Staff Training in Assisted Living Residences (STAR-VA).^4,12,19 The aim of STAR-VA was to minimize challenging dementia-related DB in CLCs. The intervention initially was established to train direct-care, assisted-living staff to provide better care to older patients displaying DB. Data revealed that documentation of DBs was, the first step to ensuring staff and patient safety.^18,40

VHA Reporting System

In 2013, the VA Office of Inspector General (OIG) found no standardized documentation of DB events across the VA health care system.⁴² Instead, DB events were documented in multiple records in various locations, including administrative and progress notes in the electronic health record (EHR), police reports, e-mails, or letters submitted to DBC chairs.⁴² This situation reduced administrators’ ability to consider all relevant information and render appropriate decisions in DB cases.⁴² In 2015, based on OIG recommendations, the VHA implemented the Disruptive Behavior Reporting System (DBRS) nationwide, which allowed all VHA staff to report DB events. The DBRS was designed to address factors likely to impede reporting and management of DB, namely, complexity of and lack of access to a central reporting system.^43,44 The DBRS is currently the primary VHA tool to document DB events.

The DBRS consists of 32 questions in 5 sections relating to the (1) location and time of DB event; (2) reporter; (3) disrupter; (4) DB event details; and (5) the person who experienced (experiencer) the event. The system also provides a list of the types of DB, such as inappropriate communication, bullying and/or intimidation, verbal or written threat of physical harm, physical violence, sexual harassment, sexual assault, and property damage. The DBRS has the potential to provide useful data on DB and DB reporting, such as the typical staff entering data and the number and/or types of DB occurring.

The DBRS complements the preexisting VHA policies and committees for care of veterans who display DB.^{1-3,14,21,24,25} The VHA Workplace Violence Prevention Program (WVPP) required facilities to submit data on DB events through a Workplace Behavioral Risk report. Data for the report were obtained from police reports, patient safety reports, DBC records, and notes in the EHR. Following implementations of DBRS, the number of DB events per year became a part of facility performance standards.

VHA is creating novel approaches to handling DB that allow health care workers to render care in a safe and effective manner guided by documented information. For example, DBCs can recommend the use of Category I Patient Record Flags (PRFs) following documented DB, which informs staff of the potential risk of DB and provides guidance on protective methods to use when meeting with the patient.^2,21,24 A survey of 140 VA hospital chiefs of staff indicated that DBC procedures were related to a decrease in the rates of assaults.¹ Additionally, VA provides training for staff in techniques to promote personal safety, such as identifying signs that precede DB, using verbal deescalation, and practicing therapeutic containment.

Resistance to Reporting

Many health care employees and employers are reticent to report DBs.^{22,31,43,45-48} Studies suggest health care organizations can cultivate a culture that is resistant to reporting DB.^49,50 This complicates the ability of the health care system to design and maintain safety protocols and safer treatment plans.^3,41,51 Worldwide, < 30% of DBs are reported.⁴⁷ One barrier may be that supervisors may not wish to acknowledge DBs on their units or may not provide sufficient staff time for training or reporting.^31,46,47 HCPs may worry that a DB report will stigmatize patients, especially those who are elderly or have cognitive impairment, brain injury, psychological illness, or developmental disability. Patients with cognitive conditions are reportedly 20% more likely to be violent toward caregivers and providers.³¹ A dementia diagnosis, for example, is associated with a high likelihood for DB.^30,52 More than 80% of DB events displayed by patients with dementia may go unreported.^26,31,50,52

Some clinicians may attribute DB to physiologic conditions that need to be treated, not reported. However, employers can face various legal liabilities if steps are not taken to protect employees.^47,51 Federal and state statutes require that organizations provide a healthy and safe employment environment for workers. This requires that employers institute reasonable protective measures, such as procedures to intervene, policies on addressing DB incidents, and/or training to minimize or deescalate DB.^51,53 Also, employees may sue employers if security measures are inadequate or deficient in properly investigating current and past evidence of DB or identifying vulnerabilities in the workplace. Unwillingness to investigate DB and safety-related workplace concerns have contributed to increased workplace violence and legal liability.^52,53 The mission of caring and trust is consistent with assuring a safe environment.

Training and Empathetic Care

To combat cultural resistance to reporting DBs, more and perhaps different contextual approaches to education and training may be needed that address ethical dilemmas and concerns of providers. The success of training relies on administrators supporting staff in reporting DB. Training must address providers’ conflicting beliefs and assist with identifying strategies to provide the best possible care for patients who display DB.^1,38 HCPs are less likely to document a DB if they feel that administrators are creating documentation that will have negative consequences for a patient. Thus, leadership is responsible for ensuring that misconceptions are dispelled through training and other efforts and information on how reported DB data will be used is communicated through strategic channels.

Education and training must consider empathic care that attempts to understand why patients behave as they do through the information gathered.⁵⁵ Empathy in health care is multifaceted: It involves comprehending a patient’s viewpoint, circumstances, and feelings and the capacity to analyze whether one is comprehending these accurately in order to demonstrate supportive care.^54,55

Improving patient and staff interaction once a problematic behavior is identified is the aim of empathic care. Increasing empathic care can improve compassionate, patient-centered interactions that begin once the patient seeks care. This approach has proven to decrease DB by patients with dementia and improve their care, lessen staff problems during interactions, and increase staff morale.²⁰ Experts call for the adoption of an interpersonal approach to patient encounters, and there is evidence that creating organizational change by moving toward compassionate care can lead to a positive impact for patients.^54,55

Future Studies

There are growth opportunities in utilization of the DBRS. Analysis of the DBRS database by the VA Central Office (VACO) showed that the system is underutilized by facilities across the VA system.⁵⁶ In response to this current underutilization, VACO is taking steps to close these gaps through increasing training to staff and promotion of the use of the DBRS. A 2015 pilot study of VHA providers showed that > 70% of providers had experienced a DB as defined by VHA, but only 34% of them reported their most recently experienced DB within the past 12 months.²⁰ Thus, DBRS use must be studied within the context that patient-perpetrated DB is underreported in health care organizations.^{5,9,29,41,43,57,58} Studies addressing national DBRS utilization patterns and the cost associated with implementing the DBRS also are needed. One study suggests that there is an association between measures of facility complexity and staff perceptions of safety, which should be considered in analyzing DBRS usage.⁵⁷ Studies addressing the role of the DBRS and misconceptions that the tool may represent a punitive tool also are needed. VHA should consider how the attribution “disruptive behavior” assigns a negative connotation and leads HCPs to avoid using the DBRS. Additionally, DB reporting may increase when HCPs understand that DB reporting is part of the comprehensive, consultative strategy to provide the best care to patients.

Conclusion

Accurate reporting of DB events enables the development of strategies for multidisciplinary teams to work together to minimize hazards and to provide interventions that provide for the safe delivery of health care to all patients. Improving reporting ensures there is an accurate representation of how disruptive events impact care provided within a facility—and what types of variables may be associated with increased risk for these types of events.

Additionally, ensuring that reporting is maximized also provides the VHA with opportunities for DBCs to offer evidence-based risk assessment of violence and consultation to staff members who may benefit from improved competencies in working with patients who display DB. These potential improvements are consistent with the VHA I CARE values and will provide data that can inform recommendations for health care in other agencies/health care organizations.

Acknowledgments
This work was supported by the Center of Innovation on Disability and Rehabilitation Research (CINDRR) of the Health Services Research and Development Service, Office of Research and Development, Department of Veterans Affairs.

While private or other public health care organizations can refuse to care for patients who have displayed disruptive behavior (DB), the VA Response to Disruptive Behavior of Patients law (38 CFR §17.107) prohibits the Veterans Health Administration (VHA) of the Department of Veterans Affairs (VA) from refusing care to veterans who display DB.¹ The VHA defines DB as any behavior that is intimidating, threatening, or dangerous or that has, or could, jeopardize the health or safety of patients, VHA staff, or others.²

VA Response to DB Law

The VA Response to Disruptive Behavior of Patients requires the VHA to provide alternative care options that minimize risk while ensuring services; for example, providing care at a different location and/or time when additional staff are available to assist and monitor the patient. This can provide a unique opportunity to capture data on DB and the results of alternative forms of caring for this population. DB may represent a symptom of a health problem. Further, patients who are refused care because of DB may pose a threat to the community if their medical conditions are not treated or managed properly.

The reason public health care organizations refuse care to persons who display DB is clear: DBs hinder business operations, are financially taxing, and put health care workers at risk.^3-10 “In 2009, the VHA spent close to $5.5 million on workers’ compensation and medical expenditures for 425 incidents–or about $130,000 per DB incident (Hodgson M, Drummond D, Van Male L. Unpublished data, 2010).” In another study, 106 of 762 nurses in 1 hospital system reported an assault by a patient, and 30 required medical attention, which resulted in a total cost of $94,156.⁸ From 2002 to 2013, incidents of serious workplace violence requiring days off for an injured worker to recover on average were 4 times more common in health care than in other industries.^6-11 Incidents of patient violence and aggression toward staff transcend specialization; however, hospital nurses and staff from the emergency, rehabilitation and gerontology departments, psychiatric unit, and home-based services are more susceptible and vulnerable to DB incidents than are other types of employees.^8,10-19

Data reported by health care staff suggest that patients rather than staff members or visitors initiate > 70% of serious physical attacks against health care workers.^9,13,20-23 A 2015 study of VHA health care providers (HCPs) found that > 60% had experienced some form of DB, verbal abuse being the most prevalent, followed by sexual abuse and physical abuse.²⁰ Of 72,000 VHA staff responding to a nationwide survey, 13% experienced, on average, ≥ 1 assault by a veteran (eg, something was thrown at them; they were pushed, kicked, slapped; or were threatened or injured by a weapon).^8,21Although 13% may seem small, the incidents may have lasting financial and emotional distress. Risk factors associated with DB include medication nonadherence, history of drug and alcohol use, disappointment with care, history of violence, and untreated mental health concerns.^19,24,25 Also, unmarried and young patients are more likely to display violence against health care workers.²⁶

To meet its legal obligations and deliver empathetic care, the VHA documents and analyzes data on all patients who exhibit DB. A local DB Committee (DBC) reviews the data, whether it occurs in an inpatient or outpatient setting, such as community-based outpatient clinics. Once a DB incident is reported, the DBC begins an evidence-based risk evaluation, including the option of contacting the persons who displayed or experienced the DB. Goals are to (1) prevent future DB incidents; (2) detect vulnerabilities in the environment; and (3) collaborate with HCPs and patients to provide optimal care while improving the patient/provider interactions.

Effects of Disruptive Behavior

DB has negative consequences for both patients and health care workers and results in poor evaluations of care from both groups.^27-32 Aside from interfering with safe medical care, DB also impacts care for other patients by delaying access to care and increasing appointment wait times due to employee absenteeism and staff shortages.^3,4,20,32,33 For HCPs, patient violence is associated with unwillingness to provide care, briefer treatment periods, and decreases in occupational satisfaction, performance, and commitment.^10,28,31 Coping with DB can compromise the HCP’s ability to stay focused and engaged in providing health care, increasing errors.^9,15,31

Harmful health effects experienced by HCPs who have been victims of DB include fear, mood disorders, anxiety, all symptoms of psychological distress and posttraumatic stress disorder (PTSD).^{10,22,30,34-36} In a study of the impact on productivity of PTSD triggered by job-related DB, PTSD symptoms were associated with withdrawal from or minimizing encounters with patients, job turnover, and troubles with thinking.^35,36 Nurses with PTSD symptoms who stayed on the job had difficulty staying cognitively focused and managing “higher level work demands that required attention to detail or communication skills.”³⁶ Due to the detrimental impact of DB, it is reasonable to expect a decrease in the quality of care rendered to patients by impacted employees. The quality of care for all patients of HCPs who have experienced a DB is poorer than that of patients of HCPs who have not experienced a DB.²⁹

Reporting Disruptive Behavior

The literature suggests that consistent and effective DB reporting is pivotal to improving the outcome and quality of care for those displaying DB.^37-39 To provide high-quality health services to veterans who display DB, the VHA must promote the management and reporting of DB. Without knowledge of the full spectrum of DB events at VHA facilities, efforts to prevent or manage DB and ensure safety may have limited impact.^7,37 Reports can be used for clinical decision making to optimize staff training in delivery of quality care while assuring staff safety. More than 80% of DB incidents occur during interactions with patients, thus this is a clinical issue that can affect the outcome of patient care.^8,21

Documented DB reports are used to analyze the degree, frequency, and nature of incidents, which might reveal risk factors and develop preventive efforts and training for specific hazards.^8,39 Some have argued that implementing a standardized DB reporting system is a crucial first step toward minimizing hazards and improving health care.^38,40,41

When DB incidents were recorded through a hospital electronic reporting system and discussed in meetings, staff reported: (1) increased awareness of DB; (2) improved ability to manage DB incidents; and (3) amplified reporting of incidents.^38,41,42 These findings support similar results from studies of an intervention implemented at VA Community Living Centers (CLCs) from 2013 to 2017: Staff Training in Assisted Living Residences (STAR-VA).^4,12,19 The aim of STAR-VA was to minimize challenging dementia-related DB in CLCs. The intervention initially was established to train direct-care, assisted-living staff to provide better care to older patients displaying DB. Data revealed that documentation of DBs was, the first step to ensuring staff and patient safety.^18,40

VHA Reporting System

In 2013, the VA Office of Inspector General (OIG) found no standardized documentation of DB events across the VA health care system.⁴² Instead, DB events were documented in multiple records in various locations, including administrative and progress notes in the electronic health record (EHR), police reports, e-mails, or letters submitted to DBC chairs.⁴² This situation reduced administrators’ ability to consider all relevant information and render appropriate decisions in DB cases.⁴² In 2015, based on OIG recommendations, the VHA implemented the Disruptive Behavior Reporting System (DBRS) nationwide, which allowed all VHA staff to report DB events. The DBRS was designed to address factors likely to impede reporting and management of DB, namely, complexity of and lack of access to a central reporting system.^43,44 The DBRS is currently the primary VHA tool to document DB events.

The DBRS consists of 32 questions in 5 sections relating to the (1) location and time of DB event; (2) reporter; (3) disrupter; (4) DB event details; and (5) the person who experienced (experiencer) the event. The system also provides a list of the types of DB, such as inappropriate communication, bullying and/or intimidation, verbal or written threat of physical harm, physical violence, sexual harassment, sexual assault, and property damage. The DBRS has the potential to provide useful data on DB and DB reporting, such as the typical staff entering data and the number and/or types of DB occurring.

The DBRS complements the preexisting VHA policies and committees for care of veterans who display DB.^{1-3,14,21,24,25} The VHA Workplace Violence Prevention Program (WVPP) required facilities to submit data on DB events through a Workplace Behavioral Risk report. Data for the report were obtained from police reports, patient safety reports, DBC records, and notes in the EHR. Following implementations of DBRS, the number of DB events per year became a part of facility performance standards.

VHA is creating novel approaches to handling DB that allow health care workers to render care in a safe and effective manner guided by documented information. For example, DBCs can recommend the use of Category I Patient Record Flags (PRFs) following documented DB, which informs staff of the potential risk of DB and provides guidance on protective methods to use when meeting with the patient.^2,21,24 A survey of 140 VA hospital chiefs of staff indicated that DBC procedures were related to a decrease in the rates of assaults.¹ Additionally, VA provides training for staff in techniques to promote personal safety, such as identifying signs that precede DB, using verbal deescalation, and practicing therapeutic containment.

Resistance to Reporting

Many health care employees and employers are reticent to report DBs.^{22,31,43,45-48} Studies suggest health care organizations can cultivate a culture that is resistant to reporting DB.^49,50 This complicates the ability of the health care system to design and maintain safety protocols and safer treatment plans.^3,41,51 Worldwide, < 30% of DBs are reported.⁴⁷ One barrier may be that supervisors may not wish to acknowledge DBs on their units or may not provide sufficient staff time for training or reporting.^31,46,47 HCPs may worry that a DB report will stigmatize patients, especially those who are elderly or have cognitive impairment, brain injury, psychological illness, or developmental disability. Patients with cognitive conditions are reportedly 20% more likely to be violent toward caregivers and providers.³¹ A dementia diagnosis, for example, is associated with a high likelihood for DB.^30,52 More than 80% of DB events displayed by patients with dementia may go unreported.^26,31,50,52

Some clinicians may attribute DB to physiologic conditions that need to be treated, not reported. However, employers can face various legal liabilities if steps are not taken to protect employees.^47,51 Federal and state statutes require that organizations provide a healthy and safe employment environment for workers. This requires that employers institute reasonable protective measures, such as procedures to intervene, policies on addressing DB incidents, and/or training to minimize or deescalate DB.^51,53 Also, employees may sue employers if security measures are inadequate or deficient in properly investigating current and past evidence of DB or identifying vulnerabilities in the workplace. Unwillingness to investigate DB and safety-related workplace concerns have contributed to increased workplace violence and legal liability.^52,53 The mission of caring and trust is consistent with assuring a safe environment.

Training and Empathetic Care

To combat cultural resistance to reporting DBs, more and perhaps different contextual approaches to education and training may be needed that address ethical dilemmas and concerns of providers. The success of training relies on administrators supporting staff in reporting DB. Training must address providers’ conflicting beliefs and assist with identifying strategies to provide the best possible care for patients who display DB.^1,38 HCPs are less likely to document a DB if they feel that administrators are creating documentation that will have negative consequences for a patient. Thus, leadership is responsible for ensuring that misconceptions are dispelled through training and other efforts and information on how reported DB data will be used is communicated through strategic channels.

Education and training must consider empathic care that attempts to understand why patients behave as they do through the information gathered.⁵⁵ Empathy in health care is multifaceted: It involves comprehending a patient’s viewpoint, circumstances, and feelings and the capacity to analyze whether one is comprehending these accurately in order to demonstrate supportive care.^54,55

Improving patient and staff interaction once a problematic behavior is identified is the aim of empathic care. Increasing empathic care can improve compassionate, patient-centered interactions that begin once the patient seeks care. This approach has proven to decrease DB by patients with dementia and improve their care, lessen staff problems during interactions, and increase staff morale.²⁰ Experts call for the adoption of an interpersonal approach to patient encounters, and there is evidence that creating organizational change by moving toward compassionate care can lead to a positive impact for patients.^54,55

Future Studies

There are growth opportunities in utilization of the DBRS. Analysis of the DBRS database by the VA Central Office (VACO) showed that the system is underutilized by facilities across the VA system.⁵⁶ In response to this current underutilization, VACO is taking steps to close these gaps through increasing training to staff and promotion of the use of the DBRS. A 2015 pilot study of VHA providers showed that > 70% of providers had experienced a DB as defined by VHA, but only 34% of them reported their most recently experienced DB within the past 12 months.²⁰ Thus, DBRS use must be studied within the context that patient-perpetrated DB is underreported in health care organizations.^{5,9,29,41,43,57,58} Studies addressing national DBRS utilization patterns and the cost associated with implementing the DBRS also are needed. One study suggests that there is an association between measures of facility complexity and staff perceptions of safety, which should be considered in analyzing DBRS usage.⁵⁷ Studies addressing the role of the DBRS and misconceptions that the tool may represent a punitive tool also are needed. VHA should consider how the attribution “disruptive behavior” assigns a negative connotation and leads HCPs to avoid using the DBRS. Additionally, DB reporting may increase when HCPs understand that DB reporting is part of the comprehensive, consultative strategy to provide the best care to patients.

Conclusion

Accurate reporting of DB events enables the development of strategies for multidisciplinary teams to work together to minimize hazards and to provide interventions that provide for the safe delivery of health care to all patients. Improving reporting ensures there is an accurate representation of how disruptive events impact care provided within a facility—and what types of variables may be associated with increased risk for these types of events.

Additionally, ensuring that reporting is maximized also provides the VHA with opportunities for DBCs to offer evidence-based risk assessment of violence and consultation to staff members who may benefit from improved competencies in working with patients who display DB. These potential improvements are consistent with the VHA I CARE values and will provide data that can inform recommendations for health care in other agencies/health care organizations.

Acknowledgments
This work was supported by the Center of Innovation on Disability and Rehabilitation Research (CINDRR) of the Health Services Research and Development Service, Office of Research and Development, Department of Veterans Affairs.

While private or other public health care organizations can refuse to care for patients who have displayed disruptive behavior (DB), the VA Response to Disruptive Behavior of Patients law (38 CFR §17.107) prohibits the Veterans Health Administration (VHA) of the Department of Veterans Affairs (VA) from refusing care to veterans who display DB.¹ The VHA defines DB as any behavior that is intimidating, threatening, or dangerous or that has, or could, jeopardize the health or safety of patients, VHA staff, or others.²

VA Response to DB Law

The VA Response to Disruptive Behavior of Patients requires the VHA to provide alternative care options that minimize risk while ensuring services; for example, providing care at a different location and/or time when additional staff are available to assist and monitor the patient. This can provide a unique opportunity to capture data on DB and the results of alternative forms of caring for this population. DB may represent a symptom of a health problem. Further, patients who are refused care because of DB may pose a threat to the community if their medical conditions are not treated or managed properly.

The reason public health care organizations refuse care to persons who display DB is clear: DBs hinder business operations, are financially taxing, and put health care workers at risk.^3-10 “In 2009, the VHA spent close to $5.5 million on workers’ compensation and medical expenditures for 425 incidents–or about $130,000 per DB incident (Hodgson M, Drummond D, Van Male L. Unpublished data, 2010).” In another study, 106 of 762 nurses in 1 hospital system reported an assault by a patient, and 30 required medical attention, which resulted in a total cost of $94,156.⁸ From 2002 to 2013, incidents of serious workplace violence requiring days off for an injured worker to recover on average were 4 times more common in health care than in other industries.^6-11 Incidents of patient violence and aggression toward staff transcend specialization; however, hospital nurses and staff from the emergency, rehabilitation and gerontology departments, psychiatric unit, and home-based services are more susceptible and vulnerable to DB incidents than are other types of employees.^8,10-19

Data reported by health care staff suggest that patients rather than staff members or visitors initiate > 70% of serious physical attacks against health care workers.^9,13,20-23 A 2015 study of VHA health care providers (HCPs) found that > 60% had experienced some form of DB, verbal abuse being the most prevalent, followed by sexual abuse and physical abuse.²⁰ Of 72,000 VHA staff responding to a nationwide survey, 13% experienced, on average, ≥ 1 assault by a veteran (eg, something was thrown at them; they were pushed, kicked, slapped; or were threatened or injured by a weapon).^8,21Although 13% may seem small, the incidents may have lasting financial and emotional distress. Risk factors associated with DB include medication nonadherence, history of drug and alcohol use, disappointment with care, history of violence, and untreated mental health concerns.^19,24,25 Also, unmarried and young patients are more likely to display violence against health care workers.²⁶

To meet its legal obligations and deliver empathetic care, the VHA documents and analyzes data on all patients who exhibit DB. A local DB Committee (DBC) reviews the data, whether it occurs in an inpatient or outpatient setting, such as community-based outpatient clinics. Once a DB incident is reported, the DBC begins an evidence-based risk evaluation, including the option of contacting the persons who displayed or experienced the DB. Goals are to (1) prevent future DB incidents; (2) detect vulnerabilities in the environment; and (3) collaborate with HCPs and patients to provide optimal care while improving the patient/provider interactions.

Effects of Disruptive Behavior

DB has negative consequences for both patients and health care workers and results in poor evaluations of care from both groups.^27-32 Aside from interfering with safe medical care, DB also impacts care for other patients by delaying access to care and increasing appointment wait times due to employee absenteeism and staff shortages.^3,4,20,32,33 For HCPs, patient violence is associated with unwillingness to provide care, briefer treatment periods, and decreases in occupational satisfaction, performance, and commitment.^10,28,31 Coping with DB can compromise the HCP’s ability to stay focused and engaged in providing health care, increasing errors.^9,15,31

Harmful health effects experienced by HCPs who have been victims of DB include fear, mood disorders, anxiety, all symptoms of psychological distress and posttraumatic stress disorder (PTSD).^{10,22,30,34-36} In a study of the impact on productivity of PTSD triggered by job-related DB, PTSD symptoms were associated with withdrawal from or minimizing encounters with patients, job turnover, and troubles with thinking.^35,36 Nurses with PTSD symptoms who stayed on the job had difficulty staying cognitively focused and managing “higher level work demands that required attention to detail or communication skills.”³⁶ Due to the detrimental impact of DB, it is reasonable to expect a decrease in the quality of care rendered to patients by impacted employees. The quality of care for all patients of HCPs who have experienced a DB is poorer than that of patients of HCPs who have not experienced a DB.²⁹

Reporting Disruptive Behavior

The literature suggests that consistent and effective DB reporting is pivotal to improving the outcome and quality of care for those displaying DB.^37-39 To provide high-quality health services to veterans who display DB, the VHA must promote the management and reporting of DB. Without knowledge of the full spectrum of DB events at VHA facilities, efforts to prevent or manage DB and ensure safety may have limited impact.^7,37 Reports can be used for clinical decision making to optimize staff training in delivery of quality care while assuring staff safety. More than 80% of DB incidents occur during interactions with patients, thus this is a clinical issue that can affect the outcome of patient care.^8,21

Documented DB reports are used to analyze the degree, frequency, and nature of incidents, which might reveal risk factors and develop preventive efforts and training for specific hazards.^8,39 Some have argued that implementing a standardized DB reporting system is a crucial first step toward minimizing hazards and improving health care.^38,40,41

When DB incidents were recorded through a hospital electronic reporting system and discussed in meetings, staff reported: (1) increased awareness of DB; (2) improved ability to manage DB incidents; and (3) amplified reporting of incidents.^38,41,42 These findings support similar results from studies of an intervention implemented at VA Community Living Centers (CLCs) from 2013 to 2017: Staff Training in Assisted Living Residences (STAR-VA).^4,12,19 The aim of STAR-VA was to minimize challenging dementia-related DB in CLCs. The intervention initially was established to train direct-care, assisted-living staff to provide better care to older patients displaying DB. Data revealed that documentation of DBs was, the first step to ensuring staff and patient safety.^18,40

VHA Reporting System

In 2013, the VA Office of Inspector General (OIG) found no standardized documentation of DB events across the VA health care system.⁴² Instead, DB events were documented in multiple records in various locations, including administrative and progress notes in the electronic health record (EHR), police reports, e-mails, or letters submitted to DBC chairs.⁴² This situation reduced administrators’ ability to consider all relevant information and render appropriate decisions in DB cases.⁴² In 2015, based on OIG recommendations, the VHA implemented the Disruptive Behavior Reporting System (DBRS) nationwide, which allowed all VHA staff to report DB events. The DBRS was designed to address factors likely to impede reporting and management of DB, namely, complexity of and lack of access to a central reporting system.^43,44 The DBRS is currently the primary VHA tool to document DB events.

The DBRS consists of 32 questions in 5 sections relating to the (1) location and time of DB event; (2) reporter; (3) disrupter; (4) DB event details; and (5) the person who experienced (experiencer) the event. The system also provides a list of the types of DB, such as inappropriate communication, bullying and/or intimidation, verbal or written threat of physical harm, physical violence, sexual harassment, sexual assault, and property damage. The DBRS has the potential to provide useful data on DB and DB reporting, such as the typical staff entering data and the number and/or types of DB occurring.

The DBRS complements the preexisting VHA policies and committees for care of veterans who display DB.^{1-3,14,21,24,25} The VHA Workplace Violence Prevention Program (WVPP) required facilities to submit data on DB events through a Workplace Behavioral Risk report. Data for the report were obtained from police reports, patient safety reports, DBC records, and notes in the EHR. Following implementations of DBRS, the number of DB events per year became a part of facility performance standards.

VHA is creating novel approaches to handling DB that allow health care workers to render care in a safe and effective manner guided by documented information. For example, DBCs can recommend the use of Category I Patient Record Flags (PRFs) following documented DB, which informs staff of the potential risk of DB and provides guidance on protective methods to use when meeting with the patient.^2,21,24 A survey of 140 VA hospital chiefs of staff indicated that DBC procedures were related to a decrease in the rates of assaults.¹ Additionally, VA provides training for staff in techniques to promote personal safety, such as identifying signs that precede DB, using verbal deescalation, and practicing therapeutic containment.

Resistance to Reporting

Many health care employees and employers are reticent to report DBs.^{22,31,43,45-48} Studies suggest health care organizations can cultivate a culture that is resistant to reporting DB.^49,50 This complicates the ability of the health care system to design and maintain safety protocols and safer treatment plans.^3,41,51 Worldwide, < 30% of DBs are reported.⁴⁷ One barrier may be that supervisors may not wish to acknowledge DBs on their units or may not provide sufficient staff time for training or reporting.^31,46,47 HCPs may worry that a DB report will stigmatize patients, especially those who are elderly or have cognitive impairment, brain injury, psychological illness, or developmental disability. Patients with cognitive conditions are reportedly 20% more likely to be violent toward caregivers and providers.³¹ A dementia diagnosis, for example, is associated with a high likelihood for DB.^30,52 More than 80% of DB events displayed by patients with dementia may go unreported.^26,31,50,52

Some clinicians may attribute DB to physiologic conditions that need to be treated, not reported. However, employers can face various legal liabilities if steps are not taken to protect employees.^47,51 Federal and state statutes require that organizations provide a healthy and safe employment environment for workers. This requires that employers institute reasonable protective measures, such as procedures to intervene, policies on addressing DB incidents, and/or training to minimize or deescalate DB.^51,53 Also, employees may sue employers if security measures are inadequate or deficient in properly investigating current and past evidence of DB or identifying vulnerabilities in the workplace. Unwillingness to investigate DB and safety-related workplace concerns have contributed to increased workplace violence and legal liability.^52,53 The mission of caring and trust is consistent with assuring a safe environment.

Training and Empathetic Care

To combat cultural resistance to reporting DBs, more and perhaps different contextual approaches to education and training may be needed that address ethical dilemmas and concerns of providers. The success of training relies on administrators supporting staff in reporting DB. Training must address providers’ conflicting beliefs and assist with identifying strategies to provide the best possible care for patients who display DB.^1,38 HCPs are less likely to document a DB if they feel that administrators are creating documentation that will have negative consequences for a patient. Thus, leadership is responsible for ensuring that misconceptions are dispelled through training and other efforts and information on how reported DB data will be used is communicated through strategic channels.

Education and training must consider empathic care that attempts to understand why patients behave as they do through the information gathered.⁵⁵ Empathy in health care is multifaceted: It involves comprehending a patient’s viewpoint, circumstances, and feelings and the capacity to analyze whether one is comprehending these accurately in order to demonstrate supportive care.^54,55

Improving patient and staff interaction once a problematic behavior is identified is the aim of empathic care. Increasing empathic care can improve compassionate, patient-centered interactions that begin once the patient seeks care. This approach has proven to decrease DB by patients with dementia and improve their care, lessen staff problems during interactions, and increase staff morale.²⁰ Experts call for the adoption of an interpersonal approach to patient encounters, and there is evidence that creating organizational change by moving toward compassionate care can lead to a positive impact for patients.^54,55

Future Studies

There are growth opportunities in utilization of the DBRS. Analysis of the DBRS database by the VA Central Office (VACO) showed that the system is underutilized by facilities across the VA system.⁵⁶ In response to this current underutilization, VACO is taking steps to close these gaps through increasing training to staff and promotion of the use of the DBRS. A 2015 pilot study of VHA providers showed that > 70% of providers had experienced a DB as defined by VHA, but only 34% of them reported their most recently experienced DB within the past 12 months.²⁰ Thus, DBRS use must be studied within the context that patient-perpetrated DB is underreported in health care organizations.^{5,9,29,41,43,57,58} Studies addressing national DBRS utilization patterns and the cost associated with implementing the DBRS also are needed. One study suggests that there is an association between measures of facility complexity and staff perceptions of safety, which should be considered in analyzing DBRS usage.⁵⁷ Studies addressing the role of the DBRS and misconceptions that the tool may represent a punitive tool also are needed. VHA should consider how the attribution “disruptive behavior” assigns a negative connotation and leads HCPs to avoid using the DBRS. Additionally, DB reporting may increase when HCPs understand that DB reporting is part of the comprehensive, consultative strategy to provide the best care to patients.

Conclusion

Accurate reporting of DB events enables the development of strategies for multidisciplinary teams to work together to minimize hazards and to provide interventions that provide for the safe delivery of health care to all patients. Improving reporting ensures there is an accurate representation of how disruptive events impact care provided within a facility—and what types of variables may be associated with increased risk for these types of events.

Additionally, ensuring that reporting is maximized also provides the VHA with opportunities for DBCs to offer evidence-based risk assessment of violence and consultation to staff members who may benefit from improved competencies in working with patients who display DB. These potential improvements are consistent with the VHA I CARE values and will provide data that can inform recommendations for health care in other agencies/health care organizations.

Acknowledgments
This work was supported by the Center of Innovation on Disability and Rehabilitation Research (CINDRR) of the Health Services Research and Development Service, Office of Research and Development, Department of Veterans Affairs.

A three-pronged treatment approach can produce responses in indolent non-Hodgkin lymphoma (iNHL), according to research published in Nature Medicine.

The approach – “in situ vaccination (ISV)” – involves intratumoral injections of Fms-like tyrosine kinase 3 ligand (Flt3L), local radiotherapy, and intratumoral injections of a TLR3 agonist (poly-ICLC).

ISV produced responses in patients with iNHL, prompting regression of tumors that were directly targeted with ISV, as well as untreated tumors.

In preclinical experiments, ISV induced tumor regression in mice but also overcame resistance to PD1 inhibition. This result led researchers to initiate a trial testing ISV in combination with pembrolizumab in patients with lymphoma and solid tumors.

“We discovered why some tumors do not respond to PD1 blockade: insufficient dendritic cells (DCs) and cross-presentation,” lead study author Joshua Brody, MD, of the Icahn School of Medicine at Mount Sinai, New York, said in an interview. “We developed a treatment, in situ vaccination (ISV), which brings DCs to the tumor, loads them with tumor antigens, and activates the DCs.”

Specifically, the researchers found that injecting Flt3L into a tumor recruits intratumoral DCs, local radiotherapy loads the DCs with tumor-associated antigens, and poly-ICLC activates DCs. This approach produced responses in mouse models of lymphoma and patients with iNHL.
 

Preclinical results

Dr. Brody and his colleagues tested ISV in A20 tumor-bearing mice. The mice received intratumoral injections of Flt3L, followed by local radiotherapy and poly-ICLC.

Tumor regression occurred within days of radiotherapy. About 40% of mice experienced tumor-free survival of at least 3 months, although most tumors recurred within 4 weeks of ISV administration.

However, the researchers observed increased PD1 and PD-L1 expression in ISV-treated mice, so the team theorized that an anti-PD1 monoclonal antibody (RMP1-14) could improve the efficacy of ISV.

The researchers found that ISV plus RMP1-14 delayed tumor growth when compared with ISV alone, and the rate of durable remissions increased from about 40% to about 80%.
 

Clinical results

Dr. Brody and his colleagues also tested ISV in a clinical trial. That trial included 11 iNHL patients – 9 with follicular lymphoma, 1 with marginal zone lymphoma, and 1 with small lymphocytic lymphoma.

The patients received nine daily injections of Flt3L (25 mcg/kg) into a target lesion, then two doses of radiation (2 Gy) to the same lesion, and eight intratumoral injections of poly-ICLC (2 mg).

“We ... have observed dramatic clinical responses; i.e., we administer ISV at one tumor site, and tumors throughout the body regress,” Dr. Brody said.

At the target lesion, there were two complete responses, six partial responses, and three cases of stable disease. At nontarget lesions, there was one complete response, two partial responses, six cases of stable disease, and two cases of progression.

ISV was considered well tolerated. One patient had grade 2 fever, three had grade 1 fever, and nine had grade 1 flu-like symptoms. Two patients did not have any adverse events.

This research was supported by Merck, Celldex Therapeutics, Oncovir, and Genentech. The authors reported relationships with Acerta Pharma, Bristol Myers Squibb, Genentech, Gilead Sciences, Seattle Genetics, Pharmacyclics, Celgene, Celldex Therapeutics, and Oncovir.

jensmith@mdedge.com

SOURCE: Hammerich L et al. Nat Med. 2019 Apr 8. doi: 10.1038/s41591-019-0410-x.

A three-pronged treatment approach can produce responses in indolent non-Hodgkin lymphoma (iNHL), according to research published in Nature Medicine.

The approach – “in situ vaccination (ISV)” – involves intratumoral injections of Fms-like tyrosine kinase 3 ligand (Flt3L), local radiotherapy, and intratumoral injections of a TLR3 agonist (poly-ICLC).

ISV produced responses in patients with iNHL, prompting regression of tumors that were directly targeted with ISV, as well as untreated tumors.

In preclinical experiments, ISV induced tumor regression in mice but also overcame resistance to PD1 inhibition. This result led researchers to initiate a trial testing ISV in combination with pembrolizumab in patients with lymphoma and solid tumors.

“We discovered why some tumors do not respond to PD1 blockade: insufficient dendritic cells (DCs) and cross-presentation,” lead study author Joshua Brody, MD, of the Icahn School of Medicine at Mount Sinai, New York, said in an interview. “We developed a treatment, in situ vaccination (ISV), which brings DCs to the tumor, loads them with tumor antigens, and activates the DCs.”

Specifically, the researchers found that injecting Flt3L into a tumor recruits intratumoral DCs, local radiotherapy loads the DCs with tumor-associated antigens, and poly-ICLC activates DCs. This approach produced responses in mouse models of lymphoma and patients with iNHL.
 

Preclinical results

Dr. Brody and his colleagues tested ISV in A20 tumor-bearing mice. The mice received intratumoral injections of Flt3L, followed by local radiotherapy and poly-ICLC.

Tumor regression occurred within days of radiotherapy. About 40% of mice experienced tumor-free survival of at least 3 months, although most tumors recurred within 4 weeks of ISV administration.

However, the researchers observed increased PD1 and PD-L1 expression in ISV-treated mice, so the team theorized that an anti-PD1 monoclonal antibody (RMP1-14) could improve the efficacy of ISV.

The researchers found that ISV plus RMP1-14 delayed tumor growth when compared with ISV alone, and the rate of durable remissions increased from about 40% to about 80%.
 

Clinical results

Dr. Brody and his colleagues also tested ISV in a clinical trial. That trial included 11 iNHL patients – 9 with follicular lymphoma, 1 with marginal zone lymphoma, and 1 with small lymphocytic lymphoma.

The patients received nine daily injections of Flt3L (25 mcg/kg) into a target lesion, then two doses of radiation (2 Gy) to the same lesion, and eight intratumoral injections of poly-ICLC (2 mg).

“We ... have observed dramatic clinical responses; i.e., we administer ISV at one tumor site, and tumors throughout the body regress,” Dr. Brody said.

At the target lesion, there were two complete responses, six partial responses, and three cases of stable disease. At nontarget lesions, there was one complete response, two partial responses, six cases of stable disease, and two cases of progression.

ISV was considered well tolerated. One patient had grade 2 fever, three had grade 1 fever, and nine had grade 1 flu-like symptoms. Two patients did not have any adverse events.

This research was supported by Merck, Celldex Therapeutics, Oncovir, and Genentech. The authors reported relationships with Acerta Pharma, Bristol Myers Squibb, Genentech, Gilead Sciences, Seattle Genetics, Pharmacyclics, Celgene, Celldex Therapeutics, and Oncovir.

jensmith@mdedge.com

SOURCE: Hammerich L et al. Nat Med. 2019 Apr 8. doi: 10.1038/s41591-019-0410-x.

A three-pronged treatment approach can produce responses in indolent non-Hodgkin lymphoma (iNHL), according to research published in Nature Medicine.

The approach – “in situ vaccination (ISV)” – involves intratumoral injections of Fms-like tyrosine kinase 3 ligand (Flt3L), local radiotherapy, and intratumoral injections of a TLR3 agonist (poly-ICLC).

ISV produced responses in patients with iNHL, prompting regression of tumors that were directly targeted with ISV, as well as untreated tumors.

In preclinical experiments, ISV induced tumor regression in mice but also overcame resistance to PD1 inhibition. This result led researchers to initiate a trial testing ISV in combination with pembrolizumab in patients with lymphoma and solid tumors.

“We discovered why some tumors do not respond to PD1 blockade: insufficient dendritic cells (DCs) and cross-presentation,” lead study author Joshua Brody, MD, of the Icahn School of Medicine at Mount Sinai, New York, said in an interview. “We developed a treatment, in situ vaccination (ISV), which brings DCs to the tumor, loads them with tumor antigens, and activates the DCs.”

Specifically, the researchers found that injecting Flt3L into a tumor recruits intratumoral DCs, local radiotherapy loads the DCs with tumor-associated antigens, and poly-ICLC activates DCs. This approach produced responses in mouse models of lymphoma and patients with iNHL.
 

Preclinical results

Dr. Brody and his colleagues tested ISV in A20 tumor-bearing mice. The mice received intratumoral injections of Flt3L, followed by local radiotherapy and poly-ICLC.

Tumor regression occurred within days of radiotherapy. About 40% of mice experienced tumor-free survival of at least 3 months, although most tumors recurred within 4 weeks of ISV administration.

However, the researchers observed increased PD1 and PD-L1 expression in ISV-treated mice, so the team theorized that an anti-PD1 monoclonal antibody (RMP1-14) could improve the efficacy of ISV.

The researchers found that ISV plus RMP1-14 delayed tumor growth when compared with ISV alone, and the rate of durable remissions increased from about 40% to about 80%.
 

Clinical results

Dr. Brody and his colleagues also tested ISV in a clinical trial. That trial included 11 iNHL patients – 9 with follicular lymphoma, 1 with marginal zone lymphoma, and 1 with small lymphocytic lymphoma.

The patients received nine daily injections of Flt3L (25 mcg/kg) into a target lesion, then two doses of radiation (2 Gy) to the same lesion, and eight intratumoral injections of poly-ICLC (2 mg).

“We ... have observed dramatic clinical responses; i.e., we administer ISV at one tumor site, and tumors throughout the body regress,” Dr. Brody said.

At the target lesion, there were two complete responses, six partial responses, and three cases of stable disease. At nontarget lesions, there was one complete response, two partial responses, six cases of stable disease, and two cases of progression.

ISV was considered well tolerated. One patient had grade 2 fever, three had grade 1 fever, and nine had grade 1 flu-like symptoms. Two patients did not have any adverse events.

This research was supported by Merck, Celldex Therapeutics, Oncovir, and Genentech. The authors reported relationships with Acerta Pharma, Bristol Myers Squibb, Genentech, Gilead Sciences, Seattle Genetics, Pharmacyclics, Celgene, Celldex Therapeutics, and Oncovir.

jensmith@mdedge.com

SOURCE: Hammerich L et al. Nat Med. 2019 Apr 8. doi: 10.1038/s41591-019-0410-x.

Chronic pain is common among veterans treated in Veterans Health Administration (VHA) facilities, and optimal management remains challenging in the context of the national opioid misuse epidemic. The Eastern Oklahoma VA Health Care System (EOVAHCS) Pain Program offers a range of services that allow clinicians to tailor multimodal treatment strategies to a veteran’s needs. In 2014, a Modality Clinic was established to assess the utility of adding noninvasive treatment devices to the pain program’s armamentarium. This article addresses the context for introducing these devices and describes the EOVAHCS Pain Program and Modality Clinic. Also discussed are procedures and findings from an initial quality improvement evaluation designed to inform decision making regarding retention, expansion, or elimination of the EOVAHCS noninvasive, pain treatment device program.

Opioid prescriptions increased from 76 million in 1991 to 219 million in 2011. In 2011, the annual cost of chronic pain in the US was estimated at $635 billion.^1-6 The confluence of an increasing concern about undertreatment of pain and overconfidence for the safety of opioids led to what former US Surgeon General Vivek H. Murthy, MD, called the opioid crisis.⁷ As awareness of its unintended consequences of opioid prescribing increased, the VHA began looking for nonopioid treatments that would decrease pain intensity. The 1993 article by Kehlet and Dahl was one of the first discussions of a multimodal nonpharmacologic strategy for addressing acute postoperative pain.⁸ Their pivotal literature review concluded that nonpharmacologic modalities, such as acupuncture, cranial manipulation, cranial electrostimulation treatment (CES), and low-level light technologies (LLLT), carried less risk and produced equal or greater clinical effects than those of drug therapies.⁸

Electrical and Cold Laser Modalities

Multimodal treatment approaches increasingly are encouraged, and nonopioid pain control has become more common across medical disciplines from physical therapy to anesthesiology.^8-10 Innovative, noninvasive devices designed for self-use have appeared on the market. Many of these devices incorporate microcurrent electrical therapy (MET), CES, and/or LLLT (also known as cold laser).^11-16 LLLT is a light modality that seems to lead to increased ATP production, resulting in improved healing and decreased inflammation.^13-16 Although CES has been studied in a variety of patient populations, its effectiveness is not well understood.¹⁶ Research on the effects of CES on neurotransmitter levels as well as activation of parts of the brain involved in pain reception and transmission should clarify these mechanisms. Research has shown improvements in sleep and mood as well as overall pain reduction.^11,16 Research has focused primarily on individual modalities rather than on combination devices and has been conducted on populations unlike the veteran population (eg, women with fibromyalgia).

Most of the devices that use electrical or LLLT cannot be used safely by patients who have implantable electrical devices or have medical conditions such as unstable seizures, pregnancy, and active malignancies.

The most common adverse effects (AEs) of CES—dizziness and headaches—are minimal compared with the AEs of pain medications. MET and LLLT AEs generally are limited to skin irritation and muscle soreness.¹¹ Most devices require a prescription, and manufacturers provide training for purchase.

The Pain Program

EOVAHCS initially established its consultative pain program in 2013 to provide support, recommendations, and education about managing pain in veterans to primary care providers (PCPs). Veterans are referred to the pain program for a face-to-face assessment and set of recommendations to assist in developing a comprehensive pain treatment plan. Consistent with its multimodal, biopsychosocial rehabilitation model approach, the program also offers several chronic pain treatment services, including patient education courses, cognitive behavioral therapy (CBT) for chronic pain, chiropractic care, biofeedback, relaxation training, steroid injections, pain coaching, and a pain modality (noninvasive device) clinic. During their assessment, veterans are evaluated for the appropriateness of these programs, including treatment through the Pain Modality Clinic.

Pain Modality Clinic

The EOVAHCS Pain Modality Clinic was created in 2014 as a treatment and device-trial program to provide veterans access to newer noninvasive, patient-driven treatment devices as part of an active chronic pain self-management plan. A crucial innovation is that these devices are designed to be used by patients in their homes. These devices can be expensive, and not every patient will benefit from their use; therefore, clinic leaders recommended a trial before a device is issued to a veteran for home use.

The Pain Modality Clinic coordinator trains clinic facilitators on the device according to manufacturer’s guidelines. Each participating veteran takes part in a device trial to confirm that he or she is able to use the recommended device independently and is likely to benefit from its use. When appropriate, veterans who do not respond to the initial device trial could test the potential benefit of another device. Although data from these device trials are collected primarily to inform clinical decision making, this information also is useful in guiding local policy regarding continued support for each of the modalities.

Veterans who have chronic or persistent pain (≥ 3 months) that interferes with function or quality of life are considered good candidates for a device trial if they are actively involved in pain self-care, logistically able to participate, able to use a device long-term, and have no contraindications. “Active involvement” could be met by participation in any pain management effort, whether a specific exercise program, CBT, or other treatment.

The Modality Clinic currently offers device trials for persistent pain with Alpha-Stim-M (AS-M; Electromedical Products International, Mineral Wells, TX), Laser Touch One (LTO; Renewal Technologies, LLC, Phoenix, AZ), and Neurolumen (Oklahoma City, OK). Neurolumen devices were not available in the clinic initially and will not be discussed further in this article.

The first Alpha-Stim machine using MET and CES technology was created in 1981 for in-office pain management. In 2012, the currently used AS-M became available.¹¹ AS-M is FDA approved for treating pain, anxiety, depression, and sleep problems and is the device used in the EOVAHCS Modality Clinic. AS-M uses probes or electrodes to send a MET waveform through the body area in pain. The device uses ear clips to provide CES, which is thought to increase alpha waves in the brain.¹¹ The LTO is a device that combines LLLT and MET technologies in a home-use design.¹⁴ LTO is FDA approved for treating painand is a portable personal pain-relief device applied to the area of pain using electroconductive gel.

Both devices are designed for long-term, self-use, making them viable parts of a multimodal, chronic pain treatment plan. Contraindications for AS-M and LTO include having a pacemaker or an implantable defibrillator, pregnancy, current malignancy, or seizures. Eligible veterans with persistent pain and high levels of depression, anxiety, and/or sleep problems generally are triaged to AS-M, whereas those who have only pain intensity issues usually are assigned to LTO. Referral to the Modality Clinic is not limited to a specific type of pain; common pain conditions seen in the clinic are spine and joint pain, arthritis pain, myofascial pain, headaches, and neuropathy.

Training and Device Trials

Eligible veterans are educated about the device and complete clinical informed consent, which is documented in the electronic health record. The veterans’ primary care and/or specialist providers are contacted for concurrence regarding veterans’ participation in the treatment.

Protocols for the device trials are based on the manufacturers’ recommendations, adjusted to what is feasible in the clinic (manufacturers approved the changes). The number of treatments per trial varies by device. For AS-M, veterans come to the clinic 5 days a week for 2 weeks. For LTO, veterans attend the clinic 5 days a week for 1 week.

At the beginning of a device trial, a trained facilitator teaches each veteran and caregiver to use the device, sets functional goals for the trial, and provides education on the trial questionnaires and daily pain logs. The veteran then follows the device protocol in the clinic where the facilitator can respond to questions and address any issues. With support from their caregivers, veterans are expected to become independent on their device use by the end of the trial. Clinic staff or the veteran can stop the device trial at any point, without affecting the veteran’s participation in or eligibility for other EOVAHCS pain programs.

This project was submitted to the University of Oklahoma Health Sciences Center Institutional Review Board and was exempted from institutional review board oversight as a retrospective, quality improvement effort. Before data analysis, the EOVAHCS Coordinator for Research and Development reviewed the procedures to ensure that all policies were being followed.

Methods

Data for veterans who completed valid treatments of AS-M or LTO from May 9, 2014 to August 20, 2016, were included in the analyses. For an AS-M treatment to be considered valid, the veteran must have attended at least 8 sessions and completed assessment instruments at baseline (preintervention) and following completion (postintervention). For an LTO treatment to be considered valid, the veteran must have attended at least 4 sessions and completed assessment measures at baseline and after completion.

Measures

Veterans completed the following measures at baseline and after trial completion:

The Beck Depression Inventory (BDI-II) is a 21-item measure designed to assess depressive symptoms. Each item assesses intensity on a 0-to-3 scale. Scores from 0 to 13 indicate minimum depression; 14 to 19, mild depression; 20 to 28, moderate depression, and 29 to 63, severe depression.¹⁷

The Beck Anxiety Inventory (BAI) is a 21-item measure of anxiety symptoms that uses a 0-to-3 scale to assess severity of subjective, somatic, or panic-related symptoms of anxiety. Scores ranging from 0 to 9 indicate minimal anxiety; 10 to 16, mild anxiety; 17 to 29, moderate anxiety, and 30 to 63, severe anxiety.¹⁸

The Pain Catastrophizing Scale (PCS) is a 13-item measure of pain catastrophizing, a crucial marker of how individuals experience pain. Items are scored on a 0-to-4 scale; scores of ≥ 30 indicate a clinically relevant level of catastrophizing.¹⁹

The Subjective Units of Distress Scale (SUD) is a single-item measure of the subjective intensity of disturbance or distress currently being experienced. It is scored from 0 to 10; 1 to 4 is mild, 5 to 6 is moderate, and 7 to 10 is severe.²⁰

The Brief Pain Inventory (BPI) measures pain intensity and the impact of pain on functioning. Four items assess pain intensity at its worst, least, and average over the previous 24 hours and at the time of assessment; responses are on a 0-to-10 scale with 10 being most severe. The pain intensity measure is the average of scores on these 4 items. Pain interference is measured with respect to 7 daily activities; general activity, walking, work, mood, enjoyment of life, relations with others, and sleep. Each of these items is scored on a 0-to-10 scale with 10 being the most severe. The pain interference measure is the average of scores on these 7 items.²¹

Participants completed a daily pain log and recorded self-ratings (0-to-10 scale) of pain and relaxation levels before and after using the device. These scores were primarily used to assist in determining whether goals, set collaboratively by the clinician and the veteran at the first session, had been met.

Analysis

Descriptive statistics were used to characterize the sample overall and by modality. Paired t tests were used to assess changes on each assessment measure over time and for each device separately. The significance of change was assessed for 8 outcomes for each device. In this context, using a conservative Bonferroni correction, significance was set at P < .006. Because AS-M is designed to address depression, anxiety, and sleep as well as pain, whereas LTO is not, device assignments were based on clinical considerations rather than randomization. Therefore, no comparisons were made between devices, and outcomes were assessed independently for the 2 devices. Analyses were performed using SAS 9.4 (Cary, NC).

Results

Device trials were initiated for 161 veterans (LTO, 70; AS-M, 91). Distribution of devices was unequal because veterans are assigned to 1 device or the other based on clinical presentation. Failure to complete a trial (n = 46; 28.6%) typically was because of travel barriers, lack of interest in continuing, and for 3 veterans, reports of headaches that they attributed to the AS-M treatment. Of the 115 participants who completed valid trials, 88 (76.5%) also completed assessment measures at pre- and postintervention (LTO = 38; AS-M = 50). None of the participants in this study completed trials with both the AS-M and LTO devices.

Most participants were male (84.1%) and rural residents (85.5%) (Table 1). 

Pain Reduction

Treatment with AS-M or LTO was associated with statistically significant reductions in pain severity (BPI), pain interference (BPI), daily pain intensity scores (daily pain log), and pain catastrophizing (PCS) (Tables 2 and 3).

Impact on Mood

Use of AS-M was associated with statistically significant improvements in depression (BDI-II), anxiety (BAI), and distress (SUD) scores. In addition, veterans completing AS-M treatment showed a statistically significant improvement in self-reported relaxation scores. Interestingly, use of LTO also resulted in a statistically significant decrease in anxiety (BAI) and a nonstatistically significant decrease in depression (BDI-II).

Figure 1 and 2 illustrates the clinical impact of each device in shifting participants from 1 level of symptom severity to another. 

Discussion

Use of both AS-M and LTO at EOVAHC was associated with reduced pain intensity. The devices also had positive effects beyond pain in areas such as depression, anxiety, and distress. Remission of depression and anxiety symptoms has been associated with significant decline in pain symptoms, suggesting that pain is best treated through multimodal approaches.²²

In the context of the opioid crisis, the availability of effective nonopioid, nonpharmacologic, noninvasive treatments for chronic pain is needed. The Joint Commission recently expanded its pain management guidelines to support hospitals offering nonpharmacologic pain treatments.²³ Integrating AS-M, LTO, or similar products into standard pain management practices allows for other treatment pathways with positive outcomes for providers and patients. The Joint Commission also recommends an interdisciplinary approach, defined as a process whereby health care professionals from different disciplines collaborate to diagnose and treat patients experiencing difficult pain conditions. This approach facilitates multimodal management because these disciplines contribute knowledge about a variety of treatment options. Devices such AS-M and LTO are well suited to interdisciplinary pain management because they are not seen as being under the purview of a specific health care specialty.

Limitations

Our findings are limited because they are derived from a retrospective, quality improvement evaluation of outcomes from a single clinic. Findings must be considered in the context of the relatively small samples of veterans. Because analyses were conducted as part of a quality improvement effort, veterans were offered a specific device based on clinical indications, there were no comparisons between devices, and there was no comparison group. Although most participants were using medication and other treatments as part of their pain treatment plan, all reported continued pain intensity before use of a device. Analyses did not control for variation in treatments received concurrently. Last, the logs used to collect self-report data on daily pain and relaxation levels were not validated.

The data highlight a clear need for research to better understand the long-term effects of these devices as well as the characteristics of patients who respond best to each device. Noninvasive treatments for pain often are dismissed as placebos. Rigorously designed, controlled studies will help demonstrate that these devices offer a statistically significant benefit beyond any placebo effect.

Conclusion

Understanding of chronic pain and its treatment will continue to evolve. It is clear that each person dealing with chronic pain requires a tailored combination of treatments and multimodal approaches, which is more effective than any single treatment. Nonpharmacologic, noninvasive devices pose fewer risks and seem to be more effective in reducing pain intensity than traditional treatments, including medications or surgical intervention. In light of the current emphasis on evidence-based health care and as the evidence for the effectiveness of noninvasive pain devices modalities grows, it is likely that treatments incorporating modalities such as MET, CES, and LLLT will become common options for managing chronic pain.

Chronic pain is common among veterans treated in Veterans Health Administration (VHA) facilities, and optimal management remains challenging in the context of the national opioid misuse epidemic. The Eastern Oklahoma VA Health Care System (EOVAHCS) Pain Program offers a range of services that allow clinicians to tailor multimodal treatment strategies to a veteran’s needs. In 2014, a Modality Clinic was established to assess the utility of adding noninvasive treatment devices to the pain program’s armamentarium. This article addresses the context for introducing these devices and describes the EOVAHCS Pain Program and Modality Clinic. Also discussed are procedures and findings from an initial quality improvement evaluation designed to inform decision making regarding retention, expansion, or elimination of the EOVAHCS noninvasive, pain treatment device program.

Opioid prescriptions increased from 76 million in 1991 to 219 million in 2011. In 2011, the annual cost of chronic pain in the US was estimated at $635 billion.^1-6 The confluence of an increasing concern about undertreatment of pain and overconfidence for the safety of opioids led to what former US Surgeon General Vivek H. Murthy, MD, called the opioid crisis.⁷ As awareness of its unintended consequences of opioid prescribing increased, the VHA began looking for nonopioid treatments that would decrease pain intensity. The 1993 article by Kehlet and Dahl was one of the first discussions of a multimodal nonpharmacologic strategy for addressing acute postoperative pain.⁸ Their pivotal literature review concluded that nonpharmacologic modalities, such as acupuncture, cranial manipulation, cranial electrostimulation treatment (CES), and low-level light technologies (LLLT), carried less risk and produced equal or greater clinical effects than those of drug therapies.⁸

Electrical and Cold Laser Modalities

Multimodal treatment approaches increasingly are encouraged, and nonopioid pain control has become more common across medical disciplines from physical therapy to anesthesiology.^8-10 Innovative, noninvasive devices designed for self-use have appeared on the market. Many of these devices incorporate microcurrent electrical therapy (MET), CES, and/or LLLT (also known as cold laser).^11-16 LLLT is a light modality that seems to lead to increased ATP production, resulting in improved healing and decreased inflammation.^13-16 Although CES has been studied in a variety of patient populations, its effectiveness is not well understood.¹⁶ Research on the effects of CES on neurotransmitter levels as well as activation of parts of the brain involved in pain reception and transmission should clarify these mechanisms. Research has shown improvements in sleep and mood as well as overall pain reduction.^11,16 Research has focused primarily on individual modalities rather than on combination devices and has been conducted on populations unlike the veteran population (eg, women with fibromyalgia).

Most of the devices that use electrical or LLLT cannot be used safely by patients who have implantable electrical devices or have medical conditions such as unstable seizures, pregnancy, and active malignancies.

The most common adverse effects (AEs) of CES—dizziness and headaches—are minimal compared with the AEs of pain medications. MET and LLLT AEs generally are limited to skin irritation and muscle soreness.¹¹ Most devices require a prescription, and manufacturers provide training for purchase.

The Pain Program

EOVAHCS initially established its consultative pain program in 2013 to provide support, recommendations, and education about managing pain in veterans to primary care providers (PCPs). Veterans are referred to the pain program for a face-to-face assessment and set of recommendations to assist in developing a comprehensive pain treatment plan. Consistent with its multimodal, biopsychosocial rehabilitation model approach, the program also offers several chronic pain treatment services, including patient education courses, cognitive behavioral therapy (CBT) for chronic pain, chiropractic care, biofeedback, relaxation training, steroid injections, pain coaching, and a pain modality (noninvasive device) clinic. During their assessment, veterans are evaluated for the appropriateness of these programs, including treatment through the Pain Modality Clinic.

Pain Modality Clinic

The EOVAHCS Pain Modality Clinic was created in 2014 as a treatment and device-trial program to provide veterans access to newer noninvasive, patient-driven treatment devices as part of an active chronic pain self-management plan. A crucial innovation is that these devices are designed to be used by patients in their homes. These devices can be expensive, and not every patient will benefit from their use; therefore, clinic leaders recommended a trial before a device is issued to a veteran for home use.

The Pain Modality Clinic coordinator trains clinic facilitators on the device according to manufacturer’s guidelines. Each participating veteran takes part in a device trial to confirm that he or she is able to use the recommended device independently and is likely to benefit from its use. When appropriate, veterans who do not respond to the initial device trial could test the potential benefit of another device. Although data from these device trials are collected primarily to inform clinical decision making, this information also is useful in guiding local policy regarding continued support for each of the modalities.

Veterans who have chronic or persistent pain (≥ 3 months) that interferes with function or quality of life are considered good candidates for a device trial if they are actively involved in pain self-care, logistically able to participate, able to use a device long-term, and have no contraindications. “Active involvement” could be met by participation in any pain management effort, whether a specific exercise program, CBT, or other treatment.

The Modality Clinic currently offers device trials for persistent pain with Alpha-Stim-M (AS-M; Electromedical Products International, Mineral Wells, TX), Laser Touch One (LTO; Renewal Technologies, LLC, Phoenix, AZ), and Neurolumen (Oklahoma City, OK). Neurolumen devices were not available in the clinic initially and will not be discussed further in this article.

The first Alpha-Stim machine using MET and CES technology was created in 1981 for in-office pain management. In 2012, the currently used AS-M became available.¹¹ AS-M is FDA approved for treating pain, anxiety, depression, and sleep problems and is the device used in the EOVAHCS Modality Clinic. AS-M uses probes or electrodes to send a MET waveform through the body area in pain. The device uses ear clips to provide CES, which is thought to increase alpha waves in the brain.¹¹ The LTO is a device that combines LLLT and MET technologies in a home-use design.¹⁴ LTO is FDA approved for treating painand is a portable personal pain-relief device applied to the area of pain using electroconductive gel.

Both devices are designed for long-term, self-use, making them viable parts of a multimodal, chronic pain treatment plan. Contraindications for AS-M and LTO include having a pacemaker or an implantable defibrillator, pregnancy, current malignancy, or seizures. Eligible veterans with persistent pain and high levels of depression, anxiety, and/or sleep problems generally are triaged to AS-M, whereas those who have only pain intensity issues usually are assigned to LTO. Referral to the Modality Clinic is not limited to a specific type of pain; common pain conditions seen in the clinic are spine and joint pain, arthritis pain, myofascial pain, headaches, and neuropathy.

Training and Device Trials

Eligible veterans are educated about the device and complete clinical informed consent, which is documented in the electronic health record. The veterans’ primary care and/or specialist providers are contacted for concurrence regarding veterans’ participation in the treatment.

Protocols for the device trials are based on the manufacturers’ recommendations, adjusted to what is feasible in the clinic (manufacturers approved the changes). The number of treatments per trial varies by device. For AS-M, veterans come to the clinic 5 days a week for 2 weeks. For LTO, veterans attend the clinic 5 days a week for 1 week.

At the beginning of a device trial, a trained facilitator teaches each veteran and caregiver to use the device, sets functional goals for the trial, and provides education on the trial questionnaires and daily pain logs. The veteran then follows the device protocol in the clinic where the facilitator can respond to questions and address any issues. With support from their caregivers, veterans are expected to become independent on their device use by the end of the trial. Clinic staff or the veteran can stop the device trial at any point, without affecting the veteran’s participation in or eligibility for other EOVAHCS pain programs.

This project was submitted to the University of Oklahoma Health Sciences Center Institutional Review Board and was exempted from institutional review board oversight as a retrospective, quality improvement effort. Before data analysis, the EOVAHCS Coordinator for Research and Development reviewed the procedures to ensure that all policies were being followed.

Methods

Data for veterans who completed valid treatments of AS-M or LTO from May 9, 2014 to August 20, 2016, were included in the analyses. For an AS-M treatment to be considered valid, the veteran must have attended at least 8 sessions and completed assessment instruments at baseline (preintervention) and following completion (postintervention). For an LTO treatment to be considered valid, the veteran must have attended at least 4 sessions and completed assessment measures at baseline and after completion.

Measures

Veterans completed the following measures at baseline and after trial completion:

The Beck Depression Inventory (BDI-II) is a 21-item measure designed to assess depressive symptoms. Each item assesses intensity on a 0-to-3 scale. Scores from 0 to 13 indicate minimum depression; 14 to 19, mild depression; 20 to 28, moderate depression, and 29 to 63, severe depression.¹⁷

The Beck Anxiety Inventory (BAI) is a 21-item measure of anxiety symptoms that uses a 0-to-3 scale to assess severity of subjective, somatic, or panic-related symptoms of anxiety. Scores ranging from 0 to 9 indicate minimal anxiety; 10 to 16, mild anxiety; 17 to 29, moderate anxiety, and 30 to 63, severe anxiety.¹⁸

The Pain Catastrophizing Scale (PCS) is a 13-item measure of pain catastrophizing, a crucial marker of how individuals experience pain. Items are scored on a 0-to-4 scale; scores of ≥ 30 indicate a clinically relevant level of catastrophizing.¹⁹

The Subjective Units of Distress Scale (SUD) is a single-item measure of the subjective intensity of disturbance or distress currently being experienced. It is scored from 0 to 10; 1 to 4 is mild, 5 to 6 is moderate, and 7 to 10 is severe.²⁰

The Brief Pain Inventory (BPI) measures pain intensity and the impact of pain on functioning. Four items assess pain intensity at its worst, least, and average over the previous 24 hours and at the time of assessment; responses are on a 0-to-10 scale with 10 being most severe. The pain intensity measure is the average of scores on these 4 items. Pain interference is measured with respect to 7 daily activities; general activity, walking, work, mood, enjoyment of life, relations with others, and sleep. Each of these items is scored on a 0-to-10 scale with 10 being the most severe. The pain interference measure is the average of scores on these 7 items.²¹

Participants completed a daily pain log and recorded self-ratings (0-to-10 scale) of pain and relaxation levels before and after using the device. These scores were primarily used to assist in determining whether goals, set collaboratively by the clinician and the veteran at the first session, had been met.

Analysis

Descriptive statistics were used to characterize the sample overall and by modality. Paired t tests were used to assess changes on each assessment measure over time and for each device separately. The significance of change was assessed for 8 outcomes for each device. In this context, using a conservative Bonferroni correction, significance was set at P < .006. Because AS-M is designed to address depression, anxiety, and sleep as well as pain, whereas LTO is not, device assignments were based on clinical considerations rather than randomization. Therefore, no comparisons were made between devices, and outcomes were assessed independently for the 2 devices. Analyses were performed using SAS 9.4 (Cary, NC).

Results

Device trials were initiated for 161 veterans (LTO, 70; AS-M, 91). Distribution of devices was unequal because veterans are assigned to 1 device or the other based on clinical presentation. Failure to complete a trial (n = 46; 28.6%) typically was because of travel barriers, lack of interest in continuing, and for 3 veterans, reports of headaches that they attributed to the AS-M treatment. Of the 115 participants who completed valid trials, 88 (76.5%) also completed assessment measures at pre- and postintervention (LTO = 38; AS-M = 50). None of the participants in this study completed trials with both the AS-M and LTO devices.

Most participants were male (84.1%) and rural residents (85.5%) (Table 1). 

Pain Reduction

Treatment with AS-M or LTO was associated with statistically significant reductions in pain severity (BPI), pain interference (BPI), daily pain intensity scores (daily pain log), and pain catastrophizing (PCS) (Tables 2 and 3).

Impact on Mood

Use of AS-M was associated with statistically significant improvements in depression (BDI-II), anxiety (BAI), and distress (SUD) scores. In addition, veterans completing AS-M treatment showed a statistically significant improvement in self-reported relaxation scores. Interestingly, use of LTO also resulted in a statistically significant decrease in anxiety (BAI) and a nonstatistically significant decrease in depression (BDI-II).

Figure 1 and 2 illustrates the clinical impact of each device in shifting participants from 1 level of symptom severity to another. 

Discussion

Use of both AS-M and LTO at EOVAHC was associated with reduced pain intensity. The devices also had positive effects beyond pain in areas such as depression, anxiety, and distress. Remission of depression and anxiety symptoms has been associated with significant decline in pain symptoms, suggesting that pain is best treated through multimodal approaches.²²

In the context of the opioid crisis, the availability of effective nonopioid, nonpharmacologic, noninvasive treatments for chronic pain is needed. The Joint Commission recently expanded its pain management guidelines to support hospitals offering nonpharmacologic pain treatments.²³ Integrating AS-M, LTO, or similar products into standard pain management practices allows for other treatment pathways with positive outcomes for providers and patients. The Joint Commission also recommends an interdisciplinary approach, defined as a process whereby health care professionals from different disciplines collaborate to diagnose and treat patients experiencing difficult pain conditions. This approach facilitates multimodal management because these disciplines contribute knowledge about a variety of treatment options. Devices such AS-M and LTO are well suited to interdisciplinary pain management because they are not seen as being under the purview of a specific health care specialty.

Limitations

Our findings are limited because they are derived from a retrospective, quality improvement evaluation of outcomes from a single clinic. Findings must be considered in the context of the relatively small samples of veterans. Because analyses were conducted as part of a quality improvement effort, veterans were offered a specific device based on clinical indications, there were no comparisons between devices, and there was no comparison group. Although most participants were using medication and other treatments as part of their pain treatment plan, all reported continued pain intensity before use of a device. Analyses did not control for variation in treatments received concurrently. Last, the logs used to collect self-report data on daily pain and relaxation levels were not validated.

The data highlight a clear need for research to better understand the long-term effects of these devices as well as the characteristics of patients who respond best to each device. Noninvasive treatments for pain often are dismissed as placebos. Rigorously designed, controlled studies will help demonstrate that these devices offer a statistically significant benefit beyond any placebo effect.

Conclusion

Understanding of chronic pain and its treatment will continue to evolve. It is clear that each person dealing with chronic pain requires a tailored combination of treatments and multimodal approaches, which is more effective than any single treatment. Nonpharmacologic, noninvasive devices pose fewer risks and seem to be more effective in reducing pain intensity than traditional treatments, including medications or surgical intervention. In light of the current emphasis on evidence-based health care and as the evidence for the effectiveness of noninvasive pain devices modalities grows, it is likely that treatments incorporating modalities such as MET, CES, and LLLT will become common options for managing chronic pain.

Chronic pain is common among veterans treated in Veterans Health Administration (VHA) facilities, and optimal management remains challenging in the context of the national opioid misuse epidemic. The Eastern Oklahoma VA Health Care System (EOVAHCS) Pain Program offers a range of services that allow clinicians to tailor multimodal treatment strategies to a veteran’s needs. In 2014, a Modality Clinic was established to assess the utility of adding noninvasive treatment devices to the pain program’s armamentarium. This article addresses the context for introducing these devices and describes the EOVAHCS Pain Program and Modality Clinic. Also discussed are procedures and findings from an initial quality improvement evaluation designed to inform decision making regarding retention, expansion, or elimination of the EOVAHCS noninvasive, pain treatment device program.

Opioid prescriptions increased from 76 million in 1991 to 219 million in 2011. In 2011, the annual cost of chronic pain in the US was estimated at $635 billion.^1-6 The confluence of an increasing concern about undertreatment of pain and overconfidence for the safety of opioids led to what former US Surgeon General Vivek H. Murthy, MD, called the opioid crisis.⁷ As awareness of its unintended consequences of opioid prescribing increased, the VHA began looking for nonopioid treatments that would decrease pain intensity. The 1993 article by Kehlet and Dahl was one of the first discussions of a multimodal nonpharmacologic strategy for addressing acute postoperative pain.⁸ Their pivotal literature review concluded that nonpharmacologic modalities, such as acupuncture, cranial manipulation, cranial electrostimulation treatment (CES), and low-level light technologies (LLLT), carried less risk and produced equal or greater clinical effects than those of drug therapies.⁸

Electrical and Cold Laser Modalities

Multimodal treatment approaches increasingly are encouraged, and nonopioid pain control has become more common across medical disciplines from physical therapy to anesthesiology.^8-10 Innovative, noninvasive devices designed for self-use have appeared on the market. Many of these devices incorporate microcurrent electrical therapy (MET), CES, and/or LLLT (also known as cold laser).^11-16 LLLT is a light modality that seems to lead to increased ATP production, resulting in improved healing and decreased inflammation.^13-16 Although CES has been studied in a variety of patient populations, its effectiveness is not well understood.¹⁶ Research on the effects of CES on neurotransmitter levels as well as activation of parts of the brain involved in pain reception and transmission should clarify these mechanisms. Research has shown improvements in sleep and mood as well as overall pain reduction.^11,16 Research has focused primarily on individual modalities rather than on combination devices and has been conducted on populations unlike the veteran population (eg, women with fibromyalgia).

Most of the devices that use electrical or LLLT cannot be used safely by patients who have implantable electrical devices or have medical conditions such as unstable seizures, pregnancy, and active malignancies.

The most common adverse effects (AEs) of CES—dizziness and headaches—are minimal compared with the AEs of pain medications. MET and LLLT AEs generally are limited to skin irritation and muscle soreness.¹¹ Most devices require a prescription, and manufacturers provide training for purchase.

The Pain Program

EOVAHCS initially established its consultative pain program in 2013 to provide support, recommendations, and education about managing pain in veterans to primary care providers (PCPs). Veterans are referred to the pain program for a face-to-face assessment and set of recommendations to assist in developing a comprehensive pain treatment plan. Consistent with its multimodal, biopsychosocial rehabilitation model approach, the program also offers several chronic pain treatment services, including patient education courses, cognitive behavioral therapy (CBT) for chronic pain, chiropractic care, biofeedback, relaxation training, steroid injections, pain coaching, and a pain modality (noninvasive device) clinic. During their assessment, veterans are evaluated for the appropriateness of these programs, including treatment through the Pain Modality Clinic.

Pain Modality Clinic

The EOVAHCS Pain Modality Clinic was created in 2014 as a treatment and device-trial program to provide veterans access to newer noninvasive, patient-driven treatment devices as part of an active chronic pain self-management plan. A crucial innovation is that these devices are designed to be used by patients in their homes. These devices can be expensive, and not every patient will benefit from their use; therefore, clinic leaders recommended a trial before a device is issued to a veteran for home use.

The Pain Modality Clinic coordinator trains clinic facilitators on the device according to manufacturer’s guidelines. Each participating veteran takes part in a device trial to confirm that he or she is able to use the recommended device independently and is likely to benefit from its use. When appropriate, veterans who do not respond to the initial device trial could test the potential benefit of another device. Although data from these device trials are collected primarily to inform clinical decision making, this information also is useful in guiding local policy regarding continued support for each of the modalities.

Veterans who have chronic or persistent pain (≥ 3 months) that interferes with function or quality of life are considered good candidates for a device trial if they are actively involved in pain self-care, logistically able to participate, able to use a device long-term, and have no contraindications. “Active involvement” could be met by participation in any pain management effort, whether a specific exercise program, CBT, or other treatment.

The Modality Clinic currently offers device trials for persistent pain with Alpha-Stim-M (AS-M; Electromedical Products International, Mineral Wells, TX), Laser Touch One (LTO; Renewal Technologies, LLC, Phoenix, AZ), and Neurolumen (Oklahoma City, OK). Neurolumen devices were not available in the clinic initially and will not be discussed further in this article.

The first Alpha-Stim machine using MET and CES technology was created in 1981 for in-office pain management. In 2012, the currently used AS-M became available.¹¹ AS-M is FDA approved for treating pain, anxiety, depression, and sleep problems and is the device used in the EOVAHCS Modality Clinic. AS-M uses probes or electrodes to send a MET waveform through the body area in pain. The device uses ear clips to provide CES, which is thought to increase alpha waves in the brain.¹¹ The LTO is a device that combines LLLT and MET technologies in a home-use design.¹⁴ LTO is FDA approved for treating painand is a portable personal pain-relief device applied to the area of pain using electroconductive gel.

Both devices are designed for long-term, self-use, making them viable parts of a multimodal, chronic pain treatment plan. Contraindications for AS-M and LTO include having a pacemaker or an implantable defibrillator, pregnancy, current malignancy, or seizures. Eligible veterans with persistent pain and high levels of depression, anxiety, and/or sleep problems generally are triaged to AS-M, whereas those who have only pain intensity issues usually are assigned to LTO. Referral to the Modality Clinic is not limited to a specific type of pain; common pain conditions seen in the clinic are spine and joint pain, arthritis pain, myofascial pain, headaches, and neuropathy.

Training and Device Trials

Eligible veterans are educated about the device and complete clinical informed consent, which is documented in the electronic health record. The veterans’ primary care and/or specialist providers are contacted for concurrence regarding veterans’ participation in the treatment.

Protocols for the device trials are based on the manufacturers’ recommendations, adjusted to what is feasible in the clinic (manufacturers approved the changes). The number of treatments per trial varies by device. For AS-M, veterans come to the clinic 5 days a week for 2 weeks. For LTO, veterans attend the clinic 5 days a week for 1 week.

At the beginning of a device trial, a trained facilitator teaches each veteran and caregiver to use the device, sets functional goals for the trial, and provides education on the trial questionnaires and daily pain logs. The veteran then follows the device protocol in the clinic where the facilitator can respond to questions and address any issues. With support from their caregivers, veterans are expected to become independent on their device use by the end of the trial. Clinic staff or the veteran can stop the device trial at any point, without affecting the veteran’s participation in or eligibility for other EOVAHCS pain programs.

This project was submitted to the University of Oklahoma Health Sciences Center Institutional Review Board and was exempted from institutional review board oversight as a retrospective, quality improvement effort. Before data analysis, the EOVAHCS Coordinator for Research and Development reviewed the procedures to ensure that all policies were being followed.

Methods

Data for veterans who completed valid treatments of AS-M or LTO from May 9, 2014 to August 20, 2016, were included in the analyses. For an AS-M treatment to be considered valid, the veteran must have attended at least 8 sessions and completed assessment instruments at baseline (preintervention) and following completion (postintervention). For an LTO treatment to be considered valid, the veteran must have attended at least 4 sessions and completed assessment measures at baseline and after completion.

Measures

Veterans completed the following measures at baseline and after trial completion:

The Beck Depression Inventory (BDI-II) is a 21-item measure designed to assess depressive symptoms. Each item assesses intensity on a 0-to-3 scale. Scores from 0 to 13 indicate minimum depression; 14 to 19, mild depression; 20 to 28, moderate depression, and 29 to 63, severe depression.¹⁷

The Beck Anxiety Inventory (BAI) is a 21-item measure of anxiety symptoms that uses a 0-to-3 scale to assess severity of subjective, somatic, or panic-related symptoms of anxiety. Scores ranging from 0 to 9 indicate minimal anxiety; 10 to 16, mild anxiety; 17 to 29, moderate anxiety, and 30 to 63, severe anxiety.¹⁸

The Pain Catastrophizing Scale (PCS) is a 13-item measure of pain catastrophizing, a crucial marker of how individuals experience pain. Items are scored on a 0-to-4 scale; scores of ≥ 30 indicate a clinically relevant level of catastrophizing.¹⁹

The Subjective Units of Distress Scale (SUD) is a single-item measure of the subjective intensity of disturbance or distress currently being experienced. It is scored from 0 to 10; 1 to 4 is mild, 5 to 6 is moderate, and 7 to 10 is severe.²⁰

The Brief Pain Inventory (BPI) measures pain intensity and the impact of pain on functioning. Four items assess pain intensity at its worst, least, and average over the previous 24 hours and at the time of assessment; responses are on a 0-to-10 scale with 10 being most severe. The pain intensity measure is the average of scores on these 4 items. Pain interference is measured with respect to 7 daily activities; general activity, walking, work, mood, enjoyment of life, relations with others, and sleep. Each of these items is scored on a 0-to-10 scale with 10 being the most severe. The pain interference measure is the average of scores on these 7 items.²¹

Participants completed a daily pain log and recorded self-ratings (0-to-10 scale) of pain and relaxation levels before and after using the device. These scores were primarily used to assist in determining whether goals, set collaboratively by the clinician and the veteran at the first session, had been met.

Analysis

Descriptive statistics were used to characterize the sample overall and by modality. Paired t tests were used to assess changes on each assessment measure over time and for each device separately. The significance of change was assessed for 8 outcomes for each device. In this context, using a conservative Bonferroni correction, significance was set at P < .006. Because AS-M is designed to address depression, anxiety, and sleep as well as pain, whereas LTO is not, device assignments were based on clinical considerations rather than randomization. Therefore, no comparisons were made between devices, and outcomes were assessed independently for the 2 devices. Analyses were performed using SAS 9.4 (Cary, NC).

Results

Device trials were initiated for 161 veterans (LTO, 70; AS-M, 91). Distribution of devices was unequal because veterans are assigned to 1 device or the other based on clinical presentation. Failure to complete a trial (n = 46; 28.6%) typically was because of travel barriers, lack of interest in continuing, and for 3 veterans, reports of headaches that they attributed to the AS-M treatment. Of the 115 participants who completed valid trials, 88 (76.5%) also completed assessment measures at pre- and postintervention (LTO = 38; AS-M = 50). None of the participants in this study completed trials with both the AS-M and LTO devices.

Most participants were male (84.1%) and rural residents (85.5%) (Table 1). 

Pain Reduction

Treatment with AS-M or LTO was associated with statistically significant reductions in pain severity (BPI), pain interference (BPI), daily pain intensity scores (daily pain log), and pain catastrophizing (PCS) (Tables 2 and 3).

Impact on Mood

Use of AS-M was associated with statistically significant improvements in depression (BDI-II), anxiety (BAI), and distress (SUD) scores. In addition, veterans completing AS-M treatment showed a statistically significant improvement in self-reported relaxation scores. Interestingly, use of LTO also resulted in a statistically significant decrease in anxiety (BAI) and a nonstatistically significant decrease in depression (BDI-II).

Figure 1 and 2 illustrates the clinical impact of each device in shifting participants from 1 level of symptom severity to another. 

Discussion

Use of both AS-M and LTO at EOVAHC was associated with reduced pain intensity. The devices also had positive effects beyond pain in areas such as depression, anxiety, and distress. Remission of depression and anxiety symptoms has been associated with significant decline in pain symptoms, suggesting that pain is best treated through multimodal approaches.²²

In the context of the opioid crisis, the availability of effective nonopioid, nonpharmacologic, noninvasive treatments for chronic pain is needed. The Joint Commission recently expanded its pain management guidelines to support hospitals offering nonpharmacologic pain treatments.²³ Integrating AS-M, LTO, or similar products into standard pain management practices allows for other treatment pathways with positive outcomes for providers and patients. The Joint Commission also recommends an interdisciplinary approach, defined as a process whereby health care professionals from different disciplines collaborate to diagnose and treat patients experiencing difficult pain conditions. This approach facilitates multimodal management because these disciplines contribute knowledge about a variety of treatment options. Devices such AS-M and LTO are well suited to interdisciplinary pain management because they are not seen as being under the purview of a specific health care specialty.

Limitations

Our findings are limited because they are derived from a retrospective, quality improvement evaluation of outcomes from a single clinic. Findings must be considered in the context of the relatively small samples of veterans. Because analyses were conducted as part of a quality improvement effort, veterans were offered a specific device based on clinical indications, there were no comparisons between devices, and there was no comparison group. Although most participants were using medication and other treatments as part of their pain treatment plan, all reported continued pain intensity before use of a device. Analyses did not control for variation in treatments received concurrently. Last, the logs used to collect self-report data on daily pain and relaxation levels were not validated.

The data highlight a clear need for research to better understand the long-term effects of these devices as well as the characteristics of patients who respond best to each device. Noninvasive treatments for pain often are dismissed as placebos. Rigorously designed, controlled studies will help demonstrate that these devices offer a statistically significant benefit beyond any placebo effect.

Conclusion

Understanding of chronic pain and its treatment will continue to evolve. It is clear that each person dealing with chronic pain requires a tailored combination of treatments and multimodal approaches, which is more effective than any single treatment. Nonpharmacologic, noninvasive devices pose fewer risks and seem to be more effective in reducing pain intensity than traditional treatments, including medications or surgical intervention. In light of the current emphasis on evidence-based health care and as the evidence for the effectiveness of noninvasive pain devices modalities grows, it is likely that treatments incorporating modalities such as MET, CES, and LLLT will become common options for managing chronic pain.